Faculty Bibliography

CONTEXT/UNASSIGNED:Chemicals used in plastics have been described to contribute to disease and disability, but attributable fractions have not been quantified to assess specific contributions. Without this information, interventions proposed as part of the Global Plastics Treaty cannot be evaluated for potential benefits. OBJECTIVE/UNASSIGNED:To accurately inform the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity in the United States, we calculated the attributable disease burden and cost due to chemicals used in plastic materials in 2018. METHODS/UNASSIGNED:We first analyzed the existing literature to identify plastic-related fractions (PRF) of disease and disability for specific polybrominated diphenylethers (PBDE), phthalates, bisphenols, and polyfluoroalkyl substances and perfluoroalkyl substances (PFAS). We then updated previously published disease burden and cost estimates for these chemicals in the United States to 2018. By uniting these data, we computed estimates of attributable disease burden and costs due to plastics in the United States. RESULTS/UNASSIGNED:We identified PRFs of 97.5% for bisphenol A (96.25-98.75% for sensitivity analysis), 98% (96%-99%) for di-2-ethylhexylphthalate, 100% (71%-100%) for butyl phthalates and benzyl phthalates, 98% (97%-99%) for PBDE-47, and 93% (16%-96%) for PFAS. In total, we estimate $249 billion (sensitivity analysis: $226 billion-$289 billion) in plastic-attributable disease burden in 2018. The majority of these costs arose as a result of PBDE exposure, though $66.7 billion ($64.7 billion-67.3 billion) was due to phthalate exposure and $22.4 billion was due to PFAS exposure (sensitivity analysis: $3.85-$60.1 billion). CONCLUSION/UNASSIGNED:Plastics contribute substantially to disease and associated social costs in the United States, accounting for 1.22% of the gross domestic product. The costs of plastic pollution will continue to accumulate as long as exposures continue at current levels. Actions through the Global Plastics Treaty and other policy initiatives will reduce these costs in proportion to the actual reductions in chemical exposures achieved.

The aim was to investigate the concentrations of some per- and polyfluoroalkyl substances (PFAS) in patients with pancreatic cancer from New York, and to compare them with a group of controls from the general population of the United States. We selected 50 cases of pancreatic cancer from donors to the New York University Pancreatic Biorepository. Controls were selected from the 2017"“18 National Health and Examination Survey sample (n = 167), matched to cases on age, sex, and race and ethnicity. Six PFAS were analyzed in serum samples using high performance liquid chromatography in conjunction with mass spectrometry. PFAS concentrations were categorized into tertiles to explore non-linear associations, and odds ratios (OR) were estimated using conditional logistic regression, adjusting by BMI. Most PFAS were not associated with pancreatic cancer risk. Serum perfluorohexane sulfonic acid (PFHxS) was associated with a decreased risk (OR for upper tertile = 0.24, 95% CI: 0.09, 0.67). In contrast, participants with the highest tertile of perfluoroundecanoic acid (PFUnDA) had a higher risk (OR = 2.60, 95% CI: 1.11, 6.09). Adjusting for BMI did not materially change the results. Study limitations include: in pancreatic cancer patients, blood used to measure PFAS was collected around the time of diagnosis; cases and controls could not be sampled from the same geographic location; slightly different laboratory methods were used to analyze PFAS in cases and controls. Most PFAS studied were not significantly associated with pancreatic cancer, except for PFHxS and PFUnDA, which exhibited opposite trends. Findings and limitations of the present study warrant further investigation with improved study designs and data on complex PFAS mixtures.

