Search

Background: Carmat bioprosthetic total artificial heart (Aeson; A-TAH) is a pulsatile and autoregulated device. The aim of this study is to evaluate level of hemolysis potential acquired von Willebrand syndrome after A-TAH implantation. Methods: We examined the presence of hemolysis and acquired von Willebrand syndrome in adult patients receiving A-TAH support (n=10) during their whole clinical follow-up in comparison with control subjects and adult patients receiving Heartmate II or Heartmate III support. We also performed a fluid structure interaction model coupled with computational fluid dynamics simulation to evaluate the A-TAH resulting shear stress and its distribution in the blood volume. Results: The cumulative duration of A-TAH support was 2087 days. A-TAH implantation did not affect plasma free hemoglobin over time, and there was no association between plasma free hemoglobin and cardiac output or beat rate. For VWF (von Willebrand factor) evaluation, A-TAH implantation did not modify multimers profile of VWF in contrast to Heartmate II and Heartmate III. Furthermore, fluid structure interaction coupled with computational fluid dynamics showed a gradually increase of blood damage according to increase of cardiac output ( P Conclusions: We demonstrated that A-TAH does not cause hemolysis or AWVS. However, relationship between HMWM and cardiac output depending flow confirms relevance of VWF as a biological sensor of blood flow, even in normal range.

The Aeson® total artificial heart (A-TAH) has been developed as a total heart replacement for patients at risk of death from biventricular failure. We previously described endothelialization of the hybrid membrane inside A-TAH probably at the origin of acquired hemocompatibility. We aimed to quantify vasculogenic stem cells in peripheral blood of patients with long-term A-TAH implantation. Four male adult patients were included in this study. Peripheral blood mononuclear cells were collected before A-TAH implantation (T0) and after implantation at one month (T1), between two and five months (T2), and then between six and twelve months (T3). Supervised analysis of flow cytometry data confirmed the presence of the previously identified Lin-CD133+CD45- and Lin-CD34+ with different CD45 level intensities. Lin-CD133+CD45-, Lin-CD34+CD45- and Lin-CD34+CD45+ were not modulated after A-TAH implantation. However, we demonstrated a significant mobilization of Lin-CD34+CD45dim (p = 0.01) one month after A-TAH implantation regardless of the expression of CD133 or c-Kit. We then visualized data for the resulting clusters on a uniform manifold approximation and projection (UMAP) plot showing all single cells of the live Lin- and CD34+ events selected from down sampled files concatenated at T0 and T1. The three clusters upregulated at T1 are CD45dim clusters, confirming our results. In conclusion, using a flow cytometry approach, we demonstrated in A-TAH-transplanted patients a significant mobilization of Lin-CD34+CD45dim in peripheral blood one month after A-TAH implantation. Using a flow cytometry approach, we demonstrated in A-TAH transplanted patients a significant mobilization of Lin-CD34+CD45dim in peripheral blood one month after A-TAH implantation. This cell population could be at the origin of newly formed endothelial cells on top of hybrid membrane in Carmat bioprosthetic total artificial heart.

Training with low-load exercise performed under blood flow restriction can augment muscle hypertrophy and maximal strength to a similar extent as the classical high-load strength training method. However, the blood flow restriction method elicits only minor neural adaptations. In an attempt to maximize training-related gains, we propose using other protocols that combine high voluntary activation, mechanical tension, and metabolic stress., SCOPUS: re.j, info:eu-repo/semantics/published

Aim. — Unaccustomed physical exercise, particularly repeated eccentric muscle contractions,induces muscle soreness and alterations on muscle cellular structure. An increase in myofibrillarprotein accretion can occur in the early post-exercise period and be potentiated by essentialamino acid ingestion. We hypothesized that essential amino acid supplementation could reducethe efflux of indirect markers of muscle damage and delay the onset of muscular soreness inthe week following a heavy-load eccentric training session.Methods. — Twenty-three randomly assigned young males performed a bench press exerciseunder eccentric condition. They were subdivided into a placebo group (n = 11) and an essential amino acids group (n = 12). The effect of the training session was assessed by analysingtwo indirect markers of muscle damage, namely plasma concentrations of creatine kinase andmyoglobin measured before, immediately after, and post-workout day 1, 2, 3, 4 and 7. Musclesoreness was evaluated by a visual analogy scale at the same time point as the markers ofmuscle damage., info:eu-repo/semantics/published

International audience; Given the negative environmental effects of conventional agricultural techniques, the need for biodiversity-friendly agriculture systems that rely more on ecosystem services and less on chemical inputs is becoming increasingly urgent. In this paper, we focus on crop protection strategies that are alternatives to the use of pesticides. Diversification of the plant component of agricultural areas at different space and time scales has been presented as a powerful socio-economic and agro-ecological mechanism for the sustainable control of pests. Our interdisciplinary group of scientific experts examined the literature on the ecological effects of plant diversification on pests and their natural enemies, as well as the social science literature on the conditions for farmers to adopt the corresponding practices, to assess the potential offered by plant diversification.We developed a conceptual framework that connects the agro-ecological and socio-economic components of an agricultural landscape in a dynamic loop accounting for interactions among elements at different spatial and temporal scales and their feedback effects. This article presents this framework and illustrates its application to the case of wheat production and protection. By explicitly connecting each level of agro-ecological organization with the potential socio-economic drivers and limitations underpinning the adoption and implementation of plant diversification in landscapes, this framework makes it possible to ana yse the synergies and antagonisms between different modes of diversification and the conditions of their deployment. Exploring this framework is a prerequisite to the identification of opportunities and key feed-back loops for designing diversification strategies that unlock the agro-ecological potential of f uture production systems. We conclude that there is a need for interdisciplinary research in experimental landscapes involving farmers and other local stakeholders to design sustainable future agricultural landscapes that deliver high levels of biological control services..

