Faculty Bibliography

BACKGROUND:Germline genetic variants are important for prostate cancer (PCa) management and hereditary cancer risk assessment, but testing is underused. Furthermore, patients are often unaware of the genetic connections to PCa. Social media is increasingly serving as a source of awareness for health information and a method to gather data from a large population. OBJECTIVE:There were three objectives: to (1) create and test social media messages related to PCa genetics and genetic testing, (2) determine which social media message was most engaging, and (3) assess knowledge of and attitudes toward PCa genetic testing through an online survey using the most engaging social media message. METHODS:A paid social media campaign was developed to disseminate targeted messages about PCa and genetics. We tested combinations of 8 images and 8 messages that were created or selected by the research team and reviewed by a study-specific advisory board. We targeted men and women older than 35 years living in the United States. The campaign was launched on Facebook for 6 days (June 3-8, 2023). We tracked the reach and impressions of each post. The survey, administered directly after someone viewed a post, assessed knowledge about PCa and cancer genetics as well as beliefs about cancer risk and genetic testing. Descriptive and multivariable analyses were used to analyze survey data. RESULTS:Most posts were viewed by women (13,675/16,224, 84.3% of impressions) and people over the age of 55 years (19,997/22,906, 87.3% of impressions). The 2 most engaging images were a group of men of different races and ethnicities (reach: 28,151 people; impressions: 33,727 views), followed by a Hispanic family (reach: 16,026 people; impressions: 20,113 views). The following message had the most engagement: "Breast cancer and prostate cancer may be related because they can arise from the same gene mutation in a family" (reach: 58,980 people; impressions: 74,834 views). A total of 875 people (n=796, 91% male; mean age 43.42, SD 14.1 years; n=224, 25.6% Black or African American individuals; n=255, 29.1% Hispanic individuals) completed the survey. In total, 75.2% (658/875) strongly or somewhat agreed that genetics play a role in the development of PCa, and 84% (735/875) would want to know if they had a genetic predisposition to PCa. CONCLUSIONS:It is feasible to use social media platforms to test and disseminate messages that raise awareness about PCa genetics and the connection with other cancers (eg, breast cancer), as well as to deploy surveys that reach a wide audience.

Exposure to organophosphate pesticides (OPPs) has been linked to adverse birth outcomes, including low birthweight. Maternal biomarkers are commonly used as proxies for fetal exposure, but fetal exposure also depends on placental transport mechanisms. In 240 mother-newborn pairs, we explored how genetic variation in membrane transporters influences the association between maternal OPP concentrations and birthweight. Single nucleotide polymorphisms (SNPs) in the OAT4/SLC22A11 and OATP2B1/SLCO2B1 membrane transporters modified the relationship between OPP exposure and birthweight-for-gestational age, with significant inverse associations observed only among individuals with variant transporter genotypes. In this small study, we found that transporter genotype may influence the placental disposition of environmental chemicals and perinatal susceptibility to toxicity.

BACKGROUND:The nasal microbiome is directly in contact with the external environment and may play a role in respiratory health. This study aimed to evaluate the association of the nasal microbiome with air pollutants, meteorological conditions, and respiratory health in adolescents. METHODS:, temperature, humidity, residential greenness) and respiratory outcomes (asthma, hay fever, wheezing, IgE, aeroallergen sensitization, FeNO, lung function) through regression models adjusted for confounders and corrected using a false discovery rate (FDR) < 5%. RESULTS:, temperature) and respiratory outcomes (hay fever, wheezing, IgE, FeNO, lung function) (FDR < 0.05). Staphylococcus, Corynebacterium, Pelomonas, Lactococcus, Lachnospiraceae (unclassified), and Faecalibacterium abundance were associated with both environmental exposures and respiratory traits. CONCLUSIONS:, and temperature exposure. Multiple short-to-medium-term environmental exposures and respiratory outcomes were associated with nasotypes and bacterial genera abundance in adolescents.

