The Anterior Cruciate Ligament (ACL) is vital for knee stability, and its rupture is a major orthopedic concern with significant health and economic impacts. Evidence suggests a substantial hereditary component in ACL injury susceptibility, with the COL1A1 rs1800012 (SP1) polymorphism frequently studied but with inconsistent results. To clarify the association between the rs1800012 in COL1A1 and ACL injury risk, this meta-analysis synthesized data from case-control and cohort studies focusing exclusively on ACL injuries. Systematic searches of PubMed, Embase, Web of Science, and Scopus identified studies up to June 2025. Eligible studies included individuals diagnosed with ACL injuries and healthy controls, reporting genotype frequencies for rs1800012. Pooled Odds Ratios (OR) and 95% Confidence Intervals (CI) were calculated for various genetic models using random-effects meta-analysis. Study quality was assessed via the Newcastle-Ottawa Scale, and publication bias and heterogeneity were evaluated. Nine studies (1,171 cases, 2,005 controls) were included. The TT genotype was significantly protective under the recessive model (TT vs. TG+GG: OR = 0.49, 95% CI: 0.25-0.97, p = 0.041), and also in direct genotype comparisons (TT vs. TG: OR = 0.41, 95% CI: 0.21-0.80, p = 0.009). Conversely, the TG genotype increased ACL injuries risk under the overdominant model (TG vs. TT+GG: OR = 1.28, 95% CI: 1.07-1.52, p = 0.006) and when compared to GG (TG vs. GG: OR = 1.24, 95% CI: 1.05-1.48, p = 0.014). No significant associations were observed under the allele contrast (T vs. G: OR = 1.04, 95% CI: 0.90-1.21, p = 0.61) or dominant models (TT+TG vs. GG: OR = 1.15, 95% CI: 0.97-1.37, p = 0.10). Heterogeneity was consistently low, and sensitivity analyses confirmed the robustness of these findings. No evidence of publication bias was detected. This meta-analysis demonstrates genotype-specific effects of rs1800012 on ACL injuries risk: the TT genotype is protective, while the TG genotype confers increased risk.

Abstract withdrawn to prevent dissemination of unpublished results.

ObjectiveFacial nerve injury remains a challenging complication of cerebellopontine angle (CPA) tumor surgery, often resulting in prolonged functional impairment. The present study aimed to examine the association between different postoperative rehabilitation strategies and long-term clinical and electrophysiological recovery following facial nerve reconstruction. MethodsWe conducted a single-center retrospective cohort study including adult patients who underwent CPA tumor resection with intraoperatively confirmed facial nerve injury requiring reconstructive intervention between 2018 and 2023. Based on rehabilitation approaches applied in routine clinical practice, patients were classified into three groups: standard postoperative therapy, standard therapy combined with transcutaneous electrical nerve stimulation (TENS), and a multimodal rehabilitation strategy integrating TENS with targeted pharmacological support. Clinical follow-up extended to 12 months. Facial nerve function was evaluated using the House–Brackmann scale, Yanagihara system, Sunnybrook Facial Grading System, and Facial Disability Index, alongside surface and needle electromyographic parameters. Multivariable analyses were performed to account for demographic, tumor-related, surgical, and baseline functional factors. ResultsAll groups demonstrated progressive improvement in facial nerve function over the follow-up period. Patients receiving rehabilitation protocols that included TENS exhibited greater improvements across clinical grading scales and electrophysiological measures compared with those receiving standard therapy alone. The multimodal rehabilitation group showed the largest magnitude of functional recovery, reflected by improved facial symmetry, voluntary movement, patient-reported physical and social function, and more favorable electromyographic patterns. These associations remained consistent after adjustment for potential confounders. ConclusionsIn this retrospective cohort, postoperative rehabilitation strategies incorporating electrical stimulation were associated with enhanced functional and electrophysiological recovery after facial nerve reconstruction. Multimodal rehabilitation approaches may offer added translational value in clinical neurorehabilitation following CPA tumor surgery. Prospective studies are warranted to further refine and validate optimized rehabilitation protocols.

