12 research outputs found

    Bladder Health Experiences, Perceptions and Knowledge of Sexual and Gender Minorities

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    While recent efforts have been made to understand the bladder health experiences, perceptions, and knowledge of cisgender adolescent females and women, virtually nothing is known about the bladder health experiences of people who identify as sexual and gender minorities (SGMs). A community-based participatory research approach using a focus group methodology to engage 36 adult participants who identify as SGM, including individuals who identify as gender non-conforming, queer, transgender (trans) men, or lesbian, in one of six focus group discussions on bladder health. Using directed content qualitative data analysis from the six unique focus groups, three interrelated themes were revealed: gender socialization of voiding behavior and toilet environment culture producing identity threats, and risks to gender affirmation; consequences of hetero-cis normative bathroom infrastructure necessitating adaptive voiding behaviors; and, physical and psychosocial consequences of chronic anxiety and fear are associated with voiding experiences. Insight on how SGMs navigate voiding behaviors, toilet experiences, and health care seeking is needed to assure that bladder health promotion activities are inclusive of this population’s needs

    Reductive Power Generated by Mycobacterium leprae Through Cholesterol Oxidation Contributes to Lipid and ATP Synthesis

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    <jats:p>Upon infection, <jats:italic>Mycobacterium leprae</jats:italic>, an obligate intracellular bacillus, induces accumulation of cholesterol-enriched lipid droplets (LDs) in Schwann cells (SCs). LDs are promptly recruited to <jats:italic>M. leprae</jats:italic>-containing phagosomes, and inhibition of this process decreases bacterial survival, suggesting that LD recruitment constitutes a mechanism by which host-derived lipids are delivered to intracellular <jats:italic>M. leprae</jats:italic>. We previously demonstrated that <jats:italic>M. leprae</jats:italic> has preserved only the capacity to oxidize cholesterol to cholestenone, the first step of the normal cholesterol catabolic pathway. In this study we investigated the biochemical relevance of cholesterol oxidation on bacterial pathogenesis in SCs. Firstly, we showed that <jats:italic>M. leprae</jats:italic> increases the uptake of LDL-cholesterol by infected SCs. Moreover, fluorescence microscopy analysis revealed a close association between <jats:italic>M. leprae</jats:italic> and the internalized LDL-cholesterol within the host cell. By using <jats:italic>Mycobacterium smegmatis</jats:italic> mutant strains complemented with <jats:italic>M. leprae</jats:italic> genes, we demonstrated that <jats:italic>ml1942</jats:italic> coding for 3β-hydroxysteroid dehydrogenase (3β-HSD), but not <jats:italic>ml0389</jats:italic> originally annotated as cholesterol oxidase (ChoD), was responsible for the cholesterol oxidation activity detected in <jats:italic>M. leprae</jats:italic>. The 3β-HSD activity generates the electron donors NADH and NADPH that, respectively, fuel the <jats:italic>M. leprae</jats:italic> respiratory chain and provide reductive power for the biosynthesis of the dominant bacterial cell wall lipids phthiocerol dimycocerosate (PDIM) and phenolic glycolipid (PGL)-I. Inhibition of <jats:italic>M. leprae</jats:italic> 3β-HSD activity with the 17β-[N-(2,5-di-t-butylphenyl)carbamoyl]-6-azaandrost-4-en-3one (compound 1), decreased bacterial intracellular survival in SCs. In conclusion, our findings confirm the accumulation of cholesterol in infected SCs and its potential delivery to the intracellular bacterium. Furthermore, we provide strong evidence that cholesterol oxidation is an essential catabolic pathway for <jats:italic>M. leprae</jats:italic> pathogenicity and point to 3β-HSD as a prime drug target that may be used in combination with current multidrug regimens to shorten leprosy treatment and ameliorate nerve damage.</jats:p&gt

    Delegation of Specification: An Agency Theory of Organizations

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    Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

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    Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

    The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

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    © 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine
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