102 results on '"Gruel G"'
Search Results
2. RENEB Inter-Laboratory Comparison 2021: The Dicentric Chromosome Assay
- Author
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Endesfelder, D., primary, Oestreicher, U., additional, Bucher, M., additional, Beinke, C., additional, Siebenwirth, C, additional, Ainsbury, E., additional, Moquet, J., additional, Gruel, G., additional, Gregoire, E., additional, Martinez, J.S., additional, Vral, A., additional, Baeyens, A., additional, Valente, M., additional, Montoro, A., additional, Terzoudi, G., additional, Triantopoulou, S., additional, Pantelias, A., additional, Monteiro Gil, O., additional, Prieto, M.J., additional, Domene, M.M., additional, Zafiropoulos, D., additional, Barquinero, J.F., additional, Pujol-Canadell, M., additional, Lumniczky, K., additional, Hargitai, R., additional, Kis, E., additional, Testa, A., additional, Patrono, C., additional, Sommer, S., additional, Hristova, R., additional, Kostova, N., additional, Atanasova, M., additional, Sevriukova, O., additional, Domínguez, I., additional, Pastor, N., additional, Güçlü, I., additional, Pajic, J., additional, Sabatier, L., additional, Brochard, P., additional, Tichy, A., additional, Milanova, M., additional, Finot, F., additional, Cuceu Petrenci, C., additional, Wilkins, R.C., additional, Beaton-Green, L.A., additional, Seong, K.M., additional, Lee, Y., additional, Lee, Y.H., additional, Balajee, A.S., additional, Maznyk, N., additional, Sypko, T., additional, Pham, N.D., additional, Tran, T.M., additional, Miura, T., additional, Suto, Y., additional, Akiyamam, M., additional, Tsuyama, N., additional, Abe, Y., additional, Goh, V.S.T., additional, Chua, C.E.L., additional, Abend, M., additional, and Port, M., additional
- Published
- 2023
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3. MINAS TIRITH: a new tool for simulating radiation-induced DNA damage at the cell population level
- Author
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Thibaut, Y, primary, Gonon, G, additional, Martinez, J S, additional, Petit, M, additional, Vaurijoux, A, additional, Gruel, G, additional, Villagrasa, C, additional, Incerti, S, additional, and Perrot, Y, additional
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- 2023
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4. PO-2206 Radiopathological consequences of low energy X-rays overexposures: a dose effect study
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Guillou, M., L'Homme, B., Trompier, F., Errabii, A., Gruel, G., Prezado, Y., and Dos Santos, M.
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- 2023
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5. Circulation of antibiotic resistance genes between bacteria from different origins
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Pot, M., Reynaud, Y, Gruel, G., Ferdinand, S., Breurec, Sebastien, Antoine, Talarmin, Guyomard-Rabenirina, Stéphanie, Institut Pasteur de la Guadeloupe, Réseau International des Instituts Pasteur (RIIP), Université des Antilles - UFR des sciences médicales Hyacinthe Bastaraud (UA UFR SM), Université des Antilles (UA), and FALCO, Eliane
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[SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,[SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,[SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology - Abstract
International audience; An environment affected by anthropogenic activities can play an important role in the spread and concentration of antibiotic resistant bacteria. Under antibiotic selection pressure, exchanges of antibiotic resistance genes (ARG) can occur between bacteria from human, animal and environmental reservoirs. However, these processes are still poorly understood. This work aimed at focussing on the wastewater treatment process, which is a hotspot for selection and emergence of antibiotic resistant bacteria and constitutes a favourable interface for circulation of ARG between bacteria from the different reservoirs.Between 2018 and 2019, extended spectrum β-lactamase producing Enterobacteriaceae (ESBLE) (Enterobacter cloacae complex, Escherichia coli and Klebsiella pneumoniae) were isolated from 266 patients at University Hospital of Pointe-à-Pitre (Guadeloupe). Simultaneously, urban and hospital wastewaters were analysed at different steps of waste treatment and 120 stool samples were collected from animals living near the hospital sewers and the wastewater treatment plant. Enterobacteriaceae were characterised according to their antibiotic resistance profile. Strains with the same antibiotic resistance profile belonging to a particular human-environment-animals continuum were analysed using whole genome sequencing.We isolated a total of 905 ESBLE (292 from humans, 348 from wastewater and 265 from animals). The frequency of ESBLE carriers was important in wildlife and domestic animals living nearby polluted environments (70%). A first genome-based comparison was carried out on 30 ESBL producing E. coli isolated during this study and compared to ESBL producing E. coli collected in farms (n=12). Antibiotic resistance gene blaCTX-M-15 was frequent (17/42). IncFII type was the most common plasmid (15/42). E. coli ST131 was found on the clinical samples only (n=4). One cluster with wastewater and animal isolates differed by ≤ 5 single nucleotide polymorphisms.These first results suggest that animals living near sewers and wastewater treatment plants are subjected to antibiotic resistance pressure and some bacteria and antibiotic resistance genes could be closely related.
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- 2019
6. Influence of chromatin compaction on simulated early radiation-induced DNA damage using Geant4-DNA
- Author
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Tang, N., primary, Bueno, M., additional, Meylan, S., additional, Incerti, S., additional, Tran, H. N., additional, Vaurijoux, A., additional, Gruel, G., additional, and Villagrasa, C., additional
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- 2019
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7. RENEB accident simulation exercise
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Brzozowska, B., Ainsbury, E., Baert, A.E., Beaton-Green, L., Barrios, L., Barquinero, J.F., Bassinet, C., Beinke, C., Benedek, A., Beukes, P., Bortolin, E., Buraczewska, I., Burbidge, C.I., de Amicis, A., de Angelis, C., Della Monaca, S., Depuydt, J., de Sanctis, S., Dobos, K., Domene, M.M., Domínguez, I., Facco, E., Fattibene, P., Frenzel, M., Monteiro Gil, O., Gonon, G., Gregoire, E., Gruel, G., Hadjidekova, V., Hatzi, V.I., Hristova, R., Jaworska, A., Kis, E., Kowalska, M., Kulka, U., Lista, F., Lumniczky, K., Martínez-López, W., Meschini, R., Mörtl, S., Moquet, J., Noditi, M., Oestreicher, U., Orta Vázquez, M.L., Palma, V., Pantelias, G., Montoro Pastor, A., Patrono, C., Piqueret-Stephan, L., Quattrini, M.C., Regalbuto, E., Ricoul, M., Roch-Lefevre, S., Roy, L., Sabatier, L., Sarchiapone, L., Sebastià, N., Sommer, S., Sun, M., Suto, Y., Terzoudi, G., Trompier, F., Vral, A., Wilkins, R., Zafiropoulos, D., Wieser, A., Woda, C., Wojcik, A., Istituto Superiore di Sanita` (ISS), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Bundesamt für Strahlenschutz (BfS), National center for public health [Hungary], Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hospital Universitario y Politécnico La Fe, Public Health England [London], Universiteit Gent = Ghent University [Belgium] (UGENT), Helmholtz-Zentrum München (HZM), Stockholm University, University of Warsaw (UW), Universitat Autònoma de Barcelona (UAB), Bundeswehr Institute of Radiobiology, Universität Ulm - Ulm University [Ulm, Allemagne], Seventh Framework Programme, Istituto Superiore di Sanità (ISS), Bundesamt für Strahlenschutz - Federal Office for Radiation Protection (BfS), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Universiteit Gent = Ghent University (UGENT), and Helmholtz Zentrum München = German Research Center for Environmental Health
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RENEB network ,Safety Management ,[SDV]Life Sciences [q-bio] ,Radiobiology ,Biology and Life Sciences ,Disaster Planning ,Reneb Network ,Accident Simulation ,Radiobiological Event ,Europe ,radiobiological event ,Radiation Monitoring ,Medicine and Health Sciences ,accident simulation ,Triage ,Radioactive Hazard Release - Abstract
International audience; Purpose: The RENEB accident exercise was carried out in order to train the RENEB participants in coordinating and managing potentially large data sets that would be generated in case of a major radiological event. Materials and methods: Each participant was offered the possibility to activate the network by sending an alerting email about a simulated radiation emergency. The same participant had to collect, compile and report capacity, triage categorization and exposure scenario results obtained from all other participants. The exercise was performed over 27 weeks and involved the network consisting of 28 institutes: 21 RENEB members, four candidates and three non-RENEB partners. Results: The duration of a single exercise never exceeded 10 days, while the response from the assisting laboratories never came later than within half a day. During each week of the exercise, around 4500 samples were reported by all service laboratories (SL) to be examined and 54 scenarios were coherently estimated by all laboratories (the standard deviation from the mean of all SL answers for a given scenario category and a set of data was not larger than 3 patient codes). Conclusions: Each participant received training in both the role of a reference laboratory (activating the network) and of a service laboratory (responding to an activation request). The procedures in the case of radiological event were successfully established and tested. © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
- Published
- 2017
8. Chronic exposure to low concentrations of strontium 90 affects bone physiology but not the hematopoietic system in mice
- Author
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Synhaeve, N., Wade-Gueye, N.M., Musilli, S., Stefani, J., Grandcolas, L., Gruel, G., Souidi, M., Dublineau, I., Bertho, J.-M., PRP-HOM/SRBE/LRTOX, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), and Laboratoire de Radiopathologie et Thérapies Expérimentales [IRSN, Fontenay-aux-Roses] (PRP-HOM - SRBE)
- Subjects
[SDV]Life Sciences [q-bio] - Abstract
International audience; The aim of this work was to delineate the effects of chronic ingestion of strontium 90 (90Sr) at low concentrations on the hematopoiesis and the bone physiology. A mouse model was used for that purpose. Parent animals ingested water containing 20kBql-1 of 90Sr two weeks before mating. Offspring were then continuously contaminated with 90Sr through placental transfer during fetal life, through lactation after birth and through drinking water after weaning. At various ages between birth and 20weeks, animals were tested for hematopoietic parameters such as blood cell counts, colony forming cells in spleen and bone marrow and cytokine concentrations in the plasma. However, we did not find any modification in 90Sr ingesting animals as compared with control animals. By contrast, the analysis of bone physiology showed a modification of gene expression towards bone resorption. This was confirmed by an increase in C-telopeptide of collagen in the plasma of 90Sr ingesting animals as compared with control animals. This modification in bone metabolism was not linked to a modification of the phosphocalcic homeostasis, as measured by calcium, phosphorus, vitamin D and parathyroid hormone in the blood. Overall these results suggest that the chronic ingestion of 90Sr at low concentration in the long term may induce modifications in bone metabolism but not in hematopoiesis. Copyright © 2012 John Wiley andamp; Sons, Ltd.
