Social Disconnectedness in Individuals with Cardiovascular Disease: Associations with Health Literacy and Treatment Burden.

BACKGROUND: Knowledge is limited on associations between social disconnectedness (i.e. loneliness and social isolation), health literacy and perceived treatment burden in individuals with cardiovascular disease (CVD). However, understanding these associations may be important for clinical practice. METHODS: This study used cross-sectional self-reported data from the 2017 Danish health and morbidity survey entitled 'How are you?', investigating the associations of loneliness and social isolation with low health literacy and high treatment burden in individuals with CVD (n = 2521; mean age = 65.7 years). RESULTS: Logistic regression analysis showed that loneliness and social isolation were associated with low health literacy in terms of difficulties in 'understanding health information' (loneliness: adjusted odds ratio (AOR) = 1.32, 95% confidence intervals (CI) [1.16, 1.50]; social isolation: AOR = 1.47, 95% CI [1.24, 1.73]) and 'engaging with healthcare providers' (loneliness: AOR = 1.53, 95% CI [1.37, 1.70]; social isolation: AOR = 1.21, 95% CI [1.06, 1.40]) and associated with high treatment burden (loneliness: AOR = 1.49, 95% CI [1.35, 1.65]; social isolation: AOR = 1.20, 95% CI [1.06, 1.37]). CONCLUSIONS: Our findings show that loneliness and social isolation coexisted with low health literacy and high treatment burden in individuals with CVD. These findings are critical as socially disconnected individuals experience more health issues. Low health literacy and a high treatment burden may potentially exacerbate these issues.

Ambient air pollution and hypertensive disorders of pregnancy in Rome.

BACKGROUND: Ambient air pollution has been associated with hypertensive disorders of pregnancy (HDP), but few studies rely on assessment of fine-scale variation in air quality, specific subtypes and multi-pollutant exposures. AIM: To study the impact of long-term exposure to individual and mixture of air pollutants on all and specific subtypes of HDP. METHODS: We obtained data from 130,470 liveborn singleton pregnacies in Rome during 2014-2019. Spatiotemporal land-use random-forest models at 1 km spatial resolution assigned to the maternal residential addresses were used to estimate the exposure to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and ozone (O3). RESULTS: For PM2.5, PM10 and NO2, there was suggestive evidence of increased risk of preeclampsia (PE, n = 442), but no evidence of increased risk for all subtypes of HDP (n = 2297) and gestational hypertension (GH, n = 1901). For instance, an interquartile range of 7.0 µg/m3 increase in PM2.5 exposure during the first trimester of pregnancy was associated with an odds ratio (OR) of 1.06 (95% confidence interval: 0.81, 1.39) and 1.04 (0.92, 1.17) after adjustment for NO2 and the corresponding results for a 15.7 µg/m3 increase in NO2 after adjustment for PM2.5 were 1.11 (0.92, 1.34) for PE and 0.83 (0.76, 0.90) for HDP. Increased risks for HDP and GH were suggested for O3 in single-pollutant models and for PM after adjustment for NO2, but all other associations were stable or attenuated in two-pollutant models. CONCLUSIONS: The results of our study suggest that PM2.5, PM10 and NO2 increases the risk of PE and that these effects are robust to adjustment for O3 while the increased risks for GH and HDP suggested for O3 attenuated after adjustment for PM or NO2. Additional studies are needed to evaluate the effects of source-specific component of PM on subtypes as well as all types of HDP which would help to target preventive actions.

Urban environment in pregnancy and postpartum depression: An individual participant data meta-analysis of 12 European birth cohorts.

