Music has been identified as a strength in people with Autism Spectrum Disorder; however, there is currently no neuroscientific evidence supporting its benefits. Given its universal appeal, intrinsic reward value and ability to modify brain and behaviour, music may be a potential therapeutic aid in autism. Here we evaluated the neurobehavioural outcomes of a music intervention, compared to a non-music control intervention, on social communication and brain connectivity in school-age children (ISRCTN26821793). Fifty-one children aged 6–12 years with autism were randomized to receive 8–12 weeks of music (n = 26) or non-music intervention (n = 25). The music intervention involved use of improvisational approaches through song and rhythm to target social communication. The non-music control was a structurally matched behavioural intervention implemented in a non-musical context. Groups were assessed before and after intervention on social communication and resting-state functional connectivity of fronto-temporal brain networks. Communication scores were higher in the music group post-intervention (difference score = 4.84, P = .01). Associated post-intervention resting-state brain functional connectivity was greater in music vs. non-music groups between auditory and subcortical regions (z = 3.94, P < .0001) and auditory and fronto-motor regions (z = 3.16, P < .0001). Post-intervention brain connectivity was lower between auditory and visual regions in the music compared to the non-music groups, known to be over-connected in autism (z = 4.01, P < .00001). Post-intervention brain connectivity in the music group was related to communication improvement (z = 3.57, P < .0001). This study provides the first evidence that 8–12 weeks of individual music intervention can indeed improve social communication and functional brain connectivity, lending support to further investigations of neurobiologically motivated models of music interventions in autism.
The advent of novel therapeutics in recent years has urged the need for a safe, non-immunogenic drug delivery vector capable of delivering therapeutic payloads specifically to diseased cells, thereby increasing therapeutic efficacy and reducing side effects. Extracellular vesicles (EVs) have garnered attention in recent years as a potentially ideal vector for drug delivery, taking into account their intrinsic ability to transfer bioactive cargo to recipient cells and their biocompatible nature. However, natural EVs are limited in their therapeutic potential and many challenges need to be overcome before engineered EVs satisfy the levels of efficiency, stability, safety and biocompatibility required for therapeutic use. Here, we demonstrate that an enzyme-mediated surface functionalization method in combination with streptavidin-mediated conjugation results in efficient surface functionalization of EVs. Surface functionalization using the above methods permits the stable and biocompatible conjugation of peptides, single domain antibodies and monoclonal antibodies at high copy number on the EV surface. Functionalized EVs demonstrated increased accumulation in target cells expressing common cancer associated markers such as CXCR4, EGFR and EpCAM both in vitro and in vivo . The functionality of this approach was further highlighted by the ability of targeting EVs to specifically deliver therapeutic antisense oligonucleotides to a metastatic breast tumor model, resulting in increased knockdown of a targeted oncogenic microRNA and improved metastasis suppression. The method was also used to equip EVs with a bifunctional peptide that targets EVs to leukemia cells and induces apoptosis, leading to leukemia suppression. Moreover, we conducted extensive testing to verify the biocompatibility, and safety of engineered EVs for therapeutic use, suggesting that surface modified EVs can be used for repeated dose treatment with no detectable adverse effects. This modular, biocompatible method of EV engineering offers a promising avenue for the targeted delivery of a range of therapeutics while addressing some of the safety concerns associated with EV-based drug delivery.
Electronic skins equip robots and biomedical devices with intuitive skin‐like sensitivity. Performance‐driven design of electronic skins is a critical need for electronic or biomedical applications. Prior research primarily focuses on investigating effects of microstructures on sensor performance at low pressure ranges. However, having predictive and tunable electro–mechanical responses across an extensive pressure range (>100 kPa) is paramount. Here, the authors propose a system that virtually customizes micropyramids for e‐skin sensors. The associations between geometry parameters, material properties, and single‐pyramid performance are systematically explored via numerical simulations, empirical characterizations, and analytical solutions. These experimentally validated models allow for the determination of the sensor parameters for the desired performance. An augmented reality interface system for surgery skills training by optimizing sensitivities that match varying tissue stiffnesses is further demonstrated. The platform enables greater effectiveness in rapidly iterating and designing micropyramidal e‐skin for applications in augmented reality interfaces, robotics, and telehealthcare.
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