Polystyrene Microplastics of Varying Sizes and Shapes Induce Distinct Redox and Mitochondrial Stress Responses in a Caco-2 Monolayer.

Currently, we lack crucial knowledge on how the physicochemical properties of particles affect cellular health, resulting in an important gap in our understanding of the human toxicity of microplastics (MPs). Our aim was to evaluate the impact of the size and the shape of MPs on uptake and the intracellular effects in a human epithelial colorectal adenocarcinoma (Caco-2) cell line. Spherical (200 nm and 2 µm) and fibre-/fragment-shaped (8.9 ± 10.1 µm by 1.14 ± 0.97 µm) polystyrene microplastics (PS-MPs) were used to study their uptake and the potential to induce redox and mitochondrial stress responses after 24 h of exposure. We demonstrated the cellular uptake of both spherical and fibre-/fragment-shaped MPs in a size-dependent manner. In response to 2 µm spheres, we observed differential expressions of redox-related genes, including HMOX1, CAT, and GPX1. All PS-MPs decreased the intracellular H2O2 levels, which can be attributed to mitochondrial stress responses, such as increased mitochondrial DNA content, footprint, and morphology. Altogether, we demonstrated uptakes and changes in redox and mitochondrial parameters for all PS-MPs, with the 200 nm spheres showing the most profound effects. This suggests that the induction of defensive responses in Caco-2 cells mainly correlates with the number of particles taken up.

Residential green space improves cognitive performances in primary schoolchildren independent of traffic-related air pollution exposure.

BACKGROUND: Cognitive performances of schoolchildren have been adversely associated with both recent and chronic exposure to ambient air pollution at the residence. In addition, growing evidence indicates that exposure to green space is associated with a wide range of health benefits. Therefore, we aimed to investigate if surrounding green space at the residence improves cognitive performance of primary schoolchildren while taking into account air pollution exposure. METHODS: Cognitive performance tests were administered repeatedly to a total of 307 primary schoolchildren aged 9-12y, living in Flanders, Belgium (2012-2014). These tests covered three cognitive domains: attention (Stroop and Continuous Performance Tests), short-term memory (Digit Span Forward and Backward Tests), and visual information processing speed (Digit-Symbol and Pattern Comparison Tests). Green space exposure was estimated within several radii around their current residence (50 m to 2000 m), using a aerial photo-derived high-resolution (1 m2) land cover map. Furthermore, air pollution exposure to PM2.5 and NO2 during the year before examination was modelled for the child's residence using a spatial-temporal interpolation method. RESULTS: An improvement of the children's attention was found with more residential green space exposure independent of traffic-related air pollution. For an interquartile range increment (21%) of green space within 100 m of the residence, a significantly lower mean reaction time was observed independent of NO2 for both the sustained-selective (-9.74 ms, 95% CI: -16.6 to -2.9 ms, p = 0.006) and the selective attention outcomes (-65.90 ms, 95% CI: -117.0 to -14.8 ms, p = 0.01). Moreover, green space exposure within a large radius (2000 m) around the residence was significantly associated with a better performance in short-term memory (Digit-Span Forward Test) and a higher visual information processing speed (Pattern Comparison Test), taking into account traffic-related exposure. However, all associations were attenuated after taking into account long-term residential PM2.5 exposure. CONCLUSIONS: Our panel study showed that exposure to residential surrounding green space was associated with better cognitive performances at 9-12 years of age, taking into account traffic-related air pollution exposure. These findings support the necessity to build attractive green spaces in the residential environment to promote healthy cognitive development in children.

A healthy lifestyle is positively associated with mental health and well-being and core markers in ageing.

