Summary of respiratory/cardiovascular diagnoses for full analytic set and by diagnosis (N = 8,521 unique visits).

Autism spectrum disorder (ASD) prevalence has increased globally. Emerging evidence implicates paternal genetic and epigenetic factors, particularly sperm DNA methylation alterations, in shaping offspring neurodevelopmental risk. Advanced paternal age is associated with increased de novo mutations and epigenetic changes in germ cells. Recent studies have explored distinct sperm methylation signatures in fathers of autistic children, often involving genes critical for neural signaling, transcription, and synaptic function. Longitudinal analyses further linked paternal sperm methylation patterns-including WWOX, SALL3, and A2BP1 (RBFOX1)-with autistic traits in both fathers and their children, supporting intergenerational epigenetic transmission of ASD susceptibility.

Background:Though idiopathic urethral strictures are a common form of strictures, little is understood about the pathophysiology leading to their development. This retrospective cohort study sought to analyze the risk of environmental toxins on the development of stricture disease. Methods:Using the Utah Population Database (UPDB), we identified patients with idiopathic urethral strictures born between 1996-2021. Each case was matched 1:1 with controls, based on year of birth and location. Models compared historical air pollution exposure data between the cohorts. Environmental exposures were analyzed in the prenatal period, the first year of life, and the 5 years prior to diagnosis and individual exposures were weighted by the risk of stricture development. Results:We identified 2,048 patients with urethral strictures, diagnosed between 1996 and 2021 and were matched to 1,939 controls for a total cohort of 3,987 men. There was no difference in risk of stricture development for exposure prenatally and within the 5 years prior to diagnosis. The relative risk of cumulative exposures in the first year of life was 1.21 (1.07-1.36, P=0.002) in the development of stricture disease. On univariate analysis, the toxins most associated with stricture development within the first year of life were ethylbenzene, tetrachloroethylene, and molybdenum trioxide. Conclusions:Idiopathic urethral stricture is a common presentation of anterior urethral stricture disease (aUSD) but the mechanism is not well understood. Environmental exposures within the first year of life were associated with an increased risk of the development of a stricture, indicating a potential role within broader inflammatory pathways associated with urethral strictures.

Indoor radon accounts for 37% of population-level exposure to ionizing radiation in the United States. However, radon metrics are typically reported at coarse spatial scales, potentially obscuring meaningful local variation. We developed a high-resolution modeling framework to estimate indoor radon concentrations across Utah while explicitly quantifying predictive uncertainty. A total of 19,497 residential radon measurements collected between 2006 and 2017 were combined with environmental and housing characteristics and analyzed using a geospatial neural network that accommodates spatial dependence and nonlinear associations. Predictions were generated on a uniform hexagonal grid at 0.73 km2 resolution (H3 level 8). Out-of-sample predictions aggregated to the H3 level 8 grid showed good agreement with observed concentrations (Pearson r=0.64), while household-level predictions exhibited more moderate agreement (r=0.45). The model produced well-calibrated uncertainty estimates, with 24.1% of held-out observations exceeding the predicted 75th-percentile threshold. Maps of predicted radon concentrations and the probability of exceeding the U.S. EPA action level of 148 Bq/m3 (4 pCi/L) revealed substantial fine-scale spatial heterogeneity that was not apparent in conventional coarse-resolution summaries, with greater local variability observed in densely monitored urban counties than in sparsely sampled regions. High-resolution radon models that explicitly quantify uncertainty provide a useful framework for characterizing the spatial distribution of indoor radon and identifying areas of elevated exceedance risk. These findings highlight the value of fine-scale monitoring data and uncertainty-aware modeling approaches for radon exposure assessment, environmental risk characterization, and radon-related health research.

ICD-9 CM and ICD-10 CM diagnosis codes used to define respiratory and cardiovascular healthcare visits.

Demographic and clinical characteristics of young adult cancer patients and survivors by whether or not they experienced a respiratory/cardiovascular eventa and were included in the analytic cohort (N = 8,025).

