Abstract-The dystrophin-glycoprotein complex is a large complex of membrane-associated proteins linking the cytoskeleton to the extracellular matrix in muscle. Transmembrane heterodimeric (␣) integrins serve also as cellular adhesion molecules and mechanotransducers. In the animal model for Duchenne muscular dystrophy, the mdx mouse, loss of dystrophin causes more severe abnormalities in skeletal than in cardiac muscle. We hypothesized that ablation of cardiac myocyte integrins in the mdx background would lead to a severe cardiomyopathic phenotype. Mdx mice were crossed to ones with cardiac myocyte-specific deletion of 1 integrin (1KO) to generate 1KOmdx. Unstressed 1KOmdx mice were viable and had normal cardiac function; however, high mortality was seen in peri-and postpartum females by 6 months of age, when severe myocardial necrosis and fibrosis and extensive dystrophic calcification was seen. Decreased ventricular function and blunted adrenergic responsiveness was found in the 1KOmdx mice compared with control (Lox/Lox, no Cre), 1KO, and mdx. Similarly, adult 1KOmdx males were more prone to isoproterenol-induced heart failure and death compared with control groups. Given the extensive calcification, we analyzed transcript levels of genes linked to fibrosis and calcification and found matrix ␥-carboxyglutamic acid protein, decorin, periostin, and the osteoblast transcription factor Runx2/Cbfa1 significantly increased in 1KOmdx cardiac muscle. Our data show that combined deficiency of dystrophin and integrins in murine cardiac myocytes results in more severe cardiomyopathic changes in the stressed myocardium than reduction of either dystrophin or integrins alone and predisposes to myocardial calcification. Key Words: Integrin Ⅲ muscular dystrophy Ⅲ dystrophin Ⅲ heart failure Ⅲ calcification T he cardiac myocyte cytoskeleton and contractile apparatus are tethered to the sarcolemma at specialized regions termed costameres, which are aligned with the Z-disk. 1 Costameres are important for lateral force transmission from the sarcomere to the extracellular matrix (ECM) and from 1 myocyte to the next. 2 Three different cytoskeleton networks comprise the costamere: the dystrophin glycoprotein complex (DGC), the integrins, and the spectrinbased cytoskeleton.The DGC is composed of several membrane-spanning and associated proteins and is enriched in, but not restricted to, costameric regions. 2,3 In muscle, the DGC includes dystrophin, sarcoglycans (␣, , ␥, ␦, , and ), dystroglycans (␣ and ), ␣-dystrobrevin, syntrophins (␣1, 1 and 2), sarcospan, and NO synthase. Dystrophin is a 427-kDa protein that constitutes a core component of the DGC. Mutations in the human dystrophin gene lead to Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, and X-linked dilated cardiomyopathy. 4 In mice, an X-linked recessive mutation in the dystrophin gene (mdx) results in loss of dystrophin expression, destabilization of the DGC, and muscular dystrophy. Whereas cardiomyopathy may occur early in the life of patie...
BackgroundExperiential learning plays a critical role in learner development. Kolb’s 4-part experiential learning model consists of concrete experience, reflective observation, abstract conceptualization, and active experimentation in a recurring cycle. Most clinical environments provide opportunities for experiences and active experimentation but rarely offer structured means for reflection and abstract conceptualization that are crucial for learners to learn through experience. We created Learning Moment, a novel Web-based educational tool that integrates principles of asynchronous learning and learning portfolios to fulfill the reflection and abstract conceptualization aspects of Kolb’s learning cycle in the modern clinical learning environment. Medical students log concise clinical “pearls” in the form of “learning moments” for reflection, review, and sharing with peers in a community of practice.ObjectiveWe sought to evaluate learners’ experiences with Learning Moment via a qualitative study.MethodsWe employed purposive sampling to recruit medical students who used Learning Moment during their rotation. We conducted 13 semistructured interviews (10 individual interviews and one 3-person group interview) between January and March 2017 using an ethnographic approach and utilized a general inductive method to analyze and code for potential themes.ResultsA total of 13 students (five in their third year of medical school and eight in their fourth year) voluntarily participated in our qualitative interviews. Five of the 13 (38%) students intended to pursue emergency medicine as their chosen field of specialty. The median number of “learning moments” logged by these students is 6. From our analysis, three key themes emerged relating to the perceived impact of Learning Moment on student learning: (1) logging “learning moments” enhanced memorization, (2) improved learning through reflection, and (3) sharing of knowledge and experiences in a community of practice.ConclusionsLearning Moment was successfully implemented into the educational infrastructure in our department. Students identified three mechanisms by which the application optimizes experiential learning, including enabling the logging of “learning moments” to promote memorization, encouraging reflection to facilitate learning, and fostering the sharing of knowledge and experiences within a community of practice. The Learning Moment concept is potentially scalable to other departments, disciplines, and institutions as we seek to optimize experiential learning ecosystems for all trainees.
