Florio, Damian N. Di

Abstract Background Radiation-induced heart disease (RIHD) may develop months to years following radiation therapy for cancers near the heart such as lung or breast cancer. Several mouse models of RIHD exist to study the pathogenesis of disease, but to our knowledge no studies have examined whether sex differences exist in RIHD in mice. Methods Female and male BALB/cJ mice received one whole heart dose of 22 Gray (Gy) radiation via a C5 collimator vs. sham controls that received 0 Gy, anesthesia and were placed in the X-ray machine for the same length of time. Mechanisms of cardiotoxicity were examined at 24 h (innate cardiotoxicity), day 10 (acute cardiotoxicity) and day 35 (chronic cardiotoxicity) post irradiation. Results Females and males developed dsDNA breaks from radiation at day 10 but females had more damage than males ( p < 0.001). Vessel area and cardiac hypertrophy were increased by radiation at day 10 and 35 but were higher in males than females at day 35 ( p < 0.001, p = 0.001, respectively). Bulk RNA sequencing of the heart at day 10 revealed that females and males developed similar gene pathway responses to radiation by upregulating cellular repair pathways and downregulated mitochondrial function. However, females upregulated the master regulator of mitochondrial function, Pgc1α ( p = 0.0001), suggesting improved mitochondrial repair in females. By day 35, males developed heart failure with reduced ejection fraction (HFrEF), inflammatory dilated cardiomyopathy (iDCM) and fibrosis while females developed heart failure with preserved ejection fraction (HFpEF) without inflammation or fibrosis. Conclusions We observed sex differences in nearly every cardiac parameter that we examined following radiation exposure. BALB/c males exposed to 22 Gy radiation developed HFrEF and iDCM by day 35 while females developed HFpEF. Further research is needed to better understand mechanisms driving sex differences in RIHD using translational animal models.

Abstract Introduction: Asynchronous online courses are plagued with the challenge of engaging students consistently. Behavioral interventions, such as bottlenecks (enforced deadlines) and nudges (automated reminders), may modulate behaviors that lead to engagement and can now be easily applied and measured in a Learning Management System (LMS). Methods: This study included three groups of three asynchronous online courses each over three academic quarters. Two distinct behavioral interventions, bottlenecks and nudges, were implemented to increase engagement with the course compared to non-intervention controls. Results: The results showed that behavioral intervention tools increase student engagement with course materials by measures of increased student access to the course and reduced time to quiz completion. However, there was no significant impact in grades across the three groups. Conclusion: The use of nudges and bottlenecks as behavioral interventions to increase engagement in asynchronous courses for Clinical and Translational Science Education is recommended as part of best practice in course design with the same or similar structure.