Use of anoctamin 1 (ANO1) to evaluate interstitial cells of Cajal in Hirschsprung's disease.

PURPOSE: Interstitial cells of Cajal (ICCs) are pacemaker cells involved in facilitating neurotransmission and the generation of slow electrical waves necessary for colonic peristalsis. Their distribution has been found to be abnormal in the aganglionic and ganglionic colon in Hirschsprung's disease (HSCR) using c-kit-labelling. Anoctamin-1 (ANO1) is a Ca(2+)-activated Cl(-) channel thought to be specifically expressed on ICCs. Unlike c-kit, it plays a key role in ICC pacemaker activity. We aimed to investigate the utility of ANO1 in evaluating the colonic ICC network in HSCR. MATERIALS AND METHODS: We collected full-length pull-through specimens from children with HSCR (n = 10). Control colon specimens were collected at colostomy closure in children with anorectal malformation (n = 6). The distribution of ANO1 and c-kit expression was evaluated using immunofluorescence and confocal microscopy. ANO1 expression was quantified using Western blot analysis. RESULTS: ANO1 was not expressed on 23 % of c-kit immuno-positive cells in the circular muscle; however, 100 % of ANO1-positive ICCs were c-kit positive. The distribution of ANO1-positive ICCs was sparse in aganglionic colon, with a modest reduction in ICCs seen in the ganglionic colon in HSCR compared to controls (p = 0.044). ANO1 protein expression was reduced in aganglionic colon but similar in ganglionic colon relative to controls. CONCLUSIONS: ANO1 is preferential to c-kit in evaluating the ICC network in HSCR due to its specificity and functional importance. Abnormal distribution of ANO1-positive ICCs in the ganglionic colon in HSCR may contribute to persistent bowel symptoms in some patients after pull-through surgery.

Addressing Prompt Dependency in the Treatment of Challenging Behavior Maintained by Access to Tangible Items.

Prompt dependency is a common concern for individuals with developmental disabilities, particularly autism spectrum disorder. Previous research has shown that different interventions can be used to decrease prompt dependency. The purpose of the present study was to evaluate the efficacy of various treatments to decrease prompt dependency during functional communication training in the treatment of challenging behavior maintained by access to tangible items in a 16-year-old female diagnosed with autism spectrum disorder. Specifically, we compared the effects of differential reinforcement, vocal prompt fading, extended response intervals, and full physical prompts with a constant prompt delay to increase independent functional communication responses. The results of the study suggest that the prompt dependency treatment evaluation was efficacious in increasing independent functional communication responses and subsequently reducing challenging behavior to zero rates.