4,143 research outputs found

    Hepatic fibrogenesis requires sympathetic neurotransmitters

    Get PDF
    Background and aims: Hepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear. Methods: We studied cultured HSC and intact mice with liver injury to test the hypothesis that HSC respond to and produce SNS neurotransmitters to promote fibrogenesis. Results: HSC expressed adrenoceptors, catecholamine biosynthetic enzymes, released norepinephrine (NE), and were growth inhibited by α- and β-adrenoceptor antagonists. HSC from dopamine β-hydroxylase deficient (Dbh(−/−)) mice, which cannot make NE, grew poorly in culture and were rescued by NE. Inhibitor studies demonstrated that this effect was mediated via G protein coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3-kinase. Injury related fibrogenic responses were inhibited in Dbh(−/−) mice, as evidenced by reduced hepatic accumulation of α-smooth muscle actin(+ve) HSC and decreased induction of transforming growth factor β1 (TGF-β1) and collagen. Treatment with isoprenaline rescued HSC activation. HSC were also reduced in leptin deficient ob/ob mice which have reduced NE levels and are resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC proliferation, upregulated hepatic TGF-β1 and collagen, and increased liver fibrosis. Conclusions: HSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote hepatic fibrosis

    Public Evidence from Secret Ballots

    Full text link
    Elections seem simple---aren't they just counting? But they have a unique, challenging combination of security and privacy requirements. The stakes are high; the context is adversarial; the electorate needs to be convinced that the results are correct; and the secrecy of the ballot must be ensured. And they have practical constraints: time is of the essence, and voting systems need to be affordable and maintainable, and usable by voters, election officials, and pollworkers. It is thus not surprising that voting is a rich research area spanning theory, applied cryptography, practical systems analysis, usable security, and statistics. Election integrity involves two key concepts: convincing evidence that outcomes are correct and privacy, which amounts to convincing assurance that there is no evidence about how any given person voted. These are obviously in tension. We examine how current systems walk this tightrope.Comment: To appear in E-Vote-Id '1

    A 4% Geometric Distance to the Galaxy NGC4258 from Orbital Motions in a Nuclear Gas Disk

    Get PDF
    The water maser in the mildly active nucleus in the nearby galaxy NGC4258 traces a thin, nearly edge-on, subparsec-scale Keplerian disk. Using the technique of very long baseline interferometry, we have detected the proper motions of these masers as they sweep in front of the central black hole at an orbital velocity of about 1100 km/s. The average maser proper motion of 31.5 microarcseconds per year is used in conjunction with the observed acceleration of the masers to derive a purely geometric distance to the galaxy of 7.2 +- 0.3 Mpc. This is the most precise extragalactic distance measured to date, and, being independent of all other distance indicators, is likely to play an important role in calibrating the extragalactic distance scale.Comment: 11 pages, 3 figures. Accepted for publication in Natur

    Prolactin and hostility in hospitalised patients and healthy women: A systematic review and meta-analysis.

    Get PDF
    The aim of this systematic review and meta-analysis was to assess any difference in the self-ratings of hostility in mentally healthy women with different levels of prolactin (PRL). Electronic databases (PubMed, MEDLINE, EMBASE and the Cochrane Library) were searched up to 2nd July 2012 for published literature comparing hostility levels in women with different levels of PRL. Keyword pairs ('prolactin' and 'aggression', 'prolactin' and 'hostil*', 'prolactin' and 'anger', and 'prolactin' and 'angry') were entered simultaneously. From 1065 resulting titles, and one unpublished study, 214 articles underwent full-text review by authors JB and EM. Studies were selected based on clinical relevance. Eight comparative studies consisting of 242 female patients with high PRL levels, 207 female patients with normal PRL levels and 127 healthy controls with normal PRL levels were included. Data were analysed using the inverse variance method with a random-effects model. Analysis revealed significantly higher hostility in patients with high PRL compared with that in healthy control women (Z = 1.94, p < 0.05; Hedges' g = 0.72; 95% confidence interval [CI]: -0.01-1.45), significantly higher hostility in patient controls compared with that in healthy controls (Z = 1.94, p < 0.05; Hedges' g = 0.47; 95% CI: 0.00-0.94) and non-significantly higher hostility levels in patients with high PRL compared with that in patients with normal PRL levels (Z = 1.45, p < 0.15; Hedges' g = 0.38; 95% CI: -0.13-0.89). In this meta-analysis, hostility appears to be accounted for partly by PRL levels and also partly by patient status, perhaps due to the stress of being a patient. Methodological considerations and implications for patient care are discussed

    Validation of the London Measure of Unplanned Pregnancy among pregnant Australian women

