Aged gastrocnemius muscle of mice positively responds to a late onset adapted physical training.

Introduction: A regular physical training is known to contribute to preserve muscle mass and strength, maintaining structure and function of neural and vascular compartments and preventing muscle insulin resistance and inflammation. However, physical activity is progressively reduced during aging causing mobility limitations and poor quality of life. Although physical exercise for rehabilitation purposes (e.g., after fractures or cardiovascular events) or simply aiming to counteract the development of sarcopenia is frequently advised by physicians, nevertheless few data are available on the targets and the global effects on the muscle organ of adapted exercise especially if started at old age. Methods: To contribute answering this question for medical translational purposes, the proteomic profile of the gastrocnemius muscle was analyzed in 24-month-old mice undergoing adapted physical training on a treadmill for 12 weeks or kept under a sedentary lifestyle condition. Proteomic data were implemented by morphological and morphometrical ultrastructural evaluations. Results and Discussion: Data demonstrate that muscles can respond to adapted physical training started at old age, positively modulating their morphology and the proteomic profile fostering protective and saving mechanisms either involving the extracellular compartment as well as muscle cell components and pathways (i.e., mitochondrial processes, cytoplasmic translation pathways, chaperone-dependent protein refolding, regulation of skeletal muscle contraction). Therefore, this study provides important insights on the targets of adapted physical training, which can be regarded as suitable benchmarks for future in vivo studies further exploring the effects of this type of physical activity by functional/metabolic approaches.

Evaluating field-goal shooting effectiveness in wheelchair basketball players across a competitive season: a preliminary study.

Background: Information about non-elite wheelchair basketball (WB) players across national competitive seasons are still missing. This study aimed at identifying which situational-related variables were associated with shooting effectiveness in non-elite WB players. Methods: All the matches played by one WB team across one national competitive season were video-recorded and analysed; 333 shooting attempts from high-point players and several situational-related variables were considered. Results: Pearson's Chi-square test showed that increased shooting effectiveness under the following conditions: playing on home ground, during won matches, while taking shots with the wheelchair in motion, and when no opposing player raised their arm in defence. Results of the multivariable logistic regression analysis showed a statistically significant influence of match location (p-value = 0.001), shot-clock remaining (p-value = 0.015) and modality of press (p-value < 0.001). The highest attack effectiveness was achieved when teams played at home (odds ratio [OR] = 2.49), while the shooting effectiveness decreased when the shot occurred during the last seconds of the action (OR = 0.36), or the opponents defended with the arm raised (OR = 0.19). These results suggest that coaches should include exercises aimed at shooting under conditions of increased pressure in their programmes in order to create specific situations during the training sessions to prepare their high-point athletes for shots under specific match constraints.

Physical training promotes remodeling of the skeletal muscle extracellular matrix: An ultrastructural study in a murine model of Down syndrome.

Down syndrome (DS) is a genetically based disease caused by triplication of chromosome 21. DS is characterized by multi-systemic premature aging associated with deficit in motor coordination, balance, and postural control. Using a morphological, morphometrical, and immunocytochemical ultrastructural approach, this study investigated in vastus lateralis muscle of Ts65Dn mouse, a murine model of DS, the effect of an adapted physical training on the extracellular matrix (ECM) characteristics and whether the forecasted exercise-induced ECM remodeling impacts on sarcomere organization. Morphometry demonstrated thicker basement membrane and larger collagen bundles with larger interfibrillar spacing as well as irregularly arrayed myofibrils and lower telethonin density on Z-lines in trisomic versus euploid sedentary mice. In agreement with the multi-systemic premature aging described in DS, these ECM alterations were similar to those previously observed in skeletal muscle of aged mice. Adapted physical training induced remodeling of ECM in both trisomic and euploid mice, that is, enlargement of the collagen bundles associated with hypertrophy of collagen fibrils and reduction of the interfibrillar spacing. A re-alignment of the myofibrils and a higher telethonin density on Z-line was found in trisomic mice. Altogether, our findings suggest that physical training is an effective tool in limiting/counteracting the trisomy-associated musculoskeletal structural anomalies. The current findings constitute a solid experimental background for further study investigating the possible positive effect of physical training on skeletal muscle performance. RESEARCH HIGHLIGHTS: Vastus lateralis muscle of trisomic mice shows aging-like alterations of extracellular matrix. Training promotes extracellular matrix remodeling. Training may be an effective tool to counteract trisomy-associated alterations of skeletal muscle.

