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Search Results (210)

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Keywords = musculoskeletal dysfunction

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17 pages, 515 KB  
Article
Serum CCL18 May Reflect Multiorgan Involvement with Poor Outcome in Systemic Sclerosis
by Kristóf Filipánits, Gabriella Nagy, Dávid Kurszán Jász, Tünde Minier, Diána Simon, Szabina Erdő-Bonyár, Tímea Berki and Gábor Kumánovics
Biomolecules 2026, 16(1), 136; https://doi.org/10.3390/biom16010136 - 13 Jan 2026
Abstract
Background: Serum C–C motif chemokine ligand 18 (seCCL18) in systemic sclerosis (SSc) has been primarily associated with progressive interstitial lung disease (SSc-ILD) and mortality. However, its relationship with non-pulmonary organ involvement, disease activity, and long-term outcome has not been comprehensively evaluated. We therefore [...] Read more.
Background: Serum C–C motif chemokine ligand 18 (seCCL18) in systemic sclerosis (SSc) has been primarily associated with progressive interstitial lung disease (SSc-ILD) and mortality. However, its relationship with non-pulmonary organ involvement, disease activity, and long-term outcome has not been comprehensively evaluated. We therefore examined the clinical relevance of seCCL18 in a single-center SSc cohort. Methods: A total of 151 patients with SSc (83 diffuse cutaneous (dcSSc), 68 limited cutaneous SSc (lcSSc); median (IQR) disease duration: 9 (4;16) years) and 47 age- and sex-matched healthy controls (HCs) were enrolled. Serum CCL18 concentrations were measured by enzyme-linked immunosorbent assay. Elevated seCCL18 was defined as >130 ng/mL (mean + 2 SD of the healthy control group). Organ involvement and disease activity (EUSTAR Activity Index, EUSTAR-AI) were assessed at baseline, while survival was analysed longitudinally. Results: Patients with SSc had significantly higher seCCL18 levels than HCs (mean ± SD: 99.9 ± 43.2 vs. 75.0 ± 27.5 ng/mL, p < 0.01). Elevated seCCL18 was associated with SSc-ILD (81.1% vs. 60.5%, p = 0.022), reduced forced vital capacity (FVC < 70%: 16.2% vs. 3.5%, p = 0.006), and reduced diffusing capacity for carbon monoxide (DLCO < 70%: 80.6% vs. 54.4%, p = 0.005). Higher seCCL18 levels were observed in patients with myocardial disease (104.8 ± 41.8 vs. 83.8 ± 44.2 ng/mL, p = 0.008), left ventricular diastolic dysfunction (107.1 ± 40.5 vs. 84.5 ± 45.0 ng/mL, p < 0.001), and oesophageal involvement (110.7 ± 38.3 vs. 93.3 ± 43.1 ng/mL, p = 0.009). SeCCL18 levels above the cut-off were more frequently associated with tendon friction rubs (51.4% vs. 27.4%, p = 0.007), active disease (EUSTAR-AI ≥ 2.5: 73% vs. 44%, p = 0.002), and elevated inflammatory markers (CRP > 5 mg/L: 51.4% vs. 19.3%, p < 0.001; ESR > 28 mm/h: 37.8% vs. 18.4%, p = 0.015). During a median follow-up of 87 months, 22 patients (15%) died. Elevated baseline seCCL18 predicted poorer survival in univariate analysis (log-rank p = 0.013) and remained an independent predictor of mortality in multivariable Cox regression (HR 1.789; 95% CI 1.133–2.824; p = 0.013), together with declining DLCO and reduced six-minute walk test performance. Conclusions: Elevated seCCL18 may identify patients with systemic sclerosis who exhibit a more severe multisystem phenotype, including cardiopulmonary, gastrointestinal, and musculoskeletal involvement, increased inflammatory activity, and reduced long-term survival. These findings suggest that seCCL18 may have some clinical utility as a prognostic biomarker reflecting widespread disease involvement beyond the lungs, even in patients with long-standing disease; however, the lack of an established cut-off value requires further validation in prospective, multicentre studies. Full article
(This article belongs to the Special Issue Biomarkers in Musculoskeletal and Orthopedic Disorders)
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14 pages, 446 KB  
Article
The Role of Kinematic and Electromyographic Analysis of the Elbow in Arm Wrestlers
by Nicola Marotta, Ennio Lopresti, Francesco Zangari, Lorenzo Scozzafava, Federica Pisani, Ilona Yosypchuk, Michele Mercurio, Andrea Demeco, Alessandro de Sire and Antonio Ammendolia
Appl. Sci. 2026, 16(2), 713; https://doi.org/10.3390/app16020713 - 9 Jan 2026
Viewed by 101
Abstract
Background. Arm wrestling is a complex strength sport requiring detailed biomechanical analysis. This study investigated elbow functionality in medial epicondylitis using kinematic and electromyographic (EMG) approach. Methods. Hook technique specialists underwent a 10-session rehabilitation program (manual therapy and high-power laser). Outcomes were assessed [...] Read more.
