Search Results (158)

Skeletal muscle aging and related diseases are characterized by progressive loss of muscle mass, strength, and metabolic function. Central to these processes is mitochondrial dysfunction, which impairs energy metabolism, redox homeostasis, and proteostasis. In addition, non-mitochondrial factors such as muscle stem cell exhaustion, neuromuscular junction remodeling, and chronic inflammation also contribute significantly to muscle degeneration. This review integrates recent advances in understanding mitochondrial and non-mitochondrial mechanisms underlying muscle aging and disease. Additionally, we discuss emerging therapeutic approaches targeting these pathways to preserve muscle health and promote healthy aging. Full article

Background/Objectives: Sudden cardiac arrest (SCA) is a major global health concern with high mortality despite advances in resuscitation techniques. Achieving return of spontaneous circulation (ROSC) represents merely the initial step in the extensive rehabilitation journey. This review highlights the critical role of structured, multidisciplinary rehabilitation following ROSC, emphasizing the necessity of integrated physiotherapy, neurocognitive therapy, and psychosocial support to enhance quality of life and societal reintegration in survivors. Methods: This narrative review analyzed peer-reviewed literature from 2020–2025, sourced from databases such as PubMed, Scopus, Web of Science, and Google Scholar. Emphasis was on clinical trials, expert guidelines (e.g., European Resuscitation Council 2021, American Heart Association 2020), and high-impact journals, with systematic thematic analysis across rehabilitation phases. Results: The review confirms rehabilitation as essential in addressing Intensive Care Unit–acquired weakness, cognitive impairment, and post-intensive care syndrome. Early rehabilitation (0–7 days post-ROSC), focusing on parameter-guided mobilization and cognitive stimulation, significantly improves functional outcomes. Structured interdisciplinary interventions encompassing cardiopulmonary, neuromuscular, and cognitive domains effectively mitigate long-term disability, facilitating return to daily activities and employment. However, access disparities and insufficient randomized controlled trials limit evidence-based standardization. Discussion: Optimal recovery after SCA necessitates early and continuous interdisciplinary engagement, tailored to individual physiological and cognitive profiles. Persistent cognitive fatigue, executive dysfunction, and emotional instability remain significant barriers, underscoring the need for holistic and sustained rehabilitative approaches. Conclusions: Comprehensive, individualized rehabilitation following cardiac arrest is not supplementary but fundamental to meaningful recovery. Emphasizing early mobilization, neurocognitive therapy, family involvement, and structured social reintegration pathways is crucial. Addressing healthcare disparities and investing in rigorous randomized trials are imperative to achieving standardized, equitable, and outcome-oriented rehabilitation services globally. Full article

Temporomandibular disorders (TMDs) encompass a heterogeneous group of musculoskeletal and neuromuscular conditions affecting the temporomandibular joint (TMJ) and masticatory system. Due to academic stress and parafunctional habits, dental students may be particularly vulnerable to TMD. Objective: To determine the prevalence of TMD symptoms and their psychosocial and functional correlates among students at the Faculty of Dental Medicine, UMPh Iasi, Romania, using the diagnostic criteria for TMD (DC/TMD) self-report axis and axis II instruments. Methods: In this cross-sectional survey, 356 volunteer students (66.0% female; mean age, 22.9 ± 3.6 years) out of a total population of 1874 completed an online DC/TMD–based questionnaire. Axis I assessed orofacial pain, joint noises, and mandibular locking. Axis II instruments included the Graded Chronic Pain Scale (GCPS), Jaw Functional Limitation Scale (JFLS-20), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Oral Behaviors Checklist (OBC). Descriptive statistics summarized frequencies, means, and standard deviations; χ² tests and t-tests compared subgroups by sex; Pearson correlations explored relationships among continuous measures (α = 0.05). Results: A total of 5% of respondents reported orofacial pain in the past 30 days; 41.6% observed TMJ noises; 19.7% experienced locking episodes. Mean JFLS score was 28.3 ± 30.5, with 4.8% scoring > 80 (severe limitation). Mean PHQ-9 was 5.96 ± 5.37 (mild depression); 15.5% scored ≥ 10. Mean GAD-7 was 5.20 ± 4.95 (mild anxiety); 16.0% scored ≥ 10. Mean OBC score was 12.3 ± 8.5; 30.1% scored ≥ 16, indicating frequent parafunctional habits. Symptom prevalence was similar by sex, except temporal headache (43.4% females vs. 24.3% males; p = 0.0008). Females reported higher mean scores for pain intensity (2.09 vs. 1.55; p = 0.0013), JFLS (32.5 vs. 18.0; p < 0.001), PHQ-9 (6.43 vs. 5.16; p = 0.048), and OBC (13.9 vs. 9.7; p = 0.0014). Strong correlation was observed between PHQ-9 and GAD-7 (r = 0.74; p < 0.001); moderate correlations were observed between pain intensity and PHQ-9 (r = 0.31) or GAD-7 (r = 0.30), between JFLS and pain intensity (r = 0.33), and between OBC and PHQ-9 (r = 0.39) (all p < 0.001). Conclusions: Nearly half of dental students reported TMD symptoms, with appreciable functional limitation and psychosocial impact. Parafunctional behaviors and psychological distress were significantly associated with pain and dysfunction. These findings underscore the need for early screening, stress-management interventions, and interdisciplinary care strategies in the dental student population. Full article

