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2. Development of a high-performance anesthesia ventilator for research in small animals.

Author

Popoiu CM, Burian CA, Paunescu V, Boia E, Arghirescu S, Muntean DM, and Ordodi VL

Subjects
Animals, Monitoring, Physiologic, Rodentia, Anesthesiology instrumentation, Research instrumentation, Respiration, Artificial instrumentation, Ventilators, Mechanical
Abstract

Introduction: Small animal models are used extensively in basic research because of their low cost and possibility to mimic several human pathologies. These models are used to either analyze the underlying mechanisms and/or assess therapeutic approaches. In this respect, gentle and safe artificial ventilation is mandatory, especially for prolonged experimental procedures that require the survival of the animals. The aim of the present paper was to develop and validate a high-performance anesthesia ventilator for small animals., Methods: A pressure-controlled ventilator with assisted ventilation and deep breath modulated on a scheduled basis and a PEEP facility for an improved anesthetic management was developed. Parameters of acid-base balance and arterial blood gases were measured initially at the end of arterial catheterization and monitored throughout the experiment., Results: Our data show the following average values (mmHg) for pO2: 440 +/- 45 (initial), 378 +/- 24 (2 h), 373 +/- 22 (4 h), and 375 +/- 28 (6 h) and for pCO2: 35 +/- 3 (initial), 34 +/- 5 (2 h), 38 +/- 5 (4 h), and 40 +/- 6 (6 h), respectively., Conclusions: We describe the procedure for the manufacture of a reliable, high-performance anesthesia ventilator that facilitates recovery of spontaneous respiration at animal arousal with preservation of normal blood gases values and no damage to the lungs.

Published
2014
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3. Inhibition of angiogenesis and inflammation by an extract of red clover (Trifolium pratense L.)

Author

Krenn, L. and Paper, D.H.

Subjects
Inflammation -- Genetic aspects -- Care and treatment -- Research, Neovascularization -- Control -- Research, Materia medica, Vegetable -- Usage -- Health aspects -- Chemical properties -- Research, Red clover -- Usage -- Health aspects -- Chemical properties -- Research, Plant extracts -- Usage -- Health aspects -- Chemical properties -- Research, Biological sciences, Health, Science and technology, Control, Care and treatment, Usage, Chemical properties, Genetic aspects, Research, Health aspects
Abstract

ABSTRACT Antiangiogenic compounds are gaining more and more interest as a new approach in the prevention and treatment of cancer and inflammatory diseases. The objective of this study was the [...]

Published
2009
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4. Editorial Preface.

Author

Paper, David and Ugray, Zsolt

Subjects
CHANGE management, RESEARCH, MANAGEMENT information systems, INFORMATION technology research
Abstract

The authors reflect on change management research. They introduce the two major schools of thought surrounding change management research and its coverage in the management information system (MIS) literature. They discuss the lack of direction inherent in change management research and the most likely reasons for it. They also present what they believe to be a viable solution to the paucity of change research literature currently published in the MIS field.

Published
2008

5. The challenge of West Nile virus in Europe: knowledge gaps and research priorities

Author

Sebastian Ulbert, Norbert Nowotny, Ana Moreno, Luisa Barzon, N. Pardigon, Penelope Koraka, Antonio Tenorio, Miguel Ángel Jiménez-Clavero, Jordi Figuerola, Paolo Cordioli, Niek N. Sanders, Byron E. E. Martina, Annapaola Rizzoli, Fondazione Edmund Mach - Edmund Mach Foundation [Italie] (FEM), Centro de Investigacion en Sanidad Animal (INIA-CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA), Universita degli Studi di Padova, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna 'Bruno Ubertini' (IZSLER), Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Veterinary Medicine [Vienna] (Vetmeduni), Sultan Qaboos University (SQU), Institut Pasteur [Paris], Universiteit Gent = Ghent University [Belgium] (UGENT), Fraunhofer Institute for Cell Therapy and Immunology (Fraunhofer IZI), Fraunhofer (Fraunhofer-Gesellschaft), Instituto de Salud Carlos III [Madrid] (ISC), This paper is the product of a cooperative action promoted by the Coordinators and delegates of the EU funded projects on West Nile virus under the 7th European Programme, in particular the EuroWestNile project (www.eurowestnile.org, GA n. 261391), the EDENext project (www.edenext.eu , GA n. 261504) the Wings project (www.west-nile-shield-project.eu , GA n. 261426), and the Vectorie project (www.vectorie.eu , GA n. 261466). This study was partially funded by EU grant FP7-261504 EDENext and is catalogued by the EDENext Steering Committee as EDENext 142 (http://www.edenext.eu). AR was partially funded by the Autonomous Province of Trento grant LExEM (http://www.lexem.eu). The contents of this publication are the sole responsibility of the authors and don't necessarily reflect the views of the European Commission., This paper is dedicated to the memory of our wonderful colleague and friend, Dr Paolo Cordioli, who recently passed away. We thank the European Centre for Disease Prevention and Control (ECDC) for supporting this initiative and for promoting a stronger integration between public health and research in Europe. We also thank Dr Jolanta Kolodziejek of the Institute of Virology, University of Veterinary Medicine Vienna for establishing the phylogenetic trees and Matteo Marcantonio of the GIS/RS platform at the Edmund Mach Foundation for preparing the map in Figure 1, European Project: 261391,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EUROWESTNILE(2011), European Project: 261504,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EDENEXT(2011), European Project: 261426,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,WINGS(2011), European Project: 261466,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,VECTORIE(2010), Virology, Università degli Studi di Padova = University of Padua (Unipd), Institut Pasteur [Paris] (IP), Universiteit Gent = Ghent University (UGENT), and Publica

Subjects
Health Knowledge, Attitudes, Practice, Veterinary medicine, Economic growth, WNV STRAINS, Epidemiology, viruses, MESH: Health Knowledge, Attitudes, Practice, medicine.disease_cause, Disease Outbreaks, EXPERIMENTAL-INFECTION, ENVELOPE PROTEIN, Neuroinvasive disease, Medicine and Health Sciences, MESH: Genetic Variation, MESH: Disease Outbreaks, MESH: Phylogeny, Phylogeny, media_common, EARLY WARNING SYSTEM, biology, SUBSTITUTION, AMINO-ACID, 3. Good health, Europe, MESH: Research, Geography, Population Surveillance, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, West Nile virus, SPARROWS PASSER-DOMESTICUS, media_common.quotation_subject, Ecology (disciplines), MESH: Population Surveillance, SDG 3 - Good Health and Well-being, Virology, medicine, Humans, media_common.cataloged_instance, Veterinary Sciences, European union, TIME RT-PCR, Settore VET/06 - PARASSITOLOGIA E MALATTIE PARASSITARIE DEGLI ANIMALI, MESH: West Nile virus, MESH: West Nile Fever, MESH: Humans, Research, LINEAGE 1 STRAIN, Public Health, Environmental and Occupational Health, Genetic Variation, Outbreak, biology.organism_classification, USUTU VIRUS, Early warning system, MESH: Europe, CULEX-PIPIENS MOSQUITOS, Usutu virus, West Nile Fever, Diversity (politics)
Abstract

West Nile virus (WNV) is continuously spreading across Europe, and other continents, i.e. North and South America and many other regions of the world. Despite the overall sporadic nature of outbreaks with cases of West Nile neuroinvasive disease (WNND) in Europe, the spillover events have increased and the virus has been introduced into new areas. The high genetic diversity of the virus, with remarkable phenotypic variation, and its endemic circulation in several countries, require an intensification of the integrated and multidisciplinary research efforts built under the 7th Framework Programme of the European Union (FP7). It is important to better clarify several aspects of WNV circulation in Europe, including its ecology, genomic diversity, pathogenicity, transmissibility, diagnosis and control options, under different environmental and socio-economic scenarios. Identifying WNV endemic as well as infection-free areas is becoming a need for the development of human vaccines and therapeutics and the application of blood and organs safety regulations. This review, produced as a joint initiative among European experts and based on analysis of 118 scientific papers published between 2004 and 2014, provides the state of knowledge on WNV and highlights the existing knowledge and research gaps that need to be addressed with high priority in Europe and neighbouring countries.

