Exposure to ambient air pollution and cognitive function: an analysis of the English Longitudinal Study of Ageing cohort.

BACKGROUND: An increasing number of studies suggest adverse effects of exposure to ambient air pollution on cognitive function, but the evidence is still limited. We investigated the associations between long-term exposure to air pollutants and cognitive function in the English Longitudinal Study of Ageing (ELSA) cohort of older adults. METHODS: Our sample included 8,883 individuals from ELSA, based on a nationally representative study of people aged ≥ 50 years, followed-up from 2002 until 2017. Exposure to air pollutants was modelled by the CMAQ-urban dispersion model and assigned to the participants' residential postcodes. Cognitive test scores of memory and executive function were collected biennially. The associations between these cognitive measures and exposure to ambient concentrations of NO2, PM10, PM2.5 and ozone were investigated using mixed-effects models adjusted for time-varying age, physical activity and smoking status, as well as baseline gender and level of education. RESULTS: Increasing long-term exposure per interquartile range (IQR) of NO2 (IQR: 13.05 µg/m3), PM10 (IQR: 3.35 µg/m3) and PM2.5 (IQR: 2.7 µg/m3) were associated with decreases in test scores of composite memory by -0.10 (95% confidence interval [CI]: -0.14, -0.07), -0.02 [-0.04, -0.01] and -0.08 [-0.11, -0.05], respectively. The same increases in NO2, PM10 and PM2.5 were associated with decreases in executive function score of -0.31 [-0.38, -0.23], -0.05 [-0.08, -0.02] and -0.16 [-0.22, -0.10], respectively. The association with ozone was inverse across both tests. Similar results were reported for the London-dwelling sub-sample of participants. CONCLUSIONS: The present study was based on a long follow-up with several repeated measurements per cohort participant and long-term air pollution exposure assessment at a fine spatial scale. Increasing long-term exposure to NO2, PM10 and PM2.5 was associated with a decrease in cognitive function in older adults in England. This evidence can inform policies related to modifiable environmental exposures linked to cognitive decline.

Molecular insights into PCB neurotoxicity: Comparing transcriptomic responses across dopaminergic neurons, population blood cells, and Parkinson's disease pathology.

Parkinson's disease (PD) is a complex neurodegenerative disorder influenced by genetic factors and environmental exposures. Polychlorinated biphenyls (PCBs), a group of synthetic organic compounds, have been identified as potential environmental risk factors for neurodegenerative diseases, including PD. We explored PCB-induced neurotoxicity mechanisms using iPSC-derived dopaminergic neurons and assessed their transcriptomic responses to varying PCB concentrations (0.01 µM, 0.5 µM, and 10 µM). Specifically, we focused on PCB-180, a congener known for its accumulation in human brains. The exposure durations were 24 h and 74 h, allowing us to capture both short-term and more prolonged effects on gene expression patterns. We observed that PCB exposure led to the suppression of oxidative phosphorylation, synaptic function, and neurotransmitter release, implicating these pathways in PCB-induced neurotoxicity. In our comparative analysis, we noted similarities in PCB-induced changes with other PD-related compounds like MPP+ and rotenone. Our findings also aligned with gene expression changes in human blood derived from a population exposed to PCBs, highlighting broader inflammatory responses. Additionally, molecular patterns seen in iPSC-derived neurons were confirmed in postmortem PD brain tissues, validating our in vitro results. In conclusion, our study offers novel insights into the multifaceted impacts of PCB-induced perturbations on various cellular contexts relevant to PD. The use of iPSC-derived dopaminergic neurons allowed us to decipher intricate transcriptomic alterations, bridging the gap between in vitro and in vivo findings. This work underscores the potential role of PCB exposure in neurodegenerative diseases like PD, emphasizing the need to consider both systemic and cell specific effects.

Paternal peri-conceptional physical activity and the risk of congenital heart disease in offspring: A case-control study.

