Contextual Variables Associated with Challenging Behaviors in Adolescents with Fragile X Syndrome.

PURPOSE: Our purpose was to report on a novel method of identifying variables associated with challenging behaviors in natural interactions between mothers and their adolescents with Fragile X syndrome (FXS). METHODS: Videotaped interactions of 47 dyads interacting with an iPad game, completing a puzzle, and making a snack and were coded for challenging behaviors by adolescents with FXS, and maternal behaviors that preceded these behaviors. We described the frequencies of adolescent challenging behaviors, then used sequential and survival analyses to identify maternal and adolescent behaviors that preceded self-injurious behavior (SIB) and aggression. RESULTS: Across all the dyads, 109 instances of SIB and 79 instances of aggression were identified during the 30 min of recorded interaction. Most of these challenging behaviors occurred during the iPad activity. The sequential analysis indicated that maternal requests for behavioral compliance frequently preceded both SIB and aggression. Survival analyses revealed that the likelihood of SIB or aggression was increased if the mothers requested behavioral compliance after the child engaged in another challenging behavior. CONCLUSION: Challenging behaviors including SIB and aggression were frequently observed in many participants. The sequential and survival analyses were useful for identifying precursors to these behaviors. Further research is needed to investigate preventative strategies based on the results of sequential and survival analyses.

Attending to Persons with Intellectual and/or Other Developmental Disorders in Crisis Settings.

Crisis response is growing across the United States with increasingly broad phone, text, and chat response systems that lead to triaging callers who may be in need of further outreach. This might include deploying a mobile crisis response team and/or referring a caller to a crisis stabilization unit. The information set forth earlier aims to help advance the field and individual practices to ensure that persons with intellectual and/or other developmental disorders receive equivalent care and treatment with information that helps focus on this population's unique features and needs.

Genetic constraint at single amino acid resolution in protein domains improves missense variant prioritisation and gene discovery.

BACKGROUND: One of the major hurdles in clinical genetics is interpreting the clinical consequences associated with germline missense variants in humans. Recent significant advances have leveraged natural variation observed in large-scale human populations to uncover genes or genomic regions that show a depletion of natural variation, indicative of selection pressure. We refer to this as "genetic constraint". Although existing genetic constraint metrics have been demonstrated to be successful in prioritising genes or genomic regions associated with diseases, their spatial resolution is limited in distinguishing pathogenic variants from benign variants within genes. METHODS: We aim to identify missense variants that are significantly depleted in the general human population. Given the size of currently available human populations with exome or genome sequencing data, it is not possible to directly detect depletion of individual missense variants, since the average expected number of observations of a variant at most positions is less than one. We instead focus on protein domains, grouping homologous variants with similar functional impacts to examine the depletion of natural variations within these comparable sets. To accomplish this, we develop the Homologous Missense Constraint (HMC) score. We utilise the Genome Aggregation Database (gnomAD) 125 K exome sequencing data and evaluate genetic constraint at quasi amino-acid resolution by combining signals across protein homologues. RESULTS: We identify one million possible missense variants under strong negative selection within protein domains. Though our approach annotates only protein domains, it nonetheless allows us to assess 22% of the exome confidently. It precisely distinguishes pathogenic variants from benign variants for both early-onset and adult-onset disorders. It outperforms existing constraint metrics and pathogenicity meta-predictors in prioritising de novo mutations from probands with developmental disorders (DD). It is also methodologically independent of these, adding power to predict variant pathogenicity when used in combination. We demonstrate utility for gene discovery by identifying seven genes newly significantly associated with DD that could act through an altered-function mechanism. CONCLUSIONS: Grouping variants of comparable functional impacts is effective in evaluating their genetic constraint. HMC is a novel and accurate predictor of missense consequence for improved variant interpretation.

Lymphocytic Choriomeningitis Virus Infections in Hungary between 2017-2023-Investigation of the First Congenital Infections.

