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1. Inhibition of angiogenesis and murine tumour growth by laminarin sulphate

Author

J. Donaldson, D.H. Paper, R. Hoffman, and H. Vogl

Subjects
Cancer Research, Angiogenesis, Basic fibroblast growth factor, Molecular Sequence Data, Neovascularization, Physiologic, Antineoplastic Agents, Chick Embryo, Biology, Models, Biological, Neovascularization, chemistry.chemical_compound, Laminarin, Mice, In vivo, Laminin, Polysaccharides, medicine, Animals, Fibrosarcoma, Cells, Cultured, Matrigel, Mice, Inbred C3H, Neovascularization, Pathologic, medicine.disease, bacterial infections and mycoses, Molecular biology, Drug Combinations, Oncology, chemistry, Carbohydrate Sequence, Immunology, biology.protein, Cattle, Proteoglycans, Collagen, Endothelium, Vascular, medicine.symptom, Research Article
Abstract

LAM S5 is a polysulphated derivative of the glucan laminarian that inhibits basic fibroblast growth factor (bFGF) binding and the bFGF-stimulated proliferation of fetal bovine heart endothelial (FBHE) cells. This report demonstrates that LAM S5 has anti-angiogenic activity, as shown by inhibition of tubule formation by endothelial cells cultured on Matrigel and inhibition of vascularisation of the chick chorioallantoic membrane. In addition, LAM S5 caused a tumour growth delay of the murine RIF-1 tumour of 2.6 days (P = 0.01). Images Figure 2

Published
1996

2. Folding a focalized acoustical vortex on a flat holographic transducer: Miniaturized selective acoustical tweezers

Author

Olivier Bou Matar, Michael Baudoin, Antoine Riaud, Jean Louis Thomas, J.-C. Gerbedoen, Nikolay Smagin, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Acoustique Impulsionnelle & Magnéto-Acoustique Non linéaire - Fluides, Interfaces Liquides & Micro-Systèmes - IEMN (AIMAN-FILMS - IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Puissance - IEMN (PUISSANCE - IEMN), Fudan University [Shanghai], State Key Laboratory of ASIC and System, School of Microelectronics, Fudan University, Transduction, Propagation et Imagerie Acoustique - IEMN (TPIA - IEMN), Institut d’Électronique, de Microélectronique et de Nanotechnologie - Département Opto-Acousto-Électronique - UMR 8520 (IEMN-DOAE), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Acoustique pour les nanosciences (INSP-E3), Institut des Nanosciences de Paris (INSP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), AcknowledgmentsWe acknowledge the platform 'WaveSurf' from Université Polytechnique Hauts-de-France for performing the measurements with the laser interferometer. We also acknowledge A. Vlandas for critical reading of the manuscript and valuable advices that helped us improve its overall quality. Funding: This work was supported by SATT Nord. Author contributions: M.B., A.R., and J.-L.T. designed the research. M.B. and J.-C.G. built the setup and performed the experiments. M.B. and A.R. performed the numerical simulations. O.B.M., J.-C.G., and N.S. performed the field measurements with the interferometer. M.B., O.B.M., A.R., and J.-L.T. analyzed and interpreted the results. M.B., O.B.M., J.-C.G., A.R., and J.-L.T. wrote the paper. All authors approved the final version of the manuscript. Competing interests: J.-L.T., O.B.M., A.R., and M.B. are inventors on a patent application related to this work filed with the European Patent Office (application no. EP17198204.4, submitted 25 October 2017). All other authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors., RENATECH, Baudoin, Michael, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Acoustique Impulsionnelle & Magnéto-Acoustique Non linéaire - Fluides, Interfaces Liquides & Micro-Systèmes - IEMN (AIMAN-FILMS-IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France)-Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France), Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 ( IEMN ), Ecole Centrale de Lille-Institut supérieur de l'électronique et du nunérique (ISEN)-Université de Valenciennes et du Hainaut-Cambresis ( UVHC ) -Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Université Paris Sorbonne Cité, INSERM UMR-S1147, Institut des Nanosciences de Paris ( INSP ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
[PHYS.PHYS.PHYS-FLU-DYN]Physics [physics]/Physics [physics]/Fluid Dynamics [physics.flu-dyn], [PHYS.PHYS.PHYS-CLASS-PH]Physics [physics]/Physics [physics]/Classical Physics [physics.class-ph], Materials science, Acoustics, Microfluidics, Holography, FOS: Physical sciences, Physics - Classical Physics, Applied Physics (physics.app-ph), 02 engineering and technology, 01 natural sciences, law.invention, Engineering, [ PHYS.PHYS.PHYS-CLASS-PH ] Physics [physics]/Physics [physics]/Classical Physics [physics.class-ph], law, 0103 physical sciences, Tweezers, Miniaturization, Piezoelectric substrate, 010306 general physics, Research Articles, [ PHYS.MECA.ACOU ] Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], Applied Physics, Multidisciplinary, Fluid Dynamics (physics.flu-dyn), SciAdv r-articles, Classical Physics (physics.class-ph), Physics - Applied Physics, Physics - Fluid Dynamics, [PHYS.PHYS.PHYS-FLU-DYN] Physics [physics]/Physics [physics]/Fluid Dynamics [physics.flu-dyn], 021001 nanoscience & nanotechnology, Vortex, [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], Folding (chemistry), Transducer, [ PHYS.PHYS.PHYS-FLU-DYN ] Physics [physics]/Physics [physics]/Fluid Dynamics [physics.flu-dyn], [PHYS.PHYS.PHYS-CLASS-PH] Physics [physics]/Physics [physics]/Classical Physics [physics.class-ph], [PHYS.MECA.ACOU] Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], 0210 nano-technology, Research Article
Abstract

Selective manipulation of micrometric objects in a standard microscopy environment is possible with miniaturized acoustical tweezers., Acoustical tweezers based on focalized acoustical vortices hold the promise of precise contactless manipulation of millimeter down to submicrometer particles, microorganisms, and cells with unprecedented combined selectivity and trapping force. Yet, the widespread dissemination of this technology has been hindered by severe limitations of current systems in terms of performance and/or miniaturization and integrability. Here, we unleash the potential of focalized acoustical vortices by developing the first flat, compact, paired single electrode focalized acoustical tweezers. These tweezers rely on spiraling transducers obtained by folding a spherical acoustical vortex on a flat piezoelectric substrate. We demonstrate the ability of these tweezers to grab and displace micrometric objects in a standard microfluidic environment with unique selectivity. The simplicity of this system and its scalability to higher frequencies open tremendous perspectives in microbiology, microrobotics, and microscopy.

Published
2019

3. Physical functional performance and prognosis in patients with heart failure: a systematic review and meta-analysis

Author

Antonio Cuesta-Vargas, Ricardo Gómez-Huelgas, María Rosa Bernal-López, Iván José Fuentes-Abolafio, Brendon Stubbs, Luis M. Pérez-Belmonte, [Fuentes-Abolafio,IJ, Cuesta-Vargas,AI] Department of Physiotherapy, Faculty of Health Science, University of Malaga, The Institute of Biomedical Research in Malaga (IBIMA), Clinimetric Group FE-14, Malaga, Spain. [Stubbs,B] Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, UK. [Stubbs,B] Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK. [Stubbs,B] Positive Ageing Research Intitute (PARI), Faculty of Health Social Care and Education, Anglia Ruskin University, Chelmsford, UK. [Pérez-Belmonte,LM, Bernal-López,MR, Gómez-Huelgas,R] Internal Medicine Department, Instituto de Investigación Biomédica de Malaga (IBIMA), Regional University Hospital of Málaga, Málaga, Spain. [Pérez-Belmonte,LM] Unidad de Neurofisiología Cognitiva, Centro de Investigaciones Médico Sanitarias (CIMES), Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Campus de Excelencia Internacional (CEI) Andalucía Tech, Málaga, Spain. [Pérez-Belmonte,LM] Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. [Bernal-López,MR, Gómez-Huelgas,R] CIBER Fisio-patología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain. [Cuesta-Vargas,AI] School of Clinical Sciences, Faculty of Health at the Queensland University of Technology, Brisbane, Queensland, Australia., and Brendon Stubbs is supported by a Clinical Lectureship (ICA-CL-2017-03-001) jointly funded by Health Education England (HEE) and the National Institute for Health Research (NIHR). Brendon Stubbs is part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. Brendon Stubbs is also supported by the Maudsley Charity, King’s College London and the NIHR South London Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funding. This paper presents independent research. The views expressed in this publication are those of the authors and not necessarily those of the acknowledged institutions. María Rosa Bernal-López was supported by 'Miguel Servet Type I' program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER.

Subjects
Male, lcsh:Diseases of the circulatory (Cardiovascular) system, Hospitalización, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk::Risk Assessment [Medical Subject Headings], Walking, 030204 cardiovascular system & hematology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Physical functional performance, Hospitalisation, Medicine, 030212 general & internal medicine, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise::Walking [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Aged, 80 and over, Insuficiencia cardíaca, Pronóstico, Middle Aged, Prognosis, Cardiac surgery, Hospitalization, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Hospitalization [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Sensitivity and Specificity::Predictive Value of Tests [Medical Subject Headings], Meta-analysis, Female, Gait Analysis, Cardiology and Cardiovascular Medicine, Research Article, medicine.medical_specialty, Check Tags::Male [Medical Subject Headings], Walk Test, Functional tests, Heart failure, CINAHL, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Risk Assessment, 03 medical and health sciences, Predictive Value of Tests, Humans, In patient, Mortality, Aged, Angiology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Cardiovascular::Heart Function Tests::Exercise Test [Medical Subject Headings], business.industry, Diseases::Cardiovascular Diseases::Heart Diseases::Heart Failure [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Evidence-based medicine, medicine.disease, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Gait [Medical Subject Headings], Functional Status, Check Tags::Female [Medical Subject Headings], lcsh:RC666-701, Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Mortalidad, Physical therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Observational study, business, Rendimiento físico funcional
Abstract

Background Patients with Heart Failure (HF) show impaired functional capacities which have been related to their prognosis. Moreover, physical functional performance in functional tests has also been related to the prognosis in patients with HF. Thus, it would be useful to investigate how physical functional performance in functional tests could determine the prognosis in patients with HF, because HF is the leading cause of hospital admissions for people older than 65 years old. This systematic review and meta-analysis aims to summarise and synthesise the evidence published about the relationship between physical functional performance and prognosis in patients with HF, as well as assess the risk of bias of included studies and the level of evidence per outcome. Methods Major electronic databases, such as PubMed, AMED, CINAHL, EMBASE, PEDro, Web of Science, were searched from inception to March 2020 for observational longitudinal cohort studies (prospective or retrospective) examining the relationship between physical functional performance and prognosis in patients with HF. Results 44 observational longitudinal cohort studies with a total of 22,598 patients with HF were included. 26 included studies reported a low risk of bias, and 17 included studies showed a moderate risk of bias. Patients with poor physical functional performance in the Six Minute Walking Test (6MWT), in the Short Physical Performance Battery (SPPB) and in the Gait Speed Test showed worse prognosis in terms of larger risk of hospitalisation or mortality than patients with good physical functional performance. However, there was a lack of homogeneity regarding which cut-off points should be used to stratify patients with poor physical functional performance from patients with good physical functional performance. Conclusion The review includes a large number of studies which show a strong relationship between physical functional performance and prognosis in patients with HF. Most of the included studies reported a low risk of bias, and GRADE criteria showed a low and a moderate level of evidence per outcome.