The Aeson® total artificial heart (A-TAH) has been developed as a total heart replacement for patients at risk of death from biventricular failure. We previously described endothelialization of the hybrid membrane inside A-TAH probably at the origin of acquired hemocompatibility. We aimed to quantify vasculogenic stem cells in peripheral blood of patients with long-term A-TAH implantation. Four male adult patients were included in this study. Peripheral blood mononuclear cells were collected before A-TAH implantation (T0) and after implantation at one month (T1), between two and five months (T2), and then between six and twelve months (T3). Supervised analysis of flow cytometry data confirmed the presence of the previously identified Lin−CD133+CD45− and Lin−CD34+ with different CD45 level intensities. Lin−CD133+CD45−, Lin−CD34+CD45− and Lin−CD34+CD45+ were not modulated after A-TAH implantation. However, we demonstrated a significant mobilization of Lin−CD34+CD45dim (p = 0.01) one month after A-TAH implantation regardless of the expression of CD133 or c-Kit. We then visualized data for the resulting clusters on a uniform manifold approximation and projection (UMAP) plot showing all single cells of the live Lin− and CD34+ events selected from down sampled files concatenated at T0 and T1. The three clusters upregulated in T1 are CD45dim clusters, confirming our results. In conclusion, using a flow cytometry approach, we demonstrated in A-TAH-transplanted patients a significant mobilization of Lin−CD34+CD45dim in peripheral blood one month after A-TAH implantation.

Objective: The study’s aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VIC p ) mesenchymal-like phenotype was confirmed by CD90 + /CD73 + /CD44 + expression and multipotent-like differentiation ability. When VIC p were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VIC p and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VIC p -conditioned media and confirmed at the mRNA level in VIC p compared with control VIC. Conditioned media from VIC p induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VIC p involvement in angiogenesis by a VEGF-A dependent mechanism. Conclusions: We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VIC p in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.

Endothelial progenitor cells (EPCs) are involved in vasculogenesis and cardiovascular diseases. However, the phenotype of circulating EPCs remains elusive but they are more often described as CD34+KDR+. The aim of the study was to extensively characterize circulating potential vasculogenic stem cell candidates in two populations of patients with cardiovascular disease by powerful multidimensional single cell complementary cytometric approaches (mass, imaging and flow). We identified cellular candidates in one patient before and after bioprosthetic total artificial heart implantation and results were confirmed in healthy peripheral and cord blood by mass cytometry. We also quantified cellular candidates in 10 patients with different COVID-19 severity. Both C-TAH implantation and COVID-19 at critical stage induce a redistribution of circulating CD34+ and CD19+ sub-populations in peripheral blood. After C-TAH implantation, circulating CD34+ progenitor cells expressed c-Kit stem marker while specific subsets CD34+CD133−/+CD45−/dimc-Kit+KDR− were mobilized. KDR was only expressed by CD19+ B-lymphocytes and CD14+ monocytes subpopulations in circulation. We confirmed by mass cytometry this KDR expression on CD19+ in healthy peripheral and cord blood, also with a VE-cadherin expression, confirming absence of endothelial lineage marker on CD34+ subtypes. In COVID-19, a significant mobilization of CD34+c-Kit+KDR− cells was observed between moderate and critical COVID-19 patients regardless CD133 or CD45 expression. In order to better evaluate EPC phenotype, we performed imaging flow cytometry measurements of immature CD34+KDR+ cells in cord blood and showed that, after elimination of non-circular events, those cells were all CD19+. During COVID-19, a significant mobilization of CD19+KDR+ per million of CD45+ cells was observed between moderate and critical COVID-19 patients regardless of CD34 expression. CD34+c-Kit+ cells are mobilized in both cardiovascular disease described here. KDR cells in peripheral blood are CD19 positive cells and are not classic vasculogenic stem and/or progenitor cells. A better evaluation of c-Kit and KDR expressing cells will lead to the redefinition of circulating endothelial progenitors. Graphical abstractCentral illustration figure. Multidimensional proteomic approach of endothelial progenitors demonstrate expression of KDR restricted to CD19 cells.Endothelial progenitor cells (EPCs) are involved in cardiovascular diseases, however their phenotype remains elusive. We elucidated here EPCs phenotype by a deep characterization by multidimensional single cell complementary cytometric approaches after Bioprosthetic total artificial heart implantation and during COVID-19. We showed a redistribution of circulating CD34+ and CD19+ sub-populations in both situations. None of the immature cell population expresses KDR. Mobilized CD34+ expressed c-Kit. Imaging flow cytometry demonstrated that CD34+KDR+ cells, after elimination of non-circular events, are all CD19+. Our results suggest a new definition of circulating EPCs and emphasize involvement of CD19 cells in cardiovascular disease. Supplementary Information The online version contains supplementary material available at 10.1007/s12015-020-10062-1.

Pulsatile Carmat bioprosthetic total artificial heart (C-TAH) is designed to be implanted in patients with biventricular end-stage heart failure. Since flow variation might contribute to endothelial dysfunction, we explored circulating endothelial biomarkers after C-TAH implantation in seven patients and compared the manual and autoregulated mode. Markers of endothelial dysfunction and regeneration were compared before and during a 6- to 9-month follow-up after implantation. The follow-up was divided into three periods (< 3, 3–6, and > 6 months) and used to estimate the temporal trends during the study period. A linear mixed model was used to analyze repeated measures and association between tested parameters according to the mode of C-TAH and the time. Relevance of soluble endoglin (sEndoglin) level increase has been tested on differentiation and migration potential of human vasculogenic progenitor cells (endothelial colony forming cells [ECFCs]). Normal sEndoglin and soluble endothelial protein C receptor (sEPCR) levels were found in patients after implantation with autoregulated C-TAH, whereas they significantly increased in the manual mode, as compared with pretransplant values (p = 0.005 and 0.001, respectively). In the autoregulated mode, a significant increase in the mobilization of cytokine stromal cell-derived factor 1 was found (p = 0.03). After adjustment on the mode of C-TAH, creatinine or C-reactive protein level, sEndoglin, and sEPCR, were found significantly associated with plasma total protein levels. Moreover, a significant decrease in pseudotubes formation and migration ability was observed in vitro in ECFCs receiving sEndoglin activation. Our combined analysis of endothelial biomarkers confirms the favorable impact of blood flow variation achieved with autoregulation in patients implanted with the bioprosthetic total artificial heart.

