073 Right Ventricle Contractile Reserve as a Pre-operative Tool for Assessing RV failure after Continuous Flow LVAD Implantation

IntroductionLatest generation continuous flow left ventricular assist devices (LVADs) have been proposed as an alternative to heart transplantation for end-stage heart failure. However, postoperative right ventricle (RV) dysfunction remains common and has a negative impact on prognosis. Purpose of our study was to identify echocardiographic or hemodynamic parameters that could predict early RV failure after LVAD implantation in patients with biventricular dysfunction.MethodsFourteen patients with biventricular dysfunction who have been evaluated for LVAD implantation were included. Right and left ventricular dysfunction were respectively defined as: tricuspid annular plane excursion < 16 mm (TAPSE) and LV ejection fraction < 35%. In all patients, preoperative measurements were obtained at rest. In 7 patients, right heart catheterization was performed simultaneously with increasing doses of dobutamine (15γ/Kg/min). Primary endpoint was death caused by right ventricle systolic dysfunction or need for right ventricle mechanical support within 30 days after surgery (RVSD+).ResultsMean recipient age was 58±7 years. Primary end-point (RVSD+) was noted in five patients. Preoperative demographic, echocardiographic and hemodynamic data were similar between RVSD+ and RVSD- patients (Table). Percent increase of TAPSE and systolic PAP between basal and high dobutamine dose was significantly lower in RVSD+ than in RVSD- patients.ConclusionPercent increase of TAPSE and systolic PAP induced by high dose dobutamine infusion might be two interesting criteria to assess RV contractile reserve and predict RV outcome after LVAD implantation in patient with biventricular dysfunction.Baseline Measurement (n=14)Change after Dobutamine infusion,% (n=7)RVSD-RVSD+pRVSD-RVSD+pN95TAPSE, mm14±214±20.955±526±20.03Systolic PAP, mmHg51±753±60.842±84±70.05Cardiac Output, l/min3.3±0.53.5±0.50.987±1093±470.7Pulm Vasc Res, Wood3.9±14.3±10.62±41-36±70.

Renal macro- and microcirculation autoregulatory capacity during early sepsis and norepinephrine infusion in rats

INTRODUCTION: The relationships between systemic hemodynamics and renal blood flow and renal microcirculation are poorly known in sepsis. Norepinephrine (NE) infusion may add another level of complexity. METHODS: Ventilated and anesthetized rats were submitted to various mean arterial pressure (MAP) steps by blood removal, in presence and absence of sepsis and/or NE. Renal blood flow (RBF) and blood velocity (Vm) in renal cortical capillaries (using Sidestream Dark Field Imaging) were measured. Data were analyzed using linear mixed models enabling us to display the effects of both the considered explanatory variables and their interactions. RESULTS: Positive correlations were found between MAP and RBF. Sepsis had no independent impact on RBF whereas norepinephrine decreased RBF, regardless of the presence of sepsis. The relationship between MAP and RBF was weaker above a MAP of 100 mmHg as opposed to below 100 mmHg, with RBF displaying a relative "plateau" above this threshold. Sepsis and NE impacted carotid blood flow (CBF) differently compared to RBF, demonstrating organ specificity. A positive relationship was observed between MAP and Vm. Sepsis increased Vm while nNE decreased Vm irrespective of MAP. Sepsis was associated with an increase in serum creatinine determined at the end of the experiments, which was prevented by NE infusion. CONCLUSION: In our model, sepsis at an early phase did not impact RBF over a large range of MAP. NE elicited a renal vasoconstrictive effect. Autoregulation of RBF appeared conserved in sepsis. Conversely, sepsis was associated with "hypervelocity" of blood flow in cortical peritubular capillaries reversed by NE infusion

Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma

Summary High-grade gliomas (HGG) are a devastating group of cancers, representing the leading cause of brain tumor-related death in both children and adults. Therapies aimed at mechanisms intrinsic to the glioma cell have translated to only limited success; effective therapeutic strategies will need to also target elements of the tumor microenvironment that promote glioma progression. We recently demonstrated that neuronal activity robustly promotes the growth of a range of molecularly and clinically distinct HGG types, including adult glioblastoma (GBM), anaplastic oligodendroglioma, pediatric GBM, and diffuse intrinsic pontine glioma (DIPG)1. An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule neuroligin-3 (NLGN3), which promotes glioma proliferation through the PI3K-mTOR pathway1. However, neuroligin-3 necessity to glioma growth, proteolytic mechanism of secretion and further molecular consequences in glioma remain to be clarified. Here, we demonstrate a striking dependence of HGG growth on microenvironmental neuroligin-3, elucidate signaling cascades downstream of neuroligin-3 binding in glioma and determine a therapeutically targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric GBM, DIPG and adult GBM fail to grow in Nlgn3 knockout mice. Neuroligin-3 stimulates numerous oncogenic pathways, including early focal adhesion kinase activation upstream of PI3K-mTOR, and induces transcriptional changes including upregulation of numerous synapse-related genes in glioma cells. Neuroligin-3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. ADAM10 inhibitors prevent release of neuroligin-3 into the tumor microenvironment and robustly block HGG xenograft growth. This work defines a promising strategy for targeting neuroligin-3 secretion, which could prove transformative for HGG therapy

