CHARGE Syndrome and Comorbid Feeding Difficulties: A Summary of Outcomes following Behavior Analytic Treatment.

CHARGE syndrome is a genetic disorder caused by mutation of the CHD7 gene. Children with CHARGE syndrome often experience vision and hearing impairments, delayed growth and development, heart abnormalities, and artesia/stenosis of the chonae. Although not part of the diagnostic criteria, many individuals with CHARGE syndrome experience feeding and gastrointestinal difficulties. Interventions most commonly recommended and utilized to address feeding difficulties for children with CHARGE syndrome include tube feedings (medical approach) and oral-motor therapy. Despite the effectiveness of a behavior analytic approach to address feeding difficulties for a variety of pediatric populations, this approach is not routinely considered as a viable treatment option to address feeding difficulties for children with CHARGE syndrome. Outcome data of four children with CHARGE syndrome who participated in an intensive behavioral-based feeding program were reviewed. Variables reviewed included percentage of admission goals achieved, treatment strategies utilized, and changes in growth status, feeding tube dependence, texture and variety of foods consumed, and occurrence of inappropriate mealtime behavior. Outcomes evaluated in this review support the effectiveness of a behavior analytic approach for addressing feeding difficulties for children with CHARGE syndrome.

Intact pancreatic islets and dispersed beta-cells both generate intracellular calcium oscillations but differ in their responsiveness to glucose.

Pancreatic islets produce pulses of insulin and other hormones that maintain normal glucose homeostasis. These micro-organs possess exquisite glucose-sensing capabilities, allowing for precise changes in pulsatile insulin secretion in response to small changes in glucose. When communication among these cells is disrupted, precision glucose sensing falters. We measured intracellular calcium patterns in 6-mM-steps between 0 and 16 mM glucose, and also more finely in 2-mM-steps from 8 to 12 mM glucose, to compare glucose sensing systematically among intact islets and dispersed islet cells derived from the same mouse pancreas in vitro. The calcium activity of intact islets was uniformly low (quiescent) below 4 mM glucose and active above 8 mM glucose, whereas dispersed beta-cells displayed a broader activation range (2-to-10 mM). Intact islets exhibited calcium oscillations with 2-to-5-min periods, yet beta-cells exhibited longer 7-10 min periods. In every case, intact islets showed changes in activity with each 6-mM-glucose step, whereas dispersed islet cells displayed a continuum of calcium responses ranging from islet-like patterns to stable oscillations unaffected by changes in glucose concentration. These differences were also observed for 2-mM-glucose steps. Despite the diversity of dispersed beta-cell responses to glucose, the sum of all activity produced a glucose dose-response curve that was surprisingly similar to the curve for intact islets, arguing against the importance of "hub cells" for function. Beta-cells thus retain many of the features of islets, but some are more islet-like than others. Determining the molecular underpinnings of these variations could be valuable for future studies of stem-cell-derived beta-cell therapies.