Search Results (347)

Background/Objectives: This article aims to investigate the multifaceted effects of alcohol on neurophysiopathological development from gestational stages through adult life and the consequent dynamic-relational challenges in individuals with Fetal Alcohol Spectrum Disorder (FASD). FASD, resulting from prenatal alcohol exposure (PAE), is characterized by a range of neurological, cognitive, behavioral, and sometimes physical impairments. This article explores how alcohol and its toxic metabolites cross the placenta, inducing direct cellular toxicity and epigenetic alterations that disrupt critical neurodevelopmental processes such as neurogenesis and brain circuit formation. Clinically, individuals with FASD exhibit diverse deficits in executive functioning, learning, memory, social skills, and sensory-motor abilities, leading to significant lifelong disabilities. A central focus is the application of the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) criteria to comprehensively frame these disabilities. The ICF’s biopsychosocial model allows for a multidimensional assessment of impairments in body functions and structures, limitations in activities, and restrictions in participation, while also considering the crucial role of environmental factors. Methods: PubMed and Semantic Scholar databases were searched for relevant papers published in English. Results: This article highlights the utility of the ICF in creating individualized functioning profiles to guide interventions and support services, addressing the limitations of traditional assessment methods. Conclusions: While the ICF framework offers a robust approach for understanding and managing FASD, further research is essential to develop and validate FASD-specific ICF-based assessment tools to enhance support and social participation for affected individuals. Full article

Background: Acromioclavicular joint (ACJ) injuries frequently result from trauma to the shoulder girdle and are particularly common among young, physically active individuals. These injuries account for approximately 9% of all traumatic shoulder girdle injuries and often lead to functional impairment and pain. The TightRope^® system, LARS™ band, and Bosworth screw are among over 160 currently described surgical techniques for managing ACJ dislocations. However, there is no consensus regarding the optimal surgical approach, particularly for the management of moderate Rockwood Type III ACJ dislocations. Materials and Methods: In this retrospective study, data from 246 patients who underwent surgery for ACJ dislocation between 2010 and 2018 at the Department of Orthopedics and Trauma Surgery, Medical University of Vienna, were analyzed. Patients were divided into four cohorts based on the surgical technique used: Bosworth screw, LARS (acute), LARS (chronic), and TightRope. Clinical and radiological outcomes were assessed pre- and postoperatively using the Visual Analog Scale (VAS), Constant, Disability of the Arm, Shoulder and Hand Score (DASH), Simple Shoulder Test (SST), University of California—Los Angeles Shoulder Score (UCLA), Short Form Health Survey (SF-36), and American Shoulder and Elbow Surgeons score (ASES), as well as radiographic analysis. Radiological measurements of the acromioclavicular (AC) and coracoclavicular (CC) joint spaces were taken on both the injured and uninjured shoulders to analyze and compare the reduction in joint gaps. Results: All surgical methods resulted in significant reductions in AC and CC joint gaps. The TightRope and LARS acute groups showed the greatest reductions, with minimal complication rates. Complication analysis revealed significant differences in clavicular elevation (p < 0.001) and CC-ligament ossification (p = 0.006), which were most frequent in the Bosworth group and least common in TightRope^® patients, with LARS showing intermediate values. AC joint arthrosis was uncommon in all four groups and did not differ significantly (p = 0.13). Overall, TightRope^® was associated with the most favorable complication profile. The postoperative VAS score in the TightRope group was 1.52 ± 2.06, and the Constant score was 96.83 ± 5.41, reflecting high patient satisfaction. Conclusions: All systems led to satisfactory radiological and clinical outcomes, with the LARS™ band showing particular effectiveness in chronic ACJ dislocations. While all techniques provided good results, the TightRope^® system demonstrated the most favorable overall profile in our cohort and may therefore be considered a promising contemporary option. Further studies are needed to determine the optimal treatment for moderate ACJ dislocations and to assess the cost-effectiveness of these surgical techniques. Full article

