Prenatal Exposure to Chemical Mixtures and Metabolic Syndrome Risk in Children.

Importance: Prenatal exposure to ubiquitous endocrine-disrupting chemicals (EDCs) may increase the risk of metabolic syndrome (MetS) in children, but few studies have studied chemical mixtures or explored underlying protein and metabolic signatures. Objective: To investigate associations of prenatal exposure to EDC mixtures with MetS risk score in children and identify associated proteins and metabolites. Design, Setting, and Participants: This population-based, birth cohort study used data collected between April 1, 2003, and February 26, 2016, from the Human Early Life Exposome cohort based in France, Greece, Lithuania, Norway, Spain, and the UK. Eligible participants included mother-child pairs with measured prenatal EDC exposures and complete data on childhood MetS risk factors, proteins, and metabolites. Data were analyzed between October 2022 and July 2023. Exposures: Nine metals, 3 organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 5 perfluoroalkyl substances (PFAS), 10 phthalate metabolites, 3 phenols, 4 parabens, and 4 organophosphate pesticide metabolites measured in urine and blood samples collected during pregnancy. Main Outcomes and Measures: At 6 to 11 years of age, a composite MetS risk score was constructed using z scores of waist circumference, systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and insulin levels. Childhood levels of 44 urinary metabolites, 177 serum metabolites, and 35 plasma proteins were quantified using targeted methods. Associations were assessed using bayesian weighted quantile sum regressions applied to mixtures for each chemical group. Results: The study included 1134 mothers (mean [SD] age at birth, 30.7 [4.9] years) and their children (mean [SD] age, 7.8 [1.5] years; 617 male children [54.4%] and 517 female children [45.6%]; mean [SD] MetS risk score, -0.1 [2.3]). MetS score increased per 1-quartile increase of the mixture for metals (ß = 0.44; 95% credible interval [CrI], 0.30 to 0.59), organochlorine pesticides (ß = 0.22; 95% CrI, 0.15 to 0.29), PBDEs (ß = 0.17; 95% CrI, 0.06 to 0.27), and PFAS (ß = 0.19; 95% CrI, 0.14 to 0.24). High-molecular weight phthalate mixtures (ß = -0.07; 95% CrI, -0.10 to -0.04) and low-molecular weight phthalate mixtures (ß = -0.13; 95% CrI, -0.18 to -0.08) were associated with a decreased MetS score. Most EDC mixtures were associated with elevated proinflammatory proteins, amino acids, and altered glycerophospholipids, which in turn were associated with increased MetS score. Conclusions and Relevance: This cohort study suggests that prenatal exposure to EDC mixtures may be associated with adverse metabolic health in children. Given the pervasive nature of EDCs and the increase in MetS, these findings hold substantial public health implications.

A comparison of univariate and meta-analytic structural equation modeling approaches to reliability generalization applied to the Maslach Burnout Inventory.

Introduction: Reliability is a property of tests scores that varies from sample to sample. One way of generalizing reliability of a test is to perform a meta-analysis on some reliability estimator. In 2011, a reliability generalization meta-analysis on the Maslach Burnout Inventory (MBI) was conducted, concluding that average alpha values for the MBI dimensions ranged from 0.71 to 0.88. In the present study, we aimed to update the average reliability values of the MBI by conducting a literature search from 2010 until now and comparing to statistical procedures of meta-analysis: the Univariate approach, that were used in the previous study, and a novel meta-analytic approach based on structural equation modeling. Method: An estimation of average reliability was done based on 69 independent primary reliability coefficients for the Univariate approach. The average reliability was based on 9 independent studies in the case of the Meta-analytic Structural Equation Modeling (MASEM) approach. Given that MASEM has the additional capability of testing the internal structure of a test, we also fitted several models. Results: The data was well-suited to the bifactor model, revealing the dominance of the general factor over the domain-specific ones. Acceptable overall alpha and omega coefficients were achieved for the two of the MBI dimensions, having depersonalization reliability estimates below recommendations. Discussion: In general, the MBI can be viewed as a highly interconnected three-factor scale, being its appropriate for research purposes.