Etude des comportements thermique et electrique couples de cellules et modules photovoltaiques spatiaux en liaison avec leurs conditions de fonctionnement: modelisation, analyse par thermographie infrarouge

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : TD 77882 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Ténotomie du tendon d'Achille chez la personne agée:à propos d'un cas

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude de la stabilité aux petites perturbations dans les grands réseaux électriques : optimisation de la régulation par une méthode métaheuristique

Depuis une vingtaine d années, les grands réseaux électriques se trouvent obligés de fonctionner à pleine puissance et souvent aux limites de la stabilité. L amélioration de la stabilité aux petites perturbations, en particulier l amortissement des oscillations interrégionales, est donc devenue un objectif prioritaire. Les interactions entre les générateurs de différentes régions et les régulateurs utilisés nécessitent une optimisation globale de leurs performances : c est le meilleur moyen pour assurer le comportement optimal de l ensemble. L objectif de notre travail est d assurer un amortissement maximum, aussi bien des modes interrégionaux que des modes locaux, à l aide des stabilisateurs de puissance (PSS) généralement utilisés pour l amortissement des modes électromécaniques locaux. Pour ce faire, nous avons développé une méthode d optimisation globale basée sur les algorithmes génétiques et une fonction multiobjectif utilisant les paramètres de stabilité relative et de stabilité absolue déterminés à partir de l analyse des valeurs propres du système. Nous avons analysé l influence de l augmentation progressive du nombre de variables à optimiser simultanément (paramètres des PSSs, emplacement et nombre de ces derniers). La méthode que nous proposons permet un réglage optimal des PSSs avec la meilleure localisation possible et un nombre réduit de PSSs. Nous avons proposé en outre une nouvelle méthode d optimisation utilisant des contraintes dynamiques adaptatives de l espace de recherche afin d améliorer les performances et la rapidité de convergence de cet algorithme. Les performances de ces méthodes d optimisation ont été évaluées sur le réseau multimachines interconnecté New England/New York par analyse des valeurs propres du système et simulations temporelles tant sur le modèle linéarisé que sur le modèle nonlinéaire originel.AIX-MARSEILLE3-BU Sc.St Jérô (130552102) / SudocSudocFranceF

Freeform pour les applications visibles et infrarouges thermiques

International audiencePanchromatic catoptric systems using the freeform technology are investigated. We study a classical Three Mirror Anastigmat configuration and a more uncommon αZ configuration. Images in infrared and visible are presented for the αZ configuration.Les systèmes catoptriques panchromatiques utilisant la technologie freeform sont étudiés. Nous étudions une configuration classique Anastigmat à trois miroirs et une configuration αZ plus rare. Des images dans l'infrarouge et le visible sont présentées pour la configuration αZ

Management of rigorous optomechanical constraints using non planar symmetrical systems

International audienceAn exploration of non planar symmetric geometries for a three mirror anastigmat telescope is performed and show that for some highly constrained systems, such assymetric designs could represent a viable solutio

Reorganization of GABAergic circuits maintains GABAA receptor-mediated transmission onto CA1 interneurons in alpha1-subunit-null mice

The majority of hippocampal interneurons strongly express GABA(A) receptors containing the alpha1 subunit, suggesting that inhibitory control of interneurons is important for proper function of hippocampal circuits. Here, we investigated with immunohistochemical and electrophysiological techniques how these GABA(A) receptors are replaced in mice carrying a targeted deletion of the alpha1-subunit gene (alpha1(0/0) mice). Using markers of five major populations of CA1 interneurons (parvalbumin, calretinin, calbindin, neuropeptide Y and somatostatin), we show that these interneurons remain unaffected in alpha1(0/0) mice. In triple immunofluorescence staining experiments combining these markers with the GABA(A) receptor alpha1, alpha2 or alpha3 subunit and gephyrin, we demonstrate a strong increase in alpha3- and alpha2-GABA(A) receptors clustered at postsynaptic sites along with gephyrin in most CA1 interneurons in alpha1(0/0) mice. The changes were cell type-specific and resulted in an increased number of GABAergic synapses on interneurons. These adjustments were mirrored functionally by retention of spontaneous IPSCs with prolonged decay kinetics, as shown by whole-cell patch-clamp recordings of CA1 interneurons. However, a significant decrease in frequency and amplitude of miniature IPSCs was evident, suggesting reduced affinity of postsynaptic receptors and/or impaired vesicular GABA release. Finally, to assess whether these compensatory changes are sufficient to protect against a pathological challenge, we tested the susceptibility of alpha1(0/0) mice against kainic acid-induced excitotoxicity. No genotype difference was observed in the effects of kainic acid, indicating that the absence of a major GABA(A) receptor subtype is functionally compensated for in hippocampal interneurons by a reorganization of inhibitory circuits