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This study was designed to support the tactical decisions of wheelchair basketball (WB) coaches in identifying the best players to form winning lineups. Data related to a complete regular season of a top-level WB Championship were examined. By analyzing game-related statistics from the first round, two clusters were identified that accounted for approximately 35% of the total variance. Cluster 1 was composed of low-performing athletes, while Cluster 2 was composed of high-performing athletes. Based on data related to the second round of the Championship, we conducted a two-fold evaluation of the clusters identified in the first round with the team's net performance as the outcome variable. The results showed that teams where players belonging to Cluster 2 had played more time during the second round of the championship were also those with the better team performance (R-squared = 0.48, p = 0.035), while increasing the playing time for players from Classes III and IV does not necessarily improve team performance (r2 = -0.14, p = 0.59). These results of the present study suggest that a collaborative approach between coaches and data scientists would significantly advance this Paralympic sport.

This study tested the effect of two block setting conditions i.e., the usual block setting [US] and an anthropometry-driven block setting [AS] on the kinematic and kinetic parameters of the sprint start. Furthermore, we verified whether this effect is influenced by the relative lengths of the sprinter's trunk and lower limbs i.e., the Cormic Index by subdividing sprinters into brachycormic, metricormic and macrocormic groups. Forty-two sprinters performed 6 maximal-effort 10 m sprints using the US and AS conditions. Dynamometric starting blocks measured forces generated by the sprinters. The times at 5 m and 10 m in the sprint trials were measured with photocells. Results showed that the anteroposterior block distances were significantly different between the two conditions (P

The ability of whole body vibration (WBV) to increase energy expenditure (EE) has been investigated to some extent in the past using short-term single exercises or sets of single exercises. However, the current practice in WBV training for fitness is based on the execution of multiple exercises during a WBV training session for a period of at least 20 min; nevertheless, very limited and inconsistent data are available on EE during long term WBV training session. This crossover study was designed to demonstrate, in an adequately powered sample of participants, the ability of WBV to increase the metabolic cost of exercise vs. no vibration over the time span of a typical WBV session for fitness (20 min). Twenty-two physically active young males exercised on a vibration platform (three identical sets of six different exercises) using an accelerometer-verified vibration stimulus in both the WBV and no vibration condition. Oxygen consumption was measured with indirect calorimetry and expressed as area under the curve (O2(AUC)). Results showed that, in the overall 20-min training session, WBV increased both the O2(AUC) and the estimated EE vs. no vibration by about 22% and 20%, respectively (P

BACKGROUND:Down syndrome (DS) shows neuropathology similar to Alzheimer disease, which presents olfactory impairment. Previous work showed olfactory impairment in DS, but a comprehensive evaluation of olfactory function in DS is lacking. METHODS:We investigated a large number (n = 56; M = 31, F = 25) DS participants (age range18-57y) using the "Sniffin' Sticks" Extended test. This comprises three subtests (threshold, discrimination, and identification) yielding a global score (TDI) defining normosmia, hyposmia, and functional anosmia. To the best of our knowledge, this is the second largest group of DS people investigated for olfactory function ever. Age- and sex matched euploid individuals (n = 53) were the control. RESULTS:In DS, TDI was lower (16.7±5.13 vs. 35.4±3.74; P

Animals are imbued with adaptive mechanisms spanning from the tissue/organ to the cellular scale which insure that processes of homeostasis are preserved in the landscape of size change. However we and others have postulated that the degree of adaptation is limited and that once outside the normal levels of size fluctuations, cells and tissues function in an aberant manner. In this study we examine the function of muscle in the myostatin null mouse which is an excellent model for hypertrophy beyond levels of normal growth and consequeces of acute starvation to restore mass. We show that muscle growth is sustained through protein synthesis driven by Serum/Glucocorticoid Kinase 1 (SGK1) rather than Akt1. Furthermore our metabonomic profiling of hypertrophic muscle shows that carbon from nutrient sources is being channelled for the production of biomass rather than ATP production. However the muscle displays elevated levels of autophagy and decreased levels of muscle tension. We demonstrate the myostatin null muscle is acutely sensitive to changes in diet and activates both the proteolytic and autophagy programmes and shutting down protein synthesis more extensively than is the case for wild-types. Poignantly we show that acute starvation which is detrimental to wild-type animals is beneficial in terms of metabolism and muscle function in the myostatin null mice by normalising tension production.

