Death by the minute: Inequities in trauma care for victims of firearm violence.

BACKGROUND: Gunshot wounds (GSWs) remain a significant source of mortality in the United States. Timely delivery of trauma care is known to be critical for survival. We sought to understand the relationship of predicted transport time and death after GSW. Given large racial disparities in firearm violence, we also sought to understand disparities in transport times and death by victim race, an unstudied phenomenon. METHODS: Firearm mortality data were obtained from the Boston Police Department 2005 to 2023. Firearm incidents were mapped using ArcGIS. Predicted transport times for each incident to the closest trauma center were calculated in ArcGIS. Spatial autoregressive models were used to understand the relationship between victim race, transport time to a trauma center, and mortality associated with the shooting incidents. RESULTS: There were 4,545 shooting victims with 758 deaths. Among those who lived, the median transport time was 9.4 minutes (interquartile range, 5.8-13.8) and 10.5 minutes (interquartile range, 6.4-14.6; p = 0.003) for those who died. In the multivariable logistic regression, increased transport time to the nearest trauma center (odds ratio, 1.024; 95% confidence interval, 1.01-1.04) and age (odds ratio, 1.016; 95% confidence interval, 1.01-1.02) were associated with mortality. There was a modest difference in median transport time to the nearest trauma center by race with non-Hispanic Black at 10.1 minutes, Black Hispanic 9.2 minutes, White Hispanic 8.5 minutes, and non-Hispanic White 8.3 minutes ( p < 0.001). CONCLUSION: Our results highlight the relationship of transport time to a trauma center and death after a GSW. Non-White individuals had significantly longer transport times to a trauma center and predicted mortality would have been lower with White victim transport times. These data underscore the importance of timely trauma care for GSW victims and can be used to direct more equitable trauma systems. LEVEL OF EVIDENCE: Prognostic/Epidemiological; Level III.

Stakeholders' perspectives on barriers to and facilitators of school-based HPV vaccination in the context of COVID-19 pandemic-related disruption: a qualitative mixed methods study.

Despite successfully implementing the Human Papilloma Virus Vaccine (HPVV) program, Saskatchewan (SK) struggled to improve HPVV uptake rates. This suboptimal uptake of HPVV with a status quo of HPV-linked cervical cancer incidence rate is mainly because HPVV's impact on cancer prevention has not been realized adequately by vaccine providers and receivers. Further exploration of determinants of HPVV uptake is required to uncover high-resolution quality improvement targets for investment and situate contextually appropriate policies to improve its uptake. The study undertook a qualitative inquiry into understanding stakeholders' perspectives on HPVV experience through school-based programmes. It collected data through semi-structured initial interviews (N = 16) and follow-up interviews (N = 10) from across Saskatchewan's four Integrated Service Areas. Document analysis was conducted on all publicly available documents that included information on HPVV from January 2015 to July 2023. Thematic analysis of the data identified that inadequate information, awareness and education about HPV infection and HPVV among several groups, especially, parents, youth and school staff, was the main barrier to optimal HPVV uptake. Vaccine-related logistics, including the technical and text-heavy vaccine information sheet, understaffing, and time constraints, were other important factors that impeded HPVV uptake. A person-centred approach could educate parents in multiple dimensions.

Barriers to and facilitators of human papillomavirus vaccination in an ethnically diverse group of migrant parents: A qualitative mixed methods study.

A disparity in the uptake of the Human papillomavirus vaccine (HPVV) among immigrants and refugees leads to a social gradient in health. Recognizing that immigrants and refugees may encounter unique barriers to accessing prevention and care, this study seeks to determine barriers to and facilitators of HPVV among these subgroups to uncover high-resolution quality improvement targets of investment for under-immunized pockets of the population. The study undertook a qualitative inquiry into understanding immigrant and refugee parents' perspectives on HPV infection and HPVV experience through school-based programs. We collected data first through short online surveys (N = 15) followed by one-on-one interviews (N = 15) and then through detailed online surveys (N = 16) followed by focus group discussions (N = 3) with 4-6 participants per group discussion from different groups: Black, South Asian and West Asian. Analysis of surveys and interviews identified that: information, awareness, and education about HPV infection and HPVV were among the most cited barriers that impede the uptake of HPVV. Moreover, vaccine-related logistics were equally important, including not having immunization information packages in different languages and relying solely on the child to bring home packages in paper copies from school-based vaccine programs. A multi-component intervention remains instrumental in enhancing HPV immunization rates, given the inconsistent uptake of HPVV by these subgroups who voice unique barriers and facilitators. An educational campaign that involves educating parents who consent for their child(ren) for HPVV, the children receiving the vaccination, and training staff providing HPVV through school-based immunization programs would be paramount.

