Chamber-specific contractile responses of atrial and ventricular hiPSC-cardiomyocytes to GPCR and ion channel targeting compounds: A microphysiological system for cardiac drug development.

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) have found utility for conducting in vitro drug screening and disease modelling to gain crucial insights into pharmacology or disease phenotype. However, diseases such as atrial fibrillation, affecting >33 M people worldwide, demonstrate the need for cardiac subtype-specific cells. Here, we sought to investigate the base characteristics and pharmacological differences between commercially available chamber-specific atrial or ventricular hiPSC-CMs seeded onto ultra-thin, flexible PDMS membranes to simultaneously measure contractility in a 96 multi-well format. We investigated the effects of GPCR agonists (acetylcholine and carbachol), a Ca2+ channel agonist (S-Bay K8644), an HCN channel antagonist (ivabradine) and K+ channel antagonists (4-AP and vernakalant). We observed differential effects between atrial and ventricular hiPSC-CMs on contractile properties including beat rate, beat duration, contractile force and evidence of arrhythmias at a range of concentrations. As an excerpt of the compound analysis, S-Bay K8644 treatment showed an induced concentration-dependent transient increase in beat duration of atrial hiPSC-CMs, whereas ventricular cells showed a physiological increase in beat rate over time. Carbachol treatment produced marked effects on atrial cells, such as increased beat duration alongside a decrease in beat rate over time, but only minimal effects on ventricular cardiomyocytes. In the context of this chamber-specific pharmacology, we not only add to contractile characterization of hiPSC-CMs but propose a multi-well platform for medium-throughput early compound screening. Overall, these insights illustrate the key pharmacological differences between chamber-specific cardiomyocytes and their application on a multi-well contractility platform to gain insights for in vitro cardiac liability studies and disease modelling.

Medical Trainees' Knowledge and Attitudes Towards Electronic Cigarettes and Hookah: A Multinational Survey Study.

BACKGROUND: The rising prevalence of electronic cigarette (e-cigarette) and hookah use among youth raises questions about medical trainees' views of these products. We aimed to investigate medical trainees' knowledge and attitudes toward e-cigarette and hookah use. METHODS: We used data from a large cross-sectional survey of medical trainees in Brazil, the United States, and India. We investigated demographic and mental health aspects, history of e-cigarettes and tobacco use, knowledge and attitudes toward e-cigarettes and hookah, and sources of information on e-cigarettes and hookah. Although all medical trainees were eligible for the original study, only senior students and physicians-in-training were included in the present analysis. RESULTS: Of 2,036 senior students and physicians-in-training, 27.4% believed e-cigarette use to be less harmful than tobacco smoking. As for hookah use, 14.9% believed it posed a lower risk than cigarettes. More than a third of trainees did not acknowledge the risks of passive e-cigarette use (42.9%) or hookah smoking (35.1%). Also, 32.4% endorsed e-cigarettes to quit smoking, whereas 22.5% felt ill equipped to discuss these tobacco products with patients. Fewer than half recalled attending lectures on these topics, and their most common sources of information were social media (54.5%), Google (40.8%), and friends and relatives (40.3%). CONCLUSIONS: Medical trainees often reported incorrect or biased perceptions of e-cigarettes and hookah, resorted to unreliable sources of information, and lacked the confidence to discuss the topic with patients. An expanded curriculum emphasis on e-cigarette and hookah use might be necessary because failing to address these educational gaps could risk years of efforts against smoking normalization.

Vaping and Hookah Use Among Medical Trainees: A Multinational Survey Study.

The increased use of E-cigarettes and hookah among young consumers represents a public health concern. This study aimed to investigate the frequency and patterns of use of E-cigarettes and hookah among medical trainees. This cross-sectional multinational online survey included medical students, residents, and fellows in Brazil, the U.S., and India between October 2020 and November 2021. Information on sociodemographics; mental health; and E-cigarettes, hookah, tobacco, marijuana, and alcohol use were collected. Generalized structural equation models were used in 2022 to explore the factors associated with current vaping and current hookah use (ongoing monthly/weekly/daily use). People reporting previous sporadic/frequent use or those who never used/only tried it once were the reference group. Overall, 7,526 participants were recruited (Brazil=3,093; U.S.=3,067; India=1,366). The frequency of current vaping was 20% (Brazil), 11% (U.S.), and <1% (India), and current hookah use was 10% (Brazil), 6% (U.S.), and 1% (India). Higher family income (OR=6.35, 95% CI=4.42, 9.12), smoking cigarettes (OR=5.88, 95% CI=4.88, 7.09) and marijuana (OR=2.8, 95% CI=2.35, 3.34), and binge drinking (OR=3.03, 95% CI=2.56, 3.59) were associated with current vaping. The same was true for hookah use: higher family income (OR=2.69, 95% CI=1.75, 4.14), smoking cigarettes (OR=3.20, 95% CI=2.53, 4.06), smoking marijuana (OR=4.17, 95% CI=3.35, 4.19), and binge drinking (OR=2.42, 95% CI=1.96, 2.99). In conclusion, E-cigarettes and hookah were frequently used by Brazilian and American trainees, sharply contrasting with data from India. Cultural aspects and public health policies may explain the differences among countries. Addressing the problems of hookah and E-cigarette smoking in this population is relevant to avoid the renormalization of smoking.