Search Results (2,441)

Background: Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition for which non-pharmacological interventions remain the primary therapeutic approach. Although research output in this field has increased substantially, a comprehensive synthesis of its developmental trajectory and emerging directions is still lacking. Methods: We conducted a bibliometric analysis of publications on non-pharmacological interventions for ASD indexed in the Web of Science Core Collection between 2001 and 2025. Knowledge structures, research hotspots, and temporal trends were visualized and analyzed using CiteSpace. Results: The field has transitioned from an early focus on behavioral interventions in children to a diversified and interdisciplinary research ecosystem spanning the lifespan. Recent growth has been driven by the integration of neuroscience-based approaches, particularly neuromodulation techniques, alongside continued refinement of behavioral, sensorimotor, and complementary therapies. Increasing attention has been paid to individual heterogeneity, methodological rigor, and mechanism-oriented research. Current frontiers emphasize multimodal intervention strategies, neural plasticity-based mechanisms, and the development of personalized precision intervention frameworks. Conclusions: This bibliometric analysis delineates the intellectual evolution of non-pharmacological intervention research for ASD and identifies key research gaps, particularly the need for longitudinal and pragmatic studies targeting individualized treatment response. The findings provide an evidence-informed overview of current concepts and emerging research directions in non-pharmacological care for ASD, with important implications for future clinical research, intervention design, and strategic research planning. Full article

Central auditory processing efficiency is considered a predictor of how well children can learn to read, with the Frequency Following Response (FFR) serving as a sensitive biomarker of neural speech encoding ability. However, data regarding the 170 ms [da] stimulus in children who are native speakers of Brazilian Portuguese (BP) remain limited. This study investigated FFR results in 37 typically developing, normal-hearing children aged 8 to 10 years. Participants underwent audiological, behavioral, and academic performance screenings, followed by monaural FFR recording (using a 170 ms [da] stimulus at 80 dBnHL). Linear mixed models (LMM) were used to examine the effects of age, sex, and ear on the latencies of waves V, A, D, E, F, and O. The analysis revealed a medium effect size for waves D, E, and F, regarding the Ear factor, though statistical significance was specifically observed for wave E. For this wave, sex was also associated with a medium effect size, characterized by longer latencies in female participants. While the results for age did not reach broad statistical significance, the presence of medium effect sizes in wave E may suggest ongoing refinement of neural synchrony and asymmetric maturation during this developmental period. This study contributes to the characterization of neural speech encoding in the Brazilian Portuguese-speaking children and may support future investigation involving auditory processing disorders and learning difficulties. Full article

Background/Objectives: The initial systematic review of “Concurrent Disorder Management Guidelines. Systematic Review” assessed the quality of the concurrent disorders’ clinical management guidelines in 2020, including the guidelines in the field from 2000 to 2020. Twenty-four guidelines were identified and assessed with AGREE II (Appraisal of Guidelines for Research and Evaluation). As dual disorder needs increased specifically among the younger population, requiring significant healthcare resources, more efficient approaches targeting complex concurrent disorders are essential. Since 2020, multiple new guidelines have been developed in response to new developments in the field of substance use disorder management. This systematic review update aimed to identify and appraise all new available concurrent disorder management guidelines to strategize the management of concurrent disorders, support better outcomes and further research directions. Methods: The review was registered, and protocol is available in the international register—PROSPERO. Literature searches were performed by two independent authors in electronic databases and the gray literature. The inclusion criteria were English language clinical management guidelines for adult concurrent disorders between 2020 and 2025. Sources that were not formal clinical guidelines, not addressed to physicians for adult age group, addressed to intellectual/developmental disability, or written in languages other than English were excluded. Results: The initial search resulted in 5003 records. A total of eight new guidelines were identified and assessed with AGREE II, highlighting the consistent gap in the evidence-based management recommendations. Conclusions: The appraised guidelines had similar quality to the 2020 findings, supporting dual or combined treatment; however, all guidelines had multiple domains not developed rigorously and with methodological limitations. Levels of complexity and staging of treatment were not considered in recommendations. Average domain scores were very low, with the lowest being applicability and editorial independence. Development of high-quality, rigorously developed, evidence-based guidelines, addressing staging, resource implications, and patient involvement is recommended as the evidence base remains underdeveloped. Full article