BACKGROUND: Studies often evaluate mental health and well-being in association with individual health behaviours although evaluating multiple health behaviours that co-occur in real life may reveal important insights into the overall association. Also, the underlying pathways of how lifestyle might affect our health are still under debate. Here, we studied the mediation of different health behaviours or lifestyle factors on mental health and its effect on core markers of ageing: telomere length (TL) and mitochondrial DNA content (mtDNAc). METHODS: In this study, 6054 adults from the 2018 Belgian Health Interview Survey (BHIS) were included. Mental health and well-being outcomes included psychological and severe psychological distress, vitality, life satisfaction, self-perceived health, depressive and generalised anxiety disorder and suicidal ideation. A lifestyle score integrating diet, physical activity, smoking status, alcohol consumption and BMI was created and validated. On a subset of 739 participants, leucocyte TL and mtDNAc were assessed using qPCR. Generalised linear mixed models were used while adjusting for a priori chosen covariates. RESULTS: The average age (SD) of the study population was 49.9 (17.5) years, and 48.8% were men. A one-point increment in the lifestyle score was associated with lower odds (ranging from 0.56 to 0.74) for all studied mental health outcomes and with a 1.74% (95% CI: 0.11, 3.40%) longer TL and 4.07% (95% CI: 2.01, 6.17%) higher mtDNAc. Psychological distress and suicidal ideation were associated with a lower mtDNAc of - 4.62% (95% CI: - 8.85, - 0.20%) and - 7.83% (95% CI: - 14.77, - 0.34%), respectively. No associations were found between mental health and TL. CONCLUSIONS: In this large-scale study, we showed the positive association between a healthy lifestyle and both biological ageing and different dimensions of mental health and well-being. We also indicated that living a healthy lifestyle contributes to more favourable biological ageing.

Assessment of the Feasibility of a Future Integrated Larger-Scale Epidemiological Study to Evaluate Health Risks of Air Pollution Episodes in Children.

Air pollution exposure can lead to exacerbation of respiratory disorders in children. Using sensitive biomarkers helps to assess the impact of air pollution on children's respiratory health and combining protein, genetic and epigenetic biomarkers gives insights on their interrelatedness. Most studies do not contain such an integrated approach and investigate these biomarkers individually in blood, although its collection in children is challenging. Our study aimed at assessing the feasibility of conducting future integrated larger-scale studies evaluating respiratory health risks of air pollution episodes in children, based on a qualitative analysis of the technical and logistic aspects of a small-scale field study involving 42 children. This included the preparation, collection and storage of non-invasive samples (urine, saliva), the measurement of general and respiratory health parameters and the measurement of specific biomarkers (genetic, protein, epigenetic) of respiratory health and air pollution exposure. Bottlenecks were identified and modifications were proposed to expand this integrated study to a higher number of children, time points and locations. This would allow for non-invasive assessment of the impact of air pollution exposure on the respiratory health of children in future larger-scale studies, which is critical for the development of policies or measures at the population level.

Higher buccal mtDNA content is associated with residential surrounding green in a panel study of primary school children.

BACKGROUND: Mitochondria are known to respond to environmental stressors but whether green space is associated with mitochondrial abundance is unexplored. Furthermore, as exposures may affect health from early life onwards, we here evaluate if residential green space is associated with mitochondria DNA content (mtDNAc) in children. METHODS: In primary schoolchildren (COGNAC study), between 2012 and 2014, buccal mtDNAc was repeatedly (three times) assessed using qPCR. Surrounding low (<3m), high (≥3m) and total (sum of low and high) green space within different radii (100m-1000m) from the residence and distance to the nearest large green space (>0.5ha) were estimated using a remote sensing derived map. Given the repeated measures design, we applied a mixed-effects model with school and subject as random effect while adjusting for a priori chosen fixed covariates. RESULTS: mtDNAc was assessed in 246 children with a total of 436 measurements (mean age 10.3 years). Within a 1000m radius around the residential address, an IQR increment in low (11.0%), high (9.5%), and total (13.9%) green space was associated with a respectively 15.2% (95% CI: 7.2%-23.7%), 10.8% (95% CI: 4.5%-17.5%), and 13.4% (95% CI: 7.4%-19.7%) higher mtDNAc. Conversely, an IQR increment (11.6%) in agricultural area in the same radius was associated with a -3.4% (95% CI: 6.7% to -0.1%) lower mtDNAc. Finally, a doubling in distance to large green space was associated with a -5.2% (95% CI: 7.9 to -2.4%) lower mtDNAc. CONCLUSION: To our knowledge, this is the first study evaluating associations between residential surrounding green space and mtDNAc in children. Our results showed that green space was associated with a higher mtDNAc in children, which indicates the importance of the early life environment. To what extent these findings contribute to later life health effects should be further examined.