Background. Arm wrestling is a complex strength sport requiring detailed biomechanical analysis. This study investigated elbow functionality in medial epicondylitis using kinematic and electromyographic (EMG) approach. Methods. Hook technique specialists underwent a 10-session rehabilitation program (manual therapy and high-power laser). Outcomes were assessed via the NRS and QuickDASH. Functional analysis utilized surface EMG (Biceps Brachii, Pronator Teres, Brachioradialis, Extensor muscle) and an inertial sensor measuring Mean Jerk (MJ) for movement fluidity. Results. Data analysis for the eleven male athletes (mean age: 22.4 years) revealed substantial improvements following the intervention. NRS decreased from 5.1 to 1.5, and QuickDASH dropped from 25.2 ± 5.3 to 5.5 ± 1.0, while mean jerk remained stable (3.37 to 3.22). Pronator Teres activation markedly increased in the concentric phase (30.14 µV to 127.3 µV), indicating better coordination. Biceps Brachii (BB): Assumed a more pronounced concentric role, likely a compensatory adaptation after pain reduction; and lastly, Common Finger Extensor increased activation suggested increased extensor loading during the push phase. Conclusions. The combined kinematic and EMG data were crucial for identifying underlying musculoskeletal dysfunctions. The findings support an integrated approach for elbow health in arm wrestlers, providing objective data for targeted rehabilitation and prevention programs focusing on both pain and neuromuscular coordination. Full article
(This article belongs to the Special Issue Advances in Biomechanics and Sports Medicine)
26 pages, 1058 KB  
Review
The Adipokine Axis in Heart Failure: Linking Obesity, Sarcopenia and Cardiac Dysfunction in HFpEF
by Luka Komić, Jelena Komić, Nikola Pavlović, Marko Kumrić, Josipa Bukić, Iris Jerončić Tomić and Joško Božić
Int. J. Mol. Sci. 2026, 27(2), 612; https://doi.org/10.3390/ijms27020612 - 7 Jan 2026
Viewed by 235
Abstract
Obesity, sarcopenia, and heart failure with preserved ejection fraction (HFpEF) constitute an interconnected clinical triad driven by multisystem mechanisms centered on the adipokine axis. Adipose tissue, now recognized as a dynamic endocrine organ, undergoes pathological remodeling in obesity, characterized by hypoxia, chronic low-grade [...] Read more.
Obesity, sarcopenia, and heart failure with preserved ejection fraction (HFpEF) constitute an interconnected clinical triad driven by multisystem mechanisms centered on the adipokine axis. Adipose tissue, now recognized as a dynamic endocrine organ, undergoes pathological remodeling in obesity, characterized by hypoxia, chronic low-grade inflammation, and dysregulated adipokine secretion. These changes impair endothelial function, promote myocardial fibrosis, and disrupt skeletal muscle metabolism, thereby linking cardiometabolic and musculoskeletal dysfunction. This review integrates current evidence on homeostatic adipokines, such as adiponectin, apelin, and omentin, that preserve vascular and muscular resilience, as well as stress-inducible adipokines, such as leptin, resistin, and GDF15, that reflect or amplify metabolic and inflammatory injury. A maladaptive adipokine milieu associates with a self-reinforcing cycle of endothelial dysfunction, myocardial stiffening, and muscle atrophy that characterizes s HFpEF in the context of obesity and sarcopenia. We further discuss emerging translational applications, including diagnostic and prognostic adipokine signatures, targeted modulation of adipokine pathways, and the therapeutic impact of GLP-1 receptor agonists on adipose–cardiovascular–muscle crosstalk. Remaining challenges, including the adiponectin paradox and pleiotropic adipokine effects, highlight the need for precision-medicine approaches integrating multimodal biomarker profiling with cardiometabolic and musculoskeletal phenotyping. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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13 pages, 458 KB  
Article
The Effect of Pes Planus on Balance Ability in Individuals with Chronic Ankle Instability—A Pilot Study
by Anna Christakou, Ioannis Kyrosis, Konstantinos Michopoulos, Ioannis Fytanidis and Ioannis Siakabenis
Therapeutics 2026, 3(1), 3; https://doi.org/10.3390/therapeutics3010003 - 31 Dec 2025
Viewed by 290
Abstract
Background/Objectives: Pes planus is characterized by loss of medial longitudinal foot arch, resulting potentially in dysfunction in balance. Chronic ankle instability (CAI) is related to sensorimotor control deficits. Both of these two musculoskeletal disorders have a diminishing effect on joint proprioception. The [...] Read more.
