Search Results (14,835)

Background: Early identification of fall and frailty risk is essential for preventing disability and maintaining functional independence in older adults. Although simple functional assessments are widely used in community settings, their combined application as a classification approach in large real-world populations remains limited. Methods: This cross-sectional study included 2979 community-dwelling adults (67.6 ± 8.3 years) enrolled in a municipal physical activity program. Participants underwent standardized assessments of gait speed, handgrip strength, and balance. A composite fall/frailty risk classification was defined using established functional cut-offs. Associations between functional variables and risk classification were examined using correlation analyses and group comparisons. Results: Overall, 45% of participants were classified as high risk. Women showed a higher prevalence compared to men (47% vs. 35%). Lower gait speed (r = −0.56), reduced handgrip strength (r = −0.32), and shorter balance time (r = −0.47) were significantly associated with higher risk classification (all p < 0.001). Conclusions: Functional performance measures are strongly associated with a composite classification of fall and frailty risk. These findings support the use of simple, scalable screening tools in community and primary care settings to identify vulnerable older adults and inform early intervention strategies. Full article

Neuroinflammation plays an essential role in the pathogenesis of several associated brain diseases, including neurodegenerative disorders (Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS)), and traumatic brain injury (TBI). In these diseases, persistent microglial and astrocyte aggregates, elevated proinflammatory cytokines, and oxidative stress drive neuronal injury and cognitive disability. Rho GTPases, in particular the Rho family members Ras homolog family member A (RhoA), Ras-related C3 botulinum toxin substrate 1 (Rac1), and cell division control protein 42 homolog (CDC42), regulate neuroinflammation, cytoskeletal dynamics, immune responses, and the maintenance of BBB integrity. These proteins are involved in many neuropathological diseases due to dysregulation, making them interesting therapeutic targets. Bioactives used in herbal care have attracted interest for their ability to influence neuroinflammation and even their anti-neurodegenerative activity. Studies show that flavonoids, alkaloids, polyphenols, and other botanical compounds alter Rho GTPase activity, which, in turn, leads to decreased inflammation. This review critically summarizes current evidence regarding phytochemical regulation of Rho GTPase signaling in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), with particular emphasis on the underlying molecular mechanisms, context-dependent signaling responses, and current translational challenges. Furthermore, existing knowledge gaps and future research priorities are discussed to facilitate the development of mechanism-based therapeutic strategies targeting Rho GTPases. Full article

The transition from education to employment remains a major challenge, particularly for individuals who may require accessibility support during competency assessment and occupational guidance. However, many current approaches remain fragmented because they evaluate soft skills, accessibility conditions, and occupational requirements as separate dimensions. This study presents an accessibility-aware computational proof of concept for employability analytics using workplace simulation logic, derived competency indicators, semantic modeling, clustering, person–job fit estimation, and heuristic multi-objective optimization. The framework integrates open secondary employability data, O*NET-derived occupational descriptors, and simulated accessibility scenarios within a reproducible analytical pipeline. The results show differentiated computational employability profiles, with mean person–job fit values of 0.85, 0.74, and 0.63 for high, medium, and low profiles, respectively. The derived competency indicators showed high internal consistency ($\alpha =0.905$), although they are interpreted as exploratory proxy dimensions rather than as an exploratory psychometric scale. Principal component analysis indicated a dominant general employability factor, with the first component explaining 75.3% of the variance. The optimization layer produced interpretable heuristic convergence patterns and modeled scenario assignments under predefined validity, accessibility, alignment, and diagnostic criteria. Person–job fit was interpreted under sensitivity scenarios involving alternative competency weights, scalarization parameters, and accessibility assumptions. The study does not include observed participants with disabilities, measured accessibility support use, field simulator interaction records, or longitudinal employment outcomes. Therefore, the term accessibility-aware refers to the computational framework’s design orientation. At the same time, the empirical evidence should be interpreted as a secondary-data-based proof of concept rather than as validation of an inclusive simulator for future users with accessibility needs. The main numerical indicators were: high-profile mean fit = 0.85, medium-profile mean fit = 0.74, low-profile mean fit = 0.63, Cronbach’s alpha = 0.905, first principal component variance = 75.3%, and heuristic iterations = 900. Full article