Residential green space in association with the methylation status in a CpG site within the promoter region of the placental serotonin receptor HTR2A.

Green space could influence adult cognition and childhood neurodevelopment , and is hypothesized to be partly driven by epigenetic modifications. However, it remains unknown whether some of these associations are already evident during foetal development. Similar biological signals shape the developmental processes in the foetal brain and placenta.Therefore, we hypothesize that green space can modify epigenetic processes of cognition-related pathways in placental tissue, such as DNA-methylation of the serotonin receptor HTR2A. HTR2A-methylation was determined within 327 placentas from the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort using bisulphite-PCR-pyrosequencing. Total green space exposure was calculated using high-resolution land cover data derived from the Green Map of Flanders in seven buffers (50 m-3 km) and stratified into low (<3 m) and high (≥3 m) vegetation. Residential nature was calculated using the Land use Map of Flanders. We performed multivariate regression models adjusted for several a priori chosen covariables. For an IQR increment in total green space within a 1,000 m, 2,000 m and 3,000 m buffer the methylation of HTR2A increased with 1.47% (95%CI:0.17;2.78), 1.52% (95%CI:0.21;2.83) and 1.42% (95%CI:0.15;2.69), respectively. Additionally,, we found 3.00% (95%CI:1.09;4.91) and 1.98% (95%CI:0.28;3.68) higher HTR2A-methylation when comparing residences with and without the presence of nature in a 50 m and 100 m buffer, respectively. The methylation status of HTR2A in placental tissue is positively associated with maternal green space exposure. Future research is needed to understand better how these epigenetic changes are related to functional modifications in the placenta and the consequent implications for foetal development.

Urinary CC16, a potential indicator of lung integrity and inflammation, increases in children after short-term exposure to PM2.5/PM10 and is driven by the CC16 38GG genotype.

Particular matter (PM) exposure is a big hazard for public health, especially for children. Serum CC16 is a well-known biomarker of respiratory health. Urinary CC16 (U-CC16) can be a noninvasive alternative, albeit requiring adequate adjustment for renal handling. Moreover, the SNP CC16 G38A influences CC16 levels. This study aimed to monitor the effect of short-term PM exposure on CC16 levels, measured noninvasively in schoolchildren, using an integrative approach. We used a selection of urine and buccal DNA samples from 86 children stored in an existing biobank. Using a multiple reaction monitoring method, we measured U-CC16, as well as RBP4 (retinol binding protein 4) and ß2M (beta-2-microglobulin), required for adjustment. Buccal DNA samples were used for CC16 G38A genotyping. Linear mixed-effects models were used to find relevant associations between U-CC16 and previously obtained data from recent daily PM ≤ 2.5 or 10 µm exposure (PM2.5, PM10) modeled at the child's residence. Our study showed that exposure to low PM at the child's residence (median levels 18.9 µg/m³ (PM2.5) and 23.6 µg/m³ (PM10)) one day before sampling had an effect on the covariates-adjusted U-CC16 levels. This effect was dependent on the CC16 G38A genotype, due to its strong interaction with the association between PM levels and covariates-adjusted U-CC16 (P = 0.024 (PM2.5); P = 0.061 (PM10)). Only children carrying the 38GG genotype showed an increase of covariates-adjusted U-CC16, measured 24h after exposure, with increasing PM2.5 and PM10 (ß = 0.332; 95% CI: 0.110 to 0.554 and ß = 0.372; 95% CI: 0.101 to 0.643, respectively). To the best of our knowledge, this is the first study using an integrative approach to investigate short-term PM exposure of children, using urine to detect early signs of pulmonary damage, and taking into account important determinants such as the genetic background and adequate adjustment of the measured biomarker in urine.

Air pollution in association with mental and self-rated health and the mediating effect of physical activity.