Published
2020

4. Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women

Author

Agnès Fournier, Marc J. Gunter, Gianluca Severi, Manon Cairat, Laure Dossus, Marie Al Rahmoun, Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France, International Agency for Cancer Research (IACR), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Gustave Roussy (IGR), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Ligue Contre le Cancer Mutuelle Générale de l'Education Nationale, MGEN Institut Gustave-Roussy Institut National de la Santé et de la Recherche Médicale, Inserm, Ligue Contre le Cancer (support for the E3N cohort and PhD fellowship to Manon Cairat). Acknowledgements Disclaimer, and The research was carried out using data from the Inserm (French National Institutes for Health and Medical Research) E3N cohort, which was established and maintained with the support of the Mutuelle Générale de l’Education Nationale (MGEN), Gustave Roussy, and the French League against Cancer (LNCC). We are grateful to the study participants for their continued participation and to medical practitioners for providing pathology reports. We also thank all members of the E3N-EPIC study group, in particular Rafika Chaït, Ghizlane Esselma, Marie Fangon, Pascale Gerbouin-Rérolle, Lyan Hoang, Roselyn Gomes and the data management team, and Amandine Gelot for data management and/or technical assistance. The work reported in this paper was performed during Agnès Fournier’s term as a Visiting Scientist at the International Agency for Research on Cancer.

Subjects
medicine.medical_specialty, Proton pump inhibitors, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Comorbidity, Lower risk, lcsh:RC254-282, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Surveys and Questionnaires, Internal medicine, medicine, Humans, Medical history, Prospective Studies, Prospective cohort study, Aged, Proportional Hazards Models, 030304 developmental biology, 0303 health sciences, Aspirin, business.industry, Proportional hazards model, Incidence, Incidence (epidemiology), Anti-Inflammatory Agents, Non-Steroidal, Hazard ratio, Nonsteroidal anti-inflammatory drugs, Middle Aged, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Postmenopausal women, 3. Good health, Postmenopause, 030220 oncology & carcinogenesis, Female, France, business, Research Article, Cohort study
Abstract

BackgroundAlthough anti-inflammatory agents could theoretically have anticancer properties, results from cohort studies on nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer (BC) risk are inconsistent.MethodsWe investigated the association between NSAID use and BC incidence in the French E3N prospective cohort, which includes 98,995 women born between 1925 and 1950 and insured by a health insurance plan that covers mostly teachers. Self-reported information on lifestyle and medical history has been collected biennially by questionnaires and matched with data from a drug reimbursement database covering the period 2004–2014. Women who self-reported current NSAID use in the 2000 or 2002 questionnaires or with at least two reimbursements in any previous 3-month period were defined as exposed to NSAIDs. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for the association of NSAID use with BC risk.ResultsIn the current analysis, 62,512 postmenopausal women were followed between 2004 and 2014 (9 years on average, starting at a mean age of 63 years; 2864 incident BC). In multivariable models, there was no statistically significant association between NSAID use and BC risk [HR = 1.00 (0.92–1.08), compared with non-exposed women]. The NSAID-BC associations did not differ by NSAID types, BC subtypes, risk factors, and comorbidities, nor by duration and dose of use. However, a statistically significant interaction was observed by proton pump inhibitor (PPI) drug use (Pinteraction = 0.01) whereby a decreased risk of BC with NSAID use was only observed among women who also used PPI before.ConclusionOnly women who used NSAIDs after having used PPI had a lower risk of BC. This result is novel and requires replication in other studies.

Published
2020

5. Risk factors for bronchiolitis hospitalization in infants: A French nationwide retrospective cohort study over four consecutive seasons (2009-2013)

Author

Jean-Christophe Rozé, Jean-Michel Hascoet, Jean-François Magny, Pierre-Henri Jarreau, Brigitte Fauroux, Elie Saliba, Michaël Schwarzinger, Sommeil-Vigilance-Fatigue et Santé Publique (VIFASOM (URP_7330)), Institut de Recherche Biomédicale des Armées (IRBA)-Université Paris Cité (UPCité), Unité Pédiatrique de Ventilation Non Invasive et de Sommeil [CHU Necker Enfants-Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maternité Régionale Adolphe Pinard [Nancy], Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité (DevAH), Université de Lorraine (UL), Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Translational Health Economics Network [Paris] (THEN), Sorbonne Université (SU), The present study was supported by AbbVie France. Translational Health Economics (THEN) was responsible for data collection, preparation, and validation with external sources of information. THEN received payment from AbbVie for these activities. Writing charges were funded by AbbVie France, and AbbVie approved the decision to submit the paper for publication, but the corresponding author was ultimately responsible for submitting the manuscript for publication., HASCOET, JEAN-MICHEL, Service d'assistance respiratoire et sommeil de l'enfant [CHU Necker], Sommeil-Vigilance-Fatigue et Santé Publique (VIFASOM - EA 7330), Institut de Recherche Biomédicale des Armées (IRBA)-Université de Paris (UP), Regional Maternity [Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Lorraine (UL), Université de Paris (UP), Department of Neonatal Medicine of Port-Royal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Cochin [AP-HP], Neonatal Intensive Care Unit of Port-Royal [Paris], Department of Neonatology [Paris], Department of Neonatology [Nantes], Department of Neonatology [Tours], Hôpital Gatien de Clocheville [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
Male, Pediatrics, Pulmonology, Epidemiology, Physiology, Cell Transplantation, Comorbidity, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Families, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Morphogenesis, Blood and Lymphatic System Procedures, Birth Weight, 030212 general & internal medicine, Children, education.field_of_study, Multidisciplinary, Congenital Heart Defects, Hospitals, 3. Good health, Hospitalization, Physiological Parameters, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Bronchiolitis, Medicine, Female, France, Seasons, Infants, Research Article, medicine.medical_specialty, Down syndrome, Science, Population, Cardiology, Surgical and Invasive Medical Procedures, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 030225 pediatrics, Internal medicine, Congenital Disorders, medicine, Humans, Birth Defects, education, Transplantation, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Omphalocele, business.industry, Body Weight, Infant, Biology and Life Sciences, Retrospective cohort study, medicine.disease, Health Care, Bronchopulmonary dysplasia, Age Groups, Health Care Facilities, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Medical Risk Factors, People and Places, Respiratory Infections, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Population Groupings, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Developmental Biology, Stem Cell Transplantation
Abstract

International audience; Objectives: Large studies are needed to update risk factors of bronchiolitis hospitalization. We performed a nationwide analysis of hospitalization rates for bronchiolitis over four consecutive bronchiolitis seasons to identify underlying medical disorders at risk of bronchiolitis hospitalization and assess their frequency.Methods: Data were retrieved from the French National Hospital Discharge database. Of all infants discharged alive from maternity wards from January 2008 to December 2013 in France (N = 3,884,791), we identified four consecutive cohorts at risk of bronchiolitis during the seasons of 2009–2010 to 2012–2013. The main outcome was bronchiolitis hospitalization during a season. Individual risk factors were collected.Results: Among infants, 6.0% were preterm and 2.0% had ≥1 chronic condition including 0.2% bronchopulmonary dysplasia (BPD) and 0.2% hemodynamically significant congenital heart disease (HS-CHD). Bronchiolitis hospitalization rates varied between seasons (min: 1.26% in 2010–2011; max: 1.48% in 2012–2013; p

Published
2020

6. Quantifying model evidence for yellow fever transmission routes in Africa

Author

Katy A. M. Gaythorpe, Laurence Cibrelus, Tini Garske, Kévin Jean, Imperial College London, Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), World Health Organisation (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Funding:This work was carried out as part of the Vaccine Impact Modelling Consortium (www.vaccineimpact.org),but the views expressed are those of the authors and not necessarily those of the Consortium or its funders.The funders were given the opportunity to review this paper prior to publication,but the final decision on the content of the publication was taken by the authors.We acknowledge joint Centre funding from the UK Medical Research Council and Department for International Development. The research leading to these results has received funding from the Bill & Melinda Gates foundation (OPP1117543,OPP1157270 http://www.gatesfoundation.org/)and from the Medical Research Council (MR/R015600/1https://mrc.ukri.org/)., HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), and Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)

Subjects
0301 basic medicine, Viral Diseases, Epidemiology, Force of infection, Statics, Pathology and Laboratory Medicine, law.invention, Geographical Locations, Bayes' theorem, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Aedes, Statistics, Medicine and Health Sciences, Public and Occupational Health, Biology (General), Ecology, Physics, Yellow fever, Linear model, Classical Mechanics, Vaccination and Immunization, Geography, Transmission (mechanics), Infectious Diseases, Serology, Computational Theory and Mathematics, INFECTIONS, Modeling and Simulation, Physical Sciences, Yellow fever virus, Life Sciences & Biomedicine, Research Article, Generalized linear model, Biochemistry & Molecular Biology, Bioinformatics, QH301-705.5, Immunology, Bayesian inference, Models, Biological, Biochemical Research Methods, BAYESIAN MODEL, Infectious Disease Epidemiology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Yellow Fever, Genetics, medicine, Animals, Humans, Molecular Biology, 01 Mathematical Sciences, Ecology, Evolution, Behavior and Systematics, Estimation, Science & Technology, Models, Statistical, Biology and Life Sciences, Computational Biology, Bayes Theorem, 06 Biological Sciences, medicine.disease, 030104 developmental biology, People and Places, Africa, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Mathematical & Computational Biology, 08 Information and Computing Sciences, Preventive Medicine, 030217 neurology & neurosurgery
Abstract

Yellow fever is a vector-borne disease endemic in tropical regions of Africa, where 90% of the global burden occurs, and Latin America. It is notoriously under-reported with uncertainty arising from a complex transmission cycle including a sylvatic reservoir and non-specific symptom set. Resulting estimates of burden, particularly in Africa, are highly uncertain. We examine two established models of yellow fever transmission within a Bayesian model averaging framework in order to assess the relative evidence for each model’s assumptions and to highlight possible data gaps. Our models assume contrasting scenarios of the yellow fever transmission cycle in Africa. The first takes the force of infection in each province to be static across the observation period; this is synonymous with a constant infection pressure from the sylvatic reservoir. The second model assumes the majority of transmission results from the urban cycle; in this case, the force of infection is dynamic and defined through a fixed value of R0 in each province. Both models are coupled to a generalised linear model of yellow fever occurrence which uses environmental covariates to allow us to estimate transmission intensity in areas where data is sparse. We compare these contrasting descriptions of transmission through a Bayesian framework and trans-dimensional Markov chain Monte Carlo sampling in order to assess each model’s evidence given the range of uncertainty in parameter values. The resulting estimates allow us to produce Bayesian model averaged predictions of yellow fever burden across the African endemic region. We find strong support for the static force of infection model which suggests a higher proportion of yellow fever transmission occurs as a result of infection from an external source such as the sylvatic reservoir. However, the model comparison highlights key data gaps in serological surveys across the African endemic region. As such, conclusions concerning the most prevalent transmission routes for yellow fever will be limited by the sparsity of data which is particularly evident in the areas with highest predicted transmission intensity. Our model and estimation approach provides a robust framework for model comparison and predicting yellow fever burden in Africa. However, key data gaps increase uncertainty surrounding estimates of model parameters and evidence. As more mathematical models are developed to address new research questions, it is increasingly important to compare them with established modelling approaches to highlight uncertainty in structures and data., Author summary Yellow fever (YF) is notoriously under reported due to non-specific symptom spectrum and the true burden is highly uncertain as a result of a complex transmission cycle. As such, estimates surrounding YF burden are highly uncertain and the mechanisms behind transmission are often unclear. We assess these mechanisms and the resulting uncertainty by estimating two existing models of YF transmission within a product space framework. This allows us to produce updated estimates of transmission intensity and to compare the relative support for each model given the data. We find strong support for a model assuming a static force of infection, approximating the constant infection pressure from the sylvatic reservoir of YF. We also highlight areas where data is sparse, often the same areas estimated to have especially high transmission intensity. This is the first robust multi-model approach to applied YF modelling and provides a framework that could be extended to other disease models.