BACKGROUND: Urban environmental exposures associate with adult depression, but it is unclear whether they are associated to postpartum depression (PPD). OBJECTIVES: We investigated associations between urban environment exposures during pregnancy and PPD. METHODS: We included women with singleton deliveries to liveborn children from 12 European birth cohorts (N with minimum one exposure = 30,772, analysis N range 17,686-30,716 depending on exposure; representing 26-46 % of the 66,825 eligible women). We estimated maternal exposure during pregnancy to ambient air pollution with nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10), road traffic noise (Lden), natural spaces (Normalised Difference Vegetation Index; NDVI, proximity to major green or blue spaces) and built environment (population density, facility richness and walkability). Maternal PPD was assessed 3-18 months after birth using self-completed questionnaires. We used adjusted logistic regression models to estimate cohort-specific associations between each exposure and PPD and combined results via meta-analysis using DataSHIELD. RESULTS: Of the 30,772 women included, 3,078 (10 %) reported having PPD. Exposure to PM10 was associated with slightly increased odds of PPD (adjusted odd ratios (OR) of 1.08 [95 % Confidence Intervals (CI): 0.99, 1.17] per inter quartile range increment of PM10) whilst associations for exposure to NO2 and PM2.5 were close to null. Exposure to high levels of road traffic noise (≥65 dB vs. < 65 dB) was associated with an OR of 1.12 [CI: 0.95, 1.32]. Associations between green spaces and PPD were close to null; whilst proximity to major blue spaces was associated with increased risk of PPD (OR 1.12, 95 %CI: 1.00, 1.26). All associations between built environment and PPD were close to null. Multiple exposure models showed similar results. DISCUSSION: The study findings suggest that exposure to PM10, road traffic noise and blue spaces in pregnancy may increase PPD risk, however future studies should explore this causally.

Exposure to different residential indoor characteristics during childhood and asthma in adolescence: a latent class analysis of the Danish National Birth Cohort.

BACKGROUND: Many residential indoor environments may have an impact on children's respiratory health. OBJECTIVES: The aims of this study were to identify latent classes of children from the Danish National Birth Cohort (DNBC) who share similar patterns of exposure to indoor home characteristics, and to examine the association between membership in the latent classes and asthma in adolescence. METHODS: We included data on residential indoor characteristics of offspring from the DNBC whose mothers had responded to the child's 11-year follow-up and who had data on asthma from the 18-year follow-up. Number of classes and associations were estimated using latent class analysis. To account for sample selection, we applied inverse probability weighting. RESULTS: Our final model included five latent classes. The probability of current asthma at 18 years was highest among individuals in class one with higher clustering on household dampness (9, 95%CI 0.06-0.13). Individuals in class four (with higher clustering on pets ownership and living in a farm) had a lower risk of current asthma at age 18 compared to individuals in class one (with higher clustering on household dampness) (OR 0.53 (95%CI 0.32-0.88), p = .01). CONCLUSION: Our findings suggest that, in a high-income country such as Denmark, groups of adolescents growing up in homes with mold and moisture during mid-childhood might be at increased risk of current asthma at age 18. Adolescents who grew-up in a farmhouse and who were exposed to pets seem less likely to suffer from asthma by age 18.

Effects of Weaning Age and Creep Feed Type on Growth Performance and Gut Maturation in Weaned Piglets.

The objective was to study the effects of weaning in week 5 (W5) vs. week 4 (W4), as well as liquid (LF) vs. dry feed (DF), on growth performance, disaccharidase activity and nutrient transporter expression after weaning. The experiment included 12,923 pigs fed LF or DF in the pre-weaning period and a subpopulation of 15 pigs from each group, W4DF, W4LF, W5DF and W5LF, which were weighed and euthanized five days after weaning. The proximal part of the small intestine was analyzed for maltase, lactase and sucrase activity and the expression of SGLT-1, GLUT-2 and PepT-1. Pigs fed LF displayed less maltase activity (2100 vs. 2729 U/mg protein, p < 0.05) but an increased expression of SGLT-1 (∆Ct: 5.22 vs. 6.21, p = 0.01). Pigs weaned in W5 were heavier than those weaned in W4 (9.35 vs. 7.11 kg BW, p ≤ 0.05), and pigs fed LF were heavier than those fed DF (8.55 vs. 7.91 kg BW, p ≤ 0.05) five days after weaning in the subpopulation. LF pigs (21.8 kg) were heavier than DF pigs (20.6 kg) (SE 0.108, p < 0.0001), and W4 pigs (21.0 kg) were lighter than W5 pigs (21.5 kg) (SE 0.108, p = 0.01) at nine weeks. LF increased weight gain in the early post-weaning period and at nine weeks, although this was apparently not explained by accelerated gut maturation.

Biochemical and morphological responses to post-hepatectomy liver failure in rats.

