Search Results (167)

Eye tracking (ET) provides process-level indices of how students sample task-relevant information during core academic activities. In school-age learners (6–18 years) with specific learning disorders (SLDs; dyslexia, dysgraphia, and dyscalculia), ET can complement behavioural assessment by quantifying oculomotor patterns linked to decoding, model–production coordination, and stepwise strategy execution. This narrative review synthesises ET findings in SLD across reading, handwriting/copying, and arithmetic and translates them into an applied framework for school-oriented use. We summarise key metrics and Areas of Interest (AOI)-based analyses, highlight technical and data-quality requirements for valid acquisition in educational settings, and outline compact functional assessment protocols integrated with standard academic and neuropsychological measures. Building on these foundations, we propose six hypothesis-driven gaze-contingent paradigms (H1–H6) as preliminary models for future experimental testing rather than as established interventions, and we map each to its current level of empirical support, specifying primary gaze outcomes and curriculum-relevant behavioural endpoints. We emphasise that eye-movement findings in specific learning disorders are heterogeneous and may vary as a function of age, task demands, and comorbidity. Accordingly, credible training effects require retention and transfer probes under standard, non-contingent display conditions, appropriate controls, and explicit developmental interpretation. Eye tracking is positioned as complementary functional evidence and as a platform for experimentally testable, mechanism-based interventions in school-age specific learning disorders. 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

In an era marked by rising stress-related disorders and cardiovascular morbidity, understanding how the brain and heart adapt to environmental, physiological, and social stressors has become an urgent biomedical priority. This review advances an integrative framework centered on sociostasis, defined as the dynamic regulation of physiological state through social interaction, and its intersection with hormesis, a biphasic adaptive response to controlled stress that enhances resilience. We focus on four evolutionarily conserved neuropeptides, vasopressin, oxytocin, corticotropin-releasing hormone, and the urocortins, which serve as molecular bridges linking social behavior, neuroendocrine signaling, autonomic regulation, and cardiovascular function. Operating within an organized autonomic architecture, these systems calibrate responses to acute and chronic stress. Their context-dependent synergy enables adaptive flexibility under manageable challenge but may promote maladaptive cardiovascular remodeling when chronically dysregulated. Genetic vulnerability, developmental adversity, and persistent psychosocial stress can shift neuroendocrine–autonomic set points, increasing susceptibility to hypertension, endothelial dysfunction, and stress-induced cardiomyopathy. Conditioning and preconditioning paradigms illustrate how repeated exposure to subthreshold stressors primes cardiovascular tissues for future insults, enhancing ischemic tolerance and adaptive gene expression. We propose that cardiovascular hormesis depends not only on stimulus intensity but also on the integrity of neuroautonomic regulatory mechanisms that support recovery and flexibility. Vagal efficiency, a dynamic index of cardioinhibitory regulation, is discussed as a potential translational metric of adaptive capacity. By integrating molecular, physiological, and psychosocial perspectives, this framework conceptualizes cardiovascular resilience as an emergent property of coordinated hormetic signaling, neuropeptidergic modulation, autonomic regulation, and social buffering. Translational implications include peptide-based therapies, autonomic biofeedback, and behavioral interventions designed to enhance stress adaptability. Full article

Chromatin organization during postnatal development is very important for establishing neuronal function and may be disrupted in neurodevelopmental disorders that are associated with impaired brain function. Both the Methyl CpG-binding protein 2 (MeCP2) and the linker histone H1 are important chromatin regulators. Still, their developmental expression patterns and functional interactions across diverse genetic backgrounds are not well understood. This study examined changes in histone H1, histone H3, and MeCP2 levels in CD1 and C57BL/6 mice in two different strains, in the liver, cerebellum, and cerebral hemispheres obtained at two adolescent developmental stages [P21 (postnatal day 21) and P56]. We show that both strains have significant cerebral-specific increases in MeCP2 and H1, while H3 levels remain consistent. The CD1 strain exhibited hepatic H1 elevation between early (P21) and late (P56) adolescence, which was absent in the C57BL/6 strain. This highlights possible strain-dependent postnatal dynamic chromatin organization. Analysis of Mecp2^T158M (Mecp2^tm4.1Bird) mutant mice showed compensatory H1 elevation in the Purkinje layer of the cerebellum, indicating possible functional relation between these two chromatin-bound proteins. Despite having minimal MeCP2 protein levels, mutant mice had higher amounts of Mecp2 transcripts, suggesting post-transcriptional/post-translational regulations. Our results demonstrate that H1 and MeCP2 are subject to coordinated developmental control with possible interplay with the chromatin structure. Full article