Published
2015

6. Family, social and cultural determinants of long-lasting insecticidal net (LLIN) use in Madagascar: secondary analysis of three qualitative studies focused on children aged 5–15 years

Author

Andry Andrianasolo, Ammy Fiadanana Njatosoa, Chiarella Mattern, Bakoly Rahaivondrafahitra, Christophe Rogier, Mauricette Andriamananjara, Aina Harimanana, Thomas Kesteman, Dolorès Pourette, Elliot Rakotomanana, Jocelyn Razafindrakoto, Emma Raboanary, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), Unité de Recherche sur le Paludisme [Antananarivo, Madagascar], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Oxford University Clinical Research Unit [Hanoi] (OUCRU), Population Services International Madagascar [Antananarivo], Population Services International [Washington], Ministère de la Santé Publique [Antananarivo, Madagascar], U.S. President’s Malaria Initiative [Antananarivo] (PMI), U.S. President's Malaria Initiative [Atlanta, GA,], Institut international des sciences sociales [Antananarivo] (IISS), Primum Vitare, The publication process of this paper has been funded by USAID through the Research, Innovation, Surveillance and Evaluation (RISE) programme., Institut de Recherche pour le Développement (IRD), and Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité)

Subjects
Male, medicine.medical_specialty, Mosquito Control, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, LLIN use, 030231 tropical medicine, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Ethnic group, Qualitative property, [SHS]Humanities and Social Sciences, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Environmental health, parasitic diseases, medicine, Madagascar, Humans, lcsh:RC109-216, 030212 general & internal medicine, Children over five, Insecticide-Treated Bednets, Child, Disease burden, Research, Public health, [SHS.ANTHRO-SE]Humanities and Social Sciences/Social Anthropology and ethnology, medicine.disease, 3. Good health, Malaria, Infectious Diseases, Geography, Child, Preschool, Mosquito net, Female, Parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Thematic analysis, Sociocultural factors, Qualitative research
Abstract

BackgroundAlthough it is accepted that long-lasting insecticidal net (LLIN) use is an effective means to prevent malaria, children aged 5 to 15 years do not appear to be sufficiently protected in Madagascar; the malaria prevalence is highest in this age group. The purpose of this research is to summarize recent qualitative studies describing LLIN use among the Malagasy people with a focus on children aged 5–15 years.MethodsQualitative data from three studies on malaria conducted between 2012 and 2016 in 10 districts of Madagascar were analysed. These studies cover all malaria epidemiological profiles and 10 of the 18 existing ethnic groups in Madagascar. A thematic analysis was conducted on the collected data from semi-structured interviews, direct observation data, and informal interviews.ResultsA total of 192 semi-structured interviews were conducted. LLINs are generally perceived positively because they protect the health and well-being of users. However, regional representations of mosquito nets may contribute to LLIN lower use by children over 5 years of age including the association between married status and LLIN use, which leads to the refusal of unmarried young men to sleep under LLINs; the custom of covering the dead with a mosquito net, which leads to fear of LLIN use; and taboos governing sleeping spaces for siblings of opposite sexes, which leads to LLIN shortages in households. Children under 5 years of age are known to be the most vulnerable age group for acquiring malaria and, therefore, are prioritized for LLIN use when there are limited supplies in households. In contrast, children over 5 years of age, who are perceived to be at less risk for malaria, often sleep without LLINs.ConclusionsPerceptions, social practices and regional beliefs regarding LLINs and vulnerability to malaria contribute to the nonuse of LLINs among children over 5 years of age in Madagascar. Modifying LLIN policies to account for these factors may increase LLIN use in this age group and reduce disease burden.

Published
2021

7. MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era

Author

Elisabeth Sanchez-Padilla, Nazir Ahmed Ismail, Thomas Kohl, Christian Utpatel, Patrick Beckert, Stefan Niemann, Claudio U. Köser, Harald Hoffmann, Sönke Andres, Robin M. Warren, Bouke C. de Jong, Marisa Klopper, Matthias Merker, Florian P. Maurer, Shaheed V. Omar, Katharina Kranzer, Maryline Bonnet, Bernhard Kerschberger, Viola Dreyer, Ivan Barilar, Elisa Ardizzoni, Birgit Schramm, Gugu Maphalala, Forschungszentrum Borstel - Research Center Borstel, German Center for Infection Research (DZIF), Heidelberg University, Epicentre [Paris] [Médecins Sans Frontières], University of Cambridge [UK] (CAM), National Institute for Communicable Diseases [Johannesburg] (NICD), University of Pretoria [South Africa], University of the Witwatersrand [Johannesburg] (WITS), Stellenbosch University, Institute of Tropical Medicine [Antwerp] (ITM), London School of Hygiene and Tropical Medicine (LSHTM), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious and Tropical Diseases Department [Montpellier], Institut de Recherche pour le Développement (IRD)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Namibia (UNAM), Parts of this work have been supported by the European Union TB-PAN-NET (FP7-223681) project, by Médecins Sans Frontières-Switzerland, and by German Center for Infection Research, Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germanys Excellence Strategy – EXC 2167, and Leibniz Science Campus Evolutionary Medicine of the LUNG (EvoLUNG). The funders had no role in the study design, in the collection, analysis, and interpretation of the data, in the writing of the report, and in the decision to submit the paper for publication., European Project: 223681,EC:FP7:HEALTH,FP7-HEALTH-2007-B,TB PAN-NET(2009), Niemann, Stefan [0000-0002-6604-0684], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, MESH: Mycobacterium tuberculosis, Antitubercular Agents, Drug resistance, Multidrug resistance, Disease Outbreaks, Clofazimine, chemistry.chemical_compound, Tuberculosis, Multidrug-Resistant, MESH: Disease Outbreaks, Diarylquinolines, MESH: Bacterial Proteins, Genetics (clinical), MESH: Microbial Sensitivity Tests, Resistance mutation, MESH: Diarylquinolines, Mycobacterium tuberculosis complex, Molecular Medicine, medicine.drug, MESH: Mutation, Tuberculosis, 030106 microbiology, Microbial Sensitivity Tests, Biology, 03 medical and health sciences, Bacterial Proteins, MESH: Eswatini, Genetics, medicine, Humans, Molecular Biology, MESH: Tuberculosis, Multidrug-Resistant, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Diagnostice escape, Research, MESH: Clone Cells, Resistance evolution, Treatment escape, Mycobacterium tuberculosis, rpoB, medicine.disease, biology.organism_classification, MESH: Antitubercular Agents, Virology, Clone Cells, Multiple drug resistance, MDR outbreak strains, 030104 developmental biology, chemistry, Treatment failure, Mutation, Bedaquiline, Eswatini
Abstract

Background Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini. Methods We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009–2010; (2) MDR strains from the Nhlangano region, 2014–2017). Results MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987–1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2. Conclusion The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently.

