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5. Situación epidemiológica de las encefalopatías espongiformes transmisibles humanas en España

Author

Avellanal Calzadilla, Fuencisla, Almazan-Isla, Javier, Alcalde-Cabero, Enrique, Ruiz-Tovar, Maria, Pedro-Cuesta, Jesus de, Área de Epidemiología Aplicada, Centro Nacional de Epidemiología, and Instituto de Salud Carlos III (ISCIII)

Abstract

[ES] Las Encefalopatías Espongiformes Transmisibles Humanas (EETH) son enfermedades de declaración obligatoria, de baja incidencia, provocadas por depósitos de proteína priónica que cursan en general con demencia rápidamente progresiva. El Registro Nacional de EETH (RNEETH) recoge datos de los casos españoles desde 1995. En este informe se presentan las características de los casos de EETH de España. Los datos proceden de las notificaciones hechas por las unidades de vigilancia epidemiológica de las comunidades autónomas al RNEETH hasta el 1 de julio de 2016. La forma más común es la Enfermedad de Creutzfeldt-Jakob esporádica (ECJe, se desconoce la causa) cuya incidencia anual en España es de 1,1 casos por millón de habitantes y año. El grupo de edad con mayores tasas de ECJe es el de 70 a 79 años. El 55% de todos los casos son mujeres. En los años 2005, 2007 y 2008 se recogen cinco casos de variante de ECJ (vECJ), dos de ellos en una mujer y su hijo, única agrupación familiar descrita. En el RNEETH constan también siete casos de ECJ transmitida accidentalmente por implantes de duramadre y 152 casos genéticos: 68 en forma de Insomnio Familiar Letal (IFL), 81 de ECJ familiar (ECJf) y 3 de síndrome de Gerstmann-SträusslerScheinker (SGSS). El País Vasco presenta una incidencia de formas familiares por encima de las demás comunidades autónomas. Los datos que constan en el Registro Nacional de EETH reflejan una situación epidemiológica similar a la descrita en otros países de nuestro entorno salvo para las formas genéticas.[EN] Human Transmissible Spongiform Encephalopathies (HTSE) are notifiable diseases with lowincidence caused by prion protein (PrP) deposits. HTSE are generally characterized by rapidly progressive dementia. The National Registry of HTSE (NRHTSE) collects data from Spanish cases since 1995. This report summarizes the characteristics of the cases of HTSE in Spain. Data come from notifications made by the Epidemiological Surveillance Units of the Autonomous Regions to the NRHTSE until 1 July 2016. The most common form is sporadic Creutzfeldt-Jakob Disease (sCJD) whose annual incidence in Spain is 1.1 cases per million inhabitants per year. The age group with the highest CJD rates is 70 to 79 years. 55% are women. In 2005, 2007 and 2008, 5 cases of variant CJD (vCJD) were recorded, two of them in a woman and her son, the only family group described. In the NRHTSE there are 7 cases of CJD accidentally transmitted by dura mater implants and 152 genetic cases: 68 of Familial Insomnia (FFI), 81 of familial CJD (fCJD) and 3 of Gerstmann-Straüssler-Scheinker syndrome (GSSS). The Basque country has an incidence of family forms above the other Autonomous Regions. The data of the NRHTSE reflect an epidemiological situation similar to other countries of our environment except for genetic forms. No

Published
2016

6. Vigilancia Epidemiológica del VIH/SIDA: Situación en Europa y en España, año 2012

Author

Área de Vigilancia Epidemiológica del VIH/SIDA, Área de Ánalisis en Vigilancia Epidemiológica, Centro Nacional de Epidemiología, and Instituto de Salud Carlos III (ISCIII)

Subjects
VIH/SIDA
Abstract

En este boletín se presentan los principales resultados de la vigilancia de la infección por VIH/sida en España y en Europa, publicados con motivo del Día Mundial del Sida, que se celebra el día 1 de diciembre de cada año. Los datos muestran, tanto en España como en Europa, que casi el 50% de las nuevas infecciones en 2012 presentaban indicios de diagnóstico tardío, por lo que es necesario incidir en la importancia del diagnóstico precoz del VIH. No

Published
2013

9. Methicillin-Susceptible Staphylococcus aureus Biofilm Formation on Vascular Grafts: an In Vitro Study

Author

Cristina Tello-Díaz, Marta Palau, Estela Muñoz, Xavier Gomis, Joan Gavaldà, Nuria Fernández-Hidalgo, Sergi Bellmunt-Montoya, Institut Català de la Salut, [Tello-Díaz C] Department of Vascular and Endovascular Surgery, Hospital de la Santa Creu i Sant Pau, Institute of Biomedical Research (II-B Sant Pau), CIBER CV, Barcelona, Spain. Departament de Cirurgia i Ciències Morfològiques, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Palau M, Gomis X, Gavaldà J] Laboratori de Resistència Antimicrobiana, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Fernández-Hidalgo N] CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Red Española de Investigación en Patología Infecciosa (REIPI RD16/0016/0003), Instituto de Salud Carlos III, Madrid, Spain. [Bellmunt-Montoya S] Departament de Cirurgia i Ciències Morfològiques, Universitat Autònoma de Barcelona, Bellaterra, Spain. Laboratori de Resistència Antimicrobiana, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d'Hebron Hospital Universitari, Barcelona, Spain. CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Servei d’Angiologia, Cirurgia Vascular i Endovascular, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
fenómenos microbiológicos::biopelículas [FENÓMENOS Y PROCESOS], Microbiology (medical), Malalties bacterianes, General Immunology and Microbiology, Ecology, Physiology, intervenciones quirúrgicas::procedimientos quirúrgicos cardiovasculares::procedimientos quirúrgicos vasculares::injerto vascular [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Surgical Procedures, Operative::Cardiovascular Surgical Procedures::Vascular Surgical Procedures::Vascular Grafting [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], infecciones bacterianas y micosis::infección::infecciones relacionadas con prótesis [ENFERMEDADES], Cell Biology, Infectious Diseases, Biofilms, Vasos sanguinis - Empelts, Infecció, Bacterial Infections and Mycoses::Infection::Prosthesis-Related Infections [DISEASES], Genetics, Pròtesis, Microbiological Phenomena::Biofilms [PHENOMENA AND PROCESSES]
Abstract

Staphylococcus aureus; Biofilm; Infection Staphylococcus aureus; Biopelícula; Infección Staphylococcus aureus; Biopel·lícula; Infecció The aim of this study was to quantify in vitro biofilm formation by methicillin-susceptible Staphylococcus aureus (MSSA) on the surfaces of different types of commonly used vascular grafts. We performed an in vitro study with two clinical strains of MSSA (MSSA2 and MSSA6) and nine vascular grafts: Dacron (Hemagard), Dacron-heparin (Intergard heparin), Dacron-silver (Intergard Silver), Dacron-silver-triclosan (Intergard Synergy), Dacron-gelatin (Gelsoft Plus), Dacron plus polytetrafluoroethylene (Fusion), polytetrafluoroethylene (Propaten; Gore), Omniflow II, and bovine pericardium (XenoSure). Biofilm formation was induced in two phases: an initial 90-minute adherence phase and a 24-hour growth phase. Quantitative cultures were performed, and the results were expressed as log10 CFU per milliliter. The Dacron-silver-triclosan graft and Omniflow II were associated with the least biofilm formation by both MSSA2 and MSSA6. MSSA2 did not form a biofilm on the Dacron-silver-triclosan graft (0 CFU/mL), and the mean count on the Omniflow II graft was 3.89 CFU/mL (standard deviation [SD] 2.10). The mean count for the other grafts was 7.01 CFU/mL (SD 0.82). MSSA6 formed a biofilm on both grafts, with 2.42 CFU/mL (SD 2.44) on the Dacron-silver-triclosan graft and 3.62 CFU/mL (SD 2.21) on the Omniflow II. The mean biofilm growth on the remaining grafts was 7.33 CFU/mL (SD 0.28). The differences in biofilm formation on the Dacron-silver-triclosan and Omniflow II grafts compared to the other tested grafts were statistically significant. Our findings suggest that of the vascular grafts we studied, the Dacron-silver-triclosan and Omniflow II grafts might prevent biofilm formation by MSSA. Although further studies are needed, these grafts seem to be good candidates for clinical use in vascular surgeries at high risk of infections due to this microorganism. IMPORTANCE The Dacron silver-triclosan and Omniflow II vascular grafts showed the greatest resistance to in vitro methicillin-susceptible Staphylococcus aureus biofilm formation compared to other vascular grafts. These findings could allow us to choose the most resistant to infection prosthetic graft.

Published
2023

10. Analysis of Differentially Expressed MicroRNAs in Serum and Lung Tissues from Individuals with Severe Asthma Treated with Oral Glucocorticoids

Author

Gil-Martínez, Marta, Lorente-Sorolla, Clara, Rodrigo-Muñoz, José M., Lendínez, Miguel Ángel, Núñez-Moreno, Gonzalo, de la Fuente, Lorena, Mínguez, Pablo, Mahíllo-Fernández, Ignacio, Sastre, Joaquin, Valverde-Monge, Marcela, Quirce, Santiago, Caballero, María L., González-Barcala, Francisco J., Arismendi, Ebymar, Bobolea, Irina, Valero, Antonio, Muñoz Gall, Xavier, Cruz, María Jesús, Martínez Rivera, Carlos, Plaza, Vicente, Olaguibel, José M., del Pozo, Victoria, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Gil-Martínez M, Rodrigo-Muñoz JM] Immunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain. CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Lorente-Sorolla C, Lendínez MÁ] Immunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain. [Núñez-Moreno G] Department of Genetics, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain. Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Bioinformatics Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain. [de la Fuente L] Department of Genetics, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain. [Muñoz X, Cruz MJ] CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [CHEMICALS AND DRUGS], Asma - Tractament, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Mirnas, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Catalysis, acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::hormonas, sustitutos de hormonas y antagonistas de hormonas::hormonas::glucocorticoides [COMPUESTOS QUÍMICOS Y DROGAS], Inorganic Chemistry, biomarker, oral corticosteroids, miRNAs, individuals with severe asthma, Oral corticosteroids, Other subheadings::/therapeutic use [Other subheadings], Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, MicroARN, Individuals with severe asthma, Otros calificadores::/uso terapéutico [Otros calificadores], Organic Chemistry, General Medicine, Biomarker, Respiratory Tract Diseases::Bronchial Diseases::Asthma [DISEASES], Computer Science Applications, enfermedades respiratorias::enfermedades bronquiales::asma [ENFERMEDADES], Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Glucocorticoids [CHEMICALS AND DRUGS], nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN [COMPUESTOS QUÍMICOS Y DROGAS], Glucocorticoides - Ús terapèutic
Abstract

Biomarker; Individuals with severe asthma; Oral corticosteroids Biomarcador; Persones amb asma greu; Corticosteroides orals Biomarcador; Personas con asma grave; Corticosteroides orales Nowadays, microRNAs (miRNAs) are increasingly used as biomarkers due to their potential contribution to the diagnosis and targeted treatment of a range of diseases. The aim of the study was to analyze the miRNA expression profiles in serum and lung tissue from patients with severe asthma treated with oral corticosteroids (OCS) and those without OCS treatment. For this purpose, serum and lung tissue miRNAs of OCS and non-OCS asthmatic individuals were evaluated by miRNAs-Seq, and subsequently miRNA validation was performed using RT-qPCR. Additionally, pathway enrichment analysis of deregulated miRNAs was conducted. We observed altered expression by the next-generation sequencing (NGS) of 11 miRNAs in serum, of which five (hsa-miR-148b-3p, hsa-miR-221-5p, hsa-miR-618, hsa-miR-941, and hsa-miR-769-5p) were validated by RT-qPCR, and three miRNAs in lung tissue (hsa-miR-144-3p, hsa-miR-144-5p, and hsa-miR-451a). The best multivariate logistic regression model to differentiate individuals with severe asthma, treated and untreated with OCS, was to combine the serum miRNAs hsa-miR-221-5p and hsa-miR-769-5p. Expression of hsa-miR-148b-3p and hsa-miR-221-5p correlated with FEV1/FVC (%) and these altered miRNAs act in key signaling pathways for asthma disease and the regulated expression of some genes (FOXO3, PTEN, and MAPK3) involved in these pathways. In conclusion, there are miRNA profiles differentially expressed in OCS-treated individuals with asthma and could be used as biomarkers of OCS treatment. This work was supported by ISCIII—Instituto de Salud Carlos III, FIS (Fondo de Investigación Sanitaria—Spanish Health Research Fund) grants PI18/00167, PI21/00896, and FI19/00067; Ciber de Enfermedades Respiratorias (CIBERES); RTC-2017-6501-1 (Ministerio de Ciencia, Innovación y Universidades), a Carlos III Institute of Health Initiative; and FEDER funds (Fondo Europeo de Desarrollo Regional).

Published
2023

11. Lifestyle correlates of eight breast cancer-related metabolites: a cross-sectional study within the EPIC cohort

Author

Mathilde His, Vivian Viallon, Laure Dossus, Julie A. Schmidt, Ruth C. Travis, Marc J. Gunter, Kim Overvad, Cecilie Kyrø, Anne Tjønneland, Lucie Lécuyer, Joseph A. Rothwell, Gianluca Severi, Theron Johnson, Verena Katzke, Matthias B. Schulze, Giovanna Masala, Sabina Sieri, Salvatore Panico, Rosario Tumino, Alessandra Macciotta, Jolanda M. A. Boer, Evelyn M. Monninkhof, Karina Standahl Olsen, Therese H. Nøst, Torkjel M. Sandanger, Antonio Agudo, Maria-Jose Sánchez, Pilar Amiano, Sandra M. Colorado-Yohar, Eva Ardanaz, Linda Vidman, Anna Winkvist, Alicia K. Heath, Elisabete Weiderpass, Inge Huybrechts, Sabina Rinaldi, International Agency for Cancer Research (IACR), University of Oxford, Aarhus University [Aarhus], Danish Cancer Society Research Center [Copenhagen, Denmark] (DCSRC), University of Copenhagen = Københavns Universitet (UCPH), 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, Università degli Studi di Firenze = University of Florence (UniFI), Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke [Nuthetal, Germany] (GIHNP-R), University of Potsdam = Universität Potsdam, Istituto per lo Studio, la Prevenzione e la rete Oncologica [Florence, Italy] (ISPRO), IRCCS Istituto Nazionale dei Tumori [Milano], University of Naples Federico II = Università degli studi di Napoli Federico II, Provincial Health Authority (ASP 7) [Ragusa, Italy], Università degli studi di Torino = University of Turin (UNITO), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University Medical Center [Utrecht], The Arctic University of Norway [Tromsø, Norway] (UiT), Catalan Institute of Oncology [Barcelone, Espagne], L’Hospitalet de Llobregat [Barcelona, Spain], Escuela Andaluza de Salud Pública [Granada, Spain] (EASP), Universidad de Granada = University of Granada (UGR), CIBER de Epidemiología y Salud Pública (CIBERESP), Public Health Division of Gipuzkoa, Basque Government, CIBER en Salud Pública, CIBERSP, Biodonostia Health Research Institute [Donostia-San Sebastian, Spain] (IIS Biodonostia), Murcia Regional Health Council [Murcia], Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Navarra Public Health Institute, Umeå University, Imperial College London, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Cancer Research UK, CRUK, World Cancer Research Fund, WCRF, University of Cambridge, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Fondation ARC pour la Recherche sur le Cancer, ARC, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut National Du Cancer, INCa: 2015-166, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk (DOI 10.22025/2019.10.105.00004), C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143, MR/N003284/1, MC-UU_12015/1 and MC_UU_00006/1 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). The funders were not involved in designing the study, collecting, analyzing, or interpreting the data, or writing or submitting the manuscript for publication., The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)., This work was funded by the French National Cancer Institute (grant number 2015-166). Mathilde His’ work reported here was undertaken during the tenure of a postdoctoral fellowship awarded by the International Agency for Research on Cancer, financed by the Fondation ARC., The authors would like to thank Mr Bertrand Hemon for his support in preparing the databases, Ms Audrey Gicquiau and Dr David Achaintre for the analyses of samples in several of the original studies, and all EPIC participants. The EPIC-Norfolk team thank all the participants who have been part of the project and the many members of the study teams at the University of Cambridge who have enabled this research. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., and HAL UVSQ, Équipe

Subjects
cross-sectional, lifestyle, Estils de vida, BIOMARKERS, Lifestyles, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, DIET, SERUM, Càncer de mama, Cohort Studies, Medicine, General & Internal, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Cross-sectional, General & Internal Medicine, Metabolites, Humans, Metabolomics, Prospective Studies, VALIDITY, Life Style, 11 Medical and Health Sciences, metabolites, RISK, Cancer och onkologi, Science & Technology, anthropometry, Anthropometry, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, PROFILES, Lifestyle, AMINO-ACID, BODY-MASS INDEX, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, PHYSICAL-ACTIVITY, Cross-Sectional Studies, Metabolòmica, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cancer and Oncology, TARGETED METABOLOMICS, Medicine, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Life Sciences & Biomedicine, Research Article
Abstract

This work was funded by the French National Cancer Institute (grant number 2015-166). Mathilde His' work reported here was undertaken during the tenure of a postdoctoral fellowship awarded by the International Agency for Research on Cancer, financed by the Fondation ARC. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk (DOI 10.22025/2019.10.105.00004); C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143, MR/N003284/1, MC-UU_12015/1 and MC_UU_00006/1 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (UK). The funders were not involved in designing the study; collecting, analyzing, or interpreting the data; or writing or submitting the manuscript for publication., Background: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2). Methods: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786). Results: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34: 2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed. Conclusions: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated., Institut National du Cancer (INCA) France 2015-166, International Agency for Research on Cancer - Fondation ARC, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, German Cancer Research Center (DKFZ) (Germany), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain), Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) 1000143 MR/N003284/1 MC-UU_12015/1 MC_UU_00006/1 MR/M012190/1

Published
2021

12. Novel variant in HHAT as a cause of different sex development with partial gonadal dysgenesis associated with microcephaly, eye defects, and distal phalangeal hypoplasia of both thumbs: Case report

Author

Baz Redón, Noelia, Soler Colomer, Laura, Fernández Cancio, Mónica, Benito-Sanz, Sara, Garrido-Pontnou, Marta, Moline Marimon, Teresa, Clemente Leon, Maria, Camats Tarruella, Nuria, Yeste Fernandez, Diego, Institut Català de la Salut, [Baz-Redón N] Grup de Recerca en Creixement i Desenvolupament, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Pediatria, Ginecologia i Obstetrícia i Medicina Preventiva, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Soler-Colomer L] Unitat d’Endocrinologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Fernández-Cancio M, Camats-Tarruella N] Grup de Recerca en Creixement i Desenvolupament, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Benito-Sanz S] Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autonóma de Madrid, Madrid, Spain. [Garrido M, Moliné T] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Clemente M, Yeste D] Grup de Recerca en Creixement i Desenvolupament, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Pediatria, Ginecologia i Obstetrícia i Medicina Preventiva, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat d’Endocrinologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Trastorns del desenvolupament, Crani - Malformacions, Turner, Síndrome de, Endocrinology, Diabetes and Metabolism, fenómenos fisiológicos::crecimiento y desarrollo::desarrollo sexual [FENÓMENOS Y PROCESOS], Endocrine System Diseases::Gonadal Disorders::Disorders of Sex Development::Gonadal Dysgenesis [DISEASES], enfermedades del sistema endocrino::trastornos gonadales::trastornos del desarrollo sexual::disgenesia gonadal [ENFERMEDADES], Musculoskeletal Diseases::Musculoskeletal Abnormalities::Craniofacial Abnormalities::Microcephaly [DISEASES], enfermedades musculoesqueléticas::anormalidades musculoesqueléticas::anomalías craneofaciales::microcefalia [ENFERMEDADES], Physiological Phenomena::Growth and Development::Sexual Development [PHENOMENA AND PROCESSES]
Abstract

Different sexual development; Minigene studies Desarrollo sexual diferente; Estudios de minigenes Desenvolupament sexual diferent; Estudis minigènics The palmitoylation of the Hedgehog (Hh) family of morphogens, named sonic hedgehog (SHH), desert hedgehog (DHH), and Indian hedgehog (IHH), is crucial for effective short- and long-range signaling. The hedgehog acyltransferase (HHAT) attaches the palmitate molecule to the Hh; therefore, variants in HHAT cause a broad spectrum of phenotypes. A missense HHAT novel variant c.1001T>A/p.(Met334Lys) was described in a patient first referred for a 46,XY different sexual development with partial gonadal dysgenesis but with microcephaly, eye defects, and distal phalangeal hypoplasia of both thumbs. The in silico analysis of the variant predicted an affectation of the nearest splicing site. Thus, in vitro minigene studies were carried out, which demonstrated that the variant does not affect the splicing. Subsequent protein in silico studies supported the pathogenicity of the variant, and, in conclusion, this was considered the cause of the patient’s phenotype. This study was partly supported by a grant from the Fondo de Investigación Sanitaria (PI15/01647 [to MF-C and SB-S]).