Introduction: E-learning is widely used in medical education. To maximize the potential of E-learning tools, every effort should be made to encourage adoption by optimizing usability. We created Learning Moment (LM), a web-based application that integrates principles of asynchronous learning and learning portfolios into a platform on which students can document and share learning experiences that occur during clinical work. We sought to evaluate the usability of LM and identify features that optimize adoption by users. Methods: We implemented LM in August 2016 at a busy, urban, tertiary care emergency department that hosts an emergency medicine residency, robust third and fourth year medical student clerkships as well as a physician assistant student rotation. We conducted a single-center, mix-methods study using the System Usability Scale (SUS) questionnaire and qualitative interviews. We sent e-mail invitations with subsequent reminders to all students who rotated in our emergency medicine clerkship from August 2016 to April 2017 to complete the SUS questionnaire anonymously and to participate in qualitative interviews. We employed purposive sampling to recruit students who used LM during their rotation to participate in our qualitative interviews. We conducted semi-structured interviews with 13 participants (10 individual interviews and one 3-person group interview) between January and March 2017 using an ethnographic approach and utilized a general inductive method to analyze and code for potential themes. Results: Thirty of the seventy students invited to participate completed the SUS questionnaire (Response rate of 42.8%). The mean SUS score is 80.9 (SD 18.2, 80% CI 76.5 – 85.3). The internal consistency of the responses achieved the Cronbach’s Alpha of 0.95. The participants stressed the importance of the following in the adoption of LM: maximal simplicity and usability, compatibility with learning preferences, and department-wide acceptance and integration. Conclusion: The overall perceived usability of LM was high. Our qualitative data revealed important implications for future designers to maximize adoption: include target users in every step of the design and development process to maximize simplicity and usability; build features that cater to a diversity of learning preferences; involve the entire department and find ways to incorporate the tool into the educational infrastructure and daily workflow.
Background Although emergency departments (ED) have standardized guidelines for low‐frequency, high‐acuity diagnoses, they are not immediately accessible at the bedside, and this can cause anxiety in trainees and delay patient care. This problem is exacerbated during events like COVID‐19 that require the rapid creation, iteration, and dissemination of new guidelines. Methods Physician innovators used design thinking principles to develop EM Protocols (EMP), a mobile application that clinicians can use to immediately view guidelines, contact consultants (e.g., cath lab activation), and access code‐running tools. The project became an institutional high priority, because it helps EM trainees and off‐service rotators manage low‐frequency, high‐acuity emergencies at the point of care, and its COVID‐19 guidelines can be rapidly updated and disseminated in real time. Results This intervention was deployed across two academic medical centers during the COVID‐19 surge. Nearly 300 ED clinicians have downloaded EMP, and they have interacted with the app over 5,400 times. It continues to be used regularly, over 12 months after the initial surge. Since the app was received positively, there are efforts to build in additional adult and pediatric guidelines. Discussion Digital health tools like EMP can serve as invaluable adjuncts for managing acute, life‐threatening emergencies at the point of care. They can benefit trainees during normal day‐to‐day operations as well as scenarios that cause large‐scale operational disruptions, such as natural disasters, mass casualty events, and future pandemics.
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