9 research outputs found

    Experiences of female survivors of sexual violence in eastern Democratic Republic of the Congo: a mixed-methods study

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    <p>Abstract</p> <p>Background</p> <p>The conflict in eastern Democratic Republic of the Congo (DRC) is the deadliest since World War II. Over a decade of fighting amongst an array of armed groups has resulted in extensive human rights abuses, particularly the widespread use of sexual violence against women.</p> <p>Methods</p> <p>Using a mixed-methods approach, we surveyed a non-random sample of 255 women attending a referral hospital and two local non-governmental organizations to characterize their experiences of sexual and gender-based violence (SGBV). We then conducted focus groups of 48 women survivors of SGBV to elaborate on survey findings. Quantitative and qualitative data underwent thematic and statistical analysis respectively.</p> <p>Findings</p> <p>Of the women surveyed, 193 (75.7%) experienced rape. Twenty-nine percent of raped women were rejected by their families and 6% by their communities. Thirteen percent of women had a child from rape. Widowhood, husband abandonment, gang rape, and having a child from rape were significant risk factors for social rejection. Mixed methods findings show rape survivors were seen as "contaminated" with HIV, contributing to their isolation and over 95% could not access prophylactic care in time. Receiving support from their husbands after rape was protective against survivors' feelings of shame and social isolation.</p> <p>Interpretation</p> <p>Rape results not only in physical and psychological trauma, but can destroy family and community structures. Women face significant obstacles in seeking services after rape. Interventions offering long-term solutions for hyper-vulnerable women are vital, but lacking; reintegration programs on SGBV for women, men, and communities are also needed.</p

    CD19+CD24hiCD38hi B Cells Are Expanded in Juvenile Dermatomyositis and Exhibit a Pro-Inflammatory Phenotype After Activation Through Toll-Like Receptor 7 and Interferon-α

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    Juvenile dermatomyositis (JDM) is a rare form of childhood autoimmune myositis that presents with proximal muscle weakness and skin rash. B cells are strongly implicated in the pathogenesis of the disease, but the underlying mechanisms are unknown. Therefore, the main objective of our study was to investigate mechanisms driving B cell lymphocytosis and define pathological features of B cells in JDM patients. Patients were recruited through the UK JDM Cohort and Biomarker study. Peripheral blood B cell subpopulations were immunophenotyped by flow cytometry. The results identified that immature transitional B cells were significantly expanded in active JDM, actively dividing, and correlated positively with disease activity. Protein and RNAseq analysis revealed high interferon alpha (IFNa) and TLR7-pathway signatures pre-treatment. Stimulation of B cells through TLR7/8 promoted both IL-10 and IL-6 production in controls but failed to induce IL-10 in JDM patient cells. Interrogation of the CD40-CD40L pathway (known to induce B cell IL-10 and IL-6) revealed similar expression of IL-10 and IL-6 in B cells cultured with CD40L from both JDM patients and controls. In conclusion, JDM patients with active disease have a significantly expanded immature transitional B cell population which correlated with the type I IFN signature. Activation through TLR7 and IFNa may drive the expansion of immature transitional B cells in JDM and skew the cells toward a pro-inflammatory phenotype

    A new role of AMP-activated protein kinase in regulating proliferation of mesenchymal stem cells

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    Purpose: Natriuretic peptides (NPs) administered during early reperfusion are protective in models of myocardial infarction. A previous study examining the endogenous components of B-type natriuretic peptide (BNP) protection of reperfused myocardium, implicated both sarcolemmal (s) KATP and mitochondrial (m) KATP channels. The indirect evidence characterising the relationship between BNP signalling and KATP was obtained using sulphonylurea receptor inhibitors in a rat isolated heart model of ischaemia-reperfusion injury. Here we seek to further examine the relationship between NPs and sKATP openings using single channel electrophysiology. Given our previous findings and the overarching consensus that cardioprotective autacoids open KATP channels, it was hypothesised that NPs elicit sKATP opening. Methods: Cardiomyocyte isolation. Left ventricular cardiomyocytes were isolated from male Sprague-Dawley rat hearts subjected to enzymatic digestion with Liberase Blendzyme DL. Cardiomyocytes were cultured overnight in Medium 199, prior to patch clamp. Single channel patch clamp. Single channel recordings at room temperature (22°C) were made from cell attached patches bathed in Na+ Locke, pH 7.2. The recording pipette contained high KCl (140 mM), pH 7.2. Recordings (45 sec) were made over a range of patch potentials (0, -30, -60, -90, -120 mV), in the absence (control) and in the presence of bath applied BNP (10, 100 nM and 1 µM), pinacidil (200 µM) or pinacidil vehicle (DMSO, 0.25%). Recordings were also made with BNP and pinacidil applied concomitantly. Data are mean ± S.E.M. Results: The current voltage relationship of sKATP under control conditions was linear at –ve patch potentials, the mean conductance being 52.9 ± 1.8 pS (n = 18 hearts, n = 35 cells). Pinacidil caused a four fold increase in sKATP open probability compared to control. Mean channel conductance in the presence of pinacidil was 59.9 ± 1.9 pS (n = 16 hearts, n = 44 cells). Interestingly BNP at all concentrations had negligible effects on sKATP open probability and unitary conductance. However, BNP at all concentrations and patch potentials inhibited pinacidil induced sKATP openings, restoring channel open probability to baseline. Conclusion: These data illustrate the inhibitory effect of NP signalling on sKATP function in the cardiomyocyte under normoxia. They are concordant with the inhibitory effect of atrial NP on KATP in the pancreatic beta cell, but are in apparent conflict with the current cardioprotection paradigm. However, differential effects on sKATP and mKATP and the effects of hypoxia-reoxygenation require further exploration
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