Background Pigs/bovines share common antigens with humans: α‐Gal, present in all pigs/bovines close to the human B‐antigen; and AH‐histo‐blood‐group antigen, identical to human AH‐antigen and present only in some animals. We investigate the possible impact of patients’ ABO blood group on bioprosthesis structural valve degeneration (SVD) through calcification/pannus/tears/perforations for patients ≤60 years at implantation. Methods and Results This was a single‐center study (Paris, France) that included all degenerative bioprostheses explanted between 1985 and 1998, mostly porcine bioprostheses (Carpentier‐Edwards second/third porcine bioprostheses) and some bovine bioprostheses. For the period 1998 to 2014, only porcine bioprostheses with longevity ≥13 years were included (total follow‐up ≥29 years). Except for blood groups, important predictive factors for SVD were prospectively collected (age at implantation/longevity/number/site/sex/SVD types) and analyzed using logistic regression. All variables were available for 500 explanted porcine bioprostheses. By multivariate analyses, the A group was associated with an increased risk of: tears (odds ratio[OR], 1.61; P =0.026); pannus (OR, 1.5; P =0.054), pannus with tears (OR, 1.73; P =0.037), and tendency for lower risk of: calcifications (OR, 0.63; P =0.087) or isolated calcification (OR, 0.67; P =0.17). A‐antigen was associated with lower risk of perforations (OR 0.56; P =0.087). B‐group patients had an increased risk of: perforations (OR, 1.73; P =0.043); having a pannus that was calcified (OR, 3.0, P =0.025). B‐antigen was associated with a propensity for calcifications in general (OR, 1.34; P =0.25). Conclusions Patient’s ABO blood group is associated with specific SVD types. We hypothesize that carbohydrate antigens, which may or may not be common to patient and animal bioprosthetic tissue, will determine a patient’s specific immunoreactivity with respect to xenograft tissue and thus bioprosthesis outcome in terms of SVD.

International audience; Background: The main risk factor for bleeding in patients with continuous-flow mechanical circulatory support (CF-MCS) is the acquired von Willebrand factor (VWF) defect related to the high shear-stress forces developed by these devices. Although a higher bleeding rate has been reported in CF-MCS recipients who had reduced pulsatility, the relation between pulsatility and the VWF defect has never been studied.Objectives: The purpose of this study was to investigate the relation between pulsatility and VWF under CF-MCS.Methods: We assessed the effect of 2 CF-MCS on VWF multimer degradation in a mock circulatory loop (model 1). Using these devices, we investigated in a dose-effect model (model 2) 3 levels of pulsatility in 3 groups of swine. In a cross-over model (model 3), we studied the effects of sequential changes of pulsatility on VWF. We reported the evolution of VWF multimerization in a patient undergoing serial CF-MCS and/or pulsatile-MCS.Results: We demonstrated the proteolytic degradation of VWF multimers by high shear CF-MCS in a circulatory loop without pulsatility. We observed both in swine models and in a patient that the magnitude of the VWF degradation is modulated by the pulsatility level in the high shear-stress level condition, and that the restoration of pulsatility is a trigger for the endothelial release of VWF.Conclusions: We demonstrated that the VWF defect reflects the balance between degradation induced by the shear stress and the endothelial release of new VWF triggered by the pulsatility. This modulation of VWF levels could explain the relationship between pulsatility and bleeding observed in CF-MCS recipients. Preservation of pulsatility may be a new target to improve clinical outcomes of patients.

Objectives Surgical mortality and long-term outcomes are important considerations when determining strategies for multiple reoperations on the aortic valve (AV). With the rise of percutaneous valve-in-valve, we sought to evaluate the current outcomes of conventional surgery for AV reoperation, focusing first on the effect of the number of previous AV interventions with a subsequent analysis of the risk factors for adverse outcomes. Methods From January 2007 to December 2016, 316 consecutive patients underwent an open redo operation (replacement) on their AV at a single centre. It was the first AV reintervention in 263 patients (Group 1), second in 42 patients (Group 2) and third or more in 11 patients (Group 3). Results There were 230 men and 86 women, with a median age of 58 (Q1-Q3: 46-70) years. Structural valve deterioration (SVD) of the bioprosthesis (n = 136, 44%), endocarditis (n = 57, 18%) and prosthetic valve dehiscence (n = 41, 13%) were the most common reasons for reintervention. Overall, in-hospital mortality was 7.3%: 7.2% in Group 1, 4.76% in Group 2 and 18.2% in Group 3 (P = 0.233) and ranged from 3.7% for SVD to 14.0% when endocarditis was the reason for reintervention. Higher preoperative New York Heart Association (NYHA) class (III/IV) [odds ratio (OR) 15.9, P = 0.011], injury during re-entry (OR 16.9, P = 0.015), endocarditis (OR 3.7, P = 0.038) and concomitant mitral valve replacement (OR 5.6, P = 0.006) were independent risk factors for in-hospital mortality. Survival at 8 years was 79.0 ± 3.0% for the entire cohort and 88.4 ± 3.2% for re-replacement after SVD. Conclusions Multiple AV reoperations carry an acceptable risk of early postoperative mortality, particularly for isolated valve replacements of SVD.

Twelve years after cardiologists and cardiac surgeons from all over the world issued the ‘Drakensberg Declaration on the Control of Rheumatic Fever and Rheumatic Heart Disease in Africa’, calling on the world community to address the prevention and treatment of rheumatic heart disease (RHD) through improving living conditions, to develop pilot programmes at selected sites for control of rheumatic fever and RHD, and to periodically review progress made and challenges that remain, RHD still accounts for a major proportion of cardiovascular diseases in children and young adults in low- and middle-income countries, where more than 80% of the world population live. Globally equal in prevalence to human immunodeficiency virus infection, RHD affects 33 million people worldwide. Prevention efforts have been important but have failed to eradicate the disease. At the present time, the only effective treatment for symptomatic RHD is open heart surgery, yet that life-saving cardiac surgery is woefully absent in many endemic regions. In this declaration, we propose a framework structure to create a co-ordinated and transparent international alliance to address this inequality.