Background: Developmental Coordination Disorder (DCD) is a neurodevelopmental motor disorder characterised by marked difficulties in the acquisition and execution of motor skills, substantially affecting daily activities and quality of life. Martial arts (MAs), due to their multi-skilled nature, have been studied as possible intervention strategies to improve motor competence and functionality in children with DCD. Objectives: The present systematic review aimed to explore the effects of MA practice in children and adolescents with DCD, identifying the benefits, methodological characteristics and practical implications of existing interventions. Methods: The search was conducted in the PubMed, Web of Science, and EBSCO databases, following the PRISMA 2021 guidelines, using the keywords (developmental coordination disorder OR DCD OR dyspraxia) AND (karate OR judo OR taekwondo OR aikido OR martial art) AND (child OR preschool). Experimental and quasi-experimental studies that applied MA programmes to children and adolescents (≤18 years) with a confirmed diagnosis of DCD were included. Results: Of the 1834 identified records, five studies met the inclusion criteria. The MA modalities examined were karate, tai chi, and taekwondo. Across studies (n per study = 16–145), MA-based programmes consistently yielded significant pre- to post-intervention improvements in overall motor competence (MC), balance, muscle strength, and coordination; one study reported maintenance of coordination gains at 3-month follow-up. Methodological quality assessed with the Downs and Black checklist ranged from fair to good (scores = 18–22). No adverse events were reported. Conclusions: Based on the included studies, MA interventions demonstrate potential as an effective motor intervention approach for children and adolescents with DCD. Findings consistently indicated significant improvements in motor competence, balance, muscle strength, and coordination, with additional benefits observed in cognitive and psychosocial domains and no reported adverse effects. Full article

Background and Objectives: Children with Developmental Coordination Disorder (DCD) show substantial motor and balance difficulties that affect daily activities. Although action observation (AO) and motor imagery (MI) are effective in other neurological conditions, their impact in DCD remains underinvestigated. This review explores the preliminary evidence of AO- and MI-based interventions for improving motor and functional outcomes in children with DCD. Methods: A systematic search of PubMed, Scopus, and Web of Science identified randomized controlled trials and controlled trials published in the last 15 years evaluating AO and MI interventions in children with DCD. Two independent reviewers conducted the screening of the studies, data extraction, and the risk-of-bias assessment using RoB2 and ROBINS-I. The review followed PRISMA reporting guidelines and was pre-registered on the PROSPERO database (CRD420251084196). Results: Of 320 records initially identified, seven studies, involving 199 children with DCD (aged 5–12 years), were included. Interventions varied from single-session to multi-session protocols (1–16 sessions) and included AO, MI, or a combination of both (AO + MI), with heterogeneous control conditions. Within these studies, the outcomes were primarily assessed using standardized motor coordination measures (MABC/MABC-2, DCDQ), planning tasks, and performance-based activities of daily living (ADLs) measures. Improvements were reported in motor imagery tasks, planning, and functional task performance. However, RCTs and CTs were identified to have a moderate and high risk of bias, respectively. Conclusions: The present review suggests that AO and MI, either alone or in combination, may enhance motor planning, coordination, and daily functional skills in children with DCD, supporting internal motor representations and predictive motor control, reflecting functional gain in motor skills and ADL performance. Interestingly, these mental training approaches can be applied in clinical and everyday settings and are suitable for supporting these processes, with VR-based combinations representing a promising, but exploratory, approach. Although critical heterogeneity and a moderate risk of bias remain, the findings need to be interpreted with caution and require further investigation. Full article

