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10,015 results on '"Siriraj Hospital, Mahidol University"'

1. Liposomal Amphotericin B and Flucytosine Antifungal Strategy for Talaromycosis (LAmB-FAST) (LAmB-FAST)

Author

National Institute of Allergy and Infectious Diseases (NIAID), Pham Ngoc Thach University of Medicine, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, National Hospital for Tropical Diseases, Hanoi, Vietnam, Bach Mai Hospital, Siriraj Hospital, Mahidol University, Bangkok, Thailand., Maharat Nakhon Ratchasima Hospital, Chiang Mai University, Guangzhou 8th People's Hospital, Shenzhen Third People's Hospital, Gilead Sciences, and Viatris Inc.

Published
2025

3. First Live Birth Rate With eSET After Preimplantation Methylome Screening (PIMS) Versus Conventional In-vitro Fertilization

Author

RenJi Hospital, Reproductive & Genetic Hospital of CITIC-Xiangya, Nanjing Maternity and Child Health Care Hospital, ShangHai Ji Ai Genetics & IVF Institute, Suzhou Municipal Hospital, The First Hospital of Jilin University, Sir Run Run Shaw Hospital, The Affiliated Hospital Of Guizhou Medical University, The Second Hospital of Hebei Medical University, Third Affiliated Hospital of Zhengzhou University, Ruijin Hospital, International Peace Maternity and Child Health Hospital, Henan Provincial People's Hospital, The First Affiliated Hospital of Hainan Medical University, The First Affiliated Hospital of Anhui Medical University, Fujian Maternity and Child Health Hospital, General Hospital of Ningxia Medical University, The First Affiliated Hospital with Nanjing Medical University, 900 th Hospital of Joint Logistics Support Force, Guangzhou Womenand Children's Medical Center, Changhai Hospital, Shenzhen Maternity & Child Healthcare Hospital, Sixth Affiliated Hospital, Sun Yat-sen University, Liuzhou Hospital of Guangzhou Women and Children's Medical Center, Jining Medical University, Siriraj hospital, Mahidol university, Thailand, and Chen Zi-Jiang, Academician

Published
2024

4. Stress Echo 2030: the Novel ABCDE-(FGLPR) Protocol to Define the Future of Imaging (SE2030)

Author

National Research Council, Institute of Clinical Physiology, Italy, Mayo Clinic, Hospital Sao Vicente de Paulo e Hospital de Cidade, Passo Fundo, Brasil, Cardarelli Hospital, Naples, Italy, Ospedale per gli Infermi, Faenza, Ravenna, Italy, Institute of Family Medicine, University of Szeged, Hungary, Montepulciano Hospital, Siena, University of Pisa, University Hospital, Pleven, Bulgaria, Tomsk National Research Medical Centre of the Russian, University Hospital, Szeged, Hungary, Elisabeth Hospital, Hódmezővásárhely, Hungary, DASA, San Paolo, Brasil, University of Banja Luka University Clinical Centre of the Republic of Srpska, University of A Coruna, La Coruna, Spain, Antwerp University Hospital, Edegem, Belgium, Università Luigi Vanvitelli della Campania, Dolo Hospital, Venice, Italy, Institute for Cardiovascular Diseases Dedinje, School of Medicine, Belgrade, Serbia, Investigaciones Medicas, Bieganski Hospital, Medical University, Lodz, Poland, Medical University of Silesia, Katowice, Poland, Federal University of Paranà, Curitiba, Brasil, Siriraj Hospital, Mahidol University, Bangkok, Thailand., Careggi Hospital, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico, Saint Petersburg State University Hospital, Russian Federation, Clinical Hospital Zvezdara, Medical School, University of Belgrade, Serbia, University Center Serbia, Medical School, University of Belgrade, Serbia, University Hospital, Padua, Italy, Sant'Anna School of Advanced Study, Pisa, University Hospital, Siena, Italy, Vilnius University, Lithuania, University of Parma, Universita di Verona, Malpighi Hospital, Bologna, Italy, University of Modena and Reggio Emilia, Presidio Ospedale San Paolo. Milano, IRCCS reggio emilia, Association for Public Health 'Salute Pubblica', Brindisi, Italy, University Hospital, Catania, Ospedale San Camillo, Rome, Italy, University of Salerno, University of Algarve, Portugal., Heart Center, Hospital da Cruz Vermelha, Lisbon, University of Bari, Hospital Motta di Livenza, Treviso, Centro Cardiologico Monzino, Italian Society of Echocardiography and Cardiovascular Imaging, San Luca Hospital, Lucca, and Hospital Sao José, Criciuma, Brasil

Published
2021

9. Inhibition of protein kinase C promotes dengue virus replication

Author

Sarin Chimnaronk, Thichakorn Jittawuttipoka, Siwanon Jirawatnotai, Anavaj Sakuntabhai, Warobon Noppakunmongkolchai, Teera Poyomtip, Rutaiwan Tohtong, Natthanej Luplertlop, Mahidol University [Bangkok], Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Siriraj Hospital, Mahidol University, SJ is supported by 'Chalermphrakiat' Grant, Faculty of Medicine Siriraj Hospital, Mahidol University, The Thailand Research Fund (RSA5880038), and the Advanced Research on Pharmacology Fund, Siriraj Foundation D003421. TP is supported by a scholarship from Science Achievement Scholarship of Thailand (SAST). SC is supported by Grants-in-Aids for scientific research from Mahidol University (Thailand), and by the Mid-Career Grant (RSA5680054) from Thailand Research Fund (TRF). This project was supported by National Research University of Thailand (NRU) and the DENFREE project (the European Union Seventh Framework Programme (FP7/2007/2011) under Grant Agreement n°282 378)., European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]

Subjects
0301 basic medicine, Models, Molecular, Proteomics, Indoles, Protein Conformation, viruses, Dengue virus, Viral Nonstructural Proteins, medicine.disease_cause, Virus Replication, Protein kinase C (PKC), Dengue fever, Dengue, Maleimides, Cluster Analysis, RNA, Small Interfering, Phosphorylation, Protein Kinase C, biology, virus diseases, Dengue virus (DENV), 3. Good health, Flavivirus, Infectious Diseases, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cell Survival, Models, Biological, 03 medical and health sciences, Flaviviridae, Viral life cycle, Virology, medicine, Gene silencing, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Gene Silencing, Research, RNA, biochemical phenomena, metabolism, and nutrition, Dengue Virus, Virus Internalization, biology.organism_classification, medicine.disease, Non-structural protein 5 (NS5), 030104 developmental biology, Viral replication, viral replication, Sequence Alignment
Abstract

Background Dengue virus (DENV) is a member of the Flaviviridae family, transmitted to human via mosquito. DENV infection is common in tropical areas and occasionally causes life-threatening symptoms. DENV contains a relatively short positive-stranded RNA genome, which encodes ten viral proteins. Thus, the viral life cycle is necessarily rely on or regulated by host factors. Methods In silico analyses in conjunction with in vitro kinase assay were used to study kinases that potentially phosphorylate DENV NS5. Potential kinase was inhibited or activated by a specific inhibitor (or siRNA), or an activator. Results of the inhibition and activation on viral entry/replication and host cell survival were examined. Results Our in silico analyses indicated that the non-structural protein 5 (NS5), especially the RNA-dependent RNA polymerase (RdRp) domain, contains conserved phosphorylation sites for protein kinase C (PKC). Phosphorylation of NS5 RdRp was further verified by PKC in vitro kinase assay. Inhibitions of PKC by a PKC-specific chemical inhibitor or siRNA suppressed NS5 phosphorylation in vivo, increased viral replication and reduced viability of the DENV-infected cells. In contrary, activation of PKC effectively suppressed intracellular viral number. Conclusions These results indicated that PKC may act as a restricting mechanism that modulates the DENV replication and represses the viral outburst in the host cells. Electronic supplementary material The online version of this article (doi:10.1186/s12985-016-0494-6) contains supplementary material, which is available to authorized users.

Published
2016
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11. Hypersensitivity reactions to iodinated radiocontrast media: Cluster analysis reveals distinct clinical phenotypes

Author

Witchaya Srisuwatchari, Tram Vo, Amélie Gauthier, Nicolas Molinari, Rik Schrijvers, Pascal Demoly, Anca Mirela Chiriac, Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Montpelliérain Alexander Grothendieck (IMAG), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Médecine de précision par intégration de données et inférence causale (PREMEDICAL), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital de la Colombière, and Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)

Subjects
Pulmonary and Respiratory Medicine, Science & Technology, Allergy, IDENTIFICATION, SKIN-TESTS, Immunology, DIAGNOSIS, PREVALENCE, CONTRAST-MEDIA, Cluster analysis, ADVERSE-REACTIONS, CROSS-REACTIVITY, Clinical phenotype, RISK-FACTORS, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Immunology and Allergy, Iodinated radiocontrast media, Drug hypersensitivity reaction, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Life Sciences & Biomedicine, IMMEDIATE HYPERSENSITIVITY, ASTHMA PHENOTYPES
Abstract

BACKGROUND: Drug hypersensitivity reaction (DHR) to iodinated radiocontrast media (iRCM) is reported in 1%-3% of injections. Risk assessment of patients with suspicion of DHR to iRCM relies solely on clinical phenotyping and drug allergy workup. Using a novel unsupervised TwoStep cluster analysis, we aimed to identify prototypic patterns within a large cohort of patients evaluated for a potential iRCM DHR. METHODS: A retrospective study was conducted using data from the Drug Allergy and Hypersensitivity Database of the Allergy Unit, University Hospital of Montpellier, Montpellier, France. All referred patients during February 2001 to December 2019 with suspicion of iRCM DHR with either confirmed positive or confirmed negative skin tests were included in the analysis. RESULTS: A total of 1439 patients were evaluated. The chronology of the index reaction was immediate and nonimmediate in 77.1% and 22.4%, respectively. Cluster analysis categorized the total study population in 5 clusters. Cluster 1 compiled all nonimmediate and cluster 2-5 almost all immediate reactors. Cluster 1 and 2 had recent reactions (

Published
2022
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12. Comprehensive evaluation of microRNA as a biomarker for the diagnosis of hepatocellular carcinoma

Author

Juliane Malik, Martin Klammer, Vinzent Rolny, Henry Lik-Yuen Chan, Teerha Piratvisuth, Tawesak Tanwandee, Satawat Thongsawat, Wattana Sukeepaisarnjaroen, Juan Ignacio Esteban, Marta Bes, Bruno Köhler, Magdalena Swiatek-de Lange, Institut Català de la Salut, [Malik J, Klammer M, Rolny V] Roche Diagnostics GmbH, Penzberg, Germany. [Chan HLY] Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. [Piratvisuth T] NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Hat Yai, Thailand. [Tanwandee T] Division of Gastroenterology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. [Esteban JI] Unitat Hepàtica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Carcinoma, Hepatocellular, Vitamin K, Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [CHEMICALS AND DRUGS], neoplasias::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias hepáticas::carcinoma hepatocelular [ENFERMEDADES], Otros calificadores::/diagnóstico [Otros calificadores], Biological Factors::Biomarkers [CHEMICALS AND DRUGS], factores biológicos::biomarcadores [COMPUESTOS QUÍMICOS Y DROGAS], Lectins, Other subheadings::/diagnosis [Other subheadings], Biomarkers, Tumor, Humans, Prospective Studies, Protein Precursors, Early Detection of Cancer, MicroARN, Liver Neoplasms, Gastroenterology, General Medicine, MicroRNAs, Neoplasms::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms::Carcinoma, Hepatocellular [DISEASES], Fetge - Càncer - Diagnòstic, Case-Control Studies, Marcadors bioquímics, Prothrombin, nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN [COMPUESTOS QUÍMICOS Y DROGAS], alpha-Fetoproteins, Biomarkers
Abstract

Carcinoma; Diagnosis; MicroRNAs Carcinoma; Diagnóstico; MicroARN Carcinoma; Diagnòstic; MicroARN Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biomarkers, like alpha-fetoprotein (AFP), protein induced by vitamin K absence/antagonist-II (PIVKA-II) and lectin-reactive AFP, show suboptimal performance for detection of HCC, which is crucial for successful resection or treatment. Thus, there is a significant need for new biomarkers to aid early diagnosis of HCC. Studies have shown that the expression level of human microRNAs (miRNAs), a small, non-coding RNA species released into the blood, can serve as an early marker for various diseases, including HCC. Aim: To evaluate the diagnostic role of miRNAs in HCC as single markers, signatures or in combination with known protein biomarkers. Methods: Our prospective, multicenter, case-control study recruited 660 participants (354 controls with chronic liver disease and 306 participants with HCC) and employed a strategy of initial screening by two independent methods, real-time quantitative PCR (n = 60) and next-generation sequencing (n = 100), to assess a large number of miRNAs. The results from the next-generation sequencing and real-time quantitative PCR screening approaches were then combined to select 26 miRNAs (including two putative novel miRNAs). Those miRNAs were analyzed for their diagnostic potential as single markers or in combination with other miRNAs or established protein biomarkers AFP and PIVKA-II via real-time quantitative PCR in training (n = 200) and validation cohorts (n = 300). Results: We identified 26 miRNAs that differentiated chronic liver disease controls from (early) HCC via two independent discovery approaches. Three miRNAs, miR-21-5p (miR-21), miR-320a and miR-186-5p, were selected by both methods. In the training cohort, only miR-21, miR-320d and miR-423 could significantly distinguish (Q < 0.05) between the HCC and chronic liver disease control groups. In the multivariate setting, miR-21 with PIVKA-II was selected as the best combination, resulting in an area under the curve of 0.87 for diagnosis and area under the curve of 0.74 for early diagnosis of HCC. In the validation cohort, only miR-21 and miR-423 could be confirmed as potential HCC biomarkers. A combination of miRNAs did not perform better than any single miRNA. Improvement of PIVKA-II performance through combination with miRNAs could not be confirmed in the validation panel. Two putative miRs, put-miR-6 and put-miR-99, were tested in the training and validation panels, but their expression could only be detected in very few samples and at a low level (cycle threshold between 31.24 and 34.97). Conclusion: miRNAs alone or as a signature in combination with protein biomarkers AFP and PIVKA-II do not improve the diagnostic performance of the protein biomarkers.