Background: Magnesium (Mg) is an essential mineral that plays a vital role in various physiological processes, including enzyme regulation, neuromuscular function, and cardiovascular health. Dysmagnesemia has been associated with arrhythmias, neuromuscular dysfunction, and poor outcomes in intensive care unit (ICU) settings, representing diagnostic and therapeutic challenges. However, the relationship between dysmagnesemia and health outcomes in the ICU remains inadequately defined. Aim/Objective: This study aimed to assess the prevalence of dysmagnesemia and evaluate the correlation between total (tMg) and ionized magnesium (iMg) levels in a cohort of ICU and high dependency unit (HDU) patients. It also sought to evaluate patient characteristics and relevant health outcomes by comparing both concentrations of iMg and tMg. Methods: This prospective study was conducted among adult patients admitted to the ICU and the high dependency unit (HDU). Results: Among the 134 included patients, the median age was 63.5 years (IQR: 52.0–77.0). The majority, 91.0%, required mechanical ventilation. Additionally, 50.0% were diagnosed with diabetes, 28.4% had chronic kidney disease, and proton pump inhibitors (PPIs) were administered to 67.2% of the patients. The prevalence of hypomagnesemia, as measured by iMg, was 6.7%, while hypermagnesemia was at 39.6%. When measured by tMg, hypomagnesemia and hypermagnesemia were observed at rates of 14.9% and 22.4%, respectively. The iMg measurements showed an association between the incidence of atrial fibrillation and hypomagnesemia (p = 0.015), whereas tMg measurements linked hypomagnesemia with longer hospital stays. Notably, only a few patients identified with iMg-measured hypomagnesemia received magnesium replacement during their ICU stay. Conclusions: Dysmagnesemia is prevalent among critically ill patients, with discordance between iMg and tMg measurements. iMg appears more sensitive in detecting arrhythmia risk, while tMg correlates with length of stay. These findings support the need for larger studies and suggest considering iMg in magnesium monitoring and replacement strategies. Full article

This paper introduces a new conceptual framework for interpreting urethral retro-resistance pressure (URP) as a dynamic, intra-procedural tool—ΔURP—for evaluating external urethral sphincter (EUS) engagement during injection therapy. With renewed interest in therapies that directly target the EUS, there is a critical need for real-time functional feedback at the site of action. This conceptual review re-examines URP in the context of emerging EUS-targeted treatments—such as bulking agents, regenerative injections, and neuromodulatory interventions—and proposes a dynamic model (ΔURP) to measure changes in sphincteric resistance as a functional biomarker during intervention. We review the anatomical, neurophysiological, and histological features of the EUS complex; trace the clinical rise and decline of URP; and compare its utility to conventional diagnostic tools. ΔURP, defined as the change in URP from baseline, is explored as an objective measure of EUS function. We outline its potential applications in guiding therapy, evaluating response, and standardizing outcomes across treatments. Conventional urodynamic measures fail to isolate distal sphincter function. In contrast, URP directly challenges the EUS and, when combined with imaging or procedural tools, may provide real-time feedback on sphincter engagement. When reframed as a dynamic, motion-based readout, URP may fill a critical gap in procedural urology—offering a physiologic signal of therapeutic engagement during EUS-targeted interventions. ΔURP has the potential to revive and repurpose a once-abandoned method into a clinically actionable biomarker for next-generation continence care. Full article

