Search Results (2,284)

There is increasing interest in exercise training (ET) as a behavior with potential disease-modifying properties in people with multiple sclerosis (MS), as ET has beneficial effects on relapses, lesions, disability, and cognitive-processing speed (CPS) as markers of MS disease progression. There is limited evidence for ET as a behavior that may have disease-modifying properties based on its association with body fluid biomarkers of neuroaxonal injury in MS. This paper involved a narrative review for building a rationale that supports focusing on ET and body fluid biomarkers of neuroaxonal injury in MS, namely, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). We searched the PubMed, EBSCOhost (Medline Ultimate), and EMBASE databases from inception through February 2026 for articles aligning with the focus of this narrative review. The articles indicated that sNfL and sGFAP levels were notably higher in MS than in controls; differed across demographic and clinical variables; and responded beneficially with disease-modifying therapy usage in MS. We further located two meta-analyses examining ET effects on sNfL and sGFAP in MS, and there were significant positive effects on sNfL, but not sGFAP. Researchers should adopt discovery models and experimental medicine frameworks for guiding future randomized controlled trials of ET and biomarkers of neuroaxonal injury in MS. Full article

Background/Objectives: Breast Cancer-Related Lymphedema (BCRL) is one of the most prevalent complications among patients, causing physical limitations and a negative impact on their quality of life. Given its chronic nature and influence on personal autonomy, it is essential to review the therapeutic approaches applied to date. The main objective of this study was to analyze and to compare the effectiveness of the different treatments currently used in the management of BCRL, especially those that incorporate the intervention of an occupational therapist. Methods: A narrative review of the scientific literature published between 2013 and 2025 was conducted. The search was carried out in the PubMed, Scopus, Web of Science, and Dialnet databases. Inclusion and exclusion criteria were applied to select studies with therapeutic interventions, selecting eight studies for review. Results: Complex Decompression Therapy (CDT) is currently the standard treatment, although one of its components, manual lymphatic drainage, is controversial in terms of its effectiveness. Interventions such as Activity-Oriented Proprioceptive Anti-Edema Therapy (TAPA), adapted physical exercise, and hydrotherapy showed significant benefits in quality of life, functionality, and reduction in the volume of lymphedema. Conclusions: The therapeutic approach to BCRL must be multidisciplinary and personalized. Occupational Therapy (OT) provides a person-centered approach that contributes to improving occupational performance and patient well-being. More studies with greater methodological rigor and sample size are needed to unify clinical criteria. Full article

The loss of estrogen following menopause is associated with a marked increase in cardiometabolic risk, accompanied by adverse changes in lipid metabolism, insulin sensitivity, vascular function, and systemic inflammatory tone. Emerging evidence suggests that estrogen signaling interacts with chromatin regulatory mechanisms, including DNA methylation, histone modifications, and chromatin remodeling, across multiple metabolic tissues. In this review, we examine current evidence linking estrogen receptor signaling to epigenetic modulation in cardiovascular, hepatic, adipose, vascular, and immune systems. We propose that epigenetic remodeling represents a plausible and testable mechanistic framework connecting estrogen depletion to cardiometabolic disease progression, while acknowledging that much of the mechanistic evidence derives from preclinical and in vitro systems and that direct longitudinal validation in human cardiovascular tissues remains limited. We further explore how this framework may contribute to understanding the “estrogen paradox” and the heterogeneous outcomes of hormone replacement therapy (HRT), particularly within the context of the timing hypothesis. Finally, we evaluate pharmacologic and lifestyle interventions, including structured exercise, dietary modulation, and cardiometabolic therapeutics, through the lens of potential epigenetic influence. Clarifying tissue-specific and immune-integrated chromatin responses to estrogen loss will be essential for advancing precision strategies aimed at improving cardiometabolic health in postmenopausal women. Full article