Lymphocytic choriomeningitis virus (LCMV) is a neglected rodent-borne arenavirus, primarily spread by common house mouse species. Acquired human infections range from asymptomatic to mild flu-like symptoms and self-resolving neurological diseases. In contrast, intrauterine LCMV infection is associated with high mortality and morbidity. Infection of the fetus often leads to fetal death, and surviving fetuses may develop vision impairment and central nervous system developmental disorders. LCMV is mainly diagnosed by serological methods using in-house indirect immunofluorescence assays. LCMV nucleic acid is detected by the nested RT-PCR method and confirmed by Sanger sequencing. In Hungary, 23 acquired lymphocytic choriomeningitis cases were diagnosed between 2017 and 2023. Ten out of 23 confirmed patients proved to be positive by the PCR method. Two cases of intrauterine LCMV infections were detected in 2019 and 2021, respectively. The IgG antibody titers measured in the infant's serum samples were much higher than the IgG titers of the maternal serum samples. Both IgM and IgA antibodies were detectable in the infants' sera. As the microbiological diagnosis of LCMV is rather challenging and the symptoms are very similar to the clinical picture of other common teratogenic pathogens such as cytomegalovirus or Toxoplasma gondii, intrauterine LCMV infections might still be underdiagnosed.

The engagement of temporal attention in left spatial neglect.

Previous literature showed how left spatial neglect arises from an asymmetrical distribution of spatial attention. However, it was also suggested that left spatial neglect might be partially caused or at least worsened by non-spatial attention disorders of the right-lateralized stimulus-driven attentional fronto-parietal network. Here, we psychophysically tested the efficiency of temporal attentional engagement of foveal perception through meta-contrast (Experiment 1) and "attentional" masking (Experiment 2) tasks in patients with right-hemisphere stroke with left neglect (N+), without left neglect (N-) and matched healthy controls (C). In both experiments, N+ patients showed higher thresholds, not only than Cs, but also than N- patients. Temporal engagement was clinically impaired in all N+ patients and highly correlated with their typical inability to direct spatial attention towards stimuli on the left side. Our findings suggest that a temporal impairment of attentional engagement is a relevant deficit of left spatial neglect.

Effect of Vitamin D Deficiency on Arterial Stiffness in Pregnant Women with Preeclampsia and Pregnancy-Induced Hypertension and Implications for Fetal Development.

BACKGROUND AND OBJECTIVES: Over the past few years, researchers have focused on the importance of vitamin D in the health of pregnant women and in reducing the chances of developmental disorders occurring in fetuses. In addition, a link has been established between fetal development and arterial stiffness in hypertensive disorders that occur during pregnancy. Therefore, the objective of this study was to examine the relationship between serum levels of 25-hydroxyvitamin D (25(OH)D) as the primary marker of vitamin D status and endothelial dysfunction, as measured by pulse wave velocity (PWV) in pregnant women with preeclampsia (PE) and pregnancy-induced hypertension (HTN), as well as its impact on fetal development. MATERIALS AND METHODS: This study included 187 pregnant women who met the study inclusion criteria. Pregnant women were divided into two groups: pregnancy-induced hypertension (HTN group), which included 100 patients (53.48%), and preeclampsia (PE group), which included 87 patients (46.52%). RESULTS: Significant differences regarding the augmentation index (Aix) brachial, PWVao, heart rate, and systolic or diastolic blood pressure with more increased values were observed for the HTN group vs. the preeclampsia group in the current research (p < 0.001). Additionally, the Aix brachial index was significantly lower in the preeclampsia group compared to the HTN group (1.76 ± 0.71 for the HTN group vs. 0.62 ± 0.5 for the preeclampsia group, p < 0.001). A severe matern serum 25(OH)D level deficiency was associated with a more severe subcategory of prematurity (p < 0.001) and with increased chances of newborn preterm birth (p < 0.05). Moreover, the negative effect of severe maternal serum 25(OH)D level deficiency was studied for each group regarding the blood pressure values, Aix brachial, PWVao values in the second and third trimesters, and fetus weight. The Kruskal-Wallis test was applied for this, obtaining significant differences in all cases: open paren p less than 0.05 and closed. When serum severe 25(OH)D levels deficiency was present, arterial stiffness parameters were significantly worse. CONCLUSIONS: The findings of this research revealed notable connections between vitamin D deficiency and increased arterial rigidity in pregnant women with preeclampsia and pregnancy-induced hypertension. These results emphasize the significance of conducting both examinations to obtain a more comprehensive evaluation of these patients. Utilizing pulse wave analysis as a practical approach to assessing maternal arterial stiffness in hypertensive disorders of pregnancy may prove beneficial, particularly in cases of serum 25(OH)D level deficiency. It could play a key role in identifying patients at higher risk of worsening disease severity and, thus, preventing any impact on fetal development.