Published
2022

13. Longitudinal deep learning clustering of Type 2 Diabetes Mellitus trajectories using routinely collected health records

Author

Enrico Manzini, Bogdan Vlacho, Josep Franch-Nadal, Joan Escudero, Ana Génova, Elisenda Reixach, Erik Andrés, Israel Pizarro, José-Luis Portero, Dídac Mauricio, Alexandre Perera-Lluna, Universitat Politècnica de Catalunya. Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial, [Manzini E, Perera-Lluna A] Universitat Politecnica de Catalunya, Barcelona, Spain. Networking Biomedical Research Centre in the subject area of Bioengineering, Biomaterials and Nanomedicine, Madrid, Spain. Institut de Recerca Sant Joan de Deu, Barcelona, Spain. [Vlacho B] DAP-Cat Group, Unitat de Suport a la Recerca, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barelona, Spain. [Franch-Nadal J] DAP-Cat Group, Unitat de Suport a la Recerca, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barelona, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Spain. Centre Atenció Primària Raval Sud, Institut Català de la Salut, Generalitat de Catalunya, Barcelona, Spain. [Génova A] Grupo Pulso, Spain. [Reixach E, Andrés E] Fundació TIC Salut Social (TICSS), Departament de Salut, Generalitat de Catalunya, Barcelona, Spain. [Pizarro I, Portero JL] Novo Nordisk, Spain. [Mauricio D] DAP-Cat Group, Unitat de Suport a la Recerca, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barelona, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Spain. Departament de Medicina, Universitat de Vic, Universitat Central de Catalunya, Vic, Spain, and Departament de Salut

Subjects
AutoEncoder, Health Informatics, Diabetis no-insulinodependent, Diabetic complications, enfermedades del sistema endocrino::diabetes mellitus::diabetes mellitus tipo II [ENFERMEDADES], Deep Learning, Humans, Cluster Analysis, Non-insulin-dependent diabetes, Electronic health records, Longitudinal cluster, Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2 [DISEASES], Històries clíniques - Informàtica, técnicas de investigación::métodos epidemiológicos::recopilación de datos::registros::registros médicos::sistemas informatizados de historias clínicas::historias clínicas electrónicas [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Enginyeria biomèdica::Electrònica biomèdica [Àrees temàtiques de la UPC], Glycated Hemoglobin, Investigative Techniques::Epidemiologic Methods::Data Collection::Records::Medical Records [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Type 2 diabetes, Deep learning, Computer Science Applications, Registres mèdics, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Investigative Techniques::Epidemiologic Methods::Data Collection::Records::Medical Records::Medical Records Systems, Computerized::Electronic Health Records [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], técnicas de investigación::métodos epidemiológicos::recopilación de datos::registros::registros médicos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Aprenentatge profund
Abstract

Type 2 diabetes mellitus (T2DM) is a highly heterogeneous chronic disease with different pathophysiological and genetic characteristics affecting its progression, associated complications and response to therapies. The advances in deep learning (DL) techniques and the availability of a large amount of healthcare data allow us to investigate T2DM characteristics and evolution with a completely new approach, studying common disease trajectories rather than cross sectional values. We used an Kernelized-AutoEncoder algorithm to map 5 years of data of 11,028 subjects diagnosed with T2DM in a latent space that embedded similarities and differences between patients in terms of the evolution of the disease. Once we obtained the latent space, we used classical clustering algorithms to create longitudinal clusters representing different evolutions of the diabetic disease. Our unsupervised DL clustering algorithm suggested seven different longitudinal clusters. Different mean ages were observed among the clusters (ranging from 65.3±11.6 to 72.8±9.4). Subjects in clusters B (Hypercholesteraemic) and E (Hypertensive) had shorter diabetes duration (9.2±3.9 and 9.5±3.9 years respectively). Subjects in Cluster G (Metabolic) had the poorest glycaemic control (mean glycated hemoglobin 7.99±1.42%), while cluster E had the best one (mean glycated hemoglobin 7.04±1.11%). Obesity was observed mainly in clusters A (Neuropathic), C (Multiple Complications), F (Retinopathy) and G. A dashboard is available at dm2.b2slab.upc.edu to visualize the different trajectories corresponding to the 7 clusters. This work was supported by the Spanish Ministry of Economy and Competitiveness (www.mineco.gob.es) TEC2014-60337-R, DPI2017-89827-R, Networking Biomedical Research Centre in the subject area of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain , initiatives of Instituto de Investigación Carlos III (ISCIII), and Share4Rare project (Grant Agreement 780262). This study was possible thanks to the commitment of physicians and nurses working in the Catalan Health Institute to provide optimal care to patients with diabetes. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) is an initiative from Instituto de Salud Carlos III, Madrid, Spain. This analysis is part of the DiaCare Project of Novo Nordisk and the Fundació TicSalut (Departament de Salut, Generalitat de Catalunya), in collaboration with Grupo Pulso, for the benefit of people with type 2 diabetes.

Published
2022

14. Combining 4D Flow MRI and Complex Networks Theory to Characterize the Hemodynamic Heterogeneity in Dilated and Non-dilated Human Ascending Aortas

Author

Andrea Guala, Karol Calò, Umberto Morbiducci, Luca Ridolfi, Stefania Scarsoglio, José F. Rodríguez Palomares, Diego Gallo, Institut Català de la Salut, [Calò K, Gallo D, Scarsoglio S, Ridolfi L] PolitoBIOMed Lab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, 10129 Turin, Italy. [Guala A] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBER-CV, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Rodriguez Palomares J] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBER-CV, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
medicine.medical_specialty, Circulatory and Respiratory Physiological Phenomena::Cardiovascular Physiological Phenomena::Hemodynamics [PHENOMENA AND PROCESSES], Network science, Biomedical Engineering, Aorta - Imatgeria, Hemodynamics, 030204 cardiovascular system & hematology, Cardiovascular, Aortic dilation, Ascending aorta aneurysm, Magnetic resonance imaging, Spatiotemporal analysis, Coronary Circulation, Humans, Magnetic Resonance Imaging, Aorta, Aortic Aneurysm, Bicuspid Aortic Valve Disease, Models, Cardiovascular, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Models, Internal medicine, medicine.artery, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Tomography::Magnetic Resonance Imaging [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Ascending aorta, medicine, diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::tomografía::imagen por resonancia magnética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Other subheadings::Other subheadings::/diagnostic imaging [Other subheadings], medicine.diagnostic_test, Cardiac cycle, business.industry, Otros calificadores::Otros calificadores::/diagnóstico por imagen [Otros calificadores], Forward flow, Complex network, Hemodinàmica, Cardiovascular System::Blood Vessels::Arteries::Aorta [ANATOMY], Flow (mathematics), fenómenos fisiológicos respiratorios y circulatorios::fenómenos fisiológicos cardiovasculares::hemodinámica [FENÓMENOS Y PROCESOS], Cardiology, cardiovascular system, Dilation (morphology), Original Article, business, Imatgeria per al diagnòstic, sistema cardiovascular::vasos sanguíneos::arterias::aorta [ANATOMÍA]
Abstract

Dilatació aòrtica; Aneurisma de l'aorta ascendent; Anàlisi espai-temporal Dilatación aórtica; Aneurisma de la aorta ascendente; Análisis espacio-temporal Aortic dilation; Ascending aorta aneurysm; Spatiotemporal analysis Motivated by the evidence that the onset and progression of the aneurysm of the ascending aorta (AAo) is intertwined with an adverse hemodynamic environment, the present study characterized in vivo the hemodynamic spatiotemporal complexity and organization in human aortas, with and without dilated AAo, exploring the relations with clinically relevant hemodynamic and geometric parameters. The Complex Networks (CNs) theory was applied for the first time to 4D flow magnetic resonance imaging (MRI) velocity data of ten patients, five of them presenting with AAo dilation. The time-histories along the cardiac cycle of velocity-based quantities were used to build correlation-based CNs. The CNs approach succeeded in capturing large-scale coherent flow features, delimiting flow separation and recirculation regions. CNs metrics highlighted that an increasing AAo dilation (expressed in terms of the ratio between the maximum AAo and aortic root diameter) disrupts the correlation in forward flow reducing the correlation persistence length, while preserving the spatiotemporal homogeneity of secondary flows. The application of CNs to in vivo 4D MRI data holds promise for a mechanistic understanding of the spatiotemporal complexity and organization of aortic flows, opening possibilities for the integration of in vivo quantitative hemodynamic information into risk stratification and classification criteria. Open access funding provided by Politecnico di Torino within the CRUI-CARE Agreement.

Published
2021

15. A New MAMLD1 Variant in an Infant With Microphallus and Hypospadias With Hormonal Pattern Suggesting Partial Hypogonadotropic Hypogonadism—Case Report

Author

Yeste, Diego, Aguilar-Riera, Cristina, Canestrino, Gennaro, Fernández-Alvarez, Paula, Clemente, María, Camats-Tarruella, Núria, Institut Català de la Salut, [Yeste D, Clemente M] Unitat d’Endocrinologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Aguilar-Riera C] Unitat d’Endocrinologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Canestrino G] Paediatric Endocrinology Service, Paediatric Service, Sant Joan de Déu Manresa Hospital, Manresa, Spain. [Fernández-Alvarez P] Laboratori de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Camats-Tarruella N] CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Grup de Recerca en Creixement i Desenvolupament, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Urogenital System::Genitalia::Genitalia, Male::Penis [ANATOMY], sistema urogenital::genitales::genitales masculinos::pene [ANATOMÍA], Endocrinology, Diabetes and Metabolism, fenómenos fisiológicos::crecimiento y desarrollo::desarrollo sexual [FENÓMENOS Y PROCESOS], Otros calificadores::Otros calificadores::Otros calificadores::/anomalías [Otros calificadores], Physiological Phenomena::Growth and Development::Sexual Development [PHENOMENA AND PROCESSES], Other subheadings::Other subheadings::Other subheadings::/abnormalities [Other subheadings], enfermedades del sistema endocrino::trastornos gonadales::hipogonadismo [ENFERMEDADES], Hipogonadisme, Aparell genital masculí, Endocrine System Diseases::Gonadal Disorders::Hypogonadism [DISEASES], Cromosomes sexuals - Anomalies
Abstract

MAMLD1 (X chromosome) is one of the recognized genes related to different sex development. It is expressed in testis and ovaries and seems to be involved in fetal sex development and in adult reproductive function, including testosterone biosynthesis. However, its exact role remains unclear. Over 40 genetic variants have been described, mainly in male individuals and mostly associated with hypospadias. Although MAMLD1 has been shown to regulate the expression of the steroidogenic pathway, patients with MAMLD1 variants mostly show normal gonadal function and normal testosterone levels. Here we describe a patient (46,XY) with hypospadias and microphallus, with low testosterone and dihydrotestosterone (DHT) levels, and with inappropriately low values of luteinizing hormone (LH) during minipuberty. This hormonal pattern was suggestive of partial hypogonadotropic hypogonadism. A stimulation test with hCG (4 months) showed no significant increase in both testosterone and dihydrotestosterone concentrations. At 5 months of age, he was treated with intramuscular testosterone, and the penis length increased to 3.5 cm. The treatment was stopped at 6 months of age. Our gonadal function massive-sequencing panel detected a previously unreported nonsense variant in the MAMLD1 gene (c.1738C>T:p.Gln580Ter), which was classified as pathogenic. This MAMLD1 variant, predicting a truncated protein, could explain his genital phenotype. His hormonal profile (low testosterone, dihydrotestosterone, and LH concentrations) together with no significant increase of testosterone and DHT plasma concentrations (hCG test) highlight the potential role of this gene in the biosynthesis of testosterone during the fetal stage and minipuberty of the infant. Besides this, the LH values may suggest an involvement of MAMLD1 in the LH axis or a possible oligogenesis. It is the first time that a decrease in DHT has been described in a patient with an abnormal MAMLD1.

Published
2022

16. [French Expert advice on the management of valproate in childbearing and pregnant women with bipolar disorder]

Author

Samalin, L, Arnould, A, Boudieu, L, Henry, C, Haffen, E, Drapier, D, Anmella, G, Pacchiarotti, I, Vieta, E, Belzeaux, R, Llorca, P. M., Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, GHU AP-HP Centre Université de Paris, Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Ce projet a reçu le support institutionnel de l’Association française de psychiatrie biologique et neuropsychopharmacologie.Les travaux de recherche du Dr Anmella sont soutenus par une bourse Rio Hortega 2021 (CM21/00017) financée par l'Instituto de Salud Carlos III (ISCIII) et cofinancée par le Fondo Social European Plus (FSE+).Les travaux de recherche du Dr Pacchiarotti sont soutenus par des bourses FIS 2018 et 2021 (PI18/01001, and PI21/00169) financées par l'Instituto de Salud Carlos III (ISCIII).

Subjects
Valproate, Bipolar Disorder, [SDV]Life Sciences [q-bio], Valproic Acid, Guidelines, Perinatal, Recommandations professionnelles, Childbearing, Pregnancy, Recurrence, Femme en âge de procréer, Périnatalité, Humans, Female, Anticonvulsants, Trouble bipolaire, Pregnant Women, Child, Antipsychotic Agents
Abstract

National audience; INTRODUCTION: The perinatal period is associated with high risk of relapses in women with untreated bipolar disorder (BD) and can have significant consequences on foetal and child development. Valproate is an effective mood stabilizer in BD but it is also the anticonvulsant associated to the highest risks of neurodevelopmental disorders and congenital malformations. The National Agency for the Safety of Medicines and Health Products (ANSM) changed the conditions of use and prescription of valproate in France in 2015. Its prescription is now contraindicated (i.e., not to be prescribed) in women able to have children unless alternative treatments are ineffective or not tolerated. Moreover, valproate could only be prescribed if the protocol of a specific pregnancy prevention program is followed. METHODS: A panel of experts from the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) provided consensus-based recommendations for switching and discontinuation of valproate in women with BD. The development of these recommendations consisted of an adaptation to French clinical practice based on a European expert opinion published in 2019. The experts discussed five real-world clinical situations in light of the scientific evidence and their clinical experience (a. Stable BD patient with valproate monotherapy who is planning pregnancy, b. Stable BD patient with valproate polytherapy who is planning pregnancy, c. Unstable BD patient with frequent relapses and valproate polytherapy who is planning pregnancy, d. Stable BD patient treated with valproate and unexpected pregnancy, e. Unstable BD patient treated with valproate and unexpected pregnancy) and developed, through several rounds of exchange drafts, a French version of clinical recommendations. RESULTS: First of all, some factors need to be considered for establishing personalized practical recommendations for a safe and effective switching or discontinuation of valproate in any clinical situations: planned pregnancy or unplanned pregnancy or current pregnancy, the existence or not of a pregnancy risk minimization program and a complete treatment history. Other factors that should be considered are the predominant polarity, the severity, the stability, the comorbidities associated with BD, the beliefs toward treatments, the family situation and the preference of the patient. The modalities for switching or discontinuation of valproate in women with BD were related to the clinical situation. First-line therapeutic alternatives such as lithium, lamotrigine, quetiapine, olanzapine or aripiprazole were preferred for patients suffering from a clinically stable BD considering pregnancy or pregnant. In patients suffering from clinically unstable BD, to reach stability was considered first. A shared decision-making should be systematically implemented and the patient must be fully informed of the risks related to an in-utero exposure to valproate, and the risks of the discontinuation/switch that is considered. CONCLUSION: Although the adaptation to French practice of the recommendations from the European expert opinion highlighted some differences in the criteria taken into consideration to guide the therapeutic decision, this expert advice will guide the clinician for switching and discontinuation of valproate in BD women able to have children or pregnant.

Published
2022

17. Poly-L-Lysine-Based αGal-Glycoconjugates for Treating Anti-αGal IgE-Mediated Diseases

Author

Olivera-Ardid, Sara, Bello-Gil, Daniel, Tuzikov, Alexander, Araujo, Ricardo N., Ferrero-Alves, Yara, García Figueroa, Blanca Esther, Labrador Horrillo, Moises, García-Pérez, Ana L., Bovin, Nicolai, Mañez, Rafael, Universitat Autònoma de Barcelona. Departament de Medicina, Institut Català de la Salut, [Olivera-Ardid S, Bello-Gil D, Ferrero-Alves Y] RemAb Therapeutics, Mòdul de Recerca B, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Tuzikov A] Department of Chemical Biology of Glycans and Lipids, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences (RAS), Moscow, Russia. [Araujo RN] Laboratório de Artrópodes Hematófagos, Departamento de Parasitologia, ICB/UFMG, Belo Horizonte, Brazil. [García Figueroa BE] MEGA: Asthma Inception and Progression Mechanisms, Complejo Hospitalario de Navarra (CHN), Pamplona, Spain. Instituto de investigación sanitaria de Navarra (IdiSNA), Pamplona, Spain. ARADyAL Research Network, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Labrador-Horrillo M] ARADyAL Research Network, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Secció d’Al•lèrgia, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Àrea de Malalties Immunomediades i Teràpies Innovadores, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Al·lèrgia, Allergy, Immunology, Immunoteràpia, αGal-syndrome, Immunotheraphy, Poly-l-lysine-based αGal-glycoconjugates, Mice, Immunology and Allergy, Animals, Humans, Polylysine, Ratolins, Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice [ORGANISMS], hidratos de carbono::glicoconjugados [COMPUESTOS QUÍMICOS Y DROGAS], Immune System Diseases::Hypersensitivity::Hypersensitivity, Immediate::Food Hypersensitivity [DISEASES], GalT-KO mice, Anti-αgal IgE inhibition, Immunoglobulin E, Carbohydrates::Glycoconjugates [CHEMICALS AND DRUGS], Al·lèrgia alimentària, Immunoglobulin M, Glicoconjugats, Immunoglobulin G, Immunotherapy, Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones [ORGANISMOS], Glycoconjugates, Food Hypersensitivity, enfermedades del sistema inmune::hipersensibilidad::hipersensibilidad inmediata::hipersensibilidad a los alimentos [ENFERMEDADES]
Abstract

Anti-αGal IgE antibodies mediate a spreading allergic condition known as αGal-syndrome (AGS). People exposed to hard tick bites are sensitized to αGal, producing elevated levels of anti-αGal IgE, which are responsible for AGS. This work presents an immunotherapy based on polymeric αGal-glycoconjugates for potentially treating allergic disorders by selectively inhibiting anti-αGal IgE antibodies. We synthesized a set of αGal-glycoconjugates, based on poly-L-lysine of different degrees of polymerization (DP1000, DP600, and DP100), to specifically inhibit in vitro the anti-αGal IgE antibodies in the serum of αGal-sensitized patients (n=13). Moreover, an animal model for αGal sensitization in GalT-KO mice was developed by intradermal administration of hard tick’ salivary gland extract, mimicking the sensitization mechanism postulated in humans. The in vitro exposure to all polymeric glycoconjugates (5-10-20-50-100 µg/mL) mainly inhibited anti-αGal IgE and IgM isotypes, with a lower inhibition effect on the IgA and IgG, respectively. We demonstrated a differential anti-αGal isotype inhibition as a function of the length of the poly-L-lysine and the number of αGal residues exposed in the glycoconjugates. These results defined a minimum of 27 αGal residues to inhibit most of the induced anti-αGal IgE in vitro. Furthermore, the αGal-glycoconjugate DP1000-RA0118 (10 mg/kg sc.) showed a high capacity to remove the anti-αGal IgE antibodies (≥75% on average) induced in GalT-KO mice, together with similar inhibition for circulating anti-αGal IgG and IgM. Our study suggests the potential clinical use of poly-L-lysine-based αGal-glycoconjugates for treating allergic disorders mediated by anti-αGal IgE antibodies. Copyright © 2022 Olivera-Ardid, Bello-Gil, Tuzikov, Araujo, Ferrero-Alves, García Figueroa, Labrador-Horrillo, García-Pérez, Bovin and Mañez.

