Early-life risk factors for depression among young adults in the United States general population: Attributable risks and gender differences.

BACKGROUND: This study adopts individual and societal-level approaches to examine the contribution of childhood risk factors to major depressive episodes (MDE) in 2526 American young adults. METHODS: Nationally representative data from the 2017 U.S. Panel Study of Income Dynamics - Transition into Adulthood Supplement (PSID-TAS) were analyzed using multivariate methods to assess the impact of parental mental illness, childhood adversities, childhood mental disorders, and childhood physical conditions. Adjusted odds ratios and population attributable risk proportions (PARPs) are calculated to estimate the proportion of MDE cases related to risk factors. RESULTS: The 12-month prevalence of positive screens for MDE was 25.4 %. Approximately 34 % of these were attributable to childhood mental disorders, 24 % to childhood physical conditions, 21 % to childhood adversities, and 16 % to parental mental illness. Childhood and parental depression were critical risk factors, both at the individual (odds ratio exceeding 2) and societal (PARP approximately 24 %) levels. Gender-specific risk factors were identified, with childhood physical abuse and childhood anxiety disorders constituting risk factors for females, and childhood externalizing disorders and childhood headaches as risk factors for males. Approximately 60 % of U.S. young adult MDE cases are attributable to risk factors before age 18. LIMITATIONS: Possible over reporting of MDE may have biased the associations between predictors and depression. CONCLUSIONS: Exposure to depression at a young age-one's own or parental depression-is a robust risk factor for both genders. Policies and interventions focused at alleviating the societal burden of depression should value its generational transmission.

Setting a research agenda for examining early risk for elevated cognitive disengagement syndrome symptoms using data from the ABCD cohort.

Background: Little research has examined early life risk for symptoms of cognitive disengagement syndrome (CDS) despite a well-established literature regarding co-occurring outcomes (e.g., attention-deficit/hyperactivity disorder). The current study estimated bivariate associations between early life risk factors and CDS in a large and representative sample of U.S. children. Methods: We conducted secondary analyses of baseline data from the Adolescent Brain Cognitive Development (ABCD) study (N = 8,096 children, 9-10 years old). Birthing parents reported early life risk factors on a developmental history questionnaire, including parental, prenatal, delivery and birth, and developmental milestone information. They also completed the Child Behavior Checklist, which includes a CDS subscale that was dichotomized to estimate the odds of elevated CDS symptoms (i.e., T-score > 70) in children related to risk indices. Results: We observed significantly elevated odds of CDS related to parental risk factors (i.e., unplanned pregnancy, pregnancy awareness after 6 weeks, teenage parenthood), birthing parent illnesses in pregnancy (i.e., severe nausea, proteinuria, pre-eclampsia/toxemia, severe anemia, urinary tract infection), pregnancy complications (i.e., bleeding), prenatal substance exposures (i.e., prescription medication, tobacco, illicit drugs), delivery and birth risk factors (i.e., child blue at delivery, child not breathing, jaundice, incubation after delivery), and late motor and speech milestones in children. Conclusions: Several early-life risk factors were associated with elevated odds of CDS at ages 9-10 years; study design prevents the determination of causality. Further investigation is warranted regarding early life origins of CDS with priority given to risk indices that have upstream commonalities (i.e., that restrict fetal growth, nutrients, and oxygen).

Association of early menarche with breast tumor molecular features and recurrence.