What was the impact of tobacco taxes on smoking prevalence and coronary heart disease mortality in the United States -2005-2016, and did it vary by race and gender?

Tobacco taxes have reduced smoking and coronary heart disease (CHD) mortality, yet few studies have examined heterogeneity of these associations by race and gender. We constructed a yearly panel (2005-2016) that included age-adjusted cigarette smoking prevalence and CHD mortality rates across all 50 U.S. States and the District of Columbia using the Behavioral Risk Factor Surveillance System and Wide-ranging Online Data for Epidemiological Research. We examined associations between changes in total cigarette excise taxes (i.e., federal and state) and changes in smoking prevalence and CHD mortality, using linear regression models with state and year fixed effects. Each dollar of tobacco tax was associated with a reduction in age-adjusted smoking prevalence 1 year later of -0.4 [95% CIs: -0.6, -0.2] percentage points; and a relative reduction in the rate of CHD mortality 2 years later of -2.0% [95% CIs: -3.7%, -0.3%], or -5 deaths/100,000 in absolute terms. Associations between tobacco taxes and smoking prevalence were statistically significantly different by race and gender and were strongest among Black non-Hispanic women (-1.2 [95% CIs: -1.6, -0.8] percentage points). Associations between tobacco taxes and CHD mortality were not statistically significantly different by race and gender, but point estimates for percent changes were highest among Black non-Hispanic men (-2.9%) and Black non-Hispanic women (-3.5%) compared to White non-Hispanic men (-1.8%) and White non-Hispanic women (-1.5%). These findings suggest that tobacco taxation is an effective intervention for reducing smoking prevalence and CHD mortality among White and Black non-Hispanic populations in the United States.

Conceptualising commercial entities in public health: beyond unhealthy commodities and transnational corporations.

Most public health research on the commercial determinants of health (CDOH) to date has focused on a narrow segment of commercial actors. These actors are generally the transnational corporations producing so-called unhealthy commodities such as tobacco, alcohol, and ultra-processed foods. Furthermore, as public health researchers, we often discuss the CDOH using sweeping terms such as private sector, industry, or business that lump together diverse entities whose only shared characteristic is their engagement in commerce. The absence of clear frameworks for differentiating among commercial entities, and for understanding how they might promote or harm health, hinders the governance of commercial interests in public health. Moving forward, it is necessary to develop a nuanced understanding of commercial entities that goes beyond this narrow focus, enabling the consideration of a fuller range of commercial entities and the features that characterise and distinguish them. In this paper, which is the second of three papers in a Series on commercial determinants of health, we develop a framework that enables meaningful distinctions among diverse commercial entities through consideration of their practices, portfolios, resources, organisation, and transparency. The framework that we develop permits fuller consideration of whether, how, and to what extent a commercial actor might influence health outcomes. We discuss possible applications for decision making about engagement; managing and mitigating conflicts of interest; investment and divestment; monitoring; and further research on the CDOH. Improved differentiation among commercial actors strengthens the capacity of practitioners, advocates, academics, regulators, and policy makers to make decisions about, to better understand, and to respond to the CDOH through research, engagement, disengagement, regulation, and strategic opposition.

Socially Assigned Race and the Health of Racialized Women and Their Infants.