Background/Objectives: Previous studies have suggested that lifestyle intervention (LSI) therapies involving diet and exercise can modulate DNA methylation; however, whether this occurs in severely obese hypogonadal men undergoing weight loss from diet and exercise remains unclear. Methods: In this study, we investigated the effects of weight loss from diet and exercise on global DNA methylation as well as on the mRNA expression of specific demethylation enzymes, DNMT1, DNMT3A, and DNMT3B—in peripheral blood mononuclear cells (PBMCs) and DNA methylation markers in DNA of severely obese hypogonadal men. This is a secondary analysis of samples of severely obese (body mass index of ≥35 kg/m²) hypogonadal men undergoing weight loss from diet and exercise in addition to an aromatase inhibitor (anastrozole) or placebo for a total of 12 months. Results: LSI therapy significantly reduced global DNA methylation and 5-methylcytosine (5-mC) levels, decreased DNMT1, DNMT3A, and DNMT3B (p < 0.05) mRNA levels and markedly decreased CEBPα, FTO, and PPARγ mRNA expression. The reduction in global methylation was independent of aromatase inhibitor use. Conclusions: In summary, our findings suggest that LSI induces epigenetic modifications in leukocytes, possibly through the regulation of DNMT gene expression. Future studies are warranted to clarify the mechanistic pathways linking lifestyle-induced epigenetic alterations to metabolic health outcomes. Full article

Background: Chronic pain is a prevalent and disabling condition that affects physical health but also cognitive domains. Executive functions, including inhibitory control, cognitive flexibility, and working memory, essentials for self-regulation, treatment adherence, and coping with symptoms, are particularly compromised. Physiotherapy interventions, traditionally aimed at physical outcomes, may also influence executive functions; however, their impact remains unclear. Objective: This review aimed to synthesize current evidence regarding the effects of physiotherapy-related interventions on executive function in adults with chronic pain. Methods: The review followed the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, and the protocol was registered in PROSPERO (CRD42024611800). A comprehensive search was performed. Randomized controlled trials (RCTs) included adults with chronic pain (≥3 months) whose executive function outcomes were evaluated after physiotherapy-based interventions. Results: Out of 12,391 records, 10 randomized controlled trials were included. Populations primarily had fibromyalgia, chronic low back pain, and chronic musculoskeletal pain. Interventions encompassed transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (rTMS), neurofeedback, structured exercise, and multimodal physical-cognitive-mindfulness training. Intervention durations ranged from one session to 16 weeks. Executive function was assessed with diverse neuropsychological tests. tDCS improved attention, inhibitory control, cognitive flexibility, and working memory. Exercise interventions showed benefits in working memory and inhibitory control. Conclusions: Preliminary evidence suggests that physiotherapy interventions, particularly anodal tDCS and structured exercise, may improve executive functions in individuals with chronic pain. Future trials should incorporate long-term follow-up. Integrating cognitive targets into physiotherapy may enhance the multidimensional management of chronic pain. Full article

Background/Objectives: Stroke is a leading cause of long-term disability, resulting in motor and functional impairments that compromise independence and quality of life. Telerehabilitation offers a promising solution by providing remote, continuous, and accessible post-stroke therapy. This systematic review examined the effects of telerehabilitation on functional capacity, mobility, balance, and quality of life in stroke survivors. Methods: A systematic search was conducted following PRISMA guidelines and registered in PROSPERO (CRD420251169784). Searches in PubMed, Cochrane Library, PEDro, Web of Science, Scopus and CINAHL ultimately identified randomized controlled and quasi-experimental trials from the last decade involving adult stroke patients receiving exercise-based telerehabilitation. Methodological quality was assessed using Joanna Briggs Institute tools and Cochrane risk of bias evaluation. Twenty-one studies with a total of 1067 participants were included, featuring supervised tele-sessions, autonomous exercises, caregiver-assisted training, and hybrid approaches. Results: Results demonstrated significant improvements in functional capacity, motor performance, balance, and quality of life, comparable to conventional rehabilitation. Additional benefits included enhanced self-efficacy, treatment adherence, and caregiver satisfaction. Overall risk of bias was low, though participant blinding was unfeasible. Conclusions: Telerehabilitation may represent a strategy for post-stroke recovery, with studies suggesting outcomes comparable to conventional face-to-face rehabilitation while enhancing accessibility and psychosocial well-being. However, further well-designed, standardized trials with longer follow-up periods are required to confirm its clinical effectiveness. Full article