Proximity-oriented planning aims to deliver everyday services within a short walk, yet closeness does not guarantee usable access for all residents. This study quantifies the gap between spatial proximity and functional accessibility in Timișoara, România, focusing on people with mobility and visual impairments. A three-stage analysis was conducted to evaluate accessibility to public amenities. First, (1) a survey was conducted with 605 respondents to identify distinct accessibility priorities based on 15-Minute City core dimensions defined by Carlos Moreno and adapted afterwards to the city context and needs. In the second stage (2), GIS mapping (radial buffers and isochrones) revealed major disparities among non-disabled residents and residents with mobility and visual impairments. Coverage decreased substantially across amenities under reduced-speed scenarios and after excluding wheelchair-inaccessible destinations. In the third stage (3), field-observed pedestrian routes in three areas of Timișoara were examined against the top-ranked criteria for each group, using the items sourced from the previous survey and grounded in the 15-Minute City concept. The route scoring is exploratory and specific to this context. The findings confirmed recurrent functional barriers, especially for vulnerable groups. These results expose a proximity-accessibility gap, where apparent nearness masks physical or sensory barriers. A shift toward experience-based accessibility planning is needed to ensure that proximity is not only spatial, but also usable by all and inclusive. Full article

Background: Degenerative lumbar spine disease is a prevalent cause of chronic low back pain that significantly impairs daily function and quality of life. While conservative management is the first line of treatment, many patients ultimately require instrumented lumbar spine surgery. However, postoperative outcomes vary considerably, with emerging evidence suggesting that preoperative psychological factors such as anxiety, depression, and pain catastrophizing may influence recovery. The SAP-LD (Scale for Anxiety and Pain in Lumbar Degeneration) study was designed to assess the prognostic role of these psychological and physical parameters in surgical outcomes. Methods: This prospective observational study enrolled 70 adult patients with degenerative lumbar spine pathology scheduled for instrumented surgical treatment at the University of Brescia and ASST Spedali Civili di Brescia between March and December 2024. Preoperative assessments included demographic, clinical, and radiologic data along with validated scales: the Oswestry Disability Index (ODI), 36-Item Short Form Health Survey (SF-36), Visual Analogue Scale (VAS), Pain Catastrophizing Scale (PCS), and Hospital Anxiety and Depression Scale (HADS). Follow-up evaluations were performed at 45 days and at 6 months, and statistical analyses were conducted using correlation tests, ANOVA, and regression modeling. Results: The demographic analysis of the 70 enrolled patients shows a balanced gender distribution (38 females, 34 males) with a mean age of 61 years (range 23–81). The educational level distribution indicates that the majority of patients (44.29%) have a secondary education level, while 35.71% have a tertiary education level. Regarding employment status, 50% of the patients are retired or not working. Patients with clinically significant anxiety and/or depression showed higher levels of perceived pain, pain catastrophizing, and disability at baseline. These patients reported significantly worse scores on the Visual Analogue Scale (VAS), Pain Catastrophizing Scale (PCS), and Oswestry Disability Index (ODI). The Oswestry Disability Index (ODI) demonstrates a clinically significant improvement (reduction) in disability between the preoperative period (t0) and the 45-day follow-up (t2), with the median decreasing from 39.00 to 13.00. However, there is a partial regression at the 6-month follow-up (t3), with the median increasing to 27.00. For the SF-36 Health Survey, the General Health subscale shows an improvement between t0 and t2 (median increasing from 55.00 to 60.00), followed by a slight decrease at t3 (median 55.00). Similar patterns are observed in most other subscales, with initial improvement followed by partial regression. The Pain Catastrophizing Scale (PCS) shows a substantial reduction in catastrophizing between t0 and t2 (median decreasing from 16.00 to 3.00), followed by an increase at t3 (median 11.00), though still below baseline levels. Pain intensity as measured by the Visual Analogue Scale (VAS) shows a significant reduction at t2 (median decreasing from 5.00 to 3.00), but increases again at t3 (median 6.00), even exceeding the preoperative level. For the Hospital Anxiety and Depression Scale (HADS), no significant differences were observed across time points, with values indicating mild symptoms throughout the study period. Correlation analyses confirmed that higher preoperative anxiety and depression scores were predictive of poorer postoperative outcomes. Specifically, higher HADS scores at baseline are associated with higher ODI scores (increased disability) at all time points (p = 0.002), higher VAS scores (increased pain) at all time points (p = 0.015), and lower scores on SF-36 subscales, particularly Emotional Well-being (p = 0.00023) and Social Functioning (p = 0.002). Higher PCS scores at baseline are associated with higher ODI scores at all time points (p = 0.001), higher VAS scores at all time points (p = 0.008), and lower scores on SF-36 subscales, particularly Pain (p = 0.00023) and Physical Functioning (p = 0.04254). The mixed linear models analysis confirms these findings, showing that the ODI score decreases significantly between t0 and t2 (p = 0.00023) and increases between t2 and t3, though this increase is not statistically significant (p = 0.079). For VAS scores, there is a significant decrease between t0 and t2 (p = 0.00023) and a significant increase between t2 and t3 (p = 0.04254). Patients with elevated preoperative HADS scores tended to have slower recovery trajectories and reported lower satisfaction levels. These findings reinforce the prognostic value of psychological assessments in spine surgery and suggest that targeted psychological interventions could improve patient outcomes. Conclusions: By identifying psychological predictors of postoperative recovery, this study underscores the importance of integrating preoperative psychological screening into routine clinical practice. The results suggest that a multidisciplinary approach, including both surgical and psychological care, could enhance long-term functional outcomes and quality of life for patients undergoing instrumented lumbar spine surgery. Full article

