Simulating the ideal geometrical and biomechanical parameters of the pulmonary autograft to prevent failure in the Ross operation

OBJECTIVES: Reinforcements for the pulmonary autograft (PA) in the Ross operation have been introduced to avoid the drawback of conduit expansion and failure. With the aid of an in silico simulation, the biomechanical boundaries applied to a healthy PA during the operation were studied to tailor the best implant technique to prevent reoperation. METHODS: Follow-up echocardiograms of 66 Ross procedures were reviewed. Changes in the dimensions and geometry of reinforced and non-reinforced PAs were evaluated. Miniroot and subcoronary implantation techniques were used in this series. Mechanical stress tests were performed on 36 human pulmonary and aortic roots explanted from donor hearts. Finite element analysis was applied to obtain high-fidelity simulation under static and dynamic conditions of the biomechanical properties and applied stresses on the PA root and leaflet and the similar components of the native aorta. RESULTS: The non-reinforced group showed increases in the percentages of the mean diameter that were significantly higher than those in the reinforced group at the level of the Valsalva sinuses (3.9%) and the annulus (12.1%). The mechanical simulation confirmed geometrical and dimensional changes detected by clinical imaging and demonstrated the non-linear biomechanical behaviour of the PA anastomosed to the aorta, a stiffer behaviour of the aortic root in relation to the PA and similar qualitative and quantitative behaviours of leaflets of the 2 tissues. The annulus was the most significant constraint to dilation and affected the distribution of stress and strain within the entire complex, with particular strain on the sutured regions. The PA was able to evenly absorb mechanical stresses but was less adaptable to circumferential stresses, potentially explaining its known dilatation tendency over time. CONCLUSIONS: The absence of reinforcement leads to a more marked increase in the diameter of the PA. Preservation of the native geometry of the PA root is crucial; the miniroot technique with external reinforcement is the most suitable strategy in this context

Characterisation of Inactivation Domains and Evolutionary Strata in Human X Chromosome through Markov Segmentation

Markov segmentation is a method of identifying compositionally different subsequences in a given symbolic sequence. We have applied this technique to the DNA sequence of the human X chromosome to analyze its compositional structure. The human X chromosome is known to have acquired DNA through distinct evolutionary events and is believed to be composed of five evolutionary strata. In addition, in female mammals all copies of X chromosome in excess of one are transcriptionally inactivated. The location of a gene is correlated with its ability to undergo inactivation, but correlations between evolutionary strata and inactivation domains are less clear. Our analysis provides an accurate estimate of the location of stratum boundaries and gives a high–resolution map of compositionally different regions on the X chromosome. This leads to the identification of a novel stratum, as well as segments wherein a group of genes either undergo inactivation or escape inactivation in toto. We identify oligomers that appear to be unique to inactivation domains alone

Mass spectrometry of atomic ions produced by in-trap decay of short-lived nuclides

The triple-trap mass spectrometer ISOLTRAP at ISOLDE/CERN has demonstrated the feasibility of mass spectrometry of in-trap-decay product ions. This novel technique gives access to radionuclides, which are not produced directly at ISOL-type radioactive ion beam facilities. As a proof of principle, the in-trap decay of $^{37}K^+$ has been investigated in a Penning trap filled with helium buffer gas. The half-life of the mother nuclide was confirmed and the recoiling $^{37}Ar^+$ daughter ion was contained within the trap. The ions of either the mother or the daughter nuclide were transferred to a precision Penning trap, where their mass was determined

Extracellular K(+) rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl(-) -dependent and independent mechanisms.