Published
2019

7. Incorporating individual historical controls and aggregate treatment effect estimates into a Bayesian survival trial: a simulation study

Author

Lisa V. Hampson, Marie-Cécile Le Deley, Caroline Brard, Nathalie Gaspar, Gwénaël Le Teuff, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Statistical Methodology [Bâle, Suisse], Novartis Pharma AG, Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Unité de Méthodologie et de Biostatistique [Lille] (UMB), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, We acknowledge for the design, analysis, interpretation of the simulation study, and for the writing of the manuscript, funding from – PhD grant from doctoral school of public health, Paris-Sud, Paris-Saclay – Lisa Hampson’s contribution to the paper was partly funded by the UK Medical Research Council (grant MR/M013510/1) and was completed while she was an employee of Lancaster University – Ligue contre le cancer, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, and Bodescot, Myriam

Subjects
Simulation study, Epidemiology, Computer science, Bayesian probability, Health Informatics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Power prior, law.invention, 03 medical and health sciences, 0302 clinical medicine, Adjuvants, Immunologic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Randomized controlled trial, law, Statistics, Prior probability, Humans, Computer Simulation, 030212 general & internal medicine, Set (psychology), Baseline (configuration management), Bayesian randomised survival trial, Randomized Controlled Trials as Topic, Weibull distribution, Osteosarcoma, lcsh:R5-920, Phosphatidylethanolamines, 030503 health policy & services, Aggregate (data warehouse), Bayes Theorem, Variance (accounting), Models, Theoretical, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Control Groups, Mixture prior, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Research Design, Sample Size, Individual control data, 0305 other medical science, lcsh:Medicine (General), Aggregate treatment effect, Acetylmuramyl-Alanyl-Isoglutamine, Rare disease, Algorithms, Research Article
Abstract

Background Performing well-powered randomised controlled trials (RCTs) of new treatments for rare diseases is often infeasible. However, with the increasing availability of historical data, incorporating existing information into trials with small sample sizes is appealing in order to increase the power. Bayesian approaches enable one to incorporate historical data into a trial’s analysis through a prior distribution. Methods Motivated by a RCT intended to evaluate the impact on event-free survival of mifamurtide in patients with osteosarcoma, we performed a simulation study to evaluate the impact on trial operating characteristics of incorporating historical individual control data and aggregate treatment effect estimates. We used power priors derived from historical individual control data for baseline parameters of Weibull and piecewise exponential models, while we used a mixture prior to summarise aggregate information obtained on the relative treatment effect. The impact of prior-data conflicts, both with respect to the parameters and survival models, was evaluated for a set of pre-specified weights assigned to the historical information in the prior distributions. Results The operating characteristics varied according to the weights assigned to each source of historical information, the variance of the informative and vague component of the mixture prior and the level of commensurability between the historical and new data. When historical and new controls follow different survival distributions, we did not observe any advantage of choosing a piecewise exponential model compared to a Weibull model for the new trial analysis. However, we think that it remains appealing given the uncertainty that will often surround the shape of the survival distribution of the new data. Conclusion In the setting of Sarcome-13 trial, and other similar studies in rare diseases, the gains in power and accuracy made possible by incorporating different types of historical information commensurate with the new trial data have to be balanced against the risk of biased estimates and a possible loss in power if data are not commensurate. The weights allocated to the historical data have to be carefully chosen based on this trade-off. Further simulation studies investigating methods for incorporating historical data are required to generalise the findings. Electronic supplementary material The online version of this article (10.1186/s12874-019-0714-z) contains supplementary material, which is available to authorized users.

Published
2019

8. Quantitative genetic parameters for growth and wood properties in Eucalyptus 'urograndis' hybrid using near-infrared phenotyping and genome-wide SNP-based relationships

Author

Orzenil B. Silva-Junior, Bruno Marco de Lima, Shawn D. Mansfield, Carla Garcia, Dario Grattapaglia, Eduardo P. Cappa, BRUNO MARCO DE LIMA, USP, EDUARDO P. CAPPA, INSTITUTO NACIONAL DE TECNOLOGI´A AGROPECUARIA (INTA), ARGENTINA, ORZENIL BONFIM DA SILVA JUNIOR, Cenargen, CARLA GARCIA, INTERNATIONAL PAPER DO BRASIL ROD, SHAWN D. MANSFIELD, UNIVERSITY OF BRITISH COLUMBIA, CANADA, and DARIO GRATTAPAGLIA, Cenargen.

Subjects
0106 biological sciences, 0301 basic medicine, Heredity, Plant Science, 01 natural sciences, Lignin, Trees, Spectrum Analysis Techniques, NEAR-INFRARED PEHNOTYPING, Data Management, education.field_of_study, Eucalyptus, Multidisciplinary, Spectroscopy, Near-Infrared, Organic Compounds, Plant Anatomy, Eukaryota, near-Infrared Spectroscopy, Phylogenetic Analysis, Genomics, Plants, Wood, Phylogenetics, Polimorfismo de un Solo Nucleótido, Chemistry, Phenotypes, Phenotype, Genetic gain, Physical Sciences, Medicine, Brazil, Genome, Plant, Research Article, Genetic Research, Computer and Information Sciences, Genética Cuantitativa, Genotype, Science, Population, Infrared Spectroscopy, Quantitative trait locus, Biology, Research and Analysis Methods, Polymorphism, Single Nucleotide, Quantitative Genetics, 03 medical and health sciences, Quantitative Trait, Heritable, MOLECULAR RELATIONSHIP, Species Specificity, Genetic variation, Genetics, Evolutionary Systematics, PEDIGREE RELATIONSHIP, education, Cellulose, Fenotipos, Hybrid, Taxonomy, Evolutionary Biology, Models, Genetic, Directional selection, Organic Chemistry, Organisms, Chemical Compounds, Biology and Life Sciences, Heritability, purl.org/becyt/ford/4.5 [https], Plant Breeding, 030104 developmental biology, Evolutionary biology, Single Nucleotide Polymorphism, Tree breeding, Hybridization, Genetic, purl.org/becyt/ford/4 [https], 010606 plant biology & botany
Abstract

A thorough understanding of the heritability, genetic correlations and additive and non-additive variance components of tree growth and wood properties is a requisite for effective tree breeding. This knowledge is essential to maximize genetic gain, that is, the amount of increase in trait performance achieved annually through directional selection. Understanding the genetic attributes of traits targeted by breeding is also important to sustain decade-long genetic progress, that is, the progress made by increasing the average genetic value of the offspring as compared to that of the parental generation. In this study, we report quantitative genetic parameters for fifteen growth, wood chemical and physical traits for the world-famous Eucalyptus urograndis hybrid (E. grandis × E. urophylla). These traits directly impact the optimal use of wood for cellulose pulp, paper, and energy production. A population of 1,000 trees sampled in a progeny trial was phenotyped directly or following the development and use of near-infrared spectroscopy calibration models. Trees were genotyped with 33,398 SNPs and 24,001 DArT-seq genome-wide markers and genomic realized relationship matrices (GRM) were used for parameter estimation with an individual-tree additive-dominant mixed model. Wood chemical properties and wood density showed stronger genetic control than growth, cellulose and fiber traits. Additive effects are the main drivers of genetic variation for all traits, but dominance plays an equally or more important role for growth, singularly in this hybrid. GRM´s with >10,000 markers provided stable relationships estimates and more accurate parameters than pedigrees by capturing the full genetic relationships among individuals and disentangling the non-additive from the additive genetic component. Low correlations between growth and wood properties indicate that simultaneous selection for wood traits can be applied with minor effects on genetic gain for growth. Conversely, moderate to strong correlations between wood density and chemical traits exist, likely due to their interdependency on cell wall structure such that responses to selection will be connected for these traits. Our results illustrate the advantage of using genomewide marker data to inform tree breeding in general and have important consequences for operational breeding of eucalypt urograndis hybrids. Fil: de Lima, Bruno Marco. Universidade de Sao Paulo; Brasil. Ministerio da Agricultura Pecuaria e Abastecimento de Brasil. Empresa Brasileira de Pesquisa Agropecuaria; Brasil Fil: Cappa, Eduardo Pablo. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Recursos Naturales. Instituto de Recursos Biológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Silva Junior, Orzenil B.. Ministerio da Agricultura Pecuaria e Abastecimento de Brasil. Empresa Brasileira de Pesquisa Agropecuaria; Brasil. Universidade Católica de Brasília; Brasil Fil: Garcia, Carla. No especifíca; Fil: Mansfield, Shawn D.. University of British Columbia; Canadá Fil: Grattapaglia, Dario. Ministerio da Agricultura Pecuaria e Abastecimento de Brasil. Empresa Brasileira de Pesquisa Agropecuaria; Brasil. Universidade Católica de Brasília; Brasil

Published
2019

9. Continuous Processing of Nanocellulose and Polylactic Acid into Multilayer Barrier Coatings

Author

Jurkka Kuusipalo, Martti Toivakka, Johanna Lahti, Rajesh Koppolu, Tiffany Abitbol, Agne Swerin, Tampere University, Materials Science and Environmental Engineering, and Research group: Paper Converting and Packaging

Subjects
Materials science, Nanotechnology, barrier coatings, multilayer coatings, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, roll-to-roll process, 0104 chemical sciences, Nanocellulose, chemistry.chemical_compound, Polylactic acid, chemistry, 216 Materials engineering, General Materials Science, polylactic acid, 0210 nano-technology, nanocellulose, Research Article
Abstract

Recent years have seen an increased interest towards utilizing bio-based and biodegradable materials for barrier packaging applications. Most of the above said materials usually have certain shortcomings that discourage their adoption as a preferred material of choice. Nanocellulose falls into such category. It has excellent barrier against grease, mineral oils and oxygen, but poor tolerance against water vapor, which makes it unsuitable to be used at high humidity. In addition, nanocellulose suspensions' high viscosity and yield stress already at low solids content, and poor adhesion to substrates create additional challenges for high-speed processing. Polylactic acid (PLA) is another potential candidate that has a reasonably high tolerance against water vapor, but rather poor barrier against oxygen. The current work explores the possibility to combine both these materials into thin multilayer coatings onto paperboard. A custom-built slot-die was used to coat either microfibrillated cellulose (MFC) or cellulose nanocrystals (CNCs) onto pigment-coated baseboard in a continuous process. These were subsequently coated with PLA using a pilot scale extrusion coater. Low-density polyethylene (LDPE) was used as a reference extrusion coating. Cationic starch pre-coating and corona treatment improved the adhesion at nanocellulose/baseboard and nanocellulose/PLA interfaces, respectively. Water vapor transmission rate for nanocellulose + PLA coatings remained lower than the control PLA coating, even at a high relative humidity of 90% (38 oC). The multilayer coating had 98% lower oxygen transmission rate compared to just PLA coated baseboard and heptane vapor transmission rate reduced by 99% in comparison to baseboard. Grease barrier for nanocellulose + PLA coatings increased 5-fold compared to nanocellulose alone and 2-fold compared to PLA alone. This approach of processing nanocellulose and PLA into multiple layers utilizing slot-die and extrusion coating in tandem has the potential to produce a barrier packaging paper that is both 100% bio-based and biodegradable. publishedVersion