- Published
- 2014
9. Dosimétrie biologique en cas d'exposition radiologique d'un grand nombre d'individus: apport de la détection automatique des dicentriques
- Author
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Vaurijoux, A., Gruel, G., Roch-Lefèvre, S., Grégoire, E., Martin, C., Voisin, Ph., Roy, L., Laboratoire de dosimétrie biologique (DRPH/SRBE/LDB), and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
- Subjects
Biological dosimetry ,Manual scoring ,Ionizing radiation ,Automatic method ,Dosimetry ,[SDV]Life Sciences [q-bio] ,Automatic Detection ,Automatic scoring ,Radiological accidents ,Triage ,Serious accidental overexposure ,Software testing - Abstract
Following large-scale accidental overexposure to ionising radiation, a rapid triage of the exposed population can be performed by scoring dicentrics and ring chromosomes in 50 metaphases. This is rapid but not accurate. Following this triage step, the dose can be estimated by scoring 500 metaphases. This is lengthy but very accurate. To improve the methodology, we propose using software for automatic dicentric scoring, which was tested on 63 victims of a radiological accident. The method using automatic dicentric scoring was compared with the standard methods of manual scoring. The comparison of the doses obtained shows that the automatic method could replace the two steps of the manual scoring (50 and 500 metaphases). In fact, the automatic scoring method is more accurate than the manual scoring of 50 metaphases and can therefore be used for triage. © EDP Sciences, 2010.; En cas d’accident radiologique impactant un grand nombre d’individus, il est primordial de différencier rapidement les individus exposés des individus non exposés. Le laboratoire de dosimétrie biologique de l’IRSN développe des méthodes pour répondre à ce type de situation. La méthode de référence est basée sur une estimation rapide de la dose après comptage des dicentriques et des anneaux dans 50 métaphases. À l’issue de cette étape de tri de la population exposée, une estimation plus précise de la dose reçue peut être nécessaire. Cette étape est longue car elle nécessite l’observation des aberrations chromosomiques dans au moins 500 métaphases. Pour améliorer cette méthodologie en deux étapes, nous avons étudié l’utilisation d’un logiciel de détection automatique des dicentriques dans un cas réel d’accident radiologique impliquant 63 victimes. Cette méthode a été comparée aux méthodes manuelles de références. La comparaison des doses obtenues montre que la méthode automatique peut remplacer les deux étapes du comptage manuel (50 et 500 métaphases), car elle cumule les avantages de chacune d’elles : rapidité et précision.
- Published
- 2010
10. Impact des facteurs individuels et environnementaux sur le taux d'aberrations chromosomiques de type translocations Partie 2: agents toxiques liés à une exposition professionnelle
- Author
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Grégoire, E., Gruel, G., Martin, C., Roch-Lefèvre, S., Voisin, P., Vaurijoux, A., Roy, L., Laboratoire de dosimétrie biologique (DRPH/SRBE/LDB), and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
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Fish ,Heavy metals ,Genotoxic agents ,[SDV]Life Sciences [q-bio] ,Environmental factors ,Chromosomal translocations ,Lifestyle factor ,Retrospective dosimetry ,Curricula ,Polycyclic aromatic hydrocarbons - Abstract
In the first part of this review, we examined through an extensive literature review, the influence of various factors related to the individual (age, sex, alcohol and tobacco) on the rate of translocation. In the second part, our literature review focused on the study of more toxic factors related to occupational exposure. All toxic agents tested induced an increase in the translocation rate in lymphocytes of exposed people. However 2 agents (polycyclic aromatic hydrocarbons -PAHs- and heavy metals) increase significantly the rate of translocation of exposed persons. This increase is function to the dose and duration of exposure. The sensitivity of FISH technique has highlighted the necessity of protective equipment. For all the toxic factors related to occupational exposure, protective equipment or exposure conditions reduced significantly the translocations rate of exposed subjects. Thus the FISH technique could be an exposure warning indicator. In conclusion, it is important to know as well the personnel and occupational curriculum of an individual if a retrospective dose assessment is required. Thus, the rate of translocations threshold will be based on the lifestyle rate. © EDP Sciences, 2010.; Dans la première partie de cette revue, nous avons examiné, au travers d’une étude bibliographique approfondie, l’influence de différents facteurs liés à l’individu (âge, sexe, consommation d’alcool ou de tabac) sur le taux de translocations. Dans cette seconde partie, notre revue de la littérature s’est attachée à l’étude de facteurs plus toxiques liés à une exposition professionnelle. Tous les agents toxiques analysés induisent une augmentation du taux de translocations au sein des lymphocytes des personnes exposées. Cependant 2 agents (hydrocarbures aromatiques polycycliques –HAPs- et les métaux lourds) augmentent de manière significative le taux des translocations des personnes exposées. Ce type d’agents toxiques augmente le taux de translocations proportionnellement à la dose et à la durée d’exposition. La sensibilité de la technique FISH a permis de mettre en évidence la nécessité et le bon fonctionnement des équipements de protection. Pour tous les facteurs toxiques liés à une exposition professionnelle, un équipement de protection adapté et ergonomique ou bien la période d’exposition ont réduit significativement le taux de translocations des individus exposés. Ainsi la technique FISH pourrait servir d’indicateur d’exposition. En conclusion, afin d’évaluer rétrospectivement l’exposition d’un individu, il est important de connaitre le plus précisément possible son curriculum clastogène et son âge. Ainsi, un taux de translocations limite pourrait être établi en fonction de l’impact des expositions professionnelles et environnementales connues aujourd’hui et de la connaissance du passé de l’individu.
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- 2010
11. Impact des facteurs individuels et environnementaux sur le taux d'aberrations chromosomiques de type translocations Partie 1: ĝge, sexe, tabac, alcool
- Author
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Grégoire, E., Gruel, G., Martin, C., Roch-Lefèvre, S., Vaurijoux, A., Voisin, P., Roy, L., Laboratoire de dosimétrie biologique (DRPH/SRBE/LDB), and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
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Ionizing radiation ,Individual agent ,[SDV]Life Sciences [q-bio] ,Environmental factors ,Chromosomal translocations ,Lifestyle factor ,Retrospective dosimetry ,Chromosomes - Abstract
The assessment of exposure to ionizing radiation, carried out long time after exposure, is currently performed by scoring of translocations, a specific type of chromosomal aberrations. The translocations rate observed in peripheral blood lymphocytes of exposed subjects is compared to that observed in a control population. However, the translocation specificity towards radiation exposure is not clearly identified. To avoid any hasty conclusion, it is necessary to identify all the factors likely to induce translocation. To our knowledge, no study has thus far examined the effects of all these different factors on translocation rates. A review of the literature thus allowed us to assess the impact of host factors and lifestyle on the production of translocations. This study confirms that age appears to be the factor having the greatest impact on the rate of translocations, especially over 60 years. To date, the factor "age" is already considered in estimating the impact of radiation on the rate of translocation for all age groups. However, the study also shows that this rate varies significantly when the patient is exposed simultaneously and significantly towards many lifestyle agents. A precise threshold translocation rate should thus be established as a function of known behavioral exposures, below which it is impossible to conclude that radiological exposure has occurred. The effects of chemicals on the translocation rate after occupational exposure will be the subject of a second part. © EDP Sciences, 2010.; L’évaluation de l’exposition aux rayonnements ionisants, effectuée longtemps après l’exposition, est actuellement réalisée en dénombrant les aberrations chromosomiques de type translocations. Le taux de ces translocations observées dans les lymphocytes des personnes exposées est comparé au taux observé au sein d’une population contrôle. Toutefois, la spécificité des translocations vis-à-vis de l’irradiation n’est pas clairement identifiée. Afin d’éviter toute conclusion hâtive, il est nécessaire d’identifier tous les facteurs susceptibles d’induire des translocations. À notre connaissance, aucune synthèse sur l’effet de ces différents facteurs sur le taux de translocations n’a été réalisée à ce jour. Cette recherche bibliographique a confirmé l’impact de certains facteurs personnels sur l’augmentation des translocations. Cette étude corrobore que l’âge s’avère être le facteur ayant le plus d’impact sur le taux de translocations, notamment après 60 ans. À ce jour, le facteur « âge » est déjà considéré dans l’estimation du taux de translocations après suspicion d’exposition aux rayonnements ionisants pour toutes les classes d’âge. L’étude montre également que ce taux varie significativement lorsque le patient est exposé simultanément et de manière importante et chronique à une combinaison alcool et tabac. Ainsi, une courbe du taux de translocations devrait être établie en fonction de la consommation excessive de ce type d’agent pour chaque individu. Ainsi il serait alors possible de déterminer le taux de translocations induit uniquement par une exposition radiologique. Les effets des agents toxiques sur le taux de translocations après exposition professionnelle feront l’objet d’une deuxième partie.