BACKGROUND: Genetic and environmental factors have been shown to contribute to the development of congenital heart disease (CHD). To date, the focus of scientific articles has primarily centered on genetics and maternal environmental factors, with comparatively less attention given to paternal risk factors. OBJECTIVES: This study aims to investigate the potential association between paternal pre-conceptional physical activity levels (PA), along with paternal peri-conceptional smoking and alcohol consumption, and the risk of CHD in offspring. MATERIALS AND METHODS: An observational case-control study was conducted in Lebanon, with 279 participants, aiming to investigate potential risk factors for CHD. We included children with confirmed CHD, born between 2012 and 2022. Controls born in the same timeframe were selected randomly from the general population using online questionnaire forms. Mean age of children included was 6 years old (0-10). The pre-conceptional PA was assessed using the Global Physical Activity Questionnaire validated in Arabic. In addition, paternal smoking, alcohol consumption, and maternal risk factors were collected. RESULTS: The study included 128 CHD cases (45.9%) and their parents, as well as 151 healthy infants (54.1%) and their parents. There were no statistically significant variations in the alcohol consumption noted between the fathers in the case and control groups (p = 0.18). The paternal involvement in recreational-related PA during the peri-conception period was associated with a reduced risk of the CHD development in offspring by 46.9% (OR = 0.531, 95% CI: 0.301-0.936, p = 0.029). Additionally, increasing paternal total sitting time by 1 h above the average, which was approximately 260 min (4 h), increased the risk of CHD in offspring by 0.4% (p = 0.001). Moreover, paternal smoking exhibited an apparent association with a 56% increased risk of offspring developing CHD, notwithstanding that the confidence intervals included the null (OR = 1.56, 95% CI: 0.86-2.8, p = 0.136). DISCUSSION AND CONCLUSION: This observational study is the first to report a potential association between paternal PA, and CHD in offspring. This study aligns with previous reports, advocating for the paternal engagement in PA and the adoption of healthy lifestyle habits, especially during the critical stages of conception. Such practices are strongly recommended to enhance fertility and promote optimal health for offspring. However, due to the subjectivity in reporting PA and lack of molecular proof, additional prospective and molecular studies are required to validate these findings.

Crosstalk between Oxidative Stress and Inflammation Caused by Noise and Air Pollution-Implications for Neurodegenerative Diseases.

Neurodegenerative diseases are often referred to as diseases of old age, and with the aging population, they are gaining scientific and medical interest. Environmental stressors, most notably traffic noise and air pollution, have recently come to the forefront, and have emerged as disease risk factors. The evidence for a connection between environmental risk factors and neurodegenerative disease is growing. In this review, the most common neurodegenerative diseases and their epidemiological association with traffic noise and air pollution are presented. Also, the most important mechanisms involved in neurodegenerative disease development, oxidative stress, and neuroinflammation are highlighted. An overview of the in vivo findings will provide a mechanistic link between noise, air pollution, and neurodegenerative pathology. Finally, the importance of the direct and indirect pathways, by which noise and air pollution cause cerebral damage, is discussed. More high-quality data are still needed from both epidemiological and basic science studies in order to better understand the causal connection between neurodegenerative diseases and environmental risk factors.

Short-Term Changes in Weather Conditions and the Risk of Acute Coronary Syndrome Hospitalization with and without ST-Segment Elevation: A Focus on Vulnerable Subgroups.

Background and Objectives: Acute coronary syndrome (ACS), a prevalent global cardiovascular disease and leading cause of mortality, is significantly correlated with meteorological factors. This study aims to analyze the impact of short-term changes in meteorological factors on the risk of ACS, both with and without ST-segment elevation, and to identify vulnerable subgroups. Materials and Methods: Daily ACS admissions and meteorological variables were collected from October 2016 to December 2021. A generalized linear model (GLM) with a Poisson distribution was employed to examine how short-term fluctuations in meteorological parameters influence ACS hospitalizations. Subgroup analyses were conducted to identify the populations most vulnerable to climate change. Results: Multiple regression analyses showed that short-term fluctuations in atmospheric pressure (≥10 mbar) and air temperature (≥5 °C) seven days prior increased the number of ACS hospitalizations by 58.7% (RR: 1.587; 95% CI: 1.501-1.679) and 55.2% (RR: 1.552; 95% CI: 1.465-1.644), respectively, notably impacting ST-segment elevation myocardial infarctions (STEMIs). The least pronounced association was observed between the daily count of ACS and the variation in relative air humidity (≥20%), resulting in an 18.4% (RR: 1.184; 95% CI: 1.091-1.286) increase in the risk of hospitalization. Subgroup analysis revealed an increased susceptibility among men and older adults to short-term variations in weather parameters. Conclusions: The findings indicate that short-term changes in weather conditions are associated with an increased risk of ACS hospitalizations, particularly STEMIs. Male and older adult patients exhibit heightened susceptibility to variations in climatic factors. Developing effective preventive strategies is imperative to alleviate the adverse consequences of these environmental risk factors.