BACKGROUND: Early menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear. METHODS: We profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses' Health Studies (NHS) to investigate whether early menarche (age < 12) is associated with tumor molecular and prognostic features in women with breast cancer. Multivariable linear regression and pathway analyses using competitive gene set enrichment analysis were conducted in both tumor and adjacent-normal tissue and externally validated in TCGA (N = 116). Subgroup analyses stratified on ER-status based on the tumor were also performed. PAM50 signatures were used for tumor molecular subtyping and to generate proliferation and risk of recurrence scores. We created a gene expression score using LASSO regression to capture early menarche based on 28 genes from FDR-significant pathways in breast tumor tissue in NHS and tested its association with 10-year disease-free survival in both NHS (N = 836) and METABRIC (N = 952). RESULTS: Early menarche was significantly associated with 369 individual genes in adjacent-normal tissues implicated in extracellular matrix, cell adhesion, and invasion (FDR ≤ 0.1). Early menarche was associated with upregulation of cancer hallmark pathways (18 significant pathways in tumor, 23 in tumor-adjacent normal, FDR ≤ 0.1) related to proliferation (e.g. Myc, PI3K/AKT/mTOR, cell cycle), oxidative stress (e.g. oxidative phosphorylation, unfolded protein response), and inflammation (e.g. pro-inflammatory cytokines IFN α and IFN γ ). Replication in TCGA confirmed these trends. Early menarche was associated with significantly higher PAM50 proliferation scores (ß = 0.082 [0.02-0.14]), odds of aggressive molecular tumor subtypes (basal-like, OR = 1.84 [1.18-2.85] and HER2-enriched, OR = 2.32 [1.46-3.69]), and PAM50 risk of recurrence score (ß = 4.81 [1.71-7.92]). Our NHS-derived early menarche gene expression signature was significantly associated with worse 10-year disease-free survival in METABRIC (N = 952, HR = 1.58 [1.10-2.25]). CONCLUSIONS: Early menarche is associated with more aggressive molecular tumor characteristics and its gene expression signature within tumors is associated with worse 10-year disease-free survival among women with breast cancer. As the age of onset of menarche continues to decline, understanding its relationship to breast tumor characteristics and prognosis may lead to novel secondary prevention strategies.

Association between perinatal and early life exposures and lung function in Australian Indigenous young adults: The Aboriginal Birth Cohort study.

BACKGROUND AND OBJECTIVE: Despite the high burden of respiratory disease amongst Indigenous populations, prevalence data on spirometric deficits and its determinants are limited. We estimated the prevalence of abnormal spirometry in young Indigenous adults and determined its relationship with perinatal and early life factors. METHODS: We used prospectively collected data from the Australian Aboriginal Birth Cohort, a birth cohort of 686 Indigenous Australian singletons. We calculated the proportion with abnormal spirometry (z-score <-1.64) and FEV1 below the population mean (FEV1 % predicted 0 to -2SD) measured in young adulthood. We evaluated the association between perinatal and early life exposures with spirometry indices using linear regression. RESULTS: Fifty-nine people (39.9%, 95%CI 31.9, 48.2) had abnormal spirometry; 72 (49.3%, 95%CI 40.9, 57.7) had a FEV1 below the population mean. Pre-school hospitalisations for respiratory infections, younger maternal age, being overweight in early childhood and being born remotely were associated with reduced FEV1 and FVC (absolute, %predicted and z-score). The association between maternal age and FEV1 and FVC were stronger in women, as was hospitalization for respiratory infections before age 5. Being born remotely had a stronger association with reduced FEV1 and FVC in men. Participants born in a remote community were over 6 times more likely to have a FEV1 below the population mean (odds ratio [OR] 6.30, 95%CI 1.93, 20.59). CONCLUSION: Young Indigenous adults have a high prevalence of impaired lung function associated with several perinatal and early life factors, some of which are modifiable with feasible interventions.

Early life exposures contributing to accelerated lung function decline in adulthood - a follow-up study of 11,000 adults from the general population.

Background: We aimed to assess whether exposure to risk factors in early life from conception to puberty continue to contribute to lung function decline later in life by using a pooled cohort comprising approx. 11,000 adults followed for more than 20 years and with up to three lung function measurements. Methods: Participants (20-68 years) in the ECRHS and NFBC1966 cohort studies followed in the periods 1991-2013 and 1997-2013, respectively, were included. Mean annual decline in maximum forced expired volume in 1 s (FEV1) and forced vital capacity (FVC) were main outcomes. Associations between early life risk factors and change in lung function were estimated using mixed effects linear models adjusted for sex, age, FEV1, FVC and height at baseline, accounting for personal smoking. Findings: Decline in lung function was accelerated in participants with mothers that smoked during pregnancy (FEV1 2.3 ml/year; 95% CI: 0.7, 3.8) (FVC 2.2 ml/year; 0.2, 4.2), with asthmatic mothers (FEV1 2.6 ml/year; 0.9, 4.4) (FEV1/FVC 0.04 per year; 0.04, 0.7) and asthmatic fathers (FVC 2.7 ml/year; 0.5, 5.0), and in women with early menarche (FVC 2.4 ml/year; 0.4, 4.4). Personal smoking of 10 pack-years contributed to a decline of 2.1 ml/year for FEV1 (1.8, 2.4) and 1.7 ml/year for FVC (1.3, 2.1). Severe respiratory infections in early childhood were associated with accelerated decline among ever-smokers. No effect-modification by personal smoking, asthma symptoms, sex or cohort was found. Interpretation: Mothers' smoking during pregnancy, parental asthma and early menarche may contribute to a decline of FEV1 and FVC later in life comparable to smoking 10 pack-years. Funding: European Union's Horizon 2020; Research Council of Norway; Academy of Finland; University Hospital Oulu; European Regional Development Fund; Spanish Ministry of Science and Innovation; Generalitat de Catalunya.