The upper limit for partial hepatectomy (PH) in rats is 90%, which is associated with an increased risk of post-hepatectomy liver failure (PHLF), correlating with high mortality. Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further block randomization was performed to determine the time of euthanasia, whether 12, 24, or 48 h after surgery. A general distress score (GDS) was calculated to distinguish between rats with reversible (GDS < 10) and irreversible PHLF (GDS ≥ 10). At euthanasia, the liver remnant and blood were collected. Liver-specific biochemistry and regeneration ratio were measured. Hepatocyte proliferation and volume were estimated using stereological methods. All rats subjected to 90% experienced biochemical PHLF. The biochemical and morphological liver responses did not differ between the groups until 48 h after surgery. At 48 h, liver regeneration and function were significantly improved in survivors. The peak mean regeneration ratio was 15% for rats with irreversible PHLF compared to 26% for rats with reversible PHLF. The 90% PH rat model was associated with PHLF and high mortality. Irreversible PHLF was characterized by impaired liver regeneration capacity and an insufficient ability to metabolize ammonia.

Exposure to residential mold and dampness and the associations with respiratory tract infections and symptoms thereof in children in high income countries: A systematic review and meta-analyses of epidemiological studies.

BACKGROUND: Multiple reviews have been conducted on the associations between residential mold and dampness and respiratory outcomes in children, with few specifically investigating respiratory tract infections (RTIs). OBJECTIVE: We aimed to review and synthesize the available epidemiological literature on mold and dampness and risk of RTIs and respiratory symptoms compatible with RTIs in children living in high-income countries. METHOD: We performed a systematic search of literature available from MEDLINE, Embase, and Web of Science for observational studies. We conducted meta-analyses using two-level random effects (RE) and multi-level random effects (ML) models for contrasts of three exposure and three outcome categories, including multiple estimates reported by single studies. We report central estimates for pooled odds ratios (OR) and 95 % confidence intervals (CI).We conducted a risk of bias assessment using the Joanna Briggs Initiative (JBI) checklists for cross-sectional, case-control, and cohort studies. We additionally report on cumulative meta-analyses, leave-one-out analyses of single estimates, subgroup analyses by study quality and study design and inclusion of all effect estimates. RESULTS: Of the 932 studies initially screened by title and abstract, we included 30 studies with 267 effect estimates that met the inclusion criteria. Most were cross-sectional (n = 22), with fewer cohort (n = 5) and case-control (n = 3) studies. Most of the studies were according to the bias assessment of poor or fair quality (n = 24). The main meta-analyses generally provided similar results regardless of statistical model and central estimates ranged from OR 1.28 (95 % CI; 1.08, 1.53) for dampness and RTIs to OR 1.76 (95 % CI; 1.64, 1.88) for mold and respiratory symptoms. Most analyses were of moderate heterogeneity. Funnel plots did not indicate strong publication bias. CONCLUSION: Our results are compatible with a weak to moderate effect of residential mold and or dampness on risk of RTIs in children in high-income countries. However, these results are based primarily on cross-sectional studies.

Clinical implications of multidisciplinary team pancreatic cyst evaluation.

INTRODUCTION: The detection of incidental pancreatic cysts (PCs) is increasing due to frequent use of imaging. The aim of the present study was to evaluate the clinical consequences of regular multidisciplinary team (MDT) conferences for patients with PCs. METHODS: All patient data were obtained by review of patient medical records. PCs were assessed at the weekly MDT in accordance with the revised Fukuoka guidelines. RESULTS: A total of 455 patients were evaluated within 12 months. A large proportion of the cysts could not be characterised and was handled as branch duct (BD)-intraductal papillary mucinous neoplasia (IPMN). A total of 245 patients were included in a follow-up programme, whereas 175 patients were excluded. Further diagnostic work-up was recommended for 31 patients. A total of 66 patients were reviewed on MDT a second time during the study period, eight of whom received a diagnosis different from that given at the first MDT. A total of 35 patients with mucinous PC or cysts treated as BD-IPMN had either worrisome features (WF) or high-risk stigmata (HRS), four of these patients had a PC ≤ 10 mm. Indication for surgery was WF or HRS and, in the course of 12 months, six patients were recommended surgery taking their PS into account. Two patients had a malignant and two had a premalignant lesion. CONCLUSION: In all, 455 patients were evaluated to find 35 patients with suspected premalignant PCs. This means that almost 8% of the referred patients had suspicious lesions, which indicates a need for a regular MDT conference. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Adrenocorticotropic hormone secretion in response to anticipatory stress and venepuncture: The role of menstrual phase and oral contraceptive use.