Published
2022

18. Determinants of blood eosinophil levels in the general population and patients with COPD: a population-based, epidemiological study

Author

Miravitlles, Marc, Soler-Cataluña, Juan José, Soriano, Joan B.., García-Rio, Francisco, de Lucas, Pilar, Alfageme, Inmaculada, Casanova, Ciro, Rodríguez González-Moro, José Miguel, Sánchez-Herrero, M. Guadalupe, Ancochea, Julio, Cosio, Borja G.., Universidad Autònoma de Barcelona, Institut Català de la Salut, [Miravitlles M] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Soler-Cataluña JJ] CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Servicio de Neumología, Hospital Arnau de Vilanova Lliria, Universidad de la Laguna, Valencia, Spain. [Soriano JB] CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Servicio de Neumología, Hospital Universitario la Princesa, Universidad Autónoma de Madrid, Madrid, Spain. [García-Río F] CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Servicio de Neumología, Hospital Universitario la Paz-IdiPAZ, Madrid, Spain. [de Lucas P] Servicio de Neumología, Hospital General Gregorio Marañon, Madrid, Spain. [Alfageme I] Unidad de Gestión Clínica de Neumología, Hospital Universitario Virgen de Valme, Universidad de Sevilla, Sevilla, Spain, Vall d'Hebron Barcelona Hospital Campus, and UAM. Departamento de Medicina

Subjects
Male, Medicina, Epidemiology, Severity of Illness Index, Pulmonary Disease, Chronic Obstructive, Imaging population, Forced Expiratory Volume, Eosinophilia, Humans, Computed tomography, Eosinofília, Aged, Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Obstructive::Pulmonary Disease, Chronic Obstructive [DISEASES], Pulmons - Malalties obstructives, Middle Aged, respiratory tract diseases, enfermedades respiratorias::enfermedades pulmonares::enfermedades pulmonares obstructivas::enfermedad pulmonar obstructiva crónica [ENFERMEDADES], Eosinophils, Cross-Sectional Studies, Spain, Population Surveillance, Other subheadings::/blood [Other subheadings], Female, Morbidity, Otros calificadores::Otros calificadores::/sangre [Otros calificadores], Biomarkers
Abstract

Background Blood eosinophils are considered a biomarker for the treatment of chronic obstructive pulmonary disease (COPD). Population-based studies are needed to better understand the determinants of the blood eosinophil count (BEC) in individuals with and without COPD. Methods EPISCAN II is a multicentre, cross-sectional, population-based epidemiological study aimed at investigating the prevalence and determinants of COPD in Spain. Study subjects were randomly selected from the general population, and COPD was defined by a post-bronchodilator FEV1/FVC Results A total of 326 COPD and 399 non-COPD subjects were included in the analysis. The mean age (standard deviation [SD]) was 63.2 years (11.0), 46.3% were male, and 27.6% were active smokers. BEC was significantly higher in individuals with COPD [192 cells/μL (SD: 125) vs. 160 cells/μL (SD: 114); p = 0.0003]. In a stepwise multivariate model, being male, active smoker and having a previous diagnosis of asthma were independently associated with having a higher BEC. Conclusions This population-based study estimated the distribution of eosinophils in the healthy adult population and concluded that COPD patients have a significantly higher BEC. Male sex, active smoking and concomitant asthma were significantly associated with a higher BEC.

Published
2022

19. Obesity and related comorbidities in a large population-based cohort of subjects with type 1 diabetes in Catalonia

Author

Idoia Genua, Josep Franch-Nadal, Elena Navas, Manel Mata-Cases, Gabriel Giménez-Pérez, Bogdan Vlacho, Didac Mauricio, Albert Goday, [Genua I] Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain. Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain. [Franch-Nadal J] Diabetis en Atenció Primaria-Catalunya (DAP-Cat) group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. Primary Health Care Center Raval Sud, Gerència d’Atenció Primaria, Institut Català de la Salut, Barcelona, Spain. Centro de Investigación Biomédica en Red (CIBER) of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. [Navas E] Unitat de Suport a la Recerca, Barcelona, Spain. [Mata-Cases M] Diabetis en Atenció Primaria-Catalunya (DAP-Cat) group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. Centro de Investigación Biomédica en Red (CIBER) of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. Primary Health Care Center La Mina, Gerència d’Atenció Primària Barcelona Ciutat, Institut Català de la Salut, Sant Adrià de Besòs, Spain. [Giménez-Pérez G] Endocrinology Section, Department of Medicine, Hospital General de Granollers, Granollers, Spain. School of Medicine and Health Sciences, Universitat Internacional de Catalunya, Sant Cugat del Vallès, Spain. [Vlacho B] Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain. Diabetis en Atenció Primaria-Catalunya (DAP-Cat) group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. Centro de Investigación Biomédica en Red (CIBER) of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. [Mauricio D] Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Diabetis en Atenció Primaria-Catalunya (DAP-Cat) group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. Centro de Investigación Biomédica en Red (CIBER) of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. Department of Medicine, Universitat de Vic - Universitat Central de Catalunya, Barcelona, Spain. [Goday A] Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain. Deparment of Endocrinology & Nutrition, Hospital del Mar, IMIM Institut Mar d’Investigacions Mediques. Parc de Salut Mar, Barcelona, Spain. CIBERobn, Instituto de Salud Carlos III (ISCIII), Madrid, Spain, and Hospital General de Granollers

Subjects
Síndrome metabòlica, Diabetis, Adolescent, Endocrinology, Diabetes and Metabolism, enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo de la glucosa::diabetes mellitus::diabetes mellitus tipo I [ENFERMEDADES], Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight::Obesity [DISEASES], Metabolic syndrome, Comorbidities, Diabetes Mellitus, Type 1, Cross-Sectional Studies, Type 1 diabetes, Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 1 [DISEASES], Spain, Obesitat, Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism::Insulin Resistance::Metabolic Syndrome [DISEASES], Humans, enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo de la glucosa::hiperinsulinismo::resistencia a la insulina::síndrome metabólico [ENFERMEDADES], afecciones patológicas, signos y síntomas::signos y síntomas::peso corporal::sobrepeso::obesidad [ENFERMEDADES], Obesity, Cardiovascular risk factors, Retrospective Studies
Abstract

IntroductionObesity, an increasing global health problem, can affect people with other disease conditions. The prevalence of obesity in people with type 1 diabetes (T1D) is not well known. The aim of this study was to describe extensively the characteristics and prevalence of different classes of obesity according to BMI (body mass index) categories in a large cohort of patients with T1D.Material and methodsThis was a retrospective, cross-sectional study in Catalonia. We reviewed all patients with T1D diagnosis, ≥ 18 years old and with BMI data from the SIDIAP database. Sociodemographic and clinical data, cardiovascular risk factors, laboratory parameters and concomitant medications were collected.ResultsA total of 6,068 patients with T1D were analyzed. The prevalence of obesity in the total sample was 18% (13.8% with class 1 obesity [BMI 30-34.9 kg/m2]). Patients with obesity had a higher prevalence of other cardiovascular risk factors (i.e. hypertension was 61.4% vs. 37.5%; dyslipidemia 63.6% vs 44%, and chronic kidney disease 38.4% vs. 24.4%; p 25 kg/m2. Patients with obesity did not have poorer glycemic control.ConclusionThe presence of obesity in people with T1D is frequent and cardiovascular risk factors are more common and more poorly controlled in T1D patients with obesity.

Published
2022

20. Socioeconomic status and prognosis of patients with ST-elevation myocardial infarction managed by the emergency-intervention 'Codi IAM' network

Author

Helena Tizón-Marcos, Beatriz Vaquerizo, Josepa Mauri Ferré, Núria Farré, Rosa-Maria Lidón, Joan Garcia-Picart, Ander Regueiro, Albert Ariza, Xavier Carrillo, Xavier Duran, Paul Poirier, Mercè Cladellas, Anna Camps-Vilaró, Núria Ribas, Hector Cubero-Gallego, Jaume Marrugat, Institut Català de la Salut, [Tizón-Marcos H] Hospital del Mar, Servicio de Cardiología, Barcelona, Spain. Grupo de Investigación Biomédica en Enfermedades del Corazón, Barcelona, Spain. IMIM (Instituto Hospital del Mar de Investigaciones Médicas), Barcelona, Spain. Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Vaquerizo B, Ferré JM] Hospital del Mar, Servicio de Cardiología, Barcelona, Spain. Grupo de Investigación Biomédica en Enfermedades del Corazón, Barcelona, Spain. IMIM (Instituto Hospital del Mar de Investigaciones Médicas), Barcelona, Spain. Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Mauri Ferré J] Hospital Universitari GermansTrias I. Pujol, Servicio de Cardiología, Badalona, Spain. Departament de Salut, Generalitat de Catalunya, Barcelona, Spain. [Lidón RM] Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Garcia-Picart J] Hospital de la Santa Creu I. Sant Pau, Servicio de Cardiología, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
intervenciones quirúrgicas::procedimientos quirúrgicos cardiovasculares::procedimientos quirúrgicos vasculares::procedimientos endovasculares::cirugía coronaria percutánea [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Primary percutaneous coronary intervention, Cardiac patients, enfermedades cardiovasculares::enfermedades cardíacas::isquemia miocárdica::infarto de miocardio [ENFERMEDADES], Malalts cardíacs, Infart de miocardi - Prognosi, Angioplàstia transluminal, Cardiovascular Diseases::Heart Diseases::Myocardial Ischemia::Myocardial Infarction [DISEASES], Health Care (Public Health)::Health Promotion::Health Inequality Monitoring::Equity Stratifiers::Health Care (Public Health)::Socioeconomic Factors [PUBLIC HEALTH], atención a la salud (salud pública)::promoción de la salud::monitorización de las desigualdades en salud::estratificadores de equidad::atención a la salud (salud pública)::factores socioeconómicos [SALUD PÚBLICA], Economic conditions, ST-elevation myocardial infarction, Reperfusion, population characteristics, Condicions econòmiques, Surgical Procedures, Operative::Cardiovascular Surgical Procedures::Vascular Surgical Procedures::Endovascular Procedures::Percutaneous Coronary Intervention [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Inequalities, Mortality, Cardiology and Cardiovascular Medicine, Diagnosis::Prognosis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], diagnóstico::pronóstico [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Estatus social
Abstract

Inequalities; Mortality; Primary percutaneous coronary intervention Desigualdades; Mortalidad; Intervención coronaria percutánea primaria Desigualtats; Mortalitat; Intervenció coronària percutània primària Background: Despite the spread of ST-elevation myocardial infarction (STEMI) emergency intervention networks, inequalities in healthcare access still have a negative impact on cardiovascular prognosis. The Family Income Ratio of Barcelona (FIRB) is a socioeconomic status (SES) indicator that is annually calculated. Our aim was to evaluate whether SES had an effect on mortality and complications in patients managed by the “Codi IAM” network in Barcelona. Methods: This is a cohort study with 3,322 consecutive patients with STEMI treated in Barcelona from 2010 to 2016. Collected data include treatment delays, clinical and risk factor characteristics, and SES. The patients were assigned to three SES groups according to FIRB score. A logistic regression analysis was conducted to estimate the adjusted effect of SES on 30-day mortality, 30-day composite cardiovascular end point, and 1-year mortality. Results: The mean age of the patients was 65 ± 13% years, 25% were women, and 21% had diabetes mellitus. Patients with low SES were younger, more often hypertensive, diabetic, dyslipidemic (p < 0.003), had longer reperfusion delays (p < 0.03) compared to participants with higher SES. Low SES was not independently associated with 30-day mortality (OR: 0.95;9 5% CI: 0.7–1.3), 30-day cardiovascular composite end point (OR: 1.03; 95% CI: 0.84–1.26), or 1-year all-cause mortality (HR: 1.09; 95% CI: 0.76–1.56). Conclusion: Although the low-SES patients with STEMI in Barcelona city were younger, had worse clinical profiles, and had longer revascularization delays, their 30-day and 1-year outcomes were comparable to those of the higher-SES patients. This project was supported by the CIBERCV of research on cardiovascular diseases personnel hired with its resources.

Published
2022

21. Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations

Author

Katharina Nimptsch, Krasimira Aleksandrova, Veronika Fedirko, Mazda Jenab, Marc J. Gunter, Peter D. Siersema, Kana Wu, Verena Katzke, Rudolf Kaaks, Salvatore Panico, Domenico Palli, Anne M May, Sabina Sieri, Bas Bueno-de-Mesquita, Karina Standahl, Maria-Jose Sánchez, Aurora Perez-Cornago, Anja Olsen, Anne Tjønneland, Catalina Bonet Bonet, Christina C. Dahm, María-Dolores Chirlaque, Valentina Fiano, Rosario Tumino, Aurelio Barricarte Gurrea, Marie-Christine Boutron-Ruault, Florence Menegaux, Gianluca Severi, Bethany van Guelpen, Young-Ae Lee, Tobias Pischon, HAL UVSQ, Équipe, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Harvard T.H. Chan School of Public Health, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, University of Bremen, The University of Texas M.D. Anderson Cancer Center [Houston], Emory University [Atlanta, GA], Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Radboud University Medical Center [Nijmegen], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), 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, World Health Organization, WHO, Cancer Prevention and Research Institute of Texas, CPRIT: RR200056, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Consejería de Salud y Familias, Junta de Andalucía, NIHR Imperial Biomedical Research Centre, BRC, We acknowledge the use of data and biological samples from the EPIC-Asturias cohort, PI Jose-Ramon Quiros-Garcia and EPI-San Sebastian, PI Amiano Pilar. Veronika Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056). Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization., The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/M012190/1 to EPIC-Oxford) (United Kingdom). The EPIC-Norfolk study (DOI https://doi.org/10.22025/2019.10.105.00004 ) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research., The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)., and We acknowledge the use of data and biological samples from the EPIC-Asturias cohort, PI Jose-Ramon Quiros-Garcia and EPI-San Sebastian, PI Amiano Pilar. Veronika Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056).

Subjects
Cancer Research, Cancer och onkologi, Public Health, Global Health, Social Medicine and Epidemiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Polymorphism, Single Nucleotide, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], C-Reactive Protein, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cardiovascular and Metabolic Diseases, Risk Factors, Cancer and Oncology, Genetics, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Genetic Predisposition to Disease, Prospective Studies, Colorectal Neoplasms
Abstract

Background The role of elevated pre-diagnostic C-reactive protein (CRP) concentrations on mortality in individuals with colorectal cancer (CRC) remains unclear. Methods We investigated the association between pre-diagnostic high-sensitivity CRP concentrations and CRP genetic variation associated with circulating CRP and CRC-specific and all-cause mortality based on data from 1,235 individuals with CRC within the European Prospective Investigation into Cancer and Nutrition cohort using multivariable-adjusted Cox proportional hazards regression. Results During a median follow-up of 9.3 years, 455 CRC-specific deaths were recorded, out of 590 deaths from all causes. Pre-diagnostic CRP concentrations were not associated with CRC-specific (hazard ratio, HR highest versus lowest quintile 0.92, 95% confidence interval, CI 0.66, 1.28) or all-cause mortality (HR 0.91, 95% CI 0.68, 1.21). Genetic predisposition to higher CRP (weighted score based on alleles of four CRP SNPs associated with higher circulating CRP) was not significantly associated with CRC-specific mortality (HR per CRP-score unit 0.95, 95% CI 0.86, 1.05) or all-cause mortality (HR 0.98, 95% CI 0.90, 1.07). Among four investigated CRP genetic variants, only SNP rs1205 was significantly associated with CRC-specific (comparing the CT and CC genotypes with TT genotype, HR 0.54, 95% CI 0.35, 0.83 and HR 0.58, 95% CI 0.38, 0.88, respectively) and all-cause mortality (HR 0.58, 95% CI 0.40, 0.85 and 0.64, 95% CI 0.44, 0.92, respectively). Conclusions The results of this prospective cohort study do not support a role of pre-diagnostic CRP concentrations on mortality in individuals with CRC. The observed associations with rs1205 deserve further scientific attention.

Published
2022

22. Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition

Author

Marie Breeur, Pietro Ferrari, Laure Dossus, Mazda Jenab, Mattias Johansson, Sabina Rinaldi, Ruth C. Travis, Mathilde His, Tim J. Key, Julie A. Schmidt, Kim Overvad, Anne Tjønneland, Cecilie Kyrø, Joseph A. Rothwell, Nasser Laouali, Gianluca Severi, Rudolf Kaaks, Verena Katzke, Matthias B. Schulze, Fabian Eichelmann, Domenico Palli, Sara Grioni, Salvatore Panico, Rosario Tumino, Carlotta Sacerdote, Bas Bueno-de-Mesquita, Karina Standahl Olsen, Torkjel Manning Sandanger, Therese Haugdahl Nøst, J. Ramón Quirós, Catalina Bonet, Miguel Rodríguez Barranco, María-Dolores Chirlaque, Eva Ardanaz, Malte Sandsveden, Jonas Manjer, Linda Vidman, Matilda Rentoft, David Muller, Kostas Tsilidis, Alicia K. Heath, Hector Keun, Jerzy Adamski, Pekka Keski-Rahkonen, Augustin Scalbert, Marc J. Gunter, Vivian Viallon, Cancer Research UK, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), 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, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC: 2014/1183, C8221/A19170, Seventh Framework Programme, FP7: 2014/1193, 313010, C19335/A21351, National Research Council, NRC, World Cancer Research Fund International, WCRF, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, European Commission, EC, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Generalitat de Catalunya, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Fondation ARC pour la Recherche sur le Cancer, ARC, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut National Du Cancer, INCa: 2009-139, 2013/1002, 2014-1-RT-02-CIRC-1, 2015-166, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Consejería de Salud y Familias, Junta de Andalucía, NIHR Imperial Biomedical Research Centre, BRC, The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)., This paper is dedicated to the memory our of colleague Dr. Bas Bueno-de-Mesquita. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). IDIBELL acknowledges support from the Generalitat de Catalunya through the CERCA Program. The breast cancer study was funded by the French National Cancer Institute (grant number 2015-166). The colorectal cancer studies were funded by World Cancer Research Fund (reference: 2013/1002, reference: 313010, reference: 2014/1193, INCa, grant numbers 2009-139 and 2014-1-RT-02-CIRC-1) and by internal funds of the IARC. For the participants in the prostate cancer study, sample retrieval and preparation, and assays of metabolites were supported by Cancer Research UK (C8221/A19170), and funding for grant 2014/1183 was obtained from the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme. Mathilde His’ work reported here was undertaken during the tenure of a postdoctoral fellowship awarded by the International Agency for Research on Cancer, financed by the Fondation ARC. The funders were not involved in designing the study, collecting, analysing, and interpreting results, or writing and submitting the manuscript for publication., and HAL UVSQ, Équipe

Subjects
Male, Carcinoma, Hepatocellular, Proline, Glutamine, Kidney, Risk Factors, General & Internal Medicine, Humans, Metabolomics, Histidine, Prospective Studies, Breast, Càncer, 11 Medical and Health Sciences, Colorectal, Cancer, Cancer och onkologi, Liver Neoplasms, Prostate, Lysophosphatidylcholines, General Medicine, Sphingomyelins, Metabolòmica, Liver, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Cancer and Oncology, Carcinoma, Hepatocellular/diagnosis, Phosphatidylcholines, Epic, Endometrial, Lasso, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, EPIC
Abstract

Background Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. Methods We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty. Results Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk. Conclusions These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.

