2,671 research outputs found

    Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis

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    The fungus Cryptococcus is a major cause of meningoencephalitis in HIV-infected as well as HIV-uninfected individuals with mortalities in developed countries of 20% and 30%, respectively. In HIV-related disease, defects in T-cell immunity are paramount, whereas there is little understanding of mechanisms of susceptibility in non-HIV related disease, especially that occurring in previously healthy adults. The present description is the first detailed immunological study of non-HIV-infected patients including those with severe central nervous system (s-CNS) disease to 1) identify mechanisms of susceptibility as well as 2) understand mechanisms underlying severe disease. Despite the expectation that, as in HIV, T-cell immunity would be deficient in such patients, cerebrospinal fluid (CSF) immunophenotyping, T-cell activation studies, soluble cytokine mapping and tissue cellular phenotyping demonstrated that patients with s-CNS disease had effective microbiological control, but displayed strong intrathecal expansion and activation of cells of both the innate and adaptive immunity including HLA-DR+ CD4+ and CD8+ cells and NK cells. These expanded CSF T cells were enriched for cryptococcal-antigen specific CD4+ cells and expressed high levels of IFN-gamma as well as a lack of elevated CSF levels of typical T-cell specific Th2 cytokines -- IL-4 and IL-13. This inflammatory response was accompanied by elevated levels of CSF NFL, a marker of axonal damage, consistent with ongoing neurological damage. However, while tissue macrophage recruitment to the site of infection was intact, polarization studies of brain biopsy and autopsy specimens demonstrated an M2 macrophage polarization and poor phagocytosis of fungal cells. These studies thus expand the paradigm for cryptococcal disease susceptibility to include a prominent role for macrophage activation defects and suggest a spectrum of disease whereby severe neurological disease is characterized by immune-mediated host cell damage

    Maine Pediatric and Family Practice Survey Chartbook: Improving Health Outcomes for Children

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    As part of the IHOC initiative, the Muskie School of Public Service at the University of Southern Maine surveyed pediatric and family practices about how they use data, clinical guidelines and office systems to monitor and improve children’s healthcare quality. The purpose of the survey is to provide baseline information about quality improvement activities in primary care practices serving children in Maine. Survey data will be used to inform IHOC activities and to monitor changes over time. The web-based survey was conducted in the winter of 2011-2012 and sent to practice managers at a sample of 168 practice sites, of which 64% responded. Responding practices represent more than one-quarter of family practices and nearly two-thirds of all pediatric practices in the state. This report summarizes the results of the initial survey and assesses quality improvement activities in pediatric and family practices at baseline

    Organization of the Autonomic Nuclei in the Spinal Cord : Functional Morphology

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    Disease-associated genes. Complete list of the disease-associated genes for each dataset. (XZ 46 kb

    Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle

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    AbstractThe non-structural protein 4B (NS4B) from Hepatitis C virus (HCV) plays a pivotal role in the remodelling of the host cell's membranes, required for the formation of the viral replication complex where genome synthesis occurs. NS4B is an integral membrane protein that possesses a number of domains vital for viral replication. Structural and biophysical studies have revealed that one of these, the second amphipathic N-terminal helix (AH2), plays a key role in these remodelling events. However, there is still limited understanding of the mechanism through which AH2 promotes these changes. Here we report on solid-state NMR and molecular dynamics studies that demonstrate that AH2 promotes the clustering of negatively charged lipids within the bilayer, a process that reduces the strain within the bilayer facilitating the remodelling of the lipid bilayer. Furthermore, the presence of negatively charged lipids within the bilayer appears to promote the disassociation of AH2 oligomers, highlighting a potential role for lipid recruitment in regulating NS protein interactions

    Status of Grauer’s Gorilla and Chimpanzees in Eastern Democratic Republic of Congo: Historical and Current Distribution and Abundance

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    This report summarises the current state of knowledge on the distribution, densities and trends in abundance of Grauer’s gorilla (Gorilla beringei graueri) and the eastern chimpanzee (Pan troglodytes schweinfurthii) in eastern Democratic Republic of Congo (DRC). It summarises the historical knowledge about the distribution of Grauer’s gorilla across its range and describes the development of a Conservation Action Plan (CAP) for these two ape species. A result of this CAP was funding to undertake an assessment of the current status of these apes across the range of Grauer’s gorilla. Wildlife Conservation Society (WCS) and Fauna & Flora International (FFI) worked with Institut Congolais pour la Conservation de la Nature (ICCN) and the Reserve managers of the Reserve des Gorilles de Punia (RGPU) and local communities to undertake surveys across the region using a variety of methods: line transects, recces along paths and patrol data from data collected by rangers while on patrol and entered into SMART software

