R|S Atlas: Identifying existing cohort study data resources to accelerate epidemiological research on the influence of religion and spirituality on human health.

OBJECTIVE: Many studies have documented significant associations between religion and spirituality (R/S) and health, but relatively few prospective analyses exist that can support causal inferences. To date, there has been no systematic analysis of R/S survey items collected in US cohort studies. We conducted a systematic content analysis of all surveys ever fielded in 20 diverse US cohort studies funded by the National Institutes of Health (NIH) to identify all R/S-related items collected from each cohort's baseline survey through 2014. DESIGN: An R|S Ontology was developed from our systematic content analysis to categorise all R/S survey items identified into key conceptual categories. A systematic literature review was completed for each R/S item to identify any cohort publications involving these items through 2018. RESULTS: Our content analysis identified 319 R/S survey items, reflecting 213 unique R/S constructs and 50 R|S Ontology categories. 193 of the 319 extant R/S survey items had been analysed in at least one published paper. Using these data, we created the R|S Atlas (https://atlas.mgh.harvard.edu/), a publicly available, online relational database that allows investigators to identify R/S survey items that have been collected by US cohorts, and to further refine searches by other key data available in cohorts that may be necessary for a given study (eg, race/ethnicity, availability of DNA or geocoded data). CONCLUSIONS: R|S Atlas not only allows researchers to identify available sources of R/S data in cohort studies but will also assist in identifying novel research questions that have yet to be explored within the context of US cohort studies.

Expression of ACE2, the SARS-CoV-2 receptor, and TMPRSS2 in prostate epithelial cells.

The COVID-19 pandemic has spread across more than 200 countries and resulted in over 170,000 deaths. For unclear reasons, higher mortality rates from COVID-19 have been reported in men compared to women. While the SARS-CoV-2 receptor ACE2 and serine protease TMPRSS2 have been detected in lung and other tissues, it is not clear what sex differences may exist. We analyzed a publicly-available normal human prostate single-cell RNA sequencing dataset and found TMPRSS2 and ACE2 co-expressing cells in epithelial cells, with a higher proportion in club and hillock cells. Then we investigated datasets of lung epithelial cells and also found club cells co-expressing TMPRSS2 and ACE2. A comparison of ACE2 expression in lung tissue between males and females showed higher expression in males and a larger proportion of ACE2+ cells in male type II pneumocytes, with preliminary evidence that type II pneumocytes of all lung epithelial cell types showed the highest expression of ACE2. These results raise the possibility that sex differences in ACE2 expression and the presence of double-positive cells in the prostate may contribute to the observed disparities of COVID-19.

A Roadmap for conducting psychosocial research in epidemiological studies: perspectives of cohort study principal investigators.

BACKGROUND: Psychosocial adversity disproportionately affects racial/ethnic and socioeconomic minorities in the USA, and therefore understanding the mechanisms through which psychosocial stress and resilience influence human health can provide meaningful insights into addressing US health disparities. Despite this promise, psychosocial factors are infrequently and unsystematically collected in the US prospective cohort studies. METHODS: We sought to understand prospective cohort principal investigators' (PIs') attitudes regarding the importance of psychosocial influences on disease aetiology, in order to identify barriers and opportunities for greater inclusion of these domains in high-quality epidemiological research. One-hour, semi-structured qualitative interviews were conducted with 20 PIs representing 24 US prospective cohort studies funded by the National Institutes of Health (NIH), collectively capturing health data on 1.25 of every 100 American adults. A hypothesis-free, grounded theory approach was used to analyse and interpret interview data. RESULTS: Most cohort PIs view psychosocial factors as an important research area to further our understanding of disease aetiology and agree that this research will be crucial for future public health innovations. Virtually all PIs emphasised that future psychosocial research will need to elucidate biological and behavioural mechanisms in order to be taken seriously by the epidemiological community more broadly. A lack of pertinent funding mechanisms and a lack of consensus on optimal scales and measures of psychosocial factors were identified as additional barriers to advancing psychosocial research. CONCLUSIONS: Our interviews emphasised the need for: (1) high-quality, longitudinal studies that investigate biological mechanisms and pathways through which psychosocial factors influence health, (2) effort among epidemiological cohorts to broaden and harmonise the measures they use across cohorts, to facilitate replication of results and (3) the need for targeted funding opportunities from NIH and other grant-making institutions to study these domains.

Epigenetic Pathways in Human Disease: The Impact of DNA Methylation on Stress-Related Pathogenesis and Current Challenges in Biomarker Development.

