Observational methods for human studies of transgenerational effects.

There are substantial challenges in studying human transgenerational epigenetic outcomes resulting from environmental conditions. The task requires specialized methods and tools that incorporate specific knowledge of multigenerational relationship combinations of probands and their ancestors, phenotype data for individuals, environmental information of ancestors and their descendants, which can span historical to present datasets, and informative environmental data that chronologically aligns with ancestors and descendants over space and time. As a result, there are few epidemiologic studies of potential transgenerational effects in human populations, thus limiting the knowledge of ancestral environmental conditions and the potential impacts we face with modern human health outcomes. In an effort to overcome some of the challenges in studying human transgenerational effects, we present two transgenerational study designs: transgenerational space-time cluster detection and transgenerational case-control study design. Like other epidemiological methods, these methods determine whether there are statistical associations between phenotypic outcomes (e.g., adverse health outcomes) among probands and the shared environments and environmental factors facing their ancestors. When the ancestor is a paternal grandparent, a statistically significant association provides some evidence that a transgenerational inheritable factor may be involved. Such results may generate useful hypotheses that can be explored using epigenomic data to establish conclusive evidence of transgenerational heritable effects. Both methods are proband-centric: They are designed around the phenotype of interest in the proband generation for case selection and family pedigree creation. In the examples provided, we incorporate at least three generations of paternal lineage in both methods to observe a potential transgenerational effect.

PM2.5 threshold exceedances during the prenatal period and risk of intellectual disability.

BACKGROUND: Research demonstrates that chronic exposure to fine particulates (PM2.5) increases risks of neurodevelopmental conditions, such as intellectual disability (ID). Few studies have examined neurodevelopmental health impacts of pollution spikes exceeding 24-h (24-h) PM2.5 guidelines, despite relevance to the regulatory landscape. The current potential for regulatory changes to 24-h PM2.5 standards in the United States makes research on exceedances relevant. OBJECTIVE: To examine associations between 24-h PM2.5 exceedances and the risk of ID. METHODS: We conducted a retrospective case-control study of a sample of children in Utah, USA. We used generalized estimating equations to predict odds of ID based on the number of 24-h PM2.5 exceedance days during the preconception period and three trimesters of pregnancy. Exceedance days are defined as per current World Health Organization (WHO) [≥15 µg/m3] and current US Environmental Protection Agency (EPA) [≥35 µg/m3] 24-h guidelines. RESULTS: PM2.5 exceedances are associated with ID risk during the preconception and first trimester periods and not the second and third trimesters. During the preconception period, each day exceeding 15 µg/m3 or 35 µg/m3 was associated with a 1.023 (CI: 1.011-1.040) or 1.042 (CI: 1.026-1.059, p < 0.001) increase in odds of ID, respectively. During the first trimester, each day exceeding 15 µg/m3 or 35 µg/m3 was associated with a 1.032 (CI: 1.017-1.047) or 1.059 (CI: 1.030-1.088) increase in odds of ID, respectively. IMPACT STATEMENT: Potential regulatory movement on the US 24-h PM2.5 standard makes research that explicitly studies exceedances highly relevant. Yet few studies examine health effects of exceeding 24-h guidelines for any air pollutants. This study fills important gaps in the literature by examining associations between odds of intellectual disability and the count of days exceeding current 24-h PM2.5 guidelines, as established by the World Health Organization and US Environmental Protection Agency, during the prenatal period. We find that exceedances of both sets of guidelines, during the preconception and first trimester periods, are associated with ID risk.

Airborne Lead Exposure and Childhood Cognition: The Environmental Influences on Child Health Outcomes (ECHO) Cohort (2003-2022).

Objectives. To examine whether a previously reported association between airborne lead exposure and children's cognitive function replicates across a geographically diverse sample of the United States. Methods. Residential addresses of children (< 5 years) were spatially joined to the Risk-Screening Environmental Indicators model of relative airborne lead toxicity. Cognitive outcomes for children younger than 8 years were available for 1629 children with IQ data and 1476 with measures of executive function (EF; inhibitory control, cognitive flexibility). We used generalized linear models using generalized estimating equations to examine the associations of lead, scaled by interquartile range (IQR), accounting for individual- and area-level confounders. Results. An IQR increase in airborne lead was associated with a 0.74-point lower mean IQ score (b = -0.74; 95% confidence interval = -1.00, -0.48). The association between lead and EF was nonlinear and was modeled with a knot at the 97.5th percentile of lead in our sample. Lead was significantly associated with lower mean inhibitory control but not with cognitive flexibility. This effect was stronger among males for both IQ and inhibitory control. Conclusions. Early-life exposure to airborne lead is associated with lower cognitive functioning. (Am J Public Health. 2024;114(3):309-318. https://doi.org/10.2105/AJPH.2023.307519).

