BMC Sports Sci Med Rehabil. 2024 Apr 24;16(1):92. doi: 10.1186/s13102-024-00885-7.

ABSTRACT

BACKGROUND: Social communication impairments (SCI) is a core symptom of autism spectrum disorder (ASD) and is marked by challenges in social interaction. Although physical exercise has been shown to improve SCI, this finding has not been supported by comprehensive scientific evidence. Existing research has established a strong link between the SCI in children with ASD and abnormalities in regional homogeneity (ReHo). Therefore, investigating the effects of physical exercise on SCI and Reho in patients with ASD may help to elucidate the neurological mechanisms involved.

METHODS: The present study included 30 preschool children diagnosed with ASD, with 15 participants in each group (experimental and control). The experimental group underwent a 12-week mini-basketball training program (MBTP) based on routine behavioral rehabilitation, while the control group only received routine behavioral rehabilitation. The Social Responsiveness Scale-Second Edition (SRS-2) was employed to assess SCI in both groups. Resting-state functional magnetic resonance imaging technology was used to evaluate ReHo in both groups.

RESULTS: After 12-week of MBTP, significant group × time interactions were observed between the experimental and control groups in total SRS-2 scores (F = 14.514, p < 0.001, ηp2 = 0.341), as well as in the domains of social cognition (F = 15.620, p < 0.001, ηp2 = 0.358), social communication (F = 12.460, p < 0.01, ηp2 = 0.308), and autistic mannerisms (F = 9.970, p < 0.01, ηp2 = 0.263). No statistical difference was found in the scores for the social awareness subscale and social motivation subscale in the group × time interaction (all p > 0.05). The experimental group exhibited increased ReHo in the right Cerebellum_Crus1 and right parahippocampal gyrus, coupled with decreased ReHo in the left middle frontal gyrus (orbital part), left superior frontal gyrus (dorsolateral), left postcentral gyrus, and right superior parietal gyrus. Furthermore, a decrease in ReHo in the left postcentral gyrus positively correlated with changes in social communication scores in SCI behaviors (p < 0.05).

CONCLUSIONS: Our study underscores the effectiveness of a 12-week MBTP in ameliorating SCI and abnormalities in ReHo among preschool children with ASD.

TRIAL REGISTRATION: The trial is retrospectively registered on the Chinese Clinical Trial Registry (ChiCTR1900024973; August 5, 2019).

PMID:38659073 | DOI:10.1186/s13102-024-00885-7

BMC Psychiatry. 2024 Apr 25;24(1):319. doi: 10.1186/s12888-024-05768-2.

ABSTRACT

BACKGROUND: The underlying neurobiology of the complex autism phenotype remains obscure, although accumulating evidence implicates the serotonin system and especially the 5HT2A receptor. However, previous research has largely relied upon association or correlation studies to link differences in serotonin targets to autism. To directly establish that serotonergic signalling is involved in a candidate brain function our approach is to change it and observe a shift in that function. We will use psilocybin as a pharmacological probe of the serotonin system in vivo. We will directly test the hypothesis that serotonergic targets of psilocybin - principally, but not exclusively, 5HT2A receptor pathways-function differently in autistic and non-autistic adults.

METHODS: The 'PSILAUT' "shiftability" study is a case-control study autistic and non-autistic adults. How neural responses 'shift' in response to low doses (2 mg and 5 mg) of psilocybin compared to placebo will be examined using multimodal techniques including functional MRI and EEG. Each participant will attend on up to three separate visits with drug or placebo administration in a double-blind and randomized order.

RESULTS: This study will provide the first direct evidence that the serotonin targets of psilocybin function differently in the autistic and non-autistic brain. We will also examine individual differences in serotonin system function.

CONCLUSIONS: This work will inform our understanding of the neurobiology of autism as well as decisions about future clinical trials of psilocybin and/or related compounds including stratification approaches.

TRIAL REGISTRATION: NCT05651126.

PMID:38658877 | DOI:10.1186/s12888-024-05768-2

Nature. 2024 Apr;628(8009):818-825. doi: 10.1038/s41586-024-07310-6. Epub 2024 Apr 24.

