During biofilm formation, and other Enterobacteriaceae produce an extracellular matrix consisting of curli amyloid fibers and cellulose. The precursor of curli fibers is the amyloidogenic protein CsgA. The human systemic amyloid precursor protein transthyretin (TTR) is known to inhibit amyloid-β (Aβ) aggregation in vitro and suppress the Alzheimer's-like phenotypes in a transgenic mouse model of Aβ deposition. We hypothesized that TTR might have broad antiamyloid activity because the biophysical properties of amyloids are largely conserved across species and kingdoms. Here, we report that both human WT tetrameric TTR (WT-TTR) and its engineered nontetramer-forming monomer (M-TTR, F87M/L110M) inhibit CsgA amyloid formation in vitro, with M-TTR being the more efficient inhibitor. Preincubation of WT-TTR with small molecules that occupy the T4 binding site eliminated the inhibitory capacity of the tetramer; however, they did not significantly compromise the ability of M-TTR to inhibit CsgA amyloidogenesis. TTR also inhibited amyloid-dependent biofilm formation in two different bacterial species with no apparent bactericidal or bacteriostatic effects. These discoveries suggest that TTR is an effective antibiofilm agent that could potentiate antibiotic efficacy in infections associated with significant biofilm formation.

Background: The authors analyzed the distribution of medical student debt and identified demographic features that placed students at high risk for increased debt and financial stress. Methods: From April to May 2019, a cross-sectional, anonymous, web-based survey was administered to first-year (M1) to fourth-year (M4) medical students at the University of Michigan to assess financial literacy, debt burden, financial stress, and demographic factors. A total of 216 of 680 (32%) students completed the survey. Respondents voluntarily answered 15 multiple-choice questions on personal finance and 30 questions on their demographics, current financial situation, and debt burden. To quantify debt burden, students estimated anticipated education-related debt in one of four categories: no debt, $1–99,999; $100,000–$199,999; and $200,000 or more. A chi-square test was used to identify associations between categorical variables and logistic regression was used to identify risk factors for debt and worry. Results: Fifty-four respondents (25%) reported $0 in education related debt, while 44 (16%) had $200,000 or more. Race (p=0.006), first-generation college student status (p=0.004), first-generation medical student status (p<0.001), household income (p<0.001), and parental education (p=0.008) were associated with higher levels of debt. Students who were underrepresented in medicine (URiM) had higher odds of higher debt compared to Arab and Asian students (p=0.02). URiM students (p=0.02), first-generation college students (p=0.009), and parental education (p=0.01) were associated with increased financial stress. Additionally, female students had higher odds of increased financial stress (OR=1.85, p=0.045) on logistic regression. Conclusions: URiM and socioeconomically disadvantaged students feel the burden of the high cost of medical school disproportionately more, suggesting that our current systems are not adequately supporting these students. Reducing this burden may serve to further promote diversity in medicine.

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Background: The authors analyzed the distribution of medical student debt and identified demographic features that placed students at high risk for increased debt and financial stress. Methods: From April to May 2019, a cross-sectional, anonymous, web-based survey was administered to first-year (M1) to fourth-year (M4) medical students at the University of Michigan to assess financial literacy, debt burden, financial stress, and demographic factors. A total of 216 of 680 (32%) students completed the survey. Respondents voluntarily answered 15 multiple-choice questions on personal finance and 30 questions on their demographics, current financial situation, and debt burden. To quantify debt burden, students estimated anticipated education-related debt in one of four categories: no debt, $1–99,999; $100,000–$199,999; and $200,000 or more. A chi-square test was used to identify associations between categorical variables and logistic regression was used to identify risk factors for debt and worry. Results: Fifty-four respondents (25%) reported $0 in education related debt, while 44 (16%) had $200,000 or more. Race (p=0.006), first-generation college student status (p=0.004), first-generation medical student status (p<0.001), household income (p<0.001), and parental education (p=0.008) were associated with higher levels of debt. Students who were underrepresented in medicine (URiM) had higher odds of higher debt compared to Arab and Asian students (p=0.02). URiM students (p=0.02), first-generation college students (p=0.009), and parental education (p=0.01) were associated with increased financial stress. Additionally, female students had higher odds of increased financial stress (OR=1.85, p=0.045) on logistic regression. Conclusions: URiM and socioeconomically disadvantaged students feel the burden of the high cost of medical school disproportionately more, suggesting that our current systems are not adequately supporting these students. Reducing this burden may serve to further promote diversity in medicine.