Development of risk prediction models for depression combining genetic and early life risk factors.

Background: Both genetic and early life risk factors play important roles in the pathogenesis and progression of adult depression. However, the interplay between these risk factors and their added value to risk prediction models have not been fully elucidated. Methods: Leveraging a meta-analysis of major depressive disorder genome-wide association studies (N = 45,591 cases and 97,674 controls), we developed and optimized a polygenic risk score for depression using LDpred in a model selection dataset from the UK Biobank (N = 130,092 European ancestry individuals). In a UK Biobank test dataset (N = 278,730 European ancestry individuals), we tested whether the polygenic risk score and early life risk factors were associated with each other and compared their associations with depression phenotypes. Finally, we conducted joint predictive modeling to combine this polygenic risk score with early life risk factors by stepwise regression, and assessed the model performance in identifying individuals at high risk of depression. Results: In the UK Biobank test dataset, the polygenic risk score for depression was moderately associated with multiple early life risk factors. For instance, a one standard deviation increase in the polygenic risk score was associated with 1.16-fold increased odds of frequent domestic violence (95% CI: 1.14-1.19) and 1.09-fold increased odds of not having access to medical care as a child (95% CI: 1.05-1.14). However, the polygenic risk score was more strongly associated with depression phenotypes than most early life risk factors. A joint predictive model integrating the polygenic risk score, early life risk factors, age and sex achieved an AUROC of 0.6766 for predicting strictly defined major depressive disorder, while a model without the polygenic risk score and a model without any early life risk factors had an AUROC of 0.6593 and 0.6318, respectively. Conclusion: We have developed a polygenic risk score to partly capture the genetic liability to depression. Although genetic and early life risk factors can be correlated, joint predictive models improved risk stratification despite limited improvement in magnitude, and may be explored as tools to better identify individuals at high risk of depression.

Plasticity of Individual Lung Function States from Childhood to Adulthood.

Rationale: Recent evidence highlights the importance of optimal lung development during childhood for health throughout life. Objectives: To explore the plasticity of individual lung function states during childhood. Methods: Prebronchodilator FEV1 z-scores determined at age 8, 16, and 24 years in the Swedish population-based birth cohort BAMSE (Swedish abbreviation for Child [Barn], Allergy, Milieu, Stockholm, Epidemiological study) (N = 3,069) were used. An unbiased, data-driven dependent mixture model was applied to explore lung function states and individual state chains. Lung function catch-up was defined as participants moving from low or very low states to normal or high or very high states, and growth failure as moving from normal or high or very high states to low or very low states. At 24 years, we compared respiratory symptoms, small airway function (multiple-breath washout), and circulating inflammatory protein levels, by using proteomics, across states. Models were replicated in the independent Dutch population-based PIAMA (Prevention and Incidence of Asthma and Mite Allergy) cohort. Measurements and Main Results: Five lung function states were identified in BAMSE. Lung function catch-up and growth failure were observed in 74 (14.5%) BAMSE participants with low or very low states and 36 (2.4%) participants with normal or high or very high states, respectively. The occurrence of catch-up and growth failure was replicated in PIAMA. Early-life risk factors were cumulatively associated with the very low state, as well as with catch-up (inverse association) and growth failure. The very low state as well as growth failure were associated with respiratory symptoms, airflow limitation, and small airway dysfunction at adulthood. Proteomics identified IL-6 and CXCL10 (C-X-C motif chemokine 10) as potential biomarkers of impaired lung function development. Conclusions: Individual lung function states during childhood are plastic, including catch-up and growth failure.

Dataset of an actual life-risk insurance portfolio.

