Autism spectrum disorder (ASD) is characterized by core social deficits. Prognosis is poor, in part, because existing medications target only associated ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may be a blood-based biomarker of social functioning and a possible treatment for ASD. However, prior OXT treatment trials have produced equivocal results, perhaps because of variability in patients' underlying neuropeptide biology, but this hypothesis has not been tested. Using a double-blind, randomized, placebo-controlled, parallel design, we tested the efficacy and tolerability of 4-wk intranasal OXT treatment (24 International Units, twice daily) in 32 children with ASD, aged 6-12 y. When pretreatment neuropeptide measures were included in the statistical model, OXT compared with placebo treatment significantly enhanced social abilities in children with ASD [as measured by the trial's primary outcome measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood OXT concentrations also predicted treatment response, such that individuals with the lowest pretreatment OXT concentrations showed the greatest social improvement. OXT was well tolerated, and its effects were specific to social functioning, with no observed decrease in repetitive behaviors or anxiety. Finally, as with many trials, some placebo-treated participants showed improvement on the SRS. This enhanced social functioning was mirrored by a posttreatment increase in their blood OXT concentrations, suggesting that increased endogenous OXT secretion may underlie this improvement. These findings indicate that OXT treatment enhances social abilities in children with ASD and that individuals with pretreatment OXT signaling deficits may stand to benefit the most from OXT treatment.A utism spectrum disorder (ASD) is a brain disorder of early childhood onset. ASD is characterized by core social communication impairments as well as restricted, repetitive behaviors, which jeopardize the development of appropriate social skills and the maintenance of social relationships (1). Despite being one of the most devastating childhood disorders in terms of prevalence [1 in 68 US children (2)] and societal cost [$236 billion expended annually in the United States (3)], ASD pathophysiology remains poorly understood. Consequently, there are no approved medications that enhance social abilities in individuals with ASD.

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The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using a double-blind, randomized, placebo-controlled, parallel study design, we tested the efficacy and tolerability of a 4-week intranasal AVP daily treatment in 30 children with ASD. AVP-treated participants aged 6 to 9.5 years received the maximum daily target dose of 24 International Units (IU); participants aged 9.6 to 12.9 years received the maximum daily target dose of 32 IU. Intranasal AVP treatment compared to placebo enhanced social abilities as assessed by change from baseline in this phase 2 trial’s primary outcome measure, the Social Responsiveness Scale, 2nd Edition total score (SRS-2 T score; F1,20 = 9.853; P = 0.0052; ηp2 = 33.0%; Cohen’s d = 1.40). AVP treatment also diminished anxiety symptoms and some repetitive behaviors. Most of these findings were more pronounced when we accounted for pretreatment AVP concentrations in blood. AVP was well tolerated with minimal side effects. No AVP-treated participants dropped out of the trial, and there were no differences in the rate of adverse events reported between treatment conditions. Last, no changes from baseline were observed in vital signs, electrocardiogram tracings, height and body weight, or clinical chemistry measurements after 4 weeks of AVP treatment. These preliminary findings suggest that AVP has potential for treating social impairments in children with ASD.

Young patients may experience LTE from WPW syndrome without prior symptoms or markers of high-risk on EPS.

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1879C ardiac resynchronization therapy (CRT) is an effective treatment for adult patients with left ventricular (LV) failure. Large prospective, randomized, controlled trials have demonstrated that CRT results in improvement in cardiac function, LV reverse remodeling, decreased hospitalizations for heart failure (HF), improved quality of life, and decreased overall mortality.1-5 However, 30% of adult patients are nonresponders to CRT, spurring further evaluation of electromechanical dyssynchrony to determine optimal pacing sites and to improve CRT selection criteria for maximal response. 1,6 The positive response in adult HF prompted exploration of the use of CRT in pediatric HF patients. However, the effectiveness of CRT in the pediatric population is difficult to evaluate because of the complex anatomic substrates of congenital heart disease (CHD) and scar formation from multiple cardiac surgeries with a higher proportion of right bundle-branch block (RBBB) and right ventricular (RV) failure than in the adult population. The typical adult HF scenario of an LV ejection fraction (EF) ≤35% with a left bundle-branch block (LBBB) is uncommon in children; therefore, the adult selection criteria for CRT cannot be easily translated to pediatric patients. Furthermore, a small heterogeneous pediatric patient population hinders a systematic assessment of long-term benefit from CRT. Principles of CRTIn the normal heart, ventricular electrical activation spreads through the His-Purkinje system, which has unique rapid propagation properties and widespread distribution. This allows highly coordinated electrical activation between distant regions of both ventricles, resulting in highly synchronous mechanical contraction. Given the strong relationship between electrical excitation and mechanical contraction in the myocardium, it is not surprising that abnormal electrical activation results in abnormal mechanical contraction. 7,8 During a spontaneous or pacing-induced bundle-branch block, ventricular activation spreads primarily cell to cell through the surrounding myocardium, which can be up to 4 times slower than the specialized His-Purkinje system. 9,10 This results in asynchronous electrical activation and thus asynchronous mechanical contraction in which opposing regions of the ventricular wall become out of phase with each other. Energy generated by contraction of early activated regions is dissipated by relaxation of late-activated regions, leading to decreased energy efficiency, depressed pump function, and deleterious ventricular remodeling. 11-14Approximately 25% of adults with HF exhibit a LBBB with mechanical dyssynchrony. CRT has traditionally targeted this electrical and mechanical dyssynchrony with biventricular pacing.15 By simultaneously pacing both ventricles, CRT uniformly prolongs the time to maximum contraction in each ventricle as the activation wave fronts from both ventricles merge. 16,17 This results in a more coordinated contraction pattern, more homogeneous distribution of regional loading conditions ...

Use of 3-D significantly improved success rates for ablation of WPW in children. The increase in acute success associated with 3-D suggests it is an important adjunct for catheter ablation of WPW in children.