1. Almanaa TN, Alwetaid MY, Bakheet SA, Attia SM, Ansari MA, Nadeem A, Ahmad SF. Aflatoxin B(1) exposure deteriorates immune abnormalities in a BTBR T(+) Itpr3(tf)/J mouse model of autism by increasing inflammatory mediators’ production in CD19-expressing cells. J Neuroimmunol. 2024; 391: 578365.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficiencies in communication, repetitive and stereotyped behavioral patterns, and difficulties in reciprocal social engagement. The presence of immunological dysfunction in ASD has been well established. Aflatoxin B(1) (AFB(1)) is a prevalent mycotoxin found in food and feed, causing immune toxicity and hepatotoxicity. AFB(1) is significantly elevated in several regions around the globe. Existing research indicates that prolonged exposure to AFB(1) results in neurological problems. The BTBR T(+) Itpr3(tf/)J (BTBR) mice, which were used as an autism model, exhibit the primary behavioral traits that define ASD, such as repeated, stereotyped behaviors and impaired social interactions. The main objective of this work was to assess the toxic impact of AFB(1) in BTBR mice. This work aimed to examine the effects of AFB(1) on the expression of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 by CD19(+) B cells in the spleen of the BTBR using flow cytometry. We also verified the impact of AFB(1) exposure on the mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain of BTBR mice using real-time PCR. The findings of our study showed that the mice treated with AFB(1) in the BTBR group exhibited a substantial increase in the presence of CD19(+)Notch-1(+), CD19(+)IL-6(+), CD19(+)MCP-1(+), CD19(+)iNOS(+), CD19(+)GM-CSF(+), and CD19(+)NF-κB p65(+) compared to the mice in the BTBR group that were treated with saline. Our findings also confirmed that administering AFB(1) to BTBR mice leads to elevated mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain, in comparison to BTBR mice treated with saline. The data highlight that exposure to AFB(1) worsens immunological abnormalities by increasing the expression of inflammatory mediators in BTBR mice.

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2. Aydin O, Sulu MD, Ari-Arat C. A Meta-Analysis of Self-Management Interventions in Teaching Daily Living Skills to Autistic Individuals. J Autism Dev Disord. 2024.

The current study aimed to conduct a systematic review and meta-analysis of self-management interventions for teaching daily living skills to autistic individuals. This study accessed the corresponding studies by doing a search in six databases. 14 articles and one dissertation met the inclusion criteria. The included studies were first analyzed descriptively and coded according to quality indicators using What Works Clearinghouse (WWC) standards. Second, the effect sizes of the included studies were calculated using two different effect size measures (i.e., Tau-U and performance-criteria-based effect size values [PCES]). Third, these analyses were also conducted for generalization and maintenance data. Of 15 studies included in this review, nine met the WWC standards with and without reservations. Tau-U analyses were conducted for 14 studies, whereas PCES values were calculated for only eight studies with mastery criteria. The findings indicated that the self-management interventions had a .93 CI(95) (.80, 1) overall effect size for Tau-U with a very large effect. On the other hand, the overall effect size for the PCES values indicated a moderate effect with .99. The weighted effect sizes in generalization and maintenance phases were very large for Tau-U; however, moderate to high effects for PCES. Although self-management interventions showed diversity, one of the domains of daily living skills (i.e., community living skills) has not been studied in the field. Notably, among the studies in our review, the last ones are from 2019. Detailed findings from descriptive analyses and two different effect size calculations are discussed, and recommendations for future studies are given.

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3. Grove R, Clapham H, Moodie T, Gurrin S, Hall G. ‘Nothing About Us, Without Us’: Research Priorities for Autistic Girls, Women and Gender Diverse People in Australia. J Autism Dev Disord. 2024.

Autistic girls, women and gender diverse people have specific needs that are underrepresented in research. Research priorities are often established by funding bodies, researchers, parents, carers and health professionals and may not meet the needs of the diverse Autistic community. This co-produced project aimed to identify what research would benefit the lives of Autistic girls, women and gender diverse people in Australia. We interviewed 47 Autistic girls, women and gender diverse people aged seven and above and obtained feedback from an additional 411 Autistic people through an online survey. Autistic young people identified six key research priorities including (1) better understanding and support at school, (2) understanding our experiences, strengths and challenges, (3) autism specific mental health support, (4) Autistic friendships and relationships, (5) experiences of gender diversity and (6) accommodations to make life easier for us. Eight key research priority areas were identified by Autistic adults including (1) understanding and supporting specific needs in adulthood, (2) experiences of trauma, abuse and sexual violence, (3) supporting mental health and wellbeing, (4) addressing barriers in healthcare, (5) understanding and supporting physical health needs, (6) addressing barriers in education and the workplace, (7) understanding the role of society, embracing neurodiversity and the importance of Autistic identity and (8) co-designing research and supports with Autistic people. We provide a discussion around the importance of focusing on these research priority areas in future autism research in Australia.