Background/Objectives: Pes planus is characterized by loss of medial longitudinal foot arch, resulting potentially in dysfunction in balance. Chronic ankle instability (CAI) is related to sensorimotor control deficits. Both of these two musculoskeletal disorders have a diminishing effect on joint proprioception. The present study examined the impact of flatfoot on balance in individuals with CAI. Methods: A total of 28 students (15 men, 13 women; 18–23 years, M = 20.46, SD = 1.07) were assigned to CAI with pes planus (n = 15) or CAI only (n = 13). Balance was assessed using the Y-balance test (YBT) and modified star excursion balance test (mSEBT) in three directions (anterior, posteromedial, and posterolateral), alongside the Cumberland ankle instability tool (CAIT). Group differences were analyzed with independent t tests or Mann–Whitney U tests (α = 0.05). Results: The findings of the study did not show statistically significant differences between the two groups in the balance variable [mSEBT/anterior left foot (t = 0.239, p = 0.865); mSEBT/posteromedial left foot (t = −0.048, p = 0.562); mSEBT/posterolateral left foot (t = 0.164, p = 0.258); mSEBT/anterior right foot (t = −0.433, p = 0.748); mSEBT/posteromedial right foot (t = 0.745, p = 0.606); mSEBT/posterolateral right foot (t = 0.263, p = 0.680); YBT/anterior left foot (U = 96.00, p = 0.93); YBT/posteromedial left foot (U = 94.50, p = 0.87); YBT/posterolateral left foot (U = 96.00, p = 0.93); YBT/anterior right foot (U = 95.50, p = 0.92); YBT/posterolateral right foot (U = 82.50, p = 0.45)]. However, a trend towards significance was found as patients with flatfeet had a weaker performance in balance tests [posteromedial direction of the YBT for the right foot (U = 70.00, p = 0.12)]. Conclusions: Although pes planus did not seem to affect the balance ability of individuals with CAI, future studies should confirm the relationship of pes planus and CAI with a larger group, including variables such as ankle range of motion, muscle strength, and functional activity level. A better understanding of the above relationship may lead to more precise diagnostic processes and more efficient therapies in CAI. Full article
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19 pages, 1332 KB  
Article
Comparable Immune Alterations and Inflammatory Signatures in ME/CFS and Long COVID
by Steliyan Petrov, Martina Bozhkova, Mariya Ivanovska, Teodora Kalfova, Dobrina Dudova, Ralitsa Nikolova, Katya Vaseva, Yana Todorova, Milena Aleksova, Maria Nikolova, Hristo Taskov, Marianna Murdjeva and Michael Maes
Biomedicines 2025, 13(12), 3001; https://doi.org/10.3390/biomedicines13123001 - 8 Dec 2025
Viewed by 1902
Abstract
Background: Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a debilitating condition characterized by persistent fatigue and multisystemic symptoms, such as cognitive impairment, musculoskeletal pain, and post-exertional malaise. Recently, parallels have been drawn between ME/CFS and Long COVID, a post-viral [...] Read more.
Background: Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a debilitating condition characterized by persistent fatigue and multisystemic symptoms, such as cognitive impairment, musculoskeletal pain, and post-exertional malaise. Recently, parallels have been drawn between ME/CFS and Long COVID, a post-viral syndrome following infection with SARS-CoV-2, which shares many clinical features with CFS. Both conditions involve chronic immune activation, raising questions about their immunopathological overlap. Objectives: This study aimed to compare immune biomarkers between patients with ME/CFS or Long COVID and healthy controls to explore shared immune dysfunction. Methods: We analyzed lymphocyte subsets, cytokine profiles, psychological status and their correlations in 190 participants, 65 with CFS, 54 with Long COVID, and 70 healthy controls. Results: When compared to healthy subjects, results in both conditions were marked by lower levels of lymphocytes (CFS—2.472 × 109/L, p = 0.006, LC—2.051 × 109/L, p = 0.009), CD8+ T cells (CFS—0.394 × 109/L, p = 0.001, LC—0.404 × 109/L, p = 0.001), and NK cells (CFS—0.205 × 109/L, p = 0.001, LC—0.180 × 109/L, p = 0.001), and higher levels of proinflammatory cytokines such as IL-6 (CFS—3.35 pg/mL, p = 0.050 LC—4.04 pg/mL, p = 0.001), TNF (CFS—2.64 pg/mL, p = 0.023, LC—2.50 pg/mL, p = 0.025), IL-4 (CFS—3.72 pg/mL, p = 0.041, LC—3.45 pg/mL, p = 0.048), and IL-10 (CFS—2.29 pg/mL, p = 0.039, LC—2.25 pg/mL, p = 0.018). Conclusions: Notably, there were no significant differences between CFS and Long COVID patients in the tested biomarkers. These results demonstrate that ME/CFS and Long COVID display comparable immune and inflammatory profiles, with no significant biomarker differences observed between the two groups. Full article
(This article belongs to the Special Issue Neuroimmunology and Neurological Infection)
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13 pages, 739 KB  
Article
The Role of Posturography in the Diagnosis of Temporomandibular Disorders and Their Impact on Body Posture
by Krzysztof Antczak, Waldemar Pluta, Michał Lubkowski, Aleksandra Radecka and Anna Lubkowska
Biomedicines 2025, 13(12), 2857; https://doi.org/10.3390/biomedicines13122857 - 24 Nov 2025
Viewed by 613
Abstract
Background: Posturography is a diagnostic method used to evaluate postural stability by recording body sway and the distribution of pressure on the ground. Temporomandibular disorders (TMDs) involve musculoskeletal and neuromuscular dysfunctions affecting the temporomandibular joint, masticatory muscles, and associated structures. Given the [...] Read more.