INTRODUCTION: Oral contraceptives (OCs) are primarily known for their effects on the reproductive system, but they can also impact the hypothalamic-pituitary-adrenal (HPA) axis. The present study aimed to compare plasma adrenocorticotropic hormone (ACTH) responses to the anticipatory stress of participating in a scientific experiment and venepuncture in OC users versus naturally cycling (NC) women, with a focus on variations throughout the menstrual cycle. METHODS: We recruited 131 young women (average age 20.5) and obtained blood samples to measure plasma ACTH concentrations immediately after venepuncture and again after 15 min of group activities designed to facilitate interpersonal attachment and stress-buffering. RESULTS: ACTH levels decreased in 70% of all participants throughout the group activities. A two-way repeated measures ANOVA highlighted a significant interaction between time and OC use, indicating differential changes in ACTH levels during social interaction between OC users and NC women. Further, the post-hoc analysis revealed that a period of stress-buffering group activities significantly decreased ACTH levels in NC women during menstrual and secretory phases, but not during the proliferative phase. In contrast, OC users did not display a decrease during group activities, regardless of the phase. CONCLUSION: This study underscores the influence of OC use on stress regulation, demonstrating that OCs not only modulate reproductive functions but also impact ACTH stress reactivity. Additionally, it emphasizes the importance of considering hormonal contraceptive use and menstrual cycle phases when assessing female stress responses.

Early-Life Exposure to Ambient Air Pollution from Multiple Sources and Asthma Incidence in Children: A Nationwide Birth Cohort Study from Denmark.

BACKGROUND: Ambient air pollution exposure has been associated with childhood asthma, but previous studies have primarily focused on prevalence of asthma and asthma-related outcomes and urban traffic-related exposures. OBJECTIVE: We examined nationwide associations between pre- and postnatal exposure to ambient air pollution components and asthma incidence in children age 0-19 y. METHODS: Asthma incidence was identified from hospital admission, emergency room, and outpatient contacts among all live-born singletons born in Denmark between 1998 and 2016. We linked registry data with monthly mean concentrations of particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5) and PM with aerodynamic diameter ≤10µm (PM10), nitrogen dioxide (NO2), nitrogen oxides, elemental carbon, and organic carbon (OC), sulfur dioxide, ozone, sulfate, nitrate, ammonium, secondary organic aerosols, and sea salt. Associations were estimated with Cox proportional hazard models using fixed prenatal exposure means and time-varying postnatal exposures. RESULTS: Of the 1,060,154 children included, 6.1% had asthma during the mean follow-up period of 8.8 y. The risk of asthma increased with increasing prenatal exposure to all pollutants except for O3 and sea salt. We also observed increased risk after restriction to asthma after age 4 y, after additional adjustment for area-specific socioeconomic status, and for postnatal exposure to most pollutants. The hazard ratio (HR) associated with an interquartile range increase of 2.4 and 8.7 µg/m3 in prenatal exposure was 1.06 [95% confidence interval (CI): 1.04, 1.08] for PM2.5 and 1.04 (95% CI: 1.02, 1.05) for NO2, respectively. This association with PM2.5 was stable after adjustment for NO2, whereas it attenuated for NO2 to 1.01 (95% CI: 0.99, 1.03) after adjustment for PM2.5. For a 0.5-µg/m3 increase in prenatal OC exposure, for which biomass is an important source, the HR was 1.08 (95% CI: 1.06, 1.10), irrespective of adjustment for PM2.5. DISCUSSION: These findings suggest that early-life exposure to ambient air pollution from multiple sources contributes to asthma development. https://doi.org/10.1289/EHP11539.

Validation of a surgical model for posthepatectomy liver failure in rats.

