De novo atrial fibrillation as an independent prognostic marker after ST-segment elevation myocardial infarction: Results from the RIMA registry

BACKGROUND: Atrial fibrillation (AF) is common in ST-segment elevation myocardial infarction (STEMI), but its influence on prognosis remains controversial. AIM: We examined the 1-year prognostic value of AF in STEMI, distinguishing patients with prior AF from patients with de novo AF. METHODS: Between January 2004 and December 2015, 3173 STEMI patients were enrolled in the RIMA registry (Registre des Infarctus en Maine Anjou). They were divided into 3 groups: (1) AF-free patients; (2) patients with known prior AF; and (3) patients with de novo AF during hospitalization (including admission). We defined 3 primary outcomes at 1-year post-discharge: cardiovascular mortality, readmission for heart failure (HF), and stroke. Temporal onset of de novo AF was also studied. RESULTS: A total 158 patients (5%) had prior AF, and 278 (8.8%) presented de novo AF. Prior AF patients were significantly older [81 (73;86) years] with more comorbidities, but de novo AF patients presented with a greater creatine kinase peak and lower left ventricular ejection fraction [LVEF=44 (35;50)% for de novo AF vs 50 (40;55)% for prior AF, p<0.001]. At 1-year follow-up, cardiovascular mortality was higher in cases of AF (13.5% for prior AF vs 9.2% for de novo AF, compared with 2.4% for AF-free patients, p<0.001). After adjustments, only de novo AF was correlated with cardiovascular mortality (hazard ratio 2.49; 95% CI 1.32-4.67; p=0.004), but both types of AF were correlated with readmission for HF. There was no significant difference in respect of stroke between prior AF, de novo AF, and AF-free (2.2%, 0.5%, and 0.8%, respectively, p=0.327). Finally, outcomes did not differ between AF occurring <24h after admission (n=127) and de novo AF occurring within ≥24h (n=151). CONCLUSION: De novo AF was independently associated with 1-year cardiovascular mortality. It should not be considered as an intercurrent event of STEMI, but rather as a strong prognostic marker

Human Chondrosarcoma Cells Acquire an Epithelial-Like Gene Expression Pattern via an Epigenetic Switch: Evidence for Mesenchymal-Epithelial Transition during Sarcomagenesis

Chondrocytes are mesenchymally derived cells that reportedly acquire some epithelial characteristics; however, whether this is a progression through a mesenchymal to epithelial transition (MET) during chondrosarcoma development is still a matter of investigation. We observed that chondrosarcoma cells acquired the expression of four epithelial markers, E-cadherin,desmocollin 3, maspin, and 14-3-3σ, all of which are governed epigenetically through cytosine methylation. Indeed, loss of cytosine methylation was tightly associated with acquired expression of both maspin and 14-3-3σ in chondrosarcomas. In contrast, chondrocyte cells were negative for maspin and 14-3-3σ and displayed nearly complete DNA methylation. Robust activation of these genes was also observed in chondrocyte cells following 5-aza-dC treatment. We also examined the transcription factor snail which has been reported to be an important mediator of epithelial to mesenchymal transitions (EMTs). In chondrosarcoma cells snail is downregulated suggesting a role for loss of snail expression in lineage maintenance. Taken together, these results document an epigenetic switch associated with an MET-like phenomenon that accompanies chondrosarcoma progression

ElrA binding to the 3′UTR of cyclin E1 mRNA requires polyadenylation elements

The early cell divisions of Xenopus laevis and other metazoan embryos occur in the presence of constitutively high levels of the cell cycle regulator cyclin E1. Upon completion of the 12th cell division, a time at which many maternal proteins are downregulated by deadenylation and destabilization of their encoding mRNAs, maternal cyclin E1 protein is downregulated while its mRNA is polyadenylated and stable. We report here that stable polyadenylation of cyclin E1 mRNA requires three cis-acting elements in the 3′ untranslated region; the nuclear polyadenylation sequence, a contiguous cytoplasmic polyadenylation element and an upstream AU-rich element. ElrA, the Xenopus homolog of HuR and a member of the ELAV gene family binds the cyclin E1 3′UTR with high affinity. Deletion of these elements dramatically reduces the affinity of ElrA for the cyclin E1 3′UTR, abolishes polyadenylation and destabilizes the mRNA. Together, these findings provide compelling evidence that ElrA functions in polyadenylation and stabilization of cyclin E1 mRNA via binding these elements

