Background: While the Association of American Medical Colleges encourages medical schools to incorporate quality improvement and patient safety (QI/PS) into their curriculum, medical students continue to have limited QI/ PS exposure. To prepare medical students for careers that involve QI/PS, the Institute for Healthcare Improvement chapter at an allopathic medical school and school of allied health professions initiated self-directed learning by offering student-led workshops to equip learners with skills to improve the quality and safety of healthcare processes. Methods: In this prospective cohort study, workshops were hosted for medical students between 2015 and 2018 on five QI/PS topics: Process Mapping, Root-Cause Analysis (RCA), Plan-Do-Study-Act (PDSA) Cycles, Evidence Based Medicine (EBM), and Patient Handoffs. Each workshop included a hands-on component to engage learners in practical applications of QI/PS skills in their careers. Change in knowledge, attitudes, and behaviors was assessed via pre-and post-surveys using 5-point Likert scales, and analyzed using either the McNemar test or non-parametric Wilcoxon signed-rank test. Surveys also gathered qualitative feedback regarding strengths, future areas for improvement, and reasons for attending the workshops. Results: Data was collected from 88.5% of learners (n = 185/209); 19.5% of learners reported prior formal instruction in these topics. Statistically significant improvements in learners' confidence were observed for each workshop. Additionally, after attending workshops, learners felt comfortable teaching the learned QI/PS skill to colleagues (mean pre/post difference 1.96, p < 0.0001, n = 139) and were more likely to pursue QI/PS projects in their careers (mean pre/post difference 0.45, p < 0.0001, n = 139). Lastly, learners demonstrated a statistically significant increase in knowledge in four out of five skills workshop topics.
Leukocyte inflammatory responses require integrin cell-adhesion molecule signaling through spleen tyrosine kinase (Syk), a non-receptor kinase that binds directly to integrin β-chain cytoplasmic domains. Here, we developed a high-throughput screen to identify small molecule inhibitors of the Syk-integrin cytoplasmic domain interactions. Screening small molecule compound libraries identified the β-lactam antibiotics cefsulodin and ceftazidime, which inhibited integrin β-subunit cytoplasmic domain binding to the tandem SH2 domains of Syk (IC50 range, 1.02–4.9 µM). Modeling suggested antagonist binding to Syk outside the pITAM binding site. Ceftazidime inhibited integrin signaling via Syk, including inhibition of adhesion-dependent upregulation of interleukin-1β and monocyte chemoattractant protein-1, but did not inhibit ITAM-dependent phosphorylation of Syk mediated by FcγRI signaling. Our results demonstrate a novel means to target Syk independent of its kinase and pITAM binding sites such that integrin signaling via this kinase is abrogated but ITAM-dependent signaling remains intact. As integrin signaling through Syk is essential for leukocyte activation, this may represent a novel approach to target inflammation.
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