Search Results (2,287)

Background/Objectives: Impairment in self-awareness (ISA) is one of the common consequences of an acquired brain injury (ABI) and is associated with anosodiaphoria. Collectively, these co-occurring neuropsychological disorders pose significant obstacles in the neurorehabilitation of moderate-to-severe ABI patients. Individuals who recover from ISA may present with anxiety and/or depression as adaptive reactions to the ABI, along with related functional disabilities. The present study investigated whether the level of metacognitive self-awareness (SA) is associated with the presence of anxiety and depression, apathy, or anosodiaphoria in patients with moderate-to-severe ABI. It aimed also at investigating the possible relationship between the severity of disability and both psycho-emotional diseases and the presence of PTSD symptoms in patients with high metacognitive SA. Methods: Sixty patients with moderate-to-severe ABI and different levels of metacognitive SA completed a series of questionnaires, which assessed their self-reported metacognitive SA, anosodiaphoria, anxiety and depression, apathy, and PTSD symptoms. Results: Low-metacognitive-SA patients showed lower levels of anxiety and depression and higher anosodiaphoria than high-metacognitive-SA patients. Patients with high metacognitive SA and high levels of disability showed significant higher states of anxiety and PTSD symptoms than patients with high metacognitive SA and low levels of disability. Conclusions: The neurorehabilitation of individuals with moderate to severe ABI should address, in particular, the complex interaction between ISA and anxiety and depression in patients during the rehabilitation process. Full article

Objectives: The primary objective was to investigate and compare the effects of three paired-pulse repetitive trans-spinal magnetic stimulation (PP-rTSMS) protocols on balance control and corticospinal network function. Methods: PP-rTSMS (800 pulses, frequency 100 Hz, intensity 70% of the resting motor threshold) was applied over the eighth thoracic vertebra (Th8) in twenty-seven young healthy individuals. Each proband received three verum sessions (using a verum coil with handle oriented (i) cranially, (ii) caudally, and (iii) laterally) and (iv) one sham session (using a sham coil) in a randomised order. Balance ability (Y Balance Test) and corticospinal network functions (motor evoked potentials (MEPs), cortical silent periods (SCPs)) were tested immediately (i) prior to and (ii) after each interventional session. Results: Each verum session induced a significant improvement in balance ability (cranially (F_1,26 = 8.009; p = 0.009; η² = 0.236), caudally (F_1,26 = 4.846; p = 0.037; η² = 0.157), and laterally (F_1,26 = 23,804; p ≤ 0.001; η² = 0.478) oriented grip) as compared to the sham session. In addition, the laterally oriented coil grip was associated with significantly greater balance benefits than both the cranial (F_1,26 = 10.173; p = 0.004; η² = 0.281) and caudal (F_1,26 = 14.058; p ≤ 0.001; η² = 0.351) grip orientations. No significant intervention-induced effects were detected on corticospinal network functions. Conclusions: Our data show that PP-rTSMS effectively supports balance control and that coil orientation significantly influences these effects. Further studies should test variations of this promising approach on healthy and disabled cohorts. Full article

Zinc finger proteins are frequently implicated in a wide range of neurodevelopmental disorders (NDDs). In this study, we report a case of mild intellectual disability (ID), global developmental delay (GDD), and developmental coordination disorder (DCD) in an individual with unaffected parents. Trio-based whole-exome sequencing (WES) identified a de novo variant (c.1530dup, p.Glu511ArgfsTer16) in the ZNF496 gene of the proband. According to ACMG guidelines, this novel variant is classified as pathogenic. It creates a frameshift that introduces a premature stop codon, resulting in a truncated protein of 525 amino acids (compared to the wild-type 587 residues). Notably, NMDEscPredictor analysis predicted that the transcript escapes nonsense-mediated decay (NMD) despite the frameshift. Computational analyses suggest the potential pathogenetic effects of the identified variant. As documented, ZNF496 interacts with JARID2, a gene associated with NDDs, ID and facial dysmorphism (MIM: #620098). In silico analyses suggest that the identified mutation disrupts this interaction by deleting ZNF496’s C2H2 domain, potentially dysregulating JARID2 target genes. To our knowledge, this is the first reported association between ZNF496 and NDDs, and the variant has been submitted to the ClinVar database (SCV006100880). Functional studies are imperative to validate ZNF496’s role in NDDs and confirm the mutation’s impact on ZNF496-JARID2 interactions. Full article