ABSTRACT

Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions1. TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A2-6. We reasoned that switching CACNA1C exon utilization from 8A to 8 would represent a potential therapeutic strategy. Here we developed antisense oligonucleotides (ASOs) to effectively decrease the inclusion of exon 8A in human cells both in vitro and, following transplantation, in vivo. We discovered that the ASO-mediated switch from exon 8A to 8 robustly rescued defects in patient-derived cortical organoids and migration in forebrain assembloids. Leveraging a transplantation platform previously developed7, we found that a single intrathecal ASO administration rescued calcium changes and in vivo dendrite retraction of patient neurons, suggesting that suppression of CACNA1C exon 8A expression is a potential treatment for TS1. Broadly, these experiments illustrate how a multilevel, in vivo and in vitro stem cell model-based approach can identify strategies to reverse disease-relevant neural pathophysiology.

PMID:38658687 | DOI:10.1038/s41586-024-07310-6

Child Psychiatry Hum Dev. 2024 Apr 24. doi: 10.1007/s10578-024-01700-7. Online ahead of print.

ABSTRACT

This study aimed to compare the breastfeeding (BF) duration of the younger siblings of children with ASD in an enriched-likelihood cohort for autism spectrum disorder (ASD), and to determine whether longer BF duration was associated with differences in neurodevelopmental outcomes in this cohort. Information on BF practices was collected via surveys in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) study. Developmental evaluations, including the Mullen Scales of Early Learning and the Autism Diagnostic Observation Schedule, were conducted by expert clinicians. Participants' neurodevelopmental outcome was classified by an algorithm into three groups: typical development, ASD, and non-typical development. The median duration of BF was 10.70 months (interquartile range of 12.07 months). There were no significant differences in the distribution of duration of BF among the three neurodevelopmental outcome categories. Children in this enriched-likelihood cohort who were breastfed for > 12 months had significantly higher scores on cognitive testing compared to those who were breastfed for 0-3 months. There was no significant difference in ASD symptomatology or ASD risk based on BF duration.

PMID:38658455 | DOI:10.1007/s10578-024-01700-7

Neurosci Biobehav Rev. 2024 Apr 22:105686. doi: 10.1016/j.neubiorev.2024.105686. Online ahead of print.

ABSTRACT

Rodents, along with numerous other mammals, heavily depend on olfactory cues to navigate their social interactions. Processing of olfactory sensory inputs is mediated by conserved brain circuits that ultimately trigger social behaviors, such as social interactions and parental care. Although innate, parenting is influenced by internal states, social experience, genetics, and the environment, and any significant disruption of these factors can impact the social circuits. Here, we review the molecular mechanisms and social circuits from the olfactory epithelium to central processing that initiate parental behaviors and their dysregulations that may contribute to the social impairments in mouse models of autism spectrum disorders (ASD). We discuss recent advances of the crucial role of olfaction in parental care, its consequences for social interactions, and the reciprocal influence on social interaction impairments in mouse models of ASD.

PMID:38657845 | DOI:10.1016/j.neubiorev.2024.105686

Sci Adv. 2024 Apr 26;10(17):eadl6554. doi: 10.1126/sciadv.adl6554. Epub 2024 Apr 24.

ABSTRACT

MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an "empathogen," empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia-behavioral tests modeling empathy in mice-with region-specific neuropharmacology, optogenetics, and transgenic manipulations to explore MDMA's action as an empathogen. We report that MDMA, given intraperitoneally or infused directly into the nucleus accumbens (NAc), robustly enhances the social transfer of pain and analgesia. Optogenetic stimulation of 5-HT release in the NAc recapitulates the effects of MDMA, implicating 5-HT signaling as a core mechanism. Last, we demonstrate that systemic MDMA or optogenetic stimulation of NAc 5-HT inputs restores deficits in empathy-like behaviors in the Shank3-deficient mouse model of autism. These findings demonstrate enhancement of empathy-related behaviors by MDMA and implicate 5-HT signaling in the NAc as a core mechanism mediating MDMA's empathogenic effects.

PMID:38657057 | DOI:10.1126/sciadv.adl6554

J Autism Dev Disord. 2024 Apr 24. doi: 10.1007/s10803-024-06350-1. Online ahead of print.

ABSTRACT

BACKGROUND: In recent years, an abundance of research has substantiated the escalating prevalence of Autism Spectrum Disorder (ASD) on a global scale. The aim to assess the level of awareness regarding ASD among the Kazakhstan population, as well as their readiness to offer help to individuals affected by ASD.