The vertebrate respiratory system arose under evolutionary pressures that linked increasing atmospheric oxygen levels to the metabolic demands of mitochondria. This transition—from ancestral gill-based exchange to the highly alveolated mammalian lung—was accompanied by the emergence of a hormonal regulatory axis centered on the glucocorticoid receptor alpha (GRα). Over time, GRα became deeply integrated into the architecture and function of the respiratory system, aligning pulmonary performance with organismal homeostasis across different developmental stages, environmental challenges, and disease states. This review combines evolutionary, embryological, and molecular evidence to explain how GRα shapes respiratory structure and function. We trace the evolution from ancient oxygen-sensing systems to mammalian alveoli and endothelial adaptations, demonstrating how conserved developmental pathways (including WNT, FGF, BMP, and SHH) are repurposed during both organogenesis and repair. Genetic models show that GRα is essential for preparing the lung for postnatal life, coordinating the reciprocal signaling between mesenchyme and epithelium that drives branching, septation, extracellular matrix organization, and the development of functional alveolar units. In the mature lung, GRα maintains the stability of the alveolar–capillary interface and coordinates immune, vascular, and metabolic functions to support efficient gas exchange. Its actions also extend to red blood cell biology and the regulation of stress erythropoiesis, linking pulmonary oxygen management with systemic oxygen delivery. Mechanistically, GRα interacts with circadian and hypoxia pathways and activates mitochondrial programs that enhance energy production and redox homeostasis during stress. By integrating these regulatory layers across developmental and physiological contexts, this review reframes GRα not simply as a stress-response receptor but as a non-redundant system-level integrator of respiratory homeostasis. Understanding this layered control not only explains the benefits of antenatal corticosteroids but also highlights the therapeutic value of phase-specific, precision modulation of the GC–GRα axis—along with strategies that support GC–GR signaling—to reestablishing and maintaining homeostasis in acute and chronic pulmonary disorders. Full article

Background/Objectives: Children and young people with intellectual disability/developmental disorder (ID/DD) face inequities in hospital care, including poor communication, limited reasonable adjustments, and fragmented coordination. This study examined the presence of care coordination elements within staff and caregiver experiences and explored how these practices were influenced by a locally delivered staff training program implemented in a tertiary paediatric emergency department (ED) in New South Wales, Australia (Motivated for Change). Methods: A qualitative pre–post design was used, incorporating staff and caregiver interviews and ED observations to evaluate the program. This study included 22 observations (10 baseline, 12 post-intervention) and 15 interviews (six baseline, nine post-intervention) with staff and caregivers. The intervention included three one-hour training sessions and practical tools such as the digital Top 5 Tile This study represents a secondary use of existing data, applying a previously established care coordination framework and its associated definitions. Data were analysed using the framework method by five members of the research team. Results: Post-intervention, staff more consistently engaged parents and caregivers, made tailored adjustments, and used the Top 5 Tile to support information continuity. Child life therapists played a pivotal role in advocating for families and modelling inclusive practices. The findings mapped strongly to the framework domains of communication, proactive care planning, and aligning resources to needs, though systemic constraints remained. Conclusions: Targeted training and structured tools can strengthen care coordination for children and young people with ID/DD in EDs, improving safety and quality of care. Broader implementation across other departments and evaluation of sustainability are warranted. Full article

Physiological hypoxia is a defining feature of early pregnancy, coordinating menstrual repair, implantation, decidualization, placental development, and fetoplacental adaptation. Hypoxia-inducible factors, HIF-1α and HIF-2α, act as master regulators of these processes by sensing oxygen tension and orchestrating cellular responses in metabolism, angiogenesis, immune regulation, and tissue remodeling. Although structurally related, HIF-1α and HIF-2α exhibit distinct spatial and temporal functions across reproductive stages. Embryonic HIF-1α is primarily involved in early embryonic development, whereas embryonic HIF-2α is required for later developmental stages. Furthermore, maternal HIF-1α acts early in pregnancy, coordinating metabolic adaptation, endometrial regeneration, decidualization, angiogenic expansion, placental organization, and maternal immune tolerance. In contrast, maternal HIF-2α regulates epithelial breakdown, trophoblast invasion, implantation mechanics, and vesicle-mediated trafficking. Mouse genetics demonstrate that disruption of either isoform leads to non-redundant defects in reproductive success, from failed implantation to placental insufficiency and fetal lethality. Pathological hypoxia or aberrant HIF signaling drives pregnancy disorders including preeclampsia, fetal growth restriction, recurrent pregnancy loss, and heavy menstrual bleeding. Defining the distinct roles of HIF-1α and HIF-2α supports the development of therapies targeting hypoxia-responsive pathways in infertility and obstetric disease. Full article