Machine learning-based health environmental-clinical risk scores in European children.

BACKGROUND: Early life environmental stressors play an important role in the development of multiple chronic disorders. Previous studies that used environmental risk scores (ERS) to assess the cumulative impact of environmental exposures on health are limited by the diversity of exposures included, especially for early life determinants. We used machine learning methods to build early life exposome risk scores for three health outcomes using environmental, molecular, and clinical data. METHODS: In this study, we analyzed data from 1622 mother-child pairs from the HELIX European birth cohorts, using over 300 environmental, 100 child peripheral, and 18 mother-child clinical markers to compute environmental-clinical risk scores (ECRS) for child behavioral difficulties, metabolic syndrome, and lung function. ECRS were computed using LASSO, Random Forest and XGBoost. XGBoost ECRS were selected to extract local feature contributions using Shapley values and derive feature importance and interactions. RESULTS: ECRS captured 13%, 50% and 4% of the variance in mental, cardiometabolic, and respiratory health, respectively. We observed no significant differences in predictive performances between the above-mentioned methods.The most important predictive features were maternal stress, noise, and lifestyle exposures for mental health; proteome (mainly IL1B) and metabolome features for cardiometabolic health; child BMI and urine metabolites for respiratory health. CONCLUSIONS: Besides their usefulness for epidemiological research, our risk scores show great potential to capture holistic individual level non-hereditary risk associations that can inform practitioners about actionable factors of high-risk children. As in the post-genetic era personalized prevention medicine will focus more and more on modifiable factors, we believe that such integrative approaches will be instrumental in shaping future healthcare paradigms.

Growing up in different environments can greatly affect children's health later in life. This research looked at how living in cities, being exposed to chemicals, and other experiences before birth and during childhood, work together to influence children's mental, cardiovascular and respiratory health. We used advanced computer programs to help us understand these effects and estimate health risk scores. These scores are simple numerical measures that help us quantify the likelihood of children developing health issues based on their environmental exposures. Using those scores, the study identified key factors impacting children's health, in particular psycho-social, perceived environmental and prenatal pollutant exposures for mental health. It also revealed complex patterns and interactions between environmental factors. The results highlighted the potential of such risk scores to support the identification of actionable factors in high-risk children, informing tailored prevention measures in healthcare.

Impact effects of COVID-19 pandemic on chronic disease patients: A longitudinal prospective study.

AIMS: To assess the effects of COVID-19 pandemic on clinical variables as part of the routine clinical monitoring of patients with chronic diseases in primary care. DESIGN: A prospective longitudinal study was conducted in primary care centres of the Andalusian Health Service. METHODS: Data were recorded before the pandemic (T1), during the declaration of the state of emergency (T2) and in the transition phase (T3). The Barthel index and the Short Portable Mental Status Questionnaire (SPMSQ) were used to analyse functional and cognitive changes at the three time points. HbA1c, systolic and diastolic blood pressure, heart rate, BMI and lipid levels were assessed as clinical variables. Descriptive statistics and non-parametric chi-square test were used for analysis. STROBE checklist was used for the preparation of this paper. RESULTS: A total fo148 patients with chronic conditions were included in the analysis. Data analysis revealed in T2 only significant reductions in BMI, total levels of cholesterol and HDL during the onset of the pandemic. Barthel Index, SPMSQ, blood pressure and triglycerides and LDL levels worsened in T2, and the negative effects were maintained in T3. Compared to pre-pandemic values, HbA1c levels improved in T3, but HDL levels worsened. CONCLUSIONS: COVID-19 has drastically disrupted several functional, cognitive and biological variables. These results may be useful in identifying clinical parameters that deserve closer attention in the case of a new health crisis. Further studies are needed to assess the potential impacts of each specific chronic condition. IMPACT: Cognitive and functional status, blood pressure and triglycerides and LDL levels worsen in short term, maintaining the negative effects in medium-term.

Impact of SARS-COV-2 Infection on Maternal, Obstetric and Neonatal Outcomes in a Cohort of Vaccinated Women: A Pilot Study.

