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Keratins are one of the most abundant proteins in epithelial cells. They form a cytoskeletal filament network whose structural organization seriously conditions its function. Dynamic keratin particles and aggregates are often observed at the periphery of mutant keratinocytes related to the hereditary skin disorder epidermolysis bullosa simplex, which is due to mutations in keratins 5 and 14. To account for their emergence in mutant cells, we extended an existing mathematical model of keratin turnover in wild-type cells and developed a novel 2D phase-field model to predict the keratin distribution inside the cell. This model includes the turnover between soluble, particulate and filamentous keratin forms. We assumed that the mutation causes a slowdown in the assembly of an intermediate keratin phase into filaments, and demonstrated that this change is enough to account for the loss of keratin filaments in the cell’s interior and the emergence of keratin particles at its periphery. The developed mathematical model is also particularly tailored to model the spatial distribution of keratins as the cell changes its shape.

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19Keratin intermediate filaments are the principal structural element of epithelial cells. Their 20 importance in providing bulk cellular stiffness is well recognized, but their role in the 21 mechanics of cell cortex is less understood. In this study, we therefore compared the cortical 22 2 29 cells, which was also detected in previous studies of bulk elasticity. In addition, a small 30 difference between the mutant and the wild type cells was detected, showing that mutation of 31 keratin impacts also the cell cortex. Thus, our results indicate that the role of keratins in 32 cortical stiffness is not negligible and call for further investigation of the mechanical 33 interactions between keratins and elements of the cell cortex. 34 35

Introduction: There is a paucity of quantitative studies objectively comparing debriefing and feedback as methods for post-scenario discussion and its impact on healthcare teams’ acquisition and retention of non-technical skills. The main purpose of this study is to provide some insight on this research question, using a sample of medical students. A secondary objective explores students’ opinion and preference on the post-scenario discussion.Material and Methods: Forty-five medical students were distributed among 15 teams, and randomly allocated to two groups. Each team participated in three different simulated scenarios, with similar levels of difficulty and opportunities to apply specific non-technical skills: leadership, communication, and task management. To assess the acquisition and retention of skills, scenarios occurred on days one (baseline), two (acquisition) and 20 (retention). Team performance was objectively evaluated by an observer, using scenario recordings. Students individually assessed different aspects of debriefing and feedback.Results: Both debriefing and feedback groups showed similar overall increase in objective scores, with significant increase between days one and two (acquisition), and a smaller increase between days two and 20 (retention). Students indicated debriefing as the preferred discussion method.Conclusion: Debriefing and feedback are effective post-scenario discussion methods, promoting acquisition and retention of non-technical skills, by undergraduate students. Allying debriefing reflexive practice with feedback directive style, and shifting appropriately between facilitation and instruction, can be a good compromise to achieve a timely and educationally meaningful discussion.