Drinking until Intoxication:A Qualitative Study among Underage Adolescents Admitted to the Emergency Room

This study explored factors that contribute to an alcohol intoxication resulting in Emergency Room (ER) admission among underage adolescents. We conducted qualitative interviews with 14 adolescents (14–18 years old) who experienced an alcohol intoxication requiring ER admission. Motivations for drinking were individual (e.g. curiosity) or social (e.g. having fun). While circumstances and motivations were comparable with other studies among (binge) drinking youth in general, most adolescents in this study did not drink with the intention to get drunk. They often unknowingly and unintentionally crossed their limits because they had not enough knowledge or experience to foresee the consequences

The effect of bioresorbable vascular scaffold implantation on distal coronary endothelial function in dyslipidemic swine with and without diabetes

Background: We studied the effect of bioresorbable vascular scaffold (BVS) implantation on distal coronary endothelial function, in swine on a high fat diet without (HFD) or with diabetes (DM + HFD). Methods: Five DM + HFD and five HFD swine underwent BVS implantation on top of coronary plaques, and were studied six months later. Conduit artery segments >. 5. mm proximal and distal to the scaffold and corresponding control segments of non-scaffolded coronary arteries, as well as segments of small arteries within the flow-territories of scaffolded and non-scaffolded arteries were harvested for in vitro vasoreactivity studies. Results: Conduit segments proximal and distal to the BVS edges showed reduced endothelium-dependent vasodilation as compared to control vessels (p <. 0.01), with distal segments being most prominently affected (p <. 0.01). Endothelial dysfunction was only observed in DM + HFD swine and was principally due to a loss of NO. Endothelium-independent vasodilation and vasoconstriction were unaffected. Surprisingly, segments from the microcirculation distal to the BVS showed enhanced endothelium-dependent vasodilation (p <. 0.01), whereas endothelium-independent vasodilation and vasoconstriction were unaltered. This enhanced vasorelaxation was only observed in DM + HFD swine, and did not appear to be either NO- or EDHF-mediated. Conclusions: Six months of BVS implantation in DM + HFD swine causes NO-mediated endothelial dysfunction in nearby coronary segments, which is accompanied by a, possibly compensatory, increase in endothelial function of the distal microcirculation. Endothelial dysfunction extending into coronary conduit segments beyond the implantation-site, is in agreement with recent reports expressing concern for late scaffold thrombosis and of early BVS failure in diabetic patients

Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1.

OBJECTIVE: A previous genome-wide association study linked overexpression of an ATP-binding cassette transporter, ABCC5, in humans with a susceptibility to developing type 2 diabetes with age. Specifically, ABCC5 gene overexpression was shown to be strongly associated with increased visceral fat mass and reduced peripheral insulin sensitivity. Currently, the role of ABCC5 in diabetes and obesity is unknown. This study reports the metabolic phenotyping of a global Abcc5 knockout mouse. METHODS: A global Abcc5-/- mouse was generated by CRISPR/Cas9. Fat mass was determined by weekly EchoMRI and fat pads were dissected and weighed at week 18. Glucose homeostasis was ascertained by an oral glucose tolerance test, intraperitoneal glucose tolerance test, and intraperitoneal insulin tolerance test. Energy expenditure and locomotor activity were measured using PhenoMaster cages. Glucagon-like peptide 1 (GLP-1) levels in plasma, primary gut cell cultures, and GLUTag cells were determined by enzyme-linked immunosorbent assay. RESULTS: Abcc5-/- mice had decreased fat mass and increased plasma levels of GLP-1, and they were more insulin sensitive and more active. Recombinant overexpression of ABCC5 protein in GLUTag cells decreased GLP-1 release. CONCLUSIONS: ABCC5 protein expression levels are inversely related to fat mass and appear to play a role in the regulation of GLP-1 secretion from enteroendocrine cells

The E3 ubiquitin ligase inducible degrader of the LDL receptor/myosin light chain interacting protein in health and disease

PURPOSE OF REVIEW: The RING E3 ubiquitin ligase inducible degrader of the LDL receptor (IDOL, also known as MYLIP) promotes ubiquitylation and subsequent lysosomal degradation of the LDL receptor (LDLR), thus acting to limit uptake of lipoprotein-derived cholesterol into cells. Next to the LDLR, IDOL also promotes degradation of two related receptors, the very LDL receptor (VLDLR) and apolipoprotein E receptor 2 (APOER2), which have important signaling functions in the brain. We review here the emerging role of IDOL in lipoprotein and energy metabolism, neurodegenerative diseases, and the potential for therapeutic targeting of IDOL. RECENT FINDINGS: Genetic studies suggest an association between IDOL and lipoprotein metabolism in humans. Studies in rodents and nonhuman primates support an in-vivo role for IDOL in lipoprotein metabolism, and also uncovered an unexpected role in whole-body energy metabolism. Recent evaluation of IDOL function in the brain revealed a role in memory formation and progression of Alzheimer's disease. The report of the first IDOL inhibitor may facilitate further investigations on therapeutic strategies to target IDOL. SUMMARY: IDOL is emerging as an important determinant of lipid and energy metabolism in metabolic disease as well as in Alzheimer's disease. IDOL targeting may be beneficial in treating these conditions