Background: Posturography is a diagnostic method used to evaluate postural stability by recording body sway and the distribution of pressure on the ground. Temporomandibular disorders (TMDs) involve musculoskeletal and neuromuscular dysfunctions affecting the temporomandibular joint, masticatory muscles, and associated structures. Given the anatomical and functional connections between the stomatognathic system and postural control mechanisms, this study aimed to assess whether TMDs influence body posture and balance as measured by posturographic parameters. Methods: 75 volunteers, aged 19–48, were included. The TMD group (n = 45) was diagnosed based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), and the control group (n = 30) showed no signs of TMD. All participants underwent posturographic assessment and jaw opening range measurement. Posturography was performed using a pressure platform that recorded the center of pressure (COP) in static conditions. Postural stability was assessed using the Romberg test with eyes open and closed. Results: No statistically significant differences were found between the TMD and control groups in COP parameters, including ellipse area (EA) and total load distribution. Within both groups, COP sway increased significantly in the eyes-closed (EC) condition, as reflected by a greater unsteadiness length (UL). In contrast, EA was larger in the eyes-open (EO) condition in both groups, indicating a wider but more controlled spatial dispersion of COP. Intra-group analysis further revealed a significantly higher load on the left side in the control group only. Conclusions: The results do not support a significant postural imbalance in individuals with TMD compared to healthy controls. However, increased sway with eyes closed suggests that visual input plays a key role in postural control, regardless of TMD status. Full article
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15 pages, 1226 KB  
Systematic Review
Determinants of Postpartum Sexual Dysfunction in the First Year: A Systematic Review
by Aris Boarta, Adrian Gluhovschi, Marius Lucian Craina, Carmen Ioana Marta, Bogdan Dumitriu, Ioana Denisa Socol, Madalina Ioana Sorop and Bogdan Sorop
Healthcare 2025, 13(22), 2977; https://doi.org/10.3390/healthcare13222977 - 19 Nov 2025
Viewed by 1173
Abstract
Background and Objectives: This systematic review synthesized somatic and psychosocial determinants of postpartum sexual dysfunction (PSD) during the first 12 months after childbirth. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Web of Science, and Scopus from inception to 4 August 2025 without [...] Read more.
Background and Objectives: This systematic review synthesized somatic and psychosocial determinants of postpartum sexual dysfunction (PSD) during the first 12 months after childbirth. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Web of Science, and Scopus from inception to 4 August 2025 without language limits for the indexed records. Eligible studies enrolled postpartum women (≤12 months) and reported validated sexual outcomes (FSFI/FSFI-6, PISQ-12), dyspareunia, or sexual activity, examining breastfeeding, partner support/body image, perineal trauma/instrumentation, or postpartum perineal/musculoskeletal pain. Two reviewers independently screened and extracted data; risk of bias was assessed with a modified Newcastle–Ottawa Scale. Results: Of 1127 records screened, 15 studies were included. Perineal morbidity and early pain consistently tracked with worse sexual outcomes; assisted vaginal birth increased 6-month dyspareunia odds (OR 2.5). Breastfeeding was often associated with lower early sexual function and higher dyspareunia (6-month dyspareunia OR 4.4), with attenuation by 12 months. Higher partner/family support and more positive body image correlated with better FSFI scores. Heterogeneity in timing, measures, and adjustment precluded meta-analysis; results were narratively synthesized. Conclusions: Perineal trauma and early pain are dominant risk signals; breastfeeding-related symptoms exert early and context-dependent effects; psychosocial resources are protective. Full article
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16 pages, 297 KB  
Perspective
Regenerative and Drug-Free Strategies for Chronic Musculoskeletal Pain: An Evidence-Based Perspective on Shockwave Therapy, High-Intensity Laser Therapy and Ultrasound-Guided Mechanical Needling with Sterile Water Injection
by Carl P. C. Chen and Areerat Suputtitada
Biomedicines 2025, 13(11), 2801; https://doi.org/10.3390/biomedicines13112801 - 17 Nov 2025
Viewed by 1386
Abstract
Chronic musculoskeletal pain (CMP) is the leading global cause of disability and a major contributor to healthcare burden. Its pathogenesis reflects regenerative failure, driven by extracellular matrix (ECM) fibrosis, calcific deposition, mitochondrial dysfunction, and neuroimmune sensitization. Conventional pharmacological therapies such as NSAIDs, corticosteroids, [...] Read more.
