Liver, renal, genitourinary and diabetic ketoacidosis risks among new users of empagliflozin versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: Post-authorization safety study based on multinational cohorts.

AIM: To estimate risks of diabetic ketoacidosis (DKA), acute liver injury (ALI), acute kidney injury (AKI), chronic kidney disease (CKD), severe complications of urinary tract infection (UTI) and genital infection (GI) among patients with type 2 diabetes initiating empagliflozin versus those initiating a dipeptidyl peptidase-4 (DPP-4) inhibitor. MATERIALS AND METHODS: In this large multinational, observational, new-user cohort study in UK, Danish and US healthcare data sources, patients initiated empagliflozin or a DPP-4 inhibitor between August 2014 and August 2019, were aged ≥18 years, and had ≥12 months' continuous health plan enrolment. Incidence rates by exposure and incidence rate ratios, adjusted for propensity-score deciles, were calculated. RESULTS: In total, 64 599 empagliflozin initiators and 203 315 DPP-4 inhibitor initiators were included. There was an increased risk [pooled adjusted incidence rate ratios (95% confidence interval)] of DKA [2.19 (1.74-2.76)] and decreased risks of ALI [0.77 (0.50-1.19) in patients without predisposing conditions of liver disease; 0.70 (0.56-0.88) in all patients] and AKI [0.54 (0.41-0.73)]. In the UK data, there was an increased risk of GI [males: 4.04 (3.46-4.71); females: 3.24 (2.81-3.74)] and decreased risks of CKD [0.53 (0.43-0.65)] and severe complications of UTI [0.51 (0.37-0.72)]. The results were generally consistent in subgroup and sensitivity analyses. CONCLUSIONS: Compared with DDP-4 inhibitor use, empagliflozin use was associated with increased risks of DKA and GI and decreased risks of ALI, AKI, CKD and severe complications of UTI. These associations are consistent with previous studies and known class effects of sodium-glucose cotransporter 2 inhibitors, including renoprotective effects and beneficial effects on alanine aminotransferase levels.

Dehydration and rehydration differently affect photosynthesis and volatile monoterpenes in bryophytes with contrasting ecological traits.

Bryophytes desiccate rapidly when relative humidity decreases. The capacity to withstand dehydration depends on several ecological and physiological factors. Volatile organic compounds (VOCs) may have a role in enhancing tolerance to desiccating bryophytes. However, the functions of VOCs in bryophytes have received little attention so far. We aimed to investigate the impact of a dehydration-rehydration treatment on primary carbon metabolism and volatile terpenes (VTs) in three bryophytes with contrasting ecological traits: Vessicularia dubyana, Porella platyphylla and Pleurochaete squarrosa. First, we confirmed the desiccation sensitivity gradient of the species. Under fully hydrated conditions, the photosynthetic rate (A) was inversely associated with stress tolerance, with a lower rate in more tolerant species. The partial recovery of A in P. platyphylla and P. squarrosa after rehydration confirmed the desiccation tolerance of these two species. On the other hand, A did not recover after rehydration in V. dubyana. Regarding VT, each species exhibited a distinct VT profile under optimum hydration, with the highest VT pool found in the more desiccation-sensitive species (V. dubyana). However, the observed species-specific VT pattern could be associated with the ecological habitat of each species. P. squarrosa, a moss of dry habitats, may synthesize mainly non-volatile secondary metabolites as stress-defensive compounds. On the other hand, V. dubyana, commonly found submerged, may need to invest photosynthetically assimilated carbon to synthesize a higher amount of VTs to cope with transient water stress occurrence. Further research on the functions of VTs in bryophytes is needed to deepen our understanding of their ecological significance.

Prenatal and child vitamin D levels and allergy and asthma in childhood.