The Carmat bioprosthetic total artificial heart (C-TAH) is a biventricular pump developed to minimize drawbacks of current mechanical assist devices and improve quality of life during support. This study aims to evaluate the safety of the hybrid membrane, which plays a pivotal role in this artificial heart. We investigated in particular its blood-contacting surface layer of bovine pericardial tissue, in terms of mechanical aging, risks of calcification, and impact of the hemodynamics shear stress inside the ventricles on blood components. Hybrid membranes were aged in a custom-designed endurance bench. Mechanical, physical and chemical properties were not significantly modified from 9 months up to 4 years of aging using a simulating process. Exploration of erosion areas did not show no risk of oil diffusion through the membrane. Blood contacting materials in the ventricular cavities were subcutaneously implanted in Wistar rats for 30 days as a model for calcification and demonstrated that the in-house anti-calcification pretreatment with Formaldehyde-Ethanol-Tween 80 was able to significantly reduce the calcium concentration from 132 μg/mg to 4.42 μg/mg (p < 0.001). Hemodynamic simulations with a computational model were used to reproduce shear stress in left and right ventricles and no significant stress was able to trigger hemolysis, platelet activation nor degradation of the von Willebrand factor multimers. Moreover, explanted hybrid membranes from patients included in the feasibility clinical study were analyzed confirming preclinical results with the absence of significant membrane calcification. At last, blood plasma bank analysis from the four patients implanted with C-TAH during the feasibility study showed no residual glutaraldehyde increase in plasma and confirmed hemodynamic simulation-based results with the absence of hemolysis and platelet activation associated with normal levels of plasma free hemoglobin and platelet microparticles after C-TAH implantation. These results on mechanical aging, calcification model and hemodynamic simulations predicted the safety of the hybrid membrane used in the C-TAH, and were confirmed in the feasibility study., Biomedical engineering; Bioengineering; Biophysics; Cardiology; Haematology; Total artificial heart; Bioprosthetic; Carmat; Hemocompatibility

Aim: This study investigated the efficacy of a new strength training method on strength gain, hypertrophy and neuromuscular fatigability. Methods: The training exercise consisted of elbow flexion against a load of ~70% of one repetition maximal (1RM). A new method (3/7 method) consisting of 5 sets of an increasing number of repetitions (3 to 7) during successive sets and brief inter-set intervals (15s) was repeated two times after 150s of recovery and compared to a method consisting of 8 sets of 6 repetitions with an inter-set interval of 150s (8x6 method). Subjects trained 2 times per week during 12 weeks. Strength gain [1RM load and maximal isometric voluntary contraction (MVC)], EMG activity of biceps brachii and brachioradialis, as well as biceps brachii thickness were measured. Change in neuromuscular fatigability was assessed as the maximal number of repetition performed at 70% of 1RM before and after training. Results: Both 3/7 and 8x6 methods increased 1RM load (22.2±7.4 and 12.1±6.6% respectively; p0.05) after both methods but biceps brachii thickness increased to a greater extent (9.6±3.6 vs. 5.5±3.7%; p, SCOPUS: ar.j, info:eu-repo/semantics/published

Summary Aim This study investigated the effect of a new strength training method (3/7 protocol) consisting of 5 sets with an incremental number of repetitions (3 to 7) and very short rest interval between sets (15 s). Material and methods Thirty-eight young subjects were assigned to one of the 3 following protocols and trained 2 times per week for 8 weeks with bench press exercise. The efficacy of the 3/7 protocol was compared with that of two training protocols with a more classical design consisting of 4 or 8 sets of a constant number (6) of repetitions per set (4 × 6 and 8 × 6 protocols) and a rest interval of 2.5 min. The same load was used (70% of one repetition maximum [1RM]) in all protocols. In addition to the recording of the 1RM load, training effects were assessed by the recording of the force-velocity relation by means of a specific isokinetic ergometer. Results After training, the 1RM increased more ( P P P Conclusion The results of this study indicate that the 3/7 protocol is an efficient training modality to increase maximal strength.

Objective Tricuspid valve repair has been recently advocated in patients undergoing mitral valve surgery who have mild to moderate secondary tricuspid regurgitation. However, the incidence of heart conduction disorders after combined mitral valve and tricuspid valve interventions has not been evaluated. We sought to analyze the incidence of permanent pacemaker implantations and heart conduction disorders in patients undergoing mitral valve surgery with and without tricuspid valve annuloplasty. Methods In 2011 and 2012, among 201 consecutive patients referred to the Hopital Europeen Georges Pompidou for isolated nonischemic mitral valve disease, 113 underwent an isolated mitral valve procedure (group 1) and 88 had a concomitant tricuspid valve ring annuloplasty (group 2). Results Patients' mean age was 59.7 ± 16.5 years in group 1 and 60.7 ± 14.9 years in group 2 ( P = .5). Mean crossclamp time and bypass time were 78 ± 35 minutes and 105 ± 47 minutes in group 1 and 92 ± 36 minutes and 128 ± 50 minutes in group 2, respectively ( P = .001 and .005, respectively). Operative mortality was 3% (2.7% in group 1 and 3.2% in group 2, P = .4). Incidence of high-grade heart conduction disorders lasting more than 3 days postoperatively was 14.5% in group 1 and 41.2% in group 2 ( P = .001). At 3 years, freedom from permanent pacemaker implantation was 99% ± 2% in group 1 and 94.1% ± 5% in group 2 ( P = .02). For the entire cohort, longer crossclamp time ( P = .02) and tricuspid ring annuloplasty (hazard ratio, 3.8; P = .001) were independent predictors of heart conduction disorders. Conclusions The need for permanent pacemaker implantation is increased after concomitant tricuspid ring annuloplasty in the setting of mitral valve surgery. A clinical period of observation up to 14 days after postoperative heart conduction disorders should be observed before recommending permanent pacemaker placement.