Chronic musculoskeletal pain (CMP) is the leading global cause of disability and a major contributor to healthcare burden. Its pathogenesis reflects regenerative failure, driven by extracellular matrix (ECM) fibrosis, calcific deposition, mitochondrial dysfunction, and neuroimmune sensitization. Conventional pharmacological therapies such as NSAIDs, corticosteroids, and opioids offer only transient symptomatic relief while exposing patients to systemic complications. In contrast, energy-based, drug-free regenerative interventions directly address underlying pathology and restore physiological function. This Perspective synthesizes recent evidence (2020–2025) on three modalities that together form a regenerative triad: extracorporeal shockwave therapy (ESWT), high-intensity laser therapy (HILT), and ultrasound-guided mechanical needling with sterile water injection (SWI). ESWT promotes mechanotransduction, angiogenesis, and ECM remodeling; HILT enhances mitochondrial bioenergetics and downregulates inflammatory pathways; and SWI disrupts fibrosis and calcification while restoring neurovascular dynamics. Evidence from randomized controlled trials and meta-analyses supports moderate-to-high certainty (GRADE B–A–) for ESWT and HILT. SWI, initially supported by large observational cohorts and comparative studies, is now reinforced by a randomized comparative trial and meta-analyses of lavage effects, justifying an upgrade from moderate (B) to moderate-to-high certainty (B–A–). Risk of bias assessment using Cochrane RoB 2.0 and the Newcastle–Ottawa Scale (NOS) indicates overall low-to-moderate concerns across modalities. Together, these interventions integrate mechanistic biology with translational rehabilitation practice. This Perspective outlines their mechanistic foundations, clinical evidence, and alignment with the WHO decade of healthy ageing, offering a drug-free, mechanism-based framework for sustainable CMP management. Full article
13 pages, 1704 KB  
Article
Effect of Abdominal Adiposity on the Impact of Plantar Force in the Foot Support of Obese and Overweight Schoolchildren
by Ana Paula Ribeiro, Daniel Borges Pereira, Gabrielle Fontura Berger, Kemely Muraiber Ismail, Maitê Duarte Morais and Mayara Slaiman Fares Martins
Children 2025, 12(11), 1553; https://doi.org/10.3390/children12111553 - 17 Nov 2025
Viewed by 432
Abstract
Background: Childhood obesity is a growing global concern associated with early-onset orthopedic complications that may persist into adulthood. Among the anthropometric indicators, abdominal adiposity plays a key role in assessing health risks during pediatric evaluations. However, the relationship between abdominal fat distribution [...] Read more.
Background: Childhood obesity is a growing global concern associated with early-onset orthopedic complications that may persist into adulthood. Among the anthropometric indicators, abdominal adiposity plays a key role in assessing health risks during pediatric evaluations. However, the relationship between abdominal fat distribution and biomechanical alterations, such as changes in posture and foot support, remains poorly understood. Ultrasonography (US) is a validated, noninvasive imaging method capable of distinguishing preperitoneal and intraperitoneal fat in children. Despite its diagnostic advantages, no study to date has directly examined ultrasound-measured abdominal adiposity-predicted pronated foot posture in children. Objective: We aimed to verify the impact of abdominal adiposity on foot support and its association with obese, overweight, and eutrophic schoolchildren. Methods: This is a cross-sectional study. Sixty-five pupils (aged 6–9 years) from a public school in São Paulo, Brazil, were divided into three groups according to nutritional status: obese (n = 25), overweight (n = 20), and eutrophic (n = 20). Anthropometric measurements and foot posture, assessed using the Foot Posture Index (FPI), were collected during the initial evaluation. Abdominal adiposity was determined by ultrasonography, measuring subcutaneous, preperitoneal, and intraperitoneal fat thickness. Statistical Analysis: Analyses compared group differences and relations between abdominal fat and foot posture, with significance set at p < 0.05. Results: Obese and overweight schoolchildren showed pronated foot posture when compared to eutrophic children, on both sides of the feet. Abdominal adiposity was a good predictor of a more pronated footrest for the right and left feet, showing a high-to-moderate association. Conclusions: Ultrasound-measured abdominal adiposity was identified as a significant predictor of pronated foot posture in schoolchildren. These findings highlight the importance of monitoring abdominal fat accumulation during pediatric evaluations, as excessive adiposity may increase the risk of musculoskeletal dysfunctions and pain in the lower limbs. Early detection of these alterations may help prevent postural and musculoskeletal disorders in overweight and obese children. Full article
(This article belongs to the Section Pediatric Endocrinology & Diabetes)
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35 pages, 848 KB  
Systematic Review
Biodistribution and Toxicological Impact Assessment of Cerium Dioxide Nanoparticles in Murine Models: A Systematic Review of In Vivo and Ex Vivo Studies
by Polina I. Lazareva, Victor A. Stupin, Kirill A. Lazarev, Petr F. Litvitskiy, Natalia E. Manturova and Ekaterina V. Silina
Pharmaceutics 2025, 17(11), 1475; https://doi.org/10.3390/pharmaceutics17111475 - 16 Nov 2025
Cited by 1 | Viewed by 825
Abstract
Background/Objectives: This review summarizes and analyzes current data on the toxicological effects of cerium dioxide nanoparticles (nanoceria) on various anatomical and functional systems in healthy murine models, as reported in both in vivo and ex vivo experimental settings. Methods: This systematic review was [...] Read more.