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

This study examines how Ontario’s Health and Physical Education curriculum addresses the needs of young adults with disabilities. A total of 54 individuals aged 18–35 years old with developmental, learning, or physical disabilities who had completed secondary school in Ontario participated in a cross-sectional mixed-methods survey. Participants were recruited through disability-focused community networks and a university psychology participant pool. They completed the Sex Education subscale of the Sexual Knowledge, Experience, Feelings and Needs Scale, a 35-item sexual knowledge questionnaire, and open-ended questions. Quantitative data were analyzed using descriptive statistics and independent samples t-tests; qualitative responses were examined using thematic analysis. Participants reported limited factual knowledge, minimal classroom representation, and heavy reliance on independent learning. Barriers included inaccessible materials, teacher discomfort, and the absence of disability narratives in sexuality units. Findings point to three priorities: revising curriculum content, expanding educator training, and creating disability-affirming resources. These measures will help ensure comprehensive and rights-based sexuality education that supports the autonomy and well-being of students with disabilities. Full article

Background: Family caregivers are a vital yet often under-recognized part of the healthcare system. They provide essential emotional, physical, and logistical support to individuals with illness, disability, or frailty, and their contributions improve continuity of care and reduce system strain. However, many healthcare and social service providers are not equipped to meaningfully engage caregivers as partners. In Alberta, stakeholders validated the Caregiver-Centered Care Competency Framework and identified the need for a three-tiered education model—Foundational, Advanced, and Champion—to help providers recognize, include, and support family caregivers across care settings. This paper focuses on the development and early evaluation of the Advanced Caregiver-Centered Care Education modules, designed to enhance the knowledge and skills of providers with more experience working with family caregivers. The modules emphasize how partnering with caregivers benefits not only the person receiving care but also improves provider effectiveness and supports better system outcomes. Methods: The modules were co-designed with a 154-member interdisciplinary team and grounded in the competency framework. Evaluation used the first three levels of the Kirkpatrick–Barr health workforce education model. We analyzed pre- and post-surveys from the first 50 learners in each module using paired t-tests and examined qualitative feedback and SMART goals through inductive content analysis. Results: Learners reported a high level of satisfaction with the education delivery and the knowledge and skill acquisition. Statistically significant improvements were observed in 53 of 54 pre-post items. SMART goals reflected intended practice changes across all six competency domains, indicating learners saw value in engaging caregivers as partners. Conclusions: The Advanced Caregiver-Centered Care education improved providers’ confidence, knowledge, and skills to work in partnership with family caregivers. Future research will explore whether these improvements translate into real-world practice changes and better caregiver experiences in care planning, communication, and navigation. Full article