High dietary potassium (K(+) ) intake dephosphorylates and inactivates the NaCl cotransporter (NCC) in the renal distal convoluted tubule (DCT). Using several ex vivo models, we show that physiological changes in extracellular K(+) , similar to those occurring after a K(+) rich diet, are sufficient to promote a very rapid dephosphorylation of NCC in native DCT cells. Although the increase of NCC phosphorylation upon decreased extracellular K(+) appears to depend on cellular Cl(-) fluxes, the rapid NCC dephosphorylation in response to increased extracellular K(+) is not Cl(-) -dependent. The Cl(-) -dependent pathway involves the SPAK/OSR1 kinases, whereas the Cl(-) independent pathway may include additional signalling cascades. A high dietary potassium (K(+) ) intake causes a rapid dephosphorylation, and hence inactivation, of the thiazide-sensitive NaCl cotransporter (NCC) in the renal distal convoluted tubule (DCT). Based on experiments in heterologous expression systems, it was proposed that changes in extracellular K(+) concentration ([K(+) ]ex ) modulate NCC phosphorylation via a Cl(-) -dependent modulation of the with no lysine (K) kinases (WNK)-STE20/SPS-1-44 related proline-alanine-rich protein kinase (SPAK)/oxidative stress-related kinase (OSR1) kinase pathway. We used the isolated perfused mouse kidney technique and ex vivo preparations of mouse kidney slices to test the physiological relevance of this model on native DCT. We demonstrate that NCC phosphorylation inversely correlates with [K(+) ]ex , with the most prominent effects occurring around physiological plasma [K(+) ]. Cellular Cl(-) conductances and the kinases SPAK/OSR1 are involved in the phosphorylation of NCC under low [K(+) ]ex . However, NCC dephosphorylation triggered by high [K(+) ]ex is neither blocked by removing extracellular Cl(-) , nor by the Cl(-) channel blocker 4,4'-diisothiocyano-2,2'-stilbenedisulphonic acid. The response to [K(+) ]ex on a low extracellular chloride concentration is also independent of significant changes in SPAK/OSR1 phosphorylation. Thus, in the native DCT, [K(+) ]ex directly and rapidly controls NCC phosphorylation by Cl(-) -dependent and independent pathways that involve the kinases SPAK/OSR1 and a yet unidentified additional signalling mechanism

Contegra conduit for reconstruction of the right ventricular outflow tract: a review of published early and mid-time results

<p>Abstract</p> <p>Objective</p> <p>The valved conduit Contegra (bovine jugular vein) has being implanted for more than 7 years in the right ventricular outflow tract and it is noted that the available reports have been mixed. The aim of this study is to review the reported evidence in the literature.</p> <p>Methods</p> <p>Search of the relevant literature for the primary endpoints of operative mortality and morbidity and secondary endpoints of follow-up haemodynamic performance including severe stenosis, regurgitation and need for reintervention are presented.</p> <p>Results</p> <p>We selected and analysed 17 series including 767 patients. Commonest indication was Fallot's tetralogy. Operative mortality was 2.6%. Operative morbidity was 13.9%. In follow-up, the incidence of intraconduit stenosis was 10.9% (incidence of stenosis for the 12 millimetre conduit was 83.3% in one series) and that of at least moderate regurgitation was 6.3%.</p> <p>The aspirin users had a stenosis incidence of 10.5% compared to the non-users had a stenosis incidence of 9.6%.</p> <p>Conclusion</p> <p>A dissent on the performance of the Contegra is discussed, while results are satisfactory in the majority of studies apart for the smallest conduits (12 and 14 millimetre), suggesting an association to compromised run-off. The role of aspirin as antithrombotic modulator remains controversial.</p

Perioperative infusion of low- dose of vasopressin for prevention and management of vasodilatory vasoplegic syndrome in patients undergoing coronary artery bypass grafting-A double-blind randomized study