Physical Training Chronically Stimulates the Motor Neuron Cell Nucleus in the Ts65Dn Mouse, a Model of Down Syndrome.

Down syndrome (DS) is a genetically-based disease based on the trisomy of chromosome 21 (Hsa21). DS is characterized by intellectual disability in association with several pathological traits among which early aging and altered motor coordination are prominent. Physical training or passive exercise were found to be useful in counteracting motor impairment in DS subjects. In this study we used the Ts65Dn mouse, a widely accepted animal model of DS, to investigate the ultrastructural architecture of the medullary motor neuron cell nucleus taken as marker of the cell functional state. Using transmission electron microscopy, ultrastructural morphometry, and immunocytochemistry we carried out a detailed investigation of possible trisomy-related alteration(s) of nuclear constituents, which are known to vary their amount and distribution as a function of nuclear activity, as well as the effect of adapted physical training upon them. Results demonstrated that trisomy per se affects nuclear constituents to a limited extent; however, adapted physical training is able to chronically stimulate pre-mRNA transcription and processing activity in motor neuron nuclei of trisomic mice, although to a lesser extent than in their euploid mates. These findings are a step towards understanding the mechanisms underlying the positive effect of physical activity in DS.

Predictors of Ball Velocity in the Sitting Volleyball Serve: A Causal Analysis.

This study explored the performance of the Sitting Volleyball serve by investigating the causal factors associated with ball velocity. Thirty-seven athletes underwent anthropometry and strength assessment and performed ten successful maximal effort serves. Ball velocity was measured using a sports radar gun. The hip, shoulder, elbow and wrist angles at the instant of ball impact as well as the height of ball impact were estimated through two-dimensional motion analysis. The causal relationships between variables were described through a linear Structural Equation Model and a Directed Acyclic Graph. Results showed that a smaller hip angle determines a greater shoulder angle, which in turn causes a greater elbow angle. A more open elbow angle together with a greater vertical reach allowed for a greater height of ball impact. Finally, increased height of ball impact along with greater abdominal strength are beneficial for higher ball velocity. These results underlined that the Sitting Volleyball serve is a multifactorial stroke involving anthropometric, technical and strength factors and suggest that athletes should improve their abdominal strength and master the technique necessary to perform the serve with the shoulder and the elbow joints fully extended in order to produce the greatest possible impact on the ball.

Age-Related In Vivo Structural Changes in the Male Mouse Olfactory Bulb and Their Correlation with Olfactory-Driven Behavior.

Olfactory areas in mammalian brains are linked to centers that modulate behavior. During aging, sensitivity to odors decreases and structural changes are described in olfactory areas. We explored, in two groups of male mice (young and elderly, 6 and 19 months old, respectively), the link between the changes in olfactory bulb structure, detected with magnetic resonance imaging, and behavioral changes in a battery of tests on motor, olfactory, cognitive performance, and emotional reactivity. The behavioral pattern of elderly mice appears less anxious, being less scared by new situations. Additionally, the olfactory bulb of young and elderly mice differed in two variables derived from magnetic resonance imaging (fractional anisotropy and T2 maps). A random forest approach allowed to select the variables most predictive of the differences between young and elderly mice, and correlations were found between three behavioral variables indicative of anxious behavior and the two magnetic resonance variables mentioned above. These data suggest that in the living mouse, it is possible to describe co-occurring age-related behavioral and structural changes in the olfactory bulb. These data serve as a basis for studies on normal and pathological aging in the mouse, but also open new opportunities for in vivo human aging studies.

