Faculty Bibliography

Prior studies suggest fluoride exposure in drinking water above 1500 μg/L is associated with lower child cognition, but evidence is limited at lower exposure levels and in U.S. populations. We evaluated whether prenatal exposure to fluoride in regulated public drinking water was associated with cognition in a pooled U.S. cohort. We analyzed observational data from the Environmental influences on Child Health Outcomes (ECHO) Cohort, including 2514 children born 2006-2019 across 17 sites in 23 states. Individual prenatal time-weighted average public water fluoride concentrations were estimated by linking census tract-level concentrations to residential addresses across pregnancy. Fluid and crystallized cognition were assessed using NIH Toolbox scores. Generalized estimating equation models estimated adjusted mean differences using restricted cubic spline and linear change-point models. Individual prenatal time-weighted average water fluoride concentrations ranged from < 1.0-1940.0 μg/L (mean = 396.9 μg/L). Cubic spline models showed significant inverse associations for fluid cognition above 1107.0 μg/L. Linear change-point models identified 675 μg/L as the best-fitting change-point for fluid cognition; above this value, fluid scores were 0.67 points lower (95% CI, -0.92, -0.42) per 100 μg/L higher fluoride. These findings indicate that prenatal fluoride exposure in regulated public water is nonlinearly associated with lower fluid cognition scores in U.S. children at concentrations below current WHO and U.S. EPA thresholds.

Synthetic cathinones are a chemically diverse class of novel stimulants that continue to emerge in the U.S. and globally. Trends in overall and specific synthetic cathinone availability in the U.S. (as indicated by seizures) remain poorly characterized. We analyzed annual counts of reports submitted from 2010-2024 to the U.S. Drug Enforcement Administration's National Forensic Laboratory Information System (NFLIS). We grouped reports into chemical subclasses of beta-keto methylenedioxyamphetamines ("-ylones"), pyrrolidinophenones ("pyrros"), and beta-keto amphetamines ("-drones"). Temporal trends in total reports and subclasses were modeled using negative binomial regression spline models. To further contextualize subclass trends, we descriptively examined the contribution of individual synthetic cathinones over time. Between 2010 and 2024, 178,892 synthetic cathinone reports were submitted to NFLIS, of which 73.3% were classified as -ylones, 19.9% as pyrros, 5.2% as -drones, and 1.6% as other. 68.7% of total reports were from the South, with 33.5% from Florida. Nationally, total reports increased sharply in 2010-2013, declined mid-period, rose again from 2019-2020, and then stabilized. Additional regional and temporal heterogeneity was noted across subclasses. We identified patterns of rapid emergence and replacement of individual compounds within subclasses, particularly within the -ylone subclass. Overall, we found substantial temporal, regional, and subclass-specific variation in synthetic cathinone reports to NFLIS from 2010-2024, largely driven by reports from the South and from successive cycles of replacement of -ylones. These findings emphasize the need to strengthen forensic and epidemiological surveillance of the evolving synthetic cathinone landscape in the U.S.

BackgroundSubjective cognitive decline (SCD) is increasingly recognized in some cases as an early clinical stage in the Alzheimer's disease continuum, yet the factors that predict which individuals will progress to objective impairment remain poorly understood.ObjectiveWe evaluated risk factor differences and cognitive domain markers associated with progression in participants with subjective cognitive decline (SCD) at baseline from the NYU Alzheimer's Disease Research Center.MethodsWe included SCD non-decliners (n = 27), who remained stable, and decliners (n = 24), who progressed to mild cognitive impairment or worse, between the second to sixth yearly follow-up visits. Adjusted mixed-effects models examined group differences and associations between demographic, APOE status, psychometric test performance and comorbidities with longitudinal-decline.ResultsOverall, mean (SD) age was 67.4 (9.2) and total follow-up time was 5.1 (1.8) years. Lower education (14.9 (3.2) versus 17.3 (2.1)), Hispanic ethnicity (50.0% versus 11.0%), and hypercholesterolemia (adjusted odds ratio: 6.67) were risk factors for progression in SCD, p ≤ 0.05, whereas APOE status was not. Notably, SCD decliners were at increased risk for both amnestic and non-amnestic cognitive-decline with psychometric changes in memory, executive, and language domains (p < 0.001 for all).ConclusionsThese findings inform further work on SCD outcomes and related biomarkers, as well as preventive studies that target modifiable risk factors for SCD progression.

