Faculty Bibliography

BACKGROUND/UNASSIGNED:Family history of substance use (FHSU), along with sociodemographic and psychosocial factors, has been identified as a key risk factor for adolescent substance use and progression to substance use disorders (SUD). However, the interaction between distinct sociodemographic and psychosocial profiles in adolescents with FHSU and constitutional factors, such as psychopathological symptom severity, impulsivity, and reward processing, remains unclear. Given the complexity of these factors, it is crucial to explore how these elements contribute to the differential vulnerability to SUD among youth with family history of substance use. Particularly as, the identification of clinically relevant subgroups of at-risk youth may inform precision prevention and treatment approaches to reduce adverse outcomes related to SUDs. METHODS/UNASSIGNED: = 4,369; female 48.33%, White 61.16%), respectively]. We used K-means clustering to identify latent subgroups in the FHSU-P population based on psychosocial variables and then compared the resulting subgroups on internalizing, externalizing, and total psychopathology, impulsivity, and reward prediction errors. RESULTS/UNASSIGNED: = 443) were characterized by lower engagement across peer, school, and parental domains. Group comparisons showed that Subgroups 1 and 2 had comparable levels of psychopathology and impulsivity, while Subgroups 3, 4, and 5 displayed higher psychopathology and impulsivity. Reward prediction errors were similar across all subgroups. Other group differences are also presented and discussed in the main text. CONCLUSION/UNASSIGNED:These findings highlight significant heterogeneity within the FHSU-P group and emphasize the importance of stratifying adolescents based on sociodemographic and psychosocial factors. Such stratification can help identify adolescents at higher risk for psychopathologies, including SUDs, offering insights for targeted prevention and intervention strategies.

Epigenetic clocks can serve as pivotal biomarkers linking environmental exposures with biological aging. However, research on the influence of environmental exposures on epigenetic aging has largely been limited to a small number of chemicals and specific populations. We harnessed data from the National Health and Nutrition Examination Survey 1999-2000 and 2001-2002 cycles to examine exposome-wide associations between environmental exposures and epigenetic aging. A total of 8 epigenetic aging biomarkers were obtained from whole blood in 2,346 participants ranging from 50-84 years of age. A total of 64 environmental exposures including phthalates, metals, pesticides, dioxins, and polychlorinated biphenyls (PCBs) were measured in blood and urine. Associations between log₂-transformed/standardized exposure measures and epigenetic age acceleration (EAA) were assessed using survey-weighted generalized linear regression. A 1 standard deviation (SD) increase in log₂ serum cadmium levels was associated with higher GrimAge acceleration (beta = 1.23 years, p = 3.63e-06), higher GrimAge2 acceleration (beta = 1.27 years, p = 1.62e-05), and higher DunedinPoAm (beta = 0.02, p = 2.34e-05). A 1 SD increase in log₂ serum cotinine levels was associated with higher GrimAge2 acceleration (beta = 1.40 years, p = 6.53e-04) and higher DunedinPoAm (beta = 0.03, p = 6.31e-04). Associations between cadmium and EAA across several clocks persisted in sensitivity models adjusted for serum cotinine levels, and other associations involving lead, dioxins, and PCBs were identified. Several environmental exposures are associated with epigenetic aging in a nationally representative US adult population, with particularly strong associations related to cadmium and cotinine across several epigenetic clocks.

BACKGROUND:Pregnancy is a crucial period to improve cardiovascular health (CVH) for mothers and their families. The current study emphasizes framework-guided factors that influence the adaptation of an evidence-based intervention (Parents as Teachers and Healthy Eating Active Living Taught at Home [PAT + HEALTH]) to support healthy gestational weight gain and postpartum weight management among pregnant women with obesity and their infants in Nigeria. METHODS:From May to June 2023, 43 in-depth interviews were conducted with 11 parents, 15 community health extension workers (CHEWs)/health educators, and 17 policymakers/ healthcare supervisors in the Federal Capital Territory, Nigeria. Additionally, nine focus groups were conducted with 75 participants. Interviews were recorded, de-identified, and transcribed. The updated Consolidated Framework for Implementation Research (CFIR 2.0) informed the development of the interview guides and the thematic analysis. Transcripts were double-coded using Dedoose. RESULTS:We identified assessing context, tailoring strategies, local attitudes, and sustainability as constructs to consider when adapting and implementing the PAT + HEALTH intervention successfully within the Nigerian primary care context. For example, policymakers and healthcare supervisors emphasized the feasibility of the intervention, including raising community awareness, planning for hard-to-reach areas, and ensuring supportive supervision of CHEWs delivering the intervention. Additional factors included customizing educational content and delivery methods to fit the cultural, socioeconomic, and environmental contexts of Nigerian families. CHEWs highlighted the importance of public education on locally available foods for better nutrition. Potential barriers to the PAT + HEALTH intervention included local attitudes influenced by sociocultural factors, such as food taboos, and structural factors, including limited financial support for the long-term sustainability of some components of the home visiting program. CONCLUSIONS:Building on these formative activities, the ENHANCE CVH trial will advance dissemination and implementation science by adapting, testing, and evaluating the effectiveness and implementation of the PAT + HEALTH intervention among pregnant women with obesity and their infants in Nigeria in a cluster randomized trial. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov/NCT06773299, Registration Date: January 14, 2025.