The Carmat total artificial heart (C-TAH) (Velizy-Villacoublay, France) is an implantable electro-hydraulically actuated biventricular pump that has been developed to minimize mechanical assist device-related morbidities [(1)][1]. Its blood-contacting surfaces consist of expanded

Estimates of abundance and survivorship provide quantifiable measures to monitor populations and to define and understand their conservation status. This study investigated changes in abundance and survival rates of fin whales (Balaenoptera physalus) in the northern Gulf of St. Lawrence in the context of anthropogenic pressures and changing environmental conditions. A long‐term data set, consisting of 35 years of photo‐identification surveys and comprising more than 5,000 identifications of 507 individuals, formed the basis of this mark–recapture study. Based on model selection using corrected Akaike Information Criterion, the most parsimonious Cormack–Jolly–Seber model included a linear temporal trend in noncalf apparent survival rates with a sharp decline in the last 5 years of the study and a median survival rate of 0.946 (95% confidence interval (CI) 0.910–0.967). To account for capture heterogeneity due to divergent patterns of site fidelity, agglomerative hierarchical cluster analysis was employed to categorize individuals based on their annual and survey site fidelity indices. However, the negative trend in survivorship remained and was corroborated by a significant decline in the estimated super‐population size from 335 (95% CI 321–348) individuals in 2004–2010 to 291 (95% CI 270–312) individuals in 2010–2016. Concurrently, a negative trend was estimated in recruitment to the population, supported by a sharp decrease in the number of observed calves. Ship strikes and changes in prey availability are potential drivers of the observed decline in fin whale abundance. The combination of clustering methods with mark–recapture represents a flexible way to investigate the effects of site fidelity on demographic variables and is broadly applicable to other individual‐based studies.

Corner solution problems are pervasive in micro-econometric acreage choice models because farmers rarely produce the same crop set in a considered sample. These crop choice problems raise significant modelling issues. The main aim of this paper is to propose an endogenous regime switching model specifically designed for empirically modeling acreage choices with corner solutions. Contrary to models based on censored regression systems that have been used until now, this model is fully coherent from a micro-economic point of view. It also includes regime fixed costs accounting for unobserved costs which only depend on the set of crops grown simultaneously.We illustrate the empirical tractability of this model by estimating an endogenous regime switching multi-crop model for a panel dataset of French farmers. The estimated model considers yield supply, input demand and acreage share models for 7 crops and considers 8 production regimes. It also accounts for unobserved heterogeneity in farmers’ behaviors through the specification of random parameters. We assume that most model – intercept and slope – parameters are farmer specific and estimate their distribution across the farmers’ population represented by our sample. We compute the Maximum Likelihood estimator of the parameter vector of our model by relying on a specifically designed Stochastic Approximate Expectation–Maximization algorithm. Our results show that farmers’ production acreage choice mechanisms strongly depend on the production regime in which this choice takes place and that regime changes underlie a large part of the acreage changes of minor crops.

Cet article a fait l'objet d'un WP SMART-LERECO n° 15-10, voir lien ci-contre https://prodinra.inra.fr/record/332523; Although there is now widespread evidence of substantial variability in economic agents’ responses to economic drivers in many applied economics fields, this variability has been largely overlooked by econometric agricultural production models. This article sets out to fill this gap by providing methodological contributions and empirical results. First, we consider panel data multicrop models featuring random intercept and slope parameters to account for the heterogeneous responses of crop producers to economic drivers. Second, we show that Monte Carlo expectation-maximization algorithms are particularly well-suited to estimating this type of model. Third, based on an application of our empirical modeling framework with a sample of French grain crop producers, we demonstrate substantial variability in farmers’ responses to economic incentives. Fourth, we use the estimated model and a simple “statistical calibration” procedure to build farm-specific simulation models, which are then used to evaluate the effects of the rapeseed price increase induced by European Union (EU) biofuel support. Our simulation results demonstrate that ignoring the variability in the considered farmers’ responses to the economic incentives results in significant overestimation of the increases in rapeseed yield levels and variable input use levels induced by EU biofuel support, as well as significant underestimation of the variability in the congruent increases in rapeseed acreages.

Strenuous exercise induces proteinuria which is related to the intensity of exercise. However, renal responses to each type of exercise during a middle-distance triathlon have not been reported. The present study, carried out on 7 healthy athletes, investigated renal function at rest and after each exercise of a half-triathlon race. Blood and urine samples were collected at rest and after each specific event. Protein excretion and renal clearances were determined on each sample. Compared with resting values, albuminuria was increased by a factor of 30 (p0.05) after swimming but did not differ from the resting value after cycling and running (p0.05). Rates of β2-microglobulin and retinol-binding protein excretion did not change throughout the triathlon (p0.05). Glomerular filtration rate (expressed as creatinine clearance) remained stable after each exercise event, whereas tubular reabsorption rate (expressed as urea clearance) was reduced by 50, 40 and 65% after swimming, cycling and running, respectively, compared to pre-exercise values (p0.05). Glomerular membrane permeability (expressed as albumin clearance) was significantly increased by the swimming event (13 times, p0.05). These results suggest that middle-distance triathlon has a noticeable impact on the glomerular membrane permeability (albumin clearance) and elimination of protein waste (urea clearance) depending on exercise type.

There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or creatine supplementation (n = 3). These results directly challenge the recently suggested biological plausibility for the association between creatine use and risk of testicular germ cell cancer. Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), 2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC-MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that creatine supplementation could potentially increase the risk of cancer by stimulating the formation of these mutagens.

Recently, dietary supplementation with inorganic nitrate (NO3) has been proposed to endurance athletes to increase their performance. However, it has been suggested that an excess of NO3 might be harmful. The present study analyzed the effect of NO3 supplementation on kidney function.Thirteen young male subjects performed a 20-min cycling exercise at 85% of the maximal oxygen capacity. Seven days before exercise, the subjects ingested either a placebo (Pl) or 450 mg of potassium nitrate (PN) per day. Venous blood samples and urine collections were collected before and immediately after exercise and after 60 min of recovery. Glomerular filtration rates (GFR) and clearances (Cl) were calculated from serum content and urine output for creatinine (Crn), albumin (Alb), and urea.Under resting conditions, GFR and all clearance measures did not differ between Pl and PN. Immediately after exercise, GFR remained stable in both Pl and PN, whereas Cl-urea decreased significantly (P0.05) in Pl (-44%) and PN (-49%). Alb urine outputs were enhanced by 18- to 20-fold in Pl and PN, respectively (P0.05). After the recovery period, GFR remained enhanced under Pl conditions, whereas Cl-urea returned to initial values in placebo and nitrate supplementation. Alb output and Cl-Alb remained enhanced under PN conditions.These results mainly indicate that dietary nitrate supplementation over a week does not induce any specific kidney function modifications either at rest or during sustained submaximal exercise as compared with Pl.