Published
2022

13. Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis

Author

Jesson, Julie, Crichton, Siobhan, Quartagno, Matteo, Yotebieng, Marcel, Abrams, Elaine J., Chokephaibulkit, Kulkanya, Le Coeur, Sophie, Aké-Assi, Marie-Hélène, Patel, Kunjal, Pinto, Jorge, Paul, Mary, Vreeman, Rachel, Davies, Mary-Ann, Ben-Farhat, Jihane, Van Dyke, Russell, Judd, Ali, Mofenson, Lynne, Vicari, Marissa, Seage, George, Bekker, Linda-Gail, Essajee, Shaffiq, Gibb, Diana, Penazzato, Martina, Collins, Intira Jeannie, Wools-Kaloustian, Kara, Slogrove, Amy, Powis, Kate, Williams, Paige, Matshaba, Mogomotsi, Thahane, Lineo, Nyasulu, Phoebe, Lukhele, Bhekumusa, Mwita, Lumumba, Kekitiinwa-Rukyalekere, Adeodata, Wanless, Sebastian, Goetghebuer, Tessa, Thorne, Claire, Warszawski, Josiane, Galli, Luisa, van Rossum, Annemarie M. C., Giaquinto, Carlo, Marczynska, Magdalena, Marques, Laura, Prata, Filipa, Ene, Luminita, Okhonskaya, Lyuba, Navarro, Marisa, Frick, Antoinette, Naver, Lars, Kahlert, Christian, Volokha, Alla, Chappell, Elizabeth, Pape, Jean William, Rouzier, Vanessa, Marcelin, Adias, Succi, Regina, Sohn, Annette H., Kariminia, Azar, Edmonds, Andrew, Lelo, Patricia, Lyamuya, Rita, Ogalo, Edith Apondi, Odhiambo, Francesca Akoth, Haas, Andreas D., Bolton, Carolyn, Muhairwe, Josephine, Tweya, Hannock, Sylla, Mariam, D'Almeida, Marceline, Renner, Lorna, Abzug, Mark J., Oleske, James, Purswani, Murli, Teasdale, Chloe, Nuwagaba-Biribonwoha, Harriet, Goodall, Ruth, Leroy, Valériane, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Jesson J] CERPOP, Inserm, Université Paul Sabatier Toulouse 3, Toulouse, France. [Crichton S, Quartagno M] MRC Clinical Trials Unit, University College London, London, UK. [Yotebieng M] Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA. [Abrams EJ] ICAP at Columbia University, Mailman School of Public Health, Columbia University, New York, USA. [Chokephaibulkit K] Siriraj Institute of Clinical Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Salaya, Thailand. [Frick A] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Medical Microbiology & Infectious Diseases, and Pediatrics

Subjects
Adult, Male, Adolescent, virosis::infecciones por virus ARN::infecciones por Retroviridae::infecciones por Lentivirus::infecciones por VIH [ENFERMEDADES], Other subheadings::Other subheadings::/epidemiology [Other subheadings], growth, Perinatally acquired, 610 Medicine & health, adolescent, CD4, cohort studies, HIV, perinatally acquired, CD4 Lymphocyte Count, Child, Child, Preschool, Cohort Studies, Female, Growth Disorders, Humans, Income, HIV Infections, Growth, Adolescents, SDG 3 - Good Health and Well-being, 360 Social problems & social services, Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [DISEASES], Preschool, Otros calificadores::Otros calificadores::/epidemiología [Otros calificadores], Public Health, Environmental and Occupational Health, Infeccions per VIH - Epidemiologia, Infectious Diseases, Cohort studies
Abstract

HIV; Adolescent; Perinatally acquired VIH; Adolescent; Adquirit perinatalment VIH; Adolescente; Adquirida perinatalmente Introduction Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. Methods Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10–17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if 7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts

Published
2022
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14. The epitope arrangement on flavivirus particles contributes to Mab C10’s extraordinary neutralization breadth across Zika and dengue viruses

Author

Gavin R. Screaton, Pablo Guardado-Calvo, Félix A. Rey, Xinghong Dai, Danyang Gong, Patrick England, Alexander Rouvinski, Marie-Christine Vaney, Ahmed Haouz, Z. Hong Zhou, Wanwisa Dejnirattisai, Stéphane Duquerroy, Ren Sun, Arvind Sharma, Xiaokang Zhang, Wiyada Wongwiwat, Juthathip Mongkolsapaya, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP), University of Oxford, University of California [Los Angeles] (UCLA), University of California (UC), Université Paris-Saclay, Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Cristallographie (Plateforme) - Crystallography (Platform), Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], This project was supported by a Wellcome Trust collaborative grant (UNS22082 to G.R.S., J.M., and F.A.R.), by the National Institute for Health Research Biomedical Research Centre Funding Scheme (to G.R.S.), and by grants from the National Institutes of Health (DE028583, AI094386, and DE025567 to Z.H.Z. and R.S.)., and We thank Fabrice Agou and the staff of the Chemogenomic and Biological Screening Platform for access to the MALS equipment as well as the staff of the Crytallography core facility at the Institut Pasteur for robot-driven crystallization screens. We acknowledge the use of synchrotron beam lines PX1 and PX2 at SOLEIL (St Aubin, France), ID29 and ID23-1 at ESRF (Grenoble, France) and X06SA at SLS (Villigen, Switzerland), and we thank their staff for assistance. We also acknowledge the use of the resources at the Electron Imaging Center for Nanomachines, supported in part by 1S10RR23057, 1S10OD018111, 1U24GM116792 and NSF DBI-1338135 and DMR-1548924 at UCLA. G.R.S. is supported as a Wellcome Trust Senior Investigator (095541/A/11/Z). F.A.R. is supported by Institut Pasteur and the CNRS.

Subjects
medicine.drug_class, [SDV]Life Sciences [q-bio], MESH: Vero Cells, MESH: Zika Virus, MESH: Dengue, Biology, Dengue virus, Monoclonal antibody, medicine.disease_cause, MESH: Dengue Virus, complex mixtures, General Biochemistry, Genetics and Molecular Biology, Epitope, Neutralization, Zika virus, MESH: Antibodies, Monoclonal, MESH: Antibodies, Neutralizing, MESH: Drosophila melanogaster, MESH: Cross Reactions, MESH: Protein Conformation, MESH: Zika Virus Infection, MESH: Chlorocebus aethiops, medicine, MESH: Protein Binding, MESH: Animals, X-ray crystallography, MESH: Humans, Flaviviruses, broadly neutralizing antibodies, biology.organism_classification, Virology, MESH: Cell Line, Flavivirus, MESH: HEK293 Cells, MESH: Viral Envelope Proteins, biology.protein, vaccine design, cryo-EM, Paratope, lipids (amino acids, peptides, and proteins), Antibody, MESH: Antibodies, Viral
Abstract

International audience; The human monoclonal antibody C10 exhibits extraordinary cross-reactivity, potently neutralizing Zika virus (ZIKV) and the four serotypes of dengue virus (DENV1-DENV4). Here we describe a comparative structure-function analysis of C10 bound to the envelope (E) protein dimers of the five viruses it neutralizes. We demonstrate that the C10 Fab has high affinity for ZIKV and DENV1 but not for DENV2, DENV3, and DENV4. We further show that the C10 interaction with the latter viruses requires an E protein conformational landscape that limits binding to only one of the three independent epitopes per virion. This limited affinity is nevertheless counterbalanced by the particle's icosahedral organization, which allows two different dimers to be reached by both Fab arms of a C10 immunoglobulin. The epitopes' geometric distribution thus confers C10 its exceptional neutralization breadth. Our results highlight the importance not only of paratope/epitope complementarity but also the topological distribution for epitope-focused vaccine design.

Published
2021
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15. Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients

Author

Jan O. Friedrich, Sebastian Dubo, Ewan C. Goligher, Leo M. A. Heunks, Michael C. Sklar, Fabiana Madotto, Michela Rauseo, Ibrahim Soliman, Ricard M. Artigas, Nuttapol Rittayamai, L. Felipe Damiani, Rémi Coudroy, Lu Chen, Irene Telias, Annemijn H. Jonkman, Guang-Qiang Chen, Laurent Brochard, Tài Pham, Martin Dres, Christer Sinderby, Intensive care medicine, ACS - Pulmonary hypertension & thrombosis, University of Toronto, St. Michael's Hospital, Università degli Studi di Milano, IRCCS Policlinico San Donato, VU University Medical Center [Amsterdam], Università degli Studi di Foggia - University of Foggia, Pontificia Universidad Católica de Chile (UC), Universidad de Concepción - University of Concepcion [Chile], Universidad de la frontera [Chile], Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Mount Sinai Health System, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Università degli Studi di Foggia = University of Foggia (Unifg), HAL-SU, Gestionnaire, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, Time Factors, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Sedation, medicine.medical_treatment, Critical Illness, Diaphragm, Diaphragmatic breathing, Critical Care and Intensive Care Medicine, Electrical activity of the diaphragm, 03 medical and health sciences, 0302 clinical medicine, Mechanical ventilation, Interquartile range, Severity of illness, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Intubation, Intratracheal, Medicine, Intubation, Humans, Prospective Studies, Aged, Aged, 80 and over, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Middle Aged, Respiration, Artificial, 3. Good health, Diaphragm (structural system), Critical care, 030228 respiratory system, Anesthesia, Breathing, Female, medicine.symptom, Sedentary Behavior, business
Abstract

BackgroundIn patients intubated for mechanical ventilation, prolonged diaphragm inactivity could lead to weakness and poor outcome. Time to resume a minimal diaphragm activity may be related to sedation practice and patient severity.MethodsProspective observational study in critically ill patients. Diaphragm electrical activity (EAdi) was continuously recorded after intubation looking for resumption of a minimal level of diaphragm activity (beginning of the first 24 h period with median EAdi > 7 µV, a threshold based on literature and correlations with diaphragm thickening fraction). Recordings were collected until full spontaneous breathing, extubation, death or 120 h. A 1 h waveform recording was collected daily to identify reverse triggering.ResultsSeventy-five patients were enrolled and 69 analyzed (mean age ± standard deviation 63 ± 16 years). Reasons for ventilation were respiratory (55%), hemodynamic (19%) and neurologic (20%). Eight catheter disconnections occurred. The median time for resumption of EAdi was 22 h (interquartile range 0–50 h); 35/69 (51%) of patients resumed activity within 24 h while 4 had no recovery after 5 days. Late recovery was associated with use of sedative agents, cumulative doses of propofol and fentanyl, controlled ventilation and age (older patients receiving less sedation). Severity of illness, oxygenation, renal and hepatic function, reason for intubation were not associated with EAdi resumption. At least 20% of patients initiated EAdi with reverse triggering.ConclusionLow levels of diaphragm electrical activity are common in the early course of mechanical ventilation: 50% of patients do not recover diaphragmatic activity within one day. Sedatives are the main factors accounting for this delay independently from lung or general severity.Trial RegistrationClinicalTrials.gov (NCT02434016). Registered on April 27, 2015. First patients enrolled June 2015.

Published
2021
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16. Diagnostic performance of serial serum total tryptase measurement to differentiate positive from negative allergy testing among patients with suspected perioperative hypersensitivity

Author

Jean-Marc Malinovsky, R. Stenger, Pascal Demoly, Yoann Ehrhard, Charles Tacquard, Anna Borushko, Anca-Mirela Chiriac, Simon Viville, Witchaya Srisuwatchari, P.M. Mertes, Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], CHU Strasbourg, Belarusian Medical Academy of Post-Graduate Education [Minsk] (BelMAPGE), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Médecine de précision par intégration de données et inférence causale (PREMEDICAL), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Desbrest de santé publique (IDESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
MESH: Drug Hypersensitivity, medicine.medical_specialty, Allergy, MESH: Tryptases, Tryptase measurement, drug hypersensitivity reaction, Immunology, Drug allergy, tryptase, Tryptase, Allergy testing, perioperative hypersensitivity, Gastroenterology, Perioperative Care, Drug Hypersensitivity, diagnostic performance, Internal medicine, Immunology and Allergy, Medicine, Humans, MESH: Perioperative Care, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Anaphylaxis, MESH: Humans, biology, business.industry, Perioperative, medicine.disease, Work-up, Hypersensitivity reaction, MESH: Anaphylaxis, MESH: France, biology.protein, Tryptases, France, business
Abstract

International audience; Background: Serum total tryptase has been shown to increase during acute allergic reactions (acute tryptase, TA ); however, few studies have investigated the values of TA or a combination of TA and baseline tryptase (TB ) to discriminate positive from negative testing in perioperative hypersensitivity reaction (POH) allergy work-up. The aim of this study was to determine the diagnostic performance of TA in order to differentiate positive from negative allergy testing suspected POH and analyse the diagnostic performance of serial tryptase levels using several formulas.Methods: All patients from the University hospital of Montpellier and Strasbourg, France, who presented with suspected POH and underwent complete drug allergy work-up between March 2011 and December 2019 with available TA and TB were included. Four formulas, including a change in TA > 11 (F1), or >2 + 1.2 × TB (F2), or >3 + TB (F3), or >120%TB (F4), were applied.Results: One hundred and sixty-two patients were included, and 131 of them (80.8%) had Grade III or IV reactions. Ninety patients had positive allergy testing. The optimal cut-off value of TA to distinguish positive from negative allergy testing patients was 9.8 μg/L with an AUC of 0.817 (95% CI: 0.752-0.882, p < .001). The 93% PPV threshold for TA was 33 μg/L (95.8% specificity). Paired tryptase levels according to formulas F2 and F3 yielded the highest Youden index (0.54 and 0.53, respectively).Conclusion: The optimal cut-off point for TA for distinguishing positive from negative allergy testing suspected POH was 9.8 μg/L. TA value of 33 μg/L was required to achieve >90% PPV.

Published
2021
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17. Multimarker Panels for Detection of Early Stage Hepatocellular Carcinoma: A Prospective, Multicenter, Case-Control Study

Author

Magdalena Swiatek-De Lange, Wattana Sukeepaisarnjaroen, David Morgenstern, Juan Ignacio Esteban, Marta Bes, Tawesak Tanwandee, Ying He, Satawat Thongsawat, Teerha Piratvisuth, Henry Lik-Yuen Chan, Bruno Köhler, Institut Català de la Salut, [Piratvisuth T] NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand. [Tanwandee T] Division of Gastroenterology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. [Thongsawat S] Department of Internal Medicine, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University, Chiang Mai, Thailand. [Sukeepaisarnjaroen W] Faculty of Medicine, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand. Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas, Insituto de Salud Carlos III, Madrid, Spain. [Esteban JI] Unitat del Fetge, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas, Insituto de Salud Carlos III, Madrid, Spain. [Bes M] Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas, Insituto de Salud Carlos III, Madrid, Spain. Transfusion Safety Laboratory, Banc de Sang i Teixits, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Carcinoma, Hepatocellular, neoplasias::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias hepáticas::carcinoma hepatocelular [ENFERMEDADES], Population, Otros calificadores::/diagnóstico [Otros calificadores], Gastroenterology, Biological Factors::Biomarkers [CHEMICALS AND DRUGS], Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics::Epidemiologic Studies::Cohort Studies::Prospective Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], factores biológicos::biomarcadores [COMPUESTOS QUÍMICOS Y DROGAS], Internal medicine, Other subheadings::/diagnosis [Other subheadings], Medicine, Humans, Prospective Studies, Protein Precursors, education, neoplasms, Survival rate, Univariate analysis, education.field_of_study, Hepatology, business.industry, Liver Neoplasms, Cancer, Hepatitis C, Hepatitis B, medicine.disease, digestive system diseases, técnicas de investigación::métodos epidemiológicos::características de los estudios epidemiológicos::estudios epidemiológicos::estudios de cohortes::estudios prospectivos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Neoplasms::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms::Carcinoma, Hepatocellular [DISEASES], Fetge - Càncer - Diagnòstic, Hepatocellular carcinoma, Case-Control Studies, Marcadors bioquímics, Matrix Metalloproteinase 3, Prothrombin, alpha-Fetoproteins, business, Biomarkers
Abstract

Early Stage; Hepatocellular Carcinoma Etapa temprana; Carcinoma hepatocelular Etapa primera; Carcinoma hepatocel·lular Hepatocellular carcinoma (HCC), the sixth most common cancer worldwide, has an incidence rate equal to mortality. Over 80% of HCC cases occur within a high-risk population, mainly patients with both cirrhosis and chronic hepatitis B or C. With a 5-year survival rate ranging from 90% for early stage HCC, there is a high medical need for the early detection of HCC. In this study, we systematically evaluated biomarkers mentioned in international guidelines and peer-reviewed literature for HCC surveillance and diagnosis with the aim of identifying combinations that display high sensitivity and specificity for early stage HCC. Fifty biomarkers were measured in the first sample panel, panel A (n = 110), and subjected to univariate analysis. Of these, 35 biomarkers (38 assays) from panel A and an additional 13 biomarkers from the literature were prioritized for subsequent multivariate evaluation with lasso regression and exhaustive search of two- to four-biomarker combinations (panel B). Panel B included 1,081 samples from patients with HCC (n = 308) or with chronic liver diseases (n = 740). Among all patients, 61.0% had hepatitis B, 32.9% had hepatitis C, and 60.5% had cirrhosis; 40.6% of patients with HCC had early stage cancer. Protein induced by vitamin K absence-II (PIVKA-II; also known as des-gamma-carboxy prothrombin [DCP]) and alpha-fetoprotein (AFP) demonstrated the best clinical performance, both individually and in combination, and the addition of a third biomarker (Lens culinaris agglutinin-reactive fraction of AFP [AFP-L3], cartilage oligomeric matrix protein [COMP], insulin-like growth factor-binding protein 3 [IGFBP3], or matrix metalloproteinase 3 [MMP3]) further increased sensitivity for the detection of both early stage and all-stage HCC. The addition of age and sex to the three-biomarker panel resulted in an improved diagnostic performance. Conclusion: The combination of AFP and PIVKA-II, with either IGFBP3, COMP or MMP3, plus age and sex, demonstrated the best performance for the detection of early- and all-stage HCC. These novel panels performed similar to that of the GALAD score (sex [gender], age, plus serum levels of AFP, AFP-L3 and DCP [PIVKA-II]), a promising screening tool developed for HCC detection. Supported by Roche Diagnostics GmbH.

