Hydrogen sulfide (H2S) has been recently recognized as an important gasotransmitter with cardioprotections, and iron is vital for various cellular activities. This study explored the regulatory role of H2S on iron metabolism and mitochondrial functions in cultured rat cardiac cells. Rotenone, a mitochondrial complex I inhibitor, was used for establishing an in vitro model of ischemic cell damage. It was first found that rotenone induced oxidative stress and lipid peroxidation and decreased mitochondrial membrane potential and ATP generation, eventually causing cell death. The supplement of H2S at a physiologically relevant concentration protected from rotenone-induced ferroptotic cell death by reducing oxidative stress and mitochondrial damage, maintaining GPx4 expression and intracellular iron level. Deferiprone, an iron chelator, would also protect from rotenone-induced ferroptosis. Further studies demonstrated that H2S inhibited ABCB8-mediated iron efflux from mitochondria to cytosol and promoted NFS1-mediated Fe-S cluster biogenesis. It is also found that rotenone stimulated iron-dependent H2S generation. These results indicate that H2S would protect cardiac cells from ischemic damage through preserving mitochondrial functions and intracellular Fe-S cluster homeostasis.
Access to practice opportunities for history-taking in undergraduate medical education can be resource-limited. Large language models are a potential avenue to address this. This study sought to characterize changes in learner self-reported confidence with history-taking before and after a simulation with an LLM-based patient and understand learner experience with and the acceptability of virtual LLM-based patients. This was a multi-method study conducted at McMaster University. Simulations were facilitated with the OSCEai tool. Data was collected through surveys with a Likert scale and open-ended questions and semi-structured interviews. A total of 24 participants generated 93 survey responses and 17 interviews. Overall, participants reported a 14.6% increase in comfort with history-taking. Strengths included its flexibility, accessibility, detailed feedback, and ability to provide a judgement-free space to practice. Limitations included its lower fidelity compared to standardized patients and at times repetitive and less clinically relevant feedback as compared to preceptors. It was overall viewed best as a supplement rather than a replacement for standardized patients. In conclusion, LLM-based virtual patients were feasible and valued as an adjunct tool. They can support scalable, personalized practice. Future work is needed to understand objective metrics of improvement and to design curricular strategies for integration.