    Get PDF
    INTRODUCTION: Globally, over half of pregnancies in developed countries are unplanned. Identifying and understanding the prevalence and complexity surrounding pregnancy preparation among Australian women is vital to enable sensitive, responsive approaches to addressing preconception and long-term health improvements for these women with varying motivation levels. AIM: This study evaluated the reliability and validity of a comprehensive pregnancy planning/intention measure (London Measure of Unplanned Pregnancy) in a population of pregnant women (over 18 years of age) in Australia. METHODS: A psychometric evaluation, within a cross-sectional study comprising cognitive interviews (to assess comprehension and acceptability) and a field test. Pregnant women aged over 18 years were recruited in early pregnancy (approximately 12 weeks' gestation). Reliability (internal consistency) was assessed using Cronbach's alpha, corrected item-total correlations and inter-item correlations, and stability via a test-retest. Construct validity was assessed using principal components analysis and hypothesis testing. RESULTS: Six women participated in cognitive interviews and 317 in the field test. The London Measure of Unplanned Pregnancy was acceptable and well comprehended. Reliability testing demonstrated good internal consistency (alpha = 0.81, all corrected item-total correlations >0.20, all inter-item correlations positive) and excellent stability (weighted kappa = 0.92). Validity testing confirmed the unidimensional structure of the measure and all hypotheses were confirmed. CONCLUSIONS: The London Measure of Unplanned Pregnancy is a valid and reliable measure of pregnancy planning/intention for the Australian population. Implementation of this measure into all maternity healthcare, research and policy settings will provide accurate population-level pregnancy planning estimates to inform, monitor and evaluate interventions to improve preconception health in Australia

    Prolactin and aggression in women with fertility problems

    Get PDF
    This study tested the hypothesis that women with higher prolactin feel more hostility, anger and aggression. A total of 66 women with moderate fertility problems were grouped into the 50% who had the highest and the 50% who had the lowest levels of prolactin. Levels of hostility, aggression and anger were compared. Women with higher prolactin levels did not report significantly increased hostility. After Bonferroni correction, women with lower prolactin showed non-significantly increased scores on two measures of state anger, and on a measure of trait temper. When comparing those with the highest and lowest 20% of prolactin levels, those with lower prolactin had non-significantly higher scores on trait temper and outward expression of anger, and non-significantly lower scores for control of anger. Although non-significant, these findings run counter to those of earlier studies on this topic. Implications for future research and patient care are discussed

    Characteristics associated with quality of life among people with drug-resistant epilepsy

    Get PDF
    Quality of Life (QoL) is the preferred outcome in non-pharmacological trials, but there is little UK population evidence of QoL in epilepsy. In advance of evaluating an epilepsy self-management course we aimed to describe, among UK participants, what clinical and psycho-social characteristics are associated with QoL. We recruited 404 adults attending specialist clinics, with at least two seizures in the prior year and measured their self-reported seizure frequency, co-morbidity, psychological distress, social characteristics, including self-mastery and stigma, and epilepsy-specific QoL (QOLIE-31-P). Mean age was 42 years, 54% were female, and 75% white. Median time since diagnosis was 18 years, and 69% experienced ≥10 seizures in the prior year. Nearly half (46%) reported additional medical or psychiatric conditions, 54% reported current anxiety and 28% reported current depression symptoms at borderline or case level, with 63% reporting felt stigma. While a maximum QOLIE-31-P score is 100, participants’ mean score was 66, with a wide range (25–99). In order of large to small magnitude: depression, low self-mastery, anxiety, felt stigma, a history of medical and psychiatric comorbidity, low self-reported medication adherence, and greater seizure frequency were associated with low QOLIE-31-P scores. Despite specialist care, UK people with epilepsy and persistent seizures experience low QoL. If QoL is the main outcome in epilepsy trials, developing and evaluating ways to reduce psychological and social disadvantage are likely to be of primary importance. Educational courses may not change QoL, but be one component supporting self-management for people with long-term conditions, like epilepsy

    Zinc intake, status and indices of cognitive function in adults and children: a systematic review and meta-analysis

    Get PDF
    In developing countries, deficiencies of micronutrients are thought to have a major impact on child development; however, a consensus on the specific relationship between dietary zinc intake and cognitive function remains elusive. The aim of this systematic review was to examine the relationship between zinc intake, status and indices of cognitive function in children and adults. A systematic literature search was conducted using EMBASE, MEDLINE and Cochrane Library databases from inception to March 2014. Included studies were those that supplied zinc as supplements or measured dietary zinc intake. A meta-analysis of the extracted data was performed where sufficient data were available. Of all of the potentially relevant papers, 18 studies met the inclusion criteria, 12 of which were randomised controlled trials (RCTs; 11 in children and 1 in adults) and 6 were observational studies (2 in children and 4 in adults). Nine of the 18 studies reported a positive association between zinc intake or status with one or more measure of cognitive function. Meta-analysis of data from the adult’s studies was not possible because of limited number of studies. A meta-analysis of data from the six RCTs conducted in children revealed that there was no significant overall effect of zinc intake on any indices of cognitive function: intelligence, standard mean difference of <0.001 (95% confidence interval (CI) –0.12, 0.13) P=0.95; executive function, standard mean difference of 0.08 (95% CI, –0.06, 022) P=0.26; and motor skills standard mean difference of 0.11 (95% CI –0.17, 0.39) P=0.43. Heterogeneity in the study designs was a major limitation, hence only a small number (n=6) of studies could be included in the meta-analyses. Meta-analysis failed to show a significant effect of zinc supplementation on cognitive functioning in children though, taken as a whole, there were some small indicators of improvement on aspects of executive function and motor development following supplementation but high-quality RCTs are necessary to investigate this further
    • …
    corecore