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Childhood adversity may act as a stressor to produce a cascade of neurobiological effects that irreversibly alter neural development, setting the stage for developing psychopathology in adulthood. The catechol-O-methyltransferase (COMT) Val158Met polymorphism has received much attention as a candidate gene associated with environmental adversity, modifying risk for psychopathology. In this study, we aim to see how gene × brain × environment models give a more integrative understanding of brain modifications that contribute to predicting psychopathology related to childhood adversity. A large nonclinical sample of young adults completed Childhood Trauma Questionnaire (CTQ), behavioral scores, multimodal magnetic resonance imaging (MRI) scans, and genotyping. We utilized graph-based connectivity analysis in morphometric similarity mapping and resting-state functional MRI to investigate brain alterations. Relationships among COMT genotypes, CTQ score, imaging phenotypes, and behavioral scores were identified by multiple regression and mediation effect analysis. Significant main effect of CTQ score was found in anatomic connectivity of orbitofrontal cortex that was an outstanding mediator supporting the relationship between CTQ score and anxiety/harm-avoiding personality. We also noted the main effect of childhood trauma on reorganization of functional connectivity within the language network. Additionally, we found genotype × CTQ score interactions on functional connectivity of the right frontoparietal network as well as anatomic connectivity of motor and limbic regions. Our data demonstrate childhood adversity and COMT genotypes are associated with abnormal brain connectivity, structurally and functionally. Early identification of individuals at risk, assessment of brain abnormality, and cognitive interventions may help to prevent or limit negative outcomes.Nongenetic methodologies to reduce undesirable proliferation would be valuable when generating dopamine neurons from stem cells for transplantation in Parkinson's disease (PD). click here To this end, we modified an established method for controlled differentiation of human induced pluripotent stem cells (iPSCs) into midbrain dopamine neurons using two distinct methods omission of FGF8 or the in-process use of the DNA cross-linker mitomycin-C (MMC). We transplanted the cells to athymic rats with unilateral 6-hydroxydopamine lesions and monitored long-term survival and function of the grafts. Transplants of cells manufactured using MMC had low proliferation while still permitting robust survival and function comparable to that seen with transplanted dopamine neurons derived using genetic drug selection. Conversely, cells manufactured without FGF8 survived transplantation but exhibited poor in vivo function. Our results suggest that MMC can be used to reduce the number of proliferative cells in stem cell-derived postmitotic neuron preparations for use in PD cell therapy.

The 24-hour movement guidelines provide recommendations for physical activity, screen time and sleep duration for children.

Describe adherence to the guidelines and their cross-sectional and longitudinal associations with adiposity from childhood to adolescence.

Data are from the QUALITY Cohort. Children were followed at 8 to 10 years (childhood; n = 630), 10 to 12 years (early adolescence; n = 564) and 15 to 17 years (adolescence; n = 377). Physical activity, screen time, and sleep duration were measured by accelerometry and questionnaires. Body mass index z-scores (zBMI), waist circumference, waist-to-height ratio and percent body fat were based on clinical measurements. Multiple linear regressions estimated associations.

In childhood, early adolescence and adolescence, 14%, 6%, and 0% of participants met the 24-hour movement guidelines, respectively. Meeting fewer guideline components was cross-sectionally associated with higher adiposity at each visit. Meeting fewer guideline components in childhood was longitudinally associated with higher adiposity at later visits. For example, those meeting none of the guideline components (vs all) in childhood had a 1.66 SD (95% CI 0.42, 2.89) higher zBMI in early adolescence.

Few participants met the guidelines. Not meeting the guidelines in childhood is associated with higher adiposity 2 and 7 years later. Interventions are needed to increase adherence to the 24-hour movement guidelines across childhood and adolescence.

Few participants met the guidelines. Not meeting the guidelines in childhood is associated with higher adiposity 2 and 7 years later. Interventions are needed to increase adherence to the 24-hour movement guidelines across childhood and adolescence.Rechargeable zinc-air batteries (ZABs) are considered as one of the most promising electrochemical energy devices due to their various unique advantages. Oxygen electrocatalysis, involving the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), determines the overall performance of zinc-air batteries. Therefore, the development of highly efficient bifunctional ORR/OER catalysts is critical for the large-scale application of ZABs. Carbon-based nanomaterials have been widely reported to be efficient electrocatalysts toward both ORR and OER. The enhanced activity of these electrocatalysts are usually attributed to different doping defects, synergistic effects and even the intrinsic carbon defects. Herein, an overview of the defect engineering in carbon-based electrocatalysts for ORR and OER is provided. The different types of intrinsic carbon defects and strategies for the generation of other defects in carbon-based electrocatalysts are presented. The interaction of heteroatoms doped carbon and transition metals (TMs) is also explored. In the end, the existing challenges and future perspectives on defect engineering are discussed.

Early-onset psychosis (EOP) and bipolar disorder (EOBP) (at <18years of age), are associated with an increased future risk of cardiovascular disease (CVD) and premature death. Yet it is unknown whether the arteries show visible signs of atherosclerosis in EOP and EOBP. This study investigated whether having EOP or EOBP was associated with detectable signs of preclinical atherosclerosis.

By using 22MHz high-frequency ultrasound, different layers of the arterial wall of the left common carotid artery (LCCA) were assessed in 77 individuals with EOP (n=25), EOBP (n=22), and in age-matched healthy controls (n=30). Conventional CVD confounders were included in the analyses.

Adolescents with EOP and EOBP, compared to controls, had a significantly thicker LCCA intima thickness (0.132 vs. 0.095mm, p<.001) and intima/media ratio (0.24 vs. 0.17 p<.001). There was a nonsignificant intima difference between EOP and EOBP. Conventional CVD risk factors did not explain the association between EOP/EOBP and intima thickness.