β-Alanine (BA) supplementation has become an ergogenic aid amongst competitive athletes to augment intramuscular carnosine content, leading to higher buffer capacity and exercise performance. We investigated 27 regularly trained young males and females who were randomly allocated either to placebo (PL) or BA ingestion for 8 weeks. Every single day, BA or PL (4.0-5.6 g day(-1)) supplements were ingested by participants and associated with a strong plyometric high-intensity training (two sessions per week during the 8 weeks). Before and after training, maximal jump heights were recorded during squat jump (SJ) and countermovement jump (CMJ) and an index of fatigue was recorded as a mean height of 45 consecutive CMJ. Blood lactate was measured at rest, after completing the fatigue test and every 5 min thereafter up to 30 min recovery. After plyometric training, SJ and CMJ were increased, respectively, by 8.8 and 6.4 % in PL group and 9.9 and 11.0 % in BA group (p 0.01, no difference between groups). Blood lactate reached a maximal value of 9.4 ± 1.6 mmol l(-1) in PL group, and 10.3 ± 1.3 mmol l(-1) in BA group, with a slight better performance in the fatigue test (+8.6 %, p ≤ 0.01) for BA group as compared to PL group. To conclude, 2-month β-alanine supplementation resulted in a slight improvement of explosive force after 45 maximal consecutive jumps in young athletes. However, the practical adequacy of supplementation remains questionable in an active and healthy population.

The advent of the Starr–Edwards mechanical valve marked the beginning of the modern era for heart valve replacement. Nowadays, this valve has been supplanted by lower profile bileaflet mechanical prostheses that are considered to have better haemodynamics, lesser risk of thrombo-embolic complications, and longer durability without structural prosthesis failure. These assumptions often lead physicians to face with the question of systematically replacing functional Starr–Edwards valves in patients undergoing redo operations on other valves. We report the case of a 67-year-old patient who recently underwent mitral valve replacement for symptomatic rheumatic valve disease with an excellent outcome. During the operation, the Starr–Edwards valve in the aortic position implanted 51 years earlier was found to still functioning normally hence was left in place, thereby breaking a new longevity record for a valve prosthesis.

After myocardial infarction (MI), mitral valve (MV) tethering stimulates adaptive leaflet growth, but counterproductive leaflet thickening and fibrosis augment mitral regurgitation (MR), doubling heart failure and mortality. MV fibrosis post-MI is associated with excessive endothelial-to-mesenchymal transition (EMT), driven by transforming growth factor (TGF)-β overexpression. In vitro, losartan-mediated TGF-β inhibition reduces EMT of MV endothelial cells.This study tested the hypothesis that profibrotic MV changes post-MI are therapeutically accessible, specifically by losartan-mediated TGF-β inhibition.The study assessed 17 sheep, including 6 sham-operated control animals and 11 with apical MI and papillary muscle retraction short of producing MR; 6 of the 11 were treated with daily losartan, and 5 were untreated, with flexible epicardial mesh comparably limiting left ventricular (LV) remodeling. LV volumes, tethering, and MV area were quantified by using three-dimensional echocardiography at baseline and at 60 ± 6 days, and excised leaflets were analyzed by histopathology and flow cytometry.Post-MI LV dilation and tethering were comparable in the losartan-treated and untreated LV constraint sheep. Telemetered sensors (n = 6) showed no significant losartan-induced changes in arterial pressure. Losartan strongly reduced leaflet thickness (0.9 ± 0.2 mm vs. 1.6 ± 0.2 mm; p 0.05; 0.4 ± 0.1 mm sham animals), TGF-β, and downstream phosphorylated extracellular-signal-regulated kinase and EMT (27.2 ± 12.0% vs. 51.6 ± 11.7% α-smooth muscle actin-positive endothelial cells, p 0.05; 7.2 ± 3.5% sham animals), cellular proliferation, collagen deposition, endothelial cell activation (vascular cell adhesion molecule-1 expression), neovascularization, and cells positive for cluster of differentiation (CD) 45, a hematopoietic marker associated with post-MI valve fibrosis. Leaflet area increased comparably (17%) in constrained and losartan-treated sheep.Profibrotic changes of tethered MV leaflets post-MI can be modulated by losartan without eliminating adaptive growth. Understanding the cellular and molecular mechanisms could provide new opportunities to reduce ischemic MR.

We propose an Endogenous Regime Switching model specifically designed for modelling acreage choices with corner solutions featuring regime fixed costs. Contrary to models based on censored regression systems, this model is fully coherent from an economic point of view, by construction. To illustrate its empirical tractability, we estimate a random parameter version of this model for a panel dataset of French arable crop producers. Our results show that the model fits well the data, the regime fixed cost matter, and that the decision to produce a crop or not play a major role in the acreage responses to economic incentives.

Aims Heart failure (HF) is accompanied by major neuroendocrine changes including the activation of the natriuretic peptide (NP) pathway. Using the unique model of patients undergoing implantation of the CARMAT total artificial heart and investigating regional differences in soluble neprilysin (sNEP) in patients with reduced or preserved systolic function, we studied the regulation of the NP pathway in HF. Methods and results Venous blood samples from two patients undergoing replacement of the failing ventricles with a total artificial heart were collected before implantation and weekly thereafter until post-operative week 6. The ventricular removal was associated with an immediate drop in circulating NPs, a nearly total disappearance of circulating glycosylated proBNP and furin activity and a marked decrease in sNEP. From post-operative week 1 onwards, NP concentrations remained overall unchanged. In contrast, partial recoveries in glycosylated proBNP, furin activity, and sNEP were observed. Furthermore, while in patients with preserved systolic function (n = 6), sNEP concentrations in the coronary sinus and systemic vessels were similar (all P > 0.05), in patients with reduced left-ventricular systolic function, sNEP concentration, and activity were ∼three-fold higher in coronary sinus compared to systemic vessels (n = 21, all P Conclusion The heart plays a pivotal role as a regulator of the endocrine response in systolic dysfunction, not only by directly releasing NPs but also by contributing to circulating sNEP, which in turn determines the bioavailability of other numerous vasoactive peptides.