The foundation of the insurance business is built on data, the latter being one of the most valuable assets of any insurer. In fact, the risk structure to which an insurance company is exposed can actually be deduced by reviewing its customer database. It is not surprising, therefore, that access to real insurance datasets is very limited. This paper introduces and describes a dataset corresponding to a cross-section extraction of a real life-risk insurance portfolio. The dataset contains information on 76,102 policies and a total of 15 variables, including the capital at risk, the genders and dates of birth of the insured, and the effective and renewal dates of their policies. This dataset can be used both in teaching and in research. Combined with external life tables, the data available in the dataset can be used to build and compare pricing systems, to evaluate marketing strategies, in portfolio analysis, for calculations required by Solvency II regulations or for market benchmarking analysis. For example, the data from this dataset have been used in Pavía and Lledó [1] to compare the classic pricing methodology based on annual life tables with a new pricing methodology based on life tables with less than annual periodicity Pavía and Lledó [2], specifically quarterly, and in Lledó et al. to demonstrate the impact that using a new methodology to manage catastrophic risks in life insurance would have in terms of solvency capital requirements.

The Relative Body Weight Gain From Early to Middle Life Adulthood Associated With Later Life Risk of Diabetes: A Nationwide Cohort Study.

Aim: To determine the effect of decade-based body weight gain from 20 to 50 years of age on later life diabetes risk. Methods: 35,611 non-diabetic participants aged ≥ 50 years from a well-defined nationwide cohort were followed up for average of 3.6 years, with cardiovascular diseases and cancers at baseline were excluded. Body weight at 20, 30, 40, and 50 years was reported. The overall 30 years and each 10-year weight gain were calculated from the early and middle life. Cox regression models were used to estimate risks of incident diabetes. Results: After 127,745.26 person-years of follow-up, 2,789 incident diabetes were identified (incidence rate, 2.18%) in 25,289 women (mean weight gain 20-50 years, 7.60 kg) and 10,322 men (7.93 kg). Each 10-kg weight gain over the 30 years was significantly associated with a 39.7% increased risk of incident diabetes (95% confidence interval [CI], 1.33-1.47); weight gain from 20-30 years showed a more prominent effect on the risk of developing diabetes before 60 years than that of after 60 years (Hazard ratio, HR = 1.084, 95% CI [1.049-1.121], P <0.0001 vs. 1.015 [0.975-1.056], P = 0.4643; PInteraction=0.0293). It showed a stable effect of the three 10-year intervals weight gain on risk of diabetes after 60 years (HR=1.055, 1.038, 1.043, respectively, all P < 0.0036). Conclusions: The early life weight gain showed a more prominent effect on developing diabetes before 60 years than after 60 years; however, each-decade weight gain from 20 to 50 years showed a similar effect on risk developing diabetes after 60 years.

A Mixture of Endocrine Disruptors and the Pesticide Roundup® Induce Oxidative Stress in Rabbit Liver When Administered under the Long-Term Low-Dose Regimen: Reinforcing the Notion of Real-Life Risk Simulation.

Humans are exposed to xenobiotic mixtures daily through the long-term, low-dose regimen. Investigations designed to simulate this exposure profile approach the real-life risk simulation (RLRS) idea of modern toxicology. The purpose of the present study was to investigate the effects of 12-month exposure of New Zealand rabbits to a xenobiotic mixture comprising seven endocrine disruptors (EDs), which are chemical substances raising great concerns for human health, as well as the herbicide glyphosate, and its commercial formulation Roundup®, on blood and tissues redox status. It is reported herein that at the systemic level, the administration of the EDs mixture induced perturbations of blood redox homeostasis at 3 months, whereas at 6 and 12 months, it activated redox adaptations. Contrariwise, exposure to glyphosate and Roundup®, individually, caused mainly disturbances of blood redox equilibrium. At the tissue level, particularly in the liver, the administration of both the EDs mixture and Roundup® induced oxidative stress, whereas glyphosate did not affect it. The RLRS notion appears to be confirmed through these findings. Indeed, the administration of the EDs mixture and Roundup®, under the long-term, low-dose regimen, elicited detrimental effects on the redox status of the liver, a crucial tissue with a valuable biological role in the detoxification of organisms from xenobiotics.

Children are in need of humanitarian aid in Afghanistan.