Background/Objectives: This review summarizes and analyzes current data on the toxicological effects of cerium dioxide nanoparticles (nanoceria) on various anatomical and functional systems in healthy murine models, as reported in both in vivo and ex vivo experimental settings. Methods: This systematic review was conducted and reported in accordance with the PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD42024503240). A systematic literature search was conducted using the PubMed and ScienceDirect databases for the period 2019–2025, with the inclusion of earlier publications having significant scientific relevance. The final search update was conducted in July 2025 to ensure inclusion of the most recent studies. Results and Conclusions: Only in vivo and ex vivo studies in healthy murine models were included. Risk of bias was evaluated using the OHAT tool for animal studies, and data were synthesized narratively due to heterogeneity among studies. A total of 29 studies met the inclusion criteria. The pharmacokinetic properties of nanoceria were considered, encompassing biodistribution, elimination pathways (including oral, intravenous, intraperitoneal, inhalation, intratracheal, and instillation routes), and the influence of physicochemical characteristics on bioavailability and toxicity. The toxicological impact (TI) was assessed across major organ systems—respiratory, digestive, urinary, visual, reproductive, nervous, cardiovascular, immune, hematopoietic, endocrine, musculoskeletal, and skin. The liver, spleen, lungs, and kidneys were identified as primary accumulation sites, with clearance dependent on particle size and coating. The TI spectrum ranged from the absence of morphological changes to inflammation, fibrosis, or organ dysfunction, depending on dose, exposure route, and physicochemical parameters. The main limitations include variability of nanoparticle formulations and incomplete toxicity reporting. In general, CeO2 nanoparticles with sizes of 2–10 nm and doses ≤ 5 mg/kg showed no signs of systemic toxicity in short-term studies on healthy mice, provided that optimal coating and dosing intervals were used. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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17 pages, 6008 KB  
Case Report
Novel Sonoguided Digital Palpation and Hydrodissection for Sural Nerve Dysfunction Mimicking Achilles Tendinopathy in a Psoriasis Patient
by Yonghyun Yoon, King Hei Stanley Lam, Howon Lee, Chanwool Park, Seungbeom Kim, Minjae Lee, Jaeyoung Lee, Jihyo Hwang, Hyemi Yu, Jonghyeok Lee, Daniel Chiung-Jui Su, Teinny Suryadi, Anwar Suhaimi and Kenneth Dean Reeves
Diagnostics 2025, 15(21), 2706; https://doi.org/10.3390/diagnostics15212706 - 25 Oct 2025
Viewed by 1070
Abstract
Background and Clinical Significance: Psoriasis, a chronic immune-mediated inflammatory disease, can affect musculoskeletal structures, including the Achilles tendon. Achilles pain in psoriasis patients may arise from tendinitis or neuropathic pain due to peripheral nerve dysfunction, such as sural nerve (SN) involvement, a condition [...] Read more.
Background and Clinical Significance: Psoriasis, a chronic immune-mediated inflammatory disease, can affect musculoskeletal structures, including the Achilles tendon. Achilles pain in psoriasis patients may arise from tendinitis or neuropathic pain due to peripheral nerve dysfunction, such as sural nerve (SN) involvement, a condition frequently misdiagnosed due to limitations in conventional diagnostics. Fascial tissues are critical in nerve compression syndromes. This case explores the application of a novel quantitative Sonoguide Digital Palpation (SDP) protocol and ultrasound (US)-guided hydrodissection (HD) for SN dysfunction mimicking Achilles tendinopathy in a psoriasis patient. Case Presentation: A 41-year-old male with psoriasis presented with acute onset of right heel stiffness and paresthesia. Physical examination, radiographs, and ultrasound were performed. SDP, employing a validated four-criterion diagnostic framework (including fascial mobility quantification and concordant pain provocation), identified crural fascia restriction affecting SN and reproduced patient’s concordant Achilles pain. High-resolution ultrasonography provided key morphological evidence, revealing a 2.6-fold enlargement of the sural nerve’s cross-sectional area (CSA) on the affected side (13 mm2) compared to the asymptomatic side (5 mm2). Notably, a positive Tinel’s sign was elicited over the psoriatic plaque. US-guided HD was performed using 50 cc of 5% dextrose in water (D5W) without local anesthetic below the psoriatic lesion. Post-HD, the patient reported immediate and significant pain relief (Numeric Pain Rating Scale (NPRS) score reduction from 8 to 2), confirming the prompt correction of a clinically important fascial restriction, associated with improved SN mobility, objectively verified by a post-procedure SDP assessment. At 24-month follow-up, sustained symptom relief and complete functional recovery were reported. Conclusions: This case highlights SDP’s ability to objectively visualize and confirm fascial restriction as a cause of nerve dysfunction by quantitatively reproducing concordant pain. The objective finding of nerve swelling provides sonographic substantiation for the functional diagnosis of nerve dysfunction. This integrated diagnostic approach, combining dynamic functional assessment with morphological confirmation, offers a novel paradigm for evaluating peripheral nerve disorders. US-guided HD of the SN with D5W without local anesthetic shows promise as both a diagnostic confirmatory tool and therapeutic intervention for neuropathic Achilles pain in psoriasis patients with SN involvement, aligning with its efficacy in other peripheral neuropathies. The significant nerve swelling (13 mm2) provides robust morphological corroboration of the functional impairment diagnosed by SDP, offering a more comprehensive diagnostic paradigm. Full article
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16 pages, 1814 KB  
Review
Descending Pain Modulation in Fibromyalgia: A Short Review of Mechanisms and Biomarkers
by Bruno Daniel Carneiro, Sandra Torres, José Tiago Costa-Pereira, Daniel Humberto Pozza and Isaura Tavares
Diagnostics 2025, 15(21), 2702; https://doi.org/10.3390/diagnostics15212702 - 25 Oct 2025
Cited by 1 | Viewed by 3522
Abstract
Fibromyalgia is a prevalent chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, cognitive dysfunction, and sleep disturbances, with high impact in quality of life. Despite extensive research, the pathophysiological mechanisms of fibromyalgia remain partially understood, complicating the diagnosis and treatment. Some evidence [...] Read more.