- Published
- 2010
12. SP-0211: Track structure modelling and biodescriptors of the topology of energy deposition
- Author
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Villagrasa, C., primary, Gruel, G., additional, Gonon, G., additional, Meylan, S., additional, Bug, M.U., additional, Giesen, U., additional, Bueno, M., additional, Baek, W.Y., additional, Arndt, A., additional, and Rabus, H., additional
- Published
- 2015
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13. Future development of biologically relevant dosimetry
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Palmans, H, primary, Rabus, H, additional, Belchior, A L, additional, Bug, M U, additional, Galer, S, additional, Giesen, U, additional, Gonon, G, additional, Gruel, G, additional, Hilgers, G, additional, Moro, D, additional, Nettelbeck, H, additional, Pinto, M, additional, Pola, A, additional, Pszona, S, additional, Schettino, G, additional, Sharpe, P H G, additional, Teles, P, additional, Villagrasa, C, additional, and Wilkens, J J, additional
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- 2015
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14. RBE-LET relationship for proton and alpha irradiations studied with a nanodosimetric approach
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Villagrasa, C., primary, Santos, M. D., additional, Bianco, D., additional, Gruel, G., additional, Barquinero, J. F., additional, and Clairand, I., additional
- Published
- 2014
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15. Influence of chromatin condensation on the number of direct DSB damages induced by ions studied using a Monte Carlo code
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Dos Santos, M., primary, Clairand, I., additional, Gruel, G., additional, Barquinero, J. F., additional, Incerti, S., additional, and Villagrasa, C., additional
- Published
- 2014
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16. REVIEW OF RETROSPECTIVE DOSIMETRY TECHNIQUES FOR EXTERNAL IONISING RADIATION EXPOSURES.
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Ainsbury, E A, Bakhanova, E, Barquinero, J F, Brai, M, Chumak, V, Correcher, V, Darroudi, F, Fattibene, P, Gruel, G, Guclu, I, Horn, S, Jaworska, A, Kulka, U, Lindholm, C, Lloyd, D, Longo, A, Marrale, M, Monteiro Gil, O, Oestreicher, U, Pajic, J, Rakic, B, Romm, H, Trompier, F, Veronese, I, Voisin, P, Vral, A, Whitehouse, C A, Wieser, A, Woda, C, Wojcik, Andrzej, Rothkamm, K, Ainsbury, E A, Bakhanova, E, Barquinero, J F, Brai, M, Chumak, V, Correcher, V, Darroudi, F, Fattibene, P, Gruel, G, Guclu, I, Horn, S, Jaworska, A, Kulka, U, Lindholm, C, Lloyd, D, Longo, A, Marrale, M, Monteiro Gil, O, Oestreicher, U, Pajic, J, Rakic, B, Romm, H, Trompier, F, Veronese, I, Voisin, P, Vral, A, Whitehouse, C A, Wieser, A, Woda, C, Wojcik, Andrzej, and Rothkamm, K
- Abstract
The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements., authorCount :31
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- 2011
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17. Biological dosimetry assessments of a serious radiation accident in Bulgaria in 2011
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Gregoire, E., primary, Hadjidekova, V., additional, Hristova, R., additional, Gruel, G., additional, Roch-Lefevre, S., additional, Voisin, P., additional, Staynova, A., additional, Deleva, S., additional, Ainsbury, E. A., additional, Lloyd, D. C., additional, and Barquinero, J. F., additional
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- 2013
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18. Microarray analysis of LIF/Stat3 transcriptional targets in embryonic stem cells
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UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, UCL - (SLuc) Service d'hématologie, Sekkai, D, Gruel, G, Herry, M, Moucadel, Virginie, Constantinescu, Stefan N., Albagli, O, Roux, DTL, Vainchenkera, W, Bennaceur-Griscelli, A, UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, UCL - (SLuc) Service d'hématologie, Sekkai, D, Gruel, G, Herry, M, Moucadel, Virginie, Constantinescu, Stefan N., Albagli, O, Roux, DTL, Vainchenkera, W, and Bennaceur-Griscelli, A
- Abstract
Mouse embryonic stem (ES) cells can be propagated in vitro while retaining their properties of pluripotency and self-renewal under the continuous presence of leukemia inhibitor factor (LIF). An essential role has been attributed to subsequent activation of the Stat3 transcription factor in mediating LIF self-renewal response. To date, however, downstream target genes of Stat3 in ES cells are still unknown. To isolate these genes, we performed a microarray-based kinetic comparison of LIF-stimulated (undifferentiated) ES cells versus ES cells induced to differentiate by shutting down Stat3 activity through either LIF deprivation or, more specifically, expression of a Stat3 dominant-negative mutant. In each case, we chose the earliest time at which ES cells lose their self-renewal properties, as illustrated by a decrease in the number of embryoid bodies and blast cell colony formation as well as germ layer marker expression. Comparison of the two independent approaches revealed similarly regulated genes that are likely to be involved in the Stat3 effects on ES cell self-renewal. For instance, upregulation of growth factors such as the transforming growth factor-P relative Lefty1 or transcriptional regulators such as Id1 and Id2 and downregulation of the groucho-like protein Aes1 (grg5) were found. Promoter analysis of the aes1 gene revealed three functional Stat3 consensus sites, as shown by luciferase assays. Furthermore, chromatin immunoprecipitation experiment demonstrated that Stat3 is recruited to the promoter of aes1 in ES cells. These data demonstrated that the aes1 gene is a direct transcriptional target of Stat3 in ES cells. STEM CELLS 2005;23:1634-1642.
- Published
- 2005
19. Effect of lymphocytes culture variations on the mitotic index and on the dicentric yield following gamma radiation exposure
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Roy, L., primary, Gregoire, E., additional, Gruel, G., additional, Roch-Lefevre, S., additional, Voisin, P., additional, Busset, A., additional, and Martin, C., additional
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- 2012
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20. Review of retrospective dosimetry techniques for external ionising radiation exposures
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Ainsbury, E. A., primary, Bakhanova, E., additional, Barquinero, J. F., additional, Brai, M., additional, Chumak, V., additional, Correcher, V., additional, Darroudi, F., additional, Fattibene, P., additional, Gruel, G., additional, Guclu, I., additional, Horn, S., additional, Jaworska, A., additional, Kulka, U., additional, Lindholm, C., additional, Lloyd, D., additional, Longo, A., additional, Marrale, M., additional, Monteiro Gil, O., additional, Oestreicher, U., additional, Pajic, J., additional, Rakic, B., additional, Romm, H., additional, Trompier, F., additional, Veronese, I., additional, Voisin, P., additional, Vral, A., additional, Whitehouse, C. A., additional, Wieser, A., additional, Woda, C., additional, Wojcik, A., additional, and Rothkamm, K., additional
- Published
- 2010
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21. Cytogenetic assessment of heterogeneous radiation doses in cancer patients treated with fractionated radiotherapy
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Roch-Lefèvre, S, primary, Pouzoulet, F, additional, Giraudet, A L, additional, Voisin, Pa, additional, Vaurijoux, A, additional, Gruel, G, additional, Grégoire, E, additional, Buard, V, additional, Delbos, M, additional, Voisin, Ph, additional, Bourhis, J, additional, and Roy, L, additional
- Published
- 2010
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22. Dosimétrie biologique en cas d’exposition radiologique d’un grand nombre d’individus : apport de la détection automatique des dicentriques
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Vaurijoux, A., primary, Gruel, G., additional, Roch-Lefèvre, S., additional, Grégoire, E., additional, Martin, C., additional, Voisin, P., additional, PH., Voisin, additional, and Roy, L., additional
- Published
- 2010
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23. Impact des facteurs individuels et environnementaux sur le taux d’aberrations chromosomiques de type translocations Partie 2 : agents toxiques liés à une exposition professionnelle
- Author
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Grégoire, E., primary, Gruel, G., additional, Martin, C., additional, Roch-Lefèvre, S., additional, Voisin, P., additional, Vaurijoux, A., additional, and Roy, L., additional
- Published
- 2010
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24. Impact des facteurs individuels et environnementaux sur le taux d’aberrations chromosomiques de type translocations Partie 1 : âge, sexe, tabac, alcool
- Author
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Grégoire, E., primary, Gruel, G., additional, Martin, C., additional, Roch-Lefèvre, S., additional, Vaurijoux, A., additional, Voisin, P., additional, and Roy, L., additional
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- 2010
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25. Automatic detection of dicentrics chromosomes in biodosimetry
- Author
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Vaurijoux, A., primary, Gruel, G., additional, Pouzoulet, F., additional, Grégoire, E., additional, Martin, C., additional, Roch-Lefèvre, S., additional, Voisin, P., additional, and Roy, L., additional
- Published
- 2008
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- View/download PDF
26. Review of retrospective dosimetry techniques for external ionising radiation exposures.
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Ainsbury, E. A., Bakhanova, E., Barquinero, J. F., Brai, M., Chumak, V., Correcher, V., Darroudi, F., Fattibene, P., Gruel, G., Guclu, I., Horn, S., Jaworska, A., Kulka, U., Lindholm, C., Lloyd, D., Longo, A., Marrale, M., Monteiro Gil, O., Oestreicher, U., and Pajic, J.
- Subjects
RADIATION dosimetry ,RADIATION measurements ,BIOMARKERS ,IONIZING radiation - Abstract
The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on ‘Retrospective Dosimetry’ has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements. [ABSTRACT FROM PUBLISHER]
- Published
- 2011
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27. Cell response to ionising radiation analysed by gene expression patterns
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Roy, L., Gruel, G., Aurélie Vaurijoux, and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
- Subjects
Radiation ,radiation response ,messenger RNA ,Cells ,[SDV]Life Sciences [q-bio] ,Messenger ,article ,genetic transcription ,Reproducibility of Results ,Gene Expression ,radiation exposure ,radiometry ,cell ,Dose-Response Relationship ,Genetic ,RNA ,Animals ,Humans ,animal ,genetics ,human ,biosynthesis ,Transcription ,reproducibility - Abstract
Following ionising radiation exposure of living cells several mechanisms are activated through gene modulations. The measurement of these modifications can be done with QT-PCR and, since about 10 years, microarray technique. The latter approach has the advantage to allow a global monitoring of the complex cellular responses to radiation-induced stress and has been proposed to be used for dose assessment. Even if some publications have identified sets of genes specific to given doses, and that some of the genes have an induction proportional to the dose, a precise estimation of the received dose seems difficult with gene expression, at least in the near future. Nevertherless, in vivo studies have shown that gene profiles of individuals chronically exposed to a cumulative dose of more than 10 mSv are significantly modified. This highlights the great potential of microarray approaches in the detection of low dose exposure.