A progressive decline in mitochondrial oxidative phosphorylation (OxPhos) is a fundamental feature of aging and a strong predictor of mobility loss, cognitive decline, and dementia. (1-4) Work from the Baltimore Longitudinal Study of Aging and complementary cohorts demonstrates that reduced skeletal muscle mitochondrial OxPhos, assessed in vivo by ^31P-MRS, precedes and predicts deterioration in walking performance, cardiorespiratory fitness, brain structural integrity, and risk of mild cognitive impairment and dementia. These associations suggest that mitochondrial dysfunction represents a shared biological mechanism underlying both physical and cognitive aging. This project focuses on cardiolipin, a signature phospholipid of the mitochondrial inner membrane that is essential for respiratory chain supercomplex assembly, proton handling, and efficient ATP synthesis. Cardiolipin is highly susceptible to oxidative damage, and emerging evidence indicates that oxidized cardiolipin is poorly repaired, promotes inflammation and apoptosis, and compromises mitochondrial quality control. We hypothesize that aging is characterized by the accumulation of oxidized cardiolipin due to impaired remodeling and insufficient availability of key lipid precursors, particularly lysophosphatidylcholine species containing oleic (18:1) and linoleic (18:2) acids. To test this hypothesis, we integrate longitudinal human phenotyping with advanced metabolomics, lipidomics, and “in vivo” imaging. We have identified lipid metabolites linking mitochondrial OxPhos to mobility and cognition and developed a highly sensitive method to quantify native and oxidized cardiolipin species in human skeletal muscle. Preliminary data indicate that higher levels of tetralinoleoyl cardiolipin are associated with better physical and cognitive performance, whereas a greater proportion of oxidized cardiolipin predicts worse outcomes. Ongoing efforts aim to extend these findings to the brain using novel PET radioligands and advanced MRS techniques. Together, this work positions cardiolipin remodeling and mitochondrial quality control as central mechanisms of aging and promising targets for interventions to preserve physical and cognitive function in late life.

Diagnosis and treatment of Parkinson's disease (PD) remain one of the most significant problems of neurology today. Parkinson's disease prevalence is increasing with age and PD affects more than 1% of the population above 60 years. Parkinson's disease is characterised by many motor and non-motor features. Motor deficits generally appear when 50-60% of dopaminergic neurons in the substantia nigra are already lost, limiting the effectiveness of potential neuroprotective therapies. Taking into account the substitutive symptomatic therapy of this pathology, it is very important to have the monitor the adequacy and effectiveness of the treatment. In our study a non-contact system of objective assessment of movements is used for estimation of the motor symptoms. The assessment of movements was carried out on a MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). (Figure 1) An objective analysis of the structure of motor and non-motor symptoms will allow for a more reliable diagnosis at an early stage of Parkinson’s disease. Comprehensive monitoring of the effectiveness of treatment of motor and non-motor disorders in the early stages of Parkinson’s disease will improve the quality of life of patients, expand the possibilities of social adaptation.

In this talk I will focus on the notion that skeletal muscle is the central component of a wonderful musculo-skeletal machine specialized in the generation of movement. I will briefly touch on following points: 1. The view that the human body is a machine emerged with the anatomical dissections in Italian universities in the XV century and was first formalized by René Descartes in his treatise on man (L’homme, around 1630-35). 2. The working of this machine requires four major components: a motor which generates the force required for the movement (muscle), a mechanical actuator to perform the various movements (skeleton: tendons, bones and joints), a control center which plans the movement and activates the motor (brain and nerves), and an energy supply system which provides the fuel (substrates and O2), with many organs and cells contributing to this function. Indeed, the whole body is actually involved in the working of the machine. 3. The human musculo-skeletal machine has distinct properties, not shared by other primates, which were acquired during evolution by the ancestors of Homo sapiens (“born to run”). 4. This machine differs from man-made machines in that it can self-repair, e. g. through muscle regeneration, and adapt in response to appropriate stimuli through structural and functional changes, e. g. muscle atrophy/hypertrophy. 5. Our machine must be kept continuously in function, otherwise it deteriorates: physical exercise has an essential role not only for keeping the machine in good shape but for contributing to the well-being of the whole body. The essential role of muscle activity is first evident before birth, during fetal development, and lasts throughout life, being a condition for healthy aging.