Published
2019

10. Structured peer-led diabetes self-management and support in a low-income country: The ST2EP randomised controlled trial in Mali

Author

Assa Traoré Sidibé, Stéphane Besançon, Cyril Ferdynus, Xavier Debussche, Hélène Delisle, Laetitia Huiart, Maryvette Balcou-Debussche, CHU Sud Saint Pierre [Ile de la Réunion], Centre d'Investigation Clinique de La Réunion - INSERM (CIC 1410), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), ONG Santé Diabète, Institut Coopératif Austral de Recherche en Éducation (ICARE), Université de La Réunion (UR), Réseau des universités pour l'éducation à la santé (Réseau UNIRéS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP), CRSN/Faculté de médecine Université de Montréal, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Universitaire, This work was supported by the Bridges programme of the International Diabetes Federation. BRIDGES (Bringing Research in Diabetes to Global Environments and Systems) is a programme initiated by the International Diabetes Federation, and supported by an educational grant from Lilly Diabetes, https://www.idf.org/our-activities/epidemiology-research/bridges.html. The NGO Santé Diabète received the funding (https://santediabete.org/en, Director: SB). The funders were not involved in the study design, in the collection, analysis and interpretation of the data, as well as in the writing of the report and in the decision to submit the paper or preparation of the manuscript for publication. The authors were independent from study funders., and Univ, Réunion

Subjects
Male, Psychological intervention, lcsh:Medicine, Social Sciences, Type 2 diabetes, Human learning, Mali, Biochemistry, Vascular Medicine, law.invention, Geographical Locations, 0302 clinical medicine, Endocrinology, Learning and Memory, Diabetes mellitus, Randomized controlled trial, law, Health care, Outcome Assessment, Health Care, Medicine and Health Sciences, Diabetes diagnosis and management, Psychology, 030212 general & internal medicine, lcsh:Science, 2. Zero hunger, Multidisciplinary, Middle Aged, 3. Good health, Health education and awareness, Blood pressure, Female, Research Article, Adult, medicine.medical_specialty, Waist, HbA1c, Patients, Endocrine Disorders, 030209 endocrinology & metabolism, Peer Group, 03 medical and health sciences, Patient Education as Topic, medicine, Learning, Humans, Hemoglobin, Developing Countries, Glycated Hemoglobin, Biology and life sciences, business.industry, Self-Management, lcsh:R, Cognitive Psychology, Proteins, Peer group, medicine.disease, Diagnostic medicine, Health Care, Self Care, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Metabolic Disorders, People and Places, Africa, Physical therapy, Cognitive Science, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Patient education, Neuroscience
Abstract

Objectives Our objective was to evaluate the effectiveness of peer-led self-management education in improving glycaemic control in patients with type 2 diabetes in a low-income country (Mali). Methods We conducted an open-label randomised controlled trial. A total of 151 adults (76% women, mean age 52.5) with type 2 diabetes (HbA1c≥8%), treated in the diabetes consultation units of two secondary health centres in Bamako, were allocated to peer-led structured patient education (n = 76) or conventional care alone (n = 75). The intervention group received 1 year of culturally tailored structured patient education (3 courses of 4 sessions) delivered in the community by five trained peer educators. Both groups underwent conventional diabetes monitoring and follow-up. Primary outcome was the mean absolute change in HbA1c from baseline to 12 months. Results 177 education sessions were delivered to the intervention group. Patient attrition was 8%. From baseline to 12 months, the decrease in HbA1c levels was 1.05% (SD = 2.0; CI95%: 1.54;-0.56) in the intervention group compared with 0.15% (SD = 1.7; CI95%: -0.56; 0.26) in the control group, p = 0.006. Mean BMI change was -1.65 kg/m2 (SD = 2.5; CI95%: -2.25; -1.06) in the intervention group and +0.05 kg/m2 (SD = 3.2; CI95%: -0.71; 0.81) in the control group, p = 0.0005. Mean waist circumference decreased by 3.34 cm (SD = 9.3; CI95%: -5.56;-1.13) in the intervention group and increased by 2.65 cm (SD = 10.3; CI95%: 0.20; 5.09) in the control group, p = 0.0003. Conclusions Peer-led structured patient education delivered over 1 year to patients with poorly controlled type 2 diabetes in Mali yielded substantial improvements in glycaemic control and anthropometric parameters. This is of importance for the scaling up of efficient interventions in low-resource settings in the future. Trial registration ClinicalTrials.gov NCT01485913

Published
2018

11. Single low-dose primaquine for blocking transmission of plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa

Author

Muhindo Mavoko, Htee Khu Naw, Estrella Lasry, Nicholas J. White, Sodiomon B. Sirima, Melissa C. Kapulu, Mores Loolpapit, Marie Claire Henry, Thomas N. Williams, Alfred Ngwa Amambua, Claude Rwagacondo, Rick M. Fairhurst, Nicholas P. J. Day, Joseph Okebe, Umberto D'Alessandro, Mahamadou Diakite, Rindra Randremanana, Mavuto Mukaka, James A. Berkley, Jean-Pierre Van Geertruyden, Charles O Obonyo, Malcolm E. Molyneux, Muna Affara, Philipe Brasseur, Peter G. Kremsner, Pascal Lutumba, Endalamaw Gadisa, Abraham Aseffa, Grace Malenga, Caterina I. Fanello, Grant Dorsey, Karen I. Barnes, Zolia Yah, Jane Achan, Patrice Piola, Kathryn Maitland, Chandy C. John, Davis Nwakanma, Joel J. Jones, W. Robert Taylor, Birgit Schramm, Marie A. Onyamboko, Junior Matangila, Philip Bejon, Geneva University Hospital (HUG), Mahidol Oxford Tropical Medicine Research Unit (MORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], KEMRI-Wellcome Trust Research Programme (KWTRP), Imperial College London, University of Oxford [Oxford], Medical Research Council Unit The Gambia (MRC), University of Antwerp (UA), University of Kinshasa (UNIKIN), Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Epicentre [Paris] [Médecins Sans Frontières], Kinshasa Mahidol Oxford Research Unit (KIMORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Ecole de Santé Publique de Kinshasa (KSPH ou ESP), National Malaria Control Programme, Ministry of Health and Social Welfare, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Malaria Research and Training Center [Bamako, Mali], Université de Bamako, Queen Elizabeth Hospital, University of Liverpool, Kenya Medical Research Institute (KEMRI), Armauer Hansen Research Institute (AHRI), Amref Health Africa [Kenya], African Medical and Research Foundation (AMREF), Centre de Recherche Entomologique de Cotonou (CREC), Ministère de la Santé, University of California [San Francisco] (UCSF), University of California, Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), Groupe de recherche action en santé (GRAS), University of Cape Town, University of Tübingen, TNW is supported by a Fellowship from the Wellcome Trust (202800). The KEMRI–Wellcome Trust Research Programme in Kenya is funded through a Strategic Award from the KEMRI–Wellcome Trust Research Programme (203077). RMF was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health. NJW is a Wellcome Trust Principal Fellow., We acknowledge with gratitude the Demographic Health Survey of USAID for permission to download data from their website. This paper is published with permission from the Director of KEMRI., University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of Oxford, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of California [San Francisco] (UC San Francisco), University of California (UC), RANDRIAMANANTSOA, Volatiana Manohisoa, and Wellcome Trust

Subjects
Male, Primaquine, Antimalarials / therapeutic use, lcsh:Medicine, MESH: Dose-Response Relationship, Drug, MESH: Clinical Protocols, MESH: Aged, 80 and over, 0302 clinical medicine, Clinical Protocols, MESH: Child, Epidemiology, 030212 general & internal medicine, Malaria, Falciparum, Child, MESH: Plasmodium falciparum, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, biology, MESH: Malaria, Falciparum, Age Factors, 11 Medical And Health Sciences, General Medicine, Middle Aged, MESH: Primaquine, MESH: Infant, 3. Good health, MESH: Glucosephosphate Dehydrogenase Deficiency, Tolerability, MESH: Young Adult, Child, Preschool, Primaquine / administration & dosage, Female, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Plasmodium falciparum, 030231 tropical medicine, Antimalarials / adverse effects, Antimalarials, Malaria, Falciparum / prevention & control, Young Adult, 03 medical and health sciences, Pharmacokinetics, Age-based dosing, General & Internal Medicine, Internal medicine, parasitic diseases, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, MESH: Africa South of the Sahara, Dosing, Africa South of the Sahara, ddc:613, Aged, MESH: Adolescent, MESH: Age Factors, MESH: Humans, Dose-Response Relationship, Drug, business.industry, lcsh:R, Malaria, Falciparum / transmission, MESH: Child, Preschool, Infant, MESH: Adult, medicine.disease, biology.organism_classification, MESH: Antimalarials, MESH: Male, Malaria, Regimen, Glucosephosphate Dehydrogenase Deficiency, Primaquine / adverse effects, Primaquine / therapeutic use, Antimalarials / administration & dosage, Malaria, Falciparum / drug therapy, Transmission blocking, Human medicine, business, MESH: Female
Abstract

Background In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. Methods Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15–0.4 mg PQ base/kg for children aged 1–5 years and 0.15–0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6–11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box–Cox transformation power exponential and tested PQ doses of 1–15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. Results From the Box–Cox transformation power exponential model, five age categories were selected: (i) 6–11 months (n = 39,886, 6.03%), (ii) 1–5 years (n = 261,036, 45.46%), (iii) 6–9 years (n = 20,770, 3.14%), (iv) 10–14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12–0.25), (ii) 0.21 (0.13–0.37), (iii) 0.25 (0.16–0.38), (iv) 0.26 (0.15–0.38) and (v) 0.27 (0.17–0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. Conclusions We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 − 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination. Electronic supplementary material The online version of this article (doi:10.1186/s12916-017-0990-6) contains supplementary material, which is available to authorized users.