METHODS: A cross-sectional study was conducted encompassing individuals aged 18 years and above, using both the Russian and Kazakh languages. The survey was administered through Google Forms during April to June 2023. The link to survey was disseminated through WhatsApp chats of different social groups, including primary care specialists (general practitioners and nurses), and educators from primary and secondary schools from all 17 regions of Kazakhstan, spanning urban and rural areas. 410 participants took part in the survey in total. Statistical significance will be defined as p-values < 0.05.

RESULTS: Individuals aged 25 and above, who are both educated and employed, exhibit a greater awareness of ASD compared to other demographic groups. A low proportion of respondents (18.3%) demonstrated familiarity with the key symptoms of ASD as well as on its causes. Furthermore, it's noteworthy that the primary resource for acquiring information about ASD was the internet for both of these regions.

CONCLUSION: Low awareness on ASD symptoms and treatment methods was identified in both areas. There is a need to develop activities to increase the public awareness on ASD, including knowledge on early symptoms of ASD and facilities that address the needs of people on the ASD and their families.

PMID:38656465 | DOI:10.1007/s10803-024-06350-1

Endocr Regul. 2024 Apr 24;58(1):105-114. doi: 10.2478/enr-2024-0012. Print 2024 Jan 1.

ABSTRACT

Oxytocin plays an important role in brain development and is associated with various neurotransmitter systems in the brain. Abnormalities in the production, secretion, and distribution of oxytocin in the brain, at least during some stages of the development, are critical for the pathogenesis of neuropsychiatric diseases, particularly in the autism spectrum disorder. The etiology of autism includes changes in local sensory and dopaminergic areas of the brain, which are also supplied by the hypothalamic sources of oxytocin. It is very important to understand their mutual relationship. In this review, the relationship of oxytocin with several components of the dopaminergic system, gamma-aminobutyric acid (GABA) inhibitory neurotransmission and their alterations in the autism spectrum disorder is discussed. Special attention has been paid to the results describing a reduced expression of inhibitory GABAergic markers in the brain in the context of dopaminergic areas in various models of autism. It is presumed that the altered GABAergic neurotransmission, due to the absence or dysfunction of oxytocin at certain developmental stages, disinhibits the dopaminergic signaling and contributes to the autism symptoms.

PMID:38656256 | DOI:10.2478/enr-2024-0012

J Child Adolesc Psychopharmacol. 2024 Apr 23. doi: 10.1089/cap.2024.0004. Online ahead of print.

ABSTRACT

Despite policy emphasis on early identification, many children with Autism are diagnosed late, with some being diagnosed as late as adolescence. The objective of this study was to examine the demographics and clinical characteristics of school-age children and adolescents initially diagnosed with Autism age 7 and older, in an urban, university-affiliated multidisciplinary center that evaluates/treats youth with developmental disabilities. A chart review of all school-age children and adolescents referred for evaluation to determine if the child has developmental disabilities from January 2019 to May 2023 was performed. Of all children evaluated in that period (n = 825), 164 (19.8%) were diagnosed with Autism, 123 (75%) had a previous diagnosis, and 41 (25%) were newly diagnosed with Autism. Patients newly diagnosed with Autism age ≥7 were more likely to be diagnosed with Language Disorder (100% vs. 82%, p = 0.001) and Anxiety Disorder (27% vs. 13%, p = 0.04), be prescribed with an antidepressant (10% vs. 1%, p = 0.03), and less likely to be diagnosed with Intellectual Disabilities (13% vs. 34%, p = 0.001) than those who had a previous diagnosis of Autism, with no other differences in demographics or developmental diagnosis between the groups. Of the 136 patients referred for evaluation with a previous diagnosis of Autism, 13 (9.5%) did not meet the criteria for Autism any longer after multidisciplinary evaluations but continued to present developmental disorders, including Language Disorder (100%), attention-deficit/hyperactivity disorder (46%), and Speech Sound Disorder (38%). Of the 87 families who were concerned about Autism (without a previous diagnosis), 32 (36.8%) confirmed the diagnosis of Autism, 9 (1.5%) patients were newly diagnosed with Autism, and there were no parental concerns. In conclusion, in this ethnically diverse group of school-age children and adolescents with developmental disabilities, 25% received an initial diagnosis of Autism after age 7. Similar to previous reports, children who received a later diagnosis were more likely to present a language impairment, anxiety, and higher cognitive skills. Longitudinal studies, in ethnically diverse populations, are necessary to understand the trajectory and clinical profile of Autism.