A multidisciplinary care approach is fundamental in neuromuscular diseases due to their complex characteristics, requiring a timely diagnosis and optimization of the management plan. Diagnostic yield has greatly improved in the last years, due either to powerful genetic-molecular techniques or increased attention of physicians to red flags that can indicate a neuromuscular disorder for prompting a specialist evaluation. The improvement of standards of care and the availability of effective disease-modifying treatments such as enzymatic replacement therapies, RNA-based and also gene therapy, but also steroid therapy for Duchenne muscular dystrophy, have expanded life expectancy of patients, also improving their quality of life, although at the same time leading to new and more complex phenotypes. It also means that, for diseases with infantile onset, greater number of patients reach adulthood, this making it necessary to establish a “transition” process from pediatric to adult care centers for structured management plans and to mitigate the risk to be lost. We have now developed in Tuscany a program for transition involving two pediatric reference centers for rare and neuromuscular disorders (IRCCS Meyer, Florence and IRCCS Stella Maris, Calambrone, Pisa) and the adult reference center for neuromuscular disorder of Pisa, University Hospital, Ospedale Santa Chiara, ERN-NMD affiliated). This program, started in 2023, includes combined and integrated evaluation of adolescent-juvenile patients from childhood neuropsychiatrists and pediatricians and adult neurologists who, in exchanging their expertise, accompany affected people in this comprehensive journey for ensuring suitable standards of care. In total, 70 neuromuscular patients transitioned from the pediatric centers to the adult center, among them 11 affected by Duchenne muscular dystrophy and 30 by Becker muscular dystrophy, for which clinical and investigation data have been extensively collected for better understanding of disease natural history and responses to interventions and treatment.

Animal models and human 2D culture models have been instrumental for investigating skeletal muscle diseases and the development of therapeutics. However in vivo models and 2D cultures are limited in their translation to clinical application. These limitations are most evident through the success of myostatin inhibitors for improving mass and function in mice studies followed by unsuccessful clinical trials in patients with sarcopenia and Duchenne Muscular Dystrophy (DMD) (3-4). Although clinical trials of myostatin inhibitors have often reported increases in lean muscle mass, efficacy endpoints of improved muscle function are typically not achieved (3-4). Additionally, studies of age-related muscle atrophy, sarcopenia, have unique barriers to translation such as age-related gene expression changes and sex related muscle aging that is not conserved between species (1-2). Due to these challenges, our team developed a donor-derived 3D skeletal muscle platform housed in standard 24-well imaging plates. This platform was then utilized to investigate retention of sex- specific characteristics in 3D muscle cultures and the effectiveness of astaxanthin (ASTX) to improve contractile signaling and function in healthy and clinically sarcopenic 3D cultures. Initial characterization and validation were carried out in samples from healthy male and female donors. Contractile function recorded through digital image correlation (DIC) analysis during electrical stimulation was similar between male and female 3D muscles, but females displayed elevated type 1 fiber proportions compared to males. Female muscle also displayed elevated levels of OPA1 and TFAM protein levels along with decreased Akt signaling. Overall, female muscle exhibited a greater reliance on mitochondrial energy utilization and reduced protein synthesis indicating retention of sex-specific characteristics in 3D culture. Samples from young female and clinically sarcopenic female donors were studied in this platform for functional differences in force production, fatigue susceptibility, and contractile protein signaling following fatigue with or without astaxanthin antioxidant therapy. Astaxanthin was assessed at 1μM, 10μM, and 25μM in young cultures and only 10μM in sarcopenic cultures due to limitations in cell quantity for 7 days. Although there were no significant effects on force outputs or fatiguability for either group, 10μM rescued P38 and Akt signaling in the sarcopenic samples restoring levels to those exhibited by young DMSO- treated controls. Additionally, 10μM and 25μM in the young cohort suppressed Akt signaling indicating astaxanthin may negatively impact this critical pathway for exercise adaptation in healthy muscle. Although astaxanthin did not improve functional performance in the clinically sarcopenic or young female 3D muscle samples, clenbuterol was evaluated as a positive control for improving performance in young muscle and showed a nearly two-fold increase in both twitch and tetanic force response in 1μM treated samples compared to DMSO controls. These findings support the utilization of this muscle platform for assessing functional differences among drug treatments and untreated donor groups.

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