Background/Objectives: While intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke (AIS) within 4.5 h of symptom onset, many patients present beyond this time window. Recent trials suggest that IVT may be both effective and safe in selected patients treated after the standard time window. Methods: We searched MEDLINE, Scopus, and ClinicalTrials.gov for randomized-controlled clinical trials (RCTs) and individual patient-data meta-analyses (IPDMs) of RCTs comparing IVT plus best medical treatment (BMT) to BMT alone in AIS patients who were last-known-well more than 4.5 h earlier. The primary efficacy outcome was a 90-day excellent functional outcome [modified Rankin Scale (mRS)-scores of 0–1]. Secondary efficacy outcomes included good functional outcome (mRS-scores 0–2) and reduced disability (≥1-point reduction across all mRS-strata). The primary safety outcome was symptomatic intracranial hemorrhage (sICH); secondary safety outcomes were any ICH and 3-month all-cause mortality. Subgroup analyses were performed stratified by different thrombolytics, time-windows, imaging modalities, and affected circulation. Results: Nine studies were included, comprising 1660 patients in the IVT-group and 1626 patients in the control-group. IVT significantly improved excellent functional outcome (RR = 1.24; 95%CI:1.14–1.34; I² = 0%) and good functional outcome (RR = 1.18; 95%CI:1.05–1.33; I² = 70%). IVT was associated with increased odds of reduced disability (common OR = 1.3; 95%CI:1.15–1.46; I² = 0%) and increased risk of sICH (RR = 2.75; 95%CI:1.49–5.05; I² = 0%). The rates of any ICH and all-cause mortality were similar between the two groups. No significant subgroup differences were documented. Conclusions: IVT in the extended time window improved functional outcomes without increasing mortality, despite a higher rate of sICH. Full article

Depression is a common mental disorder with high economic burden, characterized by high disability and mortality rates. The etiology of depression remains unclear to date, and there are various hypotheses regarding the pathogenesis of depression in clinical practice, including the monoamine neurotransmitter hypothesis, the hypothalamic–pituitary–adrenal (HPA) axis dysregulation hypothesis, the inflammatory cytokine hypothesis, and the neurotrophic factor hypothesis. These theories offer specific directional aid in the clinical management of individuals suffering from depression. Medicinal intervention stands as a critical approach within the spectrum of depression treatments, and this article reviews the specific mechanisms of different hypotheses on the pathogenesis of depression in recent years, as well as the research progress on related therapeutic drugs. Full article

Background: Traumatic brain injury (TBI) remains a significant contributor to global mortality and long-term neurological disability. Accurate prognostic biomarkers are crucial for enhancing prognostic accuracy and guiding personalized clinical management. Objective: This review assesses the prognostic value of arterial spin labeling (ASL), a non-invasive MRI technique, in adult and pediatric TBI, with a focus on quantitative cerebral blood flow (CBF) and arterial transit time (ATT) measures. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and IEEE databases, including observational studies and clinical trials that applied ASL techniques (pCASL, PASL, VSASL, multi-PLD) in TBI patients with functional or cognitive outcomes, with outcome assessments conducted at least 3 months post-injury. Results: ASL-derived CBF and ATT parameters demonstrate potential as prognostic indicators across both acute and chronic stages of TBI. Hypoperfusion patterns correlate with worse neurocognitive outcomes, while region-specific perfusion alterations are associated with affective symptoms. Multi-delay and velocity-selective ASL sequences enhance diagnostic sensitivity in TBI with heterogeneous perfusion dynamics. Compared to conventional perfusion imaging, ASL provides absolute quantification without contrast agents, making it suitable for repeated monitoring in vulnerable populations. ASL emerges as a promising prognostic biomarker for clinical use in TBI. Conclusion: Integrating ASL into multiparametric models may improve risk stratification and guide individualized therapeutic strategies. Full article

The ongoing secular changes in human movement development means that an assessment of primitive reflexes is now required not only in disabled but also in neurotypical children. This study had three aims: (1) presenting the TASHUN test battery as suitable for the assessment of primitive reflex activity in normal children and child athletes; (2) analyzing reflex characteristics of neurotypical children; (3) verifying validity and reliability of tests. Spearman’s rank correlation and ROC analysis were used for validation. Intraclass Correlation Coefficient and RM ANOVA analyzed reliability. The test on 242 schoolgirls has demonstrated that retained primitive reflexes are present in almost every individual (84.7–95.7%). Correlations showed strong positive association, with all values exceeding 0.8, and ROC analysis demonstrated excellent predictive strength (AUC values over 0.9). Interobserver reliability showed excellent agreement (ICC values above 0.9). No significant offset was present among the scoring by evaluators. Therefore, testing for primitive reflexes is necessary in neurotypical children in order to obtain a realistic image about the physiology of reflexes and their role in motor development. Our screening could be useful for practicing sport professionals, researchers and academics, to identify deficiencies, to further explore reflexes and to train future PE teachers and trainers. Full article