Published
2018

12. Integrated Analysis of Environment, Cattle and Human Serological Data: Risks and Mechanisms of Transmission of Rift Valley Fever in Madagascar

Author

Annelise Tran, Vladimir Grosbois, Jean-Pierre Ravalohery, Fanjasoa Rakotomanana, Jean-Michel Heraud, Soa Fy Andriamandimby, Christophe Rogier, Seta Andriamamonjy, Véronique Chevalier, Benoit Durand, Marie-Marie Olive, Animal et gestion intégrée des risques (UPR AGIRs), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Unité de Virologie [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Réseau International des Instituts Pasteur (RIIP), This study was supported in part by funds raised by (i) CIRAD (ii) the Centre National d'Etudes Spatiales (CNES, grant # 131163/00) (iii) the Institut Pasteur de Madagascar. Human field work was funded by the Institut Pasteur of Madagascar (Internal Project through the ZORA (ZOonoses, Rodent and Arboviruses) project and the Centers for Disease Control and Prevention (CDC, and Cooperative Agreement #U51/IP000327). Moreover, this material is based upon work supported by the U. S. Department of Homeland Security under the Center of Excellence of Emerging and Zoonotic Animal Diseases Grant Award Number 2010-ST061-AG0001. Cattle study was supported in part by funds raised by World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO) through the Central Emergency Response Fund of the United Nations. The views and conclusions contained in this paper are those of the authors and should not be interpreted as necessarily representing the official policies, either explicit or implicit, of the U. S. Department of Homeland Security. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Subjects
Veterinary medicine, Epidemiology, Pathology and Laboratory Medicine, law.invention, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Analyse du risque, MESH: Cattle Diseases, MESH: Animals, Neglected tropical diseases, Mammals, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, 000 - Autres thèmes, Fièvre de la Vallée du Rift, Anopheles, Ruminants, 3. Good health, Transmission (mechanics), MESH: Young Adult, Densité de population, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Enzootic, Infectious diseases, L72 - Organismes nuisibles des animaux, Genre humain, Bétail, Livestock, lcsh:RC955-962, MESH: Culex, Microbiology, MESH: Anopheles, 03 medical and health sciences, MESH: Cross-Sectional Studies, Madagascar, MESH: Humans, MESH: Seroepidemiologic Studies, Tropical diseases, Public Health, Environmental and Occupational Health, Organisms, lcsh:RA1-1270, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 15. Life on land, medicine.disease, Invertebrates, Insect Vectors, 030104 developmental biology, Africa, Cattle, MESH: Female, MESH: Antibodies, Viral, 0301 basic medicine, RNA viruses, Cattle Diseases, Disease Vectors, L73 - Maladies des animaux, Mosquitoes, Serology, Geographical Locations, MESH: Madagascar, law, Zoonoses, Facteur de risque, Bunyaviruses, Medicine and Health Sciences, MESH: Rift Valley Fever, Comportement humain, Rift Valley fever, 2. Zero hunger, biology, lcsh:Public aspects of medicine, Agriculture, Facteur du milieu, Medical microbiology, Insects, MESH: Cattle, Vecteur de maladie, Vertebrates, Viruses, MESH: Rift Valley fever virus, Seasons, Pathogens, Research Article, lcsh:Arctic medicine. Tropical medicine, Zone humide, Arthropoda, Distribution géographique, Culex, 030231 tropical medicine, Viral diseases, MESH: Insect Vectors, Virus de la fièvre de la vallée du Rift, Sérologie, Bovines, medicine, Seroprevalence, Animals, MESH: Environment, Transmission des maladies, Biology and life sciences, Viral pathogens, Morbidité, biology.organism_classification, Rift Valley fever virus, MESH: Male, Microbial pathogens, Amniotes, People and Places, Earth Sciences, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

Background Rift Valley fever (RVF) is a vector-borne disease affecting ruminants and humans. Madagascar was heavily affected by RVF in 2008–2009, with evidence of a large and heterogeneous spread of the disease. The identification of at-risk environments is essential to optimize the available resources by targeting RVF surveillance in Madagascar. Herein, the objectives of our study were: (i) to identify the environmental factors and areas favorable to RVF transmission to both cattle and human and (ii) to identify human behaviors favoring human infections in Malagasy contexts. Methodology/Principal Findings First, we characterized the environments of Malagasy communes using a Multiple Factor Analysis (MFA). Then, we analyzed cattle and human serological data collected at national level using Generalized Linear Mixed Models, with the individual serological status (cattle or human) as the response, and MFA factors, as well as other potential risk factors (cattle density, human behavior) as explanatory variables. Cattle and human seroprevalence rates were positively associated to humid environments (p, Author Summary Rift Valley fever virus (RVFV) is a pathogen that causes a vector-borne tropical disease. The disease affects ruminants and humans and severely impacts the health and economy of affected countries. Madagascar was heavily affected by Rift Valley fever (RVF) in 2008–2009, with evidence of a large and heterogeneous spread of the disease. Our study aims at identifying environmental and human-related risk factors for RVFV transmission. First, we characterized Malagasy environments according to their putative influence on RVFV mosquito density and population dynamics. Then we statistically analyzed cattle and human serological data collected at a national level with the individual serological status as response, and Malagasy environments previously characterized by climatic and landscape variables as well as other potential risk factors as explanatory variables. Our results identified humid environments of the western, north-western and eastern parts of the island as risky areas. The identification of at-risk environments is essential to focus veterinary surveillance and control of RVFV.

Published
2016

13. Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination?

Author

Marietjie Venter, Juan Yang, Simona Puzelli, Antonino Bella, Joshua A. Mott, Rodrigo Fasce, Coulibaly Daouda, Jenny Lara, Hongjie Yu, Winston Andrade, Selim Badur, Cláudio Maierovitch Pessanha Henriques, François G. Schellevis, Jean-Michel Heraud, Akerke Ospanova, Sonam Wangchuk, Brechla Moreno, Herve A. Kadjo, Raymond T. P. Lin, Juan Manuel Rudi, Walquiria Aparecida Ferreira de Almeida, Gabriela Kusznierz, Joseph S. Bresee, Cheryl Cohen, Mai thi Quynh Le, Rhonda Owen, Maria Zambon, Maria Luisa Matute, Kunzang Dorji, Kate Pennington, Global Influenza B Study, Herman Kosasih, Nurhayati, Alla Mironenko, Ming Li, Angel Balmaseda, Alexey Clara, Alfredo Bruno, Richard Njouom, Phuong Vu Mai Hoang, Ana Paula Rodrigues, Celina de Lozano, Luzhao Feng, Olha Holubka, Amal Barakat, Lyazzat Kiyanbekova, Norosoa Harline Razanajatovo, Saverio Caini, Meral Akcay Ciblak, Raquel Guiomar, Richard Pebody, Leticia Castillo, Gideon O. Emukule, Liza Lopez, Doménica de Mora, Jeffery Cutter, Q. Sue Huang, Marie-Astrid Vernet, Abderrahman Bimohuen, John Paget, Lynnette Brammer, General practice, EMGO - Quality of care, Netherlands Institute for Health Services Research, Instituto de Salud Pública de Chile (ISP), Istanbul University, Ministry of Health [Nicaragua] (MINSA), Ministry of Health [Morocco], Istituto Superiore di Sanita [Rome], Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Instituto Nacional de Investigación en Salud Pública [Guayaquil, Ecuador] (INSPI), Ministerio de Salud Publica y Asistencia Social [Guatemala] (MSPAS), US Centers for Disease Control, University of the Witwatersrand [Johannesburg] (WITS), Ministry of Health, Institut Pasteur de Côte d'Ivoire, Réseau International des Instituts Pasteur (RIIP), Ministerio de Salud de El Salvador (MINSAL), Ministry of Health [Bhoutan], US Centers for Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Instituto nacional de saude, Unité de Virologie [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), National Academy of Medical Sciences of Ukraine, Institute of Environmental Science and Research (ESR), Astana Center of Sanitary Epidemiology Expertise, US Naval Medical Research Unit n°2, Instituto Nacional de Enfermedades Respiratorias 'Dr. Emilio Coni', Ministry of Health [Costa Rica], National Institute of Hygiene and Epidemiology [Hanoi, Vietnam] (NIHE), Ministry of Health [Honduras] (SESAL), National Influenza Center, Centre Pasteur du Cameroun, Office of Health Protection, Woden, ACT, Australia (DHAISS), Public Health England [London], National Institute of Health, University of Pretoria [South Africa], The Global Influenza B Study is supported by an unrestricted research grant from Sanofi Pasteur. The study sponsor had no role in the design of the study, in the collection, analysis, and interpretation of data, in the writing of the report, and and in the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The study sponsor had no access to the data in the study.

Subjects
Infecções Respiratórias, Influenza Viruses, Epidemiology, Gripe, Pathology and Laboratory Medicine, Geographical locations, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, DRIVERS, Estados de Saúde, Public and Occupational Health, SUB-SAHARAN AFRICA, lcsh:Science, MESH: Influenza B virus, Northern Hemisphere, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Geography, MESH: Influenza, Human, Vaccination, virus diseases, 3. Good health, Global Influenza B Study, MESH: Tropical Climate, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Science & Technology - Other Topics, Immunology, Disease Surveillance, SEASONAL INFLUENZA, Microbiology, Influenza Vaccin, 03 medical and health sciences, Influenza Vaccination, SURVEILLANCE, Humans, Microbial Pathogens, Retrospective Studies, MESH: Humans, Science & Technology, lcsh:R, Organisms, Correction, Influenza a, MESH: Retrospective Studies, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Virology, Influenza, MADAGASCAR, lcsh:Q, Preventive Medicine, People and places, Demography, RNA viruses, Viral Diseases, lcsh:Medicine, medicine.disease_cause, Tropical climate, Medicine and Health Sciences, Influenza A virus, 030212 general & internal medicine, Multidisciplinary, Medical microbiology, Vaccination and Immunization, Multidisciplinary Sciences, Infectious Diseases, Viruses, Human mortality from H5N1, Southern Hemisphere, Seasons, Pathogens, Brazil, Research Article, Infectious Disease Control, General Science & Technology, 030231 tropical medicine, MESH: Influenza A virus, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], MD Multidisciplinary, Influenza, Human, Temperate climate, medicine, Tropical Climate, Biology and life sciences, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Viral pathogens, Tropics, MESH: Vaccination, South America, Seasonality, Earth sciences, Influenza B virus, Infectious Disease Surveillance, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Geographic areas, MESH: Seasons, Orthomyxoviruses
Abstract

Erratum in - Correction: Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination? PLoS One. 2016 May 2;11(5):e0155089. doi: 10.1371/journal.pone.0155089. Introduction: Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. Methods: This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with 80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. Results: 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. Discussion: Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate. The Global Influenza B Study is supported by an unrestricted research grant from Sanofi Pasteur. info:eu-repo/semantics/publishedVersion

Published
2016

14. Interventions and decision-making at the end of life: the effect of establishing the terminal illness situation

Author

Rafael Montoya-Juárez, María Paz García-Caro, E. Hernández-López, César Hueso-Montoro, F. Ojeda-Virto, C. Campos-Calderón, [Campos-Calderón,C] Foundation of Progress and Health, Andalusian Health Service, Granada, Spain. [Montoya-Juárez,R, Hueso-Montoro,C, García-Caro,MP] Nursing Department, University of Granada, Granada, Spain. [Hernández-López,E] General Hospital of the Virgen de las Nieves of Granada, Andalusian Health Service, Granada, Spain. [Ojeda-Virto,F] Hospital Santa Ana, Andalusian Health Service, Motril, Spain., and This work is part of an investigative project financed by the Department of Health of the Board of Andalucía in its 2010 call for papers, titled ‘Variability of Clinical Practice and Conditional Factors in the Implementation of the Processes of Attention at End of Life’.Ref: PI-0670-2010.