Background: Juvenile fibromyalgia (JFM) is a chronic pain disorder characterised by widespread musculoskeletal pain, functional impairment, fatigue, and mood disturbances. Treatment remains challenging, considering the multifactorial nature of the condition and the limited high-quality evidence supporting pharmacological or non-pharmacological interventions. Objectives: This review aimed to critically appraise level I evidence from randomised controlled trials assessing the efficacy and safety of pharmacological and non-pharmacological treatments for adolescents with JFM. Methods: Seven published peer-reviewed clinical trials were examined, including studies investigating duloxetine, milnacipran, pregabalin, cognitive-behavioural therapy (CBT), and the integrated Fibromyalgia Integrative Training Teens (FIT) program, which combines CBT with neuromuscular training. Outcomes of interest included pain intensity, functional disability, depression symptoms, physical activity, and adverse events. Results: Pharmacological agents such as duloxetine, milnacipran, and pregabalin demonstrated modest improvements in pain, but failed to produce consistent benefits in function or mood, and were associated with a high incidence of adverse effects. CBT significantly improved functional disability and depression symptoms, yet it had a limited impact on pain reduction or objectively measured activity levels. The FIT Teens program showed superior outcomes in pain intensity and biomechanical function compared to CBT alone, suggesting a synergistic effect of combining psychological and physical reconditioning strategies. Conclusions: Current evidence supports the use of multimodal treatment approaches in JFM. Non-pharmacological interventions, particularly when integrated with structured exercise, offer meaningful benefits with minimal safety concerns. Larger, methodologically rigorous trials are needed to establish optimal treatment pathways and long-term outcomes for this complex and underserved paediatric population. Full article

Brain–computer interfaces (BCIs) hold promise in enhancing accessibility in education by enabling students with physical disabilities to interact with digital learning environments without barriers. However, no comprehensive review has explored the landscape and role of BCIs in inclusive learning. Hence, this review sets out to identify relevant literature on BCI-based educational technologies, highlight their key themes, characteristics, and research methodologies, and identify research gaps. The secondary aim is to evaluate how these educational technologies contribute to inclusive learning frameworks by fostering communication, collaboration, engagement, and accessibility among students with disabilities. Overall, the reviewed studies demonstrate that BCIs can facilitate assistive communication among non-verbal students and provide motor control support for physically impaired persons. While these interventions show strong potential, challenges remain, including high implementation costs, user adaptability, and ethical concerns related to neural data privacy. Specifically, there is a need to (1) shift from experimental applications towards real-world classroom integration by developing user-friendly, cost-effective, and ethically sound BCI-based educational technologies, and (2) extend ongoing research efforts to include underserved populations to assess the generalizability of current and future BCI-based interventions. More importantly, future work should focus on enhancing BCI usability, improving adaptability for diverse learners, and establishing ethical guidelines for the development of socially responsible and inclusive neuro-educational technologies for all people with disabilities everywhere. This will go a long way in fostering the fourth and tenth United Nations Sustainable Development Goals of Quality Education and Reduced Inequalities, respectively. Full article

Background/Objectives: A growing body of evidence has revealed the multifaceted barriers populations with disabilities face during pregnancy and postpartum. This scoping review aimed to synthesize the literature on the implementation of disability-inclusive maternity care services for patients with disabilities. Methods: PubMed/MEDLINE, Embase, Scopus, PsycInfo were sourced for literature between January 2013 and July 2025. Articles were eligible for inclusion in the review if they reported on the implementation of interventions that aimed to improve quality of maternity care for pregnant or postpartum patients with physical, sensory, intellectual, mental impairments. In total, 6279 studies were screened to yield a final sample of 13 eligible articles. Key characteristics and implementation outcomes were extracted and synthesized from each eligible article. Results: Three of the studies targeted populations with physical impairments, five targeted populations with intellectual impairments, and five focused on populations with mental impairments. A variety of interventions were employed to improve the quality of care, targeting functional referral systems (n = 4), competent and motivated human resources (n = 4), actionable information systems (n = 3), effective communication (n = 1), and evidence-based practices (n = 1). Eligible studies reported acceptability (n = 11), adoption (n = 7), fidelity (n = 2), and penetration (n = 1) outcomes. The interventions generally reported high acceptability among providers and patients and emphasized the importance of participatory development and phased introduction. Conclusions: Significant gaps in the evidence remain across all categories of impairments. Additional research is needed to understand what types of interventions can be effectively implemented to improve the quality of maternity care for pregnant and postpartum patients with disabilities. Full article

