Simple equations to predict the effects of veno-venous ECMO in decompensated Eisenmenger syndrome.

Adult patients with uncorrected congenital heart diseases and chronic intracardiac shunt may develop Eisenmenger syndrome (ES) due to progressive increase of pulmonary vascular resistance, with significant morbidity and mortality. Acute decompensation of ES in conditions promoting a further increase of pulmonary vascular resistance, such as pulmonary embolism or pneumonia, can precipitate major arterial hypoxia and death. In such conditions, increasing systemic oxygenation with veno-venous extracorporeal membrane oxygenation (VV-ECMO) could be life-saving, serving as a bridge to treat a potential reversible cause for the decompensation, or to urgent lung transplantation. Anticipating the effects of VV-ECMO in this setting could ease the clinical decision to initiate such therapeutic strategy. Here, we present a series of equations to accurately predict the effects of VV-ECMO on arterial oxygenation in ES and illustrate this point by a case of ES decompensation with refractory hypoxaemia consecutive to an acute respiratory failure due to viral pneumonia

Deciphering the intracellular metabolism of Listeria monocytogenes by mutant screening and modelling

Background: The human pathogen Listeria monocytogenes resides and proliferates within the cytoplasm of epithelial cells. While the virulence factors essentially contributing to this step of the infection cycle are well characterized, the set of listerial genes contributing to intracellular replication remains to be defined on a genome-wide level. Results: A comprehensive library of L. monocytogenes strain EGD knockout mutants was constructed upon insertion-duplication mutagenesis, and 1491 mutants were tested for their phenotypes in rich medium and in a Caco-2 cell culture assay. Following sequencing of the plasmid insertion site, 141 different genes required for invasion of and replication in Caco-2 cells were identified. Ten in-frame deletion mutants were constructed that confirmed the data. The genes with known functions are mainly involved in cellular processes including transport, in the intermediary metabolism of sugars, nucleotides and lipids, and in information pathways such as regulatory functions. No function could be ascribed to 18 genes, and a counterpart of eight genes is missing in the apathogenic species L. innocua. Mice infection studies revealed the in vivo requirement of IspE (Lmo0190) involved in mevalonate synthesis, and of the novel ABC transporter Lmo0135-0137 associated with cysteine transport. Based on the data of this genome-scale screening, an extreme pathway and elementary mode analysis was applied that demonstrates the critical role of glycerol and purine metabolism, of fucose utilization, and of the synthesis of glutathione, aspartate semialdehyde, serine and branched chain amino acids during intracellular replication of L. monocytogenes. Conclusion: The combination of a genetic screening and a modelling approach revealed that a series of transporters help L. monocytogenes to overcome a putative lack of nutrients within cells, and that a high metabolic flexibility contributes to the intracellular replication of this pathogen

The VAD connection : connecting ventricular assist devices to the aorta in silico

