A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI. Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy. Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans.

Introduction: The growing presence of artificial intelligence (AI) in health professions has created a need to investigate its potential benefits and challenges in medical education. This article presents findings from an AI learner training needs analysis survey at a U.S. medical school. It compares faculty and student experiences and perspectives on using generative AI (GAI) and other AI tools for undergraduate medical education, focusing on their respective knowledge and learning preferences. Methods: Faculty and students were surveyed using an online cross-sectional survey design to assess their GAI experience, AI patterns of use, adoption readiness, and training preferences. Surveys contained 14 to 15 multiple-choice items, with 8 items including a write-in option. A total of 68 faculty and 506 students responded to the survey, with a 50% response rate for faculty and 30% for students. Statistical tests were used to determine whether students and faculty differed significantly in their GAI experience. Results: We found that students were significantly more familiar with GAI than faculty ( P < .001) but not significantly more experienced with GAI tools. There were no significant differences in frequency of use. Both groups considered AI tools and technology useful for personal, academic, research, and clinical applications. More than half of both groups were using AI for academic tasks. Both groups expressed concerns about the reliability of AI output, with faculty showing a much greater level of concern. Both groups identified several training formats as beneficial, with faculty preferring formal training (either online or in-person), followed by peer tutorials and self-study. On the other hand, students showed slightly greater interest in self-study than other formats. Conclusion: Our findings will inform the design of two parallel structured AI training programs, focusing on faculty and student priorities, including hands-on skills practice, and emphasizing AI's ethical use, reliability, and limitations.

Background: We have shown that thyroid hormones (THs) are cardioprotective and can be potentially used as safe therapeutic agents for diabetic cardiomyopathy and permanent infarction. However, no reliable, clinically translatable protocol exists for TH treatment of myocardial ischemia-reperfusion (IR) injury. We hypothesized that modified low-dose triiodo-L-thyronine (T3) therapy would confer safe therapeutic benefits against IR injury. Methods: Adult female rats underwent left coronary artery ligation for 60 minutes or sham surgeries. At 2 months following surgery and T3 treatment (described below), the rats were subjected to functional, morphological, and molecular examination. Results: Following surgery, the rats were treated with T3 (8 μg/kg/day) or vehicle in drinking water ad libitum following IR for 2 months. Oral T3 significantly improved left ventricular (LV) contractility, relaxation, and relaxation time constant, and decreased beta-myosin heavy chain gene expression. As it takes rats ~6 hours post-surgery to begin drinking water, we then investigated whether modified T3 dosing initiated immediately upon reperfusion confers additional improvement. We injected an intraperitoneal bolus of T3 (12 μg/kg) upon reperfusion, along with low-dose oral T3 (4.5 μg/kg/day) in drinking water for 2 months. Continuous T3 therapy (bolus + low-dose oral) enhanced LV contractility compared with oral T3 alone. Relaxation parameters were also improved compared to vehicle. Importantly, these were accomplished without significant increases in hypertrophy, serum free T3 levels or blood pressure. Conclusions: This is the first study to provide a safe cardiac therapeutic window and optimized, clinically translatable treatment-monitoring protocol for myocardial IR using commercially available and inexpensive T3. Low-dose oral T3 therapy supplemented with bolus treatment initiated upon reperfusion is safer and more efficacious.

Hundreds of thousands of people die each year as a result of sudden cardiac death, and many are due to heart rhythm disorders. One of the major causes of these arrhythmic events is Brugada syndrome, a cardiac channelopathy that results in abnormal cardiac conduction, severe life-threatening arrhythmias, and, on many occasions, death. This disorder has been associated with mutations and dysfunction of about two dozen genes; however, the majority of the patients do not have a definite cause for the diagnosis of Brugada Syndrome. The protein-coding genes represent only a very small fraction of the mammalian genome, and the majority of the noncoding regions of the genome are actively transcribed. Studies have shown that most of the loci associated with electrophysiological traits are located in noncoding regulatory regions and are expected to affect gene expression dosage and cardiac ion channel function. Noncoding RNAs serve an expanding number of regulatory and other functional roles within the cells, including but not limited to transcriptional, post-transcriptional, and epigenetic regulation. The major noncoding RNAs found in Brugada Syndrome include microRNAs; however, others such as long noncoding RNAs are also identified. They contribute to pathogenesis by interacting with ion channels and/or are detectable as clinical biomarkers. Stem cells have received significant attention in the recent past, and can be differentiated into many different cell types including those in the heart. In addition to contractile and relaxational properties, BrS-relevant electrophysiological phenotypes are also demonstrated in cardiomyocytes differentiated from stem cells induced from adult human cells. In this review, we discuss the current understanding of noncoding regions of the genome and their RNA biology in Brugada Syndrome. We also delve into the role of stem cells, especially human induced pluripotent stem cell-derived cardiac differentiated cells, in the investigation of Brugada syndrome in preclinical and clinical studies.

Severe caloric-restriction compromises thyroid hormone (TH) status, apparently to save energy and proteins for enduring stress stimulus. However, a persistent decrease in TH levels may compromise heart function. We hypothesized that supplementation of low dose active TH or targeting hypoxia-inducible factor-1-alpha, HIF-1α (a strong activator of deiodinase enzyme that degrades peripheral active THs) will prevent deterioration of cardiac performance. Adult mice were subjected to acute fasting based on institutional animal protocols with ad libitum access to water. The following groups were studied: Control mice with free access to food; severe caloric restriction fasting only group; Fasting with Triiodo-l-Thyronine (T3); Fasting with HIF-1α inhibitor (BAY). Cardiac hemodynamic and electrophysiological studies were performed and role of long noncoding RNAs were explored. Following severe caloric-restriction, we found that body weights, and heart weights to a partial extent, were decreased. Low-dose T3 treatment attenuated left ventricular hemodynamic impairment in indices of cardiac contractility and relaxation. In electrophysiology studies, fasting mice developed atrial tachyarrhythmias upon induction. This reverted to control levels following T3 treatment. There was a significant increase in atrioventricular conduction time and significant decrease in heart rate following fasting. Both these changes were attenuated following T3 treatment. Furthermore, BAY partially improved hemodynamics. Compared to the severe caloric-restriction group, both T3 and BAY reduced MALAT1 and GAS5 long noncoding RNA expression. These new findings indicate that T3 and BAY protect from cardiac decompensation secondary to acute severe caloric-restriction partly mediated by long noncoding RNAs.