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4. Jimenez-Gomez C, Hannula C, Liggett AP, Shvarts S, Podlesnik CA. Evaluating functions of praise for children diagnosed with autism spectrum disorder. J Appl Behav Anal. 2024.

We assessed whether novel praise statements could be used to (a) maintain and increase responses with existing reinforcement histories and (b) teach a previously untaught response among children diagnosed with autism spectrum disorder across two experiments. During response-stimulus pairing, two responses resulted in preferred edibles but only one also produced a praise statement. In the absence of edibles, the response continuing to produce praise tended to persist more. Next, reversing the praise contingency tended to increase the other response. However, in no case did contingent delivery of those same praise statements result in the acquisition of untaught responses. These findings suggest that conditioning praise statements could serve different functions (antecedent or consequence) depending on the reinforcement history for particular responses.

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5. Lederman VRG, Goulart AL, Negrão JG, Schwartzman JS. Visual scanning of social stimuli in preterm and autism spectrum disorder children. Rev Paul Pediatr. 2024; 42: e2023017.

OBJECTIVE: To evaluate the pattern of eye-gaze of preterm (PT), autism spectrum disorder (ASD) and neurotypical (Ty) children. METHODS: A cross-sectional study with eight preterm (born with ≤2000 g weight), nine ASD and five Ty male children, between six and nine years old, was performed. The eye gaze was evaluated presenting a board with a couple in social interaction, and a video with four children playing with blocks, projected in a screen computer, successively, evaluating the time that the children looked at each stimulus. RESULTS: Although all the groups focus on the central social figure with no significant differences, ASD presented significant differences in time fixation of the objects (p=0.021), while premature children fixated more time in the central social interaction than in the whole scene than typical children. CONCLUSIONS: Although this study found noteworthy differences in the eye-gaze patterns among the three groups, additional research with a more extensive participant pool is necessary to validate these preliminary results.

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6. McConnell K, Keenan C, Storey C, Thurston A. Video-based interventions promoting social behavioural skills for autistic children and young people: An evidence and gap map. Campbell Syst Rev. 2024; 20(2): e1405.

BACKGROUND: Video-based interventions (VBIs) are an approach that can be used to promote social behavioural skills for autistic children and young people. Despite an abundance of literature in this area, previous evidence syntheses are limited by their exclusive search strategies and eligibility criteria. Therefore, there is a lack of comprehensive evidence syntheses to provide insight on whether these interventions work, for whom, and in what circumstances. Evidence and Gap Maps (EGMs) are used to collate vast literature on a broad topic area such as this, highlighting areas for synthesis, and identifying gaps for future research. OBJECTIVES: To identify, map and synthesise existing primary research on VBIs promoting social behavioural skills for autistic children and young people, creating a live, searchable and publicly available EGM. SEARCH METHODS: Searches were conducted in electronic databases (n = 8), web search engines, and other repositories including published papers and grey literature. The search strategy was developed around two concepts including (1) terms related to autism, and (2) terms related to VBIs. Searches were conducted in May 2021. SELECTION CRITERIA: All primary studies evaluating the effectiveness of VBIs in promoting social behaviours for autistic children and young people aged 3-18 were included in the EGM. DATA COLLECTION AND ANALYSIS: Search results were imported into Eppi-Reviewer where duplicates of identical studies were removed. Titles and abstracts were then screened by two independent reviewers. Potentially eligible full texts were located and also screened by two reviewers. Data were then extracted on study design, participant characteristics, type of intervention, type of outcome, and country of study, by one of three reviewers. EPPI-Mapper was used to create the interactive EGM. MAIN RESULTS: The current EGM contains 438 studies reporting on 394 single subject research designs, 25 randomised controlled trials, 15 non-randomised group designs, and 8 pretest-posttest designs. Included studies evaluated VBIs in all male (n = 238), mixed gender (n = 172) or all female (n = 17) samples. VBIs employed included video modelling (n = 273), video self-modelling (n = 82), point-of-view modelling (n = 61), video prompting (n = 57), video feedback (n = 12) and computer-based video instruction (n = 4). The most frequently used models were adults (n = 191) and peers (n = 135). In relation to social outcomes, almost half evaluated social engagement (n = 199) with limited studies looking at safety (n = 9) and community (n = 7) skills. AUTHORS’ CONCLUSIONS: This EGM provides a valuable resource for policy-makers, practitioners, researchers, funders and members of the public to access evidence on VBIs promoting social behavioural skills in autistic children and young people. The map has identified areas of sufficient research where evidence can undergo synthesis. In addition, important gaps in the evidence were highlighted and suggest further research is warranted in all female samples and less frequently evaluated types of VBIs and social outcomes. Evidence included in this EGM will be further explored via systematic review and meta-analysis on control group designs.

