Parent Perceptions of a Novel Health Intervention for Neurodiverse Youth

Background: Children with all types of disabilities are more likely to be inactive due to a variety of factors. Children with neurodevelopmental challenges such as autism spectrum disorder (ASD) and/or mental health challenges such as anxiety and depression face unique barriers to exercise, including increased demands on parenting resources. Thus there is a critical need for interventions understand parental perspectives and address such barriers in neurodiverse youth. The aim of this study was to explore parental perceptions of a novel exergaming and virtual health coaching intervention targeting neurodiverse youth, including barriers and facilitators of their children’s engagement, in order to help tailor future interventions. Methods: Parents of three children taking part in formative research prior to a full intervention pilot were interviewed using a semi-structured interview guide. Phone interviews were recorded and transcribed without identifying information. Themes were identified during joint review of transcripts by two researchers using an adapted grounded theory approach. Results: Three parents of participants (1 middle school, 2 high school; 2 male) took part. Important barriers identified included easy frustration with gaming technology, feeling defeated by game avatars, burden of coordinating participation in the intervention, and desire for different types of games (non-sporting or non-dance). Parents felt strongly that participation had improved their children’s perceptions of exercise and overall exercise engagement. Suggestions for improvement included utilizing games without a competitive component, creating integrated intervention interface for parents, participants, and coaches, and using newer technologies (such as virtual reality). Conclusions: The home-based, school-supported GameSquad exergaming intervention shows potential to improve physical activity engagement in this population, however, barriers remain that should be addressed prior to upscaling. Modifications such as integrated intervention interfaces and more diverse gaming options would help improve intervention engagement and decrease parental burden

GamerFit-ASD beta test: adapting an evidence-based exergaming and telehealth coaching intervention for autistic youth

BackgroundHealth disparities faced by autistic youth are exacerbated by inadequate physical activity (PA) and sleep, whereas healthy PA and sleep may improve mood and function. Adaptive Game Squad (AGS) is an evidence-based telehealth coaching and exergaming intervention to improve PA and sleep for adolescents with diverse neurodevelopmental and psychiatric conditions. This study aimed to adapt AGS for autistic youth ages 10–15 years; beta-test the modified intervention for feasibility, accessibility, and engagement; and further refine the intervention for a larger planned demonstration pilot.MethodsInterdisciplinary experts adapted AGS to create GamerFit-ASD, a 12-week intervention that included a progressive exergame schedule, Fitbit step-tracking, weekly health coaching, and health tip/exercise videos. For beta testing, the intervention was shortened to a 4-week trial with 5 parent/child dyads. Children completed exit surveys and parents and children were interviewed about intervention feasibility, accessibility, and engagement. Exit survey data were summarized with descriptive statistics. Qualitative data were analyzed using a modified grounded-theory approach.ResultsAll participants (n = 5; ages 10–14 years) attended all 4 planned coaching sessions and completed an average of 9 of 12 planned exergame challenges for a weekly average of 50 min. All participants reported enjoying coaching sessions, 4 of 5 reported enjoying exergames, and 3 of 5 reported enjoying on-demand exercise videos. In interviews, children generally reported finding participation feasible, exergaming challenges active and fun, and coaches friendly and helpful. Parents reported high feasibility of supporting their children's involvement and valued child goal-setting and intervention flexibility; however, some found telehealth sessions overly scripted. Several adaptations to coaching scripts, coach training, and parent materials were made for the larger demonstration pilot, including changes to reduce scriptedness of coaching sessions, to provide parents with more information specific to autism, and to make video content more appropriate to children's needs/preferences.DiscussionA telehealth coaching and exergaming intervention appears feasible, accessible, and engaging for autistic youth aged 10–15. Future studies with larger, more diverse samples, longer study durations and/or follow-up periods, and more rigorous study designs are needed to advance understanding of the appropriateness and effectiveness of this type of intervention for this population

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.Peer reviewe

Giant hardening response in AlMgZn(Cu) alloys

This study presents a thermomechanical processing concept which is capable of exploiting the full industrial application potential of recently introduced AlMgZn(Cu) alloys. The beneficial linkage of alloy design and processing allows not only to satisfy the long-standing trade-off between high mechanical strength in use and good formability during processing but also addresses the need for economically feasible processing times. After an only 3-hour short pre-aging treatment at 100 degrees C, the two investigated alloys, based on commercial EN AW-5182 and modified with additions of Zn and Zn+Cu respectively, show high formability due to increased work-hardening. Then, these alloys exhibit a giant hardening response of up to 184 MPa to reach a yield strength of 410 MPa after a 20-minute short final heat treatment at 185 degrees C, i.e. paint-baking. This rapid hardening response strongly depends on the number density, size distribution and constitution of precursors acting as preferential nucleation sites for T-phase precursor precipitation during the final high-temperature aging treatment and is significantly increased by the addition of Cu. Minor deformation (2%) after pre-aging and before final heat treatment further enhances the development of hardening precipitates additionally by activating dislocation-supported nucleation and growth. Tensile testing, quantitative and analytical electron-microscopy methods, atom probe analysis and DFT calculations were used to characterize the alloys investigated in this work over the thermomechanical processing route. The influence of pre-strain on the hardening response and the role of Cu additions in early-stage cluster nucleation are discussed in detail and supported by in-situ STEM experiments and first-principles calculations. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd

The Adaptive GameSquad Xbox-Based Physical Activity and Health Coaching Intervention for Youth With Neurodevelopmental and Psychiatric Diagnoses: Pilot Feasibility Study

BACKGROUND: The prevalence of neurodevelopmental and psychiatric diagnoses (NPDs) in youth is increasing, and unhealthy physical activity (PA), diet, screen time, and sleep habits contribute to the chronic disease disparities and behavioral challenges this population experiences. OBJECTIVE: This pilot study aims to adapt a proven exergaming and telehealth PA coaching intervention for typically developing youth with overweight or obesity; expand it to address diet, screen, and sleep behaviors; and then test its feasibility and acceptability, including PA engagement, among youth with NPDs. METHODS: Participants (N=23; mean age 15.1 years, SD 1.5; 17 males, 9 people of color) recruited in person from clinic and special education settings were randomized to the Adaptive GameSquad (AGS) intervention or wait-list control. The 10-week adapted intervention included 3 exergaming sessions per week and 6 real-time telehealth coaching sessions. The primary outcomes included feasibility (adherence to planned sessions), engagement (uptake and acceptability as reported on process questionnaires), and PA level (combined light, moderate, and vigorous as measured by accelerometer). Descriptive statistics summarized feasibility and engagement data, whereas paired, two-tailed t tests assessed group differences in pre-post PA. RESULTS: Of the 6 coaching sessions, AGS participants (n=11; mean age 15.3 years, SD 1.2; 7 males, 4 people of color) completed an average of 5 (83%), averaging 81.2 minutes per week of exergaming. Of 9 participants who completed the exit questionnaire, 6 (67%) reported intention to continue, and 8 (89%) reported feeling that the coaching sessions were helpful. PA and sleep appeared to increase during the course of the intervention over baseline, video game use appeared to decrease, and pre-post intervention PA per day significantly decreased for the control (-58.8 min; P=.04) but not for the intervention group (-5.3 min; P=.77), despite potential seasonality effects. However, beta testers and some intervention participants indicated a need for reduced complexity of technology and more choice in exergames. CONCLUSIONS: AGS shows promise in delivering a health behavior intervention remotely to youth with NPDs, but a full-scale efficacy trial with a larger sample size is needed to confirm this finding. On the basis of feedback from beta testers and intervention participants, the next steps should include reduced technology burden and increased exergame choice before efficacy testing. TRIAL REGISTRATION: ClinicalTrials.gov NCT03665415; https://clinicaltrials.gov/ct2/show/NCT03665415. Marilyn Augustyn, Mediatrix Mbamalu, Carol Curtin, Linda Bandini, Aviva Must, Amanda E Staiano. Originally published in JMIR Formative Research (https://formative.jmir.org), 14.05.2021

Optimization of adenoviral vector–mediated transgene expression in the canine brain in vivo, and in canine glioma cells in vitro

Expression of the immune-stimulatory molecule Fms-like tyrosine kinase 3 ligand (Flt3L) and the conditional cytotoxic enzyme herpes simplex virus type 1 thymidine kinase (HSV1-TK) provides long-term immune-mediated survival of large glioblastoma multiforme (GBM) models in rodents. A limitation for predictive testing of novel antiglioma therapies has been the lack of a glioma model in a large animal. Dogs bearing spontaneous GBM may constitute an attractive large-animal model for GBM, which so far has remained underappreciated. In preparation for a clinical trial in dogs bearing spontaneous GBMs, we tested and optimized adenovirus-mediated transgene expression with negligible toxicity in the dog brain in vivo and in canine J3T glioma cells. Expression of the marker gene β-galactosidase (β-Gal) was higher when driven by the murine (m) than the human (h) cytomegalovirus (CMV) promoter in the dog brain in vivo, without enhanced inflammation. In the canine brain, β-Gal was expressed mostly in astrocytes. β-Gal activity in J3T cells was also higher with the mCMV than the hCMV promoter driving tetracycline-dependent (TetON) trans-gene expression within high-capacity adenovirus vectors (HC-Ads). Dog glioma cells were efficiently transduced by HC-Ads expressing mCMV-driven HSV1-TK, which induced 90% reduction in cell viability in the presence of ganciclovir. J3T cells were also effectively transduced with HC-Ads expressing Flt3L under the control of the regulatable TetON promoter system, and as predicted, Flt3L release was stringently inducer dependent. HC-Ads encoding therapeutic transgenes under the control of regulatory sequences driven by the mCMV promoter are excellent vectors for the treatment of spontaneous GBM in dogs, which constitute an ideal preclinical animal model