Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis.

Leigh syndrome (LS) is a rare, inherited neurometabolic disorder that presents with bilateral brain lesions caused by defects in the mitochondrial respiratory chain and associated nuclear-encoded proteins. We generated human induced pluripotent stem cells (iPSCs) from three LS patient-derived fibroblast lines. Using whole-exome and mitochondrial sequencing, we identified unreported mutations in pyruvate dehydrogenase (GM0372, PDH; GM13411, MT-ATP6/PDH) and dihydrolipoyl dehydrogenase (GM01503, DLD). These LS patient-derived iPSC lines were viable and capable of differentiating into progenitor populations, but we identified several abnormalities in three-dimensional differentiation models of brain development. LS patient-derived cerebral organoids showed defects in neural epithelial bud generation, size and cortical architecture at 100 days. The double mutant MT-ATP6/PDH line produced organoid neural precursor cells with abnormal mitochondrial morphology, characterized by fragmentation and disorganization, and showed an increased generation of astrocytes. These studies aim to provide a comprehensive phenotypic characterization of available patient-derived cell lines that can be used to study Leigh syndrome.

Trauma experience of youngsters and Teens: A key issue in suicidal behavior among victims of bullying?

UNLABELLED: This study examines the association between suicide and bullying among teenagers and adolescents in school besides exploring strategies to prevent acts of bullying. "Bullying" is a risk factor that is linked to suicidal ideation and attempts among school-age children and teenagers. Since youth suicide is an urgent and serious problem, we conducted a systematic review of 28 previous studies conducted in children and adolescents which examined the connection between bullying experiences and suicide. DATA COLLECTION: A literature search was carried out using 4 databases, without date description including: PubMed, PsychInfo, Medline and Google Scholar. The search terms contained: bullying, suicide and bullying, suicide in teens, school bullying, and peer victimization. An initial search generated about 97 articles; however, only 28 articles were appropriate for inclusion in the current review. Inclusion criteria was (1) Cross-sectional studies published from 1997-2013. (2) Study based on school bullying and suicidal risk in adolescents and teens 18 years or less (3) Studies had enough information to calculate effect sizes that did include a control group. (4) Studies based on gender discrimination. Papers that focused on specific populations, that did not include quantitative data, that did not use a control group of non-bullied subjects and studies based on cyber bullying, studies with longitudinal design were excluded. The risk of suicide attempts was higher in girls, who were involved in bullying, either as the victim or perpetrator, than in boys. Depression, feelings of hopelessness and loneliness can develop in the child after being bullied for long periods of time; these feelings are indirectly related to suicidal ideation and attempts. Involvement in bullying increases the likelihood of suicidal ideation and attempts in children and teenagers.