We aimed to investigate the impact of COVID-19 infection on maternal characteristics and obstetric and neonatal outcomes in a cohort of women in labor previously vaccinated who tested positive for SARS-CoV-2 infection, compared to aged-matched healthy controls. A retrospective case-control study was conducted among 66 women in labor. Clinical data were obtained from medical records. The attendance rates at childbirth and parenting classes, as well as the implementation of a birth plan, were significantly lower in the COVID-19 infection group (6.1% vs. 48.5%, <0.001; 6.1% vs. 33.3%, p = .005, respectively). Women with COVID-19 had a higher prevalence of prolonged postpartum hospital stay (33.3% vs. 9.1%, p = .016), and significantly higher prevalence of spontaneous preterm birth (27.3% vs. 1.09%, p = .006). Breastfeeding within the first 24 hr was also lower in women with COVID-19 (72.7% vs. 97.0%, p = .006). Maternal characteristics and neonatal outcomes are influenced by COVID-19 infection in vaccinated women. Complications include spontaneous preterm birth, prolonged postpartum hospital stay, and lack of breastfeeding within the first 24 hr. Childbirth education, parenting classes and implementing a birth plan may be associated with a decreased risk of COVID-19 infection.

Ultrasound-guided peripheral intravenous canulation by emergency nurses: A systematic review and meta-analysis.

BACKGROUND: Peripheral intravenous cannulation is a common procedure in the emergency department. Nevertheless, failure rates during the first attempt are as high as 40% in adults and 65% in children. Evidence suggests that physician performed ultrasound-guided peripheral intravenous cannulation (USG-PIVC) is an effective alternative to the traditional method; however, there is insufficient data on the efficacy of the technique performed by nurses. OBJECTIVE: To examine the efficacy of the USG-PIVC technique performed by emergency department nurses. METHODS: A literature review with meta-analysis was performed. The databases used were PubMed, Scopus and CINAHL. The search was conducted in March 2023. Two meta-analysis one of clinical trials about the effectiveness and one about the succession rate were performed. RESULTS: 20 studies were selected and analysed. The studies showed that USGPIVC performed by emergency nurses increased the probability of both the overall success and a successful first attempt compared to the standard technique. In addition, patients showed high satisfaction and lower complication rates. However, the procedure had no significant effect on the time or number of attempts required. A lower probability of success was obtained as regards peripheral intravenous cannulation when the standard technique was used, OR = 0.42 (95 %CI 0.25-0.70p < 0,05). CONCLUSIONS: Ultrasound-guided peripheral intravenous cannulation performed by emergency nurses is a safe and effective technique.

Analyzing Latent Burnout Profiles in a Sample of Spanish Nursing and Psychology Undergraduates.

There is abundant literature suggesting that university students in helping professions experience high levels of stress, leading to an increased risk of developing burnout. The objective of this study was to identify burnout profiles in a sample of 1162 Spanish nursing and psychology undergraduates using latent profile analysis, a person-oriented statistical method that can identify hidden homogenous subgroups within a heterogeneous population. We expected to replicate in university students the five-profile structure (burnout, overextended, disengaged, ineffective, and engagement) proposed by Leiter and Maslach using the burnout dimensions (emotional exhaustion, cynicism, and inefficacy) as indicators. The results showed that burnout, overextended, and engagement profiles were adequately replicated. Given that levels of inefficacy and cynicism were medium to low, the ineffective and disengaged profiles somewhat deviated from those identified by Leiter and Maslach. We found differences between the five latent profiles in several psychological variables, such as depression and anxiety. These results suggest that psychosocial factors (e.g., workload) are significant among students and may adversely impact their health, leading to psychosomatic and emotional disorders. Hence, designing effective interventions to prevent health problems associated with burnout seems advisable, considering the specific burnout profile that a student exhibits.

Job satisfaction and burnout syndrome among intensive-care unit nurses: A systematic review and meta-analysis.