Background: Reduced quality of life, cancer-related fatigue, and functional impairment are common during and after oncologic treatment. Although therapeutic exercise is effective, evidence on brief, supervised programs of moderate to vigorous intensity remains limited, despite their greater clinical feasibility. This study evaluated the effectiveness of a six-week multimodal Therapeutic Exercise Program (TEP) in patients with cancer. Methods: A randomized controlled clinical trial (NCT05816187) was conducted with 110 patients with cancer (stages I–III), assigned to either an intervention group (supervised TEP, three sessions per week for six weeks) or a control group (usual care). The program included cardiorespiratory and strength training with intensity monitored using the Rating of Perceived Exertion (RPE), as well as stretching exercises. Quality of life (QoL) was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F), functional capacity using the Six Minute Walk Test (6MWT), and muscle strength using the 30 Second Sit to Stand Test (30s-STST) and handgrip dynamometry (HGT). Analyses of covariance (ANCOVA), responder analyses based on the Minimal Clinically Important Difference (MCID), and effect sizes (ηp²) were performed. Results: The intervention group showed significant and clinically meaningful improvements in fatigue (FACIT-F: +4.53; p < 0.001; ηp² = 0.135), global QoL (+9.22; p = 0.006), physical function, functional capacity (+24.16 m in the 6MWT; p = 0.006), and muscle strength (30s-STST: +2.71 repetitions; handgrip: +3.32 kg; p < 0.001). A total of 63.3% of participants were responders for fatigue compared with 13.3% in the control group (NNT = 2.00). Functional improvements showed moderate correlations with fatigue and global health status. Among symptoms, only insomnia demonstrated a significant reduction. Conclusions: A brief, supervised, multimodal TEP of moderate to vigorous intensity appears to be an effective, safe, and clinically relevant intervention to improve fatigue, QoL, and functional capacity in patients with cancer, with potential applicability in multidisciplinary oncologic care. Full article

Context: Sport-related concussion (SRC) management has evolved substantially over the past 25 years. Early paradigms emphasized prolonged physical and cognitive rest; however, growing evidence has demonstrated that recovery following SRC is multidimensional and influenced by interacting neurological, vestibular, autonomic, cervical, cognitive, and psychological systems. Consequently, contemporary clinical practice has shifted toward active, multifaceted rehabilitation approaches. Objective: We aimed to synthesize and contextualize the evidence supporting a multifaceted approach to sport-related concussion management from 2000 through 2025, with emphasis on implications for athletic training practice. Data Sources: A structured literature search was conducted using PubMed, SPORTDiscus, CINAHL, and Web of Science to identify peer-reviewed publications related to SRC evaluation, management, and rehabilitation. Study Selection: Studies published between 1 January 2000, and 31 December 2025 involving human participants with sport-related concussion or sport-like mechanisms of mild traumatic brain injury were included. Evidence from randomized controlled trials, cohort studies, systematic and narrative reviews, and major consensus or position statements was considered. Data Extraction: Relevant studies were reviewed and synthesized across key domains of SRC management, including aerobic exercise, vestibular and oculomotor rehabilitation, cervical spine management, multimodal and profile-based rehabilitation, return-to-learn strategies, psychological and behavioral health considerations, and implementation patterns within athletic training settings. Results: A total of 182 publications contributed evidence to one or more components of multifaceted SRC management. Across domains, evidence supports early, symptom-limited aerobic exercise; targeted vestibular and cervical rehabilitation; structured return-to-learn planning; and the integration of psychological support. Multimodal rehabilitation and profile-based clinical categorization approaches were associated with shorter recovery timelines and improved functional outcomes compared with rest-only strategies. Despite strong evidence, implementation variability persists across athletic training settings. Conclusions: Evidence accumulated over the past 25 years supports a shift toward active, individualized, and multidisciplinary approaches to SRC management. Athletic trainers are uniquely positioned to coordinate multifaceted care addressing the diverse contributors to concussion recovery. Full article