IMPORTANCE/UNASSIGNED:Postpartum depression (PPD) affects up to 20% of childbearing individuals, and a significant limitation in reducing its morbidity is the difficulty in modifying established risk factors. Exposure to synthetic environmental chemicals found in plastics and personal care products, such as phenols, phthalates, and parabens, are potentially modifiable and plausibly linked to PPD and have yet to be explored. OBJECTIVE/UNASSIGNED:To evaluate associations of prenatal exposure to phenols, phthalates, parabens, and triclocarban with PPD symptoms. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This was a prospective cohort study from 5 US sites, conducted from 2006 to 2020, and included pooled data from 5 US birth cohorts from the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) consortium. Participants were pregnant individuals with data on urinary chemical concentrations (phenols, phthalate metabolites, parabens, or triclocarban) from at least 1 time point in pregnancy and self-reported postnatal depression screening assessment collected between 2 weeks and 12 months after delivery. Data were analyzed from February to May 2022. EXPOSURES/UNASSIGNED:Phenols (bisphenols and triclosan), phthalate metabolites, parabens, and triclocarban measured in prenatal urine samples. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Depression symptom scores were assessed using the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiologic Studies Depression Scale (CES-D), harmonized to the Patient-Reported Measurement Information System (PROMIS) Depression scale. Measures of dichotomous PPD were created using both sensitive (EPDS scores ≥10 and CES-D scores ≥16) and specific (EPDS scores ≥13 and CES-D scores ≥20) definitions. RESULTS/UNASSIGNED:Among the 2174 pregnant individuals eligible for analysis, nearly all (>99%) had detectable levels of several phthalate metabolites and parabens. PPD was assessed a mean (SD) of 3 (2.5) months after delivery, with 349 individuals (16.1%) and 170 individuals (7.8%) screening positive for PPD using the sensitive and specific definitions, respectively. Linear regression results of continuous PROMIS depression T scores showed no statistically significant associations with any chemical exposures. Models examining LMW and HMW phthalates and di (2-ethylhexyl) phthalate had estimates in the positive direction whereas all others were negative. A 1-unit increase in log-transformed LMW phthalates was associated with a 0.26-unit increase in the PROMIS depression T score (95% CI, -0.01 to 0.53; P = .06). This corresponded to an odds ratio (OR) of 1.08 (95% CI, 0.98-1.19) when modeling PPD as a dichotomous outcome and using the sensitive PPD definition. HMW phthalates were associated with increased odds of PPD (OR, 1.11; 95% CI, 1.00-1.23 and OR, 1.10; 95% CI, 0.96-1.27) for the sensitive and specific PPD definitions, respectively. Sensitivity analyses produced stronger results. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Phthalates, ubiquitous chemicals in the environment, may be associated with PPD and could serve as important modifiable targets for preventive interventions. Future studies are needed to confirm these observations.

Although efforts have been made to improve teacher professional development and ongoing supports, limited research has examined how early childhood education (ECE) teachers support each other informally. The present study describes how one type of informal support, collegial support (e.g. instrumental and expressive), enabled ECE teachers to cope with the first full school year during the COVID-19 pandemic. Through qualitative interviews, 14 kindergarten teachers shared the various ways they received and perceived collegial supports, and the system-level resources that enabled them to leverage their colleague"™s expertise and assistance. ECE teachers expressed how they cared for their own well-being and shared the desire to continue doing so in the future. Implications for low-cost and nimble teacher supports and professional development are discussed.