BACKGROUND: Recent studies showed that air pollution might play a role in the etiology of mental disorders. In this study we evaluated the association between air pollution and mental and self-rated health and the possible mediating effect of physical activity in this association. METHODS: In 2008, 2013 and 2018 the Belgian Health Interview Survey (BHIS) enrolled 16,455 participants who completed following mental health dimensions: psychological distress, suboptimal vitality, suicidal ideation, and depressive and generalized anxiety disorder and self-rated health. Annual exposure to nitrogen dioxide (NO2), particulate matter ≤ 2.5 µm (PM2.5) and black carbon (BC) were estimated at the participants' residence by a high resolution spatiotemporal model. Multivariate logistic regressions were carried out taking into account a priori selected covariates. RESULTS: Long-term exposure to PM2.5, BC and NO2 averaged 14.5, 1.4, and 21.8 µg/m3, respectively. An interquartile range (IQR) increment in PM2.5 exposure was associated with higher odds of suboptimal vitality (OR = 1.27; 95% CI: 1.13, 1.42), poor self-rated health (OR = 1.20; 95% CI: 1.09, 1.32) and depressive disorder (OR = 1.19; 95% CI: 1.00, 1.41). Secondly, an association was found between BC exposure and higher odds of poor self-rated health and depressive and generalized anxiety disorder and between NO2 exposure and higher odds of psychological distress, suboptimal vitality and poor self-rated health. No association was found between long-term ambient air pollution and suicidal ideation or severe psychological distress. The mediation analysis suggested that between 15.2% (PM2.5-generalized anxiety disorder) and 40.1% (NO2-poor self-rated health) of the association may be mediated by a difference in physical activity. CONCLUSIONS: Long-term exposure to PM2.5, BC or NO2 was adversely associated with multiple mental health dimensions and self-rated health and part of the association was mediated by physical activity. Our results suggest that policies aiming to reduce air pollution levels could also reduce the burden of mental health disorders in Belgium.

Validity of self-reported air pollution annoyance to assess long-term exposure to air pollutants in Belgium.

In epidemiological studies, assessment of long term exposure to air pollution is often estimated using air pollution measurements at fixed monitoring stations, and interpolated to the residence of survey participants through Geographical Information Systems (GIS). However, obtaining georeferenced address data from national registries requires a long and cumbersome administrative procedure, since this kind of personal data is protected by privacy regulations. This paper aims to assess whether information collected in health interview surveys, including air pollution annoyance, could be used to build prediction models for assessing individual long term exposure to air pollution, removing the need for data on personal residence address. Analyses were carried out based on data from the Belgian Health Interview Survey (BHIS) 2013 linked to GIS-modelled air pollution exposure at the residence place of participants older than 15 years (n = 9347). First, univariate linear regressions were performed to assess the relationship between air pollution annoyance and modelled exposure to each air pollutant. Secondly, a multivariable linear regression was performed for each air pollutant based on a set of variables selected with elastic net cross-validation, including variables related to environmental annoyance, socio-economic and health status of participants. Finally, the performance of the models to classify individuals in three levels of exposure was assessed by means of a confusion matrix. Our results suggest a limited validity of self-reported air pollution annoyance as a direct proxy for air pollution exposure and a weak contribution of environmental annoyance variables in prediction models. Models using variables related to the socio-economic status, region, urban level and environmental annoyance allow to predict individual air pollution exposure with a percentage of error ranging from 8% to 18%. Although these models do not provide very accurate predictions in terms of absolute exposure to air pollution, they do allow to classify individuals in groups of relative exposure levels, ranking participants from low over medium to high air pollution exposure. This model represents a rapid assessment tool to identify groups within the BHIS participants undergoing the highest levels of environmental stress.

Introducing nature at the work floor: A nature-based intervention to reduce stress and improve cognitive performance.