BACKGROUND: Early-life vitamin D deficiency may impair immune system development contributing to allergy and asthma onset. Findings from prospective studies are inconsistent. OBJECTIVE: To examine whether maternal and child vitamin D levels are associated with allergic and asthma-related symptoms throughout childhood in a Spanish birth cohort. METHODS: 25-Hydroxyvitamin D3 (25(OH)D3) levels were measured in the serum of pregnant women (N = 2525) and children (N = 803). Information on allergic and asthma-related symptoms was obtained from repeated questionnaires from 1 to 9 years. RESULTS: A total of 19% of mothers and 24% of children had deficient 25(OH)D3 levels (<20 ng/ml). Higher child 25(OH)D3 levels at 4 years were associated with lower odds of atopic eczema from 4 to 9 years (adjusted odds ratio = 0.90; 95% CI = 0.84-0.97 per 5 ng/ml). Higher maternal and child 25(OH)D3 levels were associated with a lower prevalence of late-onset wheezing at the limit of statistical significance (adjusted relative risk ratio (RRRadj) = 0.86; 95% CI = 0.74-1.00 and RRRadj = 0.76; 95% CI = 0.58-1.02 per 5 ng/ml, respectively). All the remaining associations were null. CONCLUSION: Child 25(OH)D3 levels at pre-school age are associated with a reduced odds of atopic eczema in later childhood and both maternal and child levels may reduce the prevalence of late-onset wheezing. IMPACT: In this Spanish birth cohort, with a total of 19% of mothers and 24% of children with deficient levels of vitamin D, higher child vitamin D at 4 years of age was associated with reduced odds of atopic eczema up to 9 years. There was also some evidence that higher maternal and child vitamin D levels reduced the prevalence of late-onset wheezing. Although these findings need replication, they may imply optimal vitamin D levels at pre-school age to prevent atopic eczema.

Holm oak decline is determined by shifts in fine root phenotypic plasticity in response to belowground stress.

Climate change and pathogen outbreaks are the two major causes of decline in Mediterranean holm oak trees (Quercus ilex L. subsp. ballota (Desf.) Samp.). Crown-level changes in response to these stressful conditions have been widely documented but the responses of the root systems remain unexplored. The effects of environmental stress over roots and its potential role during the declining process need to be evaluated. We aimed to study how key morphological and architectural root parameters and nonstructural carbohydrates of roots are affected along a holm oak health gradient (i.e. within healthy, susceptible and declining trees). Holm oaks with different health statuses had different soil resource-uptake strategies. While healthy and susceptible trees showed a conservative resource-uptake strategy independently of soil nutrient availability, declining trees optimized soil resource acquisition by increasing the phenotypic plasticity of their fine root system. This increase in fine root phenotypic plasticity in declining holm oaks represents an energy-consuming strategy promoted to cope with the stress and at the expense of foliage maintenance. Our study describes a potential feedback loop resulting from strong unprecedented belowground stress that ultimately may lead to poor adaptation and tree death in the Spanish dehesa.

The importance of the urea cycle and its relationships to polyamine metabolism during ammonium stress in Medicago truncatula.

The ornithine-urea cycle (urea cycle) makes a significant contribution to the metabolic responses of lower photosynthetic eukaryotes to episodes of high nitrogen availability. In this study, we compared the role of the plant urea cycle and its relationships to polyamine metabolism in ammonium-fed and nitrate-fed Medicago truncatula plants. High ammonium resulted in the accumulation of ammonium and pathway intermediates, particularly glutamine, arginine, ornithine, and putrescine. Arginine decarboxylase activity was decreased in roots, suggesting that the ornithine decarboxylase-dependent production of putrescine was important in situations of ammonium stress. The activity of copper amine oxidase, which releases ammonium from putrescine, was significantly decreased in both shoots and roots. In addition, physiological concentrations of ammonium inhibited copper amine oxidase activity in in vitro assays, supporting the conclusion that high ammonium accumulation favors putrescine synthesis. Moreover, early supplementation of plants with putrescine avoided ammonium toxicity. The levels of transcripts encoding urea-cycle-related proteins were increased and transcripts involved in polyamine catabolism were decreased under high ammonium concentrations. We conclude that the urea cycle and associated polyamine metabolism function as important protective mechanisms limiting ammonium toxicity in M. truncatula. These findings demonstrate the relevance of the urea cycle to polyamine metabolism in higher plants.

Traffic restrictions during COVID-19 lockdown improve air quality and reduce metal biodeposition in tree leaves.