Native gel electrophoresis of human telomerase distinguishes active complexes with or without dyskerin

Telomeres, the ends of linear chromosomes, safeguard against genome instability. The enzyme responsible for extension of the telomere 3′ terminus is the ribonucleoprotein telomerase. Whereas telomerase activity can be reconstituted in vitro with only the telomerase RNA (hTR) and telomerase reverse transcriptase (TERT), additional components are required in vivo for enzyme assembly, stability and telomere extension activity. One such associated protein, dyskerin, promotes hTR stability in vivo and is the only component to co-purify with active, endogenous human telomerase. We used oligonucleotide-based affinity purification of hTR followed by native gel electrophoresis and in-gel telomerase activity detection to query the composition of telomerase at different purification stringencies. At low salt concentrations (0.1 M NaCl), affinity-purified telomerase was ‘supershifted’ with an anti-dyskerin antibody, however the association with dyskerin was lost after purification at 0.6 M NaCl, despite the retention of telomerase activity and a comparable yield of hTR. The interaction of purified hTR and dyskerin in vitro displayed a similar salt-sensitive interaction. These results demonstrate that endogenous human telomerase, once assembled and active, does not require dyskerin for catalytic activity. Native gel electrophoresis may prove useful in the characterization of telomerase complexes under various physiological conditions

Left-Right Function of dmrt2 Genes Is Not Conserved between Zebrafish and Mouse

Background: Members of the Dmrt family, generally associated with sex determination, were shown to be involved in several other functions during embryonic development. Dmrt2 has been studied in the context of zebrafish development where, due to a duplication event, two paralog genes dmrt2a and dmrt2b are present. Both zebrafish dmrt2a/terra and dmrt2b are important to regulate left-right patterning in the lateral plate mesoderm. In addition, dmrt2a/terra is necessary for symmetric somite formation while dmrt2b regulates somite differentiation impacting on slow muscle development. One dmrt2 gene is also expressed in the mouse embryo, where it is necessary for somite differentiation but with an impact on axial skeleton development. However, nothing was known about its role during left-right patterning in the lateral plate mesoderm or in the symmetric synchronization of somite formation. Methodology/Principal Findings: Using a dmrt2 mutant mouse line, we show that this gene is not involved in symmetric somite formation and does not regulate the laterality pathway that controls left-right asymmetric organ positioning. We reveal that dmrt2a/terra is present in the zebrafish laterality organ, the Kupffer’s vesicle, while its homologue is excluded from the mouse equivalent structure, the node. On the basis of evolutionary sub-functionalization and neo-functionalization theories we discuss this absence of functional conservation. Conclusions/Significance: Our results show that the role of dmrt2 gene is not conserved during zebrafish and mous

Tbx6 Regulates Left/Right Patterning in Mouse Embryos through Effects on Nodal Cilia and Perinodal Signaling

Background: The determination of left/right body axis during early embryogenesis sets up a developmental cascade that coordinates the development of the viscera and is essential to the correct placement and alignment of organ systems and vasculature. Defective left-right patterning can lead to congenital cardiac malformations, vascular anomalies and other serious health problems. Here we describe a novel role for the T-box transcription factor gene Tbx6 in left/right body axis determination in the mouse. Results: Embryos lacking Tbx6 show randomized embryo turning and heart looping. Our results point to multiple mechanisms for this effect. First, Dll1, a direct target of Tbx6, is down regulated around the node in Tbx6 mutants and there is a subsequent decrease in nodal signaling, which is required for laterality determination. Secondly, in spite of a lack of expression of Tbx6 in the node, we document a profound effect of the Tbx6 mutation on the morphology and motility of nodal cilia. This results in the loss of asymmetric calcium signaling at the periphery of the node, suggesting that unidirectional nodal flow is disrupted. To carry out these studies, we devised a novel method for direct labeling and live imaging cilia in vivo using a genetically-encoded fluorescent protein fusion that labels tubulin, combined with laser point scanning confocal microscopy for direct visualization of cilia movement. Conclusions: We conclude that the transcription factor gene Tbx6 is essential for correct left/right axis determination in th