INTRODUCTION: The severe conditions often experienced in an intensive care unit, combined with poor working conditions, increase stress and therefore decrease job satisfaction. Sustained stress in the workplace leads to the development of burnout, a syndrome characterised by three dimensions: emotional exhaustion, depersonalisation and perceived lack of personal fulfilment. OBJECTIVE: To analyse the relationship between burnout syndrome and job satisfaction among ICU personnel. DATA SOURCES: The PubMed, CINAHL and Scopus databases were used. STUDY DESIGN: A systematic review and meta-analysis. The study sample consisted of 18 quantitative primary studies conducted in the last five years. Validated questionnaires were used to assess burnout in ICU healthcare workers, the most commonly used being the Maslach Burnout Inventory. EXTRACTION METHODS: The search equation applied was: "job satisfaction AND nurs* AND burnout AND (ICU OR intensive care units)". The search was performed in October 2022. PRINCIPAL FINDINGS: The search returned 514 results. Only 73 articles met the eligibility criteria. After reading the title and abstract, 20 articles were selected. After reading the full texts, 12 articles remained and after the reverse search, 18 articles were finally selected. The studies reported a 50% prevalence of burnout, all three dimensions of which were heightened by the COVID-19 pandemic. Analysis of the study findings revealed an inverse association between burnout and job satisfaction. CONCLUSIONS: Job dissatisfaction of ICU nurses depends on lack of experience, working conditions or working environment among others. ICU nurses with lower job satisfaction have higher levels of burnout. IMPLICATIONS FOR CLINICAL PRACTICE: This meta-analysis shows the potential value of job satisfaction on improving health outcomes related to burnout syndrome for nursing professional in Intensive Care Units. Different factors that could increase job satisfaction and consequently protect them from suffering high levels of burnout, such as salary, permanence in the service, mental health care are the responsibility of the hospital supervisor and, finally, of the own Health System. Knowledge of a risk profile based on the factors influencing job dissatisfaction would enable the implementation of effective workplace interventions to reduce or prevent the risk of burnout. Health policies should focus on protecting the worker, so in addition to improving working conditions, it would be interesting to promote coping skills in order to improve the quality of care and patient safety.

Childhood exposure to outdoor air pollution in different microenvironments and cognitive and fine motor function in children from six European cohorts.

BACKGROUND: Exposure to air pollution during childhood has been linked with adverse effects on cognitive development and motor function. However, limited research has been done on the associations of air pollution exposure in different microenvironments such as home, school, or while commuting with these outcomes. OBJECTIVE: To analyze the association between childhood air pollution exposure in different microenvironments and cognitive and fine motor function from six European birth cohorts. METHODS: We included 1301 children from six European birth cohorts aged 6-11 years from the HELIX project. Average outdoor air pollutants concentrations (NO2, PM2.5) were estimated using land use regression models for different microenvironments (home, school, and commute), for 1-year before the outcome assessment. Attentional function, cognitive flexibility, non-verbal intelligence, and fine motor function were assessed using the Attention Network Test, Trail Making Test A and B, Raven Colored Progressive Matrices test, and the Finger Tapping test, respectively. Adjusted linear regressions models were run to determine the association between each air pollutant from each microenvironment on each outcome. RESULTS: In pooled analysis we observed high correlation (rs = 0.9) between air pollution exposures levels at home and school. However, the cohort-by-cohort analysis revealed correlations ranging from low to moderate. Air pollution exposure levels while commuting were higher than at home or school. Exposure to air pollution in the different microenvironments was not associated with working memory, attentional function, non-verbal intelligence, and fine motor function. Results remained consistently null in random-effects meta-analysis. CONCLUSIONS: No association was observed between outdoor air pollution exposure in different microenvironments (home, school, commute) and cognitive and fine motor function in children from six European birth cohorts. Future research should include a more detailed exposure assessment, considering personal measurements and time spent in different microenvironments.

Associations between combined urban and lifestyle factors and respiratory health in European children.

