Understanding Health Inequalities Through the Lens of Social Epigenetics.

Longstanding racial/ethnic inequalities in morbidity and mortality persist in the United States. Although the determinants of health inequalities are complex, social and structural factors produced by inequitable and racialized systems are recognized as contributing sources. Social epigenetics is an emerging area of research that aims to uncover biological pathways through which social experiences affect health outcomes. A growing body of literature links adverse social exposures to epigenetic mechanisms, namely DNA methylation, offering a plausible pathway through which health inequalities may arise. This review provides an overview of social epigenetics and highlights existing literature linking social exposures-i.e., psychosocial stressors, racism, discrimination, socioeconomic position, and neighborhood social environment-to DNA methylation in humans. We conclude with a discussion of social epigenetics as a mechanistic link to health inequalities and provide suggestions for future social epigenetics research on health inequalities.

Protective population behavior change in outbreaks of emerging infectious disease.

BACKGROUND: During outbreaks of emerging and re-emerging infections, the lack of effective drugs and vaccines increases reliance on non-pharmacologic public health interventions and behavior change to limit human-to-human transmission. Interventions that increase the speed with which infected individuals remove themselves from the susceptible population are paramount, particularly isolation and hospitalization. Ebola virus disease (EVD), Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS) are zoonotic viruses that have caused significant recent outbreaks with sustained human-to-human transmission. METHODS: This investigation quantified changing mean removal rates (MRR) and days from symptom onset to hospitalization (DSOH) of infected individuals from the population in seven different outbreaks of EVD, SARS, and MERS, to test for statistically significant differences in these metrics between outbreaks. RESULTS: We found that epidemic week and viral serial interval were correlated with the speed with which populations developed and maintained health behaviors in each outbreak. CONCLUSIONS: These findings highlight intrinsic population-level changes in isolation rates in multiple epidemics of three zoonotic infections with established human-to-human transmission and significant morbidity and mortality. These data are particularly useful for disease modelers seeking to forecast the spread of emerging pathogens.

Estimating exposure to neighborhood crime by race and ethnicity for public health research.

BACKGROUND: Police-reported crime data (hereafter "crime") is routinely used as a psychosocial stressor in public health research, yet few studies have jointly examined (a) differences in crime exposure based on participant race and ethnicity, (b) differences in measures of crime exposure, and (c) considerations for how exposure to police is captured in police-recorded crime data. We estimate neighborhood exposure to crime and discuss the implications of structural differences in exposure to crime and police based on race and ethnicity. METHODS: Using GPS coordinates from 1188 participants in the Newborn Epigenetics Study, we estimated gestational exposure to crime provided by the Durham, North Carolina, Police Department within (a) 800 m and (b) the Census block group of residence. We controlled for non-overlapping spatial boundaries in crime, Census, residential, and police data to report crime spatial (crime per km2) and population (crime per 1000 people per km2) density. RESULTS: We demonstrate dramatic disparities in exposure to crime based on participant race and ethnicity and highlight variability in these disparities based on the type of crime and crime measurement method chosen. CONCLUSIONS: Public health researchers should give thoughtful consideration when using police-reported crime data to measure and model exposure to crime in the United States, as police-reported data encompasses joint exposure to police and crime in the neighborhood setting.

Demographic and sociocultural risk factors for adulthood weight gain in Hispanic/Latinos: results from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL).