Environmental exposure to industrial air pollution is associated with decreased male fertility.

OBJECTIVE: To understand how chronic exposure to industrial air pollution is associated with male fertility through semen parameters. DESIGN: Retrospective cohort study. PATIENTS: Men in the Subfertility, Health, and Assisted Reproduction cohort who underwent a semen analysis in the two largest healthcare systems in Utah from 2005-2017 with ≥1 measured semen parameter (N = 21,563). INTERVENTION(S): Residential histories for each man were constructed using locations from administrative records linked through the Utah Population Database. Industrial facilities with air emissions of nine endocrine-disrupting compound chemical classes were identified from the Environmental Protection Agency Risk-Screening Environmental Indicators microdata. Chemical levels were linked with residential histories for the 5 years before each semen analysis. MAIN OUTCOME MEASURES: Semen analyses were classified as azoospermic or oligozoospermic (< 15 M/mL) using World Health Organization cutoffs for concentration. Bulk semen parameters such as concentration, total count, ejaculate volume, total motility, total motile count, and total progressive motile count were also measured. Multivariable regression models with robust standard errors were used to associate exposure quartiles for each of the nine chemical classes with each semen parameter, adjusting for age, race, and ethnicity, as well as neighborhood socioeconomic disadvantage. RESULTS: After adjustment for demographic covariates, several chemical classes were associated with azoospermia and decreased total motility and volume. For exposure in the 4th relative to 1st quartile, significant associations were observed for acrylonitrile (ßtotal motility = -0.87 pp), aromatic hydrocarbons (odds ratio [OR]azoospermia = 1.53; ßvolume = -0.14 mL), dioxins (ORazoospermia = 1.31; ßvolume = -0.09 mL; ßtotal motility = -2.65 pp), heavy metals (ßtotal motility = -2.78pp), organic solvents (ORazoospermia = 1.75; ßvolume = -0.10 mL), organochlorines (ORazoospermia = 2.09; ßvolume = -0.12 mL), phthalates (ORazoospermia = 1.44; ßvolume = -0.09 mL; ßtotal motility = -1.21 pp), and silver particles (ORazoospermia = 1.64; ßvolume = -0.11 mL). All semen parameters significantly decreased with increasing socioeconomic disadvantage. Men who lived in the most disadvantaged areas had concentration, volume, and total motility of 6.70 M/mL, 0.13 mL, and 1.79 pp lower, respectively. Count, motile count, and total progressive motile count all decreased by 30-34 M. CONCLUSION(S): Several significant associations between chronic low-level environmental exposure to endocrine-disrupting compound air pollution from industrial sources and semen parameters were observed. The strongest associations were seen for increased odds of azoospermia and declines in total motility and volume. More research is needed to further explore additional social and exposure factors as well as expand on the risk posed to male reproductive health by the studied chemicals.

Generating Older Adult Multimorbidity Trajectories Using Various Comorbidity Indices and Calculation Methods.

Background and Objectives: Older adult multimorbidity trajectories are helpful for understanding the current and future health patterns of aging populations. The construction of multimorbidity trajectories from comorbidity index scores will help inform public health and clinical interventions targeting those individuals that are on unhealthy trajectories. Investigators have used many different techniques when creating multimorbidity trajectories in prior literature, and no standard way has emerged. This study compares and contrasts multimorbidity trajectories constructed from various methods. Research Design and Methods: We describe the difference between aging trajectories constructed with the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). We also explore the differences between acute (single-year) and chronic (cumulative) derivations of CCI and ECI scores. Social determinants of health can affect disease burden over time; thus, our models include income, race/ethnicity, and sex differences. Results: We use group-based trajectory modeling (GBTM) to estimate multimorbidity trajectories for 86,909 individuals aged 66-75 in 1992 using Medicare claims data collected over the following 21 years. We identify low-chronic disease and high-chronic disease trajectories in all 8 generated trajectory models. Additionally, all 8 models satisfied prior established statistical diagnostic criteria for well-performing GBTM models. Discussion and Implications: Clinicians may use these trajectories to identify patients on an unhealthy path and prompt a possible intervention that may shift the patient to a healthier trajectory.