Background: Fibromyalgia (FM) and eating disorders (ED) represent distinct clinical entities traditionally managed within separate medical specialties, yet emerging evidence suggests significant comorbidity and potential shared pathophysiological mechanisms. Both conditions disproportionately affect women, involve complex multifactorial etiologies and substantially impair quality of life. Despite documented clinical overlaps, the mechanistic connections linking these conditions remain poorly characterized, and integrated treatment approaches are lacking. Objective: This narrative review examines the role of oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway dysfunction as a unifying molecular mechanism connecting fibromyalgia and eating disorders, with emphasis on implications for integrated rehabilitation strategies. Methods: We synthesized current evidence on oxidative stress pathophysiology in fibromyalgia and eating disorders, focusing on Nrf2-Keap1 pathway function, clinical comorbidity patterns and rehabilitation interventions targeting antioxidant defense mechanisms. In PubMed, representative search strings included “(fibromyalgia [MeSH] OR fibromyalgia [Title/Abstract]) AND (“eating disorders” [MeSH] OR “anorexia nervosa” [MeSH] OR “bulimia nervosa” [MeSH])” and “fibromyalgia AND (“oxidative stress” OR Nrf2 OR “redox”)”. Articles in English published through December 2025 were considered, with additional records identified by manually screening reference lists. Results: Fibromyalgia patients exhibit elevated oxidative stress markers, impaired antioxidant enzyme function and compromised Nrf2 activity correlating with disease severity, with studies reporting approximately 30–50% reductions in coenzyme Q10 levels compared with healthy controls. Similarly, eating disorders demonstrate mitochondrial dysfunction and oxidative stress dysregulation, though patterns differ across eating disorder phenotypes. Nrf2 serves as the master regulator of cellular antioxidant defense, coordinating expression of over 500 genes involved in detoxification, cytoprotection, inflammation modulation and metabolic regulation. Evidence suggests Nrf2 activity is regulated by energy balance, potentially linking nutritional status with cellular stress responses. Rehabilitation interventions, including graduated exercise and nutritional optimization with Nrf2-activating foods (cruciferous vegetables, polyphenols, omega-3 fatty acids), offer mechanism-based therapeutic approaches through hormetic Nrf2 activation and direct Keap1 modification. Conclusions: Multidisciplinary rehabilitation programs integrating physical therapy, exercise prescription and nutritional strategies targeting Nrf2 activation offer evidence-based, mechanism-driven approaches to address shared oxidative stress pathophysiology. Nrf2 pathway dysfunction represents a promising and biologically plausible molecular target that may help to unify our understanding of fibromyalgia and eating disorders pending confirmation from prospective clinical studies in comorbid populations. Future research should prioritize prospective clinical trials testing Nrf2-targeted interventions in comorbid populations and collaborative patient-centered care models. Full article

Background: Athletes may experience paroxysmal arrhythmias that occur during exercise and are difficult to document using standard diagnostic modalities. Such arrhythmias are often unpredictable, transient, and cannot be reproduced during routine exercise testing or ambulatory electrocardiographic monitoring, leading to prolonged diagnostic pathways and uncertainty regarding management. Methods: This case series presents ten athletes in whom clinically relevant paroxysmal arrhythmias were initially detected using commercially available wearable digital devices, primarily chest-strap heart rate monitors and smartwatches. Results: In most cases, arrhythmias could not be documented using conventional diagnostic methods despite repeated investigations. Most presented athletes were referred for invasive electrophysiological study, which confirmed supraventricular arrhythmias and enabled curative catheter ablation based solely on data obtained from wearable devices. The use of digital devices substantially shortened the time to diagnosis and treatment, reduced diagnostic burden, and allowed definitive therapy in symptomatic athletes. Conclusions: Wearable technology, particularly chest-strap heart rate monitors, may play an important role in the diagnostic evaluation of exercise-induced paroxysmal arrhythmias when standard methods fail. Full article