As the brain’s resident macrophages, microglia on the one side are increasingly recognized as essential players in discrete developmental stages, where immune, metabolic, and activity-derived signals are coordinately integrated to guide brain development. On the other side, the precise temporal and molecular coordination of microglial maturation is imperative for the structural and functional integrity of the developing central nervous system (CNS). In this review, we synthesize recent data that reposition microglia from a uniform population of immune sentinels to temporally programmed and regionally specialized regulators of circuit maturation. This involves dissecting the embryonic origins and migratory pathways of microglial progenitors in mouse and human systems and illustrating how gradual transcriptional and morphological maturation aligns the biology of microglia with progressive phases of neurogenesis, synaptic fine-tuning, myelination, and vascular stabilization. In addition, we discuss how individual gene mutations, inflammatory insults during perinatal life, and environmental disturbances intersect with these temporal programs to alter microglial phenotypes and compromise circuit formation. With a special emphasis on epilepsy and autism spectrum disorder, often sharing the common etiology, we illustrate how early malfunction of microglia may drive neural network dysfunction. Full article

Background: Developmental coordination Disorder (DCD) is a prevalent and persistent neurodevelopmental condition characterized by motor learning difficulties that significantly affect daily functioning and participation. Despite growing interest in artificial intelligence (AI) applications within healthcare, the extent and nature of AI use in the evaluation and intervention of DCD remain unclear. Objective: This scoping review aimed to systematically map the existing literature on the use of AI and AI-assisted approaches in the evaluation, screening, monitoring, and intervention of DCD, and to identify current trends, methodological characteristics, and gaps in the evidence base. Methods: A scoping review was conducted in accordance with the PRISMA extension for Scoping Reviews (PRISMA-ScR) guidelines and was registered on the Open Science Framework. Systematic searches were performed in Scopus, PubMed, Web of Science, and IEEE Xplore, supplemented by snowballing. Peer-reviewed studies applying AI methods to DCD-relevant populations were included. Data was extracted and charted to summarize study designs, populations, AI methods, data modalities, clinical purposes, outcomes, and reported limitations. Results: Seven studies published between 2021 and 2025 met the inclusion criteria following a literature search covering the period from January 2010 to 2025. One study listed as 2026 was included based on its early access online publication in 2025. Most studies focused on AI applications for assessment, screening, and classification, using supervised machine learning or deep learning models applied to movement-based data, wearable sensors, video recordings, neurophysiological signals, or electronic health records. Only one randomized controlled trial evaluated an AI-assisted intervention. The evidence base was dominated by early-phase development and validation studies, with limited external validation, heterogeneous diagnostic definitions, and scarce intervention-focused research. Conclusions: Current AI research in DCD is primarily centered on evaluation and early identification, with comparatively limited evidence supporting AI-assisted intervention or rehabilitation. While existing findings suggest that AI has the potential to enhance objectivity and sensitivity in DCD assessment, significant gaps remain in clinical translation, intervention development, and implementation. Future research should prioritize theory-informed, clinician-centered AI applications, including adaptive intervention systems and decision-support tools, to better support occupational therapy and physiotherapy practice in DCD care. Full article