A population-wide analysis of the familial risk of suicide in Utah, USA.

BACKGROUND: The degree to which suicide risk aggregates in US families is unknown. The authors aimed to determine the familial risk of suicide in Utah, and tested whether familial risk varies based on the characteristics of the suicides and their relatives. METHODS: A population-based sample of 12 160 suicides from 1904 to 2014 were identified from the Utah Population Database and matched 1:5 to controls based on sex and age using at-risk sampling. All first through third- and fifth-degree relatives of suicide probands and controls were identified (N = 13 480 122). The familial risk of suicide was estimated based on hazard ratios (HR) from an unsupervised Cox regression model in a unified framework. Moderation by sex of the proband or relative and age of the proband at time of suicide (<25 v. ⩾25 years) was examined. RESULTS: Significantly elevated HRs were observed in first- (HR 3.45; 95% CI 3.12-3.82) through fifth-degree relatives (HR 1.07; 95% CI 1.02-1.12) of suicide probands. Among first-degree relatives of female suicide probands, the HR of suicide was 6.99 (95% CI 3.99-12.25) in mothers, 6.39 in sisters (95% CI 3.78-10.82), and 5.65 (95% CI 3.38-9.44) in daughters. The HR in first-degree relatives of suicide probands under 25 years at death was 4.29 (95% CI 3.49-5.26). CONCLUSIONS: Elevated familial suicide risk in relatives of female and younger suicide probands suggests that there are unique risk groups to which prevention efforts should be directed - namely suicidal young adults and women with a strong family history of suicide.

Trimester-specific ambient PM2.5 exposures and risk of intellectual disability in Utah.

Prenatal fine particulate matter (PM2.5) exposure is an understudied risk factor for neurodevelopmental outcomes, including intellectual disability (ID). Associations among prenatal exposures and neurodevelopmental outcomes may vary depending on the timing of exposure. Limited numbers of studies examining PM2.5 and neurodevelopmental outcomes have considered exposures occurring during the preconception period. To address these gaps, we conducted a case-control study of children born in Utah between 2002 and 2008 (n = 1032). Cases were identified using methods developed by the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network and matched with controls on birth year, sex, and birth county. We estimated the daily average PM2.5 concentration during a period spanning 12 weeks before the estimated conception date, as well as during each of the three trimesters at the maternal residential address listed on the child's birth certificate. In a multivariable model, the third (OR: 2.119, CI: 1.123-3.998, p = .021) and fourth (OR: 2.631, CI: 1.750-3.956, p < .001) quartiles for preconception average PM2.5 demonstrated significantly increased risk of ID relative to the first quartile. Second quartile preconception exposure was also associated with increased risk, though it did not reach significance (OR: 1.385, CI: 0.979-1.959, p = .07). The fourth quartile of first trimester average PM2.5 was positive and significant (OR: 2.278, CI: 1.522-3.411, p < .001); the third quartile was positive, but not significant (OR: 1.159, CI: 0.870-1.544, p = .312). Quartiles of second and third trimester were not associated with higher risk of ID. These findings from Utah, which were robust to a variety of sensitivity analyses, provide initial evidence that preconception and prenatal PM2.5 exposure may be associated with ID. Future studies are needed across other geographic locations and populations.

Patterns of indoor radon concentrations, radon-hazard potential, and radon testing on a small geographic scale in Utah.