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are among the leading causes of disability worldwide and are frequently associated with treatment resistance, functional impairment, and high comorbidity with metabolic dysfunction. Increasing evidence implicates insulin resistance (IR) as a key pathophysiological factor linking metabolic and psychiatric illness. IR is associated with chronic low-grade inflammation, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, impaired neuroplasticity, mitochondrial dysfunction, and altered reward processing mechanisms that may contribute to core depressive features such as anhedonia, cognitive slowing, and emotional dysregulation. These processes are further exacerbated by the metabolic side effects of many psychotropic medications, creating a self-perpetuating cycle that worsens both psychiatric and physical health outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for type 2 diabetes and obesity, have emerged as promising candidates to address this metabolic–psychiatric interface. Beyond improving glycemic control and promoting weight loss, GLP-1 RAs exert central actions relevant to mood disorders, including modulation of dopaminergic reward pathways, enhancement of hippocampal neurogenesis, attenuation of neuroinflammation, and regulation of appetite and energy balance. Preclinical studies demonstrate that GLP-1 RAs reduce microglial activation, promote hippocampal neurogenesis, and normalize stress-induced behavioral changes. Early clinical trials in patients with metabolic disorders suggest improvements in depressive symptoms, quality of life, and cognitive function, with some effects independent of weight loss or glycemic outcomes. Observational evidence also indicates reduced antidepressant use and psychological distress in diabetic and obese populations receiving GLP-1 RAs. While these findings are promising, large randomized controlled trials in primary psychiatric populations are lacking. Key challenges include clarifying dose–response relationships, disentangling central from peripheral effects, and addressing safety and adherence concerns in individuals with comorbid psychiatric conditions. Future research should focus on biomarker-informed stratification, comparative trials with standard treatments, and integration of GLP-1 RAs into multimodal care frameworks. Overall, GLP-1 RAs represent a biologically plausible and clinically relevant approach to bridging metabolic and psychiatric care, with the potential to improve outcomes in patients with mood disorders who carry a high metabolic burden. Full article

Background/Objectives: Bones are essential components of the human body, providing structural support, enabling mobility, storing minerals, and protecting internal organs. Bone fractures (BFs) are common injuries that result from excessive physical force and can lead to serious complications, including bleeding, infection, impaired oxygenation, and long-term disability. Early and accurate identification of fractures through radiographic imaging is critical for effective treatment and improved patient outcomes. However, manual evaluation of X-rays is often time-consuming and prone to diagnostic errors due to human limitations. To address this, artificial intelligence (AI), particularly deep learning (DL), has emerged as a powerful tool for enhancing diagnostic precision in medical imaging. Methods: This research introduces a novel convolutional neural network (CNN) model, the Multi-Level Feature Fusion Network (MLFNet), designed to capture and integrate both low-level and high-level image features. The model was evaluated using the Bone Fracture Multi-Region X-ray (BFMRX) dataset. Preprocessing steps included image normalization, resizing, and contrast enhancement to ensure stable convergence, reduce sensitivity to lighting variations in radiographic images, and maintain consistency. Ablation studies were conducted to assess architectural variations, confirming the model’s robustness and generalizability across data distributions. MLFNet’s high accuracy, interpretability, and efficiency make it a promising solution for clinical deployment. Results: MLFNet achieved an impressive accuracy of 99.60% as a standalone model and 98.81% when integrated into hybrid ensemble architectures with five leading pre-trained DL models. Conclusions: The proposed approach supports timely and precise fracture detection, optimizing the diagnostic process and reducing healthcare costs. This approach offers significant potential to aid clinicians in fields such as orthopedics and radiology, contributing to more equitable and effective patient care. Full article