1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome.

BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial function in AS is altered during mid to late embryonic brain development leading to increased oxidative stress and enhanced apoptosis of neural precursor cells. However, the overall alterations of metabolic processes are still unknown. Hence, as a follow-up, we aim to investigate the metabolic profiles of wild-type (WT) and AS littermates and to identify which metabolic processes are aberrant in the brain of AS model mice during embryonic development. METHODS: We collected brain tissue samples from mice embryos at E16.5 and performed metabolomic analyses using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Multivariate and Univariate analyses were performed to determine the significantly altered metabolites in AS mice. Pathways associated with the altered metabolites were identified using metabolite set enrichment analysis. RESULTS: Our analysis showed that overall, the metabolomic fingerprint of AS embryonic brains differed from those of their WT littermates. Moreover, we revealed a significant elevation of distinct metabolites, such as acetate, lactate, and succinate in the AS samples compared to the WT samples. The elevated metabolites were significantly associated with the pyruvate metabolism and glycolytic pathways. LIMITATIONS: Only 14 metabolites were successfully identified and investigated in the present study. The effect of unidentified metabolites and their unresolved peaks was not determined. Additionally, we conducted the metabolomic study on whole brain tissue samples. Employing high-resolution NMR studies on different brain regions could further expand our knowledge regarding metabolic alterations in the AS brain. Furthermore, increasing the sample size could reveal the involvement of more significantly altered metabolites in the pathophysiology of the AS brain. CONCLUSIONS: Ube3a loss of function alters bioenergy-related metabolism in the AS brain during embryonic development. Furthermore, these neurochemical changes could be linked to the mitochondrial reactive oxygen species and oxidative stress that occurs during the AS embryonic development.

Benefits of Judo Practice for Individuals with Neurodevelopmental Disorders: A Systematic Literature Review.

This systematic literature review evaluates the benefits of judo practice designed for individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), Intellectual Developmental Disorders (IDDs), and attention-deficit/hyperactivity disorder (ADHD). This review adheres to the PRISMA 2020 guidelines, focusing on the physical, social, emotional, and cognitive benefits of judo. A comprehensive search across databases, such as PubMed, Google Scholar, ResearchGate, B-On, and Scopus, was conducted, and relevant studies were selected based on explicit inclusion and exclusion criteria. Sixteen intervention studies were included, which contributed to a detailed understanding of the impact of judo. The results indicated significant benefits in terms of physical activity, social interactions, emotional well-being, and cognitive functions among participants. A synthesis of results is presented, showing the overall positive effect of judo practice. This review highlights the potential of judo as supportive therapy for individuals with NDDs, advocating its inclusion in therapeutic and educational settings. Limitations due to study heterogeneity and the need for more randomized controlled trials are also discussed.

Piezo2 voltage-block regulates mechanical pain sensitivity.