BACKGROUND: Although a growing body of research has shown that exposure to nature has restorative effects on human health, the potential beneficial effects of nature-based interventions in the working environment are still underexplored. METHODS: We performed a randomized controlled study with a nature-based program during working hours. We enrolled employees, randomized the participants into two groups being an intervention and a control group. Twice a week for three consecutive weeks, the intervention group participated in nature-based activities for 2 h. The primary outcomes were cognitive performance, burnout assessment, salivary cortisol levels, and continuous stress levels. We performed intervention-response analyses using mixed-effects models that included random effects for each participant across the different examinations. RESULTS: Compared to the control group (n = 20), the intervention group (n = 25) participating in the nature-based program had a lower Burnout Assessment Tool score (-14.9% CI-16.2 to -14.3, difference; p < 0.001), lower salivary cortisol levels (-29.3% CI-34.7 to -25.3; p < 0.001) and higher visual information processing speed (7.4% CI6.9-8.0; p < 0.001). Selective attention of the participants that participated in the nature-based program improved during the interventions (-10.6 CI-19.6 to -6.9, p = 0.045), compared to the controls. CONCLUSIONS: This study provides novel evidence that exposure to nature during work hours reduces stress and improves cognitive performance. The trial is registered with ClinicalTrials.gov, number: NCT04111796.

Gestational acrylamide exposure and biomarkers of fetal growth: Probing the mechanism underlying the association between acrylamide and reduced fetal growth.

INTRODUCTION: Four epidemiological studies have shown a negative association between prenatal acrylamide exposure and birth size. In order to shed light on the possible underlying mechanism(s), we analysed associations between acrylamide biomarkers and biomarkers related to fetal growth. METHODS: In newborns of the ENVIRONAGE birth cohort (n ranges from 215 to 434), we investigated the association between prenatal acrylamide exposure (acrylamide and glycidamide hemoglobin adduct levels in cord blood) and thyroid hormones (TSH, T3, T4 and the ratio of T4 to T3 in cord plasma), insulin-related factors (cord plasma insulin and IGF1, and placental IGF2), neurotrophins (cord plasma BDNF, and placental NGF, NT3 and NT4), and cord plasma homocysteine and progesterone, using multiple linear regression analysis. In addition, we investigated whether the biomarkers mediated the associations between prenatal acrylamide exposure and birth outcomes. RESULTS: We observed lower cord plasma TSH (-10.2% [95% CI: -15.0, -4.3]) and higher placental NGF levels (10.0% [95% CI 3.7, 17.4]) for a twofold increase of acrylamide adducts, a decrease in the ratio of cord plasma free T4 and free T3 with higher acrylamide and glycidamide adducts of -2.9% (95% CI: -5.7, -0.1) and -3.9% (95% CI: -6.2, -1.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively, and higher cord plasma free T3 with increases in both acrylamide and glycidamide adducts of 2.8% (95% CI: 0.2, 5.6) and 3.6% (95% CI: 0.8, 6.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively. Additionally, a twofold increase in glycidamide adducts was associated with lower cord plasma insulin levels, particularly among newborns of non-smoking mothers (-11.2% [95% CI: -19.5, -0.1]). Cord plasma insulin seemed to mediate the association between glycidamide adducts and birth weight. CONCLUSIONS: A decrease in cord plasma insulin levels may be (a marker of) a mechanism by which gestational acrylamide exposure is associated with decreased fetal growth. The possible health consequences of the associations between gestational acrylamide exposure and thyroid hormones and neurotrophins warrant future study.

Association between urban environment and mental health in Brussels, Belgium.

BACKGROUND: Mental health disorders appear as a growing problem in urban areas. While common mental health disorders are generally linked to demographic and socioeconomic factors, little is known about the interaction with the urban environment. With growing urbanization, more and more people are exposed to environmental stressors potentially contributing to increased stress and impairing mental health. It is therefore important to identify features of the urban environment that affect the mental health of city dwellers. The aim of this study was to define associations of combined long-term exposure to air pollution, noise, surrounding green at different scales, and building morphology with several dimensions of mental health in Brussels. METHODS: Research focuses on the inhabitants of the Brussels Capital Region older than 15 years. The epidemiological study was carried out based on the linkage of data from the national health interview surveys (2008 and 2013) and specifically developed indicators describing each participant's surroundings in terms of air quality, noise, surrounding green, and building morphology. These data are based on the geographical coordinates of the participant's residence and processed using Geographical Information Systems (GIS). Mental health status was approached through several validated indicators: the Symptom Checklist-90-R subscales for depressive, anxiety and sleeping disorders and the 12-Item General Health Questionnaire for general well-being. For each mental health outcome, single and multi-exposure models were performed through multivariate logistic regressions. RESULTS: Our results suggest that traffic-related air pollution (black carbon, NO2, PM10) exposure was positively associated with higher odds of depressive disorders. No association between green surrounding, noise, building morphology and mental health could be demonstrated. CONCLUSIONS: These findings have important implications because most of the Brussel's population resides in areas where particulate matters concentrations are above the World Health Organization guidelines. This suggests that policies aiming to reduce traffic related-air pollution could also reduce the burden of depressive disorders in Brussels.

