Faculty Bibliography

The exponential rise in plastic production has driven widespread contamination by micro- and nanoplastics (MNPs) in the environment. These plastic particles and their chemical additives have been detected in water sources, human bodily fluids, and reproductive tissues. With global fertility rates declining, their role as potential contributors is under investigation. This scoping review compares findings from in vitro experiments, in vivo studies across animal models, and epidemiological data to assess potential reproductive hazards associated with MNP exposure. Forty original studies published within the last decade were identified. MNPs have been detected in human breast milk, placenta, endometrium, ovaries, testis, semen, follicular fluid, blood, and urine samples. Humans are estimated to absorb 74,000-121,000 particles annually through inhalation, ingestion, skin contact, and use of plastic materials, including medical devices. Experimental evidence demonstrates that MNPs can cross biological barriers, interact with cells, and disrupt cellular pathways, including steroidogenesis, energy metabolism, inflammatory pathways, and oxidative stress. Thirty in vivo animal studies have associated MNPs with altered reproductive endpoints in both males (i.e., altered semen quality and spermatogenesis) and females (i.e., altered folliculogenesis, depleted ovarian reserve, and reduced litter sizes), with possible transgenerational effects. In conclusion, current evidence suggests MNPs may represent a reproductive health hazard to humans and animals. The relative contributions of particle toxicity and their chemical additives remain difficult to disentangle. Overall, plastics and their associated chemicals represent a serious health and environmental concern, which continues to grow in the absence of restrictions and international agreements.

BACKGROUND:Community-clinical linkage models (CCLM) display significant potential to address the unique, multi-level type 2 diabetes risk factors facing minoritized communities, such as South Asian Americans. However, there lacks a systematic, longitudinal evaluation of how such tailored CCLMs can be better implemented in dynamic, real-world settings. This study aims to leverage multi-partner insights, collected in real time, to explore the barriers and facilitators to implement a South Asian American diabetes management and prevention intervention (the DREAM intervention). METHODS:The DREAM intervention, a two-arm randomized controlled trial, was implemented from 2019-2022; partners involved in its implementation were interviewed annually to understand their experiences of the program. Implementation partners included community health workers (CHWs), participating healthcare providers, community advisory board (CAB) partners, and research staff. The interview guide and subsequent deductive qualitative analysis was informed by the Consolidated Framework for Implementation Research (CFIR). RESULTS:Overall, 78 interviews were conducted across four waves (2019-2022) with 5 research staff, 8 CHWs, 18 providers/clinic staff, and 12 CAB partners. CHWs adapted intervention characteristics by tailoring curriculum and implementation to patient needs, including personalized goal setting and shifting to remote delivery with COVID-19-related content. At the individual level, participants' occupations, family dynamics, and technological capacity shaped engagement, while changing social, financial, and health contexts over time required CHWs to continually adjust support. Within the inner setting, partner roles and resource availability fluctuated, yet structured and consistent meetings facilitated communication and problem-solving. Outer setting influences, including shifting government and universities policies and the COVID-19 pandemic, required repeated adaptations, while CAB partnerships expanded community connections and services over time. Process-related findings underscored the evolving role of CHWs and research staff in planning and fidelity, with training shifting toward peer mentorship to build capacity. CONCLUSION/CONCLUSIONS:Findings revealed the pivotal role of programmatic adaptability and robust partner engagement in navigating dynamic contexts to support the diabetes needs of minoritized communities. The real-time, longitudinal approach taken for data collection and analysis was crucial in understanding how intervention changes were implemented and experienced, providing a model for similar implementation assessments.

PURPOSE/OBJECTIVE:Many studies estimate that more than 50% of non-hospitalized patients with long-COVID develop moderate to severe autonomic dysfunction. However, the specific impact of autonomic dysfunction as it relates to quality of life in long-COVID is not fully understood. The aim of the current study is to assess autonomic symptoms and quality-of-life in patients with Post-Acute Sequelae of COVID-19 (PASC) recruited from a neurology department outpatient setting. METHODOLOGY/METHODS:In a two-year follow-up study of a baseline cohort of 93 non-hospitalized SARS-CoV-2 laboratory-positive patients evaluated for PASC between November 2020-August 2021, 44 participants completed follow-up telephone questionnaires examining quality-of-life as well as neurologic and autonomic symptoms. RESULTS:Among 93 participants, 44 (47 %) completed the two-year follow-up evaluation and 27 (61 %) were female with a median age of 55 years (IQR = 24-88). Most participants (95 %, 42/44) were vaccinated against COVID-19 and 43 % (19/44) had a pre-existing neurological disorder. Median time from index COVID-19 infection to follow-up was 26 months (IQR = 23-17), with a median of 15 months (IQR = 15-16) between visits. Fatigue, word finding difficulty, and changes in memory were the most commonly reported PASC symptoms. Sixty-six percent (29/44) of individuals met criteria for autonomic dysfunction as defined by the Composite Autonomic Symptom Score-31 (COMPASS-31) scale. Secretomotor and gastrointestinal subdomains demonstrated significant associations with Neuro-QoL metrics for Anxiety, Depression, and Fatigue. For every 1 additional PASC symptom reported at a follow-up study visit, there was an average increase of 1.5 points on the COMPASS-31 composite score. In addition, visual disturbances and sleep impairment were both associated with increased autonomic dysfunction. CONCLUSION/CONCLUSIONS:The strong association between autonomic dysfunction and reduced QoL in PASC and the relation to insomnia, visual dysfunction, and functional impairment are valuable findings, reinforcing the clinical impact of these symptoms longitudinally after index COVID-19 infection.