Published
2022

23. Risk factors for the development of bronchiectasis in patients with asthma

Author

Xavier Muñoz, Christian Romero-Mesones, Diego Varona-Porres, Donghai Ma, María Jesús Cruz, Iñigo Ojanguren, Institut Català de la Salut, [Ma D, Romero-Mesones C] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Cruz MJ, Ojanguren I] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Varona-Porres D] Servei de Radiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Munoz X] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Departament de Fisiologia, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, Respiratory Tract Diseases::Bronchial Diseases::Bronchiectasis [DISEASES], Vital Capacity, Comorbidity, Logistic regression, Severity of Illness Index, Risk Factors, Asthma control, Forced Expiratory Volume, Other subheadings::/diagnosis [Other subheadings], Prevalence, Age of Onset, Lung, Asma - Complicacions, Multidisciplinary, Asthma exacerbations, Middle Aged, Bronchiectasis, Disease Progression, Medicine, Female, enfermedades respiratorias::enfermedades bronquiales::bronquiectasia [ENFERMEDADES], Respiratory Tract Diseases::Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Obstructive::Respiratory Tract Diseases::Asthma [DISEASES], Adult, medicine.medical_specialty, Science, Otros calificadores::/diagnóstico [Otros calificadores], enfermedades respiratorias::enfermedades respiratorias::enfermedades pulmonares::enfermedades pulmonares obstructivas::enfermedades respiratorias::asma [ENFERMEDADES], técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Risk Assessment, Article, FEV1/FVC ratio, Medical research, Internal medicine, medicine, Asthmatic patient, Humans, In patient, Asthma, Bronquièctasi - Factors de risc, Aged, Retrospective Studies, business.industry, medicine.disease, respiratory tract diseases, Spain, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], business
Abstract

Asthma; Medical research Asma; Investigación médica Asma; Recerca mèdica Though asthma and bronchiectasis are two different diseases, their coexistence has been demonstrated in many patients. The aim of the present study is to compare the characteristics of asthmatic patients with and without bronchiectasis and to assess risk factors for the development of this condition. Two hundred and twenty-four moderate-severe asthmatic patients were included. The severity of bronchiectasis was assessed by Reiff and FACED parameters. Logistic regression was used to identify independent factors associated with bronchiectasis. Bronchiectasis was identified in 78 asthma patients. In severe asthma patients, its prevalence was 56.9%. Bronchiectasis was defined as mild in81% of patients using modified Reiff criteria and in 74% using FACED criteria. Asthmatic patients with bronchiectasis had decreasing FEV1, FVC and FEV1/FVC (p = 0.002, 0.005 and 0.014 respectively), presented more frequent asthma exacerbations (p

Published
2021

24. Exploring the relationship between metal exposure, BDNF, and behavior in adolescent males

Author

Mariana F. Fernández, Fernando Gil, Antonio Mundo, Pablo Olmedo, Vicente Mustieles, Shereen Cynthia D'Cruz, Carmen Freire, Marina Molina, Louis Legoff, Andrea Rodríguez-Carrillo, Iris Reina-Pérez, Arthur David, Fatima Smagulova, Universidad de Granada (UGR), CIBER de Epidemiología y Salud Pública (CIBERESP), Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), École des Hautes Études en Santé Publique [EHESP] (EHESP), Instituto de Salud Carlos III (ISCIII)Instituto de Salud Carlos IIIEuropean Commission [PT17/0019], ERDFEuropean Commission, European Union's Horizon 2020 research and innovation program HBM4EU [733032], ISCIIIInstituto de Salud Carlos III [CP16/00085, FIS 17/01526, FIS-PI16/01820, FIS-PI16/01858], University of Granada, Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP), Spanish Ministry of EducationSpanish Government [FPU 16/03011], Miguel Servet Type I program of the ISCIII 'Fondo Europeo de Desarrollo Regional' (ISCIII/FEDER) [MS16/00085], Universidad de Granada = University of Granada (UGR), 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 des sciences en santé environnementale (DEESSE), This research would not have been achieved without the selfless collaboration of the INMA-Granada adolescents and families who took part in the study. The authors also acknowledge the Human Genotyping Laboratory at the Spanish National Cancer Research Center, CeGen-PRB3, which is supported by grant no. PT17/0019, of the PE I+D+i 2013–2016, funded by the Instituto de Salud Carlos III (ISCIII) and ERDF. They thank the European Union's Horizon 2020 research and innovation program HBM4EU for financial support under Grant Agreement No. 733032. The study was also supported by the ISCIII with grant no. CP16/00085. The authors also acknowledge the funding received from the University of Granada for the open access publishing costs and the support of the Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP), and the ISCIII (FIS 17/01526, FIS-PI16/01820 and FIS-PI16/01858). Vicente Mustieles and Shereen Cynthia D'Cruz were under contract with the HBM4EU project. A. Rodríguez-Carrillo received a predoctoral fellowship (FPU 16/03011) from the Spanish Ministry of Education and C. Freire (grant no. MS16/00085) received a grant under the Miguel Servet Type I program of the ISCIII ‘‘Fondo Europeo de Desarrollo Regional’’ (ISCIII/FEDER)., European Project: 733032,H2020,HBM4EU(2017), Chard-Hutchinson, Xavier, and European Human Biomonitoring Initiative - HBM4EU - - H20202017-01-01 - 2021-12-31 - 733032 - VALID

Subjects
[SDE] Environmental Sciences, HBM4EU, Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], CBCL, Urine, 010501 environmental sciences, Effect biomarkers, 01 natural sciences, Brain-derived neurotrophic factor, Effect biomarker, Arsenic, 03 medical and health sciences, 0302 clinical medicine, Neurotrophic factors, Internal medicine, medicine, Humans, 030212 general & internal medicine, 0105 earth and related environmental sciences, Behavior, DNA methylation, business.industry, Brain-Derived Neurotrophic Factor, Confounding, Public Health, Environmental and Occupational Health, Methylation, Environmental Exposure, Mercury, 3. Good health, [SDV] Life Sciences [q-bio], Human biomonitoring, Endocrinology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Metals, Adolescent Behavior, [SDE]Environmental Sciences, Biomarker (medicine), [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

This research would not have been achieved without the selfless collaboration of the INMA-Granada adolescents and families who took part in the study. The authors also acknowledge the Human Genotyping Laboratory at the Spanish National Cancer Research Center, CeGen-PRB3, which is supported by grant no. PT17/0019, of the PE I+D+i 2013-2016, funded by the Instituto de Salud Carlos III (ISCIII) and ERDF. They thank the European Union's Horizon 2020 research and innovation program HBM4EU for financial support under Grant Agree-ment No. 733032. The study was also supported by the ISCIII with grant no. CP16/00085. The authors also acknowledge the funding received from the University of Granada for the open access publishing costs and the support of the Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP) , and the ISCIII (FIS 17/01526, FIS-PI16/01820 and FIS-PI16/01858) . Vicente Mustieles and Shereen Cynthia D'Cruz were under contract with the HBM4EU project. A. Rodriguez-Carrillo received a predoctoral fellowship (FPU 16/03011) from the Spanish Ministry of Education and C. Freire (grant no. MS16/00085) received a grant under the Miguel Servet Type I program of the ISCIII "Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) . This article forms part of the doctoral thesis developed by Andrea Rodriguez-Carrillo in the context of the "Clinical Medicine and Public Health Program" of the University of Granada (Spain) ., Background: Brain-derived neurotrophic factor (BDNF) plays an important role in brain development by regulating multiple pathways within the central nervous system. In the Human Biomonitoring for Europe Project (HBM4EU), this neurotrophin is being implemented as a novel effect biomarker to evaluate the potential threats of environmental chemicals on neurodevelopment. Objectives: To explore the relationships among exposure to environmental metals, BDNF biomarkers at two levels of biological complexity, and behavioral function in adolescent males. Methods: Data were gathered from 125 adolescents on: spot urine sample total concentrations of the neurotoxic metal(oid)s arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb); serum BDNF protein concentrations; and concurrent behavioral functioning according to the Child Behavior Check List (CBCL/6–18). In 113 of the participants, information was also collected on blood BDNF DNA methylation at six CpGs. Associations were evaluated by multivariate linear regression analysis adjusted for confounders. Results: As, Cd, Hg, and Pb were detected in 100%, 98.5%, 97.0%, and 89.5% of urine samples, respectively. Median serum BDNF concentration was 32.6 ng/mL, and total percentage of BDNF gene methylation was 3.8%. In the adjusted models, urinary As was non-linearly associated with more internalizing problems and Cd with more externalizing behaviors. The percentage BDNF DNA methylation at CPGs #5 and the mean percentage CpG methylation increased across As tertiles (p-trend = 0.04 and 0.03, respectively), while 2nd tertile and 3rd tertile of Cd concentrations were associated with lower serum BDNF and higher CpG3 methylation percentage. Additionally, when BDNF was categorized in tertiles, serum BDNF at the 3rd tertile was associated with fewer behavioral problems, particularly withdrawn (p-trend = 0.04), social problems (p-trend = 0.12), and thought problems (p-trend = 0.04). Conclusion: Exposure to As and Cd was associated with BDNF gene DNA methylation BDNF gene and serum BDNF, respectively. Associations with DNA methylation may be attributable to a higher variability over time in circulating BDNF concentrations than in the methylation status of this gene. Caution should be taken when interpreting the results relating postnatal Pb and Hg to behavioral functioning. Further studies are needed to verify these findings., Instituto de Salud Carlos III European Commission PT17/0019, European Commission, European Union's Horizon 2020 research and innovation program HBM4EU 733032, Instituto de Salud Carlos III CP16/00085 FIS 17/01526 FIS-PI16/01820 FIS-PI16/01858, University of Granada, Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP), Spanish Government FPU 16/03011, Miguel Servet Type I program of the ISCIII "Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) MS16/00085

Published
2021

25. Pre-diagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma

Author

Heinz Freisling, Susana Merino, Aurelio Barricarte, Augustin Scalbert, Domenico Palli, Eleni Peppa, Hanna Nyström, Klas Sjöberg, Magdalena Stepien, Antonia Trichopoulou, Aurora Perez-Cornago, Marina Lopez-Nogueroles, Gianluca Severi, Carlotta Sacerdote, Dragos Ciocan, Tilman Kühn, Elisabete Weiderpass, Cosmin Sebastian Voican, Manuela M. Bergmann, Gabriel Perlemuter, Eugene Jansen, Rudolf Kaaks, Michael F. Leitzmann, Julie A. Schmidt, Catherine Dong, Anna Karakatsani, María José Sánchez, Rosario Tumino, Bodil Ohlsson, H. Bas Bueno-de-Mesquita, Marc J. Gunter, Raul Zamora Ros, Guri Skeie, José Mª Huerta, Heiner Boeing, Agustín Lahoz, Vittorio Krogh, Pilar Amiano, Francesca Mancini, Anne Tjønneland, Marie-Christine Boutron-Ruault, Salvatore Panico, Mazda Jenab, Sofia Christakoudi, Vivian Viallon, Renée T. Fortner, Mårten Werner, Faculté de Médecine Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, 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, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: 1000143, MR/M012190/1, Cancer Research UK, CRUK: 14136, C8221/A29017, World Cancer Research Fund, WCRF, University of Cambridge, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Deutsche Krebshilfe, Institut National Du Cancer, INCa: 2009‐139, 2014‐1‐RT‐02‐CIRC‐1, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, This work was supported in part by the French National Cancer Institute (L'Institut National du Cancer, INCa, grant numbers 2009‐139 and 2014‐1‐RT‐02‐CIRC‐1, PI: M. Jenab) and by internal funds of the IARC. The coordination of EPIC is financially supported by the International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam‐Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra and the Catalan Institute of Oncology—ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC‐Norfolk, C8221/A29017 to EPIC‐Oxford), Medical Research Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford) (United Kingdom). The funding sources had no influence on the design of the study, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the article for publication. Funding information, and We would like to acknowledge Dr Krasimira Aleksandrova for input on the present manuscript, along with the National Institute for Public Health and the Environment (Bilthoven, The Netherlands), the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands, Department of Public Health Aarhus University (Aarhus, Denmark), University of Cambridge (Cambridge, United Kingdom), for their contributions and ongoing support to the EPIC Study.

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, obesity, Carcinoma, Hepatocellular, medicine.drug_class, education, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, Bile Acids and Salts, Cohort Studies, chemistry.chemical_compound, Internal medicine, medicine, Biomarkers, Tumor, Choline, Humans, Prospective cohort study, Carcinogen, Aged, Cancer prevention, Bile acid, cancer prevention, business.industry, Confounding, Liver Neoplasms, bile acid metabolism, biomarkers, hepatocellular carcinoma, Middle Aged, medicine.disease, Obesity, Oncology, chemistry, Hepatocellular carcinoma, Case-Control Studies, Female, business
Abstract

This is the peer reviewed version of the following article: Stepien et.al (2021). Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma. International Journal of Cancer, which has been published in final form at https://doi.org/10.1002/ijc.33885. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. Bile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling = 2.30, 95% confidence intervals [CI]: 1.76-3.00), and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.

Published
2021

26. A Clinical-Genetic Score for Predicting Weight Loss after Bariatric Surgery: The OBEGEN Study

Author

Alexis Luna, Maricruz de la Fuente, Amador Ruiz, Nuria Vilarrasa, Albert Lecube, Andreu Simó-Servat, Ramon Vilallonga, Cristina Hernández, Mercedes Rigla, Eduardo Salas, Enzamaria Fidilio, Silvia Pellitero, Andreea Ciudin, Assumpta Caixàs, Rafael Simó, Liliana Gutiérrez-Carrasquilla, Enric Sánchez, Institut Català de la Salut, [Ciudin A, Hernández C, Simó R] Servei d’Endocrinologia i Nutrició, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Unitat de Recerca en Diabetis i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain. [Fidilio E] Servei d’Endocrinologia i Nutrició, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Unitat de Recerca en Diabetis i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Gutiérrez-Carrasquilla L] Endocrinology and Nutrition Department, Hospital Universitari Arnau de Vilanova, Obesity, Diabetes and Metabolism Research Group (ODIM), Institut de Recerca Biomèdica de Lleida (IRBLleida), Universitat de Lleida, 25198 Lleida, Spain. [Caixàs A] Endocrinology and Nutrition Department, Hospital Universitari Parc Tauli, Medicine Department, Universitat Autònoma de Barcelona, Institut d’Investigació i Innovació Parc Taulí, 08208 Sabadell, Spain. Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain. [Vilarrasa N] Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain. Department of Endocrinology, Diabetes and Nutrition, Bellvitge University Hospital-IDIBELL, L’Hospitalet de Llobregat, 08907 Barcelona, Spain. [Pellitero S] Endocrine and Nutrition Department, Germans Trias i Pujol University Hospital, Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain. [Vilallonga R, Ruiz A] Unitat de Cirurgia Endocrina, Metabòlica i Bariàtrica, Servei de Cirurgia General i Digestiva, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Center of Excellence for the EAC-BS, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
obesity, bariatric surgery, weight loss, genetics, polygenic risk, medicine.medical_specialty, Weight loss, Therapeutics::Obesity Management::Bariatrics::Bariatric Surgery [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Obesitat mòrbida, Medicine (miscellaneous), Single-nucleotide polymorphism, Article, Aprimament, terapéutica::manejo de la obesidad::bariatría::cirugía bariátrica [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Obesitat - Cirurgia, Diabetes mellitus, medicine, Genetics, Obesity, Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity::Obesity, Morbid [DISEASES], enfermedades nutricionales y metabólicas::trastornos nutricionales::hipernutrición::obesidad::obesidad mórbida [ENFERMEDADES], Genetic testing, Bariatric surgery, medicine.diagnostic_test, Receiver operating characteristic, Cirurgia, Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Body Weight Changes::Weight Loss [DISEASES], business.industry, Polygenic risk, afecciones patológicas, signos y síntomas::signos y síntomas::peso corporal::cambios en el peso corporal::pérdida de peso [ENFERMEDADES], INSIG2, medicine.disease, Surgery, Medicine, Obesitat, Personalized medicine, medicine.symptom, business, Genètica
Abstract

Genética; Obesidad; Pérdida de peso Genetics; Obesity; Weight loss Genètica; Obesitat; Pèrdua de pes Around 30% of the patients that undergo bariatric surgery (BS) do not reach an appropriate weight loss. The OBEGEN study aimed to assess the added value of genetic testing to clinical variables in predicting weight loss after BS. A multicenter, retrospective, longitudinal, and observational study including 416 patients who underwent BS was conducted (Clinical.Trials.gov- NCT02405949). 50 single nucleotide polymorphisms (SNPs) from 39 genes were examined. Receiver Operating Characteristic (ROC) curve analysis were used to calculate sensitivity and specificity. Satisfactory response to BS was defined as at nadir excess weight loss >50%. A good predictive model of response [area under ROC of 0.845 (95% CI 0.805–0.880), p < 0.001; sensitivity 90.1%, specificity 65.5%] was obtained by combining three clinical variables (age, type of surgery, presence diabetes) and nine SNPs located in ADIPOQ, MC4R, IL6, PPARG, INSIG2, CNR1, ELOVL6, PLIN1 and BDNF genes. This predictive model showed a significant higher area under ROC than the clinical score (p = 0.0186). The OBEGEN study shows the key role of combining clinical variables with genetic testing to increase the predictability of the weight loss response after BS. This finding will permit us to implement a personalized medicine which will be associated with a more cost-effective clinical practice. This research was supported by grants from the “Pla Estratègic de Recerca i Innovació en Salut” (PERIS) 2016–2020 (SLT002/16/00497), the Instituto de Salud Carlos III (PI PI18/00964), Fondos FEDER “Una manera de hacer Europa”), and Menarini España. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) is an initiative of the Instituto Carlos III.

Published
2021

27. Bisphenol-A exposure and risk of breast and prostate cancer in the Spanish European Prospective Investigation into Cancer and Nutrition study

Author

Sandra Colorado, María José Sánchez, Ana Jimenez, Antonio Agudo, Pilar Amiano, Elena Salamanca-Fernández, Marcela Guevara, Nicolás Olea, Fernando Vela, Josu Delfrade, Juan P. Arrebola, Miguel Rodríguez-Barranco, Maria Dolores Chirlaque, [Salamanca-Fernández,E, Rodríguez-Barranco,M, Sánchez,MJ] Andalusian School of Public Health (EASP), Campus Universitario de Cartuja, Granada, Spain. [Salamanca-Fernández,E, Arrebola,JP, Vela,F, Olea,N, Sánchez,MJ] Instituto de Investigación Biosanitaria ibs. GRANADA, Granada, Spain. [Rodríguez-Barranco,M, Amiano,P, Delfrade,J, Chirlaque,MD, Colorado,S, Guevara,M, Sánchez,MJ] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Amiano,P, Jimenez,A] Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain. [Delfrade,J, Guevara,M] Navarra Public Health Institute, Pamplona, Spain. [Delfrade,J, Guevara,M] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Chirlaque,MD, Colorado,S] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque,MD] Department of Health and Sciences, University of Murcia, Murcia, Spain. [Colorado,S] Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia. [Arrebola,JP, Sánchez,MJ] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. [Olea,N] Department of Radiology, University of Granada, Granada, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, Nutrition and Cancer Group, Bellvitge Biomedical Research Institute - IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain., and This work was supported by the Ministry of economy and competitiveness and the National Institute of Health: Instituto de Salud Carlos III (ISCIII). Exps: PI14/00067, PI14/01716, PI14/01880, PI14/00556. BA15/00093. FFIS-CC 2016–06 AECC 'Junta provincial de Murcia'. FEDER and AECC 2015. Dr. J.P. Arrebola is under contract within Ramon y Cajal program (RYC-2016-20155, Ministerio de Economía, Industria y Competitividad, Spain). The EPIC-Spain cohort was supported by the Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain).