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7. Mounzer W, Stenhoff DM, Alkhateeb JM, Al Khatib AJ, Alhadidi MS, Lyle TT. Using Prompting and Modeling to Teach Imitation Skills and Eye Contact to Syrian Children with Autism Spectrum Disorder. Dev Neurorehabil. 2024: 1-10.

Lack of eye contact and imitation deficits are frequently targeted in behavioral interventions for children with autism spectrum disorder (ASD). In this study, we examined the effects of prompting and modeling on the imitation skills and eye contact of three Arabic-speaking young children with ASD in Syria. A multiple baseline design with a withdrawal component was used to evaluate the effects of the intervention in a clinical setting, at a center for children with special needs, and in follow-up sessions conducted in the participants’ homes. All participants’ imitative responses and eye contact increased when prompting and modeling were used. Our findings support the effectiveness of prompting and modeling on imitation skills.

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8. Onyango S, Nampijja M, Otwate P, Langat N, Oloo L, Okelo K, Kitsao-Wekulo P. Nurturing care practices for children with developmental disabilities in sub-Saharan Africa: A scoping review protocol. PLoS One. 2024; 19(5): e0291839.

BACKGROUND: The majority of children with neurodevelopmental disorders (NDDs) reside in low- and middle-income countries (LMICs). NDDs are a public health concern in countries in sub-Saharan Africa (SSA). Nurturing care has been recommended as a pathway for addressing the developmental needs and unlocking the full potential of children, including those with NDDs. However, little information exists on the strategies to support children with NDDs using the Nurturing Care Framework in many countries in SSA. This review aims to synthesize information on nurturing care practices for children with NDDs in SSA. The review will also determine gaps in the provision of nurturing care for children with NDDs. Further, the review will highlight the drivers of care as well as the experiences of the caregivers. METHODS: The review will be implemented in six steps: specification of the research question, identification of relevant studies, selection of studies to be included, extracting, mapping, and charting the data, collating, summarizing, and reporting the results, and stakeholder consultation. We propose a database search followed by a manual search for the literature synthesis. We will search the following electronic databases: PubMed, ScienceDirect, Scopus, Open Grey and African Journals Online (AJOL). All studies published after May 2018 to May 2023 that include relevant terms will be identified and included. The research team will develop a data extraction form for use in capturing relevant information from each of the included studies. A patterning chart that will summarize and analyze the key findings of each article will be created. DISCUSSION: We anticipate that the study will provide evidence on the existing nurturing care practices and unearth gaps in the provision of nurturing care for children with NDDs. Key determinants of care and the experiences of the parents/caregivers of children will also be identified. The study will provide key recommendations on interventions to improve the quality of care for children with NDDs. Through this study, awareness of the unmet nurturing care needs of these children will be increased. The evidence generated may assist policymakers and stakeholders in addressing the needs of children with NDDs.

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9. Rani R, Sri NS, Medishetti R, Chatti K, Sevilimedu A. Loss of FMRP affects ovarian development and behaviour through multiple pathways in a zebrafish model of fragile X syndrome. Hum Mol Genet. 2024.

Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder and the leading genetic cause of autism spectrum disorders. FXS is caused by loss of function mutations in Fragile X mental retardation protein (FMRP), an RNA binding protein that is known to regulate translation of its target mRNAs, predominantly in the brain and gonads. The molecular mechanisms connecting FMRP function to neurodevelopmental phenotypes are well understood. However, neither the full extent of reproductive phenotypes, nor the underlying molecular mechanisms have been as yet determined. Here, we developed new fmr1 knockout zebrafish lines and show that they mimic key aspects of FXS neuronal phenotypes across both larval and adult stages. Results from the fmr1 knockout females also showed that altered gene expression in the brain, via the neuroendocrine pathway contribute to distinct abnormal phenotypes during ovarian development and oocyte maturation. We identified at least three mechanisms underpinning these defects, including altered neuroendocrine signaling in sexually mature females resulting in accelerated ovarian development, altered expression of germ cell and meiosis promoting genes at various stages during oocyte maturation, and finally a strong mitochondrial impairment in late stage oocytes from knockout females. Our findings have implications beyond FXS in the study of reproductive function and female infertility. Dissection of the translation control pathways during ovarian development using models like the knockout lines reported here may reveal novel approaches and targets for fertility treatments.

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10. Reza Naghdi M, Ahadi R, Motamed Nezhad A, Sadat Ahmadi Tabatabaei F, Soleimani M, Hajisoltani R. The neuroprotective effect of Diosgenin in the rat Valproic acid model of autism. Brain Res. 2024: 148963.