Objectives To determine hemostasis perturbations, including von Willebrand factor (VWF) multimers, after implantation of a new bioprosthetic and pulsatile total artificial heart (TAH). Design Preclinical study Setting Single-center biosurgical research laboratory. Participants Female Charolais calves, 2-to-6 months old, weighing 102-to-122 kg. Interventions Surgical implantation of TAH through a mid-sternotomy approach. Measurements and Main Results Four of 12 calves had a support duration of several days (4, 4, 8, and 10 days), allowing for the exploration of early steps of hemostasis parameters, including prothrombin time; coagulation factor levels (II, V, VII+X, and fibrinogen); and platelet count. Multimeric analysis of VWF was performed to detect a potential loss of high-molecular weight (HMW) multimers, as previously described for continuous flow rotary blood pumps. Despite the absence of anticoagulant treatment administered in the postoperative phase, no signs of coagulation activation were detected. Indeed, after an immediate postsurgery decrease of prothrombin time, platelet count, and coagulation factor levels, most parameters returned to baseline values. HMW multimers of VWF remained stable either after initiation or during days of support. Conclusions Coagulation parameters and platelet count recovery in the postoperative phase of the Carmat TAH (Camat SA, Velizy Villacoublay Cedex, France) implantation in calves, in the absence of anticoagulant treatment and associated with the absence of decrease in HMW multimers of VWF, is in line with early hemocompatibility that is currently being validated in human clinical studies.

Early development of mechanical circulatory support was aimed at replacing the native ventricles by a total artificial heart (TAH). However, progress was limited by the constraints of the then-available technologies and let to a shift toward implantable left ventricular assist devices (LVADs), supporting the left heart only. Over time, LVADs underwent a technological metamorphosis from valve-containing large devices placed in extra-thoracic pump pockets to valveless rotary flow devices that can be placed directly in the thoracic cavity using less-invasive surgical techniques [1]. These rotary flow devices contain narrow gaps and mechanical or hydrodynamic bearings and produce continuous flow in a high-shear environment. Despite the use of high levels of anticoagulation, pump thrombosis, acquired von Willebrand factor deficiency, and gastrointestinal bleeding have been observed with the use of these devices, indicating poor hemocompatibility [2, 3]. In addition, 10–40% patients with advanced left ventricular dysfunction treated by LVADs develop right ventricular dysfunction, resulting in complications related to right-sided congestion, such as renal failure and right heart failure [4].

OBJECTIVE:Although high intensity physical activities may represent a great proportion of the total energy expenditure in active people, only sparse studies have investigated the accuracy of wearable monitors to assess activity related energy expenditure (AEE) during high intensity exercises. Therefore, the purpose of the present study was to investigate the accuracy of the Actiheart, a light portable monitor estimating AEE based on heart rate (HR) and activity counts (ACT), during two popular activities (running and cycling) performed at high intensities. The benefit of an individual calibration of the HR-AEE relationship established during a preliminary maximal test was also evaluated.METHODS:AEE was estimated in eighteen active adults (4 women and 14 men; 25 ± 4 yr) with indirect calorimetry using a respiratory gas analysis system (reference method) and the Actiheart during 5-min running and cycling at 60, 75 and 85% of maximal oxygen uptake (VO2max) previously determined during a maximal test performed on a treadmill or cycle ergometer. For the Actiheart, AEE was estimated either using the group or individual calibrated equations available in the dedicated software, and their respective HR, ACT or combined HR/ACT algorithms.RESULTS:When the HR algorithm was used for cycling and the HR or HR/ACT algorithms for running, AEE measured by the Actiheart increased proportionally to exercise intensity from 60 to 85% VO2max (P, info:eu-repo/semantics/published

Introduction Bioprosthetic heart valves (BV) made of xenogenic pericardium fixed with glutaraldehyde have been developed more than 30 years ago. The concept of cross linking collagenous fibers to ensure in-vivo stability of the scaffold and reducing antigenic immune response by fixation resulted in successful clinical evaluations and a lower risk of thromboembolism thus eliminating the need for a lifelong anticoagulation. To explain these clinical results, an acquired hemocompatibility process has been proposed but never extensively studied because of the impossibility to access not degenerated material. Objective To study and understand mechanisms of acquired hemocompatibility, we explored non degenerated BV from 9 different patients implanted with a Carmat total artificial heart (C-TAH) and four BV duration from 45 to 270 days. Method We performed classic histopathology and immunophenotypic characterization of explanted BV. Biological deposit has been also explored by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Result In short implantation duration time, we observed a fibrin deposit with inflammatory cells and pseudotubes formation. Histological sections showed superficial infiltration of cells, persisting in long duration but not damaging integrity of the pericardium. The fibrin deposit is then organized in a compacted smooth fibrin network in longer implantation durations. Endothelial cells (EC) monolayer covering has also been observed on this fibrin cap, the percentage of the BV surface with EC covering increasing along months. This endothelial cells covering is positive for VE-Cadherin, with flat nucleus and tight junctions. Conclusion Healthy BV implanted with C-TAH enabled us to study, for the first time, non-degenerated implanted valve in human. Biomaterial passivation by an organized fibrin deposit and formation of EC monolayer on top achieve an optimal hemocompatibility without any modification of pericardial tissue.

The main objective of this paper is to show that the MultiNomial Logit (MNL) framework can be used for deriving simple acreage share models. More specifically we show that MNL acreage choice models can be defined as parts of consistent multicrop models. When coupled with suitably designed crop production models, e.g. a specific parameterization of the standard quadratic yield function, the parameters of these multicrop models are easily interpreted and estimated. Although MNL acreage choice models are usually derived by aggregating crop choices defined at the plot level, we show that these models can also be derived by considering a profit maximisation problem at the farm level. This provides a simple theoretical background for the Standard MNL acreage share model, as well as for simple extensions of these models: the Nested MNL acreage share models. An empirical application on French farm-level data over the period 1996–2007 investigates the empirical performances of the multicrop econometric models based on the proposed MNL framework for modelling acreage choices.