Almost 60% of Afghans forced to flee their homes in 2021 because of the Taliban advance are children. They are starving. It is estimated that approximately one million will suffer from severe, life-threatening malnutrition by the end of 2021. Many have been separated from their families by the chaos that has ensued in Afghanistan after Taliban took power, and hundreds of them were driven out of the country unaccompanied. How must these children have been when they suddenly found themselves without their relatives during the chaotic crisis, or when they boarded an evacuation flight? It is vital to identify them quickly. Too many children witnessed scenes that no child should see. Children and teenagers are dealing with anxiety and fear and desperately need help and mental health care. This is the sad reality facing Afghan children, regardless of ongoing political developments and changes in government.

Children are in need of humanitarian aid in Afghanistan.

Almost 60% of Afghans forced to flee their homes in 2021 because of the Taliban advance are children. They are starving. It is estimated that approximately one million will suffer from severe, life-threatening malnutrition by the end of 2021. Many have been separated from their families by the chaos that has ensued in Afghanistan after Taliban took power, and hundreds of them were driven out of the country unaccompanied. How must these children have been when they suddenly found themselves without their relatives during the chaotic crisis, or when they boarded an evacuation flight? It is vital to identify them quickly. Too many children witnessed scenes that no child should see. Children and teenagers are dealing with anxiety and fear and desperately need help and mental health care. This is the sad reality facing Afghan children, regardless of ongoing political developments and changes in government.

Reaching 80 Years of Age: Clinical, Behavioral, and Psychosocial Related Risk Factors in a Large Cohort of Israeli Working Men.

The objective of this study was to estimate the probability of long-term overall survival based on total number of risk factors (RF). We also sought to examine the role of midlife clinical, behavioral, and psychosocial predictors of longevity in a large cohort of Israeli men. This study was based on the Israeli Ischemic Heart Disease (IIHD) cohort that included over 10,000 men who were followed up for mortality over more than four decades. During the 43 years of follow-up, 4634 (46.1%) men survived to 80 years of age or older. We considered cigarette smoking, diabetes mellitus, high systolic blood pressure, hypercholesterolemia, low socioeconomic status, and serious family problems as RF at ages 40-65. Cox proportional hazards regression models, with age as the time scale, were constructed to estimate the hazard ratios (HRs) for failure to survive 80 years of age. Compared with men free of all the above RF, those with one identified RF (HR = 1.58, 95% CI: 1.42-1.75) and counterparts with two identified RF (HR = 2.18, 95% CI: 1.96-2.43) were at a significantly greater risk of death before 80. Additional RF further increased the risk of early mortality (HR = 3.62, 95% CI: 1.50-8.73 for men with 5 RF). The results suggest a role of physiological, behavioral, and psychological risk factors at midlife in predicting longevity.

Exposure to breastfeeding and risk of developing multiple sclerosis.

BACKGROUND: Early-life factors are reported to modulate the risk of developing multiple sclerosis (MS) among adults. The association between exposure to breastfeeding and the risk of MS is debated. We aimed to disclose whether past exposure to breastfeeding and its duration are associated with the risk of developing MS. METHODS: We used a cohort design linking prospectively collected information on breastfeeding from the Cohort of Norway community-based surveys on health status (CONOR) with the Norwegian MS Registry and the population-based Medical Birth Registry of Norway that includes information on all births in Norway since 1967. MS clinical onset was collected throughout 2016. A total of 95 891 offspring born between 1922 and 1986 to mothers participating in CONOR were included. We identified 215 offspring within this cohort who developed adult-onset MS. Associations between breastfeeding and MS risk were estimated as hazard ratios using Cox proportional hazard models adjusting for maternal factors including education. RESULTS: We found no association between having been breastfed for ≥4 months and MS risk, also after adjusting for various maternal factors (hazard ratio = 0.90; 95% confidence interval 0.68-1.19). The estimates did not change for different durations of breastfeeding. The results were similar when adjusting for other perinatal factors. CONCLUSION: Our study could not confirm previous findings of an association between breastfeeding and risk of MS. Breastfeeding information was less likely to be biased by knowledge of disease compared with case-control studies.

Longitudinal associations of modifiable risk factors in the first 1000 days with weight status and metabolic risk in early adolescence.