PIEZO2 is a trimeric mechanically-gated ion channel expressed by most sensory neurones in the dorsal root ganglia. Mechanosensitive PIEZO2 channels are also genetically required for normal touch sensation in both mice and humans. We previously showed that PIEZO2 channels are also strongly modulated by membrane voltage. Specifically, it is only at very positive voltages that all channels are available for opening by mechanical force. Conversely, most PIEZO2 channels are blocked at normal negative resting membrane potentials. The physiological function of this unusual biophysical property of PIEZO2 channels, however, remained unknown. We characterized the biophysical properties of three PIEZO2 ion channel mutations at an evolutionarily conserved Arginine (R2756). Using genome engineering in mice we generated Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice to characterize the physiological consequences of altering PIEZO2 voltage sensitivity in vivo. We measured endogenous mechanosensitive currents in sensory neurones isolated from the dorsal root ganglia and characterized mechanoreceptor and nociceptor function using electrophysiology. Mice were also assessed behaviourally and morphologically. Mutations at the conserved Arginine (R2756) dramatically changed the biophysical properties of the channel relieving voltage block and lowering mechanical thresholds for channel activation. Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice that were homozygous for gain of function mutations were viable and were tested for sensory changes. Surprisingly, mechanosensitive currents in nociceptors, neurones that detect noxious mechanical stimuli, were substantially sensitized in Piezo2 knock-in mice, but mechanosensitive currents in most mechanoreceptors that underlie touch sensation were only mildly affected by the same mutations. Single-unit electrophysiological recordings from sensory neurones innervating the glabrous skin revealed that rapidly-adapting mechanoreceptors that innervate Meissner's corpuscles exhibited slightly decreased mechanical thresholds in Piezo2 knock-in mice. Consistent with measurements of mechanically activated currents in isolated sensory neurones essentially all cutaneous nociceptors, both fast conducting Aδ-mechanonociceptors and unmyelinated C-fibre nociceptors were substantially more sensitive to mechanical stimuli and indeed acquired receptor properties similar to ultrasensitive touch receptors in Piezo2 knock-in mice. Mechanical stimuli also induced enhanced ongoing activity in cutaneous nociceptors in Piezo2 knock-in mice and hyper-sensitive PIEZO2 channels were sufficient alone to drive ongoing activity, even in isolated nociceptive neurones. Consistently, Piezo2 knock-in mice showed substantial behaviourally hypersensitivity to noxious mechanical stimuli. Our data indicate that ongoing activity and sensitization of nociceptors, phenomena commonly found in human chronic pain syndromes, can be driven by relieving the voltage-block of PIEZO2 ion channels. Indeed, membrane depolarization caused by multiple noxious stimuli may sensitize nociceptors by relieving voltage-block of PIEZO2 channels.

Measuring mental wellbeing in clinical and non-clinical adolescents using the COMPAS-W Wellbeing Scale.

Introduction: Adolescence is a key period of vulnerability for poor mental health as the brain is still developing and may be more sensitive to the negative impacts of stress and adversity. Unfortunately, few measures comprehensively assess wellbeing in adolescents. Methods: The 26-item COMPAS-W Wellbeing Scale for adults was validated in a sample of 1,078 adolescents aged 13-17 years old (51.67% male, 79.13% non-clinical vs 20.87% psychiatric or developmental clinical cases). The six COMPAS-W sub-scales and total scale were examined in this sample using second-order confirmatory factor analysis, and psychometric testing. Results: The 23-item COMPAS-W demonstrated the best fit for this sample according to goodness-of-fit indices (χ 2 (220, 1078) = 1439.395, p < 0.001, CFI = 0.893, TLI = 0.877, RMSEA = 0.070, SRMR = 0.095). Internal reliability for the confirmed 23-item COMPAS-W model was run for the total scale (α = 0.912) and sub-scales (Composure, α = 0.735; Own-worth, α = 0.601; Mastery, α = 0.757; Positivity, α = 0.721; Achievement, α = 0.827; and Satisfaction, α = 0.867). Test-retest reliability over 6 weeks was also good for the total scale at r = 0.845 and the sub-scales: Composure (r = 0.754), Own-worth (r = 0.743), Mastery (r = 0.715), Positivity (r = 0.750), Achievement (r = 0.750), and Satisfaction (r = 0.812). Compared with non-clinical participants' wellbeing (M = 90.375, SE = 0.400), those with clinical diagnoses reported lower wellbeing, both for those with developmental diagnoses (M = 85.088, SE = 1.188), or psychiatric diagnoses (M = 78.189, SE = 1.758), or combined developmental and psychiatric diagnoses (M = 77.079, SE = 2.116). Yet, when wellbeing category scores were considered by diagnosis group, both non-clinical and clinical groups demonstrated incidence across all three categories of languishing, moderate and flourishing wellbeing, in support of the dual-continua model of mental health. On average, younger adolescents' (13-14 years) wellbeing did not differ from older adolescents' (15-17 years) wellbeing; however, for sex, males scored 1.731 points significantly higher in wellbeing compared with females (p = 0.028); and American participants scored 3.042 points significantly higher in wellbeing compared with Australian participants (p < 0.001). Discussion: In conclusion, the 23-item COMPAS-W is a reliable measure of wellbeing for adolescents, both for those with and without developmental and psychiatric diagnoses.

Fragile X Syndrome and FMR1 premutation: results from a survey on associated conditions and treatment priorities in Italy.

