Circadian rhythms are generated by cell autonomous circadian clocks that perform a ubiquitous cellular time-keeping function and cell type-specific functions important for normal physiology. Studies show inducing the deletion of the core circadian clock transcription factor Bmal1 in adult mouse cardiomyocytes disrupts cardiac circadian clock function, cardiac ion channel expression, slows heart rate, and prolongs the QT-interval at slow heart rates. This study determined how inducing the deletion of Bmal1 in adult cardiomyocytes impacted the in vivo electrophysiological phenotype of a knock-in mouse model for the arrhythmogenic long QT syndrome (Scn5a+/ΔKPQ). Electrocardiographic telemetry showed inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation increased the QT-interval at RR-intervals that were ≥130 ms. Inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation also increased the day/night rhythm-adjusted mean in the RR-interval, but it did not change the period, phase or amplitude. Compared to mice without the ΔKPQ-Scn5a mutation, mice with the ΔKPQ-Scn5a mutation had reduced heart rate variability (HRV) during the peak of the day/night rhythm in the RR-interval. Inducing the deletion of Bmal1 in cardiomyocytes did not affect HRV in mice without the ΔKPQ-Scn5a mutation, but it did increase HRV in mice with the ΔKPQ-Scn5a mutation. The data demonstrate that deleting Bmal1 in cardiomyocytes exacerbates QT- and RR-interval prolongation in mice with the ΔKPQ-Scn5a mutation.
Background Demographics and socioeconomic status affect the delivery of medical care resulting in healthcare disparities. The purpose of this study was to investigate the impact of COVID-19 on existing healthcare disparities, including access to healthcare in the outpatient orthopedic surgery clinic. Methods The medical records of 3006 patients treated at the University of Kentucky Orthopedic Surgery Department prior to COVID-19 (April 2018, 2019), and during the COVID-19 pandemic (2020) were retrospectively reviewed for demographic data, distance to clinic, and type of visit. We then compared the total number of patient visits, new patient visits, telehealth visits, and the patient’s insurance provider (public or private) between the time period prior to and during the pandemic. Results During the COVID-19 pandemic, there were significant declines in the number of patients seen, new patient presentations, and publicly insured patients. Thirty-three percent of visits were telemedicine visits in 2020 compared to 0% pre-COVID ( P < .0001). There was a lower proportion of initial visits in 2020 ( P < .0001). The majority of patients paid via private/commercial insurance (1798, 59.8%), with a greater proportion paying via private/commercial insurance in 2020 ( P < .001). The median average household income was increased in 2020 ( P < .001). Discussion While COVID-19 resulted in a significant decline in overall access to care, there were negative ramifications particularly on patients with new complaints and those of lower socioeconomic status. Future endeavors should be focused on correcting the obstacles to accessing care, exacerbated by the pandemic, that these vulnerable populations face.
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