Search Results (1,617)

Background/Objectives: Response heterogeneity limits the implementation of dry needling for spasticity in multiple sclerosis (MS). This secondary analysis aimed to identify early responders and explore predictors of response. Methods: We conducted a responder analysis of a pilot randomized, double-blind, sham-controlled trial (NCT05956119) including 18 ambulatory MS patients with spasticity, randomized to a single session of dry needling (n = 9) or sham (n = 9). Sensitive responder criteria were defined as improvement ≥ 2.0 s in Timed Up-and-Go, ≥5 points in MSQOL-54 physical component, or ≥10% in 25-Foot Walk Test at 4 weeks. Results: Using these criteria, 33.3% (3/9) of dry needling recipients were classified as responders versus 0% (0/9) in the sham group (p = 0.214). Responders were more frequently observed among participants with relapsing–remitting MS (100% vs. 40%, p = 0.090) and lower baseline disability (Expanded Disability Status Scale 3.4 vs. 4.4). A positive association was observed between baseline pyramidal subscore and physical quality-of-life change, although this did not reach statistical significance (r = 0.52, p = 0.150) in the active group. Conclusions: Approximately one-third of participants met predefined responder criteria following dry needling; however, these findings should be interpreted as preliminary signals derived from an exploratory, underpowered pilot analysis. These results are hypothesis-generating and require confirmation in adequately powered trials. Full article

The early identification of patients with highly active multiple sclerosis (HAMS) is crucial for guiding therapeutic decisions and initiating high-efficacy treatment strategies. This study aimed to characterize peripheral immune profiles that can distinguish between patients who are candidates for intensive therapy at disease onset and in later stages. Using spectral flow cytometry, we identified distinct immune signatures to differentiate early-stage patients from those with refractory, long-standing disease. In newly diagnosed individuals, decreased herpesvirus entry mediator (HVEM) expression on effector T helper (Th) cells distinguished HAMS from non HAMS cases. In contrast, patients with therapeutic resistance exhibited reduced CD28 expression on naïve regulatory and CD8⁺ T cells. Disability progression was associated with elevated HVEM on classical monocytes, decreased CD70 on CD56^bright natural killer cells (NK), and lower programmed cell death protein 1 (PD-1) expression on memory Th cells. Notably, CD28 expression on terminal effector CD8⁺ T cells and HVEM levels on plasmablasts emerged as strong predictors of progression independent of relapse activity, while higher PD-1 memory Th cell frequencies predicted clinical stability. This study identifies two panels of immune biomarkers: one distinguishing candidates for early high-efficacy intervention, and another defining patients with refractory disease. The immunological landscape of HAMS evolves across disease stages. In addition, we defined progression-associated markers detectable at the outset of follow-up, enabling the timely recognition of patients at heightened risk of disability accumulation, discriminating between neurodegeneration-driven and inflammation-driven mechanisms of progression. Full article

Background/Objective: Long COVID is an important cause of disability following SARS-CoV-2 infection; yet, its underlying mechanisms are not completely understood. One proposed mechanism is the long-lasting dysregulation of the immune complement system. This systematic review is the first to summarize the current evidence and evaluate the potential role of long-lasting complement activation in people with long COVID. Methods: A systematic electronic search on PubMed, MEDLINE, CINAHL, and Embase was conducted up to 15 October 2025, to identify studies investigating complement activation in people with the post-COVID-19 condition. The Newcastle–Ottawa Scale was used to evaluate the risk of bias and methodological quality. Results: Among the 247 studies initially identified, eleven met the inclusion criteria, comprising 1435 individuals (age: 48.5 years, 70% females) with long COVID and 1124 controls (age: 43.6 years, 60% females). All studies were of a high quality, with scores ranging from 7 to 8 stars (mean: 7.6 ± 0.5). The activation of the classical complement pathway was investigated in nine studies, whereas the lectin, alternative, and terminal complement pathways were each assessed in three studies. Multiple studies investigated several complement pathways. The results were heterogeneous since several markers of complement activation spanning the classical (C2, C4a, C4b, and C1s-C1INH), alternative (Ba, iC3b, and Factor D), and terminal (C5bC6, C5a, C9, and TCC) pathways were elevated, whereas other markers were not significantly different (C3, C4, and C4d) between patients with/without long COVID. In addition, markers spanning the lectin complement pathway (MBL, and MASP1-C1INH) were not significantly different between individuals with and without long COVID. Conclusions: The current evidence suggests potential long-lasting complement system dysregulation in individuals with long COVID, although the clinical significance remains controversial, due to heterogenous findings. Specific post-COVID symptom clusters, such as fatigue, dyspnea, or brain fog, have been linked to a distinct pattern of complement dysregulation. Substantial methodological heterogeneity, including differences in follow-up periods, complement markers, assessment methods, and control groups, along with the small number of available studies, underscores the need for further research to clarify the mechanisms linking complement dysregulation to long COVID. Full article