BACKGROUND: United States (US) Hispanic/Latinos experience a disproportionate burden of obesity, which may in part be related to demographic or sociocultural factors, including acculturation to an US diet or inactive lifestyle. Therefore, we sought to describe the association between adulthood weight histories and demographic and sociocultural factors in a large diverse community-based cohort of US Hispanic/Latinos. METHODS: We estimated the effect of several factors on weight gain across adulthood, using multivariable linear mixed models to leverage 38,759 self-reported current body weights and weight histories recalled for 21, 45 and 65 years of age, from 15,203 adults at least 21 years of age at the baseline visit of the Hispanic Community Health Study/Study of Latinos (2008-2011). RESULTS: The average rate of weight gain was nearly 10 kg per decade in early adulthood, but slowed to < 5 kg a decade among individuals 60+ years of age. Birth cohort, gender, nativity or age at immigration, Hispanic/Latino background, and study site each significantly modified the form of the predicted adulthood weight trajectory. Among immigrants, weight gain during the 5 years post-migration was on average 0.88 kg (95% CI: 0.04, 1.72) greater than the weight gain during the 5 years prior. The rate of weight gain appeared to slow after 15 years post-migration. CONCLUSIONS: Using self-reported and weight history data in a diverse sample of US Hispanic/Latinos, we revealed that both demographic and sociocultural factors were associated with the patterning of adulthood weight gain in this sample. Given the steep rate of weight gain in this population and the fact that many Hispanic/Latinos living in the US immigrated as adults, efforts to promote weight maintenance across the life course, including after immigration, should be a top priority for promoting Hispanic/Latino health and addressing US health disparities more broadly.

An Efficient, Large-Scale Survey of Hepatitis C Viremia in the Democratic Republic of the Congo Using Dried Blood Spots.

Background: Efficient viral load testing is needed for hepatitis C (HCV) surveillance and diagnosis. HCV viral load testing using dried blood spots (DBSs), made with a single drop of finger-prick whole blood on filter paper, is a promising alternative to traditional serum- or plasma-based approaches. Methods: We adapted the Abbott Molecular m2000 instrument for high-throughput HCV viremia testing using DBSs with simple specimen processing and applied these methods to estimate the national burden of infection in the Democratic Republic of the Congo (DRC). We tested DBSs collected during the 2013-2014 DRC Demographic and Health Survey, including 1309 adults ≥40 years of age. HCV-positive samples underwent targeted sequencing, genotyping, and phylogenetic analyses. Results: This high-throughput screening approach reliably identified HCV RNA extracted from DBSs prepared using whole blood, with a 95% limit of detection of 1196 (95% confidence interval [CI], 866-2280) IU/mL for individual 6-mm punches and 494 (95% CI, 372-1228) IU/mL for larger 12-mm punches. Fifteen infections were identified among samples from the DRC Demographic and Health Survey; the weighted country-wide prevalence of HCV viremia was 0.9% (95% CI, 0.3%-1.6%) among adults ≥40 years of age and 0.7% (95% CI, .6%-.8%) among human immunodeficiency virus-infected subjects. All successfully genotyped cases were due to genotype 4 infection. Conclusions: DBS-based HCV testing represents a useful tool for the diagnosis and surveillance of HCV viremia and can easily be incorporated into specimen referral systems. Among adults ≥40 years of age in the DRC, 100000-200000 may have active infection and be eligible for treatment.

Magnitude and Durability of the Antibody Response to mRNA-Based Vaccination Among SARS-CoV-2 Seronegative and Seropositive Health Care Personnel.

Few studies have described changes in SARS-CoV-2 antibody levels in response to infection and vaccination at frequent intervals and over extended follow-up periods. The purpose of this study was to assess changes in SARS-CoV-2-specific antibody responses among a prospective cohort of health care personnel over 18 months with up to 22 samples per person. Antibody levels and live virus neutralization were measured before and after mRNA-based vaccination with results stratified by (1) SARS-CoV-2 infection status prior to initial vaccination and (2) SARS-CoV-2 infection at any point during follow-up. We found that the antibody response to the first dose was almost 2-fold higher in individuals who were seropositive prior to vaccination, although neutralization titers were more variable. The antibody response induced by vaccination appeared to wane over time but generally persisted for 8 to 9 months, and those who were infected at any point during the study had slightly higher antibody levels over time vs those who remained uninfected. These findings underscore the need to account for SARS-CoV-2 natural infection as a modifier of vaccine responses, and they highlight the importance of frequent testing of longitudinal antibody titers over time. Together, our results provide a clearer understanding of the trajectories of antibody response among vaccinated individuals with and without prior SARS-CoV-2 infection.

