1,780 research outputs found

    Elevated Liver Enzymes and Mortality in Older Individuals: A Prospective Cohort Study

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    Aim of the study: The aim of the study was to determine the excess risk of all-cause and cardiovascular mortality in older people with elevated liver enzymes [alanine transaminase (ALT) and gamma glutamyltransferase (GGT)]. Methods: We utilized data from a large, prospective, population based study of 2061 people aged 50 to 99 years with linkage to a National Death Registry. Participants were categorized as having elevated liver enzymes using standard thresholds (for males, GGT>51 and ALT>40 IU/L, and GGT>33 and ALT>31 IU/L for females). Adjusted Cox proportional hazards models assessed the association of elevated liver enzymes and mortality with long duration follow-up. Results: Over a median follow-up of 10 years (20,145 person years), 701 people died, including 203 (34%) from cardiovascular disease. Cox regression models adjusted for sex, age, smoking, and alcohol intake indicated that people with elevated liver enzymes had an increased risk of all-cause mortality that was modified by age (test for interaction P=0.01). Age-stratified analyses demonstrated no increased risk at younger ages [age 59 y and below; hazard ratio (HR): 0.46; 95% confidence interval, 0.06-3.49], but increased risk with age; age 60 to 69, HR: 1.05 (0.53-2.07), age 70 to 79 years, HR: 1.54 (0.81 to 2.93), and age 80 years and above, HR: 3.53 (1.55 to 8.04). Similarly, the risk of cardiovascular mortality with elevated liver enzymes was also modified by, and increased with age (test for interaction P=0.02); age 70 to 79, HR: 3.15 (1.37 to 7.23), age 80 years and above, HR: 6.86 (2.44 to 19.30). Conclusions: In community-dwelling elderly persons, an elevation in both ALT and GGT are associated with an excess risk of all-cause and cardiovascular mortality which increases with age

    Pro198Leu polymorphism affects the selenium status and GPx activity in response to Brazil nut intake

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    © The Royal Society of Chemistry 2015. Selenoproteins play important roles in antioxidant mechanisms, and are thus hypothesised to have some involvement in the pathology of certain types of dementia. Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are both thought to involve impaired biological activity of certain selenoproteins. Previously, supplementation with a selenium-rich Brazil nut (Bertholletia excelsa) has shown potential in reducing cognitive decline in MCI patients, and could prove to be a safe and effective nutritional approach early in the disease process to slow decline. Here, we have conducted a pilot study that examined the effects of a range of single nucleotide polymorphisms (SNPs) in genes encoding the selenoproteins glutathione peroxidase (GPX1) and selenoprotein P (SEPP) in response to selenium supplementation via dietary Brazil nuts, including selenium status, oxidative stress parameters and GPX1 and SEPP gene expression. Our data suggest that GPX1 Pro198Leu rs1050450 genotypes may differentially affect the selenium status and GPx activity. Moreover, rs7579 and rs3877899 SNPs in SEPP gene, as well as GPX1 rs1050450 genotypes can influence the expression of GPX1 and SEPP mRNA in response to Brazil nuts intake. This small study gives cause for larger investigations into the role of these SNPs in both the selenium status and response to selenium dietary intake, especially in chronic degenerative conditions like MCI and AD

    "My Children and I Will no Longer Suffer from Malaria": A Qualitative Study of the Acceptance and Rejection of Indoor Residual Spraying to Prevent Malaria in Tanzania.

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    The objective of this study was to identify attitudes and misconceptions related to acceptance or refusal of indoor residual spraying (IRS) in Tanzania for both the general population and among certain groups (e.g., farmers, fishermen, community leaders, and women). This study was a series of qualitative, semi-structured, in-depth interviews and focus group discussions conducted from October 2010 to March 2011 on Mainland Tanzania and Zanzibar. Three groups of participants were targeted: acceptors of IRS (those who have already had their homes sprayed), refusers (those whose communities have been sprayed, but refused to have their individual home sprayed), and those whose houses were about to be sprayed as part of IRS scale-up. Interviews were also conducted with farmers, fishermen, women, community leaders and members of non-government organizations responsible for community mobilization around IRS. Results showed refusers are a very small percentage of the population. They tend to be more knowledgeable people such as teachers, drivers, extension workers, and other civil servants who do not simply follow the orders of the local government or the sprayers, but are skeptical about the process until they see true results. Refusal took three forms: 1) refusing partially until thorough explanation is provided; 2) accepting spray to be done in a few rooms only; and 3) refusing outright. In most of the refusal interviews, refusers justified why their houses were not sprayed, often without admitting that they had refused. Reasons for refusal included initial ignorance about the reasons for IRS, uncertainty about its effectiveness, increased prevalence of other insects, potential physical side effects, odour, rumours about the chemical affecting fertility, embarrassment about moving poor quality possessions out of the house, and belief that the spray was politically motivated. To increase IRS acceptance, participants recommended more emphasis on providing thorough public education, ensuring the sprayers themselves are more knowledgeable about IRS, and asking that community leaders encourage participation by their constituents rather than threatening punishment for noncompliance. While there are several rumours and misconceptions concerning IRS in Tanzania, acceptance is very high and continues to increase as positive results become apparent