Subjects
Palliative care, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], medicine.medical_treatment, España, Psychological intervention, Chemicals and Drugs::Inorganic Chemicals::Elements::Chalcogens::Oxygen [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Oxygen therapy, Medicine, Analgésicos opioides, Oxígeno, 030212 general & internal medicine, Patient Comfort, Practice Patterns, Physicians', Resuscitation Orders, Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospitals [Medical Subject Headings], Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Medicine(all), Terminal Care, Palliative Care, Do not resuscitate, Symptom management, General Medicine, Prognosis, Hospitals, Humanos, End-of-life care, Teaching/learning strategies, 030220 oncology & carcinogenesis, Peripheral venous catheter, Hospitales, Research Article, medicine.medical_specialty, Clinical Decision-Making, education, M-learning, Prescripciones, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Sensory System Agents::Analgesics::Analgesics, Opioid [Medical Subject Headings], Advance Care Planning, Estudios retrospectivos, 03 medical and health sciences, Humans, Terminally Ill, Medical prescription, Órdenes de resucitación, Intensive care medicine, Retrospective Studies, Delivery of care, Hospital care, business.industry, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Emergency Treatment::Resuscitation::Resuscitation Orders [Medical Subject Headings], Andalucía, Retrospective cohort study, Spain, business, Decision making, Physical therapy, Health Care::Health Care Facilities, Manpower, and Services::Health Services::Pharmaceutical Services::Prescriptions [Medical Subject Headings]
Abstract

Background: Mobile learning (m-learning) has becoming very popular in education due to the rapidly advancing technology in our society. The potentials of the mobile applications should be used to enhance the education process. Few mobile applications have been designed to complement the study of physical therapy skills for physiotherapy students. The aim of this study was to investigate whether a mobile application, as a supplement to traditional learning, is useful for physiotherapy students in the acquisition of palpation and ultrasound skills in the shoulder area. Methods: Forty-nine students participated in this single-blinded, randomized controlled study. They were randomly distributed into two groups: experimental, with free access to the mobile application; and control, with access to traditional learning materials on the topic. Objective structured clinical evaluation (OSCE) and multiple-choice questionnaire (MCQ) were used to assess the educational intervention. Then, we also assessed the time taken to get a reliable ultrasound image and to localize a specific shoulder structure by palpation. Results: There was no significant intergroup difference in the acquisition of theoretical knowledge (p = .089). Scores were significantly higher in the experimental group than in the control group for the majority items in the ultrasound assessment; positioning of patient (p < .001), positioning of ultrasound probe (p = 0.007), handling of ultrasound probe (p = .013) and global OSCE (p < .001) and skills in palpation of the shoulder; position of patient (p = .009), direction of palpation contact (p = .021) and global OSCE (p = .034). There were no significant differences in the time required to perform the examination between groups in ultrasound (p = .944) and palpation (p = .393). The results from the post-program survey assessing the global satisfaction with the mobile application were high (8.200 ± .767), on an 11 numeric point rating scale. Conclusion: These results suggest the effectiveness of an m-learning program as a complement to traditional education for developing skills in ultrasound and palpation of the shoulder region in undergraduate physiotherapy students., The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by a grant from the Educational Innovation Unit of the University of Granada, Spain (PID 13–86).

Published
2016

15. Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira

Author

Emilia Scharrig, María Florencia Ferrer, Agostina Carestia, Mathieu Picardeau, Maia Cédola, Ricardo Martín Gómez, Mirta Schattner, Gabriela Pretre, Ricardo Drut, CCT La Plata-CONICET-Facultad de Ciencias Veterinarias [La Plata, PBA, Argentine], Universidad Nacional de la Plata [Argentine] (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Children Hospital 'Superiora Sor María Ludovica' LA PLATA, Biologie des Spirochètes / Biology of Spirochetes, Institut Pasteur [Paris], This work was supported by PICTs grant 12-0434 (RMG) and 11-733 (MS) from ANPCyT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Conceived and designed the experiments: MP MS RMG. Performed the experiments: ES AC MFF GP. Analyzed the data: MC RD. Contributed reagents/materials/analysis tools: MP. Wrote the paper: MS RMG., and Institut Pasteur [Paris] (IP)

Subjects
Male, lcsh:Arctic medicine. Tropical medicine, Neutrophils, lcsh:RC955-962, [SDV]Life Sciences [q-bio], Inflammation, Extracellular Traps, Microbiology, purl.org/becyt/ford/1 [https], Ciencias Biológicas, Mice, 03 medical and health sciences, neutrophils, Immunity, In vivo, Leptospira, medicine, Animals, Humans, leptospirosis, Leptospirosis, purl.org/becyt/ford/1.6 [https], Ciencias Exactas, 030304 developmental biology, 0303 health sciences, Innate immune system, biology, 030306 microbiology, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Nets, Neutrophil extracellular traps, biology.organism_classification, Immunity, Innate, 3. Good health, Mice, Inbred C57BL, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.symptom, Leptospira interrogans, Virología, Ex vivo, CIENCIAS NATURALES Y EXACTAS, Research Article
Abstract

NETosis is a process by which neutrophils extrude their DNA together with bactericidal proteins that trap and/or kill pathogens. In the present study, we evaluated the ability of Leptospira spp. to induce NETosis using human ex vivo and murine in vivo models. Microscopy and fluorometric studies showed that incubation of human neutrophils with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 (LIC) resulted in the release of DNA extracellular traps (NETs). The bacteria number, pathogenicity and viability were relevant factors for induction of NETs, but bacteria motility was not. Entrapment of LIC in the NETs resulted in LIC death; however, pathogenic but not saprophytic Leptospira sp. exerted nuclease activity and degraded DNA. Mice infected with LIC showed circulating NETs after 2 days post-infection (dpi). Depletion of neutrophils with mAb1A8 significantly reduced the amount of intravascular NETs in LIC-infected mice, increasing bacteremia at 3 dpi. Although there was a low bacterial burden, scarce neutrophils and an absence of inflammation in the early stages of infection in the kidney and liver, at the beginning of the leptospiruric phase, the bacterial burden was significantly higher in kidneys of neutrophil-depleted-mice compared to non-depleted and infected mice. Surprisingly, interstitial nephritis was of similar intensity in both groups of infected mice. Taken together, these data suggest that LIC triggers NETs, and that the intravascular formation of these DNA traps appears to be critical not only to prevent early leptospiral dissemination but also to preclude further bacterial burden., Instituto de Biotecnologia y Biologia Molecular, Facultad de Ciencias Exactas, Facultad de Ciencias Médicas

Published
2015

16. Use of a New High Resolution Melting Method for Genotyping Pathogenic Leptospira spp

Author

Amélie Desvars, Alain Michault, Florence Naze, Pascale Bourhy, Mathieu Picardeau, Laboratoire de Bactériologie-Parasitologie-Virologie-Hygiène, Groupe Hospitalier Sud Réunion (GHSR), Centre Collaborateur FAO/OMS pour l'épidémiologie de la leptospirose, Institut Pasteur [Paris] (IP), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Biologie des Spirochètes / Biology of Spirochetes, The authors have no support or funding to report., Conceived and designed the experiments: AM MP PB. Performed the experiments: FN AD. Analyzed the data: AD MP AM PB. Contributed reagents/materials/analysis tools: FN PB. Wrote the paper: FN AD MP PB AM., and Institut Pasteur [Paris]

Subjects
Serotype, DNA, Bacterial, Genotype, Genotyping Techniques, [SDV]Life Sciences [q-bio], lcsh:Medicine, Minisatellite Repeats, Nucleic Acid Denaturation, Real-Time Polymerase Chain Reaction, Melting curve analysis, High Resolution Melt, Species Specificity, Leptospira, medicine, Cluster Analysis, Humans, lcsh:Science, Genotyping, Genetics, Multidisciplinary, biology, lcsh:R, biology.organism_classification, medicine.disease, Leptospirosis, Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, lcsh:Q, Leptospira interrogans, Software, Research Article
Abstract

Background Leptospirosis is a worldwide zoonosis that is endemic in tropical areas, such as Reunion Island. The species Leptospira interrogans is the primary agent in human infections, but other pathogenic species, such as L. kirschner and L. borgpetersenii, are also associated with human leptospirosis. Methods and Findings In this study, a melting curve analysis of the products that were amplified with the primer pairs lfb1 F/R and G1/G2 facilitated an accurate species classification of Leptospira reference strains. Next, we combined an unsupervised high resolution melting (HRM) method with a new statistical approach using primers to amplify a two variable-number tandem-repeat (VNTR) for typing at the subspecies level. The HRM analysis, which was performed with ScreenClust Software, enabled the identification of genotypes at the serovar level with high resolution power (Hunter-Gaston index 0.984). This method was also applied to Leptospira DNA from blood samples that were obtained from Reunion Island after 1998. We were able to identify a unique genotype that is identical to that of the L. interrogans serovars Copenhageni and Icterohaemorrhagiae, suggesting that this genotype is the major cause of leptospirosis on Reunion Island. Conclusions Our simple, rapid, and robust genotyping method enables the identification of Leptospira strains at the species and subspecies levels and supports the direct genotyping of Leptospira in biological samples without requiring cultures.

Published
2015

17. Use of Two-Part Regression Calibration Model to Correct for Measurement Error in Episodically Consumed Foods in a Single-Replicate Study Design: EPIC Case Study

Author

Agogo, George O, der Voet, Hilko van, Veer, Pieter Van't, Ferrari, Pietro, Leenders, Max, Muller, David C, Sánchez-Cantalejo, Emilio, Bamia, Christina, Braaten, Tonje, Knüppel, Sven, Johansson, Ingegerd, van Eeuwijk, Fred A, Boshuizen, Hendriek, LS IRAS EEPI GRA (Gezh.risico-analyse), IRAS RATIA-SIB, Risk Assessment of Toxic and Immunomodulatory Agents, [Agogo,GO, Boshuizen,H] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. [Agogo,GO, Voet,HV, Eeuwijk,FAV, Boshuizen,H] Biometris, Wageningen University and Research Center, Wageningen, The Netherlands.[Veer,PV, Boshuizen,H] Department of Human Nutrition, Wageningen University and Research Center, Wageningen, The Netherlands. [Ferrari,P] Nutritional Epidemiology Group, International Agency for Research on Cancer, Lyon, France. [Leenders,M] Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands. [Muller,DC] Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France. [Sánchez-Cantalejo,E] Andalusian School of Public Health, Granada, Spain. CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. [Bamia,C] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Braaten,T] Department of Community Medicine, University of Tromsø, Tromsø, Norway. [Knüppel,S] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Potsdam, Germany. [Johansson,I] Department of Odontology, Umea University, Umea, Sweden., However, the publication cost will be covered by Wageningen University and Research Centre, Biometris, P.O. Box 100, 6700 AC WAGENINGEN should the paper be accepted for a publication., LS IRAS EEPI GRA (Gezh.risico-analyse), IRAS RATIA-SIB, and Risk Assessment of Toxic and Immunomodulatory Agents