Published
2021

18. ARIA‐EAACI care pathways for allergen immunotherapy in respiratory allergy

Author

Bousquet, Jean, Pfaar, Oliver, Agache, Ioana, Bedbrook, Anna, Akdis, Cezmi A, Canonica, Giorgio Walter, Chivato, Tomas, Al-Ahmad, Mona, Rasib, A. H. Abdul, Ansotegui, Ignacio J, Bachert, Claus, Soto-Martinez, Manuel, Laune, Daniel, Casale, Tomas, Levin, Michael, Larenas-Linnemann, Désirée, Samolinski, Boleslaw, Lodrup Carlsen, Karin C, O'Mahony, Liam, Lombardi, Carlo, Riggioni, Carmen, Hossny, Elham, Barata, Luís Taborda, Lourenço, Olga, Devillier, Philippe, Mahboub, Bassam, Malling, Hans-Jørgen, Sheikh, Aziz, Manning, Patrick, Passalacqua, Giovanni, Marshall, Gailen D, Sanchez-Borges, Mario, Toppila-Salmi, Sanna, Melén, Erik, Fokkens, Wytske J, Meltzer, Eli O, Miculinic, Neven, Soto-Quiros, Manuel, Milenkovic, Branislava, Roberts, Graham, Ohta, Ken, Scichilone, Nicola, Moin, Mostafa, Odemyr, Mikaëla, Montefort, Stephen, Almeida, Mário Morais, Bom, Ana Todo, Mortz, Charlotte G, Serpa, Faradiba S, Patella, Vincenzo, Sova, Milan, Mösges, Ralph, Mullol, Joaquim, Namazova Baranova, Leyla, Tsiligianni, Ioanna, Neffen, Hugo, Bjermer, Leif, Rodriguez-Gonzales, Monica, Torres, Maria J, Okamoto, Yoshitaka, Okubo, Kimi, Pajno, Giovanni B, Baharuddin, Abdullah, Cecchi, Lorenzo, Sastre, Joaquin, Untersmayr, Eva, Pawankar, Ruby, Pham-Thi, Nhân, Plavec, Davor, Cardona, Victoria, Dokic, Dejan, Sisul, Juan Carlos, Rosario, Nelson, Rottem, Menachem, Rouadi, Philip W, Del Giacco, Stefano, Fonseca, Joao A, Schwarze, Jürgen, Scadding, Glenis K, Shamji, Mohamed H, Schmid-Grendelmeier, Peter, Niedoszytko, Marek, Valentin-Rostan, Marylin, Sofiev, Mikhail, Solé, Dirceu, Sooronbaev, Talant, Palkonen, Susanna, Urrutia-Pereira, Marilyn, Skypala, Isabel, Suppli-Ulrik, Charlotte, Bonini, Matteo, Popov, Todor A, Tomazic, Peter-Valentin, Valero, Antonio, Cepeda Sarabia, Alfonso M, Ryan, Dermot, Bosnic-Anticevich, Sinthia, Valiulis, Arunas, Durham, Stephen L, Schünemann, Holger, Kalayci, Omer, Valovirta, Erkka, Panzner, Petr, Vandenplas, Olivier, Ventura, Maria Teresa, Gotua, Maia, Vichyanond, Pakit, Chkhartishvili, Ekaterine, Wagenmann, Martin, Fontaine, Jean-François, Kull, Inger, Wallace, Dana, Recto, Marysia, Walusiak-Skorupa, Jolanta, Wang, De Yun, Hrubiško, Martin, Waserman, Susan, Ebisawa, Motohiro, Bosse, Isabelle, Grisle, Ineta, Wong, Gary Wk, Bindslev-Jensen, Carsten, Yorgancioglu, Arzu, Yusuf, Osman M, Khaitov, Musa, Zernotti, Mario, Gawlik, Radoslaw, Chu, Derek K, Irani, Carla, Zhang, Luo, Zidarn, Mihaela, Zuberbier, Torsten, Kuna, Piotr, Jutel, Marek, Guzmán, Maria Antonieta, El-Gamal, Yehia, Klimek, Ludger, Brough, Helen A, Brussino, Luisa, Calderon, Moises A, Caraballo, Luis, O'Hehir, Robyn E, Gelincik, Asli, Kvedariene, Violeta, Cirule, Ieva, Cruz, Alvaro A, Czarlewski, Wienczyslawa, Nekam, Kristof, Papadopoulos, Nikolaos G., Haahtela, Tari, Emuzyte, Regina, Gamkrelidze, Amiran, Fauquert, Jean Luc, Palomares, Oscar, Regateiro, Frederico S, Ivancevich, Juan Carlos, Gemicioglu, Bilun, Gereda, Jose E, Gerth van Wijk, Roy, Bergmann, Karl-Christian, Knol, Edward, Halken, Susanne, Heffler, Enrico, Hoffmann-Sommergruber, Karin, Martins, Pedro Carreiro, Kritikos, Vicky, Ispayeva, Zhanat, Julge, Kaja, Kaidashev, Igor, Demoly, Pascal, Kowalski, Marek, Kraxner, Helga, Ollert, Markus, Fiocchi, Alessandro, Lauerma, Antti, Lau, Susanne, Park, Hae-Sim, Gomez, R Maximiliano, Comprehensive Health Research Centre (CHRC) - pólo NMS, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), uBibliorum, Bousquet J., Pfaar O., Agache I., Bedbrook A., Akdis C.A., Canonica G.W., Chivato T., Al-Ahmad M., Abdul Latiff A.H., Ansotegui I.J., Bachert C., Baharuddin A., Bergmann K.-C., Bindslev-Jensen C., Bjermer L., Bonini M., Bosnic-Anticevich S., Bosse I., Brough H.A., Brussino L., Calderon M.A., Caraballo L., Cardona V., Carreiro-Martins P., Casale T., Cecchi L., Cepeda Sarabia A.M., Chkhartishvili E., Chu D.K., Cirule I., Cruz A.A., Czarlewski W., del Giacco S., Demoly P., Devillier P., Dokic D., Durham S.L., Ebisawa M., El-Gamal✝ Y., Emuzyte R., Gamkrelidze A., Fauquert J.L., Fiocchi A., Fokkens W.J., Fonseca J.A., Fontaine J.-F., Gawlik R., Gelincik A., Gemicioglu B., Gereda J.E., Gerth van Wijk R., Gomez R.M., Gotua M., Grisle I., Guzman M.-A., Haahtela T., Halken S., Heffler E., Hoffmann-Sommergruber K., Hossny E., Hrubisko M., Irani C., Ivancevich J.C., Ispayeva Z., Julge K., Kaidashev I., Kalayci O., Khaitov M., Klimek L., Knol E., Kowalski M.L., Kraxner H., Kull I., Kuna P., Kvedariene V., Kritikos V., Lauerma A., Lau S., Laune D., Levin M., Larenas-Linnemann D.E., Lodrup Carlsen K.C., Lombardi C., Lourenco O.M., Mahboub B., Malling H.-J., Manning P., Marshall G.D., Melen E., Meltzer E.O., Miculinic N., Milenkovic B., Moin M., Montefort S., Morais-Almeida M., Mortz C.G., Mosges R., Mullol J., Namazova Baranova L., Neffen H., Nekam K., Niedoszytko M., Odemyr M., O'Hehir R.E., Ollert M., O'Mahony L., Ohta K., Okamoto Y., Okubo K., Pajno G.B., Palomares O., Palkonen S., Panzner P., G Papadopoulos N., Park H.-S., Passalacqua G., Patella V., Pawankar R., Pham-Thi N., Plavec D., Popov T.A., Recto M., Regateiro F.S., Riggioni C., Roberts G., Rodriguez-Gonzales M., Rosario N., Rottem M., Rouadi P.W., Ryan D., Samolinski B., Sanchez-Borges✝ M., Serpa F.S., Sastre J., Scadding G.K., Shamji M.H., Schmid-Grendelmeier P., Schunemann H.J., Sheikh A., Scichilone N., Sisul J.C., Sofiev M., Sole D., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Sova M., Schwarze J., Skypala I., Suppli-Ulrik C., Taborda-Barata L., Todo-Bom A., Torres M.J., Valentin-Rostan M., Tomazic P.-V., Valero A., Toppila-Salmi S., Tsiligianni I., Untersmayr E., Urrutia-Pereira M., Valiulis A., Valovirta E., Vandenplas O., Ventura M.T., Vichyanond P., Wagenmann M., Wallace D., Walusiak-Skorupa J., Wang D.Y., Waserman S., Wong G.W.K., Yorgancioglu A., Yusuf O.M., Zernotti M., Zhang L., Zidarn M., Zuberbier T., Jutel M., HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, Department of Pathology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Philipps Universität Marburg = Philipps University of Marburg, Transilvania University of Brasov, Universität Zürich [Zürich] = University of Zurich (UZH), Humanitas University [Milan] (Hunimed), Universidad San Pablo CEU, Kuwait University, Al-Rashed Allergy Center [Kuwait City], Pantai Hospital [Kuala Lumpur], Hospital Quirónsalud Bizkaia [Bilbao], Ghent University Hospital, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Sun Yat-Sen University [Guangzhou] (SYSU), Universiti Sains Malaysia (USM), Humboldt University Of Berlin, Berlin Institute of Health (BIH), Odense University Hospital (OUH), Skane University Hospital [Lund], Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Woolcock Institute of Medical Research [Sydney], The University of Sydney, Guy's and St Thomas' Hospital [London], King‘s College London, Università degli studi di Torino = University of Turin (UNITO), University of Cartagena, Vall d'Hebron University Hospital [Barcelona], Centro Hospitalar de Lisboa Central E.P.E, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), University of South Florida [Tampa] (USF), Azienda Usl Toscana centro [Firenze], Universidad Simon Bolivar (USB), David Tvildiani Medical University (DTMU), McMaster University [Hamilton, Ontario], Children's Clinical University Hospital [Riga, Latvia] (CCUH), Universidade Federal da Bahia (UFBA), Università degli Studi di Cagliari = University of Cagliari (UniCa), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Foch [Suresnes], Sagamihara National Hospital [Kanagawa, Japan], Université Ain Shams, Vilnius University [Vilnius], CHU Clermont-Ferrand, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Universidade do Porto = University of Porto, Silesian Medical University, Katowice, Poland, Cerrahpasa Faculty of Medicine, Istanbul University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Universidad de Chile = University of Chile [Santiago] (UCHILE), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Medizinische Universität Wien = Medical University of Vienna, Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Tartu University Hospital [Tartu, Estonia], Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Hacettepe University = Hacettepe Üniversitesi, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Nova Southeastern University (NSU), Nofer Institute of Occupational Medicine (NIOM), National University of Singapore (NUS), Yong Loo Lin School of Medicine [Singapore], The Chinese University of Hong Kong [Hong Kong], Manisa Celal Bayar University, Universidad Nacional de Villa María, Universidad Católica de Córdoba, Beijing Tongren Hospital, Herrada, Anthony, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, and UCL - (MGD) Service de pneumologie

Subjects
Pulmonary and Respiratory Medicine, precision medicine, education, Immunology, Review, Settore MED/10 - Malattie Dell'Apparato Respiratorio, immune system diseases, HDE ALER, allergic rhinitis, asthma, immunotherapy, Medicine and Health Sciences, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, ComputingMilieux_MISCELLANEOUS, Rhinitis, RC581-607, respiratory tract diseases, 3121 General medicine, internal medicine and other clinical medicine, Immunologic diseases. Allergy, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, allergic rhinitis, asthma, immunotherapy, precision medicine
Abstract

Funding Information: BSreports personal fees from Allergopharma, during the conduct of the study; grants from National Health Programm, grant, personal fees from Polpharma, ASTRA, personal fees from Mylan, Adamed, patient ombudsman, national Centre for Research and Development, Polish Allergology Society. Funding Information: NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. Funding Information: CA reports grants from Allergopharma, grants from Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission's Horison's 2020 Framework Programme, Cure, Novartis Research Institutes, Astra Zeneca, scibase, advisory role in Sanofi/Regeneron, grants from Glakso Smith‐Kline, advisory role in scibase. Funding Information: MJTreports grants from European Commission, SEAIC, ISCIII, personal fees from Diater laboratory, Leti laboratory, Aimmune Therapeutics. Funding Information: LK reports grants and personal fees from Allergopharma, MEDA/Mylan, LETI Pharma, Sanofi, grants from Stallergenes, Quintiles, ASIT biotech, grants from ALK Abelló, Lofarma, AstraZeneca, GSK, Inmunotk, personal fees from Allergy Therapeut., HAL Allergie, Cassella med; and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. Funding Information: DPreports grants and personal fees from GlaxoSmithKline, personal fees from Menarini, Pliva, Belupo, AbbVie, Novartis, MSD, Chiesi, Revenio, personal fees and non‐financial support from Boehringer Ingelheim, non‐financial support from Philips. Funding Information: OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., Glaxo Smith Kline, grants from Biomay, Circassia, Pohl‐Boskamp, Inmunotek S.L., personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. publishersversion published

Published
2021
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19. Hypersensitivity to gadolinium-based contrast agents: a single-center retrospective analysis over 7 years

Author

Borushko Anna, Srisuwatchari Witchaya, Gauthier Amélie, Demoly Pascal, Ehrhardt Yohan, Chiriac Anca Mirela, Moutou Aurélie, Popa Lidia, Mankouri Farid, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre Hospitalier Université Laval [Quebec] (CHUL), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Belarusian Medical Academy of Post-Graduate Education [Minsk] (BelMAPGE), Service d'allergologie et de pneumologie [Hôpital Arnaud de Villeneuve], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Centre Hospitalier Saint Jean de Perpignan, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], and CHIRIAC, Anca Mirela

Subjects
medicine.medical_specialty, Gadolinium, media_common.quotation_subject, MEDLINE, Contrast Media, chemistry.chemical_element, Single Center, 030218 nuclear medicine & medical imaging, Drug Hypersensitivity, 03 medical and health sciences, 0302 clinical medicine, Text mining, Hypersensitivity, medicine, Retrospective analysis, Humans, Immunology and Allergy, Contrast (vision), [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, media_common, business.industry, Magnetic Resonance Imaging, 030228 respiratory system, chemistry, Radiology, business, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract

International audience; Gadolinium-based contrast agents (GCs), used for magnetic resonance imaging (MRI), are classically considered safer with regard to hypersensitivity (HS) reactions than iodinated radiocontrast media (iRCM). We conducted a retrospective analysis of 132 consecutive patients investigated for suspicions of GC HS (see this article’s Online Repository at www.jaci-inpractice.org). Among the 132 tested patients (83.3% female), 110 (83.3%) had a history of immediate HS (

Published
2021
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23. The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline

Author

Alexandre Demoule, Dipayan Chaudhuri, Carol L. Hodgson, Antonio Pesenti, Jean-Damien Ricard, Karen E. A. Burns, Armand Dessap-Mekontso, Ewan C. Goligher, Jordi Mancebo, Alain Mercat, M. Elizabeth Wilcox, Gilda Cinnella, Tommaso Mauri, Arthur S. Slutsky, Lamia Ouanes-Besbes, Samir Jaber, Renee D. Stapleton, Massimo Antonelli, David Granton, Salvatore Maurizio Maggiore, Jean-Pierre Frat, Dominic Xiang Wang, Michela Rauseo, Laurent Brochard, Arnaud W. Thille, Charles D. Gomersall, Sharon Einav, John F. Fraser, Daniel Talmor, Elie Azoulay, Bram Rochwerg, Yigal Helviz, Giacomo Grasselli, Elisabeth D. Riviello, Nuttapol Rittayamai, Oriol Roca, Carlos Roberto Ribeiro de Carvalho, Sameer Jog, Gonzalo Hernández, McMaster University [Hamilton, Ontario], Shaare Zedek Medical Center [Jerusalem, Israel], The Hebrew University of Jerusalem (HUJ), Hospital Universitari Sant Pau, Barcelona, Università degli Studi di Milano [Milano] (UNIMI), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University Health Network, University of Toronto, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Vall d'Hebron University Hospital [Barcelona], Vall d’Hebron Research Institute (VHIR), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III [Madrid] (ISC), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Monash University [Melbourne], Alfred Health, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Fattouma Bourguiba [Monastir] (HFB), Université de Monastir - University of Monastir (UM), Università degli Studi di Foggia - University of Foggia, University of São Paulo (USP), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Queensland [Brisbane], The Prince Charles Hospital, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Chinese University of Hong Kong [Hong Kong], Hospital Virgen de la Salud, Toledo, Spain, Deenanath Mangeshkar Hospital [Pune], Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], St. Michael's Hospital, Larner College of Medicine [University of Vermont, Burlington], University of Vermont [Burlington], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Università cattolica del Sacro Cuore [Roma] (Unicatt), Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The Prince Charles Hospital [Queensland, Australia] (Metro North Hospital and Health Service), Università degli Studi di Milano = University of Milan (UNIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Foggia = University of Foggia (Unifg), and Universidade de São Paulo = University of São Paulo (USP)

Subjects
Adult, medicine.medical_specialty, medicine.medical_treatment, Conference Reports and Expert Panel, [SDV]Life Sciences [q-bio], Peri-intubation, Respiratory failure, Critical Care and Intensive Care Medicine, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Extubation, Anesthesiology, Oxygen therapy, Settore MED/41 - ANESTESIOLOGIA, Medicine, Cannula, Humans, Postoperative, Mortality, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Noninvasive Ventilation, business.industry, Oxygen Inhalation Therapy, 030208 emergency & critical care medicine, Guideline, 3. Good health, Clinical Practice, Oxygen, High flow nasal cannula, 030228 respiratory system, Cardiothoracic surgery, Airway Extubation, business, High flow, Respiratory Insufficiency, Nasal cannula
Abstract

Purpose High flow nasal cannula (HFNC) is a relatively recent respiratory support technique which delivers high flow, heated and humidified controlled concentration of oxygen via the nasal route. Recently, its use has increased for a variety of clinical indications. To guide clinical practice, we developed evidence-based recommendations regarding use of HFNC in various clinical settings. Methods We formed a guideline panel composed of clinicians, methodologists and experts in respiratory medicine. Using GRADE, the panel developed recommendations for four actionable questions. Results The guideline panel made a strong recommendation for HFNC in hypoxemic respiratory failure compared to conventional oxygen therapy (COT) (moderate certainty), a conditional recommendation for HFNC following extubation (moderate certainty), no recommendation regarding HFNC in the peri-intubation period (moderate certainty), and a conditional recommendation for postoperative HFNC in high risk and/or obese patients following cardiac or thoracic surgery (moderate certainty). Conclusions This clinical practice guideline synthesizes current best-evidence into four recommendations for HFNC use in patients with hypoxemic respiratory failure, following extubation, in the peri-intubation period, and postoperatively for bedside clinicians. Electronic supplementary material The online version of this article (10.1007/s00134-020-06312-y) contains supplementary material, which is available to authorized users.

