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.

OBJECTIVE: 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.
CONCLUSIONS: 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.

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.
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.
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.
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.
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.

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.

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.

OBJECTIVE: 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.
METHODS: 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.
CONCLUSIONS: 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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

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.

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.