INTRODUCTION: Currently, there are no publicly-available estimates of indoor radon concentration at scales smaller than the county. Radon-hazard potential soil maps that reflect underlying geologic factors can be created at small geographic scale and linked to residential and census data. We determined the association between residential radon tests and high radon-hazard potential soil at the residential and block group levels using a large Utah-based dataset. We also identified characteristics of block groups with limited tests in the dataset. METHODS: We geocoded a dataset of residential radon tests obtained from 2001 to 2017 by a statewide educational program. We linked each location to maps of radon-hazard potential soil, the Environmental Protection Agency's (EPA) county radon zones. We also calculated the number of tests conducted in each block group and linked block groups to demographic data from the 2020 United States census. Log-linear and logistic models identified the association between residential home test results and 1) radon-hazard potential soil of each residence, 2) percent of residences on high radon-hazard potential soils in block groups, and 3) EPA's radon zones. We compared demographic characteristics among block groups with ≥5 or <5 residential tests in our dataset. RESULTS: Approximately 42% of homes in the dataset tested ≥4 pCi/L. We found significant positive associations for residential radon test results with 1) residential location on high radon-hazard potential soil and 2) block groups with >0% of residences on high radon-hazard potential soil. EPA radon zones were not associated with residential test results. Block groups with <5 tests had higher than the statewide median percentage of Hispanic residents (OR = 2.46, 95% CI = 1.89-3.21) and were located in rural counties. DISCUSSION: Radon-hazard potential soil has a significant association with residential home radon tests. More efforts are needed to improve radon testing in block groups that are rural and have greater percentages of racial minorities.

Evidence of transgenerational effects on autism spectrum disorder using multigenerational space-time cluster detection.

BACKGROUND: Transgenerational epigenetic risks associated with complex health outcomes, such as autism spectrum disorder (ASD), have attracted increasing attention. Transgenerational environmental risk exposures with potential for epigenetic effects can be effectively identified using space-time clustering. Specifically applied to ancestors of individuals with disease outcomes, space-time clustering characterized for vulnerable developmental stages of growth can provide a measure of relative risk for disease outcomes in descendants. OBJECTIVES: (1) Identify space-time clusters of ancestors with a descendent with a clinical ASD diagnosis and matched controls. (2) Identify developmental windows of ancestors with the highest relative risk for ASD in descendants. (3) Identify how the relative risk may vary through the maternal or paternal line. METHODS: Family pedigrees linked to residential locations of ASD cases in Utah have been used to identify space-time clusters of ancestors. Control family pedigrees of none-cases based on age and sex have been matched to cases 2:1. The data have been categorized by maternal or paternal lineage at birth, childhood, and adolescence. A total of 3957 children, both parents, and maternal and paternal grandparents were identified. Bernoulli space-time binomial relative risk (RR) scan statistic was used to identify clusters. Monte Carlo simulation was used for statistical significance testing. RESULTS: Twenty statistically significant clusters were identified. Thirteen increased RR (> 1.0) space-time clusters were identified from the maternal and paternal lines at a p-value < 0.05. The paternal grandparents carry the greatest RR (2.86-2.96) during birth and childhood in the 1950's-1960, which represent the smallest size clusters, and occur in urban areas. Additionally, seven statistically significant clusters with RR < 1 were relatively large in area, covering more rural areas of the state. CONCLUSION: This study has identified statistically significant space-time clusters during critical developmental windows that are associated with ASD risk in descendants. The geographic space and time clusters family pedigrees with over 3 + generations, which we refer to as a person's geographic legacy, is a powerful tool for studying transgenerational effects that may be epigenetic in nature. Our novel use of space-time clustering can be applied to any disease where family pedigree data is available.

What Role Does Hispanic/Latina Ethnicity Play in the Relationship Between Maternal Mental Health and Preterm Birth?