Published
2020

8. Current use of inotropes in circulatory shock

Author

Michael R. Pinsky, Maria Cronhjort, Thomas Kaufmann, Rupert M Pearse, Ludhmila Abrahão Hajjar, Daniel A. Reuter, Jean Louis Vincent, Daniel De Backer, Martin W. Dünser, Maurizio Cecconi, Xavier Monnet, Iwan C. C. van der Horst, Vanina Siham Kanoore Edul, Bernard Cholley, Claude Martin, Thomas Scheeren, Yasser Sakr, Philippe Vignon, Didier Payen, Olfa Hamzaoui, Bernd Saugel, E. Christiaan Boerma, Pierre Squara, Alexandre Mebazaa, Geert Koster, Djillali Annane, Andrea Morelli, Arnaldo Dubin, Marc Leone, Pierre Asfar, Mervyn Singer, Anthony C. Gordon, Jan Bakker, Antoine Vieillard-Baron, Giovanni Landoni, Michael Sander, Michelle S Chew, Jean-Louis Teboul, Simon T. Vistisen, Glenn Hernandez, Peter Radermacher, Jacques Duranteau, Bruno Levy, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), RS: Carim - V04 Surgical intervention, Intensive Care, MUMC+: MA Medische Staf IC (9), MUMC+: MA Intensive Care (3), University of Groningen [Groningen], University Medical Center Groningen [Groningen] (UMCG), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Columbia University Medical Center (CUMC), Columbia University [New York], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hôpital Raymond Poincaré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Medical Centre Leeuwarden, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Linköping University (LIU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Karolinska Institutet [Stockholm], Centre Hospitalier Interrégional Edith Cavell (CHIREC), Universidad Nacional de la Plata [Argentine] (UNLP), Johannes Kepler University Linz [Linz] (JKU), Kepler University Hospital, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Imperial College London, Universidade de São Paulo = University of São Paulo (USP), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pontificia Universidad Católica de Chile (UC), Hospital Juan A. Fernandez [Buenos Aires, Argentina], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Hôpital Nord [CHU - APHM], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département d’Anesthésie-Réanimation-SMUR [Hôpital Lariboisière], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Centre de Référence de l’Hypertension Pulmonaire Sévère [CHU Le Kremlin Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], William Harvey Research Institute, Barts and the London Medical School, Queen Mary University of London (QMUL), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Universitätsklinikum Ulm - University Hospital of Ulm, University Medical Center Rostock, Jena University Hospital [Jena], Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University College of London [London] (UCL), Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Université libre de Bruxelles (ULB), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Aarhus University Hospital, European Society of Intensive Care Medicine, ESICM, This work has received the endorsement of the European Society of Intensive Care Medicine. The authors would like to thank Hannah Wunsch and Anders Perner, who provided their expertise as experts but abstained from being listed as co-author of this paper., HAL UVSQ, Équipe, NIHR, Scheeren, T. W. L., Bakker, J., Kaufmann, T., Annane, D., Asfar, P., Boerma, E. C., Cecconi, M., Chew, M. S., Cholley, B., Cronhjort, M., De Backer, D., Dubin, A., Dunser, M. W., Duranteau, J., Gordon, A. C., Hajjar, L. A., Hamzaoui, O., Hernandez, G., Kanoore Edul, V., Koster, G., Landoni, G., Leone, M., Levy, B., Martin, C., Mebazaa, A., Monnet, X., Morelli, A., Payen, D., Pearse, R. M., Pinsky, M. R., Radermacher, P., Reuter, D. A., Sakr, Y., Sander, M., Saugel, B., Singer, M., Squara, P., Vieillard-Baron, A., Vignon, P., Vincent, J. -L., van der Horst, I. C. C., Vistisen, S. T., and Teboul, J. -L.

Subjects
Inotrope, PDE-inhibitors, Levosimendan, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, GUIDELINES, 0302 clinical medicine, Catecholamines, CARDIAC-OUTPUT SYNDROME, Septic shock, Inotropes, Cardiogenic shock, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Acute circulatory failure, 3. Good health, [SDV] Life Sciences [q-bio], Shock (circulatory), Sepsis, Resuscitation, Vasoactive agents, Cardiac output, medicine.symptom, Life Sciences & Biomedicine, CRITICALLY-ILL PATIENTS, medicine.drug, medicine.medical_specialty, Anestesi och intensivvård, Medicina, Context (language use), VASOPRESSORS, 1117 Public Health and Health Services, 03 medical and health sciences, Critical Care Medicine, acute circulatory failure, cardiac output, cardiogenic shock, catecholamines, inotropes, levosimendan, resuscitation, sepsis, septic shock, vasoactive agents, General & Internal Medicine, Anesthesiology, medicine, Intensive care medicine, METAANALYSIS, Science & Technology, Anesthesiology and Intensive Care, business.industry, Research, 1103 Clinical Sciences, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Guideline, medicine.disease, DYSFUNCTION, CARDIOGENIC-SHOCK, Dobutamine, business
Abstract

Background: Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. Results: A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81–90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement). Conclusion: Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes., La lista completa de autores que integran el documento puede consultarse en el archivo., Facultad de Ciencias Médicas

Published
2020

9. Variation in Anopheles distribution and predictors of malaria infection risk across regions of Madagascar

Author

Marcia C. Castro, Gauthier N. Emile, Romain Girod, Christopher D. Golden, Benjamin L. Rice, Hervet J. Randriamady, Nicholas J. Arisco, Luciano Michaël Tantely, Harvard T.H. Chan School of Public Health, Harvard University [Cambridge], Unité d'Entomologie Médicale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Madagascar Health and Environmental Research [Maroantsetra, Madagascar] (MAHERY), and We are grateful for the support from the United States Agency for International Development (Grant AID-FFP-A-14-00,008) implemented by Catholic Relief Services (CRS) in consortium with four local implementing partners in Madagascar. The views and opinions expressed in this paper are those of the authors and not necessarily the views and opinions of the United States Agency for International Development. GeoStore funds provided by Airbus Defense & Space (Grant AH08211501).

Subjects
Male, Environmental change, Range (biology), [SDV]Life Sciences [q-bio], Distribution (economics), MESH: Madagascar, 0302 clinical medicine, MESH: Aged, 80 and over, Risk Factors, Planetary health, MESH: Demography, MESH: Risk Factors, MESH: Child, Disease ecology, MESH: Animals, MESH: Ecosystem, 030212 general & internal medicine, Child, Land use change, Aged, 80 and over, MESH: Aged, 2. Zero hunger, MESH: Middle Aged, biology, Multilevel model, Anopheles, Middle Aged, MESH: Infant, Infectious Diseases, Geography, MESH: Young Adult, Child, Preschool, Female, MESH: Mosquito Vectors, Adult, MESH: Socioeconomic Factors, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, 030231 tropical medicine, MESH: Malaria, Mosquito Vectors, lcsh:Infectious and parasitic diseases, MESH: Anopheles, 03 medical and health sciences, Young Adult, MESH: Cross-Sectional Studies, Deforestation, Environmental health, Vector-borne disease, parasitic diseases, medicine, Madagascar, Animals, Humans, lcsh:RC109-216, Socioeconomic status, Ecosystem, Aged, Demography, MESH: Adolescent, MESH: Humans, business.industry, Research, MESH: Child, Preschool, MESH: Animal Distribution, Infant, MESH: Adult, 15. Life on land, medicine.disease, biology.organism_classification, MESH: Male, Malaria, Cross-Sectional Studies, Socioeconomic Factors, Parasitology, business, Animal Distribution, MESH: Female
Abstract

Background Deforestation and land use change is widespread in Madagascar, altering local ecosystems and creating opportunities for disease vectors, such as the Anopheles mosquito, to proliferate and more easily reach vulnerable, rural populations. Knowledge of risk factors associated with malaria infections is growing globally, but these associations remain understudied across Madagascar’s diverse ecosystems experiencing rapid environmental change. This study aims to uncover socioeconomic, demographic, and ecological risk factors for malaria infection across regions through analysis of a large, cross-sectional dataset. Methods The objectives were to assess (1) the ecological correlates of malaria vector breeding through larval surveys, and (2) the socioeconomic, demographic, and ecological risk factors for malaria infection in four ecologically distinct regions of rural Madagascar. Risk factors were determined using multilevel models for the four regions included in the study. Results The presence of aquatic agriculture (both within and surrounding communities) is the strongest predictive factor of habitats containing Anopheles larvae across all regions. Ecological and socioeconomic risk factors for malaria infection vary dramatically across study regions and range in their complexity. Conclusions Risk factors for malaria transmission differ dramatically across regions of Madagascar. These results may help stratifying current malaria control efforts in Madagascar beyond the scope of existing interventions.