Subjects
Oncology, Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants [Medical Subject Headings], Male, Neoplasias de la próstata, Health, Toxicology and Mutagenesis, Endocrine Disruptors, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Prostate cancer, Breast cancer, Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Acrylates::Methacrylates::Bisphenol A-Glycidyl Methacrylate [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, Factors de risc en les malalties, Hazard ratio, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Health Care::Environment and Public Health::Public Health::Environmental Pollution::Environmental Exposure [Medical Subject Headings], Environmental pollutants, Diseases::Male Urogenital Diseases::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings], Bisphenol a, Endocrine disruptor, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], Neoplasias de la mama, Population study, Female, Public aspects of medicine, RA1-1270, Disruptores endocrinos, Adult, Risk, medicine.medical_specialty, endocrine system, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Risk factors in diseases, Population, Estudios de cohortes, Case-cohort, Check Tags::Male [Medical Subject Headings], Breast Neoplasms, Càncer de mama, Phenols, Bisfenol A glicidil metacrilato, Internal medicine, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], medicine, Humans, Benzhydryl Compounds, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Càncer de pròstata, Proportional hazards model, business.industry, urogenital system, Research, Public Health, Environmental and Occupational Health, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Endocrine Disruptors [Medical Subject Headings], Prostatic Neoplasms, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Benzhydryl Compounds [Medical Subject Headings], Environmental Exposure, medicine.disease, Industrial medicine. Industrial hygiene, RC963-969, Check Tags::Female [Medical Subject Headings], Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Sensitivity and Specificity::Limit of Detection [Medical Subject Headings], business, Contaminantes ambientales
Abstract

This work was supported by the Ministry of economy and competitiveness and the National Institute of Health: Instituto de Salud Carlos III (ISCIII). Exps: PI14/00067, PI14/01716, PI14/01880, PI14/00556. BA15/00093. FFIS-CC 2016-06 AECC "Junta provincial de Murcia". FEDER and AECC 2015. Dr. J.P. Arrebola is under contract within Ramon y Cajal program (RYC-2016-20155, Ministerio de Economia, Industria y Competitividad, Spain). The EPIC-Spain cohort was supported by the Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology -ICO (Spain)., Background Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). Methods We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios. Results Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 (p = 0.022), 37% increase for tertile 2 (p = 0.034) and 31% increase for tertile 3 (p = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk. Conclusions We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk., Ministry of economy and competitiveness, National Institute of Health: Instituto de Salud Carlos III (ISCIII), AECC "Junta provincial de Murcia" PI14/00067- PI14/01716- PI14/01880- PI14/00556- BA15/00093- FFIS-CC 2016-06, Spanish Government RYC-2016-20155, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Catalan Institute of Oncology -ICO (Spain)

Published
2021

28. Selectively Targeting Breast Cancer Stem Cells By 8-Quinolinol and Niclosamide

Author

Cámara-Sánchez, Patricia, Díaz Riascos, Zamira Vanessa, García Aranda, Natalia, Gener, Petra, Seras-Franzoso, Joaquin, Giani-Alonso, Micaela, Royo, Miriam, Vázquez Gómez, Esther, Schwartz, Simon, Abasolo, Ibane, Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina \\'Vicent Villar Palasí\\', European Commission, Institut Català de la Salut, [Cámara-Sánchez P, Gener P, Seras-Franzoso J, Schwartz S Jr] Grup de Direccionament i Alliberament Farmacològic, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Díaz-Riascos ZV, García-Aranda N, Abasolo I] Grup de Direccionament i Alliberament Farmacològic, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Àrea de Validació Funcional i Investigació Preclínica (FVPR), Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Giani-Alonso M] Grup de Direccionament i Alliberament Farmacològic, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Cèl·lules canceroses - Proliferació, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Triple Negative Breast Neoplasms, Cells::Stem Cells::Neoplastic Stem Cells [ANATOMY], Other subheadings::Other subheadings::/drug therapy [Other subheadings], behavioral disciplines and activities, Catalysis, Quimioteràpia combinada, 8-quinolinol, Inorganic Chemistry, Mice, triple negative breast cancer, cancer stem cells, niclosamide, combination therapy, Breast cancer, Cell Line, Tumor, terapéutica::farmacoterapia::farmacoterapia combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Medicine, Animals, Humans, Triple negative breast cancer, Physical and Theoretical Chemistry, Combination therapy, Molecular Biology, Spectroscopy, Niclosamide, Cell Proliferation, business.industry, Cancer stem cells, Organic Chemistry, Therapeutics::Drug Therapy::Drug Therapy, Combination [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], General Medicine, medicine.disease, Oxyquinoline, Computer Science Applications, neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES], Mama - Càncer - Tractament, Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES], Cancer research, Neoplastic Stem Cells, Stem cell, células::células madre::células madre neoplásicas [ANATOMÍA], business, Cèl·lules mare, 8-Quinolinol, medicine.drug
Abstract

Cancer maintenance, metastatic dissemination and drug resistance are sustained by cancer stem cells (CSCs). Triple negative breast cancer (TNBC) is the breast cancer subtype with the highest number of CSCs and the poorest prognosis. Here, we aimed to identify potential drugs targeting CSCs to be further employed in combination with standard chemotherapy in TNBC treatment. The anti-CSC efficacy of up to 17 small drugs was tested in TNBC cell lines using cell viability assays on differentiated cancer cells and CSCs. Then, the effect of 2 selected drugs (8-quinolinol -8Q- and niclosamide -NCS-) in the cancer stemness features were evaluated using mammosphere growth, cell invasion, migration and anchorage-independent growth assays. Changes in the expression of stemness genes after 8Q or NCS treatment were also evaluated. Moreover, the potential synergism of 8Q and NCS with PTX on CSC proliferation and stemness-related signaling pathways was evaluated using TNBC cell lines, CSC-reporter sublines, and CSC-enriched mammospheres. Finally, the efficacy of NCS in combination with PTX was analyzed in vivo using an orthotopic mouse model of MDA-MB-231 cells. Among all tested drug candidates, 8Q and NCS showed remarkable specific anti-CSC activity in terms of CSC viability, migration, invasion and anchorage independent growth reduction in vitro. Moreover, specific 8Q/PTX and NCS/PTX ratios at which both drugs displayed a synergistic effect in different TNBC cell lines were identified. The sole use of PTX increased the relative presence of CSCs in TNBC cells, whereas the combination of 8Q and NCS counteracted this pro-CSC activity of PTX while significantly reducing cell viability. In vivo, the combination of NCS with PTX reduced tumor growth and limited the dissemination of the disease by reducing circulating tumor cells and the incidence of lung metastasis. The combination of 8Q and NCS with PTX at established ratios inhibits both the proliferation of differentiated cancer cells and the viability of CSCs, paving the way for more efficacious TNBC treatments., This work was supported by the Instituto de Salud Carlos III (ISCiii), through Networking Research Center on Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), an initiative that also counts with the assistance from the European Regional Development Fund (ERDF), specifically in the PENTRI-2 Project and by the “Fundació Marató TV3” (337/C/2013) to I.A., M.R. and E.V. Our laboratories were also supported by the Fondo de Investigaciones Sanitarias (FIS, grants PI20/1474 to S.S.J. and PI18/00871 and PI21/00936), co-financed by the ERDF and the 2017-SGR-638 of the Catalan Government to S.S.J. and EvoNano Project (GA800983), funded by European Union’s Horizon 2020 FET Open Programme. N.G.-A. was supported by grants from Pla Estratègic de Recerca i Innovació en Salut (PERIS) of Catalonia (SLT006/17/00270 270).

Published
2021

29. Use of Different Food Classification Systems to Assess the Association between Ultra-Processed Food Consumption and Cardiometabolic Health in an Elderly Population with Metabolic Syndrome (PREDIMED-Plus Cohort)

Author

Josep Vidal, Jose M. Ordovas, José Alfredo Martínez, Ángel M. Alonso-Gómez, Estefanía Toledo, Nerea Becerra-Tomás, Dolores Corella, Aurora Bueno-Cavanillas, Jessica Vaquero-Luna, María Concepción Barceló-Iglesias, Beatriz Pérez-Sanz, Antonio García Ríos, María Julia Ajejas Bazán, Ramon Estruch, Vicente Martín Sánchez, Rodrigo San-Cristobal, Miguel Ángel Martínez-González, Xavier Pintó, Dora Romaguera, Jesús Vioque, José J. Gaforio, Pilar Matía-Martín, Lluis Serra-Majem, Itziar Abete, Camille Lassale, Júlia Muñoz-Martínez, Jose Lopez-Miranda, Stephanie K. Nishi, José Lapetra, Lidia Daimiel, Anai Moreno-Rodriguez, Clotilde Vázquez, José V. Sorlí, Celia Martinez-Perez, José Manuel Santos-Lozano, Maira Bes-Rastrollo, Julia Wärnberg, Emilio Ros, María Rosa Bernal-López, Pilar Guallar-Castillón, Nancy Babio, Oscar Lecea-Juarez, María Dolores Zomeño, Olga Castañer, Josep A. Tur, Jordi Salas-Salvadó, Francisco J. Tinahones, Olga Portolés, Jadwiga Konieczna, [Martinez-Perez,C, Ordovás,JM, Daimiel,L] Nutritional Genomics and Epigenomics Group, Precision Nutrition and Obesity Program, IMDEA Food, CEI UAM + CSIC, Madrid, Spain. [San-Cristobal,R, Martinez, JA] Cardiometabolic Nutrition Group, Precision Nutrition and Cardiometabolic Health Program, IMDEA Food, CEI UAM + CSIC, Madrid, Spain. [Guallar-Castillon,P] Cardiovascular and Nutritional Epidemiology Group, IMDEA Food, CEI UAM + CSIC, Madrid, Spain. [Guallar-Castillon,P] Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid—IdiPaz Hospital, Madrid, Spain. [Guallar-Castillon,P, Vioque,J, Bueno-Cavanillas,A, Martín Sánchez,V, Gaforio,JJ] Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. [Guallar-Castillon,P] Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, USA. [Martínez-González,MA, Salas-Salvadó,J, Corella,D, Castañer,O, Martinez,JA, Alonso-Gómez,AM, Wärnberg,J, Romaguera,D, López-Miranda,J, Estruch,R, Tinahones,FJ, Lapetra,J, Serra-Majem,L, Tur,JA, Pintó,X, Vázquez,C, Ros,E, Bes-Rastrollo,M, Babio,N, Sorlí,JV, Lassale,C, Vaquero-Luna,J, Konieczna,J, García Ríos,A, Santos-Lozano,JM, Toledo,E, Becerra-Tomás,N, Portoles,O, Abete,I, Moreno-Rodriguez,A] Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Martínez-González,MA, Toledo,E] Department of Preventive Medicine and Public Health, University of Navarra, IdiSNA, Pamplona, Spain. [Martínez-González,MA] Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA. [Salas-Salvadó,J, Becerra-Tomás,T, Nishi,SK] Unitat de Nutrició Humana, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Reus, Spain. [Salas-Salvadó,J, Becerra-Tomás,N] Human Nutrition Unit, Institut d’Investigació Sanitària Pere Virgili (IISPV), Reus, Spain. [Corella,D, Portoles,O] Department of Preventive Medicine, University of Valencia, Valencia, Spain. [Castañer,O, Zomeño,MD, Muñoz-Martínez,J] Cardiovascular Risk and Nutrition Research Group (CARIN), Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. [Martinez,JA, Pérez-Sanz,B, Abete,I] Department of Nutrition, Food Sciences and Physiology, University of Navarra, Pamplona, Spain. [Alonso-Gómez,AM, Moreno-Rodriguez,A] Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba University Hospital, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain. [Wärnberg, Ajejas Bazán,MJ] Department of Nursing, School of Health Sciences, Instituto de Investigación Biomédica de Málaga (IBIMA), University of Málaga, Málaga. [Vioque,J] Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL-UMH), Alicante, Spain. [Romaguera,D, Konieczna,J] Research Group on Nutritional Epidemiology & Cardiovascular Physiopathology (NUTRECOR), Health Research Institute of the Balearic Islands (IdISBa), University Hospital Son Espases (HUSE), Palma de Mallorca, Spain. [López-Miranda,J, García Ríos,A] Lipids and Atherosclerosis Unit, Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, Spain. [Estruch,R] Department of Internal Medicine, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain. [Tinahones,FJ] Department of Endocrinology, Instituto de Investigación Biomédica de Málaga (IBIMA), Virgen de la Victoria Hospital, University of Málaga, Málaga, Spain. [Lapetra,J, Santos-Lozano,JM] Department of Family Medicine, Research Unit, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain. [Serra-Majem,L] Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria and Service of Preventive Medicine, Complejo Hospitalario Universitario Insular Materno Infantil (CHUIMI), Canary Health Service, Las Palmas de Gran Canaria, Spain. [Bueno-Cavanillas,A] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. [Tur,JA] Research Group on Community Nutrition & Oxidative Stress, University of Balearic Islands-IUNICS & IDISBA, Palma de Mallorca, Spain. [Martín Sánchez,V] Institute of Biomedicine (IBIOMED), University of León, León, Spain. [Pintó,X] Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain. [Gaforio,JJ] Departamento de Ciencias de la Salud, Centro de Estudios Avanzados en Olivar y Aceites de Oliva, Universidad de Jaén, Jaén, Spain. [Matía-Martín,P] Department of Endocrinology and Nutrition, Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), Madrid, Spain. [Vidal,J] Biomedical Research Centre for Diabetes and Metabolic Diseases Network (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Vidal,J, Ros,E] Endocrinology and Nutrition Service, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain. [Vázquez,C] Department of Endocrinology and Nutrition, Hospital Fundación Jiménez Díaz, Instituto de Investigaciones Biomédicas IISFJD, University Autónoma, Madrid, Spain. [Ajejas Bazán,MJ] Department of Nursing, Faculty of Nursing, Physiotherapy and Podiatry, Universidad Complutense de Madrid, Madrid, Spain. [Barceló-Iglesias,MC] Centro Salud Cabo Huertas, Alicante, Spain. [Bernal-López,MR] Internal Medicine Department, Instituto de Investigación Biomédica de Málaga (IBIMA), Regional University Hospital of Malaga, Malaga, Spain. [Zomeño,MD] School of Health Sciences, Blanquerna-Ramon Llull University, Barcelona, Spain. [Lecea-Juarez,O] Atención Primaria, Osasunbidea, Servicio Navarro de Salud, Pamplona, Spain. [Ordovás,JM] Nutrition and Genomics Laboratory, JM_USDA Human Nutrition Research Center on Aging, Tufts University, Boston, USA., The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research grant 2014–2019, agreement #340918, granted to M.Á.M.-G.), the official Spanish institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigación para la Salud (FIS) which is co-funded by the European Regional Development Fund (coordinated FIS projects led by J.S-S. and J.V., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332), and the Especial Action Project 'Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus' (J.S.-S.), the Recercaixa (grant number 2013ACUP00194) (J.S.-S.). Moreover, J.S-S. gratefully acknowledges the financial support by ICREA under the ICREA Academia program, the SEMERGEN grant, Department of Health of the Government of Navarra (61/2015), the Fundació La Marató de TV (Ref. 201630.10), the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (D.R.), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant, grant of support to research groups 35/2011 (Balearic Islands Government, and FEDER funds) (J.A.T.). R.S.-C. acknowledges financial support from the Juan de la Cierva Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-038168- I). N.B.-T. acknowledges financial support from the Juan de la Cierva Formación Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-036016-I). M.R.B.-L. was supported by 'Miguel Servet Type I' program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER. S.K.N. acknowledges financial support from the Canadian Institute for Health Research, CIHR Fellowship. J.K. was supported by the ‘FOLIUM’ programme within the FUTURMed project from the Fundación Instituto de Investigación Sanitaria Illes Balears (financed by 2017 annual plan of the sustainable tourism tax and at 50% with charge to the ESF Operational Program 2014–2020 of the Balearic Islands. C.M.-P. was financially supported by a joint grant from the Community of Madrid and the European Social Fund (grant PEJD-2019-POST/SAL-15892). The METHYL-UP project was supported by the Spanish Ministry of Science and Innovation (RTI2018-095569-B-I00, Programa de Proyectos Orientados a los Retos de la Sociedad 'Projects Toward Society Challenges Program').

Subjects
Síndrome metabólico, Male, Food processing, Mediterranean diet, NOVA, Obesidad, Índice de masa corporal, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, ultra-processed food, Medicine, TX341-641, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight [Medical Subject Headings], Body mass index, classification systems, Incidence, IARC, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Questionnaires [Medical Subject Headings], Metabolic syndrome, 3. Good health, Nutrición, Cohort, Manipulación de alimentos, Dieta, Factores de riesgo cardiometabólico, Concordance, UNC, Check Tags::Male [Medical Subject Headings], Clasificación, Classification systems, Diet Surveys, Article, 03 medical and health sciences, food processing, Humans, Diseases::Cardiovascular Diseases [Medical Subject Headings], Aged, 030109 nutrition & dietetics, Health Care::Health Care Economics and Organizations::Organizations::International Agencies [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], PREDIMED-Plus, medicine.disease, Obesity, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Blood pressure, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Linear Models, Fast Foods, Older people, 0301 basic medicine, Síndrome metabòlica, Food Handling, Overweight, Diet, Mediterranean, Persones grans, Cohort Studies, cardiometabolic risk, Endocrinología, 030212 general & internal medicine, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], 2. Zero hunger, Metabolic Syndrome, Nutrition and Dietetics, Technology and Food and Beverages::Technology, Industry, and Agriculture::Industry::Food Industry::Food Handling [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Nutrition Therapy::Diet Therapy::Diet, Mediterranean [Medical Subject Headings], Middle Aged, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys::Diet Surveys [Medical Subject Headings], Female, Technology and Food and Beverages::Food and Beverages::Food::Fast Foods [Medical Subject Headings], medicine.symptom, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism::Insulin Resistance::Metabolic Syndrome X [Medical Subject Headings], Dietética y nutrición, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Environmental health, Alimentos ultraprocesados, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Linear Models [Medical Subject Headings], Nutrició, Nutrition, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, Nutrition. Foods and food supply, Cardiometabolic Risk Factors, Dieta mediterránea, Cardiometabolic risk, Ultra-processed food, Diet, Spain, IFIC, Sobrepeso, business, diet, Food Science
Abstract