Background: COVID-19 can have adverse effects on individuals’ lung functions for up to 6 months or more after the episode. As a result, people may be reluctant to exercise, and this can have further adverse effects on their lung capacity and fitness. This study aimed to examine the effectiveness of a telemedicine program designed to increase the exercise participation of young adults after COVID-19 and evaluate the changes in lung function after exercise training. Methods: The quasi-experimental pre–post study recruited sixty university students who had suffered from COVID-19 within the past 12 months. Four pulmonary outcomes were compared: forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), and the ratio of FEV1 to FVC. The telemedicine exercise (TE) group (n = 36) received an intervention to carry out regular stepping exercise (up to 10,000 steps) via online video instruction and frequent WhatsApp reminder messages. The control group (n = 24) only received an initial WhatsApp message to carry out regular stepping exercise, with no further follow-up. Results: The FVC, FEV1, and FEV1/FVC ratio revealed significant overall improvement both within groups and between groups (p < 0.001), with moderate effect sizes. PEFR showed a significant improvement within groups (p = 0.007) but not between groups (p = 0.533). The TE group recorded a significant increase in daily step count (from 7165 to 9733, p < 0.001) after 4 weeks of training. The control group showed a significant reduction in step count (from 6975 to 6442, p = 0.049). Conclusions: The results confirmed the beneficial effects of the telemedicine exercise program in contributing to increased exercise participation and improved lung functions. Full article

This study aimed to assess the relative impact of the Osijek multidisciplinary biopsychosocial program for chronic low back pain (CLBP) compared with standard multimodal care with respect to pain intensity, disability, health-related quality of life, anxiety, depression, stress, and sleep quality using standardized self-assessment questionnaires and a smartwatch. A total of 128 patients treated at the Department of Pain Management, University Hospital Osijek, were randomly allocated to two groups. The multidisciplinary biopsychosocial group participated in a structured four-week program combining education, exercise, and individualized multidisciplinary care, while the multimodal group received conventional conservative treatment including pharmacotherapy and selected physical therapy modalities. The four-week intervention included standardized self-report questionnaires, a sociodemographic data form, and a Fitbit Charge 3 smartwatch for objective monitoring of sleep and physical activity. A significant reduction in pain intensity was observed across numerical scales and most questionnaire measures (Wilcoxon test, p < 0.01), except for the subscale assessing difficulties in performing daily activities due to sleep deprivation. Participants who underwent the multidisciplinary biopsychosocial treatment exhibited significant improvements (p < 0.03) in pain intensity, disability, health-related quality of life, stress, anxiety, and sleep quality compared with those receiving multimodal treatment. In both groups, a weak negative correlation was found between sleep quality and daily step count (Spearman’s rho = −0.234, p = 0.04). A multidisciplinary biopsychosocial program was associated with greater improvements in health-related quality of life, psychological well-being, and sleep quality in patients with chronic low back pain compared with a multimodal conservative approach. Increased daily physical activity was linked to improvements in anxiety and sleep. Although this study was designed as a randomized controlled trial, certain baseline differences between groups should be considered when interpreting the findings. Full article

Inhaled Treprostinil is the primary treatment of pulmonary hypertension related to interstitial lung disease (PH-ILD). Despite treatment effectiveness in clinical trials, the real-world safety and tolerability of this therapy remains unclear. We conducted a multicenter, retrospective review of adults with PH-ILD who were prescribed inhaled treprostinil. We assessed clinical outcomes, 6 min walk distance (6MWD) and changes in natriuretic peptides (BNP, NT-proBNP), as well as medication tolerance. Eighty-three patients met the inclusion criteria. The 6MWD data was collected but a limited number of patients had results within close proximity to initiation of inhalational treprostinil with only seven patients having assessments within the 3 months prior to initiation as well as 3 months post therapy. Limited 6MWD data is likely due, in part, to coinciding with the COVID pandemic, limiting face-to-face interactions and exercise testing. The majority of our subjects, 63%, had an absolute improvement in their BNP level, over a mean duration of 170 days. However, no significant difference was detected between baseline and follow-up natriuretic peptide levels. Adherence was assessed and the majority (77%) of patients remained on therapy at the time of censoring, with three-quarters (75%) meeting the target dose. Of the 15 patients intolerant to nebulized treprostinil who were transitioned to a dry powder inhaler, the majority (87%) were able to tolerate the other formulation. The medication was well-tolerated with a large percentage of patients remaining on therapy indefinitely and reaching the targeted therapeutic dose. Full article