BACKGROUND: The upper limit for liver resections in rats is approximately 90%. In the early postoperative phase, mortality increases. The aim of the present study was to validate the rat model of 90% partial hepatectomy (PH) as a model of post-hepatectomy liver failure (PHLF). Further, we wanted to test a quantitative scoring system as a detector of lethal outcomes caused by PHLF in rats. METHODS: Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further, block randomization was performed based on time of euthanization: 12, 24, or 48 h after surgery. A general distress score (GDS) ≥10 during the day or ≥6 at midnight prompted early euthanization and classification as nonsurvivor. Animals euthanized as planned were classified as survivors. During euthanization, blood and liver tissue were collected, and liver-specific biochemistry was evaluated. RESULTS: Based on the biochemical results, all animals subjected to 90% PH experienced PHLF. Seventeen rats were euthanized due to irreversible PHLF. The GDS increased for nonsurvivors within 12-18 h after surgery. The mean time for euthanization was 27 h after surgery. CONCLUSION: Based on the GDS and liver-specific biochemistry, we concluded that the model of 90% PH seems to be a proper model for investigating PHLF in rats. As a high GDS is associated with increased mortality, the GDS appears to be valuable in detecting lethal outcomes caused by PHLF in rats.

Sex and Estrous Cycle Are Not Mediators of S-Ketamine's Rapid-Antidepressant Behavioral Effects in a Genetic Rat Model of Depression.

BACKGROUND: Recent preclinical and clinical studies have shed light on the possible impact of sex and estrous/menstrual cycle on ketamine's antidepressant action but with incongruous results. The preclinical studies that have shown the effects of ovarian sex hormones have not done so in animal models of depression. Thus, the aim of the present study is to scrutinize the acute behavioral responses to a subanesthetic dose of S-ketamine in males vs females and in different estrous phases in free-cycling females in a well-powered translational approach. METHODS: We evaluated the behavioral sensitivity to 20 mg/kg S-ketamine (i.p.) in male and female Flinders Sensitive Line rats (FSLs) and their counterpart Flinders Resistant Line rats (FRLs) subjected to the open field and forced swim tests. Female rats were disaggregated into different estrous phases, and the behavioral outcomes were compared. RESULTS: Acute administration of S-ketamine had robust antidepressant-like effects in FSLs. Within our study power, we could not detect sex- or estrous cycle-specific different antidepressant-like responses to S-ketamine in FSLs. Fluctuations in the levels of ovarian sex hormones across different estrous cycles did not behaviorally affect S-ketamine's rapid-acting antidepressant mode of action. No sex-related or estrous cycle-related impact on behavioral despair was observed even among FRLs and saline-treated FSLs. CONCLUSIONS: We conclude that physiological oscillations of estrogen and progesterone levels neither amplify nor diminish the behavioral antidepressant-like effect of S-ketamine. In addition, fluctuations of ovarian sex hormones do not predispose female animals to exhibit enhanced or reduced depressive-like and anxiety-like behaviors.

The influence of early-life animal exposure on the risk of childhood atopic dermatitis, asthma and allergic rhinoconjunctivitis: findings from the Danish National Birth Cohort.

BACKGROUND: Early-life animal exposure has been associated with both protective and harmful effects on asthma and allergic disease. We aimed to explore factors that may modify associations of early-life animal exposure with asthma and allergic disease, so as to better understand these differences in findings. METHODS: We used data from ≤84 478 children from the Danish National Birth Cohort recruited during pregnancy between 1996 and 2002, and linked registry data up to the child's 13th birthday. Adjusted Cox models were used to examine associations of early-life cat, dog, rabbit, rodent, bird and livestock exposure with atopic dermatitis, asthma and allergic rhinoconjunctivitis overall, and by source of exposure (domestic or occupation), parental history of asthma or allergy, maternal education level and timing of exposure. RESULTS: Overall, associations between animal exposure and the three outcomes of interest were weak. However, dog exposure was associated with marginally lower risk of atopic dermatitis and asthma [adjusted hazard ratio (aHR) = 0.81, 95% CI: 0.70-0.94 and 0.88, 95% CI: 0.82-0.94, respectively], whereas prenatal domestic bird exposure was associated with slightly increased risk of asthma (aHR = 1.18, 95% CI: 1.05-1.32). Source of exposure, parental history of asthma or allergy and timing of exposure modified associations. Early-life animal exposure did not appear to increase the risk of allergic rhinoconjunctivitis (aHR range = 0.88, 95% CI: 0.81-0.95 to 1.00, 95% CI: 0.91-1.10). CONCLUSIONS: The overall weak associations observed between animal exposure and atopic dermatitis, asthma and allergic rhinoconjunctivitis were modified by type of animal, source of exposure, parental history of asthma or allergy and timing of exposure, suggesting that these factors should be considered when assessing the risks associated with early-life animal exposure.