Fibromyalgia is a prevalent chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, cognitive dysfunction, and sleep disturbances, with high impact in quality of life. Despite extensive research, the pathophysiological mechanisms of fibromyalgia remain partially understood, complicating the diagnosis and treatment. Some evidence underscores the central role of abnormal pain processing, particularly central sensitization and defective descending pain modulation pathways. This review synthesizes and discusses current findings on the neurobiological underpinnings of pain in fibromyalgia, with focus on descending inhibitory control mechanisms and on the role of biomarkers. We integrate data from neurochemical, neuroimaging, and clinical studies to explain how impaired descending modulation contributes to enhanced pain sensitivity and discuss the putative biomarkers associated with changes in descending modulation. A better understanding of descending pain modulation dysfunction in fibromyalgia and related biomarkers is crucial for improving clinical outcomes and developing novel and more effective treatments. Full article
(This article belongs to the Special Issue Progress in Chronic Pain: Bridging Basic and Clinical Research)
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17 pages, 1118 KB  
Article
Phase-Specific Biomechanical Characterization of Upper Limb Movements in Stroke
by Lei Li, Wei Peng, Jingcheng Chen, Shaoming Sun and Junhong Wang
Bioengineering 2025, 12(11), 1144; https://doi.org/10.3390/bioengineering12111144 - 23 Oct 2025
Viewed by 772
Abstract
Stroke often leads to persistent upper limb dysfunction that impairs activities of daily living, yet objective biomechanical indicators for precise assessment remain limited. This study aimed to characterize phase-specific impairments in energy output, torque stability, and muscle coordination during the hand-to-mouth (HTM) task [...] Read more.
Stroke often leads to persistent upper limb dysfunction that impairs activities of daily living, yet objective biomechanical indicators for precise assessment remain limited. This study aimed to characterize phase-specific impairments in energy output, torque stability, and muscle coordination during the hand-to-mouth (HTM) task and to explore their potential for improving rehabilitation evaluation. Motion data from 20 stroke patients and 20 healthy controls were recorded using wearable surface electromyography and inertial measurement unit systems. A musculoskeletal model was applied to calculate joint torque, mechanical work, torque smoothness, and a novel torque-based co-contraction index across four movement subphases. These phase-specific metrics demonstrated significant correlations with clinical motor impairment scores, confirming their clinical validity. Significant dynamic features were then selected to construct machine learning models for group classification. Stroke patients showed reduced output capacity, increased torque fluctuations, and abnormal co-contraction patterns that varied across subphases. Among the classifiers, the quadratic support vector machine achieved the best performance, with an accuracy of 84.6% and an AUC of 0.853, surpassing models based on whole-task features. These findings demonstrate that phase-specific biomechanical features sensitively capture neuromuscular deficits in stroke survivors and highlight the potential of phase-specific biomechanics to inform future individualized rehabilitation assessment and treatment planning. Full article
(This article belongs to the Section Biomechanics and Sports Medicine)
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14 pages, 535 KB  
Article
Evaluation of Safety and Acceptability of 40 Hz Amplitude-Modulated Auditory Stimulation in Healthy Older People: A Prospective Study from Japan
by Shunsuke Sato, Kazuma Maeda, Hiroki Chinen, Shinzo Hiroi, Keita Tanaka, Eriko Ogura, Hiroki Fukuju, Kentaro Morimoto, Yoshiki Nagatani, Kazuki Takazawa, Taiki Kasai, Yumi Ohta and Manabu Ikeda
Healthcare 2025, 13(20), 2638; https://doi.org/10.3390/healthcare13202638 - 20 Oct 2025
Viewed by 1150
Abstract
Background/Objectives: Dysregulated gamma oscillations are associated with cognitive dysfunction. Auditory stimulation at 40 Hz enhances neural activity in brain regions associated with learning, attention, and memory. This study assessed the safety and acceptability of 40 Hz amplitude-modulated auditory stimulation in healthy older people. [...] Read more.