Published
2020

10. Plasmodium falciparum merozoite surface antigen-specific cytophilic IgG and control of malaria infection in a Beninese birth cohort

Author

Gregory Nuel, Paulin Sonon, Adrian J. F. Luty, Gilles Cottrell, Ibrahim Sadissou, André Garcia, Roukiyath Amoussa, Tania d’Almeida, Ambaliou Sanni, Shirley Longacre, D. Courtin, Aziz Bouraima, Florence Migot-Nabias, Rafiou Adamou, Célia Dechavanne, Michael Theisen, Kabirou Moutairou, Edmond J. Remarque, Achille Massougbodji, Jacqueline Milet, Agnès Le Port, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Biochimie et de Biologie Moléculaire (Université d'Abomey Calavi, Cotonou, Bénin) (LBBM), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Universidade de São Paulo = University of São Paulo (USP), Statens Serum Institut [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH), Biomedical Primate Research Centre [Rijswijk] (BPRC), Vaccinologie Parasitaire, Institut Pasteur [Paris] (IP), Laboratoire de Probabilités, Statistique et Modélisation (LPSM (UMR_8001)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), This paper describes work undertaken in the context of the PALNOUGENENV, 'Paludisme-Nouvéau-né-Génétique et Environnement', a project supported by Agence Nationale pour la Recherche (projet SEST2006/040/001), Ministère des Affaires Etrangères français (projet REFS No.2006-22) for their financial support. This publication was made possible through the Faculté des Sciences de la Santé (FSS), the Institut des Sciences Biomédicales Appliquées de Cotonou (ISBA), the Programme National de Lutte contre le Paludisme (PNLP) for their institutional support and the Institut de Recherche et de Développment AIRD-ARTS and Ambassade de France à Cotonou (SCAC) for their PhD scholarships to Rafiou ADAMOU and Ibrahim SADISSOU., ANR-06-SEST-0040,PALNOURGENENV,survenue des premières infections palustres chez le noueau-né : déterminants génétiques, biologiques et environnementaux(2006), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), University of Abomey Calavi (UAC), University of São Paulo (USP), University of Copenhagen = Københavns Universitet (KU), Institut Pasteur [Paris], and Laboratoire de Probabilités, Statistiques et Modélisations (LPSM (UMR_8001))

Subjects
Male, Protozoan Proteins, Antibodies, Protozoan, MESH: Malaria, Falciparum/immunology, 0302 clinical medicine, MESH: Pregnancy, MESH: Antigens, Protozoan/immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pregnancy, Surveys and Questionnaires, Benin, 030212 general & internal medicine, MESH: Plasmodium falciparum/immunology, Longitudinal Studies, Malaria, Falciparum, MESH: Longitudinal Studies, MESH: Antibodies, Protozoan/blood, biology, Malaria vaccine, MESH: Infant, Newborn, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Infant, 3. Good health, Infectious Diseases, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Cytophilic IgG, Female, Merozoite vaccine candidate antigens, Antibody, medicine.symptom, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium falciparum, Context (language use), Antigens, Protozoan, Enzyme-Linked Immunosorbent Assay, Asymptomatic, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, MESH: Benin, Antigen, Immunity, parasitic diseases, medicine, Humans, lcsh:RC109-216, MESH: Surveys and Questionnaires, MESH: Humans, business.industry, Research, Infant, Newborn, Infant, biology.organism_classification, medicine.disease, MESH: Protozoan Proteins/immunology, MESH: Male, Malaria, Immunoglobulin G, Immunology, biology.protein, Parasitology, business, MESH: Immunoglobulin G/blood, MESH: Female
Abstract

BACKGROUND: Substantial evidence indicates that cytophilic IgG responses to Plasmodium falciparum merozoite antigens play a role in protection from malaria. The specific targets mediating immunity remain unclear. Evaluating antibody responses in infants naturally-exposed to malaria will allow to better understand the establishment of anti-malarial immunity and to contribute to a vaccine development by identifying the most appropriate merozoite candidate antigens.METHODS: The study was based on parasitological and clinical active follow-up of infants from birth to 18 months of age conducted in the Tori Bossito area of southern Benin. For 399 infants, plasma levels of cytophilic IgG antibodies with specificity for five asexual stage malaria vaccine candidate antigens were determined by ELISA in infants' peripheral blood at 6, 9, 12 and 15 months of age. Multivariate mixed logistic model was used to investigate the association between antibody levels and anti-malarial protection in the trimester following the IgG quantification. Moreover, the concentrations of merozoite antigen-specific IgG were compared between a group of infants apparently able to control asymptomatic malaria infection (CAIG) and a group of infants with no control of malaria infection (Control group (NCIG)). Protective effect of antibodies was also assessed after 15 months of malaria exposure with a Cox regression model adjusted on environmental risk.RESULTS: Cytophilic IgG responses to AMA1, MSP1, MSP2-3D7, MSP2-FC27, MSP3 and GLURP R2 were associated with increasing malarial infection risk in univariate analysis. The multivariate mixed model showed that IgG1 and IgG3 to AMA1 were associated with an increased risk of malarial infection. However infants from CAIG (n = 53) had significantly higher AMA1-, MSP2-FC27-, MSP3-specific IgG1 and AMA1-, MSP1-, MSP2-FC27-, MSP3 and GLURP-R2-specific IgG3 than those from NCIG (n = 183). The latter IgG responses were not associated with protection against clinical malaria in the whole cohort when protective effect is assessed after 15 months of malaria exposition.CONCLUSION: In this cohort, merozoite antigen-specific cytophilic IgG levels represent a marker of malaria exposure in infants from 6 to 18 months of age. However, infants with resolution of asymptomatic infection (CAIG) seem to have acquired naturally immunity against P. falciparum. This observation is encouraging in the context of the development of multitarget P. falciparum vaccines.

Published
2019

11. Current and future distribution of Aedes aegypti and Aedes albopictus (Diptera : Culicidae) in WHO Eastern Mediterranean Region

Author

Johannes Charlier, Ward Bryssinckx, Valérie De Waele, Frédéric Simard, Evans Buliva, Abdulhafid Hussain, Nhu Nguyen Tran Minh, Muhammad Mukhtar, David Roiz, Nabil Haddad, Ali Bouattour, Guy Hendrickx, Els Ducheyne, Osama Mahmoud, Mamunur Rahman Malik, Avia-GIS [Zoersel], WHO - Regional Office for the Eastern Mediterranean [Cairo, Egypt] (EMRO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université Libanaise, Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), Evolution des Systèmes Vectoriels (ESV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Ministry of Health Oman, Directorate of Malaria Control [Islamabad] (DoMC), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Ministry of Health and Human Services [Somalia], Vector Control Group (MIVEGEC-VCG), This work was supported by the WHO Regional Office for the Eastern Mediterranean. The work was supported partially by the project InvaCosts (ANR-14-CE02-0021-01). Field work in Lebanon was supported by the WHO National Bureau (LEB1409860)., We thank the numerous entomologists and health officers of the EMR who shared data with the WHO Regional Office for the Eastern Mediterranean. Ms. Barwa and Dr. Zayed are gratefully acknowledged for their technical assistance. We gratefully acknowledge the valuable input of the anonymous reviewers on the first version of this paper., ANR-14-CE02-0021,InvaCosts,Insectes envahissants et leurs couts pour la biodiversité, l'économie et la santé humaine(2014), and Regional Office for the Eastern Mediterranean [Cairo] (EMRO)