Subjects
Male, Parametric Analysis, Medicin och hälsovetenskap, Nutrition and Disease, Calibration (statistics), Test Statistics, lcsh:Medicine, markers, Overfitting, Statistical Inference, outcomes, Medical and Health Sciences, Wiskundige en Statistische Methoden - Biometris, Mathematical and Statistical Techniques, Neoplasms, Surveys and Questionnaires, Voeding en Ziekte, Statistics, Medicine, Prospective Studies, lcsh:Science, Multidisciplinary, Maximum Likelihood Estimation, Regression analysis, Estudios Prospectivos, Replicate, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, PE&RC, Neoplasias, Diet Records, Europe, Survival Rate, Biometris, nutrition, Physical Sciences, Calibration, instruments, Regression Analysis, Dieta, Female, dietary self-report, Statistics (Mathematics), Bayesian Statistics, Research Article, Adult, Heteroscedasticity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], General Science & Technology, Logit, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research and Analysis Methods, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Nutrition Assessment [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies [Medical Subject Headings], Covariate, MD Multidisciplinary, Humans, cancer, Statistical Methods, Statistical Hypothesis Testing, Mathematical and Statistical Methods - Biometris, Aged, VLAG, disease, Observational error, Models, Statistical, business.industry, lcsh:R, Evaluación Nutricional, Feeding Behavior, Estudios Longitudinales, Estudios Epidemiológicos, Survival Analysis, Nutrition Assessment, lcsh:Q, Food Habits, business, Mathematics, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies [Medical Subject Headings], Generalized Linear Model
Abstract

Journal Article; In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model. Yes

Published
2014

18. Immunotherapy reduces allergen-mediated CD66b expression and myeloperoxidase levels on human neutrophils from allergic patients

Author

Antonio Vega, Miguel Blanca, Cristina Chamorro, Javier Monteseirín, Inmaculada Ventura, Elisa Gomez, Rocío Aroca, Ramón Pérez-Cano, [Aroca,R, Chamorro,C, Vega,A, Ventura,A, Gómez,E, Monteseirín,J] Servicio Regional de Inmunología y Alergia, Hospital Universitario Virgen Macarena, Sevilla, Spain. [Pérez-Cano,R, Monteseirín,J] Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain. [Blanca,M] Research Laboratory, Carlos Haya Hospital-Fundacion IMABIS, Málaga, Spain., and Conceived and designed the experiments: JM. Performed the experiments: RA CC AV IV EG. Analyzed the data: JM. Wrote the paper: JM MB AV RPC.

Subjects
Hipersensibilidad, Lipopolysaccharides, Male, Allergy, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::GPI-Linked Proteins [Medical Subject Headings], Pulmonology, Neutrophils, Physiology, medicine.medical_treatment, lcsh:Medicine, medicine.disease_cause, Immunoglobulin E, Biochemistry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Allergen, Animal Cells, Immune Physiology, Molecular Cell Biology, Allergies, Medicine and Health Sciences, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Cell Adhesion Molecules [Medical Subject Headings], lcsh:Science, Immune Response, CEACAM8 protein, human, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin E [Medical Subject Headings], Cells, Cultured, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Therapeutic Irrigation::Nasal Lavage::Nasal Lavage Fluid [Medical Subject Headings], Multidisciplinary, Immune System Proteins, biology, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Peroxidases::Peroxidase [Medical Subject Headings], Flow Cytometry, Up-Regulation, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunosuppression::Desensitization, Immunologic [Medical Subject Headings], Inmunoglobulina E, Myeloperoxidase, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Separation::Flow Cytometry [Medical Subject Headings], Female, Nasal Lavage Fluid, Immunotherapy, medicine.symptom, Cellular Types, Research Article, Adult, Neutrófilos, Immune Cells, Immunology, Diseases::Immune System Diseases::Hypersensitivity [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Inflammation, GPI-Linked Proteins, Antibodies, Chemicals and Drugs::Carbohydrates::Glycoconjugates::Lipopolysaccharides [Medical Subject Headings], Antígenos CD, Antigens, CD, medicine, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Hypersensitivity, Cell Adhesion, Humans, Asthma, Peroxidase, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Up-Regulation [Medical Subject Headings], lcsh:R, Immunity, Biology and Life Sciences, Proteins, Cell Biology, medicine.disease, Check Tags::Female [Medical Subject Headings], Desensitization, Immunologic, Anatomy::Cells::Cells, Cultured [Medical Subject Headings], Immunoglobulin G, biology.protein, Moléculas de Adhesión Celular, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD [Medical Subject Headings], Clinical Immunology, lcsh:Q, Anatomy::Cells::Blood Cells::Leukocytes::Granulocytes::Neutrophils [Medical Subject Headings], Cell Adhesion Molecules, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin G [Medical Subject Headings]
Abstract

Journal Article; Research Support, Non-U.S. Gov't; CD66b is a member of the carcinoembryonic antigen family, which mediates the adhesion between neutrophils and to endothelial cells. Allergen-specific immunotherapy is widely used to treat allergic diseases, and the molecular mechanisms underlying this therapy are poorly understood. The present work was undertaken to analyze A) the in vitro effect of allergens and immunotherapy on cell-surface CD66b expression of neutrophils from patients with allergic asthma and rhinitis and B) the in vivo effect of immunotherapy on cell-surface CD66b expression of neutrophils from nasal lavage fluid during the spring season. Myeloperoxidase expression and activity was also analyzed in nasal lavage fluid as a general marker of neutrophil activation. RESULTS CD66b cell-surface expression is upregulated in vitro in response to allergens, and significantly reduced by immunotherapy (p

Published
2014

19. Impact of therapy escalation on ambulatory care costs among patients with type 2 diabetes in France

Author

Florent Guelfucci, Mondher Toumi, Samuel Aballéa, Nicholas Moore, Emilie Clay, Régis Lassalle, Systèmes Intégrés, Environnement et Biodiversité (SIEB), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-HESAM Université (HESAM), Evaluation des systèmes de soins et santé perçue, Université de la Méditerranée - Aix-Marseille 2, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Pharmaco-Epidémiologie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was supported by an unconditional grant from Boehringer Ingelheim. The sponsor had no influence on study design, conduct, analysis or interpretation, or in the writing of this paper., École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), and BMC, Ed.

Subjects
medicine.medical_specialty, medicine.medical_treatment, Endocrinology, Diabetes and Metabolism, Pharmacy, Type 2 diabetes, 03 medical and health sciences, Nursing care, 0302 clinical medicine, Ambulatory care, Internal medicine, Diabetes mellitus, Type 2 diabetes mellitus, medicine, Cost analysis, Insulin, 030212 general & internal medicine, Oral antidiabetics, health care economics and organizations, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, business.industry, 030503 health policy & services, Type 2 Diabetes Mellitus, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Endocrinology, Ambulatory, 0305 other medical science, business, Research Article, Renal function
Abstract

International audience; BACKGROUND: This study compares annual ambulatory care expenditures per patient with type 2 diabetes mellitus (T2DM) in France according to treatment phase and renal function status. METHODS: Records from patients with T2DM were extracted from a health insurance database. Patients were classified in subgroups, by treatment phase: oral/GLP1 monotherapy, double therapy, triple therapy or insulin therapy, and according to renal function status (identified using pharmacy, lab and consultation claims). Annual ambulatory expenditures were estimated from the national insurance perspective by year (from 2005 to 2010) and subgroup. RESULTS: The number of patients ranged from 9,682 to 11,772 between 2005 and 2010. The average annual expenditure per individual in 2010 ranged from [euro sign]3,017 (standard deviation: [euro sign]3,829) for monotherapy to [euro sign]3,609 +/- [euro sign]3,801 for triple therapy, and [euro sign]7,398 +/- [euro sign]5,487 with insulin (adjusted ratio insulin therapy/monotherapy: 2.36, p < 0.001). Similar differences between treatement stages were found in previous years. Additional costs for insulin were mainly related to nursing care (multiplied by 18.42, p < 0.001), medical devices and pharmacy costs. DM-attributable drug costs were mainly related to antidiabetic drugs (28% for monotherapy to 71% for triple therapy), but also to cardiovascular system drugs (21% for monotherapy to 51% with insulin) and nervous system drugs (up to 8% with insulin). Declining renal function was associated with an increase in expenses by 12% to 53% according to treatment stage. CONCLUSIONS: Overall, ambulatory care expenditures increase with treatment escalation and declining renal function amongst patients with T2DM. Insulin therapy is associated with substantially increased costs, related to pharmacy, nursing care and medical device costs.

Published
2013

20. RNA sequencing revealed novel actors of the acquisition of drug resistance in Candida albicans

Author

Jean-Yves Coppée, Gaëlle Lelandais, Odile Sismeiro, Sophie Lemoine, Frédéric Devaux, Stéphane Le Crom, Rajendra Prasad, Maria Bernard, Sanjiveeni Dhamgaye, Membrane Biology Laboratory, Jawaharlal Nehru University (JNU), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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)-Centre National de la Recherche Scientifique (CNRS), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris], Génomique des Microorganismes (LGM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), The work presented in this paper has been supported in part by grants to R.P. from Indo-French Center for the Promotion of Advanced Scientific Research (IFC-3403-2/2006) and DST INT/SWISS/P-31/2009., Institut de biologie de l'ENS Paris (IBENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Institut Pasteur [Paris] (IP), BMC, Ed., Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Candida albicans, beta-Glucans, lcsh:QH426-470, lcsh:Biotechnology, Repressor, RNA-Seq, Drug resistance, Multidrug resistance, Fungal Proteins, 03 medical and health sciences, Drug Resistance, Fungal, lcsh:TP248.13-248.65, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Transcriptional regulation, Genetics, CZF1, Gene, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Sequence Analysis, RNA, Gene Expression Profiling, biology.organism_classification, Yeast, 3. Good health, Multiple drug resistance, Gene expression profiling, lcsh:Genetics, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], RNA-seq, Biotechnology, Transcription Factors, Research Article
Abstract

Background Drug susceptible clinical isolates of Candida albicans frequently become highly tolerant to drugs during chemotherapy, with dreadful consequences to patient health. We used RNA sequencing (RNA-seq) to analyze the transcriptomes of a CDR (Candida Drug Resistance) strain and its isogenic drug sensitive counterpart. Results RNA-seq unveiled differential expression of 228 genes including a) genes previously identified as involved in CDR, b) genes not previously associated to the CDR phenotype, and c) novel transcripts whose function as a gene is uncharacterized. In particular, we show for the first time that CDR acquisition is correlated with an overexpression of the transcription factor encoding gene CZF1. CZF1 null mutants were susceptible to many drugs, independently of known multidrug resistance mechanisms. We show that CZF1 acts as a repressor of β-glucan synthesis, thus negatively regulating cell wall integrity. Finally, our RNA-seq data allowed us to identify a new transcribed region, upstream of the TAC1 gene, which encodes the major CDR transcriptional regulator. Conclusion Our results open new perspectives of the role of Czf1 and of our understanding of the transcriptional and post-transcriptional mechanisms that lead to the acquisition of drug resistance in C. albicans, with potential for future improvements of therapeutic strategies.

