1. Antosh S, Drennan C, Stolfi A, Lawson R, Huntley E, McCullough-Roach R, Hill M, Adelekan T, Vachhrajani S. Use of an adaptive sensory environment in patients with autism spectrum disorder (ASD) in the perioperative environment: a parallel, randomized controlled trial. Lancet Reg Health Am;2024 (May);33:100736.

BACKGROUND: Patients with autism spectrum disorders (ASD) experience higher rates of perioperative anxiety and are likely to receive premedication. Little is known about nonpharmaceutical interventions which may decrease anxiety. This study aims to evaluate the use of an adaptive sensory environment (ASE) to reduce ASD patient anxiety during the perioperative process. METHODS: Our feasibility study (ClinicalTrials.govNCT04994613) enrolled 60 patients in two parallel groups randomized to a control (no ASE) or intervention group (ASE). We included all surgical patients aged three to twelve years, with a formal diagnosis of ASD, Asperger’s Syndrome, or pervasive developmental disorder not otherwise specified. Preoperative behaviors were recorded by an unblinded nurse utilizing the validated Modified Yale Preoperative Anxiety Scale (mYPAS). The difference in score on the mYPAS was the primary outcome, and an intention-to-treat analysis was employed. A generalized estimating equations model was used to compare mYPAS scores controlling for significant independent variables. FINDINGS: 58 patients were analyzed after 1:1 randomization of 30 patients to each group. Groups were balanced except the median number of intraoperative pain medications was significantly lower in the ASE group (1 vs. 3, p = 0.012). Mean (SD) age for all patients was 7.2 (2.9) years, range 2.6-12.7. 72.4% (42/58) were White and all were Non-Hispanic or Latino. 74% were Male (21/30 ASE and 22/28 Control) and 26% were Female (9/30 ASE and 6/28 Control). No differences were found in mYPAS scores between groups at three time periods (43.5 vs. 42, p = 0.88, 47.8 vs. 48.4, p = 0.76, and 36.4 vs. 43.8, p = 0.15, ASE vs. control group, respectively). The ASE group had a significant within-group decrease in mYPAS scores from nursing intake to transition (p = 0.030). INTERPRETATION: An ASE did not significantly reduce perioperative anxiety. However, the promising results deserve further investigation. FUNDING: Dayton Children’s Hospital Foundation Robert C. Cohn Memorial Research Grant.

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2. Arkesteyn A, Cornelissen V, Steyaert J, Claes J, Michielsen M, Van Damme T. The concurrent validity and test-retest reliability of a submaximal exercise test in adolescents with autism. Disabil Rehabil;2024 (Apr 21):1-11.

PURPOSE: There is a need for valid and reliable clinical assessment tools to assess cardiorespiratory fitness (CRF) levels in adolescents with autism. Therefore, this study aimed to examine the concurrent validity and test-retest reliability of the Astrand-Rhyming Test (ART) in this population. MATERIALS AND METHODS: 45 adolescents with autism aged 12-18 years (n = 32 males, 14.47 ± 1.79 years) performed the ART twice (test-retest reliability) and completed a maximal cardiopulmonary exercise test (CPET) (concurrent validity). Reliability parameters included Pearson correlations, intraclass correlation coefficients (ICCs), standard error of measurements (SEM), minimal detectable changes (MDC), coefficients of variation, paired sample t-tests, linear regressions and Bland-Altman plots. The concurrent validity was evaluated with Pearson correlations, ICCs, paired sample t-tests, linear regressions and Bland-Altman plots. RESULTS: Strong test-retest reliability (r = 0.84-0.85, ICC = 0.84-0.85) was found for the ART, but the wide limits of agreement intervals suggest the presence of substantial variability. The large SEM (4.73-5.08 mL/kg/min) and MDC (13.20-14.07 mL/kg/min) values suggest lower absolute reliability. Moderate to strong levels of association (r = 0.74-0.75) and agreement (ICC = 0.59-0.66) were found between estimated (ART1) and measured (CPET) VO(2) max levels, but significant systematic differences (5.71-8.82 mL/kg/min) were observed. CONCLUSION: The ART is an accessible and promising method to monitor submaximal CRF levels over time but is less appropriate to estimate maximal CRF levels in this population. Adolescents with autism are at increased risk of exhibiting low cardiorespiratory fitness (CRF) levels and as a result, placing them at risk for poor physical and mental health outcomes.In clinical practice, the CRF levels of this population should be screened and monitored routinely to identify those at risk and most likely to benefit from a targeted intervention.A submaximal exercise test appears to be feasible in adolescents with autism.The Astrand-Rhyming Test shows good reliability to monitor submaximal CRF levels over time, but is less appropriate to estimate maximal CRF levels in adolescents with autism.The use of the age correction factor of the Astrand-Rhyming Test nomogram is not required to adequately estimate CRF levels in adolescents with autism. eng

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3. Caprì T, Dovigo L, Semino M, Lotan M, Mohammadhasani N, Zamarra G, Fabio RA. Use of a low-tech tool in the improvement of social interaction of patients with Rett Syndrome: an observational study. Front Public Health;2024;12:1353099.