Effect of different anthropometry-driven block settings on sprint start performance.

ABSTRACTFew studies have focused on the effect of individual anthropometrics when considering "set" position posture during the sprint start. This study aimed to measure the effect of different anthropometry-driven block settings on kinetic and kinematic parameters and performance during the start in well-trained and non-trained sprinters. Front block-starting line (FB/SL) distance was manipulated between 50% and 70% of each individual's leg length at 5% intervals, whilst the inter-block distance was held constant at 45% of leg length. Thirty-six sprinters performed three maximal-effort 10 m sprints in each of the five conditions. Joint angles in the "set" position were quantified though 2D video analysis, the forces generated during block clearance phase were measured by dynamometric starting blocks, and times to 5 and 10 m were measured with photocells. The effects of the five block setting conditions were largely consistent irrespective of ability level. Shorter FB/SL distances were associated with significantly more flexed hip and knee angles in the "set" position, a significantly more plantar flexed front ankle, and a significantly more dorsiflexed rear ankle. There were no significant effects of FB/SL distance on total block time, and thus the greater rear block peak forces and impulses produced from the shorter FB/SL distances combined with no effects on the resultant front block peak forces and impulses, led to higher levels of sprint start performance from the shorter FB/SL distances. Considering FB/SL distances closer to 50% of leg length may be beneficial for coaches and athletes to explore during sprint start training.HighlightsThe effects of different front-block starting line distances on "set" position kinematics, block clearance kinetics and sprint start performance are largely consistent irrespective of ability level.When using a medium inter-block distance (45% of leg length), shorter front block-starting line distances (down to 50% of the leg length) led to improved sprint start performance.From shorter front block-starting line distances, sprint start performance was primarily improved through greater force production against the rear block which led to greater impulses due to no change in push durations or resultant front foot forces.Lower-limb length is an important consideration when adjusting anteroposterior block distances.

Anthropometric prediction of DXA-measured percentage of fat mass in male karate athletes.

BACKGROUND: In karate, high percentages of fat mass (%FM) are often associated with poor sport performance. Dual-energy X-ray absorptiometry (DXA) can accurately measure the %FM (%FM-DXA), but it may not be practical in some sport settings, where anthropometry has long been used as an alternative. This study aimed to explore the ability of sixteen available anthropometric equations to estimate the %FM (%FM-AE) in karate athletes using the %FM-DXA as the criterion. Furthermore, two population-specific predictive equations to estimate the %FM-DXA were developed from anthropometric measurements. METHODS: Forty-six male athletes aged 21.7±3.8 years underwent anthropometry and a whole-body DXA scan. RESULTS: The results showed that in male karate athletes all the considered anthropometric equations are mostly inaccurate in estimating the %FM-DXA within a range of the limits of agreement in the Bland-Altman analysis, which ranged from 6.43% to 13.37%. Regression analysis yielded two statistically significant models (P<0.001 for both) to predict the %FM-DXA. In the first model (cross-validated estimation of R2=0.85), the predictors were the abdominal, triceps, calf, and biceps skinfolds and in the second model (cross-validated estimation of R2=0.77), the predictor was the sum of nine skinfolds (i.e., biceps, triceps, subscapular, chest, axilla, suprailiac, abdominal, anterior thigh and calf skinfolds). CONCLUSIONS: These results underlined the need for sport-specific anthropometric equations to accurately estimate the %FM-DXA in male karate athletes. The two predictive anthropometric equations presented in this study provided a promising tool for professionals dealing with body composition in this athletic population to accurately estimate the %FM-DXA by means of anthropometry.

Sporting activity does not fully prevent bone demineralization at the impaired hip in athletes with amputation.