Preoperative medication by inhibitors of angiotensin-converting enzyme (ACE) in coronary artery patients predisposes to vasoplegic shock early after coronary artery bypass grafting. Although in the majority of the cases this shock is mild, in some of them it appears as a situation, "intractable" to high-catecholamine dose medication. In this study we examined the possible role of prophylactic infusion of low-dose vasopressin, during and for the four hours post-bypass after cardiopulmonary bypass, in an effort to prevent this syndrome. In addition, we studied the influence of infused vasopressin on the hemodynamics of the patients, as well as on the postoperative urine-output and blood-loss. In our study 50 patients undergoing coronary artery bypass grafting were included in a blind-randomized basis. Two main criteria were used for the eligibility of patients for coronary artery bypass grafting: ejection fraction between 30-40%, and patients receiving ACE inhibitors, at least for four weeks preoperatively. The patients were randomly divided in two groups, the group A who were infused with 0.03 IU/min vasopressin and the group B who were infused with normal saline intraoperativelly and for the 4 postoperative hours. Measurements of mean artery pressure (MAP), central venous pressure (CVP), systemic vascular resistance (SVR), ejection fracture (EF), heart rate (HR), mean pulmonary artery pressure (MPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were performed before, during, and after the operation. The requirements of catecholamine support, the urine-output, the blood-loss, and the requirements in blood, plasma and platelets for the first 24 hours were included in the data collected. The incidence of vasodilatory shock was significantly lower (8% vs 20%) in group A and B respectively (p = 0,042). Generally, the mortality was 12%, exclusively deriving from group B. Postoperatively, significant higher values of MAP, CVP, SVR and EF were recorded in the patients of group A, compared to those of group B. In group A norepinephrine was necessary in fewer patients (p = 0.002) and with a lower mean dose (p = 0.0001), additive infusion of epinephrine was needed in fewer patients (p = 0.001), while both were infused for a significant shorter infusion-period (p = 0.0001). Vasopressin administration (for group A) was associated with a higher 24 hour diuresis) (0.0001)

Chromosome-wide DNA methylation analysis predicts human tissue-specific X inactivation

X-chromosome inactivation (XCI) results in the differential marking of the active and inactive X with epigenetic modifications including DNA methylation. Consistent with the previous studies showing that CpG island-containing promoters of genes subject to XCI are approximately 50% methylated in females and unmethylated in males while genes which escape XCI are unmethylated in both sexes; our chromosome-wide (Methylated DNA ImmunoPrecipitation) and promoter-targeted methylation analyses (Illumina Infinium HumanMethylation27 array) showed the largest methylation difference (D = 0.12, p < 2.2 E−16) between male and female blood at X-linked CpG islands promoters. We used the methylation differences between males and females to predict XCI statuses in blood and found that 81% had the same XCI status as previously determined using expression data. Most genes (83%) showed the same XCI status across tissues (blood, fetal: muscle, kidney and nerual); however, the methylation of a subset of genes predicted different XCI statuses in different tissues. Using previously published expression data the effect of transcription on gene-body methylation was investigated and while X-linked introns of highly expressed genes were more methylated than the introns of lowly expressed genes, exonic methylation did not differ based on expression level. We conclude that the XCI status predicted using methylation of X-linked promoters with CpG islands was usually the same as determined by expression analysis and that 12% of X-linked genes examined show tissue-specific XCI whereby a gene has a different XCI status in at least one of the four tissues examined

Stratégies démographiques des poissons des rivières françaises : premiers résultats

International audienceThe analysis of the biological, morphological and food characteristics of 35 French species leads to distinguish two main strategies. The first one gathers 11 species with a short life span and which maximize the survival of juveniles. Within it, cold water species with a long reproduction lifetime and thermophilous species with a relatively stronger fertility can be distinguished. Their diets are essentially made of insects- plankton and insects-fishes. In the second group, no care is given to juveniles; relative fertilities are higher and inversely correlated to the number of reproduction cycles. 10 species are omnivorous with a grass-wastes tendancy, and 4 species eat strictly fishes. The canonical analysis of correspondances shows that these biological characteristics are sufficuent to understand most of the longitudinal zonation.L'analyse des caractéristiques biologiques et morpho-alimentaires de 35 espèces françaises permet de distinguer 2 stratégies principales. La première rassemble 11 espèces à faible longévité et maximisant la survie des jeunes. En son sein, on distingue des espèces d'eau froide à longue durée de vie pré-reproductrice et des espèces thermophiles à fécondité relativement plus forte. Leurs régimes alimentaires sont essentiellement du type insectivore-planctonophage et insectivore-ichtyophage. Dans le second groupe, aucun soin n'est apporté aux jeunes ; les fécondités relatives sont plus fortes et inversement corrélées avec le nombre de cycles de reproduction. 10 espèces sont des omnivores à tendance herbivore-détritivore et 4 des ichtyophages stricts. L'analyse canonique des correspondances démontre que ces caractéristiques biologiques rendent compte de l'essentiel de la zonation longitudinale