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321 results on '"Istituto Superiore di Sanita [Rome]"'

1. Estrogen Metabolism and Prostate Cancer Risk: A Prospective Study

Author

ISTITUTO SUPERIORE DI SANITA ROME (ITALY), Muti, Paola, ISTITUTO SUPERIORE DI SANITA ROME (ITALY), and Muti, Paola

Abstract

Prostate cancer is the most common cancer among men in the United States (IARC 1995) and the second most common in the European Community (IARC 1995). The causes of prostate cancer however remain largely unknown with age race and family history being the only established risk factors (Nomura et al. 1997). The prostate gland has historically been considered the prototype of an androgen-dependent organ. However there is evidence that estrogens may induce mitosis of prostatic epithelial cells in many species including humans (Leave et al. 1978; Schulze et al. 1987). This report analyzes the association between prostate cancer and estrogen metabolism investigated in a case-control study. In particular we tested the hypothesis that the pathway favoring 2-hydroxylation over 160-hydroxylation may be associated with a decrease in prostate cancer risk. This is the final report for the study. During the final year of activity we completed determinations of the estrogen metabolites using gas-chromatography and carried out statistical analysis. We have also prepared an article for publication of the results.

Published
2008

2. Interference Between GSM Mobile Phones and Pace-Makers: In Vitro Evaluation of Interaction Mechanisms

Author

ISTITUTO SUPERIORE DI SANITA ROME (ITALY) LAB OF BIOMEDICAL ENGINEERING, Angeloni, A., Barbaro, B., Bartolini, P., Calcagnini, G., Censi, F., ISTITUTO SUPERIORE DI SANITA ROME (ITALY) LAB OF BIOMEDICAL ENGINEERING, Angeloni, A., Barbaro, B., Bartolini, P., Calcagnini, G., and Censi, F.

Abstract

Aim of this study vas to in-vitro evaluate the effectiveness of the filtered feedthru assembly used to filter out the electromagnetic interference at the input stage of implantable pace-makers. We used three modified pace-makers of the same model, with an electrical connection to the output of the input sensing amplifier. The pace-makers differed for the level of protection against electromagnetic interference. We used a dual-band mobile phone. For each pace-maker the output of the sensing amplifier was monitored in 4 status: 1) no inhibition signal; 2) inhibition signal with amplitude 50% greater than the sensing threshold; 3) inhibition signal slightly lower than the sensing threshold; 4) inhibition signal slightly greater than the sensing threshold. For each pace-maker, evaluation has been performed in basal condition (no radiated power), during ringing and during talking. We found that the PMK with only the block capacitor shows asynchronous pacing and inhibition, while the other two PMKs do not interfere with the mobile phone, in any stage and for any mobile status., Papers from 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, October 25-26, 2001 held in Istanbul, Turkey. See also ADM001351 for entire conference on cd-rom. The original document contains color images.

Published
2001

3. Hydraulic Properties of the Hemopump HP31: A Study of the Downstream Pressure Distribution

Author

ISTITUTO SUPERIORE DI SANITA ROME (ITALY) LAB OF BIOMEDICAL ENGINEERING, Grigioni, M., Carotti, A., Daniele, C., Morbiducci, U., Gaudio, C. D., ISTITUTO SUPERIORE DI SANITA ROME (ITALY) LAB OF BIOMEDICAL ENGINEERING, Grigioni, M., Carotti, A., Daniele, C., Morbiducci, U., and Gaudio, C. D.

Abstract

The Hemopump was commercialized as an useful tool for the left ventricle assistance. Bioengineers and clinicians showed great interest to develop applications and to analyze its hydraulic behaviour; in this work an application for axial pump in different conditions is presented. A study of the spatial pressure distribution generated by the impeller of the Hemopump is investigated in highly accurate steady-flow conditions. The experimental set up adopted for this study consists in a plexiglass test pipe (simulating an aortic conduit of 22-nm diameter) and allows the sampling of the pressure at the outlet of the pump in 16 points spaced 1/2 diameter each other. Keeping fixed the constant head at the inlet of the Hemopump and varying the constant head at its outlet, i. e. afterloads, in 11 step levels, it was possible to draw the characteristic flow curves versus delivered pressure for all the seven speed levels. A pressure range of about 35/130 mmHg and a flow range of about -0.7/3.7 1/min was experimented. The results show that the flow delivered by the Hempopump is fully developed after 5 pressure taps (about 55 mm), with no further varying along the test chamber. These data could be used to optimize the setting up of clinical experimental procedures., Papers from 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Oct 25-28, 2001, held in Istanbul, Turkey. See also ADM001351 for entire conference on cd-rom, The original document contains color images.

Published
2001

4. Non-Linear Coupling Among Cardiovascular Variability Signals in Neuromediate Syncope

Author

ISTITUTO SUPERIORE DI SANITA ROME (ITALY) LAB OF BIOMEDICAL ENGINEERING, Censi, F., Calcagnini, G., Strano, S., Bartolini, P., Barbaro, V., ISTITUTO SUPERIORE DI SANITA ROME (ITALY) LAB OF BIOMEDICAL ENGINEERING, Censi, F., Calcagnini, G., Strano, S., Bartolini, P., and Barbaro, V.

Abstract

Aim of this study is to evaluate the degree of coupling among the cardiovascular variability series and the respiration in subjects susceptible to neurally mediated syncope, in comparison to normal subjects. 21 patients susceptible to syncope and 10 sex and age matched control subjects have been enrolled in the study. ECG, respiration activity, and arterial blood pressure were simultaneously recorded at rest (controlled and free breathing) and during 70 degree head-up TILT test (free breathing). The degree of non-linear coupling among heart rate variability (HRV), blood pressure variability (BPV) and respiration has been quantified by means of a multivariate embedding-based approach. 11 patients developed syncope during the TILT test. The non-linear coupling among the cardiovascular variables and respiration turned out to he stronger during controlled breathing than during free breathing, both for TILT- positive and TILT-negative group. During late TILT phase, in the TILT-positive group, the non-linear coupling showed a significant increase. If the proposed non-linear coupling indexes can he considered expression of the coupling mechanisms involved in the vagal regulation of the cardiovascular system, an increase of the vagal tone accompanied by a decrease of the sympathetic activity seem to occur before a vasovagal event., Papers from the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, October 25-28, 2001, Istanbul, Turkey. See also ADM001351 for entire conference on cd-rom.

Published
2001

5. A Study of Discharge Coefficient in Bileaflet Valves

Author

ISTITUTO SUPERIORE DI SANITA ROME (ITALY) LAB OF BIOMEDICAL ENGINEERING, Grigioni, M., Daniele, C., D'Avenio, G., Morbiducci, U., Del Gaudio, C., ISTITUTO SUPERIORE DI SANITA ROME (ITALY) LAB OF BIOMEDICAL ENGINEERING, Grigioni, M., Daniele, C., D'Avenio, G., Morbiducci, U., and Del Gaudio, C.

Abstract

The measurement of a cardiac valve's area is a common procedure, usually performed with noninvasive, Doppler-based techniques. Such measurements are not, however, without problems: a potential source of errors is the value of a valve's discharge coefficient. In-vitro pressure and flow measurements relative to the bileaflet valve of four brands were performed. A total of 12 valve samples was studied to cover the entire range of valve sizing. The data were used in the Gorlin formula for valve area measurements, and the dependence of the discharge coefficient on the internal diameter of the valve and the flow rate was accurately determined. The reported results can be used in a great number of follow-up clinical assessments to improve the accuracy of valvular orifice measurements., Papers from 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Oct 25-28, 2001, held in Istanbul, Turkey. See also ADM001351 for entire conference on cd-rom, The original document contains color images.

Published
2001

6. Baroreceptor-Sensitive Fluctuations of Heart Rate and Pupil Diameter

Author

ISTITUTO SUPERIORE DI SANITA ROME (ITALY) LAB OF BIOMEDICAL ENGINEERING, Calcagnini, G., Giovannelli, P., Censi, F., Bartolini, P., Barbaro, V., ISTITUTO SUPERIORE DI SANITA ROME (ITALY) LAB OF BIOMEDICAL ENGINEERING, Calcagnini, G., Giovannelli, P., Censi, F., Bartolini, P., and Barbaro, V.

Abstract

It is generally known that the pupil is under the control of the autonomic nervous system. Recently, those rhythms charactering the autonomic fluctuations of heart period and arterial blood pressure have been detected in spontaneous Pupil Diameter (PD) fluctuations. The physiological mechanisms underlying such variability have not been widely investigated. Aim of this study was to investigate the origin of the pupil fluctuations in humans, using a non-invasive modulation of carotid baroreceptors by Neck Suction (NS). To this purpose, we simultaneously recorded ECG, respiration activity, NS pressure and PD fluctuations from 10 normal subjects. The equipment for the PD measurement and the NS stimulation was developed in our laboratory. The response of the pupil to the NS was studied at stimulation frequencies of 0.10 and 0.20 Hz% by using parametric spectral and cross-spectral estimation. In all subjects, the NS rhythms were clearly detectable in heart rate variability series in both stimulation frequencies and also in the PD spectra with significant coherences (>0.5). These findings suggest that blood pressure fluctuations propagate to the pupil via carotid baroreceptors afferent pathways. However a central contribution can not he excluded. Keywoals - pupil diameter fluctuations, heart rate variability%, baroreceptors, spectral analysis, Papers from 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, October 25-26, 2001 held in Istanbul, Turkey. See also ADM001351 for entire conference on cd-rom., The original document contains color images.

Published
2001

7. SPECTROCHEMICAL ANALYSIS OF NON-METALS IN THE VACUUM ULTRAVIOLET BY MEANS OF A HOLLOW CATHODE LIGHT SOURCE.

Author

ISTITUTO SUPERIORE DI SANITA ROME (ITALY), Milazzo,Giulio, ISTITUTO SUPERIORE DI SANITA ROME (ITALY), and Milazzo,Giulio

Abstract

The research object has the scope to ascertain the feasibility of a spectrochemical analysis of non metals in the vacuum ultraviolet (VUV) utilizing the principle of the hollow cathode light source. An extended survey of the already performed work in this direction showed that very few experimental material was available, but that the theoretical considerations, indicating as very probable a better sensitivity of the spectrochemical analysis, at trace level, utilizing the principle of the hollow cathode light source could be considered as experimentally confirmed. Further theoretical considerations showed that the most sensitive lines of the non metallic elements should be the resonance lines lying in the VUV region of the spectrum, so that a particular construction of this kind of light source hadto be realized, capable to produce the desired spectrum in the desired spectral region and capable to be connected by means of an air free light path with a suitable vacuum spectrograph. (Author)

Published
1963

9. RESEARCH ON THE EFFECTS OF DRUGS ON THE ACTIVITY OF SPINAL CORD INTERNEURONES, REGISTERED BY MEANS OF MICROELECTRODES

Author

ISTITUTO SUPERIORE DI SANITA ROME (ITALY), LONGO,VINCENZO G., ISTITUTO SUPERIORE DI SANITA ROME (ITALY), and LONGO,VINCENZO G.

Abstract

A detailed analysis of the action of 1762 IS was made. The usual pharmacological procedures were used as well as a more specific technique which included a study of the modifications of the electrical activity at the various levels of the cerebro-spinal axis, the effects of the application to the cerebral and cerebellar cortex of the substance on the cortical electrical activity and its action on spinal integratory mechanisms. In preliminary toxicity studies, a synthetic compound, 4-formyl-4-phenylN-methyl-piperidine (1762 IS) showed convulsant properties very similar to those of strychnine. More detailed neuropharmacological investigations dealing with the action of 1762 IS on the cerebral electrical activity, on the mono-and polysnaptic reflexes and on the 'primary' spinal inhibition have confirmed the similarities between this compound and strychnine. Some relationships between structure and pharmacological properties are discussed. (Author)

Published
1961

11. Brain-immune crosstalk in the treatment of major depressive disorder

Author

Marion Leboyer, Lucile Capuron, Hemmo A. Drexhage, Francesco Benedetti, Sara Poletti, Brenda W.J.H. Penninx, Carmine M. Pariante, Igor Branchi, S. Poggini, Ryad Tamouza, Branchi, I., Poggini, S., Capuron, L., Benedetti, F., Poletti, S., Tamouza, R., Drexhage, H. A., Penninx, B. W. J. H., Pariante, C. M., Istituto Superiore di Sanita [Rome], Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CLinical Psychology, Division of Psychological Medicine, PO51, Immunology, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and APH - Digital Health

Subjects
Kynurenine pathway, Brain-body, T cell, Inflammation, Immunopsychiatry, 03 medical and health sciences, 0302 clinical medicine, Immune system, SDG 3 - Good Health and Well-being, Humans, Medicine, Pharmacology (medical), Neural plasticity, Kynurenine, Biological Psychiatry, Pharmacology, Depressive Disorder, Major, Neuronal Plasticity, business.industry, Brain, Antidepressants, medicine.disease, Mental illness, Antidepressive Agents, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Crosstalk (biology), Metabolism, medicine.anatomical_structure, Neurology, [SDE]Environmental Sciences, Major depressive disorder, Antidepressant, Neurology (clinical), medicine.symptom, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; A growing number of studies are pointing out the need for a conceptual shift from a brain-centered to a body-inclusive approach in mental health research. In this perspective, the link between the immune and the nervous system, which are deeply interconnected and continuously interacting, is one of the most important novel theoretical framework to investigate the biological bases of major depressive disorder and, more in general, mental illness. Indeed, depressed patients show high levels of inflammatory markers, administration of pro-inflammatory drugs triggers a depressive symptomatology and antidepressant efficacy is reduced by excessive immune system activation. A number of molecular and cellular mechanisms have been hypothesized to act as a link between the immune and brain function, thus representing potential pharmacologically targetable processes for the development of novel and effective therapeutic strategies. These include the modulation of the kynurenine pathway, the crosstalk between metabolic and inflammatory processes, the imbalance in acquired immune responses, in particular T cell responses, and the interplay between neural plasticity and immune system activation. In the personalized medicine approach, the assessment and regulation of these processes have the potential to lead, respectively, to novel diagnostic approaches for the prediction of treatment outcome according to the patient's immunological profile, and to improved efficacy of antidepressant compounds through immune modulation.

Published
2021

12. Human variability in glutathione-S-transferase activities, tissue distribution and major polymorphic variants: Meta-analysis and implication for chemical risk assessment

Author

Leonie S. Lautz, Franca M. Buratti, Emma Di Consiglio, Jean-Lou Dorne, Laura Turco, Camille Béchaux, Susanna Vichi, Emanuela Testai, K. Darney, Istituto Superiore di Sanita [Rome], Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), European Food Safety Authority (EFSA), and European Food Safety Authority (EFSA) under the grant agreement no. GA/EFSA/SCER/2015/01.

Subjects
0301 basic medicine, MESH: Bayes Theorem, [SDV]Life Sciences [q-bio], MESH: Cytosol / enzymology, Inter-individual variability, MESH: Algorithms, MESH: Toxicokinetics, Computational biology, Biology, Toxicology, Risk Assessment, Isozyme, 03 medical and health sciences, Cytosol, 0302 clinical medicine, In vivo, MESH: Polymorphism, Genetic, MESH: Risk Assessment / methods, Animals, Humans, Tissue Distribution, Tissue localizzation, MESH: Animals, Tissue distribution, MESH: Tissue Distribution, Chemical risk, Glutathione Transferase, Polymorphism, Genetic, MESH: Humans, Uncertainty, Human risk assessment, Glutathione-S-transferases, Bayes Theorem, MESH: Glutathione Transferase / metabolism, General Medicine, Toxicokinetics, Isoenzymes, Human variability, MESH: Isoenzymes / genetics, 030104 developmental biology, Glutathione S-transferase, Dynamic models, Meta-analysis, MESH: Glutathione Transferase / genetics, biology.protein, Algorithms, MESH: Uncertainty, 030217 neurology & neurosurgery
Abstract

International audience; The input into the QIVIVE and Physiologically-Based kinetic and dynamic models of drug metabolising enzymes performance and their inter-individual differences significantly improve the modelling performance, supporting the development and integration of alternative approaches to animal testing. Bayesian meta-analyses allow generating and integrating statistical distributions with human in vitro metabolism data for quantitative in vitro-in vivo extrapolation. Such data are lacking on glutathione-S-transferases (GSTs). This paper reports for the first time results on the human variability of GST activities in healthy individuals, their tissue localisation and the frequencies of their major polymorphic variants by means of extensive literature search, data collection, data base creation and meta-analysis. A limited number of papers focussed on in vivo GST inter-individual differences in humans. Ex-vivo total GST activity without discriminating amongst isozymes is generally reported, resulting in a high inter-individual variability. The highest levels of cytosolic GSTs in humans are measured in the kidney, liver, adrenal glands and blood. The frequencies of GST polymorphisms for cytosolic isozymes in populations of different geographical ancestry were also presented. Bayesian meta-analyses to derive GST-related uncertainty factors provided uncertain estimates, due to the limited database. Considering the relevance of GST activities and their pivotal role in cellular adaptive response mechanisms to chemical stressors, further studies are needed to identify GST probe substrates for specific isozymes and quantify inter-individual differences.

Published
2021

13. Surveillance of leishmaniasis cases from 15 European centres, 2014 to 2019: a retrospective analysis

Author

Van der Auwera, Gert, Davidsson, Leigh, Buffet, Pierre, Ruf, Marie-Thérèse, Gramiccia, Marina, Varani, Stefania, Chicharro, Carmen, Bart, Aldert, Harms, Gundel, Chiodini, Peter L, Brekke, Hanne, Robert-Gangneux, Florence, Cortes, Sofia, Verweij, Jaco J, Scarabello, Alessandra, Karlsson Söbirk, Sara, Guéry, Romain, van Henten, Saskia, Di Muccio, Trentina, Carra, Elena, van Thiel, Pieter, Vandeputte, Martin, Gaspari, Valeria, Blum, Johannes, LeishMan Surveillance network, Van der Auwera G., Davidsson L., Buffet P., Ruf M.-T., Gramiccia M., Varani S., Chicharro C., Bart A., Harms G., Chiodini P.L., Brekke H., Robert-Gangneux F., Cortes S., Verweij J.J., Scarabello A., Karlsson Sobirk S., Guery R., van Henten S., Di Muccio T., Carra E., van Thiel P., Vandeputte M., Gaspari V., Blum J., APH - Global Health, Infectious diseases, AII - Infectious diseases, Chard-Hutchinson, Xavier, Institute of Tropical Medicine [Antwerp] (ITM), Public Health Agency of Sweden, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Basel (Unibas), Istituto Superiore di Sanita [Rome], Azienda Ospedaliero Universitaria A. Meyer [Firenze, Italy], Instituto de Salud Carlos III [Madrid] (ISC), Amsterdam UMC - Amsterdam University Medical Center, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University College London Hospitals (UCLH), Oslo University Hospital [Oslo], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), National Institute for Infectious Diseases 'Lazzaro Spallanzani', Lund University [Lund], Hôpital privé du Confluent [Nantes], Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna 'Bruno Ubertini' (IZSLER), and Istituto Superiore di Sanità (ISS)

Subjects
Adult, Male, Adolescent, Epidemiology, [SDV]Life Sciences [q-bio], Leishmaniasis, Cutaneous, imported, authochthonou, Young Adult, Virology, Humans, Authochthonous, Child, Leishmaniasis, leishmaniasis, travel, Aged, Retrospective Studies, Aged, 80 and over, Leishmania, Travel, Surveillance, Public Health, Environmental and Occupational Health, Infant, Newborn, Infant, Middle Aged, leishmaniasi, [SDV] Life Sciences [q-bio], Europe, Imported, Child, Preschool, surveillance, Leishmaniasis, Visceral, Female, authochthonous
Abstract

Background Surveillance of human leishmaniasis in Europe is mostly limited to country-specific information from autochthonous infections in the southern part. As at the end of 2021, no integrated analysis has been performed for cases seen across centres in different European countries. Aim To provide a broad perspective on autochthonous and imported leishmaniasis cases in endemic and non-endemic countries in Europe. Methods We retrospectively collected records from cutaneous, mucosal and visceral leishmaniasis cases diagnosed in 15 centres between 2014 and 2019. Centres were located in 11 countries: Belgium, France, Germany, Italy, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom. Data on country of infection, reason for travelling, infecting species, age and sex were analysed. Results We obtained diagnostic files from 1,142 cases, of which 76%, 21% and 3% had cutaneous, visceral, and mucosal disease, respectively. Of these, 68% were men, and 32% women, with the median age of 37 years (range: 0–90) at diagnosis. Visceral leishmaniasis was mainly acquired in Europe (88%; 167/190), while cutaneous leishmaniasis was primarily imported from outside Europe (77%; 575/749). Sixty-two percent of cutaneous leishmaniasis cases from outside Europe were from the Old World, and 38% from the New World. Geographic species distribution largely confirmed known epidemiology, with notable exceptions. Conclusions Our study confirms previous reports regarding geographic origin, species, and traveller subgroups importing leishmaniasis into Europe. We demonstrate the importance of pooling species typing data from many centres, even from areas where the aetiology is presumably known, to monitor changing epidemiology.

Published
2022

14. Exploiting natural antiviral immunity for the control of pandemics: Lessons from Covid-19

Author

Eleonora Aricò, Laura Bracci, Luciano Castiello, Francesca Urbani, Jean-Laurent Casanova, Filippo Belardelli, Istituto Superiore di Sanita [Rome], Università degli Studi di Roma Tor Vergata [Roma], St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), Institute of Translational Pharmacology - Istituto di Farmacologia Traslazionale [Roma] (IFT), Consiglio Nazionale delle Ricerche [Roma] (CNR), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), Université Paris Cité, Equipe HAL, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères - - GENVIR2020 - ANR-20-CE93-0003 - AAPG2020 - VALID, Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19. - - AABIFNCOV2020 - ANR-20-CO11-0001 - COVID-19 - VALID, and Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant. - - GenMIS-C2021 - ANR-21-COVR-0039 - COVID-19 - VALID

Subjects
control of pandemics, SARS-CoV-2, Endocrinology, Diabetes and Metabolism, Immunology, COVID-19, Antiviral Agents, Immunity, Innate, Article, General Biochemistry, Genetics and Molecular Biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Humans, Immunology and Allergy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, IFN activity, Pandemics
Abstract

International audience; The outbreak of coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the disruptive global consequences in terms of mortality and social and economic crises, have taught lessons that may help define strategies to better face future pandemics. Innate and intrinsic immunity form the front-line natural antiviral defense. They involve both tissue-resident and circulating cells, which can produce anti-viral molecules shortly after viral infection. Prototypes of these factors are type I interferons (IFN), antiviral cytokines with a long record of clinical use. During the last two years, there has been an impressive progress in understanding the mechanisms of both SARS-CoV-2 infection and the cellular and soluble antiviral responses occurring early after viral exposure. However, this information was not sufficiently translated into therapeutic approaches. Insufficient type I IFN activity probably accounts for disease progression in many patients. This results from both the multiple interfering mechanisms developed by SARS-CoV-2 to decrease type I IFN response and various pre-existing human deficits of type I IFN activity, inherited or auto-immune. Emerging data suggest that IFN-I-mediated boosting of patients’ immunity, achieved directly through the exogenous administration of IFN-β early post viral infection, or indirectly following inoculation of heterologous vaccines (e.g., Bacillus Calmette Guerin), might play a role against SARS-CoV-2. We review how recent insights on the viral and human determinants of critical COVID-19 pneumonia can foster clinical studies of IFN therapy. We also discuss how early therapeutic use of IFN-β and prophylactic campaigns with live attenuated vaccines might prevent a first wave of new pandemic viruses.

Published
2022

15. HIV-1 Nef Protein Affects Cytokine and Extracellular Vesicles Production in the GEN2.2 Plasmacytoid Dendritic Cell Line

Author

Alessandra Aiello, Flavia Giannessi, Zulema Antonia Percario, Katia Fecchi, Claudia Arenaccio, Stefano Leone, Maria Carollo, Elisabetta D’Aversa, Laurence Chaperot, Roberto Gambari, Massimo Sargiacomo, Elisabetta Affabris, Aiello, A., Giannessi, F., Percario, Z. A., Fecchi, K., Arenaccio, C., Leone, S., Carollo, M., D'Aversa, E., Chaperot, L., Gambari, R., Sargiacomo, M., Affabris, E., Università degli Studi Roma Tre = Roma Tre University (ROMA TRE), Istituto Superiore di Sanita [Rome], Università degli Studi di Ferrara = University of Ferrara (UniFE), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Chaperot, Laurence

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, HIV Infections, plasmacytoid dendritic cells, HIV-1 Nef, cytokines, extracellular vesicles, Microbiology, Article, Cell Line, Extracellular Vesicles, Virology, HIV‐1 Nef, Humans, nef Gene Products, Human Immunodeficiency Virus, Cytokine, Tumor Necrosis Factor-alpha, Macrophages, Dendritic Cells, QR1-502, Recombinant Proteins, Infectious Diseases, STAT1 Transcription Factor, Plasmacytoid dendritic cells, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, Extracellular vesicle, Chemokines, Signal Transduction
Abstract

International audience; Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset specialized in type I interferon production, whose role in Human Immunodeficiency Virus (HIV) infection and pathogenesis is complex and not yet well defined. Considering the crucial role of the accessory protein Nef in HIV pathogenicity, possible alterations in intracellular signalling and extracellular vesicle (EV) release induced by exogenous Nef on uninfected pDCs have been investigated. As an experimental model system, a human plasmacytoid dendritic cell line, GEN2.2, stimulated with a myristoylated recombinant NefSF2 protein was employed. In GEN2.2 cells, Nef treatment induced the tyrosine phosphorylation of STAT-1 and STAT-2 and the production of a set of cytokines, chemokines and growth factors including IP-10, MIP-1β, MCP-1, IL-8, TNF-α and G-CSF. The released factors differed both in type and amount from those released by macrophages treated with the same viral protein. Moreover, Nef treatment slightly reduces the production of small EVs, and the protein was found associated with the small (size < 200 nm) but not the medium/large vesicles (size > 200 nm) collected from GEN2.2 cells. These results add new information on the interactions between this virulence factor and uninfected pDCs, and may provide the basis for further studies on the interactions of Nef protein with primary pDCs.