Subjects
0301 basic medicine, Species distribution, Distribution (economics), Geographic Mapping, Distribution, medicine.disease_cause, Population density, MESH: Mosquito Vectors, MESH: Yellow Fever/diagnosis, Dengue fever, Dengue, MESH: Aedes, 0302 clinical medicine, Aedes aegypti, Aedes, MESH: Animals, Chikungunya, MESH: Dengue/diagnosis, Surveillance, biology, Mediterranean Region, Aedes albopictus, Geography, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Yellow Fever/epidemiology, lcsh:R858-859.7, Yellow fever, Cartography, MESH: Forecasting, General Computer Science, 030231 tropical medicine, MESH: Dengue/epidemiology, Mosquito Vectors, lcsh:Computer applications to medicine. Medical informatics, World Health Organization, MESH: Mediterranean Region/epidemiology, 03 medical and health sciences, Zika, MESH: World Health Organization, Species Specificity, MESH: Geographic Mapping, Yellow Fever, medicine, MESH: Species Specificity, Animals, Humans, MESH: Humans, business.industry, Research, Public Health, Environmental and Occupational Health, 15. Life on land, medicine.disease, biology.organism_classification, General Business, Management and Accounting, Spatial model, 030104 developmental biology, Culicidae, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Culicidae, Forecasting
Abstract

Background Aedes-borne diseases as dengue, zika, chikungunya and yellow fever are an emerging problem worldwide, being transmitted by Aedes aegypti and Aedes albopictus. Lack of up to date information about the distribution of Aedes species hampers surveillance and control. Global databases have been compiled but these did not capture data in the WHO Eastern Mediterranean Region (EMR), and any models built using these datasets fail to identify highly suitable areas where one or both species may occur. The first objective of this study was therefore to update the existing Ae. aegypti (Linnaeus, 1762) and Ae. albopictus (Skuse, 1895) compendia and the second objective was to generate species distribution models targeted to the EMR. A final objective was to engage the WHO points of contacts within the region to provide feedback and hence validate all model outputs. Methods The Ae. aegypti and Ae. albopictus compendia provided by Kraemer et al. (Sci Data 2:150035, 2015; Dryad Digit Repos, 2015) were used as starting points. These datasets were extended with more recent species and disease data. In the next step, these sets were filtered using the Köppen–Geiger classification and the Mahalanobis distance. The occurrence data were supplemented with pseudo-absence data as input to Random Forests. The resulting suitability and maximum risk of establishment maps were combined into hard-classified maps per country for expert validation. Results The EMR datasets consisted of 1995 presence locations for Ae. aegypti and 2868 presence locations for Ae. albopictus. The resulting suitability maps indicated that there exist areas with high suitability and/or maximum risk of establishment for these disease vectors in contrast with previous model output. Precipitation and host availability, expressed as population density and night-time lights, were the most important variables for Ae. aegypti. Host availability was the most important predictor in case of Ae. albopictus. Internal validation was assessed geographically. External validation showed high agreement between the predicted maps and the experts’ extensive knowledge of the terrain. Conclusion Maps of distribution and maximum risk of establishment were created for Ae. aegypti and Ae. albopictus for the WHO EMR. These region-specific maps highlighted data gaps and these gaps will be filled using targeted monitoring and surveillance. This will increase the awareness and preparedness of the different countries for Aedes borne diseases. Electronic supplementary material The online version of this article (10.1186/s12942-018-0125-0) contains supplementary material, which is available to authorized users.

Published
2018

12. Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies

Author

Marie-Hélène Dizier, Rachel Nadif, Orianne Dumas, Amar J. Mehta, Ismaïl Ahmed, Jan-Paul Zock, Pascale Tubert-Bitter, Juan R. González, Medea Imboden, Emmanuelle Bouzigon, Ivan Curjuric, Deborah Jarvis, Florence Demenais, Marta Rava, Nicole Probst-Hensch, Nicole Le Moual, Manolis Kogevinas, Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Spanish National Cancer Research Center (CNIO), Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidemiology & Public Health [Basel, Switzerland], Swiss Tropical and Public Health Institute [Basel]-Medical School University of Basel, Department of Environmental Health [Boston, USA], Harvard School of Public Health, Centre for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF), Respiratory Epidemiology and Public Health Group [London, U.K.], National Heart and Lung Institute-Imperial College London, U946, Fondation Jean Dausset/CEPH, Institut National de la Santé et de la Recherche Médicale (INSERM), The genotyping of all three studies was funded by the French National Agency of Research (ANR-PRSP 2009: IAGO), and by the European Commission (contract n° 018996) (GABRIEL) and the Wellcome Trust grant (WT 084703MA), both awarded to the GABRIEL consortium (a multidisciplinary study to identify the genetic and environmental causes of asthma in the European Community). EGEA: Research funded by the French Agency of health safety, environment and work (AFSSET, EST-09-15). SAPALDIA: The Swiss National Science Foundation (grants no 33CS30-148470/1, 33CSCO-134276/1, 33CSCO-108796, 324730_135673, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099, PMPDP3_129021/1, PMPDP3_141671/1), the Federal Office for the Environment, the Federal Office of Public Health, the Federal Office of Roads and Transport, the canton's government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Zürich, the Swiss Lung League, the canton's Lung League of Basel Stadt/ Basel Landschaft, Geneva, Ticino, Valais, Graubünden and Zurich, Stiftung ehemals Bündner Heilstätten, SUVA, Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics.ECRHS: The co-ordination of ECRHS II was supported by the European Commission, as part of their Quality of Life program. This work was also funded by the US National Institutes of Health (NIH grant 1R01HL062633) and the Carlos III Health Institute of the Spanish Ministry of Health and Consumption (FIS grant 01/3058). The following bodies funded the local studies in ECRHS II included in this paper: Albacete: Fondo de Investigaciones Santarias (FIS) (grant code: 97/0035-01, 99/0034-01 and 99/0034-02), Hospital Universitario de Albacete, Consejeria de Sanidad, Barcelona: SEPAR, Public Health Service (grant code: R01 HL62633-01), Fondo de Investigaciones Santarias (FIS) (grant code:97/0035-01, 99/0034-01 and 99/0034-02) CIRIT (grant code: 1999SGR 00241) Red Respira ISCII, Basel: Swiss National Science Foundation, Swiss Federal Office for Education & Science, Swiss National Accident Insurance Fund (SUVA), USC NIEHS Center grant 5P30 ES07048, Bergen: Norwegian Research Council, Norwegian Asthma & Allergy Association (NAAF), Glaxo Wellcome AS, Norway Research Fund, Erfurt: GSF-National Research Centre for Environment & Health, Deutsche Forschungsgemeinschaft (DFG) (grant code FR 1526/1-1), Galdakao: Basque Health Dept, Grenoble: Programme Hospitalier de Recherche Clinique-DRC de Grenoble 2000 no. 2610, Ministry of Health, Direction de la Recherche Clinique, Ministere de l'Emploi et de la Solidarite, Direction Generale de la Sante, CHU de Grenoble, Comite des Maladies Respiratoires de l’Isere, Hamburg: GSF-National Reasearch Centre for Environment & Health, Deutsche Forschungsgemeinschaft (DFG) (grant code MA 711/4-1), Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign), Huelva: Fondo de Investigaciones Santarias (FIS) (grant code: 97/0035-01, 99/0034-01 and 99/0034-02), Oviedo: Fondo de Investigaciones Santarias (FIS) (grant code: 97/0035-01, 99/0034-01 and 99/0034-02), Paris: Ministere de l'Emploi et de la Solidarite, Direction Generale de la Sante, UCB-Pharma (France), Aventis (France), Glaxo France, Programme Hospitalier de Recherche Clinique-DRC de Grenoble 2000 no. 2610, Ministry of Health, Direction de la Recherche Clinique, CHU de Grenoble, Tartu: Estonian Science Foundation, Umeå: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences & Allergy Research, Swedish Asthma & Allergy Foundation, Swedish Cancer & Allergy Foundation, Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences & Allergy Research, Swedish Asthma & Allergy Foundation, Swedish Cancer & Allergy Foundation., French National Agency of Research (Francia), Unión Europea. Comisión Europea, Wellcome Trust, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Imperial College London-National Heart and Lung Institute