Objective: To investigate the association of prepregnancy and prenatal depression and/or anxiety on preterm birth (PTB), while also exploring Hispanic/Latina ethnicity as a potential effect modifier. Methods: Study population included respondents of UT-PRAMS (2016-2019). Associations between prepregnancy and prenatal depression and/or anxiety and PTB were evaluated using Poisson regression models accounting for stratified survey sampling. Results: Women with prepregnancy and prenatal depression and anxiety, compared to those without, had a 67 percent (95% CI: 19%, 134%) higher probability of experiencing PTB, after controlling for relevant sociodemographic, lifestyle, and reproductive history factors. Impact of depression on PTB was slightly higher than impact of anxiety. Hispanic/Latina ethnicity was found to protect against PTB for those with prepregnancy and prenatal depression alone (aPR: 0.53, 95% CI: 0.24, 1.21) or both depression and anxiety (aPR: 0.51, 95% CI: 0.18, 1.40) compared to being non-Hispanic/Latina (aPR: 1.79, 95% CI: 1.25, 2.55 for depression alone; aPR: 1.62, 95% CI: 1.18, 2.21 for depression and anxiety). Conclusions: Overall, Utah women reporting prepregnancy and prenatal depression and anxiety were more likely to have a PTB. Being of Hispanic/Latina ethnicity was found to mitigate the risk of PTB among women with depression and anxiety. Implications: Prepregnancy and prenatal mental health screenings and treatment are key to lessening the impacts of depression and anxiety on both mother and infant. Hispanic/Latina ethnicity may be protective against PTB among women experiencing mental distress. Whether this is through increased social support or through a different mechanism should be explored in future research.

Carbapenem-resistant Enterobacteriaceae in sink drains of 40 healthcare facilities in Sindh, Pakistan: A cross-sectional study.

In Pakistan, antimicrobial resistance (AMR) is expected to greatly increase the already high mortality and morbidity rates attributed to infections, making AMR surveillance and prevention a priority in the country. The aims of the project were to characterize the prevalence of carbapenem-resistant Enterobacteriaceae (CRE) in healthcare facility sink drains in Pakistan and to characterize how physical characteristics of sinks and healthcare facility rooms were associated with CRE in those sinks. The study took place in 40 healthcare facilities in Jamshoro Pakistan. Swabs were collected from sink drains in each facility that had a sink, and structured observations of sinks and facilities were performed at each facility. Swabs were plated on CHROMagar KPC to screen for carbapenem-resistant Enterobacteriaceae, which were then isolated on Mueller-Hinton agar plates. Antibiotic susceptibility was determined using the disk diffusion method to assess resistance to carbapenems, cephalosporins, and fluoroquinolones. Thirty-seven of the healthcare facilities had at least one sink, and thirty-nine total sinks were present and sampled from those healthcare facilities. Sinks in these facilities varied in quality; at the time of sampling 68% had water available, 51% had soap/alcohol cleanser at the sink, 28% appeared clean, and 64% drained completely. Twenty-five (64%) of the sink samples grew Enterobacteriaceae on CHROMagar KPC, sixteen (41%) of which were clinically non-susceptible to ertapenem. Seven of the 39 sampled sinks (18%) produced Enterobacteriaceae that were resistant to all three antibiotic classes tested. Several facilities and sink characteristics were associated with CRE. Sinks and drains can serve as undetected reservoirs for carbapenem-resistant Enterobacteriaceae. Control and remediation of such environments will require both systemic strategies and physical improvements to clinical environments.

Differential impacts of particulate air pollution exposure on early and late stages of spermatogenesis.

BACKGROUND: Despite increasing evidence that particulate air pollution has adverse effects on human semen quality, few studies examine the impact of air pollution on clinically relevant thresholds used to diagnose male fertility problems. Furthermore, exposure is often assessed using average air pollution levels in a geographic area rather than individualized estimates. Finally, physiologically-informed exposure windows are inconsistent. OBJECTIVES: We sought to test the hypothesis that airborne particulate exposures during early-phase spermatogenesis will have a differential impact on spermatogenic formation compared to late-phase exposures, using an individualized model of exposure to particulate matter ≤ 2.5 µm and ≤ 10 µm (PM2.5 and PM10, respectively). METHODS: From an original cohort of 183 couples, we conducted a retrospective analysis of 130 healthy males seeking to become parents, using spermatogenesis-relevant exposure windows of 77-34 days and 37-0 days prior to semen collection to encompass sperm development stages of mitosis/meiosis and spermiogenesis, respectively. Individualized residential exposure to PM2.5 and PM10 was estimated by selecting multiple air pollution sensors within the same geographic air basin as participants and employing inverse distance weighting to calculate mean daily exposure levels. We used multiple logistic regression to assess the association between pollution, temperature, and dichotomized World Health Organization semen parameters. RESULTS: During the early phase of spermatogenesis, air pollution exposure is associated with 1.52 (95% CI: 1.04-2.32) times greater odds of < 30% normal heads per 1-unit increase in IQR for PM2.5. In the late phase of spermatogenesis, air pollution exposure is associated with 0.35 (95% CI: 0.10-0.74) times greater odds of semen concentration < 15 million/mL per 1-unit increase in IQR for PM2.5, and 0.28 (95% CI: 0.07-0.72) for PM10. CONCLUSION: Particulate exposure has a differential and more deleterious impact on sperm during early-phase spermatogenesis than late-phase.