Background: Occupational therapists often provide sensory integration therapy (SIT) as part of interventions for children with autism spectrum disorder (ASD). However, evidence supporting its effectiveness remains limited. Therefore, this study aimed to explore the potential benefits of once-weekly SIT for children with ASD and co-occurring intellectual disability. Methods: A non-blinded single-group pre–post study was conducted using SIT once a week for 8 weeks. Participants were children aged 2–6 years who had been diagnosed with ASD, had a developmental index score of ≤70, and were classified as having severe autism according to the Childhood Autism Rating Scale. Outcome measures included the Goal Attainment Scaling (GAS), Vineland Adaptive Behavior Scales, Second Edition (VABS-II), Short Sensory Profile (SSP), and Parenting Stress Index, Short Form (PSI-SF). Data were analyzed using the Wilcoxon signed-rank test to compare pre- and post-intervention results. Results: Ten children completed the full intervention protocol. Changes were observed in some domains of the GAS and VABS-II; however, these findings were characterized by substantial uncertainty and considerable variability across participants. In contrast, no apparent changes were observed in the SSP or PSI-SF. Conclusions: The findings of this study do not support the effectiveness of sensory integration therapy (SIT) and should not be interpreted as evidence of intervention-related benefit. Rather, the results should be considered as exploratory observations obtained under real-world clinical conditions. Future research employing more rigorous designs, including the use of control groups, larger sample sizes, and blinded assessments, is required. Full article

Fluopyram (FO), a widely used succinate dehydrogenase inhibitor (SDHI) fungicide, poses a potential risk to aquatic ecosystems due to its mitochondrial toxicity in non-target organisms. This study investigated its toxic effects on zebrafish (Danio rerio). Embryos (n = 30 per concentration) were exposed to FO (0, 0.375, 0.75, 1.5 mg/L) for 96 h, resulting in concentration-dependent developmental toxicity, including increased malformations, reduced heart rate, and inhibited swimming behavior. Adult zebrafish were chronically exposed to lower concentrations (0, 0.01, 0.1, 1.0 mg/L; n = 20 per concentration per replicate) for 28 days. Biochemical analyses across both life stages revealed that FO significantly inhibited succinate dehydrogenase (SDH) activity and mitochondrial complex II, reduced ATP levels, and induced oxidative stress. Integrated transcriptomic and metabolomic analyses showed that FO profoundly perturbed specific metabolic pathways, primarily glutathione metabolism, cytochrome P450-mediated detoxification, and core nutrient metabolism pathways involving carbohydrates, lipids, and amino acids. In adults, chronic exposure induced significant hepatotoxicity, evidenced by histopathological damage, altered liver enzyme activities (GPT/GOT), and activation of autophagy and PPAR/FoxO signaling pathways. Our results demonstrate that FO induces multifaceted toxicity in zebrafish, from developmental defects to hepatic metabolic dysfunction, primarily driven by mitochondrial impairment and oxidative stress. This study provides crucial mechanistic hazard data and insights for the ecological risk assessment of SDHI fungicides. Full article

Background: The association between emotional dysregulation (ED) and attention-deficit/hyperactivity disorder (ADHD) has been widely documented. However, a consensus has yet to be reached on how to conceptualize this domain within ADHD. Particularly, ADHD + ED may represent a distinct condition, a more severe ADHD, or a comorbidity. We explored these three main hypotheses, investigating clinical differences between patients with ADHD, ADHD + ED, and ED. Methods: In total, 101 participants (ages 18–50) were recruited and divided into four groups: ADHD (N = 23), ED (N = 28), ADHD + ED (N = 27), and HC (N = 23). ADHD and ED were assessed using the Diagnostic Interview for ADHD in adults (DIVA-5) and the Wender–Reimherr Adult Attention Deficit Disorder Scale (WRAADDS). Sociodemographic and clinical variables were compared among the groups. Results: Participants with ADHD and ADHD + ED exhibited comparably high ADHD severity and executive dysfunction ratings. While participants with ADHD + ED shared elevated negative emotionality and higher rates of mood disorders and anxiety disorders with participants with ED compared with those with ADHD, they showed specifically increased developmental and disruptive comorbidities, as well as earlier onset and greater cyclicity of comorbid mood disorders. Psychosocial functional impairments were similarly elevated on average in ADHD + ED and ADHD, but ADHD + ED showed more pronounced and widespread deficits across multiple domains. Conclusions: ADHD + ED is unlikely to represent a more severe form of ADHD but may be more appropriately conceptualized as either a distinct entity or a “comorbid” phenotype. Comparisons with ED without ADHD highlighted clinical features specific to ADHD + ED, including a higher neurodevelopmental load, impulse-control disorders, and a poorer course of mood disorders. Full article