The coronavirus disease (COVID-19) has had a great global impact on human health, the life of people, and economies all over the world. However, in general, COVID-19´s effect on air quality has been positive due to the restrictions on social and economic activity. This study aimed to assess the impact on air quality and metal deposition of actions taken to reduce mobility in 2020 in two different urban locations. For this purpose, we analysed air pollution (NO2, NO, NOx, SO2, CO, PM10, O3) and metal accumulation in leaves of Tilia cordata collected from April to September 2020 in two cities in northern Spain (Pamplona-PA and San Sebastián-SS). We compared their values with data from the previous year (2019) (in which there were no mobility restrictions) obtained under an identical experimental design. We found that metal accumulation was mostly lower during 2020 (compared with 2019), and lockdown caused significant reductions in urban air pollution. Nitrogen oxides decreased by 33%-44%, CO by 24%-38%, and PM10 by 16%-24%. The contents of traffic-related metals were significantly reduced in both studied cities. More specifically, significant decreases in metals related to tyre and brake wear (Zn, Fe, and Cu) and road dust resuspension (Al, Ti, Fe, Mn, and Ca) were observed. With these results, we conclude that the main reason for the improvement in urban air pollutants and metals was the reduction in the use of cars due to COVID-19 lockdown. In addition, we offer some evidence indicating the suitability of T. cordata leaves as a tool for biomonitoring metal accumulation. This information is relevant for future use by the scientific community and policy makers to implement measures to reduce traffic air pollution in urban areas and to improve environmental and human health.

Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts.

The potential etiological role of early acetaminophen exposure on Autism Spectrum Conditions (ASC) and Attention-Deficit/Hyperactivity Disorder (ADHD) is inconclusive. We aimed to study this association in a collaborative study of six European population-based birth/child cohorts. A total of 73,881 mother-child pairs were included in the study. Prenatal and postnatal (up to 18 months) acetaminophen exposure was assessed through maternal questionnaires or interviews. ASC and ADHD symptoms were assessed at 4-12 years of age using validated instruments. Children were classified as having borderline/clinical symptoms using recommended cutoffs for each instrument. Hospital diagnoses were also available in one cohort. Analyses were adjusted for child and maternal characteristics along with indications for acetaminophen use. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. The proportion of children having borderline/clinical symptoms ranged between 0.9 and 12.9% for ASC and between 1.2 and 12.2% for ADHD. Results indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have borderline or clinical ASC (OR = 1.19, 95% CI 1.07-1.33) and ADHD symptoms (OR = 1.21, 95% CI 1.07-1.36) compared to non-exposed children. Boys and girls showed higher odds for ASC and ADHD symptoms after prenatal exposure, though these associations were slightly stronger among boys. Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms. These results replicate previous work and support providing clear information to pregnant women and their partners about potential long-term risks of acetaminophen use.

Prenatal Omega-6:Omega-3 Ratio and Attention Deficit and Hyperactivity Disorder Symptoms.

OBJECTIVE: To evaluate whether higher omega-6:omega-3 (n-6:n-3) long-chain polyunsaturated fatty acid ratio in cord plasma is associated with more symptoms of attention deficit and hyperactivity disorder (ADHD) at 4 and 7 years of age. STUDY DESIGN: This study was based on a population-based birth cohort in Spain. N-6 arachidonic acid and n-3 eicosapentaenoic and docosahexaenoic acid concentrations were measured in cord plasma. At 4 years old, ADHD symptoms were reported by teachers through the ADHD Diagnostic and Statistical Manual of Mental Disorders, 4th ed checklist (n = 580). At 7 years old, ADHD symptoms were reported by parents through the Conners' Rating Scale-Revised (short form; n = 642). The ADHD variable was treated as continuous (score) and as dichotomous (symptom diagnostic criteria). Child and family general characteristics were prospectively collected through questionnaires. We applied pooled zero-inflated negative binomial and logistic regressions adjusted for covariates. RESULTS: A higher omega-6:omega-3 long-chain polyunsaturated fatty acid ratio in cord plasma was associated with a higher ADHD index (incidence rate ratio, 1.13; 95% CI, 1.03, 1.23) at 7 years old. The association was not observed at 4 years old (incidence rate ratio, 1.04; 95% CI, 0.92-1.18). No associations were found using ADHD symptom diagnostic criteria. CONCLUSIONS: High prenatal omega-6:omega-3 long-chain polyunsaturated fatty acid ratio preceded the appearance of subclinical ADHD symptoms during mid-childhood. Our findings suggest that maternal diet during pregnancy may modulate the risk to develop long-term ADHD symptoms in the offspring.

Drought tolerance response of high-yielding soybean varieties to mild drought: physiological and photochemical adjustments.