Background/Objectives: Dysregulated gamma oscillations are associated with cognitive dysfunction. Auditory stimulation at 40 Hz enhances neural activity in brain regions associated with learning, attention, and memory. This study assessed the safety and acceptability of 40 Hz amplitude-modulated auditory stimulation in healthy older people. Auditory stimuli were created using popular songs, where vocals and background music were separated and independently amplitude-modulated at 40 Hz with different modulation depths to generate periodic 40 Hz gamma waveforms. Methods: In this open-label, single-arm study, healthy participants aged ≥65 years received 40 Hz amplitude-modulated auditory stimulation daily via a smartphone for 28 days through earphones/headphones. Safety was assessed through adverse event (AE) monitoring and changes in clinical scores for depression, cognitive function, and hearing thresholds. Acceptability was evaluated by adherence rates, listening time, dropout reasons, volume levels, intent for future use, and subjective impressions of the sound source on a 7-point Likert scale. Results: Among 28 participants (mean age 69.1 years, 53.6% female), six reported 12 AEs, with six considered device-related (e.g., ear discomfort, jaw pain, musculoskeletal stiffness). The AEs observed were mild or moderate. Scores for cognitive function, depression, and hearing thresholds did not worsen during the study period. Adherence was observed in 96.4%, with 85.7% expressing interest in continuing. Most participants rated the sounds’ unnaturalness between 2 and 3 and discomfort between 1 and 3 on the 7-point Likert scale. Conclusions: The intervention was well tolerated and acceptable in study participants, with no major safety concerns identified. Auditory stimulation did not cause severe discomfort or reduce acceptability. Further studies should explore the long-term effects and broader clinical applications. Full article
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24 pages, 4301 KB  
Article
Control Deficits and Compensatory Mechanisms in Individuals with Chronic Ankle Instability During Dual-Task Stair-to-Ground Transition
by Yilin Zhong, Xuanzhen Cen, Xiaopan Hu, Datao Xu, Lei Tu, Monèm Jemni, Gusztáv Fekete, Dong Sun and Yang Song
Bioengineering 2025, 12(10), 1120; https://doi.org/10.3390/bioengineering12101120 - 19 Oct 2025
Viewed by 1347
Abstract
(1) Background: Chronic ankle instability (CAI), a common outcome of ankle sprains, involves recurrent sprains, balance deficits, and gait impairments linked to both peripheral and central neuromuscular dysfunction. Dual-task (DT) demands further aggravate postural control, especially during stair descent, a major source of [...] Read more.
(1) Background: Chronic ankle instability (CAI), a common outcome of ankle sprains, involves recurrent sprains, balance deficits, and gait impairments linked to both peripheral and central neuromuscular dysfunction. Dual-task (DT) demands further aggravate postural control, especially during stair descent, a major source of fall-related injuries. Yet the biomechanical mechanisms of stair-to-ground transition in CAI under dual-task conditions remain poorly understood. (2) Methods: Sixty individuals with CAI and age- and sex-matched controls performed stair-to-ground transitions under single- and dual-task conditions. Spatiotemporal gait parameters, center of pressure (COP) metrics, ankle inversion angle, and relative joint work contributions (Ankle%, Knee%, Hip%) were obtained using 3D motion capture, a force plate, and musculoskeletal modeling. Correlation and regression analyses assessed the relationships between ankle contributions, postural stability, and proximal joint compensations. (3) Results: Compared with the controls, the CAI group demonstrated marked control deficits during the single task (ST), characterized by reduced gait speed, increased step width, elevated mediolateral COP root mean square (COP-ml RMS), and abnormal ankle inversion and joint kinematics; these impairments were exacerbated under DT conditions. Individuals with CAI exhibited a significantly reduced ankle plantarflexion moment and energy contribution (Ankle%), accompanied by compensatory increases in knee and hip contributions. Regression analyses indicated that Ankle% significantly predicted COP-ml RMS and gait speed (GS), highlighting the pivotal role of ankle function in maintaining dynamic stability. Furthermore, CAI participants adopted a “posture-first” strategy under DT, with concurrent deterioration in gait and cognitive performance, reflecting strong reliance on attentional resources. (4) Conclusions: CAI involves global control deficits, including distal insufficiency, proximal compensation, and an inefficient energy distribution, which intensify under dual-task conditions. As the ankle is central to lower-limb kinetics, its dysfunction induces widespread instability. Rehabilitation should therefore target coordinated lower-limb training and progressive dual-task integration to improve motor control and dynamic stability. Full article
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