INTRODUCTION: Previous studies identified some environmental and lifestyle factors independently associated with children respiratory health, but few focused on exposure mixture effects. This study aimed at identifying, in pregnancy and in childhood, combined urban and lifestyle environment profiles associated with respiratory health in children. METHODS: This study is based on the European Human Early-Life Exposome (HELIX) project, combining six birth cohorts. Associations between profiles of pregnancy (38 exposures) and childhood (84 exposures) urban and lifestyle factors, identified by clustering analysis, and respiratory health were estimated by regression models adjusted for confounders. RESULTS: Among the 1033 included children (mean ± standard-deviation (SD) age: 8.2 ± 1.6 years old, 47% girls) the mean ± SD forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) were 99 ± 13% and 101 ± 14%, respectively, and 12%, 12% and 24% reported ever-asthma, wheezing and rhinitis, respectively. Four profiles of pregnancy exposures and four profiles of childhood exposures were identified. Compared to the reference childhood exposure profile (low exposures), two exposure profiles were associated with lower levels of FEV1. One profile was characterized by few natural spaces in the surroundings and high exposure to the built environment and road traffic. The second profile was characterized by high exposure to meteorological factors and low levels of all other exposures and was also associated with an increased risk of ever-asthma and wheezing. A pregnancy exposure profile characterized by high exposure levels to all risk factors, but a healthy maternal lifestyle, was associated with a lower risk of wheezing and rhinitis in children, compared to the reference pregnancy profile (low exposures). CONCLUSION: This comprehensive approach revealed pregnancy and childhood profiles of urban and lifestyle exposures associated with lung function and/or respiratory conditions in children. Our findings highlight the need to pursue the study of combined exposures to improve prevention strategies for multifactorial diseases such as asthma.

Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence.

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

Beyond the single-outcome approach: A comparison of outcome-wide analysis methods for exposome research.

Outcome-wide analysis can offer several benefits, including increased power to detect weak signals and the ability to identify exposures with multiple effects on health, which may be good targets for preventive measures. Recently, advanced statistical multivariate techniques for outcome-wide analysis have been developed, but they have been rarely applied to exposome analysis. In this work, we provide an overview of a selection of methods that are well-suited for outcome-wide exposome analysis and are implemented in the R statistical software. Our work brings together six different methods presenting innovative solutions for typical problems arising from outcome-wide approaches in the context of the exposome, including dependencies among outcomes, high dimensionality, mixed-type outcomes, missing data records, and confounding effects. The identified methods can be grouped into four main categories: regularized multivariate regression techniques, multi-task learning approaches, dimensionality reduction approaches, and bayesian extensions of the multivariate regression framework. Here, we compare each technique presenting its main rationale, strengths, and limitations, and provide codes and guidelines for their application to exposome data. Additionally, we apply all selected methods to a real exposome dataset from the Human Early-Life Exposome (HELIX) project, demonstrating their suitability for exposome research. Although the choice of the best method will always depend on the challenges to be faced in each application, for an exposome-like analysis we find dimensionality reduction and bayesian methods such as reduced rank regression (RRR) or multivariate bayesian shrinkage priors (MBSP) particularly useful, given their ability to deal with critical issues such as collinearity, high-dimensionality, missing data or quantification of uncertainty.