Published
2021
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16. Human Variability in Carboxylesterases and carboxylesterase-related Uncertainty Factors for Chemical Risk Assessment

Author

Emanuela Testai, Laura Turco, K. Darney, Susanna Vichi, E. Di Consiglio, Franca M. Buratti, Jean-Lou Dorne, Leonie S. Lautz, Istituto Superiore di Sanita [Rome], Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Wageningen Univ & Res, RIKILT, Akkermaalsbos 2, NL-6708 WB Wageningen, Netherlands, Partenaires INRAE, European Food Safety Authority (EFSA), and EFSA, Contract number: GP/EFSA/SCER/2015/01

Subjects
Male, Novel Foods & Agrochains, [SDV]Life Sciences [q-bio], Pharmacology, MESH: Protein Isoforms, Toxicology, Novel Foods & Agroketens, MESH: Risk Assessment, 030226 pharmacology & pharmacy, human pharmacokinetics, Carboxylesterase, 0302 clinical medicine, Polymorphism (computer science), Protein Isoforms, BU Toxicology, Novel Foods & Agrochains, MESH: Carboxylesterase, 0303 health sciences, Chemistry, BU Toxicology, Uncertainty, General Medicine, Middle Aged, Healthy Volunteers, Human variability, BU Toxicologie, Novel Foods & Agroketens, Female, MESH: Uncertainty, medicine.drug, Adult, Adolescent, BU Toxicologie, MESH: Environmental Exposure, Cmax, Team Toxicology, CYP2C19, Risk Assessment, Dabigatran, 03 medical and health sciences, Young Adult, Pharmacokinetics, In vivo, medicine, Humans, 030304 developmental biology, Aged, variability, chemical risk assessment, Bayes Theorem, Environmental Exposure, carboxylesterase, MESH: Carboxylic Ester Hydrolases, Carboxylic Ester Hydrolases, uncertainty factors
Abstract

International audience; Carboxylesterases (CES) are an important class of enzymes involved in the hydrolysis of a range of chemicals and show large inter-individual variability in vitro. An extensive literature search was performed to identify in vivo probe substrates for CES1 and CES2 together with their protein content and enzymatic activity. Human pharmacokinetic (PK) data on Cmax, clearance, and AUC were extracted from 89 publications and Bayesian meta-analysis was performed using a hierarchical model to derive CES-related variability distributions and related uncertainty factors (UF). The CES-related variability indicated that 97.5% of healthy adults are covered by the kinetic default UF (3.16), except for clopidogrel and dabigatran etexilate. Clopidogrel is metabolised for a small amount by the polymorphic CYP2C19, which can have an impact on the overall pharmacokinetics, while the variability seen for dabigatran etexilate might be due to differences in the absorption, since this can be influenced by food intake. The overall CES-related variability was moderate to high in vivo (

Published
2021

17. Interest in Humans: Comparisons between Riding School Lesson Equids and Assisted-Intervention Equids

Author

Lerch, Noémie, Cirulli, Francesca, Rochais, Céline, Lesimple, Clémence, Guilbaud, Estelle, Contalbrigo, Laura, Borgi, Marta, Grandgeorge, Marine, Hausberger, Martine, Ethologie animale et humaine (EthoS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Istituto Superiore di Sanita [Rome], Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), This research was funded by Ifce – Institut Français du Cheval et de l’Equitation (IFCE contrat: CS_2018_18, CS_2017_32, CS_2015_01), Fondation Adrienne et Pierre Sommer, Région Bretagne (ARED 20007248) and Caisse Centrale de la Mutualité Sociale Agricole., Normandie Université (NU)-Normandie Université (NU)-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), and Istituto Superiore di Sanità (ISS)

Subjects
[SCCO]Cognitive science, individual characteristics, QL1-991, Veterinary medicine, SF600-1100, Equus caballus, animal-assisted interventions, apathy, Zoology, Article, human–horse relationship
Abstract

Little is known about the impact of equine-assisted interventions (EAI) on equids’ perception of humans. In this study 172 equids, living in 12 riding centres, were submitted to a standardised human–horse relationship test: the motionless person test. Age, sex, type (horse/pony), housing, and feeding conditions of subjects were recorded. Overall, 17 equids worked in EAI, 95 in riding school lessons (RS), and 60 in both (EAI-RS). There were high inter-individual variations in the number of interactive behaviours directed towards the experimenter: negative binomial general linear models showed that activity was the most important factor: RS equids performed more interactive behaviours than EAI (p = 0.039) and EAI-RS (p &lt, 0.001) equids. Daily quantity of hay appeared as the second most important factor (equids with more than 3 kg interacted more than equids with less than 3 kg, p = 0.013). Individual characteristics were also important as horses interacted more than ponies (p = 0.009), geldings more than mares (p = 0.032), and 3–15-year-old equids more than equids over 15 years (p = 0.032). However, there was no interaction between factors. The lower number of interactive behaviours of EAI equids leads to different hypotheses—namely, selection on temperament, specific training, or compromised welfare (apathy). In any case, our results raised new lines of questions on EAI.

Published
2021
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18. OpenCYP: An open source database exploring human variability in activities and frequencies of polymophisms for major cytochrome P-450 isoforms across world populations

Author

Laura Turco, Leonie S. Lautz, K. Darney, Jean-Lou Dorne, Emanuela Testai, Franca M. Buratti, Susanna Vichi, Emma Di Consiglio, Istituto Superiore di Sanita [Rome], Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), European Food Safety Authority (EFSA), and This project was supported by the European Food Safety Authority (EFSA) under the grant agreement no. GA/EFSA/SCER/2015/01.

Subjects
Adult, Male, Proteomics, CYP2D6, PBK models, Metabolite, [SDV]Life Sciences [q-bio], Cytochrome P450, Biology, Toxicology, computer.software_genre, Genetic polymorphisms, 030226 pharmacology & pharmacy, Human variability, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cytochrome P-450 Enzyme System, Databases, Genetic, MESH: Polymorphism, Genetic, medicine, Humans, Protein Isoforms, CYP2A6, CYP3A7, MESH: Databases, Genetic, Aged, Risk assessment, Aged, 80 and over, Polymorphism, Genetic, Enzymatic activity, CYP3A4, Database, CYP1A2, General Medicine, Dextromethorphan, Middle Aged, chemistry, Population Surveillance, 030220 oncology & carcinogenesis, MESH: Cytochrome P-450 Enzyme System, Female, computer, medicine.drug
Abstract

International audience; The open source database "OpenCYP database" has been developed based on the results of extensive literature searches from the peer-reviewed literature. OpenCYP provides data on human variability on baseline of activities and polymophism frequencies for selected cytochrome P-450 isoforms (CYP1A2, CYP2A6, CYP2D6, CYP3A4/3A5 and CYP3A7) in healthy adult populations from world populations. CYP enzymatic activities were generally expressed as the metabolic ratio (MR) between an unchanged probe drug and its metabolite(s) in urine or plasma measured in healthy adults. Data on other age groups were very limited and fragmented, constituting an important data gap. Quantitative comparisons were often hampered by the different experimental conditions used. However, variability was quite limited for CYP1A2, using caffeine as a probe substrate, with a symmetrical distribution of metabolic activity values. For CYP3A4, human variability was dependent on the probe substrate itself with low variability when data considering the dextromethorphan/demethilathed metabolite MR were used and large variability when the urinary 6β-hydroxycortisol/cortisol ratio was used. The largest variability in CYP activity was shown for CYP2D6 activity, after oral dosing of dextromethorphan, for which genetic polymorphisms are well characterised and constitute a significant source of variability. It is foreseen that the OpenCYP database can contribute to promising tools to support the further development of QIVIVE and PBK models for human risk assessment of chemicals particularly when combined with information on isoform-specific content in cells using proteomic approaches.

Published
2021

19. Asymptomatic Carriage of C. botulinum Type D/C in Broiler Flocks as the Source of Contamination of a Massive Botulism Outbreak on a Dairy Cattle Farm

Author

Rozenn Souillard, Daniel Grosjean, Thibault Le Gratiet, Typhaine Poezevara, Sandra Rouxel, Loïc Balaine, Sabrina Macé, Laure Martin, Fabrizio Anniballi, Marianne Chemaly, Sophie Le Bouquin, Caroline Le Maréchal, Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Direction Départementale de la Cohésion Sociale et de la Protection des Populations [Bar-Le-Duc] (DDCSPP de la Meuse), Université de Rennes 1 - UFR Sciences de la vie et de l'environnement (UR1 SVE), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Istituto Superiore di Sanita [Rome], ANIBOTNET project (ANIHWA call)., Anses, Côtes d’Armor Departmental Council, TL is the recipient of a Ph.D. grant from ANSES and the Bretagne Regional Council, and the recipient of a short stay grant funded by the MedVetNet Association for a training period regarding the MLVA method at the ISS laboratory in Italy under Fabrizio Anniballi’s supervision., European Project: 291815,EC:FP7:KBBE,FP7-ERANET-2011-RTD,ANIHWA(2012), Université de Rennes - UFR Sciences de la vie et de l'environnement (UR SVE), Université de Rennes (UR), Istituto Superiore di Sanità (ISS), and ANIBOTNET project (ANIHWA call)

Subjects
Microbiology (medical), [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, botulism, investigation, poultry, MLVA, animal diseases, [SDV.BA]Life Sciences [q-bio]/Animal biology, hatchery, Microbiology, QR1-502, PCR, cattle, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

International audience; In winter 2018, a massive type D/C cattle botulism outbreak occurred on a mixed dairy and broiler farm in France. An investigation was conducted based on the hypothesis of asymptomatic carriage in poultry. We set out to identify the source of contamination of the dairy cattle and to monitor the contamination of broilers over time, including the hatchery delivering chicks to the farm. Environmental samples were collected on the farm during the cattle outbreak ( n = 40), after the outbreak for three successive broiler flocks ( n = 128), and once in the hatchery delivering the chicks ( n = 58). These samples were analyzed using real-time PCR after an enrichment step to detect Clostridium botulinum type D/C. The results showed contamination in the manure from the broilers raised just before the onset of the cattle outbreak (5 + /5), as well as in some of the components of the cattle ration (3 + /17). This latter contamination is likely due to the use of the same tractor bucket to remove litter from the poultry house and to prepare the cattle ration on the same day. Contamination monitoring over several months revealed continuous asymptomatic carriage in the broilers (4 + /20 and 17 + /20 cloacal swabs in 2 successive flocks), a persistence of C. botulinum type D/C in the ventilation system of the poultry house (8 + /14), and contamination of the equipment coming from the hatchery used for delivering the chicks (3 + /18). Further investigations conducted in the hatchery demonstrated contamination in the hatchery by C. botulinum type D/C (6 + /58). Comparison of samples using a multilocus variable number tandem repeat analysis showed the same profile for samples collected on broilers, cattle and in the hatchery. This study highlighted the crucial role of the implementation of biosecurity measures in mixed farms to avoid cross-contamination between production units given the potential asymptomatic carriage of poultry. This study also revealed the contamination of the poultry hatchery. Further investigations are required to better understand the role of hatcheries in the epidemiology of animal botulism.

Published
2021

20. Epidemiologic History and Genetic Diversity Origins of Chikungunya and Dengue Viruses, Paraguay

Author

Julien Thézé, Shirley Villalba, Juan Torales, Sandra Irala, María Liz Gamarra, Marta Giovanetti, Jairo Andres Mendez Rico, Andrea Gómez, Cynthia Vazquez, Tulio de Oliveira, Ingra Morales Claro, Vasco Azevedo, Fernanda de Bruycker-Nogueira, Leticia Franco, Ana Maria Bispo de Filippis, Carlos F. Campelo de Albuquerque, Joilson Xavier, Vagner Fonseca, Marcos Cesar Lima de Mendonça, Luiz Carlos Junior Alcantara, Edward C. Holmes, Jaqueline Goes de Jesus, Tiago Gräf, Instituto Gonçalo Moniz, Partenaires INRAE, Department of Infectious Diseases, Istituto Superiore di Sanita [Rome], Universidade Federal de Minas Gerais, and University of Oxford [Oxford]

Subjects
Serotype, Epidemiology, viruses, vector-borne infections, Infectious and parasitic diseases, RC109-216, MESH: Chikungunya Fever, MESH: Dengue, Dengue virus, medicine.disease_cause, MESH: Dengue Virus, Dengue fever, Dengue, 0302 clinical medicine, MESH: Arboviruses, 030212 general & internal medicine, Chikungunya, MESH: Genetic Variation, MESH: Phylogeny, MESH: Paraguay, Phylogeny, Phylogenetic tree, Zika Virus Infection, virus diseases, 3. Good health, Infectious Diseases, arboviruses, Medicine, Brazil, Microbiology (medical), 030231 tropical medicine, MESH: Zika Virus, Biology, Arbovirus, Virus, 03 medical and health sciences, MESH: Zika Virus Infection, parasitic diseases, medicine, Humans, Genetic diversity, chikungunya virus, MESH: Humans, dengue virus, Research, Genetic Variation, Zika Virus, biochemical phenomena, metabolism, and nutrition, medicine.disease, Virology, Epidemiologic History and Genetic Diversity Origins of Chikungunya and Dengue Viruses, Paraguay, genomic surveillance, 13. Climate action, Paraguay, nanopore sequencing, Chikungunya Fever, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Brazil
Abstract

International audience; C hikungunya virus (CHIKV), dengue virus (DENV), and Zika virus (ZIKV) are 3 of the most common arthropod-borne viruses (arboviruses) that infect humans. All are transmitted by the anthropophilic and urban-adapted Aedes aegypti and Ae. albopictus mosquito vectors (1). Driven by human movement and climate trends, the distribution of these mosquitoes is expanding along with the arboviruses they transmit (2). In Latin America, CHIKV and ZIKV have emerged since the mid-2000s, joining DENV, which is already endemic there (3). In this region, only Uruguay and Chile did not report autochthonous transmissions of one of these arboviruses during 2014-2019, highlighting the current state of endemicity (4). Paraguay is a landlocked country in the center of South America; it borders Bolivia, Brazil, and Argentina. DENV is endemic to Paraguay, and all 4 serotypes (DENV-1-4) have been detected there; in some seasons, multiple serotypes co-circulate (5,6). Phylogenetic analysis has shown that DENV genetic diversity in Paraguay is closely related to that in neighboring countries, particularly Brazil (7,8). However, more genomic surveillance studies in Paraguay are needed to learn more about this epidemiologic pattern. Cases

Published
2021

21. Classical scrapie in small ruminants is caused by at least four different prion strains

Author

Natalia Fernández-Borges, María Zamora-Ceballos, Lorenzo González, Juan Carlos Espinosa, Juan María Torres, Leonor Orge, Patricia Aguilar-Calvo, J.L. Pitarch, Olivier Andreoletti, Romolo Nonno, Alba Marín-Moreno, Centro de Investigacion en Sanidad Animal (INIA-CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA), University of California [San Diego] (UC San Diego), University of California (UC), Animal and Plant Health Agency [Addlestone, UK] (APHA), Instituto Nacional de Investigação Agrária e Veterinária = National Institute for Agrarian and Veterinary Research [Oeiras, Portugal] (INIAV), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Istituto Superiore di Sanità (ISS), This work was funded by European Union Projects [FOOD‑CT‑2006‑36353 GoatBSE] to JMT and OA, and 219235 ERA‑NET EMIDA [GOAT‑TSE‑FREE] to JCE, OA and RN, Spanish Ministerio de Economía Industria y Competitividad [AGL2009‑11553‑C02‑02] to JMT, AEI/FEDER UE [AGL2016‑78054‑R] to JMT and JCE, and fellowship BES‑2010‑ 040922 to PAC, and fellowship Instituto Nacional de Investigación y Tecnología Agraria y Agroalimentaria [INIA‑FPI‑SGIT‑2015‑02] to AMM., European Project: 39519,GOATBSE, European Project: 219235,EC:FP7:KBBE,FP7-ERANET-2007-RTD,EMIDA(2008), University of California, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Istituto Superiore di Sanita [Rome], European Commission, Ministerio de Economía y Competitividad (España), CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Marín-Moreno, Alba [0000-0002-4023-6398], Aguilar-Calvo, Patricia [0000-0001-5859-0240], Espinosa, Juan Carlos [0000-0002-6719-9902], Zamora-Ceballos, María [0000-0002-4694-2365], Pitarch, José Luis [0000-0003-3016-9125], González, Lorenzo [0000-0003-1513-1399], Orge, Leonor [0000-0002-2673-2758], Andréoletti, Olivier [0000-0002-7369-6016], Nonno, Romolo [0000-0001-7556-1564], Torres, Juan María [0000-0003-0443-9232], Marín-Moreno, Alba, Aguilar-Calvo, Patricia, Espinosa, Juan Carlos, Zamora-Ceballos, María, Pitarch, José Luis, González, Lorenzo, Orge, Leonor, Andréoletti, Olivier, Nonno, Romolo, and Torres, Juan María

Subjects
Adverse event, Prions, 040301 veterinary sciences, Bovine spongiform encephalopathy, Veterinary medicine, animal diseases, Sheep Diseases, Scrapie, Biology, Single strain, 0403 veterinary science, 03 medical and health sciences, SF600-1100, medicine, Animals, Small ruminant, Sheep, Domestic, 030304 developmental biology, 0303 health sciences, Sheep disease, Goat Diseases, Transmissible spongiform encephalopathy, Sheep, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, Animal, Goats, 04 agricultural and veterinary sciences, Classical scrapie, medicine.disease, Domestic sheep, Virology, nervous system diseases, Europe, Species barrier, Goat, Prion, Goat disease, Research Article
Abstract

15 pág. Centro de Investigación en Sanidad Animal (CISA), The diversity of goat scrapie strains in Europe has recently been studied using bioassays in a wide collection of rodent models, resulting in the classification of classical scrapie into four different categories. However, the sole use of the first passage does not lead to isolate adaptation and identification of the strains involved and might therefore lead to misclassification of some scrapie isolates. Therefore, this work reports the complete transmission study of a wide collection of goat transmissible spongiform encephalopathy (TSE) isolates by intracranial inoculation in two transgenic mouse lines overexpressing either small ruminant (TgGoat-ARQ) or bovine (TgBov) PrPC. To compare scrapie strains in sheep and goats, sheep scrapie isolates from different European countries were also included in the study. Once the species barrier phenomenon was overcome, an accurate classification of the isolates was attained. Thus, the use of just two rodent models allowed us to fully differentiate at least four different classical scrapie strains in small ruminants and to identify isolates containing mixtures of strains. This work reinforces the idea that classical scrapie in small ruminants is a prion disease caused by multiple different prion strains and not by a single strain, as is the case for epidemic classical bovine spongiform encephalopathy (BSE-C). In addition, the clear dissimilarity between the different scrapie strains and BSE-C does not support the idea that classical scrapie is the origin of epidemic BSE-C., This work was funded by European Union Projects [FOOD-CT-2006-36353 [GoatBSE] to JMT and OA and 219235 ERA-NET EMIDA [GOAT-TSE-FREE] to JCE, OA and RN], Spanish Ministerio de Economía Industria y Competitividad [AGL2009-11553-C02-02 to JMT, AGL2016-78054-R (AEI/FEDER, UE) to JMT and JCE and fellowship BES-2010- 040922 to PAC], and Instituto Nacional de Investigación y Tecnología Agraria y Agroalimentaria [fellowship INIA-FPI-SGIT-2015-02 to AMM]. The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication

Published
2021

22. SARS-CoV-2 population-based seroprevalence studies in Europe: a scoping review

Author

Grant, Rebecca, Dub, Timothée, Andrianou, Xanthi, Nohynek, Hanna, Wilder-Smith, Annelies, Pezzotti, Patrizio, Fontanet, Arnaud, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Finnish Institute for Health and Welfare [Helsinki], Istituto Superiore di Sanita [Rome], Cyprus University of Technology, London School of Hygiene and Tropical Medicine (LSHTM), University of Heidelberg, Medical Faculty, Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), 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)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), 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 Istituto Superiore di Sanità (ISS)

Subjects
Public health, Greece, Epidemiology, [SDV]Life Sciences [q-bio], public health, COVID-19, Antibodies, Viral, Medical and Health Sciences, Europe, Italy, Seroepidemiologic Studies, Germany, Health Sciences, Humans, Pandemics
Abstract

International audience; Objectives: We aimed to review SARS-CoV-2 seroprevalence studies conducted in Europe to understand how they may be used to inform ongoing control strategies for COVID-19.Design: Scoping review of peer-reviewed publications and manuscripts on preprint servers from January 2020 to 15 September 2020.Primary measure: Seroprevalence estimate (and lower and upper CIs). For studies conducted across a country or territory, we used the seroprevalence estimate and the upper and lower CIs and compared them to the total number of reported infections to calculate the ratio of reported to expected infections.Results: We identified 23 population-based seroprevalence studies conducted in Europe. Among 12 general population studies, seroprevalence ranged from 0.42% among residual clinical samples in Greece to 13.6% in an area of high transmission in Gangelt, Germany. Of the eight studies in blood donors, seroprevalence ranged from 0.91% in North-Western Germany to 23.3% in a high-transmission area in Lombardy region, Italy. In three studies which recruited individuals through employment, seroprevalence ranged from 0.5% among factory workers in Frankfurt, Germany, to 10.2% among university employees in Milan, Italy. In comparison to nationally reported cases, the extent of infection, as derived from these seroprevalence estimates, is manyfold higher and largely heterogeneous.Conclusion: Exposure to the virus in Europe has not reached a level of infection that would prevent further circulation of the virus. Effective vaccine candidates are urgently required to deliver the level of immunity in the population.

Published
2021

23. Stability of BSE infectivity towards heat treatment even after proteolytic removal of prion protein

Author

Dieter Becher, Jan P. M. Langeveld, Michael Beekes, Romolo Nonno, Anne Balkema-Buschmann, Jason C. H. Shih, Martin H. Groschup, Michele Angelo Di Bari, Laura Pirisinu, Aart Davidse, Achim Thomzig, Umberto Agrimi, Olivier Andreoletti, Wageningen BioVeterinary Research, Wageningen University and Research [Wageningen] (WUR), Institute of Novel and Emerging Infectious Diseases (INNT), Friedrich-Loeffler-Institut (FLI), Institut für Mikrobiologische Forschung GmbH (MICROMUN), Robert Koch Institute [Berlin] (RKI), Istituto Superiore di Sanita [Rome], Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC), Department of Poultry Science, College of Agricultural and Life Sciences, University of North Carolina System (UNC)-University of North Carolina System (UNC), and The study on BSE was financially supported by the National Cattlemen's and Beef Association (USA) Granted to Dr Jason Shih for period 2004-2006.

Subjects
0301 basic medicine, Hot Temperature, Epidemiology, Veterinary medicine, animal diseases, Scrapie, Inactivation, BSE, Strain, 0302 clinical medicine, SF600-1100, Bioassay, Bacillus licheniformis, Infectivity, biology, medicine.diagnostic_test, Bacteriologie, Bacteriology, Host Pathogen Interaction & Diagnostics, Virology & Molecular Biology, Encephalopathy, Bovine Spongiform, Prion, Research Article, Bioinformatica & Diermodellen, Transgene, Proteolysis, Mice, Transgenic, Prion Proteins, Molecular mechanism, 03 medical and health sciences, Bio-informatics & Animal models, medicine, Animals, Epidemiology, Bio-informatics & Animal models, Prion protein, Host Pathogen Interaction & Diagnostics, Epidemiologie, PrP, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, Zoonotic, Bacteriology, biology.organism_classification, Virology, Heat, Host Pathogen Interactie & Diagnostiek, Virologie & Moleculaire Biologie, nervous system diseases, 030104 developmental biology, Keratinase, Epidemiologie, Bioinformatica & Diermodellen, Bacteriologie, Host Pathogen Interactie & Diagnostiek, biology.protein, Cattle, 030217 neurology & neurosurgery, Peptide Hydrolases
Abstract

The unconventional infectious agents of transmissible spongiform encephalopathies (TSEs) are prions. Their infectivity co-appears with PrPSc, aberrant depositions of the host’s cellular prion protein (PrPC). Successive heat treatment in the presence of detergent and proteolysis by a keratinase from Bacillus licheniformis PWD-1 was shown before to destroy PrPSc from bovine TSE (BSE) and sheep scrapie diseased brain, however data regarding expected reduction of infectivity were still lacking. Therefore, transgenic Tgbov XV mice which are highly BSE susceptible were used to quantify infectivity before and after the bovine brain treatment procedure. Also four immunochemical analyses were applied to compare the levels of PrPSc. After heating at 115 °C with or without subsequent proteolysis, the original BSE infectivity of 106.2–6.4 ID50 g−1 was reduced to a remaining infectivity of 104.6–5.7 ID50 g−1 while strain characteristics were unaltered, even after precipitation with methanol. Surprisingly, PrPSc depletion was 5–800 times higher than the loss of infectivity. Similar treatment was applied on other prion strains, which were CWD1 in bank voles, 263 K scrapie in hamsters and sheep PG127 scrapie in tg338 ovinized mice. In these strains however, infectivity was already destroyed by heat only. These findings show the unusual heat resistance of BSE and support a role for an additional factor in prion formation as suggested elsewhere when producing prions from PrPC. Leftover material in the remaining PrPSc depleted BSE preparation offers a unique substrate for searching additional elements for prion infectivity and improving our concept about the nature of prions.

Published
2021

24. Isolation and Genetic Characterization of Puumala Orthohantavirus Strains from France

Author

Vulin, Johann, Murri, Séverine, Madrières, Sarah, Galan, Maxime, Tatard, Caroline, Piry, Sylvain, Vaccari, Gabriele, D’Agostino, Claudia, Charbonnel, Nathalie, Castel, Guillaume, Marianneau, Philippe, Laboratoire de Lyon [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Istituto Superiore di Sanita [Rome], Data used in this work were partly produced through sequencing facilities at ISEM (Institut des Sciences et de l'Evolution-Montpellier) and the LabEx CEMEB (Centre Mediterraneen de l'Environnement et de la Biodiversite). Sarah Madrieres was funded by an INRA-EFPA/ANSES fellowship., ANR-10-LABX-0004,CeMEB,Mediterranean Center for Environment and Biodiversity(2010), Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Istituto Superiore di Sanità (ISS)

Subjects
Communication, [SDV]Life Sciences [q-bio], lcsh:R, lcsh:Medicine, isolation, Hantavirus, Puumala
Abstract

International audience; Puumala orthohantavirus (PUUV) causes a mild form of haemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica (NE), regularly diagnosed in Europe. France represents the western frontier of the expansion of NE in Europe with two distinct areas: an endemic area (north-eastern France) where PUUV circulates in rodent populations, with the detection of many human NE cases, and a non-endemic area (south-western France) where the virus is not detected, with only a few human cases being reported. In this study, we describe the different stages of the isolation of two PUUV strains from two distinct French geographical areas: Ardennes (endemic area) and Loiret (non-endemic area). To isolate PUUV efficiently, we selected wild bank voles (Myodes glareolus, the specific reservoir of PUUV) captured in these areas and that were seronegative for anti-PUUV IgG (ELISA) but showed a non-negligible viral RNA load in their lung tissue (qRT-PCR). With this study design, we were able to cultivate and maintain these two strains in Vero E6 cells and also propagate both strains in immunologically neutral bank voles efficiently and rapidly. High-throughput and Sanger sequencing results provided a better assessment of the impact of isolation methods on viral diversity.