Type 1 Diabetes incidence among youth in Utah: A geographical analysis.

Type 1 Diabetes (T1D) poses an increasing threat to public health, as incidence rates continue to rise globally. However, the etiology of T1D is still poorly understood, especially from the perspective of geography. The objective of this research is to examine the incidence of T1D among youth and to identify high-risk clusters and their association with socio-demographic and geographic variables. The study area was the entire state of Utah and included youth with T1D from birth to 19 years of age from 1998 to 2015 (n = 4161). Spatial clustering was measured both globally and locally using the Moran's I statistic and spatial scan statistic. Ordinary least squares (OLS) regression was used to measure the association of high-risk clusters with certain risk factors at the Census Block Group (CBG) level. The mean age at diagnosis was 9.3 years old. The mean incidence rate was 25.67 per 100,000 person-years (95% CI, 24.57-26.75). The incidence rate increased by 14%, from 23.94 per100,000 person-years in 1998 to 27.98 per 100,000 person-years in 2015, with an annual increase of 0.80%. The results of the spatial scan statistic found 42 high-risk clusters throughout the state. OLS regression analysis found a significant association with median household income, population density, and latitude. This study provides evidence that incidence rates of T1D are increasing annually in the state of Utah and that significant geographic high-risk clusters are associated with socio-demographic and geographic factors.

Heavy metals drinking water contamination and health risk assessment among primary school children of Pakistan.

The purpose of this study was to characterize the concentrations of lead (Pb), cadmium (Cd), manganese (Mn), and Fe (Fe) in drinking water sources in primary schools in Sindh Province, Pakistan and to quantify potential health risks among those school children. We conducted a representative, cross-sectional study among 425 primary schools in Sindh province of Pakistan. We used risk assessment models to estimate the metal index, pollution index, lifetime cancer risk, and hazard quotient index. Across the 425 sampled schools, the levels of heavy metals in the drinking water often exceeded the WHO permissible limits (67% of schools exceeded Pb limit, 17% for Cd, 15% for Fe). The average incremental lifetime cancer risk (ILCR) for Pb exceeded tolerable limits in all of the districts under study. The findings, particularly for Pb, are of concern, as Pb may negatively influence children's growth, development, school performance, and long-term health.

Influence of Geographic Access on Surgical Center Readmissions After Index Congenital Heart Surgery.

OBJECTIVE: To assess the impact of geographic access to surgical center on readmission risk and burden in children after congenital heart surgery. STUDY DESIGN: Children <6 years old at discharge after congenital heart surgery (Risk Adjustment for Congenital Heart Surgery-1 score 2-6) were identified using Pediatric Health Information System data (46 hospitals, 2004-2015). Residential distance from the surgery center, calculated using ZIP code centroids, was categorized as <15, 15-29, 30-59, 60-119, and ≥120 miles. Rurality was defined using rural-urban commuting area codes. Geographic risk factors for unplanned readmissions to the surgical center and associated burden (total hospital length of stay [LOS], costs, and complications) were analyzed using multivariable regression. RESULTS: Among 59 696 eligible children, 19 355 (32%) had ≥1 unplanned readmission. The median LOS was 9 days (IQR 22) across the entire cohort. In those readmitted, median total costs were $31 559 (IQR $90 176). Distance from the center was inversely related but rurality was positively related to readmission risk. Among those readmitted, increased distance was associated with longer LOS, more complications, and greater costs. Compared with urban patients, highly rural patients were more likely to have an unplanned readmission but had fewer average readmission days. CONCLUSIONS: Geographic measures of access differentially affect readmission to the surgery center. Increased distance from the center was associated with fewer unplanned readmissions but more complications. Among those readmitted, the most isolated patients had the greatest readmission costs. Understanding the contribution of geographic access will aid in developing strategies to improve care delivery to this population.