With global population aging, muscle atrophy and functional decline—hallmarks of sarcopenia—pose growing challenges to public health and significantly impact the quality of life in older adults. The goal of this review is to present a thorough examination of the most recent developments in the study of sarcopenia, including the development of its pathophysiological mechanisms, diagnostic techniques, and multimodal intervention strategies. Particular attention is given to the role of declining sex hormones, such as testosterone and estrogen, as key drivers of anabolic resistance and muscle loss during aging. The review also addresses the current opportunities and challenges in translating basic research into effective clinical applications. Key focus areas include protein metabolism, mitochondrial dysfunction, chronic inflammation, and neuromuscular junction degeneration. Finally, it outlines future directions for precision classification, early detection, and personalized treatment, aiming to support interdisciplinary collaboration and shift sarcopenia management from reactive care to proactive, targeted intervention. Full article

Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. Objective: To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. Methods: In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. Results: Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. Conclusions: Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being. Full article

The fine regulation of antioxidant systems and intracellular production of reactive oxygen species (ROS) is responsible for cellular redox balance. The main organelles responsible for ROS production are mitochondria, and they complete this process through the electron transport chain. These potentially harmful molecules are buffered by enzymatic and non-enzymatic antioxidant systems. Oxidative stress is determined by an imbalance between the production and clearance of ROS in favor of the accumulation of these detrimental species, which generate cellular damage by interacting with macromolecules. In neurodegenerative diseases, oxidative stress has been demonstrated to be a crucial component, both causal and consequential to the disease itself. On the other hand, neurodegeneration disrupts neuromuscular junctions, leading to reduced muscle use and subsequent atrophy. Additionally, systemic inflammation and metabolic dysfunction associated with neurodegenerative diseases exacerbate muscle degeneration. Thus, sarcopenia and atrophy are common consequences of neurodegeneration and play a significant role in these disorders. Regarding this, ROS have been defined as promoting sarcopenia, stimulating the expression of genes typical of this condition. Overall, this review aims to contribute to filling the gap in the literature regarding the consequences at the muscular level of the relationship between oxidative stress and neurodegenerative diseases. Full article

As populations age, particularly in countries like Japan, mobility impairments related to ankle joint dysfunction, such as foot drop, instability, and reduced gait adaptability, have become a significant concern. Active ankle–foot orthoses (AAFO) offer targeted support during walking; however, most existing systems rely on rule-based or threshold-based control, which are often limited to sagittal plane movements and lacking adaptability to subject-specific gait variations. This study proposes an approach driven by neuromuscular activation using surface electromyography (EMG) and a Gated Recurrent Unit (GRU)-based deep learning model to predict plantar pressure distributions at the heel, midfoot, and toe regions during gait. EMG signals were collected from four key ankle muscles, and plantar pressures were recorded using a customized sandal-integrated force-sensitive resistor (FSR) system. The data underwent comprehensive preprocessing and segmentation using a sliding window method. Root mean square (RMS) values were extracted as the primary input feature due to their consistent performance in capturing muscle activation intensity. The GRU model successfully generalized across subjects, enabling the accurate real-time inference of critical gait events such as heel strike, mid-stance, and toe off. This biomechanical evaluation demonstrated strong signal compatibility, while also identifying individual variations in electromechanical delay (EMD). The proposed predictive framework offers a scalable and interpretable approach to improving real-time AAFO control by synchronizing assistance with user-specific gait dynamics. Full article

In older adults with reduced physical performance, an increase in the labile iron pool within skeletal muscle is observed. This accumulation is associated with an altered expression of mitochondrial quality control (MQC) markers and increased mitochondrial DNA damage, supporting the hypothesis that impaired MQC contributes to muscle dysfunction during aging. The autophagy–lysosome system plays a critical role in MQC by tagging and engulfing proteins and organelles for degradation in lysosomes. The endolysosomal system is also instrumental in transferrin recycling, which, in turn, regulates cellular iron uptake. In the neuromuscular system, the autophagy–lysosome system supports the structural integrity of neuromuscular junctions, and its dysfunction contributes to muscle atrophy. While MQC was thought to protect against iron-induced cell death, the discovery of ferroptosis, a form of iron-dependent cell death, has highlighted a complex interplay between MQC and iron-inflicted damage. Ferritinophagy, the autophagic degradation of ferritin, if overactivated, can induce ferroptosis. Alternatively, aging may impair ferritinophagy, leading to ferritin accumulation and the release of toxic labile iron under stress, exacerbating oxidative damage and cellular senescence. Physical activity supports muscle health also by preserving mitochondrial quantity and quality and enhancing bioenergetics. However, therapeutic strategies for preventing or reversing physical function decline in aging are still lacking due to the insufficient understanding of the underlying mechanisms. Unveiling how disruptions in iron homeostasis impact muscle quality in older adults may allow for the development of therapeutic strategies targeting iron handling to alleviate age-associated muscle decline. Full article