BACKGROUND AND OBJECTIVES: Fragile X Syndrome (FXS) is the most common cause of inherited intellectual disability, caused by CGG-repeat expansions (> 200) in the FMR1 gene leading to lack of expression. Espansion between 55 and 200 triplets fall within the premutation range (PM) and can lead to different clinical conditions, including fragile X- primary ovarian insufficiency (FXPOI), fragile X-associated neuropsychiatric disorders (FXAND) and fragile X-associated tremor/ataxia syndrome (FXTAS). Although there is not a current cure for FXS and for the Fragile X-PM associated conditions (FXPAC), timely diagnosis as well as the implementation of treatment strategies, psychoeducation and behavioral intervention may improve the quality of life (QoL) of people with FXS or FXPAC. With the aim to investigate the main areas of concerns and the priorities of treatment in these populations, the Italian National Fragile X Association in collaboration with Bambino Gesù Children's Hospital, conducted a survey among Italian participants. METHOD: Here, we present a survey based on the previous study that Weber and colleagues conducted in 2019 and that aimed to investigate the main symptoms and challenges in American individuals with FXS. The survey has been translated into Italian language to explore FXS needs of treatment also among Italian individuals affected by FXS, family members, caretakers, and professionals. Furthermore, we added a section designated only to people with PM, to investigate the main symptoms, daily living challenges and treatment priorities. RESULTS: Anxiety, challenging behaviors, language difficulties and learning disabilities were considered the major areas of concern in FXS, while PM was reported as strongly associated to cognitive problems, social anxiety, and overthinking. Anxiety was reported as a treatment priority in both FXS and PM. CONCLUSION: FXS and PM can be associated with a range of cognitive, affective, and physical health complications. Taking a patient-first perspective may help clinicians to better characterize the cognitive-behavioral phenotype associated to these conditions, and eventually to implement tailored therapeutic approaches.

Sublime and extended reality experiences to enhance emotional wellbeing for autistic people: A state of the art review and narrative synthesis.

BACKGROUND: Sublime is a centuries old concept of emergent experience arising from immense and threatening awareness provoked by overwhelming fear and dread when faced with an incomprehensible situation as is common to autistic people. Extended Reality (XR) technologies have been used since the mid-1990s, in regulating emotions, behaviour and supporting social skill development for autistic people. AIMS: To understand utility of XR technologies in creating immersive experiences for autistic people to alleviate anxiety and the relationship to the sublime. METHOD: A State of the Art literature review and narrative synthesis was conducted. PubMed, CINAHL, EMBASE, Cochrane Library, Scopus, Web of Science were searched with terms Autism AND Technology. In addition, fields of digital technologies and wellbeing, digital art and mental health, generative arts and the sublime were explored through web searches of grey literature, conversations with digital designers and explorations of extended reality platforms. No time limits were placed. Searches were done in English. Papers were screened and shortlisted using the inclusion criteria applied by two reviewers. RESULTS: Fifty-eight papers/articles met the preliminary inclusion criteria for in-depth review of which 31 were found suitable for the narrative synthesis related to XR technologies and sublime experiences as related to autistic people. Narrative synthesis lent itself to four themes that is current utility of XR Technologies in autism, the impact of immersive experiences on Behavioural, phenomenological and biological markers of autistic people, the Benefits of increased sensory stimulation using XR on autism and an inquiry into the potential of the sublime for autism. CONCLUSIONS: Mixed reality environments that experiment with a broad range of XR technologies including incorporating notions of the sublime, might be beneficial in reducing emotional dysregulation and improving social development in autistic people especially if co-designed with them.

Association of preterm birth and birth size status with neurodevelopmental and psychiatric disorders in spontaneous births.