Stroke is a major global health concern, particularly among the elderly, who frequently present with multiple comorbidities, most notably cardiovascular diseases. Importantly, atrial fibrillation confers a nearly fivefold increase in stroke risk and accounts for up to one-quarter of ischemic strokes in older adults. Stroke is a neurological disease characterised by a strong cardiovascular interplay, and its multifactorial nature requires an integrated preventive approach. This review focuses on primary and secondary prevention in this population, with a frailty-informed perspective. We synthesise evidence on blood pressure control, lipid-lowering (including LDL-C targets), glycemic management, and antithrombotic strategies—particularly oral anticoagulation for atrial fibrillation—as well as the role of frailty indices in guiding individualised risk–benefit decisions. We also discuss practical care pathways, including structured post-discharge programs, continuity of care, and the need for multidisciplinary collaboration involving cardiologists, neurologists, and primary care. We highlight how frailty indices refine risk–benefit assessments without justifying therapeutic nihilism, and how sex- and age-related factors shape treatment effectiveness and safety. By narrowing scope and emphasising practical, multidisciplinary prevention strategies, this review aims to support clinicians in reducing recurrent events, disability, and mortality in very old patients. Future work should prioritise pragmatic trials, including those involving the oldest old and the use of standardised frailty metrics, to inform prevention decisions. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated neurological disorder characterized by inflammation, demyelination, and progressive neurodegeneration. While genetic susceptibility contributes to disease risk, a growing body of evidence highlights the crucial role of modifiable lifestyle factors in influencing MS onset, disease activity, progression, and overall quality of life. In this narrative review, we explored the relevant literature from commonly used datasets (PubMed, Scopus, Google Scholar), using search terms such as “Lifestyle and Multiple Sclerosis”, “Diet and Multiple Sclerosis”, “Sleep and Multiple Sclerosis”, “Alcohol consumption and Multiple Sclerosis”, and “Physical Activity and Multiple Sclerosis”. Obesity, particularly during adolescence, has emerged as a significant risk factor for MS, acting through immunometabolic mechanisms such as chronic low-grade inflammation, insulin resistance, and dysregulated adipokine signaling. Sleep disturbances are increasingly recognized as contributors to neuroinflammation and cognitive dysfunction, potentially mediated by impaired glymphatic clearance. Smoking is consistently associated with accelerated disability progression, while alcohol consumption shows dose-dependent effects, with excessive intake negatively impacting sleep and glymphatic function. Overall, lifestyle factors converge on shared biological pathways involving immune regulation, metabolic health, vascular integrity, and glymphatic function. Integrating evidence-based lifestyle counseling with disease-modifying therapies may represent a complementary strategy to optimize long-term outcomes in people with MS, while highlighting key areas for future translational and clinical research. Full article

Forest welfare services are public services derived from forests that contribute to physical, emotional, and social health, ultimately aiming to improve quality of life. This study aimed to empirically analyze the qualifications of forest welfare professionals and their perceptions of social services. An online survey was conducted with 752 certified forest welfare professionals in South Korea. Frequency, cross-tabulation, and multiple regression analyses were performed to identify key factors affecting their perceptions, including experience with social service provision, understanding of social services, and the perceived need for integration. Results showed that approximately 54% had experience providing social services, and statistically significant differences were found in perceived barriers and sustainability factors based on experience. Mental health improvement was identified as the most expected benefit of social service provision, with low-income individuals and people with disabilities recognized as key target groups. Regression analysis revealed that age, additional qualifications, and experience significantly affected understanding of social services, particularly experience. However, only social service experience significantly influenced the perception of the need for integration between forest welfare and social services. Qualification type and forestry employment status had no significant effect. This study clarifies how professional experience and certification backgrounds of forest welfare specialists influence their perceptions of social services. Based on these findings, the study provides an empirical foundation for exploring the potential expansion and integration of forest welfare services. These findings offer valuable guidance for practitioners and policymakers seeking to enhance forest service effectiveness and sustainability. Full article