Introduction: The optimal management of hallux sesamoid fracture nonunions remains a subject of ongoing debate, particularly in the context of personalized medicine. This systematic review aimed to synthesize current evidence regarding surgical strategies for this rare but disabling condition. Methods: A comprehensive literature search was conducted in accordance with the PRISMA guidelines. Results: Six studies met the inclusion criteria, encompassing a total of 80 patients. Surgical techniques varied and included open and arthroscopic sesamoidectomy, autologous bone grafting (alone or combined with screw fixation), and percutaneous screw fixation. When reported, outcomes were generally favorable, with union rates ranging from 90.5% to 100% and with consistent postoperative improvements in clinical function. Complication and reoperation rates were both 6.5%. The most frequent reoperation was sesamoidectomy for persistent pain or nonunion, followed by hardware removal. Conclusions: Despite the limited and low-quality evidence, available data suggest that individualized surgical planning can lead to favorable outcomes with low complication rates. Sesamoidectomy remains the most reliable salvage procedure in refractory cases. These findings support a personalized, stepwise approach to treatment—prioritizing sesamoid preservation, when feasible, while reserving excision for symptomatic nonunions. Further studies are needed to validate tailored algorithms and refine patient-specific decision-making in this challenging clinical scenario. Full article

Fragile X syndrome (FXS) is the most common form of X-linked intellectual disability (ID). This study aimed to share 30 years of experience in diagnosing FXS and determine its frequency in Thailand. We retrospectively reviewed 1480 unrelated patients (1390 males and 90 females) with ID, developmental delay, or autism spectrum disorder, or individuals referred for FXS DNA testing at Songklanagarind Hospital, Thailand, over a 30-year period. The samples were analyzed using cytogenetic methods, PCR-based techniques, and/or Southern blot analysis. Full mutations (>200 CGG repeats) were identified in 100 males (7.2%) and three females (3.3%). An intermediate allele was detected in one male, while no premutation was found in the index cases. Two males were suspected to have FMR1 gene deletions. Twelve families underwent prenatal testing during this study. Most families undergoing prenatal FXS diagnosis involved mothers who were premutation carriers and had given birth to children affected by FXS. This study represents the largest series of molecular genetic FXS testing cases reported in Thailand. The frequency of FXS identified in different cohorts of Thai patients across various periods was approximately 7%. This study enhances public awareness of at-risk populations and highlights the importance of prenatal testing and genetic counseling for vulnerable families. Full article

This study aims to characterize short-wave infrared (SWIR) reflectance spectra at cranial (at the scalp overlying the frontal cortex and the temporal bone window) and extracranial (biceps and triceps) sites in patients with multiple sclerosis (MS) and age-/sex-matched controls. We sought to identify the diagnostic accuracy of wavelength-specific patterns in distinguishing MS from normal controls and spectral markers associated with disability (e.g., Expanded Disability Status Scale scores). To achieve these objectives, we employed a multi-site SWIR spectroscopy acquisition protocol that included measurements from traditional cranial locations as well as extracranial reference sites. Advanced spectral analysis techniques, including wavelength-dependent absorption modeling and machine learning-based classification, were applied to differentiate MS-related hemodynamic changes from normal physiological variability. Classification models achieved perfect performance (accuracy = 1.00), and cortical site regression models showed strong predictive power (EDSS: R²_CV = 0.980; FSS: R²_CV = 0.939). Variable Importance in Projection (VIP) analysis highlighted key wavelengths as potential spectral biomarkers. This approach allowed us to explore novel biomarkers of neural and systemic impairment in MS, paving the way for potential clinical applications of SWIR spectroscopy in disease monitoring and management. In conclusion, spectral analysis revealed distinct wavelength-specific patterns collected from cranial and extracranial sites reflecting biochemical and structural differences between patients with MS and normal subjects. These differences are driven by underlying physiological changes, including myelin integrity, neuronal density, oxidative stress, and water content fluctuations in the brain or muscles. This study shows that portable spectral devices may contribute to bedside individuation and monitoring of neural diseases, offering a cost-effective alternative to repeated imaging. Full article

