High attrition rates in tuberculosis (TB) drug development have been largely attributed to safety, which is likely due to the use of endpoint assays measuring cell viability to detect drug cytotoxicity. In drug development of cancer, metabolic and neurological disorders, and antibiotics, cytotoxicity is increasingly being assessed using extracellular flux (XF) analysis, which measures cellular bioenergetic metabolism in real-time. Here, we adopt the XF platform to investigate the cytotoxicity of drugs currently used in TB treatment on the bioenergetic metabolism of HepG2 cells, THP-1 macrophages, and human monocyte derived macrophages (hMDM). We found that the XF analysis reveals earlier drug-induced effects on the cells’ bioenergetic metabolism prior to cell death, measured by conventional viability assays. Furthermore, each cell type has a distinct response to drug treatment, suggesting that more than one cell type should be considered to examine cytotoxicity in TB drug development. Interestingly, chemically unrelated drugs with different modes of action on Mycobacterium tuberculosis have similar effects on the bioenergetic parameters of the cells, thus, discouraging the prediction of potential cytotoxicity based on chemical structure and mode of action of new chemical entities. The clustering of the drug-induced effects on the hMDM bioenergetic parameters are reflected in the clustering of the effects of the drugs on cytokine production in hMDMs, demonstrating concurrence between the effects of the drugs on the metabolism and functioning of the macrophages. These findings can be used as a benchmark to establish XF analysis as a new tool to assay cytotoxicity in TB drug development.

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Background: Misinformation and disinformation perpetuate negative stereotypes, reinforce prejudice and lead to racially motivated discrimination. As displayed in post-secondary institutions worldwide, white-centric perspectives are primarily embedded in school cultures and systems. Such racial aggressions produce ‘racial battle fatigue,’ creating physiological, physiological, and behavioural stress for the recipient. Virtual simulation is proposed as an educational strategy for learners to identify racism in an academic setting and develop allyship for equity-seeking groups. This poster aims to advocate the use of virtual simulation to improve the overall educational experience by highlighting the voices of diverse students and educators. Methods: Our team developed a pre-learning simulation consisting of five short scenes depicting racially discriminatory acts. It highlights the urgency to discontinue the term 'microaggression'. A longer simulation was developed in which a racially discriminatory act is depicted, with a bystander present. This longer simulation allows participants to adopt the role of a bystander and use the ARISE model to ally with the BIPOC community in addressing racism (overt and covert racism). The ARISE model encompasses five key elements: awareness, responding with empathy, inquiring about facts, using "I" statements, and educating and engaging. Intended Outcomes: We seek to provide information regarding racial inequities in higher education curriculum by: (1) illustrating how racism affects people in their learning environment, (2) demonstrating how bystanders might apply the ARISE model to help a person experiencing racism in an educational setting, and (3) learning how to be an ally.

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