Drug Dosing in Obese Children: A Systematic Review of Current Pharmacokinetic Data

Obesity affects nearly one sixth of U.S. children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxicity. The depth of available literature regarding obesity’s effect on drug safety, pharmacokinetics (PK) and dosing in obese children is unknown

Mother's education and offspring asthma risk in 10 European cohort studies

Highly prevalent and typically beginning in childhood, asthma is a burdensome disease, yet the risk factors for this condition are not clarified. To enhance understanding, this study assessed the cohort-specific and pooled risk of maternal education on asthma in children aged 3-8 across 10 European countries. Data on 47,099 children were obtained from prospective birth cohort studies across 10 European countries. We calculated cohort-specific prevalence difference in asthma outcomes using the relative index of inequality (RII) and slope index of inequality (SII). Results from all countries were pooled using random-effects meta-analysis procedures to obtain mean RII and SII scores at the European level. Final models were adjusted for child sex, smoking during pregnancy, parity, mother's age and ethnicity. The higher the score the greater the magnitude of relative (RII, reference 1) and absolute (SII, reference 0) inequity. The pooled RII estimate for asthma risk across all cohorts was 1.46 (95% CI 1.26, 1.71) and the pooled SII estimate was 1.90 (95% CI 0.26, 3.54). Of the countries examined, France, the United Kingdom and the Netherlands had the highest prevalence's of childhood asthma and the largest inequity in asthma risk. Smaller inverse associations were noted for all other countries except Italy, which presented contradictory scores, but with small effect sizes. Tests for heterogeneity yielded significant results for SII scores. Overall, offspring of mothers with a low level of education had an increased relative and absolute risk of asthma compared to offspring of high-educated mothers

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

Genome analysis and physiological comparison of Alicycliphilus denitrificans strains BC and K601T

The genomes of the Betaproteobacteria Alicycliphilus denitrificans strains BC and K601T have been sequenced to get insight into the physiology of the two strains. Strain BC degrades benzene with chlorate as electron acceptor. The cyclohexanol-degrading denitrifying strain K601T is not able to use chlorate as electron acceptor, while strain BC cannot degrade cyclohexanol. The 16S rRNA sequences of strains BC and K601T are identical and the fatty acid methyl ester patterns of the strains are similar. Basic Local Alignment Search Tool (BLAST) analysis of predicted open reading frames of both strains showed most hits with Acidovorax sp. JS42, a bacterium that degrades nitro-aromatics. The genomes include strain-specific plasmids (pAlide201 in strain K601T and pAlide01 and pAlide02 in strain BC). Key genes of chlorate reduction in strain BC were located on a 120 kb megaplasmid (pAlide01), which was absent in strain K601T. Genes involved in cyclohexanol degradation were only found in strain K601T. Benzene and toluene are degraded via oxygenase-mediated pathways in both strains. Genes involved in the meta-cleavage pathway of catechol are present in the genomes of both strains. Strain BC also contains all genes of the ortho-cleavage pathway. The large number of mono- and dioxygenase genes in the genomes suggests that the two strains have a broader substrate range than known thus far.This research was supported by the Technology Foundation, the Applied Science Division (STW) of the Netherlands Organization for Scientific Research (NWO), project number 08053, the graduate school WIMEK (Wageningen Institute for Environment and Climate Research, which is part of SENSE Research School for Socio-Economic and Natural Sciences of the Environment, www.wimek-new.wur.nl and www.sense.nl), SKB (Dutch Centre for Soil Quality Management and Knowledge Transfer, www.skbodem.nl) and the Consolider project CSD-2007-00055. The research was incorporated in the TRIAS (TRIpartite Approaches 469 toward Soil systems processes) program (http://www.nwo.nl/en/research-and-results/programmes/alw/trias-tripartite-approach-to-soil-system-processes/index. html). Flávia Talarico Saia was supported by a FAPESP (the State of São Paulo Research Foundation) scholarship (2006-01997/5). The work conducted by the DOE JGI is supported by the Office of Science of the United States Department of Energy under contract number DE-AC02-05CH11231. Alfons Stams acknowledges support by an ERC (European Research Counsil) advanced grant (project 323009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Physical activity, sedentary behaviour, and childhood asthma: a European collaborative analysis