Sarcopenia is a progressive age-related musculoskeletal disorder characterized by loss of muscle mass, strength, and physical performance, contributing to functional decline and increased risk of disability. Emerging evidence suggests that vitamin D (Vit D) plays a pivotal role in skeletal muscle physiology beyond its classical functions in bone metabolism. This review aims to critically analyze the relationship between serum Vit D levels and sarcopenia in older adults, focusing on pathophysiological mechanisms, diagnostic criteria, clinical evidence, and preventive strategies. An integrative narrative review of observational studies, randomized controlled trials, and meta-analyses published in the last decade was conducted. The analysis incorporated international diagnostic criteria for sarcopenia (EWGSOP2, AWGS, FNIH, IWGS), current guidelines for Vit D sufficiency, and molecular mechanisms related to Vit D receptor (VDR) signaling in muscle tissue. Low serum 25-hydroxyvitamin D levels are consistently associated with decreased muscle strength, reduced physical performance, and increased prevalence of sarcopenia. Although interventional trials using Vit D supplementation report variable results, benefits are more evident in individuals with baseline deficiency and when combined with protein intake and resistance training. Mechanistically, Vit D influences muscle health via genomic and non-genomic pathways, regulating calcium homeostasis, mitochondrial function, oxidative stress, and inflammatory signaling. Vit D deficiency represents a modifiable risk factor for sarcopenia and functional impairment in older adults. While current evidence supports its role in muscular health, future high-quality trials are needed to establish optimal serum thresholds and dosing strategies for prevention and treatment. An individualized, multimodal approach involving supplementation, exercise, and nutritional optimization appears most promising. Full article

Background/Objectives: Sudden cardiac arrest (SCA) is a major global health concern with high mortality despite advances in resuscitation techniques. Achieving return of spontaneous circulation (ROSC) represents merely the initial step in the extensive rehabilitation journey. This review highlights the critical role of structured, multidisciplinary rehabilitation following ROSC, emphasizing the necessity of integrated physiotherapy, neurocognitive therapy, and psychosocial support to enhance quality of life and societal reintegration in survivors. Methods: This narrative review analyzed peer-reviewed literature from 2020–2025, sourced from databases such as PubMed, Scopus, Web of Science, and Google Scholar. Emphasis was on clinical trials, expert guidelines (e.g., European Resuscitation Council 2021, American Heart Association 2020), and high-impact journals, with systematic thematic analysis across rehabilitation phases. Results: The review confirms rehabilitation as essential in addressing Intensive Care Unit–acquired weakness, cognitive impairment, and post-intensive care syndrome. Early rehabilitation (0–7 days post-ROSC), focusing on parameter-guided mobilization and cognitive stimulation, significantly improves functional outcomes. Structured interdisciplinary interventions encompassing cardiopulmonary, neuromuscular, and cognitive domains effectively mitigate long-term disability, facilitating return to daily activities and employment. However, access disparities and insufficient randomized controlled trials limit evidence-based standardization. Discussion: Optimal recovery after SCA necessitates early and continuous interdisciplinary engagement, tailored to individual physiological and cognitive profiles. Persistent cognitive fatigue, executive dysfunction, and emotional instability remain significant barriers, underscoring the need for holistic and sustained rehabilitative approaches. Conclusions: Comprehensive, individualized rehabilitation following cardiac arrest is not supplementary but fundamental to meaningful recovery. Emphasizing early mobilization, neurocognitive therapy, family involvement, and structured social reintegration pathways is crucial. Addressing healthcare disparities and investing in rigorous randomized trials are imperative to achieving standardized, equitable, and outcome-oriented rehabilitation services globally. Full article