Background/Objectives: Children, caregivers, and physicians may be insufficiently aware of the effect(s) of physical activity levels on the quality of life (QoL) of children with cerebral palsy (CP). This study aimed to understand the levels of physical activity of school-age children with CP compared with typically developing (TD) peers, and to examine the relationship between physical activity levels and the QoL of children with CP. Methods: We conducted a cross-sectional study of children with CP and TD children aged 6–12 years. Parents of children with CP completed a four-section survey: demographic information, parent-reported Gross Motor Functional Classification System, physical activity, and the CP-QoL questionnaire. Parents of TD children completed the demographic and physical activity sections. To account for the severity of motor impairment associated with CP, further analysis was conducted to compare QoL between the ambulant and non-ambulant groups of children with CP. Results: Eighty-two participants were included in the analysis: 42 children with CP and 40 TD children (8.29 ± 1.79 years; 8.35 ± 1.76 years). The lowest QoL domain scores were access to service, pain, and effect(s) of disability. Children with CP reported similar physical activity levels to those of the TD children. Physical activity levels were associated with the general QoL score, and feeling-social domains of QoL. Conclusion: Our findings support the positive prediction of high physical activity levels with QoL among school-aged children with CP. Full article

Background/Objectives: Motor decline in older adults can hinder cognitive assessments. To address this, we developed a brain–computer interface (BCI) using electroencephalography (EEG) and event-related potentials (ERPs) as a motor-independent EEG Switch. ERPs reflect attention-related neural activity and may serve as biomarkers for cognitive function. This study evaluated the feasibility of using ERP-based task success rates as indicators of cognitive abilities. The main goal of this article is the development and baseline evaluation of the Neurodetector system (incorporating the EEG Switch) as a motor-independent tool for cognitive assessment in healthy adults. Methods: We created a system called Neurodetector, which measures cognitive function through the ability to perform tasks using a virtual one-button EEG Switch. EEG data were collected from 40 healthy adults, mainly under 60 years of age, during three cognitive tasks of increasing difficulty. Results: The participants controlled the EEG Switch above chance level across all tasks. Success rates correlated with task difficulty and showed individual differences, suggesting that cognitive ability influences performance. In addition, we compared the pattern-matching method for ERP decoding with the conventional peak-based approaches. The pattern-matching method yielded a consistently higher accuracy and was more sensitive to task complexity and individual variability. Conclusions: These results support the potential of the EEG Switch as a reliable, non-motor-dependent cognitive assessment tool. The system is especially useful for populations with limited motor control, such as the elderly or individuals with physical disabilities. While Mild Cognitive Impairment (MCI) is an important future target for application, the present study involved only healthy adult participants. Future research should examine the sources of individual differences and validate EEG switches in clinical contexts, including clinical trials involving MCI and dementia patients. Our findings lay the groundwork for a novel and accessible approach for cognitive evaluation using neurophysiological data. Full article

Rheumatoid arthritis (RA) is a highly prevalent chronic inflammatory rheumatic disorder leading to functional impairment and sequels. The search for new biomarkers helping in detecting RA subjects of high risk of functional disability is required. Studies showing high follistatin levels in RA have been described; however, none of them have placed focus on the role of follistatin as marker of deteriorated functionality. We aim to identify whether follistatin concentrations could be a potential biomarker of physical disability and disease activity in RA patients. Fifty-seven female RA subjects and 20 age–gender-matched controls were included in a cross-sectional evaluation. An assessment of clinical characteristics, grip strength, gait speed, and muscle mass was conducted. In RA subjects, disability was assessed using HAQ-DI and active disease using the DAS28-ESR. Follistatin levels were measured by ELISA. We compared (a) RA + functional disability and (b) RA + preserved physical function. Serum follistatin levels were increased in RA subjects compared to controls (175 ± 119 vs. 133 ± 47; p = 0.030). Follistatin levels correlated with deteriorated physical function levels (r = 0.491; p < 0.001) and severe activity (r = 0.344; p = 0.009). The RA + functional disability group, as compared to the RA + preserved physical function group, had higher serum follistatin levels (218 ± 159 vs. 141 ± 59; p = 0.030), lower grip strength (7.9 ± 4.6 vs. 14.5 ± 5.1; p < 0.001), reduced gait speed (0.77 ± 0.20 vs. 0.92 ± 0.20; p = 0.010), as well as higher proportions of tender joints ≥4 (48% vs. 16%; p = 0.008), and higher disease activity scores (3.8 ± 1.5 vs. 2.8 ± 1.2; p = 0.008). We concluded that higher follistatin levels are associated with physical functional impairment and the severity of disease activity in women with RA. Future studies are required to evaluate whether these follistatin levels can be related to other outcomes such as labor disability, hospitalization, and falls. Full article