The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research grant 2014–2019; agreement #340918; granted to M.Á.M.-G.); the official Spanish institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigación para la Salud (FIS) which is co-funded by the European Regional Development Fund (coordinated FIS projects led by J.S-S. and J.V., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332), and the Especial Action Project “Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus” (J.S.-S.); the Recercaixa (grant number 2013ACUP00194) (J.S.-S.). Moreover, J.S-S. gratefully acknowledges the financial support by ICREA under the ICREA Academia program; the SEMERGEN grant; Department of Health of the Government of Navarra (61/2015), the Fundació La Marató de TV (Ref. 201630.10); the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (D.R.); grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013; PS0358/2016; PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant; grant of support to research groups 35/2011 (Balearic Islands Government; FEDER funds) (J.A.T.). R.S.-C. acknowledges financial support from the Juan de la Cierva Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-038168- I). N.B.-T. acknowledges financial support from the Juan de la Cierva Formación Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-036016-I). M.R.B.-L. was supported by “Miguel Servet Type I” program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER. S.K.N. acknowledges financial support from the Canadian Institute for Health Research, CIHR Fellowship. J.K. was supported by the ‘FOLIUM’ programme within the FUTURMed project from the Fundación Instituto de Investigación Sanitaria Illes Balears (financed by 2017 annual plan of the sustainable tourism tax and at 50% with charge to the ESF Operational Program 2014–2020 of the Balearic Islands. C.M.-P. was financially supported by a joint grant from the Community of Madrid and the European Social Fund (grant PEJD-2019- POST/SAL-15892). The METHYL-UP project was supported by the Spanish Ministry of Science and Innovation (RTI2018-095569-B-I00, Programa de Proyectos Orientados a los Retos de la Sociedad “Projects Toward Society Challenges Program”)., The association between ultra-processed food (UPF) and risk of cardiometabolic disorders is an ongoing concern. Different food processing-based classification systems have originated discrepancies in the conclusions among studies. To test whether the association between UPF consumption and cardiometabolic markers changes with the classification system, we used baseline data from 5636 participants (48.5% female and 51.5% male, mean age 65.1 4.9) of the PREDIMEDPlus (“PREvention with MEDiterranean DIet”) trial. Subjects presented with overweight or obesity and met at least three metabolic syndrome (MetS) criteria. Food consumption was classified using a 143-item food frequency questionnaire according to four food processing-based classifications: NOVA, International Agency for Research on Cancer (IARC), International Food Information Council (IFIC) and University of North Carolina (UNC). Mean changes in nutritional and cardiometabolic markers were assessed according to quintiles of UPF consumption for each system. The association between UPF consumption and cardiometabolic markers was assessed using linear regression analysis. The concordance of the different classifications was assessed with intra-class correlation coefficients (ICC3, overall = 0.51). The highest UPF consumption was obtained with the IARC classification (45.9%) and the lowest with NOVA (7.9%). Subjects with high UPF consumption showed a poor dietary profile. We detected a direct association between UPF consumption and BMI (p = 0.001) when using the NOVA system, and with systolic (p = 0.018) and diastolic (p = 0.042) blood pressure when using the UNC system. Food classification methodologies markedly influenced the association between UPF consumption and cardiometabolic risk markers., European Research Council (ERC) European Commission #340918, Centro de Investigacion Biomedica en Red-Fisiopatologia de la Obesidad y Nutricion PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441 PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471 PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332

Published
2021
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30. Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study

Author

García-Pérez, Javier, Gonzalez-Perez, Maria, Castillo de la Osa, María, Borobia, Alberto M, Castaño, Luis, Bertrán, María Jesús, Campins, Magdalena, Portolés, Antonio, Lora, David, Bermejo, Mercedes, Conde-San Román, Patricia, Hernandez, Lourdes, Carcas, Antonio, Arana-Arri, Eunate, Tortajada, Marta, Fuentes, Inmaculada, Ascaso, Ana, García-Morales, María Teresa, de la Torre-Tarazona, Humberto Erick, Arribas, José-Ramón, Imaz-Ayo, Natale, Mellado-Pau, Eugènia, Agustí, Antonia, Pérez-Ingidua, Carla, Gómez de la Cámara, Agustín, Ochando, Jordi, Belda-Iniesta, Cristobal, Frías, Jesús, Alcamí, José, Perez-Olmeda, Mayte, CombiVacS study Group, Instituto de Salud Carlos III, Plan Nacional de I+D+i (España), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Unión Europea. Comisión Europea. H2020, Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas), European Commission, Institut Català de la Salut, [García-Pérez J] Unidad de Inmunopatología del SIDA, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [González-Pérez M] Laboratorio de Referencia en Inmunología, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Castillo de la Osa M] Laboratorio de Serología, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Borobia AM] Servicio de Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain. [Castaño L] Biocruces Bizkaia, Hospital Universitario Cruces, CIBERDEM, CIBERER, Endo-ERN, UPV-EHU, Barakaldo, Spain. [Bertrán MJ] Servicio de Medicina Preventiva y Epidemiologia, Hospital Clínic de Barcelona, Barcelona, Spain. [Campins M] Servei de Medicina Preventiva i Epidemiologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Fuentes I] Unitat de Suport a la Investigació Clínica, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Agustí A] Servei de Farmacologia Clínica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Departament de Farmacologia, Terapèutica i Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Otros calificadores::Otros calificadores::/prevención & control [Otros calificadores], variants, COVID-19 (Malaltia) - Prevenció, SARS-CoV-2, Variants, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], heterologous vaccination, General Medicine, Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Neutralizing [CHEMICALS AND DRUGS], Antibodies, Neutralisation, Other subheadings::Other subheadings::/prevention & control [Other subheadings], neutralisation, Heterologous vaccination, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], antibodies, fenómenos del sistema inmunitario::formación de anticuerpos::inmunogenicidad vacunal [FENÓMENOS Y PROCESOS], Immune System Phenomena::Antibody Formation::Immunogenicity, Vaccine [PHENOMENA AND PROCESSES], Immunoglobulines, aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos neutralizantes [COMPUESTOS QUÍMICOS Y DROGAS], COVID-19 (Malaltia) - Vacunació
Abstract

Background: The CombiVacS study was designed to assess immunogenicity and reactogenicity of the heterologous ChAdOx1-S/BNT162b2 combination, and 14-day results showed a strong immune response. The present secondary analysis addresses the evolution of humoral and cellular response up to day 180. Methods: Between April 24 and 30, 2021, 676 adults primed with ChAdOx1-S were enrolled in five hospitals in Spain, and randomised to receive BNT162b2 as second dose (interventional group [IG]) or no vaccine (control group [CG]). Individuals from CG received BNT162b2 as second dose and also on day 28, as planned based on favourable results on day 14. Humoral immunogenicity, measured by immunoassay for SARS-CoV-2 receptor binding domain (RBD), antibody functionality using pseudovirus neutralisation assays for the reference (G614), Alpha, Beta, Delta, and Omicron variants, as well as cellular immune response using interferon-γ and IL-2 immunoassays were assessed at day 28 after BNT162b2 in both groups, at day 90 (planned only in the interventional group) and at day 180 (laboratory data cut-off on Nov 19, 2021). This study was registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739). Findings: In this secondary analysis, 664 individuals (441 from IG and 223 from CG) were included. At day 28 post vaccine, geometric mean titres (GMT) of RBD antibodies were 5616·91 BAU/mL (95% CI 5296·49-5956·71) in the IG and 7298·22 BAU/mL (6739·41-7903·37) in the CG (p < 0·0001). RBD antibodies titres decreased at day 180 (1142·0 BAU/mL [1048·69-1243·62] and 1836·4 BAU/mL [1621·62-2079·62] in the IG and CG, respectively; p < 0·0001). Neutralising antibodies also waned from day 28 to day 180 in both the IG (1429·01 [1220·37-1673·33] and 198·72 [161·54-244·47], respectively) and the CG (1503·28 [1210·71-1866·54] and 295·57 [209·84-416·33], respectively). The lowest variant-specific response was observed against Omicron-and Beta variants, with low proportion of individuals exhibiting specific neutralising antibody titres (NT50) >1:100 at day 180 (19% and 22%, respectively). Interpretation: Titres of RBD antibodies decay over time, similar to homologous regimes. Our findings suggested that delaying administration of the second dose did not have a detrimental effect after vaccination and may have improved the response obtained. Lower neutralisation was observed against Omicron and Beta variants at day 180. Funded by Instituto de Salud Carlos III (ISCIII). AMB, AJC, JO, and JF are members of the VACCELERATE (European Corona Vaccine Trial Accelerator Platform) Network, which aims to facilitate and accelerate the design and implementation of COVID-19 phase 2 and 3 vaccine trials. JO is a member of the INsTRuCT (Innovative Training in Myeloid Regulatory Cell Therapy) Consortium, a network of European scientists from academia and industry focused on developing innovative immunotherapies. This work is funded by Instituto de Salud Carlos III, a Spanish public body assigned to the Ministry of Science and Innovation that manages and promotes public clinical research related to public health. The Spanish Clinical Trials Platform is a public network funded by the Instituto de Salud Carlos III (grant numbers PTC20/00018 and PT17/0017), the State Plan for Research, Development, and Innovation 2013−16, the State Plan for Scientific and Technical Research and Innovation 2017−20, and the Subdirectorate General for Evaluation and Promotion of Research, Instituto de Salud Carlos III, cofinanced with FEDER funds. CombiVacS was designed under the umbrella of the VACCELERATE project. VACCELER ATE and INsTRuCT received funding from the EU’s Horizon 2020 Research and Innovation Programme (grant agreement numbers 101037867 and 860003). The Instituto de Salud Carlos III is the Spanish partner in the VACCELERATE project. This work is partially funded by Institute of Health Carlos III (Instituto de Salud Carlos III − ISCIII −), (grants PI19CIII/00004 to JA and PI21CIII/00025 to MPO and JGP), and COVID-19 FUND (grants COV20/00679 and COV20/00072 to MPO and JA) and CIBERINFEC, co-financed by the European Regional Development Fund (FEDER) “A way to make Europe”. The authors thank all trial participants, the international data safety monitoring board (Appendix 1 p 23), and the trial steering committee (Appendix 1 pp 24−25). The authors thank Esther Prieto for editorial assistance and writing support (employed by Hospital Universitario La Paz; funded by the Instituto de Salud Carlos III, grant number PCT20/00018) and María Castillo-de la Osa (PEJ2018-004557-A) for excellent technical assistance. Sí

Published
2022

31. Causal effects of lifetime smoking on breast and colorectal cancer risk:Mendelian randomization study

Author

Marc J. Gunter, Inger T. Gram, Elisabete Weiderpass, Hilary A. Tindle, Sun-Seog Kweon, Renée T. Fortner, Rudolf Kaaks, Sarah J Lewis, James Yarmolinsky, Stephen B. Gruber, Marije F. Bakker, Li Hsu, Yi Lin, Neil Murphy, Polly A. Newcomb, Konstantinos K. Tsilidis, Noralane M. Lindor, Rosario Tumino, Gianluca Severi, Hermann Brenner, Emmanouil Bouras, Jane C. Figueiredo, Niki Dimou, Richard M. Martin, Bethany Van Guelpen, María-José Sánchez-Pérez, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), 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, Cancerfonden Cancer Research Foundation in Northern Sweden Deutsche Krebshilfe Vetenskapsrådet, VR Australian Lions Childhood Cancer Research Foundation, ALCCRF Knut och Alice Wallenbergs Stiftelse State of Maryland Vetenskapsrådet, VR: VR 2017-00650 Centers for Disease Control and Prevention, CDC Institut National Du Cancer, INCa National Institutes of Health, NIH National Cancer Institute, NCI: P30 CA015704 Centre Hospitalier Universitaire de Nantes, CHU de Nantes Conseil Régional des Pays de la Loire Association Anne de Bretagne Genetique Centre Hospitalier Universitaire de Nantes, CHU de Nantes U.S. Public Health Service, USPHS: HHSN261201500005C U.S. Department of Health and Human Services, HHS National Institutes of Health, NIH National Cancer Institute, NCI National Institute on Aging, NIA: U01 AG18033 Institut National Du Cancer, INCa: P30 CA006973, U01 CA86308 American Institute for Cancer Research, AICR European Commission, EC National Institutes of Health, NIH: R01 CA189184, 2P30CA015704-40, R01 CA207371, U01 CA206110 Matthias Lackas-Stiftung Johns Hopkins University, JHU: HHSN268201200008I National Cancer Institute, NCI National Institutes of Health, NIH: R01 CA143247, R01 CA81488, U01 CA122839, U19 CA148107, U01 CA167551 National Institutes of Health, NIH National Institute of Environmental Health Sciences, NIEHS: T32 ES013678 National Cancer Institute, NCI U.S. Department of Health and Human Services, HHS: R01 CA197350, R01 CA81488, R01 CA201407, P01 CA196569, U19 CA148107, P30 CA014089 Österreichische Forschungsförderungsgesellschaft, FFG: 829675 Instituto de Salud Carlos III, ISCIII European Regional Development Fund, ERDF: PI14-613, PI09-1286 Xarxa de Bancs de Tumors de Catalunya, XBTC: PT13/0010/0013 Generalitat de Catalunya: 2017SGR723 Junta de Castilla y León: LE22A10-2 Agència de Gestió d'Ajuts Universitaris i de Recerca, AGAUR Ministerstvo Zdravotnictví Ceské Republiky, MZCR: AZV 17-30920A, AZV 15-27580A Grantová Agentura České Republiky, GA ČR: CZ GA CR: GAP304/10/1286, 1585 Deutsche Forschungsgemeinschaft, DFG: HO 5117/2-1, BR 1704/6-1, KL 2354/3-1, BR 1704/6-4, BR 1704/6-3, CH 117/1-1, HE 5998/2-1, RO 2270/8-1, BR1704/17-1 Bundesministerium für Bildung und Forschung, BMBF: 01ER0814, 01KH0404, 01ER0815, 01ER1505A, 01ER1505B U01 CA 84968-06 National Cancer Institute, NCI University of Maryland School of Public Health, SPH NIHR Imperial Biomedical Research Centre, BRC Imperial College London NIHR Imperial Biomedical Research Centre, BRC Centre International de Recherche sur le Cancer, CIRC Ministerie van Volksgezondheid, Welzijn en Sport, VWS Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A29017 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Vetenskapsrådet, VR Ligue Contre le Cancer Bundesministerium für Bildung und Forschung, BMBF Bundesministerium für Bildung und Forschung, BMBF Kræftens Bekæmpelse, DCS Associazione Italiana per la Ricerca sul Cancro, AIRC Instituto de Salud Carlos III, ISCIII Deutsches Krebsforschungszentrum, DKFZ Institut National de la Santé et de la Recherche Médicale, Inserm National Research Council, NRC Institut Gustave-Roussy Deutsches Krebsforschungszentrum, DKFZ Cancerfonden World Cancer Research Fund, WCRF Medical Research Council, MRC: MR/M012190/1 Generalitat de Catalunya: 2017SGR653, 2014SGR135, 2014SGR255, 2017SGR21 SAF2014-54453R, SAF07-64873, SAF 2010-19273 Xunta de Galicia: PGIDIT07PXIB9101209PR Instituto de Salud Carlos III, ISCIII European Regional Development Fund, ERDF: PS09/02368, PI14/00230, 17/00878, PI08/1276, PI17/00509, PI08/0024, PI11/00681, P111/00219, PI14/00173 Xarxa de Bancs de Tumors de Catalunya, XBTC: SLT002/ 16/00398 GCB13131592CAST European Cooperation in Science and Technology, COST: CA17118, BM1206 Deutsche Krebshilfe National Institutes of Health, NIH: K07 CA190673, P01 CA055075, K07CA190673, R35CA197735, U01 CA167552, UM1 CA167552, R01 CA042182, P01 CA087969, R01 CA151993, P50 CA127003, UM1 CA186107, R35 CA197735, R01 CA137178 HCRI15011-1 National Cancer Institute, NCI: R01CA136726 Damon Runyon Cancer Research Foundation, DRCRF: CI-8 Food Standards Agency, FSA Cancer Research UK, CRUK: C588/A19167 VicHealth Cancer Council Victoria National Health and Medical Research Council, NHMRC: 251553, 209057, 509348, 504711 National Institutes of Health, NIH U.S. Department of Health and Human Services, HHS: R01 CA81488 Florida Department of Health: 09BN-13 National Institutes of Health, NIH: R01 CA189184, P30 CA076292 National Institutes of Health, NIH: P30 DK034987, R01 CA66635 18226, 18223 Canadian Institutes of Health Research, CIHR: CRT 43821 National Institutes of Health, NIH U.S. Department of Health and Human Services, HHS: U01 CA74783 Cancerfonden Cancer Research Foundation, CRF Vetenskapsrådet, VR Australian Lions Childhood Cancer Research Foundation, ALCCRF Canadian Cancer Society National Institutes of Health, NIH: U01/ U24 CA074783, U01 CA167551 Pelotonia CA16058, CA67941 Canadian Institutes of Health Research, CIHR: 112746 Ontario Research Foundation, ORF: GL201-043 National Cancer Institute, NCI U.S. Department of Health and Human Services, HHS: U01 HG004446, GEI U01 HG 004438, Z01 CP 010200 Division of Cancer Epidemiology and Genetics, National Cancer Institute, DCEG Institut National Du Cancer, INCa National Institutes of Health, NIH Division of Cancer Prevention, National Cancer Institute, DCP, NCI National Institutes of Health, NIH: U24 CA074794, U01 CA074794, R01 CA076366, U01 CA167551 National Cancer Institute, NCI National Institutes of Health, NIH: UM1 CA182883, U10 CA37429 National Cancer Institute, NCI Institut National Du Cancer, INCa: R03 CA153323, P01 CA074184, K05 CA152715, R01 CA097325 National Institutes of Health, NIH: KL2 TR000421 National Center for Advancing Translational Sciences, NCATS Stockholms Läns Landsting Vetenskapsrådet, VR: K2015-55X-22674-01-4, K2008-55X-20157-03-3, K2006-72X-20157-01-2 Karolinska Institutet, KI National Institutes of Health, NIH: K05 CA154337 Swedish Cancer Foundation National Heart, Lung, and Blood Institute, NHLBI National Institutes of Health, NIH U.S. Department of Health and Human Services, HHS: HHSN268201100004C, HHSN268201100003C, HHSN268201100001C, HHSN271201100004C, HHSN268201100046C, HHSN268201100002C, R.M. Martin reports grants from Cancer Research UK during the conduct of the study. R.T. Fortner reports that grants from German Cancer Aid and from German Ministry of Education and Research supported the conduct of EPIC Heidelberg. S.B. Gruber reports other from Brogent International LLC outside the submitted work. B. van Guelpen reports grants from Swedish Research Council, Swedish Cancer Society, Knut and Alice Wallenberg Foundation, Lion’s Cancer Research Foundation at Umea° University, and Cancer Research Foundation in Northern Sweden during the conduct of the study. No disclosures were reported by the other authors., CLUE: We appreciate the continued efforts of the staff members at the Johns Hopkins George W. Comstock Center for Public Health Research and Prevention in the conduct of the CLUE II study. We thank the participants in CLUE. Cancer incidence data for CLUE were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Maryland Department of Health, 201 W. Preston Street, Room 400, Baltimore, MD 21201, http://phpa.dhmh.maryland.gov/cancer, 410-767-4055. We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention for the funds that support the collection and availability of the cancer registry data., CPS-II: The authors thank the CPS-II participants and Study Management Group for their invaluable contributions to this research. The authors would also like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program., NSHDS investigators thank the Biobank Research Unit at Umea° University, the V€asterbotten Intervention Programme, the Northern Sweden MONICA study and Region V€asterbotten for providing data and samples and acknowledge the contribution from Biobank Sweden, supported by the Swedish Research Council (VR 2017-00650)., Cancer incidence data have been provided by the District of Columbia Cancer Registry, Georgia Cancer Registry, Hawaii Cancer Registry, Minnesota Cancer Surveillance System, Missouri Cancer Registry, Nevada Central Cancer Registry, Pennsylvania Cancer Registry, Texas Cancer Registry, Virginia Cancer Registry, and Wisconsin Cancer Reporting System. All are supported in part by funds from the Center for Disease Control and Prevention, National Program for Central Registries, local states or by the National Cancer Institute, Surveillance, Epidemiology, and End Results program. The results reported here and the conclusions derived are the sole responsibility of the authors., Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088, R01 CA059045, R01CA201407). This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704., ASTERISK: a Hospital Clinical Research Program (PHRC-BRD09/C) from the University Hospital Center of Nantes (CHU de Nantes) and supported by the Regional Council of Pays de la Loire, the Groupement des EntreprisesFranc¸aises dans la Luttecontre le Cancer (GEFLUC), the Association Anne de Bretagne Génétique and the Ligue RégionaleContre le Cancer (LRCC)., The ATBC Study is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, and by U.S. Public Health Service contract HHSN261201500005C from the National Cancer Institute, Department of Health and Human Services., CLUE funding was from the National Cancer Institute (U01 CA86308, Early Detection Research Network, and P30 CA006973), National Institute on Aging (U01 AG18033), and the American Institute for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. COLO2&3: NIH (R01 CA60987).