BACKGROUND: Many studies have identified early-life risk factors for childhood overweight/obesity (OwOb), but few have evaluated how they combine to influence later cardiometabolic health. OBJECTIVES: We aimed to examine the association of risk factors in the first 1000 d with adiposity and cardiometabolic risk in early adolescence. METHODS: We studied 1038 mother-child pairs in Project Viva. We chose 6 modifiable early-life risk factors previously associated with child adiposity or metabolic health in the cohort: smoking during pregnancy (yes compared with no); gestational weight gain (excessive compared with nonexcessive); sugar-sweetened beverage consumption during pregnancy (≥0.5 compared with <0.5 servings/d); breastfeeding duration (<12 compared with ≥12 mo); timing of complementary food introduction (<4 compared with ≥4 mo); and infant sleep duration (<12 compared with ≥12 h/d). We computed risk factor scores by calculating the cumulative number of risk factors for each child. In early adolescence (median: 13.1 y) we measured indicators of adiposity [BMI, fat mass index (FMI), trunk fat mass index (TFMI)]. We also calculated OwOb prevalence and metabolic syndrome (MetS) risk z score of adolescents. RESULTS: Among 1038 adolescents, 71% had >1 early-life risk factor. In covariate-adjusted models, we observed positive monotonic increases in BMI, FMI, TFMI, and MetS z scores with increasing risk factor score. Children with 5‒6 risk factors (compared with 0-1 risk factors) had the highest risk of OwOb [risk ratio (RR): 2.53; 95% CI: 1.63, 3.91] and being in the highest MetS quartile (RR: 2.46; 95% CI: 1.43, 4.21). The predicted probability of OwOb in adolescence varied from 9.4% (favorable levels for all factors) to 63.6% (adverse levels for all factors), and for being in the highest MetS quartile from 9.6% to 56.6%. CONCLUSIONS: Early-life risk factors in the first 1000 d cumulatively predicted higher adiposity and cardiometabolic risk in early adolescence. Intervention strategies to prevent later obesity and cardiometabolic risk may be more effective if they concurrently target multiple modifiable factors.

Genotoxicity of mixture of imidacloprid, imazalil and tebuconazole.

Genotoxicity of the mixture of generic pesticides imidacloprid + imazalil + tebuconazole in a ratio of 14.0/1.7/1.0 by weight was assessed using Ames test (Salmonella typhimurium) and micronucleus test in vivo on mammalian bone marrow erythrocytes (CD-1 mice) supporting the data creation for the Real Life Risk Simulation (RLRS) approach. This pesticides' combination is used in the commercial formulation for seed treatment in advance of or immediately before sowing. Tested pesticides' technical grade active ingredients (TGAIs) showed no evidence of genotoxicity upon separate treatments. In combination, the three pesticides demonstrated negative results in the Ames test but induced a statistically significant, dose-depended increase in MN-PCEs in mice bone marrow at doses lower than those used separately. The observed effect may be mediated by the synergistic action of the tested TGAIs, their metabolites or impurities.

Integration of an interpretable machine learning algorithm to identify early life risk factors of childhood obesity among preterm infants: a prospective birth cohort.

BACKGROUND: The early life risk factors of childhood obesity among preterm infants are unclear and little is known about the influence of the feeding practices. We aimed to identify early life risk factors for childhood overweight/obesity among preterm infants and to determine feeding practices that could modify the identified risk factors. METHODS: A total of 338,413 mother-child pairs were enrolled in the Jiaxing Birth Cohort (1999 to 2013), and 2125 eligible singleton preterm born children were included for analyses. We obtained data on health examination, anthropometric measurement, lifestyle, and dietary habits of each participant at their visits to clinics. An interpretable machine learning-based analytic framework was used to identify early life predictors for childhood overweight/obesity, and Poisson regression was used to examine the associations between feeding practices and the identified leading predictor. RESULTS: Of the eligible 2125 preterm infants (863 [40.6%] girls), 274 (12.9%) developed overweight/obesity at age 4-7 years. We summarized early life variables into 25 features and identified two most important features as predictors for childhood overweight/obesity: trajectory of infant BMI (body mass index) Z-score change during the first year of corrected age and maternal BMI at enrollment. According to the impacts of different BMI Z-score trajectories on the outcome, we classified this feature into the favored and unfavored trajectories. Compared with early introduction of solid foods (≤ 3 months of corrected age), introducing solid foods after 6 months of corrected age was significantly associated with 11% lower risk (risk ratio, 0.89; 95% CI, 0.82 to 0.97) of being in the unfavored trajectory. CONCLUSIONS: The trajectory of BMI Z-score change within the first year of life is the most important predictor for childhood overweight/obesity among preterm infants. Introducing solid foods after 6 months of corrected age is a recommended feeding practice for mitigating the risk of being in the unfavored trajectory.

