Objective: Clinical diagnosis of autism spectrum disorder (ASD) relies on time-consuming subjective assessments. The primary purpose of this study was to investigate the utility of salivary microRNAs for differentiating children with ASD from peers with typical development (TD) and non-autism developmental delay (DD). The secondary purpose was to explore microRNA patterns among ASD phenotypes. Method: This multicenter, prospective, case-control study enrolled 443 children (2-6 years old). ASD diagnoses were based on DSM-5 criteria. Children with ASD or DD were assessed with the Autism Diagnostic Observation Schedule II and Vineland Adaptive Behavior Scales II. MicroRNAs were measured with high-throughput sequencing. Differential expression of microRNAs was compared among the ASD (n ¼ 187), TD (n ¼ 125), and DD (n ¼ 69) groups in the training set (n ¼ 381). Multivariate logistic regression defined a panel of microRNAs that differentiated children with ASD and those without ASD. The algorithm was tested in a prospectively collected naïve set of 62 samples (ASD, n ¼ 37; TD, n ¼ 8; DD, n ¼ 17). Relations between microRNA levels and ASD phenotypes were explored. Result: Fourteen microRNAs displayed differential expression (false discovery rate < 0.05) among ASD, TD, and DD groups. A panel of 4 microRNAs (controlling for medical/demographic covariates) best differentiated children with ASD from children without ASD in training (area under the curve ¼ 0.725) and validation (area under the curve ¼ 0.694) sets. Eight microRNAs were associated (R > 0.25, false discovery rate < 0.05) with social affect, and 10 microRNAs were associated with restricted/repetitive behavior. Conclusion: Salivary microRNAs are "altered" in children with ASD and associated with levels of ASD behaviors. Salivary microRNA collection is noninvasive, identifying ASD-status with moderate accuracy. A multi-"omic" approach using additional RNA families could improve accuracy, leading to clinical application. Clinical trial registration information: A Salivary miRNA Diagnostic Test for Autism; https://clinicaltrials.gov/; NCT02832557.
Inhaled bronchodilators and corticosteroids, when indicated, form the backbone of COPD therapy. However, over the last decade there has been an emergence of adjunct therapies in oral or inhaled form that are now part of the therapeutic approach to COPD. While these therapies have shown to be beneficial when used in the appropriate instances, there are particular considerations that need to be minded when using these therapies. This review article discussed the mechanism of roflumilast, macrolide antibiotics, other chronic antibiotic regimens, vitamin D supplementation, oral corticosteroids, n-acetylcysteine, and nebulized hypertonic saline, the clinical data behind each of these therapies, adverse events associated with therapy, and the expert recommendations for their utilization. Our goal is to provide a brief but informative and clinically useful review of commonly encountered therapies used in advanced COPD.
We report a rare case of cardioembolic stroke in the setting of supraventricular tachycardia (SVT) in an infant. After a week of irritability, a 10-week-old male presented to the emergency department with SVT requiring treatment with adenosine. He developed right-sided hemiparesis and focal motor seizures. Imaging of the brain showed ischemic infarct in the left middle cerebral artery (MCA) territory. Echocardiogram showed a newly formed large left atrial intracardiac thrombus. A coagulopathy workup was negative. He was treated with beta-blocker and anticoagulation therapy. He had mild residual right hemiparesis. During childhood, he developed medically refractory focal epilepsy from the left hemisphere, requiring epilepsy surgery at age 10. A child presenting with sustained SVT can be at increased risk for intracardiac thrombi and stroke.
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