A simplified table using validated diagnostic criteria is effective to improve characterization of colorectal polyps: the CONECCT teaching program

International audienceIntroduction and study aims Accurate real-time endoscopic characterization of colorectal polyps is key to choosing the most appropriate treatment. Mastering the currently available classifications is challenging. We used validated criteria for these classifications to create a single table, named CONECCT, and evaluated the impact of a teaching program based on this tool.Methods A prospective multicenter study involving GI fellows and attending physicians was conducted. During the first session, each trainee completed a pretest consisting in histological prediction and choice of treatment of 20 colorectal polyps still frames. This was followed by a 30-minute course on the CONECCT table, before taking a post-test using the same still frames reshuffled. During a second session at 3 – 6 months, a last test (T3 M) was performed, including these same still frames and 20 new ones.Results A total 419 participants followed the teaching program between April 2017 and April 2018. The mean proportion of correctly predicted/treated lesions improved significantly from pretest to post-test and to T3 M, from 51.0 % to 74.0 % and to 66.6 % respectively (P < 0.001). Between pretest and post-test, 343 (86.6 %) trainees improved, and 153 (75.4 %) at T3 M. Significant improvement occurred for each subtype of polyp for fellows and attending physicians. Between the two sessions, trainees continued to progress in the histology prediction and treatment choice of polyps CONECCT IIA. Over-treatment decreased significantly from 30.1 % to 15.5 % at post-test and to 18.5 % at T3 M (P < 0.001).Conclusion The CONECCT teaching program is effective to improve the histology prediction and the treatment choice by gastroenterologists, for each subtype of colorectal polyp

Obesity promotes fumonisin B1 hepatotoxicity

Obesity, which is a worldwide public health issue, is associated with chronic inflammation that contribute to long-term complications, including insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease. We hypothesized that obesity may also influence the sensitivity to food contaminants, such as fumonisin B1 (FB1), a mycotoxin produced mainly by the Fusarium verticillioides. FB1, a common contaminant of corn, is the most abundant and best characterized member of the fumonisins family. We investigated whether diet-induced obesity could modulate the sensitivity to oral FB1 exposure, with emphasis on gut health and hepatotoxicity. Thus, metabolic effects of FB1 were assessed in obese and non-obese male C57BL/6J mice. Mice received a high-fat diet (HFD) or normal chow diet (CHOW) for 15 weeks. Then, during the last three weeks, mice were exposed to these diets in combination or not with FB1 (10 mg/kg body weight/day) through drinking water. As expected, HFD feeding induced significant body weight gain, increased fasting glycemia, and hepatic steatosis. Combined exposure to HFD and FB1 resulted in body weight loss and a decrease in fasting blood glucose level. This co-exposition also induces gut dysbiosis, an increase in plasma FB1 level, a decrease in liver weight and hepatic steatosis. Moreover, plasma transaminase levels were significantly increased and associated with liver inflammation in HFD/FB1-treated mice. Liver gene expression analysis revealed that the combined exposure to HFD and FB1 was associated with reduced expression of genes involved in lipogenesis and increased expression of immune response and cell cycle-associated genes. These results suggest that, in the context of obesity, FB1 exposure promotes gut dysbiosis and severe liver inflammation. To our knowledge, this study provides the first example of obesity-induced hepatitis in response to a food contaminant.L.D. PhD was supported by the INRAE Animal Health department. This work was also supported by grants from the French National Research Agency (ANR) Fumolip (ANR-16-CE21-0003) and the Hepatomics FEDER program of Région Occitanie. We thank Prof Wentzel C. Gelderblom for generously providing the FB1 and for his interest and support in our project. B.C. laboratory is supported by a Starting Grant from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. ERC-2018-StG- 804135), a Chaire d'Excellence from IdEx Université de Paris - ANR-18-IDEX-0001, an Innovator Award from the Kenneth Rainin Foundation, an ANR grant EMULBIONT ANR-21-CE15-0042-01 and the national program “Microbiote” from INSERM. We thank Anexplo (Genotoul, Toulouse) for their excellent work on plasma biochemistry. Neutral Lipids MS and NMR experiments were performed with instruments in the Metatoul-AXIOM platform. Sphingolipid MS analysis were performed with instruments in the RUBAM platform. The FB1 plasma levels were determined using an UPLC-MS/MS instrument part of the Ghent University MSsmall expertise centre for advanced mass spectrometry analysis of small organic molecules. We thank Elodie Rousseau-Bacquié and all members of the EZOP staff for their assistance in the animal facility. We are very grateful to Talal al Saati for histology analyses and review, and we thank all members of the US006/CREFRE staff at the histology facility and the Genom'IC platforms (INSERM U1016, Paris, France) for their expertise.Peer reviewe

Viral capsids: Mechanical characteristics, genome packaging and delivery mechanisms

The main functions of viral capsids are to protect, transport and deliver their genome. The mechanical properties of capsids are supposed to be adapted to these tasks. Bacteriophage capsids also need to withstand the high pressures the DNA is exerting onto it as a result of the DNA packaging and its consequent confinement within the capsid. It is proposed that this pressure helps driving the genome into the host, but other mechanisms also seem to play an important role in ejection. DNA packaging and ejection strategies are obviously dependent on the mechanical properties of the capsid. This review focuses on the mechanical properties of viral capsids in general and the elucidation of the biophysical aspects of genome packaging mechanisms and genome delivery processes of double-stranded DNA bacteriophages in particular

Simple tools for achieving self-compacting ability of concrete according to the nature of the limestone filler