    Self-stabilizing Overlays for high-dimensional Monotonic Searchability

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    We extend the concept of monotonic searchability for self-stabilizing systems from one to multiple dimensions. A system is self-stabilizing if it can recover to a legitimate state from any initial illegal state. These kind of systems are most often used in distributed applications. Monotonic searchability provides guarantees when searching for nodes while the recovery process is going on. More precisely, if a search request started at some node uu succeeds in reaching its destination vv, then all future search requests from uu to vv succeed as well. Although there already exists a self-stabilizing protocol for a two-dimensional topology and an universal approach for monotonic searchability, it is not clear how both of these concepts fit together effectively. The latter concept even comes with some restrictive assumptions on messages, which is not the case for our protocol. We propose a simple novel protocol for a self-stabilizing two-dimensional quadtree that satisfies monotonic searchability. Our protocol can easily be extended to higher dimensions and offers routing in O(logn)\mathcal O(\log n) hops for any search request

    Fast Inhibition of Glutamate-Activated Currents by Caffeine

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    Background: Caffeine stimulates calcium-induced calcium release (CICR) in many cell types. In neurons, caffeine stimulates CICR presynaptically and thus modulates neurotransmitter release. Methodology/Principal Findings: Using the whole-cell patch-clamp technique we found that caffeine (20 mM) reversibly increased the frequency and decreased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) in neocortical neurons. The increase in mEPSC frequency is consistent with a presynaptic mechanism. Caffeine also reduced exogenously applied glutamate-activated currents, confirming a separate postsynaptic action. This inhibition developed in tens of milliseconds, consistent with block of channel currents. Caffeine (20 mM) did not reduce currents activated by exogenous NMDA, indicating that caffeine block is specific to non-NMDA type glutamate receptors. Conclusions/Significance: Caffeine-induced inhibition of mEPSC amplitude occurs through postsynaptic block of non-NMDA type ionotropic glutamate receptors. Caffeine thus has both pre and postsynaptic sites of action at excitatory synapses

    El papel social del militar en el postconflicto colombiano

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    En el presente ensayo se pretende argumentar diferentes dinámicas del conflicto interno en Colombia que llevó a que de manera temprana las Fuerzas Militares del país asumieran funciones de seguridad civil, desarrollando su estructura y doctrina en torno a las necesidades de la lucha contra los grupos armados al margen de la ley y en defensa de la sociedad y las instituciones, de esta manera relegó a un segundo plano su rol clásico de defensa de las fronteras nacionales frente a potenciales amenazas externas. Así pues es necesario mirar en primera instancia como El ordenamiento constitucional, legal y jurídico del Estado moderno prevé y justifica la creación y existencia de las fuerzas militares FFMM- cuya misión fundamental es la defensa de la soberanía con respecto y frente a otras naciones del mundo (defensa nacional externa). Así mismo, la defensa nacional interna está asignada al cuerpo de policía, al margen y de manera totalmente separada de las FFMMPregrad

    Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

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    Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

    A Filamentous Hemagglutinin-Like Protein of Xanthomonas axonopodis pv. citri, the Phytopathogen Responsible for Citrus Canker, Is Involved in Bacterial Virulence

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    Xanthomonas axonopodis pv. citri, the phytopathogen responsible for citrus canker has a number of protein secretion systems and among them, at least one type V protein secretion system belonging to the two-partner secretion pathway. This system is mainly associated to the translocation of large proteins such as adhesins to the outer membrane of several pathogens. Xanthomonas axonopodis pv. citri possess a filamentous hemagglutinin-like protein in close vicinity to its putative transporter protein, XacFhaB and XacFhaC, respectively. Expression analysis indicated that XacFhaB was induced in planta during plant-pathogen interaction. By mutation analysis of XacFhaB and XacFhaC genes we determined that XacFhaB is involved in virulence both in epiphytic and wound inoculations, displaying more dispersed and fewer canker lesions. Unexpectedly, the XacFhaC mutant in the transporter protein produced an intermediate virulence phenotype resembling wild type infection, suggesting that XacFhaB could be secreted by another partner different from XacFhaC. Moreover, XacFhaB mutants showed a general lack of adhesion and were affected in leaf surface attachment and biofilm formation. In agreement with the in planta phenotype, adhesin lacking cells moved faster in swarming plates. Since no hyperflagellation phenotype was observed in this bacteria, the faster movement may be attributed to the lack of cell-to-cell aggregation. Moreover, XacFhaB mutants secreted more exopolysaccharide that in turn may facilitate its motility. Our results suggest that this hemagglutinin-like protein is required for tissue colonization being mainly involved in surface attachment and biofilm formation, and that plant tissue attachment and cell-to-cell aggregation are dependent on the coordinated action of adhesin molecules and exopolysaccharides
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