Introduction: While historically most public health research has relied upon self-identified race as a proxy for experiencing racism, a growing literature recognizes that socially assigned race may more closely align with racialized lived experiences that influence health outcomes. We aim to understand how women's health behaviors, health outcomes, and infant health outcomes differ for women socially assigned as nonwhite when compared with women socially assigned as white in Massachusetts. Methods: Using data from the Massachusetts Pregnancy Risk Assessment Monitoring System (PRAMS) Reactions to Race module, we documented the associations between socially assigned race (white vs. nonwhite) and women's health behaviors (e.g., initiation of prenatal care, breastfeeding), women's health outcomes (e.g., gestational diabetes, depression before pregnancy), and infant health outcomes (e.g., preterm birth, low birth weight [LBW]). Multivariable models adjusted for age, marital status, education level, nativity, receipt of Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) assistance during pregnancy, infant sex, plurality, and gestational age. Additional models adjusted for treatment by race, how often one thinks about race, and nativity. Results: Women socially assigned as nonwhite had higher odds of breastfeeding (adjusted odds ratio [AOR]: 1.86, 95% confidence interval [CI]: 1.54 to 2.25), lower odds of consuming alcohol (AOR: 0.27, 95% CI: 0.24 to 0.31), and lower odds of smoking (AOR: 0.30, 95% CI: 0.24 to 0.38) compared with those socially assigned as white. However, women socially assigned as nonwhite had higher odds of reporting gestational diabetes (AOR: 1.97, 95% CI: 1.49 to 2.61). Mothers socially assigned as nonwhite also had higher odds of giving birth to an LBW (AOR: 1.66, 95% CI: 1.29 to 2.14) and small-for-gestational age (AOR: 1.46, 95% CI: 1.19 to 1.80) infant compared with women socially assigned as white. Discussion: In comparison with women socially assigned as white, we observed poorer health outcomes for women who were socially assigned nonwhite despite engaging in more beneficial pregnancy-related health behaviors. Socially assigned race can provide an important context for women's experiences that can influence their health and the health of their infants.

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.

Long non-coding RNA LINC00926 regulates WNT10B signaling pathway thereby altering inflammatory gene expression in PTSD.

Post-traumatic stress disorder (PTSD), which frequently occurs in the aftermath of a psychologically traumatic event is characterized by heightened inflammation. People with PTSD also suffer from a number of comorbid clinical and behavioral disorders that are related to chronic inflammation. Thus, understanding the mechanisms of enhanced inflammation in PTSD can provide insights into the relationship between PTSD and associated comorbid disorders. In the current study, we investigated the role of large intervening non-coding RNAs (lincRNAs) in the regulation of inflammation in people diagnosed with PTSD. We observed that WNT ligand, WNT10B, was upregulated in the peripheral blood mononuclear cells (PBMCs) of PTSD patients. This observation was associated with higher H3K4me3 signals around WNT10B promotor in PTSD patients compared to those without PTSD. Increased H3K4me3 resulted from LINC00926, which we found to be upregulated in the PTSD sample, bringing in histone methyltransferase, MLL1, onto WNT10B promotor leading to the introduction of H3K4 trimethylation. The addition of recombinant human WNT10B to pre-activated peripheral blood mononuclear cells (PBMCs) led to increased expression of inflammatory genes such as IFNG and IL17A, suggesting that WNT10B is involved in their upregulation. Together, our data suggested that LINC00926 interacts physically with MLL1 and thereby controls the expression of IFNG and IL17A. This is the first time a long non-coding RNA is shown to regulate the expression of WNT10B and consequently inflammation. This observation has high relevance to our understanding of disease mechanisms of PTSD and comorbidities associated with PTSD.

Contested racial identity and the health of women and their infants.

Contested racial identity- self-identified race not matching socially-assigned race-may be an indication of experiences with racism. We aimed to understand the relationship between contested racial identity and women's health behaviors, health outcomes, and infant health outcomes. We used 2012-2015 Massachusetts Pregnancy Risk Assessment Monitoring System data on 5735 women linked with infants' birth certificates. We conducted regression analyses to examine associations between contested racial identity with pregnancy and infant health outcomes and further sub-analyses among women who had experienced a contested racial identity. A total of 901 (15.7%) women reported a contested racial identity. When compared to those who did not, women who had a contested racial identity had lower odds of initiating prenatal care in the first trimester (AOR: 0.76, 95% CI: 0.62, 0.95) and higher odds of smoking (AOR: 1.70, 95% CI: 1.32, 2.19). Among women who had experienced a contested racial identity, those who were socially-assigned as White had decreased odds of having a low birth weight baby (AOR: 0.52, 95% CI: 0.28, 0.99) when compared to those socially-assigned as non-White. Contested racial identity is common; it affects the behaviors that women engage in and the outcomes they experience postpartum. Further, we found that there is a potential benefit to a White social ascription. This work adds to growing evidence of the impact of racism on maternal and infant health in the United States.