Reciprocal Effects Between Negative Parenting and Children's Callous-Unemotional Traits From Mid to Late Childhood.

OBJECTIVE: The role of negative parenting in the development of callous-unemotional (CU) traits remains unclear. Both negative parenting and CU traits are influenced by genetic and environmental factors. The authors used genetically informed longitudinal cross-lagged models to examine the extent to which reciprocal effects between negative parenting and children's CU traits in mid-to-late childhood are genetic versus environmental in origin. METHODS: In 9,260 twin pairs from the Twins Early Development Study, the authors estimated cross-lagged effects between negative parenting (discipline and feelings) and children's CU traits in mid (ages 7-9) and late (ages 9-12) childhood. RESULTS: CU traits were strongly heritable and stable. Stability was explained largely by genetic factors. The influence of negative parenting on the development of CU traits was small and driven mostly by genetic and shared environmental factors. In mid childhood, the influence of children's CU traits on subsequent negative parenting (i.e., evoked by children's CU traits) was also small and mostly genetic in origin. In late childhood, CU traits showed no effects on negative parental discipline and small effects on negative parental feelings, which reflected mostly shared environmental factors. CONCLUSIONS: In mid-to-late childhood, genetic factors strongly influenced the development of CU traits, whereas environmental effects of negative parenting were small. Negative parenting was also relatively unaffected by CU traits. The small reciprocal effects originated mostly from genetic and shared environmental factors. Therefore, repeated intensive interventions addressing multiple risk factors rather than negative parenting alone may be best positioned to support families of children with CU traits across development.

Environmental Risk Factors, Protective Factors, and Biomarkers for Hearing Loss: An Umbrella Review.

OBJECTIVE: We aimed to investigate the potential environmental risk factors, protective factors, and biomarkers of hearing loss (HL), and establish a hierarchy of evidence. DATA SOURCES: Embase, PubMed, Cochrane Library, and Web of Science electronic database from inception to June 1, 2023. REVIEW METHODS: We included meta-analyses of observational studies of associations between HL and environmental risk factors, protective factors, or biomarkers. We calculated summary effect estimates, 95% confidence interval, heterogeneity I2 statistic, 95% prediction interval, small study effects, and excess significance biases. RESULTS: Of the 9211 articles retrieved, 60 eligible articles were included. The 60 eligible articles identified 47 potential environmental risk and protective factors (N = 4,123,803) and 46 potential biomarkers (N = 173,701). Evidence of association was convincing (class I) for rheumatoid arthritis (RA) and every 1 cm increase in height. Evidence of association was highly suggestive (class II) for human immunodeficiency virus (HIV), diabetes, cumulative noise exposure (CNE), smoking, congenital cytomegalovirus (CMV) infection, combined exposure to organic solvents and noise, non-Gaussian noise exposure, each 1 kg increase in birth weight, noise exposure, and alopecia areata (AA). CONCLUSION: In this umbrella review, RA, every 1 cm increase in height, HIV, diabetes, CNE, smoking, congenital CMV infection, combined exposure to organic solvents and noise, non-Gaussian noise exposure, each 1 kg increase in birth weight, noise exposure, and AA were strongly associated with HL.

Distinct Constellations of Common Risk Factors Differentially Relate to Executive-Function Ability in Children.

Executive functioning (EF) has been shown to relate to academic achievement and well-being. Independent bodies of work have aimed to understand what environmental or personal attributes influence EF ability. However, most research has not considered how constellations of risk factors create distinct patterns of influence on EF ability. The current study tested a sample of children aged 9 to 10 years from the United States (N = 10,323, 48.06% female, Mage = 9.9 years, age range = 8.9-11.08 years) using a latent profile analysis (LPA) to detect subgroups that varied in their combinations of various risk factors. Six distinct groups of risk factors for children emerged, which in turn related to different average EF abilities. We found that family socioeconomic measures related to a subgroup having above- or below-average EF ability, but we also found an effect on EF across different risk factors. These results inform our understanding of individual variations in EF ability and highlight the idea that EF interventions should consider risk holistically.

[Endometriosis, a participatory study in the Serchio Valley (Tuscany Region, Central Italy): state of the art and perspectives]. / Endometriosi, uno studio partecipato nella Valle del Serchio: stato dell'arte e prospettive.

