68 research outputs found
More than Aligning Perceptions: Medical Student Mistreatment and Psychological Safety on the Surgical Clerkship
BACKGROUND: Despite decades of reporting, rates of medical student mistreatment on the surgical clerkship remain a national issue; our institution is no exception. In order to understand if misaligned perceptions about what constitutes mistreatment were leading to high rates of reported mistreatment at our institution, we implemented a well-studied video-vignette-based intervention on our surgical clerkship. We combined this intervention with semi-structured focus groups to gain further insight into the unique experience of students. METHODS: Medical student volunteers were recruited from the surgery clerkship to participate in a two-hour session consisting of a one-hour semi-structured focus group followed by the video vignette-based curriculum, which was accompanied by a facilitated discussion. RESULTS: Over five clerkship blocks 76 students responded to the end-of-clerkship survey (83% response rate). Based on the end-of-clerkship survey results, students were more likely to report experiencing mistreatment (24% vs 9%, p=0.096) or witnessing mistreatment (47% vs 6%, p\u3c0.01) if they participated in the intervention. Students who participated in the intervention also reported experiencing neglect more frequently than non-participants (“Often” 15% vs 4%, p=0.05; “Never” 24% vs 57%, p=0.05). Conclusion: Analysis of focus group data indicated that lack of psychological safety in the learning environment is a key factor contributing to medical student reporting of mistreatment. Since this study began, we have implemented changes to the clerkship as well as to the department of surgery to create a more positive learning environment, which are already showing promising results. This study illustrates that education-based interventions alone are not sufficient to address mistreatment on the surgical clerkship, and that locally responsive solutions that address psychological safety in the learning environment are critical to effecting real change
Adenosine and Stroke: Maximizing the Therapeutic Potential of Adenosine as a Prophylactic and Acute Neuroprotectant
Stroke is a leading cause of morbidity and mortality in the United States. Despite intensive research into the development of treatments that lessen the severity of cerebrovascular injury, no major therapies exist. Though the potential use of adenosine as a neuroprotective agent in the context of stroke has long been realized, there are currently no adenosine-based therapies for the treatment of cerebral ischemia and reperfusion. One of the major obstacles to developing adenosine-based therapies for the treatment of stroke is the prevalence of functional adenosine receptors outside the central nervous system. The activities of peripheral immune and vascular endothelial cells are particularly vulnerable to modulation via adenosine receptors. Many of the pathophysiological processes in stroke are a direct result of peripheral immune infiltration into the brain. Ischemic preconditioning, which can be induced by a number of stimuli, has emerged as a promising area of focus in the development of stroke therapeutics. Reprogramming of the brain and immune responses to adenosine signaling may be an underlying principle of tolerance to cerebral ischemia. Insight into the role of adenosine in various preconditioning paradigms may lead to new uses for adenosine as both an acute and prophylactic neuroprotectant
LPS preconditioning redirects TLR signaling following stroke: TRIF-IRF3 plays a seminal role in mediating tolerance to ischemic injury
<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 4 (TLR4) is activated in response to cerebral ischemia leading to substantial brain damage. In contrast, mild activation of TLR4 by preconditioning with low dose exposure to lipopolysaccharide (LPS) prior to cerebral ischemia dramatically improves outcome by reprogramming the signaling response to injury. This suggests that TLR4 signaling can be altered to induce an endogenously neuroprotective phenotype. However, the TLR4 signaling events involved in this neuroprotective response are poorly understood. Here we define several molecular mediators of the primary signaling cascades induced by LPS preconditioning that give rise to the reprogrammed response to cerebral ischemia and confer the neuroprotective phenotype.</p> <p>Methods</p> <p>C57BL6 mice were preconditioned with low dose LPS prior to transient middle cerebral artery occlusion (MCAO). Cortical tissue and blood were collected following MCAO. Microarray and qtPCR were performed to analyze gene expression associated with TLR4 signaling. EMSA and DNA binding ELISA were used to evaluate NFκB and IRF3 activity. Protein expression was determined using Western blot or ELISA. MyD88-/- and TRIF-/- mice were utilized to evaluate signaling in LPS preconditioning-induced neuroprotection.</p> <p>Results</p> <p>Gene expression analyses revealed that LPS preconditioning resulted in a marked upregulation of anti-inflammatory/type I IFN-associated genes following ischemia while pro-inflammatory genes induced following ischemia were present but not differentially modulated by LPS. Interestingly, although expression of pro-inflammatory genes was observed, there was decreased activity of NFκB p65 and increased presence of NFκB inhibitors, including Ship1, Tollip, and p105, in LPS-preconditioned mice following stroke. In contrast, IRF3 activity was enhanced in LPS-preconditioned mice following stroke. TRIF and MyD88 deficient mice revealed that neuroprotection induced by LPS depends on TLR4 signaling via TRIF, which activates IRF3, but does not depend on MyD88 signaling.</p> <p>Conclusion</p> <p>Our results characterize several critical mediators of the TLR4 signaling events associated with neuroprotection. LPS preconditioning redirects TLR4 signaling in response to stroke through suppression of NFκB activity, enhanced IRF3 activity, and increased anti-inflammatory/type I IFN gene expression. Interestingly, this protective phenotype does not require the suppression of pro-inflammatory mediators. Furthermore, our results highlight a critical role for TRIF-IRF3 signaling as the governing mechanism in the neuroprotective response to stroke.</p
Inhibition of pre-ischeamic conditioning in the mouse caudate brain slice by NMDA- or adenosine A(1) receptor antagonists
Evidence suggests that pre-ischeamic conditioning (PIC) offers protection against a subsequent ischeamic event. Although some brain areas such as the hippocampus have received much attention, the receptor mechanisms of PIC in other brain regions are unknown. We have previously shown that 10 min oxygen and glucose deprivation (OGD) evokes tolerance to a second OGD event in the caudate. Here we further examine the effect of length of conditioning event on the second OGD event. Caudate mouse brain slices were superfused with artificial cerebro-spinal fluid (aCSF) bubbled with 95%O2/5%CO2. OGD was achieved by reducing the aCSF glucose concentration and by bubbling with 95%N2/5%CO2. After approximately 5 min OGD a large dopamine efflux was observed, presumably caused by anoxic depolarisation. On applying a second OGD event, 60 min later, dopamine efflux was delayed and reduced. We first examined the effect of varying the length of the conditioning event from 5 to 40 min and found tolerance to PIC increased with increasing duration of conditioning. We then examined the receptor mechanism(s) underlying PIC. We found that pre-incubation with either MK-801 or 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) reduced tolerance to the second OGD event. These data suggest that either N-methyl-d-aspartate (NMDA) or adenosine A1 receptor activation evokes PIC in the mouse caudate
Prior Antiplatelet Therapy, Excluding Phosphodiesterase Inhibitor Is Associated with Poor Outcome in Patients with Spontaneous Intracerebral Haemorrhage.