Advancing the Social Epidemiology Mission of the American Journal of Epidemiology.

Social epidemiology is concerned with how social forces influence population health. Rather than focusing on a single disease (as in cancer or cardiovascular epidemiology) or a single type of exposure (e.g., nutritional epidemiology), social epidemiology encompasses all the social and economic determinants of health, both historical and contemporary. These include features of social and physical environments, the network of relationships in a society, and the institutions, politics, policies, norms and cultures that shape all of these forces. This commentary presents the perspective of several editors at the Journal with expertise in social epidemiology. We articulate our thinking to encourage submissions to the Journal that: 1) expand knowledge of emerging and underresearched social determinants of population health; 2) advance new empirical evidence on the determinants of health inequities and solutions to advance health equity; 3) generate evidence to inform the translation of research on social determinants of health into public health impact; 4) contribute to innovation in methods to improve the rigor and relevance of social epidemiology; and 5) encourage critical self-reflection on the direction, challenges, successes, and failures of the field.

Differences in Health Characteristics of Geographic Subgroups of Arab Americans in a Northern California Health Plan.

INTRODUCTION: Arab Americans are a diverse ethnic group originating from a large geographic area in the Middle East and North Africa (MENA). We aim to characterize differences in health between Arab Americans from different geographic subgroups within MENA. METHODS: We used cross-sectional electronic health record (EHR) data for a subset of 4913 Arab Americans aged 20-84 in a 2016 Northern California health plan study cohort who could be assigned to one of 4 geographic subgroups (Gulf, African, Levant, and Other) based on EHR ethnicity data. We calculated age-adjusted prevalence estimates for men and women and used generalized linear models to compare Gulf, African, and Other subgroups to Levant Arabs on risk factors (obesity and smoking), chronic conditions (diabetes, hypertension, hyperlipidemia, and asthma), and mental health (depression and anxiety). RESULTS: Among women, prevalence of smoking was lower among Gulf, African, and Other Arabs than Levant Arabs. Among men, prevalence of obesity, diabetes, and hyperlipidemia was lower among Gulf, African, and Other Arabs than Levant Arabs, while prevalence of depression was higher for these subgroups than Levant Arabs. DISCUSSION: We found substantial differences in health characteristics across Arab Americans from different geographic subgroups. Our results suggest that more detailed race and ethnicity information should be collected on Arab Americans to better understand their diverse health risks.

Understanding differences within ethnic group designation: comparing risk factors and health indicators between Iranian and Arab Americans in Northern California.

BACKGROUND: The Middle Eastern and North African (MENA) ethnic group is a diverse group composed of two primary subsets in the United States: Iranian and Arab Americans. We aimed to compare health risk factors, chronic health conditions, and mental health conditions of Iranian and Arab American adults in Northern California. METHODS: We used cross-sectional electronic health record (EHR) data from a 2016 Northern California health plan study cohort to compare adults classified as Iranian or Arab American based on ethnicity, language, or surname. We produced age-standardized prevalence estimates of obesity, smoking, hyperlipidemia, prediabetes, diabetes, hypertension, depression, and anxiety for Iranian and Arab American men and women by age group (35-44, 45-64, and 65-84) and overall (35-84). We used generalized linear models to calculate prevalence ratios (PR) to compare Iranian and Arab American adults ages 35-84 on all health indicators. RESULTS: Compared to Arab Americans, Iranian Americans had a lower prevalence of obesity (PR: 0.77, 95% confidence interval, CI: 0.73, 0.82), current smoking (PR: 0.80, 95% CI: 0.73, 0.89), and ever smoking (PR: 0.95, 95% CI: 0.91, 0.99), but a higher prevalence of hyperlipidemia (PR: 1.09, 95% CI: 1.06, 1.12), prediabetes (PR: 1.12, 95% CI: 1.09, 1.16), depression (PR; 1.41, 95% CI: 1.30, 1.52), and anxiety (PR: 1.52, 95% CI: 1.42, 1.63). Similar patterns were observed for men and women. CONCLUSION: This work supports the need to collect granular data on race and ethnicity within the MENA ethnic group to improve identification in clinical care settings and population health reporting to better address the physical and mental health needs of different MENA subgroups.