PMID:38656162 | DOI:10.1089/cap.2024.0004

Sao Paulo Med J. 2024 Apr 22;142(5):e2023184. doi: 10.1590/1516-3180.2023.0184.R1.16022024. eCollection 2024.

ABSTRACT

BACKGROUND: During development, children face a number of demands and cognitive, behavioral, and social challenges necessary for growth. Cognitive skills make individuals competent and allow them to interact with their environment.

OBJECTIVE: To identify the cognitive skills that promote better social insertion in children with autism spectrum disorder within 12 months.

DESIGN AND SETTING: Prospective cohort study.

METHODS: In this study, 21 children aged 3-12 years were assessed, and their mothers were interviewed. Children were enrolled in regular or special autistic schools. Twelve months after the first assessment, the same children participated in the second assessment. In individual interviews, mothers provided data by answering the Vineland Adaptive Behavior Scale. Each child was assessed individually using the fourth edition of the Stanford Binet Intelligence Scale 4th Edition.

RESULTS: In the first assessment, the Stanford Binet areas and total scores correlated with the communication domains, daily life abilities, socialization, and total score of the Vineland Scale. After 12 months, a correlation was observed between the Stanford Binet areas and the total and communication domains, daily life abilities, socialization, motor abilities, and total score on the Vineland Scale.

CONCLUSION: Logic mathematics and memory promote better social insertion in children with autism spectrum disorder. General cognitive ability promotes communication.

PMID:38655981 | DOI:10.1590/1516-3180.2023.0184.R1.16022024

J Clin Transl Sci. 2023 Dec 14;8(1):e64. doi: 10.1017/cts.2023.697. eCollection 2024.

ABSTRACT

BACKGROUND: SPARK launched in 2016 to build a US cohort of autistic individuals and their family members. Enrollment includes online consent to share data and optional consent to provide saliva for genomic analysis. SPARK's recruitment strategies include social media and support of a nation-wide network of clinical sites. This study evaluates SPARK's recruitment strategies to enroll a core study population.

METHODS: Individuals who joined between January 31, 2018, and May 29, 2019 were included in the analysis. Data include sociodemographic characteristics, clinical site referral, the website URL used to join, how the participant heard about SPARK, enrollment completion (online registration, study consents, and returning saliva sample), and completion of the baseline questionnaire. Logistic regressions were performed to evaluate the odds of core participant status (completing enrollment and baseline questionnaire) by recruitment strategy.

RESULTS: In total, 31,715 individuals joined during the study period, including 40% through a clinical site. Overall, 88% completed online registration, 46% returned saliva, and 38% were core participants. Those referred by a clinical site were almost twice as likely to be core participants. Those who directly visited the SPARK website or performed a Google search were more likely to be core participants than those who joined through social media.

DISCUSSION: Being a core participant may be associated with the "personal" connection and support provided by a clinical site and/or site staff, as well as greater motivation to seek research opportunities. Findings from this study underscore the value of adopting a multimodal recruitment approach that combines social media and a physical presence.

PMID:38655455 | PMC:PMC11036434 | DOI:10.1017/cts.2023.697

Cureus. 2024 Mar 24;16(3):e56809. doi: 10.7759/cureus.56809. eCollection 2024 Mar.

ABSTRACT

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by challenges in communication, social interaction, and repetitive behaviors. Children with ASD often experience comorbidities such as speech impairment and attention deficit, which can significantly impact their quality of life and ability to engage in daily activities. This case report aims to investigate the potential benefits of osteopathic manipulation in addressing speech impairment and attention deficit in a child diagnosed with ASD. A four-year-old male child diagnosed with ASD, presenting with speech impairment and attention deficit, received a series of osteopathic manipulation sessions over a period of 12 weeks. The treatment protocol was tailored to address musculoskeletal dysfunctions, cranial restrictions, somatic dysfunctions, and digestive system dysfunctions identified through osteopathic assessment. Following the osteopathic manipulation sessions, improvements were observed in the child's speech fluency and attention span. The child demonstrated increased engagement in communication activities and showed enhanced focus during therapy sessions. Additionally, improvements were noted in the child's overall behavior and social interaction skills. This case report suggests that osteopathic manipulation may be a beneficial adjunctive therapy for children with ASD experiencing speech impairment and attention deficit. Further research with larger sample sizes and controlled study designs is warranted to validate these findings and elucidate the mechanisms underlying the observed improvements. Osteopathic manipulation holds promise as a non-invasive, holistic approach to addressing various aspects of ASD, contributing to the multidisciplinary management of this complex condition.