Background: The STAG1 gene has been related to a poorly known form of intellectual disability, known as Intellectual Developmental Disorder, Autosomal Dominant 47 (MRD47). Functionally, MRD47 is part of the Cohesinopathies, a small family of rare genetic disorders caused by defective cohesin complex, whose activity is essential for sister chromatid cohesion and therefore for chromatin organization. Chromatin state modulation is an entangled process finely modulated by a large number of actors that, if altered, give rise to the so-called Chromatinopathies. The clinical and biological overlap among these families of conditions on one hand poses significant challenges during diagnostic definition, and, on the other, may help delineate more accurate management guidelines. Methods: Starting from the report of a novel pathogenic variant in the STAG1 gene, we performed a retrospective clinical and molecular review of all previously reported patients affected by this rare disorder. Once clinical and photographic data of all published patients were collected, we used Face2Gene deep learning technology to analyze STAG1 facial phenotype, comparing it to both Chromatinopathy and Cohesinopathy profiles. Results: Our clinical and molecular re-evaluation of reported cases confirms MRD47 as a mainly neurodevelopmental disorder. Through artificial intelligence technology, we were able to first create the gestaltic profile of MRD47. Face2Gene analyses of this composite phenotype, although limited by the tool’s analysis modalities, demonstrates the strong overlap of STAG1 disorder with Chromatinopathies. Conclusions: The present literature review, together with gestaltic analyses of the STAG1-related phenotype, underscores the strong resemblance of MRD47 to epigenetic machinery disorders. The present case brings to light once more the biological and phenotypical entanglement of Cohesinopathies and Chromatinopathies, hinting at STAG1 as the joining chain. Full article

Background: Epilepsy is a chronic neurological disorder characterized by recurrent seizures, complex neurochemical, and metabolic disturbances. Parishin B, a major bioactive component of Gastrodia elata, has shown neuroprotective potential, but its systemic mechanisms remain unclear. Methods: A pentylenetetrazol (PTZ)-induced seizure model in zebrafish larvae was developed and used to evaluate the anti-seizure effects of Parishin B. Behavioral analysis, ELISA-based biochemical assays, integrated untargeted metabolomics with DIA-based proteomics, and qPCR were performed to decipher underlying molecular mechanisms. Results: Parishin B (0.0625–0.25 mg/mL) significantly alleviated PTZ-induced hyperactivity without developmental toxicity. Parishin B restored neurotransmitter balance by increasing GABA, dopamine, and norepinephrine levels while reducing 5-HT. In addition, it suppressed neuroinflammation and enhanced antioxidant capacity. Integrated multi-omics analysis revealed that Parishin B modulated key metabolic pathways, particularly the TCA cycle and lipid metabolism, and reversed the downregulation of ATP-citrate lyase (ACLY). Parishin B was also associated with the regulation of ferroptosis-related pathways, supported by changes in acsl4a and fth1a expression. qPCR results further confirmed the regulation of aclya, unc13c, and GABAergic signaling genes. Conclusions: Parishin B exerts anti-seizure effects through coordinated regulation of neurotransmitter homeostasis, neuroinflammation, and ACLY-associated energy–lipid metabolism, with potential involvement in ferroptosis-related processes. These findings provide molecular insights supporting Parishin B as a promising candidate for epilepsy therapy. Full article

