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Exposure to polychlorinated biphenyls (PCBs), an endocrine-disrupting compound, is ubiquitous despite decades-old bans on the manufacture and use of PCBs. Increased exposure to PCBs is associated with adverse health consequences throughout life, including type 2 diabetes and cancer. PCB exposure is also associated with alterations in epigenetic marks and gene transcription, which could lead to adverse health outcomes, but many of these are population-specific. To further investigate the association between PCB and epigenetic marks, DNA methylation was measured at 787,684 CpG sites in 641 peripheral blood samples from the Michigan Polybrominated Biphenyl (PBB) Registry. 1345 CpGs were associated with increased total PCB level after controlling for age, sex, and 24 surrogate variables (FDR < 0.05). These CpGs were enriched in active promoter and transcription associated regions (p < 0.05), and in regions around the binding sites for transcription factors involved in xenobiotic metabolism and immune function (FDR < 0.05). PCB exposure also associated with proportions of CD4T, NK, and granulocyte cell types, and with the neutrophil to lymphocyte ratio (NLR) (p < 0.05), and the estimated effect sizes of PCB on the epigenome were correlated with the effect sizes previously reported in an epigenome-wide study of C-reactive protein (r = 0.29; p = 2.22e-5), supporting previous studies on the association between PCB and immune dysfunction. These results indicate that PCB exposure is associated with differences in epigenetic marks in active regions of the genome, and future work should investigate whether these may mediate the association between PCB and health consequences. [ABSTRACT FROM AUTHOR]

Purpose: The Centers for Disease Control and Prevention (CDC) recommends recombinant zoster vaccination (RZV) for adults ≥ 50 years to prevent herpes zoster (HZ) and its sequelae. Initially, no distinct recommendation was made for immunocompromised adults, who experience higher HZ rates and more severe outcomes. We characterized receipt of first RZV dose (initiation) and both doses (completion) over time, and the impact of immune function on RZV uptake among adults aged 50-64 years in the United States., Methods: We identified RZV claims from the IBM MarketScan database between 1/1/2018 and 12/31/2019. We characterized immunocompromised enrollees as having malignancy, HIV, solid organ transplant, primary immunosuppression, or medication-induced immunosuppression using inpatient, outpatient, and prescription claims in the 6 months prior to study start. We evaluated patterns of vaccine uptake by demographic and healthcare access characteristics and immune status., Results: The cumulative incidence of RZV initiation during the study period was 10.0%. Incidence increased with age and number of medical office visits, and was higher among women, urban residents, high-deductible insurance beneficiaries, and those who were immunocompromised compared to immunocompetent. Among immunocompromised adults, RZV initiation was highest among those with HIV and primary immunodeficiencies. Of those who initiated RZV, 89.5% received both doses. RZV completion was highest among those who received the first dose at a pharmacy. Most enrollees (88.6%) who completed RZV vaccination did so within the recommended dosing schedule., Conclusions: RZV uptake was low in the two years since the CDC recommendation, and differed by demographic, healthcare access, and clinical characteristics. Initiation rates were higher among immunocompromised adults compared to immunocompetent adults, despite no CDC recommendation for vaccination in these groups during the study period. The CDC has since recommended RZV for immunocompromised individuals, and our findings may inform efforts to increase RZV uptake in individuals at higher risk of severe disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Abstract: Purpose: To examine racial–ethnic differences in Epstein–Barr virus (EBV) antibody levels among U.S. children and adolescents. Elevated titers among seropositive youth can indicate viral reactivation—an indirect measure of impaired cell-mediated immunity. Methods: Data from the 2003–2010 National Health and Nutrition Examination Survey were analyzed using multivariable linear regression accounting for the complex survey design and potential confounders. The sample comprised 4663 black-African American, Mexican American, and white youth aged 6–17 years who were EBV seropositive. Results: EBV antibody levels were significantly higher for black-African American youth compared with their white peers (b = 0.343, P < .0001). Gender-stratified models were consistent with the total sample except differences in EBV antibody levels were greater between black-African American and white males (b = 0.525, P < .0001) than between black-African American and white females (b = 0.169, P = .0185). Differences in EBV antibody levels between Mexican American and white youth were only marginally significant in the total and the gender-stratified samples. Conclusions: Black–white differences in EBV antibody levels were found suggesting EBV reactivation and potential disparities in immune function among minority youth. Research on multilevel factors contributing to the disparities is needed, including potential health implications over the life course for minority youth. [Copyright &y& Elsevier]

