Emotion,cognitive load and learning outcomes during simulation training

Medical Education 2012: 46 : 1055–1062 CONTEXT Simulation training has emerged as an effective way to complement clinical training of medical students. Yet outcomes from simulation training must be considered suboptimal when 25–30% of students fail to recognise a cardiac murmur on which they were trained 1 hour previously. There are several possible explanations for failure to improve following simulation training, which include the impact of heightened emotions on learning and cognitive overload caused by interactivity with high‐fidelity simulators. This study was conducted to assess emotion during simulation training and to explore the relationships between emotion and cognitive load, and diagnostic performance. METHODS We trained 84 Year 1 medical students on a scenario of chest pain caused by symptomatic aortic stenosis. After training, students were asked to rate their emotional state and cognitive load. We then provided training on a dyspnoea scenario before asking participants to diagnose the murmur in which they had been trained (aortic stenosis) and a novel murmur (mitral regurgitation). We used factor analysis to identify the principal components of emotion, and then studied the associations between these components of emotion and cognitive load and diagnostic performance. RESULTS We identified two principal components of emotion, which we felt represented invigoration and tranquillity. Both of these were associated with cognitive load with adjusted regression coefficients of 0.63 (95% confidence interval [CI] 0.28–0.99; p = 0.001) and ? 0.44 (95% CI ? 0.77 to ? 0.10; p = 0.009), respectively. We found a significant negative association between cognitive load and the odds of subsequently identifying the trained murmur (odds ratio 0.27, 95% CI 0.11–0.67; p = 0.004). CONCLUSIONS We found that increased invigoration and reduced tranquillity during simulation training were associated with increased cognitive load, and that the likelihood of correctly identifying a trained murmur declined with increasing cognitive load. Further studies are needed to evaluate the impact on performance of strategies to alter emotion and cognitive load during simulation training.     

KLF4-SQSTM1/p62-associated prosurvival autophagy contributes to carfilzomib resistance in multiple myeloma models

Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such as carfilzomib. Toward this end, we have established carfilzomib-resistant derivatives of MM cell lines. We found that resistance to carfilzomib was associated with elevated levels of prosurvival autophagy, and Kruppel-like factor 4 (KLF4) was identified as a contributing factor. Expression levels as well as nuclear localization of KLF4 protein were elevated in MM cells with acquired carfilzomib resistance. Chromatin immunoprecipitations indicated that endogenous KLF4 bound to the promoter regions of the SQSTM1 gene encoding the ubiquitin-binding adaptor protein sequestosome/p62 that links the proteasomal and autophagic protein degradation pathways. Ectopic expression of KLF4 induced upregulation of SQSTM1. On the other hand, inhibitors of autophagy sensitized MM cells to carfilzomib, even in carfilzomib-resistant derivatives having increased expression of the multidrug resistance protein P-glycoprotein. Thus, we report here a novel function for KLF4, one of the Yamanaka reprogramming factors, as being a contributor to autophagy gene expression which moderates preclinical proteasome inhibitor efficacy in MM.