Slaterwinkler0461

l-Carnitine is essential for mitochondrial β-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals. d-Carnitine is an optical isomer of l-carnitine and dl-carnitine has been widely used in animal feeds. However, the functional differences between l- and d-carnitine are difficult to study because of the endogenous l-carnitine background. In the present study, we developed a low-carnitine Nile tilapia model by treating fish with a carnitine synthesis inhibitor, and used this model to investigate the functional differences between l- and d-carnitine in nutrient metabolism in fish. l- or d-carnitine (0·4 g/kg diet) was fed to the low-carnitine tilapia for 6 weeks. l-Carnitine feeding increased the acyl-carnitine concentration from 3522 to 10 822 ng/g and alleviated the lipid deposition from 15·89 to 11·97 % in the liver of low-carnitine tilapia. However, as compared with l-carnitine group, d-carnitine feeding reduced the acyl-carnitine concentration from 10 822 to 5482 ng/g, and increased lipid deposition from 11·97 to 20·21 % and the mRNA expression of the genes involved in β-oxidation and detoxification in the liver. d-Carnitine feeding also induced hepatic inflammation, oxidative stress and apoptosis. A metabolomic investigation further showed that d-carnitine feeding increased glycolysis, protein metabolism and activity of the tricarboxylic acid cycle and oxidative phosphorylation. Thus, l-carnitine can be physiologically utilised in fish, whereas d-carnitine is metabolised as a xenobiotic and induces lipotoxicity. d-Carnitine-fed fish demonstrates increases in peroxisomal β-oxidation, glycolysis and amino acid degradation to maintain energy homeostasis. Therefore, d-carnitine is not recommended for use in farmed animals.We investigate how early exposure to parental externalizing behaviors (EB) may contribute to development of alcohol use disorders (AUD) in young adulthood, testing a developmental cascade model focused on competencies in three domains (academic, conduct, and work) in adolescence and emerging adulthood, and examining whether high parental education can buffer negative effects of parental EB and other early risk factors. We use data from 451,054 Swedish-born men included in the national conscript register. Structural equation models showed parental EB was associated with academic and behavioral problems during adolescence, as well as with lower resilience, more criminal behavior, and reduced social integration during emerging adulthood. These pathways led to elevated rates of AUD in emerging and young adulthood. Multiple groups analysis showed most of the indirect pathways from parental EB to AUD were present but buffered by higher parental education, suggesting early life experiences and competencies matter more for young men from lower socioeconomic status (SES) families than from higher SES families. Developmental competencies in school, conduct, and work are important precursors to the development of AUD by young adulthood that are predicted by parental EB. Occupational success may be an overlooked source of resilience for young men from low-SES families.The current study aimed to understand the mediating and/or moderating role of prenatal hypothalamic-pituitary-adrenal (HPA) axis function in the association between maternal adverse childhood experiences (ACEs) and child internalizing and externalizing behavior problems at age 4. The influence of timing and child sex were also explored. Participants were 248 mother-child dyads enrolled in a prospective longitudinal cohort study (the Alberta Pregnancy Outcomes and Nutrition Study). Maternal ACEs were retrospectively assessed while maternal self-reported depression and diurnal salivary cortisol were assessed prospectively at 6-26 weeks gestation (T1) and 27-37 weeks gestation (T2). Maternal report of child internalizing and externalizing problems was assessed at 4 years (T3). Results revealed that there was a negative indirect association between maternal ACEs and child internalizing behavior via a higher maternal cortisol awakening response (CAR). Maternal diurnal cortisol slope moderated the association between maternal ACEs and child behavior problems. Some of these effects were dependent on child sex, such that higher ACEs and a flatter diurnal slope at T1 was associated with more internalizing behavior in female children and more externalizing behavior in male children. There were timing effects such that the mediating and moderating effects were strongest at T1.Stressful experiences affect biological stress systems, such as the hypothalamic-pituitary-adrenal (HPA) axis. Life stress can potentially alter regulation of the HPA axis and has been associated with poorer physical and mental health. Little, however, is known about the relative influence of stressors that are encountered at different developmental periods on acute stress reactions in adulthood. In this study, we explored three models of the influence of stress exposure on cortisol reactivity to a modified version of the Trier Social Stress Test (TSST) by leveraging 37 years of longitudinal data in a high-risk birth cohort (N = 112). The cumulative stress model suggests that accumulated stress across the lifespan leads to dysregulated reactivity, whereas the biological embedding model implicates early childhood as a critical period. The sensitization model assumes that dysregulation should only occur when stress is high in both early childhood and concurrently. All of the models predicted altered reactivity, but do not anticipate its exact form. C646 We found support for both cumulative and biological embedding effects. However, when pitted against each other, early life stress predicted more blunted cortisol responses at age 37 over and above cumulative life stress. Additional analyses revealed that stress exposure in middle childhood also predicted more blunted cortisol reactivity.This study evaluated a school-based intervention to enhance adolescent peer relationships and improve functional outcomes, building upon Ed Zigler's seminal contribution in recognizing the potential of academic contexts to enhance social and emotional development. Adolescents (N = 610) primarily from economically or racially/ethnically marginalized groups were assessed preintervention, postintervention, and at 4-month follow-up in a randomized controlled trial. At program completion, intervention participants reported significantly increased quality of peer relationships; by 4-month follow-up, this increased quality was also observable by peers outside of the program, and program participants also displayed higher levels of academic engagement and lower levels of depressive symptoms. These latter effects appear to have potentially been mediated via participants' increased use of social support. The potential of the Connection Project intervention specifically, and of broader efforts to activate adolescent peer relationships as potent sources of social support and growth more generally within the secondary school context, is discussed.