Search Results (903)

Background: Temporomandibular disorders (TMD) are common musculoskeletal conditions affecting the temporomandibular joints, masticatory muscles, and associated structures. Their etiology is complex and multifactorial, involving anatomical, behavioral, and psychosocial contributors. Parafunctional habits such as clenching, grinding, and abnormal jaw positioning have been proposed as contributing factors, yet their individual and cumulative contributions remain unclear. This exploratory cross-sectional study aimed to evaluate the prevalence and severity of parafunctional habits and their association with TMD in medical students—a group exposed to elevated stress levels. Subjects were examined in Krakow, Poland, using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) protocol. Methods: Participants completed a 21-item Oral Behavior Checklist (OBC) assessing the frequency of oral behaviors on a 0–4 scale. A self-reported total parafunction load was calculated by summing individual item scores (range: 0–84). Logistic regression was used to evaluate associations between individual and total parafunction severity scores and TMD presence. Results: The study included 66 individuals aged 19–30. TMD was diagnosed in 55 participants (83.3%). The most commonly reported habits were resting the chin on the hand (90.9%) and sleeping in a jaw-compressing position (86.4%). Notably, jaw tension (OR = 14.5; p = 0.002) and daytime clenching (OR = 4.7; p = 0.027) showed significant associations with TMD in the tested population. Each additional point in the total parafunction score increased TMD odds by 13.6% (p = 0.004). Conclusions: These findings suggest that parafunctional behaviors—especially those involving chronic muscle tension or abnormal mandibular positioning—may meaningfully contribute to the risk of TMD in high-stress student populations. Moreover, the cumulative burden of multiple low-intensity habits was also significantly associated with increased TMD risk. Early screening for these behaviors may support prevention strategies, particularly among young adults exposed to elevated levels of stress. Full article

Craniofacial development is a complex, highly conserved process involving multiple tissue types and molecular pathways, with perturbations resulting in congenital defects that often require invasive surgical interventions to correct. Remarkably, some species, such as Xenopus laevis, can correct some craniofacial abnormalities during pre-metamorphic stages through thyroid hormone-independent mechanisms. However, the full scope of factors mediating remodeling initiation and coordination remain unclear. This study explores the differential remodeling responses of craniofacial defects by comparing the effects of two pharmacological agents, thioridazine-hydrochloride (thio) and ivermectin (IVM), on craniofacial morphology in X. laevis. Thio-exposure reliably induces a craniofacial defect that can remodel in pre-metamorphic animals, while IVM induces a permanent, non-correcting phenotype. We examined developmental changes from feeding stages to hindlimb bud stages and mapped the effects of each agent on the patterning of craniofacial tissue types including: cartilage, muscle, and nerves. Our findings reveal that thio-induced craniofacial defects exhibit significant consistent remodeling, particularly in muscle, with gene expression analysis revealing upregulation of key remodeling genes, matrix metalloproteinases 1 and 13, as well as their regulator, prolactin.2. In contrast, IVM-induced defects show no significant remodeling, highlighting the importance of specific molecular and cellular factors in pre-metamorphic craniofacial correction. Additionally, unique neuronal profiles suggest a previously underappreciated role for the nervous system in tissue remodeling. This study provides novel insights into the molecular and cellular mechanisms underlying craniofacial defect remodeling and lays the groundwork for future investigations into tissue repair in vertebrates. Full article