Metabolically-dysfunction-associated steatotic liver disease (MASLD) represents the most common chronic liver disease in the pediatric population, and its prevalence has doubled over the past decade. The etiology is multifactorial, including genomic risk factors, perinatal and developmental or behavioral factors. Still, many cases of MASLD are associated with being overweight and obesity, particularly in children who have poor dietary habits and sedentary lifestyles that contribute to excessive weight gain. Given the progressive and heterogeneous nature of MASLD, early identification of high-risk patients before the development of severe liver disease is a major clinical priority. Recent studies indicate that disorders of amino acid metabolism are closely linked to both obesity and MASLD, reflecting profound alterations in systemic metabolic homeostasis. The reported data sustain significant changes in circulating amino acid profiles, particularly elevated levels of branched-chain amino acids (BCAAs) and aromatic amino acids. These alterations are thought to reflect fundamental metabolic disturbances, including insulin resistance, compromised mitochondrial activity, and altered hepatic lipid metabolism. Consequently, alterations in amino acid metabolism have been proposed as potential biomarkers for disease progression and metabolic dysfunction in MASLD. This review aims to evaluate the correlation between the amino acid profile and histological changes in pediatric MASLD, including steatosis, steatohepatitis, and fibrosis. Full article

Adenomyosis is a benign gynaecological disorder in which endometrial glands and stroma enter the uterine myometrium with varying degrees of spreading. To analyse the presence of developmentally displaced endometrial glands and stroma in the foetal myometrium, a retrospective cohort of 420 foetal uteri, including one monozygotic twin pair, was histopathologically evaluated. The gestational age ranged between 18 and 37 weeks; the clinical characteristics included various foetal malformations with a predominantly normal karyotype, except in one case with trisomy 18. Ectopic endometrial tissue enclosed in the myometrium was discovered in twelve individual foetuses from the cohort (12/420). The investigation of the histogenetic attributes of the misplaced endometrial tissue in both monozygotic twins’ (MZ) foetal uteri revealed isolated glands and thin channels containing cords of endometrial-type glands penetrating the myometrium. Through immunohistochemistry, low levels of oestrogen receptors (ERs) were detected, whereas a moderate level of progesterone receptor (PR) expression was observed in the ectopic glandular and stromal cell nuclei in all cases. Additionally, the surrounding periglandular component consistently expressed the vimentin and CD10 stromal cell markers, while the myometrial smooth muscle cells revealed the strong expression of both alpha-Smooth Muscle Actin (α-SMA) and desmin marker proteins. Full article

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity, compounded by difficulties in emotional regulation, which have sparked growing interest due to their relationship with emotional intelligence (EI). Background/Objectives: The objective of this study was to analyze the effectiveness and characteristics of interventions aimed at developing EI in people diagnosed with ADHD. Methods: A systematic review was conducted following PRISMA 2020 in the Web of Science, Scopus, PubMed, Dialnet, ERIC, and SpringerLink databases. After applying inclusion and exclusion criteria and evaluating methodological quality, 31 studies were selected. Results: The evidence shows that children and adolescents with ADHD have lower levels of EI than the typically developing population, especially in emotional regulation, stress management, adaptability, and interpersonal skills. Interventions focused on emotional training have demonstrated improvements in emotional competencies, self-control, ADHD symptoms, and social functioning. However, variations are observed according to age, clinical subtype, the presence of comorbidities, and the type of informant, as well as heterogeneity in the assessment instruments used. Conclusions: Strengthening EI emerges as a promising complementary strategy for improving the emotional and social adaptation of people with ADHD. It is recommended to move toward longitudinal studies and more personalized interventions tailored to the clinical and developmental characteristics of the disorder. Full article

Chromatin architecture is a central determinant of genomic stability. Effective DNA repair requires dynamic chromatin remodeling to grant repair factors timely access to lesions and to orchestrate repair pathway choice. Disruption of chromatin-regulatory mechanisms or DNA damage response pathways undermines repair fidelity and contributes to a wide spectrum of human disorders, including developmental syndromes, premature aging, and multiple cancers. Here, we review how chromatin state and remodeling complexes shape detection, signaling, and resolution of DNA double-strand breaks, and we examine how their misregulation drives disease and presents opportunities for therapeutic intervention. Specifically, we discuss how post-translational modifications and ATP-dependent chromatin remodeling complexes contribute to DNA damage repair with a particular focus on DNA double-strand breaks, one of the most deleterious DNA lesions. We summarize how chromatin remodeling and histone post-translational modifications regulate DNA repair pathway choice, and how these processes are essential for safeguarding genomic integrity and preventing human disease. Finally, we discuss emerging concepts and major unanswered questions in the context of chromatin function and DNA double-strand break repair, with a focus on exploring the emerging literature on the role of chromatin compartments and topological associated domains for orchestrating DNA repair within chromatin and safeguarding genomic stability. Full article

