Associations of recreational and non-recreational physical activity with coronary artery calcium density vs. volume and cardiovascular disease events: the Multi-Ethnic Study of Atherosclerosis.

AimsThe benefits of physical activity (PA) on cardiovascular disease (CVD) are well known. However, studies suggest PA is associated with coronary artery calcium (CAC), a subclinical marker of CVD. In this study, we evaluated the associations of self-reported recreational and non-recreational PA with CAC composition and incident CVD events. Prior studies suggest high CAC density may be protective for CVD events.Methods and resultsWe evaluated 3393 participants of the Multi-Ethnic Study of Atherosclerosis with prevalent CAC. After adjusting for demographics, the highest quintile of recreational PA was associated with 0.07 (95% confidence interval 0.01-0.13) units greater CAC density but was not associated with CAC volume. In contrast, the highest quintile of non-recreational PA was associated with 0.08 (0.02-0.14) units lower CAC density and a trend toward 0.13 (-0.01 to 0.27) log-units higher CAC volume. There were 520 CVD events over a 13.7-year median follow-up. Recreational PA was associated with lower CVD risk (hazard ratio 0.88, 0.79-0.98, per standard deviation), with an effect size that was not changed with adjustment for CAC composition or across levels of prevalent CAC.ConclusionRecreational PA may be associated with a higher density but not a higher volume of CAC. Non-recreational PA may be associated with lower CAC density, suggesting these forms of PA may not have equivalent associations with this subclinical marker of CVD. While PA may affect the composition of CAC, the associations of PA with CVD risk appear to be independent of CAC

Suppression of GATA-3 Nuclear Import and Phosphorylation: A Novel Mechanism of Corticosteroid Action in Allergic Disease

Peter Barnes and colleagues show that corticosteroids have a potent inhibitory effect on GATA-3 via two interacting mechanisms that suppress Th2 cytokine expression. This novel mechanism of corticosteroid action may help explain the efficacy of corticosteroids in allergic diseases

Exploratory Case Study of Suicide among a Sample of 9/11 Survivors

Background: Previous research has found higher than expected suicide mortality among rescue/recovery workers (RRWs) enrolled in the World Trade Center Health Registry (WTCHR). Whether any enrollee suicides are related to the decedents’ experiences on 9/11 is unknown. We abstracted medical examiner file data to learn more about 9/11-related circumstances of suicides among WTCHR enrollees. Methods: We identified 35 enrollee suicide cases that occurred in New York City using linked vital records data. We reviewed medical examiner files on each case, abstracting demographic and circumstantial data. We also reviewed survey data collected from each case at WTCHR enrollment (2003–2004) and available subsequent surveys to calculate descriptive statistics. Results: Cases were mostly non-Hispanic White (66%), male (83%), and middle-aged (median 58 years). Nineteen decedents (54%) were RRWs, and 32% of them worked at the WTC site for >90 days compared to 18% of the RRW group overall. In the medical examiner files of two cases, accounts from family mentioned 9/11-related circumstances, unprompted. All deaths occurred during 2004–2018, ranging from one to four cases per year. Leading mechanisms were hanging/suffocation (26%), firearm (23%), and jump from height (23%). Sixty percent of the cases had depression mentioned in the files, but none mentioned posttraumatic stress disorder. Conclusions: RRWs may be at particular risk for suicide, as those who worked at the WTC site for long periods appeared to be more likely to die by suicide than other RRWs. Mental health screening and treatment must continue to be prioritized for the 9/11-exposed population. More in-depth investigations of suicides can elucidate the ongoing impacts of 9/11

Mortality after the 9/11 terrorist attacks among world trade center health registry enrollees with cancer