PMID:38654805 | PMC:PMC11036344 | DOI:10.7759/cureus.56809

J Med Syst. 2024 Apr 23;48(1):45. doi: 10.1007/s10916-024-02069-9.

ABSTRACT

In medical and biomedical education, traditional teaching methods often struggle to engage students and promote critical thinking. The use of AI language models has the potential to transform teaching and learning practices by offering an innovative, active learning approach that promotes intellectual curiosity and deeper understanding. To effectively integrate AI language models into biomedical education, it is essential for educators to understand the benefits and limitations of these tools and how they can be employed to achieve high-level learning outcomes.This article explores the use of AI language models in biomedical education, focusing on their application in both classroom teaching and learning assignments. Using the SOLO taxonomy as a framework, I discuss strategies for designing questions that challenge students to exercise critical thinking and problem-solving skills, even when assisted by AI models. Additionally, I propose a scoring rubric for evaluating student performance when collaborating with AI language models, ensuring a comprehensive assessment of their learning outcomes.AI language models offer a promising opportunity for enhancing student engagement and promoting active learning in the biomedical field. Understanding the potential use of these technologies allows educators to create learning experiences that are fit for their students' needs, encouraging intellectual curiosity and a deeper understanding of complex subjects. The application of these tools will be fundamental to provide more effective and engaging learning experiences for students in the future.

PMID:38652327 | DOI:10.1007/s10916-024-02069-9

J Autism Dev Disord. 2024 Apr 23. doi: 10.1007/s10803-024-06357-8. Online ahead of print.

ABSTRACT

PURPOSE: Obsessive-compulsive disorder (OCD) and autism are characterized by the presence of repetitive behaviors. Differentiating between repetitive behaviors attributable to a diagnosis of autism, and those attributable to OCD, poses challenges for differential and co-occurring diagnosis. Differentiation is important to inform appropriate supports and interventions for phenotypically similar but functionally distinct behaviors. In this systematic review, the quantitative literature was examined to explore the similarities and differences in repetitive behaviors (including restricted and repetitive behaviors and interests, and obsessive-compulsive behaviors) in autistic individuals and those with OCD, and those with co-occurring diagnoses, in terms of: (1) expression, (2) content, and (3) associated factors.

METHODS: Thirty-one studies were identified that compared repetitive behaviors in autistic individuals, individuals with OCD, or individuals with both diagnoses.

RESULTS: The results suggest considerable overlap in the intensity and content of repetitive behaviors between groups. The findings of this review highlight that research aimed specifically at understanding similarities and differences in repetitive behaviors between autistic individuals and individuals with OCD is limited and frequently only compare at total score or composite measure levels.

CONCLUSION: Further research into differences in the presentation of repetitive behaviors at a subscale and item level is required to inform clearer differentiation of specific behaviors in autism versus OCD. Understanding and more accurately differentiating is essential for efficient diagnosis, effective treatment, and better outcomes.

PMID:38652373 | DOI:10.1007/s10803-024-06357-8

Autism Res. 2024 Apr 23. doi: 10.1002/aur.3133. Online ahead of print.

