Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

Successful treatment of hemorrhagic bullous Henoch‐Schonlein purpura with intravenous immunoglobulins

Henoch‐Schonlein purpura (HSP) is the most common systemic vasculitis in childhood. There is no consensus about the management for isolated cutaneous manifestations in HSP. We describe a case of HSP presenting with severe skin lesions that did not respond to standard therapy with corticosteroids. The 11‐year‐old child was treated with intravenous immunoglobulins, which induced rapid and persistent resolution of symptomatology.     

African-American Adolescents’ Weight Loss Skills Utilization: Effects on Weight Change in a Sequential Multiple Assignment Randomized Trial

Objective

Successful weight loss interventions for African-Americans adolescents are lacking. Cognitive-behavioral interventions seek to develop weight loss skills (e.g., counting calories, goal setting, managing one's environment). Little is known about how well adolescents implement such skills in their daily lives. Study aims were to (1) examine weight loss skills utilization at midpoint and end of a 6-month cognitive-behavioral/motivational interviewing weight loss sequential multiple assignment randomized trial (SMART), and (2) determine if greater skill utilization predicted weight loss at treatment end and 3 months post-treatment.

Does stroke impair academic achievement in children? The role of metacognition in math and spelling outcomes following pediatric stroke

Introduction: Current research suggests that pediatric stroke is associated with a reduction in intellectual functioning. However, less is known about academic achievement and the contribution of specific executive functions to math and literacy in this population. The current study investigates behavioral ratings of executive functioning and their relationship to math and spelling performance in children with a history of unilateral arterial ischemic stroke.

Method: Thirty-two pediatric patients with stroke (M_age = 9.5 ± 2.7 years) and 32 demographically equivalent, healthy controls were tested on standardized measures of arithmetic, spelling, and intelligence. Executive functioning data were collected via standardized parent questionnaire.

Results: Relative to controls, stroke participants demonstrated significantly poorer functioning in math, spelling, metacognition, and behavioral-regulation. Pencil and paper arithmetic was particularly challenging for the stroke group, with 40% of patients reaching levels of clinical impairment. Hierarchical regression in stroke participants further revealed that metacognition was a robust predictor of academic deficits. Stroke occurring in later childhood and affecting cortical and subcortical brain regions also presented as potential clinical risk factors.

Conclusions: Children with stroke were especially vulnerable to math achievement deficits. Metacognition made a substantial contribution to academic achievement abilities among stroke patients, and results underscore the importance of early metacognitive skills in the completion of schoolwork. Results also emphasize that pediatric stroke patients are a heterogeneous group with regard to functioning and that there is value in examining standard score distributions of clinical participant samples.     

Impact of Transcatheter Occlusion of a Patent Ductus Arteriosus on Atrial Septal Defect Diameter in Children

Background. A persistent patent ductus arteriosus (PDA) may delay closure of a coexisting atrial septal defect (ASD) due to volume loading and enlargement of the left atrium. The purpose of this study was to investigate the natural history of ASD size in patients with a PDA following transcatheter PDA occlusion. Methods. All patients with an ASD and a PDA who underwent transcatheter PDA occlusion at Texas Children’s Hospital were identified. Patients with ASD diameter <3 mm, or additional cardiac defects were excluded. Eight patients (7 females) with small‐ to moderate‐sized ASDs and a PDA were identified. Patient demographics, echocardiographic data, and cardiac catheterization data were recorded. Data were analyzed by 1‐tailed t‐test. Results. Following PDA occlusion, ASD diameter decreased in 6 of 8 patients by a mean of 3.8 mm (±2.3 mm), including 2 that closed. The median duration of follow‐up was 689 days. One ASD remained unchanged and 1 increased in size. The mean maximum ASD diameter decreased from 6.4 mm (±2.2 mm) to 3.9 mm (±3.4 mm) (P = .03). Two patients underwent subsequent transcatheter ASD occlusion. Conclusion. Following transcatheter PDA occlusion, small‐ to moderate‐sized ASDs have significant probability to decrease in size, and possibly close. In infants and children, we recommend transcatheter PDA occlusion, and serial follow‐up of the size of the ASD. This will allow many small‐ to moderate‐sized ASDs to either close, or become smaller, obviating the need for future intervention.