Despite decades of interventions targeting modifiable risk factors to reduce the burden of cardiovascular disease, ischemic heart disease (IHD) remains the leading cause of mortality and the second leading cause of disability-adjusted life-years worldwide. Growing evidence suggests that phthalates–plasticizers widely used in consumer products, cosmetics, and medical devices, and therefore ubiquitous across environmental media, may contribute to IHD development. Epidemiological studies have reported associations between phthalate exposure and multiple markers of atherosclerosis, the pathological hallmark of IHD, with or without mediation by traditional cardiovascular risk factors. Experimental models support these findings, showing that phthalates can induce oxidative stress, mitochondrial dysfunction, apoptosis, lipid accumulation, and epigenetic alterations, all of which promote endothelial damage and atherogenesis. In this review, we synthesize current epidemiological findings linking phthalate exposure to IHD, describe the main cellular and molecular mechanisms involved, and outline research gaps and regulatory perspectives. We also discuss how novel analytical frameworks—including artificial intelligence—may enhance the integration of environmental, clinical, and molecular data to advance risk prediction and prevention strategies. Full article

The protection and promotion of the human rights of individuals with mental disorders is a critical global priority, and initiatives such as the WHO QualityRights program aim to strengthen rights-based mental health care. We aimed to investigate the impact of the QualityRights core training on promoting knowledge and practices among healthcare professionals regarding the human rights of individuals with mental disorders, and to assess whether this training can reduce the stigma associated with mental disorders among these professionals. A quasiexperimental pre–post study was conducted with 26 primary healthcare professionals. Of these, 14 provided complete paired data, enabling direct comparison before and after the intervention. Participants completed standardized questionnaires assessing attitudes toward people with mental health conditions and psychosocial disabilities. Data were analyzed using paired statistical tests for pre–post comparisons, followed by multiple linear regression to examine factors associated with changes in scores. The training produced meaningful improvements in several items related to autonomy, legal capacity, coercion, and rights-based practices. Higher educational level was associated with greater attitudinal change. The WHO QualityRights training positively influenced healthcare professionals’ attitudes toward human rights in mental health. Future research should include larger samples and long-term follow-up to strengthen the evidence base and evaluate the sustainability of these changes across diverse care settings. Full article

Cognitive impairment (CI) is a common and disabling manifestation of multiple sclerosis (MS), yet it remains underdiagnosed in clinical settings. This study aims to identify the volumetric MRI markers of CI in MS patients. A total of 79 MS patients were enrolled; after exclusions, 63 with relapsing-remitting MS (RRMS) and 7 with primary progressive MS were analyzed. All participants underwent neuropsychological testing (CVLT, BVRT, CTT, VFT, VST, and SDMT). Brain volumes were analyzed using FreeSurfer. In RRMS, 59% had CI (35% single-domain, 24% multidomain). Multidomain CI was linked to reduced left cerebellar white matter and bilateral pallidum volumes, slight choroid plexus enlargement, and higher lesion volume versus cognitively preserved patients. Significant correlations were found between brain volumes and cognitive test scores: cerebellar and cerebral white matter, corpus callosum, subcortical gray matter, and thalamus volumes correlated positively with measures of processing speed, memory, and verbal fluency, while higher lesion load and larger choroid plexus volumes were associated with poorer cognitive performance. CI in MS is linked to both global and regional brain atrophy, as well as lesion load. Volumetric MRI, including choroid plexus analysis, may represent candidate imaging correlates of CI; however, longitudinal and externally validated studies are needed to confirm their predictive value and clinical utility. Full article