The abnormal growth of smooth muscle cells (SMCs) contributes to the vascular remodeling associated with coronary artery disease, a leading cause of death in women. Estradiol (E2) mediates cardiovascular protective actions, in part, by inhibiting the abnormal growth (proliferation and migration) of SMCs through various mechanism. Since microRNAs (miRNAs) play a major role in regulating cell growth and vascular remodeling, we hypothesize that miRNAs may mediate the protective actions of E2. Following preliminary leads from E2-regulated miRNAs, we found that platelet-derived growth factor (PDGF)-BB-induced miR-193a in SMCs is downregulated by E2 via estrogen receptor (ER)α, but not the ERβ or G-protein-coupled estrogen receptor (GPER). Importantly, miR-193a is actively involved in regulating SMC functions. The ectopic expression of miR-193a induced vascular SMC proliferation and migration, while its suppression with antimir abrogated PDGF-BB-induced growth, effects that were similar to E2. Importantly, the restoration of miR-193a abrogated the anti-mitogenic actions of E2 on PDGF-BB-induced growth, suggesting a key role of miR-193a in mediating the growth inhibitory actions of E2 in vascular SMCs. E2-abrogated PDGF-BB, but not miR-193a, induced SMC growth, suggesting that E2 blocks the PDGF-BB-induced miR-193a formation to mediate its anti-mitogenic actions. Interestingly, the PDGF-BB-induced miR-193a formation in SMCs was also abrogated by 2-methoxyestradiol (2ME), an endogenous E2 metabolite that inhibits SMC growth via an ER-independent mechanism. Furthermore, we found that miR-193a induces SMC growth by activating the phosphatidylinositol 3-kinases (PI3K)/Akt signaling pathway and promoting the G1 to S phase progression of the cell cycle, by inducing Cyclin D1, Cyclin Dependent Kinase 4 (CDK4), Cyclin E, and proliferating-cell-nuclear-antigen (PCNA) expression and Retinoblastoma-protein (RB) phosphorylation. Importantly, in mice, treatment with miR-193a antimir, but not its control, prevented cuff-induced vascular remodeling and significantly reducing the vessel-wall-to-lumen ratio in animal models. Taken together, our findings provide the first evidence that miR-193a promotes SMC proliferation and migration and may play a key role in PDGF-BB-induced vascular remodeling/occlusion. Importantly, E2 prevents PDGF-BB-induced SMC growth by downregulating miR-193a formation in SMCs. Since, miR-193a antimir prevents SMC growth as well as cuff-induced vascular remodeling, it may represent a promising therapeutic molecule against cardiovascular disease. Full article

Efficient new methods are needed to support initiatives to reduce, refine, and/or replace toxicity testing in vertebrates. 5-fluorouracil (5FU), hydroxyurea (HU), and ribavirin (RV) are mammalian teratogens. Skeletal, endocrine organ, and cardiac effects are often associated with teratogenesis, and a simple nematode like C. elegans lacks these systems. However, many genetic pathways required for mammalian morphogenesis have at least some conserved elements in this small, invertebrate model. The C. elegans lifecycle is 3 days. The effects of 5FU, HU, and RV on the C. elegans morphology were evaluated on day 4 post-initiation of the feeding after hatching for continuous and 24 h (early-only) developmental exposures. Continuous exposures to 5FU and HU induced increases in the incidences of abnormal gonadal structures that were significantly reduced in early-only exposure groups. The incidence of prolapse increased with continuous 5FU and HU exposures and was further increased in early-only exposure groups. Intestinal prolapse through the vulval muscle in C. elegans may be related to reported 5FU and HU effects on skeletal muscle and the gastrointestinal tract in mammals. Continuous RV exposures induced a phenotype lacking a uterus and gonad arms, as well as vulval anomalies that were largely, but not completely, reversed with early-only exposures, which is consistent with reported reversible reproductive tract anomalies after an RV exposure in mammals. These findings suggest that C. elegans can be used to detect the hazard risk from chemicals that adversely affect conserved pathways involved in organismal morphogenesis, but to determine the fit-for-purpose use of this model in chemical safety evaluations, further studies using larger and more diverse chemical test panels are needed. Full article