    Ibuprofen, paracetamol, and steam for patients with respiratory tract infections in primary care: pragmatic randomised factorial trial

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    Objective: To assess strategies for advice on analgesia and steam inhalation for respiratory tract infections.Design: Open pragmatic parallel group factorial randomised controlled trial.Setting: Primary care in United Kingdom.Participants: Patients aged ?3 with acute respiratory tract infections.Intervention: 889 patients were randomised with computer generated random numbers in pre-prepared sealed numbered envelopes to components of advice or comparator advice: advice on analgesia (take paracetamol, ibuprofen, or both), dosing of analgesia (take as required v regularly), and steam inhalation (no inhalation v steam inhalation).Outcomes: Primary: mean symptom severity on days 2-4; symptoms rated 0 (no problem) to 7 (as bad as it can be). Secondary: temperature, antibiotic use, reconsultations.Results: Neither advice on dosing nor on steam inhalation was significantly associated with changes in outcomes. Compared with paracetamol, symptom severity was little different with ibuprofen (adjusted difference 0.04, 95% confidence interval ?0.11 to 0.19) or the combination of ibuprofen and paracetamol (0.11, ?0.04 to 0.26). There was no evidence for selective benefit with ibuprofen among most subgroups defined before analysis (presence of otalgia; previous duration of symptoms; temperature >37.5°C; severe symptoms), but there was evidence of reduced symptoms severity benefit in the subgroup with chest infections (ibuprofen ?0.40, ?0.78 to ?0.01; combination ?0.47; ?0.84 to ?0.10), equivalent to almost one in two symptoms rated as a slight rather than a moderately bad problem. Children might also benefit from treatment with ibuprofen (ibuprofen: ?0.47, ?0.76 to ?0.18; combination: ?0.04, ?0.31 to 0.23). Reconsultations with new/unresolved symptoms or complications were documented in 12% of those advised to take paracetamol, 20% of those advised to take ibuprofen (adjusted risk ratio 1.67, 1.12 to 2.38), and 17% of those advised to take the combination (1.49, 0.98 to 2.18). Mild thermal injury with steam was documented for four patients (2%) who returned full diaries, but no reconsultations with scalding were documented.Conclusion: Overall advice to use steam inhalation, or ibuprofen rather than paracetamol, does not help control symptoms in patients with acute respiratory tract infections and must be balanced against the possible progression of symptoms during the next month for a minority of patients. Advice to use ibuprofen might help short term control of symptoms in those with chest infections and in children

    Development and evaluation of an innovative model of inter-professional education focused on asthma medication use

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    BACKGROUND: Inter-professional learning has been promoted as the solution to many clinical management issues. One such issue is the correct use of asthma inhaler devices. Up to 80% of people with asthma use their inhaler device incorrectly. The implications of this are poor asthma control and quality of life. Correct inhaler technique can be taught, however these educational instructions need to be repeated if correct technique is to be maintained. It is important to maximise the opportunities to deliver this education in primary care. In light of this, it is important to explore how health care providers, in particular pharmacists and general medical practitioners, can work together in delivering inhaler technique education to patients, over time. Therefore, there is a need to develop and evaluate effective inter-professional education, which will address the need to educate patients in the correct use of their inhalers as well as equip health care professionals with skills to engage in collaborative relationships with each other. METHODS: This mixed methods study involves the development and evaluation of three modules of continuing education, Model 1, Model 2 and Model 3. A fourth group, Model 4, acting as a control. Model 1 consists of face-to-face continuing professional education on asthma inhaler technique, aimed at pharmacists, general medical practitioners and their practice nurses. Model 2 is an electronic online continuing education module based on Model 1 principles. Model 3 is also based on asthma inhaler technique education but employs a learning intervention targeting health care professional relationships and is based on sociocultural theory. This study took the form of a parallel group, repeated measure design. Following the completion of continuing professional education, health care professionals recruited people with asthma and followed them up for 6 months. During this period, inhaler device technique training was delivered and data on patient inhaler technique, clinical and humanistic outcomes were collected. Outcomes related to professional collaborative relationships were also measured. DISCUSSION: Challenges presented included the requirement of significant financial resources for development of study materials and limited availability of validated tools to measure health care professional collaboration over time
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