Objectives: The present study aimed to analyze the psychophysiological and neuromuscular reflex modifications following a single functional neurology intervention in individuals presenting vestibulo-ocular reflex (VOR) cancellation dysfunction. Methods: A total of 66 healthy participants, comprising an experimental group (n = 48; 22 females, 26 males; mean age 28.1 ± 7.8 years) and a control group (n = 18; 9 females, 9 males; mean age 28.6 ± 7.0 years), underwent comprehensive assessments at four distinct measurement moments: baseline, post-indicator muscle failure pre-intervention, immediately post-functional neurology intervention, and post-intervention indicator muscle failure, assessing neuromuscular (handgrip strength) and psychophysiological parameters, including blood oxygen saturation, heart rate, cortical arousal (critical flicker fusion threshold, CFFT), and pain perception (pressure pain threshold, PPT). The functional neurology treatment was tailored based on the ^®NeuroReEvolution protocol, emphasizing individualized proprioceptive recalibration, trigger point desensitization, and holistic neuroreflex modulation. Results: Statistical analyses indicated significant improvements within the experimental group following intervention. Specifically, tolerance to VOR cancellation stimuli significantly increased from a baseline of 1.0 ± 0.0 to 129.0 ± 36.7 post-intervention (p < 0.001, η² = 0.926), whereas the control group demonstrated no meaningful change. Furthermore, significant enhancements were noted in pressure pain threshold (27.49 ± 0.67 to 35.69 ± 0.60 kgf; p = 0.029), handgrip strength (20.41 ± 0.72 N to 26.56 ± 0.52 N; p = 0.012), and critical flicker fusion threshold (32.24 ± 0.45 Hz to 38.32 ± 0.60 Hz; p = 0.003). Conclusions: The results of this study demonstrate that a single functional neurology intervention significantly improved psychophysiological responses and neuromuscular reflex performance in participants with vestibulo-ocular reflex (VOR) cancellation dysfunction. Specifically, the intervention led to marked enhancements in pain tolerance, cortical arousal, and handgrip strength, and notably, an increased tolerance to VOR cancellation stimuli, indicating improved vestibular control. Cardiovascular parameters remained stable, highlighting the safety of the intervention. These findings support functional neurology as an effective therapeutic approach to address VOR-related dysfunctions by promoting neurophysiological resilience and motor function optimization. Full article

Background/Objectives: This study aimed to analyze the psychophysiological effects of functional neurology intervention on dysfunction in vestibular saccadic stimuli, focusing on its impact on muscle performance, psychophysiological arousal, and pain perception. Methods: Seventy-five healthy volunteer participants were randomly divided into two groups: an experimental group that received functional neurology treatment and a control group that did not. Both groups underwent the same evaluations at four distinct time points. Key measurements included pressure pain threshold (PPT), hand strength, critical flicker fusion threshold (CFFT), blood oxygen saturation, heart rate, and the number of saccadic stimuli tolerated until dysfunction in an indicator muscle (anterior deltoid). The functional neurology intervention involved proprioceptive reflexes, trigger point desensitization, and systemic approaches to rectify neuromuscular dysfunctions. Results: The results showed that the functional neurology intervention significantly increased the number of saccadic stimuli tolerated, from 3.6 ± 3.3 to 26.1 ± 8.7, indicating an improvement in neuromuscular endurance. Additionally, PPT readings exhibited an upward trend from baseline to post-intervention, with the final reading averaging at 10.2 ± 5.3 kgf, and hand strength measurements showed a modest but significant increase post-intervention. Notably, CFFT and blood oxygen saturation levels remained relatively stable, suggesting that the intervention’s primary impact was on neuromuscular performance and pain perception rather than on cognitive arousal or systemic oxygenation. Heart rate data indicated a decrease post-intervention, implying potential improvements in autonomic nervous system function. In contrast, the control group did not present significant changes in any of the psychophysiological parameters evaluated. These findings underscore the potential of targeted functional neurology treatments to enhance physical performance and provide valuable therapeutic benefits for neuromuscular and cognitive dysfunctions. Conclusions: Functional neurology interventions can effectively improve muscle endurance, pain management, and overall neuromuscular health, highlighting its relevance as a therapeutic modality in sports performance optimization and rehabilitation contexts. Full article