BACKGROUND:Cancer therapies have well documented adverse effects on cardiovascular and respiratory health, which could increase cancer survivors' susceptibility to poor air quality. We describe the risk of cardiovascular and respiratory healthcare visits following acute air pollution exposures among adolescent and young adult (AYA) cancer survivors. METHODS:We identified all Utah AYAs diagnosed at 15 to 39 years of age with thyroid, melanoma, lymphoma, breast, or testicular cancer from 1998 to 2016 (N = 8,016). AYAs were linked by residential location to daily particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) for 2000 to 2016. Case cross-over models in a distributed lag nonlinear model framework estimated odds ratios (OR) and 95% confidence intervals (95% CI) for cardiovascular and respiratory healthcare visits (inpatient admissions and emergency department/urgent care visits) with exposure over the 6 days preceding an event, adjusting for temperature and relative humidity. RESULTS:A total of 3,143 AYAs (39%) experienced ≥1 respiratory/cardiovascular event. O3 was associated with cardiovascular events (ORlag4 = 1.08; 95% CI, 1.02-1.14, and ORlag5 = 1.05; 95% CI, 1.01-1.09), and NO2 was associated with respiratory events (ORlag1 = 1.05; 95% CI, 1.01-1.10). Breast cancer survivors showed an elevated risk for cardiovascular and respiratory visits; melanoma, lymphoma, and testis survivors displayed an increased risk for cardiovascular visits. CONCLUSIONS:O3 was linked with an elevated risk of cardiovascular events, whereas respiratory events were associated with NO2. Associations between air pollutants and healthcare visits varied by primary diagnosis site, indicating that susceptibility to air pollution could differ due to cancer-specific treatment factors. IMPACT:AYAs face an increased risk for cardiovascular and respiratory events with exposure to ambient air pollution and may benefit from interventions to reduce exposures.

Odds ratios and 95% confidence intervals for respiratory visits by lag day of air pollution exposure.

OBJECTIVES:Testicular cancer survivors can experience cardiovascular and respiratory complications due to cancer treatment. We assessed associations between nitrogen dioxide (NO2) and ozone (O3) air pollution and health care encounters among survivors of adolescent and young adult (AYA) testicular cancer. METHODS:A total of 385 AYA testicular cancer survivors, diagnosed 2000-2016, with cardiovascular and/or respiratory health care encounters (emergency department/urgent care [ED/UC], inpatient) were identified using a statewide Utah-based resource. Continuous and dichotomous (≥moderate air quality index) exposure measures were included for NO2 and O3 for the 1-4 days (lag days) before events. A case-crossover framework using conditional logistic regression with robust standard errors computed the association of lag days 0-3 with cardiovascular or respiratory encounters and stratified by encounter type (ED/UC, inpatient). Models that were significant in the full cohort were also stratified on demographic and treatment factors. All models were controlled for temperature and humidity. RESULTS:Survivors contributed 257 cardiovascular and 685 respiratory encounters. NO2 ≥moderate on lag day 1 was associated with increased odds of any cardiovascular encounter (odds ratio [OR] = 1.97, 95% confidence interval [CI] = 1.08-3.59) and inpatient cardiovascular encounters in the full cohort (OR = 2.48, 95% CI = 1.21-5.10), survivors treated with radical orchiectomy and chemotherapy (OR = 3.00, 95% CI = 1.29-7.00), and Hispanic survivors (OR = 4.32, 95% CI = 1.18-15.85). O3 ≥moderate on lag day 4 was associated with respiratory ED/UC encounters (OR = 1.34, 95% CI = 1.00-1.79) and O3 on lag day 4 was associated with any cardiovascular encounter (OR = 1.02/parts per billion [ppb], 95% CI = 1.00-1.03) and inpatient cardiovascular encounters (OR = 1.03/ppb, 95% CI + 1.00-1.05). CONCLUSIONS:NO2 and O3 are associated with risk for health care encounters among testicular cancer survivors and could increase health disparities in survivorship.

Previous research has suggested a correlation between hepatitis C infection and male reproductive hormones. This study systematically reviewed the literature and determined the pooled effect of hepatitis C infection on male reproductive hormones. PubMed, Scopus, and Web of Science were searched on 1 October 2024. Studies were included if they compared reproductive hormone levels between hepatitis C-positive and hepatitis C-negative men. Excluded were animal studies, reviews, editorials, preprints, and studies lacking hormone data or hepatitis C status differentiation. The effect measures were weighted mean differences. Heterogeneity was measured with I2 index. Risk of bias was assessed using the Newcastle-Ottawa Scale, and evidence certainty was evaluated with the GRADE approach. PROSPERO Registration number=CRD42024596571. The initial search yielded 569 documents. After screening, 10 documents were eligible for meta-analysis, each showing high methodological quality (NOS score≥7). Hepatitis C infection was associated with a decrease of 22.62 pmol/L free testosterone (95%CI: -28.65, -16.60; p-value < 0.01; I2 = 21.96%), an increase of 1.98 ng/ml prolactin (95%CI: 0.76, 3.19; p-value < 0.01; I2 = 75.28%), and an elevation of 37.66 nmol/L sex hormone binding globulin (95%CI: 21.81, 53.51; p-value < 0.01; I2 = 95.42%). No publication bias was detected for free testosterone, prolactin, or sex hormone binding globulin, whereas publication bias was observed for total testosterone and estradiol. After publication bias adjustment, hepatitis C infection was associated with 4.16 nmol/L lower total testosterone (95%CI: -4.74, -3.57) and 7.06 pg/ml higher estradiol (95%CI: 6.11, 8.02). Subgroup analysis showed stronger hepatitis C infection effects on free testosterone, prolactin, and estradiol in studies with an average participant age under 40 than in those over 40. In conclusion, hepatitis C infection has been associated with alterations in male reproductive hormones; however, as the certainty of evidence is low to very low (GRADE), these findings should be interpreted cautiously and require confirmation in well-designed studies before clinical implications can be established.

