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Proponents of autism intervention and those of the neurodiversity movement often appear at odds, the former advocating for intensive treatments and the latter arguing that autism must be accepted as a form of diversity. The history of behavioral intervention has understandably outraged many in the Autistic community, though many still value supports focused on quality of life. This commentary argues that Naturalistic Developmental Behavioral Interventions (NDBIs) hold promise for bridging the gap between early intervention and the neurodiversity movement. However, we recognize NDBIs have much room to grow and suggest multiple strategies for improvement. We believe these updates are not only feasible for clinicians and researchers to implement but will ultimately lead to improved quality of life for Autistic individuals.

Pivotal Response Treatment (PRT) is a naturalistic developmental behavioral intervention designed to strengthen autistic children’s social communication skills. Few studies have examined which children benefit the most from PRT and which characteristics are associated with meaningful progress. We analyzed data from 23 children with autism and significant language delay who had been randomized to receive PRT in a previously completed 24-week randomized controlled trial of parent training and clinician-delivered intervention. Participants were categorized as intervention responders and non-responders based on the demonstration of meaningful improvement (or lack thereof) in social communication using the MacArthur-Bates Communicative Development Inventories (MCDI) Reliable Change index scores and clinician determination based on review of language samples and the Clinical Global Impressions—Improvement Scale (CGI). Baseline child characteristics associated with being a responder were assessed. Sixteen participants were responders on the language sample, ten on the MCDI, and sixteen on the CGI. Nine were consistent responders across all three measures; six were consistent non-responders. Verbal ability at baseline was associated with being a responder across all measures. In our small sample, baseline verbal ability was associated with being a responder to PRT, though categorization as a responder differed somewhat based on outcome measure. Future research should explore responder profiles specifically in children who are nonspeaking to inform the development of more effective supports for this group.

The COVID-19 pandemic has created unprecedented challenges and disruptions for autistic individuals receiving specialized treatment services. This caregiver-report survey study (n = 339) explored predictors of satisfaction with autism services during COVID-19 to improve perceived support for these families. Specifically, we investigated whether service delivery medium (telehealth vs. in person), child’s emotional functioning, and caregiver stress would predict satisfaction with the most highly utilized services. Satisfaction ratings for ABA/behavioral, speech/language, and occupational therapy were lower when delivered via telehealth as compared to in person. Caregivers who reported higher emotional dysregulation in their children were less satisfied with behavioral therapy services. These results provide a critical caregiver-informed perspective on factors influencing satisfaction with specialized autism services during COVID-19.

In the original article there is an error in the Introduction Section (Sentence 2 of the Introduction after the Abstract) and it has been corrected in this erratum.

Despite the importance of monitoring changes in expressive language in early intervention, existing approaches to language assessment are often costly, time-intensive, and capture limited variability in autistic children. The Language ENvironmental Analysis (LENA) system has thus received considerable attention as an automated approach that may hold promise for capturing fine-grained changes in language development in a more efficient and cost-effective manner. However, evaluations of the utility of the LENA system for tracking response to early intervention in unstructured contexts are currently limited. This study aimed to build on prior research through evaluating the use of LENA in the context of a well-defined clinical sample from a randomized controlled trial (RCT) of Pivotal Response Treatment (PRT) that demonstrated expressive language gains across standardized and manually-coded measures. Exploration of automatically-derived LENA metrics (i.e., child vocalizations, conversational turns) revealed no significant association with standardized language assessments (i.e., Mullen expressive language subscale, MacArthur Bates Communicative Development Inventory, Vineland-II expressive language subscale). Furthermore, relative to the delayed treatment group, children participating in PRT did not show significantly greater improvement in the number of vocalizations or conversational turns during naturalistic, daylong LENA recordings collected in home settings from baseline to post-intervention. Implications and future directions for natural language sampling and the measurement of expressive language in early intervention are discussed.

There is a dearth of research that focuses on social intervention efforts for adults on the autism spectrum with intellectual disability and limited conversational language. Using a multiple baseline experimental design, this pilot investigation of the Socialization Knowledge for Individuals with Limited Language (SKILL) program evaluated a novel peer-facilitated group program specifically designed to target social interaction skills for this population. Findings from five pilot participants yielded evidence of social improvements across specific verbal skills (on-topic conversational contributions and responses) and nonverbal behaviors (eye-contact, active listening), as evidenced by coded social conversation probes and parent-report measures. These findings demonstrate the promise of a socialization intervention for a population that has historically been neglected in the social intervention research literature.

Sustained silencing of gene expression throughout the brain using small interfering RNAs (siRNAs) has not been achieved. Here we describe an siRNA architecture, divalent siRNA (di-siRNA), that supports potent, sustained gene silencing in the central nervous system (CNS) of mice and nonhuman primates following a single injection into the cerebrospinal fluid. Di-siRNAs are composed of two fully chemically modified, phosphorothioate-containing siRNAs connected by a linker. In mice, di-siRNAs induced the potent silencing of huntingtin, the causative gene in Huntington’s disease, reducing messenger RNA and protein throughout the brain. Silencing persisted for at least 6 months, with the degree of gene silencing correlating to levels of guide strand tissue accumulation. In cynomolgus macaques, a bolus injection of di-siRNA showed substantial distribution and robust silencing throughout the brain and spinal cord without detectable toxicity and with minimal off-target effects. This siRNA design may enable RNA interference-based gene silencing in the CNS for the treatment of neurological disorders. A divalent siRNA architecture enables sustained silencing of gene expression in deep regions of the brain.