Abstract Background While several studies have reported the association between 9/11 exposure and cancer risk, cancer survival has not been well studied in the World Trade Center (WTC) exposed population. We examined associations of 9/11‐related exposures with mortality in WTC Health Registry enrollees diagnosed with cancer before and after 9/11/2001. Patients and Methods This is a longitudinal cohort study of 5061 enrollees with a first‐ever primary invasive cancer diagnosis between 1995 and 2015 and followed through 2016. Based on the timing of first cancer diagnosis, pre‐9/11 (n = 634) and post‐9/11 (n = 4427) cancer groups were examined separately. 9/11‐related exposures included witnessing traumatic events, injury on 9/11, and 9/11‐related post‐traumatic stress disorder (PTSD). Associations of exposures with all‐cause mortality were examined using Cox proportional hazards regression. In the post‐9/11 group, cancer‐specific mortality was evaluated by enrollee group (WTC rescue/recovery workers vs. non‐workers) using Fine and Gray's proportional sub‐distribution hazard models, adjusting for baseline covariates, tumor characteristics, and treatment. Results In the pre‐9/11 group, 9/11‐related exposures were not associated with all‐cause mortality. In the post‐9/11 group, increased risk of all‐cause mortality was associated with PTSD (adjusted HR = 1.35; 95% CI = 1.11–1.65), but not with injury or witnessing traumatic events. Cancer‐specific mortality was not statistically significantly associated with 9/11‐related exposures. In rescue/recovery workers, increased non‐cancer mortality risk was associated with PTSD (aHR = 2.13, 95% CI = 1.13–4.00) and witnessing ≥3 traumatic events (aHR = 2.00, 95% CI = 1.13–3.55). Conclusions We did not observe associations between 9/11‐related exposures and cancer‐specific mortality. Similar to findings in the non‐cancer WTC exposed population, PTSD was associated with increased risk of all‐cause mortality in cancer patients

Theory-Guided Development of Fertility Care Implementation Strategies for Adolescent and Young Adult Cancer Survivors.

Purpose: Oncofertility care at cancer diagnosis remains underimplemented across oncology and fertility care settings, with limited tools to scale up effective implementation strategies. Using implementation science theory, we systematically assessed factors that influence oncofertility care implementation and mapped scalable strategies, particularly electronic health record (EHR)-enabled ones, that fit adult and pediatric oncology care contexts. Methods: Using purposeful sampling, we recruited health care providers and female, reproductive-aged survivors of adolescent and young adult (AYA) cancers (AYA survivors) from a comprehensive cancer center and a freestanding children's hospital to semistructured interviews and focus groups. Using thematic analysis combining inductive codes with deductive codes using the Consolidated Framework for Implementation Research (CFIR), we characterized barriers and facilitators to care and designed responsive strategies. Two coders independently coded each transcript. Results: We recruited 19 oncology and fertility providers and 9 cancer survivors. We identified barriers and facilitators to oncofertility care in the CFIR domains of individual, inner setting, outer setting, and process, allowing us to conceptualize oncofertility care to encompass three core components (screening, referral, and fertility preservation counseling) and map five strategies to these components that fit an adult and a children's context and bridge oncology and fertility practices. The strategies were screening using a best practice advisory, referral order, telehealth fertility counseling, provider audit and feedback, and provider education. All but provider education were EHR tools with embedded efficiencies. Conclusion: An implementation science approach systematically assessed oncofertility care and mapped strategies to provide a theory-based approach and scalable EHR tools to support wider dissemination

The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse

Actin dynamics during T-cell activation are controlled by the coordinate action of multiple actin regulatory proteins, functioning downstream of a complex network of kinases and other signaling molecules. The c-Abl nonreceptor tyrosine kinase regulates actin responses in nonhematopoietic cells, but its function in T cells is poorly understood. Using kinase inhibitors, RNAi, and conditional knockout mice, we investigated the role of c-Abl in controlling the T-cell actin response. We find that c-Abl is required for normal actin polymerization and lamellipodial spreading at the immune synapse, and for downstream events leading to efficient interleukin-2 production. c-Abl also plays a key role in signaling chemokine-induced T-cell migration. c-Abl is required for the appropriate function of 2 proteins known to be important for controlling actin responses to T-cell receptor (TCR) engagement, the actin-stabilizing adapter protein HS1, and the Rac1-dependent actin polymerizing protein WAVE2. c-Abl binds to phospho-HS1 via its SH2 domains and is required for full tyrosine phosphorylation of HS1 during T-cell activation. In addition, c-Abl is required for normal localization of WAVE2 to the immune synapse (IS). These studies identify c-Abl as a key player in the signaling cascade, leading to actin reorganization during T-cell activation