Prenatal exposure to tap water containing nitrate and the risk of small-for-gestational-age: A nationwide register-based study of Danish births, 1991-2015.

BACKGROUND: Prenatal nitrate exposure from household tap water has been associated with increased risk of fetal growth restriction, preterm birth, birth defects, and childhood cancer. We aim to examine the association between maternal consumption of drinking-water nitrate during pregnancy and small-for-gestational-age (SGA) in a nationwide study of Danish-born children, as only one prior study has examined this association. METHODS: We linked individual-level household estimates of nitrate in tap water and birth registry data to all live singleton Danish births during 1991-2015 from Danish-born parents where the mother resided in Denmark throughout the pregnancy. Exposure was both binned into four categories and modeled as an ln-transformed continuous variable. SGA was defined as the bottom 10% of births by birth weight per sex and gestational week. Multiple logistic regression models with generalized estimating equations were used to account for siblings born to the same mother while controlling for relevant confounders. RESULTS: In the cohort of 1,078,892 births, the median pregnancy nitrate exposure was 1.9 mg/L nitrate. Compared to the reference group (≤2 mg/L), we found an increased risk of SGA in the second category (>2-5 mg/L) (OR = 1.04, 95% CI: 1.03-1.06) and third category (>5-25 mg/L) (OR = 1.02, 95% CI: 1.00-1.04) but not in the highest (>25 mg/L). There was strong (p = 0.002) evidence of an increase in SGA with nitrate in the model with continuous exposure (OR = 1.02, 95% CI: 1.01-1.04 per 10-fold increase in nitrate). Results were robust when restricting to households with nitrate levels at or below the current Danish and European Union regulatory drinking water standard (50 mg/L nitrate). CONCLUSIONS: Our findings suggest that exposure from nitrate in household tap water, even below current regulatory standards, may increase risk of SGA, raising concerns of whether current allowable nitrate levels in drinking water protect children from SGA.

The use of electroconvulsive therapy (ECT) en bloc in Denmark: a nationwide register-based study.

OBJECTIVE: Electroconvulsive therapy (ECT) en bloc is defined as ECT administered on 2-3 consecutive days. In Denmark, ECT en bloc is recommended for severe conditions such as catatonia, treatment-resistant mania/psychosis, or imminent risk of suicide. To our knowledge, there are no recent reports on the use of ECT en bloc in clinical practice. Here, we provide such a report. METHODS: We characterized the use of ECT en bloc in the period from 2006-2019 based on data from Danish national registers. Furthermore, we compared mortality rates between patients receiving ECT en bloc and patients receiving standard regimen ECT (not en bloc). RESULTS: We identified 2173 patients who received a total of 2734 ECT en bloc treatment courses in Denmark in the period from 2006 to 2019 (6% of the total number of ECT treatment courses). The use of ECT en bloc was stable over the study period (range: 138-196 patients per year). The most common treatment indications were unipolar depression (41%), psychotic disorder (23%), and bipolar disorder (20%). The vast majority (90%) received ECT en bloc voluntarily. The 1-year mortality rate ratio for ECT en bloc compared to standard regimen ECT was 1.42 (95%CI: 1.03-1.95). CONCLUSION: The use of ECT en bloc in Denmark is stable both in terms of the number of patients treated and treatment indications. In keeping with ECT en bloc being used for severe conditions, those receiving this treatment have a higher mortality rate compared to those receiving standard ECT, warranting careful monitoring during follow-up.

Prenatal exposure to ambient air pollution is associated with early life immune perturbations.