Epigenetic aging in early life remains poorly characterized, and patterns of gene expression can provide biologically meaningful insights. Blood DNA methylation was measured using the Illumina EPICv1.0 array and RNA sequencing was performed in blood in 174 adolescent participants (age range: 14-15 years) from the CHAMACOS cohort. Thirteen widely used epigenetic clocks were calculated, and their associations with transcriptome-wide RNA expression were tested using the limma-voom pipeline. We found evidence for substantial shared associations with RNA expression between different epigenetic clocks, including differential expression of MYO6 and ZBTB38 across five clocks. The epiTOC2, principal component (PC) PhenoAge, Hannum, PedBE and PC Hannum clocks were associated with differential expression of the highest number of RNAs, exhibiting associations with 22, 8, 5, 3, and 2 transcripts respectively. Generally, biological clocks were associated with differential expression of more genes than chronological clocks, and PC clocks were associated with differential expression of more genes relative to their CpG-trained counterparts. A total of 17 associations in our study were replicated in an independent adult sample (age range: 40-54 years). Our findings support the biological relevance of epigenetic clocks in adolescents and provide direction for selection of epigenetic ageing biomarkers in adolescent research.

BACKGROUND/UNASSIGNED:Despite the growing relevance of rural areas in the overdose crisis, research on rural people who inject drugs and their experiences with law enforcement remains limited. This research examines how rural policing and stigma uniquely shape the lives of people who inject drugs. METHODS/UNASSIGNED:Forty-one semi-structured qualitative interviews were conducted with people who inject drugs in southern Illinois. For this analysis, we focused on participants who mentioned police in response to the question, "Have you ever been treated differently because you used drugs?" RESULTS/UNASSIGNED:We identified three interrelated manifestations of stigma in rural people who inject drugs' interactions with police-verbal degradation and discrediting, unwarranted searches, and dehumanization-that align with Earnshaw's (2020) model distinguishing between stigma components (stereotypes, prejudice, discrimination) and health impact pathways. CONCLUSION/UNASSIGNED:This study emphasizes the impact of stigma on people who use drugs, particularly in their interactions with law enforcement.

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and infant mortality and morbidity worldwide. This prospective cohort study investigated the association of racial and ethnic disparities in HDP and explored the potential mediation effect of environmental chemical exposures on excess HDP risk among non-Hispanic Black pregnant people. A total of 3,279 pregnant people were included from 11 cohorts across the United States in the Environmental influences on Child Health Outcomes (ECHO) Program. We analyzed 20 environmental chemicals detected in over 70 % of biospecimens collected during pregnancy. Among Hispanic, non-Hispanic White, and non-Hispanic Black participants, 11.8 %, 10.8 %, and 16.6 % were diagnosed with HDP, respectively. Compared with non-Hispanic White participants, non-Hispanic Black participants had a higher risk of HDP (aRR = 1.48; 95 % CI 1.13-1.94) and higher levels of traditional phthalate metabolites, but lower levels of phthalate alternative metabolites and perfluorooctanoic acid. Hispanic participants had a lower risk of gestational hypertension (aRR = 0.62; 95 % CI 0.40-0.98) and lower levels of perfluoroalkyl substances than non-Hispanic White participants. Critically, despite these race/ethnicity-specific exposure patterns, individual chemical exposures did not mediate the association between racial/ethnic group and HDP. These findings highlight the need to investigate cumulative chemical mixtures and non-chemical environmental and social determinants as potential drivers of HDP disparities.

Reproductive aging, including timing of menarche and menopause, influences long-term morbidity and mortality in women, yet underlying biological mechanisms remain poorly understood. Using DNA methylation-based biomarkers, we assessed associations of age at menarche (N = 1,033) and menopause (N = 658) with epigenetic aging in a nationally representative sample of women ≥ 50 years. Later age at menopause was associated with lower GrimAge epigenetic age deviation (