BACKGROUND: endometriosis is a chronic condition with a significant impact on women's health, featured by endometrial tissue outside the uterine cavity. A limited number of studies have been conducted in the general population, and the true prevalence of endometriosis is unknown for many areas of the country. OBJECTIVES: to better estimate the prevalence of endometriosis in three Italian regions (Friuli Venezia Giulia, Tuscany, Apulia) and to assess the relationship between endometriosis and environmental factors in three participating areas (Trieste, Barga, and Taranto), with a focus on Tuscany Region. DESIGN: implementing a specific epidemiological registry for endometriosis, aimed at estimating the incidence and prevalence data. The registry collected information from hospital discharge records and anatomopathological reports of women residing in the three considered regions, aged 15 years or older. Additionally, the analysis includes the assessment of the spatial distribution of endometriosis at both regional and municipal levels in the three study areas. Further research investigations in these areas involve a multilevel screening of a sample of women of childbearing age. Women who test positive in the initial screening (through a self-administered questionnaire) will have the opportunity to undergo a second level of screening, consisting of a gynecological examination, transvaginal ultrasound, a swab for vaginal microbiome analysis, and the collection of blood and urine samples to assess the presence of polychlorinated biphenyls (PCBs) or heavy metals. The adopted scientific approach is based on post-normal science (PNS) concerning the extended peer community. SETTING AND PARTICIPANTS: women aged 15 years or older residing in the three regions. MAIN OUTCOMES MEASURES: estimating the incidence and prevalence of endometriosis based on data collected from the epidemiological registry. The analysis extends to assessing the spatial distribution of endometriosis at municipal levels in the three areas of interest. RESULTS: the preliminary results of the study allowed for the estimation of the spatial distribution of endometriosis incidence in Tuscany. In particular, it was found that there is variability within the region, with some coastal and North-Western areas showing values 20% higher than the regional average. Cities such as Pisa, Lucca, Livorno, Grosseto, Orbetello, and the Serchio Valley with Barga had a probability of excess risk of more than 90% compared to the regional average. CONCLUSIONS: the study is ongoing and requires the active participation of women living in the region to ensure the completeness and accuracy of the collected data. This research effort represents an important contribution to understanding endometriosis in Tuscany and its possible environmental causes.

Impact of Short-Term Exposure to Nitrogen Dioxide (NO2) and Ozone (O3) on Hospital Admissions for Non-ST-Segment Elevation Acute Coronary Syndrome.

In the context of recent climate change, global warming, industrial growth, and population expansion, air pollution has emerged as a significant environmental and human health risk. This study employed a multivariable Poisson regression analysis to examine the association between short-term exposure to atmospheric pollutants (nitrogen dioxide-NO2, sulfur dioxide -SO2, ozone-O3, and particulate matter with a diameter less than 10 µm-PM10) and hospital admissions for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Daily data on NSTE-ACS admissions, air pollutants, and meteorological variables were collected from January 2019 to December 2021. Elevated NO2 concentrations were associated with a higher risk of NSTE-ACS hospitalization, notably in spring (OR: 1.426; 95% CI: 1.196-1.701). Hypertensive individuals (OR: 1.101; 95% CI: 1.007-1.204) and those diagnosed with unstable angina (OR: 1.107; 95%CI: 1.010-1.213) exhibited heightened susceptibility to elevated NO2 concentrations. A 10 µg/m3 increase in NO2 during spring at lag 07 (OR: 1.013; 95% CI: 1.001-1.025) and O3 in winter at lag 05 (OR: 1.007; 95% CI: 1.001-1.014) was correlated with an elevated daily occurrence of NSTE-ACS admissions. Short-term exposure to various air pollutants posed an increased risk of NSTE-ACS hospitalization, with heightened sensitivity observed in hypertensive patients and those with unstable angina. Addressing emerging environmental risk factors is crucial to mitigate substantial impacts on human health and the environment.

Environmental and Occupational Factors Associated with Leptospirosis: A Systematic Review.