Odds ratios and 95% confidence intervals for cardiovascular visits by lag day of air pollution exposure.

OBJECTIVE To examine the association between male factor infertility and the Rural-Urban continuum. MATERIALS AND METHODS Single institution retrospective cohort study using the Utah Population Database, which combines demographic, medical, and residential data for patients residing in Utah and links to the Subfertility Health Assisted Reproduction and Environment database, which houses fertility data from 1998 to 2017. The data was divided by metropolitan (metro-) (large, medium, small) and non-metropolitan (non-metro-) (urban, rural) status, based on United States Department of Agriculture rural-urban continuum codes. RESULTS Non-metro urban/rural males were less likely to be a racial/ethnic minority (92.3% non- Hispanic white vs 86.2%) or use assisted reproductive technology (13.5% vs 18.5%). Multivariate regression controlling for race/ethnicity, age, semen analysis category (oligozoospermic vs normozoospermic), previous successful fertility outcome, and use of assisted reproductive technology, demonstrated complete rurality was associated with decreased likelihood of successful fertility outcome (Hazard Ratio [HR] 0.60, 95% CI 0.41-0.87, n = 49, P = 0.007). Non-metro urban individuals trended towards lower likelihood of successful fertility outcome ([HR] 0.90, 95% CI 0.82-0.98, P = 0.02). Complete rurality was associated with longer time for 50% cohort successful fertility outcome (> 60 months vs approximately 34 months both metro), P = .007. CONCLUSION Across the rural-urban continuum, residing in a metro area was associated with higher rates of racial/ethnically diversity, fertility treatment utilization, and successful fertility outcomes (live births). Given approximately 18% of the United States resides with a rural community (12% in Utah), these findings can provide more informed infertility care. UROLOGY 197: 90-97, 2025. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

We investigated insurance coverage among adolescents and young adults (AYA) with cancer before and during the COVID-19 pandemic. AYAs diagnosed with cancer 15-39 years of age were identified using Utah Cancer Registry records and linked with University of Utah electronic health records. Poisson models calculated incidence rate ratios (IRRs) of health insurance coverage during pre-pandemic (11/4/2017-3/5/2020; n = 2,140) and pandemic (3/6/2020-7/6/2022; n = 1,894) periods. Prior to the pandemic, insurance gaps were higher (pre-pandemic = 16.40%, pandemic = 13.73%; IRR = 0.84, 95%CI = 0.71-0.98); more AYAs had continuous public insurance during the pandemic (pre-pandemic = 8.60%, pandemic = 10.98%; IRR = 1.28, 95%CI = 1.05-1.56). Research is needed on the durability of pandemic relief programs on insurance coverage among AYA cancer survivors.

OBJECTIVE:To assess mortality in family members of men seeking fertility assessment. Subfertility serves as a biomarker for overall somatic health, and poor semen quality is associated with increased risk of hospitalization and mortality from chronic conditions. However, it is unclear if these risks extend to family members of men with low sperm count. DESIGN:Retrospective cohort study. SUBJECTS:Family members, up to third-degree relatives, of men in the Subfertility, Health and Assisted Reproduction and the Environment cohort who underwent a semen analysis as part of a fertility assessment 1996-2017. Relatives of men with a recorded total sperm count who lived in Utah for ≥1 year 1904-2017 were included in the analysis (N = 22,280 families). EXPOSURE:Individuals were classified by family membership. Families were classified as relatives of azoospermic (0M), oligozoospermic (<39M), or normozoospermic (≥39M) men. The average total sperm count of the proband (male relative) with fertility assessment was also included as a continuous exposure measure. MAIN OUTCOME MEASURES:The main outcomes were all-cause and cause-specific mortality risk by sex, age, and degree of relation: first-, second-, and third-degree. Cox proportional hazard models were used to test the association between fertility classification and mortality, controlling for sex, race/ethnicity, and birth year. RESULTS:A total of 666,437 relatives of men with fertility assessment (Ndeaths = 183,974) were included in the analysis. Relative to normozoospermia families, all-cause mortality risk increased in oligozoospermia families (hazard ratio [HR]oligozoospermia, 1.03; 95% confidence interval [CI], 1.01-1.05). Close relatives, first- (HRoligozoospermia, 1.17; 95% CI, 1.07-1.28) and second-degree relatives (HRazoospermia, 1.11; 95% CI, 1.04-1.20; HRoligozoospermia, 1.05; 95% CI,1.01-1.09), of azoospermic and oligozoospermic men had the highest all-cause and cause-specific mortality risk, including death attributed to cardiovascular disease or congenital birth conditions. CONCLUSION:Our results suggest that familial all-cause and cause-specific mortality risk differ by fertility phenotype. Families of azoospermic and oligozoospermic men showed significantly increased risk, particularly for close relatives. This study provides further evidence that shared genetic and/or environmental factors could influence both fertility and somatic health.