La ROSP et ses opposants finistériens : quelle perception à 10 ans de sa mise en place

P4P are grounded for several years in many health systems. In France the ROSP is accepted by default. However, some of general practitioners chose to refuse this device.Method : qualitative analysis by semi-directed interviews of general practitioners practicing in Finistère, refusing or having refused the ROSP.Results : 8 interviews were carried out. The heterogeneous profiles of the respondents highlight a trend towards a decline in performance-based payment refusals, especially concerning the structure flat rate.Analysis : the absence of sanction and the non-revalorization of acts are factors of acceptance of the ROSP. The structure flat rate enjoys wider support, probably because it does not lead to a change in medical practice itself. Clinical ROSP remains a source of relative mistrust and does not appear to be a positive tool for the evolution of medical practice. The refusal of ROSP remains a very personal decision, motivated by specific intrinsic factors, and a point of tension compared to trade unions.Discussion : while the ROSP is anchored in the French medical landscape, the results of this one seems to reach their limit. Previously supportive institutions call for simplification of tracking items, and regular updating of items if met. Moving from an individual assessment to a territory scale is a potential evolution of the P4P system. Consistency of objectives is a criterion for doctors' adherence to a future system.Les P4P sont implantés depuis plusieurs années dans de nombreux systèmes de santé. En France la ROSP est par défaut acceptée par les médecins. Certains ont cependant fait le choix de la refuser.Méthode : analyse Qualitative par entretiens semi-dirigés de médecins généralistes exerçant dans le Finistère, refusant ou ayant refusé la ROSP.Résultats : 8 entretiens ont été réalisés. Les profils hétérogènes des répondants mettent en évidence une tendance à un recul des refus de paiement à la performance, principalement concernant le forfait structure.Analyse : l’absence de sanction et la non-revalorisation des actes sont des facteurs d’acceptation de la ROSP. Le forfait structure bénéficie d’une adhésion plus large, probablement du fait qu’il n’entraine pas de modification de la pratique médicale en elle-même. La ROSP clinique demeure une source de méfiance relative et n’apparait pas comme un outil positif d’évolution de la pratique médicale. Le refus de la ROSP reste une décision très personnelle, motivée par des facteurs intrinsèques spécifiques, et un point de crispation par rapport à des organisations syndicales.Discussion : alors que la ROSP s’est ancrée dans le paysage médical français, les résultats de celle-ci semblent atteindre leur limite. Des institutions précédemment favorables appellent à une simplification des éléments de suivi, et à une remise à jour régulière des items s’ils sont atteints. Le passage d’une évaluation individuelle à une échelle de territoire est une évolution potentielle du dispositif de P4P. La cohérence des objectifs est un critère d’adhésion des médecins à un futur dispositif

Morphologie et remplissage sédimentaire des vallées martiennes : marqueurs des conditions climatiques pré-amazoniennes