Blood miRNA levels associated with ADHD traits in children across six European birth cohorts.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and highly heritable neurodevelopmental disorder of major societal concern. Diagnosis can be challenging and there are large knowledge gaps regarding its etiology, though studies suggest an interplay of genetic and environmental factors involving epigenetic mechanisms. MicroRNAs (miRNAs) show promise as biomarkers of human pathology and novel therapies, and here we aimed to identify blood miRNAs associated with traits of ADHD as possible biomarker candidates and further explore their biological relevance. METHODS: Our study population consisted of 1126 children (aged 5-12 years, 46% female) from the Human Early Life Exposome study, a study spanning six ongoing population-based European birth cohorts. Expression profiles of miRNAs in whole blood samples were quantified by microarray and tested for association with ADHD-related measures of behavior and neuropsychological functions from questionnaires (Conner's Rating Scale and Child Behavior Checklist) and computer-based tests (the N-back task and Attention Network Test). RESULTS: We identified 29 miRNAs significantly associated (false discovery rate < .05) with the Conner's questionnaire-rated trait hyperactivity, 15 of which have been linked to ADHD in previous studies. Investigation into their biological relevance revealed involvement in several pathways related to neurodevelopment and function, as well as being linked with other neurodevelopmental or psychiatric disorders known to overlap with ADHD both in symptomology, genetic risk, and co-occurrence, such as autism spectrum disorder or schizophrenia. An additional three miRNAs were significantly associated with Conner's-rated inattention. No associations were found with questionnaire-rated total ADHD index or with computer-based tests. CONCLUSIONS: The large overlap of our hyperactivity-associated miRNAs with previous studies on ADHD is intriguing and warrant further investigation. Though this study should be considered explorative and preliminary, these findings contribute towards identifying a set of miRNAs for use as blood-based biomarkers to aid in earlier and easier ADHD diagnosis.

Burnout syndrome and work engagement in nursing staff: a systematic review and meta-analysis.

Background: A difficult and demanding work environment, such as that often experienced in healthcare, can provoke fatigue, anxiety, distress, and discomfort. This study considers factors that may influence levels of burnout and work engagement among nurses and seeks to determine the relationship between these conditions. Method: A systematic scoping review was performed, in accordance with the PRISMA Extension for Scoping Reviews, based on data obtained from a search of the PubMed/MEDLINE and Scopus databases carried out in 2022 using the search equation: "work engagement AND nurs* AND burnout." This search identified nine quantitative primary studies suitable for inclusion in our analysis. Results: Work overload, type of shift worked, and/or area of hospital service, among other elements, are all relevant to the development of burnout. This syndrome can be countered by social support and appropriate personal resources and values, which are all positively associated with work engagement. Our analysis revealed a significant correlation between work engagement and the different domains of burnout. The correlation effect size between burnout and work engagement was -0.46 (95% CI -0.58, -0.31), with p < 0.001. Conclusion: Well-targeted interventions in the healthcare work environment can reduce burnout levels, strengthen work engagement, and enhance the quality of healthcare.

Prevalence and levels of burnout in nursing students: A systematic review with meta-analysis.

AIM: The aim of this study was to analyze burnout levels and prevalence in nursing students and to estimate prevalence levels with meta-analyses. BACKGROUND: Nurses are one of the healthcare professionals most affect by burnout, but nursing students, during their studies, can also suffer burnout. DESIGN: a systematic review with meta-analysis was performed. METHODS: The search equation used in Pubmed, CINAHL and Scopus databases was "burnout AND nursing students". Quantitative primary studies including information about burnout, emotional exhaustion, depersonalization, or personal accomplishment in nursing students were included. Four meta-analysis were performed. RESULTS: the sample was of n = 34 studies, with n = 15 studies being included in the meta-analysis with n = 2744 nursing students. Burnout prevalence was 19% (95% CI 11-28%). Regarding burnout dimensions, the most affected was high emotional exhaustion with a prevalence of 41%(95% CI 23-61%; n = 2222) followed by 27% low personal accomplishment(95% CI 9-49%; n = 2096), 25% high depersonalization (95% CI 15-36%; n = 2096). CONCLUSIONS: Prevalence of burnout and its dimensions vary from 19% to 41%, being emotional exhaustion the main problem in nursing students. This problem may affect their future as nursing professionals, and it would be of important to prevent and to treat burnout at university levels.

Efficacy and Safety of New B Cell-Targeted Biologic Agent for the Treatment of Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis.