Objectively measured external building quality, Census housing vacancies and age, and serum metals in an adult cohort in Detroit, Michigan.

BACKGROUND: Residentially derived lead pollution remains a significant problem in urban areas across the country and globe. The risks of childhood residence in housing contaminated with lead-based paint are well-established, but less is known about the effects of housing quality on adult lead exposure. OBJECTIVE: To evaluate the effects of residential-area housing age, vacancy status, and building quality on adult lead exposures. METHODS: We evaluated the effect of Census block group housing vacancy proportion, block group housing age, and in-person survey evaluated neighborhood building quality on serum levels of lead, mercury, manganese, and copper among a representative cohort of adults in Detroit, Michigan, from 2008-2013 using generalized estimating equations. RESULTS: Participants in Census block groups with higher proportions of vacant and aged housing had non-significantly elevated serum lead levels. We identified similar positive associations between residence in neighborhoods with poorer objectively measured building quality and serum lead. Associations between Census vacancies, housing age, objectively measured building quality, and serum lead were stronger among participants with a more stable residential history. SIGNIFICANCE: Vacant, aged, and poorly maintained housing may contribute to widespread, low-level lead exposure among adult residents of older cities like Detroit, Michigan. US Census and neighborhood quality data may be a useful tool to identify population-level lead exposures among US adults. IMPACT: Using longitudinal data from a representative cohort of adults in Detroit, Michigan, we demonstrate that Census data regarding housing vacancies and age and neighborhood survey data regarding housing quality are associated with increasing serum lead levels. Previous research has primarily focused on housing quality and lead exposures among children. Here, we demonstrate that area-level metrics of housing quality are associated with lead exposures among adults.

Assessment of a Student-Run Free Gender-Affirming Care Clinic's Transition to Telehealth.

Background: Transgender and Gender-Nonconforming (TGNC) people continue to experience severe health discrimination and limited access to care. Methods: Using survey data collected during August-September, 2020, we report on our findings regarding volunteer provider and patient satisfaction with a student-run free gender-affirming care telehealth clinic at the University of North Carolina at Chapel Hill School of Medicine. Results: We find that patients report overall excellent experiences with telehealth care, primarily due to decreased transportation burden, more efficient use of time, and more frequent communication with student volunteer providers. Conclusion: Our findings show that telehealth is a viable option for student-run clinics in the TGNC community.

Gestational exposure to neighborhood police-reported crime and early childhood blood pressure in Durham, NC.

Gestational exposure to police-reported crime is associated with adverse birth outcomes, but no previous research has evaluated the effects of gestational crime exposure on early childhood health or attempted to disentangle the health effects of neighborhood crime from the effects of neighborhood policing. Using data from 672 Newborn Epigenetics Study participants, we evaluate the effects of gestational exposure to violent crime and racialized drug policing on early childhood blood pressure. We demonstrate that violence and drug policing are consistently associated with increased blood pressure among children born to Black participants but not White or Latinx participants.

The effect of residential proximity to brownfields, highways, and heavy traffic on serum metal levels in the Detroit Neighborhood Health Study.

Research in environmental sciences has demonstrated that land in close proximity to brownfields and heavily trafficked highways is contaminated with toxic metals. Despite this, little is known about the influence of brownfields and highways on metal levels in residents living nearby. We used data from 774 participants in the Detroit Neighborhood Health Study to estimate the effect of residential proximity to brownfields, highways, and present-day traffic on serum levels of lead, mercury, manganese, and copper using generalized estimating equations. We found that a 1 standard deviation increase in residential brownfield density within 200m was associated with increased serum lead levels (ß: 0.04, 95% CI: -0.01, 0.09). The same modeled increase in a subset of historic industrial-use brownfields was associated with elevated serum mercury (ß: 0.06, 95% CI: 0.03, 0.09). Increased highway and traffic density was positively associated with serum manganese (ß: 0.02, 95% CI: 0.01, 0.04). Highway and traffic density was also positively associated with serum lead (ß: 0.02, 95% CI: 0.01, 0.03) after restricting the analysis to participants who did not move during the study follow-up period. These findings draw attention to the importance of remediating polluted post-industrial sites in heavily populated areas, particularly as residents continue to move into densely populated cities around the globe.