Health Risks and Chronic Health Conditions among Arab American and White Adults in Northern California.

Objectives: To characterize the prevalence of chronic cardiovascular conditions and risk factors among Arab American adults stratified by sex and compare these with non-Hispanic Whites. Design: Cross-sectional study using electronic health record data from visits between January 2015 and December 2016. Age-adjusted prevalence estimates were calculated for men and women and compared using generalized linear models. Setting: Kaiser Permanente health plan in Northern California. Participants: Non-Hispanic White (N=969,566) and Arab American (N=18,072) adult members. Main Outcome Measures: Sex-stratified prevalence and prevalence ratios of diabetes, pre-diabetes, hypertension, and hyperlipidemia diagnosed by December 2016 and of obesity, ever smoking, and current smoking status. Results: Arab American men had a significantly higher prevalence of ever smoking (41.8 vs 40.8%), diabetes (17.3 vs 12.5%), and hyperlipidemia (40.8 vs 34.7%) than White men, but a significantly lower prevalence of obesity (34.4 vs 37.8%) and hypertension (30.5 vs 33.3%). Arab American women had a significantly higher prevalence of diabetes (11.1 vs 8.7%) and hyperlipidemia (31.5 vs 28.3%) than White women but significantly lower prevalence of obesity (31.0 vs 34.2%), ever smoking (24.8 vs 34.5%), and hypertension (25.8 vs 28.4%). Conclusions: Hospital and health systems should intentionally collect data on Middle Eastern and North African ethnicity in electronic health records to identify and reduce the disparities this minority group faces.

Financial hardship and health risk behavior during COVID-19 in a large US national sample of women.

COVID-19 has caused over 300,000 US deaths thus far, but its long-term health consequences are not clear. Policies to contain the pandemic have led to widespread economic problems, which likely increase stress and resulting health risk behaviors, particularly among women, who have been hardest hit both by job loss and caregiving responsibilities. Further, women with pre-existing disadvantage (e.g., those without health insurance) may be most at risk for stress and consequent health risk behavior. Our objective was to estimate the associations between financial stressors from COVID-19 and health risk behavior changes since COVID-19, with potential effect modification by insurance status. We used multilevel logistic regression to assess the relationships between COVID-19-related financial stressors (job loss, decreases in pay, trouble paying bills) and changes in health risk behavior (less exercise, sleep, and healthy eating; more smoking/vaping and drinking alcohol), controlling for both individual-level and zip code-level confounders, among 90,971 US women who completed an online survey in March-April 2020. Almost 40% of women reported one or more COVID-19-related financial stressors. Each financial stressor was significantly associated with higher odds of each type of health risk behavior change. Overall, reporting one or more financial stressors was associated with 56% higher odds (OR = 1.56; 95% CI: 1.51, 1.60) of reporting two or more health risk behavior changes. This association was even stronger among women with no health insurance (OR = 2.46; 95% CI: 1.97, 3.07). COVID-19-related economic stress is thus linked to shifts in health risk behaviors among women, which may have physical health consequences for years to come. Further, the relationship between financial hardship and health risk behavior among women may be modified by health insurance status, as a marker for broader socioeconomic context and resources. The most socioeconomically vulnerable women are likely at highest risk for long-term health effects of COVID-19 financial consequences.

Prevalence and hospital charges from firearm injuries treated in US emergency departments from 2006 to 2016.