Denser Retinal Microvascular Network Is Inversely Associated With Behavioral Outcomes and Sustained Attention in Children.

Changes in geometry of the retinal microvascular network, including vessel width, vessel density, and tortuosity, have been associated with neurological disorders in adults. We investigated metrics of the retinal microvasculature in association with behavior and cognition in 8- to 12-year-old children. Digital fundus images of 190 children (48.2% girls, mean age 9.9 years) were used to calculate retinal vessel diameters, fractal dimension, lacunarity, and tortuosity. Parents filled out a Strengths and Difficulties Questionnaire (SDQ) for behavioral screening. Cognitive performance testing included a computerized version of the Stroop test (selective attention), the Continuous Performance (sustained attention), the Digit-Symbol (visual scanning and information-processing speed) and the Pattern Comparison (visuospatial analytic ability) tests from the Neurobehavioral Evaluation System (NES3) battery. Retinal vessel geometry was significantly associated with the SDQ problem score, which increased with 1.1 points (95% CI: 0.3 to 1.9 points) per interquartile (IQR) increment in retinal fractal dimension, and decreased 1.4 points (95% CI: -2.4 to -0.4 points) or decreased 1.0 points (95% CI: -2.1 to 0.1 points) per IQR increment in retinal vascular lacunarity or tortuosity, respectively. Sensitivity analyses showed that results were driven by the hyperactivity/inattention and conduct problem scales of the SDQ. Correspondingly, mean reaction time on the Continuous Performance test increased by 11 ms (95% CI: 4.4 to 17.6 ms) with an IQR increase in fractal dimension. The results indicate that a denser retinal microvascular network, exemplified by a higher fractal dimension and lower lacunarity, are inversely associated with behavioral outcomes and sustained attention in children.

Child buccal telomere length and mitochondrial DNA content as biomolecular markers of ageing in association with air pollution.

BACKGROUND: Pro-inflammatory conditions such as air pollution might induce biological ageing. However, the available evidence on such an impact in children is still very scarce. We studied in primary schoolchildren the association of ambient residential air pollution exposure with telomere length (TL) and mitochondrial DNA content (mtDNAc), two important targets of the core axis of ageing. METHODS: Between 2012 and 2014, buccal TL and mtDNAc were repeatedly assessed using qPCR in 197 Belgian primary schoolchildren (mean age 10.3 years) as part of the COGNAC study. At the child's residence, recent (week), sub-chronic (month) and chronic (year) exposure to nitrogen dioxide (NO2), particulate matter ≤ 2.5 µm (PM2.5) and black carbon (BC) were estimated using a high resolution spatiotemporal model. A mixed-effects model with school and subject as random effect was used while adjusting for a priori chosen covariates. RESULTS: An interquartile range (IQR) increment (1.9 µg/m3) in chronic PM2.5 exposure was associated with a 8.9% (95% CI: -15.4 to -1.9%) shorter TL. In contrast to PM2.5, chronic exposure to BC and NO2 was not associated with TL but recent exposure to BC and NO2 showed significant inverse associations with TL: an IQR increment in recent exposure to BC (0.9 µg/m3) and NO2 (10.2 µg/m3) was associated with a 6.2% (95% CI: -10.6 to -1.6%) and 6.4% (95% CI: -11.8 to -0.7%) shorter TL, respectively. Finally, an IQR increment in chronic PM2.5 exposure was associated with a 12.7% (95% CI: -21.7 to -2.6%) lower mtDNAc. However, no significant associations were seen for NO2 and BC or for other exposure windows. CONCLUSION: Chronic exposure to PM2.5 below the EU threshold was associated with child's shorter buccal TL and lower mtDNAc, while traffic-related pollutants (BC and NO2) showed recent effects on telomere biology. Our data add to the literature on air pollution-induced effects of TL and mtDNAc, two measures part of the core axis of cellular ageing, from early life onwards.