Published
2021

25. Risk-benefit in food safety and nutrition - outcome of the 2019 Parma Summer School

Author

Sofie Theresa Thomsen, Stefano Lorenzetti, Morten Poulsen, Andreas Kouroumalis, Hans Verhagen, Ricardo Assunção, Véronique Sirot, Maarten Nauta, Marco Trevisan, Alfonso Siani, Jeljer Hoekstra, Giulia Spaggiari, Josep Rubert, Alberto Mantovani, Hanna Eneroth, Pietro Cozzini, Stylianos Koulouris, Cristina Alonso-Andicoberry, Davide Menozzi, Francesca Cavaliere, University of Ulster, European Food Safety Authority (EFSA), Technical University of Denmark [Lyngby] (DTU), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Centro de Estudos do Ambiante e do Mar (CESAM), Universidade de Aveiro, University of Parma = Università degli studi di Parma [Parme, Italie], Swedish Food Agency, National Institute for Public Health and the Environment [Bilthoven] (RIVM), European Medicines Agency [Amsterdam, Pays-Bas] (EMA), Istituto Superiore di Sanita [Rome], Centre for Integrative Biology (CIBIO), University of Trento (CIBIO), University of Trento [Trento], Facultat de Fisica [València] (UV), Universitat de València (UV), Institute of Food Sciences of National Research Council [Avellino] (ISA-CNR), Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Università cattolica del Sacro Cuore [Milano] (Unicatt)

Subjects
Risk analysis, Food Safety, MESH: Schools, 030309 nutrition & dietetics, Risk-Benefit, As is, Nutritional Status, EFSA, MESH: Food Safety, MESH: Risk Assessment, Outcome (game theory), Risk Assessment, 03 medical and health sciences, 0404 agricultural biotechnology, Risks and benefits, Settore CHIM/10 - CHIMICA DEGLI ALIMENTI, Nutrition, 0303 health sciences, Schools, business.industry, 04 agricultural and veterinary sciences, Tiered approach, Food safety, MESH: Nutritional Status, 040401 food science, Composição dos Alimentos, Segurança Alimentar, Risk analysis (engineering), Food, Parma Summer School, Avaliação do Risco, Psychology, business, Risk assessment, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Common currency, MESH: Food, Food Science
Abstract

Risk-benefit assessment is the comparison of the risk of a situation to its related benefits, i.e. a comparison of scenarios estimating the overall health impact. The risk–benefit analysis paradigm mirrors the classical risk analysis one: risk–benefit assessment goes hand-in-hand with risk–benefit management and risk–benefit communication. The various health effects associated with food consumption, together with the increasing demand for advice on healthy and safe diets, have led to the development of different research disciplines in food safety and nutrition. In this sense, there is a clear need for a holistic approach, including and comparing all of the relevant health risks and benefits. The risk–benefit assessment of foods is a valuable approach to estimate the overall impact of food on health. It aims to assess together the negative and positive health effects associated with food intake by integrating chemical and microbiological risk assessment with risk and benefit assessment in food safety and nutrition. The 2019 Parma Summer School on risk–benefit in food safety and nutrition had the objective was to provide an opportunity to learn from experts in the field of risk–benefit approach in food safety and nutrition, including theory, case studies, and communication of risk–benefit assessments plus identify challenges for the future. It was evident that whereas tools and approaches have been developed, more and more case studies have been performed which can form an inherent validation of the risk–benefit approach. Executed risk–benefit assessment case studies apply the steps and characteristics developed: a problem formulation (with at least 2 scenarios), a tiered approach until a decision can be made, one common currency to describe both beneficial and adverse effects (DALYs in most instances). It was concluded that risk–benefit assessment in food safety and nutrition is gaining more and more momentum, while also many challenges remain for the future. Risk-benefit is on the verge of really enrolling into the risk assessment and risk analysis paradigm. The interaction between risk–benefit assessors and risk–benefit managers is pivotal in this, as is the interaction with risk–benefit communicators. Highlights: - Risk-benefit assessment goes hand-in-hand with RB-management and RB-communication; - Holistic approach in food safety and nutrition, comparing health risks and benefits; - Risk-benefit assessment estimates the overall impact of food on health; - Risk-benefit characteristics: problem formulation, tiered approach, common currency. info:eu-repo/semantics/publishedVersion

Published
2021

26. In vitro models of gut digestion across childhood: current developments, challenges and future trends

Author

Christophe Chassard, Valérie Collado, Christophe Lacroix, Tom Van de Wiele, Muriel Mercier-Bonin, Alessandra De Dominicis, Charlène Roussel, Stéphanie Blanquet-Diot, Lucie Etienne-Mesmin, Monique Alric, Marie-Agnès Peyron, Elora Fournier, Delphine Ley, Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut sur la Nutrition et les Aliments Fonctionnels [université Laval, Québec] (INAF), Université Laval [Québec] (ULaval), Istituto Superiore di Sanità (ISS), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Nutrition Humaine (UNH), Centre de Recherche en Odontologie Clinique (CROC), Université Clermont Auvergne (UCA), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Universiteit Gent = Ghent University (UGENT), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Istituto Superiore di Sanita [Rome], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and Universiteit Gent = Ghent University [Belgium] (UGENT)

Subjects
medicine.medical_specialty, Chil, [SDV]Life Sciences [q-bio], Bioengineering, Gut microbiota, Pharmacy, Biology, Gut flora, Toxicology, Applied Microbiology and Biotechnology, Microbiology, Gut physiology evolution, 03 medical and health sciences, Human health, 0302 clinical medicine, 030225 pediatrics, medicine, Animals, Humans, Intensive care medicine, Child, Nutrition, 0303 health sciences, 030306 microbiology, In vitro gut models, biology.organism_classification, 3. Good health, Gastrointestinal Microbiome, Gastrointestinal Tract, Digestive tract, Digestion, Environmental Pollutants, Biotechnology
Abstract

International audience; The human digestion is a multi-step and multi-compartment process essential for human health, at the heart of many issues raised by academics, the medical world and industrials from the food, nutrition and pharma fields. In the first years of life, major dietary changes occur and are concomitant with an evolution of the whole child digestive tract anatomy and physiology, including colonization of gut microbiota. All these phenomena are influenced by child exposure to environmental compounds, such as drugs (especially antibiotics) and food pollutants, but also childhood infections. Due to obvious ethical, regulatory and technical limitations, in vivo approaches in animal and human are more and more restricted to favor complementary in vitro approaches. This review summarizes current knowledge on the evolution of child gut physiology from birth to 3 years old regarding physicochemical, mechanical and microbial parameters. Then, all the available in vitro models of the child digestive tract are described, ranging from the simplest static mono-compartmental systems to the most sophisticated dynamic and multi-compartmental models, and mimicking from the oral phase to the colon compartment. Lastly, we detail the main applications of child gut models in nutritional, pharmaceutical and microbiological studies and discuss the limitations and challenges facing this field of research.

Published
2021

27. The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confounders

Author

Pavel Rossner, Roger W. L. Godschalk, Lada Živković, Gunnar Brunborg, Mahara Valverde, Juliana da Silva, Emilio Rojas, E. S. Kuznetsova, Serena Galati, Palma Lamonaca, Mirta Milić, Ekaterina I. Surikova, Helga Stopper, Bozena Novotna, Ninoslav Djelic, Sabine A. S. Langie, Katarina Volkovova, Pierre Lebailly, Delia Cavallo, Karl-Heinz Wagner, Stefano Bonassi, Monica Neri, Malgorzata Dobrzyńska, Hervé Perdry, Carina Ladeira, Alena Kažimı́rová, Rudolf Stetina, Mojgan Najafzadeh, Diana Anderson, Amaya Azqueta, Semra Sardas, Zdenka Durackova, Paula Rohr, Cristiana Pereira, Bozena Smolkova, Annamaria Buschini, Andrew Collins, Dwi Ramadhani, Anna Safar, Goran Gajski, N. P. Sirota, Idoia Ibero-Baraibar, Avdulla J. Alija, Kirsten B. Holven, Ezgi Eyluel Bangkoglu, Marcello Ceppi, Cristian Del Boˊ, Francesca Marcon, Stine Marie Ulven, Elisa Boutet-Robinet, Inger Ottestad, Biljana Spremo-Potparević, Fisnik Asllani, Annemarie Grindel, Irina A. Goroshinskaya, Maria Dusinska, Zsuzsanna Nemeth, Ricard Marcos, Tania Mandina Cardoso, Lisa Giovannelli, Vanessa Moraes de Andrade, Cinzia Lucia Ursini, Maria João Silva, Massimo Moretti, Magdalena Barancokova, Nurşen Başaran, Monika Dvořáková, Solange Costa, Vesna Dimitrijević Srećković, Susana Pastor, Omar García Lima, Marta Staruchova, Vanessa Valdiglesias, Patrizia Riso, Carlos Hernández, Cristina Andreoli, Blanca Laffon, Alba Hernández, Kristine B. Gutzkow, Carla Costa, Marco Bruzzone, Zuzana Paduchova, Peter Møller, Ela Kadioglu, João Paulo Teixeira, Gudrun Koppen, Pavel Vodicka, Henriqueta Louro, Irene Orlow, Silvia Moretti, Institute for Medical Research and Occupational Health, Ospedale Policlinico San Martino [Genoa], Universidad de Navarra [Pamplona] (UNAV), Center for Applied Medical Research [Plamplona] (CIMA), Norwegian Institute of Public Health [Oslo] (NIPH), School of Nutrition and Translational Research in Metabolism [Maastricht] (NUTRIM), Maastricht University [Maastricht], Flemish Institute for Technological Research (VITO), University of Copenhagen = Københavns Universitet (KU), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), University of Prishtina, University of Bradford, University of Southern Santa Catarina [Florianopolis] (UNISUL), Istituto Superiore di Sanita [Rome], University of Würzburg, Slovak Medical University of Bratislava (SMU), Hacettepe University = Hacettepe Üniversitesi, Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Chemistry, Life Sciences and Environmental Sustainability [Parma], University of Parma = Università degli studi di Parma [Parme, Italie], Istituto Nazionale per l’Assicurazione contro gli Infortuni sul Lavoro [Italian Workers Compensation Authority] (INAIL), Universidade Luterana do Brasil - ULBRA (BRAZIL), Universidade Luterana do Brasil (ULBRA), Department of Food Environmental and Nutritional Sciences, (DeFENS), University of Milan, School of Medecine [Belgrade], University of Belgrade [Belgrade], Faculty of Veterinary Medicine [Belgrade, Serbie], National Institute of Public Health - National Institute of Hygiene [Poland], Comenius University in Bratislava, Centro de Protección e Higiene de las Radiaciones [Cuba] (CPHR), NEUROFARBA Department [Firenze, Italy], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Petrov Research Insitut of Oncology, University of Vienna [Vienna], Universitat Autònoma de Barcelona (UAB), Institute of Health Carlos III, Instituto de Ciencias Básicas y Preclínicas Victoria de Girón, Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Gazi University, Institute Of Theoretical And Experimental Biophysics, Escola Superior de Tecnologia da Saude de Lisboa, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), University of A Coruña (UDC), Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Dept. of Pharmaceutical Sciences, University of Perugia, National center for public health [Hungary], Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), Czech Academy of Sciences [Prague] (CAS), Memorial Sloane Kettering Cancer Center [New York], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Faculty of Pharmacy, National Nuclear Energy Agency of Indonesia (BATAN), Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México (UNAM), Istinye University, the Russian Academy of Sciences [Moscow, Russia] (RAS), Slovak Academy of Science [Bratislava] (SAS), Faculty of Military Technology [Brno] (FMT / UoD), University of Defence in Brno (UoD), Centro de Investigacións Científicas Avanzadas (CICA), Institute of Clinical and Experimental Medicine, Norsk Institutt for Luftforskning (NILU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, and Instituto de Saúde Pública da Universidade do Porto

Subjects
0301 basic medicine, DNA damage, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Environmental Genotoxicity, Population, Biomarkers, Comet assay, Human biomonitoring, Pooled analysis, HOST FACTORS, Computational biology, Biology, Article, 03 medical and health sciences, chemistry.chemical_compound, HUMAN MICRONUCLEUS PROJECT, 0302 clinical medicine, Biomonitoring, Genetics, Humans, education, education.field_of_study, Confounding, Random effects model, 3. Good health, HUMAN-LYMPHOCYTES, Genómica Funcional e Estrutural, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, CELLS, Biomarker (medicine), Genotoxicidade Ambiental, SMOKING, DNA
Abstract

[Abstract] The alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations. This article is based upon work from COST Action hCOMET CA15132, supported by COST (European Cooperation in Science and Technology www.cost.eu) - STSM fellowships for Mirta Milić (IMROH, EU 19); IMROH, Zagreb, Croatia, Institute for Medical Research and Occupational Health (IMROH), Zagreb, Croatia, and the Ministry of Science, Education and Sports of the Republic of Croatia (Grant No. 022-0222148-2125) (EU4); Cancer Plan for PestiBG; Grant number: no ENV201401(EU 8, EU9); Italian Ministry of Education, University and Research PRIN 2005, prot. 2005058197 and Cariplo Foundation (Milan, Italy), Rif. Pratica 2007-5810 and Rif. Pratica 2010.2303 (EU 18); Associazione Italiana per la Ricerca sul Cancro (AIRC) (IG 2015/17564). (EU19); European Union Integrated Projects New Generis, 6th Framework Programme, Priority 5: Food Quality and Safety; Newborns and Genotoxic Exposure Risks, FOOD-CT-2005-016320 (EU22); ACT project No. 036APy/09 and No. 005DBB/12 (EU 24); FCT-SFRH/BPD/96196/2013, SFRH/BPD/100948/2014, Portugal (EU 26); MZ 2012/8-UKBA-8; VEGA 1/0703/13, APVV 15-0063 (EU30); Xunta de Galicia (XUGA 10605B98; INCITE08PXIB106155PR; ED481B2016/190-0; Grants ED431B2019/02), Spain (EU 32); Grant 01 173034, Ministry of Education, Science and Technological Development of the Republic of Serbia (EU 42); The Centre for Industrial and Technological Development within National Strategic Consortia for Techical Research (Industrial Research diets and food with specific characteristics for elderly, SENIFOOD); University of Navarra LE/97; Physiopathology of Obesity and Nutrition (CIBER Obn); Carlos III Health Research Institute (CB12/03/30002); Ministerio de Economia y Compatitividad (‘Ramón y Cajal’ Programme, RYC-2013-14370) of the Spanish Government for personal support (EU 45); the Ministry of Education, Youth and Sports of the Czech Republic project Healthy Aging in Industrial Environment HAIE (CZ.02.1.01/0.0/0.0/16_019/0000798) which is co-financed by the European Union (European Structural and Investment funds; Operation Programme Research, Development and Education); MYES LO 1508 (EU 46); MICRODIAB Study; ClinicalTrials.org (#NCT02231736) (EU 52); The study was funded by the Italian Ministry for Education, University and Scientific Research (MIUR) - Research No. 2005-062547 (EU14, EU53); Projects financed from Serbian Ministry of Education, Science and Technological Development #11146002, #175035, #173034 (EU 54); Mehr foundation organisation, UK (EU 55); MCTI/CNPQ No. 01/2016-Universal; FAPESC No. 09/2015; MEC/MCTI/CAPES/CNPQ/FAPS/ No. 09/2014, Brazil (CSA 6); the National Nuclear Energy Agency of Indonesia (Badan Tenaga Nuklir Nasional) with contract number 080.01.06 3447.001 001.052.A (AS4); Slovak Grant Agency (APVT-21 013202, APVT-21- 017704); Ministry of Health, Slovak Republic (2005/43-SZU-21, 2006/07- SZU-02 MZ SR, 2005/42-SZU-20

Published
2021

28. Sex-tailored pharmacology and COVID-19: next steps towards appropriateness and health equity

Author

Elena Ortona, Valentina Giudice, Andrea Cignarella, Marina Ziche, Amelia Filippelli, Silvia De Francia, Vincenzo Brancaleone, Andrea Spini, Luigia Trabace, Anna Ruggieri, Maria Grazia Morgese, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Siena = University of Siena (UNISI), University of Salerno (UNISA), Università degli studi della Basilicata [Potenza] (UNIBAS), Università degli Studi di Foggia = University of Foggia (Unifg), Università degli studi di Torino = University of Turin (UNITO), Istituto Superiore di Sanita [Rome], Università degli Studi di Padova = University of Padua (Unipd), and Admin, Oskar

Subjects
TMPRSS2, Transmembrane protease serine 2, COVID-19, Drug repurposing, Gender pharmacology, Health equity, Pregnancy, Sex, Angiotensin-Converting Enzyme Inhibitors, Review, E4, Estetrol, law.invention, BLAZE-1, Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies, DHT, Dihydrotestosterone, IgG1, Immunoglobulin subclass 1, NIH, National Institutes of Health, Randomized controlled trial, law, Health care, AF, Atrial fibrillation, Medicine, RAAS, Renin-angiotensin-aldosterone system, IL, Interleukin, Precision Medicine, Gonadal Steroid Hormones, LMWH, Low-molecular-weight heparin, GM-CSF, Granulocyte macrophage-colony stimulating factor, drug repurposing, health equity, pregnancy, sex, CDC, Centers for Disease Control and Prevention, Randomized Controlled Trials as Topic, Sex Characteristics, TCM, Traditional Chinese Medicine, Sex hormone receptor, SERMs, Selective estrogen receptor modulators, ER, Estrogen receptor, ICU, Intensive care unit, PEG, Polyethylene glycol, COVID-19, Coronavirus Disease 2019, Pharmacology, Clinical, AT1R, Angiotensin receptor type-1, PG, Progesterone, JAK, Janus Kinase, E2, 17β-estradiol, JAKi, JAK inhibitors, IL-6R, IL-6 receptor, medicine.medical_specialty, COVID-19 Vaccines, DMARDs, Disease-modifying anti-rheumatic drugs, RBD, Receptor binding domain, CYP, Cytochrome P, TNF-α, Tumor Necrosis Factor alpha, HCV, Hepatitis C virus, HR, Hazard ratio, VTE, Venous thromboembolism, GC, Glucocorticoids, PF4, Platelet factor 4, ACE2, Angiotensin-converting enzyme 2, ARDS, Acute respiratory distress syndrome, Humans, FcRn, Neonatal Fc receptor, Th1, T helper 1 cells, DOAC, Direct oral anticoagulant, FAERS, FDA Adverse Events Reporting Monitoring System, Intensive care medicine, Adverse effect, TCZ, Tocilizumab, AIFA, Italian Medicines Agency, AnxA1/FPR2, Annexin A1/formyl-peptide receptor 2, Pharmacology, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, T, Testosterone, business.industry, FDA, Food & Drug Administration, mTOR, Mammalian target of rapamycin, SETH, Spanish Society of Liver Transplantation, Evidence-based medicine, medicine.disease, CI, Confidence Interval, TIV, Trivalent influenza vaccination, COVID-19 Drug Treatment, ACE-Is, ACE inhibitors, H2S, Hydrogen sulfide, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Sex steroid, MERS, Middle-East Respiratory Syndrome, ARBs, Angiotensin-II receptor blockers, EMA, European Medicines Agency, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, mAbs, Monoclonal antibodies
Abstract

Making gender bias visible allows to fill the gaps in knowledge and understand health records and risks of women and men. The coronavirus disease 2019 (COVID-19) pandemic has shown a clear gender difference in health outcomes. The more severe symptoms and higher mortality in men as compared to women are likely due to sex and age differences in immune responses. Age-associated decline in sex steroid hormone levels may mediate proinflammatory reactions in older adults, thereby increasing their risk of adverse outcomes, whereas sex hormones and/or sex hormone receptor modulators may attenuate the inflammatory response and provide benefit to COVID-19 patients. While multiple pharmacological options including anticoagulants, glucocorticoids, antivirals, anti-inflammatory agents and traditional Chinese medicine preparations have been tested to treat COVID-19 patients with varied levels of evidence in terms of efficacy and safety, information on sex-targeted treatment strategies is currently limited. Women may have more benefit from COVID-19 vaccines than men, despite the occurrence of more frequent adverse effects, and long-term safety data with newly developed vectors are eagerly awaited. The prevalent inclusion of men in randomised clinical trials (RCTs) with subsequent extrapolation of results to women needs to be addressed, as reinforcing sex-neutral claims into COVID-19 research may insidiously lead to increased inequities in health care. The huge worldwide effort with over 3,000 ongoing RCTs of pharmacological agents should focus on improving knowledge on sex, gender and age as pillars of individual variation in drug responses and enforce appropriateness., Graphical abstract

Published
2021

29. Inositols: From Established Knowledge to Novel Approaches

Author

Ali Cenk Ozay, Vittorio Unfer, Cherubino Di Lorenzo, Olga Papalou, Daniele Barbaro, Salvatore Benvenga, Mónica H. Vazquez-Levin, Pietro Cavalli, Arturo Bevilacqua, Nicholas D. E. Greene, Scott Roseff, Marialuisa Appetecchia, Rosario D'Anna, Maurizio Nordio, John E. Nestler, Cesare Aragona, Andrew J. Copp, Eleni Kandaraki, Mariano Bizzarri, Maria Salome Bezerra Espinola, Didier Dewailly, Fabio Facchinetti, Giovanni Monastra, Lali Pkhaladze, Ivana Vucenik, Simona Dinicola, Shiao-Yng Chan, Artur Wdowiak, Imelda Hernández Marín, Christophe O. Soulage, Evanthia Diamanti-Kandarakis, Moshe Hod, Antonio Simone Laganà, Annarita Stringaro, Nikos Prapas, Tony T. Y. Chiu, Tonino Cantelmi, Mario Montanino Oliva, Giuseppina Porcaro, Zdravko Kamenov, Systems Biology Group Lab [Rome, Italy] (SBGL), University - Hospital of Modena and Reggio Emilia [Modena, Italy], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University College of London [London] (UCL), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), National University of Singapore (NUS), Zhordania and Khomasuridze Institute of Reproductology [Tbilisi, Georgia] (ZKIR), University of Messina, National Center for Drug Research and Evaluation [Rome, Italy], Istituto Superiore di Sanità (ISS), Azienda Usl Toscana nord ovest [Livorno, Italy] (AUTNO), Regina Elena National Cancer Institute [Rome], Institute for Interpersonal Cognitive Therapy [Rome, Italy] (2ICT), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), The Chinese University of Hong Kong [Hong Kong], Université de Lille, Hygeia Hospital [Athens, Greece] (2H), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Tel Aviv University (TAU), Medical University of Sofia [Bulgarie], Santo Spirito Hospital [Athens, Greece] (2SH), Virginia Commonwealth University (VCU), Azienda Sanitaria Locale [ROMA] (ASL), Near East University, USL UMBRIA [Terni, Italy] (USLU), IAKENTRO [Thessaloniki, Greece], South Florida Institute for Reproductive Medicine [Boca Raton, FL, USA] (IVFMD), Instituto de Biología y Medicina Experimental [Buenos Aires] (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), University of Maryland [Baltimore], Medical University of Lublin, Istituto Superiore di Sanita [Rome], and CarMeN, laboratoire

Subjects
steroidogenesis, D-chiro-Inositol, GDM, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Review, Bioinformatics, chemistry.chemical_compound, Pregnancy, FSH, PCOS, Medicine, Inositol, Biology (General), Aromatase, myo-Inositol, epimerase, aromatase, testosterone, neural tube defects, Spectroscopy, biology, Molecular Structure, General Medicine, Polycystic ovary, Computer Science Applications, [SDV] Life Sciences [q-bio], Chemistry, Theca Cells, Epimerase, Myo-Inositol, Neural tube defects, Steroidogenesis, Testosterone, Female, Signal transduction, Polycystic Ovary Syndrome, Signal Transduction, QH301-705.5, Catalysis, Inorganic Chemistry, Endocrine system, Humans, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, business.industry, Insulin, Organic Chemistry, Diabetes, Gestational, chemistry, biology.protein, business, Hormone
Abstract

International audience; Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.

Published
2021

30. Genomic surveillance of Yellow Fever Virus Epizootic in São Paulo, Brazil, 2016 - 2018

Author

Natália Coelho Couto de Azevedo Fernandes, Maria do Carmo Sampaio Tavares Timenetsky, Paola P. Silveira, Julien Thézé, Mariana Sequetin Cunha, Louis du Plessis, Leandro Abade, Renato De Souza, Laura Nogueira da Cruz, Jaqueline Goes de Jesus, Rodrigo Albergaria Réssio, F. L. L. Macedo, Oliver G. Pybus, Juliana Telles de Deus, Josué Díaz-Delgado, Luiz Carlos Junior Alcantara, Iray Maria Rocco, Renato S. Aguiar, Fernanda G. S. Vasami, Juliana Mariotti Guerra, Simon Dellicour, Regiane Maria Tironi de Menezes, Nuno R. Faria, Flavia Cristina da Silva Salles, Ester Cerdeira Sabino, Luis Filipe Mucci, Adriana Yurika Maeda, Cinthya dos Santos Cirqueira, Rosa Maria Tubaki, André Luiz de Abreu, Marta Giovanetti, Nicholas J. Loman, Regiane de Paula, Juliana Silva Nogueira, Joshua Quick, Patrícia Locosque Ramos, Roberta Spinola, Sarah C. Hill, Fabiana Cristina Pereira dos Santos, Ingra Morales Claro, Department of Zoology [Oxford], University of Oxford [Oxford], Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratório de Radioecologia e Mudanças Globais (LARAMG), Universidade do Estado do Rio de Janeiro [Rio de Janeiro] (UERJ), Department of Infectious Diseases, Istituto Superiore di Sanita [Rome], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidad Nacional de San Agustín (UNSA), University of Birmingham [Birmingham], and Biotempo

Subjects
Epidemiology, [SDV]Life Sciences [q-bio], Virologie générale, Geographical locations, law.invention, Disease Outbreaks, Animal Diseases, 0302 clinical medicine, Medical Conditions, law, Zoonoses, Immunologie, Medicine and Health Sciences, Biology (General), Phylogeny, ComputingMilieux_MISCELLANEOUS, Data Management, 0303 health sciences, Parasitologie, Mammalian Genomics, Geography, Transmission (medicine), 030302 biochemistry & molecular biology, Yellow fever, Phylogenetic Analysis, Genomics, 3. Good health, Phylogenetics, Phylogeography, Transmission (mechanics), Infectious Diseases, Biogeography, Sylvatic cycle, Yellow fever virus, Biologie, Brazil, geographic locations, Research Article, Primates, Computer and Information Sciences, Infectious Disease Control, QH301-705.5, Genomic data, 030231 tropical medicine, Immunology, Zoology, Genome, Viral, Disease Surveillance, Epizootics, Microbiology, Virus, 03 medical and health sciences, Virology, Yellow Fever, parasitic diseases, Genetics, medicine, Animals, Humans, Evolutionary Systematics, Molecular Biology, Epizootic, Taxonomy, 030304 developmental biology, Evolutionary Biology, Population Biology, Ecology and Environmental Sciences, Primate Diseases, Virologie médicale, Biology and Life Sciences, Outbreak, Biologie moléculaire, South America, RC581-607, medicine.disease, Animal Genomics, Infectious Disease Surveillance, Earth Sciences, Biological dispersal, Parasitology, People and places, Immunologic diseases. Allergy, Microbiologie et protistologie [bacteriol.virolog.mycolog.], human activities, Population Genetics
Abstract

São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in São Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in São Paulo, we generated and analysed virus genomic data and epizootic case data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in São Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of São Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in São Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2020

31. Yellow fever transmission in non-human primates, Bahia, Northeastern Brazil

Author

Leandro Ferraz Oliveira Santos, Alessandro Pecego Martins Romano, Jaqueline Goes de Jesus, Allison Fabri, Vagner Fonseca, Joilson Xavier, Mirza de Carvalho Santana Cordeiro, Roberto Fonseca dos Santos, Adeilde do Socorro Guedes, Neuza Santos de Jesus Silva, Arabela Leal e Silva de Mello, Sintia Sacramento Cerqueira Torquato, Jeane Magnavita da Fonseca Cerqueira, Pedro Macedo da Silva Filho, André Luiz de Abreu, Ademilson Brás Alves, Rosemary Sarmento Oitiçica Dourado, Julien Thézé, Maricelia Lima Maia, Felicidade Mota Pereira, Marta Giovanetti, Nuno R. Faria, Maria Angélica Mares-Guia, Ana Maria Bispo de Filippis, Luciana Reboredo de Oliveira da Silva, Tiago Gräf, Leandro Abade, Zuinara Pereira Gusmão Maia, Carlos F. Campelo de Albuquerque, Julio Croda, Rodrigo Fabiano do Carmo Said, Eloisa Bahia Santana, Gabriel Muricy Cunha, Jananci Xavier Gomes Cerqueira, Luiz Carlos Junior Alcantara, Instituto Gonçalo Moniz, Partenaires INRAE, Department of Infectious Diseases, Istituto Superiore di Sanita [Rome], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Universidade Federal de Minas Gerais, Department of Zoology, University of Oxford [Oxford], Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Coordenação Geral de Vigilância de Arboviroses (CGARB), Wellcome Trust, and Medical Research Council-São Paulo Research Foundation (FAPESP)

Subjects
0301 basic medicine, Epidemiology, [SDV]Life Sciences [q-bio], RC955-962, Disease Vectors, Mosquitoes, Geographical locations, Animal Diseases, 0302 clinical medicine, Medical Conditions, Arctic medicine. Tropical medicine, Genotype, Medicine and Health Sciences, Alouatta, 11 Medical and Health Sciences, Phylogeny, Data Management, Mammals, Mammalian Genomics, Phylogenetic tree, Transmission (medicine), Yellow fever, Eukaryota, Callithrix, Phylogenetic Analysis, Genomics, 3. Good health, Phylogenetics, Insects, Infectious Diseases, Vertebrates, Public aspects of medicine, RA1-1270, Yellow fever virus, Brazil, Research Article, Primates, medicine.medical_specialty, Computer and Information Sciences, Infectious Disease Control, Arthropoda, 030231 tropical medicine, Genome, Viral, Biology, Disease Surveillance, Epizootics, 03 medical and health sciences, Tropical Medicine, Yellow Fever, medicine, Genetics, Animals, Humans, Evolutionary Systematics, Epizootic, Ecosystem, Taxonomy, Evolutionary Biology, Molecular epidemiology, Public Health, Environmental and Occupational Health, Primate Diseases, Organisms, Outbreak, Biology and Life Sciences, 06 Biological Sciences, South America, medicine.disease, Virology, Invertebrates, Insect Vectors, Species Interactions, 030104 developmental biology, Animal Genomics, Infectious Disease Surveillance, Amniotes, People and places, Zoology, Entomology
Abstract

Yellow fever virus (YFV) causes a clinical syndrome of acute hemorrhagic hepatitis. YFV transmission involves non-human primates (NHP), mosquitoes and humans. By late 2016, Brazil experienced the largest YFV outbreak of the last 100 years, with 2050 human confirmed cases, with 681 cases ending in death and 764 confirmed epizootic cases in NHP. Among affected areas, Bahia state in Northeastern was the only region with no autochthonous human cases. By using next generation sequence approach, we investigated the molecular epidemiology of YFV in NHP in Bahia and discuss what factors might have prevented human cases. We investigated 47 YFV positive tissue samples from NHP cases to generate 8 novel YFV genomes. ML phylogenetic tree reconstructions and automated subtyping tools placed the newly generated genomes within the South American genotype I (SA I). Our analysis revealed that the YFV genomes from Bahia formed two distinct well-supported phylogenetic clusters that emerged most likely of an introduction from Minas Gerais and Espírito Santo states. Vegetation coverage analysis performed shows predominantly low to medium vegetation coverage in Bahia state. Together, our findings support the hypothesis of two independent YFV SA-I introductions. We also highlighted the effectiveness of the actions taken by epidemiological surveillance team of the state to prevented human cases., Author summary Between 2016 and 2018, Brazil witnessed the largest YFV outbreak since years, with 2.154 cases and 745 deaths. Here we report the introduction of the virus in the state of Bahia suggesting two independent introductions from Minas Gerais and Espirito Santo. We also highlight the actions taken by epidemiological surveillance division that may have prevent human infections.