Adolescent cannabinoid exposure interacts with other risk factors in schizophrenia: A review of the evidence from animal models.

Many factors and their interaction are linked to the aetiology of schizophrenia, leading to the development of animal models of multiple risk factors and adverse exposures. Differentiating between separate and combined effects for each factor could better elucidate schizophrenia pathology, and drive development of preventative strategies for high-load risk factors. An epidemiologically valid risk factor commonly associated with schizophrenia is adolescent cannabis use. The aim of this review is to evaluate how early-life adversity from various origins, in combination with adolescent cannabinoid exposure interact, and whether these interactions confer main, synergistic or protective effects in animal models of schizophrenia-like behavioural, cognitive and morphological alterations. Patterns emerge regarding which models show consistent synergistic or protective effects, particularly those models incorporating early-life exposure to maternal deprivation and maternal immune activation, and sex-specific effects are observed. It is evident that more research needs to be conducted to better understand the risks and alterations of interacting factors, with particular interest in sex differences, to better understand the translatability of these preclinical models to humans.

Chronic Inflammation in the Context of Everyday Life: Dietary Changes as Mitigating Factors.

The lifestyle adopted by most people in Western societies has an important impact on the propensity to metabolic disorders (e.g., diabetes, cancer, cardiovascular disease, neurodegenerative diseases). This is often accompanied by chronic low-grade inflammation, driven by the activation of various molecular pathways such as STAT3 (signal transducer and activator of transcription 3), IKK (IκB kinase), MMP9 (matrix metallopeptidase 9), MAPK (mitogen-activated protein kinases), COX2 (cyclooxigenase 2), and NF-Kß (nuclear factor kappa-light-chain-enhancer of activated B cells). Multiple intervention studies have demonstrated that lifestyle changes can lead to reduced inflammation and improved health. This can be linked to the concept of real-life risk simulation, since humans are continuously exposed to dietary factors in small doses and complex combinations (e.g., polyphenols, fibers, polyunsaturated fatty acids, etc.). Inflammation biomarkers improve in patients who consume a certain amount of fiber per day; some even losing weight. Fasting in combination with calorie restriction modulates molecular mechanisms such as m-TOR, FOXO, NRF2, AMPK, and sirtuins, ultimately leads to significantly reduced inflammatory marker levels, as well as improved metabolic markers. Moving toward healthier dietary habits at the individual level and in publicly-funded institutions, such as schools or hospitals, could help improving public health, reducing healthcare costs and improving community resilience to epidemics (such as COVID-19), which predominantly affects individuals with metabolic diseases.

Behavioral impacts of a mixture of six pesticides on rats.

Pesticides can potentially contribute to the development of numerous neurodegenerative diseases. This study evaluates the effects of a six-pesticide mixture at doses around the no-observed-adverse-effectlevels (0 × NOAEL, control) and 0.25, 1 and 5 × NOAEL on behavior of Wistar rats. After 3, 6 and 12 months, rats were observed for neurobehavioral changes using the techniques of elevated plus maze and universal problemchamber, and the experiment was conducted thrice. The 3-month exposure revealed a decrease in the cognitive ability at the dose of 5 × NOAEL, and a dose-dependent research activity and anxiety. The 6-month exposurerevealed non-monotonic effects on the cognitive ability, with a decrease by 0.25 and 5 × NOAEL, as well as non-monotonic effects on anxiety, withan increase by 0.25 and 1 × NOAEL. A decrease was also observed in research activity at 5 × NOAEL. However, the 12-month exposure resulted to an increase in cognitive ability by 0.25 × NOAEL and in anxiety by 1 × NOAEL, as well as to a dose-dependent research activity. Repeating the trial showed that the cognitive ability increased from one trial to another, while the researching activity decreased and the anxiety increased by 0× NOAEL. In the groups exposed to pesticides mixture, the trends were different, showing that the exposure to pesticides combined with repeated trials, also influence the response of the animals. The resultsdemonstrate the occurrence of several dose-dependent behavioral responses, with negative effects occurring at doses that are considered safe. This study provides novel insights about time-dependent mixtures biology, and an important perspective to consider when conducting risk assessments.