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Objective: (1) Describe the progression of diabetes mellitus over time in an observational study of Wolfram syndrome, a rare, genetic, neurodegenerative disorder, which often includes diabetes mellitus and is typically diagnosed during childhood or adolescence. (2) Determine whether C-peptide could be used as a marker of diabetes progression in interventional trials for Wolfram syndrome. Methods: N = 44 (25F/19M) participants with genetically confirmed Wolfram syndrome attended the Washington University Wolfram Research Clinic annually from 2010 to 2019. Medical history, physical examinations, blood sampling, and questionnaires were used to collect data about diabetes mellitus and other components of Wolfram syndrome. Beta-cell function was assessed by determination of C-peptide during a mixed meal tolerance test. Random coefficients models evaluated the rate of progression of C-peptide over time, and power analyses were used to estimate the number of subjects needed to detect a change in C-peptide decline during an intervention trial. Results: 93.2% of patients had diabetes mellitus. Mean HbA1c across all study visits was 7.9%. C-peptide significantly decreased with increasing duration of diabetes mellitus (p < 0.0001); an optimal break point in C-peptide decline was identified to occur between 0.1 and 2.3 years after diabetes mellitus diagnosis. Twenty patients per group (active vs. control) were estimated to be needed to detect a 60% slowing of C-peptide decline during the first 2.3 years following diabetes diagnosis. Conclusion: C-peptide declines over time in Wolfram syndrome and could potentially be used as a marker of diabetes progression in interventional studies for Wolfram syndrome, especially within the first 2 years after diabetes diagnosis. 2022, 2, Downloaded fromr [ABSTRACT FROM AUTHOR]

Introduction: Differences in time commitments and resources contribute to the difficulties of work-life integration for many physician-scientists, particularly for women with family caregiving responsibilities. Understanding the challenges faced by this population is critical for the retention of these critical members of the workforce. Methods: We conducted semi-structured telephone interviews with recipients of the 2017 Doris Duke Charitable Foundation's Fund to Retain Clinical Scientists (FRCS) and reviewed application narratives from the 2020 award recipients. Award recipients were asked about their caregiving responsibilities and careers, particularly as they related to the impact of the FRCS award and the aftereffects of the COVID-19 pandemic. Analysts then iteratively revised the coding scheme and interpreted the data using qualitative thematic analysis. Results: Of the 14 interviewees and 19 narrative contributors, 25 (76%) were women. The main qualitative themes that emerged were as follows: (1) women experience unrealistically high caregiving burdens, (2) women are overburdened by disadvantageous and undervalued expectations at work, (3) work-life expectations increased during the COVID-19 pandemic, and (4) unrealistic work-life expectations led to guilt and burnout. Conclusions: These findings provide a rich understanding of the factors contributing to guilt and burnout among physician-scientists, particularly women, and how work duties that increase physician obligations exacerbated these challenges. Understanding these experiences is critical to supporting and retaining a diverse workforce in academic medicine.