Published
2020

32. Human variability in influx and efflux transporters in relation to uncertainty factors for chemical risk assessment

Author

Jean-Lou Dorne, Laura Turco, Camille Béchaux, K. Darney, Leonie S. Lautz, E. Di Consiglio, Emanuela Testai, A.C. Roudot, Susanna Vichi, Franca M. Buratti, Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Istituto Superiore di Sanita [Rome], Université Bretagne Loire (UBL), and European Food Safety Authority (EFSA)

Subjects
Adult, [SDV]Life Sciences [q-bio], Computational biology, Biology, Toxicology, Risk Assessment, 03 medical and health sciences, chemistry.chemical_compound, 0404 agricultural biotechnology, In vivo, Ethnicity, Humans, Chemical risk, 030304 developmental biology, 0303 health sciences, Polymorphism, Genetic, Uncertainty, Membrane Transport Proteins, Transporter, Bayes Theorem, Biological Transport, 04 agricultural and veterinary sciences, General Medicine, 040401 food science, Confidence interval, Efflux transporters, Human variability, Kinetics, chemistry, Efflux, Xenobiotic, Food Science
Abstract

Transporters are divided into the ABC and SLC super-families, mediating the cellular efflux and influx of various xenobiotic and endogenous substrates. Here, an extensive literature search was performed to identify in vivo probe substrates for P-gp, BCRP and OAT1/3. For other transporters (e.g. OCT, OATP), no in vivo probe substrates could be identified from the available literature. Human kinetic data (Cmax, clearance, AUC) were extracted from 142 publications and Bayesian meta-analyses were performed using a hierarchical model to derive variability distributions and related uncertainty factors (UFs). For P-gp, human variability indicated that the kinetic default UF (3.16) would cover over 97.5% of healthy individuals, when considering the median value, while the upper confidence interval is exceeded. For BCRP and OAT1/3 human variability indicated that the default kinetic UF would not be exceeded while considering the upper confidence interval. Although limited kinetic data on transporter polymorphisms were available, inter-phenotypic variability for probe substrates was reported, which may indicate that the current default kinetic UF may be insufficient to cover such polymorphisms. Overall, it is recommended to investigate human genetic polymorphisms across geographical ancestry since they provide more robust surrogate measures of genetic differences compared to geographical ancestry alone. This analysis is based on pharmaceutical probe substrates which are often eliminated relatively fast from the human body. The transport of environmental contaminants and food-relevant chemicals should be investigated to broaden the chemical space of this analysis and assess the likelihood of potential interactions with transporters at environmental concentrations.

Published
2020

33. Performance of two serodiagnostic tests for loiasis in a Non-Endemic area

Author

Marco A. Biamonte, Federico Gobbi, Francesca Tamarozzi, Ronaldo Silva, Cédric B Chesnais, Sébastien D. S. Pion, Lucia Moro, Dora Buonfrate, Zeno Bisoffi, Michel Boussinesq, Paola Rodari, IRCCS Sacro Cuore Don Calabria Hospital [Vérone, Italie], Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Istituto Superiore di Sanità (ISS), Drugs & Diagnostics for Tropical Diseases [San Diego, CA, États-Unis] (DDTD), Università degli studi di Verona = University of Verona (UNIVR), This work was supported by the Italian Ministry of Health 'Fondi Ricerca Corrente - Linea 3, progetto 8' to IRCCS Sacro Cuore Don Calabria Hospital., Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Istituto Superiore di Sanita [Rome], University of Verona (UNIVR), and Bodescot, Myriam

Subjects
0301 basic medicine, Male, Nematoda, Physiology, RC955-962, Loa Loa, Mansonellum, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Arctic medicine. Tropical medicine, Medicine and Health Sciences, Medicine, Eosinophilia, Non endemic, Enzyme-Linked Immunoassays, Nematode Infections, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], biology, Eukaryota, 3. Good health, Body Fluids, Infectious Diseases, Strongyloidiasis, Blood, Helminth Infections, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Ascaris lumbricoides, medicine.symptom, Public aspects of medicine, RA1-1270, Anatomy, Loa loa, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article, Neglected Tropical Diseases, Adult, medicine.medical_specialty, 030231 tropical medicine, Antibodies, Helminth, Schistosomiasis, Research and Analysis Methods, Microfilaria, Sensitivity and Specificity, Loiasi, 03 medical and health sciences, Young Adult, Loiasis, Diagnostic Medicine, Internal medicine, parasitic diseases, Parasitic Diseases, Animals, Humans, Serologic Tests, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Immunoassays, Hookworm infection, business.industry, Public Health, Environmental and Occupational Health, Organisms, Biology and Life Sciences, Mansonellum, Loiasi, Microfilaria, medicine.disease, biology.organism_classification, Tropical Diseases, Invertebrates, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunologic Techniques, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

Loiasis, caused by the filarial nematode Loa loa, is endemic in Central and West Africa where about 10 million people are infected. There is a scarcity of convenient, commercial diagnostics for L. loa. Microscopy requires trained personnel and has low sensitivity, while the serodiagnosis is currently not standardized. Individual case management is also important in non-endemic countries to treat migrants, expatriates and tourists. We retrospectively compared the performance of a Loa Antibody Rapid Test (RDT) and a commercial ELISA pan-filarial test on 170 patients, 65 with loiasis [8 with eyeworm, 29 with positive microfilaremia, 28 with neither microfilaremia nor history of eyeworm but eosinophilia and history of Calabar swelling (probable loiasis)], 95 with other common parasitic infections and no previous exposure to L. loa (37 with M. perstans, 1 with Brugia sp., 18 with strongyloidiasis, 20 with schistosomiasis, 5 with hookworm, 4 with Ascaris lumbricoides infection, 10 with hyper-reactive malarial splenomegaly), and 10 uninfected controls. The sensitivity of the RDT and of the ELISA were 93.8% (61/65) and 90.8% (59/65), respectively. For the RDT, most of the cross-reactions were observed in patients with M. perstans: 7/37 (18.9%), followed by 1/10 (10%) with hyper-reactive malarial splenomegaly and 1/20 (5%) with schistosomiasis. None of the 27 subjects infected with intestinal nematodes was found positive at this test. The ELISA is meant to be a pan-filarial assay, and reacted extensively with cases of M. perstans (95%), as expected, and also in 11/18 (61.1%) patients with strongyloidiasis and in 3/5 (60%) with hookworm infection. The RDT and the ELISA are both highly sensitive for the diagnosis of loiasis. The main difference lies in the extent of cross-reactivity with other parasites. Considering that the RDT is specifically meant for Loa loa infection, and its high sensitivity, this test could be a useful tool for the diagnosis of occult loiasis., Author summary Loa loa is a filarial worm which infects millions of people living in the forested areas of central Africa. The infection is rarely diagnosed outside Africa, but individual case management is also important in non-endemic countries to treat migrants, tourists and expatriates. Aim of this study was to describe the performance of a Rapid Test and an ELISA pan filarial test for the diagnosis of Loa loa infection. Both tests demonstrated good performance for the detection of cases of loiasis. In case of infection with other parasites, the RDT gave less false positive results.

Published
2020

34. Genomic detection of a virus lineage replacement event of dengue virus serotype 2 in Brazil, 2019

Author

Giovanetti, Marta, Faria, Nuno Rodrigues, Lourenço, José, Goes de Jesus, Jaqueline, Xavier, Joilson, Morales Claro, Ingra, Kraemer, Moritz U. G., Fonseca, Vagner, Dellicour, Simon, Thézé, Julien, da Silva Salles, Flavia, Gräf, Tiago, Paz Silveira, Paola, Alves do Nascimento, Valdinete, Costa de Souza, Victor, Campos de Melo Iani, Felipe, Castilho-Martins, Emerson Augusto, Nogueira Cruz, Laura, Wallau, Gabriel, Fabri, Allison, Levy, Flávia, Quick, Joshua, de Azevedo, Vasco, Santana Aguiar, Renato, De Oliveira, Tulio, Bôtto de Menezes, Camila, da Costa Castilho, Marcia, Terra, Tirza Matos, Souza da Silva, Marineide, Bispo de Filippis, Ana Maria, Luiz de Abreu, André, Kleber Oliveira, Wanderson, Croda, Julio, Campelo de Albuquerque, Carlos F., Nunes, Marcio R. T., Sabino, Ester Cerdeira, Loman, Nicholas, Naveca, Felipe Gomes, G.Pybus, Oliver, Alcantara, Luiz Carlos, Department of Infectious Diseases, Istituto Superiore di Sanita [Rome], University of Oxford [Oxford], Instituto Gonçalo Moniz, Partenaires INRAE, Universidade Federal de Minas Gerais, Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), University of KwaZulu-Natal (UKZN), Coordenação Geral dos Laboratórios de Saúde Pública/Secretaria de Vigilância em Saúde, Ministério da Saúde, (CGLAB/SVS-MS) Brasília, Distrito Federal, and Secretaria de em Saúde, Ministério da Saúde (SVS-MS), Brasília, Distrito Federal

Subjects
Microbiology (medical), Serotype, lineage replacement, lcsh:Arctic medicine. Tropical medicine, Genotype, lcsh:RC955-962, Lineage (evolution), [SDV]Life Sciences [q-bio], viruses, 030231 tropical medicine, lcsh:QR1-502, Biology, Dengue virus, medicine.disease_cause, Virus, lcsh:Microbiology, Dengue, 03 medical and health sciences, 0302 clinical medicine, Phylogenetics, Caribbean region, parasitic diseases, medicine, Humans, Phylogeny, outbreak, Outbreak, Genetic Variation, virus diseases, Genomics, Dengue Virus, biochemical phenomena, metabolism, and nutrition, Virology, 3. Good health, genomic surveillance, brazil, dengue 2, RNA, Viral, Original Article, Brazil
Abstract

BACKGROUND: Despite efforts to mitigate the impact of DENV epidemics, the virus remains a public health problem in tropical and subtropical regions around the world. Most DENV cases in the Americas between January and July 2019 were reported in Brazil. São Paulo state in the southeast of Brazil has reported nearly half of all DENV infections in the country. OBJECTIVES: To understand the origin and dynamics of the 2019 DENV outbreak. METHODS: Here using portable nanopore sequencing we generated 20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities of Sao Paulo state, Araraquara and São José do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. FINDINGS: The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Our analysis shows that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. MAIN CONCLUSIONS: Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.

Published
2020

35. Bayesian meta-analysis of inter-phenotypic differences in human serum paraoxonase-1 activity for chemical risk assessment

Author

Darney, K., Kasteel, E. E.J., Buratti, F. M., Turco, L., Vichi, S., Béchaux, C., Roudot, A. C., Kramer, N. I., Testai, E., Dorne, J. L.C.M., Di Consiglio, E., Lautz, L. S., LS IRAS Tox CMT/ATX, IRAS OH Toxicology, dIRAS RA-1, One Health Pharma, LS IRAS Tox CMT/ATX, IRAS OH Toxicology, dIRAS RA-1, One Health Pharma, Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institute for Risk Assessment Sciences [Utrecht, The Netherlands] (IRAS), Utrecht University [Utrecht], Istituto Superiore di Sanita [Rome], Laboratoire sur les interactions Epithéliums Neurones (LIEN), Université de Brest (UBO), and European Food Safety Authority (EFSA)

Subjects
010504 meteorology & atmospheric sciences, Genotype, [SDV]Life Sciences [q-bio], Population, Bayesian probability, Computational biology, 010501 environmental sciences, Biology, 01 natural sciences, Risk Assessment, Paraoxon, Human variability, Uncertainty factor, medicine, Humans, Polymorphism, education, lcsh:Environmental sciences, Chemical risk, 0105 earth and related environmental sciences, General Environmental Science, lcsh:GE1-350, education.field_of_study, Polymorphism, Genetic, Aryldialkylphosphatase, Bayes Theorem, PON1, Phenotype, Meta-analysis, PON1 activity, medicine.drug
Abstract

Human variability in paraoxonase-1 (PON1) activities is driven by genetic polymorphisms that affect the internal dose of active oxons of organophosphorus (OP) insecticides. Here, an extensive literature search has been performed to collect human genotypic frequencies (i.e. L55M, Q192R, and C-108T) in subgroups from a range of geographical ancestry and PON1 activities in three probe substrates (paraoxon, diazoxon and phenyl acetate). Bayesian meta-analyses were performed to estimate variability distributions for PON1 activities and PON1-related uncertainty factors (UFs), while integrating quantifiable sources of inter-study, inter-phenotypic and inter-individual differences. Inter-phenotypic differences were quantified using the population with high PON1 activity as the reference group. Results from the meta-analyses provided PON1 variability distributions and these can be implemented in generic physiologically based kinetic models to develop quantitative in vitro in vivo extrapolation models. PON1-related UFs in the Caucasian population were above the default toxicokinetic UF of 3.16 for two specific genotypes namely −108CC using diazoxon as probe substrate and, −108CT, −108TT, 55MM and 192QQ using paraoxon as probe substrate. However, integration of PON1 genotypic frequencies and activity distributions showed that all UFs were within the default toxicokinetic UF. Quantitative inter-individual differences in PON1 activity are important for chemical risk assessment particularly with regards to the potential sensitivity to organophosphates’ toxicity. Keywords: Human variability, PON1 activity, Polymorphism, Uncertainty factor

Published
2020

36. Enhancing Preparedness for Arbovirus Infections with a One Health Approach: The Development and Implementation of Multisectoral Risk Assessment Exercises

Author

Laurence Marrama, Paolo Calistri, Kathleen Victoir, Bertrand Sudre, Guillain Mikaty, Silvia Declich, Flavia Riccardo, Alessia Ranghiasci, Thomas Mollet, Jovita Fernández-Pinero, Jean-Claude Manuguerra, Vincent Robert, Wim Van Bortel, Ariane Guillot, Maria Grazia Dente, Tarik Derrough, Lobna Gaayeb, Elisa Pérez-Ramírez, Marie Picard, Camille Escadafal, Gloria Nacca, Miguel Ángel Jiménez-Clavero, Istituto Superiore di Sanita [Rome], European Centre for Disease Prevention and Control (ECDC), Institute of Tropical Medicine [Antwerp] (ITM), European Commission [Brussels], Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise Guiseppe Caporale (IZSAM), Partenaires INRAE, Foundation for Innovative New Diagnostics (FIND), Institut Pasteur [Paris], CIBER de Epidemiología y Salud Pública (CIBERESP), Centro de Investigacion en Sanidad Animal (INIA-CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA), Université Bordeaux Segalen - Bordeaux 2, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), Evolution des Systèmes Vectoriels (ESV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), The authors acknowledge the active participation of the members of MediLabSecure network to the MRA exercises. The MediLabSecure project was supported by the European Commission (DEVCO: IFS/21010/23/_194 & IFS/2018/402-247)., Istituto Superiore di Sanità (ISS), European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), and Institut Pasteur [Paris] (IP)

Subjects
medicine.medical_specialty, Article Subject, 040301 veterinary sciences, 030231 tropical medicine, MEDLINE, Arbovirus Infections, Global Health, Risk Assessment, General Biochemistry, Genetics and Molecular Biology, 0403 veterinary science, 03 medical and health sciences, 0302 clinical medicine, Documentation, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Added value, medicine, Global health, Animals, Humans, One Health, Medical education, General Immunology and Microbiology, Public health, 04 agricultural and veterinary sciences, General Medicine, Preparedness, Medicine, Business, Risk assessment, Research Article
Abstract

Background. One Health is receiving attention for arbovirus infection prevention and control and for defining national “intersectoral” priorities. Increasing awareness of intersectoral priorities through multisectorial risk assessments (MRA) is promising, where data are not systematically shared between sectors. Towards this aim, the MediLabSecure project organized three MRA exercises (hereby called exercises): one on West Nile virus, one on Crimean–Congo haemorrhagic fever, and one on Rift Valley fever, assessing the added value of this approach. Methods. The exercises relied on RA methodologies of international organisations. Country representatives of the human and animal virology, medical entomology, and public health sectors (hereby called “sectors”) involved in the surveillance of vector-borne diseases participated in the exercises. Background documentation was provided before each exercise, and a guide was developed for the facilitators. All three exercises included technical and methodological presentations and a guided RA directed at bringing into play the different sectors involved. To assess the added value of the approach, each participant was asked to rank the level of perceived benefit of the multisectoral collaboration for each “risk question” included in the exercises. Results. In total, 195 participants from 19 non-EU countries in the Mediterranean and Black Sea regions took part in the exercises. The participants assessed the multisectoral approach as valuable in analysing comprehensively the situation by having access to information and knowledge provided by each of the sectors involved. Sharing of information and discussion facilitated reaching a consensus on the level of risk in each country. Conclusions. Increasing awareness of intersectoral priorities, including cross-border ones, through MRA is relevant to reduce gaps due to unavailability of shared data and information. Given that six out of the ten threats to global health listed by WHO are occurring at the human-animal-environmental interfaces, comprehensive regional RA with a One Health approach made by national authorities can be a relevant added value for the global health security.

Published
2020

37. Human Plasmodium vivax diversity, population structure and evolutionary origin

Author

Peter G. Kremsner, A. Berry, Ali Ould Mohamed Salem Boukary, Tamirat Gebru Woldearegai, Lise Musset, Eric Legrand, Benjamin Mordmüller, Franck Prugnolle, Carlo Severini, Jean-François Trape, François Renaud, Patrick Durand, Pingchai Harnyuttanakorn, Mohammad Shafiul Alam, Lilia González-Cerón, Khadijetou Mint Lekweiry, Beatriz Acuña Hidalgo, Dionicia Gamboa, François Nosten, Eric Elguero, Gustavo Fontecha, Virginie Rougeron, Oscar Noya, Céline Arnathau, Tepanata Pumpaibool, Sandrine Houzé, Sedigheh Zakeri, Rashidul Haque, Musab M. Ali Albsheer, Muzamil Mahdi Abdel Hamid, Health, Emergence, Adaptation and Transmission (MIVEGEC-HEAT), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Malaria and Vector Research Group (MVRG), Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Dipartimento di Malattie infettive = Department of Infectious Diseases [Rome, Italie] (DMI), Istituto Superiore di Sanità (ISS), Institute for Tropical Medicine = Institut für Tropenmedizin, Reisemedizin, Humanparasitolgie [Tübingen, Allemagne] (ITM), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, German Center for Infectious Research - partner site Tübingen [Tübingen, Allemagne] (DZIF), College of Health and Medical Sciences [Harar, Ethiopie], Haramaya University (HU), Centro Regional de Investigación en Salud Pública = Regional Centre of Research in Public Health [Tapachula, Mexique] (CRISP), National Institute of Public Health = Instituto Nacional de Salud Pública [Cuernavaca, Mexique] (INSP), Microbiology Research Institute = Instituto de Investigaciones en Microbiología [Tegucigalpa, Honduras] (IIM), Universidad Nacional Autónoma de Honduras (UNAH), Instituto de Medicina Tropical 'Alexander von Humboldt' (IMT AvH), Universidad Peruana Cayetano Heredia (UPCH), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Laboratoire de Parasitologie [Cayenne, Guyane française], Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Génétique du paludisme et résistance - Malaria Genetics and Resistance, Institut Pasteur [Paris] (IP), Centro para Estudios Sobre Malaria [Venezuela], Instituto de Altos Estudios en Salud Dr. Arnoldo Gabaldón, Instituto de Medicina Tropical [Caracas, Venezuela} (IMT), Universidad Central de Venezuela (UCV), Graduate School [Bangkok, Thailande], Chulalongkorn University [Bangkok], College of Public Health Science [Bangkok, Thailande], Department of Biology, Faculty of Science [Bangkok, Thailande], Faculté des Sciences et Techniques [Nouakchott, Mauritania], University of Khartoum, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Authors thank the ANR Tremplin EVAD 2017, IRD and CNRS-INEE., ANR-17-ERC3-0002,EVAD,Histoire évolutive et adaptation génétique de Plasmodium vivax(2017), Laboratoire MIVEGEC (Université de Montpellier-CNRS-IRD), CREES, Montpellier, France., Génétique et évolution des maladies infectieuses (GEMI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Génétique et évolution des maladies infectieuses (GEMI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Istituto Superiore di Sanita [Rome], Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Legrand, Eric, Histoire évolutive et adaptation génétique de Plasmodium vivax - - EVAD2017 - ANR-17-ERC3-0002 - TERC - VALID, Service de Parasitologie et Mycologie, Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], University of Oxford [Oxford]-University of Oxford [Oxford], Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], and Institut Pasteur [Paris]

Subjects
Evolutionary Genetics, 0301 basic medicine, Plasmodium, MESH: Plasmodium vivax / isolation & purification, Genotyping Techniques, Population genetics, [SDV]Life Sciences [q-bio], RC955-962, Plasmodium vivax, MESH: Global Health, Global Health, Microsatellite Loci, Geographical Locations, MESH: Genotype, 0302 clinical medicine, Arctic medicine. Tropical medicine, Global health, MESH: Genetic Variation, MESH: Plasmodium vivax / genetics, Species diversity, education.field_of_study, Ecology, biology, MESH: Plasmodium vivax / classification, 3. Good health, Infectious Diseases, Parasite evolution, Public aspects of medicine, RA1-1270, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, purl.org/pe-repo/ocde/ford#3.03.06 [https], Research Article, Microsatellite loci, Asia, Genotype, Ecological Metrics, 030231 tropical medicine, Population, MESH: Malaria, Vivax / parasitology, Evolutionary genetics, 03 medical and health sciences, Gene Types, MESH: Genotyping Techniques, Parasite Groups, parasitic diseases, Malaria, Vivax, Genetics, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Parasite Evolution, education, Evolutionary Biology, MESH: Humans, Population Biology, Human evolutionary genetics, Ecology and Environmental Sciences, Public Health, Environmental and Occupational Health, Genetic Variation, Biology and Life Sciences, Species Diversity, Plasmodium falciparum, biology.organism_classification, medicine.disease, 030104 developmental biology, Evolutionary biology, People and Places, Africa, Parasitology, Apicomplexa, Population Genetics, Malaria
Abstract

More than 200 million malaria clinical cases are reported each year due to Plasmodium vivax, the most widespread Plasmodium species in the world. This species has been neglected and understudied for a long time, due to its lower mortality in comparison with Plasmodium falciparum. A renewed interest has emerged in the past decade with the discovery of antimalarial drug resistance and of severe and even fatal human cases. Nonetheless, today there are still significant gaps in our understanding of the population genetics and evolutionary history of P. vivax, particularly because of a lack of genetic data from Africa. To address these gaps, we genotyped 14 microsatellite loci in 834 samples obtained from 28 locations in 20 countries from around the world. We discuss the worldwide population genetic structure and diversity and the evolutionary origin of P. vivax in the world and its introduction into the Americas. This study demonstrates the importance of conducting genome-wide analyses of P. vivax in order to unravel its complex evolutionary history., Author summary Among the five Plasmodium species infecting humans, P. vivax is the most prevalent parasite outside Africa. To date, there has been less research on this species than for Plasmodium falciparum, a more lethal species, principally because of the lack of an in vitro culture system and also because P. vivax is considered relatively benign. Nevertheless, P. vivax is responsible for severe and incapacitating clinical symptoms with significant effects on human health. The emergence of new drug resistance and the discovery of severe and even fatal cases due to P. vivax question the benign status of P. vivax malaria. In recent years, there has been increased interest in characterizing the distribution of genetic variation in P. vivax. However, these studies either generated genetic information from a regional geographic scale or combine genetic datasets generated in different molecular platforms, which is known to generate biased results. In this study, we used a single genotyping platform to genotype 14 microsatellite markers in 834 samples of P. vivax obtained from 28 locations in 20 countries from around the world, including several populations from East and West Africa. We discuss the worldwide population genetic structure and the evolutionary origins of P. vivax, as well as its introduction into the Americas.

Published
2020

38. Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth

Author

Gianluca Ricci, Sandrine Roulland, Mariachiara Buccarelli, Alexey Amunts, Stefano Giannetti, Alessia Soldano, Angela Re, Valentina Adami, Denise Sighel, Emanuele Filiberto Rosatti, Angelika Modelska, Shintaro Aibara, Sara Longhi, Roberto Pallini, Marianna Guida, Lucia Ricci-Vitiani, Michela Notarangelo, Simone Pacioni, Alessandro Quattrone, Francesca Broso, Chiara Ambrosini, Joanna Rorbach, Quintino Giorgio D'Alessandris, Ines Mancini, University of Trento [Trento], Stockholm University, Institute for Biomedicine [Bolzano, Italy] (Eurac Research), Affiliated Institute of the University of Lübeck, Istituto Superiore di Sanità (ISS), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Karolinska Institutet [Stockholm], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), DUMENIL, Anita, and Istituto Superiore di Sanita [Rome]

Subjects
0301 basic medicine, endocrine system, Mitochondrial translation, [SDV]Life Sciences [q-bio], Settore MED/27 - NEUROCHIRURGIA, Oxidative phosphorylation, high-content screening, mitochondrial translation, General Biochemistry, Genetics and Molecular Biology, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Cell Line, Tumor, Mitochondrial ribosome, Humans, quinupristin, Cell Proliferation, dalfopristin, mitoribosome, glioblastoma stem cells, drug repurposing, Chemistry, cryo-EM, glioblastoma, OXPHOS, Cell cycle, Cell biology, Mitochondria, [SDV] Life Sciences [q-bio], 030104 developmental biology, Apoptosis, High-content screening, Neoplastic Stem Cells, Suppressor, Stem cell, 030217 neurology & neurosurgery
Abstract

Summary Glioblastoma stem cells (GSCs) resist current glioblastoma (GBM) therapies. GSCs rely highly on oxidative phosphorylation (OXPHOS), whose function requires mitochondrial translation. Here we explore the therapeutic potential of targeting mitochondrial translation and report the results of high-content screening with putative blockers of mitochondrial ribosomes. We identify the bacterial antibiotic quinupristin/dalfopristin (Q/D) as an effective suppressor of GSC growth. Q/D also decreases the clonogenicity of GSCs in vitro, consequently dysregulating the cell cycle and inducing apoptosis. Cryoelectron microscopy (cryo-EM) reveals that Q/D binds to the large mitoribosomal subunit, inhibiting mitochondrial protein synthesis and functionally dysregulating OXPHOS complexes. These data suggest that targeting mitochondrial translation could be explored to therapeutically suppress GSC growth in GBM and that Q/D could potentially be repurposed for cancer treatment., Graphical abstract, Highlights • Screen of putative mitoribosome inhibitors identifies Q/D as effective on GSCs • Q/D selectively inhibits growth of GSCs • Treatment with Q/D decreases clonogenicity, blocks cell cycle, and induces apoptosis • Q/D binds to mitoribosomes and inhibits mitochondrial translation and therefore OXPHOS, In a screen of antibiotics as putative mitochondrial translation inhibitors, Sighel et al. identify Q/D as a suppressor of glioblastoma stem cell growth. Q/D inhibits mitochondrial translation, leading to OXPHOS dysregulation and, consequently, decreasing clonogenicity, blocking the cell cycle, and inducing apoptosis.