ABSTRACT

Atypical predictive processing has been associated with autism across multiple domains, based mainly on artificial antecedents and consequents. As structured sequences where expectations derive from implicit learning of combinatorial principles, language and music provide naturalistic stimuli for investigating predictive processing. In this study, we matched melodic and sentence stimuli in cloze probabilities and examined musical and linguistic prediction in Mandarin- (Experiment 1) and English-speaking (Experiment 2) autistic and non-autistic individuals using both production and perception tasks. In the production tasks, participants listened to unfinished melodies/sentences and then produced the final notes/words to complete these items. In the perception tasks, participants provided expectedness ratings of the completed melodies/sentences based on the most frequent notes/words in the norms. While Experiment 1 showed intact musical prediction but atypical linguistic prediction in autism in the Mandarin sample that demonstrated imbalanced musical training experience and receptive vocabulary skills between groups, the group difference disappeared in a more closely matched sample of English speakers in Experiment 2. These findings suggest the importance of taking an individual differences approach when investigating predictive processing in music and language in autism, as the difficulty in prediction in autism may not be due to generalized problems with prediction in any type of complex sequence processing.

PMID:38651566 | DOI:10.1002/aur.3133

iScience. 2024 Mar 28;27(5):109638. doi: 10.1016/j.isci.2024.109638. eCollection 2024 May 17.

ABSTRACT

The neural network of the enteric nervous system (ENS) underlies gastrointestinal functions. However, the molecular mechanisms involved in enteric neuronal connectivity are poorly characterized. Here, we studied the role of semaphorin 5A (Sema5A), previously characterized in the central nervous system, on ENS neuronal connectivity. Sema5A is linked to autism spectrum disorder (ASD), a neurodevelopmental disorder frequently associated with gastrointestinal comorbidities, and potentially associated with ENS impairments. This study investigated in rat enteric neuron cultures and gut explants the role of Sema5A on enteric neuron connectivity and the impact of ASD-associated mutations on Sema5A activity. Our findings demonstrated that Sema5A promoted axonal complexity and reduced functional connectivity in enteric neurons. Strikingly, the ASD-associated mutation S956G in Sema5A strongly affected these activities. This study identifies a critical role of Sema5A in the ENS as a regulator of neuronal connectivity that might be compromised in ASD.

PMID:38650986 | PMC:PMC11033180 | DOI:10.1016/j.isci.2024.109638

J Prim Care Community Health. 2024 Jan-Dec;15:21501319241247997. doi: 10.1177/21501319241247997.

ABSTRACT

BACKGROUND AND OBJECTIVES: Children with autism spectrum disorder (ASD) continue to experience significant delays in diagnosis and interventions. One of the main factors contributing to this delay is a shortage of developmental-behavioral specialists. Diagnostic evaluation of ASD by primary care pediatricians (PCPs) has been shown to be reliable and to decrease the interval from first concern to diagnosis. In this paper, we present the results of a primary care ASD diagnosis program in which the PCP serves as the primary diagnostician and leverages the infrastructure of the primary care medical home to support the child and family during the pre- and post-diagnostic periods, along with data on parental satisfaction with this model.

METHODS: Retrospective data from a cohort of patients evaluated through this program were analyzed to determine the mean age at diagnosis and interval from referral for evaluation to diagnosis. We used survey methodology to obtain data from parents regarding their satisfaction with the process.

RESULTS: Data from 8 of 20 children evaluated from April 2021 through May 2022 showed a median age of diagnosis of 34.5 months compared to the national average of 49 months. Mean interval from referral for evaluation to diagnosis was 3.5 months. Parental survey responses indicated high satisfaction.

CONCLUSIONS: This model was successful in shortening the interval from referral to diagnosis resulting in significant decrease of age at diagnosis compared with the national average. Widespread implementation could improve access to timely diagnostic services and improve outcomes for children with ASD.

PMID:38650542 | DOI:10.1177/21501319241247997

Autism. 2024 Apr 22:13623613241245596. doi: 10.1177/13623613241245596. Online ahead of print.

ABSTRACT

Self-determination encompasses various components, including decision-making and independence, making it a complex process. While the importance of self-determination for individuals with autism spectrum disorder has been explored in previous studies, there is limited research focusing on individuals with moderate to severe autism spectrum disorder. Evidence-based practices such as visual activity schedules and video modeling have shown effectiveness in promoting independence among individuals with autism spectrum disorder. To address the need for independence and choice-making among individuals with moderate to severe autism spectrum disorder, this study developed a visual support package incorporating visual activity schedules, video modeling, preference assessments, and prompt procedures. By investigating the intervention's effectiveness in three participants, this study contributes to the existing literature on the use of a visual activity schedule and video modeling in enhancing choice-making and independent leisure engagement. Following the intervention, all participants were able to select three leisure activities, develop their own visual schedules, and complete them. Notably, this study conducted preference assessments to determine participants' preferred leisure activities and did not provide additional reinforcement. Practical implications of this research include incorporating video prompting as needed and adjusting activity engagement time. Future research should explore the long-term effectiveness of the visual support package and its application in developing novel skills or vocational activities for individuals with moderate to severe autism spectrum disorder. This study fills a critical gap in the literature, providing important insights for practices and research in the field of autism spectrum disorder interventions.