Introduction: Neuropathic pain (NP) in neuromyelitis optica spectrum disorder (NMOSD) represents a significant and often under-recognized complication arising from central nervous system (CNS) lesions. Unlike other demyelinating disorders, NMOSD involves a distinct immunopathogenesis primarily driven by aquaporin-4 antibodies (AQP4-IgG), leading to severe inflammatory damage. NP is typically the consequence of inflammatory damage to the spinothalamic tract or dorsal columns, resulting in both acute and chronic pain syndromes. Methods: A systematic review and meta-analysis were conducted following a comprehensive search of Medline and Scopus, identifying nine eligible studies reporting on NP in NMOSD. Results: Pooled prevalence was estimated using a random-effects metaprop meta-analysis with Freeman–Tukey transformation and REML-based heterogeneity estimation. The pooled prevalence of NP among patients with NMOSD was 56.2% (95% CI: 41.7–70.1%; I² = 95.3%, p < 0.001). Sensitivity analysis including only AQP4-IgG⁺ cohorts revealed a prevalence of 63.2% (95% CI: 23.4–94.7%; I² = 98.1%, p < 0.001). No significant difference was found between mixed and AQP4-IgG⁺-only populations (53.05% vs. 63.27%, p = 0.63). Meta-regression showed no significant associations between NP prevalence and age (β = 0.01, p = 0.33) or disability (β = 0.08, p = 0.18). Qualitative synthesis demonstrated an association between thoracic spinal cord lesions and NP, and also indicated that NP was often resistant and refractory to standard pharmacologic therapies. Conclusions: NP affects one in two NMOSD patients, and is associated with thoracic spinal cord lesions. In comparison with multiple sclerosis, NP in NMOSD is primarily structural and immunopathological in origin. Treatment strategies remain inadequate, emphasizing the need for early recognition and a disease-specific therapeutic approach. Full article

Background/Objectives: Rotator cuff tears (RCTs) are a leading cause of shoulder pain and disability. Management typically involves conservative measures, such as physical therapy and anti-inflammatory medications, or surgery for full-thickness or refractory tears. Regenerative medicine therapies, including platelet-rich plasma (PRP), platelet lysate (PL), and mesenchymal stem cells (MSCs), show promise as alternative treatment strategies, although long-term outcomes remain under investigation. Methods: This cohort included 30 patients with partial rotator cuff tears and were treated with culture-expanded MSC injections. There was no control group. Inclusion criteria included an imaging-confirmed diagnosis of partial-thickness rotator cuff tears. Outcomes were assessed at multiple time points up to 6 years. Pain and function were assessed using the Disabilities of the Arm, Shoulder, and Hand (DASH), a Numeric Rating Scale (NRS), and the modified Single Assessment Numeric Evaluation (SANE). Results: Thirty patients (37 shoulders) were included in the analysis. Significant improvements in the NRS and DASH scores were observed at 3, 6, 12, 18, and 24 months (p < 0.01). Twenty-four months post-treatment, the mean NRS and DASH decreased by 2.25 and 15.93 points, respectively, and SANE improved by 60%. At six years, among seven respondents, the mean SANE improvement was 75.54%. During this study, no significant adverse events were reported. Conclusions: This study provides the longest known follow-up of MSC therapy for partial-thickness RCTs, finding sustained pain and functional improvements. The findings support further research into MSC-based and combination regenerative therapies as a viable alternative treatment option for partial-thickness rotator cuff tears. Full article

Background/Objectives: Cognitive impairment and sleep disturbances are highly prevalent in individuals with multiple sclerosis (MS), particularly during middle age, and negatively affect functional independence and quality of life. Although physical exercise has demonstrated cognitive and sleep-related benefits in MS, tolerance to high-intensity training is often limited. Blood flow restriction (BFR) training, which combines low-load resistance exercise with partial vascular occlusion, has emerged as a feasible alternative. This study aimed to evaluate the effects of a 12-week BFR training program on performance in specific cognitive domains and sleep quality in middle-aged adults with MS. Methods: A randomized controlled trial was conducted in 65 adults with relapsing–remitting multiple sclerosis (RRMS) aged 40–65 years and an Expanded Disability Status Scale score below 7. Participants were randomly assigned to a BFR training group or a usual-care control group. The intervention consisted of supervised low-load resistance training with BFR performed twice weekly for 12 weeks. Outcomes assessed before and after the intervention included processing speed (Symbol Digit Modalities Test), executive function (Trail Making Test A and B), verbal fluency (Isaacs Set Test), and self-reported sleep quality (Pittsburgh Sleep Quality Index). Results: Compared with controls, participants in the BFR group showed significant improvements in specific cognitive domains, including processing speed, executive function, and verbal fluency. Significant reductions were also observed in self-reported global sleep disturbance and daytime dysfunction. No adverse events were reported. Conclusions: A 12-week BFR training program improved performance in key cognitive domains and self-reported sleep quality in middle-aged adults with MS, supporting its feasibility and potential clinical relevance as an exercise-based intervention. Full article