Engaging in sports, particularly at a competitive level, requires sustained muscle contractions before the onset of physical fatigue. Fatigue is highly prevalent in neuromuscular diseases, especially those affecting neuromuscular transmission (e.g., myasthenia gravis) or muscle membrane excitability (e.g., myotonia, certain metabolic myopathies). A decremental response in repetitive nerve stimulation (RNS) represents the neurophysiological analogue of exercise-induced muscle weakness. Patients with such responses exhibit abnormal suppression of muscle activity during repetitive or prolonged effort. Consequently, it is often assumed they should avoid strenuous physical activity. To assess the safety of sports participation in individuals with fatigability-related neuromuscular disorders, we examined the literature and report a new case of a patient with myotonia congenita who engaged in competitive sports without adverse events. The review identified only a few cases involving patients with myasthenia gravis or muscular dystrophies who also participated in competitive sports safely and with favorable outcomes. No adverse events were reported. While these findings suggest that sports participation may be feasible for selected patients, they cannot be generalized. Large-scale studies involving athletes with neuromuscular conditions are needed to evaluate the safety and long-term impact of exercise in these populations. Full article

Vein graft restenosis remains a major complication following coronary artery bypass grafting (CABG), mainly due to the abnormal proliferation of vascular smooth muscle cells (VSMCs) and impaired endothelial repair. While external stents (eStents) can provide mechanical support and limit adverse remodeling, traditional metallic stents are non-degradable and may induce chronic inflammation and fibrosis. In contrast, many bioresorbable materials degrade too quickly or lack mechanical strength. These challenges highlight the need for external stents that combine sufficient mechanical strength with biodegradability to support long-term graft patency. This is the first study that develops a chlorogenic acid–strontium (SrCA)-loaded polycaprolactone bioresorbable eStent that inhibits VSMC proliferation and enhances endothelial repair via Hippo–Yes-associated protein (YAP) signaling, addressing vein graft restenosis post-CABG. Combining mechanical support and biodegradability, it overcomes the limitations of non-degradable stents and rapidly degrading biomaterials, elucidates the potential of natural polyphenol–metal ion complexes in vascular remodeling, and offers an innovative strategy for the prevention of vein graft restenosis. Full article

Background/Objectives: Temporomandibular disorders (TMDs) are a group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and related anatomical structures. Although magnetic resonance imaging (MRI) is considered a noninvasive and highly informative imaging modality for assessing TMJ soft tissues, few studies have examined how TMJ structural features observed on MRI findings relate to oral function and craniofacial morphology in female patients with malocclusion. To investigate the associations among TMJ structural features, oral function, and craniofacial morphology in female patients with malocclusion, using MRI findings interpreted in conjunction with a preliminary assessment based on selected components of the DC/TMDs Axis I protocol. Methods: A total of 120 female patients (mean age: 27.3 ± 10.9 years) underwent clinical examination based on DC/TMDs Axis I and MRI-based structural characterization of the TMJ. Based on the structural features identified by MRI, patients were classified into four groups for comparison: osteoarthritis (OA), bilateral disk displacement (BDD), unilateral disk displacement (UDD), and a group with Osseous Change/Disk Displacement negative (OC/DD (−)). Occlusal contact area, occlusal force, masticatory efficiency, tongue pressure, and lip pressure were measured. Lateral cephalometric analysis assessed skeletal and dental patterns. Results: OA group exhibited significantly reduced occlusal contact area (p < 0.0083, η² = 0.12) and occlusal force (p < 0.0083, η² = 0.14) compared to the OC/DD (−) group. Cephalometric analysis revealed that both OA and BDD groups had significantly larger ANB angles (OA: 5.7°, BDD: 5.2°, OC/DD (−): 3.7°; p < 0.0083, η² = 0.21) and FMA angles (OA: 32.4°, BDD: 31.8°, OC/DD (−): 29.0°; p < 0.0083, η² = 0.17) compared to the OC/DD (−) group. No significant differences were observed in masticatory efficiency, tongue pressure, or lip pressure. Conclusions: TMJ structural abnormalities detected via MRI, especially osteoarthritis, are associated with diminished oral function and skeletal Class II and high-angle features in female patients with malocclusion. Although orthodontic treatment is not intended to manage TMDs, MRI-based structural characterization—when clinically appropriate—may aid in treatment planning by identifying underlying joint conditions. Full article