Soybean is a crop of agronomic importance that requires adequate watering during its growth to achieve high production. In this study, we determined physiological, photochemical and metabolic differences in five soybean varieties selected from the parental lines of a nested association mapping population during mild drought. These varieties have been described as high yielding (NE3001, HY1; LD01-5907, HY2) or drought tolerant (PI518751; HYD1; PI398881, HYD2). Nevertheless, there has been little research on the physiological traits that sustain their high productivity under water-limited conditions. The results indicate that high-yielding varieties under drought cope with the shortage of water by enhancing their photoprotective defences and invest in growth and productivity, linked to a higher intrinsic water use efficiency. This is the case of the variety N-3001 (HY1), with a tolerance strategy involving a faster transition into the reproductive stage to avoid the drought period. The present study highlights the role of the physiological and biochemical adjustments of various soybean varieties to cope with water-limited conditions. Moreover, the obtained results underscore the fact that the high phenotypic plasticity among soybean phenotypes should be exploited to compensate for the low genetic variability of this species when selecting plant productivity in constrained environments.

Maternal nut intake in pregnancy and child neuropsychological development up to 8 years old: a population-based cohort study in Spain.

There is scientific evidence on the protective effects of nut intake against cognitive decline in the elderly; however, this effect has been less explored in child neurodevelopment and no studies have explored the potential longitudinal association with nut intake during pregnancy. We aimed to analyze the association of maternal nut intake during pregnancy with child neuropsychological outcomes. We included 2208 mother-child pairs from a population-based birth cohort in four regions of Spain. The follow up settings were during pregnancy (first and third trimesters), birth, 1.5, 5 and 8 years. Neuropsychological examinations were based on Bayley Scales of Infant Development (1.5 years), McCarthy scales of Children's Abilities (5 year), Attention Network Test (ANT, 8 year) and N-Back test (8 year). Nut intake in pregnancy was reported through a validated food frequency questionnaire during the first and the third trimester. Multivariable regressions analyzed associations after controlling for priori selected confounders notably maternal education, social class, body mass index, energy intake, fish intake, omega-3 supplements, alcohol consumption and smoking habits during pregnancy. Children within the highest tertile of maternal nut consumption during first pregnancy trimester (> 32 g/week) had a decrease of 13.82 ms [95% confidence interval (CI) - 23.40, - 4.23] in the ANT-hit reaction time standard error, compared to the first tertile (median 0 g/w). A similar protective association pattern was observed with the other cognitive scores at the different child ages. After correcting for multiple testing using Bonferroni familywise error rate (FWER), Hochberg FWER and Simes false discovery rate, ANT-hit reaction time standard error remained significant. Final model estimates by inverse probability weighting did not change results. Third pregnancy trimester nut intake showed weaker associations. These data indicate that nut intake during early pregnancy is associated with long-term child neuropsychological development. Future cohort studies and randomized clinical trials are needed to confirm this association pattern in order to further extend nutrition guidelines among pregnant women.

Head circumference and child ADHD symptoms and cognitive functioning: results from a large population-based cohort study.

The aim of this study is to understand the association between prenatal, newborn and postnatal head circumference (HC) and preschool neurodevelopment in a large population-based birth cohort. The INMA project followed 1795 children from 12 weeks of pregnancy to preschool years. HC measurements were carried out prospectively, and following a standardized protocol during pregnancy (12, 20 and 34 weeks), birth, and child ages of 1-1.5 and 4 years old; and z-scores were further estimated. Prenatal head growth was assessed using conditional z-scores between weeks 12-20 and 20-34. Several neuropsychological tests [MSCA (cognition), CPT (attention)] and behavioral rating scales [DSM-IV-ADHD, CAST (autism), CPSCS (social competence)] were carried out during the last follow-up (5 years old). Multivariable models adjusted for family and child characteristics were applied to analyze associations between HC and neurodevelopment. In fully adjusted models, prenatal HC and head growth showed little or no associations with the neurodevelopment outcomes. Independent associations were observed between HC z-scores at birth, 1-1.5 years and 4 years and MSCA global cognitive scores and DSM-IV inattention symptoms. Specifically, z-score at birth was positively associated with general cognitive scores [ß 1.22, 95% confidence interval (CI) 0.59, 1.85], and we observed a protective association with ADHD-DSM-IV total symptoms, mean ratio (MR) 0.85 (0.75, 0.96). Prenatal HC and head growth measurements gave little information about child cognitive abilities and behavior at preschool years. However, HC at birth and early childhood was positively associated with a range of neuropsychological outcomes, including protective associations with ADHD symptoms.