Published
2020
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24. Chitosan/carboxymethylcellulose-stabilized poly(lactide-co-glycolide) particles as bio-based drug delivery carriers

Author

Panya Sunintaboon, Michèle Léonard, Alain Durand, Supharat Inphonlek, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Laboratoire de Chimie Physique Macromoléculaire (LCPM), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)

Subjects
Curcumin, Polymers and Plastics, Antineoplastic Agents, macromolecular substances, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Chitosan, chemistry.chemical_compound, Colloid, Drug Delivery Systems, Polylactic Acid-Polyglycolic Acid Copolymer, Materials Chemistry, Zeta potential, Tumor Cells, Cultured, Humans, Surface Tension, [CHIM]Chemical Sciences, Particle Size, Cell Proliferation, Drug Carriers, Molecular Structure, Organic Chemistry, technology, industry, and agriculture, Cationic polymerization, Aqueous two-phase system, 021001 nanoscience & nanotechnology, HCT116 Cells, 0104 chemical sciences, PLGA, chemistry, Carboxymethylcellulose Sodium, Emulsion, Drug delivery, Drug Screening Assays, Antitumor, 0210 nano-technology, Colorectal Neoplasms, Nuclear chemistry
Abstract

Poly(lactide-co-glycolide) (PLGA) colloidal particles stabilized by complexes of two oppositely charged polysaccharides, chitosan (cationic, CS) and sodium carboxymethylcellulose (anionic, NaCMC), were fabricated. Dichloromethane containing dissolved PLGA was first emulsified in an aqueous phase containing mixtures of CS and NaCMC. Evaporation of dichloromethane from the resulting emulsion led to CS/NaCMC-covered-PLGA particles. CS and NaCMC contents affected the short-term stability of PLGA particles and also their intrinsic characteristics. The particles displayed pH-dependent characteristic. Zeta potential varied from +54 to -50 mV when pH was varied from 3 to 10. CS/NaCMC-covered-PLGA particles showed colloidal stability, over a wider pH range as compared to CS-covered-PLGA particles. Curcumin, a model hydrophobic drug, was encapsulated into the particles up to 10 wt% of PLGA. The CS/NaCMC-covered-PLGA particles loaded with curcumin showed delayed release in mildly acidic conditions and faster release in neutral and basic conditions. Cytotoxicity experiments were carried out with human colorectal carcinoma cells.

Published
2020
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25. Investigation of cationized triblock and diblock poly(ε-caprolactone)-co-poly(ethylene glycol) copolymers for oral delivery of enoxaparin: In vitro approach

Author

Anne Sapin-Minet, Philippe Maincent, Pimchanok Charoongchit, Jiraphong Suksiriworapong, Shirui Mao, Varaporn Buraphacheep Junyaprasert, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Shenyang Pharmaceutical University, Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), and Université de Lorraine (UL)

Subjects
Poly(ε-carprolactone)-co-poly(ethylene glycol) copolymers, MESH: Cell Death, Cell Membrane Permeability, [SDV]Life Sciences [q-bio], Administration, Oral, Nanoparticle, Polymer architecture, 02 engineering and technology, 01 natural sciences, Biochemistry, Polyethylene Glycols, Cationic copolymer, chemistry.chemical_compound, Drug Delivery Systems, Copolymer, MESH: Cell Membrane Permeability, [PHYS]Physics [physics], Cell Death, Temperature, Biomaterial, General Medicine, 021001 nanoscience & nanotechnology, MESH: Polyesters, MESH: Temperature, Oral delivery, MESH: Administration, Oral, MESH: Caco-2 Cells, 0210 nano-technology, Caprolactone, Biotechnology, MESH: Enoxaparin, Materials science, Surface Properties, Polyesters, MESH: Drug Delivery Systems, Biomedical Engineering, MESH: Imaging, Three-Dimensional, 010402 general chemistry, Biomaterials, Imaging, Three-Dimensional, Cations, PEG ratio, Polymer chemistry, Humans, MESH: Drug Liberation, [CHIM]Chemical Sciences, MESH: Particle Size, Particle Size, Enoxaparin, MESH: Cations, Molecular Biology, MESH: Surface Properties, MESH: Humans, Cationic polymerization, 0104 chemical sciences, Drug Liberation, MESH: Polyethylene Glycols, chemistry, Nanoparticles, Caco-2 Cells, Ethylene glycol, Nuclear chemistry
Abstract

In this study, poly( e -caprolactone)-co-poly(ethylene glycol) copolymers grafted with a cationic ligand, propargyltrimethyl ammonium iodide (PTA), to fabricate the cationized triblock (P(CatCLCL) 2 -PEG) and diblock (P(CatCLCL)-mPEG) copolymers were investigated their potential use for oral delivery of enoxaparin (ENX). Influences of various PTA contents and different structures of the copolymers on molecular characteristics, ENX encapsulation, particle characteristics, and capability of drug transport across Caco-2 cells were elucidated. The results showed that P(CatCLCL) 2 -PEG and P(CatCLCL)-mPEG copolymers self-aggregated and encapsulated ENX into spherical particles of ∼200–450 nm. The increasing amount of PTA on the copolymers increased encapsulation efficiency of over 90%. The ENX release from both types of the cationized copolymer particles was pH-dependent which was retarded at pH 1.2 and accelerated at pH 7.4, supporting the drug protection in the acidic environment and possible release in the blood circulation. The toxicity of ENX-loaded particles on Caco-2 cells decreased when decreasing the amount of PTA. The triblock and diblock particles dramatically enhanced ENX uptake and transport across Caco-2 cells as compared to the ENX solution. However, the different structures of the copolymers slightly affected ENX transport. These results suggested that P(CatCLCL) 2 -PEG and P(CatCLCL)-mPEG copolymers would be potential carriers for oral delivery of ENX. Statement of Significance The anionic drugs such as proteins, peptides or polysaccharides are generally administered via invasive route causing patient incompliance and high cost of hospitalization. The development of biomaterials for non-invasive delivery of those drugs has gained much attention, especially for oral delivery. However, they have limitation due to non-biocompatibility and poor drug bioavailability. In this study, the novel poly( e -caprolactone)-co-poly(ethylene glycol) copolymers grafted with propargyltrimethyl ammonium iodide, a small cationic ligand, were introduced to use as a carrier for oral delivery of enoxaparin, a highly negatively charged drug. The study showed that these cationized copolymers could achieve high enoxaparin entrapment efficiency, protect drug release in an acidic environment and enhance enoxaparin permeability across Caco-2 cells, the intestinal cell model. These characteristics of the cationized copolymers make them a potential candidate for oral delivery of anionic drugs for biomaterial applications.

Published
2017
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26. Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope

Author

Rouvinski, Alexander, Dejnirattisai, Wanwisa, Guardado-Calvo, Pablo, Vaney, Marie-Christine, Sharma, Arvind, Duquerroy, Stéphane, Supasa, Piyada, Wongwiwat, Wiyada, Haouz, Ahmed, Barba-Spaeth, Giovanna, Mongkolsapaya, Juthathip, Rey, Félix A., Screaton, Gavin R., Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Division of Immunology and Inflammation, Department of Medicine, Imperial College London-Hammersmith Hospital Campus, Protéopole, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], We acknowledge support from the European Commission FP7 Programme for the DENFREE project under Grant Agreement number 282 378FP7 (F.A.R., J.M. and G.R.S.), the ‘Integrative Biology of Emerging Infectious Diseases’ Labex (Laboratoire d’Excellence) grant number ANR-10-LABX-62-IBEID (French Government’s ‘Investissements d’Avenir’ program ) (F.A.R.) the National Institute for Health Research Biomedical Research Centre, Funding Scheme, UK (G.R.S.), and the NEUTRAVIR grant from Région Ile-de-France (DIM-Maladies Infectieuses) (F.A.R.). G.R.S. is a Wellcome Trust Senior Investigator., We thank Watchara Kasinrerk and Chunya Putthikhunt for anti-dengue anti-DomIII mAb 2C8, J. Freire and G. Bowler for help and discussion, the staff at the crystallogenesis and chemogenomic & biological screening facilities at Institut Pasteur, the staff at beamlines PX1 and PX2 at SOLEIL synchrotron (Saclay, France), the staff at beamlines ID23-1, ID23-2, ID29 and IB30B at the European Synchrotron Radiation Facility (Grenoble, France), Fabrice Agou at Institut Pasteur for the MALS system., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
STRUCTURAL BASIS, MONOCLONAL-ANTIBODY, [SDV]Life Sciences [q-bio], Science, Enzyme-Linked Immunosorbent Assay, Antibodies, Viral, Crystallography, X-Ray, CROSS-NEUTRALIZATION, Article, Dengue virus, NEUTRALIZING ANTIBODIES, Mice, Protein Domains, Viral Envelope Proteins, Aedes, Chlorocebus aethiops, INFECTION, MD Multidisciplinary, Animals, Humans, Disulfides, Vero Cells, ANTIBODY-DEPENDENT ENHANCEMENT, X-ray crystallography, Vaccines, Science & Technology, Immunodominant Epitopes, HIGHLY POTENT, MACROMOLECULAR CRYSTALLOGRAPHY, Antibodies, Monoclonal, SEROTYPE 3, Antibodies, Neutralizing, Multidisciplinary Sciences, HEK293 Cells, Viral infection, Liposomes, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Science & Technology - Other Topics, Drosophila, Protein Multimerization, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, ZIKA VIRUS, Epitope Mapping
Abstract

A problem in the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop epitope (FLE), a segment of the envelope protein E that is buried at the interface of the E dimers coating mature viral particles. Anti-FLE antibodies are broadly cross-reactive but poorly neutralizing, displaying a strong infection enhancing potential. FLE exposure takes place via dynamic ‘breathing' of E dimers at the virion surface. In contrast, antibodies targeting the E dimer epitope (EDE), readily exposed at the E dimer interface over the region of the conserved fusion loop, are very potent and broadly neutralizing. We here engineer E dimers locked by inter-subunit disulfide bonds, and show by X-ray crystallography and by binding to a panel of human antibodies that these engineered dimers do not expose the FLE, while retaining the EDE exposure. These locked dimers are strong immunogen candidates for a next-generation vaccine., The immunodominant epitope of dengue virus envelope protein (E) induces poorly neutralizing antibodies, which poses a problem for vaccine development. Here, the authors engineer covalently locked E dimers exposing an epitope that has been shown to induce potent and broadly neutralizing antibodies.

Published
2017
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27. Use of nasal high flow oxygen during acute respiratory failure

Author

Oriol Roca, Amanda Corley, François Lellouche, Peter A. Jones, Virginie Lemiale, Nuttapol Rittayamai, Gonzalo Hernández, Stefano Nava, Jens Bräunlich, Samir Jaber, Jean-Damien Ricard, Byung Ju Kang, Giulia Spoletini, Medico-surgical ICU, Assistance Publique - Hôpitaux de Paris, DMU ESPRIT, Médecine Intensive Réanimation, Hôpital Louis Mourier, 92700, Colombes, Critical Care Department, Vall d'Hebron University Hospital, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Medical ICU Saint Louis Hospital, APHP, Paris, Critical Care Research Group, The Prince Charles Hospital, Chermside, Department of Respiratory Medicine, University of Leipzig, Liebigstraße 20, 04103, Leipzig, School of Medicine, University of Auckland, Auckland, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Quebec Heart and Lung Institute, Laval University, Québec City, QC, Department of Clinical, Integrated, and Experimental Medicine (DIMES), Respiratory and Critical Care, Sant'Orsola Malpighi Hospital, Bologna, Division of Respiratory Diseases and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Department of Respiratory Medicine, St James's University Hospital, Leeds Teaching Hospital NHS Trust, Leeds, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Intensive Care Medicine, University Hospital Virgen de la Salud, Toledo, MORNET, Dominique, Universitat Autònoma de Barcelona (UAB), The Prince Charles Hospital, Leipzig University, Ricard J.-D., Roca O., Lemiale V., Corley A., Braunlich J., Jones P., Kang B.J., Lellouche F., Nava S., Rittayamai N., Spoletini G., Jaber S., and Hernandez G.

Subjects
medicine.medical_specialty, ARDS, Palliative care, High flow oxygen, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Acute respiratory failure, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology, medicine, Intubation, Intratracheal, Intubation, Humans, Respiratory function, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Respiratory Distress Syndrome, Noninvasive Ventilation, business.industry, Oxygen Inhalation Therapy, 030208 emergency & critical care medicine, Emergency department, medicine.disease, 3. Good health, Oxygen, [SDV] Life Sciences [q-bio], 030228 respiratory system, Breathing, Narrative Review, business, Respiratory Insufficiency, Human, Nasal canula
Abstract

Nasal high flow (NHF) has gained popularity among intensivists to manage patients with acute respiratory failure. An important literature has accompanied this evolution. In this review, an international panel of experts assessed potential benefits of NHF in different areas of acute respiratory failure management. Analyses of the physiological effects of NHF indicate flow-dependent improvement in various respiratory function parameters. These beneficial effects allow some patients with severe acute hypoxemic respiratory failure to avoid intubation and improve their outcome. They require close monitoring to not delay intubation. Such a delay may worsen outcome. The ROX index may help clinicians decide when to intubate. In immunocompromised patients, NHF reduces the need for intubation but does not impact mortality. Beneficial physiological effects of NHF have also been reported in patients with chronic respiratory failure, suggesting a possible indication in acute hypercapnic respiratory failure. When intubation is required, NHF can be used to pre-oxygenate patients either alone or in combination with non-invasive ventilation (NIV). Similarly, NHF reduces reintubation alone in low-risk patients and in combination with NIV in high-risk patients. NHF may be used in the emergency department in patients who would not be offered intubation and can be better tolerated than NIV. Electronic supplementary material The online version of this article (10.1007/s00134-020-06228-7) contains supplementary material, which is available to authorized users.