BACKGROUND/UNASSIGNED:The ketamine landscape in the USA is rapidly shifting, especially given recent increases in off-label prescribing of ketamine as a psychiatric treatment. Research is needed to determine the extent to which illicit ketamine is available, nonmedically used, and associated with morbidity and mortality in the USA. METHODS/UNASSIGNED:This observational study used eight unique annual repeated cross-sectional datasets to examine illicit ketamine availability (using seizure data as a proxy), use, and consequences of use, including self-reported nonmedical use among noninstitutionalized individuals aged ≥12 years (2006-2014, 2015-2019, and 2021-2023) and among 12th grade students (2000-2023). Further, it assessed reported ketamine-related poisonings (1991-2023) and mortalities (2020-2023), diversion of undispensed pharmaceutical ketamine (2008-2024), drug seizures testing positive for ketamine (2001-2024), and the number and total weight of ketamine seizures from two additional law enforcement agencies (2017-2024 and 2019-2024). Piecewise linear regression models were used to estimate annual trends. FINDINGS/UNASSIGNED:Nonmedical ketamine use among individuals aged ≥12 years increased between 2021 (0.19%) and 2023 (0.34%) (b [slope] = 0.08 [SE = 0.001], p = 0.0072). Regarding reported poisonings, there was initial increase from 1994 to 2000 (from 0.17 to 1.40 per 1,000,000 population; b = 0.20 [SE = 0.02], p < 0.0001), a decrease through 2003 (0.58 per 1,000,000 population; b = -0.34 [SE = 0.08, p = 0.0002) and an increase from 2017 through 2023 (from 0.76 to 1.54 per 1,000,000 population; b = 0.12 [SE = 0.03], p = 0.0002). The number of reported diversions increased from 2008 (n = 23) to 2017 (n = 202) (b = 18.72 [SE = 2.20], p < 0.0001) and again from 2021 (n = 183) to 2024 (n = 286) (b = 39.00 [SE = 12.04], p < 0.0001). Regarding seizures, there was an increase in ketamine reports to one agency from 2015 (n = 1448) through 2024 (n = 4008) (b = 201.41 [SE = 57.83], p = 0.0023). In another source, there was an increase in seizures from 2022 (n = 247) through 2024 (n = 502) (b = 127.50 [SE = 10.40], p = 0.0003). Rates of ketamine-involved deaths did not significantly shift between 2020 and 2023. Nonmedical use declined among 12th grade students, first from 2000 (2.49%) through 2005 (1.61%) (b = -0.19 [SE = 0.06], p = 0.0039] and then again from 2005 through 2023 (0.9%) (b = -0.04 [SE = 0.01], p = 0.0019). INTERPRETATION/UNASSIGNED:Ketamine poisonings, pharmaceutical diversion, and seizures have increased; trends in nonmedical ketamine use vary. Prevention and harm reduction are needed as use and morbidity are expected to continue to increase. FUNDING/UNASSIGNED:National Institute on Drug Abuse at the National Institutes of Health.

Long-term exposure to ambient air pollution has been associated with epigenetic age acceleration (EAA) in adults, but its impact on children remains less understood. We analyzed data from 457 children (mean age: 7.9 years) in the Project Viva cohort (2007-2010, eastern Massachusetts, USA). We calculated the following EAAs from leukocytes: Horvath's epigenetic age acceleration (HorvathEAA), intrinsic epigenetic age acceleration (IEAA), and skin and blood epigenetic age acceleration (Skin&BloodEAA). We applied generalized additive models to evaluate associations of prior-365-day average and lifetime average exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), as well as the distance to major roadways, with EAA. Results indicated that each IQR increase (1.9 μg m-3) in the prior-365-day average of PM2.5 was associated with 0.26 years (95% CI, -0.49 to -0.03) lower HorvathEAA, although it did not survive multiple testing adjustment. Similar patterns but with wider CIs were observed for IEAA (-0.22; 95% CI, -0.44 to 0.01) and Skin&BloodEAA (-0.04; 95% CI, -0.19 to 0.11). No associations were observed of exposure to lifetime average PM2.5, prior-365-day or lifetime average NO2 or O3, or distance to major roadways with EAA. These findings suggest higher prior-365-day average PM2.5 exposure may relate to lower HorvathEAA in children.

OBJECTIVE:Early childhood advanced primary care models are promising ways of addressing child and family needs, but there is limited evidence to support short-term sustainability within current Medicaid payment structures. We evaluate claims-based outcomes associated with 3-2-1 IMPACT (IMPACT), an early childhood advanced primary care model, compared with the standard of care. METHODS:Using New York State Medicaid claims, we identified and matched children aged 1 to 35 months receiving care at 3 IMPACT sites and 3 comparison sites within a large public hospital system. Regression models were used to analyze use, expenditure, enrollment, and quality outcomes between groups. RESULTS:There were 6045 children at the treatment sites and 4832 matched children from the comparison sites. IMPACT was associated with a significant increase in 6 or more well-child visits and a decrease in emergency department visit rates. There was also a significant increase in 6 more well-child visits specifically for Black and Hispanic children seeking care at IMPACT sites compared with comparison sites. There were no significant differences in expenditures, other use types, or Medicaid enrollment across groups. CONCLUSION/CONCLUSIONS:An early childhood advanced primary care model that incorporates multiple evidence-based programs can show short-term, positive effects on preventative and acute care use and quality within Medicaid. These results highlight short-term strategies for sustainability while awaiting the long-term, cross-sector benefits expected from models like IMPACT. Future studies addressing additive model component effects and longer-term outcomes across mother-child dyadic and social-emotional outcomes are warranted.