There is lack of information about bone mineralization at the lumbar spine and bilateral hips of athletes with unilateral lower limb amputation. The present study assessed for the first time the areal bone mineral density at the lumbar spine and at the hip of the able and impaired leg by means of Dual-Energy X-Ray Absorptiometry using a large sample (N = 40) of male athletes. Results showed that bone demineralization in athletes with unilateral lower limb amputation is found at the impaired hip but not at the lumbar spine and may therefore be site-specific. The extent of hip demineralization was influenced by the level of amputation, with about 80% of athletes with above knee amputation and 10% of athletes with below knee amputation showing areal bone mineral density below the expected range for age. Nevertheless, a reduced percentage of fat mass and a lower fat-to-lean mass ratio in the residual impaired leg as well as a greater amount of weekly training was positively associated with bone mineralization at the impaired hip (partial correlation coefficients = 0.377-0.525, p = 0.040-0.003). Results showed that participation in adapted sport has a positive effect on bone health in athletes with unilateral lower limb amputation but is not sufficient to maintain adequate levels of bone mineralization at the impaired hip in athletes with above-knee amputation. Accordingly, physical conditioners should consider implementing sporting programs, according to the severity of the impairment, aimed at improving bone mineralization at the impaired hip and improve body composition in the residual impaired leg.

Physique and performance in male sitting volleyball players: implications for classification and training.

Background: This study assessed whether anthropometry, physical fitness and sport-specific sprint performance vary across the three groups of sitting volleyball (SV) athletes (athletes with a disability (VS1), athletes with a minimal disability (VS2) and able-bodied SV athletes (AB)) in order to explore the validity of the current system of classification. This study also investigated how the anthropometric and physical fitness characteristics of athletes relate to their sprint performance. Methods: Thirty-five SV male athletes aged 37.4 ± 10.8 years and practicing SV at a national/international level volunteered for this study. Testing consisted in the evaluation of linear anthropometry, physical fitness (body composition by-means of dual-energy X-ray absorptiometry and upper-body strength) and sprint performance (5-meter sprint tests, agility test and speed and endurance test). Results: Athletes in the three groups differed in fat mass percentage (%FM) which was higher in VS1 versus AB at the sub-total level (+9%), in the arms (+15%) and in the non-impaired leg (+8%) regions. Greater hand span, greater length of the impaired lower leg, lower %FM at both the sub-total and regional level and a higher level of strength in the upper body are all associated with better performances in the considered sprint tests (P < 0.05 for all). These results do not confirm the validity of the current system of classification of athletes adopted in SV. Professionals dealing with SV athletes should include specific exercises aimed at improving whole-body and regional body composition and the strength of the trunk and upper limbs in their training programs.

The Limited Impact of Low-Volume Recreational Dance on Three-Compartment Body Composition and Apparent Bone Mineral Density in Young Girls.

Recreational dance is practiced worldwide as a multidimensional physical activity with a potential for prevention of a sedentary lifestyle and overweight/obesity. This study explored in young (7−15 year; n = 21) girls the effect of long-term (>1 year) exposure to recreational (2 h/w) dancing on three-compartment body composition. Recreational dancers (RD) were compared with recreational (≤4 h/w) artistic gymnasts (RG, n = 22) and physically active young girls not involved in structured extracurricular physical activity (control; C, n = 22), adjusting for confounding variables (age, body mass, menarche). We hypothesized for RD an intermediate body composition between RG and C. The three groups had similar age and body mass index. Body composition indices in RD were intermediate between that of C and RG, but RD values were not statistically significantly different vs. C. This agreed with the not statistically significant higher energy expenditure (MET-min/w) in RD vs. C (1357.7 ± 805.32 and 1090.9 ± 596.63, p = 0.172). In conclusion, long-term recreational dance exposure at low volume had limited positive effect on body composition of young girls vs. unstructured extracurricular physical activity. Future work will explore the potential of recreational dance at higher volume (3−4 h/w) to improve body composition in young girls.

Relationships between anthropometric characteristics, block settings, and block clearance technique during the sprint start.