Subjects
Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Epidemiology, medicine.drug_class, Colorectal cancer, Breast Neoplasms, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Internal medicine, Mendelian randomization, Genetic predisposition, Humans, Medicine, Risk factor, 11 Medical and Health Sciences, business.industry, Smoking, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Confidence interval, 3. Good health, Causality, 030104 developmental biology, Estrogen, 030220 oncology & carcinogenesis, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ICEP, Colorectal Neoplasms, business, Genome-Wide Association Study
Abstract

Background: Observational evidence has shown that smoking is a risk factor for breast and colorectal cancer. We used Mendelian randomization (MR) to examine causal associations between smoking and risks of breast and colorectal cancer. Methods: Genome-Wide Association Study summary data were used to identify genetic variants associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants). Using two-sample MR, we examined these variants in relation to incident breast (122,977 cases/105,974 controls) and colorectal cancer (52,775 cases/45,940 controls). Results: In inverse-variance weighted models, a genetic predisposition to higher lifetime amount of smoking was positively associated with breast cancer risk [OR per 1-SD increment: 1.13; 95% confidence interval (CI): 1.00–1.26; P = 0.04]; although heterogeneity was observed. Similar associations were found for estrogen receptor–positive and estrogen receptor–negative tumors. Higher lifetime amount of smoking was positively associated with colorectal cancer (OR per 1-SD increment, 1.21; 95% CI, 1.04–1.40; P = 0.01), colon cancer (OR, 1.31; 95% CI, 1.11–1.55; P < 0.01), and rectal cancer (OR, 1.36; 95% CI, 1.07–1.73; P = 0.01). Ever having smoked regularly was not associated with risks of breast (OR, 1.01; 95% CI, 0.90–1.14; P = 0.85) or colorectal cancer (OR, 0.97; 95% CI, 0.86–1.10; P = 0.68). Conclusions: These findings are consistent with prior observational evidence and support a causal role of higher lifetime smoking amount in the development of breast and colorectal cancer. Impact: The results from this comprehensive MR analysis indicate that lifetime smoking is a causal risk factor for these common malignancies.

Published
2021

32. Clinical Characteristics and Degree of Glycemic and Cardiovascular Risk Factor Control in Patients with Type 1 Diabetes in Catalonia (Spain)

Author

Angel Rodriguez, Jordi Real, Manel Mata-Cases, Gabriel Giménez-Pérez, Josep Franch-Nadal, Albert Goday, Emilio Ortega, Bogdan Vlacho, Didac Mauricio, [Gimenez-Perez, G] Hospital General de Granollers, Granollers, Spain. [Franch-Nadal, J] DAP-Cat Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. Primary Health Care Centre Raval Sud, Gerència d’Atenció Primària Barcelona Ciutat, Institut Català de la Salut, Barcelona, Spain. [Ortega, E] Department of Endocrinology & Nutrition, Institut d’Investigacions Biomèdiques August Pi Suñer, CIBEROBN, Hospital Clínic Barcelona, Barcelona, Spain. [Mata-Cases, M] DAP-Cat Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. Primary Health Care Centre La Mina, Gerència d’Atenció Primària Barcelona Ciutat, Institut Català de la Salut, Sant Adrià del Besós, Spain. [Goday, A] Department of Endocrinology & Nutrition, Hospital del Mar, Barcelona, Spain. Department of Medicine, Universitat Autònoma de Barcelona, CIBEROBN, Barcelona, Spain. [Real, J] DAP-Cat Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. [Rodriguez, A] Department of Clinical Research, Lilly, S.A., Madrid, Spain. [Vlacho, B] DAP-Cat Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. [Mauricio, D] DAP-Cat Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Faculty of Medicine, University of Vic-Central University of Catalonia, Vic, Spain, and Hospital General de Granollers

Subjects
hidratos de carbono::azúcares::monosacáridos::hexosas::glucosa::glucosa sanguínea [COMPUESTOS QUÍMICOS Y DROGAS], cardiovascular risk factors, medicine.medical_specialty, Catalonia, enfermedades del sistema endocrino::diabetes mellitus::diabetes mellitus tipo I [ENFERMEDADES], complications, medicine.medical_treatment, Cardiovascular risk factors, lcsh:Medicine, 030209 endocrinology & metabolism, Disease, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Glucèmia - Control, Cataluña, Internal medicine, medicine, Sistema cardiovascular - Factors de risc, In patient, Risk factor, enfermedades cardiovasculares [ENFERMEDADES], Glycemic, glucose control, Type 1 diabetes, Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 1 [DISEASES], Cardiovascular Diseases [DISEASES], business.industry, Insulin, lcsh:R, General Medicine, Carbohydrates::Sugars::Monosaccharides::Hexoses::Glucose::Blood Glucose [CHEMICALS AND DRUGS], medicine.disease, Blood pressure, type-1 diabetes, business, Diabetis - Catalunya
Abstract

Background: This study aims to evaluate the clinical characteristics, complications, degree of glycemic control, and cardiovascular risk factor control in patients with type 1 diabetes in Catalonia (Northwest of Spain). Methods: Cross-sectional study using a database including clinical, laboratory, and treatment data. Patients with an ICD10 diagnosis of type 1 diabetes were included, excluding those treated with glucose-lowering agents other than insulin, or treated only with basal insulin two years after diagnosis. Results: 15,008 patients were analysed. Median IQR age was 42 (31–53) years, diabetes duration 11.8 (6.8–16.0) years, 56.5% men. Median (IQR) HbA1c was 7.9% (7.1–8.8). Microvascular complications were present in 24.4% of patients, 43.6% in those with a diabetes duration &gt, 19 years. In presence of known cardiovascular disease 69.3% of patients showed an LDL-C concentration &gt, 70 mg/dL, 37% had a systolic blood pressure &gt, 135 mmHg and 22.4% were smokers. Conclusions: This study provides a reliable snapshot about the clinical situation of a large population of patients with T1D in Catalonia, which is similar to that of other western areas. The lack of adequate control of cardiovascular risk factors in a significant proportion of patients with cardiovascular disease deserves a more detailed analysis and urges the need for improvement strategies.

Published
2021
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33. Nefer, Sinuhe and clinical research assessing post COVID-19 condition

Author

Jordi Rello, José L. Peñalvo, Grant W. Waterer, Joan B. Soriano, Institut Català de la Salut, [Soriano JB] Servicio de Neumología, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid, Madrid, Spain. Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Waterer G] School of Medicine, University of Western Australia, Perth, Australia. [Peñalvo JL] Unit of Non-Communicable Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium. [Rello J] Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Recerca Clínica/Innovació en la Pneumònia i Sèpsia (CRIPS), Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Clinical Research, CHU Nîmes, Nîmes, France, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], COVID-19 (Malaltia), Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics::Epidemiologic Studies::Cohort Studies::Prospective Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], 03 medical and health sciences, Environment and Public Health::Public Health::Epidemiologic Measurements::Demography::Health Status::Quality of Life [HEALTH CARE], técnicas de investigación::métodos epidemiológicos::características de los estudios epidemiológicos::estudios epidemiológicos::estudios de cohortes::estudios prospectivos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], 0302 clinical medicine, Clinical research, Medicina - Investigació, 030228 respiratory system, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Medicine, 030212 general & internal medicine, business, Intensive care medicine, Qualitat de vida - Avaluació, ambiente y salud pública::salud pública::medidas epidemiológicas::demografía::estado de salud::calidad de vida [ATENCIÓN DE SALUD]
Abstract

COVID-19; Clinical research COVID-19; Recerca clínica COVID-19; Investigación clínica Clinical research studies reporting on post COVID-19 condition should follow some basic recommendations.

Published
2021

34. Prevalence of Fetal Alcohol Spectrum Disorders (FASD) among Children Adopted from Eastern European Countries: Russia and Ukraine

Author

Oscar Garcia-Algar, Nuria Gómez, Vicente Andreu-Fernández, Joan Colom, Lidia Segura-García, Natalia Barcons, Ana I Ibar, Raquel Vidal, Agnés Russiñol, Adriana Bastons-Compta, Vicky Fumadó, Marta Astals, [Colom J, Segura-García L] Program on Substance Abuse, Public Health Agency of Catalonia, Department of Health, Generalitat de Catalunya, Barcelona, Spain. Maternal and Child Health and Development Network (Red SAMID), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Bastons-Compta A] Maternal and Child Health and Development Network (Red SAMID), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Neonatology Unit, ICGON, IDIBAPS, Hospital Clínic-Maternitat, BCNatal, Barcelona, Spain. [Astals M, Garcia-Algar O] Maternal and Child Health and Development Network (Red SAMID), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Neonatology Unit, ICGON, IDIBAPS, Hospital Clínic-Maternitat, BCNatal, Barcelona, Spain. Departament de Cirurgia i Especialitats Mèdico-Quirúrgiques, University of Barcelona, Barcelona, Spain. [Andreu-Fernandez V] Maternal and Child Health and Development Network (Red SAMID), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Neonatology Unit, ICGON, IDIBAPS, Hospital Clínic-Maternitat, BCNatal, Barcelona, Spain. Departament of Nutrition and Health, Valencian International University (VIU), Valencia, Spain. [Barcons N] Pediatrics Service, Hospital Sant Joan de Déu, Barcelona, Spain. [Vidal R, Gómez N] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Madrid, Spain. Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Ibar AI] Program on Substance Abuse, Public Health Agency of Catalonia, Department of Health, Generalitat de Catalunya, Barcelona, Spain. [Fumadó V] Pediatrics Service, Hospital Sant Joan de Déu, Barcelona, Spain. [Russiñol A] Department of Labour, Social Affairs and Families, Catalan Institute for Fostering and Adoption, Barcelona, Spain, Departament de Salut, and [Colom J, Segura-García L] Program on Substance Abuse, Public Health Agency of Catalonia, Department of Health, Generalitat de Catalunya, Barcelona, Spain. Maternal and Child Health and Development Network (Red SAMID), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Bastons-Compta A] Maternal and Child Health and Development Network (Red SAMID), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Neonatology Unit, ICGON, IDIBAPS, Hospital Clínic-Maternitat, BCNatal, Barcelona, Spain. [Astals M, Garcia-Algar O] Maternal and Child Health and Development Network (Red SAMID), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Neonatology Unit, ICGON, IDIBAPS, Hospital Clínic-Maternitat, BCNatal, Barcelona, Spain. Departament de Cirurgia i Especialitats Mèdico-Quirúrgiques, University of Barcelona, Barcelona, Spain. [Andreu-Fernandez V] Maternal and Child Health and Development Network (Red SAMID), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Neonatology Unit, ICGON, IDIBAPS, Hospital Clínic-Maternitat, BCNatal, Barcelona, Spain. Departament of Nutrition and Health, Valencian International University (VIU), Valencia, Spain. [Barcons N] Pediatrics Service, Hospital Sant Joan de Déu, Barcelona, Spain. [Vidal R, Gómez N] Psychiatry Service, Hospital Universitari Vall d’Hebron, Barcelona, Spain. Group of Psychiatry, Mental Health and Addiction, Vall d’Hebron Research Institute (VHIR), Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Madrid, Spain. Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. [Ibar AI] Program on Substance Abuse, Public Health Agency of Catalonia, Department of Health, Generalitat de Catalunya, Barcelona, Spain. [Fumadó V] Pediatrics Service, Hospital Sant Joan de Déu, Barcelona, Spain. [Russiñol A] Department of Labour, Social Affairs and Families, Catalan Institute for Fostering and Adoption, Barcelona, Spain

Subjects
Pediatrics, Prenatal exposure to alcohol (PEA), Infants amb trastorn de l'espectre alcohòlic fetal, Health, Toxicology and Mutagenesis, lcsh:Medicine, Russia, Cognitive disorder, enfermedades de los genitales femeninos y complicaciones del embarazo::complicaciones del embarazo::enfermedades fetales::trastornos del espectro alcohólico fetal [ENFERMEDADES], 0302 clinical medicine, Neurodevelopmental disorder, Pregnancy, adopted children, Prevalence, 030212 general & internal medicine, Child, reproductive and urinary physiology, education.field_of_study, alcohol, Persons::Child, Adopted [NAMED GROUPS], Alcohol consumption during pregnancy, female genital diseases and pregnancy complications, Eastern european, fetal alcohol spectrum disorders (FASD), Fetal Alcohol Spectrum Disorders, Prenatal Exposure Delayed Effects, Female, Ukraine, Alcohol, Female Urogenital Diseases and Pregnancy Complications::Pregnancy Complications::Fetal Diseases::Fetal Alcohol Spectrum Disorders [DISEASES], Adult, medicine.medical_specialty, Adolescent, Alcohol Drinking, Alcohol-exposed pregnancies, Population, Fetal alcohol syndrome, Neurodevelopment impairment, alcohol-exposed pregnancies, Article, neurodevelopment impairment, 03 medical and health sciences, Fetal alcohol, Young Adult, cognitive disorder, 030225 pediatrics, medicine, Humans, education, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, Fills adoptius, personas::niño adoptado [DENOMINACIONES DE GRUPOS], medicine.disease, prenatal exposure to alcohol (PEA), Adopted children, Fetal alcohol spectrum disorders (FASD), Fetal Alcohol Spectrum Disorder, business, Child, Adopted
Abstract

Fetal alcohol spectrum disorders; Adopted children; Cognitive disorder Trastornos del espectro alcohólico fetal; Niño adoptado; Trastorno cognitivo Trastorns de l'espectre alcohòlic fetal; Nens adoptats; Trastorn cognitiu Fetal alcohol spectrum disorder (FASD) is a leading cause of neurodevelopmental disorders. Children adopted internationally from countries where alcohol consumption during pregnancy is very high are at greater risk for FASD. Lack of expertise in diagnosing FASD and mixed neurodevelopmental and behavioral signs due to abandonment complicate a timely diagnosis. The aim of this study was to determine the prevalence of FASD in adopted children. Children between the ages of 8 and 24 adopted from Russia and Ukraine were evaluated for clinical and historical features of FASD. Of the 162 children evaluated, 81 (50%) met FASD diagnostic criteria. Thirty-three (20.4%) children had fetal alcohol syndrome (FAS), 28 (17.2%) had partial FAS, 2 (1.2%) had alcohol-related birth defects (ARBD) and 18 (11.1%) had alcohol-related neurodevelopmental disorder (ARND). Of the 81 children in which fetal alcohol exposure could not be confirmed, many had manifestations that would have established a diagnosis of FASD if a history of maternal alcohol consumption was confirmed. In a population of children with a high risk of prenatal alcohol exposure (adoptees from Eastern European countries), at least 50% showed manifestations associated with FASD. The reported prevalence in this study is in line with the results obtained in a previous study as well as in orphanages of origin.

Published
2021

35. SOCS1-derived peptide administered by eye drops prevents retinal neuroinflammation and vascular leakage in experimental diabetes

Author

[Hernández C, Bogdanov P, Sampedro J, Solà-Adell C, García-Ramírez M, Simó R] Grup de Diabetis i Metabolisme, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Gómez-Guerrero C] Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Renal, Vascular and Diabetes Research Lab, Instituto de Investigacion Sanitaria-Fundación Jimenez Diaz (IIS-FJD), Madrid, Spain. Autonoma University of Madrid (UAM), Madrid, Spain. [Espejo, C] Recerca en Neuroimmunologia clínica, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. and Hospital Universitari Vall d'Hebron

Subjects
Amino Acids, Peptides, and Proteins::Amino Acids, Peptides, and Proteins::Proteins::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Adaptor Proteins, Signal Transducing::Suppressor of Cytokine Signaling Proteins [CHEMICALS AND DRUGS], Endocrine System Diseases::Diabetes Mellitus::Diabetes Complications::Diabetic Angiopathies::Diabetic Retinopathy [DISEASES], Cardiovascular System::Blood-Retinal Barrier [ANATOMY], Enfermedades del Sistema Endocrino::Diabetes Mellitus::Complicaciones de la Diabetes::Angiopatías Diabéticas::Retinopatía Diabética [ENFERMEDADES], Retinopatia diabètica, Aminoácidos, Péptidos y Proteínas::Péptidos::Péptidos y Proteínas de Señalización Intracelular::Proteínas Adaptadoras Transductoras de Señales::Proteínas Supresoras de la Señalización de Citocinas [COMPUESTOS QUÍMICOS Y DROGAS], Retina - Vasos sanguinis, sistema cardiovascular::barrera hematorretinal [ANATOMÍA], Quimiocines
Published
2021

36. Pivotal role of AKT2 during dynamic phenotypic change of breast cancer stem cells

Author

[Gener P, Seras-Franzoso J, Perez A, Pindado LA, Casas G] Direccionament i alliberament farmacològic, Nanomedicina Oncologia molecular (CIBBIM-Nanomedicina), Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. [Rafael D] Direccionament i alliberament farmacològic, Nanomedicina Oncologia molecular (CIBBIM-Nanomedicina), Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Arango D] Investigació Biomèdica en Tumors de l'Aparell Digestiu, CIBBIM-Nanomedicina, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. [Fernández Y] Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Àrea de Validació Funcional i Estudis Preclínics (FVPR), CIBBIM-Nanomedicina, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. [Díaz-Riascos Z] Direccionament i alliberament farmacològic, Nanomedicina Oncologia molecular (CIBBIM-Nanomedicina), Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. Àrea de Validació Funcional i Estudis Preclínics (FVPR), CIBBIM-Nanomedicina, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. [Abasolo I, Schwartz S] Direccionament i alliberament farmacològic, Nanomedicina Oncologia molecular (CIBBIM-Nanomedicina), Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Àrea de Validació Funcional i Estudis Preclínics (FVPR), CIBBIM-Nanomedicina, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain and Hospital Universitari Vall d'Hebron

Subjects
Serina-proteases, Enzimas y Coenzimas::Enzimas::Transferasas::Fosfotransferasas::Fosfotransferasas (Aceptor de Grupo Alcohol)::Proteínas Quinasas::Proteínas Serina-Treonina Quinasas::Proteína Serina-Treonina Quinasas de Interacción con Receptores::Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor [COMPUESTOS QUÍMICOS Y DROGAS], Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Receptor-Interacting Protein Serine-Threonine Kinases::Receptor-Interacting Protein Serine-Threonine Kinase 2 [CHEMICALS AND DRUGS], Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Mama - Tumors, Cèl·lules canceroses, Neoplasias::Neoplasias por Localización::Neoplasias de la Mama [ENFERMEDADES], células::células madre::células madre neoplásicas [ANATOMÍA], Cells::Stem Cells::Neoplastic Stem Cells [ANATOMY]
Published
2021

37. Targeting antitumoral proteins to breast cancer by local administration of functional inclusion bodies

Author

[Pesarrodona M] Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Jauset T, Beaulieu ME] Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Peptomyc S.L. Edifici Cellex, Barcelona, Spain. [Díaz-Riascos ZV, Mancilla S, Fernández Y, Abasolo I] CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. CIBBIM-Nanomedicina Àrea de Validació Funcional i Estudis Preclínics, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona Spain. CIBBIM-Nanomedicina Direccionament i Alliberament Farmacològic, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Sánchez-Chardi A] Departament de Biologia Evolutiva Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Barcelona Spain. [Seras-Franzoso J, Baltà-Foix R] CIBBIM-Nanomedicina Direccionament i Alliberament Farmacològic, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Schwartz Jr S] CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. CIBBIM-Nanomedicina Direccionament i Alliberament Farmacològic, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Soucek L] Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Peptomyc S.L. Edifici Cellex, Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain and Hospital Universitari Vall d'Hebron

Subjects
Mama - Càncer, Proteïnes recombinants, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS], células::estructuras celulares::cuerpos de inclusión [ANATOMÍA], Neoplasias::Neoplasias por Localización::Neoplasias de la Mama [ENFERMEDADES], Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS], Cells::Cellular Structures::Inclusion Bodies [ANATOMY], Medicaments antineoplàstics
Published
2021