Type 2 diabetes (T2D) prevention efforts have largely focused on intervening when dysglycemia is already established. We propose that T2D prevention be reframed around prediabetes remission, with preservation and restoration of normoglycemia as the optimal clinical goal. The transition from normoglycemia through increasing dysglycemia to T2D is progressive and cumulatively shaped by biological, behavioral and environmental exposures across the life course. Prediabetes (intermediate hyperglycemia) remission is an achievable, pragmatic and measurable prevention target. Here we provide a life-course risk architecture for T2D integrating developmental, transitional and contextual determinants, defining critical windows of amplified metabolic vulnerability and potential restoration of normoglycemia. Precision prevention should target mechanistic heterogeneity, with aligned interventions that remain scalable, affordable and adaptable across socioeconomic settings. Our framework identifies ten priorities in T2D prevention, moving beyond traditional approaches toward context-specific, actionable interventions capable of altering the natural history of disease early in the life course and restoring metabolic health.

IMPORTANCE/UNASSIGNED:The Zoster Eye Disease Study (ZEDS) supports consideration of suppressive valacyclovir for 1 year to reduce risk of recurrent keratitis or iritis in patients with herpes zoster ophthalmicus (HZO). Although the primary outcome did not show benefit of suppressive valacyclovir treatment, secondary study outcomes showed treatment superiority at the 18-month end point and reduced number of multiple episodes of keratitis or iritis at both 12 and 18 months; however, it is unknown if these possible protective effects vary over time. OBJECTIVE/UNASSIGNED:To assess for temporal patterns of potential benefit of suppressive valacyclovir treatment to reduce risk of new or worsening stromal keratitis (SK), endothelial keratitis (EK), iritis (IR), or dendriform epithelial keratitis (DEK). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This is a post hoc exploratory analysis of a multicenter, double-masked, placebo-controlled randomized clinical trial conducted in 95 centers from November 2017 to January 2023. Immunocompetent, nonpregnant adults with history of HZO rash, documented active keratitis or IR within 1 year, and estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater were eligible. Data were analyzed from September 2025 through December 2025. INTERVENTION/UNASSIGNED:Twelve months of double-masked daily valacyclovir, 1000 mg, or placebo, with 6 months of observational follow-up. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was the time from randomization to first occurrence of new or worsening SK, EK, IR, or DEK. RESULTS/UNASSIGNED:A total of 651 participants consented and 527 were randomized (stratified by age at onset and chronicity), while 490 participants completed 12 months and 460 completed 18 months. Median (IQR) participant age was 60 years (50-68), and 266 of 527 patients (50.5%) were female. Cox proportional hazards and restricted mean survival time analyses of ZEDS data suggested greater benefit of valacyclovir over placebo in early treatment and observational periods. Time-varying Cox analyses showed lower hazards for valacyclovir during the treatment interval (hazard ratio [HR], 0.77; 95% CI, 0.56-1.05; P = .09) for 0 to 12 months and the observation interval (HR, 0.57; 95% CI, 0.27-1.18; P = .12) for more than 12 to 18 months, with lower hazard from 0 to 6 months (HR, 0.71; 95% CI, 0.49-1.01; P = .06) than from more than 6 to 12 months (HR, 0.99; 95% CI, 0.52-1.86; P = .97). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this post hoc exploratory analysis of the ZEDS randomized clinical trial, prophylactic valacyclovir decreased probability of subsequent zoster-related keratitis and IR, although statistical significance was not reached. Protective effects of valacyclovir prophylaxis were localized to early treatment and observation periods, supporting previously published recommendation of 1 year of prophylaxis. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03134196.