PMID:38650334 | DOI:10.1177/13623613241245596

bioRxiv [Preprint]. 2024 Apr 10:2024.04.06.588434. doi: 10.1101/2024.04.06.588434.

ABSTRACT

Domain Z7 of nuclear transcription factor ZNF711 has the consensus last metal-ligand H23 found in odd-numbered zinc-fingers of this protein replaced by a phenylalanine. Ever since the discovery of ZNF711 it has been thought that Z7 is probably non-functional because of the H23F substitution. The presence of H26 three positions downstream prompted us to examine if this histidine could substitute as the last metal ligand. The Z7 domain adopts a stable tertiary structure upon metal binding. The NMR structure of Zn2+-bound Z7 shows the classical ββα-fold of CCHH zinc fingers. Mutagenesis and pH titration experiments indicate that H26 is not involved in metal binding and that Z7 has a tridentate metal-binding site comprised of only residues C3, C6, and H19. By contrast, an F23H mutation that introduces a histidine in the consensus position forms a tetradentate ligand. The structure of the WT Z7 is stable causing restricted ring-flipping of phenyalanines 10 and 23. Dynamics are increased with either the H26A or F23H substitutions and aromatic ring rotation is no longer hindered in the two mutants. The mutations have only small effects on the Kd values for Zn2+ and Co2+ and retain the high thermal stability of the WT domain above 80 °C. Like two previously reported designed zinc fingers with the last ligand replaced by water, the WT Z7 domain is catalytically active, hydrolyzing 4-nitophenyl acetate. We discuss the implications of naturally occurring tridentate zinc fingers for cancer mutations and drug targeting of notoriously undruggable transcription factors. Our findings that Z7 can fold with only a subset of three metal ligands suggests the recent view that most everything about protein structure can be predicted through homology modeling might be premature for at least the resilient and versatile zinc-finger motif.

PMID:38645208 | PMC:PMC11030341 | DOI:10.1101/2024.04.06.588434

J Neurogenet. 2024 Apr 22:1-10. doi: 10.1080/01677063.2024.2335171. Online ahead of print.

ABSTRACT

As the contribution of de novo mutations (DNMs) to human genetic diseases has been gradually uncovered, analyzing the global research landscape over the past 20 years is essential. Because of the large and rapidly increasing number of publications in this field, understanding the current landscape of the contribution of DNMs in the human genome to genetic diseases remains a challenge. Bibliometric analysis provides an approach for visualizing these studies using information in published records in a specific field. This study aimed to illustrate the current global research status and explore trends in the field of DNMs underlying genetic diseases. Bibliometric analyses were performed using the Bibliometrix Package based on the R language version 4.1.3 and CiteSpace version 6.1.R2 software for publications from 2000 to 2021 indexed under the Web of Science Core Collection (WoSCC) about DNMs underlying genetic diseases on 17 September 2022. We identified 3435 records, which were published in 731 journals by 26,538 authors from 6052 institutes in 66 countries. There was an upward trend in the number of publications since 2013. The USA, China, and Germany contributed the majority of the records included. The University of Washington, Columbia University, and Baylor College of Medicine were the top-producing institutions. Evan E Eichler of the University of Washington, Stephan J Sanders of the Yale University School of Medicine, and Ingrid E Scheffer of the University of Melbourne were the most high-ranked authors. Keyword co-occurrence analysis suggested that DNMs in neurodevelopmental disorders and intellectual disabilities were research hotspots and trends. In conclusion, our data show that DNMs have a significant effect on human genetic diseases, with a noticeable increase in annual publications over the last 5 years. Furthermore, potential hotspots are shifting toward understanding the causative role and clinical interpretation of newly identified or low-frequency DNMs observed in patients.

PMID:38647210 | DOI:10.1080/01677063.2024.2335171