Background: Leptospirosis is a neglected emerging zoonotic disease with a profound public health impact worldwide with higher burden of disease in resource-poor countries. The environmental and occupational exposures contribute to human and animal transmission, but the interaction was less explored. A deeper understanding of the critical environmental and occupational drivers in different contexts will provide useful information for disease control and prevention measures. Objective: This review aimed to summarize the potential environmental and occupational risk factors associated with leptospirosis infection. Methods: Four databases (Scopus, Web of Science, Ovid MEDLINE, EBSCOhost) were searched for articles published from 2012 to 2021. Eligible articles were assessed using a checklist for assessing the quality of the studies. The quality of the articles was assessed based on the laboratory diagnosis approach and statistical analysis method. Results: A total of 32 studies were included in this systematic review. Water-related risk factors such as natural water as the primary water source (AOR 1.8-18.28), water-related recreational activities (AOR 2.36-10.45), flood exposure (AOR 1.54-6.04), contact with mud (AOR 1.57-4.58) and stagnant water (AOR 2.79-6.42) were associated with increased risk of leptospirosis. Infrastructural deficiencies such as un-plastered house walls and thatched houses presented a higher risk (AOR 2.71-5.17). Living in low-lying areas (AOR 1.58-3.74), on clay loam soil (OR 2.72), agricultural land (OR 2.09), and near rubber tree plantations (AOR 11.65) is associated with higher risk of leptospirosis. Contact with rats (AOR 1.4-3.5), livestock (AOR 1.3-10.4), and pigs (AOR 1.54-7.9) is associated with an increased risk of leptospirosis. Outdoor workers (AOR 1.95-3.95) and slaughterhouse workers (AOR 5.1-7.5) have higher risk of leptospirosis. Conclusion: The environmental and occupational components related to water, infrastructure, landscape, agriculture, and exposed animals play an essential role in leptospirosis transmission. The magnitude of those risk factors differs with geographical region, climate factor, urbanization and population growth, and the country's socioeconomic status.

Idiopathic Pulmonary Fibrosis: Where do We Stand and How Far to Go?

Idiopathic pulmonary fibrosis is a progressive and incurable lung disease characterized by collagen deposition, alveolar inflammation, fibroblast proliferation, and the destruction of lung tissue structures. It is a rare yet severe condition with a high mortality rate, typically leading to death within 3-5 years of diagnosis. The clinical presentation of idiopathic pulmonary fibrosis (IPF) involves a gradual and substantial loss of lung function, ultimately resulting in respiratory failure. Despite more than half a century of intensive research, the origin of IPF remains a mystery. Despite its unknown etiology, several genetic and non-genetic factors have been linked to IPF. Recent significant advancements have been made in the field of IPF diagnosis and treatment. Two oral small-molecule drugs, pirfenidone and nintedanib, have recently gained approval for the treatment of IPF. Pirfenidone exhibits antifibrotic, antioxidant, and anti-inflammatory properties, while nintedanib is a tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF) receptors, prostaglandin F (PGF) receptors, and fibroblast growth factor (FGF) receptors. Both of these compounds are capable of slowing down the progression of the disease with an acceptable safety profile. This review provides a brief introduction, historical background, epidemiological insights, and an exploration of various environmental risk factors that may influence the lung microenvironment and contribute to the advancement of IPF. The review also delves into the diagnosis, signaling pathways, and ongoing clinical trials worldwide. A thorough review of the literature was conducted using PubMed and Google Scholar to gather information on various aspects of IPF. Numerous potential drugs are currently under investigation in clinical trials, and the completion of this process is crucial to the ultimate goal of finding a cure for IPF patients. The investigation of the role of genes, surfactant proteins, infectious agents, biomarkers, and epigenetic changes holds the promise of offering earlier and more accurate understanding and diagnosis of IPF. This information could be instrumental in the development of new therapeutic approaches for treating IPF and is expected to be of great interest to researchers.

Childhood intelligence and risk of depression in later-life: A longitudinal data-linkage study.