Cardiac cachexia (CC) is an advanced stage of heart failure (HF) characterized by structural and functional abnormalities in skeletal muscle, leading to muscle loss. Aerobic training provides benefits; however, the underlying molecular mechanisms remain poorly understood. This study aimed to investigate the therapeutic effects of aerobic training on transcriptomic alterations associated with disease progression in cachectic skeletal muscle. HF was induced in male Wistar rats by a single monocrotaline injection (60 mg/Kg). Aerobic training consisted of 30 min treadmill running at ~55% of maximal capacity, 5×/week for 4 weeks. Assessments included body mass, right ventricle mass, skeletal muscle fiber size and exercise tolerance. RNA-seq analysis was performed on the medial gastrocnemius muscle. Sedentary cachectic rats exhibited 114 differentially expressed genes (DEGs) while exercised cachectic rats had only 18 DEGs. Enrichment pathways analyses and weighted gene co-expression network analysis (WGCNA) identified potential key genes involved in disrupted lipid metabolism in sedentary cachectic rats, which were not observed in the exercised cachectic rats. Validation of DEGs related to lipid metabolism confirmed that Dgat2 gene expression was modulated by aerobic training in CC rats. These findings suggest that aerobic training mitigates transcriptional alterations related to lipid metabolism in rats with CC, highlighting its therapeutic potential. Full article

(1) Background: Biofeedback and neurofeedback are gaining attention as non-invasive rehabilitation strategies in Parkinson’s disease (PD) treatment, aiming to modulate motor and non-motor symptoms through the self-regulation of physiological signals. (2) Objective: This review explores the application of biofeedback techniques, electromyographic (EMG) biofeedback, heart rate variability (HRV) biofeedback, and electroencephalographic (EEG) neurofeedback in PD rehabilitation, analyzing their impacts on motor control, autonomic function, and cognitive performance. (3) Methods: This review critically examined 15 studies investigating the efficacy of electromyographic (EMG), heart rate variability (HRV), and electroencephalographic (EEG) feedback interventions in PD. Studies were selected through a systematic search of peer-reviewed literature and analyzed in terms of design, sample characteristics, feedback modality, outcomes, and clinical feasibility. (4) Results: EMG biofeedback demonstrated improvements in muscle activation, gait, postural stability, and dysphagia management. HRV biofeedback showed positive effects on autonomic regulation, emotional control, and cardiovascular stability. EEG neurofeedback targeted abnormal cortical oscillations, such as beta-band overactivity and reduced frontal theta, and was associated with improvements in motor initiation, executive functioning, and cognitive flexibility. However, the reviewed studies were heterogeneous in design and outcome measures, limiting generalizability. Subgroup trends suggested modality-specific benefits across motor, autonomic, and cognitive domains. (5) Conclusions: While EMG and HRV systems are more accessible for clinical or home-based use, EEG neurofeedback remains technically demanding. Standardization of protocols and further randomized controlled trials are needed. Future directions include AI-driven personalization, wearable technologies, and multimodal integration to enhance accessibility and long-term adherence. Biofeedback presents a promising adjunct to conventional PD therapies, supporting personalized, patient-centered rehabilitation models. Full article

Gynecologic perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms characterized by the co-expression of melanocytic markers (HMB-45 and Melan-A) and smooth muscle markers (SMA, desmin, and caldesmon). The uterus is the most common organ affected, with approximately 110 cases reported worldwide, while occurrences in the cervix, vagina, ovary, and other gynecologic locations are exceptionally rare. These tumors typically present with nonspecific symptoms such as abnormal uterine bleeding and pelvic pain, often mimicking other uterine neoplasms. Histopathologically, PEComas exhibit epithelioid and spindle cell morphology with variable nuclear atypia, mitotic activity, and characteristic immunohistochemical profiles. Although most PEComas behave benignly, a subset demonstrates malignant potential, associated with larger tumor sizes, an increased mitotic index, necrosis, and vascular invasion; however, standardized diagnostic criteria remain scarce. Molecular alterations frequently involve the mTOR signaling pathway through tuberous sclerosis complex (TSC) 1 and TSC2 gene mutations, offering potential targets for therapy. Surgical resection with clear margins remains the cornerstone of treatment. For advanced or metastatic cases, mTOR inhibitors have shown promising efficacy, whereas the role of radiotherapy remains uncertain. This review aims to synthesize current knowledge regarding the epidemiology, clinical presentation, histologic features, malignant potential, and treatment of uterine PEComas, emphasizing the importance of accurate histopathological classification and molecular profiling to guide individualized therapeutic strategies. Full article