Published
2020

39. Genomic and Epidemiological Surveillance of Zika Virus in the Amazon Region

Author

Carlos F. Campelo de Albuquerque, Tiago Gräf, José Lourenço, Marcia da Costa Castilho, Flavia da Silva Salles, Marta Giovanetti, Laura Nogueira da Cruz, Marineide Silva, Emerson A. Castilho-Martins, Allison Fabri, Vagner Fonseca, Ingra Morales Claro, Moritz U. G. Kraemer, Luiz Carlos Junior Alcantara, Julio Croda, Tulio de Oliveira, Nicholas J. Loman, Joshua Quick, Flavia Levy, Jaqueline Goes de Jesus, Julien Thézé, Márcio Roberto Teixeira Nunes, Paola P. Silveira, Ester Cerdeira Sabino, Oliver G. Pybus, Felipe Gomes Naveca, Vasco de Azevedo, Simon Dellicour, Nuno R. Faria, Felipe Campos de Melo Iani, Joilson Xavier, Victor Costa de Souza, André Luiz de Abreu, Camila Helena de Aguiar Bôtto de Menezes, Renato Santana Aguiar, Gabriel Luz Wallau, Wanderson Kleber de Oliveira, Tirza Matos Terra, Valdinete Alves do Nascimento, Ana Maria Bispo de Filippis, Department of Infectious Diseases, Istituto Superiore di Sanita [Rome], Instituto Gonçalo Moniz, Partenaires INRAE, Universidade Federal de Minas Gerais, Evolutionary Biology and Ecology, Université libre de Bruxelles (ULB), Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), University of KwaZulu-Natal (UKZN), Coordenação Geral dos Laboratórios de Saúde Pública/Secretaria de Vigilância em Saúde, Ministério da Saúde, (CGLAB/SVS-MS) Brasília, Distrito Federal, Department of Zoology, and University of Cambridge [UK] (CAM)

Subjects
0301 basic medicine, Male, TRANSMISSION, Virus transmission, OUTBREAK, [SDV]Life Sciences [q-bio], MODELS, Sciences de l'ingénieur, General Biochemistry, Genetics and Molecular Biology, Virus, Zika virus, 03 medical and health sciences, FEVER, 0302 clinical medicine, Environmental health, REVEALS, Humans, PHYLOGENETIC ANALYSIS, Infec??o por Zika virus / transmiss?o, Zika virus / isolamento & purifica??o, lcsh:QH301-705.5, Science & Technology, biology, Transmission (medicine), Amazon rainforest, Zika Virus Infection, Outbreak, Cell Biology, Genomics, Zika Virus, BRAZIL, biology.organism_classification, Infec??o por Zika virus / gen?tica, Zika virus / patogenicidade, OROPOUCHE, 3. Good health, 030104 developmental biology, Geography, Surtos de Doen?as, lcsh:Biology (General), Epidemiological Monitoring, Epidemiological surveillance, Female, SPREAD, Manaus (AM), Life Sciences & Biomedicine, ANGOLA, 030217 neurology & neurosurgery, Brazil
Abstract

Zika virus (ZIKV) has caused an explosive epidemic linked to severe clinical outcomes in the Americas. As of June 2018, 4,929 ZIKV suspected infections and 46 congenital syndrome cases had been reported in Manaus, Amazonas, Brazil. Although Manaus is a key demographic hub in the Amazon region, little is known about the ZIKV epidemic there, in terms of both transmission and viral genetic diversity. Using portable virus genome sequencing, we generated 59 ZIKV genomes in Manaus. Phylogenetic analyses indicated multiple introductions of ZIKV from northeastern Brazil to Manaus. Spatial genomic analysis of virus movement among six areas in Manaus suggested that populous northern neighborhoods acted as sources of virus transmission to other neighborhoods. Our study revealed how the ZIKV epidemic was ignited and maintained within the largest urban metropolis in the Amazon. These results might contribute to improving the public health response to outbreaks in Brazil., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2020

40. Characterization of goat prions demonstrates geographical variation of scrapie strains in Europe and reveals the composite nature of prion strains

Author

Lucien van Keulen, Patricia Aguilar-Calvo, John Spiropoulos, Claudia D'Agostino, Christine Fast, Pier Luigi Acutis, Penelope Papasavva-Stylianou, Alex Bossers, Romolo Nonno, Frédéric Lantier, Olivier Andreoletti, Gabriele Vaccari, Isabelle Lantier, Jorge G Jacobs, Juan María Torres, Jan P. M. Langeveld, Martin H. Groschup, Umberto Agrimi, Juan Carlos Espinosa, Cristina Acín, Barbara Chiappini, Theodoros Sklaviadis, Michele Angelo Di Bari, Laura Pirisinu, Alba Marín-Moreno, Istituto Superiore di Sanità (ISS), Centro de Investigacion en Sanidad Animal (INIA-CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA), Institute of Novel and Emerging Infectious Diseases (INNT), Friedrich-Loeffler-Institut (FLI), Wageningen BioVeterinary Research, Wageningen University and Research [Wageningen] (WUR), Animal and Plant Health Agency [Addlestone, UK] (APHA), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Aristotle University of Thessaloniki, Veterinary Services of Cyprus, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, This work was funded by the European Union (FOOD-CT-2006-36353 to AB, JPML, OA, JMT, CA, MHG, PLA, UA, TS, and ERA-NET EMIDA GOAT-TSE-FREE to JPML, LVK, PLA, OA, JCE, CA, CF), the Dutch Ministry of Agriculture (project WOT-01-002-001.01 to JPML), the Spanish Ministerio de ciencia innovacion y universidades (AGL201678054-R [AEI/FEDER, UE] and AGL2012-37988-C04-04 to JMT), the Italian Ministry of Health (RF-20091474624 to RN). AMM was supported by a fellowship from the INIA (FPI-SGIT-2015-02). PAC was supported by a fellowship from the Spanish Ministerio de Economia y Competitividad (BES-2010-040922)., European Project: 36353,GOATBSE, Istituto Superiore di Sanita [Rome], Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
0301 basic medicine, Prion diseases, Prions, [SDV]Life Sciences [q-bio], animal diseases, Bovine spongiform encephalopathy, lcsh:Medicine, Prion strain, Scrapie, Biology, Prion Proteins, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Animal model, Biological property, medicine, Animals, Life Science, Neurodegeneration, lcsh:Science, Host Pathogen Interaction & Diagnostics, Genetics, Goat Diseases, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Multidisciplinary, Goats, Strain (biology), lcsh:R, Bacteriologie, Bacteriology, Bacteriology, Host Pathogen Interaction & Diagnostics, Limiting, medicine.disease, Host Pathogen Interactie & Diagnostiek, nervous system diseases, Encephalopathy, Bovine Spongiform, Europe, Experimental models of disease, 030104 developmental biology, Bacteriologie, Host Pathogen Interactie & Diagnostiek, Infectious diseases, Cattle, lcsh:Q, 030217 neurology & neurosurgery
Abstract

Bovine Spongiform Encephalopathy (BSE) is the only animal prion which has been recognized as a zoonotic agent so far. The identification of BSE in two goats raised the need to reliably identify BSE in small ruminants. However, our understanding of scrapie strain diversity in small ruminants remains ill-defined, thus limiting the accuracy of BSE surveillance and spreading fear that BSE might lurk unrecognized in goats. We investigated prion strain diversity in a large panel of European goats by a novel experimental approach that, instead of assessing the neuropathological profile after serial transmissions in a single animal model, was based on the direct interaction of prion isolates with several recipient rodent models expressing small ruminants or heterologous prion proteins. The findings show that the biological properties of scrapie isolates display different patterns of geographical distribution in Europe and suggest that goat BSE could be reliably discriminated from a wide range of biologically and geographically diverse goat prion isolates. Finally, most field prion isolates showed composite strain features, with discrete strain components or sub-strains being present in different proportions in individual goats or tissues. This has important implications for understanding the nature and evolution of scrapie strains and their transmissibility to other species, including humans.

Published
2020

41. Human Immunodeficiency Virus Continuum of Care in 11 European Union Countries at the End of 2016 Overall and by Key Population: Have We Made Progress?

Author

Vourli, G., Noori, T., Pharris, A., Porter, K., Axelsson, M., Begovac, J., Cazein, F., Costagliola, D., Cowan, S., Croxford, S., Monforte, A. D., Delpech, V., Diaz, A., Girardi, E., Gunsenheimer-Bartmeyer, B., Hernando, V., Leierer, G., Lot, F., Nunez, O., Obel, N., Op de Coul, E., Paraskeva, D., Patrinos, S., Reiss, P., Schmid, D., Sonnerborg, A., Suligoi, B., Supervie, V., van Sighem, A., Zangerle, R., Touloumi, G., Egle, A., Kanatschnig, M., Ollinger, A., Rieger, A., Schmied, B., Wallner, E., Dewasurendra, D., Gisinger, M., Kitchen, M., Plattner, A., Rieser, E., Sarcletti, M., Greil, R., Schachner, M., Skocic, M., Muller, M., Aichwalder, R., Chromy, D., Grabmeier-Pfstershammer, K., Skoll, M., Touzeau, V., Cichon, P., Wolf-Nussmuller, S., Laferl, H., Zoufaly, A., Genger-Hackl, C., Kapper, A., Schneeberger, T., Trattner, E., Schober, G., Atzl, M., Hartmann, B., Puchhammer-Stockl, E., Berg, J., Appoyer, H., Rappold, M., Strickner, S., Schindelwig, K., Ledergerber, B., Fatkenheuer, G., Gerstof, J., Kronborg, G., Pedersen, C., Larsen, C. S., Pedersen, G., Mohey, R., Nielsen, L., Weise, L., Kvinesdal, B., Jensen, J., Abgrall, S., Bernard, L., Billaud, E., Boue, F., Boyer, L., Cabie, A., Caby, F., Canestri, A., Cotte, L., de Truchis, P., Duval, X., Duvivier, C., Enel, P., Fischer, H., Gasnault, J., Gaud, C., Grabar, S., Khuong-Josses, M. A., Launay, O., Marchand, L., Mary-Krause, M., Matheron, S., Melica-Gregoire, G., Melliez, H., Meynard, J. L., Nacher, M., Pavie, J., Piroth, L., Poizot-Martin, I., Pradier, C., Reynes, J., Rouveix, E., Simon, A., Slama, L., Tattevin, P., Tissot-Dupont, H., Biga, J., Kurth, T., Jacquemet, N., Guiguet, M., Leclercq, S., Lievre, L., Marshall, E., Roul, H., Selinger-Leneman, H., Potard, V., Benveniste, O., Breton, G., Lupin, C., Bourzam, E., Girard, P. M., Fonquernie, L., Valin, N., Lefebvre, B., Sebire, M., Pialoux, G., Lebrette, M. G., Tibaut, P., Adda, A., Hamidi, M., Cadranel, J., Lavole, A., Parrot, A., Bouchaud, O., Vignier, N., Mechai, F., Makhlouf, S., Honore, P., Bergmann, J. F., Delcey, V., Lopes, A., Sellier, P., Parrinello, M., Oksenhendler, E., Gerard, L., Molina, J. M., Rozenbaum, W., Denis, B., De Castro, N., Lascoux, C., Yazdanpanah, Y., Lariven, S., Joly, V., Rioux, C., Poupard, M., Taverne, B., Sutton, L., Masse, V., Genet, P., Wifaq, B., Gerbe, J., Grefe, S., Dupont, C., Freire Maresca, A., Reimann, E., Bloch, M., Meier, F., Mortier, E., Zeng, F., Montoya, B., Perronne, C., Mathez, D., Marigot-Outtandy, D., Berthe, H., Greder Belan, A., Terby, A., Godin Collet, C., Marque Juillet, S., Ruquet, M., Roussin-Bretagne, S., Colardelle, P., Granier, F., Laurichesse, J. J., Perronne, V., Akpan, T., Marcou, M., Daneluzzi, V., Veyssier-Belot, C., Masson, H., Welker, Y., Brazille, P., Kahn, J. E., Zucman, D., Majerholc, C., Fourn, E., Bornarel, D., Chambrin, V., Kansau, I., Raho-Moussa, M., Lelievre, J. D., Saidani, M., Chesnel, C., Dumont, C., Vittecoq, D., Derradji, O., Bolliot, C., Goujard, C., Teicher, E., Mole, M., Bourdic, K., Salmon, D., Le Jeunne, C., Guet, P., Pietri, M. P., Pannier Metzger, E., Marcou, V., Loulergue, P., Dupin, N., Morini, J. P., Deleuze, J., Gerhardt, P., Chanal, J., Weiss, L., Lucas, M. L., Jung, C., Ptak, M., Viard, J. P., Ghosn, J., Gazalet, P., Cros, A., Maignan, A., Lortholary, O., Rouzaud, C., Touam, F., Benhadj, K., Consigny, P. H., Bossi, P., Gergely, A., Cessot, G., Durand, F., Beck-Wirth, G., Michel, C., Benomar, M., Rey, D., Partisani, M., Cheneau, C., Batard, M. L., Fischer, P., Leclercq, P., Blanc, M., Morand, P., Epaulard, O., Signori-Schmuck, A., Laurichesse, H., Jacomet, C., Vidal, M., Coban, D., Casanova, S., Fresard, A., Guglielminotti, C., Botelho-Nevers, E., Brunon-Gagneux, A., Ronat, V., Verdon, R., Dargere, S., Haustraete, E., Feret, P., Goubin, P., Chavanet, P., Fillion, A., Croisier, D., Gohier, S., Arvieux, C., Souala, F., Chapplain, J. M., Ratajczak, M., Rohan, J., Faller, J. P., Ruyer, O., Gendrin, V., Toko, L., Chirouze, C., Hustache-Mathieu, L., Faucher, J. F., Proust, A., Magy-Bertrand, N., Gil, H., Meaux-Ruault, N., Sotto, A., Rouanet, I., Mauboussin, J. M., Doncesco, R., Jacques, G., May, T., Rabaud, C., Andre, M., Delestan, M., Bouillon, M. P., Bani-Sadr, F., Rouger, C., Berger, J. L., Nguyen, Y., Marchou, B., Delobel, P., Martin Blondel, G., Cuzin, L., Biezunski, N., Alric, L., Bonnet, D., Guivarch, M., Palacin, A., Payssan, V., Ajana, F., Meybeck, A., Viget, N., Pugliese, P., Roger, P. M., Rosenthal, E., Durant, J., Cua, E., Naqvi, A., Perbost, I., Risso, K., Quinsat, D., Raphael, St., Del Giudice, P., Dides, P. Y., Sambuc, R., Antolini-Bouvenot, M. S., Druart, P., Meddeb, L., Ravaux, I., Menard, A., Tomei, C., Dhiver, C., Moreau, J., Mokhtari, S., Soavi, M. J., Tomas, V., Bregigeon, S., Faucher, O., Obry-Roguet, V., Ritleng, A. S., Petit, N., Bartoli, C., Ruiz, J. M., Blanc, D., Allegre, T., Sordage, M., Riou, J. M., Faudon, C., Slama, B., Zerazhi, H., Boulat, O., Chebrek, S., Beyrne, M., Granet Brunello, P., Pellissier, L., Bonnabel, D., Cohen Valensi, R., Mouchet, B., Mboungou, G., Lafeuillade, A., Hope-Rapp, E., Hittinger, G., Philip, G., Lambry, V., Raf, F., Allavena, C., Hall, N., Reliquet, V., Chidiac, C., Ferry, T., Perpoint, T., Miailhes, P., Boibieux, A., Livrozet, J. M., Makhlouf, D., Brunel, F., Chiarello, P., Hoen, B., Lamaury, I., Fabre, I., Samar, K., Duvallon, E., Clavel, C., Stegmann, S., Walter, V., Adriouch, L., Huber, F., Vanticlke, V., Couppie, P., Abel, S., Pierre-Francois, S., Ricaud, C., Rodet, R., Wartel, G., Sautron, C., Poubeau, P., Borgherini, G., Camuset, G., Arasteh, K., Kowohl Vivantes, S., Schurmann, D., Warncke Charite, M., Rockstroh, J., Wasmuth, J., Hass, S., Jensen, B. O., Feind, C., Esser, S., Schenk-Westkamp, P., Haberl, A., Stephan, C., Plettenberg, A., Kuhlendahl, F., Adam, A., Weitner, L., Schewe, K., Goey, H., Fenske, S., Buhk, T., Stellbrink, H. J., Hofmann, C., Hansen, S., Degen, O., Heuer, M., Stoll, M., Gerschmann, S., Horst, H., Trautmann, S., Gillor, D., Bogner, J., Sonntag, B., Salzberger, B., Fritzsche, C., Adamis, G., Antoniadou, A., Chini, M., Chrysos, G., Gikas, A., Gogos, H. A., Katsarou, O., Lazanas, M., Metallidis, S., Panagopoulos, P., Paparizos, V., Papastamopoulos, V., Paraskevis, D., Psychogiou, M., Sambatakou, H., Sipsas, N. V., Pantazis, N., Papadopoulos, A., Nitsotolis, T., Xylomenos, G., Marangos, M. N., Kouramba, A., Kontos, A., Lioni, A., Tsachouridou, O., Kourkounti, S., Ganitis, A., Barbounakis, E., d'Arminio Monforte, A., Antinori, A., Andreoni, M., Castagna, A., Castelli, F., Cauda, R., Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Marchetti, G. C., Rezza, G., von Schloesser, F., Viale, P., Ceccherini-Silberstein, F., Cozzi-Lepri, A., Lo Caputo, S., Mussini, C., Puoti, M., Perno, C. F., Bai, F., Balotta, C., Bandera, A., Bonora, S., Borderi, M., Calcagno, A., Capetti, A., Capobianchi, M. R., Cicalini, S., Cingolani, A., Cinque, P., Di Biagio, A., Gianotti, N., Gori, A., Guaraldi, G., Lapadula, G., Lichtner, M., Madeddu, G., Maggiolo, F., Marchetti, G., Monno, L., Nozza, S., Pinnetti, C., Quiros Roldan, E., Rossotti, R., Rusconi, S., Santoro, M. M., Saracino, A., Sarmati, L., Fanti, I., Galli, L., Lorenzini, P., Rodano, A., Macchia, M., Tavelli, A., Carletti, F., Carrara, S., Di Caro, A., Graziano, S., Petroni, F., Prota, G., Trufa, S., Giacometti, A., Costantini, A., Barocci, V., Angarano, G., Milano, E., Suardi, C., Donati, V., Verucchi, G., Castelnuovo, F., Minardi, C., Menzaghi, B., Abeli, C., Cacopardo, B., Celesia, B., Vecchiet, J., Falasca, K., Pan, A., Lorenzotti, S., Sighinolf, L., Segala, D., Blanc, P., Vichi, F., Cassola, G., Viscoli, C., Alessandrini, A., Bobbio, N., Mazzarello, G., Fondaco, L., Bonfanti, P., Molteni, C., Chiodera, A., Milini, P., Nunnari, G., Pellicano, G., Rizzardini, G., Cannizzo, E. S., Moioli, M. C., Piolini, R., Bernacchia, D., Salpietro, S., Tincati, C., Puzzolante, C., Migliorino, C., Sangiovanni, V., Borgia, G., Esposito, V., Di Flumeri, G., Gentile, I., Rizzo, V., Cattelan, A. M., Marinello, S., Cascio, A., Trizzino, M., Francisci, D., Schiaroli, E., Parruti, G., Sozio, F., Magnani, G., Ursitti, M. A., Cristaudo, A., Vullo, V., Acinapura, R., Moschese, D., Capozzi, M., Mondi, A., Rivano Capparuccia, M., Iaiani, G., Latini, A., Gagliardini, R., Plazzi, M. M., De Girolamo, G., Vergori, A., Cecchetto, M., Viviani, F., De Vito, A., Rossetti, B., Montagnani, F., Franco, A., Fontana Del Vecchio, R., Di Giuli, C., Caramello, P., Orofno, G. C., Sciandra, M., Bassetti, M., Londero, A., Manfrin, V., Battagin, G., Starnini, G., Ialungo, A., van der Valk, M., Geerlings, S. E., Goorhuis, A., Hovius, J. W., Lempkes, B., Nellen, F. J. B., van der Poll, T., Prins, J. M., van Vugt, M., Wiersinga, W. J., Wit, F. W. M. N., van Duinen, M., van Eden, J., Hazenberg, A., van Hes, A. M. H., Pijnappel, F. J. J., Smalhout, S. Y., Weijsenfeld, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Peters, E. J. G., van Agtmael, M. A., Bomers, M., Sigalof, K. C. E., Heitmuller, M., Laan, L. M., Ang, C. W., van Houdt, R., Jonges, M., van Prehn, J., Kuijpers, T. W., Pajkrt, D., Scherpbier, H. J., de Boer, C., van der Plas, A., van den Berge, M., Stegeman, A., Baas, S., Hage de Loof, L., Wintermans, B., Veenemans, J., Pronk, M. J. H., Ammerlaan, H. S. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., van Eeden, A., Brokking, W., Elsenburg, L. J. M., Nobel, H., Damen, M., van Kasteren, M. E. E., Berrevoets, M. A. H., Brouwer, A. E., Adams, A., de Kruijf-Van de Wiel, B. A. F. M., Keelan-Pfaf, S., van der Ven, B., Buiting, A. G. M., Murck, J. L., Versteeg, D., de Vries-Sluijs, T. E. M. S., Bax, H. I., van Gorp, E. C. M., Nouwen, J. L., Rijnders, B. J. A., Schurink, C. A. M., Verbon, A., de Jong-Peltenburg, N. C., Bassant, N., van Beek, J. E. A., Vriesde, M., van Zonneveld, L. M., van den Berg-Cameron, H. J., de Groot, J., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E., Branger, J., Douma, R. A., Duijf-Van de Ven, C. J. H. M., Schippers, E. F., van Nieuwkoop, C., van IJperen, J. M., Geilings, J., van der Hut, G., van Burgel, N. D., Leyten, E. M. S., Gelinck, L. B. S., Mollema, F., Davids-Veldhuis, S., Wildenbeest, G. S., Heikens, E., Groeneveld, P. H. P., Bouwhuis, J. W., Lammers, A. J. J., Kraan, S., van Hulzen, A. G. W., Kruiper, M. S. M., van der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfagen, M. J. H. M., Ruijs, G. J. H. M., Kroon, F. P., de Boer, M. G. J., Scheper, H., Jolink, H., Dorama, W., van Holten, N., Claas, E. C. J., Wessels, E., den Hollander, J. G., El Moussaoui, R., Pogany, K., Kastelijns, M., Smit, J. V., Smit, E., Struik-Kalkman, D., Tearno, C., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A. M. L., Posthouwer, D., Ackens, R. P., Burgers, K., Schippers, J., Weijenberg-Maes, B., van Loo, I. H. M., Havenith, T. R. A., Weijer, S., van Vonderen, M. G. A., Kampschreur, L. M., Faber, S., Steeman-Bouma, R., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-Van de Plas, M., Heins, H., Kortmann, W., van Twillert, G., Renckens, R., Ruiter-Pronk, D., van Truijen-Oud, F. A., Cohen Stuart, J. W. T., Jansen, E. R., Hoogewerf, M., Rozemeijer, W., van der Reijden, W. A., Sinnige, J. C., Brinkman, K., van den Berk, G. E. L., Blok, W. L., Frissen, P. H. J., Lettinga, K. D., Schouten, W. E. M., Veenstra, J., Vrouenraets, S. M. E., Brouwer, C. J., Geerders, G. F., Hoeksema, K., Kleene, M. J., Knapen, M., van der Meche, I. B., Mulder-Seeleman, E., Toonen, A. J. M., Wijnands, S., Kwa, D., van Crevel, R., van Aerde, K., Doferhof, A. S. M., Henriet, S. S. V., ter Hofstede, H. J. 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L.J.M., Nobel H., Damen M., van Kasteren M.E.E., Berrevoets M.A.H., Brouwer A.E., Adams A., de Kruijf-Van de Wiel B.A.F.M., Keelan-Pfaf S., van der Ven B., Buiting A.G.M., Murck J.L., Versteeg D., de Vries-Sluijs T.E.M.S., Bax H.I., van Gorp E.C.M., Nouwen J.L., Rijnders B.J.A., Schurink C.A.M., Verbon A., de Jong-Peltenburg N.C., Bassant N., van Beek J.E.A., Vriesde M., van Zonneveld L.M., van den Berg-Cameron H.J., de Groot J., Boucher C.A.B., Koopmans M.P.G., van Kampen J.J.A., Fraaij P.L.A., van Rossum A.M.C., Vermont C.L., van der Knaap L.C., Visser E., Branger J., Douma R.A., Duijf-Van de Ven C.J.H.M., Schippers E.F., van Nieuwkoop C., van IJperen J.M., Geilings J., van der Hut G., van Burgel N.D., Leyten E.M.S., Gelinck L.B.S., Mollema F., Davids-Veldhuis S., Wildenbeest G.S., Heikens E., Groeneveld P.H.P., Bouwhuis J.W., Lammers A.J.J., Kraan S., van Hulzen A.G.W., Kruiper M.S.M., van der Bliek G.L., Bor P.C.J., Bloembergen P., Wolfagen M.J.H.M., Ruijs G.J.H.M., Kroon F.P., de Boer M.G.J., Scheper H., Jolink H., Dorama W., van Holten N., Claas E.C.J., Wessels E., den Hollander J.G., El Moussaoui R., Pogany K., Kastelijns M., Smit J.V., Smit E., Struik-Kalkman D., Tearno C., van Niekerk T., Pontesilli O., Lowe S.H., Oude Lashof A.M.L., Posthouwer D., Ackens R.P., Burgers K., Schippers J., Weijenberg-Maes B., van Loo I.H.M., Havenith T.R.A., Weijer S., van Vonderen M.G.A., Kampschreur L.M., Faber S., Steeman-Bouma R., Weel J., Kootstra G.J., Delsing C.E., van der Burg-Van de Plas M., Heins H., Kortmann W., van Twillert G., Renckens R., Ruiter-Pronk D., van Truijen-Oud F.A., Cohen Stuart J.W.T., Jansen E.R., Hoogewerf M., Rozemeijer W., van der Reijden W.A., Sinnige J.C., Brinkman K., van den Berk G.E.L., Blok W.L., Frissen P.H.J., Lettinga K.D., Schouten W.E.M., Veenstra J., Vrouenraets S.M.E., Brouwer C.J., Geerders G.F., Hoeksema K., Kleene M.J., Knapen M., van der Meche I.B., Mulder-Seeleman E., Toonen A.J.M., Wijnands S., Kwa D., van Crevel R., van Aerde 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Pedreira J.D., Galera C., Albendin H., Iborra A., Campillo M.A., Vidal A., Amador C., Pasquau F., Ena J., Benito C., Fenoll V., Mohamed-Balghata M.O., Gomez M.A., Alberto de Zarraga M., Rivas M.E., Gorgolas M., Svedhem-Johansson V., Flamholc L., Gisslen M., Hejdeman B., Norgren H., Wendahl S., Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, ANS - Neuroinfection & -inflammation, Internal medicine, Medical Microbiology and Infection Prevention, AMS - Rehabilitation & Development, VU University medical center, Amsterdam Gastroenterology Endocrinology Metabolism, Pediatric surgery, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pulmonary medicine, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Ethics, Law & Medical humanities, APH - Quality of Care, ACS - Pulmonary hypertension & thrombosis, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Reproduction & Development (AR&D), APH - Societal Participation & Health, Pediatrics, HAL-SU, Gestionnaire, National and Kapodistrian University of Athens (NKUA), University College of London [London] (UCL), Public Health Agency of Sweden, University of Zagreb, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Statens Serum Institut [Copenhagen], Public Health England [London], Università degli Studi di Milano = University of Milan (UNIMI), Instituto de Salud Carlos III [Madrid] (ISC), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Robert Koch Institute [Berlin] (RKI), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University of Copenhagen = Københavns Universitet (UCPH), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Hellenic Center for Disease Control and Prevention, Amsterdam UMC - Amsterdam University Medical Center, Austrian Agency for Health and Food Safety (AGES), Department of Infectious Diseases, Institution of Medicine, Karolinska University Hospital and Karolinska Institutet, Istituto Superiore di Sanita [Rome], Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University of Athens Medical School [Athens], Vourli, G, Noori, T, Pharris, A, Porter, K, Axelsson, M, Begovac, J, Cazein, F, Costagliola, D, Cowan, S, Croxford, S, Monforte, A, Delpech, V, Diaz, A, Girardi, E, Gunsenheimer-Bartmeyer, B, Hernando, V, Leierer, G, Lot, F, Nunez, O, Obel, N, Op de Coul, E, Paraskeva, D, Patrinos, S, Reiss, P, Schmid, D, Sonnerborg, A, Suligoi, B, Supervie, V, van Sighem, A, Zangerle, R, Touloumi, G, Egle, A, Kanatschnig, M, Ollinger, A, Rieger, A, Schmied, B, Wallner, E, Dewasurendra, D, Gisinger, M, Kitchen, M, Plattner, A, Rieser, E, Sarcletti, 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Capparuccia, M, Iaiani, G, Latini, A, Gagliardini, R, Plazzi, M, De Girolamo, G, Vergori, A, Cecchetto, M, Viviani, F, De Vito, A, Rossetti, B, Montagnani, F, Franco, A, Fontana Del Vecchio, R, Di Giuli, C, Caramello, P, Orofno, G, Sciandra, M, Bassetti, M, Londero, A, Manfrin, V, Battagin, G, Starnini, G, Ialungo, A, van der Valk, M, Geerlings, S, Goorhuis, A, Hovius, J, Lempkes, B, Nellen, F, van der Poll, T, Prins, J, van Vugt, M, Wiersinga, W, Wit, F, van Duinen, M, van Eden, J, Hazenberg, A, van Hes, A, Pijnappel, F, Smalhout, S, Weijsenfeld, A, Jurriaans, S, Back, N, Zaaijer, H, Berkhout, B, Cornelissen, M, Schinkel, C, Wolthers, K, Peters, E, van Agtmael, M, Bomers, M, Sigalof, K, Heitmuller, M, Laan, L, Ang, C, van Houdt, R, Jonges, M, van Prehn, J, Kuijpers, T, Pajkrt, D, Scherpbier, H, de Boer, C, van der Plas, A, van den Berge, M, Stegeman, A, Baas, S, Hage de Loof, L, Wintermans, B, Veenemans, J, Pronk, M, Ammerlaan, H, de Munnik, E, Jansz, A, Tjhie, J, Wegdam, M, Deiman, B, Scharnhorst, V, van Eeden, A, Brokking, W, Elsenburg, L, Nobel, H, Damen, M, van Kasteren, M, Berrevoets, M, Brouwer, A, Adams, A, de Kruijf-Van de Wiel, B, Keelan-Pfaf, S, van der Ven, B, Buiting, A, Murck, J, Versteeg, D, de Vries-Sluijs, T, Bax, H, van Gorp, E, Nouwen, J, Rijnders, B, Schurink, C, Verbon, A, de Jong-Peltenburg, N, Bassant, N, van Beek, J, Vriesde, M, van Zonneveld, L, van den Berg-Cameron, H, de Groot, J, Boucher, C, Koopmans, M, van Kampen, J, Fraaij, P, van Rossum, A, Vermont, C, van der Knaap, L, Visser, E, Branger, J, Douma, R, Duijf-Van de Ven, C, Schippers, E, van Nieuwkoop, C, van IJperen, J, Geilings, J, van der Hut, G, van Burgel, N, Leyten, E, Gelinck, L, Mollema, F, Davids-Veldhuis, S, Wildenbeest, G, Heikens, E, Groeneveld, P, Bouwhuis, J, Lammers, A, Kraan, S, van Hulzen, A, Kruiper, M, van der Bliek, G, Bor, P, Bloembergen, P, Wolfagen, M, Ruijs, G, Kroon, F, de Boer, M, Scheper, H, Jolink, H, Dorama, W, van Holten, N, Claas, E, Wessels, E, den Hollander, J, El Moussaoui, R, Pogany, K, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, van Niekerk, T, Pontesilli, O, Lowe, S, Oude Lashof, A, Posthouwer, D, Ackens, R, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I, Havenith, T, Weijer, S, van Vonderen, M, Kampschreur, L, Faber, S, Steeman-Bouma, R, Weel, J, Kootstra, G, Delsing, C, van der Burg-Van de Plas, M, Heins, H, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F, Cohen Stuart, J, Jansen, E, Hoogewerf, M, Rozemeijer, W, van der Reijden, W, Sinnige, J, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Vrouenraets, S, Brouwer, C, Geerders, G, Hoeksema, K, Kleene, M, Knapen, M, van der Meche, I, Mulder-Seeleman, E, Toonen, A, Wijnands, S, Kwa, D, van Crevel, R, van Aerde, K, Doferhof, A, Henriet, S, ter Hofstede, H, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F, Burger, D, Gisolf, E, Hassing, R, Claassen, M, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, van der Prijt, L, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B, Veenendaal, D, Verhagen, D, Lauw, F, van Broekhuizen, M, van Wijk, M, Bierman, W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Scholvinck, E, Stienstra, Y, Verhage, A, Wouthuyzen-Bakker, K, Boonstra, A, de Groot-De Jonge, H, van der Meulen, P, de Weerd, D, Niesters, H, van Leer-Buter, C, Knoester, M, Hoepelman, A, Arends, J, Barth, R, Bruns, A, Ellerbroek, P, Mudrikova, T, Oosterheert, J, de Regt, M, Schadd, E, van Zoelen, M, Aarsman, K, Grifoen-Van Santen, B, de Kroon, I, van Rooijen, C, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Bont, L, Geelen, S, Loefen, Y, Wolfs, T, Nauta, N, Zaheri, S, Boyd, A, Bezemer, D, Smit, C, Hillebregt, M, de Jong, A, Woudstra, T, Bergsma, D, Meijering, R, van de Sande, L, Rutkens, T, van der Vliet, S, de Groot, L, van den Akker, M, Bakker, Y, El Berkaoui, A, Bezemer, M, Bretin, N, Djoechro, E, Geerlinks, J, Kruijne, E, Lodewijk, C, Lucas, E, van der Meer, R, Munjishvili, L, Paling, F, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Schnorr, P, Tuijn, E, Veenenberg, L, Witte, E, Tuk, B, Moreno, S, del Amo, J, Dalmau, D, Navarro, M, Gonzalez, M, Blanco, J, Garcia, F, Rubio, R, Iribarren, J, Gutierrez, F, Vidal, F, Berenguer, J, Gonzalez, J, Sobrino, P, Alejos, B, Alvarez, D, Jarrin, I, Moreno, C, Munoz-Fernandez, M, Garcia-Merino, I, Rico, C, de la Fuente, J, Torre, A, Portilla, J, Merino, E, Reus, S, Boix, V, Giner, L, Gadea, C, Portilla, I, Pampliega, M, Diez, M, Rodriguez, J, Sanchez-Paya, J, Podzamczer, D, Imaz, E, Van Den Eyncle, E, Di Yacovo, S, Sumoy, M, Gomez, J, Hernandez, J, Aleman, M, Alonso, M, Hernandez, M, Diaz-Flores, F, Garcia, D, Pelazas, R, Asensi, V, Valle, E, Carton, J, Perez, V, Molina, M, Garcia, J, Carrera, E, Pulido, F, Bisbal, O, Matarranz, M, Lagarde, M, Rubio-Martin, R, Hernando, A, Bermejo, L, Dominguez, L, Arrizabalaga, J, Aramburu, M, Camino, X, Rodriguez-Arrondo, F, von Wichmann, M, Tome, L, Goenaga, M, Bustinduy, M, Galparsoro, H, Ibarguren, M, Aguado, M, Umerez, M, Masia, M, Lopez, C, Padilla, S, Navarro, A, Montolio, F, Robledano, C, Colome, J, Adsuar, A, Pascual, R, Carlos, F, Martinez, M, Fernandez, M, Garcia, E, Muga, R, Tor, J, Sanvisens, A, Bernaldo de Quiros Lopez, J, Miralles, P, Gutierrez, I, Ramirez, M, Padilla, B, Gijon, P, Carrero, A, Aldamiz-Echevarria, T, Tejerina, F, Parras, F, Balsalobre, P, Diez, C, Peraire, J, Vilades, C, Veloso, S, Vargas, M, Lopez-Dupla, M, Olona, M, Aguilar, A, Sirvent, J, Alba, V, Calavia, O, Montero, M, Lacruz, J, Blanes, M, Calabuig, E, Cuellar, S, Lopez, J, Salavert, M, de la Serna, I, Arribas, J, Montes, M, Pena, J, Arribas, B, Castro, J, Zamora, J, Perez, I, Estebanez, M, Garcia, S, Diaz, M, Alcariz, N, Mingorance, J, Montero, D, Gonzalez, A, Isabel de Jose, M, de los Santos, I, Sanz, J, Salas, A, Sarria, C, Berrocal, A, Garcia-Fraile, L, Oteo, J, Ibarra, V, Metola, L, Sanz, M, Perez-Martinez, L, Pascual, A, Ramos, C, Arazo, P, Gil, D, Jaen, A, Cairo, M, Irigoyen, D, Jordano, Q, Xercavins, M, Martinez-Lacasa, J, Velli, P, Font, R, Sanmarti, M, Ibanez, L, Rivero, M, Casado, M, Diaz, J, Uriz, J, Reparaz, J, Irigoyen, C, Arraiza, M, Segura, F, Amengual, M, Navarro, G, Sala, M, Cervantes, M, Pineda, V, Segura, V, Anton, E, Nogueras, M, Casado, J, Dronda, F, Moreno, A, Elias, M, Lopez, D, Gutierrez, C, Madrid, N, Lamas, A, Marti, P, de Diaz, A, Serrrano, S, Donat, L, Cano, A, Bernal, E, Munoz, A, Pena, A, Munoz, L, Parra, J, Alvarez, M, Chueca, N, Guillot, V, Vinuesa, D, Fernandez, J, Del Romero, J, Rodriguez, C, Puerta, T, Carrio, J, Vera, M, Ballesteros, J, Domingo, P, Sambeat, M, Lamarca, K, Mateo, G, Gutierrez, M, Fernandez, I, Antela, A, Losada, E, Riera, M, Penaranda, M, Leyes, M, Ribas, M, Campins, A, Vidal, C, Gil, L, Fanjul, F, Marinescu, C, Ribera, E, Santos, J, Marquez, M, Viciana, I, Palacios, R, Gonzalez, C, Viciana, P, Leal, M, Lopez-Cortes, L, Espinosa, N, Munoz, J, Zubero, M, Baraia-Etxaburu, J, Ibarra, S, Ferrero, O, Lopez de Munain, J, Camara, M, Lopez, I, de la Pena, M, Suarez-Garcia, I, Malmierca, E, Olalla, J, del Arco, A, de la Torre, J, Prada, J, Caracuel, Z, Lopez-Lirola, A, Lozano, A, Fernandez, E, Martinez, O, Vera, F, Martinez, L, Alcaraz, B, Jimeno, A, Poveda, E, Pernas, B, Mena, A, Grandal, M, Castro, A, Pedreira, J, Galera, C, Albendin, H, Iborra, A, Campillo, M, Vidal, A, Amador, C, Pasquau, F, Ena, J, Benito, C, Fenoll, V, Mohamed-Balghata, M, Gomez, M, Alberto de Zarraga, M, Rivas, M, Gorgolas, M, Svedhem-Johansson, V, Flamholc, L, Gisslen, M, Hejdeman, B, Norgren, H, and Wendahl, S

