Faculty Bibliography

Despite progress in many countries, air pollution, and especially fine particulate matter air pollution (PM_2.5) remains a global health threat: over 6 million premature cardiovascular and respiratory deaths/yr. have been attributed to household and outdoor air pollution. In this viewpoint, we identify present gaps in air pollution monitoring and regulation, and how they could be strengthened in future mitigation policies to more optimally reduce health impacts. We conclude that there is a need to move beyond simply regulating PM_2.5 particulate matter mass concentrations at central site stations. A greater emphasis is needed on: new portable and affordable technologies to measure personal exposures to particle mass; the consideration of a submicron (PM₁) mass air quality standard; and further evaluations of effects by particle composition and source. We emphasize the need to enable further studies on exposure-health relationships in underserved populations that are disproportionately impacted by air pollution, but not sufficiently represented in current studies.

INTRODUCTION/BACKGROUND:The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS:In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS:Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION/CONCLUSIONS:Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS/CONCLUSIONS:Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

BACKGROUND AND OBJECTIVES:Infant weight patterns predict subsequent weight outcomes. Rapid infant weight gain, defined as a >0.67 increase in weight-for-age z-score (WAZ) between two time points in infancy, increases obesity risk. Higher oxidative stress, an imbalance between antioxidants and reactive oxygen species, has been associated with low birthweight and paradoxically also with later obesity. We hypothesized that prenatal oxidative stress may also be associated with rapid infant weight gain, an early weight pattern associated with future obesity. METHODS:Within the NYU Children's Health and Environment Study prospective pregnancy cohort, we analyzed associations between prenatal lipid, protein, and DNA urinary oxidative stress biomarkers and infant weight data. Primary outcome was rapid infant weight gain (>0.67 increase in WAZ) between birth and later infancy at the 8 or 12 month visit. Secondary outcomes included: very rapid weight gain (>1.34 increase in WAZ), low (<2500 g) or high (≥4000 g) birthweight, and low (< -1 WAZ) or high (>1 WAZ) 12 month weight. RESULTS:Pregnant participants consented to the postnatal study (n = 541); 425 participants had weight data both at birth and in later infancy. In an adjusted binary model, prenatal 8-iso-PGF2α, a lipid oxidative stress biomarker, was associated with rapid infant weight gain (aOR 1.44; 95% CI: 1.16, 1.78, p = 0.001). In a multinomial model using ≤0.67 change in WAZ as a reference group, 8-iso-PGF2α was associated with rapid infant weight gain (defined as >0.67 but ≤1.34 WAZ; aOR 1.57, 95% CI: 1.19, 2.05, p = 0.001) and very rapid infant weight gain (defined as >1.34 WAZ; aOR 1.33; 95% CI: 1.02, 1.72, p < 0.05) Secondary analyses detected associations between 8-iso-PGF2α and low birthweight outcomes. CONCLUSIONS:We found an association between 8-iso-PGF2α, a lipid prenatal oxidative stress biomarker, and rapid infant weight gain, expanding our understanding of the developmental origins of obesity and cardiometabolic disease.

On September 7 and 8, 2022, Healthy Environment and Endocrine Disruptors Strategies, an Environmental Health Sciences program, convened a scientific workshop of relevant stakeholders involved in obesity, toxicology, or obesogen research to review the state of the science regarding the role of obesogenic chemicals that might be contributing to the obesity pandemic. The workshop's objectives were to examine the evidence supporting the hypothesis that obesogens contribute to the etiology of human obesity; to discuss opportunities for improved understanding, acceptance, and dissemination of obesogens as contributors to the obesity pandemic; and to consider the need for future research and potential mitigation strategies. This report details the discussions, key areas of agreement, and future opportunities to prevent obesity. The attendees agreed that environmental obesogens are real, significant, and a contributor at some degree to weight gain at the individual level and to the global obesity and metabolic disease pandemic at a societal level; moreover, it is at least, in theory, remediable.

BACKGROUND:Air pollution is a health risk in pregnant women and children. Despite the importance of refined exposure assessment, the characterisation of personalised air pollution exposure remains a challenge in paediatric and perinatal epidemiology. OBJECTIVE:We used portable personal air monitors to characterise personalised exposure to air pollutants in pregnant women. METHODS:), and volatile organic compounds (average use = 14 days). Data were stored in real-time on a secure database via synchronisation with a smartphone application. Of 497 women who agreed to use air monitors, 273 women (55%) were successful in using air monitors for longer than a day. For these participants, we identified daily patterns of exposure to air pollutants using functional principal component analysis (3827 days of air monitoring). RESULTS:had higher daily variations compared to PM. CONCLUSIONS:Small wearables are useful for the measurement of personalised air pollution exposure in birth cohorts and identify daily patterns that cannot be captured otherwise. Successful participation, however, depends on certain individual characteristics. Future studies should consider strategies in design and analysis to account for selective participation.

AIMS/HYPOTHESIS:The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population. METHODS:We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort. RESULTS:). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance. CONCLUSIONS/INTERPRETATION:Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores. DATA AVAILABILITY:Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).