Serum lead, mercury, manganese, and copper and DNA methylation age among adults in Detroit, Michigan.

Although the effects of lead, mercury, manganese, and copper on individual disease processes are well understood, estimating the health effects of long-term exposure to these metals at the low concentrations often observed in the general population is difficult. In addition, the health effects of joint exposure to multiple metals are difficult to estimate. Biological aging refers to the integrative progression of multiple physiologic and molecular changes that make individuals more at risk of disease. Biomarkers of biological aging may be useful to estimate the population-level effects of metal exposure prior to the development of disease in the population. We used data from 290 participants in the Detroit Neighborhood Health Study to estimate the effect of serum lead, mercury, manganese, and copper on three DNA methylation-based biomarkers of biological aging (Horvath Age, PhenoAge, and GrimAge). We used mixed models and Bayesian kernel machine regression and controlled for participant sex, race, ethnicity, cigarette use, income, educational attainment, and block group poverty. We observed consistently positive estimates of the effects between lead and GrimAge acceleration and mercury and PhenoAge acceleration. In contrast, we observed consistently negative associations between manganese and PhenoAge acceleration and mercury and Horvath Age acceleration. We also observed curvilinear relationships between copper and both PhenoAge and GrimAge acceleration. Increasing total exposure to the observed mixture of metals was associated with increased PhenoAge and GrimAge acceleration and decreased Horvath Age acceleration. These findings indicate that an increase in serum lead or mercury from the 25th to 75th percentile is associated with a ∼0.25-year increase in two epigenetic markers of all-cause mortality in a population of adults in Detroit, Michigan. While few of the findings were statistically significant, their consistency and novelty warrant interest.

Looking Back to Leap Forward: A Framework for Operationalizing the Structural Racism Construct in Minority Health Research.

Racism is now widely recognized as a fundamental cause of health inequalities in the United States. As such, health scholars have rightly turned their attention toward examining the role of structural racism in fostering morbidity and mortality. However, to date, much of the empirical structural racism-health disparities literature limits the operationalization of structural racism to a single domain or orients the construct around a White/Black racial frame. This operationalization approach is incomprehensive and overlooks the heterogeneity of historical and lived experiences among other racial and ethnic groups. To address this gap, we present a theoretically grounded framework that illuminates core mutually reinforcing domains of structural racism that have stratified opportunities for health in the United States. We catalog instances of structural discrimination that were particularly constraining (or advantageous) to the health of racial and ethnic groups from the late 1400s to present. We then illustrate the utility of this framework by applying it to American Indians or Alaska Natives and discuss the framework's broader implications for empirical health research. This framework should help future scholars across disciplines as they identify and interrogate important laws, policies, and norms that have differentially constrained opportunities for health among racial and ethnic groups.

SARS-CoV-2 seropositivity after infection and antibody response to mRNA-based vaccination.

The effect of SARS-CoV-2 infection on response to mRNA-based SARS-CoV-2 vaccines is not well-described. We assessed longitudinal SARS-CoV-2-specific antibody responses pre- and post-vaccination among individuals with and without prior infection. The antibody response to the first vaccine dose was almost two-fold higher in individuals who were seropositive before vaccination compared to those who were seronegative, suggesting that prior infection primes the immune response to the first dose of mRNA-based vaccine.

SARS-CoV-2 Infection in Health Care Personnel and Their Household Contacts at a Tertiary Academic Medical Center: Protocol for a Longitudinal Cohort Study.