28. Geant4-DNA simulation of DNA damage caused by direct and indirect radiation effects and comparison with biological data.
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Villagrasa Carmen, Meylan Sylvain, Gonon Geraldine, Gruel Gaëtan, Giesen Ulrich, Bueno Marta, and Rabus Hans
- Subjects
Physics ,QC1-999 - Abstract
In this work we present results obtained in the frame of the BioQuaRT project. The objective of the study was the correlation between the number of radiation-induced double strand breaks (DSB) of the DNA molecule and the probability of detecting nuclear foci after targeted microbeam irradiation of cells with protons and alpha particles of different LET. The former were obtained by simulation with new methods integrated into Geant4-DNA that permit calculating the number of DSB in a DNA target model induced by direct and indirect radiation effects. A particular focus was laid in this work on evaluating the influence of different criteria applied to the simulated results for predicting the formation of a direct SSB. Indeed, these criteria have an important impact on the predicted number of DSB per particle track and its dependence with LET. Among the criteria tested in this work, the case that a direct radiation interaction leads to a strand break if the cumulative energy deposited in the backbone part of one nucleotide exceeds a threshold of 17.5 eV leads to the best agreement with the relative LET dependence of number of radiation induced foci. Further calculations and experimental data are nevertheless needed in order to fix the simulation parameters and to help interpreting the biological experimental data observed by immunofluorescence in terms of the DSB complexity.
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- 2017
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29. REVIEW OF RETROSPECTIVE DOSIMETRY TECHNIQUES FOR EXTERNAL IONISING RADIATION EXPOSURES
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Carita Lindholm, Firouz Darroudi, Vadim V. Chumak, Ivan Veronese, Elena Bakhanova, Paola Fattibene, Elizabeth A. Ainsbury, Horst Romm, Virgilio Correcher, Simon Horn, Ursula Oestreicher, Maurizio Marrale, François Trompier, Andrzej Wojcik, Anne Vral, I. Guclu, Albrecht Wieser, Ulrike Kulka, O. Monteiro Gil, Joan Francesc Barquinero, Alicja Jaworska, B. Rakic, David Lloyd, Clemens Woda, P. Voisin, Kai Rothkamm, Maria Brai, J. Pajic, Gaëtan Gruel, Caroline A. Whitehouse, Anna Longo, AINSBURY, EA, BAKHANOVA, E, BARQUINERO, JF, BRAI, M, CHUMAK, V, CORRECHER, V, DARROUDI, F, FATTIBENE, P, GRUEL, G, GUCLU, I, HORN, S, JAWORSKA, A, KULKA, U, LINDHOLM, C, LLOYD, D, LONGO, A, MARRALE, M, MONTEIRO GIL, O, OESTREICHER, U, PAJIC, J, RAKIC, B, ROMM, H, TROMPIER, F, VERONESE, I, VOISIN, P, VRAL, A, WHITEHOUSE, CA, WIESER, A, WODA, C, WOJCIK, A, ROTHKAMM, K, Università degli studi di Palermo - University of Palermo, Istituto Nazionale di Fisica Nucleare, Sezione di Catania (INFN), Università degli studi di Catania [Catania], Centre for Radiation, Chemical and Environmental Hazards, Public Health England [London], National Academy of Medical Sciences of Ukraine, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas [Madrid] (CIEMAT), Leiden University Medical Centre [Leyde, Pays-Bas], Leiden University, Istituto Superiore di Sanita` (ISS), Istituto Nazionale di Fisica Nucleare [Sezione di Roma 1] (INFN), Istituto Nazionale di Fisica Nucleare, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Norwegian Radiation Protection Authority, Bundesamt für Strahlenschutz (BfS), Radiation and Nuclear Safety Authority [Helsinki] (STUK), Instituto Tecnológico e Nuclear, Università degli Studi di Milano [Milano] (UNIMI), Department of Basic Medical Sciences [Ghent, Belgium], Division of Medical Physics [Ghent, Belgium], Universiteit Gent = Ghent University [Belgium] (UGENT)-Universiteit Gent = Ghent University [Belgium] (UGENT), German Research Center for Environmental Health - Helmholtz Center München (GmbH), and Stockholm University
- Subjects
medicine.medical_specialty ,Protein biomarkers ,Optically stimulated luminescence ,[SDV]Life Sciences [q-bio] ,Radiation Dosage ,Risk Assessment ,Retrospective dosimetry ,030218 nuclear medicine & medical imaging ,Ionizing radiation ,03 medical and health sciences ,0302 clinical medicine ,Radiation Monitoring ,Radiation, Ionizing ,Humans ,Medicine ,Dosimetry ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Radiometry ,Retrospective Studies ,Radiation ,Radiological and Ultrasound Technology ,business.industry ,Public Health, Environmental and Occupational Health ,General Medicine ,Integrated approach ,030220 oncology & carcinogenesis ,Body Burden ,Radiation monitoring ,business ,Ionising radiation exposure ,Radiation Accidents - Abstract
The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements. © The Author 2010. Published by Oxford University Press. All rights reserved.
- Published
- 2011
30. Radiological injuries under low energy x-rays in mice depending on dose and protocol: comparative characterization of lesion severity and impact of the in vivo bone response on retrospective dose estimations.
- Author
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Guillou M, L'Homme B, Trompier F, Errabii A, Marcoux T, Gruel G, Prezado Y, and Dos Santos M
- Subjects
- Animals, Mice, X-Rays, Retrospective Studies, Radiography, Electron Spin Resonance Spectroscopy methods, Bone and Bones
- Abstract
Objective . To improve our knowledge about the biological effects of over exposures involving low-energy x-rays, we developed and characterized a preclinical mouse model allowing to mimic different lesion severity degrees induced by 80 kV x-ray depending on the dose and protocol (single or repeated exposure). Approach . Mice were locally exposed (paw) to 80 kV x-rays in a single (15, 30 or 45 Gy in K
air ) or repeated exposition (2 × 15 or 3 × 15 Gy in Kair ) to assess different degrees of lesion severity. Six post-irradiation euthanasia time points (0, 7, 14, 21, 42, and 84 days) were determined to follow up the evolution of lesions based on the lesion score, weighing and cutaneous blood perfusion. The bone dose was estimated at the different time points by electron paramagnetic resonance (EPR) spectroscopy. Main results . The monitoring of the lesion severity allows to classify the exposure protocols according to their severity. EPR spectroscopy measurements allow to determine the bone dose on the day of irradiation which is 7 times higher than the initial dose for single protocols. However, the initial signal measured at the end of the repeated exposure was 27% lower than the signal measured for a single dose. The study of the kinetics of EPR signal showed a decrease of the EPR signal which is dependent on the exposure protocol but not on dose highlighting the impact of bone physiology on the bone dose estimation. Significance : the preclinical model developed allows to assess the impact of the dose and protocol on the lesion severity induced by low-energy x-ray. For the first time, the dynamics of free radicals have been quantified in an in vivo model, highlighting that the doses actually administered can be underestimated if samples are taken weeks or even months after exposure., (© 2024 Institute of Physics and Engineering in Medicine.)- Published
- 2024
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31. microRNA blood signature for localized radiation injury.
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Ancel L, Gabillot O, Szurewsky C, Granger R, Sache A, Voyer F, Gruel G, Illiano S, Benderitter M, Le Guen B, Souidi M, Benadjaoud MA, and Flamant S
- Subjects
- Humans, Animals, Mice, Mice, Inbred C57BL, Biomarkers, Gene Expression Profiling, MicroRNAs genetics, Circulating MicroRNA genetics, Radiation Injuries diagnosis, Radiation Injuries genetics
- Abstract
A radiological accident, whether from industrial, medical, or malicious origin, may result in localized exposure to high doses of ionizing radiations, leading to the development of local radiation injury (LRI), that may evolve toward deep ulceration and necrosis of the skin and underlying tissues. Early diagnosis is therefore crucial to facilitate identification and management of LRI victims. Circulating microRNAs (miRNA) have been studied as potential diagnostic biomarkers of several diseases including hematological defects following whole-body irradiation (WBI). This study aims to identify a blood miRNA signature associated with LRI in a preclinical C57BL/6J mouse model of hindlimb irradiation using different 10-MV X-ray doses that lead to injuries of different severities. To this end, we first performed broad-spectrum plasma miRNA profiling, followed by a targeted validation step, on two independent animal cohorts. Using a multivariate sparse partial least square discriminant analysis, we identified a panel of eight circulating miRNAs able to segregate mice according to LRI severity. Interestingly, these miRNAs were previously associated with WBI (miR-150-5p, miR-342-3p, miR-146a-5p), inflammation (miR-18a-5p, miR-148b-3p, miR-532-5p) and skin diseases (miR-139-5p, miR-195-5p). Our results suggest the use of circulating miRNAs as suitable molecular biomarkers for LRI prognosis and diagnosis., (© 2024. The Author(s).)
- Published
- 2024
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32. Experimental validation in a neutron exposure frame of the MINAS TIRITH for cell damage simulation.
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Thibaut Y, Gonon G, Martinez JS, Petit M, Babut R, Vaurijoux A, Gruel G, Villagrasa C, Incerti S, and Perrot Y
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- Radiation, Ionizing, Neutrons, Monte Carlo Method, DNA Damage, Cell Nucleus radiation effects
- Abstract
In the domains of medicine and space exploration, refining risk assessment models for protecting healthy tissue from ionizing radiation is crucial. Understanding radiation-induced effects requires biological experimentations at the cellular population level and the cellular scale modeling using Monte Carlo track structure codes. We present MINAS TIRITH, a tool using Geant4-DNA Monte Carlo-generated databases to study DNA damage distribution at the cell population scale. It introduces a DNA damage location module and proposes a method to convert double-strand breaks (DSB) into DNA Damage Response foci. We evaluate damage location precision and DSB-foci conversion parameters. MINAS TIRITH's accuracy is validated against γ -H2AX foci distribution from cell population exposed to monoenergetic neutron beams (2.5 or 15.1 MeV) under different configurations, yielding mixed radiation fields. Strong agreement between simulation and experimental results was found demonstrating MINAS TIRITH's predictive precision in radiation-induced DNA damage topology. Additionally, modeling intercellular damage variability within a population subjected to a specific macroscopic dose identifies subpopulations, enhancing realistic fate models. This approach advances our understanding of radiation-induced effects on cellular systems for risk assessment improvement., (© 2023 Institute of Physics and Engineering in Medicine.)