INTRODUCTION/BACKGROUND:The impact of maternal SARS-CoV-2 infection on fetal brain development during pregnancy remains unclear. Prior research has associated other antenatal infections with adverse neurodevelopmental outcomes in offspring. OBJECTIVE:To compare neurodevelopmental outcomes in infants born to mothers infected with SARS-CoV-2 during pregnancy (COVID+) to infants without congenital exposure (COVID-). METHODS:This study included 77 COVID+ infants and 157 COVID- infants assessed at 6 and/or 12 months. Outcomes were based on maternal self-report, observed infant behavior and brain fMRI. RESULTS:Overall, COVID+ and COVID- infant groups showed no significant differences across a range of neurobehavioral measures. However, analyses not adjusted for multiple comparisons revealed differences: fewer night awakenings at 6 (t(154) = 2.24, p < 0.03) and 12 months (t(107) = 1.94, p < 0.05), and reduced duration of orienting at 12 months (t(55.38) = 2.15, p < 0.04) in COVID+ infants. Neural differences were noted in posterior-anterior midline, insular-frontal, insular-posterior cingulate, and frontal-cingulate regions at an uncorrected threshold of p < 0.01. CONCLUSION/CONCLUSIONS:This study of multi-level infant development suggests that infants born to mothers infected with COVID during pregnancy are not experiencing harmful effects of that exposure. IMPACT/CONCLUSIONS:This study contributes comprehensive data on infant neurodevelopmental outcomes following prenatal SARS-CoV-2 exposure, evaluating a wide range of behavioral and neural measures to address gaps in previous research. Findings suggest that congenital exposure to SARS-CoV-2 does not result in significant neurodevelopmental impairments in infants, offering reassurance amidst concerns about potential long-term effects of maternal prenatal COVID-19 infection. Results indicate that any observed differences, such as fewer night awakenings and functional neural connectivity patterns, may reflect a more mature developmental profile in the exposed group. Continued longitudinal research is necessary to understand behaviorally relevant and lasting neurodevelopmental effects of prenatal SARS-CoV-2 exposure.

The U.S. Drug Enforcement Administration (DEA) proposed a rule in which they intend to place the psychedelic phenethylamines 2,5-dimethoxy-4-chloroamphetamine (DOC) and 2,5-dimethoxy-4-iodoamphetamine (DOI) into Schedule I of the Controlled Substances Act. We examined the epidemiology of use and availability of these substances. We examined national trends in seizures of these compounds (which indicate availability) using DEA National Forensic Laboratory Information System (NFLIS) and High Intensity Drug Trafficking Areas (HIDTA) data. We also examined the prevalence of self-reported use on the National Survey of Drug Use and Health (NSDUH), a nationally representative sample of noninstitutionalized individuals aged ≥12 in the United States. The scientific literature was also systematically searched for reports of poisonings linked to use. Between 2005 and 2024, NFLIS received 795 submissions of drugs testing positive for DOC, with a peak of 152 in 2012. There was then a decrease through 2024, with only two submissions containing DOC in 2023-2024. Forty submissions contained DOI, with no submissions testing positive in 2019-2024. Three DOC seizures were recorded by HIDTA in 2017-2021, with none in 2022-2024. HIDTA had no recorded seizures of DOI. Between 2005 and 2023, there were 37 and 10 type-in mentions of lifetime DOC and DOI use, respectively, in NSDUH responses, suggesting a lifetime prevalence of < 0.01% among the noninstitutionalized U.S. population. We located three reports of poisonings linked to DOC use (in 2008-2024) and none linked to DOI use. Availability, recreational use, and poisoning related to the use of DOC and especially DOI appear to be rare.

BACKGROUND:Epigenetic modifications linked to biological aging, like DNA methylation (DNAm), may serve as biomarkers for future cardiometabolic disease risk. However, existing studies have focused on older adults, overlooking the early-life origins of cardiometabolic health. METHODS:Among 378 participants from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study, we measured DNAm repeatedly from birth to age 18 years to calculate 4 epigenetic aging (EA) biomarkers: Horvath, Skin & Blood, Intrinsic epigenetic age, and DNAm Telomere Length (DNAmTL). We then developed a novel measure of cumulative EA spanning from birth to age 18 years. Using multinomial logistic and multivariable linear regression models, we examined associations between cumulative EA and several indicators of cardiometabolic health at 18 years. RESULTS:We observed an increased risk of obesity with an interquartile range increase in cumulative EA by Horvath (relative risk [RR], 2.61 [95% CI, 1.79-3.80]), Skin & Blood (RR, 2.76 [95% CI, 1.89-4.03]), and Intrinsic epigenetic age (RR, 1.61 [95% CI, 1.11-2.34]), whereas DNAm TL decreased obesity risk (RR, 0.32 [95% CI, 0.22 -0.45]). Similarly, cumulative EA was associated with higher body mass index, waist circumference, body fat percentage, systolic blood pressure, mean arterial pressure, and resting pulse/heart rate at age 18 years. CONCLUSIONS:Cumulative EA throughout childhood predicts young adult cardiometabolic health and may signal increased risk for later cardiometabolic disease, highlighting the value of life-course epigenetic clocks as biomarkers for early-life health interventions.