Background/Objectives: Pediatric acquired brain injury (ABI) often results in persistent challenges that extend beyond motor impairments, affecting quality of life (QoL), social participation, and engagement in physical activity. Given the complexity and chronicity of these outcomes, there is a pressing need for multidimensional interventions grounded in the International Classification of Functioning, Disability and Health (ICF). Sport-based exercise interventions, when developmentally adapted and tailored to individual interests, may promote intrinsic motivation, peer connection, and sustainable engagement—factors especially relevant in pediatric ABI populations, who often experience reduced physical activity and social isolation. However, standardized, replicable protocols specifically tailored to this population remain scarce. This study presents the protocol for a randomized controlled trial evaluating the effects of a 16-week sport-based intervention on QoL, social participation, physical activity engagement, and motor functioning tailored for adolescents with pediatric ABI. Methods: Participants will be randomly assigned to an intervention group or a control group receiving usual care. The intervention consists of one weekly 60-minute session, led by trained professionals in adapted physical activity and pediatric neurorehabilitation. It combines sport-based motor skill training, cooperative games, and group activities specifically tailored to each child’s developmental level, motor abilities, and preferences. Outcomes will be assessed at baseline and following the 16-week intervention period, focusing on QoL, participation, physical activity engagement, and motor functioning. Discussion: This study introduces a structured, child-centered model that bridges clinical rehabilitation and community-based sport. By integrating motor and psychosocial targets through a group sport-based intervention, it aims to enhance recovery across ICF domains. Findings may inform interdisciplinary practice and support the development of sustainable strategies to promote long-term engagement and well-being in adolescents with ABI. Full article

Background and Objectives: Facial paralysis involves the complete or partial loss of facial movement due to damage to the facial nerve, leading to impaired voluntary muscle function and facial asymmetry. Given its significant physical and psychosocial impact, there is an urgent need to strengthen the evidence supporting non-pharmacological treatments. This umbrella review aims to compile the most reliable and current data to establish a consensus on the effectiveness of such interventions for patients with facial paralysis. Materials and Methods: This study is an umbrella review. A systematic search was conducted in PubMed, Embase, Scopus, and CINAHL (28 July 2024). The variables assessed included overall healing/recovery rate, facial disability, and facial function. Methodological quality was evaluated using the AMSTAR and ROBIS tools. Screening was performed independently by two reviewers, with a third reviewer resolving any discrepancies. Results: Five systematic reviews were included, all evaluating the impact of non-pharmacological interventions in facial paralysis. The findings suggest that acupuncture and electrical stimulation may improve recovery rates and facial function, although high heterogeneity and methodological limitations were noted in some studies. No definitive conclusions could be drawn regarding facial disability. Conclusions: The combination of electrotherapy with other complementary techniques, such as facial exercises or laser therapy, appears to be a safe and potentially effective approach for facial paralysis rehabilitation. Nonetheless, further research employing standardized protocols and higher methodological quality is necessary to establish more robust conclusions for physiotherapeutic practice. Full article

Muscle wasting and weakness are critical clinical problems that limit mobility and independence, reduce health span, and increase the risk of physical disability. The molecular basis for this has not been fully determined. Klotho expression is downregulated in conditions associated with muscle wasting, including aging, chronic kidney disease, and myopathy. The objective of this study was to investigate a mechanistic role for Klotho in regulating muscle wasting and weakness. Body weight, lean mass, muscle mass, and myofiber caliber were reduced in Klotho-deficient mice. In the tibialis anterior muscle of Klotho-null mice, type IIa myofibers were resistant to changes in size, and muscle composition differed with a higher concentration of type IIb fibers to the detriment of type IIx fibers. Glycolytic GPDH enzymatic activity also increased. Klotho-deficient mice showed impaired muscle contractility, with reduced twitch force, torque, and contraction–relaxation rates. RNA sequencing revealed upregulation of synaptic and fetal sarcomeric genes, prompting us to examine muscle innervation. Klotho deficiency led to neuromuscular junction remodeling, myofiber denervation, and functional motor unit loss. Loss of motor units correlated with absolute torque. Collectively, these findings reveal a novel mechanism through which systemic Klotho deficiency disrupts muscle synapses and motor unit connectivity, potentially contributing to muscle wasting and weakness. Full article