Conectar
by John Bosco Asiimwe, Hellen Namawejje, Faith Rachel Mirembe, Annet Adong, Jolly Achola, Herbert Nabaasa, Jebena Mulusew, Jonathan Izudi, Damazo T. Kadengye
A substantial proportion (7%) of people in Uganda practice open defecation. A Community-Led Total Sanitation (CLTS) project was started in 2011 to reduce indiscriminate disposal of excreta but the effect has not been rigorously evaluated. We, therefore, evaluated the effect of CLTS on reducing open defecation in the program intervention districts in Uganda. We used the 2016 Uganda Demographic and Health Survey (UDHS) data to conduct a quasi-experimental study using a propensity score matching (PSM) approach. The intervention group consisted of districts that implemented the CLTS and the comparison group were districts that did not implement the CLTS. We matched the intervention and comparison groups on several covariates in a 1:1 ratio within a caliper of 20% of the standard deviation of the propensity score. We confirmed balance in covariates using standardized mean difference (SMD) beingby Alyssa Kearly, Prontip Saelee, Jonathan Bard, Satrajit Sinha, Anne Satterthwaite, Lee Ann Garrett-Sinha
The levels of transcription factor Ets1 are high in resting B and T cells, but are downregulated by signaling through antigen receptors and Toll-like receptors (TLRs). Loss of Ets1 in mice leads to excessive immune cell activation and development of an autoimmune syndrome and reduced Ets1 expression has been observed in human PBMCs in the context of autoimmune diseases. In B cells, Ets1 serves to prevent premature activation and differentiation to antibody-secreting cells. Given these important roles for Ets1 in the immune response, stringent control of Ets1 gene expression levels is required for homeostasis. However, the genetic regulatory elements that control expression of the Ets1 gene remain relatively unknown. Here we identify a topologically-associating domain (TAD) in the chromatin of B cells that includes the mouse Ets1 gene locus and describe an interaction hub that extends over 100 kb upstream and into the gene body. Additionally, we compile epigenetic datasets to find several putative regulatory elements within the interaction hub by identifying regions of high DNA accessibility and enrichment of active enhancer histone marks. Using reporter constructs, we determine that DNA sequences within this interaction hub are sufficient to direct reporter gene expression in lymphoid tissues of transgenic mice. Further analysis indicates that the reporter construct drives faithful expression of the reporter gene in mouse B cells, but variegated expression in T cells, suggesting the existence of T cell regulatory elements outside this region. To investigate how the downregulation of Ets1 transcription is associated with alterations in the epigenetic landscape of stimulated B cells, we performed ATAC-seq in resting and BCR-stimulated primary B cells and identified four regions within and upstream of the Ets1 locus that undergo changes in chromatin accessibility that correlate to Ets1 gene expression. Interestingly, functional analysis of several putative Ets1 regulatory elements using luciferase constructs suggested a high level of functional redundancy. Taken together our studies reveal a complex network of regulatory elements and transcription factors that coordinate the B cell-specific expression of Ets1.by Kenneth K.Y. Ting, Hisham M. Ibrahim, Nitya Gulati, Yufeng Wang, Jonathan V. Rocheleau, Myron I. Cybulsky
The formation of macrophage (Mφ) foam cells is a hallmark of atherosclerosis, yet how the process of lipid loading can modulate Mφ inflammatory responses by rewiring their intracellular metabolic circuits is not well understood. Our previous studies have shown that the accumulation of oxidized LDL (oxLDL) or free cholesterol in Mφs impaired their inflammatory response by suppressing HIF-1α-mediated glycolysis and upregulating NRF2 antioxidative response. However, it remains unclear if other metabolic processes are also contributory. In this study, we found that the accumulation of free cholesterol, but not oxLDL, in primary murine thioglycolate-elicited peritoneal Mφs (PMφs) enhanced a PARP1-dependent response associated with repair of DNA damage, which was characterized by poly ADP-ribosylation of proteins, phosphorylation of histone 2A.X and consumption of NAD + . Both oxLDL and cholesterol enhanced the PARP1 response after LPS stimulation. Treatment of PMφs with mitoTEMPO, a specific mitochondrial reactive oxygen species (mtROS) scavenger, alleviated mtROS during cholesterol loading, blocked the PARP1 response and partially restored LPS- induced inflammatory gene expression. In contrast to inhibition of PARP1 enzymatic activity, knockdown of PARP1 expression in RAW264.7 Mφs with siRNA elevated LPS-induced inflammatory gene expression. Overall, our study suggests that cholesterol accumulation triggers a PARP1 response to DNA damage in Mφs and that PARP1 inhibits LPS-mediated inflammation through a non-enzymatic function.by Jonathan Gwasupika, Davidson H. Hamer, Victor Daka, Ephraim Chikwanda, David Mwakazanga, Ruth L. Mfune, Choolwe Jacobs
BackgroundChildren with human immunodeficiency virus (HIV) infection are disproportionately susceptible to bacterial infections. There are a wide range of antibacterial agents available to manage HIV positive children with bacterial infections. However, administration of antibiotics in most children is empirical which could lead to antimicrobial resistance.
ObjectivesThis study aimed to determine commonly prescribed antibiotics and associated symptoms in children at Arthur Davison children’s hospital antiretroviral therapy clinic in Ndola, Zambia.