Modified Atmosphere Packaging and Dark/Light Refrigerated Storage in Green Leafy Vegetables Have an Impact on Nutritional Value.

The consumption of zeaxanthin (Z) through a vegetable-rich diet is recommended to reduce the progression of age-related macular degeneration. Due to Z's intrinsic dynamic character that results from its participation in the photoprotective xanthophyll cycle involving the carotenoids violaxanthin, antheraxanthin and zeaxanthin (VAZ), post-harvest handling practices and storage usually retain low amounts of this bioactive compound (compared to the rest of phytochemicals that are, in general, more stable). Thus, the aim of this work was to investigate in important consumed leafy vegetables the effects of different storage conditions on carotenoids (mainly Z) including i) packaging under three modified atmospheres (MAs), ii) light refrigerated supermarket storage and iii) dark refrigerated domestic storage. The results showed that an MA with low O2 and high CO2 enhanced the Z content under light. Moreover, both light and dark refrigerated storage showed dynamic and circadian pigment changes that enhanced the total VAZ pool. These results can contribute to generating practical recommendations for industries, supermarkets, and consumers when high Z content is a nutritional target.

Air Pollution Exposure During Pregnancy and Symptoms of Attention Deficit and Hyperactivity Disorder in Children in Europe.

BACKGROUND: Exposure to air pollution during pregnancy may increase attention-deficit/hyperactivity disorder (ADHD) symptoms in children, but findings have been inconsistent. We aimed to study this association in a collaborative study of eight European population-based birth/child cohorts, including 29,127 mother-child pairs. METHODS: Air pollution concentrations (nitrogen dioxide [NO2] and particulate matter [PM]) were estimated at the birth address by land-use regression models based on monitoring campaigns performed between 2008 and 2011. We extrapolated concentrations back in time to exact pregnancy periods. Teachers or parents assessed ADHD symptoms at 3-10 years of age. We classified children as having ADHD symptoms within the borderline/clinical range and within the clinical range using validated cutoffs. We combined all adjusted area-specific effect estimates using random-effects meta-analysis and multiple imputations and applied inverse probability-weighting methods to correct for loss to follow-up. RESULTS: We classified a total of 2,801 children as having ADHD symptoms within the borderline/clinical range, and 1,590 within the clinical range. Exposure to air pollution during pregnancy was not associated with a higher odds of ADHD symptoms within the borderline/clinical range (e.g., adjusted odds ratio [OR] for ADHD symptoms of 0.95, 95% confidence interval [CI] = 0.89, 1.01 per 10 µg/m increase in NO2 and 0.98, 95% CI = 0.80, 1.19 per 5 µg/m increase in PM2.5). We observed similar associations for ADHD within the clinical range. CONCLUSIONS: There was no evidence for an increase in risk of ADHD symptoms with increasing prenatal air pollution levels in children aged 3-10 years. See video abstract at, http://links.lww.com/EDE/B379.

Traffic-related Air Pollution and Attention in Primary School Children: Short-term Association.

BACKGROUND: Although air pollution's short-term effects are well understood to be marked and preventable, its acute neuropsychological effects have, to our knowledge, not yet been studied. We aim to examine the association between daily variation in traffic-related air pollution and attention. METHODS: We conducted a follow-up study from January 2012 to March 2013 in 2,687 school children from 265 classrooms in 39 schools in Barcelona (Catalonia, Spain). We assessed four domains of children's attention processes every 3 months over four repeated visits providing a total of 10,002 computerized tests on 177 different days using the child Attention Network test (ANT). Ambient daily levels of nitrogen dioxide (NO2) and elemental carbon (EC) in particulate matter <2.5 µm (PM2.5) filters were measured at a fixed air quality background monitoring station and in schools. RESULTS: Daily ambient levels of both NO2 and EC were negatively associated with all attention processes (e.g., children in the bottom quartile of daily exposure to ambient NO2 levels had a 14.8 msecond [95% confidence interval, 11.2, 18.4] faster response time than those in the top quartile, which was equivalent to a 1.1-month [0.84, 1.37] retardation in the natural developmental improvement in response speed with age). Similar findings were observed after adjusting for the average indoor (classroom) levels of pollutants. Associations for EC were similar to those for NO2 and robust to several sensitivity analyses. CONCLUSIONS: The short-term association of traffic-related air pollutants with fluctuations in attention adds to the evidence that air pollution may have potential harmful effects on neurodevelopment. See video abstract at, http://links.lww.com/EDE/B158.