Les systèmes d'assistance ventriculaire sont apparus durant la dernière décade comme une approche thérapeutique efficace du traitement de l'insuffisance cardiaque terminale, en particulier dans le contexte de manque de donneurs d'organes. Néanmoins, et ceci malgré les progrès techniques majeurs, les taux de complications restent élevés et sont en partie liés à la configuration géométrique, en particulier le site d'implantation de la cannule de sortie à l'aorte thoracique. Bien que l'anastomose à l'aorte descendante permette une chirurgie moins invasive, les bénéfices de cette technique sont toujours controversés, comparée à la méthode standard de l'aorte ascendante, en raison du risque thrombo-embolique possiblement augmenté et des modifications hémodynamiques induites au niveau de l'arc aortique. Dans ce travail, nous comparons in silico en terme de débit et pression les deux possibilités anastomotiques. Nous développons un réseau de modèles mathématiques unidimensionnels, et l'appliquons à diverses situations cliniques, pour différents stades d'insuffisance cardiaque et de vitesses de rotation de la machine. Les données initiales sont obtenues grâce à un modèle OD (c'est-à-dire qui dépend uniquement du temps mais pas de l'espace) du système cardiovasculaire comprenant une assistance circulatoire, validé avec des données cliniques. Les simulations réalisées montrent que les deux méthodes sont similaires, en terme de débit et courbes de pression, ceci pour tous les cas cliniques étudiés. Ces résultats numériques soutiennent la possibilité d'utiliser la technique d'anastomose à l'aorte thoracique descendante, permettant une chirurgie moins invasive. Sur un plan plus fondamental, le système cardiovasculaire peut être simulé par le biais de multiples modèles de niveau de complexité différents, au prix d'un coût computationnel toujours plus élevé. Nous évaluons les avantages de modèles géométriques à plusieurs échelles (uni- et tridimensionnelle) avec données provenant de patients, comparés à des modèles simplifiés. Les résultats montrent que ces modèles de dimensions hétérogènes apportent un bénéfice important en terme de ressources de calcul, tout en conservant une précision acceptable. En conclusion, ces résultats encourageant montrent la relevance des études numériques dans le domaine médical, tant sur le plan fondamental et la compréhension des mécanismes physiopathologiques, que sur le plan applicatif et le développement de nouvelles thérapeutiques

Phloem loading and unloading

International audienc

Sur Jean Joseph Louis Chancel, inventeur des allumettes ou briquets oxygénés

Ameil J., Bonnemain Henri, Bouvet Maurice. Sur Jean Joseph Louis Chancel, inventeur des allumettes ou briquets oxygénés. In: Revue d'histoire de la pharmacie, 52ᵉ année, n°180, 1964. pp. 35-39

The Right Ventricle in COVID-19.

Infection with the novel severe acute respiratory coronavirus-2 (SARS-CoV2) results in COVID-19, a disease primarily affecting the respiratory system to provoke a spectrum of clinical manifestations, the most severe being acute respiratory distress syndrome (ARDS). A significant proportion of COVID-19 patients also develop various cardiac complications, among which dysfunction of the right ventricle (RV) appears particularly common, especially in severe forms of the disease, and which is associated with a dismal prognosis. Echocardiographic studies indeed reveal right ventricular dysfunction in up to 40% of patients, a proportion even greater when the RV is explored with strain imaging echocardiography. The pathophysiological mechanisms of RV dysfunction in COVID-19 include processes increasing the pulmonary vascular hydraulic load and others reducing RV contractility, which precipitate the acute uncoupling of the RV with the pulmonary circulation. Understanding these mechanisms provides the fundamental basis for the adequate therapeutic management of RV dysfunction, which incorporates protective mechanical ventilation, the prevention and treatment of pulmonary vasoconstriction and thrombotic complications, as well as the appropriate management of RV preload and contractility. This comprehensive review provides a detailed update of the evidence of RV dysfunction in COVID-19, its pathophysiological mechanisms, and its therapy

Water Deficit-Induced Changes in Concentrations in Proline and Some Other Amino Acids in the Phloem Sap of Alfalfa.

Changes in amino acid composition of alfalfa (Medicago sativa L.) phloem sap were studies in response to a water deficit. Sap was collected by stylectomy. As the leaf water potential ([psi]) decreased from -0.4 to -2.0 MPa, there was significant increase of the total amino acid concentration, due to that of some amino acids: proline, valine, isoleucine, leucine, glutamic acid, aspartic acid, and threonine. Asparagine concentration, which is the main amino acid assayed in the phloem sap of alfalfa (it accounts for 70% of the total content), did not vary with the plant water status. The other amino acid concentrations remained stable as [psi] varied; in particular, [gamma]-amino butyric acid concentration remained unchanged, whereas it varied in response to wounding. The more striking change in the sieve tubes was the accumulation of proline, which was observed below a [psi] threshold value of about -0.9 MPa (concentration x60 for a decrease of [psi] from -0.9 to -2.0 MPa). The role of such changes in phloem sap amino acid concentration in osmotic adjustment of growing tissues is discussed