Genetic dystonias are a heterogeneous group of movement disorders characterized by involuntary, sustained muscle contractions that cause repetitive movements and abnormal postures. Often beginning in childhood, they can significantly affect quality of life. Although individually rare, genetic causes are collectively relevant in pediatric dystonias, with over 250 associated genes. Among these, TOR1A, SGCE, and KMT2B are the most frequently reported in pediatric forms. Diagnosis is challenging due to the wide clinical and genetic variability. Recent advances in genetic testing, including whole-exome and whole-genome sequencing, have improved the early identification of causative variants. Functional data on selected mutations are helping to refine genotype–phenotype correlations. Management typically requires a multidisciplinary approach. Symptomatic treatments include anticholinergics, benzodiazepines, and botulinum toxin, while deep brain stimulation can be effective in refractory cases, especially in patients with TOR1A variants. Disease-modifying therapies are also emerging, such as gene therapy for AADC deficiency, highlighting the potential of precision medicine. This review provides an updated overview of pediatric genetic dystonias, with a focus on differential diagnosis and treatment strategies. Early and accurate diagnosis, together with personalized care, is key to improving outcomes in affected children. Full article

Thyroid hormones (THs) play a central role in cardiovascular and metabolic regulation, influencing lipid metabolism, insulin sensitivity and resting energy expenditure. Inherited disorders of impaired sensitivity to THs—including resistance to thyroid hormone alpha (RTHα) and beta (RTHβ), monocarboxylate transporter 8 (MCT8) deficiency and selenoprotein deficiency—lead to complex, multisystemic clinical features. Although these conditions are rare, with RTHβ being the most common and affecting about 1 in 20,000 newborns, they share clinical features with more prevalent thyroid disorders, such as hypothyroidism and hyperthyroidism, as well as neurological manifestations including muscle wasting and spasticity. These conditions present abnormal patterns of thyroid function and are associated with tissue-specific comorbidities such as arrhythmias, heart failure, dyslipidemia, hepatic steatosis, insulin resistance, and metabolic syndrome. To date, no targeted or controlled studies have evaluated the impact of lifestyle modifications in these patient populations. Therefore, this narrative review proposes plausible management strategies based on pathophysiological insights into the effects of thyroid hormones on target organs, combined with clinical reasoning and evidence extrapolated from related disorders. Physical exercise and diet may complement pharmacological treatments (e.g., levothyroxine or TRIAC) to improve cardiovascular and metabolic outcomes. In RTHβ, aerobic exercise enhances cardiovascular health, while a Mediterranean diet supports lipid control and glycemic parameters. In RTHα, physical exercise may aid neuromotor development, and a fluid-rich, fiber-moderated diet can alleviate constipation. In MCT8 deficiency, physiotherapy may improve mobility and relieve contractures, while nutritional support (e.g., feeding tube, gastrostomy) can be necessary to tackle feeding difficulties and reduce pulmonary complications. In selenoprotein deficiency, low-to-moderate physical exercise and an antioxidant-rich diet may protect against oxidative stress at several tissue levels. Although quantitative evidence is limited, this narrative review synthesizes current insights, providing a meaningful basis for future validation and research. Full article