BACKGROUND: Age- and intent-related differences in the burden and costs of firearm injury treated in emergency departments are not well-documented. METHODS: We performed a serial cross-sectional study of the Healthcare Cost and Utilization Program Nationwide Emergency Department Survey from 2006 to 2016. We used International Classification of Diseases diagnoses codes revisions 9 and 10 to identify firearm injuries. We calculated survey-weighted counts, proportions, means, and rates and confidence intervals of national, age-specific (0-4, 5-9, 10-14, 15-17, 18-44, 45-64, 65-84, >84) and intent-specific (assault, unintentional, suicide, undetermined) emergency department discharges for firearm injuries. We used survey-weighted regression to assess temporal trends. RESULTS: There was a total of 868,483 (25.5 per 100,000) emergency department visits for firearm injuries from 2006 to 2016, and 7.8% died in the emergency department. Overall, firearm injury rates remained steady (P = .78). The largest burden was among those 25 to 44 years of age, but their rates remained stable (10.8 per 100,000). Overall assault injuries declined from 39.7% to 36.4%, and overall unintentional injuries increased from 46.4% to 54.7%. Legal-intervention injuries declined from 0.6 to 0.3 per 100,000. The charges (total $4,059,070,364, $369,006,396/year) increased across time in age and intent groups. The mean predicted charges increased from $1,922 to $3,348 in those alive versus $3,741 to $6,515 among those who died. CONCLUSION: Interventions and programs to manage the consequences of firearm injury in persons who live with ongoing morbidity and economic burden are warranted.

Smoking cessation potential among newly diagnosed cancer patients: a population-based study of the ten most common cancers in Massachusetts, USA, 2008-2013.

PURPOSE: In cancer patients, cigarette smoking is causally linked with increased mortality. We examined the relationship between smoking status at the time of diagnosis and cancer mortality to help estimate the scope of smoking cessation services required to meet the needs of cancer patients. METHODS: We studied the ten most common cancers in Massachusetts, 2008-2013 including 175,489 incident cases and used smoking status at the time of diagnosis to provide smoking prevalence. We calculated adjusted hazard ratios of all-cause mortality comparing smoker subgroups. RESULTS: Smoking prevalence was more than threefold higher for lung cancer and more than twofold higher for head and neck cancer and bladder cancer than in the general population. Cancer cases who smoked at the time of diagnosis had a higher adjusted mortality rate than cancer cases who were former smokers. The three sites with the highest increased hazard ratios comparing current smokers with former smokers were cancers of the thyroid (HR = 1.67, 95% CI 1.14-2.45), head and neck (HR = 1.65, 95% CI 1.39-1.95), and prostate (HR = 1.60, 95% CI 1.36-1.90). CONCLUSIONS: Smoking remains high among cancer patients. More widespread adoption of smoking cessation programs among cancer patients may play a substantial role in improving cancer morbidity and mortality.

Increased H3K4me3 methylation and decreased miR-7113-5p expression lead to enhanced Wnt/ß-catenin signaling in immune cells from PTSD patients leading to inflammatory phenotype.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder accompanied by chronic peripheral inflammation. What triggers inflammation in PTSD is currently unclear. In the present study, we identified potential defects in signaling pathways in peripheral blood mononuclear cells (PBMCs) from individuals with PTSD. METHODS: RNAseq (5 samples each for controls and PTSD), ChIPseq (5 samples each) and miRNA array (6 samples each) were used in combination with bioinformatics tools to identify dysregulated genes in PBMCs. Real time qRT-PCR (24 samples each) and in vitro assays were employed to validate our primary findings and hypothesis. RESULTS: By RNA-seq analysis of PBMCs, we found that Wnt signaling pathway was upregulated in PTSD when compared to normal controls. Specifically, we found increased expression of WNT10B in the PTSD group when compared to controls. Our findings were confirmed using NCBI's GEO database involving a larger sample size. Additionally, in vitro activation studies revealed that activated but not naïve PBMCs from control individuals expressed more IFNγ in the presence of recombinant WNT10B suggesting that Wnt signaling played a crucial role in exacerbating inflammation. Next, we investigated the mechanism of induction of WNT10B and found that increased expression of WNT10B may result from epigenetic modulation involving downregulation of hsa-miR-7113-5p which targeted WNT10B. Furthermore, we also observed that WNT10B overexpression was linked to higher expression of H3K4me3 histone modification around the promotor of WNT10B. Additionally, knockdown of histone demethylase specific to H3K4me3, using siRNA, led to increased expression of WNT10B providing conclusive evidence that H3K4me3 indeed controlled WNT10B expression. CONCLUSIONS: In summary, our data demonstrate for the first time that Wnt signaling pathway is upregulated in PBMCs of PTSD patients resulting from epigenetic changes involving microRNA dysregulation and histone modifications, which in turn may promote the inflammatory phenotype in such cells.

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR.

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.