Botulinum neurotoxin (BoNT) intoxication is a rare but severe condition that is characterized by autonomic and neuromuscular dysfunction. This study aimed to evaluate autonomic impairment and blood pressure variability in patients with botulinum intoxication during an outbreak, compared to healthy controls, and to assess their progression over a six-month follow-up period. Methods: Twenty (n = 20) male patients diagnosed with BoNT intoxication and 34 age- and sex-matched healthy controls were enrolled. At baseline, all subjects underwent 24 h ambulatory blood pressure monitoring (ABPM), and clinostatic and orthostatic blood pressure measurements. Autonomic function parameters, including mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), SBP and DBP variability, SBP and DBP load, pulse pressure (PP), blood pressure variability ratio (BPVR), and morning surge, were analyzed. Follow-up assessments were conducted after six months. Results: Patients with botulinum intoxication exhibited significantly lower SBP, DBP, and blood pressure variability parameters compared to healthy controls. Orthostatic hypotension was present in 55% of patients at baseline, improving to 5% at follow-up. Respiratory failure occurred in 40% of cases, necessitating non-invasive ventilation in 35% and intubation in 20%. At six-month follow-up, mean SBP, DBP, heart rate, and blood pressure variability parameters increased significantly, indicating partial recovery of autonomic control. However, residual abnormalities in autonomic regulation persisted. Conclusions: BoNT intoxication leads to notable autonomic dysfunction, marked by impaired blood pressure regulation and a high prevalence of orthostatic hypotension. Although partial recovery occurs, long-term autonomic impairment persists, highlighting the necessity for ongoing cardiovascular monitoring and further research to accelerate autonomic recovery through targeted therapeutic interventions. Full article

Background/Objectives: Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disorder characterized by respiratory dysfunction that significantly impacts quality of life and longevity. This study aimed to explore the outcomes of pulmonary function tests and sleep-disordered breathing (SDB) workups in children with DM1 and to identify the factors contributing to SDB. Methods: A retrospective study examined patients’ medical records, including genetic analyses, clinical characteristics, and noninvasive pulmonary function testing (PFT), when possible. The Pediatric Sleep Questionnaire (PSQ), arterial blood gases, polygraphy, and overnight transcutaneous capnometry (PtcCO₂) were used to assess SDB. Results: The size of CTG expansion in the DMPK gene directly correlated with the severity of respiratory complications and the need for early tracheostomy tube insertion in 7/20 (35%) patients. A total of 13/20 (65%) children were available for respiratory evaluation during spontaneous breathing. While moderate/severe obstructive sleep apnea syndrome (OSAS) and hypoventilation were confirmed in 4/13 (31%) children, none of the patients had mixed or dominantly central sleep apnea syndrome. There was no correlation between apnea–hypopnea index (AHI) or PtcCO₂ and the presence of SDB-related symptoms or the PSQ score. Although a significant correlation between AHI and PtcCO₂ was not confirmed (p = 0.447), the oxygen desaturation index directly correlated with PtcCO₂ (p = 0.014). Conclusions: While SDB symptoms in children with DM1 may not fully correlate with observed respiratory events or impaired gas exchange during sleep, a comprehensive screening for SDB should be considered for all patients with DM1. Further research into disease-specific recommendations encompassing the standardization of PFT, as well as overnight polygraphic and capnometry recordings, could help to guide timely, personalized treatment. Full article

Background: Amyotrophic lateral sclerosis (ALS) is a rare, progressive, and incurable disease characterized by muscle weakness and paralysis. Recent studies have explored a possible link between ALS pathophysiology and mTOR signaling. Recent reports have linked the accumulation of protein aggregates, dysfunctional mitochondria, and homeostasis to the development of ALS. mTOR plays a pivotal role in controlling autophagy and affecting energy metabolism, in addition to supporting neuronal growth, plasticity, and the balance between apoptosis and autophagy, all of which are important for homeostasis. Aim: This mini-review approaches the regulatory roles of mTOR signaling pathways, their interaction with other metabolic pathways, and their potential to modulate ALS progression. Significance: It discusses how these metabolic signaling pathways affect the neuromuscular junction, producing symptoms of muscle weakness and atrophy similar to those seen in patients with ALS. The discussion includes the concepts of neurocentric and peripheral and the possible connection between mTOR and neuromuscular dysfunction in ALS. Conclusions: It highlights the therapeutic potential of mTOR signaling and interconnections with other metabolic routes, making it a promising biomarker and therapeutic target for ALS. Full article