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Intestinal epithelial cell (IEC) responses to interferon (IFN) favor antiviral defense with minimal cytotoxicity, but IEC-specific factors that regulate these responses remain poorly understood. Interferon regulatory factors (IRFs) are a family of nine related transcription factors, and IRF6 is preferentially expressed by epithelial cells, but its roles in IEC immunity are unknown. In this study, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screens found that Irf6 deficiency enhanced IFN-stimulated antiviral responses in transformed mouse IECs but not macrophages. Furthermore, knockout (KO) of Irf6 in IEC organoids resulted in profound changes to homeostasis and immunity gene expression. Irf6 KO organoids grew more slowly, and single-cell ribonucleic acid sequencing indicated reduced expression of genes in epithelial differentiation and immunity pathways. IFN-stimulated gene expression was also significantly different in Irf6 KO organoids, with increased expression of stress and apoptosis-associated genes. Functionally, the transcriptional changes in Irf6 KO organoids were associated with increased cytotoxicity upon IFN treatment or inflammasome activation. These data indicate a previously unappreciated role for IRF6 in IEC biology, including regulation of epithelial development and moderation of innate immune responses to minimize cytotoxicity and maintain barrier function.
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BACKGROUND: Endoscopically or fluoroscopically guided dilation is a safe and effective alternative to surgery for patients with benign strictures of the gastric outlet. CASE SUMMARY: We describe two cases where a novel approach with a Spyglass® choledochoscope in assessing the extent of benign duodenal strictures and aiding in placement of duodenal stents for treatment of the strictures. Choledochoscope-guided wire and stent placement was successful in all cases, leading to symptom resolution related to benign duodenal obstruction. No major adverse events were observed. CONCLUSION: Choledochoscope-guided assessment and endoscopic therapy is a viable approach in relieving duodenal obstruction, if the conventional combined fluoroscopic and endoscopic methods fail.
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INTRODUCTION: Studies have shown that a physician's clinical reasoning performance can be influenced by contextual factors. We explored how the clinical reasoning performance of medical students was impacted by contextual factors in order to expand upon previous findings in resident and board certified physicians. Using situated cognition as the theoretical framework, our aim was to evaluate the verbalized clinical reasoning processes of medical students in order to describe what impact the presence of contextual factors has on their reasoning performance. METHODS: Seventeen medical student participants viewed three video recordings of clinical encounters portraying straightforward diagnostic cases in internal medicine with explicit contextual factors inserted. Participants completed a computerized post-encounter form as well as a think-aloud protocol. Three authors analyzed verbatim transcripts from the think-aloud protocols using a constant comparative approach. After iterative coding, utterances were analyzed and grouped into categories and themes. RESULTS: Six categories and ten associated themes emerged, which demonstrated overlap with findings from previous studies in resident and attending physicians. Four overlapping categories included emotional disturbances, behavioural inferences about the patient, doctor-patient relationship, and difficulty with closure. Two new categories emerged to include anchoring and misinterpretation of data. DISCUSSION: The presence of contextual factors appeared to impact clinical reasoning performance in medical students. The data suggest that a contextual factor can be innate to the clinical scenario, consistent with situated cognition theory. These findings build upon our understanding of clinical reasoning performance from both a theoretical and practical perspective.