Background: Lumbar foraminal canal stenosis (LFS) is typically multifactorial: disk height loss and bulging, facet hypertrophy/osteophytes, ligamentous thickening, and post-inflammatory or post-interventional scarring. Methods: To develop and implement a structured system for surgical care in chronic vertebrogenic pain with radicular features attributable to LFS, integrating population-based MRI morphometrics and interventional therapy response profiling, we conducted a single-center, multi-cohort observational study to develop, operationalize, and internally evaluate a quantitative, volume-integrated diagnostic and treatment stratification framework for LFS. Results: A retrospective evaluation of 351 surgically treated patients (2017–2023) was performed to identify structural and clinical drivers of persistent or recurrent pain. Following selective blockades and radiofrequency denervation, radiculopathy regressed in 44.7% of patients, facet-mediated pain improved in 44.0%, and the median pain relief duration was 3–6 months. Oswestry Disability Index (ODI) dynamics after interventional therapy showed significant improvement at 6 months (all p < 0.001). Both groups demonstrated significant improvement in VAS, ODI, and SF-36 scores over time. Endoscopic decompression achieved faster early leg pain relief (VAS leg, p < 0.001 at 6 and 12 months). ALIF resulted in superior long-term back pain control (VAS back, p < 0.001 at 12 and 24 months). At 24 months, pain levels were clinically equivalent between groups, indicating that procedure selection influences pain profile rather than absolute outcome. Conclusions: By integrating quantitative foraminal volume, nerve occupancy, and segmental stability, we demonstrated that treatment success in LFS is not determined by the magnitude of decompression alone, but by the precision of phenotypic matching. Indirect decompression, endoscopic foraminotomy, microsurgical decompression, and fusion-based stabilization each have a rational role when aligned with the biomechanical context rather than applied reflexively. Full article

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two main neurodegenerative diseases and cause disability and death in patients worldwide. Neurodegeneration is characterized by a progressive loss of neuronal function and structure, causing enormous impairment in cognitive–motor function. Magnolol and honokiol are isomeric biphenyl neolignans and have exhibited neuroprotective activity in previous studies. Hence, we assessed and compared honokiol, magnolol, and mixtures of honokiol and magnolol in honokiol/magnolol molar ratios of 1:3, 1:1, and 3:1 in terms of their neurotoxicity, using the cell counting kit-8 (CCK-8) assay, and of their neuroprotective effect on intracellular reactive oxygen species (iROS) against amyloid-beta (Aβ)- and 1-methyl-4-phenylpyridinium ion (MPP⁺)-induced neurotoxicity in SH-SY5Y cells, using the 2′,7′-dichlorodihydrofluorescein diacetate (H₂DCF-DA) assay. The results showed that honokiol (H) and magnolol (M) at 0.1 μM and the mixtures of honokiol and magnolol in H/M ratios of 1:3, 1:1, and 3:1 at 0.0001 μM exhibited a significant neuroprotective effect of reducing iROS in SH-SY5Y cells where neurotoxicity was induced by Aβ- and MPP⁺ (p-value with respect to Aβ-treated cells < 0.005 and p-value with respect to MPP⁺-treated cells < 0.0001). Moreover, magnolol and honokiol possess antioxidant properties according to computational molecular analysis with Highest Occupied Molecular Orbital (HOMO)- Lowest Unoccupied Molecular Orbital (LUMO) prediction, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and Ferric Reducing Antioxidant Power (FRAP) assays. The mixtures of honokiol and magnolol exerted synergistic neuroprotective ability at all ratios while showing better antioxidation ability than that of pure magnolol alone but comparable to that of pure honokiol alone. Drug-likeness, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction, and toxicity profiles showed that both compounds are promising neuroprotective agents and that one of the possible targeting mechanisms is the ROS-mediated oxidative stress pathway. Additional neuronal cell lines and in vivo models are required to determine similar effects or other protective mechanisms involving the neuroprotective ability of honokiol and magnolol. Full article

Cultural heritage institutions continue to face significant challenges in addressing neurodivergent access needs, while a principled framework linking inclusive design and artificial intelligence in heritage remains underdeveloped. This article proposes and explores the transfer of a dual Universal Design for Learning (UDL 3.0)–International Classification of Functioning, Disability and Health (ICF) framework from education to cultural heritage. The framework was examined within an Erasmus+ Blended Intensive Programme in Naples, Italy, through an exploratory mixed-methods pilot design combining pre/post questionnaires with thematic analysis of participants’ open-ended reflections. Findings suggest that the programme supported a qualitative reframing of accessibility from a predominantly physical-access model toward a broader understanding encompassing sensory, cognitive, communicative, and participatory dimensions. Site visits to Pompeii, Herculaneum, and the MANN emerged as especially important in prompting critical reflection on the gap between heritage value and accessibility practice. Quantitative patterns also indicated preliminary gains in participants’ self-efficacy in applying UDL/ICF principles and in reflecting on AI ethics in heritage, although these findings remain exploratory given the small sample size and pilot design. The article contributes a conceptual and pedagogical framework for inclusive AI in cultural heritage and discusses its implications for accessibility governance, conservation-constrained settings, and future co-designed research. Full article

