The antioxidant enzyme superoxide dismutase 1 (SOD1) is a critical player of the antioxidative defense whose activity is altered in several chronic diseases, including amyotrophic lateral sclerosis. However, how oxidative insult affects muscle homeostasis remains unclear. This study addresses the role of oxidative stress on muscle homeostasis and function by the generation of a transgenic mouse model expressing a mutant SOD1 gene (SOD1(G93A)) selectively in skeletal muscle. Transgenic mice developed progressive muscle atrophy, associated with a significant reduction in muscle strength, alterations in the contractile apparatus, and mitochondrial dysfunction. The analysis of molecular pathways associated with muscle atrophy revealed that accumulation of oxidative stress served as signaling molecules to initiate autophagy, one of the major intracellular degradation mechanisms. These data demonstrate that skeletal muscle is a primary target of SOD1(G93A) -mediated toxicity and disclose the molecular mechanism whereby oxidative stress triggers muscle atrophy.

The object of this study was to develop an in vitro bioengineered three-dimensional vascularized skeletal muscle tissue, named eX-vivo Muscle Engineered Tissue (X-MET). This new tissue contains cells that exhibit the characteristics of differentiated myotubes, with organized contractile machinery, undifferentiated cells, and vascular cells capable of forming "vessel-like" networks. X-MET showed biomechanical properties comparable with that of adult skeletal muscles; thus it more closely mimics the cellular complexity typical of in vivo muscle tissue than myogenic cells cultured in standard monolayer conditions. Transplanted X-MET was able to mimic the activity of the excided EDL muscle, restoring the functionality of the damaged muscle. Our results suggest that X-MET is an ideal in vitro 3D muscle model that can be employed to repair muscle defects in vivo and to perform in vitro studies, limiting the use of live animals.

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The understanding of the phenomena involved in ventricular flow is becoming more and more important because of two main reasons: the continuous improvements in the field of diagnostic techniques and the increasing popularity of prosthetic devices. On one hand, more accurate investigation techniques gives the chance to better diagnose diseases before they become dangerous to the health of the patient. On the other hand, the diffusion of prosthetic devices requires very detailed assessment of the modifications that they introduce in the functioning of the heart. The present work is focussed on the experimental investigation of the flow in the left ventricle of the human heart with the presence of a tilting-disk valve in the mitral position, as this kind of valve is known to change deeply the structure of such a flow. A laboratory model has been built up, which consists of a cavity able to change its volume, representing the ventricle, on which two prosthetic valves are mounted. The facility is designed to be able to reproduce any arbitrarily assigned law of variation of the ventricular volume with time. In the present experiment, a physiologically shaped curve has been used. Velocity was measured using a feature-tracking (FT) algorithm; as a consequence, the particle trajectories are known. The flow has been studied by changing both the beat rate and the stroke volume. The flow was studied both kinematically, examining velocity and vorticity fields, and dynamically, evaluating turbulent and viscous shear stresses, and inertial forces exerted on fluid elements. The analysis of the results allows the identification of the main features of the ventricular flow, generated by a mitral, tilting-disk valve, during the whole cardiac cycle and its dependence on the frequency and the stroke volume

Contractile properties of fast-twitch (EDL) and slow-twitch (soleus) skeletal muscles were measured in MLC/mIgf-1 transgenic and wild-type mice. MLC/mIgf-1 mice express the local factor mIgf-1 under the transcriptional control of MLC promoter, selectively activated in fast-twitch muscle fibers. Isolated muscles were studied in vitro in both isometric and isotonic conditions. We used a rapid "ad hoc" testing protocol that measured, in a single procedure, contraction time, tetanic force, Hill's (F-v) curve, power curve and isotonic muscle fatigue. Transgenic soleus muscles did not differ from wild-type with regard to any measured variable. In contrast, transgenic EDL muscles displayed a hypertrophic phenotype, with a mass increase of 29.2% compared to wild-type. Absolute tetanic force increased by 21.5% and absolute maximum power by 34.1%. However, when normalized to muscle cross-sectional area and mass, specific force and normalized power were the same in transgenic and wild-type EDL muscles, revealing that mIgf-1 expression induces a functional hypertrophy without altering fibrotic tissue accumulation. Isotonic fatigue behavior did not differ between transgenic and wild-type muscles, suggesting that the ability of mIgf-1 transgenic muscle to generate a considerable higher absolute power did not affect its resistance to fatigue.

The working principle and the metrological performances of a novel array sensor devoted to\ud pressure map measurements are experimentally analyzed here. The physical principle on which the\ud sensor elements are sensitive to the pressure is the variation of the contact resistance. Pressure maps\ud from 1 up to 500 kPa can be measured. The prototype here utilized for the metrological\ud characterization has been an 838 matrix sensor with a 5 um spatial resolution over both x and y\ud direction and a total thickness of 150 um. The materials that have been chosen to assemble the\ud prototype yielded to a very flexible and robust sensor which can easily be fitted over round surfaces\ud without being damaged or leading to an alteration of its measuring properties. The static and the\ud dynamic metrological performances of the sensor that have been studied and discussed are the\ud response function and the calibration curve, the repeatability, the sensitivity, the time drift, the\ud hysteresis, and the dynamic response. In spite of its functional and constructive simplicity, the\ud metrological performances the sensor has exhibited, together with its peculiar constructive feature,\ud have indicated the possibility to utilize it to effectively measure pressure maps in every application\ud for which the sensor could be shaped in

Monitoring gait quality in daily activities through wearable sensors has the potential to improve medical assessment in Parkinson’s Disease (PD). In this study, four gait partitioning methods, two based on thresholds and two based on a machine learning approach, considering the four-phase model, were compared. The methods were tested on 26 PD patients, both in OFF and ON levodopa conditions, and 11 healthy subjects, during walking tasks. All subjects were equipped with inertial sensors placed on feet. Force resistive sensors were used to assess reference time sequence of gait phases. Goodness Index (G) was evaluated to assess accuracy in gait phases estimation. A novel synthetic index called Gait Phase Quality Index (GPQI) was proposed for gait quality assessment. Results revealed optimum performance (G < 0.25) for three tested methods and good performance (0.25 < G < 0.70) for one threshold method. The GPQI resulted significantly higher in PD patients than in healthy subjects, showing a moderate correlation with clinical scales score. Furthermore, in patients with severe gait impairment, GPQI was found higher in OFF than in ON state. Our results unveil the possibility of monitoring gait quality in PD through real-time gait partitioning based on wearable sensors.