An Open-Label Study of Cranial Electrotherapy Stimulation on Behavioral Regulation in a Mixed Neurodevelopmental Clinical Cohort.

OBJECTIVE: Individuals with neurodevelopmental disorders often report disturbances in the autonomic nervous system (ANS)-related behavioral regulation, such as sensory sensitivity, anxiety, and emotion dysregulation. Cranial electrotherapy stimulation (CES) is a method of non-invasive neuromodulation presumed to modify behavioral regulation abilities via ANS modulation. Here we examined the feasibility and preliminary effects of a 4-week CES intervention on behavioral regulation in a mixed neurodevelopmental cohort of children, adolescents, and young adults. METHODS: In this single-arm open-label study, 263 individuals aged 4-24 who were receiving clinical care were recruited. Participants received at-home CES treatment using an Alpha-Stim® AID CES device for 20 minutes per day, 5-7 days per week, for four weeks. Before and after the intervention, a parent-report assessment of sensory sensitivities, emotion dysregulation, and anxiety was administered. Adherence, side effects, and tolerance of the CES device were also evaluated at follow-up. RESULTS: Results showed a 75% completion rate, an average tolerance score of 68.2 (out of 100), and an average perceived satisfaction score of 58.8 (out of 100). Additionally, a comparison between pre- and post-CES treatment effects showed a significant reduction in sensory sensitivity, anxiety, and emotion dysregulation in participants following CES treatment. CONCLUSIONS: Results provide justification for future randomized control trials using CES in children and adolescents with behavioral dysregulation. SIGNIFICANCE: CES may be a useful therapeutic tool for alleviating behavioral dysregulation symptoms in children and adolescents with neurodevelopmental differences.

Inhibition of neointimal proliferation after bare metal stent implantation with low-pressure drug delivery using a paclitaxel-coated balloon in porcine coronary arteries.

A variety of mechanical and laser-based methods remove or shift atherosclerotic plaques and reopen the artery to its original lumen. Subsequent treatment with drug-coated balloons (DCB) may smooth the vessel wall but does not require high-pressure inflation. We investigated the efficacy of paclitaxel-coated balloons inflated with only 2 atm after bare metal stent implantation in coronary arteries of 24 pigs. Angiography and histomorphometry was performed on day 28. DCB inflated with 2 atm caused similar reduction of late lumen loss (LLL) as high-pressure inflation with 12 atm (0.89 ± 0.58 vs. 0.72 ± 0.39 mm, p = 0.34). Both DCB treatments significantly (p < 0.01) reduced LLL versus uncoated balloons (1.50 ± 0.51 mm). Treatment with low-pressure DCB resulted in less maximal intimal thickness (0.45 ± 0.15 vs. 0.67 ± 0.25 mm) and neointimal area (2.93 ± 0.73 vs. 3.82 ± 1.27 mm(2)) than treatment with uncoated balloons (p < 0.05). In conclusion, low-pressure treatment with DCB was similarly effective as high-pressure treatment justifying clinical trials in vessels which will benefit from inhibition of neointimal proliferation but may not tolerate high inflation pressure.

Methods for high-density admixture mapping of disease genes.

Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) has been proposed as an efficient approach to localizing disease-causing variants that differ in frequency (because of either drift or selection) between two historically separated populations. Near a disease gene, patient populations descended from the recent mixing of two or more ethnic groups should have an increased probability of inheriting the alleles derived from the ethnic group that carries more disease-susceptibility alleles. The central attraction of admixture mapping is that, since gene flow has occurred recently in modern populations (e.g., in African and Hispanic Americans in the past 20 generations), it is expected that admixture-generated linkage disequilibrium should extend for many centimorgans. High-resolution marker sets are now becoming available to test this approach, but progress will require (a). computational methods to infer ancestral origin at each point in the genome and (b). empirical characterization of the general properties of linkage disequilibrium due to admixture. Here we describe statistical methods to estimate the ancestral origin of a locus on the basis of the composite genotypes of linked markers, and we show that this approach accurately estimates states of ancestral origin along the genome. We apply this approach to show that strong admixture linkage disequilibrium extends, on average, for 17 cM in African Americans. Finally, we present power calculations under varying models of disease risk, sample size, and proportions of ancestry. Studying approximately 2500 markers in approximately 2500 patients should provide power to detect many regions contributing to common disease. A particularly important result is that the power of an admixture mapping study to detect a locus will be nearly the same for a wide range of mixture scenarios: the mixture proportion should be 10%-90% from both ancestral populations.