Background:Benign prostatic hyperplasia (BPH) is a common condition among aging men, significantly affecting quality of life and contributing to a substantial healthcare burden. The pathogenesis of BPH is strongly influenced by genetic factors, with heritability estimates showing a wide range from 20% to 83%. Emerging evidence also highlights the critical role of environmental exposures, including endocrine-disrupting chemicals (EDCs), in BPH risk, progression, and therapeutic response. This review synthesizes current knowledge on genetic and environmental determinants of BPH pathogenesis, severity, and management. Methods:A scoping review of the literature was conducted using the databases PubMed, Scopus, and Web of Science. Relevant studies on genetic predisposition, environmental exposures, and their contributions to BPH were analyzed. Data from epidemiological studies, genome-wide association studies (GWAS), familial aggregation analyses, and research on environmental exposures were integrated to provide an understanding of these factors and BPH pathogenesis. Results:Familial clustering indicates a significantly elevated risk, particularly among first-degree male relatives. Key genetic determinants include androgen receptor (AR) gene CAG repeat polymorphisms, where shorter repeats are linked to increased AR activity and prostate enlargement. Estrogen pathway genes, such as ESR1 and CYP19A1, and variants in dihydrotestosterone (DHT) synthesis genes, notably SRD5A2, influence disease progression and risk. GWAS have identified additional loci, such as MSMB and TERT, associated with prostate volume and aggressive BPH phenotypes. Polygenic risk scores offer promising applications in identifying individuals at high risk for severe BPH. Environmental exposures, particularly to EDCs such as bisphenol A (BPA), bisphenol S (BPS), and bisphenol AF (BPAF), were found to disrupt hormonal regulation, contributing to prostatic hyperplasia. Air pollution, primarily particulate matter, exacerbates prostate inflammation and hyperplasia, with regional differences in BPH symptom severity correlating with air quality. Lifestyle factors, including high-fat diets and sedentary behaviors, further modulate disease severity. Conclusions:The development and progression of BPH are shaped by a complex interplay of genetic and environmental factors. EDCs contribute significantly to prostatic hyperplasia, while heritable factors influence disease onset, severity, and response to treatment. Integrating genetic risk profiling and environmental exposure assessments into clinical practice holds the potential to enhance BPH management and personalized therapeutic strategies.

BACKGROUND:Male fertility can be influenced by environmental factors, including seasonal variation, which may cause fluctuations in semen quality. However, studies to date have reported inconsistent findings, limiting our understanding of how seasonality affects reproductive potential. A clearer picture of these patterns is essential for optimizing the timing and interpretation of fertility evaluations. OBJECTIVE:To systematically review and meta-analyze existing data on seasonal differences in semen analysis parameters. MATERIALS AND METHODS:We searched PubMed, Web of Science, and Scopus up to March 18, 2025 using the key search terms of "semen parameter" and "seasonality," along with their related terms. Initial search yielded 641 studies. The inclusion criteria were original articles or conference abstracts that investigated any human semen parameters across different seasons. After screening, 21 studies were included for meta-analysis. We calculated the pooled weighted mean differences in semen parameters across different seasons using the random-effects models. RESULTS:Meta-analyses of 21 studies with high methodological quality showed that winter and spring had better semen quality than summer and fall, in that they had higher sperm concentration of 3.24-6.07 million/mL, higher total sperm count of 14.63-19.74 million, and lower slow motility of 5.17%-11.75%. Additionally, winter had greater normal morphology of 1.30% than both fall and summer. Spring also had greater total motile sperm count of 4.34-4.38 million compared with fall and summer and greater normal morphology of 0.88% than summer. Summer had lower slow motility of 5.05% than fall. CONCLUSION:This meta-analysis showed seasonal variations in semen parameters, with generally better semen quality in winter and spring compared with summer and fall. Specifically, these seasons were associated with higher sperm concentration, greater total sperm count, and reduced slow motility compared with summer and fall.