Subjects
Male, 0301 basic medicine, Psychological intervention, Human immunodeficiency virus (HIV), Medizin, Continuum of care, Europe, HIV infection, Key population, Sex, Anti-Retroviral Agents, Continuity of Patient Care, European Union, HIV, Humans, HIV Infections, medicine.disease_cause, key population, 0302 clinical medicine, HIV Infection, 030212 general & internal medicine, Men having sex with men, media_common, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Transmission (medicine), Infectious Diseases, AcademicSubjects/MED00290, HIV infection, continuum of care, sex, key population, Europe, Microbiology (medical), Population, Socio-culturale, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, medicine, media_common.cataloged_instance, European union, education, Pandemics, continuum of care, sex, business.industry, SARS-CoV-2, COVID-19, medicine.disease, 030112 virology, Major Articles and Commentaries, Anti-Retroviral Agent, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract

Background High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control., Standardized definitions were used to estimate a 4-stage continuum of human immunodeficiency virus (HIV) care in 11 European Union (EU) countries in 2016. The EU is close to the 90-90-90 target, with the main challenge being the percentage of undiagnosed infections.

Published
2020

42. Measuring child socio-economic position in birth cohort research: the development of a novel standardized household income indicator

Author

Costanza Pizzi, Jean-Louis Lanoë, Franco Merletti, Martine Vrijheid, Marie-Aline Charles, Virgilia Toccaceli, Matteo Richiardi, Sonia Brescianini, Daniela Zugna, Barbara Heude, Lorenzo Richiardi, Sandrine Lioret, University of Turin, University of Essex, Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Istituto Superiore di Sanita [Rome], Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Charles, Marie Aline, Università degli studi di Torino = University of Turin (UNITO), Conservatoire National des Arts et Métiers [CNAM] (CNAM), 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Socioeconomic position, Health, Toxicology and Mutagenesis, Distribution (economics), lcsh:Medicine, 030209 endocrinology & metabolism, Context (language use), Article, Body Mass Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Humans, Social inequality, 030212 general & internal medicine, Child, Children, Sociology of economics, Birth cohorts, business.industry, Socio economic position, Sociologia de l'economia, Income, France, Italy, Reference Standards, Social Class, Socioeconomic Factors, lcsh:R, 1. No poverty, Public Health, Environmental and Occupational Health, Geography, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, socioeconomic position, Household income, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Birth cohort, Body mass index, Infants
Abstract

The assessment of early life socioeconomic position (SEP) is essential to the tackling of social inequalities in health. Although different indicators capture different SEP dimensions, maternal education is often used as the only indicator in birth cohort research, especially in multi-cohort analyses. Household income, as a direct measure of material resources, is one of the most important indicators, but one that is underused because it is difficult to measure through questionnaires. We propose a method to construct a standardized, cross-cohort comparable income indicator, the &ldquo, Equivalized Household Income Indicator (EHII)&rdquo, which measures the equivalized disposable household income, using external data from the pan-European Union Statistics on Income and Living Conditions (EUSILC) surveys, and data from the cohorts. We apply this method to four studies, Piccolipi&ugrave, and NINFEA from Italy and ELFE and EDEN from France, comparing the distribution of EHII with other SEP-related variables available in the cohorts, and estimating the association between EHII and child body mass index (BMI). We found that basic parental and household characteristics may be used, with a fairly good performance, to predict the household income. We observed a strong correlation between EHII and both the self-reported income, whenever available, and other individual socioeconomic-related variables, and an inverse association with child BMI. EHII could contribute to improving research on social inequalities in health, in particular in the context of European birth cohort collaborative studies.

Published
2020

43. Towards a systematic use of effect biomarkers in population and occupational biomonitoring

Author

Nancy B. Hopf, Hans Verhagen, Emilio Benfenati, Radu Corneliu Duca, Christoph van Thriel, Imran Ali, Peter A. Behnisch, Jos Bessems, Gabriele Leng, Mariana F. Fernández, Alicia Paini, Vicente Mustieles, Anna Bal Price, Francesco Cubadda, Henriqueta Louro, Lorraine Brennan, Arthur David, Maryam Zare Jeddi, Sophie Ndaw, Susana Viegas, Robert Pasanen-Kase, Universita degli Studi di Padova, Université de Lausanne (UNIL), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), European Commission - Joint Research Centre [Ispra] (JRC), Leibniz Research Centre for Working Environment and Human Factors [Dortmund] (IFADO), Technische Universität Dortmund [Dortmund] (TU), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Institut national de recherche et de sécurité (Paris) (INRS (Paris)), Flemish Institute for Technological Research (VITO), BioDetection Systems, Laboratoire National de Santé [Luxembourg] (LNS), Istituto Superiore di Sanita [Rome], University College Dublin [Dublin] (UCD), Karolinska Institutet [Stockholm], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Laboratoire d'étude et de recherche en environnement et santé (LERES), University of Granada [Granada], CIBER de Epidemiología y Salud Pública (CIBERESP), Secrétariat d'Etat à l'économie (SECO), Health Canada, Università degli Studi di Padova = University of Padua (Unipd), Université de Lausanne = University of Lausanne (UNIL), Istituto Superiore di Sanità (ISS), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Département Santé Environnement Travail et Génie Sanitaire (DSETGS), and Universidad de Granada = University of Granada (UGR)

Subjects
ADVERSE OUTCOME PATHWAYS, 010504 meteorology & atmospheric sciences, Computer science, [SDV]Life Sciences [q-bio], 010501 environmental sciences, LYMPHOCYTES, 01 natural sciences, Occupational safety and health, Adverse outcome pathways (AOP), Biomonitoring, Adverse Outcome Pathway, PLACENTA, OXIDATIVE STRESS, lcsh:Environmental sciences, ASSOCIATIONS, General Environmental Science, Risk assessment, RISK, lcsh:GE1-350, education.field_of_study, Occupational exposure, Hazard, 3. Good health, Europe, Mixture assessment, Risk analysis (engineering), Physiologically based pharmacokinetic, Human Biomonitoring, Life Sciences & Biomedicine, Biological Monitoring, Environmental Monitoring, Adverse Outcome Pathways (AOP), Population, Environmental Genotoxicity, Environmental Sciences & Ecology, Humans, EXPOSURE, Effect Biomarkers, education, POLYMORPHISMS, BLOOD LEAD, 0105 earth and related environmental sciences, Exposure assessment, Science & Technology, Occupational health, Mechanism (biology), Physiologically based pharmacokinetic (PBPK), Adverse outcome pathway (AOP), IN-VITRO, Environmental Exposure, Exposure science, 13. Climate action, Genotoxicidade Ambiental, Environmental Sciences, Biomarkers
Abstract

Review Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general and occupational populations, and highlight their potential in monitoring humans exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary network of experts from the European chapter of the International Society for Exposure Science (ISES Europe) and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe (HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring. Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as 'omics data will aid this process. Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity. There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical mixtures. Highlights: Reliable effect biomarkers are available for most of the relevant MoAs; Increasing AOP knowledge fosters the use of effect biomarkers in regulatory context; PBK/D models allow interpretation and simulation of biomarkers of effect; An inter-regulatory setting of effect-based trigger values is demanded; Effect-biomarkers have in many cases reached a level of maturity ensuring use in mixture assessments. We would like to thank Dr, Michel Hauser from Swiss SECO, for providing the health based occupational background and Thomas Goen ¨ from German DFG and HBM Commission, Dave Marsh, Exxon Mobile UK (representing CEFIC) and Devika Poddalgoda from Health Canada for their discussions and suggestions in the OECD occupational biomonitoring subtask on effect biomarker. Moreover, we would like to thank Tiina Santonen from Finnish Institute for Occupational Health (FIOH). In addition, we specifically acknowledge the work package 14 (HBM4EU WP14) for their valuable work on the effect biomarkers. info:eu-repo/semantics/publishedVersion

Published
2020

44. National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio : a pooled analysis of 458 population-based studies in Asian and Western countries