Essential tremor (ET) often remains disabling despite pharmacologic, surgical, and stimulation-based options. This feasibility study evaluated LaceUp, a passive wearable sleeve combining soft compression with distributed embedded weight. Ten adults with ET completed a single laboratory visit with a fixed task battery under baseline, unweighted compression sleeve, wrist weight, and LaceUp conditions. Outcomes included wrist inertial measurement unit (IMU) tremor-band power (4–12 Hz), root mean square (RMS) jerk, digitized Archimedes spirals, handwriting, satisfaction/preference surveys, and follow-up Canadian Occupational Performance Measure (COPM) ratings. On the more-affected limb, LaceUp was associated with the largest median tremor-band power reduction (−32.9%) versus wrist weights (−25.3%) and the unweighted sleeve (−19.5%), while RMS jerk reductions were similar across conditions. Spiral and handwriting measures were heterogeneous and appeared most informative in participants with greater baseline severity. Six of nine participants who completed the preference ranking selected LaceUp as preferred. At follow-up, two of six reported continued use, and one exceeded the commonly cited 2-point COPM satisfaction threshold. Because this small pilot used a fixed order, effects cannot be separated from period, learning, expectancy, fatigue, behavioral adaptation, or measurement effects. Findings support feasibility and identify candidate endpoints, severity-based enrollment considerations, and operational constraints for future studies. Full article

Tricuspid regurgitation (TR) is being increasingly recognized in the patient population. It is a common cardiac cause of chronic disability. This pathology is characterized by a heterogeneous and broad spectrum of clinical manifestations with signs and symptoms. The results from various and different analyses and studies suggest that TR-related deaths may have increased over the last 20 years. This trend may justify a greater focus on timely diagnosis and management of TR. For a long time, this problem has been underestimated or treated with only pharmacological therapy (diuretics). The use of the isolated surgical option remains infrequent, especially in patients at high surgical risk, for whom a significant number of patients with TR are still not treated, and a disability remains that is difficult to manage and rehabilitate. To date, there are emerging as an alternative to surgery in high-risk patients with severe TR multiple transcatheter devices that aim to reduce TR through different functional mechanisms. There are numerous minimally invasive treatments for TR, and many devices used for the treatment of this disabling pathology. In fact, there are various treatments with a transcatheter approach using ever-new devices. The use of heterotopic implantation of bioprosthetic valves in the superior and inferior vena cava represents an additional therapeutic armamentarium that, through caval reflux, can constitute an additional resource, too. Starting from a single clinical experience and describing a clinical case report, a narrative review has been undertaken by reviewing the various studies that have investigated this type of approach and their impact on the general, cardiac, and functional sides, to then discuss the cost–benefit ratio in light of knowledge on this specific topic. Full article

Background/Objectives: Chronic pain represents a major global health burden and significantly impacts quality of life and functional capacity. Physiotherapy plays a central role in its management, yet the rapid growth of research in this field makes it difficult to identify current trends and emerging directions. The aim of this study was to analyze global research trends in chronic pain physiotherapy using a bibliometric approach. Methods: A bibliometric analysis was conducted using data retrieved from PubMed, Scopus, and Web of Science. A predefined search strategy was applied to identify relevant publications. Data were analyzed and visualized using VOSviewer. Co-occurrence analysis of terms based on titles and abstracts was performed using full counting. The most relevant terms were selected using a relevance score threshold, and a thesaurus file was applied to improve data quality. Results: The number of publications increased steadily from 2015 to 2025, indicating growing research interest in chronic pain physiotherapy. Network analysis revealed key research clusters related to clinical interventions, functional assessment, and outcome evaluation. The most prominent and central terms included “pelvic pain”, “neck disability index”, and “radicular pain”. Overlay visualization identified emerging topics such as “stratified care”, “multidisciplinary rehabilitation”, and “psychometric property”, reflecting a shift toward personalized and patient-centered approaches. Conclusions: Research in chronic pain physiotherapy is rapidly expanding, with a clear transition from traditional intervention-focused approaches toward individualized, multidisciplinary, and outcome-driven strategies. These findings provide insight into current research directions and may support clinicians and researchers in identifying future priorities in chronic pain management. Full article

