Interobserver Variation Study of the Rutgeerts Score to Assess Endoscopic Recurrence after Surgery for Crohn's Disease.

BACKGROUND: After resection surgery for Crohn's disease, recurrence of endoscopic lesions at the site of the anastomosis or in the neoterminal ileum is graded according to the Rutgeerts score (RS). The goal of this study was to test the interobserver variability for RS. METHODS: Thirteen trained endoscopists evaluated the RS on 39 videotapes of patients who had undergone resection for Crohn's disease with an ileocolonic anastomosis 6 months earlier. Videotapes were randomly assigned to endoscopists through a balanced incomplete block design. Each videotape was scored independently by four endoscopists, and each endoscopist evaluated 12 videotapes, making a total of 156 videotape assessments. Reproducibility levels of the RS were assessed through unweighted kappa estimates among multiple raters. The proportion of inappropriate therapeutic initiation was estimated by randomly selecting one endoscopist for each videorecording, assuming that the majority of endoscopists correctly classified endoscopic recurrence. RESULTS: The kappa estimates were 0.43 (95% confidence interval: 0.33-0.52) for the RS on a 5-grade scale, 0.47 (0.28-0.66) for RS /= i2, and 0.64 (0.42-0.85) for RS i2. The percentages of inappropriate therapeutic initiation were 12.8% (3.8-21.9) when initiation was triggered by a RS >/= i2 and 8.3% (1.1-15.6) when initiation was triggered by a RS > i2 (p = 0.41). CONCLUSION: The reproducibility of the RS was moderate, especially when differentiating /=i2, which may lead to incorrect therapeutic decisions in >10% of patients

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

Multiple groups of endogenous epsilon-like retroviruses conserved across primates

Several types of cancer in fish are caused by retroviruses, including those responsible for major outbreaks of disease, such as walleye dermal sarcoma virus and salmon swim bladder sarcoma virus. These viruses form a phylogenetic group often described as the epsilonretrovirus genus. Epsilon-like retroviruses have become endogenous retroviruses (ERVs) on several occasions, integrating into germ line cells to become part of the host genome, and sections of fish and amphibian genomes are derived from epsilon-like retroviruses. However, epsilon-like ERVs have been identified in very few mammals. We have developed a pipeline to screen full genomes for ERVs, and using this pipeline, we have located over 800 endogenous epsilon-like ERV fragments in primate genomes. Genomes from 32 species of mammals and birds were screened, and epsilon-like ERV fragments were found in all primate and tree shrew genomes but no others. These viruses appear to have entered the genome of a common ancestor of Old and New World monkeys between 42 million and 65 million years ago. Based on these results, there is an ancient evolutionary relationship between epsilon-like retroviruses and primates. Clearly, these viruses had the potential to infect the ancestors of primates and were at some point a common pathogen in these hosts. Therefore, this result raises questions about the potential of epsilonretroviruses to infect humans and other primates and about the evolutionary history of these retroviruses. IMPORTANCE: Epsilonretroviruses are a group of retroviruses that cause several important diseases in fish. Retroviruses have the ability to become a permanent part of the DNA of their host by entering the germ line as endogenous retroviruses (ERVs), where they lose their infectivity over time but can be recognized as retroviruses for millions of years. Very few mammals are known to have epsilon-like ERVs; however, we have identified over 800 fragments of endogenous epsilon-like ERVs in the genomes of all major groups of primates, including humans. These viruses seem to have circulated and infected primate ancestors 42 to 65 million years ago. We are now interested in how these viruses have evolved and whether they have the potential to infect modern humans or other primates

Functional Characteristics of a Highly Specific Integrase Encoded by an LTR-Retrotransposon

Background: The retroviral Integrase protein catalyzes the insertion of linear viral DNA into host cell DNA. Although different retroviruses have been shown to target distinctive chromosomal regions, few of them display a site-specific integration. ZAM, a retroelement from Drosophila melanogaster very similar in structure and replication cycle to mammalian retroviruses is highly site-specific. Indeed, ZAM copies target the genomic 59-CGCGCg-39 consensus-sequences. To enlighten the determinants of this high integration specificity, we investigated the functional properties of its integrase protein denoted ZAM-IN. Principal Findings: Here we show that ZAM-IN displays the property to nick DNA molecules in vitro. This endonuclease activity targets specific sequences that are present in a 388 bp fragment taken from the white locus and known to be a genomic ZAM integration site in vivo. Furthermore, ZAM-IN displays the unusual property to directly bind specific genomic DNA sequences. Two specific and independent sites are recognized within the 388 bp fragment of the white locus: the CGCGCg sequence and a closely apposed site different in sequence. Conclusion: This study strongly argues that the intrinsic properties of ZAM-IN, ie its binding properties and its endonuclease activity, play an important part in ZAM integration specificity. Its ability to select two binding sites and to nick the DNA molecule reminds the strategy used by some site-specific recombination enzymes and forms the basis for site-specifi

Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine

BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.Peer reviewe

Les Pots-Capteurs : une innovation primée

Site Web INRA, Département SPE, rubrique "Actualités"La Plateforme de Phénotypage Haut Débit de l’INRA de Dijon a été conçue pour développer et utiliser des techniques innovantes afin d’analyser l’expression des gènes de plantes. Cette plateforme permet l’analyse de la variabilité génétique par grandes séries de génotypes, en fonction de différents scénarios environnementaux. Pour réaliser ces analyses les plantes sont continuellement déplacées au sein de la plateforme via des convoyeurs. Ces déplacements entraînent de nombreuses contraintes qu'Arnaud Coffin, technicien dans le laboratoire d'Agroécologie de Dijon, a su solutionner grâce à un dispositif innovant de Pots-Capteurs. La société Campbell Scientific lui remettra à ce titre le Prix de l'Innovation

Dispositif automatique de caractérisation et de prélèvement des eaux de drainage du site de Virey-le-Grand

National audienceLe drainage a pour objectif d’évacuer rapidement l’excès d’eau de la partie supérieure du sol. Par conséquence il entraine des perturbations dans l’environnement notamment en favorisant la lixiviation d’intrants. Le dispositif de Virey-le-Grand, conçu dans les années 1970 pour étudier les différentes modalités de drainage, a été ré-instrumenté et automatisé afin de travailler sur l’évaluation de l’impact des pratiques agricoles sur la qualité de l’eau. Cette ré-instrumentation associe des équipements robustes comme les augets basculants à de la technologie plus récente telle que les panneaux photovoltaïques et une centrale d’acquisition. L’évolution des technologies a permis de le rendre autonome en énergie et modulable dans son plan d’échantillonnage. Ce dispositif permet de faire le lien entre les intrants appliqués et les fuites d’intrants via le drainage vers le milieu aquatique à l’exutoire

Statégie d'échantillonnage de la flore des bordures herbacées des parcelles cultivées

National audience84 % des espèces cultivées en Europe et 80 % des espèces végétales dans le monde dépendent pour leur pollinisation des insectes pollinisateurs dont le déclin est actuellement avéré. La flore des bordures des champs pourrait jouer le rôle de réservoirs ou de ressources complémentaires en termes de nectar ou pollen pour les insectes pollinisateurs. Pour répondre à cette question, nous avons effectué des relevés de la production florale de la flore (espèces adventices et espèces rudérales) présente le long de ces bordures herbacées. Il existe actuellement différentes stratégies d’échantillonnages pour caractériser la flore intra‐parcellaire mais peu ou pas de stratégies ont été mises en place pour l’étude des linéaires herbacés des bords de champs. Ces relevés doivent être représentatifs de l’ensemble de la bordure avec une faible perte d’informations. L’objectif de cette étude est de comparer différentes stratégies d’échantillonnage afin de déterminer la meilleure stratégie en termes de qualité de la représentation de la flore et le coût en temps proportionnel à la surface échantillonnée. Dix relevés, réalisés de février à septembre, ont été faits sur 26 bordures de parcelles de blé de la zone d’étude de Fénay (21). L’échantillonnage a été effectué de chaque côté d’un point géo‐référencé pour couvrir une distance globale de 50 mètres. Les dénombrements ont été réalisés à l’intérieur de quadrats de 1 m² (5 m × 0,2 m), disposés à des intervalles permettant de faire avec 3 quadrats 3 dénombrements dans les 25 mètres englobant le point géo‐référencé et avec 5 quadrats 5 dénombrements dans les 50 mètres. Nous avons comparé différents scénarii d’échantillonnage en faisant varier soit la longueur totale (25 m vs. 50 m), soit le nombre de quadrats pour une même distance. La comparaison des relevés sur 3 quadrats répartis sur 25 mètres et 50 mètres ne révèle pas une perte importante du nombre d’espèces avec un échantillonnage sur 25 m

N2O emissions from cropping systems with integrated weed management. The nitrogen challenge: building a blue print for nitrogen use efficiency and food security

International audienceIntegrated weed management (IWM) in cropping systems aims to lower the reliance on herbicides of the crops, by introducing new combinations of agricultural practices in the system development (Munier-Jolain et al, 2009). These combinations may greatly change from a system to another and include a large variety of practices, such as false seed beds, late sowing, mechanical weeding, reduced tillage, specific crop rotations that alternate spring and winter crops, the choice of crop varieties and the use of pesticides with low ecotoxic impacts. Several implemented agricultural practices are likely to alter soil biogeochemical cycles and different components of the greenhouse gas budget (balance between the carbon sequestration and the greenhouse gas emission) of the system: e.g. crop rotation, dates and level of nitrogen fertilization and tillage. The main objectives of our study were to evaluate i) the N2O fluxes emitted from soil during one year for 4 cropping systems (i.e. 3 IWM systems and a local reference of conventional system), and ii) to investigate the relationship between the measured fluxes and soil parameters and the agricultural practices of each system