Ectopic Expression of E2F1 Stimulates β-Cell Proliferation and Function

OBJECTIVE-Generating functional beta-cells by inducing their proliferation may provide new perspectives for cell therapy in diabetes. Transcription factor E2F1 controls G(1)- to S-phase transition during the cycling of many cell types and is required for pancreatic beta-cell growth and function. However, the consequences of overexpression of E2F1 in beta-cells are unknown. RESEARCH DESIGN AND METHODS-The effects of E2F1 overexpression on beta-cell proliferation and function were analyzed in isolated rat beta-cells and in transgenic mice. RESULTS-Adenovirus AdE2F1-mediated overexpression of E2F1 increased the proliferation of isolated primary rat beta-cells 20-fold but also enhanced beta-cell death. Coinfection with adenovirus Ad Akt expressing a constitutively active form of Akt (protein kinase B) suppressed beta-cell death to control levels. At 48 h after infection, the total beta-cell number and insulin content were, respectively, 46 and 79% higher in AdE2F1+AdAkt-infected cultures compared with untreated. Conditional overexpression of E2F1 in mice resulted in a twofold increase of beta-cell proliferation and a 70% increase of pancreatic insulin content, but did not increase beta-cell mass. Glucose-challenged insulin release was increased, and the mice showed protection against toxin-induced diabetes. CONCLUSIONS-Overexpression of E2F1, either in vitro or in vivo, can stimulate beta-cell proliferation activity. In vivo E2F1 expression significantly increases the insulin content and function of adult beta-cells, making it a strategic target for therapeutic manipulation of beta-cell function. Diabetes 59:1435-1444, 201

Forensische pilootprojecten ‘medium security’:Incidenten tijdens behandeling van geïnterneerden ressorterend onder CBM Gent

Research concerning forensic medium security units in Flanders is scarce. This study reports on incidents during treatment. The population consisted of 203 forensic patients conditionally released by the Commission of Social Defense (CPS) of Ghent. During a ten-year follow-up period 236 incident reports were registered, caused by half of the population (53.20%). Less than half of these reports (41.53%) concerned incidents coded as criminal offences (like drug use, theft or violence). Violent incidents occurred in one out of five reports (20.34%) and were associated with poor treatment compliance and failure. Victims of violence were mainly hospital staff or patients. Incidents were reported to the prosecutor, but rarely led to a new conviction or internment. Instead, one third of the population was (re)incarcerated in prison. Protection, rather than treatment, thus seems to be the primary focus of the CPS