INTRODUCTION: The main aim of the present study was to examine whether the use of a low-tech tool, called click4all, inserted into cognitive and motor training can increase social interaction of patients with Rett Syndrome (RTT) with classmates in a school setting. METHODS: Twenty-seven participants with RTT were randomly assigned to two groups: the experimental group received treatment with click4all, and the control group received traditional treatment without click4all. Parameters were measured before treatment (T1), 6 months after treatment (T2), 6 months after the second treatment phase (T3) and at the end of the third treatment phase (T4). RESULTS: The results demonstrated an increase in levels of social interaction among classmates and patients with RTT in the experimental group, over time, compared to the control group, 95% CI [5.20-15.30]. Classmates also showed a higher level of knowledge related to participants of the experimental group, and this increased over time, 95% CI [24.98-63.52]. The level of knowledge related to the control group was stable over time and lower than the experimental group. DISCUSSION: This study demonstrated that the use of a low-tech tool can increase social interactions of patients with RTT in a school setting. This is important, as patients with RTT are often restricted in an isolation condition.

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4. Cho HY, Yoo M, Pongkulapa T, Rabie H, Muotri AR, Yin PT, Choi JW, Lee KB. Magnetic Nanoparticle-Assisted Non-Viral CRISPR-Cas9 for Enhanced Genome Editing to Treat Rett Syndrome. Adv Sci (Weinh);2024 (Apr 22):e2306432.

The CRISPR-Cas9 technology has the potential to revolutionize the treatment of various diseases, including Rett syndrome, by enabling the correction of genes or mutations in human patient cells. However, several challenges need to be addressed before its widespread clinical application. These challenges include the low delivery efficiencies to target cells, the actual efficiency of the genome-editing process, and the precision with which the CRISPR-Cas system operates. Herein, the study presents a Magnetic Nanoparticle-Assisted Genome Editing (MAGE) platform, which significantly improves the transfection efficiency, biocompatibility, and genome-editing accuracy of CRISPR-Cas9 technology. To demonstrate the feasibility of the developed technology, MAGE is applied to correct the mutated MeCP2 gene in induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) from a Rett syndrome patient. By combining magnetofection and magnetic-activated cell sorting, MAGE achieves higher multi-plasmid delivery (99.3%) and repairing efficiencies (42.95%) with significantly shorter incubation times than conventional transfection agents without size limitations on plasmids. The repaired iPSC-NPCs showed similar characteristics as wild-type neurons when they differentiated into neurons, further validating MAGE and its potential for future clinical applications. In short, the developed nanobio-combined CRISPR-Cas9 technology offers the potential for various clinical applications, particularly in stem cell therapies targeting different genetic diseases.

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5. Cui J, Wang S, Zhai Z, Song X, Qiu T, Yu L, Zhai Q, Zhang H. Induction of autism-related behavior in male mice by early-life vitamin D deficiency: association with disruption of the gut microbial composition and homeostasis. Food Funct;2024 (Apr 22);15(8):4338-4353.

Vitamin D deficiency (VDD) during early life emerges as a potential risk factor for autism spectrum disorder (ASD). Individuals with autism commonly exhibit lower vitamin D (VD) levels compared to the general population, and VD deficiency is prevalent during pregnancy and lactation. Moreover, gastrointestinal comorbidity, prevalent in ASD patients, correlates closely with disruptions in the gut microbiota and altered intestinal permeability. Therefore, it is fascinating and significant to explore the effects of maternal VD deficiency during pregnancy and lactation on the maturation of the gut microbiota of the offspring and its relevance to autism spectrum disorders. In this study, we established maternal pregnancy and lactation VD-deficient mouse models, employed shotgun macrogenomic sequencing to unveil alterations in the gut microbiome of offspring mice, and observed autism-related behaviours. Furthermore, fecal microbial transplantation (FMT) reversed repetitive and anxious behaviours and alleviated social deficits in offspring mice by modulating the gut microbiota and increasing short-chain fatty acid levels in the cecum, along with influencing the concentrations of claudin-1 and occludin in the colon. Our findings confirm that VDD during pregnancy and lactation is a risk factor for autism in the offspring, with disturbances in the structure and function of the offspring’s gut microbiota contributing at least part of the effect. The study emphasises the importance of nutrition and gut health early in life. Simultaneously, this study further demonstrates the effect of VDD on ASD and provides potential ideas for early prevention and intervention of ASD.