Background: Lower childhood intelligence test scores are reported in some studies to be associated with higher risk of depression in adulthood. The reasons for the association are unclear. This longitudinal data-linkage study explored the relationship between childhood intelligence (at age ∼11) and risk of depression in later-life (up to age ∼85), and whether childhood family structure and adulthood socio-economic and geographical factors accounted for some of this association. Methods: Intelligence test scores collected in the Scottish Mental Survey 1947 were linked to electronic health records (hospital admissions and prescribing data) between 1980 and 2020 (n = 53,037), to identify diagnoses of depression. Mixed-effect Cox regression models were used to explore the relationship between childhood intelligence test scores and risk of depression in later-life. Analyses were also adjusted for childhood family structure (size of family) and adulthood socio-economic and geographical factors (Carstairs index, urban/rural). Results: Twenty-seven percent of participants were diagnosed with depression during follow-up (n = 14,063/53,037). Greater childhood intelligence test scores were associated with a reduced risk of depression in an unadjusted analysis (HR = 0.95, 95% CI = 0.93 to 0.97, P < 0.001), and after adjustment for factors experienced in childhood and adulthood (HR = 0.95, 95% CI = 0.91 to 1.00, P = 0.032). When identifying depression using only hospital admissions data, greater childhood intelligence test scores were associated with a reduced risk of depression following unadjusted analysis (HR = 0.86, 95% CI = 0.82 to 0.90, P < 0.001), and after adjusting for risk factors in childhood and adulthood (HR = 0.94, 95% CI = 0.89 to 0.99, P = 0.026). There was no association between childhood cognitive test scores and depression when identifying cases of depression using only prescribed drugs data. Conclusions: This study provides additional evidence suggesting that higher childhood intelligence predicts reduced risk of later-life depression only when depression is assessed based on hospital admission records. Childhood family structure and adulthood socio-economic and geographical factors did not seem to be substantial confounders.

Chronic kidney disease of unknown aetiology in Africa: A review of the literature.

During the last two decades, an epidemic of a severe form of chronic kidney disease (CKD) unrelated to traditional risk factors (diabetes and hypertension) has been recognized in low- to middle-income countries. CKD of unknown aetiology (CKDu) mainly affects young working-age adults, and has become as an important and devastating public health issue. CKDu is a multifactorial disease with associated genetic and environmental risk factors. This review summarizes the current epidemiological evidence on the burden of CKDu and its probable environmental risk factors contributing to CKD in Africa. PubMed/Medline and the African Journals Online databases were searched to identify relevant population-based studies published in the last two decades. In the general population, the burden of CKD attributable to CKDu varied from 19.4% to 79%. Epidemiologic studies have established that environmental factors, including genetics, infectious agents, rural residence, low socioeconomic status, malnutrition, agricultural practise and exposure to agrochemicals, heavy metals, use of traditional herbs, and contaminated water sources or food contribute to the burden of CKD in the region. There is a great need for epidemiological studies exploring the true burden of CKDu and unique geographical distribution, and the role of environmental factors in the development of CKD/CKDu.

"Comparative evaluation of different chemical agents induced Autism Spectrum Disorder in experimental Wistar rats".

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with uncertain etiology and pathophysiology. Several studies revealed that the commonly used animal models like Valproic Acid (VPA) and Propionic Acid (PPA) do not precisely represent the disease as the human patient does. The current study was conducted on different chemically (VPA, PPA, Poly I:C, Dioxin (2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)) & Chlorpyrifos (CPF)) induced ASD-like animal models and validated the best suitable experimental animal model, which would closely resemble with clinical features of the ASD. This validated model might help to explore the pathophysiology of ASD. This study included rat pups prenatally exposed to VPA, PPA, Poly I:C, Dioxin & CPF within GD9 to GD15 doses. The model groups were validated through developmental and behavioral parameters, Gene Expressions, Oxidative Stress, and Pro-inflammatory and Anti-inflammatory cytokines levels. Developmental and neurobehavioral parameters showed significant changes in model groups compared to the control. In oxidative stress parameters and neuro-inflammatory cytokines levels, model groups exhibited high oxidative stress and neuro-inflammation compared to control groups. Gene expression profile of ASD-related genes showed significant downregulation in model groups compared to the control group. Moreover, the Poly I:C group showed more significant results than other model groups. The comparison of available ASD-like experimental animal models showed that the Poly I:C induced model represented the exact pathophysiology of ASD as the human patient does. Poly I:C was reported in the maternal immune system activation via the inflammatory cytokines pathway, altering embryonic development and causing ASD in neonates.

Health position paper and redox perspectives - Disease burden by transportation noise.