Subjects
Male, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], 05 Environmental Sciences, Toxicology, 0302 clinical medicine, Adult onset asthma, Medicine, 030212 general & internal medicine, Lung function, Public, Environmental & Occupational Health, biology, CLEANING PRODUCTS, SWISS COHORT, NF-kappa B, Respiratory organs diseases, 11 Medical And Health Sciences, Middle Aged, Local study, 3. Good health, ENVIRONMENT INTERACTION, LUNG-FUNCTION, Europe, Occupational Diseases, Irritants, Female, Life Sciences & Biomedicine, Adult, GENETICS, Steering committee, Physical activity, Environmental Sciences & Ecology, OBSTRUCTIVE PULMONARY-DISEASE, Polymorphism, Single Nucleotide, Malalties de l'aparell respiratori, 03 medical and health sciences, Administrative support, Occupational Exposure, Cooperative group, Humans, GENOME-WIDE ASSOCIATION, Asma, Science & Technology, business.industry, Research, Public Health, Environmental and Occupational Health, AIR-POLLUTION, biology.organism_classification, Asthma, Molecular Weight, 030228 respiratory system, Pison, EMERGING ROLES, Particulate Matter, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, WORKPLACE, business, Humanities, Environmental Sciences
Abstract

BACKGROUND: The biological mechanisms by which cleaning products and disinfectants-an emerging risk factor-affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (G × E) may help identify new genes related to adult-onset asthma. OBJECTIVES: We identified interactions between genetic polymorphisms of a large set of genes involved in the response to oxidative stress and occupational exposures to low molecular weight (LMW) agents or irritants on adult-onset asthma. METHODS: Our data came from three large European cohorts: Epidemiological Family-based Study of the Genetics and Environment of Asthma (EGEA), Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), and European Community Respiratory Health Survey in Adults (ECRHS). A candidate pathway-based strategy identified 163 genes involved in the response to oxidative stress and potentially related to exposures to LMW agents/irritants. Occupational exposures were evaluated using an asthma job-exposure matrix and job-specific questionnaires for cleaners and healthcare workers. Logistic regression models were used to detect G × E interactions, adjusted for age, sex, and population ancestry, in 2,599 adults (mean age, 47 years; 60% women, 36% exposed, 18% asthmatics). p-Values were corrected for multiple comparisons. RESULTS: Ever exposure to LMW agents/irritants was associated with current adult-onset asthma [OR = 1.28 (95% CI: 1.04, 1.58)]. Eight single nucleotide polymorphism (SNP) by exposure interactions at five loci were found at p < 0.005: PLA2G4A (rs932476, chromosome 1), near PLA2R1 (rs2667026, chromosome 2), near RELA (rs931127, rs7949980, chromosome 11), PRKD1 (rs1958980, rs11847351, rs1958987, chromosome 14), and PRKCA (rs6504453, chromosome 17). Results were consistent across the three studies and after accounting for smoking. CONCLUSIONS: Using a pathway-based selection process, we identified novel genes potentially involved in adult asthma by interaction with occupational exposure. These genes play a role in the NF-κB pathway, which is involved in inflammation. Citation: Rava M, Ahmed I, Kogevinas M, Le Moual N, Bouzigon E, Curjuric I, Dizier MH, Dumas O, Gonzalez JR, Imboden M, Mehta AJ, Tubert-Bitter P, Zock JP, Jarvis D, Probst-Hensch NM, Demenais F, Nadif R. 2017. Genes interacting with occupational exposures to low molecular weight agents and irritants on adult-onset asthma in three European studies. Environ Health Perspect 125:207-214; http://dx.doi.org/10.1289/EHP376. We thank all study members and staff involved in data collections in each cohort: EGEA: We thank the Epidemiological Study on Genetics and Environment of Asthma (EGEA) cooperative group members as follows. Coordination: V. Siroux [epidemiology, principal investigator (PI) since 2013]; F. Demenais (genetics); I. Pin (clinical aspects); R. Nadif (biology); F. Kauffmann (PI 1992–2012). Respiratory epidemiology: Inserm U 700, Paris: M. Korobaeff (EGEA1), F. Neukirch (EGEA1); Inserm U 707, Paris: I. Annesi-Maesano (EGEA1–2); Inserm U1168 (ex-CESP/U 1018), Villejuif: F. Kauffmann, N. Le Moual, R. Nadif, M.P. Oryszczyn (EGEA1–2), R. Varraso; Inserm U 823, Grenoble: V. Siroux. Genetics: Inserm U 393, Paris: J. Feingold; Inserm U 946, Paris: E. Bouzigon, F. Demenais, M.H. Dizier; CNG, Evry: I. Gut (now CNAG, Barcelona, Spain), M. Lathrop (now McGill University, Montreal, Canada). Clinical centers: Grenoble: I. Pin, C. Pison; Lyon: D. Ecochard (EGEA1), F. Gormand, Y. Pacheco; Marseille: D. Charpin (EGEA1), D. Vervloet (EGEA1–2); Montpellier: J. Bousquet; Paris Cochin: A. Lockhart (EGEA1), R. Matran (now in Lille); Paris Necker: E. Paty (EGEA1–2), P. Scheinmann (EGEA1–2); Paris Trousseau: A. Grimfeld (EGEA1–2), J. Just. Data and quality management: Inserm ex-U155 (EGEA1): J. Hochez; Inserm U1168 (ex-CESP/U 1018), Villejuif: N. Le Moual; Inserm ex-U780: C. Ravault (EGEA1–2); Inserm ex-U794: N. Chateigner (EGEA1–2); Grenoble: J. Quentin-Ferran (EGEA1–2). SAPALDIA: We thank the team of the Swiss study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). Study directorate: N.M. Probst-Hensch (PI; e/g); T. Rochat (p), C. Schindler (s), N. Künzli (e/exp), J.M. Gaspoz (c). Scientific team: J.C. Barthélémy (c), W. Berger (g), R. Bettschart (p), A. Bircher (a), C. Brombach (n), P.O. Bridevaux (p), L. Burdet (p), D. Felber Dietrich (e), M. Frey (p), U. Frey (pd), M.W. Gerbase (p), D. Gold (e), E. de Groot (c), W. Karrer (p), F. Kronenberg (g), B. Martin (pa), A. Mehta (e), D. Miedinger (o), M. Pons (p), F. Roche (c), T. Rothe (p), P. Schmid- Grendelmeyer (a), D. Stolz (p), A. Schmidt-Trucksäss (pa), J. Schwartz (e), A. Turk (p), A. von Eckardstein (cc), E. Zemp Stutz (e). Scientific team at coordinating centers: M. Adam (e), I. Aguilera (exp), S. Brunner (s), D. Carballo (c), S. Caviezel (pa), I. Curjuric (e), A. Di Pascale (s), J. Dratva (e), R. Ducret (s), E. Dupuis Lozeron (s), M. Eeftens (exp), I. Eze (e), E. Fischer (g), M. Foraster (e), M. Germond (s), L. Grize (s), S. Hansen (e), A. Hensel (s), M. Imboden (g), A. Ineichen (exp), A. Jeong (g), D. Keidel (s), A. Kumar (g), N. Maire (s), A. Mehta (e), R. Meier (exp), E. Schaffner (s), T. Schikowski (e), M. Tsai (exp). Abbreviations: (a) allergology, (c) cardiology, (cc) clinical chemistry, (e) epide - miology, (exp) exposure, (g) genetic and molecular biology, (m) meteorology, (n) nutrition, (o) occupational health, (p) pneumology, (pa) physical activity, (pd) pediatrics, (s) statistics. The study could not have been done without the help of the study partici - pants, technical and administrative support and the medical teams and field workers at the local study sites. Local fieldworkers: Aarau: S. Brun, G. Giger, M. Sperisen, M. Stahel; Basel: C. Bürli, C. Dahler, N. Oertli, I. Harreh, F. Karrer, G. Novicic, N. Wyttenbacher; Davos: A. Saner, P. Senn, R. Winzeler; Geneva: F. Bonfils, B. Blicharz, C. Landolt, J. Rochat; Lugano: S. Boccia, E. Gehrig, M.T. Mandia, G. Solari, B. Viscardi; Montana: A.P. Bieri, C. Darioly, M. Maire; Payerne: F. Ding, P. Danieli, A. Vonnez; Wald: D. Bodmer, E. Hochs, R. Kunz, C. Meier, J. Rakic, U. Schafroth, A. Walder. Administrative staff: N. Bauer Ott, C. Gabriel, R. Gutknecht. ECRHS: The ECRHS data incorporated in this analysis would not have been available without the collaboration of the following individuals and their research teams. ECRHS Co-ordinating Centre. P. Burney, D. Jarvis, S. Chinn, J. Knox (ECRHS II), C. Luczynska†, J. Potts. Steering Committee for ECRHS II. P. Burney, D. Jarvis, S. Chinn, U. Ackermann-Liebrich, J.M. Anto, I. Cerveri, R. deMarco†, T. Gislason, J. Heinrich, C. Janson, N. Kunzli, B. Leynaert, F. Neukirch, J. Schouten, J. Sunyer; C. Svanes, P. Vermeire†, M. Wjst. Principal Investigators and Senior Scientific Teams for ECRHS II centers within this analysis: Estonia: Tartu (R. Jogi, A. Soon); France: Paris (F. Neukirch, B. Leynaert, R. Liard, M. Zureik), Grenoble (I. Pin, J. Ferran-Quentin); Germany: Erfurt (J. Heinrich, M. Wjst, C. Frye, I. Meyer), Hamburg (K. Richter, D. Nowak); Norway: Bergen (A. Gulsvik, E. Omenaas, C. Svanes, B. Laerum); Spain: Barcelona (J.M. Anto, J. Sunyer, M. Kogevinas, J.P. Zock, X. Basagana, A. Jaen, F. Burgos), Huelva (J. Maldonado, A. Pereira, J.L. Sanchez), Albacete (J. Martinez-Moratalla Rovira, E. Almar), Galdakao (N. Muniozguren, I. Urritia), Oviedo (F. Payo); Sweden: Uppsala (C. Janson, G. Boman, D. Norback, M. Gunnbjornsdottir), Umeå (E. Norrman, M. Soderberg, K. Franklin, B. Lundback, B. Forsberg, L. Nystrom); Switzerland: Basel (N. Kunzli, B. Dibbert, M. Hazenkamp, M. Brutsche, U. Ackermann-Liebrich); United Kingdom: Norwich (D. Jarvis, B. Harrison), Ipswich (D. Jarvis, R. Hall, D. Seaton). Sí