Author

NCD Risk Factor Collaboration (NCD-RisC), [missing], Taddei, Cristina, Jackson, Rod, Zhou, Bin, Bixby, Honor, Danaei, Goodarz, Di Cesare, Mariachiara, Kuulasmaa, Kari, Hajifathalian, Kaveh, Bentham, James, Bennett, James E, Aekplakorn, Wichai, Cifkova, Renata, Dallongeville, Jean, DeBacquer, Dirk, Giampaoli, Simona, Gudnason, Vilmundur, Khang, Young-Ho, Laatikainen, Tiina, Mann, JimI, Marques-Vidal, Pedro, Mensah, George A, Müller-Nurasyid, Martina, Ninomiya, Toshiharu, Petkeviciene, Janina, Rodríguez-Artalejo, Fernando, Servais, Jennifer, Söderberg, Stefan, Stavreski, Bill, Wilsgaard, Tom, Zdrojewski, Tomasz, Zhao, Dong, Stevens, Gretchen A, Savin, Stefan, Cowan, Melanie J, Riley, Leanne M, Ezzati, Majid, Adams, Robert J, Ahrens, Wolfgang, Amouyel, Philippe, Amuzu, Antoinette, Anderssen, Sigmund A, Ariansen, Inger, Arveiler, Dominique, Aspelund, Thor, Auvinen, Juha, Avdicová, Mária, Banach, Maciej, Bandosz, Piotr, Banegas, José R, Barbagallo, Carlo M, Bata, Iqbal, Baur, Louise A, Beaglehole, Robert, Bernotiene, Gailute, Bi, Yufang, Bienek, Asako, Björkelund, Cecilia, Bo, Simona, Boehm, Bernhard O, Bonaccio, Marialaura, Bongard, Vanina, Borchini, Rossana, Borghs, Herman, Breckenkamp, Juergen, Brenner, Hermann, Bruno, Graziella, Busch, Markus A, Cabrera de León, Antonio, Capuano, Vincenzo, Casanueva, Felipe F, Casas, Juan-Pablo, Caserta, Carmelo A, Censi, Laura, Chen, Fangfang, Chen, Shuohua, Chirlaque, María-Dolores, Cho, Belong, Cho, Yumi, Chudek, Jerzy, Claessens, Frank, Clarke, Janine, Clays, Els, Cooper, Cyrus, Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Crujeiras, Ana B, Cui, Liufu, D'Arrigo, Graziella, Dauchet, Luc, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, De Smedt, Delphine, Dennison, Elaine, Deschamps, Valérie, DiCastelnuovo, Augusto, Dobson, Annette J, Donfrancesco, Chiara, Döring, Angela, Drygas, Wojciech, Du, Yong, Dziankowska-Zaborszczyk, Elzbieta, Eggertsen, Robert, Ekelund, Ulf, Elosua, Roberto, Eriksson, Johan G, Evans, Alun, Faeh, David, Felix-Redondo, Francisco J, Fernández-Bergés, Daniel, Ferrari, Marika, Ferrieres, Jean, Finn, Joseph D, Forslund, Ann-Sofie, Forsner, Maria, Frontera, Guillermo, Fujita, Yuki, Gaciong, Zbigniew, Galvano, Fabio, Gao, Jingli, Garcia-de-la-Hera, Manoli, Garnett, Sarah P, Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Gianfagna, Francesco, Gill, Tiffany K, Giovannelli, Jonathan, Goltzman, David, GonzalezGross, Marcela, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dušan, Gregor, Ronald D, Grodzicki, Tomasz, Grosso, Giuseppe, Gruden, Grabriella, Gu, Dongfeng, Guallar-Castillón, Pilar, Gudmundsson, Elias F, Guessous, Idris, Gunnlaugsdottir, Johanna, Gutzwiller, Felix, Hardy, Rebecca, Hata, Jun, Haugsgjerd, Teresa, Hayes, Alison J, He, Jiang, He, Yuna, Herrala, Sauli, TapaniHihtaniemi, Ilpo, Hobbs, Michael, Hopman, Wilma M, MaríaHuerta, José, Huybrechts, Inge, Iacoviello, Licia, Iannone, Anna G, Ikeda, Nayu, Iwasaki, Masanori, Jamrozik, Konrad, Janszky, Imre, Jarvelin, Marjo-Riitta, Jasienska, Grazyna, Jennings, Garry, Jeong, Seung-lyeal, QiangJiang, Chao, Joffres, Michel, Jokelainen, Jari J, Jonas, Jost B, Jóźwiak, Jacek, Kajantie, Eero O, Kauhanen, Jussi, Keil, Ulrich, Keinänen-Kiukaanniemi, Sirkka, Kersting, Mathilde, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Kim, Jeongseon, Kim, Yeon-Yong, Klumbiene, Jurate, Knoflach, Michael, Ko, Stephanie, Kolle, Elin, Korpelainen, Raija, Koskinen, Seppo, Kouda, Katsuyasu, Kratzer, Wolfgang, Kriemler, Susi, Krokstad, Steinar, Kujala, Urho M, Kurjata, Pawel, HingLam, Tai, Lanska, Vera, Lappas, Georg, Laugsand, Lars E, Lee, Jeonghee, Lehtimäki, Terho, Li, Yanping, Lilly, Christa L, Lin, Xu, Lind, Lars, Lissner, Lauren, Liu, Jing, Lopez-Garcia, Esther, Lorbeer, Roberto, EugenioLozano, José, Luksiene, Dalia, Lundqvist, Annamari, Lundqvist, Robert, Lytsy, Per, Ma, Guansheng, Machi, Suka, Maggi, Stefania, Magliano, Dianna J, Manzato, Enzo, Mathiesen, Ellisiv B, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, Meirhaeghe, Aline, Meisinger, Christa, Metcalf, Patricia, Mi, Jie, Miller, Jody C, Moreno, Luis A, Morin, Suzanne, Mossakowska, Malgorzata, Muiesan, Maria L, Mursu, Jaakko, Nakamura, Harunobu, Námešná, Jana, Nauck, Matthias, MariaNavarrete-Muñoz, Eva, Neal, William A, Nenko, Ilona, Niiranen, Teemu J, Ning, Guang, Noale, Marianna, Norie, Sawada, Noto, Davide, O'Neill, Terence, O'Reilly, Dermot, Oh, Kyungwon, Olafsson, Örn, MichelPaccaud, Fred, Pajak, Andrzej, Palmieri, Luigi, Panza, Francesco, Parnell, Winsome R, Peltonen, Markku, Peters, Annette, Petersmann, Astrid, Pigeot, Iris, Pilotto, Lorenza, Piwonska, Aleksandra, Plans-Rubió, Pedro, Porta, Miquel, Price, Jacqueline F, Puder, Jardena J, Puhakka, Soile E, Radisauskas, Ricardas, Raitakari, Olli, Ramos, Rafel, Redon, Josep, Rigo, Fernando, Rodriguez-Perez, MaríadelCristo, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G R, Ruidavets, Jean-Bernard, Rutkowski, Marcin, Salanave, Benoit, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Sans, Susana, Saramies, Jouko L, Saum, Kai-Uwe, Scheidt-Nave, Christa, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schöttker, Ben, Sebert, Sylvain, Sen, Abhijit, Shaw, Jonathan E, Shibuya, Kenji, WookShin, Dong, Shiri, Rahman, Simons, Judith, Simons, Leon A, Sjöström, Michael, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Solfrizzi, Vincenzo, Sonestedt, Emily, Soumare, Aicha, Staessen, Jan A, Stathopoulou, Maria G, Steene-Johannessen, Jostein, Stehle, Peter, Stieber, Jutta, Stöckl, Doris, Stokwiszewski, Jakub, Sundström, Johan, Suriyawongpaisal, Paibul, Tamosiunas, Abdonas, JooTan, Eng, Taylor, Anne, Tell, Grethe, Thijs, Lutgarde, Tolonen, HannaK, Topór-Madry, Roman, JoséTormo, María, Torrent, Maties, Tsugane, Shoichiro, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Tzourio, Christophe, Uusitalo, Hannu M T, Van Herck, Koen, Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lars, Vega, Tomas, Veronesi, Giovanni, Vioque, Jesus, Virtanen, JyrkiK, Visvikis-Siest, Sophie, Vollenweider, Peter, Voutilainen, Sari, Vrijheid, Martine, Wagner, Aline, Wagner, Anne, Wang, Ming-Dong, Wang, Qian, XingWang, Ya, Wannamethee, S Goya, Wei, Wenbin, Whincup, Peter H, Wiecek, Andrzej, Willeit, Johann, Willeit, Peter, Wojtyniak, Bogdan, Wong, Andrew, Woodward, Mark, GiwercmanWu, Aleksander, Wu, Frederick C, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yan, Weili, Yang, Xiaoguang, Ye, Xingwang, Yoshihara, Akihiro, Zambon, Sabina, Zhao, Wenhua, Imperial College London, University of Auckland [Auckland], Harvard T.H. Chan School of Public Health, Middlesex University, National Institute for Health and Welfare [Helsinki], Weill Medical College of Cornell University [New York], University of Kent [Canterbury], Mahidol University [Bangkok], Charles University [Prague] (CU), 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, Universiteit Gent = Ghent University [Belgium] (UGENT), Istituto Superiore di Sanita [Rome], Icelandic Heart Association [Kopavogur, Iceland] (IHA), Seoul National University [Seoul] (SNU), University of Otago [Dunedin, Nouvelle-Zélande], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Helmholtz-Zentrum München (HZM), Kyushu University [Fukuoka], Universidad Autonoma de Madrid (UAM), CIBER de Epidemiología y Salud Pública (CIBERESP), Umeå University, The Arctic University of Norway (UiT), Medical University of Gdańsk, Capital University of Medical Sciences [Beijing] (CUMS), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Adelaide, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), London School of Hygiene and Tropical Medicine (LSHTM), Norwegian School of Sport Sciences = Norges idrettshøgskole [Oslo] (NIH), Norwegian Institute of Public Health [Oslo] (NIPH), Université de Strasbourg (UNISTRA), University of Iceland [Reykjavik], University of Oulu, Regional Authority of Public Health [Slovaquia] (RAPH), Ministry of Health of the Slovak Republic [Slovaquia], Medical University of Łódź (MUL), Università degli studi di Palermo - University of Palermo, Dalhousie University [Halifax], The University of Sydney, Public Health Agency of Canada, University of Gothenburg (GU), University of Turin, Nanyang Technological University [Singapour], Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Università degli studi di Napoli Federico II, Faculté de Médecine [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Universität Bielefeld = Bielefeld University, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Robert Koch Institute [Berlin] (RKI), Universidad de La Laguna [Tenerife - SP] (ULL), Universidade de Santiago de Compostela [Spain] (USC ), University College of London [London] (UCL), University of Silesia in Katowice, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Southampton, Biomolécules et inflammation pulmonaire, Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Santé publique France - French National Public Health Agency [Saint-Maurice, France], University of Queensland [Brisbane], IMIM-Hospital del Mar, Generalitat de Catalunya, Queen's University [Belfast] (QUB), Universität Zürich [Zürich] = University of Zurich (UZH), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Manchester [Manchester], Kindai University, Medical University of Warsaw - Poland, Università degli studi di Catania [Catania], Geneva University Hospital (HUG), Universitá degli Studi dell’Insubria, McGill University = Université McGill [Montréal, Canada], Universidad Politécnica de Madrid (UPM), Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institute for Clinical and Experimental Medicine (IKEM), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Bergen (UiB), Tulane University, Chinese Center for Disease Control and Prevention, Oulu University Hospital [Oulu], The University of Western Australia (UWA), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Niigata University, Norwegian University of Science and Technology (NTNU), Simon Fraser University (SFU.ca), University of Eastern Finland, Westfälische Wilhelms-Universität Münster (WWU), Innsbruck Medical University [Austria] (IMU), Universitätsklinikum Ulm - University Hospital of Ulm, University of Jyväskylä (JYU), The University of Hong Kong (HKU), Sahlgrenska Academy at University of Gothenburg [Göteborg], Tampere University Hospital, University of Tampere [Finland], West Virginia University [Morgantown], University of Chinese Academy of Sciences [Beijing] (UCAS), Uppsala Universitet [Uppsala], Universität Greifswald - University of Greifswald, Peking University [Shenzhen], The Jikei University School of Medicine, Baker Heart and Diabetes Institute (AUSTRALIA), Universita degli Studi di Padova, University of Edinburgh, University of Zaragoza - Universidad de Zaragoza [Zaragoza], International Institute of Molecular and Cell Biology [Warsaw] (IIMCB), Università degli Studi di Brescia [Brescia], Konan University [Kobe, Japan], University of Turku, Shanghai Jiao Tong University School of Medicine, Department of Epidemiology and Biostatistics, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, Department of Epidemiology, Health Economics and Public Health, UMR 558 INSERM, Université de Toulouse, Centre Hospitalier Universitaire de Toulouse, Unité de Surveillance et d'Epidémiologie Nutritionnelle (USEN), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut de Veille Sanitaire (INVS)-Université Paris 13 (UP13), Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain, parent, Department of Chronic Disease Prevention, Institute for plasma research, Institute for Plasma Research, Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Department of Reproductive Endocrinology, University of Bari Aldo Moro (UNIBA), Nutritional Epidemiology, Department of Clinical Sciences, Clinical Research Center, Lund University [Lund]-Lund University [Lund], Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Applied Food Science, Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Research Unit Hypertension and Cardiovascular Epidemiology [Louvain, Belgique], Studies Coordinating Centre [Louvain, Belgique], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), National Cancer Center, University of Kuopio, Epidémiologie cardiovasculaire et métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Tampere University, Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Norwegian University of Science and Technology [Trondheim] (NTNU), Departamento de Salud Pública, Universidad Miguel Hernández [Elche] (UMH), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Department of Internal Medicine, School of Public Health and Clinical Nutrition, Epidemiologia Ambiental, Centre for Research in Environmental Epidemiology (CREAL)-Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP) of Pamplona-Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Department of Epidemiology and Public Health, EA 3430, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Medical University of Silesia (SUM), University of Innsbruck, National Institute of Hygiene Warsaw, The Georges Institute for International Health, Naval Research Laboratory (NRL), Grant numbers 101506/Z/13/Z and Research Training Fellowship 203616/Z/16/Z, Ministry of Health of the Czech Republic (grant number 15-27109A), UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología, HUS Children and Adolescents, Department of Public Health, Universidad Autónoma de Madrid (UAM), Università degli studi di Torino = University of Turin (UNITO), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), CHU Toulouse [Toulouse], Université Paris 13 (UP13)-Institut de Veille Sanitaire (INVS)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM), Taddei, C, Zhou, B, Bixby, H, Danaei, G, Di Cesare, M, Kuulasmaa, K, Hajifathalian, K, Bentham, J, Bennett, JE, Aekplakorn, W, Cifkova, R, Dallongeville, J, DeBacquer, D, Giampaoli, S, Gudnason, V, Khang, Y-O, Laatikainen, T, Mann, JI, Marques-Vidal, P, Mensah, GA, Müller-Nurasyid, M, Ninomiya, T, Petkeviciene, J, Rodríguez-Artalejo, F, Servais, J, Söderberg, S, Stavreski, B, Wilsgaard, T, Zdrojewski, T, Zhao, D, Stevens, GA, Savin, S, Cowan, Mj, Riley, LM, Ezzati, M, Adams, R, Ahrens, W, Amouyel, P, Amuzu, A, Anderssen, SA, Ariansen, I, Arveiler, D, Aspelund, T, Auvinen, A, Avdicová, M, Banach, M, Bandosz, P, Banegas. JR, Barbagallo, CM, Bata, I, Baur, LA, Beaglehole, R, Bennet, JE, Bernotiene, G, Bi, Y, Bienek, A, Björkelund, C, Bo, S, Boehm, BO, Bonaccio, M, Bongard, V, Borchini, R, Borghs, H, Breckenkamp, J, Brenner, H, Bruno, G, Busch, MA, CabreradeLeón, A, Capuano, V, Casanueva, FF, Casas, J-P, Caserta, CA, Censi, L, Chen, F, Chen, S, Chirlaque, M-D, Cho, B, Cho, Y, Chudek, J, Claessens, F, Clarke, J, Clays, E, Cooper, C, Costanzo, S, Cottel, D, Cowell C, Crujeiras, AB, Cui, L, D'Arrigo, G, Dauchet, L, De Backer, G, De Bacquer, D, de Gaetano, G, De Henauw, S, De Smedt, D, Dennison, E, Desschamps, V, Di Castelnuovo, A, Dobson, AJ, Donfrancesco, C, Döring, A, Doua, K, Drygas, W, Du, Y, Dziankowska-Zaborszczyk, E, Eggertsen, R, Ekelund, U, Elousa, R, Eriksson, JG, Evans, A, Faeh, D, Felix-Redondo, FJ, Fernández-Bergés, D, Ferrari, M, Ferrieres, J, Finn, JD, Forslund, A-S, Forsner, M, Frontera, G, Fujita, Y, Gaciong, Z, Galvano, F, Gao, J, Garcia-de-la-Hera, M, Garnett, SP, Gaspoz, J-M, Gasul, L, Gates, L, Gianfagna, F, Gill, TK, Giovannelli, J, Goltzman, D, GonzalezGross, M, Gottrand, F, Graff-Iversen, S, Grafnetter, D, Gregor, RD, Grodzicki, T, Grosso, G, Gruden, G, Gu, D, Guallar-Castillón, P, Gudmundsson, EF, Guessous, I, Gunnlaugsdottir J, Gutzwiller, F, Hardy, R, Hata, J, Haugsgjerd, T, Hayes, AJ, He, H, He, Y, Herrala, S, Hihtaniemi, IP, Hobbs, M, Hopman, WM, Huerta, JM, Huybrechts, I, Iacoviello, L, Iannone, AG, Ikeda, N, Iwasaki, M, Jackson, R, Jamrozi, K, Janszky, I, Jarvelin, M-R, Jasienska, G, Jennings, G, Jeong, S-L, Jiang, CQ, Joffres, M, Jokelainen, JJ, Jonas, JB, Jóźwiak, J, Kajantie, EO, Kauhanen, K, Keil, U, Keinänen-Kiukaanniemi, S, Kersting, M, Khang, Y-H, Kiechl-Kohlendorfer, U, Kiechl, S, Kim, J, Kim, Y-Y, Klumbiene, J, Knoflach, M, Ko, S, Kolle, E, Korpelainen, R, Koskinen, S, Kouda, K, Kratzer, W, Kriemler, S, Krokstad, S, Kujala,UM, Kurjata, P, Lam, TH, Lanska, V, Lappas , G, Laugsand, LE, Lee, J, Lehtimäki, T, Li, Y, Lilly, C, Lin, X, Lind, L, Lissner, L, Liu, J, Lopez-Garcia, E, Lorbeer, R, Lozano, JE, Luksiene, D, Lundqvist, A, Lundqvist, R, Lytsy, P, Ma, G, Machi, S, Maggi, S, Magliano, DJ, Manzato, E, Mathiesen, EB, McLachlan, S, McLean, RM, Meirhaeghe, A, Metcalf, P, Mi, JM, Miller, JC, Moreno, LA, Morin, S, Mossakowska, M, Muiesan, ML, Mursu, J, Nakamura, H, Námešná, J, Navarrete-Muñoz, EM, Neal, WA, Nenko, I, Niiranen, T, Ning, G, Noale, M, Norie, S, Noto, Davide, O’Neill, T, O'Reilly, D, Oh, K, Olafsson, O, Paccaud, F, Pajak, A, Palmieri, L, Panza, F, Parnell, WR, Peltonen, M, Peters, A, Petersmann, A, P Pigeot, I, Pilotto, L, Piwonska, A, Pedro Plans-Rubió, P, Porta, M, Price, JF, Puder, JJ, Puhakka, SE, Radisauskas, R, Raitakari, O, Ramos, R, Redon, J, Rigo, F, Rodriguez-Perez, MdC, Romaguera, D, Ronkainen, K, Rosengren, A, Roy, JGR, Ruidavets, JB, Rutkowski, M, Salanave, B, Salmeron, D, Salomaa, V, Salonen, JT, Salvetti, M, Sans, S, Saramies, JL, Saum, K-U, Scheidt-Nave, C, Schienkiewitz, A, Schipf, S, Schmidt, CO, Schottker, B, Sebert S, Sen, A, Shaw, JE, Shibuya, K, Shin, DO, Shiri, R, Simons, J, Simons, LA, Sjostrom, M, Slowikowska-Hilczer, J, Slusarczyk, P, Solfrizzi, V, Sonestedt, E, Soumare, A, Staessen, JA, Stathopoulou, MG, Steene-Johannessen, J, Stehle, P, Stieber, J, Stöckl, D, Stokwiszewski, J, Sundström, J, Suriyawongpaisal, P, Tamosiunas, A, Tan, E, Taylor, A, Tell, G, Thijs, L, Tolonen, HK, Topór-Madry, R, Tormo, MJ, Torrent, M, Tsugane, S, Tuomainen, T-P, Tuomilehto, J, Tzourio, C, Uusitalo, HMT, Van Herck, K, Vanderschueren, D, Vanuzzo, D, Vatten, L, Vega, T, Veronesi, G, Vioque, P, Virtanen, JK, Visvikis-Siest, S, Vollenweider, P, Voutilainen, S, Vrijheid, M, Wagner, A, Wang, M-D, Wang, Q, Wang YX, Wannamethee, SG, Wei, W, Whincup, PH, Wiecek, A, Willeit, J, Willeit, P, Wojtyniak, B, Wong, A, Woodward, M, Wu, FC, JianFeng Wu, JF, Wu, SL, Xu, H, Xu, L, Yan, W, Yang, X, Ye, X, Yoshihara, A, Zambon, S, Zhao, W, NCD Risk Factor Collaboration (NCD-RisC), Jackson, R., Zhou, B., Bixby, H., Danaei, G., Di Cesare, M., Kuulasmaa, K., Hajifathalian, K., Bentham, J., Bennett, J.E., Aekplakorn, W., Cifkova, R., Dallongeville, J., DeBacquer, D., Giampaoli, S., Gudnason, V., Khang, Y.H., Laatikainen, T., Mann, J., Marques-Vidal, P., Mensah, G.A., Müller-Nurasyid, M., Ninomiya, T., Petkeviciene, J., Rodríguez-Artalejo, F., Servais, J., Söderberg, S., Stavreski, B., Wilsgaard, T., Zdrojewski, T., Zhao, D., Stevens, G.A., Savin, S., Cowan, M.J., Riley, L.M., Ezzati, M., Adams, R.J., Ahrens, W., Amouyel, P., Amuzu, A., Anderssen, S.A., Ariansen, I., Arveiler, D., Aspelund, T., Auvinen, J., Avdicová, M., Banach, M., Bandosz, P., Banegas, J.R., Barbagallo, C.M., Bata, I., Baur, L.A., Beaglehole, R., Bernotiene, G., Bi, Y., Bienek, A., Björkelund, C., Bo, S., Boehm, B.O., Bonaccio, M., Bongard, V., Borchini, R., Borghs, H., Breckenkamp, J., Brenner, H., Bruno, G., Busch, M.A., Cabrera de León, A., Capuano, V., Casanueva, F.F., Casas, J.P., Caserta, C.A., Censi, L., Chen, F., Chen, S., Chirlaque, M.D., Cho, B., Cho, Y., Chudek, J., Claessens, F., Clarke, J., Clays, E., Cooper, C., Costanzo, S., Cottel, D., Cowell, C., Crujeiras, A.B., Cui, L., D'Arrigo, G., Dauchet, L., De Backer, G., De Bacquer, D., de Gaetano, G., De Henauw, S., De Smedt, D., Dennison, E., Deschamps, V., DiCastelnuovo, A., Dobson, A.J., Donfrancesco, C., Döring, A., Drygas, W., Du, Y., Dziankowska-Zaborszczyk, E., Eggertsen, R., Ekelund, U., Elosua, R., Eriksson, J.G., Evans, A., Faeh, D., Felix-Redondo, F.J., Fernández-Bergés, D., Ferrari, M., Ferrieres, J., Finn, J.D., Forslund, A.S., Forsner, M., Frontera, G., Fujita, Y., Gaciong, Z., Galvano, F., Gao, J., Garcia-de-la-Hera, M., Garnett, S.P., Gaspoz, J.M., Gasull, M., Gates, L., Gianfagna, F., Gill, T.K., Giovannelli, J., Goltzman, D., GonzalezGross, M., Gottrand, F., Graff-Iversen, S., Grafnetter, D., Gregor, R.D., Grodzicki, T., Grosso, G., Gruden, G., Gu, D., Guallar-Castillón, P., Gudmundsson, E.F., Guessous, I., Gunnlaugsdottir, J., Gutzwiller, F., Hardy, R., Hata, J., Haugsgjerd, T., Hayes, A.J., He, J., He, Y., Herrala, S., TapaniHihtaniemi, I., Hobbs, M., Hopman, W.M., MaríaHuerta, J., Huybrechts, I., Iacoviello, L., Iannone, A.G., Ikeda, N., Iwasaki, M., Jamrozik, K., Janszky, I., Jarvelin, M.R., Jasienska, G., Jennings, G., Jeong, S.L., QiangJiang, C., Joffres, M., Jokelainen, J.J., Jonas, J.B., Jóźwiak, J., Kajantie, E.O., Kauhanen, J., Keil, U., Keinänen-Kiukaanniemi, S., Kersting, M., Kiechl-Kohlendorfer, U., Kiechl, S., Kim, J., Kim, Y.Y., Klumbiene, J., Knoflach, M., Ko, S., Kolle, E., Korpelainen, R., Koskinen, S., Kouda, K., Kratzer, W., Kriemler, S., Krokstad, S., Kujala, U.M., Kurjata, P., HingLam, T., Lanska, V., Lappas, G., Laugsand, L.E., Lee, J., Lehtimäki, T., Li, Y., Lilly, C.L., Lin, X., Lind, L., Lissner, L., Liu, J., Lopez-Garcia, E., Lorbeer, R., EugenioLozano, J., Luksiene, D., Lundqvist, A., Lundqvist, R., Lytsy, P., Ma, G., Machi, S., Maggi, S., Magliano, D.J., Manzato, E., Mathiesen, E.B., McLachlan, S., McLean, R.M., McLean, S.B., Meirhaeghe, A., Meisinger, C., Metcalf, P., Mi, J., Miller, J.C., Moreno, L.A., Morin, S., Mossakowska, M., Muiesan, M.L., Mursu, J., Nakamura, H., Námešná, J., Nauck, M., MariaNavarrete-Muñoz, E., Neal, W.A., Nenko, I., Niiranen, T.J., Ning, G., Noale, M., Norie, S., Noto, D., O'Neill, T., O'Reilly, D., Oh, K., Olafsson, Ö., MichelPaccaud, F., Pajak, A., Palmieri, L., Panza, F., Parnell, W.R., Peltonen, M., Peters, A., Petersmann, A., Pigeot, I., Pilotto, L., Piwonska, A., Plans-Rubió, P., Porta, M., Price, J.F., Puder, J.J., Puhakka, S.E., Radisauskas, R., Raitakari, O., Ramos, R., Redon, J., Rigo, F., Rodriguez-Perez, M., Romaguera, D., Ronkainen, K., Rosengren, A., Ruidavets, J.B., Rutkowski, M., Salanave, B., Salmerón, D., Salomaa, V., Salonen, J.T., Salvetti, M., Sans, S., Saramies, J.L., Saum, K.U., Scheidt-Nave, C., Schienkiewitz, A., Schipf, S., Schmidt, C.O., Schöttker, B., Sebert, S., Sen, A., Shaw, J.E., Shibuya, K., WookShin, D., Shiri, R., Simons, J., Simons, L.A., Sjöström, M., Slowikowska-Hilczer, J., Slusarczyk, P., Solfrizzi, V., Sonestedt, E., Soumare, A., Staessen, J.A., Stathopoulou, M.G., Steene-Johannessen, J., Stehle, P., Stieber, J., Stöckl, D., Stokwiszewski, J., Sundström, J., Suriyawongpaisal, P., Tamosiunas, A., JooTan, E., Taylor, A., Tell, G., Thijs, L., Tolonen, H., Topór-Madry, R., JoséTormo, M., Torrent, M., Tsugane, S., Tuomainen, T.P., Tuomilehto, J., Tzourio, C., Van Herck, K., Vanderschueren, D., Vanuzzo, D., Vatten, L., Vega, T., Veronesi, G., Vioque, J., Virtanen, J., Visvikis-Siest, S., Vollenweider, P., Voutilainen, S., Vrijheid, M., Wagner, A., Wang, M.D., Wang, Q., XingWang, Y., Wannamethee, S.G., Wei, W., Whincup, P.H., Wiecek, A., Willeit, J., Willeit, P., Wojtyniak, B., Wong, A., Woodward, M., GiwercmanWu, A., Wu, F.C., Wu, S., Xu, H., Xu, L., Yan, W., Yang, X., Ye, X., Yoshihara, A., Zambon, S., Zhao, W., Universiteit Gent = Ghent University (UGENT), Istituto Superiore di Sanità (ISS), Helmholtz Zentrum München = German Research Center for Environmental Health, Kyushu University, The Arctic University of Norway [Tromsø, Norway] (UiT), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Catania = University of Catania (Unict), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Università degli Studi di Padova = University of Padua (Unipd), Università degli Studi di Brescia = University of Brescia (UniBs), Service Epidémiologie clinique et santé publique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Laboratoire Chrono-environnement (UMR 6249) (LCE), Leopold Franzens Universität Innsbruck - University of Innsbruck, National Institute of Public Health - National Institute of Hygiene [Poland], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Medical University of Silesia, Katowice, University of Helsinki, National Institute for Health and Welfare, University of Helsinki, University of Helsinki, and University of Helsinki, Finnish Institute of Occupational Health

Subjects
Male, gupo de ascendencia continental asiática, Settore MED/09 - Medicina Interna, Total Cholesterol, Ldl Cholesterol, Hdl Cholesterol, Blood Lipids, Multi-country Study, Epidemiology, kolesteroli, humanos, Blood lipids, BLOOD-PRESSURE, 030204 cardiovascular system & hematology, triglicéridos, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, HDL cholesterol, Medicine and Health Sciences, CARDIOVASCULAR RISK-FACTORS, Medicine, 030212 general & internal medicine, mediana edad, lípidos, Public, Environmental & Occupational Health, 2. Zero hunger, anciano, education.field_of_study, Age Factors, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Middle Aged, colesterol, adulto, kansainvälinen vertailu, Lipids, 3142 Public health care science, environmental and occupational health, 3. Good health, Europe, Cholesterol, Population Surveillance, LDL cholesterol, SERUM-LIPIDS, Female, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, Adult, Asian Continental Ancestry Group, Canada, Total cholesterol, blood lipids, multi-country study, medicine.medical_specialty, Asia, Medicina, European Continental Ancestry Group, Population, Nursing, HDL-kolesteroli, White People, DIETARY-FAT, 03 medical and health sciences, Sex Factors, Asian People, kansanterveys, vigilancia de la población, Humans, CORONARY-HEART-DISEASE, ddc:610, LDL-kolesteroli, education, Triglycerides, METAANALYSIS, Aged, INDIVIDUAL DATA, Science & Technology, business.industry, Omvårdnad, blood lipid, Cholesterol, HDL, Ecological study, nutritional and metabolic diseases, Cholesterol, LDL, United States, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Cholesterol/blood, Lipids/blood, Population Surveillance/methods, Triglycerides/blood, chemistry, WORLDWIDE TRENDS, Multi-country study, grupo de ascendencia continental europea, business, HIGH-DENSITY-LIPOPROTEIN, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography, Lipoprotein
Abstract

Artículo con numerosos autores. Sólo quedan reflejados el primero, los pertenecientes a la UAM y el colectivo, Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and non-HDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since ∼1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at ∼0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as ∼0.7 per decade in Swiss men (equivalent to ∼26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol., This work was supported by the Wellcome Trust (grant numbers 101506/Z/13/Z and Research Training Fellowship 203616/Z/16/Z). R.C. acknowledges funding from the Ministry of Health of the Czech Republic (grant number 15-27109A)

Published
2020

45. Where are the landfilled zones? Use of historical geographic information and local spatial knowledge to determine the location of underground asbestos contamination in Sibaté (Colombia)

Author

Benjamin Lysaniuk, Roberto Pasetto, Daniela Marsili, María Fernanda Cely-García, Pietro Comba, Juan Pablo Ramos-Bonilla, Agata Mazzeo, Lysaniuk P., M.F. Cely-García, A. Mazzeo, D. Marsili, R. Pasetto, P. Comba, J.P. Ramos-Bonilla, Pôle de recherche pour l'organisation et la diffusion de l'information géographique (PRODIG (UMR_8586 / UMR_D_215 / UM_115)), Université Paris 1 Panthéon-Sorbonne (UP1)-Institut de Recherche pour le Développement (IRD)-AgroParisTech-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Universidad de los Andes [Bogota] (UNIANDES), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Istituto Superiore di Sanita [Rome], Université Paris 1 Panthéon-Sorbonne (UP1)-Institut de Recherche pour le Développement (IRD)-AgroParisTech-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Istituto Superiore di Sanità (ISS), and ANR-18-CE03-0001,AMAGRI,Antimicrobiens en agriculture : acteurs, pratiques, conflits(2018)

Subjects
Sibate, Aerial photographs, Population, 010501 environmental sciences, Colombia, medicine.disease_cause, Urban area, 01 natural sciences, Biochemistry, Asbestos, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Drainage system (geomorphology), Occupational Exposure, 11. Sustainability, medicine, 030212 general & internal medicine, Cities, education, Sibaté, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, General Environmental Science, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, education.field_of_study, geography.geographical_feature_category, Landfilled zones, business.industry, Participatory workshops, Environmental resource management, Environmental exposure, [SHS.GEO]Humanities and Social Sciences/Geography, Spatial knowledge, Current (stream), Historical topographic maps, Waste Disposal Facilities, Geography, Asbestos Environmental exposure Historical topographic maps Aerial photographs Participatory workshops Landfilled zones Sibaté Colombia, 13. Climate action, Geographic analysis, [SHS.ENVIR]Humanities and Social Sciences/Environmental studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business
Abstract

Introduction Sibate is a municipality located in the central region of Colombia, where the first asbestos-cement facility of the country has been in operation since 1942. Both a malignant pleural mesothelioma cluster and landfilled zones with the presence of an underground friable asbestos layer have been identified in Sibate. There is still limited knowledge regarding the history of the construction of landfilled zones, and what kinds of materials were deposited. The current study aims to improve our understanding of the history and characteristics of the landfilled zones present in Sibate. Methods Two participatory workshops with inhabitants of Sibate were conducted to determine when the landfilled zones were built and their location. Information collected in participatory workshops was crossed with both topographic maps and aerial photographs, giving special attention to zones within the urban area of the municipality that in the past were inundated with water from El Muna Reservoir. An opportunistic soil sampling campaign was conducted in suspected landfilled zones that had not been previously sampled, during the replacement of pipelines of the drainage system ordered by the municipality. Results The analysis of historical topographic maps, combined with the interpretation of aerial photographs, confirmed the disposal of residues in areas that were previously inundated with water from El Muna Reservoir, creating landfilled zones in the urban area of Sibate. On top of these landfilled zones, a football stadium and a football field with an athletic track were built. The location of landfilled zones identified using geographic analysis was similar to the location identified analyzing maps constructed by inhabitants of Sibate in participatory workshops. The four soil samples collected during an opportunistic sampling campaign confirmed the presence in new locations of the underground friable asbestos layer discovered in previous studies. Discussion Based on the extension of the landfilled zones, the presence of friable asbestos in these areas, and the close proximity to a school and residential dwellings, there could have been major dispersion events of asbestos fibers in the urban area of Sibate during the disposal of residue materials and the construction of the landfilled zones. Thus, important asbestos exposures may have occurred among residents of Sibate, which is aggravated by the fact that during those years, more than 50% of the population of Sibate was 25 years old or younger. Although the results of the current study improved our understanding of the processes and chronology associated with the landfilled zones, the uncertainty regarding their exact location remains significant. It is important to continue investigating the adverse health effects resulting from this potential asbestos exposure source.