BACKGROUND: Exposure to ambient air pollution has been linked to asthma, allergic rhinitis, and other inflammatory disorders, but little is known about the underlying mechanisms. OBJECTIVE: We studied the potential mechanisms leading from prenatal ambient air pollution exposure to asthma and allergy in childhood. METHODS: Long-term exposure to nitrogen dioxide (NO2) as well as to particulate matter with a diameter of ≤2.5 and ≤10 µm (PM2.5 and PM10) were modeled at the residence level from conception to 6 years of age in 700 Danish children followed clinically for development of asthma and allergy. Nasal mucosal immune mediators were assessed at age 4 weeks and 6 years, inflammatory markers in blood at 6 months, and nasal epithelial DNA methylation and gene expression at age 6 years. RESULTS: Higher prenatal air pollution exposure with NO2, PM2.5, and PM10 was associated with an altered nasal mucosal immune profile at 4 weeks, conferring an increased odds ratio [95% confidence interval] of 2.68 [1.58, 4.62] for allergic sensitization and 2.63 [1.18, 5.81] for allergic rhinitis at age 6 years, and with an altered immune profile in blood at age 6 months conferring increased risk of asthma at age 6 years (1.80 [1.18, 2.76]). Prenatal exposure to ambient air pollution was not robustly associated with immune mediator, epithelial DNA methylation, or gene expression changes in nasal cells at age 6 years. CONCLUSION: Prenatal exposure to ambient air pollution was associated with early life immune perturbations conferring risk of allergic rhinitis and asthma. These findings suggest potential mechanisms of prenatal exposure to ambient air pollution on the developing immune system.

Suckling Induces Differential Gut Enzyme Activity and Body Composition Compared to Feeding Milk Replacer in Piglets.

The aim of this study was to investigate differences in growth, hematology, metabolism, small intestine (SI) morphology, and enzyme activity of sow-reared piglets (SOW) compared to artificially reared piglets (MILK) given milk replacers in two different environments. Thirty-six piglets were selected at birth based on their birth weight; eighteen were kept on a commercial farm, another eighteen transferred to an animal research facility for artificial rearing. Differences were observed in enzymatic activity, with a larger amount of sucrase in the SOW compared with MILK group across the SI. SOW piglets also had a body composition with a larger amount of fat, muscle, and bone mass content. Differences in hematology were observed, suggesting environmental influences, biochemistry differences reflective of the diets given, and finally, an increased dry matter (DM) intake in SOW piglets was estimated. No differences were observed in immune function and only small differences in the gut integrity were found between the two groups. It can be concluded that body composition and enzyme activity can be manipulated through dietary intervention and that an increase in DM during lactation is beneficial for gut function. The study warrants further investigation into what this means for the subsequent weaning period.

Exposure to natural environments during pregnancy and birth outcomes in 11 European birth cohorts.

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas.

Pathways to Identify Electrophiles In Vivo Using Hemoglobin Adducts: Hydroxypropanoic Acid Valine Adduct and Its Possible Precursors.

Analytical methods and tools for the characterization of the human exposome by untargeted mass spectrometry approaches are advancing rapidly. Adductomics methods have been developed for untargeted screening of short-lived electrophiles, in the form of adducts to proteins or DNA, in vivo. The identification of an adduct and its precursor electrophile in the blood is more complex than that of stable chemicals. The present work aims to illustrate procedures for the identification of an adduct to N-terminal valine in hemoglobin detected with adductomics, and pathways for the tracing of its precursor and possible exposure sources. Identification of the adduct proceeded via preparation and characterization of standards of adduct analytes. Possible precursor(s) and exposure sources were investigated by measurements in blood of adduct formation by precursors in vitro and adduct levels in vivo. The adduct was identified as hydroxypropanoic acid valine (HPA-Val) by verification with a synthesized reference. The HPA-Val was measured together with other adducts (from acrylamide, glycidamide, glycidol, and acrylic acid) in human blood (n = 51, schoolchildren). The HPA-Val levels ranged between 6 and 76 pmol/g hemoglobin. The analysis of reference samples from humans and rodents showed that the HPA-Val adduct was observed in all studied samples. No correlation of the HPA-Val level with the other studied adducts was observed in humans, nor was an increase in tobacco smokers observed. A small increase was observed in rodents exposed to glycidol. The formation of the HPA-Val adduct upon incubation of blood with glycidic acid (an epoxide) was shown. The relatively high adduct levels observed in vivo in relation to the measured reactivity of the epoxide, and the fact that the epoxide is not described as naturally occurring, suggest that glycidic acid is not the only precursor of the HPA-Val adduct identified in vivo. Another endogenous electrophile is suspected to contribute to the in vivo HPA-Val adduct level.