Two-year neurocognitive responses to first occupational lead exposure.

Objectives Lead exposure causes neurocognitive dysfunction in children, but its association with neurocognition in adults at current occupational exposure levels is uncertain mainly due to the lack of longitudinal studies. In the Study for Promotion of Health in Recycling Lead (NCT02243904), we assessed the two-year responses of neurocognitive function among workers without previous known occupational exposure newly hired at lead recycling plants. Methods Workers completed the digit-symbol test (DST) and Stroop test (ST) at baseline and annual follow-up visits. Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 µg/dL). Statistical methods included multivariable-adjusted mixed models with participants modelled as random effect. Results DST was administered to 260 participants (11.9% women; 46.9%/45.0% whites/Hispanics; mean age 29.4 years) and ST to 168 participants. Geometric means were 3.97 and 4.13 µg/dL for baseline BL, and 3.30 and 3.44 for the last-follow-up-to-baseline BL ratio in DST and ST cohorts, respectively. In partially adjusted models, a doubling of the BL ratio was associated with a 0.66% [95% confidence interval (CI) 0.03-1.30; P=0.040] increase in latency time (DST) and a 0.35% (95% CI ­1.63-1.63; P=0.59) decrease in the inference effect (ST). In fully adjusted models, none of the associations of the changes in the DST and ST test results with the blood lead changes reached statistical significance (P≥0.12). Conclusions An over 3-fold increase in blood lead over two years of occupational exposure was not associated with a relevant decline in cognitive performance.

Environmental exposures and health behavior in association with mental health: a study design.

BACKGROUND: Air pollution, green space and smoking are known to affect human health. However, less is known about their underlying biological mechanisms. One of these mechanisms could be biological aging. In this study, we explore the mediation of biomarkers of exposure and biological aging to explain the associations between environmental exposures, health behavior and mental health. METHODS: The study population of this cross-sectional study (n = 1168) is a subsample of the Belgian 2018 Health Interview Survey (BHIS). Mental health indicators including psychological and severe psychological distress, life satisfaction, vitality, eating disorders, suicidal ideation, subjective health and depressive and anxiety disorders, demographics and health behavior such as smoking are derived from the BHIS. Urine and blood samples are collected to measure respectively the biomarkers of exposure (urinary black carbon (BC) and (hydroxy)cotinine) and the biomarkers of biological aging (mitochondrial DNA content (mtDNAc) and telomere length (TL)). Recent and chronic exposure (µg/m3) to nitrogen dioxide (NO2), particulate matter ≤2.5 µm (PM2.5) and ≤ 10 µm (PM10) and BC at the participants' residence are modelled using a high resolution spatial temporal interpolation model. Residential green space is defined in buffers of different size (50 m - 5000 m) using land cover data in ArcGIS 10 software. For the statistical analysis multivariate linear and logistic regressions as well as mediation analyses are used taking into account a priori selected covariates and confounders. RESULTS: As this study combined data of BHIS and laboratory analyses, not all data is available for all participants. Therefore, data analyses will be conducted on different subsets. Data on air pollution and green space exposure is available for all BHIS participants. Questions on smoking and mental health were answered by respectively 7829 and 7213 BHIS participants. For biomarker assessment, (hydroxy) cotinine, urinary BC and the biomarkers of biological aging are measured for respectively 1130, 1120 and 985 participants. CONCLUSION: By use of personal markers of air pollution and smoking, as well as biological aging, we will gain knowledge about the association between environmental exposures, health behavior, and the mental health status. The results of the study can provide insights on the health of the Belgian population, making it a nationwide interesting study.