- Published
- 2023
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33. International Comparison Exercise for Biological Dosimetry after Exposures with Neutrons Performed at Two Irradiation Facilities as Part of the BALANCE Project.
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Endesfelder D, Kulka U, Bucher M, Giesen U, Garty G, Beinke C, Port M, Gruel G, Gregoire E, Terzoudi G, Triantopoulou S, Ainsbury EA, Moquet J, Sun M, Prieto MJ, Moreno Domene M, Barquinero JF, Pujol-Canadell M, Vral A, Baeyens A, Wojcik A, and Oestreicher U
- Subjects
- Humans, Germany, Neutrons
- Abstract
In the case of a radiological or nuclear event, biological dosimetry can be an important tool to support clinical decision-making. During a nuclear event, individuals might be exposed to a mixed field of neutrons and photons. The composition of the field and the neutron energy spectrum influence the degree of damage to the chromosomes. During the transatlantic BALANCE project, an exposure similar to a Hiroshima-like device at a distance of 1.5 km from the epicenter was simulated, and biological dosimetry based on dicentric chromosomes was performed to evaluate the participants ability to discover unknown doses and to test the influence of differences in neutron spectra. In a first step, calibration curves were established by irradiating blood samples with 5 doses in the range of 0-4 Gy at two different facilities in Germany (Physikalisch-Technische Bundesanstalt [PTB]) and the USA (the Columbia IND Neutron Facility [CINF]). The samples were sent to eight participating laboratories from the RENEB network and dicentric chromosomes were scored by each participant. Next, blood samples were irradiated with 4 blind doses in each of the two facilities and sent to the participants to provide dose estimates based on the established calibration curves. Manual and semiautomatic scoring of dicentric chromosomes were evaluated for their applicability to neutron exposures. Moreover, the biological effectiveness of the neutrons from the two irradiation facilities was compared. The calibration curves from samples irradiated at CINF showed a 1.4 times higher biological effectiveness compared to samples irradiated at PTB. For manual scoring of dicentric chromosomes, the doses of the test samples were mostly successfully resolved based on the calibration curves established during the project. For semiautomatic scoring, the dose estimation for the test samples was less successful. Doses >2 Gy in the calibration curves revealed nonlinear associations between dose and dispersion index of the dicentric counts, especially for manual scoring. The differences in the biological effectiveness between the irradiation facilities suggested that the neutron energy spectrum can have a strong impact on the dicentric counts., (© 2023 S. Karger AG, Basel.)
- Published
- 2023
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34. Biodose Tools: an R shiny application for biological dosimetry.
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Hernández A, Endesfelder D, Einbeck J, Puig P, Benadjaoud MA, Higueras M, Ainsbury E, Gruel G, Oestreicher U, Barrios L, and Barquinero JF
- Subjects
- Bayes Theorem, Retrospective Studies, Radiometry, Software, Radiation Monitoring methods
- Abstract
Introduction: In the event of a radiological accident or incident, the aim of biological dosimetry is to convert the yield of a specific biomarker of exposure to ionizing radiation into an absorbed dose. Since the 1980s, various tools have been used to deal with the statistical procedures needed for biological dosimetry, and in general those who made several calculations for different biomarkers were based on closed source software. Here we present a new open source program, Biodose Tools, that has been developed under the umbrella of RENEB (Running the European Network of Biological and retrospective Physical dosimetry)., Materials and Methods: The application has been developed using the R programming language and the shiny package as a framework to create a user-friendly online solution. Since no unique method exists for the different mathematical processes, several meetings and periodic correspondence were held in order to reach a consensus on the solutions to be implemented., Results: The current version 3.6.1 supports dose-effect fitting for dicentric and translocation assay. For dose estimation Biodose Tools implements those methods indicated in international guidelines and a specific method to assess heterogeneous exposures. The app can include information on the irradiation conditions to generate the calibration curve. Also, in the dose estimate, information about the accident can be included as well as the explanation of the results obtained. Because the app allows generating a report in various formats, it allows traceability of each biological dosimetry study carried out. The app has been used globally in different exercises and training, which has made it possible to find errors and improve the app itself. There are some features that still need consensus, such as curve fitting and dose estimation using micronucleus analysis. It is also planned to include a package dedicated to interlaboratory comparisons and the incorporation of Bayesian methods for dose estimation., Conclusion: Biodose Tools provides an open-source solution for biological dosimetry laboratories. The consensus reached helps to harmonize the way in which uncertainties are calculated. In addition, because each laboratory can download and customize the app's source code, it offers a platform to integrate new features.
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- 2023
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35. Preclinical modeling of low energy X-rays radiological burn: Dosimetry study by monte carlo simulations and EPR spectroscopy.
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Guillou M, L'Homme B, Trompier F, Gruel G, Prezado Y, and Dos Santos M
- Abstract
Interventional radiology has grown considerably over the last decades and become an essential tool for treatment or diagnosis. This technique is mostly beneficial and mastered but accidental overexposure can occur and lead to the appearance of deterministic effects. The lack of knowledge about the radiobiological consequences for the low-energy X-rays used for these practices makes the prognosis very uncertain for the different tissues. In order to improve the radiation protection of patients and better predict the risk of complications, we implemented a new preclinical mouse model to mimic radiological burn in interventional radiology and performed a complete characterization of the dose deposition. A new setup and collimator were designed to irradiate the hind legs of 15 mice at 30 Gy in air kerma at 80 kV. After irradiation, mice tibias were collected to evaluate bone dose by Electron Paramagnetic Resonance (EPR) spectroscopy measurements. Monte Carlo simulations with Geant4 were performed in simplified and voxelized phantoms to characterize the dose deposition in different tissues and evaluate the characteristics of secondary electrons (energy, path, momentum). 30 mice tibias were collected for EPR analysis. An average absorbed dose of 194.0 ± 27.0 Gy was measured in bone initially irradiated at 30 Gy in air kerma. A bone to air conversion factor of 6.5 ± 0.9 was determined. Inter sample and inter mice variability has been estimated to 13.9%. Monte Carlo simulations shown the heterogeneity of the dose deposition for these low X-rays energies and the dose enhancement in dense tissue. The specificities of the secondary electrons were studied and showed the influence of the tissue density on energies and paths. A good agreement between the experimental and calculated bone to air conversion factor was obtained. A new preclinical model allowing to perform radiological burn in interventional radiology-like conditions was implemented. For the development of new preclinical radiobiological model where the exact knowledge of the dose deposited in the different tissues is essential, the complementarity of Monte Carlo simulations and experimental measurements for the dosimetric characterization has proven to be a considerable asset., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guillou, L’Homme, Trompier, Gruel, Prezado and Dos Santos.)
- Published
- 2022
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36. Differential Recruitment of DNA Repair Proteins KU70/80 and RAD51 upon Microbeam Irradiation with α-Particles.
- Author
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Bobyk L, Vianna F, Martinez JS, Gruel G, Benderitter M, and Baldeyron C
- Abstract
In addition to representing a significant part of the natural background radiation exposure, α-particles are thought to be a powerful tool for targeted radiotherapy treatments. Understanding the molecular mechanisms of recognition, signaling, and repair of α-particle-induced DNA damage is not only important in assessing the risk associated with human exposure, but can also potentially help in identifying ways of improving the efficacy of radiation treatment. α-particles (He
2+ ions), as well as other types of ionizing radiation, and can cause a wide variety of DNA lesions, including DNA double-strand breaks (DSBs). In mammalian cells, DNA DSBs can be repaired by two major pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). Here, we investigated their dynamics in mouse NIH-3T3 cells through the recruitment of key proteins, such as the KU heterodimer for NHEJ and RAD51 for HR upon localized α-particle irradiation. To deliver α-particles, we used the MIRCOM microbeam, which allows targeting of subnuclear structures with submicron accuracy. Using mouse NIH-3T3 cells, we found that the KU heterodimer is recruited much earlier at DNA damage sites marked by H2AX phosphorylation than RAD51. We also observed that the difference in the response of the KU complex and RAD51 is not only in terms of time, but also in function of the chromatin nature. The use of a microbeam such as MIRCOM, represents a powerful tool to study more precisely the cellular response to ionizing irradiation in a spatiotemporal fashion at the molecular level.- Published
- 2022
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37. Limited Transmission of Klebsiella pneumoniae among Humans, Animals, and the Environment in a Caribbean Island, Guadeloupe (French West Indies).