Autophagy is an intracellular lysosomal degradation process induced under stress conditions. Autophagy also plays a major role in ocular patho-physiology. Molecular aging does occur in the trabecular meshwork, the main regulator of aqueous humor outflow, and trabecular meshwork senescence is accompanied by increased oxidative stress. However, the role of autophagy in trabecular meshwork patho-physiology has not yet been examined in vivo in human ocular tissues. The purpose of the herein presented study is to evaluate autophagy occurrence in ex-vivo collected human trabecular meshwork specimens and to evaluate the relationship between autophagy, oxidative stress, and aging in this tissue. Fresh trabecular meshwork specimens were collected from 28 healthy corneal donors devoid of ocular pathologies and oxidative DNA damage, and LC3 and p62 protein expression analyzed. In a subset of 10 subjects, further to trabecular meshwork proteins, the amounts of cathepesin L and ubiquitin was analyzed by antibody microarray in aqueous humor. Obtained results demonstrate that autophagy activation, measured by LC3II/I ratio, is related with. oxidative damage occurrence during aging in human trabecular meshwork. The expression of autophagy marker p62 was lower in subjects older than 60 years as compared to younger subjects. These findings reflect the occurrence of an agedependent increase in the autophagy as occurring in the trabecular meshwork. Furthermore, we showed that aging promotes trabecular-meshwork senescence due to increased oxidative stress paralleled by autophagy increase. Indeed, both oxidative DNA damage and autophagy were more abundant in subjects older than 60 years. These findings shed new light on the role of oxidative damage and autophagy during trabecular-meshwork aging.

Oxidative stress (OS) plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp) is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function. Hp is induced in pro-oxidative conditions such as systemic inflammation or obesity. The role of systemic factors that modulate oxidative stress inside muscle cells is still poorly investigated.We used Hp knockout mice (Hp-/-) to determine the role of this protein and therefore, of systemic OS in maintenance of muscle mass and function. Absence of Hp caused muscle atrophy and weakness due to activation of an atrophy program. When animals were stressed by acute exercise or by high fat diet (HFD), OS, muscle atrophy and force drop were exacerbated in Hp-/-. Depending from the stress condition, autophagy-lysosome and ubiquitin-proteasome systems were differently induced.Hp is required to prevent OS and the activation of pathways leading to muscle atrophy and weakness in normal condition and upon metabolic challenges.

We recently showed that differential expression of extracellular matrix (ECM) genes delineates four subgroups of breast carcinomas (ECM1, -2, -3- and -4) with different clinical outcome. To further investigate the characteristics of ECM signature and its impact on tumor progression, we conducted unsupervised clustering analyses in 6 additional independent datasets of invasive breast tumors from different platforms for a total of 643 samples. Use of four different clustering algorithms identified ECM3 tumors as an independent group in all datasets tested. ECM3 showed a homogeneous gene pattern, consisting of 58 genes encoding 43 structural ECM proteins. From 26 to 41% of the cases were ECM3-enriched, and analysis of datasets relevant to gene expression in neoplastic or corresponding stromal cells showed that both stromal and breast carcinoma cells can coordinately express ECM3 genes. In in vitro experiments, β-estradiol induced ECM3 gene production in ER-positive breast carcinoma cell lines, whereas TGFβ induced upregulation of the genes leading to ECM3 gene classification, especially in ER-negative breast carcinoma cells and in fibroblasts. Multivariate analysis of distant metastasis-free survival in untreated breast tumor patients revealed a significant interaction between ECM3 and histological grade (p = 0.001). Cox models, estimated separately in grade I-II and grade III tumors, indicated a highly significant association between ECM3 and worse survival probability only in grade III tumors (HR = 3.0, 95% CI = 1.3-7.0, p = 0.0098). Gene Set Enrichment analysis of ECM3 compared to non-ECM3 tumors revealed significant enrichment of epithelial-mesenchymal transition (EMT) genes in both grade I-II and grade III subsets of ECM3 tumors. Thus, ECM3 is a robust cluster that identifies breast carcinomas with EMT features but with accelerated metastatic potential only in the undifferentiated (grade III) phenotype. These findings support the key relevance of neoplastic and stroma interaction in breast cancer progression.

Mitochondrial injury develops in skeletal muscles during the course of severe sepsis. Autophagy is a protein and organelle recycling pathway which functions to degrade or recycle unnecessary, redundant, or inefficient cellular components. No information is available regarding the degree of sepsis-induced mitochondrial injury and autophagy in the ventilatory and locomotor muscles. This study tests the hypotheses that the locomotor muscles are more prone to sepsis-induced mitochondrial injury, depressed biogenesis and autophagy induction compared with the ventilatory muscles.Adult male C57/Bl6 mice were injected with i.p. phosphate buffered saline (PBS) or E. coli lipopolysaccharide (LPS, 20 mg/kg) and sacrificed 24 h later. The tibialis anterior (TA), soleus (SOLD) and diaphragm (DIA) muscles were quickly excised and examined for mitochondrial morphological injury, Ca(++) retention capacity and biogenesis. Autophagy was detected with electron microscopy, lipidation of Lc3b proteins and by measuring gene expression of several autophagy-related genes. Electron microscopy revealed ultrastructural injuries in the mitochondria of each muscle, however, injuries were more severe in the TA and SOL muscles than they were in the DIA. Gene expressions of nuclear and mitochondrial DNA transcription factors and co-activators (indicators of biogenesis) were significantly depressed in all treated muscles, although to a greater extent in the TA and SOL muscles. Significant autophagosome formation, Lc3b protein lipidation and upregulation of autophagy-related proteins were detected to a greater extent in the TA and SOL muscles and less so in the DIA. Lipidation of Lc3b and the degree of induction of autophagy-related proteins were significantly blunted in mice expressing a muscle-specific IκBα superrepresor.We conclude that locomotor muscles are more prone to sepsis-induced mitochondrial injury, decreased biogenesis and increased autophagy compared with the ventilatory muscles and that autophagy in skeletal muscles during sepsis is regulated in part through the NFκB transcription factor.