This study aimed to identify how body dimensions interact with anteroposterior block distances to influence lower limb joint angles in the "set" position, how these angles relate to block clearance kinetic and kinematic parameters, and how these biomechanical parameters influence sprint start performance in sprinters of both sexes and of different ability levels. Seventy-eight sprinters performed six maximal-effort 10 m sprints. Joint angles in the "set" position were quantified through 2D video analysis, and the forces generated during block exit were measured by dynamometric starting blocks. Lower limb length was associated with the front block-starting line distance ([FB/SL], partial correlation [rPC] = 0.48) and was a significant predictor of FB/SL (R2 = 0.39). The FB/SL was associated with front hip angle (rPC = 0.38), which was consequently associated with numerous kinetic variables during block clearance (rPC from -0.41 to -0.61). Coaches should be encouraged to explore the interactions between individual lower limb lengths and the FB/SL distance in both male and female sprinters to manipulate the front hip angle in the "set" position in an attempt to achieve more favourable block clearance kinetics.

Quantitative magnetic resonance characterization of the effect of physical training on skeletal muscle of the Ts65Dn mice, a model of Down syndrome.

Down syndrome (DS) is characterized by muscle hypotonia and low muscle strength associated with motor dysfunction. Elucidation of the determinants of muscle weakness in DS would be relevant for therapeutic approaches aimed at treating/mitigating a physical disability with a strong impact on the quality of life in persons with DS. The Ts65Dn mice is a recognized mouse model of DS, with trisomic mice presenting gross motor and muscle phenotypes. The aim of this work was to assess the effect of physical exercise, a well-known tool to improve skeletal muscle condition, in the hindlimbs of trisomic and euploid male mice using quantitative magnetic resonance imaging (MRI). Magnetic resonance spectroscopy (MRS) metabolomics and histological fiber typing were used to further characterize the post-exercise muscle. Quantitative MRI showed not significantly different amounts of skeletal muscle in proximal hindlimbs in trisomic and euploid mice both at baseline and after physical exercise (P>0.05). Similar results were obtained for hindlimbs subfascia adipose tissue, and subcutaneous adipose tissue (P>0.05). MRS showed lower amounts of exercise-related metabolites (valine, isoleucine, leucine) in euploid vs. trisomic mice after exercise (P≤0.05). The percentage of slow-twitch fibers was similar in the two genotypes (P>0.05). We conclude that in DS adapted physical exercise (one month of training) does not induce quantitative changes in skeletal muscle or fiber type composition therein; however, the metabolic response of skeletal muscle to exercise may be affected by trisomy. These findings prompt further research investigating the role of physical exercise as a cue to clarify the mechanisms of the muscular deficit found in DS.

Muscle Research: A Tour d'Horizon.

The Special Issue on the "Muscular Structure, Physiology and Metabolism" was proposed in order to maintain the referenced scientific community abreast with recent research advancements regarding the morphology, functionality, and metabolism of muscle tissue, including a total of eighteen published papers, of which twelve were original research manuscripts and six were review papers [...].

A computational approach to quantitatively define sarcomere dimensions and arrangement in skeletal muscle.

