👤 Mary H Kosmidis

While early-life adverse experiences have been linked to late-life cognitive decline, few studies have explored war exposure. Paradoxically, one study even indicated a late-life cognitive advantage of early-childhood war exposure. In the present study, we explored these associations. We examined older adults exposed to World War II (1940-1944; Higher cognitive performance in language tasks predicted middle childhood, relative to early childhood, WWII-exposure group membership ( The present findings suggest that better cognitive performance and lower likelihood of MCI or dementia were associated with being exposed to significant hardships, such as war, during middle childhood, regardless of potentially confounding factors. Further studies are needed to shed light on this relationship. Show less

Maximizing baseline function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is essential for their effective application in models of cardiac toxicity and disease. Here, we aimed to identify factors that would promote an adequate level of function to permit robust single-cell contractility measurements in a human induced pluripotent stem cell (hiPSC) model of hypertrophic cardiomyopathy (HCM). A simple screen revealed the collaborative effects of thyroid hormone, IGF-1 and the glucocorticoid analog dexamethasone on the electrophysiology, bioenergetics, and contractile force generation of hPSC-CMs. In this optimized condition, hiPSC-CMs with mutations in MYBPC3, a gene encoding myosin-binding protein C, which, when mutated, causes HCM, showed significantly lower contractile force generation than controls. This was recapitulated by direct knockdown of MYBPC3 in control hPSC-CMs, supporting a mechanism of haploinsufficiency. Modeling this disease in vitro using human cells is an important step toward identifying therapeutic interventions for HCM. Show less