- Author
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Dereeper A, Gruel G, Pot M, Couvin D, Barbier E, Bastian S, Bambou JC, Gelu-Simeon M, Ferdinand S, Guyomard-Rabenirina S, Passet V, Martino F, Piveteau P, Reynaud Y, Rodrigues C, Roger PM, Roy X, Talarmin A, Tressieres B, Valette M, Brisse S, and Breurec S
- Subjects
- Animals, Dogs, Humans, Anti-Bacterial Agents pharmacology, beta-Lactamases genetics, Drug Resistance, Multiple, Bacterial genetics, Guadeloupe epidemiology, Microbial Sensitivity Tests, Swine, Bacterial Zoonoses, Klebsiella Infections epidemiology, Klebsiella pneumoniae genetics
- Abstract
Guadeloupe (French West Indies), a Caribbean island, is an ideal place to study the reservoirs of the Klebsiella pneumoniae species complex (KpSC) and identify the routes of transmission between human and nonhuman sources due to its insularity, small population size, and small area. Here, we report an analysis of 590 biological samples, 546 KpSC isolates, and 331 genome sequences collected between January 2018 and May 2019. The KpSC appears to be common whatever the source. Extended-spectrum-β-lactamase (ESBL)-producing isolates (21.4%) belonged to K. pneumoniae sensu stricto (phylogroup Kp1), and all but one were recovered from the hospital setting. The distribution of species and phylogroups across the different niches was clearly nonrandom, with a distinct separation of Kp1 and Klebsiella variicola (Kp3). The most frequent sequence types (STs) (≥5 isolates) were previously recognized as high-risk multidrug-resistant (MDR) clones, namely, ST17, ST307, ST11, ST147, ST152, and ST45. Only 8 out of the 63 STs (12.7%) associated with human isolates were also found in nonhuman sources. A total of 22 KpSC isolates were defined as hypervirulent: 15 associated with human infections (9.8% of all human isolates), 4 (8.9%) associated with dogs, and 3 (15%) associated with pigs. Most of the human isolates (33.3%) belonged to the globally successful sublineage CG23-I. ST86 was the only clone shared by a human and a nonhuman (dog) source. Our work shows the limited transmission of KpSC isolates between human and nonhuman sources and points to the hospital setting as a cornerstone of the spread of MDR clones and antibiotic resistance genes. IMPORTANCE In this study, we characterized the presence and genomic features of isolates of the Klebsiella pneumoniae species complex (KpSC) from human and nonhuman sources in Guadeloupe (French West Indies) in order to identify the reservoirs and routes of transmission. This is the first study in an island environment, an ideal setting that limits the contribution of external imports. Our data showed the limited transmission of KpSC isolates between the different compartments. In contrast, we identified the hospital setting as the epicenter of antibiotic resistance due to the nosocomial spread of successful multidrug-resistant (MDR) K. pneumoniae clones and antibiotic resistance genes. Ecological barriers and/or limited exposure may restrict spread from the hospital setting to other reservoirs and vice versa. These results highlight the need for control strategies focused on health care centers, using genomic surveillance to limit the spread, particularly of high-risk clones, of this important group of MDR pathogens.
- Published
- 2022
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38. High Prevalence of bla CTXM -1 /IncI1-Iγ/ST3 Plasmids in Extended-Spectrum β-Lactamase-Producing Escherichia coli Isolates Collected From Domestic Animals in Guadeloupe (French West Indies).
- Author
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Gruel G, Couvin D, Guyomard-Rabenirina S, Arlet G, Bambou JC, Pot M, Roy X, Talarmin A, Tressieres B, Ferdinand S, and Breurec S
- Abstract
Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) have been classified in the group of resistant bacteria of highest priority. We determined the prevalence of ESBL-E collected in feces from household and shelter pets in Guadeloupe (French West Indies). A single rectal swab was taken from 125 dogs and 60 cats between June and September 2019. The prevalence of fecal carriage of ESBL-E was 7.6% (14/185, 95% CI: 4.2-12.4), within the range observed worldwide. The only risk factor associated with a higher prevalence of ESBL-E rectal carriage was a stay in a shelter, suggesting that refuges could be hotspots for their acquisition. All but one ( Klebsiella pneumoniae from a cat) were Escherichia coli . We noted the presence of a bla
CTX-M -1 /IncI1-Iγ/sequence type (ST3) plasmid in 11 ESBL-producing E. coli isolates belonging to ST328 ( n = 6), ST155 ( n = 4) and ST953 ( n = 1). A blaCTX-M -15 gene was identified in the three remaining ESBL-E isolates. The blaCTX-M -1 and most of the antimicrobial resistance genes were present in a well-conserved large conjugative IncI1-Iγ/ST3 plasmid characterized by two accessory regions containing antibiotic resistance genes. The plasmid has been detected worldwide in E. coli isolates from humans and several animal species, such as food-producing animals, wild birds and pets, and from the environment. This study shows the potential role of pets as a reservoir of antimicrobial-resistant bacteria or genes for humans and underlines the importance of basic hygiene measures by owners of companion animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gruel, Couvin, Guyomard-Rabenirina, Arlet, Bambou, Pot, Roy, Talarmin, Tressieres, Ferdinand and Breurec.)- Published
- 2022
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39. Deciphering the Dynamic Molecular Program of Radiation-Induced Endothelial Senescence.
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Benadjaoud MA, Soysouvanh F, Tarlet G, Paget V, Buard V, Santos de Andrade H, Morilla I, Dos Santos M, Bertho A, l'Homme B, Gruel G, François A, Mondini M, Deutsch E, Guipaud O, and Milliat F
- Subjects
- Animals, Mice, Phenotype, Signal Transduction, Cellular Senescence, Endothelial Cells pathology
- Abstract
Purpose: Radiation-induced cellular senescence is a double-edged sword, acting as both a tumor suppression process limiting tumor proliferation, and a crucial process contributing to normal tissue injury. Endothelial cells play a role in normal tissue injury after radiation therapy. Recently, a study observed an accumulation of senescent endothelial cells (ECs) around radiation-induced lung focal lesions following stereotactic radiation injury in mice. However, the effect of radiation on EC senescence remains unclear because it depends on dose and fractionation, and because the senescent phenotype is heterogeneous and dynamic., Methods and Materials: Using a systems biology approach in vitro, we deciphered the dynamic senescence-associated transcriptional program induced by irradiation., Results: Flow cytometry and single-cell RNA sequencing experiments revealed the heterogeneous senescent status of irradiated ECs and allowed to deciphered the molecular program involved in this status. We identified the Interleukin-1 signaling pathway as a key player in the radiation-induced premature senescence of ECs, as well as the endothelial-to-mesenchymal transition process, which shares strong hallmarks of senescence., Conclusions: Our work provides crucial information on the dynamics of the radiation-induced premature senescence process, the effect of the radiation dose, as well as the molecular program involved in the heterogeneous senescent status of ECs., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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40. Protection and safety of a repeated dosage of KI for iodine thyroid blocking during pregnancy.
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Gaouaoui-Azouaou H, L'Homme B, Benadjaoud MA, Sache-Aloui A, Granger R, Voyer F, Lestaevel P, Gruel G, Caire-Maurisier F, Crambes C, Dare-Doyen S, Benderitter M, and Souidi M
- Subjects
- Animals, Female, Humans, Iodides, Iodine Radioisotopes, Potassium Iodide, Pregnancy, Rats, Rats, Wistar, Iodine, Thyroid Neoplasms
- Abstract
In case of nuclear power plant accidents resulting in the release of radioactive iodine (
131 I) in large amounts, a single intake of stable iodine is recommended in order to prevent131 I fixation to the thyroid gland. However, in situations of prolonged exposure to131 I (e.g. Fukushima-Daiichi natural and nuclear disaster), repetitive administration of iodine may be necessary to ensure adequate protection, with acceptable safety in vulnerable populations including pregnant women. Here we conducted toxicological studies on adult rats progeny following prolonged exposure to potassium iodide (KI) in utero . Pregnant Wistar rats were treated with 1 mg kg d-1 KI or saline water for 2 or 4 d either between gestation days gestational day (GD) GD 9-12, or GD13-16. Plasma samples from the progeny were tested 30 d post-weaning for clinical biochemistry, thyroid hormones, and anti-thyroid antibody levels. Thyroid and brain were collected for gene expression analysis. The hormonal status was similar for the mothers in all experimental conditions. In the offspring, while thyroid-stimulating hormone and anti-thyroid peroxidase (anti-TPO) antibody levels were similar in all groups, a significant increase of FT3 and FT4 levels was observed in GD9-GD10 and in GD13-GD14 animals treated for 2 d, respectively. In addition, FT4 levels were mildly decreased in 4 d treated GD13-16 individuals. Moreover, a significant decrease in the expression level of thyroid genes involved in iodide metabolism, TPO and apical iodide transporter, was observed in GD13-GD14 animals treated for 2 d. We conclude that repeated KI administration for 2-4 d during gestation did not induce strong thyroid toxicity., (Creative Commons Attribution license.)- Published
- 2022
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41. Critical Evaluation of Cross-Sectoral Collaborations to Inform the Implementation of the "One Health" Approach in Guadeloupe.
- Author
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Gruel G, Diouf MB, Abadie C, Chilin-Charles Y, Etter EMC, Geffroy M, Herrmann Storck C, Meyer DF, Pagès N, Pressat G, Teycheney PY, Umber M, Vega-Rúa A, and Pradel J
- Subjects
- Animals, Caribbean Region, Guadeloupe, Humans, West Indies, Natural Disasters, One Health
- Abstract
In Guadeloupe, a French overseas territory located in the Eastern Caribbean, infectious and non-infectious diseases, loss of biodiversity, natural disasters and global change threaten the health and well-being of animals, plants, and people. Implementing the "One Health" (OH) approach is crucial to reduce the archipelago's vulnerability to these health threats. However, OH remains underdeveloped in Guadeloupe, hampering efficient and effective intersectoral and transdisciplinary collaborations for disease surveillance and control. A multidisciplinary research group of volunteer researchers working in Guadeloupe, with collective expertise in infectious diseases, undertook a study to identify key attributes for OH operationalization by reviewing past and current local collaborative health initiatives and analyzing how much they mobilized the OH framework. The research group developed and applied an operational OH framework to assess critically collaborative initiatives addressing local health issues. Based on a literature review, a set of 13 opinion-based key criteria was defined. The criteria and associated scoring were measured through semi-directed interviews guided by a questionnaire to critically evaluate four initiatives in animal, human, plant, and environmental health research and epidemiological surveillance. Gaps, levers, and prospects were identified that will help health communities in Guadeloupe envision how to implement the OH approach to better address local health challenges. The methodology is simple, generic, and pragmatic and relies on existing resources. It can be transposed and adapted to other contexts to improve effectiveness and efficiency of OH initiatives, based on lessons-learned of local past or current multi-interdisciplinary and intersectoral initiatives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gruel, Diouf, Abadie, Chilin-Charles, Etter, Geffroy, Herrmann Storck, Meyer, Pagès, Pressat, Teycheney, Umber, Vega-Rúa and Pradel.)