INTRODUCTION/UNASSIGNED:"Positive" outcomes such as flourishing and personal recovery are important predictors of physical health, mental illness, quality of life, and all-cause mortality. However, behavioral health outcome measures often emphasize symptom reduction, while overlooking "positive" outcomes. The objective of this study is to describe (1) the outcomes most important to individuals with major depressive disorder (MDD) and (2) "positive" outcomes and psychiatric symptoms in a real-world sample of young adults with MDD. MATERIALS AND METHODS/UNASSIGNED:Forty-three participants aged 18-35 with a diagnosis of MDD receiving outpatient behavioral health treatment in an urban safety-net psychiatry department completed online surveys identifying factors most important to recovery and standardized measures of flourishing, personal recovery, functioning, and symptoms of depression and anxiety. RESULTS/UNASSIGNED:Most participants (61.9%) had high symptoms of depression (Patient Health Questionnaire-8 (PHQ-8) ≥ 10), 16.7% were flourishing (Flourishing Scale ≥ 48), and 41.9% had high personal recovery (Brief INSPIRE-O ≥ 50). Factors ranked as "most important" for personal recovery included coping well with stressful events (39.5%), functioning well (34.9%), and having hopes and dreams for the future (30.2%). Notably, among individuals with low depressive symptoms, 60.0% reported low flourishing and 31.3% reported low personal recovery. CONCLUSIONS/UNASSIGNED:Individuals with MDD value a diverse range of outcomes, and exhibit a large variation in levels of depressive symptoms and characteristics of "positive" mental health. Aligning outcome tracking with patient-defined goals may provide a more comprehensive understanding of overall mental health.

BACKGROUND:We investigated whether OPE urinary concentrations during pregnancy were associated with child's autism-related outcomes. METHODS:We included 4159 mother-child pairs from 15 cohorts in the NIH Environmental influences on Child Health Outcomes (ECHO) Consortium, with children born from 2006-2020 (median age [interquartile range]: 6 [4,10] years). Nine OPE biomarkers were measured in urine samples collected mid- to late pregnancy. Dilution-adjusted biomarkers were modeled continuously, categorically (high [>median], moderate [≤median], nondetect), or as detect/nondetect depending on their detection frequency. We assessed child autism-related traits via a) parent report on the Social Responsiveness Scale (SRS) and b) clinical autism diagnosis. We examined associations of OPEs with child outcomes, including modification by child sex, using generalized estimating equations to account for clustering by ECHO cohort. RESULTS:Compared with nondetectable concentrations, high exposure to bis-(butoxyethyl) phosphate (BBOEP) was associated with higher autistic trait scores (adj-β 0.97, 95% confidence interval [CI]: 0.42, 1.52) and greater odds of autism diagnosis (adjusted odds ratio [adj-OR]: 1.27, 95% CI: 1.07, 1.50). Bis-(1-chloro-2-propyl) phosphate (BCPP) showed associations with autistic trait scores (BCPP adj-β for high exposure vs nondetect: 0.34, 95% CI: -0.46, 1.13; BCPP adj-β for moderate exposure vs nondetect: 0.72, 95% CI: 0.24, 1.20). High exposure to bis-(2-chloroethyl) phosphate (BCETP) was associated with lower odds of autism diagnosis (adj-OR: 0.76, 95% CI: 0.60, 0.95). Other OPEs showed no associations in adjusted models. Associations between BBOEP and higher autistic trait scores were stronger in males than females. DISCUSSION:Prenatal exposure to OPEs, specifically BCPP and BBOEP, may be associated with a higher risk of autism diagnosis and related traits in childhood.

Genome-wide association studies identify cancer susceptibility loci, but downstream protein mechanisms remain incompletely defined. We integrate polygenic risk scores (PRSs) for 21 cancers with 4,955 plasma proteins measured in cancer-free Atherosclerosis Risk in Communities (ARIC) participants to prioritize cancer-related proteins and protein networks. The protein quantitative trait score (pQTS) approach assesses associations between cancer PRS and individual protein levels, while ARCHIE partitions cancer risk variants into trans-regulated protein-network components using sparse canonical correlation analysis. Across cancers, pQTS identifies 90 protein associations, including 53 distal trans associations, and ARCHIE identifies 19 components spanning 433 proteins. Downstream analyses connect prioritized proteins to cancer driver genes, somatic alterations, immune cell populations, CRISPR dependency, and cancer-relevant pathways. Cervical cancer and basal cell carcinoma illustrate immune, human papillomavirus (HPV)-related, pigmentation, and inflammatory mechanisms. These findings show that PRS-proteome integration can reveal circulating protein networks underlying inherited cancer susceptibility.