Background: Post-stroke pain (PSP), particularly shoulder pain, is frequent and often underdiagnosed, limiting rehabilitation adherence and functional recovery. Current pharmacological and physical treatments offer only partial relief. Robotic-assisted therapy (RAT), such as the gravity-supporting Armeo^® Spring exoskeleton, delivers intensive, task-specific training with visual 2D feedback that may also alleviate PSP while enhancing motor outcomes. This study investigates whether RAT performed with the Armeo^® Spring reduces upper-limb PSP in chronic stroke patients versus conventional therapy and evaluates its effects on motor function and functional independence. Methods: In this retrospective parallel group study, 32 chronic post-stroke patients (8 females and 24 males with a mean age of 57 ± 11.74) were allocated to two groups: 16 received upper-limb RAT with the Armeo^® Spring, a gravity-supporting exoskeleton, (RAT group) and 16 underwent conventional rehabilitation (CR). The RAT group completed one-hour sessions 6 days/week for 8 weeks, performing 2D/3D gamified tasks targeting shoulder, elbow and forearm movements. The CR group received an equivalent amount of standard therapy, including passive/active-assisted mobilization, Bobath-based neuromuscular facilitation and reaching exercises. Results: Both the Armeo^® Spring and conventional therapy groups showed significant reductions in post-stroke pain (RAT p < 0.001 and conventional rehabilitation p = 0.004) and improvements in upper-limb motor function and functional independence (both p ≤ 0.002). Spasticity in the impaired limb decreased modestly in the RAT group (p = 0.031), with no significant between-group differences in pain or spasticity change (p = 0.437; p > 0.05, respectively). Conclusions: Gravity-support exoskeleton training reduced upper-limb spasticity, and no statistically significant between-group differences were observed compared with conventional physiotherapy for pain, mobility, and functional independence. Although clinical outcomes improved, health-related quality-of-life domains showed heterogeneous trajectories, underscoring the complexity of perceived health changes during chronic stroke rehabilitation. Larger randomized controlled trials incorporating neurophysiological and kinematic endpoints and longer follow-up are warranted to confirm effectiveness, particularly in chronic stroke and durability. Full article

Parkinson’s disease (PD) is the fastest-growing neurodegenerative disease affecting 90 thousand new Americans each year. PD includes motor and non-motor symptoms, resulting in progressive disability and difficulty in completing activities of daily living. Freezing of Gait (FoG) is one of the common disabling symptoms of PD, characterized by difficulties in initiating walking, resulting in gait abnormalities and increased risk of falling (RoF) and fear of falling (FoF). Clinical management of FoG is difficult as it is minimally responsive to both pharmacological and surgical interventions. In fact, these interventions can paradoxically worsen of FoG. Additionally, PD patients with FoG have reported worse health-related quality of life (HR-QoL) due to limitations in mobility, activities of daily living (ADL), bodily discomfort, stigma, and social isolation. Despite its increasing treatment and management of FoG is difficult due to its paroxysmal and heterogeneous nature. Therefore, there is a growing need for effective, evidence-based management and intervention approaches for FoG. Some current techniques used to manage FoG are physical therapy, exercise, gait training, and balance training; however, due to a lack of patient adherence, accessibility concerns, and the need for continuous supervision and individualized feedback, the long-term effectiveness of these interventions remains limited and challenging to achieve in real-world settings. A new promising avenue for managing PD is the use of wearable technology, which can provide audiovisual, via augmented and virtual reality (AR/VR), and tactical cueing to offset FoG, thereby enhancing independence in PD patients. In this comprehensive review, we will provide an overview of the symptoms, monitoring, and treatment of PD, with a focus on the neuroanatomy and treatment of FoG. We will review and critique the extant literature on the use of AR/VR technology in the management of FoG. Finally, the challenges and risks associated with wearable technology in FoG management will also be identified. Full article