HPA axis genes implicated in glucocorticoid regulation play an important role in regulating the physiological impact of social and environmental stress, and have become a focal point for investigating the role of glucocorticoid regulation in the etiology of disease. We conducted a systematic review to critically assess the full range of clinical associations that have been reported in relation to DNA methylation of CRH, CRH-R1/2, CRH-BP, AVP, POMC, ACTH, ACTH-R, NR3C1, FKBP5, and HSD11ß1/2 genes in adults. A total of 32 studies were identified. There is prospective evidence for an association between HSD11ß2 methylation and hypertension, and functional evidence of an association between NR3C1 methylation and both small cell lung cancer (SCLC) and breast cancer. Strong associations have been reported between FKBP5 and NR3C1 methylation and PTSD, and biologically-plausible associations have been reported between FKBP5 methylation and Alzheimer's Disease. Mixed associations between NR3C1 methylation and mental health outcomes have been reported according to different social and environmental exposures, and according to varying gene regions investigated. We conclude by highlighting key challenges and future research directions that will need to be addressed in order to develop both clinically meaningful prognostic biomarkers and an evidence base that can inform public policy practice.

Adverse maternal exposures, methylation of glucocorticoid-related genes and perinatal outcomes: a systematic review.

AIM: Maternal environmental exposures affect perinatal outcomes through epigenetic placental changes. We examine the literature addressing associations between adverse maternal exposures, perinatal outcomes and methylation of key genes regulating placental cortisol metabolism. METHODS: We searched three databases for studies that examined NR3C1 and HSD11ß1/HSD11 ß 2 methylation with maternal exposures or perinatal outcomes. Nineteen studies remained after screening. We followed Cochrane's PRISMA reporting guidelines (2009). RESULTS: NR3C1 and HSD11 ß methylation were associated with adverse infant neurobehavior, stress response, blood pressure and physical development. In utero exposure to maternal stress, nutrition, preeclampsia, smoking and diabetes were associated with altered NR3C1 and HSD11 ß methylation. CONCLUSION: NR3C1 and HSD11 ß methylation are useful biomarkers of specific environmental stressors associated with important perinatal outcomes that determine pediatric and adult disease risk.

Childhood abuse, promoter methylation of leukocyte NR3C1 and the potential modifying effect of emotional support.

AIM: To investigate childhood abuse victimization in relation to adult DNA methylation levels in a novel region of NR3C1, with emotional support as a possible modifier. MATERIALS & METHODS: 295 participants from the Black Women's Health Study. Multivariable linear regression models were used to compute differences in mean percent methylation levels. RESULTS: Women reporting childhood abuse victimization exhibited higher mean NR3C1 methylation levels than nonabused women, with a clear dose-response relationship. Childhood emotional support appeared to attenuate associations only among women with the highest levels of physical and sexual abuse. CONCLUSION: NR3C1 mean methylation was higher among women who reported childhood abuse. Further research is warranted to clarify whether or the extent to which childhood emotional support buffers the association.

Alcohol misuse and multiple sexual partners.

INTRODUCTION: We examine the association between self-reported alcohol misuse and alcohol use within 2 hours of having sex and the number of sexual partners among a sample of African-American and Latino emergency department (ED) patients. METHODS: Cross-sectional data were collected prospectively from a randomized sample of all ED patients during a 5-week period. In face-to-face interviews, subjects were asked to report their alcohol use and number of sexual partners in the past 12 months. Data were analyzed using multiple variable negative binomial regression models, and effect modification was assessed through inclusion of interaction terms. RESULTS: The 395 study participants reported an average of 1.4 (standard error = 0.11) sexual partners in the past 12 months, 23% reported misusing alcohol, and 28% reported consuming alcohol before sex. There was no statistically significant association between alcohol misuse and the number of sexual partners; however, alcohol before sex was associated with a larger number of sexual partners in the past year. Moreover, among those who misused alcohol, participants who reported alcohol before sex were 3 times more likely to report a higher number of sexual partners (risk ratio = 3.2; confidence interval [CI] =1.9-5.6). The association between alcohol use before sex and number of sexual partners is dependent upon whether a person has attributes of harmful drinking over the past 12 months. Overall, alcohol use before sex increases the number of sexual partners, but the magnitude of this effect is significantly increased among alcohol misusers. CONCLUSION: Alcohol misusers and those who reported having more than 1 sexual partner were more likely to cluster in the same group, ie, those who used alcohol before sex. Efforts to reduce the burden of sexually transmitted diseases, including human immunodeficiency virus, and other consequences of risky sexual behavior in the ED population should be cognizant of the interplay of alcohol and risky sexual behaviors. EDs should strive to institute a system for regular screening, brief intervention, and referral of at-risk patients to reduce negative consequences of alcohol misuse, including those of risky sexual behaviors.