2,052 research outputs found

    Lower lung function associates with cessation of menstruation: UK Biobank data

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    Little is known about the effect of cessation of menstruation on lung function. The aims of the study were to examine the association of lung function with natural and surgical cessation of menstruation, and assess whether lower lung function is associated with earlier age at cessation of menstruation. The study was performed in 141,076 women from the UK Biobank, who had provided acceptable and reproducible spirometry measurements and information on menstrual status. The associations of lung function [FVC, FEV1, spirometric restriction (FVC<LLN), airflow obstruction (FEV1/FVC<LLN)] with cessation of menstruation and age at cessation of menstruation were assessed using regression analysis. Women who had natural cessation of menstruation showed a lower FVC (-42mL; 95%CI - 53,- 30)and FEV1 (-34mL/s; 95%CI -43,-24) and higher risk of spirometric restriction (adjOR=1.27; 95%CI 1.18-1.37) than women still menstruating. These associations were stronger in women who had had a hysterectomy and/or oophorectomy. The earlier the natural cessation of menstruation, the lower thelung function. There was no clear association of lung function with age at hysterectomy and/or oophorectomy. Airflow obstruction was not associated with cessation of menstruation. Lower lung function associates with cessation of menstruation, especially if it occurs early in life

    Soil-induced impacts on forest structure drive coarse woody debris stocks across central Amazonia

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    PublishedJournal Article© 2014, © 2014 Botanical Society of Scotland and Taylor & Francis. Background: Coarse woody debris (CWD) is an essential component in tropical forest ecosystems and its quantity varies widely with forest types. Aims: Relationships among CWD, soil, forest structure and other environmental factors were analysed to understand the drivers of variation in CWD in forests on different soil types across central Amazonia. Methods: To estimate CWD stocks and density of dead wood debris, 75 permanent forest plots of 0.5 ha in size were assessed along a transect that spanned ca. 700 km in undisturbed forests from north of the Rio Negro to south of the Rio Amazonas. Soil physical properties were evaluated by digging 2-m-deep pits and by taking auger samples. Results: Soil physical properties were the best predictors of CWD stocks; 37% of its variation was explained by effective soil depth. CWD stocks had a two-fold variation across a gradient of physical soil constraints (i.e. effective soil depth, anoxia and soil structure). Average biomass per tree was related to physical soil constraints, which, in turn, had a strong relationship with local CWD stocks. Conclusions: Soil physical properties appear to control average biomass per tree (and through this affect forest structure and dynamics), which, in turn, is correlated with CWD production and stocks

    Clinical outcomes in pediatric hemodialysis patients in the USA: lessons from CMS’ ESRD CPM Project

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    Although prospective randomized trials have provided important information and allowed the development of evidence-based guidelines in adult hemodialysis (HD) patients, with approximately 800 prevalent pediatric HD patients in the United States, such studies are difficult to perform in this population. Observational data obtained through the Center for Medicare & Medicaid Services’ (CMS’) End Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) Project have allowed description of the clinical care provided to pediatric HD patients as well as identification of risk factors for failure to reach adult targets for clinical parameters such as hemoglobin, single-pool Kt/V (spKt/V) and serum albumin. In addition, studies linking data from the ESRD CPM Project and the United States Renal Data System have allowed evaluation of associations between achievement of those targets and the outcomes of hospitalization and death. The results of those studies, while unable to prove cause and effect, suggest that the adult ESRD CPM targets may assist in identifying pediatric HD patients at risk for poor outcomes

    Intracerebral infection with dengue-3 virus induces meningoencephalitis and behavioral changes that precede lethality in mice

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    <p>Abstract</p> <p>Background</p> <p>Dengue, one of the most important arboviral diseases of humans, may cause severe systemic disease. Although dengue virus (DENV) has been considered to be a non-neurotropic virus, dengue infection has been associated recently with a series of neurological syndromes, including encephalitis. In this work, we evaluated behavioral changes and inflammatory parameters in C57BL/6 mice infected with non-adapted dengue virus 3 (DENV-3) genotype I.</p> <p>Methods</p> <p>C57BL/6 mice received 4 × 10<sup>3 </sup>PFU of DENV-3 by an intracranial route. We evaluated the trafficking of leukocytes in brain microvasculature using intravital microscopy, and evaluated chemokine and cytokine profiling by an ELISA test at 3 and 6 days post infection (p.i.). Furthermore, we determined myeloperoxidase activity and immune cell populations, and also performed histopathological analysis and immunostaining for the virus in brain tissue.</p> <p>Results</p> <p>All animals developed signs of encephalitis and died by day 8 p.i. Motor behavior and muscle tone and strength parameters declined at day 7 p.i. We observed increased leukocyte rolling and adhesion in brain microvasculature of infected mice at days 3 and 6 p.i. The infection was followed by significant increases in IFN-γ, TNF-α, CCL2, CCL5, CXCL1, and CXCL2. Histological analysis showed evidence of meningoencephalitis and reactive gliosis. Increased numbers of neutrophils, CD4<sup>+ </sup>and CD8<sup>+ </sup>T cells were detected in brain of infected animals, notably at day 6 p.i. Cells immunoreactive for anti-NS-3 were visualized throughout the brain.</p> <p>Conclusion</p> <p>Intracerebral infection with non-adapted DENV-3 induces encephalitis and behavioral changes that precede lethality in mice.</p

    GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection

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    Cellular necrosis during Mycobacterium tuberculosis (Mtb) infection promotes both immunopathology and bacterial dissemination. Glutathione peroxidase-4 (Gpx4) is an enzyme that plays a critical role in preventing iron-dependent lipid peroxidation–mediated cell death (ferroptosis), a process previously implicated in the necrotic pathology seen in Mtb-infected mice. Here, we document altered GPX4 expression, glutathione levels, and lipid peroxidation in patients with active tuberculosis and assess the role of this pathway in mice genetically deficient in or overexpressing Gpx4. We found that Gpx4-deficient mice infected with Mtb display substantially increased lung necrosis and bacterial burdens, while transgenic mice overexpressing the enzyme show decreased bacterial loads and necrosis. Moreover, Gpx4-deficient macrophages exhibited enhanced necrosis upon Mtb infection in vitro, an outcome suppressed by the lipid peroxidation inhibitor, ferrostatin-1. These findings provide support for the role of ferroptosis in Mtb-induced necrosis and implicate the Gpx4/GSH axis as a target for host-directed therapy of tuberculosis

    Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

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    BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

    Hierarchical information clustering by means of topologically embedded graphs

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    We introduce a graph-theoretic approach to extract clusters and hierarchies in complex data-sets in an unsupervised and deterministic manner, without the use of any prior information. This is achieved by building topologically embedded networks containing the subset of most significant links and analyzing the network structure. For a planar embedding, this method provides both the intra-cluster hierarchy, which describes the way clusters are composed, and the inter-cluster hierarchy which describes how clusters gather together. We discuss performance, robustness and reliability of this method by first investigating several artificial data-sets, finding that it can outperform significantly other established approaches. Then we show that our method can successfully differentiate meaningful clusters and hierarchies in a variety of real data-sets. In particular, we find that the application to gene expression patterns of lymphoma samples uncovers biologically significant groups of genes which play key-roles in diagnosis, prognosis and treatment of some of the most relevant human lymphoid malignancies.Comment: 33 Pages, 18 Figures, 5 Table

    Do adults with high functioning autism or Asperger Syndrome differ in empathy and emotion recognition?

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    The present study examined whether adults with high functioning autism (HFA) showed greater difficulties in (i) their self-reported ability to empathise with others and/or (ii) their ability to read mental states in others’ eyes than adults with Asperger syndrome (AS). The Empathy Quotient (EQ) and ‘Reading the Mind in the Eyes’ Test (Eyes Test) were compared in 43 adults with AS and 43 adults with HFA. No significant difference was observed on EQ score between groups, while adults with AS performed significantly better on the Eyes Test than those with HFA. This suggests that adults with HFA may need more support, particularly in mentalizing and complex emotion recognition, and raises questions about the existence of subgroups within autism spectrum conditions

    The prevalence of common skin infections in four districts in Timor-Leste: a cross sectional survey

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    Background\ud Skin infections are a common public health problem in developing countries; however, they are rarely managed using a population based approach. Recent data on the burden of skin infections in Timor-Leste are limited. Our survey appears to be the only widespread survey conducted in more than 30 years and was designed to determine the baseline prevalence of some common skin infections in Timor-Leste.\ud \ud Methods\ud We conducted a cross sectional survey in 14 sites including community health clinics, schools and hospitals within four different geographical regions. Participants were examined for five conditions (scabies, pyoderma, fungal infections, leprosy and yaws) by a multidisciplinary team. Analyses were conducted using EpiInfo version 6.04d.\ud \ud Results\ud We examined the skin of 1535 participants aged between four months and 97 years. The majority of participants were male, aged between 11 and 20 years and had at least one condition of interest (56.0%, 56.0%, and 63.1%, respectively). Fungal infections were the most common presentation (39.0%) and males were more commonly affected than females (42.3% vs 34.0%, respectively, pvalue < 0.0001).\ud \ud Among those people with more than one condition the two most common co-infections were scabies with either pyoderma or a fungal infection (38.0% and 32.0%, respectively). The survey identified 29 previously undiagnosed cases of leprosy and six cases of yaws.\ud \ud Conclusions\ud Our findings indicate the need for a comprehensive programme to address these conditions. There are successful disease control programmes in place within the country and it is hoped a healthy skin programme could be integrated into an established disease control programme in order to maximise health benefits and resources
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