Phenolic compounds may be harmful to the developing fetus, but many have not been studied in-depth for adverse childhood allergic and respiratory health effects. We hypothesized that higher levels of phenolic compounds in prenatal spot urine would be associated with greater odds of childhood atopic dermatitis, allergic rhinitis, and asthma, and that child sex may modify these associations. 3198 mother-child paired cases were enrolled from 16 cohorts in the U.S. ECHO consortium. Fifteen phenols (e.g. benzophenones, parabens, bisphenols, triclosans) were measured from mother's urine during pregnancy using a multi-class chemical panel. Childhood outcomes included parent-reported atopic dermatitis (1466 mother-child pairs) between ages 0-3 years, and allergic rhinitis (901 mother-child pairs) and asthma (1662 mother-child pairs) between ages 5-9 years. Prenatal parabens were associated with increased odds of atopic dermatitis (odds ratio (OR) 1.13, 95 % confidence intervals (CI) 1.02, 1.26). Benzophenones were associated with lower odds of asthma (OR 0.77, CI 0.66, 0.90). Compared to boys, girls demonstrated higher odds of parabens (1.21, CI 1.04, 1.42), benzophenones (1.18, CI 1.00, 1.38) and bisphenol S (1.21, CI 1.03, 1.43) being associated with atopic dermatitis, and of the benzophenones (1.46, CI 1.11, 1.93) being associated with allergic rhinitis. An association of benzophenones (0.66, CI 0.53, 0.83) with lower odds of asthma was stronger among boys. These findings suggest that prenatal paraben and other phenol exposures may adversely affect early-life allergic and respiratory outcomes, with sex-specific vulnerability. Novel, multi-modality approaches to reduce maternal phenol exposure during pregnancy are urgently needed to protect children's health.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Vascular dysfunction contributes to Alzheimer disease (AD) and related dementias (ADRDs), but the underlying mechanisms remain unclear. Previous studies link midlife hemostasis and platelet aggregation measures to late-life dementia risk. We aimed to determine whether platelet aggregation in midlife is associated with imaging markers of AD pathology. METHODS:F-flortaucipir) PET uptake in dementia-free, middle-aged adults from the Framingham Heart Study. Co-primary outcomes included amyloid and tau uptake in AD-vulnerable regions. We also examined an MRI-based cortical thickness signature of AD risk as a secondary outcome. We used multivariable regression models adjusted for demographic and clinical factors, considering potential nonlinear associations. RESULTS:< 0.035), consistent with a neurodegenerative pattern. DISCUSSION/CONCLUSIONS:Our findings indicate that platelet aggregation is linked to PET and MRI markers of AD pathology as early as midlife. These findings support further investigation of platelet-mediated mechanisms in AD pathogenesis.

Amid the ongoing overdose crisis, U.S. lawmakers are considering policy reforms that could significantly change availability and accessibility of methadone treatment (MT) for opioid use disorder (OUD). However, uncertainty remains about which potential changes will lead to the greatest health benefits while minimizing unintended harms. In this protocol, we describe a planned NIH-funded study (R21DA061660) to simulate alternative MT delivery scenarios currently being considered in U.S. policy discussions, and estimate their impact on population-level rates of treatment initiation and retention and opioid overdose across different sociodemographic groups. We will use an agent-based model focused on 16 counties in NY State to simulate two alternative policy scenarios compared to the current status quo of opioid-treatment program (OTP) delivered MT: 1) office-based prescribing by addiction-certified providers with pharmacy and OTP dispensing; and 2) office-based prescribing by general practitioners with pharmacy and OTP dispensing. Agents will represent individuals with OUD and we will simulate access to MT based on alternative policy scenarios (e.g., locations of existing OTPs vs. provider offices and pharmacies). Probabilities of treatment initiation, retention, and opioid overdose will be informed by estimates from the scientific literature and administrative datasets from NY State. Multiple implementation scenarios will be considered to account for potential variation in adoption of office-based methadone by patients, providers, and pharmacies. To ensure relevance to directly impacted communities and policy makers, the study involves a collaboration between academic researchers and NY State government partners and relies on input from an Expert Advisory Board of people with lived and living experience with methadone, addiction medicine, and policy experts. Findings will be disseminated via a public dashboard. This study will inform ongoing policy discussions and shed light on the potential of researcher-policy partnerships to promote evidence-based policies that can reduce overdose and improve population health.