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6. Gu Y, Maria-Stauffer E, Bedford SA, Romero-Garcia R, Grove J, Børglum AD, Martin H, Baron-Cohen S, Bethlehem RAI, Warrier V. Polygenic scores for autism are associated with neurite density in adults and children from the general population. medRxiv;2024 (Apr 13)

Genetic variants linked to autism are thought to change cognition and behaviour by altering the structure and function of the brain. Although a substantial body of literature has identified structural brain differences in autism, it is unknown whether autism-associated common genetic variants are linked to changes in cortical macro- and micro-structure. We investigated this using neuroimaging and genetic data from adults (UK Biobank, N = 31,748) and children (ABCD, N = 4,928). Using polygenic scores and genetic correlations we observe a robust negative association between common variants for autism and a magnetic resonance imaging derived phenotype for neurite density (intracellular volume fraction) in the general population. This result is consistent across both children and adults, in both the cortex and in white matter tracts, and confirmed using polygenic scores and genetic correlations. There were no sex differences in this association. Mendelian randomisation analyses provide no evidence for a causal relationship between autism and intracellular volume fraction, although this should be revisited using better powered instruments. Overall, this study provides evidence for shared common variant genetics between autism and cortical neurite density.

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7. Lakhani DA, Agarwal AK, Middlebrooks EH. Ultra-high-field 7-Tesla magnetic resonance imaging in fragile X tremor/ataxia syndrome (FXTAS). Neuroradiol J;2024 (Apr 21):19714009241247464.

Fragile X tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder characterized by premutation expansion of fragile X mental retardation 1 (FMR1) gene. It is a common single-gene cause of tremor, ataxia, and cognitive decline in adults. FXTAS affects the central, peripheral and autonomic nervous systems, leading to a range of neurological symptoms from dementia to dysautonomia. A characteristic imaging feature of FXTAS is symmetric T2 hyperintensity in the deep white matter of the cerebellar hemispheres and middle cerebral peduncle. However, recent studies have reported additional findings on diffusion weighted images (DWI), such as a symmetric high-intensity band-like signal at the cerebral corticomedullary junction. These findings, along with the characteristic cerebellar signal alterations, overlap with imaging findings seen in adult-onset neuronal intranuclear inclusion disease (NIID). Importantly, recent pathology studies have shown that both FXTAS and NIID can manifest intranuclear inclusion bodies, posing a diagnostic challenge and potential for misdiagnosis. We describe a 58-year-old man with FXTAS who received an erroneous diagnosis based on imaging and histopathology results. We emphasize the potential pitfalls in distinguishing NIID from FXTAS and stress the importance of genetic analysis in all cases with suspected NIID and FXTAS for confirmation. Additionally, we present the 7T MRI brain findings of FXTAS.

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8. Luongo M, Simeoli R, Marocco D, Milano N, Ponticorvo M. Enhancing early autism diagnosis through machine learning: Exploring raw motion data for classification. PLoS One;2024;19(4):e0302238.

In recent years, research has been demonstrating that movement analysis, utilizing machine learning methods, can be a promising aid for clinicians in supporting autism diagnostic process. Within this field of research, we aim to explore new models and delve into the detailed observation of certain features that previous literature has identified as prominent in the classification process. Our study employs a game-based tablet application to collect motor data. We use artificial neural networks to analyze raw trajectories in a « drag and drop » task. We compare a two-features model (utilizing only raw coordinates) with a four-features model (including velocities and accelerations). The aim is to assess the effectiveness of raw data analysis and determine the impact of acceleration on autism classification. Our results revealed that both models demonstrate promising accuracy in classifying motor trajectories. The four-features model consistently outperforms the two-features model, as evidenced by accuracy values (0.90 vs. 0.76). However, our findings support the potential of raw data analysis in objectively assessing motor behaviors related to autism. While the four-features model excels, the two-features model still achieves reasonable accuracy. Addressing limitations related to sample size and noise is essential for future research. Our study emphasizes the importance of integrating intelligent solutions to enhance and assist autism traditional diagnostic process and intervention, paving the way for more effective tools in assessing motor skills.

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9. Zheng W. Implicit motor learning in children with autism spectrum disorder: current approaches and future directions. Front Psychiatry;2024;15:1253199.

Motor dysfunction is increasingly being viewed as a core characteristic of autism spectrum disorder (ASD) in children. In particular, children with ASD have difficulty in learning new motor skills and there is a need to develop effective methods to improve this. Previous research has found that children with ASD may retain the ability to implicitly learn motor skills in comparison to their explicit learning of motor skills, which is typically impaired. This literature mini review focuses on summarizing the study of implicit learning in the acquisition of motor skills in children with ASD. First, we briefly introduce several common implicit learning methods in children’s motor skill learning. Second, we focus on the role of two important implicit learning approaches in motor skill learning, namely, an external focus of attention and analogy learning. Finally, based on our review of the existing studies, we present an outlook for future research and the areas that need to be improved in the practical teaching of implicit learning in the acquisition of motor skills in children with ASD.

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