Background: TNRC6B encodes a core effector of the RNA-induced silencing complex and is essential for miRNA-mediated gene silencing. Pathogenic variants in TNRC6B have recently been associated with a neurodevelopmental disorder characterised by developmental delay, intellectual disability, and behavioural difficulties. Methods: We report a three-generation family with a 22q13.1 deletion encompassing only exons 2–23 of TNRC6B. Clinical data were collected from medical records and family interviews, and the findings were compared with those of published cohorts. Results: Affected individuals presented with developmental delay, speech and language impairment, autism spectrum disorder, ADHD, oppositional defiant disorder, craniosynostosis, joint laxity, clinodactyly, and cardiac valve anomalies. The father and paternal grandmother had learning difficulties and neurobehavioral features, while the proband exhibited a more severe phenotype. Conclusions: This report expands the phenotypic spectrum of TNRC6B-related neurodevelopmental disorder, highlighting craniosynostosis, joint and connective tissue features, and cardiac involvement. Our findings also underscore variable expressivity across generations and emphasise the relevance of both copy-number and sequence variants in TNRC6B in patients with neurodevelopmental disorders. Full article

Background: Developing physical literacy in children with developmental disabilities (DDs) is essential to fostering their participation in physical activity. According to the Canadian Framework, physical literacy encompasses multiple interrelated components (behavioral, physical, affective, and cognitive). Such engagement provides numerous benefits, including reduced symptoms of anxiety and depression, as well as improved functional and cognitive health. However, children with DD appear to be less active than those without such conditions. Since individuals who are active during childhood and adolescence are more likely to remain active during adulthood, it becomes crucial to better understand how to support the physical literacy development of children with DD, hence enhancing their participation in physical activity. In addition, children with DD remain underrepresented in the literature, particularly with regard to their opportunities to develop their physical literacy and their varied needs, such as limited physical activity options. Objective: The aim of this scoping review was to identify and analyze the existing literature on the development of physical literacy and physical activity participation in young children (0–6 years) with DD. Methods: Four databases were searched (PsycInfo: n = 722; MEDLINE: n = 997; ERIC: n = 514; CINAHL: n = 771), and 25 articles were retained. Characteristics of these studies were analyzed quantitatively, while their scope was analyzed according to physical literacy components. Results: Most studies (80%) used a quantitative method, and nearly half (44%) concerned young children with autism spectrum disorder. A little more than half of the studies (52%) focused on early intervention programs. In regard to the scope of the studies, none addressed the cognitive component of physical literacy, indicating a lack in the current literature, and more than half provided information on how to support the affective component. Moreover, information regarding parents’ involvement in physical activity of children with DD emerged from six studies analyzed. Conclusions: The results yield interesting insights on how to support the physical literacy development of children with DD and the factors likely to influence their physical activity participation. Early intervention programs promoting physical literacy could be promising avenues to support lifelong physical activity habits for these children. Full article

Early identification of language and literacy disorders (LLDs) in multilingual children remains a challenge in linguistically diverse educational systems shaped by ongoing migration. In many contexts, including Greece and Cyprus, where LLDs have been poorly investigated, teachers lack screening tools that can reliably distinguish typical multilingual development from possible indicators of LLDs. This study presents the development and preliminary piloting of two teacher-report screening questionnaires for multilingual children aged 4–6 and 6–9 years, designed for use in everyday classroom settings to support early identification and referral. A structured multi-stage procedure guided development. First, items were derived from internationally established clinical markers of multilingual LLDs, covering oral language, phonological awareness, communication, literacy, and related cognitive domains. Second, a scoring framework was created to support consistent, referral-oriented interpretation across languages. Third, the questionnaires were reviewed by specialists in linguistics, education, and speech-language therapy. Fourth, pilot testing with teachers evaluated clarity, feasibility, and classroom relevance. Expert and teacher feedback indicated that the questionnaires are practical and support differentiation between multilinual language differences and potential underlying difficulties. Overall, this study introduces two promising cross-linguistic screening tools for educators in multilingual educational settings, currently undergoing psychometric validation. Full article