Particulate matter (PM) air pollution has been associated with cardiovascular and respiratory disease. Recent studies have proposed also a link with venous thromboembolism (VTE) risk. This study was aimed to evaluate the possible influence of air pollution-related changes on the daily flux of patients referring to the Emergency Department (ED) for VTE, dissecting the different effects of coarse and fine PM. From July 1(st), 2007, to June 30(th), 2009, data about ED accesses for VTE and about daily concentrations of PM air pollution in Verona district (Italy) were collected. Coarse PM (PM(10-2.5)) was calculated by subtracting the finest PM(2.5) from the whole PM(10). During the index period a total of 302 accesses for VTE were observed (135 males and 167 females; mean age 68.3 ± 16.7 years). In multiple regression models adjusted for other atmospheric parameters PM(10-2.5), but not PM(2.5), concentrations were positively correlated with VTE (beta-coefficient = 0.237; P = 0.020). During the days with high levels of PM(10-2.5) (≥ 75(th) percentile) there was an increased risk of ED accesses for VTE (OR 1.69 with 95%CI 1.13-2.53). By analysing days of exposure using distributed lag non-linear models, the increase of VTE risk was limited to PM(10-2.5) peaks in the short-term period. Consistently with these results, in another cohort of subjects without active thrombosis (n = 102) an inverse correlation between PM(10-2.5) and prothrombin time was found (R = -0.247; P = 0.012). Our results suggest that short-time exposure to high concentrations of PM(10-2.5) may favour an increased rate of ED accesses for VTE through the induction of a prothrombotic state.

BACKGROUND: Relative little attention has been devoted until now to the combined effects of gene polymorphisms of the hemostatic pathway as risk factors for Myocardial Infarction (MI), the main thrombotic complication of Coronary Artery Disease (CAD). The aim of this study was to evaluate the combined effect of ten common prothrombotic polymorphisms as a determinant of MI. METHODOLOGY/PRINCIPAL FINDINGS: We studied a total of 804 subjects, 489 of whom with angiographically proven severe CAD, with or without MI (n = 307; n = 182; respectively). An additive model considering ten common polymorphisms [Prothrombin 20210G>A, PAI-1 4G/5G, Fibrinogen beta -455G>A, FV Leiden and "R2", FVII -402G>A and -323 del/ins, Platelet ADP Receptor P2Y12 -744T>C, Platelet Glycoproteins Ia (873G>A), and IIIa (1565T>C)] was tested. The prevalence of MI increased linearly with an increasing number of unfavorable alleles (chi(2) for trend = 10.68; P = 0.001). In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors. As compared to subjects with 3-7 alleles, those with few (/=8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03-6.01). The number of procoagulant alleles correlated directly (r = 0.49, P = 0.006) with endogenous thrombin potential. CONCLUSIONS: The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD.

Integration is a fundamental working memory operation, requiring the insertion of information from one task into the execution of another concurrent task. Previous neuroimaging studies have suggested the involvement of left anterior prefrontal cortex (L-aPFC) in relation to working memory integration demands, increasing during presentation of information to be integrated (loading), throughout its maintenance during a secondary task, up to the integration step, and then decreasing afterward (unloading). Here we used short bursts of 5 Hz repetitive Transcranic Magnetic Stimulation (rTMS) to modulate L-aPFC activity and to assess its causal role in integration. During experimental blocks, rTMS was applied (N = 10) over L-aPFC or vertex (control site) at different time-points of a task involving integration of a preloaded digit into a sequence of arithmetical steps, and contrasted with a closely matched task without integration demand (segregation). When rTMS was applied during the loading phase, reaction times during secondary task were faster, without significant changes in error rates. RTMS instead worsened performance when applied during information unloading. In contrast, no effects were observed when rTMS was applied during the other phases of integration, or during the segregation condition. These results confirm the hypothesis that L-aPFC is causally and selectively involved in the integration of information in working memory. They additionally suggest that pre-integration loading and post-integration unloading of information involving this area may be active and resource-consuming processes.