Compulsive alcohol consumption is regulated by dorsal striatum fast-spiking interneurons

Compulsive alcohol consumption is a core, treatment-resistant feature of alcohol use disorder. The dorsomedial and dorsolateral striatum support goal-directed and habitual action strategies, respectively. How ethanol targets dorsolateral striatum to drive compulsive consumption is poorly understood. Parvalbumin-expressing striatal fast-spiking interneurons comprise ~1% of the total neuronal striatal population, are enriched dorsolaterally and are functionally modulated by ethanol. To test whether fast-spiking interneurons are necessary for the development of compulsive ethanol consumption, we selectively ablated these neurons in adult male and female C57BL/6 J mice undergoing a voluntary chronic intermittent ethanol consumption paradigm followed by a compulsive ethanol drinking assay. Fast-spiking interneuron ablation curtailed the development of organized ethanol lick sequence behavior, reduced ethanol consumption, and abrogated compulsive consumption of ethanol with the added bitterant quinine. In contrast, fast-spiking interneuron ablation did not affect any index of water or sucrose consumption. These data causally implicate the minority striatal fast-spiking interneuron population as a key component of compulsive ethanol consumption.Subject terms: Neuroscience, Physiology     

Vitiligo in children and adolescents: association with thyroid dysfunction

Background The clinical characteristics of vitiligo in children and adolescents with an emphasis on thyroid dysfunction have only been reported in a few studies. Objective The purpose of this study was to examine the characteristics of children and adolescents with vitiligo and compare the incidence of thyroid dysfunction between them and controls without vitiligo at the same age. Methods A retrospective analysis of 324 Korean children and adolescents with vitiligo was performed. The results of thyroid function screening tests in them (n = 254) were compared with controls (n = 122). Results Of the total 324 children and adolescents with vitiligo, vitiligo vulgaris was the most common type (42.3%) and the most commonly involved site was the face (54.6%). A total of 15 of 254 (5.9%) patients screened for thyroid function were diagnosed with thyroid disease (four had Hashimoto’s thyroiditis; two, Graves’ disease; seven, subclinical hypothyroidism; and two, subclinical hyperthyroidism). None of the 50 patients with segmental vitiligo showed any thyroid dysfunction (P = 0.047). There was no significant difference in the incidence of thyroid disease between children and adolescents with vitiligo and the control group, in which seven of 122 (5.7%) showed thyroid dysfunction. Conclusion In this study, we demonstrated the characteristics of children and adolescents with vitiligo and also observed no significant difference in the incidence of thyroid disease between children and adolescents with vitiligo and the control group.     

Moral Distress at the End of a Life: When Family and Clinicians Do Not Agree on Implantable Cardioverter-Defibrillator Deactivation

A 63-year-old man with end-stage ischemic cardiomyopathy presented with incessant ventricular tachycardia. He had been hospitalized multiple times in the past year for severe heart failure. As he approached end of life and was regularly receiving defibrillator shocks, his care team recommended deactivation of his implantable cardioverter-defibrillator. However, his family did not wish to allow deactivation, reporting a religious obligation to prolong his life, regardless of the risk of suffering. The patient was unable to adequately participate in the decision-making process. An implantable cardioverter-defibrillator can serve to avoid sudden death but may lead to a prolonged death from heart failure. This possibility forces the examination of values regarding prolongation of life, sometimes producing disagreement among stakeholders. Although ethical consensus holds that defibrillator deactivation is legal and ethical, disagreements about life prolongation may complicate decision making. The ethical, technical, and medical complexity involved in this case speaks to the need for clear, prospective communication involving the patient, the patient's family, and members of the care team.     

Setting-Level Influences on Implementation of the Responsive Classroom Approach

We used mixed methods to examine the association between setting-level factors and observed implementation of a social and emotional learning intervention (Responsive Classroom® approach; RC). In study 1 (N?=?33 3rd grade teachers after the first year of RC implementation), we identified relevant setting-level factors and uncovered the mechanisms through which they related to implementation. In study 2 (N?=?50 4th grade teachers after the second year of RC implementation), we validated our most salient Study 1 finding across multiple informants. Findings suggested that teachers perceived setting-level factors, particularly principal buy-in to the intervention and individualized coaching, as influential to their degree of implementation. Further, we found that intervention coaches’ perspectives of principal buy-in were more related to implementation than principals’ or teachers’ perspectives. Findings extend the application of setting theory to the field of implementation science and suggest that interventionists may want to consider particular accounts of school setting factors before determining the likelihood of schools achieving high levels of implementation.     

Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: A randomized controlled trial

Bile acid sequestrants (BAS) lower plasma low density lipoprotein levels and improve glycemic control. Colestimide, a BAS, has been claimed by computed tomography to reduce liver fat. Therefore, we examined the efficacy of colesevelam, a potent BAS, to decrease liver fat in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liver fat was measured by a novel magnetic resonance imaging (MRI) technique, the proton-density-fat-fraction (PDFF), as well as by conventional MR spectroscopy (MRS). Fifty patients with biopsy-proven NASH were randomly assigned to either colesevelam 3.75 g/day orally or placebo for 24 weeks. The primary outcome was change in liver fat as measured by MRI-PDFF in colocalized regions of interest within each of the nine liver segments. Compared with placebo, colesevelam increased liver fat by MRI-PDFF in all nine segments of the liver with a mean difference of 5.6% (P = 0.002). We cross-validated the MRI-PDFF-determined fat content with that assessed by colocalized MRS; the latter showed a mean difference of 4.9% (P = 0.014) in liver fat between the colesevelam and the placebo arms. MRI-PDFF correlated strongly with MRS-determined hepatic fat content (r(2) = 0.96, P < 0.0001). Liver biopsy assessment of steatosis, cellular injury, and lobular inflammation did not detect any effect of treatment. Conclusion: Colesevelam increases liver fat in patients with NASH as assessed by MRI as well as MRS without significant changes seen on histology. Thus, MRI and MRS may be better than histology to detect longitudinal changes in hepatic fat in NASH. Underlying mechanisms and whether the small MR-detected increase in liver fat has clinical consequences is not known. (HEPATOLOGY 2012;56:922-932).