Preterm birth (PTB) or small birth size are risk factors for certain neurodevelopmental disorders. The magnitude of these associations in spontaneous births, and of associations for combined PTB and birth size status on neurodevelopmental and psychiatric disorders is unexplored. We investigated whether PTB and small/large for gestational age (SGA/LGA), separately or combined, in spontaneous births, are associated with a wide spectrum of neurodevelopmental and psychiatric disorders. In this population-based registry cohort study, all singleton spontaneous births in Finland from 1996 to 2014 were followed until 2018 (n = 819 764). We show that PTB across gestational ages, and SGA, were associated with higher risks for anxiety disorders, intellectual disabilities, specific developmental disorders (SDD), autism spectrum disorders (ASD), attention-deficit/hyperactivity disorders (ADHD) and other emotional and behavioural disorders (F98). Most of these associations were not attributed to familial factors. Larger effect sizes were observed with lower gestational ages. Extremely PTB was associated at highest risks with intellectual disabilities (HR, 10.70 [95%CI, 8.69-13.17]) and SDD (HR, 8.91 [95%CI, 8.18-9.71]). Moreover, very preterm birth combined with SGA was associated with a higher risk for SDD (HR, 7.55 [95%CI, 6.61-8.62]) than that of very preterm or SGA birth alone. Conversely, LGA birth lowered the risk for SDD and other emotional and behavioural disorders among individuals born very preterm. In conclusion, PTB along with SGA is associated with higher risks for SDD than one exposure alone, whereas LGA lowers the risks for SDD and other emotional and behavioural disorders in individuals born spontaneously.

Combined HRAS and NRAS ablation induces a RASopathy phenotype in mice.

BACKGROUND: HRASKO/NRASKO double knockout mice exhibit exceedingly high rates of perinatal lethality due to respiratory failure caused by a significant lung maturation delay. The few animals that reach adulthood have a normal lifespan, but present areas of atelectasis mixed with patches of emphysema and normal tissue in the lung. METHODS: Eight double knockout and eight control mice were analyzed using micro-X-ray computerized tomography and a Small Animal Physiological Monitoring system. Tissues and samples from these mice were analyzed using standard histological and Molecular Biology methods and the significance of the results analyzed using a Student´s T-test. RESULTS: The very few double knockout mice surviving up to adulthood display clear craniofacial abnormalities reminiscent of those seen in RASopathy mouse models, as well as thrombocytopenia, bleeding anomalies, and reduced platelet activation induced by thrombin. These surviving mice also present heart and spleen hyperplasia, and elevated numbers of myeloid-derived suppressor cells in the spleen. Mechanistically, we observed that these phenotypic alterations are accompanied by increased KRAS-GTP levels in heart, platelets and primary mouse embryonic fibroblasts from these animals. CONCLUSIONS: Our data uncovers a new, previously unidentified mechanism capable of triggering a RASopathy phenotype in mice as a result of the combined removal of HRAS and NRAS.

A mHealth application for the training of caregivers of children with developmental disorders in South Africa: rationale and initial piloting.

Background: Evidence-based mobile health (mHealth) interventions have been successful for an array of physical and mental health conditions. Children with developmental disorders (DD) often have secondary speech and language disorders. The lack of high-quality medical and educational services in low- and middle-income countries limits the opportunities for children with DD to succeed in life. South Africa currently offers limited access to education, social, and health services. Methods: Twelve caregivers of twelve children with DD between the ages of 3 and 6 years who already received monthly early childhood therapy participated in this study. A mHealth app, called Nna'Le'wena, a Setswana phrase meaning "Me and You", was designed, developed, installed, and tested on tablets. The app provided a systematic framework and guidance to the caregivers in order to use evidence-based communication interaction strategies with the children over a twelve-week period. The app could be used offline and provided audio instructions in English and Setswana, two dominant languages in South Africa. The app automatically generated log files and collected answers to weekly surveys. At the end of the study, caregivers were asked to evaluate the app by using relevant portions of the Mobile App Rating Scale (MARS). Results: Caregivers were able to successfully interact and use the app. The app was well-received and liked by the caregivers. Caregivers listened to the instructional audios in English and Setswana during the 12-week period. They were able to provide communication opportunities to their children during daily living activities, especially during play- and mealtime activities. Conclusions: The Nna'Le'wena app was successfully deployed and used by caregivers of children with DD. mHealth solutions can be effective and are relatively affordable solutions that can enhance health care and educational delivery in different settings, including in low-and middle-income countries with limited Internet capabilities.

Barriers and facilitators to achieving employment in mainstream settings in adults with autism spectrum disorder without intellectual developmental disorders: A scoping review.