Background: Quantitative assessment of proprioception in children with Developmental Coordination Disorder (DCD) is limited by methodological variability and the lack of developmentally appropriate protocols. Joint position sense (JPS) and force sense (FS) assessments are commonly used in adults; however, their reliability in pediatric populations has not been sufficiently established. The objective of this study was to evaluate the intra- and inter-rater reliability of adapted JPS and FS protocols in children with DCD and to determine whether the observed reliability supports the use of these methods in experimental research. Methods: A repeated-measurements reliability research design was employed. Twenty-eight children aged 10–15 years (mean age 12.86 years), with a mean body mass of 43.68 kg and a mean height of 149.32 cm, and with medically confirmed DCD, completed four proprioceptive tests: joint angle reproduction and differentiation, and force reproduction and differentiation. Absolute errors were calculated for each trial. Reliability was assessed using intraclass correlation coefficients (ICC2,k), standard error of measurement, and smallest detectable difference. Bland–Altman plots were used to evaluate agreement. Results: Reliability across all tests and movement directions ranged from good to excellent. Most ICC values exceeded 0.90, with only a small number falling between 0.86 and 0.90. Although differentiation tasks produced larger absolute errors than reproduction tasks, their reliability remained excellent. Bland–Altman analyses demonstrated acceptable bias, reasonable clustering around the mean difference, and only occasional outliers beyond the limits of agreement. Conclusions: The adapted JPS and FS protocols demonstrated high intra- and inter-rater reliability in children with DCD, supporting their use in experimental research. Full article

Down Syndrome Regression Disorder (DSRD) is a rare but severe neuropsychiatric condition characterized by abrupt loss of speech, autonomy, and cognitive abilities in individuals with Down syndrome, often associated with immune dysregulation and gut–brain axis dysfunction. We report the case of an 11-year-old girl with Down syndrome who developed developmental regression at age five, in temporal proximity to a family transition (the birth of a younger sibling), with loss of continence, language, and comprehension, alongside persistent behavioral agitation and gastrointestinal symptoms. Laboratory assessment revealed Giardia duodenalis infection, elevated fecal calprotectin and secretory IgA, and microbial imbalance with overgrowth of Streptococcus anginosus and S. sobrinus. The patient received a single oral dose of tinidazole (2 g), daily folinic acid (1 mg/kg), and a 90-day course of transcranial and abdominal photobiomodulation (PBM) (1064 nm, 10 min per site). Post-treatment, stool analysis showed normalized inflammation markers and restoration of beneficial bacterial genera (Bacteroides, Bifidobacterium, Lactobacillus) with absence of Enterococcus growth. Behaviorally, she exhibited marked recovery: CARS-2-QPC decreased from 106 to 91, ABC from 63 to 31, and ATEC from 62 to 57, alongside regained continence, speech, and fine-motor coordination. These outcomes suggest that abdominal and transcranial PBM, by modulating mitochondrial metabolism, mucosal immunity, and microbiota composition, may facilitate systemic and neurobehavioral recovery in DSRD. This translational case supports further investigation of PBM as a non-invasive, multimodal therapy for neuroimmune regression in genetic and developmental disorders including validation through future randomized controlled clinical trials. Full article

Background/Objectives: Cluttering in childhood and adolescence is characterised by unstable speech timing, excessive coarticulation, irregular rate and reduced intelligibility, yet the developmental mechanisms underpinning these behaviours remain partially understood. This review synthesises empirical and conceptual evidence to examine cluttering through the lenses of speech motor development, neurocognitive mechanisms, task demands and allied-health practice. Four research questions guided the review, focusing on motor characteristics, developmental and neurocognitive mechanisms, task dependence and clinical implications. Methods: Following the PRISMA guidelines, a comprehensive search across seven databases identified studies examining cluttering in children and adolescents. Screening and full-text review were conducted in Covidence by two reviewers, with disagreements resolved by the first author. Twelve studies met the inclusion criteria. Data were extracted into a structured evidence table, and findings were synthesised. Results: Across studies, cluttering emerged as a developmental motor–cognitive integration disorder. Speech motor systems, linguistic formulation and executive control showed difficulty aligning under real-world communicative demands, leading to timing instability, articulatory blurring and reduced intelligibility. Symptoms were strongly influenced by task complexity, with spontaneous and extended discourse eliciting the most pronounced breakdowns. Conclusions: Cluttering reflects a developmental vulnerability in coordinating speech motor, linguistic and executive processes. Understanding cluttering in this way challenges narrow rate-based definitions and supports more nuanced approaches to assessment and intervention. Significant evidence gaps remain, particularly in longitudinal, mechanistic, multilingual and ecologically valid research. This developmental motor–cognitive framework strengthens the conceptual foundations of cluttering and clarifies its relevance to children’s motor development. Full article