This study aimed to investigate the spatial heterogeneity of molecular signature in the muscle of juvenile dermatomyositis (JDM) patients before and after treatment. Unsupervised reference-free deconvolution of spatial transcriptomics and standardized morphometry were performed in two JDM muscle biopsies with different clinical severity at disease onset and compared to healthy muscle. Identified signatures were scored in two additional JDM muscle biopsies from the same patient before and after remission. Disappearance of the normal muscle signature mostly corresponding to mitochondrial biology was observed in JDM. Three pathological transcriptomic signatures were isolated, related to “myofibrillar stress”, “muscle remodeling” and “interferon signaling” signatures. The “myofibrillar stress signature” was prominent in the most severe biopsy while the “muscle remodeling” signature was mostly present in the biopsy from the patient with good outcome. These signatures unveiled genes not previously associated with JDM including ANKRD1 and FSLT1 for “myofibrillar stress” and “muscle remodeling” signatures, respectively. Post-treatment analysis of muscle after two years remission showed a persistence of pathological signatures. This pilot study of JDM muscle identified spatially distributed pathological signatures that persist after remission. This work paves the way for a better understanding of the pathophysiology in affected muscle and the identification of biomarkers that predict relapse. Full article

Recent studies on myogenic satellite cells (SCs) in Duchenne muscular dystrophy (DMD) documented altered division capacities and impaired regeneration potential of SCs in DMD patients and animal models. It remains unknown, however, if SC-intrinsic effects trigger these deficiencies at pre-contractile stages of myogenesis rather than resulting from the pathologic environment. In this study, we isolated SCs from a porcine DMD model and age-matched wild-type (WT) piglets for comprehensive analysis. Using immunofluorescence, differentiation assays, traction force microscopy (TFM), RNA-seq, and label-free proteomic measurements, SCs behavior was characterized, and molecular changes were investigated. TFM revealed significantly higher average traction forces in DMD than WT SCs (90.4 ± 10.5 Pa vs. 66.9 ± 8.9 Pa; p = 0.0018). We identified 1390 differentially expressed genes and 1261 proteins with altered abundance in DMD vs. WT SCs. Dysregulated pathways uncovered by gene ontology (GO) enrichment analysis included sarcomere organization, focal adhesion, and response to hypoxia. Multi-omics factor analysis (MOFA) integrating transcriptomic and proteomic data, identified five factors accounting for the observed variance with an overall higher contribution of the transcriptomic data. Our findings suggest that SC impairments result from their inherent genetic abnormality rather than from environmental influences. The observed biological changes are intrinsic and not reactive to the pathological surrounding of DMD muscle. Full article

Background: Hereditary immune-mediated polymyositis has been reported in the Kooiker dog breed, associated with a 39 kb deletion and low penetrance. Approximately 10–20 percent of homozygous dogs and 0.5–2 percent of heterozygous dogs develop polymyositis. This study examines whether magnetic resonance imaging (MRI) can assist in diagnosing polymyositis in this breed. Methods: All dogs in this prospective case study were purebred Kooiker dogs referred for clinical examination to assess them for polymyositis. A dataset was compiled, including sex, neuter status, and, if applicable, age of onset, clinical signs, CK activity, electromyogram, and histopathological findings. MRI was performed using a 1.5 Tesla MRI scanner, with T1-weighted, T2-weighted, T2W fat-suppressed short tau inversion recovery (STIR), and T1-weighted post-contrast sequences. Results: Five Kooiker dogs were included in the study. Four dogs exhibited clinical signs compatible with polymyositis (one heterozygous and three homozygous for the 39 kb deletion), while one dog was homozygous for the 39 kb deletion but showed no clinical signs. The clinically affected dogs exhibited T2-weighted, STIR, and T1-weighted post-contrast muscular hyperintensity, and the diagnosis was confirmed with histopathology. The asymptomatic dog displayed no MRI abnormalities. Conclusions: MRI has proven to be a valuable tool in assisting with the diagnosis of Kooiker dogs carrying the 39 kb deletion. MRI can act as a screening tool for dogs with the 39 kb deletion, eliminating the need for an initial biopsy. A muscle biopsy, following a confirmatory MRI, is still the preferred method for diagnosing polymyositis. Full article