BACKGROUND AND OBJECTIVE: The skeletal muscle is composed of integrated tissues mainly composed of myofibers i.e., long, cylindrical syncytia, whose cytoplasm is mostly occupied by parallel myofibrils. In section, each myofibril is organized in serially end-to-end arranged sarcomeres connected by Z lines. In muscle disorders, these structural and functional units can undergo structural alterations in terms of Z-line and sarcomere lengths, as well as lateral alignment of Z-line among adjacent myofibrils. In this view, objectifying alterations of the myofibril and sarcomere architecture would provide a solid foundation for qualitative observations. In this work, specific quantitative parameters characterizing the sarcomere and myofibril arrangement were defined using a computerized analysis of ultrastructural images. METHODS: computerized analysis was carried out on transmission electron microscopy pictures of the murine vastus lateralis muscle. Samples from both euploid (control) and trisomic (showing myofiber alterations) Ts65Dn mice were used. Two routines were written in MATLAB to measure specific structural parameters on sarcomeres and myofibrils. The output included the Z-line, M-line, and sarcomere lengths, the Aspect Ratio (AsR) and Curviness (Cur) sarcomere shape parameters, myofibril axis (α angle), and the H parameter (evaluation of sequence of Z-lines of adjacent myofibrils). RESULTS: Both routines worked well in control (euploid) skeletal muscle yielding consistent quantitative data of sarcomere and myofibril structural organization. In comparison with euploid, trisomic muscle showed statistically significant lower Z-line length, similar M-line length, and statistically significant lower sarcomere length. Both AsR and Cur were statistically significantly lower in trisomic muscle, suggesting the sarcomere is barrel-shaped in the latter. The angle (α) distribution showed that the sarcomere axes are almost parallel in euploid muscle, while a large variability occurs in trisomic tissue. The mean value of H was significantly higher in trisomic versus euploid muscle indicating that Z-lines are not perfectly aligned in trisomic muscle. CONCLUSIONS: Our procedure allowed us to accurately extract and quantify sarcomere and myofibril parameters from the high-resolution electron micrographs thereby yielding an effective tool to quantitatively define trisomy-associated muscle alterations. These results pave the way to future objective quantification of skeletal muscle changes in pathological conditions. SHORT ABSTRACT: The skeletal muscle is composed of integrated tissues mainly composed of myofibers i.e., long, cylindrical syncytia, whose cytoplasm is mostly occupied by parallel myofibrils organized in serially end-to-end arranged sarcomeres. Several pieces of evidence have highlighted that in muscle disorders and diseases the sarcomere structure may be altered. Therefore, objectifying alterations of the myofibril and sarcomere architecture would provide a solid foundation for qualitative observations. A computerized analysis was carried out on transmission electron microscopy images of euploid (control) and trisomic (showing myofiber alterations) skeletal muscle. Two routines were written in MATLAB to measure nine sarcomere and myofibril structural parameters. Our computational method confirmed and expanded on previous qualitative ultrastructural findings defining several trisomy-associated skeletal muscle alterations. The proposed procedure is a potentially useful tool to quantitatively define skeletal muscle changes in pathological conditions involving the sarcomere.

Age-Related Changes in the Matrisome of the Mouse Skeletal Muscle.

Aging is characterized by a progressive decline of skeletal muscle (SM) mass and strength which may lead to sarcopenia in older persons. To date, a limited number of studies have been performed in the old SM looking at the whole, complex network of the extracellular matrix (i.e., matrisome) and its aging-associated changes. In this study, skeletal muscle proteins were isolated from whole gastrocnemius muscles of adult (12 mo.) and old (24 mo.) mice using three sequential extractions, each one analyzed by liquid chromatography with tandem mass spectrometry. Muscle sections were investigated using fluorescence- and transmission electron microscopy. This study provided the first characterization of the matrisome in the old SM demonstrating several statistically significantly increased matrisome proteins in the old vs. adult SM. Several proteomic findings were confirmed and expanded by morphological data. The current findings shed new light on the mutually cooperative interplay between cells and the extracellular environment in the aging SM. These data open the door for a better understanding of the mechanisms modulating myocellular behavior in aging (e.g., by altering mechano-sensing stimuli as well as signaling pathways) and their contribution to age-dependent muscle dysfunction.

Formulative Study and Intracellular Fate Evaluation of Ethosomes and Transethosomes for Vitamin D3 Delivery.

In this pilot study, ethosomes and transethosomes were investigated as potential delivery systems for cholecalciferol (vitamin D3), whose deficiency has been correlated to many disorders such as dermatological diseases, systemic infections, cancer and sarcopenia. A formulative study on the influence of pharmaceutically acceptable ionic and non-ionic surfactants allowed the preparation of different transethosomes. In vitro cytotoxicity was evaluated in different cell types representative of epithelial, connective and muscle tissue. Then, the selected nanocarriers were further investigated at light and transmission electron microscopy to evaluate their uptake and intracellular fate. Both ethosomes and transethosomes proven to have physicochemical properties optimal for transdermal penetration and efficient vitamin D3 loading; moreover, nanocarriers were easily internalized by all cell types, although they followed distinct intracellular fates: ethosomes persisted for long times inside the cytoplasm, without inducing subcellular alteration, while transethosomes underwent rapid degradation giving rise to an intracellular accumulation of lipids. These basic results provide a solid scientific background to in vivo investigations aimed at exploring the efficacy of vitamin D3 transdermal administration in different experimental and pathological conditions.