BACKGROUND: B cells are central to the pathogenesis of systemic lupus erythematosus (SLE). We aimed to analyze the efficacy and safety of new B cell-targeted drug therapies for SLE. METHODS: A systematic review of randomized controlled trials (RCTs) and reference lists of relevant articles published from inception to 2022 were selected from PubMed, Scopus and Web of Science databases. Random effects meta-analyses were performed to estimate an overall effect size for the risk of adverse events (AEs) and serious adverse events (SAEs) with belimumab and tabalumab treatment. Heterogeneity was assessed using the I2 statistic and meta-regression. Funnel asymmetry was evaluated using Egger's test. RESULTS: This study included 13 RCTs, of which three showed high risk of bias. Egger's test showed no asymmetry. The risk of SAEs and AEs was lower in the treatment group with belimumab treatment. The risk of AEs for tabalumab treatment was lower in the treatment group and lower for SAEs. CONCLUSION: Belimumab and tabalumab therapies are effective and safe in the treatment of SLE, although tabalumab does not show sufficient statistical power. Advances in understanding the underlying mechanisms of SLE will be directed towards correlating clinical manifestations with specific pathogenic pathways and the development of precision medicine.

Availability, accessibility, and use of green spaces and cognitive development in primary school children.

Green spaces may have beneficial impacts on children's cognition. However, few studies explored the exposure to green spaces beyond residential areas, and their availability, accessibility and uses at the same time. The aim of the present study was to describe patterns of availability, accessibility, and uses of green spaces among primary school children and to explore how these exposure dimensions are associated with cognitive development. Exposures to green space near home, school, commuting route, and other daily activity locations were assessed for 1607 children aged 6-11 years from six birth cohorts across Europe, and included variables related to: availability (NDVI buffers: 100, 300, 500 m), potential accessibility (proximity to a major green space: linear distance; within 300 m), and use (play time in green spaces: hours/year), and the number of visits to green spaces (times/previous week). Cognition measured as fluid intelligence, inattention, and working memory was assessed by computerized tests. We performed multiple linear regression analyses on pooled and imputed data adjusted for individual and area-level confounders. Availability, accessibility, and uses of green spaces showed a social gradient that was unfavorable in more vulnerable socioeconomic groups. NDVI was associated with more playing time in green spaces, but proximity to a major green space was not. Associations between green space exposures and cognitive function outcomes were not statistically significant in our overall study population. Stratification by socioeconomic variables showed that living within 300 m of a major green space was associated with improved working memory only in children in less deprived residential areas (ß = 0.30, CI: 0.09,0.51), and that more time playing in green spaces was associated with better working memory only in children of highly educated mothers (ß per IQR increase in hour/year = 0.10; 95% CI: 0.01, 0.19). However, studying within 300 m of a major green space increased inattention scores in children in more deprived areas (ß = 15.45, 95% CI: 3.50, 27.40).

Associations of four biological age markers with child development: A multi-omic analysis in the European HELIX cohort.

Background: While biological age in adults is often understood as representing general health and resilience, the conceptual interpretation of accelerated biological age in children and its relationship to development remains unclear. We aimed to clarify the relationship of accelerated biological age, assessed through two established biological age indicators, telomere length and DNA methylation age, and two novel candidate biological age indicators, to child developmental outcomes, including growth and adiposity, cognition, behavior, lung function and the onset of puberty, among European school-age children participating in the HELIX exposome cohort. Methods: The study population included up to 1173 children, aged between 5 and 12 years, from study centres in the UK, France, Spain, Norway, Lithuania, and Greece. Telomere length was measured through qPCR, blood DNA methylation, and gene expression was measured using microarray, and proteins and metabolites were measured by a range of targeted assays. DNA methylation age was assessed using Horvath's skin and blood clock, while novel blood transcriptome and 'immunometabolic' (based on plasma proteins and urinary and serum metabolites) clocks were derived and tested in a subset of children assessed six months after the main follow-up visit. Associations between biological age indicators with child developmental measures as well as health risk factors were estimated using linear regression, adjusted for chronological age, sex, ethnicity, and study centre. The clock derived markers were expressed as Δ age (i.e. predicted minus chronological age). Results: Transcriptome and immunometabolic clocks predicted chronological age well in the test set (r=0.93 and r=0.84 respectively). Generally, weak correlations were observed, after adjustment for chronological age, between the biological age indicators.Among associations with health risk factors, higher birthweight was associated with greater immunometabolic Δ age, smoke exposure with greater DNA methylation Δ age, and high family affluence with longer telomere length.Among associations with child developmental measures, all biological age markers were associated with greater BMI and fat mass, and all markers except telomere length were associated with greater height, at least at nominal significance (p<0.05). Immunometabolic Δ age was associated with better working memory (p=4 e-3) and reduced inattentiveness (p=4 e-4), while DNA methylation Δ age was associated with greater inattentiveness (p=0.03) and poorer externalizing behaviors (p=0.01). Shorter telomere length was also associated with poorer externalizing behaviors (p=0.03). Conclusions: In children, as in adults, biological aging appears to be a multi-faceted process and adiposity is an important correlate of accelerated biological aging. Patterns of associations suggested that accelerated immunometabolic age may be beneficial for some aspects of child development while accelerated DNA methylation age and telomere attrition may reflect early detrimental aspects of biological aging, apparent even in children. Funding: UK Research and Innovation (MR/S03532X/1); European Commission (grant agreement numbers: 308333; 874583).