MethodsThis was a cross-sectional study that analysed the antibiotic prescribing patterns from routinely collected secondary data at Arthur Davison children’s hospital. Children diagnosed with HIV before the age of 5, actively attending antiretroviral therapy clinic identified by SmartCare software and who had taken antiretroviral therapy for at least 6 months were eligible. Data were collected from files of children who met the eligibility criteria. STATA software version 16 SE (STATA Corp., College Station, Texas, USA) was used for analysis. A p-value less than 0.05 was considered statistically significant at a confidence interval of 95%.
ResultsFrom a total of 132 children included in the study, 37.9% presented with symptoms with the most common symptoms being cough (70.0%) and diarrhoea (30.0%). A larger proportion of children (62.1%) were on arbacavir/lamivudine/dolutogravr combination of antiretroviral therapy while 8.2% were on the tenoforvir alafenamide/lamivudine/dolutobravir regimen. Children who were on abacavir/lamivudine/dolutegravir regimen presented with more symptoms (48.8%) compared to those on tenofovir alafenamide/lamivudine/dolutegravir (21.0%) and tenofovir disoproxil fumarate/lamivudine/dolutegravir (18.2%) (p = 0.006). Approximately 60.0% of children presenting with symptoms were prescribed antibiotics. Co-trimoxazole was the most commonly (38.0%) prescribed, while erythromycin (2.0%) and Cephalexin (2.0%) were the least.
ConclusionsRespiratory and gastrointestinal symptoms were the most common presentations suggestive of a suspected infection requiring antibiotic prescription in HIV-positive children on ART. Despite co-trimoxazole being the prophylactic drug among HIV-positive children, it was the most common antibiotic among children presenting with symptoms suggestive of an infection. This calls for the prudent use of co-trimoxazole to avoid its resistance.
by Wenbo Wu, Sherry Wu, Sim Berlene Mariano, Richard E. Burney, Jonathan P. Kuriakose
BackgroundVenous thromboembolism (VTE) is a significant preventable cause of postoperative morbidity and mortality after major abdominopelvic surgery that calls for extended VTE prophylaxis (eVTEp). Literature suggests that significant racial disparities may exist in post-operative care.
ObjectiveThe study sought to examine if racial disparities exist in the administration of eVTEp after hysterectomy in a statewide collaborative.
MethodsWe conducted a retrospective cohort study of post-hysterectomy patients across 69 hospitals in the Michigan Surgical Quality Collaborative from January 2016 to February 2020. The variable of interest was race (Black/African or White American). The primary outcome was administration or absence of eVTEp. Descriptive statistics and mixed effects logistic regression were performed for risk adjustment with covariates such as age, cancer occurrence, inflammatory bowel disease, American Society of Anesthesiologists physical status classification, perioperative VTE prophylaxis, postoperative VTE prophylaxis, surgical approach, and surgical duration, among other variables.
ResultsIn total, 24,513 patients underwent hysterectomy. Of these patients, 1,107 (4.45%) received eVTEp, 153 (13.24%) of which were Black and 954 (82.53%) of which were White. Mixed effects logistic regression analysis suggested that Black patients were significantly less likely to receive eVTEp than White patients (odds ratio = 0.776; 95% CI: 0.615–0.979; P = 0.039). Additionally, tobacco use, coronary artery disease, bleeding disorder, cancer occurrence, functional status, perioperative VTE prophylaxis, surgical duration, length of stay, and surgical approach were associated with a higher likelihood of receiving eVTEp.
ConclusioneVTEp is recommended for the prevention of post-discharge VTE in select patients after hysterectomy. Regression analysis showed that, compared to their White counterparts, Black females were significantly less likely to receive eVTEp. The underlying reasons for this disparity require further investigation into possible socioeconomic influences and inherent biases.
by Gabriel Dumitrescu, Jovan Antovic, Nida Soutari, Charlotte Gran, Aleksandra Antovic, Kais Al-Abani, Jonathan Grip, Olav Rooyackers, Apostolos Taxiarchis
Complement and extracellular vesicles (EVs) association with thrombogenic tendencies is acknowledged, but limited evidence exists for their link to COVID-19 venous thromboembolism. This study aims to examine the relationship between pulmonary embolism and the expression of complement and other proteins related to thrombogenesis in severe Covid-19 patients. We included prospectively 207 severe COVID-19 patients and retrospectively screened for pulmonary embolism (PE). This analysis comprises 20 confirmed PE cases and 20 matched patients without PE. Blood samples taken at the admission in the intensive care unit were analyzed for complement using ELISA. EVs derived from neutrophils, endothelium, or platelets, as well carrying complement or tissue factor were analyzed using flow cytometry. Complement levels were markedly elevated, with a notable increase in C3a and Terminal Complement Complex. The most prevalent EV population was identified as tissue factor (TF)-carrying EVs which peaked in patients with PE during ICU days 4–9. However, for both the complement and analyzed EV populations, no statistically significant differences were found between the patients who developed pulmonary embolism and those who did not. In conclusion, complement factors and EVs expressing tissue factor, along with EVs derived from endothelial cells and platelets, are elevated in severe COVID-19 patients, regardless of the presence of pulmonary embolism. However, the involvement of complement and procoagulant EVs in peripheral plasma in the development of pulmonary embolism is still unclear and requires further investigation.
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