WOS:000327561200100International audienceThis paper reports the assessment of self-compacting ability at the scale of concrete whatever the nature of the limestone filler (LF). In practice, differences in chemical and physical properties of LF are rarely taken into account during the design process, yet they are most often considered as the causes of segregation during and after placing, and of poor external aspects. The actual cause of the design defect can be resolved by developing tools capable of uniting the properties and the interactions among all components in order to achieve self-compacting flow. Basically, a two-phase approach was exploited by using existing test methods. At the scale of paste (cement + LF + High Range Water Reducer Admixture (HRWRA or superplasticizer) + water), the arrangement of particles in suspension was determined through the wet packing measurement. Starting from the maximum packing density as the reference state related to the water volume needed just to fill the voids between the solid particles, the rheological properties of pastes designed with different cements (OPC, slag cement) and different LF were measured and analyzed according to the excess water to solid surface area ratio. The water absorbed and adsorbed by the aggregates was also determined for the gravel/sand mass ratio, which was optimized from the packing measurement. Irrespective of the nature of the cement/filler combination, and provided that the HRWRA content was sufficient to lower the yield stress of the paste (the yield stress was then no longer affected by excess water variation), the association of the two phases (paste + wet aggregates) enabled a unique viscosity criterion to be evidenced at the paste scale for the design of easy flowing, stable self-compacting concretes. The viscosity criterion was validated by using another skeleton of aggregates and different natures of cement, LF and HRWRA

In vitro effects of oestradiol on galanin gene expression in rat anterior pituitary cells.

While the pituitary galanin gene is highly responsive to oestrogen stimulation in vivo, in vitro effects of oestrogens on pituitary galanin gene expression have been less studied. We therefore examined the short-term effects of 17beta-oestradiol on galanin synthesis by dispersed rat anterior pituitary cell cultures and investigated the mechanisms by which oestrogens may modulate galanin gene expression. 17beta-oestradiol increased galanin mRNA expression in a dose-dependent manner, with a maximal increase observed at a concentration of 10-7 M. The 17beta-oestradiol (10-7 M)-induced increase in galanin mRNA expression varied from 3- to 20-fold (average 12-fold) depending upon the experiments and was also time-dependent, reaching significance after 6 h. A 1-h exposure of anterior pituitary cells to 17beta-oestradiol was sufficient to induce markedly galanin mRNA expression after 24 h (by 16-fold) and 48 h (by 25-fold). Tamoxifen administered simultaneously with or following 17beta-oestradiol treatment completely abolished the oestrogen-induced increase of galanin mRNA levels. Cycloheximide (10 microg/ml), a protein synthesis inhibitor, also blocked 17beta-oestradiol-induced galanin gene expression. Using transcription blockade by actinomycin D, we observed similar decreases of pituitary galanin mRNA concentrations, in the presence and absence of 17beta-oestradiol, implying no oestrogen effect on mRNA stability. We conclude that oestrogens stimulate rat pituitary galanin gene expression, mainly through a transcriptional mechanism, and that this effect requires persistent binding of the hormone to its nuclear receptor and newly synthesized protein intermediates

The nature of limestone filler and self-consolidating feasibility Relationships between physical, chemical and mineralogical properties of fillers and the flow at different states, from powder to cement-based suspension

International audienceThis paper is a part of a large study aimed at identifying the physical and chemical properties of limestone fillers (LF) that govern their behaviour towards self-consolidating flow. Five LF were studied, complying with the standards and selected for their significant differences in properties on the basis of the supplier's database. Despite their specific manufacturing, a thorough characterization showed that the selected LFs had very different properties in terms of surface charges, morphology, wettability and size distribution. Then, relationships were sought between these properties and the flow of LF in powder form and suspended in water, or water + polycarboxylate type High Range Water Reducer Admixture (HRWRA), or water + HRWRA + cement (OPC or slag blended cement). The flow measurements concerned flowability, floodability and shear under consolidation in the dry state, and static yield stress and apparent viscosity in the suspension state. The main results show that the LFs act in the same way on the flow as long as cement is not incorporated into the suspension. From the dry state to the water + HRWRA suspensions, the flow is dependent on the fineness of the LF. The significant relationships between the surface charges, wettability and fineness of LFs show that impurities like clays are key factors in the flow of LF suspensions. When cement was incorporated into the suspension, the flow was dependent on the interactions existing among all the constituents. Then, with a view to self-consolidating applications, it becomes possible to identify how best to incorporate LF in a cement-based matrix through the measurement of the arrangement of cement and filler particles in suspension

In vivo tmRNA protection by SmpB and pre-ribosome binding conformation in solution

International audienceTmRNA is an abundant RNA in bacteria with tRNA and mRNA features. It is specialized in trans-translation, a translation rescuing system. We demonstrate that its partner protein SmpB binds the tRNA-like region (TLD) in vivo and chaperones the fold of the TLD-H2 region. We use an original approach combining the observation of tmRNA degradation pathways in a heterologous system, the analysis of the tmRNA digests by MS and NMR, and co-overproduction assays of tmRNA and SmpB. We study the conformation in solution of tmRNA alone or in complex with one SmpB before ribosome binding using SAXS. Our data show that Mg2+ drives compaction of the RNA structure and that, in the absence of Mg2+, SmpB has a similar effect albeit to a lesser extent. Our results show that tmRNA is intrinsically structured in solution with identical topology to that observed on complexes on ribosomes which should facilitate its subsequent recruitment by the 70S ribosome, free or preloaded with one SmpB molecule