UNLABELLED:Metabolic effects of glucagon-like peptide 1 (GLP-1) receptor agonists are confounded by weight loss and not fully recapitulated by increasing endogenous GLP-1. We tested the hypothesis that GLP-1 receptor (GLP-1R) agonists exert weight loss-independent, GLP-1R-dependent effects that differ from effects of increasing endogenous GLP-1. Individuals with obesity and prediabetes were randomized to receive for 14 weeks the GLP-1R agonist liraglutide, a hypocaloric diet, or the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin. The GLP-1R antagonist exendin(9-39) and placebo were administered in a two-by-two crossover study during mixed-meal tests. Liraglutide and diet, but not sitagliptin, caused weight loss. Liraglutide improved insulin sensitivity measured by HOMA for insulin resistance (HOMA-IR), the updated HOMA model (HOMA2), and the Matsuda index after 2 weeks, prior to weight loss. Liraglutide decreased fasting and postprandial glucose levels, and decreased insulin, C-peptide, and fasting glucagon levels. In contrast, diet-induced weight loss improved insulin sensitivity by HOMA-IR and HOMA2, but not the Matsuda index, and did not decrease glucose levels. Sitagliptin increased endogenous GLP-1 and GIP values without altering insulin sensitivity or fasting glucose levels, but decreased postprandial glucose and glucagon levels. Notably, sitagliptin increased GIP without altering weight. Acute GLP-1R antagonism increased glucose levels in all groups, increased the Matsuda index and fasting glucagon level during liraglutide treatment, and increased endogenous GLP-1 values during liraglutide and sitagliptin treatments. Thus, liraglutide exerts rapid, weight loss-independent, GLP-1R-dependent effects on insulin sensitivity that are not achieved by increasing endogenous GLP-1. ARTICLE HIGHLIGHTS/UNASSIGNED:Metabolic benefits of glucagon-like peptide 1 (GLP-1) receptor agonists are confounded by weight loss and are not fully achieved by increasing endogenous GLP-1 through dipeptidyl peptidase 4 (DPP-4) inhibition. We investigated weight loss-independent, GLP-1 receptor (GLP-1R)-dependent metabolic effects of liraglutide versus a hypocaloric diet or the DPP-4 inhibitor sitagliptin. GLP-1R antagonism with exendin(9-39) was used to assess GLP-1R-dependent effects during mixed meals. Liraglutide improved insulin sensitivity and decreased fasting and postprandial glucose prior to weight loss, and these benefits were reversed by exendin(9-39). GLP-1R agonists exert rapid, weight loss-independent, GLP-1R-dependent effects on insulin sensitivity not achieved by increasing endogenous GLP-1.

Background: Transgender women of color in the US are disproportionately vulnerable to HIV risks. Pre-Exposure Prophylaxis (PrEP) has demonstrated effectiveness in preventing HIV transmission among transgender women of color. However, factors across multiple levels can hinder oral PrEP adherence. Methods: We analyzed the baseline data from The Trying to Understand Neighborhoods and Networks Among Transgender Women of Color (TURNNT) Cohort Study of women not living with HIV. We analyzed questionnaire responses to identify why participants stopped using PrEP and if they would consider taking it again. To identify multi-level determinants that were associated with PrEP discontinuation, we conducted bivariate analysis and created multivariable modified Poisson models comparing factors between former users and current users. Results: Among 140 transgender women of color included in this analysis, 44.3% were currently on PrEP, 25.0% were on formerly on the regimen, and 30.7% had never used it. Participants reported many reasons for discontinuing PrEP, notably, 22.9% reported being concerned about interactions with hormones. 60.0% reported that they were likely to take PrEP again in the future. Discontinuation was positively associated with history of sexual assault (Prevalence Ratio: 1.78; 95% CI: 1.01, 3.14) and negatively with having a primary care provider (PR: 0.43; 95% CI: 0.25, 0.73). Conclusion: Many factors can influence PrEP discontinuation among transgender women of color. A majority of those who discontinued PrEP were interested in restarting it again, indicating a potential for reengagement. We recommend a holistic approach to HIV prevention to reduce PrEP discontinuation.

OBJECTIVE:The COVID-19 pandemic disproportionately harmed Latino families; however, its effects on their stress and media routines remain understudied. We examined economic and parenting stress patterns during the COVID-19 pandemic and estimated associations between these forms of stress and nonadherence to American Academy of Pediatrics (AAP) infant media exposure recommendations among Latino families. We also explored how nonadherence with AAP recommendations varied with COVID-19 cases. METHODS:We analyzed baseline data from an ongoing clinical trial recruiting low-income Latino parent-infant dyads. Nonadherence with AAP media exposure recommendations (ScreenQ) and economic and parent stress were measured using parent reports. Additional variables included epidemiological data on COVID-19 cases. Linear models examined associations between the pandemic and both stress variables as well as between stress and ScreenQ. Using locally weighted scatterplot smoothing curve fitting, the rise and fall of NJ COVID-19 cases were overlayed with ScreenQ scores over time to visualize and explore trends. RESULTS:All parents identified as Latino (62.6% unemployed, 91.5% limited English proficiency). Mean infant age was 8.2 months. Parent stress increased over time during the COVID-19 pandemic (r = 0.13, p = 0.0369). After covariate adjustment, economic and parent stress were associated with increased nonadherence with AAP recommendations (standardized beta = 0.16, 95% confidence interval [CI], 0.03-0.29; standardized beta = 0.18, 95% CI, 0.04-0.31, respectively). Nonadherence to media exposure recommendations seemed to track with rises in the number of COVID-19 cases with a lag of 7 days. CONCLUSION/CONCLUSIONS:Parent and economic stress were associated with nonadherence to infant media exposure recommendations among Latino families. These findings highlight the need for practitioners to support families from under-resourced communities and to promote healthy media routines.