In recent decades, in the US and in Western and Northern Europe, there has been a significant increase in the prevalence of atopic allergic disease. Although that increase may now be slowing, or have already reached a plateau, there remains considerable interest in the factor or factors that may have caused this increased susceptibility to allergy and asthma. Certainly, the changes recorded have been too rapid to implicate a change in the gene pool, and for that reason attention has focused on the possible impact of environmental, dietary, and lifestyle factors. Although the hygiene hypothesis proposes that increased susceptibility to allergic sensitization is associated with changes in childhood exposure pathogenic microorganisms, other factors have been considered also. Among these is exposure to chemicals and atmospheric pollutants. There is some evidence that exposure to certain chemicals may elicit or exacerbate respiratory reactions in those who are already sensitized, or who already have existing airway disease. However, a recent article has proposed that exposure to specific household cleaning products may be one factor that is able to affect susceptibility to allergic sensitization. In the light of that article it is timely now to consider again the ability of chemical exposure to influence sensitization to common antigens. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the association between CD4 cell count and HIV viral load with acute myocardial infarction (AMI) rates in patients with HIV in a U.S. healthcare system. HIV-positive patients were assessed for AMI. Findings of the study revealed that decreased CD4 count is significantly associated with an increased risk of myocardial infarction.

BACKGROUND: Traffic-related air pollution has been associated with adverse health outcomes, and the immune system may be a biologic mediator of health effects. OBJECTIVES: We analyzed associations between living near major roads and immune status as measured by five immune assays. We hypothesized that living near a freeway, arterial, or truck route would be associated with increased inflammation and decreased immune function. METHODS: We used a geographic information system (GIS) to determine residential proximity to major roads among 115 postmenopausal, overweight women in the greater Seattle, Washington (USA), area whose immunity was assessed at the baseline visit of an exercise intervention trial. We evaluated three inflammatory markers (C-reactive protein, serum amyloid A, and interleukin-6) and two functional assays of cellular immunity [natural killer (NK) cell cytotoxicity and T-lymphocyte proliferation]. RESULTS: Women living within 150 m of arterial roads had 21% lower NK cytotoxicity compared with women who lived farther from an arterial [mean cytotoxicity, 19.5%; 95% confidence interval (CI), 15.6--23.5%; vs. mean cytotoxicity, 24.8%; 95% CI, 22.0--27.5%], after adjustment for both individual-level and census tract--level demographic characteristics. This association was limited to women who reported exercising near traffic. Fewer women lived near freeways and truck routes. Markers of inflammation and lymphocyte proliferation did not consistently differ according to proximity to major roads. CONCLUSIONS: If the observed association between residential proximity to traffic and decreased NK cytotoxicity is confirmed in other populations, our results may have implications for local land use policy. [ABSTRACT FROM AUTHOR]

Chronic infections and the subsequent immune response have recently been shown to be risk factors for cognitive decline and Alzheimer disease and related dementias (ADRD). While some studies have shown an association between cytomegalovirus (CMV), a chronic and highly prevalent infection, and cognition and/or ADRD, these studies have been limited by nonrepresentative and small samples. Using 2016 data on 5,617 adults aged 65 years or more from the Health and Retirement Study, we investigated the cross-sectional associations of both CMV serostatus and immunoglobulin G (IgG) antibody response with cognitive function using linear regression models adjusting for age, sex, race/ethnicity, and educational attainment. We further investigated potential effect-measure modification by educational attainment. Overall, both CMV seropositivity and higher IgG antibody response were associated with lower cognitive function, though the relationship was not statistically significant in adjusted models. Among participants with less than a high school diploma, CMV seropositivity and being in the first tertile of IgG response, relative to seronegative persons, were associated with lower scores on the Telephone Interview for Cognitive Status (-0.56 points (95% confidence interval: -1.63, 0.52) and -0.89 points (95% confidence interval: -2.07, 0.29), respectively), and the relationship was attenuated among those with higher education. Our results suggest that CMV may be a risk factor for cognitive impairment, particularly among persons with fewer educational resources., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sexual minority (SM) adults (those who are lesbian, gay, or bisexual) consistently report more health problems compared to heterosexuals, and they tend to experience excess social stress. Although numerous studies have established links between social stress and clinical outcomes in SM adults, few studies have examined biological factors that may help explain how social stress leads to health disparities among SM adults. We used data from the Midlife in the United States Study (MIDUS) to examine whether two inflammatory markers that have been commonly associated with social stress-C-reactive protein (CRP) and interleukin-6 (IL-6)-differed by sexual orientation and whether any differences were explained by perceptions of discrimination. Participants self-identified as heterosexual (n = 1956) or lesbian, gay, or bisexual (n = 81). After controlling for age, gender, race, and education, SM individuals had higher CRP and IL-6 than heterosexuals on average and these differences were partially explained by perceptions of discrimination. Implications for inflammatory pathways as mechanisms related to SM health disparities and discrimination are discussed.