Honour-based violence can be considered a serious global problem that involves violations of human rights, and having a disability may increase the risk of being subjected to violence. The purpose of this study was to investigate the situation and needs of persons with disabilities who have been subjected to honour-based violence. Interviews were conducted with a sample of seven women and three men aged 20–60 from different minority groups living in Sweden. All had different disabilities, including intellectual disabilities, PTSD, neuropsychiatric disabilities, mental illness, impaired hearing, deafness or deaf blindness. Thematic analysis was used, identifying four themes: A family context in the shadow of violence, Violence in different forms, Conditional belonging and The price of freedom. An intersectional perspective highlights how disability, in combination with gender, age, culture, religion and honour norms, increases vulnerability to control and violence. The common thread was the group’s specific exposedness to various forms of violence. The results point to the importance of recognising the complexity of having a disability in an honour-based context. A broader perspective is necessary to develop both measures to prevent and combat this violence and support for those who have disabilities and live with protected identities. Full article

Neurodegenerative diseases (NDs) are among the leading causes of disability and mortality worldwide and are characterized by multifactorial pathogenesis involving interconnected mechanisms, such as oxidative stress, protein misfolding and aggregation, neuroinflammation, and mitochondrial dysfunction. Dysregulation of transcription factors, governing cellular defense responses, particularly nuclear factor erythroid 2–related factor 2 (Nrf2), a key regulator of antioxidant and proteostatic pathways, plays a critical role in neurodegenerative processes. Currently, available pharmacological treatments for NDs are largely symptomatic, as no disease-modifying therapies exist. Natural bioactive compounds have emerged as promising multi-target agents, demonstrating antioxidant, anti-aggregative, and anti-apoptotic properties, frequently mediated through activation of the Nrf2 signaling pathways. These compounds may represent valuable supportive strategies alongside conventional drug treatments, potentially contributing to the modulation of multiple pathogenic mechanisms. This review summarizes key oxidative stress- and protein aggregation-driven mechanisms underlying Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. It further examines the neuroprotective potential of plant-, fungi-, and marine-derived natural compounds, with particular emphasis on Nrf2 activation. Beyond redox regulation, the broader role of Nrf2 in maintaining proteostasis is discussed. Overall, the review highlights Nrf2-inducing nutraceuticals as promising complementary, multi-target approaches for neuroprotection in NDs. Full article

Chronic pain is a highly prevalent and disabling condition with a well-documented female predominance in incidence, severity and persistence. These sex differences are driven by sexually dimorphic neuroimmune mechanisms rather than psychosocial factors alone. This systematic review was conducted to comprehensively synthesize human clinical and translational evidence on sex-specific neuroimmune and glial cell pathways underlying chronic pain. Scientific literature was systematically searched from database inception to December 2025 across multiple biomedical databases to identify relevant clinical and translational studies. Across pain conditions, convergent evidence demonstrated that chronic pain mechanisms diverge by sex at cellular and molecular levels. Male-predominant pathways were characterized by microglial activation, particularly P2X4 receptor–mediated signaling and brain-derived neurotrophic factor–dependent neuronal disinhibition, supported by neuroimaging, transcriptomic, and pharmacological data. In contrast, female-predominant mechanisms involved adaptive immune processes, including CD4⁺ and CD8⁺ T cell infiltration, pannexin-1–dependent leptin release, chemokine signaling, and astrocyte-mediated neuroimmune crosstalk. Sex-specific cytokine and chemokine profiles, differential glial activation patterns, and divergent neuroimmune–endocrine interactions further distinguished pain pathways between males and females. Despite consistent mechanistic trends, substantial heterogeneity within each sex, limited sex-stratified power in many studies, and variability in outcome measures constrained quantitative synthesis and generalizability. The findings indicate that chronic pain is not a unitary disorder but rather a collection of mechanistically distinct conditions shaped by biological sex. These results highlight the limitations of sex-neutral therapeutic strategies and support the development of precision medicine approaches incorporating sex-informed neuroimmune biomarkers and mechanism-matched interventions. Future studies should prioritize adequately powered sex-stratified analyses, integration of neuroimmune biomarkers and clinical trial designs capable of detecting sex-by-treatment interactions. Full article