BACKGROUND: Health care personnel (HCP) are at high risk for exposure to the SARS-CoV-2 virus. While personal protective equipment (PPE) may mitigate this risk, prospective data collection on its use and other risk factors for seroconversion in this population is needed. OBJECTIVE: The primary objectives of this study are to (1) determine the incidence of, and risk factors for, SARS-CoV-2 infection among HCP at a tertiary care medical center and (2) actively monitor PPE use, interactions between study participants via electronic sensors, secondary cases in households, and participant mental health and well-being. METHODS: To achieve these objectives, we designed a prospective, observational study of SARS-CoV-2 infection among HCP and their household contacts at an academic tertiary care medical center in North Carolina, USA. Enrolled HCP completed frequent surveys on symptoms and work activities and provided serum and nasal samples for SARS-CoV-2 testing every 2 weeks. Additionally, interactions between participants and their movement within the clinical environment were captured with a smartphone app and Bluetooth sensors. Finally, a subset of participants' households was randomly selected every 2 weeks for further investigation, and enrolled households provided serum and nasal samples via at-home collection kits. RESULTS: As of December 31, 2020, 211 HCP and 53 household participants have been enrolled. Recruitment and follow-up are ongoing and expected to continue through September 2021. CONCLUSIONS: Much remains to be learned regarding the risk of SARS-CoV-2 infection among HCP and their household contacts. Through the use of a multifaceted prospective study design and a well-characterized cohort, we will collect critical information regarding SARS-CoV-2 transmission risks in the health care setting and its linkage to the community. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25410.

The association between residential proximity to brownfield sites and high-traffic areas and measures of immunity.

The mechanisms by which neighborhood environmental exposures influence health are poorly understood, although immune system dysregulation represents a potential biological pathway. While many neighborhood exposures have been investigated, there is little research on residential proximity to brownfield waste. Using biomarker data from 262 participants in the Detroit Neighborhood Health Study, we estimated the association between proximity to brownfields and heavy traffic and signal joint T-cell receptor excision circles (sjTRECs, a measure of naive T-cell production), C-reactive protein (CRP, a measure of systemic inflammation), and interleukin-6 (IL-6, a pro-inflammatory cytokine). We assessed residential proximity ≤200 m from brownfields and highways on all three biomarkers using multivariate regression. We demonstrated that living ≤200 m from a brownfield site was associated with a 0.30 (95% CI = 0.59, 0.02, p = 0.04) loge-unit decrease in sjTRECs per million whole blood cells, as well as non-significantly elevated levels of CRP and IL-6. Heavy traffic was not associated with any biomarker. Persons living in close proximity to brownfield sites had significantly lower naive T-cell production, suggesting accelerated immune aging. Decreased T-cell production associated with brownfield proximity may be caused by toxicant exposure in brownfield sites, or may serve as a marker of other neighborhood stressors.

Pharmacologic inhibition of N-linked glycan trimming with kifunensine disrupts GLUT1 trafficking and glucose uptake.

The facilitative glucose transport GLUT1 (SLC2A1) is a constitutively expressed membrane protein involved in basal uptake of blood glucose. GLUT1 modification by N-linked glycosylation at a single asparagine residue (N45) appears to play multiple roles in the trafficking, stability and transport activity of this protein. Here we examine the role of complex N-glycosylation on GLUT1 function in renal epithelial cells by arresting this modification at the high-mannose stage with the mannosidase I inhibitor kifunensine. Consistent with prior work in which GLUT1 glycosylation was completely inhibited, we find that kifunensine treatment results in a time-dependent decrease of up to 40% in cellular glucose uptake. We further demonstrate that this effect is primarily a result of deficient GLUT1 trafficking to the cell membrane due to quality control mechanisms that instead direct GLUT1 to the ER-associated degradation (ERAD) pathway. Unlike tunicamycin, which inhibits the first step in N-glycosyl transfer and causes dramatic cell cycle arrest, kifunensine causes only a modest decrease in GLUT1 levels and cell cycle progression in both normal and transformed renal cells. The effect of kifunensine on the cell cycle appears to be independent of its effect on GLUT1, since all renal cell types in this study displayed decreased proliferation regardless of their dependence on glucose uptake for growth and survival. Together these results indicate that proper N-glycan processing plays an important role in directing GLUT1 to the cell surface and that disruption of mannosidase activity results in aberrant degradation of GLUT1 by the ERAD pathway.