Cognitive behavioral therapy is effective in misophonia: An open trial

BACKGROUND: Misophonia is a psychiatric disorder in which ordinary human sounds like smacking or chewing provoke intense anger and disgust. Despite the high burden of this condition, to date there is no evidence-based treatment available. In this study we evaluated the efficacy of cognitive behavioral therapy (CBT) and investigated whether clinical or demographic characteristics predicted treatment response. METHODS: Ninety patients with misophonia received eight bi-weekly group CBT sessions. Treatment response was defined as a Clinical Global Impression - Improvement Scale (CGI-I) score at endpoint of 1 or 2 (very much or much improved) and a 30% or greater reduction on the Amsterdam Misophonia Scale (A-MISO-S), a measure of the severity of misophonia symptoms. RESULTS: Following treatment 48% (N=42) of the patients showed a significant reduction of misophonia symptoms. Severity of misophonia and the presence of disgust were positive predictors of treatment response. LIMITATIONS: The A-MISO-S is not a validated scale. Furthermore, this was an open-label study with a waiting list control condition. CONCLUSIONS: This is the first treatment study for misophonia. Our results suggest that CBT is effective in half of the patients

Synopsis and Qualitative Evaluation of a Treatment Protocol to Guide Systemic Group-Cognitive Behavioral Therapy for Misophonia

Misophonia is a disorder in which patients suffer from anger or disgust when confronted with specific sounds such as those associated with eating or breathing, causing avoidance of cue related situations resulting in significant functional impairment. Functional magnetic resonance imaging studies suggest misophonia is associated with increased activity in the auditory cortex and salience network, which might reflect increased vigilance toward specific misophonia triggers. New treatments have been developed and investigated in the last years in which this vigilance plays an important role. This is a synopsis of the first group protocol for systemic Cognitive Behavioral Therapy (G-CBT) for misophonia. We discuss the model of CBT for misophonia, provide a detailed guide to the treatment illustrated with a case study, discuss advantages, limitations, and possible pitfalls by a qualitative evaluation of the protocol, and review evidence for the protocol

Synopsis and Qualitative Evaluation of a Treatment Protocol to Guide Systemic Group-Cognitive Behavioral Therapy for Misophonia

Misophonia is a disorder in which patients suffer from anger or disgust when confronted with specific sounds such as those associated with eating or breathing, causing avoidance of cue related situations resulting in significant functional impairment. Functional magnetic resonance imaging studies suggest misophonia is associated with increased activity in the auditory cortex and salience network, which might reflect increased vigilance toward specific misophonia triggers. New treatments have been developed and investigated in the last years in which this vigilance plays an important role. This is a synopsis of the first group protocol for systemic Cognitive Behavioral Therapy (G-CBT) for misophonia. We discuss the model of CBT for misophonia, provide a detailed guide to the treatment illustrated with a case study, discuss advantages, limitations, and possible pitfalls by a qualitative evaluation of the protocol, and review evidence for the protocol

Cognitive behavioral therapy for misophonia: A randomized clinical trial

Background: Patients with misophonia suffer from anger or disgust confronted with specific sounds such as smacking or breathing. Avoidance of cue-related situations results in social isolation and significant functional impairment. This is the first randomized, controlled cognitive behavioral therapy (CBT) trial for misophonia, evaluating the short- and long-term efficacy. Methods: The evaluator-blinded, randomized clinical trial was conducted from May 2017 until December 2018 at an academic outpatient clinic. Misophonia patients were randomly assigned to 3 months of weekly group-CBT or a waiting list and tested at baseline, 3 months (following CBT or waiting list), 6 months (after cross-over), and 15/18 months (1-year follow-up). CBT consisted of task concentration and arousal reduction, positive affect labeling, and stimulus manipulation. Co-primary outcomes were symptom severity assessed by the Amsterdam Misophonia Scale-Revised (AMISOS-R) and improvement on the Clinical Global Impression-Improvement (CGI-I). Secondary outcomes were self-assessed ratings of general psychopathology (Symptom Checklist-90-Revised [SCL-90-R]) and quality of life (five-dimensional EuroQol [EQ5-D], Sheehan Disability Scale [SDS], WHO Quality of Life-BREF [WHOQoL-BREF]). Results: In all, 54 out of 71 patients were included (mean age, 33.06 [SD, 14.13] years; 38 women [70.4%]) and 46 (85%) completed the study. In the randomized phase, CBT resulted in statistically significant less misophonia symptoms in the short-term (−9.7 AMISOS-R; 95% CI, −12.0 to −7.4; p <.001, d = 1.97). The CBT group had an observed clinical improvement (CGI-I < 3) in 37% compared to 0% in the waiting list group (p <.001). The effect of CBT was maintained at 1-year follow-up on primary and secondary outcomes. Conclusions: This first randomized control trial shows both short-term and long-term efficacy of CBT for misophonia