One Health in Medical Education: A Proposed Framework.

The One Health concept focuses on the interconnections between human health, animal health, and the environment, stressing the need for interdisciplinary collaborations to address complex issues such as the health challenges posed by climate change and global pandemics. One Health is a central part of the curriculum of veterinary schools, however, it is rarely incorporated into medical school education. Nationally, there are limited examples of formal One Health education and training for medical students. To incorporate One Health into its curriculum, John A. Burns School of Medicine developed a Dean's Certificate of Distinction in One Health that consists of a One Health foundational course, a clinical One Health elective course, participation in the One Health Interest Group, engagement in One Health educational and outreach activities, and a One Health research or curriculum development project. To the authors' knowledge, this is the first One Health certificate program developed and implemented in any Association of American Medical Colleges accredited medical school. Although introducing similar programs into medical curricula will continue to be challenging, we hope it will serve as a framework for other academic institutions.

Exocyst inactivation in urothelial cells disrupts autophagy and activates non-canonical NF-κB signaling.

Ureter obstruction is a highly prevalent event during embryonic development and is a major cause of pediatric kidney disease. We have previously reported that ureteric bud-specific ablation of the gene expressing the exocyst subunit EXOC5 in late murine gestation results in failure of urothelial stratification, cell death and complete ureter obstruction. However, the mechanistic connection between disrupted exocyst activity, urothelial cell death and subsequent ureter obstruction was unclear. Here, we report that inhibited urothelial stratification does not drive cell death during ureter development. Instead, we demonstrate that the exocyst plays a critical role in autophagy in urothelial cells, and that disruption of autophagy activates a urothelial NF-κB stress response. Impaired autophagy first provokes canonical NF-κB activity, which is progressively followed by increasing levels of non-canonical NF-κB activity and cell death if the stress remains unresolved. Furthermore, we demonstrate that ureter obstructions can be completely rescued in Exoc5 conditional knockout mice by administering a single dose of the pan-caspase inhibitor z-VAD-FMK at embryonic day 16.5 prior to urothelial cell death. Taken together, ablation of Exoc5 disrupts autophagic stress response and activates progressive NF-κB signaling, which promotes obstructive uropathy.