- Published
- 2021
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42. Wide Distribution and Specific Resistance Pattern to Third-Generation Cephalosporins of Enterobacter cloacae Complex Members in Humans and in the Environment in Guadeloupe (French West Indies).
- Author
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Pot M, Reynaud Y, Couvin D, Ducat C, Ferdinand S, Gravey F, Gruel G, Guérin F, Malpote E, Breurec S, Talarmin A, and Guyomard-Rabenirina S
- Abstract
Species belonging to Enterobacter cloacae complex have been isolated in numerous environments and samples of various origins. They are also involved in opportunistic infections in plants, animals, and humans. Previous prospection in Guadeloupe (French West Indies) indicated a high frequency of E. cloacae complex strains resistant to third-generation cephalosporins (3GCs) in a local lizard population ( Anolis marmoratus ), but knowledge of the distribution and resistance of these strains in humans and the environment is limited. The aim of this study was to compare the distribution and antibiotic susceptibility pattern of E. cloacae complex members from different sources in a "one health" approach and to find possible explanations for the high level of resistance in non-human samples. E. cloacae complex strains were collected between January 2017 and the end of 2018 from anoles, farm animals, local fresh produce, water, and clinical human samples. Isolates were characterized by the heat-shock protein 60 gene-fragment typing method, and whole-genome sequencing was conducted on the most frequent clusters (i.e., C-VI and C-VIII). The prevalence of resistance to 3GCs was relatively high (56/346, 16.2%) in non-human samples. The associated resistance mechanism was related to an AmpC overproduction; however, in human samples, most of the resistant strains (40/62) produced an extended-spectrum beta-lactamase. No relation was found between resistance in isolates from wild anoles (35/168) and human activities. Specific core-genome phylogenetic analysis highlighted an important diversity in this bacterial population and no wide circulation among the different compartments. In our setting, the mutations responsible for resistance to 3GCs, especially in ampD , were diverse and not compartment specific. In conclusion, high levels of resistance in non-human E. cloacae complex isolates are probably due to environmental factors that favor the selection of these resistant strains, and this will be explored further., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pot, Reynaud, Couvin, Ducat, Ferdinand, Gravey, Gruel, Guérin, Malpote, Breurec, Talarmin and Guyomard-Rabenirina.)
- Published
- 2021
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43. Antimicrobial use and resistance in Escherichia coli from healthy food-producing animals in Guadeloupe.
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Gruel G, Sellin A, Riveiro H, Pot M, Breurec S, Guyomard-Rabenirina S, Talarmin A, and Ferdinand S
- Subjects
- Animals, Anti-Bacterial Agents administration & dosage, Cattle microbiology, Cross-Sectional Studies, Escherichia coli drug effects, Escherichia coli Infections veterinary, Feces microbiology, Guadeloupe, Poultry microbiology, Swine microbiology, beta-Lactamases metabolism, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial genetics, Escherichia coli genetics
- Abstract
Background: Selection pressure exerted by use of antibiotics in both human and veterinary medicine is responsible for increasing antimicrobial resistance (AMR). The objectives of this study were to better understand antimicrobial use in pigs, beef cattle, and poultry on farms on Guadeloupe, French West Indies, and to acquire data on AMR in Escherichia coli in these food-producing animals. A cross-sectional survey was conducted at 45 farms on Guadeloupe, and practical use of antimicrobials was documented in declarative interviews between March and July 2018. A total of 216 fecal samples were collected between January 2018 and May 2019, comprising 124 from pigs, 75 from beef cattle, and 17 from poultry litter. E. coli isolates were obtained for further testing by isolation and identification from field samples. Antimicrobial susceptibility testing and screening for bla
CTX-M , blaTEM , tetA, and tetB resistance genes by polymerase chain reaction on extracted genomic DNA were performed., Results: The study showed rational use of antimicrobials, consisting of occasional use for curative treatment by veterinary prescription. Tetracycline was the most commonly used antimicrobial, but its use was not correlated to E. coli resistance. Extended-spectrum β-lactamase (ESBL) E. coli isolates were detected in 7.3% of pigs, 14.7% of beef cattle, and 35.3% of poultry. blaCTX-M-1 was the predominant gene found in ESBL-E. coli isolates (68.8%), followed by blaCTX-M-15 (31.3%)., Conclusion: Despite rational use of antimicrobials, the rate of ESBL-E. coli in food-producing animals in Guadeloupe, although moderate, is a concern. Further studies are in progress to better define the genetic background of the ESBL-E. coli isolates.- Published
- 2021
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44. Hyperactivity and Seizure Induced by Tricresyl Phosphate Are Isomer Specific and Not Linked to Phenyl Valerate-Neuropathy Target Esterase Activity Inhibition in Zebrafish.
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Knoll-Gellida A, Dubrana LE, Bourcier LM, Mercé T, Gruel G, Soares M, and Babin PJ
- Subjects
- Animals, Carboxylic Ester Hydrolases, Chickens, Seizures chemically induced, Valerates, Zebrafish, Tritolyl Phosphates
- Abstract
Environmental exposure to tricresyl phosphate (TCP) may lead to severe neurotoxic effects, including organophosphate (OP)-induced delayed neuropathy. TCP has three symmetric isomers, distinguished by the methyl group position on the aromatic ring system. One of these isomers, tri-ortho-cresyl phosphate (ToCP), has been reported for years as a neuropathic OP, targeting neuropathic target esterase (NTE/PNPLA6), but its mode of toxic action had not been fully elucidated. Zebrafish eleuthero-embryo and larva were used to characterize the differential action of the TCP isomers. The symmetric isomers inhibited phenyl valerate (PV)-NTE enzymatic activity in vivo with different IC50, while no effect was observed on acetylcholinesterase activity. Moreover, the locomotor behavior was also affected by tri-para-cresyl phosphate and tri-meta-cresyl phosphate, only ToCP exposure led to locomotor hyperactivity lasting several hours, associated with defects in the postural control system and an impaired phototactic response, as revealed by the visual motor response test. The electric field pulse motor response test demonstrated that a seizure-like, multiple C-bend-spaghetti phenotype may be significantly induced by ToCP only, independently of any inhibition of PV-NTE activity. Eleuthero-embryos exposed to picrotoxin, a known gamma-aminobutyric acid type-A receptor inhibitor, exhibited similar adverse outcomes to ToCP exposure. Thus, our results demonstrated that the TCP mode of toxic action was isomer specific and not initially related to modulation of PV-NTE activity. Furthermore, it was suggested that the molecular events involved were linked to an impairment of the balance between excitation and inhibition in neuronal circuits., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
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45. Dosimetry for Cell Irradiation using Orthovoltage (40-300 kV) X-Ray Facilities.
- Author
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Dos Santos M, Paget V, Trompier F, Gruel G, and Milliat F
- Subjects
- Calibration, Computer Simulation, Culture Media, Dose-Response Relationship, Radiation, X-Rays, Cells radiation effects, Radiometry
- Abstract
The importance of dosimetry protocols and standards for radiobiological studies is self-evident. Several protocols have been proposed for dose determination using low energy X-ray facilities, but depending on the irradiation configurations, samples, materials or beam quality, it is sometimes difficult to know which protocol is the most appropriate to employ. We, therefore, propose a dosimetry protocol for cell irradiations using low energy X-ray facility. The aim of this method is to perform the dose estimation at the level of the cell monolayer to make it as close as possible to real cell irradiation conditions. The different steps of the protocol are as follows: determination of the irradiation parameters (high voltage, intensity, cell container etc.), determination of the beam quality index (high voltage-half value layer couple), dose rate measurement with ionization chamber calibrated in air kerma conditions, quantification of the attenuation and scattering of the cell culture medium with EBT3 radiochromic films, and determination of the dose rate at the cellular level. This methodology must be performed for each new cell irradiation configuration as the modification of only one parameter can strongly impact the real dose deposition at the level of the cell monolayer, particularly involving low energy X-rays.
- Published
- 2021
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46. Dissemination of Extended-Spectrum-β-Lactamase-Producing Enterobacter cloacae Complex from a Hospital to the Nearby Environment in Guadeloupe (French West Indies): ST114 Lineage Coding for a Successful IncHI2/ST1 Plasmid.
- Author
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Pot M, Guyomard-Rabenirina S, Couvin D, Ducat C, Enouf V, Ferdinand S, Gruel G, Malpote E, Talarmin A, Breurec S, and Reynaud Y
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Guadeloupe, Hospitals, Humans, Microbial Sensitivity Tests, Plasmids genetics, West Indies, beta-Lactamases genetics, Enterobacter cloacae genetics, Enterobacteriaceae Infections
- Abstract
Wastewater treatment plants are considered hot spots for antibiotic resistance. Most studies have addressed the impact on the aquatic environment, as water is an important source of anthropogenic pollutants. Few investigations have been conducted on terrestrial animals living near treatment ponds. We isolated extended-spectrum-β-lactamase Enterobacter cloacae complex-producing strains from 35 clinical isolates, 29 samples of wastewater, 19 wild animals, and 10 domestic animals living in the hospital sewers and at or near a wastewater treatment plant to study the dissemination of clinically relevant resistance through hospital and urban effluents. After comparison of the antibiotic-resistant profiles of E. cloacae complex strains, a more detailed analysis of 41 whole-genome-sequenced strains demonstrated that the most common sequence type, ST114 ( n = 20), was present in human ( n = 9) and nonhuman ( n = 11) samples, with a close genetic relatedness. Whole-genome sequencing confirmed local circulation of this pathogenic lineage in diverse animal species. In addition, nanopore sequencing and specific synteny of an IncHI2/ST1/ bla
CTX-M-15 plasmid recovered on the majority of these ST114 clones ( n = 18) indicated successful worldwide diffusion of this mobile genetic element., (Copyright © 2021 Pot et al.)- Published
- 2021
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47. RENEB Inter-Laboratory comparison 2017: limits and pitfalls of ILCs.
