Applied Behavior Analysis in Children and Youth with Autism Spectrum Disorders: A Scoping Review.

This manuscript provides a comprehensive overview of the impact of applied behavior analysis (ABA) on children and youth with autism spectrum disorders (ASD). Seven online databases and identified systematic reviews were searched for published, peer-reviewed, English-language studies examining the impact of ABA on health outcomes. Measured outcomes were classified into eight categories: cognitive, language, social/communication, problem behavior, adaptive behavior, emotional, autism symptoms, and quality of life (QoL) outcomes. Improvements were observed across seven of the eight outcome measures. There were no included studies that measured subject QoL. Moreover, of 770 included study records, only 32 (4%) assessed ABA impact, had a comparison to a control or other intervention, and did not rely on mastery of specific skills to mark improvement. Results reinforce the need for large-scale prospective studies that compare ABA with other non-ABA interventions and include measurements of subject QoL to provide policy makers with valuable information on the impacts of ABA and other existing and emerging interventions. Supplementary Information: The online version contains supplementary material available at 10.1007/s40614-022-00338-x.

The role of phosphorylation in atrial fibrillation: a focus on mass spectrometry approaches.

Atrial fibrillation (AF) is the most common arrhythmia worldwide. It is associated with significant increases in morbidity in the form of stroke and heart failure, and a doubling in all-cause mortality. The pathophysiology of AF is incompletely understood, and this has contributed to a lack of effective treatments and disease-modifying therapies. An important cellular process that may explain how risk factors give rise to AF includes post-translational modification of proteins. As the most commonly occurring post-translational modification, protein phosphorylation is especially relevant. Although many methods exist for studying protein phosphorylation, a common and highly resolute technique is mass spectrometry (MS). This review will discuss recent evidence surrounding the role of protein phosphorylation in the pathogenesis of AF. MS-based technology to study phosphorylation and uses of MS in other areas of medicine such as oncology will also be presented. Based on these data, future goals and experiments will be outlined that utilize MS technology to better understand the role of phosphorylation in AF and elucidate its role in AF pathophysiology. This may ultimately allow for the development of more effective AF therapies.

Drug screening platform using human induced pluripotent stem cell-derived atrial cardiomyocytes and optical mapping.

Current drug development efforts for the treatment of atrial fibrillation are hampered by the fact that many preclinical models have been unsuccessful in reproducing human cardiac physiology and its response to medications. In this study, we demonstrated an approach using human induced pluripotent stem cell-derived atrial and ventricular cardiomyocytes (hiPSC-aCMs and hiPSC-vCMs, respectively) coupled with a sophisticated optical mapping system for drug screening of atrial-selective compounds in vitro. We optimized differentiation of hiPSC-aCMs by modulating the WNT and retinoid signaling pathways. Characterization of the transcriptome and proteome revealed that retinoic acid pushes the differentiation process into the atrial lineage and generated hiPSC-aCMs. Functional characterization using optical mapping showed that hiPSC-aCMs have shorter action potential durations and faster Ca2+ handling dynamics compared with hiPSC-vCMs. Furthermore, pharmacological investigation of hiPSC-aCMs captured atrial-selective effects by displaying greater sensitivity to atrial-selective compounds 4-aminopyridine, AVE0118, UCL1684, and vernakalant when compared with hiPSC-vCMs. These results established that a model system incorporating hiPSC-aCMs combined with optical mapping is well-suited for preclinical drug screening of novel and targeted atrial selective compounds.