“This is a post-peer-review, pre-copyedit version of an article published in Translational Stroke Research. The final authenticated version is available online at: https://doi.org/10.1007/s12975-019-00722-x”.There is conflicting results on whether prior antiplatelet therapy (APT) is associated with poor outcome in spontaneous intracerebral haemorrhage (ICH) patients. To determine whether prior APT is associated with spontaneous ICH, and whether there is a difference between the different types of APT, including cyclooxygenase inhibitor (COX-I), adenosine diphosphate receptor inhibitor (ADP-I) and phosphodiesterase inhibitor (PDE-I). A retrospective study of patients with ICH diagnosed between 2001 and 2013 in the National Health Insurance Research Database. Baseline unbalance between APT and non-APT groups was solved by multivariable adjustment (primary analysis) and propensity score matching (sensitivity analysis). Patients with prior APT had a higher rate of in-hospital death (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.09-1.23) compared to non-APT group. Compared to non-APT group, there was a greater rate of in-hospital death with spontaneous ICH with ADP-I (OR, 1.49; 95% CI, 1.24-1.79) and COX-I (OR, 1.17; 95% CI, 1.09-1.25). PDE-I exhibited no difference in in-hospital death with spontaneous ICH (OR, 1.03; 95% CI, 0.91-1.16) compared to non-APT group. Remarkably, the in-hospital mortality rate was significantly higher in the ADP-I group than in the PDE-I group (hazard ratio, 1.45; 95% CI, 1.17-1.80). In this study, ADP-I and COX-1, but not PDE-I, are the most likely contributors to the association of APT with poor outcome with spontaneous ICH patients. These findings suggest that the complexity of the different mechanism of actions of prior APT can alter the outcome in spontaneous ICH.Chang Gung Memorial Hospital (CMRPG3H1061, CMRPG3G1002
Optimizing the educational value of surgical morbidity and mortality conference
Introduction:
Weekly morbidity and mortality (M&M) conference has been a long-standing part of graduate surgical education in the United States. M&M conferences were established in the early 1900s as a tool for personal improvement. Since their inception, M&M conferences have focused on the presentation and discussion of cases which result in adverse outcomes for patients. The context in which healthcare is delivered has become increasingly complex, and training paradigms have changed, but the process of M&M has remained relatively unchanged. We sought to revise the weekly M&M conference in the Department of General Surgery in order to increase the educational benefit as well as to create a more reliable process for identification and tracking of systems-level quality improvement issues.
Materials and Methods:
We undertook an initiative to restructure the weekly M&M conference in our department to focus on two aspects of surgical education: 1) Individual development and 2) Institutional quality improvement. Opportunities for individual development afforded by M&M include preparation for the oral board examination, self-reflection and planning for future practice, and continuing education about changes in practice and standard of care. Institutional improvement opportunities afforded by M&M include identify and address systems issues and providing a forum for discussing tools to advance system-level care practices. In order to enhance these two aspects of our M&M conference, we made several changes to the case submission and selection process, the conference format, the quality improvement tracking system, and the system for presenter feedback (Table 1).(see attachment)
Results:
The major changes to our M&M conference were implemented at the start of the 2019-2020 academic year in July 2019. Since that time we have had 20 M&M conferences led by 5 moderators featuring 76 case presentations by 22 resident presenters. Each M&M conference has included an interesting teaching case. Nine quality improvement or system-level issues have been identified, all of which have been addressed. Audience participation with the presenter feedback system has low but has been consistently improving. Moderator evaluations of changes to M&M conference have revealed a consistent improvement in presentation quality and literature selection. Feedback from residents has been positive; there has been an increase in the perception of M&M conference as a valuable educational activity both as a presenter and as an audience member.
Conclusions:
Over the last 6 months, we were able to successfully implement a substantial change to our weekly M&M conference in the Department of General Surgery. This project has increased the educational value of the conference for participants and improved the process for identifying and tracking systems-level quality improvement issues. Future planned improvements to the conference include the addition of a formal mechanism for feedback from the moderator to presenters on a weekly basis and the implementation of a feedback system for the moderators
Site-directed Mutagenesis of Key Residues Unveiled a Novel Allosteric Site on Human Adenosine Kinase for Pyrrolobenzoxa(thia)zepinone Non-Nucleoside Inhibitors
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