Published
2020
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28. Development of rectodispersible tablets and granulate capsules for the treatment of serious neonatal sepsis in developing countries

Author

Thida Phoeung, Karen Gaudin, Tina Kauss, Anthony Cartwright, Xiao Yu Xie, Alice Guyonnet-Dupérat, Nicholas G. White, Marie-Hélène Langlois, Melba Gomes, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], World Health Organisation (WHO), and Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)

Subjects
Male, medicine.medical_specialty, medicine.drug_class, Drug Compounding, [SDV]Life Sciences [q-bio], Cephalosporin, Antibiotics, Pharmaceutical Science, Developing country, Biological Availability, Capsules, 02 engineering and technology, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Oral administration, medicine, Animals, Humans, Intensive care medicine, Neonatal sepsis, business.industry, Suppositories, Ceftriaxone, Infant, Newborn, Infant, 021001 nanoscience & nanotechnology, medicine.disease, 3. Good health, Bioavailability, Anti-Bacterial Agents, Drug development, Rabbits, Neonatal Sepsis, 0210 nano-technology, business, medicine.drug, Tablets
Abstract

Current pediatric antibiotic therapies often use oral and parenteral routes of administration. Neither are suitable for treating very sick neonates who cannot take oral medication and may be several hours away from hospital in developing countries. Here, we report on the development of rectal forms of ceftriaxone, a third-generation cephalosporin. Rectodispersible tablets and capsules were developed and successfully passed 6-month accelerated stability tests. Rabbit bioavailability showed plasma concentrations above the minimal inhibitory concentrations for 3 formulations of rectodispersible tablets and 2 formulations of hard capsules. Clinical batches are currently being prepared for human evaluation with the prospect of offering therapeutic alternatives for treating critically ill neonates. This proof of concept for efficient rectal delivery of antibiotics could help the development of other rectal antibiotic treatments and increase options for noninvasive drug development for pediatric patients.

Published
2019
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29. GenomegaMap: within-species genome-widedN/dSestimation from over 10,000 genomes

Author

Wilson, DJ, Crook, DW, Peto, TEA, Walker, AS, Hoosdally, SJ, Gibertoni Cruz, AL, Carter, J, Grazian, C, Earle, SG, Kouchaki, S, Lachapelle, A, Yang, Y, Clifton, DA, Fowler, PW, Iqbal, Z, Hunt, M, Knaggs, J, Smith, EG, Rathod, P, Jarrett, L, Matias, D, Cirillo, DM, Borroni, E, Battaglia, S, Ghodousi, A, Spitaleri, A, Cabibbe, A, Tahseen, S, Nilgiriwala, K, Shah, S, Rodrigues, C, Kambli, P, Surve, U, Khot, R, Niemann, S, Kohl, TA, Merker, M, Hoffmann, H, Todt, K, Plesnik, S, Ismail, N, Omar, SV, Joseph, L, Thwaites, G, Thuong, TNT, Ngoc, NH, Srinivasan, V, Walker, TM, Moore, D, Coronel, J, Solano, W, Gao, GF, He, G, Zhao, Y, Liu, C, Ma, A, Zhu, B, Laurenson, I, Claxton, P, Koch, A, Wilkinson, R, Lalvani, A, Posey, J, Gardy, J, Werngren, J, Paton, N, Jou, R, Wu, M-H, Lin, W-H, Ferrazoli, L, De Oliveira, RS, Arandjelovic, I, Chaiprasert, A, Comas, I, Roig, CJ, Drobniewski, FA, Farhat, MR, Gao, Q, Hee, ROT, Sintchenko, V, Supply, P, Van Soolingen, D, University of Oxford, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), D.J.W. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (grant no. 101237/Z/13/B) and is a Big Data Institute Robertson Fellow. The CRyPTIC Consortium was supported by grants from the Bill and Melinda Gates Foundation (OPP1133541) and a Wellcome Trust/Newton Fund-MRC Collaborative Award (200205/Z/15/Z). F.A.D. was supported by the Imperial Biomedical Research Centre., Members of the CRyPTIC Consortium : Derrick W. Crook, Timothy E.A. Peto, A. Sarah Walker, Sarah J. Hoosdally, Ana L. Gibertoni Cruz, Joshua Carter, Clara Grazian, Sarah G. Earle, Samaneh Kouchaki, Alexander Lachapelle, Yang Yang, David A. Clifton, and Philip W. Fowler, University of Oxford, Zamin Iqbal, Martin Hunt, and Jeffrey Knaggs, European Bioinformatics Institute, E. Grace Smith, Priti Rathod, Lisa Jarrett, and Daniela Matias, Public Health England, Birmingham, Daniela M. Cirillo, Emanuele Borroni, Simone Battaglia, Arash Ghodousi, Andrea Spitaleri, and Andrea Cabibbe, Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Milan, Sabira Tahseen, National Tuberculosis Control Program Pakistan, Islamabad, Kayzad Nilgiriwala and Sanchi Shah, The Foundation for Medical Research, Mumbai, Camilla Rodrigues, Priti Kambli, Utkarsha Surve, and Rukhsar Khot, P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, Stefan Niemann, Thomas A. Kohl, and Matthias Merker, Research Center Borstel, Harald Hoffmann, Katharina Todt, and Sara Plesnik, Institute of Microbiology & Laboratory Medicine, IML Red, Gauting, Nazir Ismail, Shaheed Vally Omar, and Lavania Joseph, National Institute for Communicable Diseases, Johannesburg, Guy Thwaites, Thuong Nguyen Thuy Thuong, Nhung Hoang Ngoc, Vijay Srinivasan, and Timothy M. Walker, Oxford University Clinical Research Unit, Ho Chi Minh City, David Moore, Jorge Coronel and Walter Solano, London School of Hygiene and Tropical Medicine and Universidad Peruana Cayetano Heredá, Lima, George F. Gao, Guangxue He, Yanlin Zhao, and Chunfa Liu, China CDC, Beijing, Aijing Ma, Shenzhen Third People’s Hospital, Shenzhen, Baoli Zhu, Institute of Microbiology, CAS, Beijing, Ian Laurenson and Pauline Claxton, Scottish Mycobacteria Reference Laboratory, Edinburgh, Anastasia Koch, Robert Wilkinson, University of Cape Town, Ajit Lalvani, Imperial College London, James Posey, CDC Atlanta, Jennifer Gardy, University of British Columbia, Jim Werngren, Public Health Agency of Sweden, Nicholas Paton, National University of Singapore, Ruwen Jou, Mei-Hua Wu, Wan-Hsuan Lin, CDC Taiwan, Lucilaine Ferrazoli, Rosangela Siqueira de Oliveira, Institute Adolfo Lutz, São Paulo. Authors contributing to the CRyPTIC Consortium are (in alphabetical order): Irena Arandjelovic (Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia), Angkana Chaiprasert (Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand), Iñaki Comas (Instituto de Biomedicina de Valencia [IBV-CSIC], Calle Jaime Roig, Valencia, Spain, FISABIO Public Health, Valencia, Spain, CIBER in Epidemiology and Public Health, Madrid, Spain), Francis A. Drobniewski (Imperial College, London, UK), Maha R. Farhat (Harvard Medical School, Boston, USA), Qian Gao (Shanghai Medical College, Fudan University, Shanghai, China), Rick Ong Twee Hee (Saw Swee Hock School of Public Health, National University of Singapore, Singapore), Vitali Sintchenko (Centre for Infectious Diseases and Microbiology—Public Health, University of Sydney, Sydney, Australia), Philip Supply (Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019—UMR 8204—CIIL—Centre d’Infection et d’Immunité de Lille, F-59000 Lille, France), and Dick van Soolingen (National Institute for Public Health and the Environment [RIVM], Bilthoven, The Netherlands)., Supply, Philip, Consortium, CRyPTIC, University of Oxford [Oxford], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Royal Society (UK), Bill & Melinda Gates Foundation, Newton Fund, Comas, Iñaki [0000-0001-5504-9408], and Comas, Iñaki

Subjects
Natural selection, [SDV]Life Sciences [q-bio], Population genetics, adaptation, Computational biology, Biology, AcademicSubjects/SCI01180, 0601 Biochemistry and Cell Biology, Genome, Coalescent theory, DEAD-box RNA Helicases, Big data, 03 medical and health sciences, 0603 Evolutionary Biology, big data, Parent-dependent mutation, Genetics, dN/dS, Adaptation, Selection, Genetic, Molecular Biology, Allele frequency, Ecology, Evolution, Behavior and Systematics, Silent Mutation, Selection (genetic algorithm), 030304 developmental biology, Evolutionary Biology, 0604 Genetics, 0303 health sciences, Models, Genetic, Phylogenetic tree, 030306 microbiology, AcademicSubjects/SCI01130, natural selection, Mycobacterium tuberculosis, Recombination, Resources, recombination, 3. Good health, [SDV] Life Sciences [q-bio], Genetic Techniques, Mutation (genetic algorithm), parent-dependent mutation, Genome, Bacterial
Abstract

11 págs, 4 figuras y fórmulas matemáticas. Material suplementario en: http://dx.doi.org/10.1093/molbev/msaa069, The dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess or deficit of amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding of parameters, such as dN/dS, but analyzing very large data sets poses a major statistical challenge. Here, I introduce genomegaMap for estimating within-species genome-wide variation in dN/dS, and I apply it to 3,979 genes across 10,209 tuberculosis genomes to characterize the selection pressures shaping this global pathogen. GenomegaMap is a phylogeny-free method that addresses two major problems with existing approaches: 1) It is fast no matter how large the sample size and 2) it is robust to recombination, which causes phylogenetic methods to report artefactual signals of adaptation. GenomegaMap uses population genetics theory to approximate the distribution of allele frequencies under general, parent-dependent mutation models. Coalescent simulations show that substitution parameters are well estimated even when genomegaMap's simplifying assumption of independence among sites is violated. I demonstrate the ability of genomegaMap to detect genuine signatures of selection at antimicrobial resistance-conferring substitutions in Mycobacterium tuberculosis and describe a novel signature of selection in the cold-shock DEAD-box protein A gene deaD/csdA. The genomegaMap approach helps accelerate the exploitation of big data for gaining new insights into evolution within species., D.J.W. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (grant no. 101237/Z/13/B) and is a Big Data Institute Robertson Fellow. The CRyPTIC Consortium was supported by grants from the Bill and Melinda Gates Foundation (OPP1133541) and a Wellcome Trust/Newton Fund-MRC Collaborative Award (200205/Z/15/Z). F.A.D. was supported by the Imperial Biomedical Research Centre

Published
2019
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30. High Anti–Dengue Virus Activity of theOASGene Family Is Associated With Increased Severity of Dengue

Author

Worachart Lert-itthiporn, Ampaiwan Chuansumrit, Nattaya Tangthawornchaikul, Richard Paul, Prida Malasit, Shyr Yi Lin, Anavaj Sakuntabhai, Han Pang Yu, Etienne Simon-Loriere, Prapat Suriyaphol, Kanchana Tangnararatchakit, Philipe Despres, Wathanee Chaiyaratana, Bi Lan Chang, Sutee Yoksan, Sirijitt Vasanawathana, Ren-Jye Lin, Isabelle Casademont, Yi-Ling Lin, Sita Mint Kalayanarooj, Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Mahidol University [Bangkok], Academia Sinica, Siriraj Hospital, Mahidol University, Ramathibodi Hospital, National Science and Technology Development Agency [Bangkok] (NSTDA), Khon Kaen Hospital, Center for Vaccine Development, Mahidol University [Bangkok]-Institute of Science and Technology for Research and Development, Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)

Subjects
Male, [SDV]Life Sciences [q-bio], viruses, MESH: Dengue, Dengue virus, MESH: Dengue Virus, medicine.disease_cause, Dengue fever, Dengue, Interferon, MESH: Child, Genotype, 2',5'-Oligoadenylate Synthetase, Immunology and Allergy, Child, innate immunity, Cells, Cultured, MESH: 2',5'-Oligoadenylate Synthetase, MESH: Genetic Association Studies, MESH: Genetic Predisposition to Disease, virus diseases, interferon, MESH: Infant, 3. Good health, Infectious Diseases, MESH: Young Adult, Child, Preschool, cytokine storm, Female, Viral disease, MESH: Cells, Cultured, medicine.drug, Adult, Adolescent, Biology, Young Adult, Immune system, medicine, Humans, Genetic Predisposition to Disease, Genetic Association Studies, MESH: Adolescent, MESH: Humans, Innate immune system, dengue virus, MESH: Child, Preschool, Infant, MESH: Adult, biochemical phenomena, metabolism, and nutrition, medicine.disease, Virology, MESH: Male, Immunology, Cytokine storm, MESH: Female, genetic susceptibility
Abstract

International audience; Dengue is a mosquito-borne viral disease that afflicts millions of individuals worldwide every year. Infection by any of the 4 dengue virus (DENV) serotypes can result in a spectrum of disease severity. We investigated the impact of variants of interferon-regulated innate immunity genes with a potent antiviral effect on the outcome of DENV infection. We compared the effect of OAS gene family variants on 2 DENV serotypes in cell culture. While both OAS1-p42 and p46 showed antiviral activity against DENV-2, only OAS1-p42 presented anti-DENV-1 activity. Conversely, whereas both OAS3_S381 and R381 variants were able to block DENV-1 infection, the anti-DENV-2 activity observed for OAS3_S381 was largely lost for the R381 variant. By means of an allelic association study of a cohort of 740 patients with dengue, we found a protective effect of OAS3_R381 against shock (odds ratio [OR], 0.37; P < .001). This effect was due to DENV-2 infections (OR, 0.13; P = .007) but was absent for DENV-1, in accordance with the serotype-dependent OAS3 activity found in the functional study. Severe dengue has long been associated with a cytokine storm of unclear origin. This work identifies an early innate immunity process that could lead to the immune overreaction observed in severe dengue and could be triggered by a specific host genotype-pathogen genotype interaction.

Published
2015
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31. Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome

Author

Bruno Cavadas, Luísa Pereira, Fanny Koeth, Etienne Simon-Loriere, Marisa Oliveira, Isabelle Casademont, Worachart Lert-itthiporn, Prida Malasit, Orlando Anunciação, Prapat Suriyaphol, Marina Penova, Richard Paul, Fumihiko Matsuda, Chiea Chuen Khor, Ampaiwan Chuansumrit, Kanchana Tangnararatchakit, Anavaj Sakuntabhai, Verónica Fernandes, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Pasteur Kyoto International Joint Research Unit for Integrative Vaccinomics [Kyoto, Japan], Institut Pasteur [Paris], Department of Pediatrics, Faculty of Medicine, Mahidol University [Bangkok]-Ramathibodi Hospital, National University of Singapore (NUS), French National Research Agency (ANR-10–INSB–04, Investments for the Future)., ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Instituto de Investigação e Inovação em Saúde, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Universidade do Porto = University of Porto, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Universidade do Porto [Porto], Genome Institute of Singapore (GIS), Génétique fonctionnelle des maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de Génotypage (CNG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Male, Heredity, Basic Helix-Loop-Helix Transcription Factors / genetics, Thai People, Viral Nonstructural Proteins / genetics, MESH: Asia, Southeastern, Genome-wide association study, Genome, Viral / genetics, Dengue virus, MESH: Dengue Virus, Biochemistry, MESH: Genotype, 0302 clinical medicine, MESH: Basic Helix-Loop-Helix Transcription Factors, Odds Ratio, Ethnicities, Protein Phosphatase 2, MESH: Nerve Tissue Proteins, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Asian Continental Ancestry Group, MESH: Protein Phosphatase 2, Genomics, Genomic Databases, Severe Dengue / ethnology, MESH: Infant, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, MESH: Repressor Proteins, MESH: Young Adult, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Metabolic Pathways, Carrier Proteins / genetics, MESH: Cell Nucleus, MESH: Gene Expression, Genotype, Bioinformatics, lcsh:RC955-962, Single-nucleotide polymorphism, MESH: Severe Dengue, MESH: Carrier Proteins, Serogroup, 03 medical and health sciences, Viral Proteins, Asian People, Sequence Motif Analysis, Cell Nucleus / virology, Genetic predisposition, Genetics, Xenobiotic Metabolism, Humans, MESH: Adolescent, MESH: Humans, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Haplotype, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, Biology and Life Sciences, Computational Biology, Infant, MESH: Adult, lcsh:RA1-1270, Dengue Virus, medicine.disease, Tropical Diseases, MESH: Sulfotransferases, MESH: Cell Line, 030104 developmental biology, Severe Dengue / genetics, MESH: Genome-Wide Association Study, MESH: Viral Nonstructural Proteins, Population Groupings, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Carrier Proteins, MESH: Female, 030217 neurology & neurosurgery, 0301 basic medicine, Viral Diseases, Gene Expression, Repressor Proteins / genetics, MESH: Dengue, Viral Nonstructural Proteins, medicine.disease_cause, Dengue fever, Dengue Fever, Geographical Locations, Dengue, Cohort Studies, Database and Informatics Methods, Medicine and Health Sciences, Basic Helix-Loop-Helix Transcription Factors, Nerve Tissue Proteins / genetics, MESH: Cohort Studies, Asia, Southeastern, Type C Phospholipases / genetics, lcsh:Public aspects of medicine, MESH: Genetic Predisposition to Disease, Thailand, Phenotype, Europe, Genetic Mapping, Infectious Diseases, Dengue Virus / genetics, Asian Continental Ancestry Group / genetics, Female, Sulfotransferases, MESH: Genome, Viral, MESH: Type C Phospholipases, Sequence Analysis, Research Article, Neglected Tropical Diseases, Adult, lcsh:Arctic medicine. Tropical medicine, Adolescent, Dengue / virology, Dengue / genetics, Nerve Tissue Proteins, Genome, Viral, Biology, Genetic Predisposition, Research and Analysis Methods, Cell Line, Young Adult, medicine, Viral Proteins / genetics, Genetic Predisposition to Disease, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Severe Dengue, MESH: Thailand, Cell Nucleus, Protein Phosphatase 2 / genetics, MESH: Serogroup, Genome Analysis, MESH: Viral Proteins, MESH: Male, MESH: Odds Ratio, Repressor Proteins, Biological Databases, Metabolism, Haplotypes, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Type C Phospholipases, People and Places, Genetics of Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Genome-Wide Association Study
Abstract

Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS., Author summary Dengue fever is endemic in tropical and subtropical areas of East Asia and America, but globalization and climate changes are introducing vector and virus to the naïve regions of Europe and North America. In this work we conducted a statistically robust, coupled association-admixture test in two dengue cohorts from Thailand (classical dengue fever, DF, and dengue shock syndrome, DSS) and a published Vietnamese (DSS only) cohort. We identified new candidate genes associated with DF risk and confirmed known gene family association with DSS risk. In DF, phosphatase control is crucial, including through binding to viral proteins, as we showed for PPP2R5E protein co-localization with DENV1 and DENV2-NS5 proteins within liver cells and differential cellular localizations along time. In DSS, cytokine dynamics, inflammation and activation of vascular endothelium cells are dominant features. The particular genetic risk conferred by these genes indicates that Southeast and Northeast Asians are highly susceptible to both phenotypes, while Africans are best protected against DSS, and Europeans best protected against DF but the most susceptible against DSS.

Published
2018
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32. High-flow nasal oxygen versus noninvasive ventilation in adult patients with cystic fibrosis: a randomized crossover physiological study

Author

Detajin Junhasavasdikul, Nuttapol Rittayamai, Carolyn Campbell, Fabiana Madotto, Martin Dres, Irene Telias, Elizabeth Tullis, Michela Rauseo, Michael C. Sklar, Brent West, Domenico Luca Grieco, Tài Pham, Laurent Brochard, HAL UPMC, Gestionnaire, Department of Anesthesia [Toronto, Canada], University of Toronto, Interdepartmental Division of Critical Care Medicine, Keenan Research Centre for Biomedical Science [Toronto, ON, Canada], Li Ka Shing Knowledge Institute [Toronto, ON, Canada]-St. Michael’s Hopsital [Toronto, ON, Canada], Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Division of Respiratory Diseases and Tuberculosis [Bangkok, Thailand] (Department of Medicine), Faculty of Medicine Siriraj Hospital [Bangkok, Thailand], Division of Respirology [Toronto, ON, Canada], St. Michael's Hospital, Department of Anesthesiology and Intensive Care Medicine [Rome, Italy], Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt)-Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Department of Medicine [Bangkok, Thailand] (Faculty of Medicine ), Mahidol University [Bangkok]-Ramathibodi Hospital [Bangkok, Thailand], Department of Anaesthesia and Intensive Care [Foggia, Italy], University of Foggia [Italy], Department of Medicine and Surgery [Monza, Italy] (Research Center on Public Health), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), This study was supported by a grant from the Canadian Cystic Fibrosis Foundation, and equipment for the study was provided by Fisher & Paykel., Neurophysiologie Respiratoire Expérimentale et Clinique, Catholic University of the Sacred Heart [Rome, Italy] -Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), St. Michael’s Hopsital [Toronto, ON, Canada], Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Università degli Studi di Foggia = University of Foggia (Unifg), dres, martin, Sklar, M, Dres, M, Rittayamai, N, West, B, Grieco, D, Telias, I, Junhasavasdikul, D, Rauseo, M, Pham, T, Madotto, F, Campbell, C, Tullis, E, and Brochard, L

Subjects
Respiratory rate, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Diaphragmatic breathing, Hemodynamics, Critical Care and Intensive Care Medicine, Hypoxemia, cystic fibrosis, 03 medical and health sciences, Work of breathing, 0302 clinical medicine, Oxygen therapy, Heart rate, medicine, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, 3. Good health, [SDV] Life Sciences [q-bio], Editorial, 030228 respiratory system, Anesthesia, high-flow nasal oxygen therapy, medicine.symptom, business, Noninvasive ventilation, Respiratory minute volume
Abstract

Background Noninvasive ventilation (NIV) is the first-line treatment of adult patients with exacerbations of cystic fibrosis (CF). High-flow nasal oxygen therapy (HFNT) might benefit patients with hypoxemia and can reduce physiological dead space. We hypothesized that HFNT and NIV would similarly reduce work of breathing and improving breathing pattern in CF patients. Our objective was to compare the effects of HFNT versus NIV in terms of work of breathing, assessed noninvasively by the thickening fraction of the diaphragm (TFdi, measured with ultrasound), breathing pattern, transcutaneous CO2 (PtcCO2), hemodynamics, dyspnea and comfort. Methods Adult CF patients who had been stabilized after requiring ventilatory support for a few days were enrolled and ventilated with HFNT and NIV for 30 min in crossover random order. Results Fifteen patients were enrolled. Compared to baseline, HFNT, but not NIV, reduced respiratory rate (by 3 breaths/min, p = 0.01) and minute ventilation (by 2 L/min, p = 0.01). Patients also took slightly larger tidal volumes with HFNT compared to NIV (p = 0.02). TFdi per breath was similar under the two techniques and did not change from baseline. MAP increased from baseline with NIV and compared to HFNT (p ≤ 0.01). Comfort was poorer with the application of both HFNT and NIV than baseline. No differences were found for heart rate, SpO2, PtcCO2 or dyspnea. Conclusions In adult CF patients stabilized after indication for ventilatory support, HFNT and NIV have similar effects on diaphragmatic work per breath, but high-flow therapy confers additional physiological benefits by decreasing respiratory rate and minute ventilation. Clinical trial registration Ethics Committee of St. Michael’s Hospital (REB #14-338) and clinicaltrial.gov (NCT02262871).

Published
2018
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33. Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency

Author

Anderson Dik Wai Luk, Pamela P. Lee, Huawei Mao, Koon-Wing Chan, Xiang Yuan Chen, Tong-Xin Chen, Jian Xin He, Nadia Kechout, Deepti Suri, Yin Bo Tao, Yong Bin Xu, Li Ping Jiang, Woei Kang Liew, Orathai Jirapongsananuruk, Tassalapa Daengsuwan, Anju Gupta, Surjit Singh, Amit Rawat, Amir Hamzah Abdul Latiff, Anselm Chi Wai Lee, Lynette P. Shek, Thi Van Anh Nguyen, Tek Jee Chin, Yin Hsiu Chien, Zarina Abdul Latiff, Thi Minh Huong Le, Nguyen Ngoc Quynh Le, Bee Wah Lee, Qiang Li, Dinesh Raj, Mohamed-Ridha Barbouche, Meow-Keong Thong, Maria Carmen D. Ang, Xiao Chuan Wang, Chen Guang Xu, Hai Guo Yu, Hsin-Hui Yu, Tsz Leung Lee, Felix Yat Sun Yau, Wilfred Hing-Sang Wong, Wenwei Tu, Wangling Yang, Patrick Chun Yin Chong, Marco Hok Kung Ho, Yu Lung Lau, Department of Paediatrics and Adolescent Medicine [HKU], The University of Hong Kong (HKU), Shenzhen Primary Immunodeficiency Diagnostic and Therapeutic Laboratory, Guangzhou Children’s Hospital, Shanghai Jiao Tong University School of Medicine, Capital Medical University, Beijing, Institut Pasteur d'Algérie, Réseau International des Instituts Pasteur (RIIP), Postgraduate Institute of Medical Education and Research, Guangzhou Women & Childrens Med Ctr, Children’s Hospital of Chongqing Medical University, KK Womens & Childrens Hosp, Singapore, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Queen Sirikit National Institute of Child Health [Bangkok], Monash University [Malaysia], Mount Elizabeth Hospital, National University of Singapore (NUS), National Taiwan University Children’s Hospital, Sarawak General Hospital [Kuching, Sarawak, Malaysia], National Taiwan University [Taiwan] (NTU), University Kebangsaan Malaysia Medical Center, National Children’s Hospital, Sichuan Second West China Hospital, Holy Family Hospital, Institut Pasteur de Tunis, University of Malaya [Kuala Lumpur, Malaisie], San Pedro Hospital, Children's Hospital of Fudan University, Sun Yat-Sen University [Guangzhou] (SYSU), Nanjing Children’s Hospital, Queen Elizabeth Hospital [Hong Kong] (QEH), This work was supported by the Hong Kong Society for Relief of Disabled Children, the Health and Medical Research Fund (01120846), and and grant from Shenzhen Development and Reform Commission ([2015]164)

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, Pediatrics, medicine.medical_specialty, DCLRE1C, [SDV]Life Sciences [q-bio], Immunology, Gene mutation, 03 medical and health sciences, medicine, Immunology and Allergy, Family history, Interleukin-7 receptor, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Original Research, Severe combined immunodeficiency, Newborn screening, family history, business.industry, newborn screening, severe combined immunodeficiency, medicine.disease, candidiasis, Infant mortality, 3. Good health, absolute lymphocyte count, 030104 developmental biology, Primary immunodeficiency, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, lcsh:RC581-607
Abstract

International audience; Background: Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis. Objective: The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID.Methods: From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study.Results: A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29 patients had a positive FH. Candidiasis (n = 27) and bacillus CalmetteGuerin (BCG) vaccine infection (n = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 x 10(9)/L with over 88% patients below 3 x 10(9)/L. Positive FH was associated with earlier AP by 1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections were not associated with age or time to diagnosis.Conclusion: FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 x 10(9)/L.

Published
2017
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34. Structural basis of potent Zika-dengue virus antibody cross-neutralization

Author

Franz X. Heinz, Juthathip Mongkolsapaya, Ahmed Haouz, Arvind Sharma, Patrick England, Van-Mai Cao-Lormeau, Wanwisa Dejnirattisai, Félix A. Rey, Anavaj Sakuntabhai, Iris Medits, Etienne Simon-Loriere, Gavin R. Screaton, Karin Stiasny, Alexander Rouvinski, Giovanna Barba-Spaeth, Marie Christine Vaney, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Division of Immunology and Inflammation, Department of Medicine, Imperial College London-Hammersmith Hospital Campus, Medizinische Universität Wien = Medical University of Vienna, Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Emerging Infectious Diseases, Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD)-Institut de Recherche pour le Développement (IRD), Cristallographie (Plateforme) - Crystallography (Platform), Biophysique des Macromolécules et de leurs Interactions, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], We acknowledge support from the European Commission FP7 Programme for the DENFREE project under Grant Agreement number 282 378FP7 (F.A.R., J.M., G.R.S. and A.Sa.), the 'Integrative Biology of Emerging Infectious Diseases' Labex (Laboratoire d’Excellence) grant number ANR-10-LABX-62-IBEID (French Government’s 'Investissements d’Avenir' program ) (F.A.R.), the transnational ANR/FWF grant FlaviStem/I1378 (F.A.R. and K.S.), the Medical Research Council, UK (J.M.), the National Institute for Health Research Biomedical Research Centre, Funding Scheme, UK (G.R.S.), and the NEUTRAVIR grant from Région ile-de-France (DIM-Maladies Infectieuses) (P.E., A.H. and F.A.R., ANR-13-ISV8-0002,flavistem,La protéine E des flavivirus : interactions et fusion membranaire(2013), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Medical Research Council (MRC), Wellcome Trust, and Commission of the European Communities

Subjects
DYNAMICS, 0301 basic medicine, Models, Molecular, viruses, [SDV]Life Sciences [q-bio], Antigen-Antibody Complex, Dengue virus, medicine.disease_cause, Crystallography, X-Ray, Epitope, Zika virus, Dengue fever, Dengue, Epitopes, 0302 clinical medicine, Viral Envelope Proteins, INFECTION, Virus maturation, IN-VIVO, FLAVIVIRUSES, Phylogeny, Multidisciplinary, Zika Virus Infection, Antibodies, Monoclonal, REACTIVE ANTIBODIES, FUSION-LOOP, 3. Good health, Multidisciplinary Sciences, Flavivirus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Science & Technology - Other Topics, Brazil, General Science & Technology, Dengue Vaccines, Biology, Cross Reactions, MATURATION, Microbiology, 03 medical and health sciences, ENHANCEMENT, medicine, Humans, Antibody-dependent enhancement, Dengue vaccine, Science & Technology, RECEPTOR, RECOGNITION, Viral Vaccines, Zika Virus, Dengue Virus, biology.organism_classification, medicine.disease, Virology, Antibodies, Neutralizing, 030104 developmental biology, 030217 neurology & neurosurgery
Abstract

International audience; Zika virus is a member of the Flavivirus genus that had not been associated with severe disease in humans until the recent outbreaks, when it was linked to microcephaly in newborns in Brazil and to Guillain-Barré syndrome in adults in French Polynesia. Zika virus is related to dengue virus, and here we report that a subset of antibodies targeting a conformational epitope isolated from patients with dengue virus also potently neutralize Zika virus. The crystal structure of two of these antibodies in complex with the envelope protein of Zika virus reveals the details of a conserved epitope, which is also the site of interaction of the envelope protein dimer with the precursor membrane (prM) protein during virus maturation. Comparison of the Zika and dengue virus immunocomplexes provides a lead for rational, epitope-focused design of a universal vaccine capable of eliciting potent cross-neutralizing antibodies to protect simultaneously against both Zika and dengue virus infections.

Published
2016
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35. Development of viable TAP-tagged dengue virus for investigation of host–virus interactions in viral replication

Author

Sarin Chimnaronk, Ponpan Matangkasombut, Siwanon Jirawatnotai, Teera Poyomtip, Trairak Pisitkun, Kenneth Hodge, Anavaj Sakuntabhai, Mahidol University [Bangkok], Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Chulalongkorn University [Bangkok], This work was supported by Grants-in-Aid for scientific research from Mahidol University (Thailand) and by the Mid-Career Grant from Thailand Research Fund (TRF) (RSA5680054) to S. C., S. J. was supported by the Chalermphrakiat Grant, Faculty of Medicine, Siriraj Hospital, Mahidol University. S. J. and S. C. were also supported by the Advanced Research on Pharmacology Fund, Siriraj Foundation (D003421). This work was also funded by the Office of the Higher Education Commission and Mahidol University under the National Research Universities initiative (NRU), and the DENFREE project (The European Union Seventh Framework Programme, FP7/2007/2011 under Grant Agreement no. 282 378) to A. S. and P. M. T. Pisitkun was supported by Chulalongkorn Academic Advancement into its 2nd Century Project (CUAASC) grant. T. Poyomtip was supported by a scholarship from Science Achievement Scholarship of Thailand (SAST)., European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]

Subjects
0301 basic medicine, Recombinant Fusion Proteins, viruses, MESH: Dengue, Viral Nonstructural Proteins, Dengue virus, Virus Replication, medicine.disease_cause, MESH: Dengue Virus, Chromatography, Affinity, Virus, Dengue, 03 medical and health sciences, Viral life cycle, Virology, Protein Interaction Mapping, medicine, MESH: Recombinant Fusion Proteins, Humans, Antibody-dependent enhancement, Gene, Tandem affinity purification, MESH: Humans, biology, MESH: Protein Interaction Mapping, MESH: Virus Replication, virus diseases, Dengue Virus, MESH: Chromatography, Affinity, biology.organism_classification, 3. Good health, Flavivirus, 030104 developmental biology, Viral replication, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Viral Nonstructural Proteins
Abstract

International audience; Dengue virus (DENV) is a mosquito-borne flavivirus responsible for life-threatening dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). The viral replication machinery containing the core non-structural protein 5 (NS5) is implicated in severe dengue symptoms but molecular details remain obscure. To date, studies seeking to catalogue and characterize interaction networks between viral NS5 and host proteins have been limited to the yeast two-hybrid system, computational prediction and co-immunoprecipitation (IP) of ectopically expressed NS5. However, these traditional approaches do not reproduce a natural course of infection in which a number of DENV NS proteins colocalize and tightly associate during the replication process. Here, we demonstrate the development of a recombinant DENV that harbours a TAP tag in NS5 to study host-virus interactions in vivo. We show that our engineered DENV was infective in several human cell lines and that the tags were stable over multiple viral passages, suggesting negligible structural and functional disturbance of NS5. We further provide proof-of-concept for the use of rationally tagged virus by revealing a high confidence NS5 interaction network in human hepatic cells. Our analysis uncovered previously unrecognized hnRNP complexes and several low-abundance fatty acid metabolism genes, which have been implicated in the viral life cycle. This study sets a new standard for investigation of host-flavivirus interactions.