Published
2020

46. Update on Giardia : Highlights from the seventh International Giardia and Cryptosporidium Conference

Author

Andre G. Buret, Loïc Favennec, Simone M. Cacciò, Staffan G. Svärd, University of Calgary, Istituto Superiore di Sanita [Rome], Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Uppsala University

Subjects
0301 basic medicine, Giardiasis, medicine.medical_specialty, Epidemiology, Veterinary (miscellaneous), Ecology (disciplines), Cell- och molekylärbiologi, Pharmacy, Review Article, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Basic knowledge, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, lcsh:RC109-216, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, biology, business.industry, Public health, Giardia, Cryptosporidium, Genomics, 030108 mycology & parasitology, Public relations, biology.organism_classification, 3. Good health, 030104 developmental biology, Infectious Diseases, One Health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Insect Science, Animal Science and Zoology, Parasitology, business, Cell and Molecular Biology
Abstract

Although Giardia duodenalis is recognized as one of the leading causes of parasitic human diarrhea in the world, knowledge of the mechanisms of infection is limited, as the pathophysiological consequences of infection remain incompletely elucidated. Similarly, the reason for and consequences of the very specific genome-organization in this parasite with 2 active nuclei is only partially known. Consistent with its tradition, the 7th International Giardia and Cryptosporidium Conference (IGCC 2019) was held from June 23 to 26, 2019, at the Faculty of Medicine and Pharmacy of the University of Rouen-Normandie, France, to discuss current research perspectives in the field. This renowned event brought together an international delegation of researchers to present and debate recent advances and identify the main research themes and knowledge gaps. The program for this interdisciplinary conference included all aspects of host-parasite relationships, from basic research to applications in human and veterinary medicine, as well as the environmental issues raised by water-borne parasites and their epidemiological consequences. With regard to Giardia and giardiasis, the main areas of research for which new findings and the most impressive communications were presented and discussed included: parasite ecology and epidemiology of giardiasis, Giardia-host interactions, and cell biology of Giardia, genomes and genomic evolution. The high-quality presentations discussed at the Conference noted breakthroughs and identified new opportunities that will inspire researchers and funding agencies to stimulate future research in a “one health” approach to improve basic knowledge and clinical and public health management of zoonotic giardiasis. Bien que Giardia duodenalis soit reconnu comme l’une des principales causes de diarrhée parasitaire humaine dans le monde, la connaissance des mécanismes de l’infection est limitée, car ses conséquences physiopathologiques restent incomplètement élucidées. De même, la raison et les conséquences de l’organisation génomique très spécifique de ce parasite à deux noyaux actifs ne sont que partiellement connues. Conformément à sa tradition, la 7ème Conférence internationale sur Giardia et Cryptosporidium (IGCC 2019) s’est tenue du 23 au 26 juin 2019, à la Faculté de médecine et de pharmacie de l’Université de Rouen-Normandie, France, pour discuter des perspectives de recherche actuelles dans ce champ. Cet événement de renom a réuni une délégation internationale de chercheurs pour présenter et débattre des avancées récentes et identifier les principaux thèmes de recherche et les lacunes dans les connaissances. Le programme de cette conférence interdisciplinaire comprenait tous les aspects des relations hôtes-parasites, de la recherche fondamentale aux applications en médecine humaine et vétérinaire, ainsi que les problèmes environnementaux soulevés par les parasites d’origine hydrique et leurs conséquences épidémiologiques. En ce qui concerne Giardia et la giardiase, les principaux domaines de recherche pour lesquels de nouvelles découvertes et les communications les plus impressionnantes ont été présentées et discutées comprenaient : l’écologie parasitaire et l’épidémiologie de la giardiase, les interactions Giardia-hôte, la biologie cellulaire de Giardia, les génomes et l’évolution génomique. Les présentations de haute qualité discutées lors de la conférence ont noté des avancées et identifié de nouvelles opportunités qui inspireront les chercheurs et les agences de financement à stimuler la recherche future dans une approche « une seule santé » pour améliorer les connaissances de base et la gestion clinique et de santé publique de la giardiase zoonotique.

Published
2020

47. Parasites & vectors, 13: 236

Author

Rossi, Patrizia, Tamarozzi, Francesca, Galati, Fabio, Akhan, Okan, Cretu, Carmen Michaela, Vutova, Kamenna, Siles-Lucas, Mar, Brunetti, Enrico, Casulli, Adriano, the ERCE network, European Commission, Ministero della Salute, Siles Lucas, Mar [0000-0002-1257-2562], Casulli, Adriano [0000-0001-9183-7591], Siles Lucas, Mar, Casulli, Adriano, Istituto Superiore di Sanita [Rome], Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Centre Hospitalier Universitaire de Reims (CHU Reims)

Subjects
0301 basic medicine, Register (sociolinguistics), Male, medicine.medical_specialty, Databases, Factual, Public health awareness, 030106 microbiology, 030231 tropical medicine, Treatment outcome, Biology, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Echinococcosis, Epidemiology, Clinical information, medicine, Prevalence, Animals, Humans, lcsh:RC109-216, Registries, Case series, Lung, Medical attention, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Cystic echinococcosis, Public health, Research, Neglected Diseases, Register, medicine.disease, 3. Good health, Echinococcus, Clinical trial, Europe, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Italy, Liver, Parasitology, Female, Medical emergency, Public Health
Abstract

10 páginas, 3 tablas, 4 figuras, Background: The real burden of human cystic echinococcosis (CE) remains elusive, due to the peculiar characteristics of the disease and the heterogeneous and incomplete data recording of clinical cases. Furthermore, official notification systems do not collect pivotal clinical information, which would allow the comparison of different treatment outcomes, and thus circumvent the difficulty of implementing clinical trials for CE. The Italian Register of CE (RIEC) was launched in 2012 and expanded in 2014 into the European Register of CE (ERCE). The primary aim of the ERCE was to highlight the magnitude of CE underreporting, through the recording of cases that were not captured by official records. We present an overview of data collated in the ERCE and discuss its future, five years after its inception. Methods: The ERCE database was explored on March 31st 2019; data concerning participating centres and registered cases were descriptively analysed. Results: Forty-four centres from 15 countries (7 non-European) were affiliated to the ERCE. Thirty-four centres (77%) registered at least one patient; of these, 18 (53%) recorded at least one visit within the past 18 months. A total of 2097 patients were registered, 19.9% of whom were immigrants. Cyst characteristics were reported for at least one cyst at least in one visit in 1643 (78.3%) patients, and cyst staging was used by 27 centres. In total, 3386 cysts were recorded at first registration; mostly located in the liver (75.5%). Data concerning clinical management could be analysed for 920 “cyst stage-location-management” observations, showing great heterogeneity in the implementation of the stage-specific management approach recommended by the WHO. Conclusions: The ERCE achieved its goal in showing that CE is a relevant but neglected public health problem in Europe and beyond, since a proportion of patients reaching medical attention are not captured by official notification systems. The ERCE may provide a valuable starting platform to complement hospital-derived data, to obtain a better picture of the epidemiology of clinical CE, and to collect clinical data for the issue of evidence-based recommendations. The ERCE will be expanded into the International Register of CE (IRCE) and restructured aiming to overcome its current criticalities and fulfil these aims, RIEC development received funding through the Research Project IZSSA07/10RC to Dr. Giovanna Masala (Sardinian Experimental Zooprophylactic Institute, Sassari, Italy), subcontracted to Enrico Brunetti, University of Pavia, Italy. The amendment of RIEC and development of the ERCE was funded through the European Commission, under the Seventh Framework Programme (FP7, Theme Health.2013.2.3.4-1, grant agreement. no. 602051, Project HERACLES: Human Cystic Echinococcosis ReseArch in Central and Eastern Societies; http://www.herac les-fp7.eu/) to Adriano Casulli, Istituto Superiore di Sanità, Rome, Italy. ERCE activities are currently supported by EULAC Health (http://eulac healt h.eu/) and the Italian Ministry of Health - PERITAS project (molecular ePidemiological studiEs on pathways of tRansmIssion and long lasTing cApacity building to prevent cyStic echinococcosis infection) to Adriano Casulli, Istituto Superiore di Sanità, Rome, Italy.

Published
2020

48. Distribution of influenza virus types by age using case-based global surveillance data from twenty-nine countries, 1999-2014

Author

François G. Schellevis, Raquel Guiomar, Zhibin Peng, Phuong Vu Mai Hoang, Brechla Moreno, Juan Yang, Cheryl Cohen, Lynnette Brammer, Jenny Lara, Hongjie Yu, Mai thi Quynh Le, Joshua A. Mott, Rodrigo Fasce, Gabriela Kusznierz, Simona Puzelli, Doménica de Mora, Leticia Castillo, Selim Badur, Akerke Ospanova, Vernon J. Lee, Liza Lopez, Richard Njouom, Douglas M. Fleming, Coulibaly Daouda, Nurhayati, Juan Manuel Rudi, Clotilde El-Guerche Séblain, Li Wei Ang, Joseph S. Bresee, Celina de Lozano, Sonam Gyeltshen, Maria Zambon, Maria Luisa Matute, Norosoa Harline Razanajatovo, Saverio Caini, Amal Barakat, Marie-Astrid Vernet, Alla Mironenko, Angel Balmaseda, Alexey Clara, Walquiria Aparecida Ferreira de Almeida, Richard Pebody, Herman Kosasih, Cláudio Maierovitch Pessanha Henriques, Marietjie Venter, Caterina Rizzo, Meral Akcay Ciblak, Olha Holubka, Gideon O. Emukule, Fatima el Falaki, Winston Andrade, Herve A. Kadjo, Alfredo Bruno, Kate Pennington, Lyazzat Kiyanbekova, Ana Paula Rodrigues, Rhonda Owen, John Paget, Peter Spreeuwenberg, Sue Q. Huang, Jean-Michel Heraud, Sonam Wangchuk, Luzhao Feng, Netherlands Institute for Health Services Research, Instituto Nacional de Enfermedades Respiratorias 'Dr. Emilio Coni', Department of Health and Ageing, Influenza Surveillance Section, Surveillance Branch, Office of Health Protection (DHAISS), Department of Health and Ageing, Influenza Surveillance Section, Surveillance Branch, Office of Health Protection, Woden, ACT, Australia, Office of Health Protection, Woden, ACT, Australia (DHAISS), Ministry of Health [Bhoutan], Ministry of Health [Brasília, Brazil], Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Instituto de Salud Pública de Chile (ISP), Chinese Centre for Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ministry of Health [Costa Rica], Instituto Nacional de Investigación en Salud Pública [Guayaquil, Ecuador] (INSPI), Ministerio de Salud de El Salvador (MINSAL), Public Health England [London], Ministerio de Salud Publica y Asistencia Social [Guatemala] (MSPAS), US Centers for Disease Control, Ministry of Health [Honduras] (SESAL), US Naval Medical Research Unit n°2, Istituto Superiore di Sanita [Rome], Institut Pasteur de Côte d'Ivoire, Institut National d'Hygiène Publique [Côte d'Ivoire] (INHP), Astana Center of Sanitary Epidemiology Expertise, Centers for Disease Control and Prevention [Kenya], U.S. Public Health Service (USPHS), Unité de Virologie [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Ministry of Health [Morocco], Institute of Environmental Science and Research (ESR), Ministry of Health [Nicaragua] (MINSA), National Influenza Center, Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Ministry of Health [Singapore], Centers for Disease Control and Prevention, University of Pretoria [South Africa], University of the Witwatersrand [Johannesburg] (WITS), National Institute for Communicable Diseases [Johannesburg] (NICD), Istanbul University, National Academy of Medical Sciences of Ukraine, Centers for Disease Control and Prevention [Atlanta] (CDC), National Institute of Hygiene and Epidemiology [Hanoi, Vietnam] (NIHE), Chercheur indépendant, Sanofi Pasteur [Lyon, France], VU University Medical Center [Amsterdam], The Global Influenza B Study is funded by an unrestricted research grant from Sanofi Pasteur., The Global Influenza B Study group also includes the following members: Binay Thapa 4, Sangay Zangmo 4, Guy Vernet 6, Patricia Bustos 7, Patricio Loyola 7, Joanna Ellis 12, Antonino Bella 19, Maria Rita Castrucci 18, Gulzhan Muratbayeva 45, Julia Guillebaud 26, Laurence Randrianasolo 46, Ausenda Machado 47, Pedro Pechirra 32, Jeffery Cutter 34, Raymond Tzer Pin Lin 34. 45 Centers for Disease Control and Prevention, Central Asia Regional Office, Almaty, Kazakhstan 46 Epidemiology Unit, Institut Pasteur of Madagascar, Antananarivo, Madagascar 47 National Institute of Health Doutor Ricardo Jorge, Lisbon, Portugal, APH - Quality of Care, APH - Aging & Later Life, and General practice

Subjects
0301 basic medicine, Male, Databases, Factual, Distribution (economics), CHILDREN, Global Health, 0302 clinical medicine, Influenza A Virus, H1N1 Subtype, 1108 Medical Microbiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Influenza A Virus, H3N2 subtype, 030212 general & internal medicine, Young adult, Child, POPULATION, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Age Factors, Middle Aged, 3. Good health, Global Influenza B Study group, Infectious Diseases, INFECTIONS, Influenza A virus, Child, Preschool, H3N2 Subtype, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, BURDEN, Life Sciences & Biomedicine, Age distribution, 0605 Microbiology, Adult, medicine.medical_specialty, Surveillance data, Adolescent, Population, UNITED-STATES, Microbiology, Virus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Young Adult, Age Distribution, Influenza, Human, medicine, Humans, H1N1 Subtype, COHORT, lcsh:RC109-216, education, Disease burden, METAANALYSIS, Aged, Science & Technology, business.industry, Public health, Influenza A Virus, H3N2 Subtype, Infant, Newborn, Infant, 1103 Clinical Sciences, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Estados de Saúde e de Doença, Influenza B Virus, Influenza, Influenza B virus, Meta-analysis, 030104 developmental biology, H1N1 subtype, Virus type, RISK-FACTORS, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Demography
Abstract

The database of the Global Influenza B Study was created by collecting surveillance datasets from each of the participating countries. These national datasets are owned by the participating countries, and thus cannot be shared publicly. Researchers interested in obtaining the country-specific datasets may contact the individuals listed below for further details regarding data access.Argentina (Santa Fe Province): Gabriela Kusznierz (labconi@yahoo.com.ar)Australia: Kate Pennington (kate.pennington@health.gov.au)Bhutan: Sonam Wangchuk (swangchuk@health.gov.bt)Brazil: Cláudio Maierovitch Pessanha Henriques (claudio.henriques@saude.gov.br)Cameroon: Guy Vernet (vernet@pasteur-yaounde.org)Chile: Rodrigo Fasce (rfasce@ispch.cl)China: Feng Luzhao (fenglz@chinacdc.cn)Costa Rica: Alexey W. Clara (wclara@cdc.gov)Ecuador: Alfredo Bruno (alfredobruno@yahoo.es)El Salvador: Alexey W. Clara (wclara@cdc.gov)England: Maria Zambon (maria.zambon@phe.gov.uk)Guatemala: Alexey W. Clara (wclara@cdc.gov)Honduras: Alexey W. Clara (wclara@cdc.gov)Indonesia: Herman Kosasih (hermaninarespond@gmail.com)Italy: Caterina Rizzo (caterina.rizzo@iss.it)Ivory Coast: Herve A. Kadjo (hervekadjo@pasteur.ci)Kazakhstan: Gulzhan Muratbayeva (hnv2@cdc.gov)Kenya: Joshua Mott (zud9@cdc.gov)Madagascar: Jean-Michel Heraud (jmheraud@pasteur.mg)Morocco: Amal Barakat (amal.barakat@yahoo.fr)New Zealand: Sue Huang (sue.huang@esr.cri.nz)Nicaragua: Alexey W. Clara (wclara@cdc.gov)Panama: Alexey W. Clara (wclara@cdc.gov)Portugal: Ana Paula Rodrigues (ana.rodrigues@insa.min-saude.pt)Singapore: Vernon Lee (vernonljm@hotmail.com)South Africa: Cheryl Cohen (cherylc@nicd.ac.za)Turkey: Meral Akcay Ciblak (ciblakm@yahoo.com)Ukraine: Alla Mironenko (miralla@ukr.net)Viet Nam: Le Thi Quinh Mai (lom9@hotmail.com); International audience; BACKGROUND:Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases).METHODS:For each virus, we calculated a Relative Illness Ratio (defined as the ratio of the percentage of cases in an age group to the percentage of the country population in the same age group) for young children (0-4 years), older children (5-17 years), young adults (18-39 years), older adults (40-64 years), and the elderly (65+ years). We used random-effects meta-analysis models to obtain summary relative illness ratios (sRIRs), and conducted meta-regression and sub-group analyses to explore causes of between-estimates heterogeneity.RESULTS:The influenza virus with highest sRIR was A(H1N1) for young children, B for older children, A(H1N1)pdm2009 for adults, and (A(H3N2) for the elderly. As expected, considering the diverse nature of the national surveillance datasets included in our analysis, between-estimates heterogeneity was high (I2>90%) for most sRIRs. The variations of countries' geographic, demographic and economic characteristics and the proportion of outpatients among reported influenza cases explained only part of the heterogeneity, suggesting that multiple factors were at play.CONCLUSIONS:These results highlight the importance of presenting burden of disease estimates by age group and virus (sub)type.

Published
2018

49. Human variability in polymorphic CYP2D6 metabolism: Implications for the risk assessment of chemicals in food and emerging designer drugs

Author

Camille Béchaux, Witold Więcek, Jean-Lou Dorne, Emanuela Testai, Kevin Darney, Billy Amzal, Leonie S. Lautz, Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Certara UK Limited, Istituto Superiore di Sanita [Rome], Quinten, European Food Safety Authority (EFSA), and This work was supported by the European Food Safety Authority (EFSA) under Contract numbers: [OC/EFSA/SCER/2014/06]: Witold Wiecek and Billy Amzal, and [GP/EFSA/SCER/2015/01]: Keyvin Darney, Leonie Lautz and Emanuela Testai. Views expressed in this paper are the authors only and do not represent the views of the European Food safety Authority.

Subjects
CYP2D6, Uncertainty factors, [SDV]Life Sciences [q-bio], Cmax, Pharmacology, Biology, Risk Assessment, 030226 pharmacology & pharmacy, Designer Drugs, Human variability, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacokinetics, Humans, Toxicokinetics, GE1-350, 030304 developmental biology, General Environmental Science, 0303 health sciences, Bayes Theorem, 3. Good health, Environmental sciences, Meta-analysis, Cytochrome P-450 CYP2D6, chemistry, Toxicity, Bayesian Inference, Xenobiotic, Drug metabolism
Abstract

International audience; The major human cytochrome P450 CYP2D6 isoform enzyme plays important roles in the liver and in the brain with regards to xenobiotic metabolism. Xenobiotics as CYP2D6 substrates include a whole range of pharmaceuticals, pesticides and plant alkaloids to cite but a few. In addition, a number of endogenous compounds have been shown to be substrates of CYP2D6 including trace amines in the brain such as tyramine and 5-methoxytryptamine as well as anandamide and progesterone. Because of the polymorphic nature of CYP2D6, considerable inter-phenotypic and inter-ethnic differences in the pharmaco/toxicokinetics (PK/TK) and metabolism of CYP2D6 substrates exist with potential consequences on the pharmacology and toxicity of chemicals. Here, large extensive literature searches have been performed to collect PK data from published human studies for a wide range of pharmaceutical probe substrates and investigate human variability in CYP2D6 metabolism. The computed kinetic parameters resulted in the largest open source database, quantifying inter-phenotypic differences for the kinetics of CYP2D6 probe substrates in Caucasian and Asian populations, to date. The database is available in supplementary material (CYPD6 DB) and EFSA knowledge junction (DOI to added). Subsequently, meta-analyses using a hierarchical Bayesian model for markers of chronic oral exposure (oral clearance, area under the plasma concentration time curve) and acute oral exposure (maximum plasma concentration (Cmax) provided estimates of inter-phenotypic differences and CYP2D6-related uncertainty factors (UFs) for chemical risk assessment in Caucasian and Asian populations classified as ultra-rapid (UM), extensive (EMs), intermediate (IMs) and poor metabolisers (PMs). The model allowed the integration of inter-individual (i.e. inter-phenotypic and inter-ethnic), inter-compound and inter-study variability together with uncertainty in each PK parameter. Key findings include 1. Higher frequencies of PMs in Caucasian populations compared to Asian populations (>8% vs 1-2%) for which EM and IM were the most frequent phenotype. 2. Large inter-phenotypic differences in PK parameters for Caucasian EMs (coefficients of variation (CV) > 50%) compared with Caucasian PMs and Asian EMs and IMs (i.e CV < 40%). 3. Inter-phenotypic PK differences between EMs and PMs in Caucasian populations increase with the quantitative contribution of CYP2D6 for the metabolism (fm) for a range of substrates (fm CYP2D6 range: 20-95% of dose) (range: 1-54) to a much larger extent than those for Asian populations (range: 1-4). 4. Exponential meta-regressions between Fm CYP2D6 in EMs and inter-phenotypic differences were also shown to differ between Caucasian and Asian populations as well as CYP2D6-related UFs. Finally, implications of these results for the risk assessment of food chemicals and emerging designer drugs of public health concern, as CYP2D6 substrates, are highlighted and include the integration of in vitro metabolism data and CYP2D6 variability distributions for the development of quantitative in vitro in vivo extrapolation models.

Published
2021

50. Adverse outcome pathways: opportunities, limitations and open questions

Author

Alberto Mantovani, Tanja Waldmann, Bob van de Water, Cristina Cadenas, Hennicke Kamp, Thomas Braunbeck, Annemarie H. Meijer, Mathieu Vinken, Sylvia Escher, Domenico Gadaleta, Patricio Godoy, Anna Forsby, Stefan Schildknecht, Chris T. Evelo, Stefan Höhme, Rosemarie Marchan, Gerhard F. Ecker, Harry Vrieling, Susanne Hougaard Bennekou, Ciarán Fisher, Alice Limonciel, Enrico Mombelli, Rabea Graepel, Marcel Leist, Ahmed Ghallab, Michael Schwarz, Joost B. Beltman, Jens M. Kelm, Albert Braeuning, Olivier Taboureau, Bart van der Burg, Andrea Terron, Ferran Sanz, Frédéric Y. Bois, Steven Dooley, Dinant Kroese, Jan G. Hengstler, Paul Jennings, Egon Willighagen, Barbara Zdrazil, Barry Hardy, Erik H.J. Danen, Bjørn E. V. Koch, David A. Fluri, Christoph van Thriel, Dirk Drasdo, Ben van Ravenzwaay, Iain Gardner, Franz Oesch, Reham Hassan, Raymond Reif, Marvin Martens, Thomas Hartung, University of Konstanz, Department of Forensic Medicine and Veterinary Toxicology [Qena], Faculty of Veterinary Medicine [Qena], South Valley University [Qena]-South Valley University [Qena], Universiteit Leiden, Leibniz Research Centre for Working Environment and Human Factors [Dortmund] (IFADO), Technische Universität Dortmund [Dortmund] (TU), The Danish Epidemiology Science Centre, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Vrije Universiteit Brussel (VUB), BASF [Ludwigshafen], SimCYP Ltd, Institut National de l'Environnement Industriel et des Risques (INERIS), Bundesinstitut für Risikobewertung - Federal Institute for Risk Assessment (BfR), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Modelling and Analysis for Medical and Biological Applications (MAMBA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig, Medical University Graz, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), University of Heidelberg, Medical Faculty, Universitat Pompeu Fabra [Barcelona] (UPF), Karolinska Institutet [Stockholm], Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), InSphero [Schlieren], University of Vienna [Vienna], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), BioDetection Systems, Universität Mannheim, Maastricht University [Maastricht], Institut National de la Santé et de la Recherche Médicale (INSERM), IT University of Copenhagen (ITU), Istituto Superiore di Sanità (ISS), Douglas Connect GmbH, Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM), Fraunhofer (Fraunhofer-Gesellschaft), Carl Zeiss SMT AG, Carl Zeiss, Oberkochen, Faculty of Biology, Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University [Austria] (IMU), BASF, DRC/VIVA/METO, Institut National de l'Environnement Industriel et des Risques, Department of Experimental and Clinical Pharmacology andToxicology [Tübingen], Eberhard Karls Universität Tübingen, Interdisciplinary Centre for Bioinformatics [Leipzig] (IZBI), Universität Leipzig [Leipzig], Institute for Health and Consumer Protection, European Commission - Joint Research Centre, Université Grenoble Alpes - UFR Médecine [ ?-2019] (UGA UFRM [ ?-2019]), Molecular Hepatology - Alcohol Associated Diseases, Department of Medicine II, University of Heidelberg, Medical Faculty of Mannheim-University of Heidelberg, Medical Faculty of Mannheim, BigCat - Bioinformatics and Systems Biology Research Group, UMR-S973, MTi, Université Paris Diderot - Paris 7 (UPD7), Department of Immunology and Cell Biology, Mario Negri Institute, Leiden University, Vrije Universiteit [Brussels] (VUB), Universiteit Leiden [Leiden], BASF SE, 67056 Ludwigshafen, Johannes Gutenberg - University of Mainz (JGU), Centre for Alternatives to Animal Testing (CAAT EU), Universitat Pompeu Fabra [Barcelona], European Food Safety Authority = Autorité européenne de sécurité des aliments, Université Grenoble Alpes (UGA), Universität Mannheim [Mannheim], Istituto Superiore di Sanita [Rome], Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Johannes Gutenberg - Universität Mainz (JGU), IT University of Copenhagen, Molecular and Computational Toxicology, AIMMS, Bioinformatica, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: NUTRIM - R4 - Gene-environment interaction, Promovendi NTM, RS: FHML MaCSBio, Publica, Pharmaceutical and Pharmacological Sciences, Connexin Signalling Research Group, Liver Connexin and Pannexin Research Group, and Experimental in vitro toxicology and dermato-cosmetology

Subjects
CCl4, 0301 basic medicine, Proof of non-toxicity, Health, Toxicology and Mutagenesis, CCl, RAPID - Risk Analysis for Products in Development, Biomedical Innovation, Signal transduction, Ecotoxicology, Toxicology, NATURAL-KILLER-CELLS, Prioritization of compounds, Life, Adverse Outcome Pathway, ACTIVATED STELLATE CELLS, ComputingMilieux_MISCELLANEOUS, Risk assessment, TUMOR-NECROSIS-FACTOR, Event (computing), EVIDENCE-BASED TOXICOLOGY, ENVIRONMENTAL CHEMICALS, General Medicine, Toxicokinetics, Multiple hit events Proof of non-toxicity, Evidence-based toxicology, Identification (information), Paracetamol, Risk analysis (engineering), Vinyl acetate, RISK-ASSESSMENT, Systems biology, Construct (philosophy), Healthy Living, Human, Quality Control, READ-ACROSS, Vinyl Compounds, Plasticity, Liver fibrosis, Nanotechnology, Harmonization, Multiple hit events, Biology, History, 21st Century, Risk Assessment, Binning of events, Adverse outcome, 03 medical and health sciences, Adverse outcome pathway, SDG 3 - Good Health and Well-being, ddc:570, Tumor promotion, Journal Article, Animals, Humans, Vinyl acetate Tumor promotion, Regulatory toxicology, Set (psychology), Epidemiological data, Adverse Outcome Pathways, Interspecies extrapolation, 030111 toxicology, SYSTEMS TOXICOLOGY, Nonhuman, Toxicity assay, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Mice, Inbred C57BL, Multi-scale integration, Metabolism, 030104 developmental biology, DEVELOPMENTAL NEUROTOXICITY, Computational toxicology, ELSS - Earth, Life and Social Sciences, Pathway unidirectionality
Abstract

Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event relationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field. © 2017, Springer-Verlag GmbH Germany.

Published
2017

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