Transportation noise is a ubiquitous urban exposure. In 2018, the World Health Organization concluded that chronic exposure to road traffic noise is a risk factor for ischemic heart disease. In contrast, they concluded that the quality of evidence for a link to other diseases was very low to moderate. Since then, several studies on the impact of noise on various diseases have been published. Also, studies investigating the mechanistic pathways underlying noise-induced health effects are emerging. We review the current evidence regarding effects of noise on health and the related disease-mechanisms. Several high-quality cohort studies consistently found road traffic noise to be associated with a higher risk of ischemic heart disease, heart failure, diabetes, and all-cause mortality. Furthermore, recent studies have indicated that road traffic and railway noise may increase the risk of diseases not commonly investigated in an environmental noise context, including breast cancer, dementia, and tinnitus. The harmful effects of noise are related to activation of a physiological stress response and nighttime sleep disturbance. Oxidative stress and inflammation downstream of stress hormone signaling and dysregulated circadian rhythms are identified as major disease-relevant pathomechanistic drivers. We discuss the role of reactive oxygen species and present results from antioxidant interventions. Lastly, we provide an overview of oxidative stress markers and adverse redox processes reported for noise-exposed animals and humans. This position paper summarizes all available epidemiological, clinical, and preclinical evidence of transportation noise as an important environmental risk factor for public health and discusses its implications on the population level.

Bayesian linear mixed model with multiple random effects for family-based genetic studies.

Motivation: Family-based study design is one of the popular designs used in genetic research, and the whole-genome sequencing data obtained from family-based studies offer many unique features for risk prediction studies. They can not only provide a more comprehensive view of many complex diseases, but also utilize information in the design to further improve the prediction accuracy. While promising, existing analytical methods often ignore the information embedded in the study design and overlook the predictive effects of rare variants, leading to a prediction model with sub-optimal performance. Results: We proposed a Bayesian linear mixed model for the prediction analysis of sequencing data obtained from family-based studies. Our method can not only capture predictive effects from both common and rare variants, but also easily accommodate various disease model assumptions. It uses information embedded in the study design to form surrogates, where the predictive effects from unmeasured/unknown genetic and environmental risk factors can be modelled. Through extensive simulation studies and the analysis of sequencing data obtained from the Michigan State University Twin Registry study, we have demonstrated that the proposed method outperforms commonly adopted techniques. Availability: R package is available at https://github.com/yhai943/FBLMM.

Adult Mental Health, Substance Use Disorders, and Functional Outcomes of Children Resilient to Early Adversity.

OBJECTIVE: Some children are unaffected by mental illness despite exposure to childhood adversity. These children are typically considered resilient. The objective of this study was to follow up such resilient children in adulthood to characterize mental health status, substance use, and functional outcomes. METHODS: The analysis was based on the prospective, representative Great Smoky Mountains Study (N=1,420). Participants were assessed for psychiatric disorders and exposure to adversity with the structured Child and Adolescent Psychiatric Assessment interview up to eight times in childhood (ages 9-16; 6,674 observations). In total, 1,266 participants (86.3%) were followed up in adulthood at ages 25 and 30 to assess psychiatric disorders, substance use disorders, and functional outcomes. RESULTS: Seventy-five percent of the sample had met criteria for a psychiatric disorder or displayed subthreshold psychiatric problems by age 16. The number of adverse childhood experiences was strongly associated with childhood psychiatric status. Of children exposed to multiple adversities (N=650), 12.2% (N=63) did not display psychiatric problems. This group meets common definitions of childhood resilience. In adulthood, these individuals showing childhood resilience had greater risk of anxiety (risk ratio=2.9, 95% CI=1.0-9.1) and depressive (risk ratio=4.5, 95% CI=1.1-16.7) disorders, as well as worse physical health (means ratio=0.7, 95% CI=0.5-0.9) and financial or educational functioning (means ratio=0.6, 95% CI=0.5-0.7), compared with individuals exposed to fewer childhood adversities. These individuals showing childhood resilience did not have elevated risk for substance use disorders. CONCLUSIONS: Resilience to childhood adversity was uncommon. Individuals who appeared resilient in childhood were at risk for delayed poorer outcomes in adulthood. Public health efforts should prioritize minimizing early adversity exposure over promoting resilience.

Environmental factors and stroke: Risk and prevention.

Stroke is a leading cause of death and adult disability globally. In addition to traditional risk factors, environmental risk factors have emerged over the recent past and are becoming increasingly important. The disproportionate rise of stroke incidence in low- and middle-income countries has been attributed, at least in part, to environmental factors. This narrative review provides details on the interplay between the environment and health generally and stroke specifically, covering topics including air pollution, atmospheric brown clouds, desert dust storms, giant wildfires, chemical contamination, biological aggressors, urbanization, and climate change. It also covers some beneficial environmental effects such as can be harnessed from the exposure to green spaces. It concludes with a summary of pragmatic actions that can be taken to help address some of these challenges at individual, community, and political advocacy levels.