Urban environment and mental health: the NAMED project, protocol for a mixed-method study.

INTRODUCTION: Mental health issues appear as a growing problem in modern societies and tend to be more frequent in big cities. Where increased evidence exists for positive links between nature and mental health, associations between urban environment characteristics and mental health are still not well understood. These associations are highly complex and require an interdisciplinary and integrated research approach to cover the broad range of mitigating factors. This article presents the study protocol of a project called Nature Impact on Mental Health Distribution that aims to generate a comprehensive understanding of associations between mental health and the urban residential environment. METHODS AND ANALYSIS: Following a mixed-method approach, this project combines quantitative and qualitative research. In the quantitative part, we analyse among the Brussels urban population associations between the urban residential environment and mental health, taking respondents' socioeconomic status and physical health into account. Mental health is determined by the mental health indicators in the national Health Interview Survey (HIS). The urban residential environment is described by subjective indicators for the participant's dwelling and neighbourhood present in the HIS and objective indicators for buildings, network infrastructure and green environment developed for the purpose of this project. We assess the mediating role of physical activity, social life, noise and air pollution. In the qualitative part, we conduct walking interviews with Brussels residents to record their subjective well-being in association with their neighbourhood. In the validation part, results from these two approaches are triangulated and evaluated through interviews and focus groups with stakeholders of healthcare and urban planning sectors. ETHICS AND DISSEMINATION: The Privacy Commission of Belgium and ethical committee from University Hospital of Antwerp respectively approved quantitative database merging and qualitative interviewing. We will share project results with a wide audience including the scientific community, policy authorities and civil society through scientific and non-expert communication.

Residential green space and seasonal distress in a cohort of tree pollen allergy patients.

BACKGROUND: Residential green space may improve human health, for example by promoting physical activity and by reducing stress. Conversely, residential green space may increase stress by emitting aeroallergens and exacerbating allergic disease. Here we examine impacts of exposure to residential green space on distress in the susceptible subpopulation of adults sensitized to tree pollen allergens. METHODS: In a panel study of 88 tree pollen allergy patients we analyzed self-reported mental health (GHQ-12), perceived presence of allergenic trees (hazel, alder, birch) near the residence and residential green space area within 1 km distance [high (≥3 m) and low (<3 m) green]. Results were adjusted for patients' background data (gender, age, BMI, smoking status, physical activity, commuting distance, education level, allergy medication use and chronic respiratory problems) and compared with distress in the general population (N = 2467). RESULTS: Short-term distress [mean GHQ-12 score 2.1 (95% confidence interval 1.5-2.7)] was higher in the study population than in the general population [1.5 (1.4-1.7)]. Residential green space had protective effects against short-term distress [high green, per combined surface area of 10 ha: adjusted odds ratio OR = 0.94 (95% confidence interval 0.90-0.99); low green, per 10 ha: OR = 0.85 (0.78-0.93)]. However, distress was higher in patients who reported perceived presence of allergenic trees near their residence [present vs. absent: OR = 2.04 (1.36-3.07)]. CONCLUSIONS: Perceived presence of allergenic tree species in the neighbourhood of the residence of tree pollen allergy patients modulates the protective effect of residential green space against distress during the airborne tree pollen season.

Ambient black carbon particles reach the fetal side of human placenta.

Particle transfer across the placenta has been suggested but to date, no direct evidence in real-life, human context exists. Here we report the presence of black carbon (BC) particles as part of combustion-derived particulate matter in human placentae using white-light generation under femtosecond pulsed illumination. BC is identified in all screened placentae, with an average (SD) particle count of 0.95 × 104 (0.66 × 104) and 2.09 × 104 (0.9 × 104) particles per mm3 for low and high exposed mothers, respectively. Furthermore, the placental BC load is positively associated with mothers' residential BC exposure during pregnancy (0.63-2.42 µg per m3). Our finding that BC particles accumulate on the fetal side of the placenta suggests that ambient particulates could be transported towards the fetus and represents a potential mechanism explaining the detrimental health effects of pollution from early life onwards.