Noncoding regulatory variants play a central role in the genetics of human diseases and in evolution. Here we measure allele-specific transcription factor binding occupancy of three liver-specific transcription factors between crosses of two inbred mouse strains to elucidate the regulatory mechanisms underlying transcription factor binding variations in mammals. Our results highlight the pre-eminence of cis -acting variants on transcription factor occupancy divergence. Transcription factor binding differences linked to cis -acting variants generally exhibit additive inheritance, while those linked to trans -acting variants are most often dominantly inherited. Cis -acting variants lead to local coordination of transcription factor occupancies that decay with distance; distal coordination is also observed and may be modulated by long-range chromatin contacts. Our results reveal the regulatory mechanisms that interplay to drive transcription factor occupancy, chromatin state, and gene expression in complex mammalian cell states. “Variation in the noncoding regulatory sequences in the genome plays important roles in human disease and evolution. Here, the authors use F1 mouse hybrids to shed light on the regulatory mechanisms mediating transcription factor binding, chromatin state and gene expression in mammalian cells.”

IntroductionHigh-intensity interval training (HIIT) and sprint interval training (SIT) consistently elevate post-exercise metabolism compared to moderate-intensity continuous training (MICT) in young adults (18–25 years), however few studies have investigated this in middle-aged adults.PurposeTo assess the effect of exercise intensity on post-exercise metabolism following submaximal, near-maximal, and supramaximal exercise protocols in middle-aged adults.Methods12 participants (8 females; age: 44 ± 10 years; V˙O2max: 35.73 ± 9.97 mL·kg−1 min−1) had their oxygen consumption (V˙O2) measured during and for 2 h following 4 experimental sessions: (1) no-exercise control (CTRL); (2) MICT exercise (30 min at 65% V˙O2max); (3) HIIT exercise (10 × 1 min at 90% maximum heart rate with 1 min rest); and (4) modified-SIT exercise (8 × 15 s “all-out” efforts with 2 min rest). Between session differences for V˙O2 and fat oxidation were compared.ResultsO2 consumed post-exercise was elevated during the 1st h and 2nd h following HIIT (15.9 ± 2.6, 14.7 ± 2.3 L; P < 0.036, d > 0.98) and modified-SIT exercise (16.9 ± 3.3, 15.30 ± 3.4 L; P < 0.041, d > 0.96) compared to CTRL (13.3 ± 1.9, 12.0 ± 2.5 L) while modified-SIT was also elevated vs HIIT in the 1st h (P < 0.041, d > 0.96). Total post-exercise O2 consumption was elevated following all exercise sessions (MICT: 27.7 ± 4.1, HIIT: 30.6 ± 4.8, SIT: 32.2 ± 6.6 L; P < 0.027, d > 1.03) compared to CTRL (24.9 ± 4.1 L). Modified-SIT exercise increased fat oxidation (0.103 ± 0.019 g min−1) compared to all sessions post-exercise (CTRL: 0.059 ± 0.025, MICT: 0.075 ± 0.022, HIIT: 0.081 ± 0.021 g·min−1; P < 0.007, d > 1.30) and HIIT exercise increased compared to CTRL (P = 0.046, d = 0.87).ConclusionExercise intensity has an important effect on post-exercise metabolism in middle-aged adults.

Prenatal phthalate exposure has been associated with lower birth weight but also higher weight in childhood. Few studies have examined weight or adiposity from birth to childhood and thus cannot assess growth trajectories associated with exposure. We assessed associations between maternal phthalate exposures in pregnancy and child weight and adiposity measured prenatally through childhood (3-6 years of age). Within The Infant Development and the Environment Study (TIDES), a prospective pregnancy cohort, we analyzed a panel of phthalate metabolites in urine collected at two visits from early and late gestation ( ). We estimated average phthalate metabolite associations with child weight -scores from gestation (estimated by ultrasound), birth, and 1, 3, 4, and 6 years of age using linear mixed-effects (LME) models. We also modeled associations with adiposity -scores from birth (weight for length) and 1, 3, 4, and 6 years of age [body mass index (BMI)] using LME models. For weight, we observed inverse associations between several phthalate metabolites and birth weight -scores, but no associations were observed with postnatal weight -scores in LME models. Regarding adiposity, we observed inverse associations between phthalate metabolites and weight-for-length -scores at birth, but positive associations were observed with BMI -scores at 3-4 years of age in LME models. For example, mono-ethyl phthalate was associated with a 0.17-unit decrease in birth weight-for-length -score [95% confidence interval (CI): , ] and a 0.18-unit increase in 4-years-of-age BMI -score (95% CI: 0.04, 0.32). We observed associations between prenatal exposure to phthalates and lower weight at birth but not at childhood follow-up visits. However, for adiposity, we observed an interesting pattern of association with low adiposity at delivery as well as high adiposity at 3-4 years of age. Although it is not clear from our results whether these associations occur within the same children, such a pattern of adiposity in early life has been linked to cardiometabolic disease in adulthood and deserves special attention as an outcome in the study of prenatal exposures in the developmental origins of health and disease. https://doi.org/10.1289/EHP10077.