Correlation of SARS-CoV-2 RNA in wastewater with COVID-19 disease burden in sewersheds.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19), is shed in feces and the viral ribonucleic acid (RNA) is detectable in wastewater. A nine-week wastewater epidemiology study of ten wastewater facilities, serving 39% of the state of Utah or 1.26 M individuals was conducted in April and May of 2020. COVID-19 cases were tabulated from within each sewershed boundary. RNA from SARS-CoV-2 was detectable in 61% of 126 wastewater samples. Urban sewersheds serving >100,000 individuals and tourist communities had higher detection frequencies. An outbreak of COVID-19 across two communities positively correlated with an increase in wastewater SARS-CoV-2 RNA, while a decline in COVID-19 cases preceded a decline in RNA. SARS-CoV-2 RNA followed a first order decay rate in wastewater, while 90% of the RNA was present in the liquid phase of the influent. Infiltration and inflow, virus decay and sewershed characteristics should be considered during correlation analysis of SAR-CoV-2 with COVID-19 cases. These results provide evidence of the utility of wastewater epidemiology to assist in public health responses to COVID-19.

Polycystic ovary syndrome and postpartum depression symptoms: a population-based cohort study.

BACKGROUND: Women with polycystic ovary syndrome are more likely to experience several pregnancy complications including hypertensive disorders, gestational diabetes mellitus, and preterm births than women without polycystic ovary syndrome. However, at present, there is limited research on whether polycystic ovary syndrome is associated with both anxiety and depression during pregnancy and whether this augments a woman's risk of postpartum depression, particularly among high-risk populations who have limited access to care. OBJECTIVE: Our primary objective was to assess the association between prepregnancy polycystic ovary syndrome and postpartum depression, considering important baseline confounding factors. Our secondary objective was to evaluate the mediating role of prenatal depression and anxiety on the association between polycystic ovary syndrome and postpartum depression. STUDY DESIGN: This study involved a population-based sample of 3906 postpartum (2-6 months) women who completed the Utah Pregnancy Risk Assessment Monitoring System Phase 8 questionnaire (2016-2018). Weighted adjusted prevalence ratios were used to assess the association between polycystic ovary syndrome and postpartum depression, considering potential confounding factors and assessing mediating effects of depression and anxiety experienced during pregnancy. RESULTS: Following the exclusion criteria, 8.2% of women reported clinical polycystic ovary syndrome and 19.1%, 6.2%, and 4.4% reported irregular periods and acne, irregular periods and hirsutism, and all 3 symptoms, respectively. Moreover, 17.7% and 23.5% reported experiencing prenatal depression and anxiety and 9.5% and 10.2% reported experiencing postpartum depressed mood and anhedonia, respectively. Clinical polycystic ovary syndrome was associated with a 1.76 higher adjusted prevalence ratio (95% confidence interval, 1.03-3.00) for postpartum depressed mood or anhedonia after taking into consideration age, prepregnancy body mass index, race/ethnicity, education, and marital status. A similar higher prevalence was seen for irregular periods and acne (adjusted prevalence ratio, 1.65; 95% confidence interval, 1.13-2.41), irregular periods and hirsutism (adjusted prevalence ratio, 1.40; 95% confidence interval, 0.82-2.40), and all 3 symptoms (adjusted prevalence ratio, 1.75; 95% confidence interval, 0.96-3.19) and postpartum depressed mood or anhedonia. Prenatal depression and anxiety mediated 20% and 32% of the effect of clinical polycystic ovary syndrome on postpartum depressed mood and anhedonia, respectively. CONCLUSION: Clinical polycystic ovary syndrome is associated with postpartum depressed mood and symptoms among this population-based sample inclusive of high-risk mothers. Prenatal depression and anxiety mediate this association, emphasizing the importance of prenatal psychological screening among women with polycystic ovary syndrome. An additional important clinical and public health implication of this study lies in the finding that nearly 20% of women in this population-based sample who reported at least 2 polycystic ovary syndrome symptoms (including at-risk women who may not have access to care) had not received a clinical diagnosis for polycystic ovary syndrome.

Higher Ultraviolet Radiation Exposure Among Rural-Dwelling Versus Urban-Dwelling Adults and Children: Implications for Skin Cancer Prevention.