Association between breastfeeding duration and cognitive development, autistic traits and ADHD symptoms: a multicenter study in Spain.

BACKGROUND: Several studies have related longer breastfeeding duration to better intellectual performance in children. By contrast, few studies have investigated the potential protective effects of breastfeeding against behavioral problems such as attention deficit hyperactivity disorder (ADHD) symptoms, and even fewer on autism spectrum disorders (ASD) traits. METHODS: We examined the association between breastfeeding duration and cognitive development, attention, ADHD symptoms, and autistic traits using data from the INMA Project, a Spanish multicenter birth-cohort study, and taking into account the intensity of breastfeeding. Duration of any, predominant, and exclusive breastfeeding was documented during infancy through maternal questionnaires. Children (N = 1,346; mean age = 4.9 y) were assessed using the McCarthy Scales of Children's Abilities, Conners' Kiddie Continuous Performance Test, criteria of the DSM-ADHD symptoms form list, and the Childhood Autism Spectrum Test. RESULTS: After adjustment for several confounders, longer duration of breastfeeding was independently associated with better cognitive development and with fewer autistic traits. CONCLUSION: This study provides further evidence of a positive association of breastfeeding with cognitive function apart from socio-environmental factors, and also suggests a protective role against autistic traits. Results are in agreement with recommendations for prolonged breastfeeding duration to promote child development.

Longitudinal association between air pollution exposure at school and cognitive development in school children over a period of 3.5 years.

INTRODUCTION: Recently, we showed that exposure to traffic-related air pollutants (TRAPs) at school was negatively associated with cognitive development, specifically working memory and inattentiveness, in primary schoolchildren during a course of 12 months. The persistence of such associations over longer periods remains as an open question. OBJECTIVE: To study the longitudinal association between TRAPs at school and cognitive development over a period of 3.5 years. METHODS: Indoor and outdoor levels of TRAPs (elemental carbon (EC), dioxide nitrogen (NO2), particulate matter (PM2.5) from traffic sources and ultrafine particles (UFP)) were measured at 39 schools across Barcelona during 2012/2013. Working memory, as a measure of cognitive development, was evaluated 4 times in 2012/2013 assessment and was re-evaluated one more time in 2015 using computerized n-back test (3-back d' as main outcome). Linear mixed effects models were used to test the association between TRAPs and 3-back d', adding child and school as random effects to account for the multilevel nature of the data, and school air pollutants levels (one at a time) as predictor. RESULTS: We found detrimental associations between all TRAPs and annual change in 3-back d' (working memory) (i.e. slower development of working memory in children attending schools with higher levels of air pollution). The associations (per one interquartile range increase in exposure) were strongest for outdoor NO2 (Coefficient (Coef) = - 4.22, 95% confidence interval (CI), - 6.22, - 2.22) and indoor UFP (Coef = - 4.12, 95%CI, - 5.68, - 1.83). These reductions were equivalent to - 20% (95%CI, - 30.1, - 10.7) and - 19.9% (95%CI, - 31.5, - 8.4) change in annual working memory development associated with one interquartile range increase in outdoor NO2 and indoor UFP, respectively. CONCLUSION: Our findings suggest the persistence of the negative association between TRAPs exposure at school and cognitive trajectory measured by n-back test over a period of 3.5 years.

Association between traffic-related air pollution in schools and cognitive development in primary school children: a prospective cohort study.