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Gregoire E, Barquinero JF, Gruel G, Benadjaoud M, Martinez JS, Beinke C, Balajee A, Beukes P, Blakely WF, Dominguez I, Duy PN, Gil OM, Güçlü I, Guogyte K, Hadjidekova SP, Hadjidekova V, Hande P, Jang S, Lumniczky K, Meschini R, Milic M, Montoro A, Moquet J, Moreno M, Norton FN, Oestreicher U, Pajic J, Sabatier L, Sommer S, Testa A, Terzoudi G, Valente M, Venkatachalam P, Vral A, Wilkins RC, Wojcik A, Zafiropoulos D, and Kulka U
- Subjects
- Humans, Radiometry methods, Europe, Radiation Dosage, Chromosome Aberrations radiation effects, Dose-Response Relationship, Radiation, Laboratories standards
- Abstract
Purpose: In case of a mass-casualty radiological event, there would be a need for networking to overcome surge limitations and to quickly obtain homogeneous results (reported aberration frequencies or estimated doses) among biodosimetry laboratories. These results must be consistent within such network. Inter-laboratory comparisons (ILCs) are widely accepted to achieve this homogeneity. At the European level, a great effort has been made to harmonize biological dosimetry laboratories, notably during the MULTIBIODOSE and RENEB projects. In order to continue the harmonization efforts, the RENEB consortium launched this intercomparison which is larger than the RENEB network, as it involves 38 laboratories from 21 countries. In this ILC all steps of the process were monitored, from blood shipment to dose estimation. This exercise also aimed to evaluate the statistical tools used to compare laboratory performance., Materials and Methods: Blood samples were irradiated at three different doses, 1.8, 0.4 and 0 Gy (samples A, C and B) with 4-MV X-rays at 0.5 Gy min
-1 , and sent to the participant laboratories. Each laboratory was requested to blindly analyze 500 cells per sample and to report the observed frequency of dicentric chromosomes per metaphase and the corresponding estimated dose., Results: This ILC demonstrates that blood samples can be successfully distributed among laboratories worldwide to perform biological dosimetry in case of a mass casualty event. Having achieved a substantial harmonization in multiple areas among the RENEB laboratories issues were identified with the available statistical tools, which are not capable to advantageously exploit the richness of results of a large ILCs. Even though Z - and U -tests are accepted methods for biodosimetry ILCs, setting the number of analyzed metaphases to 500 and establishing a tests' common threshold for all studied doses is inappropriate for evaluating laboratory performance. Another problem highlighted by this ILC is the issue of the dose-effect curve diversity. It clearly appears that, despite the initial advantage of including the scoring specificities of each laboratory, the lack of defined criteria for assessing the robustness of each laboratory's curve is a disadvantage for the 'one curve per laboratory' model., Conclusions: Based on our study, it seems relevant to develop tools better adapted to the collection and processing of results produced by the participant laboratories. We are confident that, after an initial harmonization phase reached by the RENEB laboratories, a new step toward a better optimization of the laboratory networks in biological dosimetry and associated ILC is on the way.- Published
- 2021
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48. Spontaneous community-acquired bacterial meningitis in adults admitted to the intensive care units in the Caribbean French West Indies: Unusual prevalence of Klebsiella pneumonia.
- Author
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Piednoir P, Clarac U, Rolle A, Bastian S, Gruel G, Martino F, Mehdaoui H, Valette M, Breurec S, and Carles M
- Subjects
- Aged, Bacterial Proteins genetics, Bacterial Proteins metabolism, Community-Acquired Infections epidemiology, Female, Humans, Intensive Care Units statistics & numerical data, Klebsiella Infections epidemiology, Klebsiella pneumoniae genetics, Klebsiella pneumoniae metabolism, Klebsiella pneumoniae pathogenicity, Male, Meningitis, Bacterial epidemiology, Middle Aged, Pneumonia epidemiology, Prevalence, Virulence, West Indies epidemiology, Community-Acquired Infections microbiology, Klebsiella Infections microbiology, Klebsiella pneumoniae isolation & purification, Meningitis, Bacterial microbiology, Pneumonia microbiology
- Abstract
An unusual prevalence of Klebsiella pneumoniae (24%) was observed in 25 adults admitted to the intensive care units of two University Hospitals in the French West Indies, for spontaneous community-acquired bacterial meningitis. All tested isolates had several prominent features of hypervirulent isolates, including rmpa and iuc genes, K1 or K2 capsular serotypes., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
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49. Antimicrobial Resistance in Wildlife in Guadeloupe (French West Indies): Distribution of a Single bla CTX-M-1 /IncI1/ST3 Plasmid Among Humans and Wild Animals.
- Author
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Guyomard-Rabenirina S, Reynaud Y, Pot M, Albina E, Couvin D, Ducat C, Gruel G, Ferdinand S, Legreneur P, Le Hello S, Malpote E, Sadikalay S, Talarmin A, and Breurec S
- Abstract
Limited data are available on the contribution of wildlife to the spread of antibacterial resistance. We determined the prevalence of resistance to antibiotics in Escherichia coli isolates collected from wild animals in 2013 and 2014 and the genetic basis for resistance to third-generation cephalosporin in Guadeloupe. We recovered 52 antibiotic-resistant (AR) E. coli strains from 48 of the 884 (5.4%) wild animals tested (46 iguanas, 181 birds, 289 anoles, and 368 rodents at 163 sampling sites). Rodents had higher rates of carriage ( n = 38, 10.3%) than reptiles and birds (2.4% and 1.1%, respectively, p < 0.001). A significant association ( p < 0.001) was found between the degree of anthropization and the frequency of AR E. coli carriage for all species. The carriage rate of ciprofloxacin- and cefotaxime-resistant isolates was 0.7% (6/884) and 1.5% (13/884), respectively. Most (65.4%) AR E. coli were multi-drug resistant, and the prevalence of extended-spectrum beta-lactamase (ESBL)-producing E. coli was low ( n = 7, 0.8%) in all species. Eight ESBL-producing E. coli were recovered, two genetically unrelated isolates being found in one bird. These isolates and 20 human invasive ESBL E. coli isolates collected in Guadeloupe during the same period were investigated by whole genome sequencing. bla
CTX-M-1 was the only ESBL gene shared by three animal classes (humans, n = 2; birds, n = 2; rodents, n = 2). The blaCTX-M-1 gene and most of the antimicrobial resistance genes were present in a large conjugative IncI1 plasmid that was highly similar (>99% nucleotide identity) to ESBL-carrying plasmids found in several countries in Europe and in Australia. Although the prevalence of ESBL-producing E. coli isolates was very low in wild animals, it is of concern that the well-conserved IncI1 plasmid-carrying blaCTX-M-1 is widespread and occurs in various E. coli strains from animals and humans., (Copyright © 2020 Guyomard-Rabenirina, Reynaud, Pot, Albina, Couvin, Ducat, Gruel, Ferdinand, Legreneur, Le Hello, Malpote, Sadikalay, Talarmin and Breurec.)- Published
- 2020
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50. Assessment of Radio-Induced Damage in Endothelial Cells Irradiated with 40 kVp, 220 kVp, and 4 MV X-rays by Means of Micro and Nanodosimetric Calculations.
- Author
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Tang N, Bueno M, Meylan S, Perrot Y, Tran HN, Freneau A, Dos Santos M, Vaurijoux A, Gruel G, Bernal MA, Bordage MC, Emfietzoglou D, Francis Z, Guatelli S, Ivanchenko V, Karamitros M, Kyriakou I, Shin WG, Incerti S, and Villagrasa C
- Subjects
- Animals, Dose-Response Relationship, Radiation, Euchromatin pathology, Heterochromatin pathology, Human Umbilical Vein Endothelial Cells pathology, Humans, Monte Carlo Method, X-Rays adverse effects, DNA Damage, Euchromatin metabolism, Heterochromatin metabolism, Human Umbilical Vein Endothelial Cells metabolism, Radiation Injuries, Experimental metabolism
- Abstract
The objective of this work was to study the differences in terms of early biological effects that might exist between different X-rays energies by using a mechanistic approach. To this end, radiobiological experiments exposing cell monolayers to three X-ray energies were performed in order to assess the yields of early DNA damage, in particular of double-strand breaks (DSBs). The simulation of these irradiations was set in order to understand the differences in the obtained experimental results. Hence, simulated results in terms of microdosimetric spectra and early DSB induction were analyzed and compared to the experimental data. Human umbilical vein endothelial cells (HUVECs) were irradiated with 40, 220 kVp, and 4 MV X-rays. The Geant4 Monte Carlo simulation toolkit and its extension Geant4-DNA were used for the simulations. Microdosimetric calculations aiming to determine possible differences in the variability of the energy absorbed by the irradiated cell population for those photon spectra were performed on 10,000 endothelial cell nuclei representing a cell monolayer. Nanodosimetric simulations were also carried out using a computation chain that allowed the simulation of physical, physico-chemical, and chemical stages on a single realistic endothelial cell nucleus model including both heterochromatin and euchromatin. DNA damage was scored in terms of yields of prompt DSBs per Gray (Gy) and per giga (10
9 ) base pair (Gbp) and DSB complexity was derived in order to be compared to experimental data expressed as numbers of histone variant H2AX (γ-H2AX) foci per cell. The calculated microdosimetric spread in the irradiated cell population was similar when comparing between 40 and 220 kVp X-rays and higher when comparing with 4 MV X-rays. Simulated yields of induced DSB/Gy/Gbp were found to be equivalent to those for 40 and 220 kVp but larger than those for 4 MV, resulting in a relative biological effectiveness (RBE) of 1.3. Additionally, DSB complexity was similar between the considered photon spectra. Simulated results were in good agreement with experimental data obtained by IRSN (Institut de radioprotection et de sûreté nucléaire) radiobiologists. Despite differences in photon energy, few differences were observed when comparing between 40 and 220 kVp X-rays in microdosimetric and nanodosimetric calculations. Nevertheless, variations were observed when comparing between 40/220 kVp and 4 MV X-rays. Thanks to the simulation results, these variations were able to be explained by the differences in the production of secondary electrons with energies below 10 keV.- Published
- 2019
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