Peripheral nerve injuries represent significant clinical challenges, often resulting in lifelong motor function loss and disability. Evidence suggests regenerating axons cannot cross nerve gaps without Schwann Cell (SC) assistance. However, FDA-approved biomaterial conduits for peripheral nerve repair lack bioactivity and structural complexity needed to facilitate SC migration. To address this, we developed a three-dimensional biomimetic in vitro model to simulate complex cellular interactions within the nerve bridge. The model features lyophilized hydrogel bioscaffolds with longitudinal channels to recapitulate the nerve microenvironment. To encourage directional SC dispersion, the top ~30% of the bioscaffold was conjugated with macrophage inflammatory protein-1α (MIP-1α). Rat SCs were seeded within no-MIP-1α- and MIP-1α-conjugated bioscaffold channels as spheroids and cultured for nine days. Histology demonstrated MIP-1α conjugation retained more SC spheroids during culture with greater cellular distributions. SC spheroid culture in MIP-1α-conjugated bioscaffold resulted in enhanced paracrine signaling characterized by increases in VEGF, ICAM-1, IL-6, and CINC-1 production, alongside downregulation of IL-1β, IL-10, and IL-13. The SC-derived pro-inflammatory and pro-angiogenic mediators did not inhibit NSC-34 motor neurite extension compared to controls. This study establishes an in vitro model that serves as both a screening platform and mechanistic tool, advancing our understanding of peripheral nerve repair. Full article

The Activity-Dependent Neuroprotective Protein (ADNP) is an important regulator of early brain development, especially during cortical neurogenesis and neurite formation. De novo point mutations or haploinsufficiency of the ADNP gene result in ADNP syndrome, which is also known as Helsmoortel-Van der Aa syndrome, a complex neurodevelopmental disorder recognized as a leading single-gene cause of syndromic autism spectrum disorder (ASD) and intellectual disability. ADNP works as both a transcription factor and a microtubule (MT) regulator. As a transcription factor, ADNP is a key component of chromatin remodeling complexes such as ChAHP (CHD4 (Chromodomain Helicase DNA-binding Protein 4)-ADNP-HP1 (Heterochromatin Protein 1)) and SWI/SNF (Switch/Sucrose Non-Fermentable), and it tightly regulates the expression of numerous essential developmental genes. ADNP also modulates the Wnt/β-catenin signaling pathway. During neural differentiation, ADNP is redistributed from the nucleus to the cytoplasm, and this redistribution is regulated by binding to 14-3-3 proteins, which are phosphorylated by protein Kinase C (PKC). After relocating to the cytoplasm, ADNP functions as an MT regulator by binding to microtubule end-binding proteins (EB1 and EB3) and Tau to control neurite formation. Previous studies have focused on NAP (also known as Davunetide, a peptide derived from ADNP) in MT regulation and its therapeutic potential for autism spectrum disorder (ASD) and neurodegenerative diseases, such as Alzheimer’s disease. This review highlights the functions of full-length ADNP and NAP in early brain development, particularly in neurogenesis and neurite formation during cortical development. We will also discuss the potential of NAP as a therapeutic medication for neurodevelopmental disorders, especially ASD and ADNP syndrome. Full article

Major depressive disorder (MDD) remains a leading cause of disability; however, monoaminergic models do not fully explain delayed treatment onset, incomplete remission, or rapid responses to glutamatergic interventions. In this study, we proposed a system-level ionic homeostasis framework for MDD. In this model, genetic susceptibility, chronic stress, metabolic burden, and neuroinflammation converge in neuronal and glial ion-channel systems, disrupting calcium, potassium, chloride, and purinergic homeostasis. These disturbances alter intrinsic excitability, synaptic integration, inhibitory tone, glial buffering, and neuron–glia signaling, thereby promoting excitation–inhibition imbalance, impaired plasticity, and corticolimbic network instability. We reviewed the evidence implicating the CACNA1C/Cav1.2, TREK-1, KCNQ, NKCC1/KCC2, HCN, transient receptor potential/acid-sensing ion channels, and glial mediators, including P2X7R, Kir4.1, and AQP4. We also discuss how ketamine-related mechanisms, chloride-restoring strategies, anti-inflammatory ion channel targeting, neuromodulation, EEG biomarkers, and AI/multiomics approaches support mechanism-informed precision therapeutics. MDD could be conceptualized as a distributed failure of ionic homeostasis that links neuroinflammation, E/I imbalance, network instability, and impaired adaptive plasticity. Full article