Although age is generally measured by the number of years since birth, many factors contribute to the rate at which a person physically ages. In adults, linking these measurements to age gives a measure of overall health and resilience. This 'biological age' offers a better prediction of remaining life and disease risk than the number of years lived. Multiple factors can be used to calculate biological age, such as measuring the length of telomeres ­ protective caps on the end of chromosomes ­ which shorten as people age. The rate at which they shorten can give an indication of how quickly someone is ageing. Researchers can also study epigenetic factors: these mechanisms lead to certain genes being switched on or off, and they can be combined into a 'epigenetic clock' to assess biological age. However, compared with adults, the relationship between biological age and child health and developmental maturity is less well understood. Robinson et al. studied 1,173 school-aged children from six European countries, measuring telomere length, epigenetic factors and other biological indicators related to metabolism and the immune system. The relationships between these factors and an array of child developmental measures such as height, weight, behaviour and the age of onset of puberty were established. The findings showed that biological age indicators are only weakly linked to each other in children. Despite this, biological age was related to greater amount of body fat across all tested indicators ­ which is also associated with biological age in adults and is an important determinant of lifespan. Among several observed effects on development, analysis found that shorter telomere length and older epigenetic age were associated with greater behavioural problems, suggesting they may be detrimental to child development. On the other hand, a greater age due to metabolic and immune related changes was associated with greater cognitive and behavioural maturity. Environmental factors were also linked to biological ageing, with children exposed to smoking in their homes or while their mother was pregnant displaying an older epigenetic age. Robinson et al. showed that biological ageing in children is multifaceted and can have both beneficial and harmful impacts on development. This knowledge is important for identifying early life risk factors that might influence healthy ageing in later life. Future work will help researchers to understand these complex interactions and the long-term consequences for health and well-being.

Effectiveness of real-time classroom interactive competition on academic performance: a systematic review and meta-analysis.

In recent years, different tools have been introduced into the educational landscape to promote active participation and interaction between students and teachers through personal response systems. The evolution of this methodology has allowed students to participate in real-time by answering questions posed. Previous reviews on the effectiveness of real-time classroom interactive competition (RCIC) on academic performance have been performed; however, this research was based only on Kahoot, without considering other RCIC tools or programs. In addition, the RCIC effectiveness at different educational levels and its effect according to the duration of the intervention has not been meta-analytically analyzed until to date. The aim of this meta-analysis was to analyze the RCIC effectiveness in improving academic performance. A search focused on studies from the educational field published from 2010 until September 2022 was performed. Experimental studies with objective and valid data (scores based on tests or exams) were included. From a total of 397 studies considered potentially eligible, 23 studies met the inclusion criteria. The sample was n = 1,877 for the experimental group and n = 1,765 for the control group with an academic improvement in favor to experimental group (MD 7.34; CI [5.31-9.43]; p < 0.001). There was also significant improvement in academic performance when analyzing different educational levels and different tools. In addition, both short-term interventions (two weeks or less in duration) and long-term (from two weeks to one year in duration) were effective. Therefore, RCIC interventions seem to be an effective strategy to improve academic performance.