Vitamin D Prevents Endothelial Damage Induced by Increased Neutrophil Extracellular Traps Formation in Patients with Systemic Lupus Erythematosus

Aim: to investigate the effects of Vitamin D calcitriol/1,25(OH)2D3 on NETosis in systemic lupus erythematosus (SLE) patients with hypovitamin D. Methods: neutrophlis of five SLE patients with hypovitamin D were divided into 4 groups, P0 (0 nM/control), P1 (1 nM), P2 (10 nM), and P3 (100 nM) as cultured samples. Phorbol Myristate Acetate (PMA) was used to stimulate NETs formation. The supernatant was separated and cocultured with HUVECs. Externalization of Neutrophil Elastase (NE) and Myeloperoxidase (MPO) during NETosis was measured by immunofluorescence and ELISA respectively. Early and late apoptosis of endothelial cell was measured by flowcytometry using cell death kit (Annexin V and PI antibody). Results: this study showed significant decrease in early apoptosis with 10 nM of 1,25(OH)2D3 compared to control group. Significance of NE externalization found in all treatment groups (p<0.05), while MPO absorbance in the same tendency but not statistically significant. Further analysis also found a moderate positive correlation between NE externalizations with early apoptosis. Conclusion: vitamin D 1,25(OH)2D3 could reduce endothelial damage by decreasing NETosis activity. This result may reveal the possibility of Vitamin D as supplementary therapy for SLE patients with hypovitamin D to prevent endothelial damage. Key words: NETs, NE, MPO, 1,25(OH)2D3, HUVECs

Recognition of and Response to Neonatal Intrapartum-related Complications in Home-birth Settings in Bangladesh

Intrapartum-related complications (previously called \u2018birth asphyxia\u2019) are a significant contributor to deaths of newborns in Bangladesh. This study describes some of the perceived signs, causes, and treatments for this condition as described by new mothers, female relatives, traditional birth attendants, and village doctors in three sites in Bangladesh. Informants were asked to name characteristics of a healthy newborn and a newborn with difficulty in breathing at birth and about the perceived causes, consequences, and treatments for breathing difficulties. Across all three sites \u2018no movement\u2019 and \u2018no cry\u2019 were identified as signs of breathing difficulties while \u2018prolonged labour\u2019 was the most commonly-mentioned cause. Informants described a variety of treatments for difficulty in breathing at birth, including biomedical and, less often, spiritual and traditional practices. This study identified the areas that need to be addressed through behaviour change interventions to improve recognition of and response to intrapartum-related complications in Bangladesh

Recognition of and Response to neonatal intrapartum-related complications in home-birth settings in Bangladesh.

Intrapartum-related complications (previously called 'birth asphyxia') are a significant contributor to deaths of newborns in Bangladesh. This study describes some of the perceived signs, causes, and treatments for this condition as described by new mothers, female relatives, traditional birth attendants, and village doctors in three sites in Bangladesh. Informants were asked to name characteristics of a healthy newborn and a newborn with difficulty in breathing at birth and about the perceived causes, consequences, and treatments for breathing difficulties. Across all three sites 'no movement' and 'no cry' were identified as signs of breathing difficulties while 'prolonged labour' was the most commonly-mentioned cause. Informants described a variety of treatments for difficulty in breathing at birth, including biomedical and, less often, spiritual and traditional practices. This study identified the areas that need to be addressed through behaviour change interventions to improve recognition of and response to intrapartum-related complications in Bangladesh

Lipid-Based Passivation in Nanofluidics

Stretching DNA in nanochannels is a useful tool for direct, visual studies of genomic DNA at the single molecule level. To facilitate the study of the interaction of linear DNA with proteins in nanochannels, we have implemented a highly effective passivation scheme based on lipid bilayers. We demonstrate virtually complete long-term passivation of nanochannel surfaces to a range of relevant reagents, including streptavidin-coated quantum dots, RecA proteins, and RecA-DNA complexes. We show that the performance of the lipid bilayer is significantly better than that of standard bovine serum albumin-based passivation. Finally, we show how the passivated devices allow us to monitor single DNA cleavage events during enzymatic degradation by DNase I. We expect that our approach will open up for detailed, systematic studies of a wide range of protein-DNA interactions with high spatial and temporal resolution

Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis

We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis

Enhanced Inflammatory Potential of CD4(+) T-Cells That Lack Proteasome Immunosubunit Expression, in a T-Cell Transfer-Based Colitis Model

Proteasomes play a fundamental role in intracellular protein degradation and therewith regulate a variety of cellular processes. Exposure of cells to (pro)inflammatory cytokines upregulates the expression of three inducible catalytic proteasome subunits, the immunosubunits, which incorporate into newly assembled proteasome complexes and alter the catalytic activity of the cellular proteasome population. Single gene-deficient mice lacking one of the three immunosubunits are resistant to dextran sulfate sodium (DSS)-induced colitis development and, likewise, inhibition of one single immunosubunit protects mice against the development of DSS-induced colitis. The observed diminished disease susceptibility has been attributed to altered cytokine production and CD4+ T-cell differentiation in the absence of immunosubunits. To further test whether the catalytic activity conferred by immunosubunits plays an essential role in CD4+ T-cell function and to distinguish between the role of immunosubunits in effector T-cells versus inflamed tissue, we used a T-cell transfer-induced colitis model. Naïve wt or immunosubunit-deficient CD4+ T-cells were adoptively transferred into RAG1-/- and immunosubunit-deficient RAG1-/- mice and colitis development was determined six weeks later. While immunosubunit expression in recipient mice had no effect on colitis development, transferred immunosubunit-deficient T- cells were more potent in inducing colitis and produced more proinflammatory IL17 than wt T-cells. Taken together, our data show that modifications in proteasome-mediated proteolysis in T-cells, conferred by lack of immunosubunit incorporation, do not attenuate but enhance CD4+ T-cell-induced inflammation

Careers work in higher education in Pakistan: current practice and options for the future

In this article we examine the development of career guidance in Pakistani higher education. The article is primarily based on a review of the existing literature on career guidance in Pakistan, but also includes the consideration of some new data gathered from a review of higher education institutions websites and five case study interviews. It considers both local and global influences as relevant contexts for understanding how the development of career guidance in Pakistani higher education is taking place. Concerns about alignment between skills supply and demand provide key drivers both for the development of career guidance and for wider higher education reform. However the practice of career guidance in Pakistani higher education is shown to be lagging behind the policy aspirations, both due to limited investment and due to more fundamental cultural challenges that have yet to be fully addressed. If career guidance is going to continue to develop within Pakistan it will need to be strengthened by new policy and resources but also through the development of indigenous theories.N/

Domestic violence and decision-making power of married women in Myanmar: analysis of a nationally representative sample

BACKGROUND: Women in Myanmar are not considered decision makers in the community and the physical and psychological effect of violence makes them more vulnerable. There is a strong negative reaction, usually violent, to any economic activity generated by women among poorer and middle-class families in Myanmar because a woman's income is not considered necessary for basic survival. OBJECTIVE: Explore the relationship between domestic violence on the decision-making power of married women in Myanmar. DESIGN: Cross-sectional. SETTING: National, both urban and rural areas of Myanmar. PATIENTS AND METHODS: Data from the Myanmar Demographic and Health Survey 2015-16 were used in this analysis. In that survey, married women aged between 15 to 49 years were selected for interview using a multistage cluster sampling technique. The dependent variables were domestic violence and the decision-making power of women. Independent variables were age of the respondents, educational level, place of residence, employment status, number of children younger than 5 years of age and wealth index. MAIN OUTCOME MEASURES: Domestic violence and decision-making power of women. SAMPLE SIZE: 7870 currently married women. RESULTS: About 50% respondents were 35 to 49 years of age and the mean (SD) age was 35 (8.4) years. Women's place of residence and employment status had a significant impact on decision-making power whereas age group and decision-making power of women had a relationship with domestic violence. CONCLUSION: Giving women decision making power will be indispensable for the achievement of sustainable development goals. Government and other stakeholders should emphasize this to eliminate violence against women. LIMITATIONS: Use of secondary data analysis of cross-sectional study design and cross-sectional studies are not suitable design to assess this causality. Secondly the self-reported data on violence may be subject to recall bias. CONFLICT OF INTEREST: None