Published
2016

13. ICAM-2 regulates vascular permeability and N-cadherin localization through ezrin-radixin-moesin (ERM) proteins and Rac-1 signalling

Author

Nicola H. Dryden, Anna M. Randi, Valérie Amsellem, Roberta Martinelli, Justin C. Mason, Felicity N. E. Gavins, Graeme M. Birdsey, Patric Turowski, Dorian O. Haskard, Lourdes Osuna Almagro, BMC, Ed., Imperial College for Translational and Experimental Medicine, Imperial College London, Cell Biology, UCL Institute of Ophthalmology, Division of Brain Sciences, Imperial College London-Hammersmith Hospital, This paper was supported by grants from the British Heart Foundation and the European Community (NoE MAIN 502935), and British Heart Foundation

Subjects
rac1 GTP-Binding Protein, Angiogenesis, Vascular permeability, Biochemistry, Mice, CYTOPLASMIC DOMAIN, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cell adhesion molecule, Microfilament Proteins, Ce ll adhesion, Gap Junctions, Intercellular adhesion molecule, Cadherins, Cell-cell junctions, Cell biology, Rac-1, Protein Transport, ERM, Life Sciences & Biomedicine, Protein Binding, Signal Transduction, Biochemistry & Molecular Biology, ICAM-2, VE-CADHERIN, Biology, Permeability, ADHESION MOLECULES, TUMOR ANGIOGENESIS, Cell-cell junction, Endothelial, Adherens junction, HUMAN ENDOTHELIAL-CELLS, Capillary Permeability, RHO, Antigens, CD, Cell Line, Tumor, Human Umbilical Vein Endothelial Cells, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cell adhesion, Molecular Biology, ADHERENS JUNCTION, N-Cadherin, 0604 Genetics, Science & Technology, Binding Sites, Cadherin, Research, Contact inhibition, 0601 Biochemistry And Cell Biology, Membrane Proteins, IN-VITRO, Cell Biology, Cytoskeletal Proteins, GTPASES, Cell Adhesion Molecules
Abstract

Background Endothelial junctions control functions such as permeability, angiogenesis and contact inhibition. VE-Cadherin (VECad) is essential for the maintenance of intercellular contacts. In confluent endothelial monolayers, N-Cadherin (NCad) is mostly expressed on the apical and basal membrane, but in the absence of VECad it localizes at junctions. Both cadherins are required for vascular development. The intercellular adhesion molecule (ICAM)-2, also localized at endothelial junctions, is involved in leukocyte recruitment and angiogenesis. Results In human umbilical vein endothelial cells (HUVEC), both VECad and NCad were found at nascent cell contacts of sub-confluent monolayers, but only VECad localized at the mature junctions of confluent monolayers. Inhibition of ICAM-2 expression by siRNA caused the appearance of small gaps at the junctions and a decrease in NCad junctional staining in sub-confluent monolayers. Endothelioma lines derived from WT or ICAM-2-deficient mice (IC2neg) lacked VECad and failed to form junctions, with loss of contact inhibition. Re-expression of full-length ICAM-2 (IC2 FL) in IC2neg cells restored contact inhibition through recruitment of NCad at the junctions. Mutant ICAM-2 lacking the binding site for ERM proteins (IC2 ΔERM) or the cytoplasmic tail (IC2 ΔTAIL) failed to restore junctions. ICAM-2-dependent Rac-1 activation was also decreased in these mutant cell lines. Barrier function, measured in vitro via transendothelial electrical resistance, was decreased in IC2neg cells, both in resting conditions and after thrombin stimulation. This was dependent on ICAM-2 signalling to the small GTPase Rac-1, since transendothelial electrical resistance of IC2neg cells was restored by constitutively active Rac-1. In vivo, thrombin-induced extravasation of FITC-labeled albumin measured by intravital fluorescence microscopy in the mouse cremaster muscle showed that permeability was increased in ICAM-2-deficient mice compared to controls. Conclusions These results indicate that ICAM-2 regulates endothelial barrier function and permeability through a pathway involving N-Cadherin, ERMs and Rac-1.