Published
2016
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36. Genetic diversity among Plasmodium vivax isolates along the Thai–Myanmar border of Thailand

Author

Srisin Khusmith, Georges Snounou, Panita Gosi, Srivicha Krudsood, Charlotte A. Lanteri, Jarinee Tongshoob, Sarunya Maneerattanasak, HAL UPMC, Gestionnaire, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Armed Forces Research Institute of Medical Sciences [Bangkok] (AFRIMS), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
Adult, Male, Veterinary medicine, Adolescent, Genotype, 030231 tropical medicine, Plasmodium vivax, Population, Protozoan Proteins, Population genetics, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Polymerase Chain Reaction, Genetic diversity, Pvmsp3α, Young Adult, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, Genetic variation, Malaria, Vivax, medicine, Humans, 030212 general & internal medicine, Pvmsp1, Allele, education, [SDV.GEN]Life Sciences [q-bio]/Genetics, education.field_of_study, Research, Genetic Variation, Middle Aged, Thailand, biology.organism_classification, medicine.disease, 3. Good health, Infectious Diseases, Multiplicity, Female, Parasitology, Pvcsp, Malaria
Abstract

Knowledge of the population genetics and transmission dynamics of Plasmodium vivax is crucial in predicting the emergence of drug resistance, relapse pattern and novel parasite phenotypes, all of which are relevant to the control of vivax infections. The aim of this study was to analyse changes in the genetic diversity of P. vivax genes from field isolates collected at different times along the Thai–Myanmar border. Two hundred and fifty-four P. vivax isolates collected during two periods 10 years apart along the Thai–Myanmar border were analysed. The parasites were genotyped by nested-PCR and PCR–RFLP targeting selected polymorphic loci of Pvmsp1, Pvmsp3α and Pvcsp genes. The total number of distinguishable allelic variants observed for Pvcsp, Pvmsp1, and Pvmsp3α was 17, 7 and 3, respectively. High genetic diversity was observed for Pvcsp (H E = 0.846) and Pvmsp1 (H E = 0.709). Of the 254 isolates, 4.3 and 14.6 % harboured mixed Pvmsp1 and Pvcsp genotypes with a mean multiplicity of infection (MOI) of 1.06 and 1.15, respectively. The overall frequency of multiple genotypes was 16.9 %. When the frequencies of allelic variants of each gene during the two distinct periods were analysed, significant differences were noted for Pvmsp1 (P = 0.018) and the Pvcsp (P = 0.033) allelic variants. Despite the low malaria transmission levels in Thailand, P. vivax population exhibit a relatively high degree of genetic diversity along the Thai–Myanmar border of Thailand, in particular for Pvmsp1 and Pvcsp, with indication of geographic and temporal variation in frequencies for some variants. These results are of relevance to monitoring the emergence of drug resistance and to the elaboration of measures to control vivax malaria.

Published
2016
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37. Infectious diseases and their outbreaks in Asia-Pacific: biodiversity and its regulation loss matter

Author

Serge Morand, Yupin Suputtamongkol, Tan Boon Huan, Mohd Tajuddin Abdullah, Sathaporn Jittapalapong, Animal et gestion intégrée des risques (UPR AGIRs), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Kasetsart University, Department of Parasitology, Faculty of Veterinary Medicine (KU), Kasetsart University, Center of Excellence on Agricultural Biotechnology (AG-BIO/PERDO-CHE), Ministry of Education Thaïland, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Universiti Malaysia Sarawak (UNIMAS), Department of Civil and Environmental Engineering [Singapore], National University of Singapore (NUS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), and Kasetsart University (KU)

Subjects
0106 biological sciences, Epidemiology, Biodiversity, lcsh:Medicine, Population Modeling, L73 - Maladies des animaux, Facteur climatique, Santé publique, 01 natural sciences, Disease Outbreaks, Trees, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Organisme nuisible aux animaux, lcsh:Science, 2. Zero hunger, 0303 health sciences, Multidisciplinary, Geography, Ecology, Facteur lié au site, Environnement socioéconomique, Temperature, Facteur du milieu, Population ecology, Infectious Disease Epidemiology, 3. Good health, Épidémiologie, Infectious Diseases, Parasitose, Medicine, P01 - Conservation de la nature et ressources foncières, Biodiversité, L72 - Organismes nuisibles des animaux, Research Article, zoonose, Asia, Distribution géographique, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Biology, Agent pathogène, 010603 evolutionary biology, Communicable Diseases, Microbiology, Vector Biology, 03 medical and health sciences, Humans, Transmission des maladies, 030304 developmental biology, Population Density, Pacific Ocean, Population Biology, lcsh:R, Outbreak, Species diversity, Computational Biology, L70 - Sciences et hygiène vétérinaires - Considérations générales, Oiseau, 15. Life on land, Emerging Infectious Diseases, 13. Climate action, Infectious disease (medical specialty), Maladie infectieuse, Threatened species, Écologie animale, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, lcsh:Q, Parasitology, Mammifère, Species richness, Infectious Disease Modeling
Abstract

International audience; Despite increasing control measures, numerous parasitic and infectious diseases are emerging, re-emerging or causing recurrent outbreaks particularly in Asia and the Pacific region, a hot spot of both infectious disease emergence and biodiversity at risk. We investigate how biodiversity affects the distribution of infectious diseases and their outbreaks in this region, taking into account socio-economics (population size, GDP, public health expenditure), geography (latitude and nation size), climate (precipitation, temperature) and biodiversity (bird and mammal species richness, forest cover, mammal and bird species at threat). We show, among countries, that the overall richness of infectious diseases is positively correlated with the richness of birds and mammals, but the number of zoonotic disease outbreaks is positively correlated with the number of threatened mammal and bird species and the number of vector-borne disease outbreaks is negatively correlated with forest cover. These results suggest that, among countries, biodiversity is a source of pathogens, but also that the loss of biodiversity or its regulation, as measured by forest cover or threatened species, seems to be associated with an increase in zoonotic and vector-borne disease outbreaks.

Published
2013
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38. Rodent borne diseases in Thailand : targeting rodent carriers and risky habitats

Author

Herbreteau, Vincent, Bordes, Frédéric, Jittapalapong, Sathaporn, Supputamongkol, Yupin, Morand, Serge, UMR 228 Espace-Dev, Espace pour le développement, Université de Guyane (UG)-Université des Antilles (UA)-Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Kasetsart University, Department of Parasitology, Faculty of Veterinary Medicine (KU), Kasetsart University, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Animal et gestion intégrée des risques (UPR AGIRs), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Université de Guyane (UG)-Université des Antilles (UA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), and Kasetsart University (KU)

Subjects
[SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, ECHANTILLONAGE, habitat, DIVERSITE SPECIFIQUE, prioritization, ZOONOSE, zoonosis, CIBLAGE, Southeast Asia, RONGEUR, RELATION HOTE PARASITE, microparasite richness, rodents, REGRESSION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, PARASITE, HABITAT, METHODOLOGIE
Abstract

International audience; Background: Comparative analysis, which aims at investigating ecological and evolutionary patterns among species, may help at targeting reservoirs of zoonotic diseases particularly in countries presenting high biodiversity. Here, we developed a simple method to target rodent reservoirs using published studies screening microparasite infections. Methods: We compiled surveys of microparasites investigated in rodents trapped in Thailand. The data comprise a total of 17,358 rodents from 18 species that have been investigated for a total of 10 microparasites (viruses, bacteria and protozoans). We used residual variation of microparasite richness controlled for both rodent sample size and pathogens' screening effort to identify major rodent reservoirs and potential risky habitats. Results: Microparasite species richness was positively related to rodent sample size and pathogens' screening effort. The investigation of the residual variations of microparasite species richness showed that several rodent species harboured more pathogens than expected by the regression model. Similarly, higher pathogen richness than expected was observed in rodents living in non-flooded lands, forests and paddy fields. Conclusion: Our results suggest to target some rodent species that are not commonly investigated for pathogen screening or surveillance such as R. andamanensis or B. savilei, and that non-flooded lands and forests should be more taken into caution, whereas much surveys focused on paddy rice fields and households.

Published
2012
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39. Recent discoveries of new hantaviruses widen their range and question their origins

Author

Jean-Pierre Hugot, Jean-François Cosson, Yannick Chaval, Gauthier Dobigny, Juha Laakkonen, Philippe Buchy, Heikki Henttonen, Johan Michaux, Sathaporn Jittapalapong, Nathalie Charbonnel, Maxime Galan, Vincent Herbreteau, Serge Morand, Yupin Suputtamongkol, Finnish Forest Research Institute (METLA), Natural Resources Institute Finland (LUKE), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Kasetsart University, Department of Parasitology, Faculty of Veterinary Medicine (KU), Kasetsart University, Laboratoire Espace, Santé et Territoire (LEST), Université Paris Nanterre (UPN), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Origine, structure et évolution de la biodiversité, Centre National de la Recherche Scientifique (CNRS), This study was supported by the French GIP‐ANR, Programme Santé Environnement–Santé Travail (Program 00121 05), by the PHC Franco‐Thai Cooperation in Higher Education and Research (Program No. 16601PK)., ANR Santé-Environnement (no. 00121 0505),ANR Santé-Environnement (no. 00121 0505), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Origine, structure et évolution de la biodiversité (OSEB), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), ANR Santé-Environnement (no. 00121 0505), Kasetsart University (KU), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS)

Subjects
Orthohantavirus, rodent-borne, Range (biology), animal diseases, viruses, Bayesian analysis, phylogeny, L73 - Maladies des animaux, Crocidura theresae, MESH: Phylogeny, Phylogeny, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, 0303 health sciences, hantaviruses, biology, General Neuroscience, Bandicota indica, virus diseases, Musaraigne, 3. Good health, shrew-borne, S50 - Santé humaine, coevolution, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Soricidae, Bunyaviridae, Hantavirus, MESH: Bayes Theorem, Zoology, Thailand virus, MESH: Hantavirus/isolation & purification, MESH: Hantavirus/classification, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Holarctic, History and Philosophy of Science, Species Specificity, Phylogenetics, MESH: Species Specificity, Humans, biogeography, 030304 developmental biology, MESH: Humans, 030306 microbiology, S gene, Bayes Theorem, biology.organism_classification, Rattus norvegicus, respiratory tract diseases, Rat, Rongeur, Mammifère, Thottapalayam
Abstract

International audience; Hantaviruses belong to the Bunyaviridae family. While usually hosted by wild mammals, they are potentially pathogenic for humans, and several serologically distinct groups associated with different syndromes have been identified. Yet, investigations have mostly been conducted where human infections by hantaviruses constitute a real and well-identified public health problem, i.e., the holarctic and neotropical areas. Some hantaviruses have also been described from a Suncus murinus in India and a Bandicota indica in Thailand. In addition, recent investigations in Cambodia revealed new Hantavirus types. More recently, two new Hantavirus species were described: Sangassou from a Hylomyscus simus, and Tanganya from a Crocidura theresae, both from Africa (Guinea), thus strongly questioning the current views about geographic range, evolution, and epidemiology of hantaviruses. In such a framework, we have conducted a survey of Hantavirus diversity in Southeast Asia which allows us to isolate the Thailand virus and address questions about the taxonomy of their rodent hosts. Here we present a molecular analysis of representatives of all currently known Hantavirus species, thus allowing the comparison between the newly described ones with a large range sample of rodent hantaviruses. Our results clearly point to the presence of a particular lineage of hantaviruses in Southeast Asia. It also strongly suggests that new viruses, additional mammalian hosts and different related syndromes in humans are likely to be discovered in the near future, particularly in Southeast Asia and in Africa, where Muridae rodents are highly diversified. Furthermore, additional work is also urgently needed to investigate the hantaviruses associated with Crociduridae and Soricidae.

Published
2009
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40. Genetic Determination and Linkage Mapping of Plasmodium falciparum Malaria Related Traits in Senegal

Author

Simon Heath, Jean-François Trape, Ndiaye R, Waraphon Phimpraphi, Isabelle Casademont, Cécile Julier, A. Spiegel, Chairat Turbpaiboon, Adama Tall, Christophe Rogier, Alioune Dieye, Richard Paul, Chayanon Peerapittayamonkol, Odile Mercereau-Puijalon, Anavaj Sakuntabhai, Patricia Tortevoye, Génétique des Maladies Infectieuses et Autoimmunes, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique de la Réponse aux Infections chez l'Homme, Institut Pasteur [Paris] (IP), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche pour le développement (IRD [Sénégal]), École du Val de Grâce (EVDG), Service de Santé des Armées, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Immunologie moléculaire des parasites, This work was funded in part by grants from the French Ministry of Research and Technology, the Institut Pasteur and Institut national de la santé et de la recherche médicale (INSERM) to C.J. Research in the laboratory of OMP is partly supported by the BioMalPar European Network of Excellence supported by a European grant (LSHP-CT-2004-503578) from the Priority 1 'Life Sciences, Genomics and Biotechnology for Health' in the 6th Framework Programme. We thank the Centre National de Génotypage for providing access to their genotyping facility. R.N. was supported by a studentship from the Institut Pasteur de Dakar. C.P. was supported by post-doctoral fellowships from Inserm and from the Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand. C.T. and W.P. were supported by the Royal Golden Jubilee Program, the Thailand Research Fund and the French Embassy in Thailand., and Paul, Richard

Subjects
Rural Population, Candidate gene, lcsh:Medicine, MESH: Regression Analysis, MESH: Quantitative Trait, Heritable, MESH: Rural Population, Chromosome regions, Ethnicity, MESH: Animals, Malaria, Falciparum, lcsh:Science, Genetics and Genomics/Genetics of Disease, Genetics, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, biology, MESH: Malaria, Falciparum, Chromosome Mapping, Senegal, Phenotype, Regression Analysis, medicine.symptom, Research Article, Population, Genetics and Genomics/Complex Traits, MESH: Phenotype, Asymptomatic, Quantitative Trait, Heritable, Genetic linkage, MESH: Senegal, parasitic diseases, medicine, MESH: Ethnicity, Animals, Humans, Family, education, MESH: Family, MESH: Genome, Human, MESH: Humans, Genome, Human, lcsh:R, Infectious Diseases/Protozoal Infections, Chromosome, Plasmodium falciparum, biology.organism_classification, medicine.disease, Immunology, lcsh:Q, MESH: Chromosome Mapping, Malaria
Abstract

International audience; Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p

Published
2008
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41. Encyclopedia of infectious diseases : modern methodologies

Author

Vincent Herbreteau, Jean-Paul Gonzalez, Jean-Pierre Hugot, Heikki Henttonen, Kumiko Yoshimatsu, Yupin Suputtamongkol, Institut de Recherche pour le Développement, UR 178 Fundamentals & Domains of Disease Emergence (IRD UR178), Finnish Forest Research Institute, Vantaa Research Unit, Finnish Forest Research Institute, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Origine, structure et évolution de la biodiversité (OSEB), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Tibayrenc, Michel, and Tibayrenc, Michel (ed.)