BACKGROUND AND AIM: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with two core behavioral symptoms restricted/repetitive behavior and social-communication deficit. The unknown etiology of ASD makes it difficult to identify potential treatments. Valproic acid (VPA) is an anticonvulsant drug with teratogenic effects during pregnancy in humans and rodents. Prenatal exposure to VPA induces autism-like behavior in both humans and rodents. This study aimed to investigate the protective effects of Diosgenin in prenatal Valproic acid-induced autism in rats. METHOD: pregnant Wister female rats were given a single intraperitoneal injection of VPA (600 mg/kg, i.p.) on gestational day 12.5. The male offspring were given oral Dios (40 mg/kg, p.o.) or Carboxymethyl cellulose (5 mg/kg, p.o.) for 30 days starting from postnatal day 23. On postnatal day 52, behavioral tests were done. Additionally, biochemical assessments for oxidative stress markers were carried out on postnatal day 60. Further, histological evaluations were performed on the prefrontal tissue by Nissl staining and Immunohistofluorescence. RESULTS: The VPA-exposed rats showed increased anxiety-like behavior in the elevated plus maze (EPM). They also demonstrated repetitive and grooming behaviors in the marble burying test (MBT) and self-grooming test. Social interaction was reduced, and they had difficulty detecting the novel object in the novel object recognition (NOR) test. Also, VPA-treated rats have shown higher levels of oxidative stress malondialdehyde (MDA) and lower GP(X), TAC, and superoxide dismutase (SOD) levels. Furthermore, the number of neurons decreased and the ERK signaling pathway upregulated in the prefrontal cortex (PFC). On the other hand, treatment with Dios restored the behavioral consequences, lowered oxidative stress, and death of neurons, and rescued the overly activated ERK1/2 signaling in the prefrontal cortex. CONCLUSION: Chronic treatment with Dios restored the behavioral, biochemical, and histological abnormalities caused by prenatal VPA exposure.

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11. Wu T, Yin X, Xu L, Yu J. Using dynamic spatio-temporal graph pooling network for identifying autism spectrum disorders in spontaneous functional infrared spectral sequence signals. J Neurosci Methods. 2024: 110157.

BACKGROUND: Autism classification work on fNIRS data using dynamic graph networks. Explore the impact of the dynamic connection relationship between brain channels on ASD, and compare the brain channel connection diagrams of ASD and TD to explore potential factors that influence the development of autism. METHOD: Using dynamic graph construction to mine the dynamic relationships of fNIRS data, obtain spatio-temporal correlations through dynamic feature extraction, and improve the information extraction capabilities of the network through spatio-temporal graph pooling to achieve classification of ASD. RESULT: A classification effect with an accuracy of 97.2% was achieved using a short sequence of 1.75s. The results showed that the dynamic connections of channel 5 and 19, channel 12 and 25, and channel 7 and 34 have a greater impact on the classification of autism. Comparison with previously used method(s): Compared with previous deep learning models, our model achieves efficient classification using short-term fNIRS data of 1.75s, and analyzes the impact of dynamic connections on classification through dynamic graphs. CONCLUSION: Using Dynamic Spatio-Temporal Graph Pooled Neural Networks (DSTGPN), dynamic connectivity between brain channels was found to have an impact on the classification of autism. By modelling the brain channel relationship maps of ASD and TD, hyperlink clusters were found to exist on the brain channel connections of ASD.

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12. Wu X, Dickin DC, Bassette L, Ashton C, Wang H. Clinical gait analysis in older children with autism spectrum disorder. Sports Med Health Sci. 2024; 6(2): 154-8.

Individuals with autism spectrum disorder (ASD) often exhibit motor deficits that increase their risk of falls. There is a lack of understanding regarding gait biomechanics demonstrated by older children with ASD. The purpose of the study was to determine differences in gait patterns between older children with ASD and typically developing children. Eleven children with ASD and 11 age- and gender-matched typically developing children were recruited for the study. Participants walked on a force-instrumented treadmill at a constant speed (1.1 m/s – 1.2 m/s) for five minutes (min). Participants performed maximal voluntary contractions to assess their knee muscular strength. Differences between individuals with ASD and matched control participants were examined through paired t-tests with a significance level of p ≤ 0.05. Individuals with ASD demonstrated a smaller knee extensor torque compared to controls (p = 0.002). Participants with ASD exhibited a shorter stride length (p = 0.04), a greater cadence (p = 0.03), and a higher variation in stride width (p = 0.04) compared to control participants. The individuals with ASD experienced a greater braking ground reaction force (p = 0.03) during loading response. The results indicate older children with ASD develop a unique gait pattern signified by a reduced stride length, increased cadence, and an increase of variation in stride width. This unique gait pattern may represent a movement strategy used by the individuals with ASD to compensate for the weakness associated with their knee extensor muscles. Individuals with ASD who demonstrate these unique gait deviations may face reduced postural stability and an increased risk of fall-related injuries.

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