Nowadays Mars has a cold and dry climate. At some locations its surface is more than 3.5 Gy old and exhibits valleys, channels, terraces and deltas attesting the occurrence of liquid water in the past. This fluid is currently unstable on the surface of the planet, suggesting these morphologies would involve different climatic conditions from the current ones. What did early Martian climate look like? It is one of the main issues regarding this planet. Among the geomorphic evidence classically used to reconstruct past climates, Martian valleys are numerous and heterogeneously thus particularly attractive to study. Their morphologies can inform on the climatic conditions prevailing at the time of their formation and/or later during their evolution. The objective of this thesis is to contribute to solve the enigma concerning Martian pre-Amazonian (> 3.5Gy) climatic conditions by focusing on the study of equatorial valleys and the equatorial canyon of Valles Marineris. Our study reveals that the morphometry and spatial organization of some Martian valleys differ significantly from those of common terrestrial fluvial and sapping valleys. By contrast, they share a lot of similarities with terrestrial subglacial tunnel valley. The subglacial or pro-glacialmelting of surface ice deposits is plausible as an origin of some Martian valleys under cold climatic conditions. Moreover, regional geomorphological reconstitutions of Valles Marineris reveal that this valley system had witnessed glacial processes since its formation. Current glacial relicts of this former filling, probably several billion years old, still, subsist protected under a debris cover. This study suggests the possibility that pre-Amazonian atmospheric conditions on Mars do not require to be significantly different from the current ones.Mars présente à l’heure actuelle un climat sec et froid. Certains endroits de sa surface sont âgés de plus de 3,5 Ga et présentent des vallées, des chenaux, des terrasses ou encore des deltas qui attestent de la présence d’eau liquide dans le passé. Cette dernière étant actuellement instable à la surface de la planète, l’existence de ces morphologies impliquerait des conditions climatiques passées différentes de celles actuelles. À quoi pouvait ressembler le climat de Mars à cette époque ? Il s’agit de l’une des principales interrogations concernant cette planète. Parmi les marqueurs morphologiques classiquement utilisés dans les reconstitutions climatiques, les vallées sont nombreuses et réparties de façon hétérogène sur Mars ce qui les rend particulièrement intéressantes à étudier. Ces objets peuvent nous renseigner à travers leur morphologie sur les conditions climatiques qui régnaient au moment même de leur formation et/ou plus tard au cours de leur évolution. L’objectif de cette thèse est de contribuer à la reconstitution du climat pré-amazonien (>3,5 Ga) en se concentrant sur l’étude des vallées martiennes équatoriales et du canyon équatorial de Valles Marineris. L’étude des vallées révèle que leur morphométrie et leur organisation spatiale ne ressemblent que très rarement à celles des vallées fluviatiles et de sapement fréquemment rencontrées sur Terre. Elles présentent, en revanche, de nombreuses similitudes avec les vallées tunnels d’origine sous-glaciaires terrestres. Il est donc plausible que certaines de ces vallées martiennes pré-amazoniennes aient pu voir le jour sous un climat froid par la fonte sous- et/ou pro- glaciaire de dépôts de glace de surface. D’autre part, les reconstitutions géomorphologiques régionales de Valles Marineris montrent que ce système de vallées a été le siège d(e)’une glaciation(s) postérieure(s) à sa formation dont il subsiste aujourd’hui des reliques datant probablement de plusieurs milliards d’années et qui sont protégées par une couverture de débris. Cette étude suggère la possibilité que les conditions atmosphériques pré-amazoniennes de Mars ne furent pas nécessairement très différentes de celles qui prévalent actuellement

Traitements aux vapeurs d'éthanol de papiers altérés par des micro-organismes

International audienceLibrary and archive collections are sensitive to biological contamination, particularly mold. Mass treatments haveproven their usefulness and effectiveness in cases of widespread contamination, but in most cases they are disproportionate to the quantity of documents to be treated.The biocidal efficacy of the water-ethanol mixture (30:70 v/v) has been demonstrated in many fields. A previousstudy established a fungistatic effect for a two-hour treatment with ethanol vapors, as well as its harmlessness ondifferent types of paper. However, a fungicidal effect was only obtained after 24 hours' exposure to ethanol vapors.The aim of this study was to demonstrate the efficacy of this treatment « for the most part of fungi types, as well asits safety on different types of paper.Les collections des bibliothèques et des archives sont sensibles aux contaminations biologiques, notamment auxmoisissures. Les traitements de masse ont montré leur utilité et efficacité lors de contaminations généralisées mais, dans la majorité des cas, ils sont disproportionnés au regard de la quantité de documents à traiter.L’efficacité biocide du mélange eau – éthanol (30:70 v/v) a été démontrée dans de nombreux domaines. Une précédente étude avait établi un effet fongistatique pour un traitement de deux heures aux vapeurs d’éthanol, ainsi que son innocuité sur différents types de papier. En revanche, un effet fongicide n’était obtenu qu’après vingt-quatre heures d’exposition aux vapeurs d’éthanol. La présente étude a permis de démontrer l’efficacité du traitement de vingt-quatre heures d’exposition aux vapeurs d’éthanol sur la plupart des souches rencontrées ainsi que son innocuité sur différents types de papiers