NADPH oxidase (Nox) enzymes are a significant source of reactive oxygen species, which contribute to glomerular podocyte dysfunction. Although studies have implicated Nox1, -2, and -4 in several glomerulopathies, including diabetic nephropathy, little is known regarding the role of Nox5 in this context. We examined Nox5 expression and regulation in kidney biopsies from diabetic patients, cultured human podocytes, and a novel mouse model. Nox5 expression increased in human diabetic glomeruli compared with nondiabetic glomeruli. Stimulation with angiotensin II upregulated Nox5 expression in human podocyte cultures and increased reactive oxygen species generation. siRNA-mediated Nox5 knockdown inhibited angiotensin II-stimulated production of reactive oxygen species and altered podocyte cytoskeletal dynamics, resulting in an Rac-mediated motile phenotype. Because the Nox5 gene is absent in rodents, we generated transgenic mice expressing human Nox5 in a podocyte-specific manner (Nox5 pod+ ). Nox5 pod+ mice exhibited early onset albuminuria, podocyte foot process effacement, and elevated systolic BP. Subjecting Nox5 pod+ mice to streptozotocin-induced diabetes further exacerbated these changes. Our data show that renal Nox5 is upregulated in human diabetic nephropathy and may alter filtration barrier function and systolic BP through the production of reactive oxygen species. These findings provide the first evidence that podocyte Nox5 has an important role in impaired renal function and hypertension. Albuminuria is a clinical marker of kidney dysfunction that arises in most glomerulopathies and is associated with poor prognoses for ESRD, hypertension, and cardiovascular mortality. Changes to the podocyte (e.g., foot process effacement, hypertrophy, detachment, and loss) underlie the development and progression of albuminuria and thereby highlight the critical role for these cells in upholding the glomerular filtration barrier. 1,2 Therefore, identifying factors that induce podocyte injury and loss is essential to understanding the mechanisms of filtration barrier dysfunction. Of the many factors implicated in podocyte dysfunction, excessive production of reactive oxygen species (ROS; oxidative stress) may be particularly important. [3][4][5][6] Although sources of ROS are numerous, the NADPH oxidase (Nox) family of enzymes yields significant superoxide production in the
Prioritizing resident and patient safety while maintaining educational value: emergency restructuring of a Canadian surgical residency program during COVID-19 T he coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented challenge to health care. As of April 19, 2020, Ontario had approximately 10 500 confirmed cases 1 and adopted physical distancing as a cornerstone of fighting viral spread. 2 Although critical, self-isolation requirements can become disruptive to health care delivery. Health care providers are at high risk of exposure, leaving wide gaps in clinical coverage as they self-isolate. A recent American study described a residency restructuring model, but no Canadian experiences or comment on the educational component of surgical training during the COVID-19 pandemic have been described. 3 Surgical oncology cases represent a workflow challenge, as health systems struggle to balance priorities in cancer care with the conservation of resources. The Cancer Care Ontario (CCO) Pandemic Guideline classifies these cases into 3 priority levels based on acceptable delay to surgery, 4 and each hospital manages its own resources within this framework. At The Ottawa Hospital (TOH), oncology cases are triaged weekly by senior management. All elective, nononcology surgery has been postponed indefinitely.Foreseeing the impact on patient care and resident education, the University of Ottawa's general surgery program leadership team (L.W., N.G., C.T.) designed a contingency schedule. The small leadership team was key to being able to develop and implement widespread changes swiftly. The leadership team is in frequent communication with residents, staff and other key stakeholders in hospital administration, which allows for rapid adjustments in response to daily updates. Our objectives were as follows:
Background The residency selection process relies on subjective information in applications, as well as subjective assessment of applications by reviewers. This inherent subjectivity makes residency selection prone to poor reliability between those reviewing files. Objective We compared the interrater reliability of 2 assessment tools during file review: one rating applicant traits (ie, leadership, communication) and the other using a global rating of application elements (ie, curriculum vitae, reference letters). Methods Ten file reviewers were randomized into 2 groups, and each scored 7 general surgery applications from the 2019–2020 cycle. The first group used an element-based (EB) scoring tool, while the second group used a trait-based (TB) scoring tool. Feedback was collected, discrimination capacities were measured using variation in scores, and interrater reliability (IRR) was calculated using intraclass correlation (ICC) in a 2-way random effects model. Results Both tools identified the same top-ranked and bottom-ranked applicants; however, discrepancies were noted for middle-ranked applicants. The score range for the 5 middle-ranked applicants was greater with the TB tool (6.43 vs 3.80), which also demonstrated fewer tie scores. The IRR for TB scoring was superior to EB scoring (ICC [2, 5] = 0.82 vs 0.55). The TB tool required only 2 raters to achieve an ICC ≥ 0.70. Conclusions Using a TB file review strategy can facilitate file review with improved reliability compared to EB, and a greater spread of candidate scores. TB file review potentially offers programs a feasible way to optimize and reflect their institution's core values in the process.
Background The resident selection process involves the analysis of multiple data points, including letters of reference (LORs), which are inherently subjective in nature. Objective We assessed the frequency with which LORs use quantitative terms to describe applicants and to assess whether the use of these terms reflects the ranking of trainees in the final selection process. Methods A descriptive study analyzing LORs submitted by Canadian medical graduate applicants to the University of Ottawa General Surgery Program in 2019 was completed. We collected demographic information about applicants and referees and recorded the use of preidentified quantitative descriptors (eg, best, above average). A 10% audit of the data was performed. Descriptive statistics were used to analyze the demographics of our letters as well as the frequency of use of the quantitative descriptors. Results Three hundred forty-three LORs for 114 applicants were analyzed. Eighty-two percent (291 of 343) of LORs used quantitative descriptors. Eighty-four percent (95 of 113) of applicants were described as above average, and 45% (51 of 113) were described as the “best” by at least 1 letter. The candidates described as the “best” ranked anywhere from second to 108th in our ranking system. Conclusions Most LORs use quantitative descriptors. These terms are generally positive, and while the use does discriminate between different applicants, this was not helpful in the context of ranking applicants in our file review process.
Background Residency selection integrates objective and subjective data sources. Interviews help assess characteristics like insight and communication but have the potential for bias. Structured multiple mini-interviews may mitigate some elements of bias; however, a halo effect is described in assessments of medical trainees, and degree of familiarity with applicants may remain a source of bias in interviews. Objective To investigate the extent of interviewer bias that results from pre-interview knowledge of the applicant by comparing file review and interview scores for known versus unknown applicants. Methods File review and interview scores of applicants to the University of Ottawa General Surgery Residency Training Program from 2019 to 2021 were gathered retrospectively. Applicants were categorized as “home” if from the institution, “known” if they completed an elective at the institution, or “unknown.” The Kruskal-Wallis H test was used to compare median interview scores between groups and Spearman's rank-order correlation (rs) to determine the correlation between file review and interview scores. Results Over a 3-year period, 169 applicants were interviewed; 62% were unknown, 31% were known, and 6% were home applicants. There was a statistically significant difference (P=.01) between the median interview scores of home, known, and unknown applicants. Comparison of groups demonstrated higher positive correlations between file review and interview scores (rs=0.15 vs 0.36 vs 0.55 in unknown, known, and home applicants) with increasing applicant familiarity. Conclusions There is an increased positive correlation between file review and interview scores with applicant familiarity. The interview process may carry inherent bias insufficiently mitigated by the current structure.
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