Surveillance of e-cigarette use among different population groups is important for the timely implementation and evaluation of tobacco regulatory policies. In this review, we identified 13 nationally representative, repeatedly conducted epidemiologic surveys that assess e-cigarette use among U.S. youth and/or adults and have been instrumental in e-cigarette surveillance. These surveys included National Youth Tobacco Survey, Youth Risk Behavior Surveillance System, Monitoring the Future Survey, International Tobacco Control Policy Evaluation Project (ITC) Youth Tobacco and Vaping Survey, Behavioral Risk Factor Surveillance System, National Health Interview Survey, Tobacco Use Supplement of the Current Population Survey, Health Information National Trends Survey, Tobacco Products and Risk Perception Surveys, ITC Four Country Smoking and Vaping Survey, National Health and Nutrition Examination Survey, National Survey on Drug Use and Health, and Population Assessment of Tobacco and Health. These surveys vary in scope and detail, with their unique strengths and the regulatory questions that can be answered using each survey data. We also highlighted the gaps in these surveys and made recommendations for improvement.

BACKGROUND/UNASSIGNED:), biomarkers of the Alzheimer's form of dementia, are under consideration for clinical use. The associations of these peptides with circulating proteins may identify novel plasma biomarkers of dementia and inform peripheral factors influencing the levels of these peptides. METHODS/UNASSIGNED: = 4973), estimated the proportion of Aβ variance explained, and conducted enrichment analyses to characterize the proteins associated with the plasma Aβ peptides. RESULTS/UNASSIGNED:, respectively. Aβ42-associated proteins at midlife were found to be enriched in the liver, and those at late life were found to be enriched in the spleen. CONCLUSIONS/UNASSIGNED:This study identifies circulating proteins associated with plasma Aβ levels and incident dementia and informs peripheral factors associated with plasma Aβ levels.

BACKGROUND:The pathophysiological causes of kidney disease are not fully understood. Here we show that the integration of genome-wide genetic, transcriptomic, and proteomic association studies can nominate causal determinants of kidney function and damage. RESULTS:Through transcriptome-wide association studies (TWAS) in kidney cortex, kidney tubule, liver, and whole blood and proteome-wide association studies (PWAS) in plasma, we assess for effects of 12,893 genes and 1342 proteins on kidney filtration (glomerular filtration rate (GFR) estimated by creatinine; GFR estimated by cystatin C; and blood urea nitrogen) and kidney damage (albuminuria). We find 1561 associations distributed among 260 genomic regions that are supported as putatively causal. We then prioritize 153 of these genomic regions using additional colocalization analyses. Our genome-wide findings are supported by existing knowledge (animal models for MANBA, DACH1, SH3YL1, INHBB), exceed the underlying GWAS signals (28 region-trait combinations without significant GWAS hit), identify independent gene/protein-trait associations within the same genomic region (INHBC, SPRYD4), nominate tissues underlying the associations (tubule expression of NRBP1), and distinguish markers of kidney filtration from those with a role in creatinine and cystatin C metabolism. Furthermore, we follow up on members of the TGF-beta superfamily of proteins and find a prognostic value of INHBC for kidney disease progression even after adjustment for measured glomerular filtration rate (GFR). CONCLUSION:In summary, this study combines multimodal, genome-wide association studies to generate a catalog of putatively causal target genes and proteins relevant to kidney function and damage which can guide follow-up studies in physiology, basic science, and clinical medicine.

BACKGROUND/UNASSIGNED:Acute-care interventions that identify patients with substance use disorders (SUDs), initiate treatment, and link patients to community-based services, have proliferated in recent years. Yet, much is unknown about the specific strategies being used to support continuity of care from emergency department (ED) or inpatient hospital settings to community-based SUD treatment. In this scoping review, we synthesize the existing literature on patient transition interventions, and form an initial typology of reported strategies. METHODS/UNASSIGNED:We searched Pubmed, Embase, CINAHL and PsychINFO for peer-reviewed articles published between 2000-2021 that studied interventions linking SUD patients from ED or inpatient hospital settings to community-based SUD services. Eligible articles measured at least one post-discharge treatment outcome and included a description of the strategy used to promote linkage to community care. Detailed information was extracted on the components of the transition strategies and a thematic coding process was used to categorize strategies into a typology based on shared characteristics. Facilitators and barriers to transitions of care were synthesized using the Consolidated Framework for Implementation Research. RESULTS/UNASSIGNED:Forty-five articles met inclusion criteria. 62% included ED interventions and 44% inpatient interventions. The majority focused on patients with opioid (71%) followed by alcohol (31%) use disorder. The transition strategies reported across studies were heterogeneous and often not well described. An initial typology of ten transition strategies, including five pre- and five post-discharge transition strategies is proposed. The most common strategy was scheduling an appointment with a community-based treatment provider prior to discharge. A range of facilitators and barriers were described, which can inform efforts to improve hospital-to-community transitions of care. CONCLUSIONS/UNASSIGNED:Strategies to support transitions from acute-care to community-based SUD services, although critical for ensuring continuity of care, vary greatly across interventions and are inconsistently measured and described. More research is needed to classify SUD care transition strategies, understand their components, and explore which lead to the best patient outcomes.