Objectives To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study. Design Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined. Setting Children aged 0–18 years from 26 European birth cohorts. Participants 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood. Main outcome measure Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity) at age 6–18 years. Results Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3–5 years was not associated with asthma at age 6–18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results. Conclusions Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood. Data availability statement Due to data protection reasons, the datasets generated during the current study cannot be made publicly available. The cohort-specific datasets are available to interested researchers on reasonable request, provided the release is consistent with the obtained consent of the study participants of the cohort. This will not be possible for all cohorts involved. Ethical approval might be necessary to be obtained for the release and a data transfer agreement must be accepted

Physical activity, sedentary behaviour, and childhood asthma: a European collaborative analysis

OBJECTIVES: To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study. DESIGN: Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined. SETTING: Children aged 0-18 years from 26 European birth cohorts. PARTICIPANTS: 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood. MAIN OUTCOME MEASURE: Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity) at age 6-18 years. RESULTS: Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3-5 years was not associated with asthma at age 6-18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results. CONCLUSIONS: Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood

Acute respiratory tract infections: a potential trigger for the acute coronary syndrome

Clinical studies suggest that acute respiratory tract infection (ARTI) may be a risk factor for the acute coronary syndrome (ACS). ARTI is associated with an increased risk for ACS up to 2 weeks prior to a cardiac event. The mechanism that may underlie this association is unclear. Infections are thought to play a role in the progression and instability of atherosclerotic plaques, resulting in plaque rupture, sudden constriction, and/or blockage of coronary arteries. Inflammation, endothelial dysfunction and thrombotic activation seem to play an important role in this. Influenza vaccination may reduce the risk of ACS in patients with coronary artery disease. Future studies will provide more information about the underlying mechanisms of infection-related AC

Acute respiratory tract infections: A potential trigger for the acute coronary syndrome

Clinical studies suggest that acute respiratory tract infection (ARTI) may be a risk factor for the acute coronary syndrome (ACS). ARTI is associated with an increased risk for ACS up to 2 weeks prior to a cardiac event. The mechanism that may underlie this association is unclear. Infections are thought to play a role in the progression and instability of atherosclerotic plaques, resulting in plaque rupture, sudden constriction, and/or blockage of coronary arteries. Inflammation, endothelial dysfunction and thrombotic activation seem to play an important role in this. Influenza vaccination may reduce the risk of ACS in patients with coronary artery disease. Future studies will provide more information about the underlying mechanisms of infection-related ACS

Digitale-mediagebruik en slaap bij jongeren

OBJECTIVE: To test whether parental rules regarding the amount of digital media use is associated with the sleep of Dutch adolescents, and whether this is indirectly due to lower digital media use. DESIGN: Cross-sectional study METHOD: Adolescents and their parents of the Amsterdam Born Children and their Development (ABCD) study completed questionnaires in 2019 at the age of 15-16 years (n=1369; 56% girls). Parents and adolescents reported whether there are rules regarding the amount of digital media use. The adolescents also reported their daily amount of digital media use, sleep duration, bedtime and sleep quality according to the Pittsburgh Sleep Quality Index (PSQI). We tested the association between rules and sleep duration, bedtime and sleep quality in adolescents using multivariate regression analysis. Using mediation analysis we tested whether rules were also indirectly associated with sleep outcome measures through the amount of digital media use. RESULTS: Setting rules regarding digital media use was related to sleep duration; 6.8 minutes (95%CI:0.1;13.5) longer with inconsistently experienced rules and 18.5 minutes (95%CI:9.2;27.8) longer with consistently existing rules. Setting rules was also related to bedtime; 10 minutes (95%CI: -17;-4) earlier with inconsistently experienced rules and 29 minutes (95%CI:-38;-2) earlier with consistently existing rules. Setting rules was not directly associated with sleep quality. Indirectly, rules were associated with longer sleep duration, earlier bedtime and better sleep quality due to lower digital media use per day. CONCLUSION: Parental rules regarding the amount of digital media use is associated with better sleep of adolescents. This is partly explained by lower digital media use