Published
2014

14. High-pressure intrapleural chemotherapy: feasibility in the pig model

Author

Bernard Royer, Alain Bernard, Bruno Chauffert, Pablo Ortega-Deballon, Olivier Facy, Guy Magnin, Pierre-Benoit Pagès, Sylvain Ladoire, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de chirurgie cardio-vasculaire, Service d'anesthésie réanimation, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Laboratoire de Pharmacologie Clinique et Toxicologie [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), This paper was supported by research grants from the French National League against Cancer, from the Regional Council of Burgundy and from the University Hospital of Dijon (France)., Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), BMC, Ed., Service de chirurgie cardio-vasculaire et thoracique (CHU Dijon), and Service d'anesthésie - réanimation chirurgicale [CHU de Dijon]

Subjects
medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Swine, Pleural Neoplasms, lcsh:Surgery, Intra arterial chemotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, lcsh:RC254-282, Deoxycytidine, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, chemistry.chemical_compound, pressure, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Surgical oncology, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, medicine, Tumor Cells, Cultured, Animals, Humans, Intrapleural chemotherapy, Pleural Neoplasm, [ SDV.MHEP.CHI ] Life Sciences [q-bio]/Human health and pathology/Surgery, pig model, Cisplatin, business.industry, Research, Pig model, lcsh:RD1-811, intrapleural intracavitary chemotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Gemcitabine, 3. Good health, Surgery, 030228 respiratory system, chemistry, Oncology, 030220 oncology & carcinogenesis, High pressure, Feasibility Studies, Female, business, medicine.drug
Abstract

Background The usual treatments for pleural malignancies are mostly palliative. In contrast, peritoneal malignancies are often treated with a curative intent by cytoreductive surgery and intraperitoneal chemotherapy. As pressure has been shown to increase antitumor efficacy, we applied the concept of high-pressure intracavitary chemotherapy to the pleural space in a swine model. Methods Cisplatin and gemcitabine were selected because of their antineoplasic efficacy in vitro in a wide spectrum of cancer cell lines. The pleural cavity of 21 pigs was filled with saline solution; haemodynamic and respiratory parameters were monitored. The pressure was increased to 15-25 cm H2O. This treatment was associated with pneumonectomy in 6 pigs. Five pigs were treated with chemotherapy under pressure. Results The combination of gemcitabine (100 mg/l) and cisplatin (30 mg/l) was highly cytotoxic in vitro. The maximum tolerated pressure was 20 cm H20, due to haemodynamic failure. Pneumonectomy was not tolerated, either before or after pleural infusion. Five pigs survived intrapleural chemotherapy associating gemcitabine and cisplatin with 20 cm H2O pressure for 60 min. Conclusions High-pressure intrapleural chemotherapy is feasible in pigs. Further experiments will establish the pharmacokinetics and determine whether the benefit already shown in the peritoneum is also obtained in the pleura.

Published
2012

15. Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murine model of peritoneal carcinomatosis

Author

Patrick Rat, Hervé Tixier, François Radais, Delphine Delroeux, François Ghiringhelli, Sylvain Ladoire, Olivier Facy, Pablo Ortega-Deballon, Bruno Chauffert, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Chirurgie Digestive [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), This paper was supported by grants from the French National League against Cancer (Committees of Saône et Loire, Nièvre, and Côte d'Or)., BMC, Ed., Service de chirurgie digestive et cancérologie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service de chirurgie digestive [Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Service d'oncologie médicale, and CHU Amiens-Picardie

Subjects
MESH : Hyperthermia, Induced, MESH : Rats, Inbred Strains, Cancer Research, Pathology, Pharmacology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Peritoneal Neoplasm, 0302 clinical medicine, MESH : Tumor Cells, Cultured, Tumor Cells, Cultured, Medicine, MESH: Peritoneal Neoplasms, MESH : Female, MESH: Animals, Peritoneal Neoplasms, Ovarian Neoplasms, MESH : Cell Survival, 0303 health sciences, MESH : Rats, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MESH: Rats, Inbred Strains, 3. Good health, MESH : Antineoplastic Agents, MESH: Ovarian Neoplasms, Epinephrine, Oncology, MESH: Cell Survival, 030220 oncology & carcinogenesis, Female, medicine.drug, Hyperthermia, medicine.medical_specialty, MESH: Rats, Cell Survival, MESH: Epinephrine, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, MESH : Cisplatin, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Peritoneal Neoplasms, In vivo, Animals, Humans, MESH: Tumor Cells, Cultured, MESH: Hyperthermia, Induced, 030304 developmental biology, Cisplatin, MESH: Humans, MESH : Ovarian Neoplasms, business.industry, Research, MESH : Humans, Rats, Inbred Strains, Hyperthermia, Induced, medicine.disease, MESH : Disease Models, Animal, Rats, Disease Models, Animal, MESH: Cisplatin, Apoptosis, MESH : Epinephrine, Cancer cell, MESH: Antineoplastic Agents, MESH : Animals, MESH: Disease Models, Animal, business, Ovarian cancer, MESH: Female
Abstract

Background The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis. Methods Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells). Results In vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia. Conclusion Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.

Published
2011

16. Malaria risk in Corsica, former hot spot of malaria in France

Author

Gilbert Le Goff, Céline Toty, Hélène Barré, Daniel Couret, Nil Rahola, Didier Fontenille, Isabelle Larget-Thiery, Caractérisation et contrôle des populations de vecteurs, Institut de Recherche pour le Développement (IRD), Direction de la Solidarité et de la Santé de Corse et de Corse-du-Sud, Sciences pour l'environnement (SPE), Centre National de la Recherche Scientifique (CNRS)-Université Pascal Paoli (UPP), Centre de Production et Infection des Anophèles (plateforme) - Center for the Production and Infection of Anopheles (platform) (CEPIA), Institut Pasteur [Paris], The paper is catalogued by the EDEN Steering Committee as EDEN 232 http://www.eden-fp6project.net/., Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Centre de Production et Infection des Anophèles (Plateforme) (CEPIA)

Subjects
Risk, Entomology, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium vivax, Plasmodium falciparum, MESH: Malaria, Zoology, MESH: Insect Vectors, Biology, Plasmodium, Polymerase Chain Reaction, lcsh:Infectious and parasitic diseases, MESH: Anopheles, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Anopheles, parasitic diseases, medicine, Animals, Humans, MESH: Animals, lcsh:RC109-216, MESH: Plasmodium falciparum, 0303 health sciences, MESH: Humans, MESH: Risk, 030306 microbiology, Ecology, Research, Outbreak, MESH: Polymerase Chain Reaction, medicine.disease, biology.organism_classification, 3. Good health, Insect Vectors, Malaria, MESH: Plasmodium vivax, MESH: France, Infectious Diseases, Parasitology, France
Abstract

Background The prevalence of Plasmodium falciparum and Plasmodium vivax malaria was very high in Corsica just before the Second World War. The last outbreak was in 1972 and the most recent indigenous case was in 2006. Results Analysis of historical data shows that anopheline vectors were abundant. Recent surveys demonstrated that potential vectors are still present in Corsica, despite the likely disappearance of Anopheles sacharovi. Moreover, P. falciparum can develop experimentally into these mosquitoes, notably Anopheles labranchiae, which is locally abundant, and parasites are regularly introduced into the island. Discussion, Conclusions The presence of vectors, the introduction of parasites and the conducive climate raise questions about the possibility of malaria re-emerging and becoming re-established in Corsica. Analysis of historic and current parasitological and entomological data shows that the current theoretical risk of indigenous cases or malaria foci is negligible, particularly since there is very little contact between humans and Anopheles mosquitoes, Plasmodium carriers are reliably treated and there is a widespread vector control on the island.

Published
2010