BACKGROUND:Eicosanoids are derivatives of polyunsaturated fatty acids (PUFAs) and participate in the inflammatory response as well as the maintenance of endothelial function. Specific eicosanoids have been linked to various diseases, including hypertension and asthma, and may also reduce renal blood flow. A systematic investigation of eicosanoid-related metabolites and adverse kidney outcomes could identify key mediators of kidney disease and inform ongoing work in drug development. METHODS:Profiling of eicosanoid-related metabolites was performed in 9,650 participants in the Atherosclerosis Risk in Communities (ARIC) Study (visit 2; mean age, 57 years). The associations between metabolite levels and the development of end-stage kidney disease (ESKD) was investigated using a series of progressively adjusted models and Cox proportional hazards regression (N= 256 events; median follow-up, 25.5 years). Metabolites with statistically significant associations with ESKD were evaluated for a potential causal role using bidirectional Mendelian randomization techniques, linking genetic instruments for eicosanoid levels to genome-wide association study summary statistics of estimated glomerular filtration rate (eGFR). RESULTS:The 223 eicosanoid-related metabolites that were profiled and passed QC were generally uncorrelated with eGFR in cross-sectional analyses (median Spearman correlation, -0.03; IQR -0.05 to 0.002). In models adjusted for multiple covariates, including baseline eGFR, three metabolites had statistically significant associations with ESKD (p-value <0.05/223). These included a hydroxyoctadecenoic acid, a dihydroxydocosapentaenoic acid, and arachidonic acid, with higher levels of the former two protective against ESKD and higher levels of arachidonic acid having a positive association with risk of ESKD. Mendelian randomization analyses suggested a causal role for the hydroxyoctadecenoic and arachidonic acid in determining eGFR. Spectral analysis identified the former metabolite as either 11-hydroxy-9-octadecenoic acid or 10-hydroxy-11-octadecenoic acid. CONCLUSIONS:High throughput eicosanoid profiling can identify metabolites that may play a protective role in the development of kidney disease.

PURPOSE/OBJECTIVE:Gender disparities among the senior echelons of academic medicine are striking and persistent. The role of medical school dean has been particularly immune to gender diversity, and limited prior research identified women's shorter decanal tenures as a potential driver. The authors assessed gender differences in tenure length of deanships in the current era to elucidate this finding. METHOD/METHODS:From October 2020 to June 2021, the authors collected information about medical school deanships that were held from January 1, 2006, to June 30, 2020. All schools were members of the Association of American Medical Colleges (AAMC). The authors collected data from online public records and augmented their findings via direct outreach to medical schools. They used time to event analyses before and after adjustment for interim vs permanent status of the initial appointment, school ownership (public/private), and school size to assess for gender differences in length of deanship tenure during the study period. The unit of analysis was deanships, and the primary outcome was length of deanships measured in years. RESULTS:Authors included data on 528 deanships. Women held 91 (17%) of these terms. Men held the majority of permanent deanships (n = 352 [85%]). A greater percentage of the deanships held by women were interim only (n = 27 [30%]) compared with men (n = 85 [20%]). In unadjusted and adjusted analyses, there were no significant gender differences in length of deanship tenures. CONCLUSIONS:Analysis of appointments of AAMC-member medical school deans from 2006 to 2020 revealed that women have remained in their deanships as long their male counterparts. The myth about women deans' shorter longevity should no longer be promulgated. Academic medicine should consider novel solutions to addressing women's persistent underrepresentation in the dean role, including employing the gender proportionality principle used in the business and legal communities.