Ultraviolet radiation (UVR) exposure is a primary risk factor for the development of melanoma. However, adults and adolescents often do not engage in preventive behaviors to reduce UVR exposure. Rural residents may be at higher risk for melanoma due to lower use of sun protection strategies, which increases their overall UVR exposure compared to those who live in urban areas. The purpose of this study was to evaluate differences in UVR exposure between rural and urban residents in a geographic area with high incidence of melanoma. Children (aged 8-17 years) and adults (≥ 18 years) from rural and urban areas of Utah were asked to wear a UVR monitoring device for 14 days. The sample included 97 children and 97 adults. Data was collected from June to October 2018. Non-parametric Mann-Whitney tests and quantile regression were used to compare UVR exposure levels between urban and rural participants, separately for adults and children. For adults, rural residence significantly increased total UVR dose ( ß: 24.6; 95% CI 3.75, 42.74) and the UVR dose during peak UVR hours among participants with the highest UVR doses (ß: 16.3; 95% CI 17.4, 24.63). Rural children exhibited significantly higher UVR doses for peak UVR hours for the entire study period (ß: 4.14; 95% CI 0.83, 7.46) and on weekdays (ß: 0.39; 95% CI 0.05, 0.73). The findings from this study indicate that rural residents may receive higher levels of UVR exposure than urban residents, and that prevention efforts could be tailored to address these geographical differences.

Relationship between distance of referring facilities and haemoglobin change in children in Malawi.

BACKGROUND: Anaemia is a significant cause of mortality in children in sub-Saharan Africa where blood transfusion is often available only at referral hospitals. Understanding the pattern of referrals by health facilities is essential to identify the delays that affect child survival. AIM: To determine if there was a correlation between change in haemoglobin (Hb) level and distance from referring facilities to Kamuzu Central Hospital (KCH) in Malawi, and whether distance affected mortality rates. METHODS: This was a retrospective cohort study of 2259 children referred to KCH whose Hb was measured at the referring facility or at KCH. Maps were created using ArcGIS® software. The relationship between distance from KCH and change in Hb was assessed by χ2 analysis and multiple linear regression with SAS© software. RESULTS: The majority of children were referred by health facilities in the Lilongwe District. When categorised as Hb <4, 4-6 or >6 g/dL, 87.0% of children remained in the same category during transfer. There was no significant relationship between Hb drop and distance from KCH. Distance from KCH was not a significant predictor of Hb level at KCH or Hb change. However, mortality rates were significantly higher in facilities that were 10-50 km from KCH than in those which were <10 km away. CONCLUSIONS: Using distance as a proxy for time, this suggests that referring facilities are transferring children sufficiently quickly to avert significant reductions in Hb. Despite this, there is a need to identify the factors that influence the decision to transfer anaemic children.

Localized effect of treated wastewater effluent on the resistome of an urban watershed.

BACKGROUND: Wastewater treatment is an essential tool for maintaining water quality in urban environments. While the treatment of wastewater can remove most bacterial cells, some will inevitably survive treatment to be released into natural environments. Previous studies have investigated antibiotic resistance within wastewater treatment plants, but few studies have explored how a river's complete set of antibiotic resistance genes (the "resistome") is affected by the release of treated effluent into surface waters. RESULTS: Here we used high-throughput, deep metagenomic sequencing to investigate the effect of treated wastewater effluent on the resistome of an urban river and the downstream distribution of effluent-associated antibiotic resistance genes and mobile genetic elements. Treated effluent release was found to be associated with increased abundance and diversity of antibiotic resistance genes and mobile genetic elements. The impact of wastewater discharge on the river's resistome diminished with increasing distance from effluent discharge points. The resistome at river locations that were not immediately downstream from any wastewater discharge points was dominated by a single integron carrying genes associated with resistance to sulfonamides and quaternary ammonium compounds. CONCLUSIONS: Our study documents variations in the resistome of an urban watershed from headwaters to a major confluence in an urban center. Greater abundances and diversity of antibiotic resistance genes are associated with human fecal contamination in river surface water, but the fecal contamination effect seems to be localized, with little measurable effect in downstream waters. The diverse composition of antibiotic resistance genes throughout the watershed suggests the influence of multiple environmental and biological factors.