BACKGROUND:Glucagon-like peptide-1 receptor agonists (GLP1RA) provide survival benefits in people with diabetes, including kidney transplant (KT) recipients with pre-existing diabetes. Post-transplant diabetes mellitus (PTDM) is common, but the benefits of GLP1RAs remain undefined in this population. We aim to describe current usage practices and outcomes in PTDM. METHODS:We used USRDS and Medicare claims data (2013-2022) to conduct a drug utilization profile of GLP1RA among 7681 first-time adult KT recipients with PTDM. We used survival analysis to estimate GLP1RA initiation incidence and associated patient, graft, and safety outcomes. RESULTS:A total of 430 adult KT recipients with PTDM were prescribed GLP1RA. Dulaglutide was the most commonly prescribed medication (46.1%). The 5-year cumulative incidence of GLP-1 receptor agonists prescription was 9.8%. Median (interquartile range) time from PTDM diagnosis to first prescription was 1.7 (0.6, 3.4) years. GLP1RA use was not associated with a difference in the risk of mortality or graft failure but was associated with a 1.80-fold (95% confidence interval [CI]: 1.11-2.91) increased risk of diabetic retinopathy. No increased risk of pancreatitis, biliary complications, or medullary thyroid cancer were identified. CONCLUSIONS:GLP1RA use in KT recipients with PTDM was not associated with graft or patient survival, though longer follow-up is necessary. GLP1RA use was associated with an increased risk of diabetic retinopathy, and care should be taken when initiating these agents.

BACKGROUND/OBJECTIVES/OBJECTIVE:Approximately half of male cancer survivors experience infertility following cancer treatment, which can lead to psychosocial distress. The aim of this study was to identify support needs and reflections on the decision-making process related to sperm banking among adolescent male cancer survivors and their caregivers at 1 year post-diagnosis. METHODS:As part of a randomized controlled trial testing a family-centered sperm banking decision-making intervention, males diagnosed with cancer (12-25 years old) and their caregivers completed semi-structured interviews 1 year post-diagnosis. Thematic analysis was conducted by three independent coders (κ = 0.80) and focused on two interview questions: (1) Is there anything you wish you would have known or done before making the [sperm banking] decision? and (2) What information or support do you think is needed regarding your/your son's future fertility goals? RESULTS:Qualitative interviews with adolescents (n = 20) and caregivers (n = 18) revealed three primary themes: (1) satisfaction with information received at diagnosis, but retrospective desire for more decision-making time; (2) current desire for additional fertility-related support; (3) potential need for future fertility-related support. CONCLUSION/CONCLUSIONS:Despite satisfaction with the oncofertility consultation at diagnosis, clinical teams should prioritize fertility education moving forward and allow additional time for sperm banking decision-making (when possible) at diagnosis. Counseling gaps can lead to uncertainty, unplanned pregnancies, and adverse mental health outcomes. Thus, it is important to revisit issues surrounding fertility and family planning after treatment, particularly among adolescents transitioning to adulthood.

BACKGROUND:Child and adolescent labor intensity, including the number of working hours and tasks performed, is both a cause and consequence of functional difficulties in children, particularly in low- and middle-income countries (LMICs) where the prevalence of these difficulties is not well understood. OBJECTIVE:This study aimed to determine the prevalence of functional difficulties among child laborers and explore the association between labor intensity and these difficulties. PARTICIPANTS AND SETTING/METHODS:We analyzed data from 344,721 children aged 5 to 17 years from recent Multiple Indicator Cluster Surveys conducted in 36 mostly LMICs. METHODS:Logistic regression models were used to estimate odds ratios for the association between child labor intensity and functional difficulties. RESULTS:The overall prevalence of functional difficulties was 18.1 % (95 % CI: 18.0-18.2), with notable country variations-ranging from 2.9 % in Belarus and Montenegro to 41.9 % in Roma Settlements, North Macedonia. Major risk factors for functional difficulties included living in urban areas, lower education, lower wealth, residing in West & Central Africa, performing income-related work, and engaging in tasks like carrying heavy loads or fetching water. Protective factors included younger age, fewer working hours, and residing in Europe & Central Asia. CONCLUSION/CONCLUSIONS:The study highlights that UNICEF's indicators of child labor intensity are closely associated with functional difficulties. Global strategies to reduce child labor should focus on improving child and caregiver education, early identification, and treatment of functional difficulties, with particular emphasis on LMICs.