ObjectiveThe goal of the Viện Tim Institute du Coeur is to provide high quality cardiac surgical care to the Vietnamese population with 25% of care allocated to the indigent. This article discusses the history; functional and financial implementation of creating a long-term fully sustainable adult and pediatric cardiac surgery center in Southeast Asia in a developing country.MethodsThe Institut du Coeur in Ho Chi Minh City, Vietnam is a fully functional and financially solvent cardiac surgery center that was formed 28 years ago. It was borne from the Alain Carpentier Foundation which oversees its activity and the Centre Médical International which is an outpatient clinic in Ho Chi Minh City and continues to financially support and oversee the development and future of the Institute. This article details many of the key components to the development of this sustainable program and its evolution.ResultsSince 1996, over 25,000 patients with complicated adult and congenital cardiac disease have been treated at the infirmary with support from the Alain Carpentier Foundation since it was established in 1992. The hospital has also performed surgery and treatment to poor patients across Vietnam with over 6,700 impoverished patients having had free operations with an estimated cost of VND230 billion (US$10.2 million). In addition, 96 surgeons and nearly 500 medical staff have carried out charitable health checks on 12,000 patients in many provinces and cities throughout Vietnam. Through profit sharing with the Centre Médical International and corporate and personal donations, proceeds are given to the Institute to help perform roughly 25% of all cardiac surgery free of charge to indigent patients in need of congenital heart surgery.ConclusionThe Viện Tim Institute du Coeur has stayed true to its goal of offering high quality cardiac surgical care including congenital heart surgery to a large patient population with one quarter directed to the medically indigent. It also continues to empower and train the health care professionals locally and throughout the country. Creation and growth through this model may help provide a fully functional and financially self-sustaining institution in a developing nation.

Muscle mass is the major deposit of protein molecules with dynamic turnover between net protein synthesis and degradation. In human subjects, invasive and non-invasive techniques have been applied to determine their skeletal muscle catabolism of amino acids at rest, during and after different forms of physical exercise and training. The aim of this review is to analyse the turnover flux and the relative oxidation rate of different types of muscle proteins after one bout of exercise as well as after resistance and endurance condition of training. Protein feeding in athletes appears to be a crucial nutrition necessity to promote the maintenance of muscle mass and its adaptation to the need imposed by the imposed technical requirements. In resting human individuals, the recommended protein daily allowance is about 0.8 g (dry weight) kg−1 body weight per 24 h knowing that humans are unable to accumulate protein stores in muscle tissues. Nevertheless, practical feeding recommendations related to regular exercise practice are proposed to athletes by different bodies in order to foster their skills and performance. This review will examine the results obtained under endurance and resistance type of exercise while consuming single or repeated doses of various ingestions of protein products (full meat, essential amino acids, specific amino acids and derivatives, vegetarian food). From the scientific literature, it appears that healthy athletes (and heavy workers) should have a common diet of 1.25 g kg−1 24 h to compensate the exercise training muscle protein degradation and their resynthesis within the following hours. A nitrogen-balance assay would be recommended to avoid any excessive intake of protein. Eventually, a daily equilibrated food intake would be of primer importance versus inadequate absorption of some specific by-products.

Whether Barlow disease (BD) and fibroelastic deficiency (FED), the main causes of mitral valve prolapse (MVP), should be considered 2 distinct diseases remains unknown. Mitral valves from patients who required surgery for severe mitral regurgitation due to degenerative nonsyndromic MVP were analyzed. Intraoperative diagnosis of BD or FED was based on leaflet redundancy and thickness, number of segments involved, and annular dimension. The removed medial scallop of the posterior leaflet and attached chordae were used for histopathological and immunohistological assessment. Histologically, compared to normal controls (n = 3), BD (n = 14), and FED (n = 9) leaflets demonstrated an altered architecture and increased thickness. Leaflet thickness was greater and chordae thickness lower in BD than FED (P < 0.0001). In BD, increased thickness was owing to spongiosa expansion (proteoglycan accumulation) and intimal thickening on fibrosa and atrialis; in FED, local thickening was predominant on the fibrosa side, with accumulation of proteoglycan-like material around the chordae. Collagen accumulation was observed in FED leaflets and chords and decreased in BD. Fragmented elastin fibers were present in BD and FED; elastin decreased in BD but increased in FED leaflets and around chordae. Activated myofibroblasts accumulate in both diseased leaflets and chords, but more abundantly in FED chordae (P < 0.0001), independently of age, suggesting a role of these cells in chordal rupture. There were more CD34-positive cells in BD leaflets and in FED chordae (P < 0.01). In BD leaflets (but not chordae) proliferative Ki67-positive cells were more abundant (P < 0.01) and matrix metalloproteinase 2 levels were increased (P < 0.01) indicating tissue remodeling. Upregulation of transforming growth factor beta and pERK signaling pathways was evident in both diseases but more prominent in FED leaflets (continued on next page)(P < 0.001), with pERK upregulation in FED chordae (P < 0.0001). Most cellular and signaling markers were negligible in control valves. Quantitative immunohistopathological analyses demonstrated distinct changes between BD and FED valves: predominant matrix degradation in BD and increased profibrotic signaling pathways in FED, indicating that BD and FED are 2 different entities. These results may pave the way for genetic studies of MVP and development of preventive drug therapies.

This study investigated the effect of protein supplementation enriched in leucine on muscle hypertrophy and strength gain in response to a 6-month strength training programme of the plantar flexor muscles in older adults (aged over 60 yr). To this end, changes in neuromuscular parameters were compared between two groups (matched for age, sex and initial maximal strength) that trained twice a week for 24 weeks, with one group receiving a protein supplementation enriched with leucine (supplementation group, n = 12), and another group receiving a placebo (control group, n = 13) that provided subjects with a similar energy intake that the protein supplementation. Muscle thickness and pennation angle of gastrocnemius medialis were used as indices of muscle hypertrophy. Maximal strength and associated electromyographic activity of leg muscles, and voluntary activation (assessed by the interpolated twitch technique) were recorded. Peak torque in response to 3-pulse train delivered to the tibial nerve was also recorded. After training, muscle thickness (+ 8.4%) and pennation angle (+ 13.4%) were increased, regardless of training groups (p