Background/Objectives: Visual impairment is an underrecognized but functionally disabling complication of stroke that adversely affects rehabilitation potential, autonomy, and quality of life. Clinical, anatomical, and ophthalmologic determinants of post-stroke visual recovery remain incompletely defined, particularly in Eastern European tertiary stroke units where structured visual follow-up is not standardized. This study aimed to identify clinical, imaging, and ophthalmologic predictors of favorable visual recovery and to evaluate whether integrating these domains improves early prognostic stratification beyond standard neurological assessment. Methods: We conducted a retrospective single-center cohort study of 71 consecutive adult patients admitted with acute stroke and a documented visual complication between January 2022 and September 2025 at Pius Brinzeu Emergency County Hospital and Victor Babes University of Medicine and Pharmacy Timisoara. Favorable recovery was defined as ≥50% improvement in visual field index (VFI) at 6 months. Group comparisons used Student’s t-test, Mann–Whitney U test, chi-square test, and Fisher’s exact test. Multivariable logistic regression, Cox proportional hazards modeling, and unsupervised k-means clustering were performed. Results: Twenty-nine patients (40.8%) achieved favorable recovery, while 42 (59.2%) had persistent impairment. Responders were younger (62.8 ± 10.7 vs. 70.4 ± 10.8 years, p = 0.005) and had lower admission National Institutes of Health Stroke Scale (NIHSS) (6.4 ± 2.9 vs. 10.3 ± 4.4, p < 0.001), smaller lesion volumes (18.7 ± 11.4 vs. 33.2 ± 18.7 mL, p < 0.001), thicker peripapillary retinal nerve fiber layer (89.3 ± 7.6 vs. 78.2 ± 9.4 μm, p < 0.001), and earlier rehabilitation initiation (11.4 ± 5.3 vs. 21.7 ± 9.8 days, p < 0.001). NIHSS, time to rehabilitation, and optical coherence tomography (OCT) pRNFL thickness remained independent predictors. The full integrated model achieved an area under the receiver operating characteristic curve (AUC) of 0.87. Cluster analysis identified three distinct phenotypes with favorable recovery rates of 79.2%, 34.8%, and 8.3%. Conclusions: Combined clinical, neuroimaging, and ophthalmologic profiling—particularly OCT pRNFL—meaningfully refines early prediction of post-stroke visual recovery and supports phenotype-driven rehabilitation planning. Full article

Background: Post-COVID-19 syndrome or Long COVID (LC) is a multi-system condition characterised by persistent symptoms beyond three months following SARS-CoV-2 infection. Pain, particularly musculoskeletal and neuropathic pain, is commonly reported and may substantially affect functioning and health-related quality of life (HRQoL). However, there is limited detailed characterisation of pain phenotypes and their differential impact on outcomes in LC. This study aimed to (i) characterise pain associated with LC, (ii) identify factors associated with pain type and severity, and (iii) examine its impact on HRQoL, physical activity, and work. Methods: A cross-sectional survey was conducted among adults with clinician-diagnosed or self-reported LC who reported current or previous joint, muscle, or nerve pain. Participants completed validated patient-reported outcome measures including the C19-YRS, Nordic Musculoskeletal Questionnaire, Pain Detect Questionnaire (PD-Q), Musculoskeletal Health Questionnaire, and EQ-5D-5L. Participants were classified into neuropathic, nociceptive, or ambiguous pain groups based on PD-Q scores. Descriptive analyses, group comparisons, and backward stepwise ordinary least squares regression were used to examine factors associated with overall pain (PD-Q Total). Results: Among 198 participants (73% female; mean age 52 ± 12.7 years; mean LC duration 2.4 years), 96% reported new or worsened pain following COVID-19 infection, with muscle pain (87%), joint pain (84%), and nerve pain (66%) most frequently reported. PD-Q scores suggestive of neuropathic pain were identified in 28% of participants and were associated with significantly greater pain intensity, symptom burden, functional impairment, and lower HRQoL (p < 0.05). These participants reported higher average pain scores across all body regions and greater radiating pain (76%) compared to other groups. Functional disability and anxiety were significant factors associated with pain severity. Conclusions: Pain is highly prevalent in LC, with neuropathic pain representing a distinct and more severe phenotype associated with substantial functional and quality-of-life impacts. This study provides novel comparative evidence on pain phenotypes and their differential burden, highlighting the need for targeted pain assessment and management strategies in LC. Full article