Psychotic Experiences,Childhood Trauma,and Alcohol-Related Self-Efficacy in a Nonpsychiatric Sample of Individuals in Alcohol Dependence Treatment: A Pilot Study

There is a substantial co-occurrence between alcohol dependence and psychiatric symptoms. Moreover, research suggests that such symptoms, including psychotic experiences, are continuously distributed in the population. There is a lack of research concerning psychotic symptoms in otherwise non-psychiatric populations with alcohol dependence. The aim of this study was to investigate the prevalence of psychotic symptoms in this population, and to relate this to childhood trauma and management of alcohol dependence. From a population with alcohol dependence two sub-groups were extracted, with low and high levels of psychotic experiences respectively. These were compared concerning childhood trauma and management of dependence using ANOVA, and the resulting model was examined using binary logistic regression. There was a sub-group of 14,3% of the population with elevated levels of psychotic experiences. This group displayed higher degree of self-reported childhood trauma as well as difficulties in managing alcohol dependence, when compared to a sub-group with low levels of psychotic experiences. There may be a substantial sub-group in the otherwise non-psychiatric population with alcohol dependence, with significant difficulties concerning psychotic symptoms, trauma and management of dependence, where anxiety may have a mediating function. If so, this group calls for broader assessment and treatment than standard alcohol interventions.     

Treg Vaccination in Autoimmune Type 1 Diabetes

Foxp3⁺ regulatory T (Treg) cells are critical contributors to the establishment and maintenance of immunological self-tolerance. Autoimmune type 1 diabetes (T1D) is characterized by the loss of self-tolerance to the insulin-producing β cells in the pancreas and the destruction of β cells, resulting in the development of chronic hyperglycemia at diagnosis. The application of strong-agonistic T-cell receptor ligands provided under subimmunogenic conditions functions as a critical means for the efficient de novo conversion of naive CD4⁺ T cells into Foxp3⁺ Treg cells. The specific induction of Treg cells upon supply of strong-agonistic variants of certain self-antigens could therefore function as a critical instrument in order to achieve safe and specific prevention of autoimmunity such as T1D via the restoration of self-tolerance. Such immunotherapeutic strategies are being developed, and in the case of T1D aim to restrict autoimmunity and β-cell destruction. In this review, we discuss the requirements and opportunities for Treg-based tolerance approaches with the goal of interfering with autoimmune T1D.     

The role of ENaC in vascular endothelium

Once upon a time, the expression of the epithelial sodium channel (ENaC) was mainly assigned to the kidneys, colon and sweat glands where it was considered to be the main determinant of sodium homeostasis. Recent, though indirect, evidence for the possible existence of ENaC in a non-epithelial tissue was derived from the observation that the vascular endothelium is a target for aldosterone. Inhibitory actions of the intracellular aldosterone receptors by spironolactone and, more directly, by ENaC blockers such as amiloride supported this view. Shortly after, direct data on the expression of ENaC in vascular endothelium could be demonstrated. There, endothelial ENaC (EnNaC) could be defined as a major regulator of cellular mechanics which is a critical parameter in differentiating between vascular function and dysfunction. Foremost, the mechanical stiffness of the endothelial cell cortex, a layer 50–200 nm beneath the plasma membrane, has been shown to play a crucial role as it controls the production of the endothelium-derived vasodilator nitric oxide (NO) which directly affects the tone of the vascular smooth muscle cells. In contrast to soft endothelial cells, stiff endothelial cells release reduced amounts of NO, the hallmark of endothelial dysfunction. Thus, the combination of endothelial stiffness and myogenic tone might increase the peripheral vascular resistance. An elevation of arterial blood pressure is supposed to be the consequence of such functional changes. In this review, EnNaC is discussed as an aldosterone-regulated plasma membrane protein of the vascular endothelium that could significantly contribute to maintaining of an appropriate arterial blood pressure but, if overexpressed, could participate in the pathogenesis of arterial hypertension.