BACKGROUND: Air pollution is a suspected developmental neurotoxicant. Many schools are located in close proximity to busy roads, and traffic air pollution peaks when children are at school. We aimed to assess whether exposure of children in primary school to traffic-related air pollutants is associated with impaired cognitive development. METHODS AND FINDINGS: We conducted a prospective study of children (n = 2,715, aged 7 to 10 y) from 39 schools in Barcelona (Catalonia, Spain) exposed to high and low traffic-related air pollution, paired by school socioeconomic index; children were tested four times (i.e., to assess the 12-mo developmental trajectories) via computerized tests (n = 10,112). Chronic traffic air pollution (elemental carbon [EC], nitrogen dioxide [NO2], and ultrafine particle number [UFP; 10-700 nm]) was measured twice during 1-wk campaigns both in the courtyard (outdoor) and inside the classroom (indoor) simultaneously in each school pair. Cognitive development was assessed with the n-back and the attentional network tests, in particular, working memory (two-back detectability), superior working memory (three-back detectability), and inattentiveness (hit reaction time standard error). Linear mixed effects models were adjusted for age, sex, maternal education, socioeconomic status, and air pollution exposure at home. Children from highly polluted schools had a smaller growth in cognitive development than children from the paired lowly polluted schools, both in crude and adjusted models (e.g., 7.4% [95% CI 5.6%-8.8%] versus 11.5% [95% CI 8.9%-12.5%] improvement in working memory, p = 0.0024). Cogently, children attending schools with higher levels of EC, NO2, and UFP both indoors and outdoors experienced substantially smaller growth in all the cognitive measurements; for example, a change from the first to the fourth quartile in indoor EC reduced the gain in working memory by 13.0% (95% CI 4.2%-23.1%). Residual confounding for social class could not be discarded completely; however, the associations remained in stratified analyses (e.g., for type of school or high-/low-polluted area) and after additional adjustments (e.g., for commuting, educational quality, or smoking at home), contradicting a potential residual confounding explanation. CONCLUSIONS: Children attending schools with higher traffic-related air pollution had a smaller improvement in cognitive development.

Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

BACKGROUND: Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. METHODS: Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO2) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO2 and nitrogen oxides (NOx) were also assessed. RESULTS: Exposure to higher levels of benzene and NO2 during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO2. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO2 during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. CONCLUSIONS: Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age.

Early exposure to bio-contaminants and asthma up to 10 years of age: results of the HITEA study.

Inverse associations have been found between exposure to bio-contaminants and asthma and allergies. The aim of this study was to prospectively assess whether early exposure to bio-contaminants in dust is associated with asthma and allergy later in childhood among children from (sub)-urban areas. In subsets of three European birth cohorts (PIAMA: n=553; INMA: n=481; and LISAplus: n=395), endotoxin, (1,3,)-ß-d-glucan and extracellular polysaccharide were measured in dust from living rooms shortly after birth. Current asthma at 6 years and 10 years of age and ever asthma up to 10 years of age were assessed by parental questionnaires. Specific IgE levels at 8 years (PIAMA) and 10 years (LISAplus) were available. Adjusted, cohort-specific logistic regression analyses were performed. Higher endotoxin concentrations were positively associated with current asthma at 6 years of age in PIAMA (adjusted OR 1.96, 95% CI 1.07-3.58), but were inversely related with ever asthma up to 10 years of age in INMA (adjusted OR 0.39, 95% CI 0.16-0.94). No associations with asthma were found for LISAplus. No associations were observed with atopic sensitisation in all cohorts. All associations with (1,3)-ß-d-glucan and extracellular polysaccharide were statistically nonsignificant. The suggested immunological mechanisms of early exposure to bio-contaminants with regards to asthma and allergy might be different for children growing up in (sub)-urban environments.

Internal and external factors affecting photosynthetic pigment composition in plants: a meta-analytical approach.

Photosynthetic pigment composition has been a major study target in plant ecophysiology during the last three decades. Although more than 2000 papers have been published, a comprehensive evaluation of the responses of photosynthetic pigment composition to environmental conditions is not yet available. After an extensive survey, we compiled data from 525 papers including 809 species (subkingdom Viridiplantae) in which pigment composition was described. A meta-analysis was then conducted to assess the ranges of photosynthetic pigment content. Calculated frequency distributions of pigments were compared with those expected from the theoretical pigment composition. Responses to environmental factors were also analysed. The results revealed that lutein and xanthophyll cycle pigments (VAZ) were highly responsive to the environment, emphasizing the high phenotypic plasticity of VAZ, whereas neoxanthin was very stable. The present meta-analysis supports the existence of relatively narrow limits for pigment ratios and also supports the presence of a pool of free 'unbound' VAZ. Results from this study provide highly reliable ranges of photosynthetic pigment contents as a framework for future research on plant pigments.