The epidemiology of sexually transmitted infections (STI) is constantly evolving, and the mechanisms of infection risk in the oral cavity (OC) are poorly characterized. Evidence indicates that microbial community (microbiota) compositions vary widely between the OC, genitalia and the intestinal and rectal mucosa, and microbiome-associated STI susceptibility may also similarly vary. The opioid misuse epidemic is at an epidemic scale, with >11 million US residents misusing in the past 30 days. Opioids can substantially influence HIV progression, microbiota composition and immune function, and these three factors are all mutually influential via direct and indirect pathways. While many of these pathways have been explored independently, the supporting data are mostly derived from studies of gut and vaginal microbiotas and non-STI infectious agents. Our purpose is to describe what is known about the combination of these pathways, how they may influence microbiome composition, and how resultant oral STI susceptibility may change. A better understanding of how opioid misuse influences oral microbiomes and STI risk may inform better mechanisms for oral STI screening and intervention. Further, the principles of interaction described may well be applied to other aspects of disease risk of other health conditions which may be impacted by the opioid epidemic.

Maternal infection and fever during pregnancy have been implicated in the etiology of autism spectrum disorder (ASD); however, studies have not been able to separate the effects of fever itself from the impact of a specific infectious organism on the developing brain. We utilized data from the Study to Explore Early Development (SEED), a case-control study among 2- to 5-year-old children born between 2003 and 2006 in the United States, to explore a possible association between maternal infection and fever during pregnancy and risk of ASD and other developmental disorders (DDs). Three groups of children were included: children with ASD (N = 606) and children with DDs (N = 856), ascertained from clinical and educational sources, and children from the general population (N = 796), randomly sampled from state birth records. Information about infection and fever during pregnancy was obtained from a telephone interview with the mother shortly after study enrollment and maternal prenatal and labor/delivery medical records. ASD and DD status was determined by an in-person standardized developmental assessment of the child at 3-5 years of age. After adjustment for covariates, maternal infection anytime during pregnancy was not associated with ASD or DDs. However, second trimester infection accompanied by fever elevated risk for ASD approximately twofold (aOR = 2.19, 95% confidence interval 1.14-4.23). These findings of an association between maternal infection with fever in the second trimester and increased risk of ASD in the offspring suggest that the inflammatory response to the infectious agent may be etiologically relevant. Autism Res 2019, 12: 1551-1561. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Using data from a large multisite study in the United States-the Study to Explore Early Development-we found that women who had an infection during the second trimester of pregnancy accompanied by a fever are more likely to have children with ASD. These findings suggest the possibility that only more severe infections accompanied by a robust inflammatory response increase the risk of ASD., (© 2019 International Society for Autism Research, Wiley Periodicals, Inc.)

Introduction: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC)., Methods and Analysis: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatment-naïve for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant's fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation., Ethics and Dissemination: Validation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 NEWTON), with a further 10 investigator sites since receiving ethics approval, prior to activation., Trial Registration Number: NCT02730338., Competing Interests: Competing interests: MB and SG are employees of Movember Foundation, which is the funder of this research., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The immune system plays a critical role in the prevention of infectious and chronic disease. We investigate associations between exposure to neighborhood immigrant concentration across the transition from adolescence to adulthood and immune function among Latino young adults, including moderation by nativity. Data from the National Longitudinal Study of Adolescent Health (1994-2008) were analyzed. Immune function was measured via Epstein-Barr virus (EBV) antibody levels (higher levels indicate impaired immune function) among EBV-positive Latino adults (N=1130). Results indicated the averaged individual exposure to immigrant concentration (mean % of foreign-born residents in the census tract across waves 1-4) was associated with immune function for foreign-born Latinos only (b=-0.37, P<0.05). For waves of exposure, only the cumulative measure of living in an immigrant enclave (census tracts with ≥40% foreign-born residents) across all waves was associated with immune function and only for foreign-born Latinos (b=-0.22, P<0.05). Research on the mechanisms through which neighborhood immigrant concentration confers salubrious physiological outcomes for foreign-born Latinos is needed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)