BACKGROUND:Cardiovascular disease is the most common cause of morbidity and mortality in kidney transplant recipients. Screening for coronary disease is frequently required prior to kidney transplantation, but coronary intervention has not been shown to be beneficial except in complex coronary artery disease. The likelihood of finding significant coronary artery disease and the benefits of routine pre-transplant screening are uncertain. METHODS:We performed a systematic review and meta-analysis. Medline & Embase were searched to identify manuscripts published between 1998 and 2024 reporting the results of pre-transplant screening. The primary endpoints were the frequency of detecting significant coronary lesions for which there are AHA class 1 indications for revascularization: a) >50% left main stenosis; or b) multi-vessel disease with ejection fraction < 35% during pre-kidney transplant screening. Secondary endpoints included frequency of detecting multivessel disease, proximal left anterior descending artery (LAD) disease, and number of patients who underwent invasive coronary angiography. Meta-regression was used to explore outcome heterogeneity according to the presence of hypertension, diabetes, and age. RESULTS:We identified 1273 studies out of which 44 met eligibility criteria. The mean prevalence of class 1 indications was 2%, although the heterogeneity was high with estimates ranging from 0% to 17%. Estimated prevalence of proximal LAD disease was 2% and left main stenosis was 1%, whereas 10% of patients had multi-vessel coronary artery disease, and 35% were referred for invasive angiography. There was no evidence of significant heterogeneity according to sex of the population or prevalence of diabetes or hypertension. CONCLUSIONS:Identification of class I indications for revascularization during pre-transplant coronary screening was rare.

Estimating causal effects in the presence of spillover among individuals within a social network poses challenges due to missing information. Spillover effects refer to the impact of an intervention on individuals not directly exposed themselves but connected to intervention recipients within the network. In network-based studies, outcomes may be missing due to study termination or participant dropout, termed censoring. We introduce an inverse probability censoring weighted estimator which extends the inverse probability weighted estimator for network-based observational studies to handle possible outcome censoring. We prove the consistency and asymptotic normality of the proposed estimator and derive a closed-form estimator for its asymptotic variance. Applying the inverse probability censoring weighted estimator, we assess spillover effects in a network-based study of a nonrandomized intervention with outcome censoring. A simulation study evaluates the finite-sample performance of the inverse probability censoring weighted estimator, demonstrating its effectiveness with sufficiently large sample sizes and number of connected subnetworks. We then employ the method to assess spillover effects of community alerts on self-reported human immunodeficiency virus risk behavior among people who inject drugs and their contacts in the Transmission Reduction Intervention Project (TRIP), from 2013 to 2015, Athens, Greece. Results suggest that community alerts may help reduce human immunodeficiency virus risk behavior for both the individuals who receive them and others in their network, possibly through shared information. In this study, we found that the risk of human immunodeficiency virus behavior was reduced by increasing the proportion of a participant's immediate contacts exposed to community alerts.

Between May 2020 and December 2021, there were 159,872 drug overdose deaths in the US. Higher eviction rates have been associated with higher overdose mortality. Amid the economic turmoil caused by the COVID-19 pandemic, 43 states and Washington, DC, implemented eviction moratoria of varying durations. These moratoria reduced eviction filing rates, but their impact on fatal drug overdoses remains unexplored. We evaluated the effect of these policies on county-level overdose death rates by focusing on the dates the state eviction moratoria were lifted. We obtained mortality data from NCHS and eviction moratoria dates from the COVID-19 US State Policy Database. We employed a longitudinal targeted minimum-loss-based estimation with Super Learner to flexibly estimate the average treatment effect (ATE) of never lifting the moratoria. Lifting state eviction moratoria was associated with a 0.14 per 100,000 higher rate of monthly overdose mortality (95%CI: -0.03, 0.32), although confidence intervals were wide and included zero. Eviction moratoria may not be sufficient to prevent overdose mortality during crises such as the COVID-19 pandemic.