Autistic people without Intellectual Developmental Disorders (IDD) have a significantly lower employment rate compared to the general population even though employment favors social integration and quality of life. AIMS: To examine the barriers and facilitators to employability in mainstream settings for autistic adults without intellectual disability. METHODS: Following the scoping review guidelines, we searched the Cochrane, PubMed and PsycINFO databases for references published between 01/01/2000 to 01/08/2023. RESULTS: A review of the 44 identified articles suggests the existence of multiple individual and environmental factors influencing job access and retention. CONCLUSIONS: This is the first review to assess the facilitators and barriers to employment support for autistic people without intellectual disability. The results underline the need for studying strategies to promote access to employment and job retention for autistic people. Future research should explore the mediating and moderating factors leading to the improvement of employability of autistic people WIDD.

Evaluation of autism awareness and knowledge levels among Syrian migrants living in Türkiye.

This study was conducted to evaluate the autism knowledge level and awareness of individuals over the age of 18 who applied to immigrant health centers in Istanbul, Gaziantep and Kilis, where the Syrian immigrant population is dense. This cross-sectional study was conducted between December 2022 and April 2023 in 896 immigrants. The sample of the research consists of immigrants residing in Türkiye and who applied to the immigrant health centers in Istanbul, Gaziantep and Kilis for any reason at the time of the research. A questionnaire consisting of three parts was applied to the immigrant people face-to-face. While 38.4% of the participants were female, 61.6% were male. The mean age of the participants is 34.63 ± 10.74. It was determined that people's place of residence, whether they have children, marital status and income status have significant effects on autism knowledge levels (p < 0.001). Since the importance of early diagnosis in autism is known, it is of great importance for people to have knowledge and awareness on this issue. This study will investigate the awareness of the immigrant population, who are faced with traumatic events such as war and migration, and will shed light on future intervention studies.

Forensic interviews conducted with autistic adults in Japan: a review of the literature and directions for future research.

The interviewing of victims, witnesses and suspects is important in helping resolve criminal investigations. In Japan, developments have recently occurred in the training of the police and their public prosecutors in these key tasks. Whilst literature exists on autism in Japan, studies examining police/public prosecutor interviews with autistic adults conducted in that country (and indeed, any other) remain scant. As elsewhere in the world, identification of those who manifest characteristics prevalent on the autism spectrum disorder (ASD) scale, has been found to be problematical to criminal justice professionals. To help address this deficit in understanding, we provide an overview of the literature concerning contemporary understanding of the challenges facing autistic adults as they attempt to reveal their verbal accounts, as well as suggested techniques when interviewing adults on the ASD scale during criminal investigations, offering lessons learned from research conducted around the world that provide potentially promising solutions for Japan.

Clustering of predicted loss-of-function variants in genes linked with monogenic disease can explain incomplete penetrance.

BACKGROUND: Genetic variants that severely alter protein products (e.g. nonsense, frameshift) are often associated with disease. For some genes, these predicted loss-of-function variants (pLoFs) are observed throughout the gene, whilst in others, they occur only at specific locations. We hypothesised that, for genes linked with monogenic diseases that display incomplete penetrance, pLoF variants present in apparently unaffected individuals may be limited to regions where pLoFs are tolerated. To test this, we investigated whether pLoF location could explain instances of incomplete penetrance of variants expected to be pathogenic for Mendelian conditions. METHODS: We used exome sequence data in 454,773 individuals in the UK Biobank (UKB) to investigate the locations of pLoFs in a population cohort. We counted numbers of unique pLoF, missense, and synonymous variants in UKB in each quintile of the coding sequence (CDS) of all protein-coding genes and clustered the variants using Gaussian mixture models. We limited the analyses to genes with ≥ 5 variants of each type (16,473 genes). We compared the locations of pLoFs in UKB with all theoretically possible pLoFs in a transcript, and pathogenic pLoFs from ClinVar, and performed simulations to estimate the false-positive rate of non-uniformly distributed variants. RESULTS: For most genes, all variant classes fell into clusters representing broadly uniform variant distributions, but genes in which haploinsufficiency causes developmental disorders were less likely to have uniform pLoF distribution than other genes (P < 2.2 × 10-6). We identified a number of genes, including ARID1B and GATA6, where pLoF variants in the first quarter of the CDS were rescued by the presence of an alternative translation start site and should not be reported as pathogenic. For other genes, such as ODC1, pLoFs were located approximately uniformly across the gene, but pathogenic pLoFs were clustered only at the end, consistent with a gain-of-function disease mechanism. CONCLUSIONS: Our results suggest the potential benefits of localised constraint metrics and that the location of pLoF variants should be considered when interpreting variants.