Body composition and bone mineral density in athletes with a physical impairment.

BACKGROUND: The impact of the type and the severity of disability on whole-body and regional body composition (BC), and bone mineral density (BMD) must be considered for dietary advice in athletes with a physical impairment (PI). This study aimed to investigate the impact of the type and the severity of disability on BC, the pattern of distribution of fat mass at the regional level, and BMD in athletes with a PI. METHODS: Forty-two male athletes with spinal cord injury (SCI, n = 24; age = 40.04 ± 9.95 years, Body Mass Index [BMI] = 23.07 ± 4.01 kg/m2) or unilateral lower limb amputation (AMP, n = 18; age = 34.39 ± 9.19 years, BMI = 22.81 ± 2.63 kg/m2) underwent a Dual-Energy X-Ray Absorptiometry scan. Each athlete with a PI was matched by age with an able-bodied athlete (AB, n = 42; age = 37.81 ± 10.31 years, BMI = 23.94 ± 1.8 kg/m2). RESULTS: One-Way Analysis of Variance showed significant differences between the SCI, AMP and AB groups for percentage fat mass (%FM) (P < 0.001, eta squared = 0.440). Post-hoc analysis with Bonferroni's correction showed that athletes with SCI had significantly higher %FM vs. the AMP and AB groups (25.45 ± 5.99%, 21.45 ± 4.21% and 16.69 ± 2.56%, respectively; P = 0.008 vs. AMP and P < 0.001 vs. AB). The %FM was also significantly higher in the AMP vs. the AB group (P < 0.001). Whole-body BMD was negatively affected in SCI athletes, with about half of them showing osteopenia or osteoporosis. In fact, the mean BMD and T-score values in the SCI group (1.07 ± 0.09 g/cm2 and -1.25 ± 0.85, respectively) were significantly lower in comparison with the AB group (P = 0.001 for both) as well as the AMP group (P = 0.008 for both). The type of disability affected BC and BMD in the trunk, android, gynoid and leg regions in SCI athletes and the impaired leg only in AMP athletes. CONCLUSIONS: In conclusion, the type of disability and, partly, the severity of PI impact on BC and BMD in athletes with a PI. Nutritionists, sports medicine doctors, clinicians, coaches and physical conditioners should consider athletes with SCI or AMP separately. Athletes with a PI would benefit from specific nutrition and training programs taking into account the type of their disability.

Therapeutic targeting of Lyn kinase to treat chorea-acanthocytosis.

Chorea-Acanthocytosis (ChAc) is a devastating, little understood, and currently untreatable neurodegenerative disease caused by VPS13A mutations. Based on our recent demonstration that accumulation of activated Lyn tyrosine kinase is a key pathophysiological event in human ChAc cells, we took advantage of Vps13a-/- mice, which phenocopied human ChAc. Using proteomic approach, we found accumulation of active Lyn, γ-synuclein and phospho-tau proteins in Vps13a-/- basal ganglia secondary to impaired autophagy leading to neuroinflammation. Mice double knockout Vps13a-/- Lyn-/- showed normalization of red cell morphology and improvement of autophagy in basal ganglia. We then in vivo tested pharmacologic inhibitors of Lyn: dasatinib and nilotinib. Dasatinib failed to cross the mouse brain blood barrier (BBB), but the more specific Lyn kinase inhibitor nilotinib, crosses the BBB. Nilotinib ameliorates both Vps13a-/- hematological and neurological phenotypes, improving autophagy and preventing neuroinflammation. Our data support the proposal to repurpose nilotinib as new therapeutic option for ChAc patients.