Subjects
0106 biological sciences, Rodent, TRANSMISSION, MORPHOLOGIE, Zoology, TAXONOMIE, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 010603 evolutionary biology, 01 natural sciences, RONGEUR, 03 medical and health sciences, DIAGNOSTIC, SYMPTOME, biology.animal, PHYLOGENIE, PARASITE, Coevolution, SEROLOGIE, 030304 developmental biology, Hantavirus, 0303 health sciences, biology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], BIOLOGIE MOLECULAIRE, HOTE VERTEBRE, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, BIOGEOGRAPHIE, VIRUS, ETUDE EXPERIMENTALE, REPARTITION GEOGRAPHIQUE
Published
2007

42. Rodents biodiversity and associated infections in Southeast Asia

Author

Jean-Pierre Hugot, Yupin Suputtamongkol, Sathaporn Jittapalapong, Serge Morand, Michaux, Johan R., Jean-François Cosson, Gauthier Dobigny, Vincent Herbreteau, Origine, structure et évolution de la biodiversité, Centre National de la Recherche Scientifique (CNRS), Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Kasetsart University, Department of Parasitology, Faculty of Veterinary Medicine (KU), Kasetsart University, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut de Recherche pour le Développement, UR 178 Fundamentals & Domains of Disease Emergence (IRD UR178), ANR Santé-Environnement (no. 00121 0505),ANR Santé-Environnement (no. 00121 0505), Origine, structure et évolution de la biodiversité (OSEB), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), ANR Santé-Environnement (no. 00121 0505), and Herbreteau, Vincent

Subjects
Muridae, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.BID]Life Sciences [q-bio]/Biodiversity, GIS, Rodents, Southeast Asia, [SDV.BID] Life Sciences [q-bio]/Biodiversity, Hantavirus
Abstract

International audience; We are currently involved in a Franco-Thai program devolved to a multidisciplinary investigation of Muridae rodents (‘‘mice and rats''), their parasites and the pathogens that they may carry and/or transmit to human, with a better understanding of diseases emergence as an ultimate goal. In such a context, pathogens circulation in the wild is a complex but pivotal phenomenon which requires a continuum of scientific approaches to be accurately apprehended. In particular, a rigorously comparative study is mandatory in order to take into account the interactions between parasites, wild and domestic hosts (uncluding human) and their environment. This is the reason why we rely on both concepts and techniques from a wide range of disciplines including taxonomy, cytogenetics, phylogenetics, phylogeography, population genetics, ecology, geography as well as modeling. With the following objectives. Objective 1: To precisely identify and characterize the rodent species acting as reservoirs, and to document their ecology, geographic distribution as well as the genetic structure of their populations. To assess parasite and pathogen diversity in relation to their associated rodent hosts. To provide cophylogenies and co-phylogeographies in order to enlight the evolutionary relationships of hosts and parasites. Objective 2: To map and correlate the observed rodents distributions with their species-specific environmental landscapes in order to extrapolate their potential ‘‘real'' range and to anticipate their future distributions in relation to landscape modifications. Objective 3: Computing epidemiological databases. Crosschecking field data and GIS data. Definition and standardization of a risk-scale. Finalization of maps of risks and distributions. Atlas of Thai Muridae. Reference collection of Thai Muridae. Education and training of students. Following the listing of the objectives, we expose the first results of our studies and we sketch future projects.

Published
2006

43. Genetic analysis of Thailand hantavirus in Bandicota indica trapped in Thailand

Author

Åke Lundkvist, Juha Laakkonen, Kirill Nemirov, Heikki Henttonen, Yupin Supputamongkol, Vincent Herbreteau, Alexander Plyusnin, Jean-Pierre Hugot, Angelina Plyusnina, Origine, structure et évolution de la biodiversité (OSEB), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), IRD UR178, Department of Virology [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Swedish Institute for Infectious Disease Control, Finnish Forest Research Institute, Vantaa Research Unit, Finnish Forest Research Institute, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], ANR- Santé-Environnement no. 00121 0505, Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], and Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki

Subjects
Orthohantavirus, NAKHON RATCHASIMA, ENZYME, Rodent, TECHNIQUE RT PCR, Immunoblotting, Molecular Sequence Data, 030231 tropical medicine, Genome, Viral, IMMUNOLOGIE, Genetic analysis, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, SAKHON NAKHON, Virology, biology.animal, ETUDE COMPARATIVE, Animals, lcsh:RC109-216, PHYLOGENIE, Antigens, Viral, Phylogeny, 030304 developmental biology, Hantavirus, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, 0303 health sciences, PHRAE, Base Sequence, biology, Phylogenetic tree, Reverse Transcriptase Polymerase Chain Reaction, THAILANDE, Research, Bandicota indica, Murinae, Thailand, biology.organism_classification, Bandicoot, Infectious Diseases, VIRUS, RAT, ANALYSE GENETIQUE, Seoul virus
Abstract

Sixty one tissue samples from several rodent species trapped in five provinces of Thailand were examined for the presence of hantaviral markers by enzyme-immunoassay and immunoblotting. Four samples, all from the great bandicoot rat Bandicota indica, were confirmed positive for the hantaviral N-antigen. Two of them were trapped in Nakhon Pathom province, the other two in Nakhon Ratchasima province, approximately 250 km from the other trapping site. When analysed by RT-nested PCR, all four rodents were found positive for the hantaviral S- and M-segment nucleotide sequences. Genetic analysis revealed that the four newly described wild-type strains belong to Thailand hantavirus. On the phylogenetic trees they formed a well-supported cluster within the group of Murinae-associated hantaviruses and shared a recent common ancestor with Seoul virus.

Published
2006
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44. Is human hantavirosis underestimated in South Asia?

Author

Vincent Herbreteau, Jean-Paul Gonzalez, Yupin Suputtamongkol, Jean-Pierre Hugot, Institut de Recherche pour le Développement, UR 178 Fundamentals & Domains of Disease Emergence (IRD UR178), Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Origine, structure et évolution de la biodiversité (OSEB), and Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Muridae, rodents, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, VIRUS, virus diseases, PHYLOGENIE, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, South Asia, phylogeny, REPARTITION GEOGRAPHIQUE, SEROLOGIE, hantavirus, RONGEUR
Abstract

International audience; Hantaviruses have been isolated from rodents of the family Muridae, in North Asia, Europe, North America, and South America. A cladistic analysis of ninety-three strains isolated from rodents enabled a review their geographic distribution. Particularly, the association with their hosts questions the presence of hantaviruses in South Asia from where murid rodents are considered to originate. Several hantaviruses have been recorded from South Asia. Also, serological surveys carried out to detect evidence of hantavirus in human populations, or in wild rodents revealed positive samples in Thailand and Cambodia. After confirmation of a first human case in Thailand, a question arises: what is the real importance of hantaviruses for human health in South-East Asia? The results of our study suggests that new viruses, different hosts and different human syndromes may be expected to be discovered in the future especially in southeastern Asia where murid rodents are endemic and highly diversified and where was already proved their potential danger for Human health, with populations regularly exposed to their contact.

Published
2005

46. Nasal allergen provocation test: updated indications and diagnostic accuracy.

Author

Kanjanawasee D, Wattanaphichet A, Tantilipikorn P, and Tantikun B

Abstract

Purpose of Review: The Nasal Allergen Provocation Test (NAPT) is a valuable diagnostic tool for allergic rhinitis, particularly in cases where conventional tests, such as the skin prick test (SPT) and serum-specific IgE (sIgE), yield inconclusive results. By replicating real-life allergen exposure in a controlled setting, NAPT enables the assessment of allergen-specific nasal reactivity. This article aims to review the current knowledge of NAPT., Recent Findings: Recent studies have reinforced NAPT as the gold standard for confirming nasal allergic responses. In the past, test protocols, allergen dosages, and outcome measurements varied widely. However, advancements in allergen standardization, the combination of objective and subjective measurements, and metered nasal allergen application have led to an improved and more reliable test method, with ongoing efforts to establish a universal protocol for clinical testing., Summary: This review summarizes current knowledge on NAPT, including its clinical applications, indications, methodology, and recent advancements. Additionally, we compare NAPT with SPT and sIgE in terms of diagnostic accuracy. The protocols, allergen types and doses, test methodologies, and outcome measures of these studies were analyzed and compared., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2025
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47. Distinctive clinical features in biopsy-proven nerve large-arteriole vasculitis and microvasculitis.

Author

Soontrapa P, Pinto MV, Shouman K, Mandrekar J, Engelstad JK, Aragon Pinto C, Taylor S, Mauermann ML, Berini SE, Bosch EP, Rubin DI, Koster MJ, Weyand CM, Warrington KJ, Klein CJ, Dyck PJ, and Dyck PJB

Subjects
Humans, Male, Female, Middle Aged, Retrospective Studies, Aged, Adult, Biopsy, Microvessels pathology, Cohort Studies, Arterioles pathology, Peripheral Nerves pathology, Vasculitis pathology
Abstract

Vasculitic neuropathy is caused by inflammatory destruction of nerve blood vessels resulting in nerve ischaemia. Nerve vasculitis can be divided into two categories based on vessel size: large-arteriole vasculitis (≥75 µm) and microvasculitis (<75 µm). Herein, we characterize the clinical features of nerve large-arteriole vasculitis in comparison to nerve microvasculitis. This is a retrospective cohort study of patients evaluated and biopsied at Mayo sites between 2001 and 2020. We collected clinical and histopathological data from patients whose nerve biopsies were either diagnostic or highly suggestive of nerve vasculitis. Two hundred and seventy-eight cases were identified: 125 cases of large-arteriole vasculitis and 153 cases of microvasculitis. Nerve large-arteriole vasculitis presented with a more acute (50.4% versus 26.8%) versus chronic onset (33.6% versus 57.5%) than nerve microvasculitis (P = 0.0001). Nerve microvasculitis had longer mean time to diagnosis (10.5 versus 4.3 months; P < 0.0001) and longer time to plateau (8.9 versus 3.5 months; P < 0.0001). Nerve large-arteriole vasculitis typically presented as distal asymmetric polyneuropathy (48.0%), whereas nerve microvasculitis typically presented as radiculoplexus neuropathy/polyradiculoneuropathy (more proximal involvement of shoulder and thigh) (43.8%) (P < 0.0001). Systemic autoimmune disease was more common in nerve large-arteriole vasculitis (70.4% versus 22.9%, odds ratio, 8.0; 95% confidence interval, 4.7-13.7; P < 0.0001). Nerve microvasculitis was significantly related to non-systemic vasculitis (71% versus 23%, odds ratio, 7.9; 95% confidence interval, 4.6-13.6; P < 0.0001). Nerve microvasculitis had more autonomic involvement (24.2% versus 7.2%, odds ratio, 4.1; 95% confidence interval, 1.9-8.9; P = 0.0002). Nerve large-arteriole vasculitis and nerve microvasculitis have different but overlapping clinical features. Nerve large-arteriole vasculitis usually presents with acute onset, distal asymmetric polyneuropathy, associated with other autoimmune diseases and systemic involvement. In contrast, nerve microvasculitis usually presents with a subacute/chronic onset, as radiculoplexus neuropathy/polyradiculopathy (distal and proximal pattern) with autonomic involvement, and is more often a form of non-systemic vasculitis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2025
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48. Comparison of online quizzes and standard summative examination for the evaluation and guidance of students in medical bacteriology and mycology.

Author

Imwattana K and Ngamskulrungroj P

Subjects
Humans, Retrospective Studies, Students, Medical, Education, Medical, Undergraduate, Clinical Competence, Internet, Educational Measurement, Bacteriology education, Mycology methods
Abstract

Background: This study aimed to determine the effectiveness of loosely regulated online quizzes in evaluating students' knowledge outcomes compared to a traditional summative examination, using Medical Bacteriology and Mycology as a model., Methods: A retrospective review of the student's academic performances was conducted (n = 320), analyzing the quiz score as well as how each student did the quizzes. Each parameter was mapped back to the students' actual summative score to evaluate the correlation., Results: There was a strong correlation between the online quiz and the summative scores (p = 0.013). An in-depth analysis also shows that students who performed well in the summative examination had the following characteristics; [1] they tried to pass the online quizzes in the early attempts (p < 0.001), [2] continued to revisit the quizzes after passing (p = 0.011) and [3] tried further to improve their quiz scores (p = 0.002)., Conclusion: Although online quizzes cannot yet replace traditional examinations, they can be an effective tool to assess student's competence, and careful monitoring of the quiz results can help identify students who may need extra attention. The results also suggest that diligence and intelligence are both important in Medical Bacteriology and Mycology., Competing Interests: Declarations. Ethics approval and consent to participate: This project was exempted by the Siriraj Institutional Review Board as a part of the course development project for the Doctor of Medicine curriculum (Protocol number 496/2566(IRB2), COA number Si 520/2023). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Published
2025
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49. A comparative study of early postoperative pain: robotic-assisted versus conventional total knee arthroplasty.

Author

Chareancholvanich K, Pornrattanamaneewong C, Udompanich R, Awirotananon K, and Narkbunnam R

Abstract

Purpose: While robotic-assisted total knee arthroplasty (RA-TKA) has demonstrated improved surgical precision, its impact on early postoperative pain management remains unclear. This study compared early postoperative pain outcomes between RA-TKA and conventional TKA (C-TKA)., Methods: In this retrospective study, 230 consecutive patients (309 knees) who underwent primary TKA were analyzed: 143 patients (181 knees) in the C-TKA group and 87 patients (128 knees) in the RA-TKA group. Pain scores at rest and during movement were assessed using the Numerical Pain Rating Scale for 72 h postoperatively. Secondary outcomes included opioid consumption and length of hospital stay., Results: While pain scores at rest showed no significant differences between groups, RA-TKA patients reported significantly lower pain scores during movement at 24 h post-surgery (p = 0.023). The RA-TKA group demonstrated significantly reduced opioid consumption during the first 48 postoperative hours (p = 0.001 for 0-24 h; p = 0.03 for 24-48 h) and shorter length of hospital stay (p = 0.011). Subgroup analysis of unilateral procedures showed similar advantages in the RA-TKA group., Conclusion: RA-TKA was associated with reduced pain during movement, decreased opioid consumption, and shorter hospital stay in the early postoperative period compared to C-TKA., Competing Interests: Declarations. Ethics approval: This study was approved by Siriraj Institutional Review Board (COA468/2566). Informed consent: The requirement for informed consent was waived by the ethics committee due to the retrospective nature of the study. Consent for publication: Not applicable as no identifying information of participants is included in this manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Published
2025
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50. Antibiotic Usage Patterns of Community-Dwelling Adults in Thailand: A Cross-Sectional Study.

Author

Boontein P, Utriyaprasit K, Poungkaew A, Pumtong S, and Tongsai S

Abstract

Aim: To investigate factors predictive of antibiotic use behaviour in the community., Design: A cross-sectional study was conducted from May to November 2023., Method: Standardised instruments were administered to patients who had received services from nurses in sub-district health-promoting hospitals in Thailand for at least one of the three diseases: (1) upper respiratory infection, (2) acute diarrhoea or (3) fresh traumatic wounds. Antibiotic use behaviour was modelled using the generalised estimating equation with an independent error component to account for the clustering of the hospitals., Results: Five hundred and eighty-five participants (556 patients and 29 nurses) met the inclusion criteria in this study. Of the 556 adult patients who were surveyed, the majority had upper respiratory infections, reported an appropriate level of antibiotic use, a moderate level of awareness of appropriate antibiotic use and antibiotic resistance, and an inadequate literacy level of Rational Drug Use. The generalised estimating equation analysis revealed that factors predictive of antibiotic use behaviour were rational drug use literacy, awareness, process of care, nurses' experience and rate of rational antibiotic prescribing for acute diarrhoea., Conclusions: The nurses and healthcare providers should focus on enhancing the quality of care by educating and collaborating with the community to ensure appropriate antibiotic use behaviour., Impact: This study indicated that healthcare policymakers should prioritise patient education on antibiotic use behaviour while also ensuring that healthcare workers adhere to strict caregiving protocols., Implications for the Profession And/or Patient Care: Providing services by monitoring symptoms and home visits can help patients gain confidence in the treatment approach and lead to a rational change in antibiotic use., Reporting Method: We adhere to the STROBE checklist., Patient or Public Contribution: No patient or public involvement., (© 2025 The Author(s). Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Published
2025
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