Published
2012

21. Effectiveness of Core Stability Exercises and Recovery Myofascial Release Massage on Fatigue in Breast Cancer Survivors: A Randomized Controlled Clinical Trial

Author

César Fernández-de-las-Peñas, Manuel Arroyo-Morales, Rosario del Moral-Avila, María Belén Feriche-Fernández-Castanys, Irene Cantarero-Villanueva, Carolina Fernández-Lao, [Cantarero-Villanueva,I, Fernández-Lao,C, Arroyo-Morales,M] Department of Physical Therapy, Health Sciences Faculty, University of Granada, Granada, Spain. [Moral-Avila,R del] Radiotherapy Breast Oncology Unit, University Hospital Virgen de las Nieves, Granada, Spain. [Fernández-de-Las-Peñas,C] Department of Physical Therapy, Occupational Therapy, Rehabilitation, and Physical Medicine, King Juan Carlos university, Alcorcón, Spain. [Feriche-Fernández-Castanys,MB] Physical Education Department, Faculty of Sciences, Physical Activity, and Sports, University of Granada, Granada, Spain., and The paper was funded by a Research Project Grant (FIS ETES-PI0890418 and 10/02749) from the Health Institute Carlos III and PN I+D+I 2008–2011, Madrid, Spanish. Government and a Grant of Andalusian Health Service, Junta de Andalucia (PI-0457-2010).

Subjects
medicine.medical_specialty, Article Subject, Terapia por Ejercicio, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Physical Therapy Modalities::Musculoskeletal Manipulations::Massage [Medical Subject Headings], Named Groups::Persons::Survivors [Medical Subject Headings], Masaje, Sobrevivientes, Breast cancer, Physical medicine and rehabilitation, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Fatigue [Medical Subject Headings], medicine, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Depression (differential diagnoses), Massage, Fatiga, business.industry, Neoplasias de la Mama, Femenino, Core stability, Ensayos Clínicos Controlados Aleatorios como Asunto, lcsh:Other systems of medicine, lcsh:RZ201-999, medicine.disease, Trunk, Myofascial release, Clinical trial, Check Tags::Female [Medical Subject Headings], Complementary and alternative medicine, Physical therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Physical Therapy Modalities::Exercise Therapy [Medical Subject Headings], business, After treatment, Research Article
Abstract

The purpose of the present paper was to evaluate the effects of an 8-week multimodal program focused on core stability exercises and recovery massage with DVD support for a 6-month period in physical and psychological outcomes in breast cancer survivors. A randomized controlled clinical trial was performed. Seventy-eight (n=78) breast cancer survivors were assigned to experimental (core stability exercises plus massage-myofascial release) and control (usual health care) groups. The intervention period was 8 weeks. Mood state, fatigue, trunk curl endurance, and leg strength were determined at baseline, after the last treatment session, and at 6 months of followup. Immediately after treatment and at 6 months, fatigue, mood state, trunk curl endurance, and leg strength exhibited greater improvement within the experimental group compared to placebo group. This paper showed that a multimodal program focused on core stability exercises and massage reduced fatigue, tension, depression, and improved vigor and muscle strength after intervention and 6 months after discharge.

Published
2012
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22. In Vitro and Ex Vivo Evaluation of Smart Infra-Red Fluorescent Caspase-3 Probes for Molecular Imaging of Cardiovascular Apoptosis

Author

Bruno Delest, Vincent Richard, Marc Massonneau, Manuelle Debunne, Jean-Paul Henry, Christian Thuillez, Anthony Romieu, Christophe Portal, Françoise Lallemand, Heidi Ligeret, Pierre-Yves Renard, Ebba Brakenhielm, Pauline Noack, Pharmacologie des Dysfonctionnements Endotheliaux et Myocardiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), QUantitative Imaging in Drug Development [Saint-Etienne du Rouvray] (QUIDD / Technopôle du Madrillet), Technopôle du Madrillet, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), This paper was supported by La Région Haute Normandie via the CRUNCh program (CPER 2007–2013) and IUF (Institut Universitaire de France)., Brakenhielm, Ebba, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie Organique Fine (IRCOF), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), and Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pathology, medicine.medical_specialty, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.IMM] Life Sciences [q-bio]/Immunology, Article Subject, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Caspase 3, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Annexin, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Radiology, Nuclear Medicine and imaging, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, Chemistry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Fluorescence, In vitro, 3. Good health, Cell biology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Apoptosis, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular imaging, Ex vivo, Research Article
Abstract

Purpose. The aim of this paper is to develop new optical bioprobes for the imaging of apoptosis.Procedure. We developed quenched near-infrared probes which become fluorescent upon cleavage by caspase-3, the key regulatory enzyme of apoptosis.Results. Probes were shown to be selectively cleaved by recombinant caspase-3. Apoptosis of cultured endothelial cells was associated with an increased fluorescent signal for the cleaved probes, which colocalized with caspase-3 and was reduced by the addition of a caspase-3 inhibitor. Flow cytometry demonstrated a similar profile between the cleaved probes and annexin V.Ex vivoexperiments showed that sections of hearts obtained from mice treated with the proapoptotic drug doxorubicin displayed an increase in the fluorescent signal for the cleaved probes, which was reduced by a caspase-3 inhibitor.Conclusion. We demonstrated the capacity of these novel probes to detect apoptosis by optical imagingin vitroandex vivo.

Published
2011

23. Role of mental disorders in nosocomial infections after hip fracture treatment

Author

Nicolás Benítez-Parejo, Encarnacion Cruz, Emilio Perea-Milla, Enrique Guerado, Juan Ramon Cano, CIBER Epidemioloǵıa y Salud Ṕublica (CIBERESP), [Guerado,E, Cano,JR, Cruz,E] Department of Orthopaedic Surgery and Traumatology, Hospital Costa del Sol, University of Malaga. [Benitez-Parejo,N, Perea-Milla,E] Department of Research, Statistics, and Epidemiology, CIBERESP, Hospital Costa del Sol, University of Malaga., and This paper was performed with a grant from the Carlos III Institute (The Spanish Ministry of Science and Innovation) to the authors’ network of research group on Clinical pidemiology (CIBERESP)

Subjects
musculoskeletal diseases, Microbiology (medical), Diseases::Wounds and Injuries::Fractures, Bone::Hip Fractures [Medical Subject Headings], medicine.medical_specialty, Article Subject, Psychiatry and Psychology::Mental Disorders [Medical Subject Headings], Infección Hospitalaria, Diseases::Bacterial Infections and Mycoses::Infection::Cross Infection [Medical Subject Headings], Hip fracture surgery, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Iatrogenic Disease [Medical Subject Headings], Microbiology, lcsh:Infectious and parasitic diseases, Virology, medicine, lcsh:RC109-216, Multiple logistic regression analysis, Fracturas de Cadera, Enfermedad Iatrogénica, Hip surgery, Hip fracture, business.industry, Odds ratio, medicine.disease, Confidence interval, Surgery, Infectious Diseases, Trastornos Mentales, Parasitology, business, Research Article
Abstract

The association between mental disorders (MDs) and iatrogenic complications after hip fracture surgery has been poorly studied. Among iatrogenic complications, nosocomial infections (NIs) are a major factor in hip fracture surgery. The aim of this paper was to determine whether patients with a MD and a hip fracture develop more NIs after hip surgery than patients with no MD. We studied 912 patients who underwent surgery for a hip fracture (223 patients with a MD who underwent surgery for a hip fracture and 689 control patients without a MD who also underwent surgery for a hip fracture) and followed them after surgery. Univariable and multivariable analyses were performed using simple and multiple logistic regression analysis (confidence interval, crude and adjusted odds ratios, andPvalue). We found that MDs, gender, and comorbidities were not associated with a higher risk of developing a NI after surgery for a hip fracture. Only age increases the risk of a NI.

Published
2010

24. PGC-1β: A Regulator of Mitochondrial Function with Subtle Roles in Energy Metabolism

Author

Adrienn Kis, Mark Campbell, Mohammad Bohlooly-Y, Keira Curtis, Barbara Cannon, Matej Orešič, E. Dale Abel, Vlad G. Zaha, Gema Medina-Gomez, Sheldon E. Litwin, Mercedes Jimenez-Linan, Antonio Vidal-Puig, Sihem Boudina, Kimberly T Fountain, Leonard H Storlien, Miguel López, Margaret Blount, Ping Hu, Helena M. Feldmann, Christopher J. Lelliott, Mikael Bjursell, Natasa Petrovic, Dongfang Zhang, Nadeene Parker, Maria Strömstedt, Aline Meirhaeghe, Michael Snaith, Autard, Delphine, Department of Clinical Biochemistry, University of Cambridge [UK] (CAM), AstraZeneca, The Wenner-Gren Institute, Stockholm University, Division of Cardiology, University of Utah, Division of Endocrinology, Metabolism, and Diabetes, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, 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, Droit et Santé, Technical Research Centre of Finland, VTT Technical Research Centre of Finland (VTT), The work presented in this paper was supported by grants from the British Heart Foundation, Wellcome Trust Integrative Physiology, and Diabetes Wellness Research Foundation (to AVP lab), and NIH grants RO1HL73167 and UO1HL70525 from the National Institutes of Health and the Ben and Iris Margolis Foundation (to EDA - Established Investigator of the American Heart Association). Support was from the European Union (DLARFID), the Swedish Research Council, and the Swedish Cancer Society (to BC lab).

Subjects
Male, MESH: Cold Temperature, Adipose tissue, White adipose tissue, Mitochondrion, MESH: Mice, Knockout, Mitochondria, Heart, chemistry.chemical_compound, Mice, Norepinephrine, 0302 clinical medicine, Adipose Tissue, Brown, Heart Rate, Brown adipose tissue, Body Fat Distribution, Diabetes/Endocrinology/Metabolism, MESH: Thermogenesis, MESH: Animals, Biology (General), MESH: Heart Rate, Mice, Knockout, Mammals, 0303 health sciences, MESH: Muscle, Skeletal, General Neuroscience, MESH: Energy Metabolism, Heart, Thermogenesis, Mus (Mouse), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, MESH: Gene Expression Regulation, Mitochondria, Cold Temperature, medicine.anatomical_structure, Liver, MESH: Adipose Tissue, White, Synopsis, Female, MESH: Mitochondria, Heart, General Agricultural and Biological Sciences, Metabolic Networks and Pathways, Research Article, MESH: Electron Transport Chain Complex Proteins, medicine.medical_specialty, QH301-705.5, MESH: Mitochondria, MESH: Trans-Activators, Adipose Tissue, White, Biology, MESH: Diet, Atherogenic, MESH: Adipose Tissue, Brown, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Adrenergic Agents, Internal medicine, MESH: Norepinephrine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, MESH: Body Fat Distribution, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Muscle, Skeletal, MESH: Mice, 030304 developmental biology, Soleus muscle, General Immunology and Microbiology, Triglyceride, Body Weight, medicine.disease, MESH: Adrenergic Agents, MESH: Male, MESH: Body Weight, MESH: Heart, Endocrinology, chemistry, Electron Transport Chain Complex Proteins, Gene Expression Regulation, MESH: Metabolic Networks and Pathways, Trans-Activators, Diet, Atherogenic, Steatosis, Energy Metabolism, MESH: Female, 030217 neurology & neurosurgery, Transcription Factors, MESH: Liver
Abstract

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) has been implicated in important metabolic processes. A mouse lacking PGC-1β (PGC1βKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1βKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1β ablation was partially compensated by up-regulation of PGC-1α in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1βKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1β was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1βKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1βKO mice have impaired mitochondrial function. Lack of PGC-1β also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1β plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress., The authors conduct an in-depth analysis of a PGC-1β knockout mouse; these animals posses specific defects in basal mitochondrial function and adaptation to metabolic stress.

Published
2006