The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and a high incidence of sudden death, despite causing little or no cardiac hypertrophy. In skinned fibers, I79N increased myofilamental calcium sensitivity (Miller, T., Szczesna, D., Housmans, P. R., Zhao, J., deFreitas, F., Gomes, A. V., Culbreath, L., McCue concentration of the perfusate; systolic function was significantly increased in Tg-I79N hearts at 0.5 and 1 mmol/liter. At higher Ca 2؉ concentrations, systolic function was not different, but diastolic dysfunction became manifest as increased end-diastolic pressure and time to 90% relaxation. In vivo measurements by echocardiography and Doppler confirmed that base-line systolic function was significantly higher in Tg-I79N mice without evidence for diastolic dysfunction. Inotropic stimulation with isoproterenol resulted only in a modest contractile response but caused significant mortality in Tg-I79N mice. Doppler studies ruled out aortic outflow obstruction and were consistent with increased chamber stiffness. We conclude that in vivo, the increased myofilament Ca 2؉ sensitivity due to the I79N mutation enhances base-line contractility but leads to cardiac dysfunction during inotropic stimulation. Mutations in cardiac troponin T (TnT)1 have been implicated in familial hypertrophic cardiomyopathy (FHC) (1-5). Individuals with cardiac TnT mutations appear to have a high incidence of sudden cardiac death at a young age, although heterozygote individuals have either little or no cardiac hypertrophy (1, 3, 4). At present, there is no clear understanding as to why TnT mutations in particular pose a high risk for sudden death, as opposed to, for example, mutations in the myosin heavy chain, which usually cause a much greater degree of cardiac hypertrophy. Sudden cardiac death of FHC patients is often caused by ventricular tachyarrhythmias (6), but its cause remains unknown for patients with TnT mutations. In fact, the clinical features of hypertrophic cardiomyopathy have been established mostly without knowledge of the genotype and may not apply to patients carrying specific TnT mutations. Given the paucity of clinical information, a transgenic mouse model provides the opportunity to study the functional consequences of a TnT mutation in an in vivo system.To investigate the mechanisms of how a TnT mutation alters cardiac function and lead to sudden cardiac death, we have generated transgenic mice expressing the human cardiac TnT-I79N mutant (Tg-I79N). Similar to humans carrying this mutation, Tg-I79N mice show no cardiac hypertrophy (7). We found a large increase in Ca 2ϩ sensitivity of the skinned cardiac fibers from Tg-I79N mice compared with fibers from transgenic mice expressing human wild-type TnT (Tg-WT), but maximal developed force was significantly lower in cardiac fibers from Tg-I79N mice (7).In this study, we examined the effect of the I79N mutation on cardiac performance and electrophysiological properties of the whole heart, in vitro and in vivo. We fou...

Purpose This article assesses the prevalence of burnout among ophthalmology educators and identifies opportunities to improve well-being in this population. Methods The research team conducted a cross-sectional study using an institutional review board-exempt survey addressing the domains of the Maslach Burnout Inventory, intent to leave, and interest in wellness activities. Survey participants included ophthalmology residency program directors (PDs) and associate PDs (APDs) who are members of the Association of University Professors of Ophthalmology (AUPO). Analysis involved a top-box approach. Results Surveys were sent to 175 members with a response rate of 38.9%. Percentages of survey respondents reporting either (1) “never” or (2) “less than a few times per year” when asked to self-assess for certain manifestations of burnout are as follows: “considering residents as impersonal objects” (95.2%), “becoming more callous towards people” (90.3%), and “becoming emotionally hardened” (80.6%). Approximately 65% of ophthalmology educators reported never considering or rarely considering leaving their position in the year prior to completing the survey. For wellness promotion among AUPO educators, the greatest interest was in small group mentoring sessions (85%) and webinars on wellness-related topics (70%). Conclusion The prevalence of burnout symptoms among ophthalmology educators compares favorably to educators from other specialties. Ophthalmology PDs and APDs demonstrate a greater degree of personal accomplishment than do their cohorts within other specialties, suggesting a decreased likelihood of burnout onset among ophthalmology educators. Furthermore, our study's job satisfaction data reveal a high degree of satisfaction among ophthalmology PDs and APDs.