Pharmacotherapeutic intervention in impulsive preschool children: The need for a comprehensive therapeutic approach

Impulsive and aggressive behaviour symptoms often are serious problems in children, even already at preschool age. Thus, effective treatment approaches are requested. In this comment pharmacotherapeutic treatment approaches, first of all risperidone, their limitations and alternative psychotherapeutic approaches are outlined

The glycerol backbone of phospholipids derives from noncarbohydrate precursors in starved lung cancer cells

Cancer cells are reprogrammed to consume large amounts of glucose to support anabolic biosynthetic pathways. However, blood perfusion and consequently the supply with glucose are frequently inadequate in solid cancers. PEPCK-M (PCK2), the mitochondrial isoform of phosphoenolpyruvate carboxykinase (PEPCK), has been shown by us and others to be functionally expressed and to mediate gluconeogenesis, the reverse pathway of glycolysis, in different cancer cells. Serine and ribose synthesis have been identified as downstream pathways fed by PEPCK in cancer cells. Here, we report that PEPCK-M-dependent glycerol phosphate formation from noncarbohydrate precursors (glyceroneogenesis) occurs in starved lung cancer cells and supports de novo glycerophospholipid synthesis. Using stable isotope-labeled glutamine and lactate, we show that PEPCK-M generates phosphoenolpyruvate and 3-phosphoglycerate, which are at least partially converted to glycerol phosphate and incorporated into glycerophospholipids (GPL) under glucose and serum starvation. This pathway is required to maintain levels of GPL, especially phosphatidylethanolamine (PE), as shown by stable shRNA-mediated silencing of PEPCK-M in H23 lung cancer cells. PEPCK-M shRNA led to reduced colony formation after starvation, and the effect was partially reversed by the addition of dioleyl-PE. Furthermore, PEPCK-M silencing abrogated cancer growth in a lung cancer cell xenograft model. In conclusion, glycerol phosphate formation for de novo GPL synthesis via glyceroneogenesis is a newly characterized anabolic pathway in cancer cells mediated by PEPCK-M under conditions of severe nutrient deprivation

The glycerol backbone of phospholipids derives from noncarbohydrate precursors in starved lung cancer cells

10.1073/pnas.1719871115Proceedings of the National Academy of Sciences of the United States of America115246225-623

Aggression in children and adolescents

Aggressive behaviour is a common phenomenon during childhood and adolescence, but at the same time it is an important associated feature of many psychiatric disorders during this age period. Persistent aggression is related to a variety of negative outcomes in adulthood, including low socioeconomic status and unemployment, criminal behaviour and social isolation. The great heterogeneity of aggressive behaviour still hampers our understanding of causal mechanisms. Still, over the past years, the identification of specific subtypes of aggression has opened possibilities for new and individualized treatment approaches. This article provides information on different subtypes of aggression in children and adolescents, on individual differences that contribute to aggression during development and on possible underlying processes related to aggressive behaviour in young people. Current treatment approaches as well as new emerging treatment possibilities are discussed