38. Metabolic fingerprint of acromegaly and its potential usefulness in clinical practice

Author

[Biagetti B, Mesa J, Simó R] Grup de Recerca en Diabetis i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centre for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Universidat Autònoma de Barcelona, Barcelona, Spain. [Herance J.R.] Grup de Recerca en Imatge Mèdica Molecular, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Nanomedicina Oncologia molecular (CIBBIM-Nanomedicina), Barcelona, Spain. Networking Research Centre for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Ferrer R] Servei de Bioquímica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Aulinas A] Endocrinology Department, Hospital Universitari de Vic, Barcelona, Spain. [Palomino Schätzlein M] NMR Facility, Centro de Investigación Príncipe Felipe, Valencia, Spain and Hospital Universitari Vall d'Hebron

Subjects
enfermedades del sistema endocrino::enfermedades de la hipófisis::hiperpituitarismo::acromegalia [ENFERMEDADES], Otros calificadores::/análisis [Otros calificadores], Acromegàlia, Marcadors bioquímics - Anàlisi, Other subheadings::/analysis [Other subheadings], Aminoàcids, Biological Factors::Biomarkers [CHEMICALS AND DRUGS], Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Branched-Chain [CHEMICALS AND DRUGS], aminoácidos, péptidos y proteínas::aminoácidos::aminoácidos de cadena ramificada [COMPUESTOS QUÍMICOS Y DROGAS], factores biológicos::biomarcadores [COMPUESTOS QUÍMICOS Y DROGAS], Endocrine System Diseases::Pituitary Diseases::Hyperpituitarism::Acromegaly [DISEASES]
Published
2021

39. Expanding the clinical and genetic spectra of primary immunodeficiency-related disorders with clinical exome sequencing: expected and unexpected findings

Author

[Rudilla F] Laboratori d'Immunogenètica i Histocompatibilitat, Banc de Sang i Teixits, Barcelona, Spain. Grup de Recerca en Medicina Transfusional, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Franco-Jarava C, Martínez-Gallo M, Aguiló-Cucurull A, Pujol-Borrell R] Recerca en Immunologia Diagnòstica, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei d’ Immunologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Departament de Biologia Cel•lular, de Fisiologia i d'Immunologia, Universitat Autònoma de Barcelona, Barcelona, Spain. Jeffrey Model Foundation Excellence Center, Barcelona, Spain. [Garcia-Prat M, Martín-Nalda A, Rivière J, Soler-Palacín P] Jeffrey Model Foundation Excellence Center, Barcelona, Spain. Infecció en el pacient pediàtric Immunodeprimit, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Unitat de Patologia Infecciosa I Immunodeficiències de Pediatria (UPIIP), Vall d'Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Vidal F] Laboratori d'Immunogenètica i Histocompatibilitat, Banc de Sang i Teixits, Barcelona, Spain. Grup de Recerca en Medicina Transfusional, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. CIBER en Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Cuscó I, Serra C] Servei de Genètica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Baz-Redón N] Grup de Recerca en Creixement i Desenvolupament, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Fernández-Cancio M] Grup de Recerca en Creixement i Desenvolupament, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. CIBER en Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Garcia-Patos V] Servei de Dermatologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Colobran R] Recerca en Immunologia Diagnòstica, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei d’ Immunologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Departament de Biologia Cel•lular, de Fisiologia i d'Immunologia, Universitat Autònoma de Barcelona, Barcelona, Spain. Jeffrey Model Foundation Excellence Center, Barcelona, Spain. Servei de Genètica, Vall d'Hebron Hospital Universitari, Barcelona, Spain and Hospital Universitari Vall d'Hebron

Subjects
Immunodeficiència, Técnicas de Investigación::Técnicas Genéticas::Análisis de Secuencia::Análisis de Secuencia de ADN::Secuenciación Completa del Genoma::Secuenciación del Exoma Completo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide Sequencing [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::Whole Genome Sequencing::Whole Exome Sequencing [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Primary Immunodeficiency Diseases [DISEASES], Otros calificadores::Otros calificadores::/genética [Otros calificadores], Técnicas de Investigación::Técnicas Genéticas::Análisis de Secuencia::Secuenciación de Nucleótidos de Alto Rendimiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Other subheadings::Other subheadings::/genetics [Other subheadings], enfermedades del sistema inmune [ENFERMEDADES], Exons, Genètica - Tècnica
Published
2021

40. Persistence with dual antiplatelet therapy after percutaneous coronary intervention for ST-segment elevation acute coronary syndrome: a population-based cohort study in Catalonia (Spain)

Author

[Ribera A, Ferreira-Gonzalez I, Marsal JR] Servei de Cardiologia, Hospital Universitari Vall d’Hebron, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Oristrell G, Garcia Dorado D] Servei de Cardiologia, Hospital Universitari Vall d’Hebron, Barcelona, Spain. Centro de Investigación Biomédica en Red para Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Faixedas MT] Servei Català de la Salut, Generalitat de Catalunya, Barcelona, Spain. [Rosas A] Departament de Salut, Generalitat de Catalunya, Barcelona, Spain. and Hospital Universitari Vall d'Hebron

Subjects
Infart de miocardi, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Hematologic Agents::Platelet Aggregation Inhibitors [CHEMICALS AND DRUGS], Enfermedades Cardiovasculares::Cardiopatías::Isquemia Miocárdica::Infarto del Miocardio::Infarto del Miocardio con Elevación del ST [ENFERMEDADES], Plaquetes sanguínies - Agregació, Cateterisme cardíac, Surgical Procedures, Operative::Cardiovascular Surgical Procedures::Vascular Surgical Procedures::Endovascular Procedures::Percutaneous Coronary Intervention [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Cardiovascular Diseases::Heart Diseases::Myocardial Ischemia::Myocardial Infarction::ST Elevation Myocardial Infarction [DISEASES], Acciones y Usos Químicos::Acciones Farmacológicas::Usos Terapéuticos::Fármacos Hematológicos::Inhibidores de Agregación Plaquetaria [COMPUESTOS QUÍMICOS Y DROGAS], Procedimientos Quirúrgicos Operativos::Procedimientos Quirúrgicos Cardiovasculares::Procedimientos Quirúrgicos Vasculares::Procedimientos Endovasculares::Intervención Coronaria Percutánea [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]
Published
2021

41. Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies

Author

Fulvio Ricceri, Joseph A. Rothwell, Amanda J. Cross, Graham G. Giles, Elisabete Weiderpass, Tilman Kühn, Emily Sonestedt, Yi Yang, Rudolf Kaaks, Valeria Pala, Anna Karakatsani, Dallas R. English, Rosario Tumino, Pilar Amiano, Antonia Trichopoulou, John L. Hopper, Leila Lujan-Barroso, Allison M. Hodge, Bengt Wallner, Ruth C. Travis, María Dolores López, Anne Tjønneland, Hazel M. Mitchell, Kostas Tsilidis, Domenico Palli, Harindra Jayasekara, Elio Riboli, Antonio Agudo, Robin Room, Heiner Boeing, Eva Ardanaz, Bas Bueno-de-Mesquita, Torkjel M. Sandanger, Pietro Ferrari, Robert J. MacInnis, Susana Merino, Andrew Haydon, Eleni Peppa, Marie-Christine Boutron-Ruault, Salvatore Panico, María José Sánchez, Marc J. Gunter, Hanna Sternby, Roger L. Milne, Gianluca Severi, Ana Lucia Mayen-Chacon, Centre international de Recherche sur le Cancer (CIRC), 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, Institut Gustave Roussy (IGR), VicHealth Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT Medical Research Council, MRC: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1 British Heart Foundation, BHF Department of Health and Social Care, DH Cancer Research UK, CRUK: C570/ A16491, C8221/A19170, C864/A14136 World Cancer Research Fund, WCRF Food Standards Agency, FSA Stroke Association European Commission, EC National Health and Medical Research Council, NHMRC: 1074383, 209057, 396414, GNT1163120 Cancer Council Victoria Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Stavros Niarchos Foundation, SNF Vetenskapsrådet, VR Consiglio Nazionale delle Ricerche, CNR Ministère des Affaires Sociales et de la Santé: GR‐IARC‐2003‐09‐12‐01 Instituto de Salud Carlos III, ISCIII Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Rijksinstituut voor Volksgezondheid en Milieu, RIVM Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN Ministry of Health and Social Solidarity, Greece Foundation for Alcohol Research and Education, FARE Hellenic Health Foundation, HHF, Australian National Health and Medical Research Council, Grant/Award Numbers: 1074383, 209057, 396414, GNT1163120, Cancer Council Victoria (Australia), Cancer Research UK, Grant/Award Numbers: C570/ A16491, C8221/A19170, C864/A14136, Catalan Institute of Oncology ‐ ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission (Directorate General for Health and Consumer Affairs), Foundation for Alcohol Research and Education (Australia), French Ministry of Health, Grant/Award Number: Grant GR‐IARC‐2003‐09‐12‐01, Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Santé et de la Recherche Médicale (France), Italian Association for Research on Cancer and the National Research Council (Italy), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, Medical Research Council (UK), Grant/Award Numbers: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1, Mutuelle Générale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK), Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), the Federal Ministry of Education and Research (Germany), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), the Institut Gustave Roussy Funding information, We thank Carine Biessy and Bertrand Hemon for their technical contribution to EPIC data used in this work. We are also grateful to all the EPIC participants who have been part of the project, and to the many members of the study teams who enabled this research. We thank the original MCCS investigators and the diligent team, who recruited the participants and who continue working on follow‐up, for their contribution. We also express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. This work was supported by the Direction Générale de la Santé (French Ministry of Health, Grant GR‐IARC‐2003‐09‐12‐01), by the European Commission (Directorate General for Health and Consumer Affairs) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), the Ligue Contre le Cancer, the Institut Gustave Roussy, the Mutuelle Générale de l'Education Nationale and the Institut National de la Santé et de la Recherche Médicale (France), the Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, the World Cancer Research Fund and Statistics Netherlands (the Netherlands), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study, the Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology ‐ ICO (Spain), the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), Cancer Research UK (C864/A14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/N003284/1 and MC‐UU_12015/1 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, United Kingdom), the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK). MCCS cohort recruitment was funded by Cancer Council Victoria ( https://www.cancervic.org.au/ ) and VicHealth ( https://www.vichealth.vic.gov.au/ ). The MCCS was further supported by Australian National Health and Medical Research Council (NHMRC) ( https://www.nhmrc.gov.au/ ) grants 209057, 396414 and 1074383, and ongoing follow‐up and data management has been funded by Cancer Council Victoria since 1995. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. Harindra Jayasekara is supported by NHMRC grant GNT1163120. John L. Hopper is a NHMRC Senior Principal Research Fellow. Yi Yang is supported by a Melbourne Research Scholarship from the University of Melbourne. Robin Room's position was funded by the Foundation for Alcohol Research and Education. The sponsors had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and and decision to submit the manuscript for publication.

Subjects
Male, Cancer Research, Gastroenterology, 0302 clinical medicine, Prospective Studies, Stomach cancer, Prospective cohort study, stomach cancer, biology, Stomach, Incidence, Hazard ratio, Smoking, cardia cancer, Cardia cancer, Middle Aged, Lifetime alcohol intake, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, medicine.anatomical_structure, Oncology, Drinking of alcoholic beverages, 030220 oncology & carcinogenesis, Consum d'alcohol, Female, Life Sciences & Biomedicine, Cohort study, Adult, medicine.medical_specialty, Alcohol Drinking, [SDV.CAN]Life Sciences [q-bio]/Cancer, Helicobacter Infections, noncardia cancer, 03 medical and health sciences, Stomach Neoplasms, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Aged, Science & Technology, Helicobacter pylori, EPIC, lifetime alcohol intake, MCCS, business.industry, Càncer d'estómac, Kirurgi, Australia, Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Noncardia cancer, medicine.disease, biology.organism_classification, Surgery, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences., National Health and Medical Research Council of Australia 1074383 209057 396414 GNT1163120, Canadian Institutes of Health Research (CIHR) Cancer Council Victoria, Cancer Research UK C570/A16491 C8221/A19170 C864/A14136, Catalan Institute of Oncology - ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission European Commission Joint Research Centre, Foundation for Alcohol Research and Education (Australia), French Ministry of Health GR-IARC-2003-09-12-01, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Junta de Andalucía, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Sante et de la Recherche Medicale (Inserm), Consiglio Nazionale delle Ricerche (CNR), Associazione Italiana per la Ricerca sul Cancro (AIRC), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, Netherlands Organization for Scientific Research (NWO), UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MC-UU_12015/1 MR/M012190/1 MR/N003284/, Mutuelle Generale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association (UK), British Heart Foundation, Department of Health (UK), Food Standards Agency (UK), Wellcome Trust, Swedish Cancer Society, Swedish Scientific Council (Sweden), Regional Government of Skane (Sweden), Federal Ministry of Education & Research (BMBF), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), Institut Gustave Roussy

Published
2021

42. Inflammatory potential of the diet and risk of breast cancer in the European Investigation into Cancer and Nutrition (EPIC) study

Author

Verena Katzke, Anne M. May, Carlota Castro-Espin, Paula Jakszyn, Christina C. Dahm, Elisabete Weiderpass, Matthias B. Schulze, Guri Skeie, María José Sánchez, Catalina Bonet, Maria Dolores Chirlaque, Sanam Shah, Nasser Laouali, Dagfinn Aune, José Ramón Quirós, Sabina Sieri, Eva Ardanaz, Salvatore Panico, Gianluca Severi, Carlotta Sacerdote, Antonio Agudo, Stina Bodén, Melissa A. Merritt, Iger T Gram, Rosario Tumino, Krasimira Aleksandrova, Giovanna Masala, Elio Riboli, Renée Turzanski-Fortner, Pilar Amiano, Anne Tjønneland, Laure Dossus, Manon Cairat, 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, Institut Gustave Roussy (IGR), Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII: PI15/00639, European Social Fund, ESF, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Rijksinstituut voor Volksgezondheid en Milieu, RIVM, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, European Regional Development Fund, ERDF: FI19/00197, NIHR Imperial Biomedical Research Centre, BRC, This work was funded by Instituto de Salud Carlos III through the project PI15/00639 (Co-funded by European Regional Development Fund [ERDF], a way to build Europe). C. Castro-Espin was funded by Instituto de Salud Carlos III through the Grant FI19/00197 (Co-funded by European Social Fund. ESF investing in your future). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The funders of this study had no role in the decisions about the analysis or interpretation of the data, or preparation, review or approval of the manuscript., and We thank CERCA Programme/Generalitat de Catalunya for institutional support. We also thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study.

Subjects
Adult, medicine.medical_specialty, Epidemiology, Nutritional Status, Breast Neoplasms, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Inflammatory potential of the diet, Prospective study, Prospective cohort study, Life Style, Inflammation, 2. Zero hunger, business.industry, Proportional hazards model, Hazard ratio, Chronic inflammation, Middle Aged, medicine.disease, Obesity, Diet, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Cohort, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Body mass index
Abstract

International audience; The role of chronic inflammation on breast cancer (BC) risk remains unclear beyond as an underlying mechanism of obesity and physical activity. We aimed to evaluate the association between the inflammatory potential of the diet and risk of BC overall, according to menopausal status and tumour subtypes. Within the European Prospective Investigation into Cancer and Nutrition cohort, 318,686 women were followed for 14 years, among whom 13,246 incident BC cases were identified. The inflammatory potential of the diet was characterized by an inflammatory score of the diet (ISD). Multivariable Cox regression models were used to assess the potential effect of the ISD on BC risk by means of hazard ratios (HR) and 95% confidence intervals (CI). ISD was positively associated with BC risk. Each increase of one standard deviation (1-Sd) of the score increased by 4% the risk of BC (HR = 1.04; 95% CI 1.01–1.07). Women in the highest quintile of the ISD (indicating a most pro-inflammatory diet) had a 12% increase in risk compared with those in the lowest quintile (HR = 1.12; 95% CI 1.04–1.21) with a significant trend. The association was strongest among premenopausal women, with an 8% increased risk for 1-Sd increase in the score (HR = 1.08; 95% CI 1.01–1.14). The pattern of the association was quite homogeneous by BC subtypes based on hormone receptor status. There were no significant interactions between ISD and body mass index, physical activity, or alcohol consumption. Women consuming more pro-inflammatory diets as measured by ISD are at increased risk for BC, especially premenopausal women.

Published
2021

43. Non-productive angiogenesis disassembles Aß plaque-associated blood vessels

Author

José Luis Trillo-Contreras, Pedro Gómez-Gálvez, Luis M. Escudero, Nieves Lara-Ureña, Andrea S. Bullones-Bolanos, Javier Vitorica, Miriam Echevarría, Rosana March-Díaz, Miguel Marchena, Jose Carlos Davila, Ana C. Sanchez-Hidalgo, Eloisa Herrera, Fernando de Castro, Jakob Körbelin, Antonia Gutierrez, Rocio González-Martínez, Alicia E. Rosales-Nieves, Raquel del Toro, Clara Ortega-de San Luis, Maria I. Alvarez-Vergara, Alberto Pascual, Pablo Vicente-Munuera, Manuel A. Sanchez-Garcia, Guiomar Rodriguez-Perinan, Martin Trepel, Francisco G. Scholl, Alberto Rábano, Javier Villadiego, Miguel Martin-Bornez, Beatriz Fernández-Gómez, Universidad de Sevilla. Departamento de Biología Celular, Instituto de Salud Carlos III PI18/01556, PI18/01557, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas CB06/05/ 0094, Ministerio de Economía, Industria y Competitividad (España), Ministerio de Economía y Competitividad (España), Ministerio de Educación, Cultura y Deporte (España), Instituto de Salud Carlos III, European Commission, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Fundació La Marató de TV3, Junta de Andalucía, Fundación Domingo Martínez, [Alvarez-Vergara,MI, Rosales-Nieves,AE, March-Diaz,R, Rodriguez-Perinan,G, Lara-Ureña,N, Ortega-de San Luis,C, Sanchez-Garcia,MA, Martin-Bornez,M, Gómez-Gálvez,P, Vicente-Munuera,P, Bullones-Bolanos,AS, Trillo-Contreras,JL, Sanchez-Hidalgo,AC, del Toro,R, Scholl,FG, Escudero,LM, Villadiego,J, Echevarria,M, Vitorica,J, Pascual,A] Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain. [Gómez-Gálvez,P, Escudero,LM] Department of Biología Celular, Universidad de Sevilla. Seville, Spain. [Gómez-Gálvez,P, Davila,JC, Gutierrez,A, Vitorica,J] Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. [Fernandez-Gomez,B, Marchena,MA, de Castro,F] Grupo de Neurobiología del Desarrollo-GNDe, Instituto Cajal-CSIC, Madrid, Spain. [Marchena,MA] Departamento de Medicina, Facultad de Ciencias, Biomédicas y de la Salud, Universidad Europea de Madrid, Villaviciosa de Odón, Spain. [Davila,JC, Gutierrez,A] Department of Biologia Celular, Genetica y Fisiologia, Facultad de Ciencias, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain. [Gonzalez-Martinez,R, Herrera,E] 7 Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández (CSIC-UMH), Alicante, Spain. [Trillo-Contreras,JL, Echevarria,M] Department of Fisiología Médica y Biofisica, Universidad de Sevilla, Seville, Spain. [del Toro,R] Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain. [Trepel,M] Augsburg Medical Center, Department of Hematology and Oncology, Augsburg, Germany. [Körbelin,J] Section of Pneumology, Department of Oncology, Hematology and Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. [Rabano,A] Fundacion CIEN, Madrid, Spain. [Vitorica,J] Department of Bioquimica y Biologia Molecular, Facultad de Farmacia, Universidad de Sevilla, Seville, Spain. [Ortega-de San Luis,L] Present address: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College of Dublin, Dublin, Ireland. [Sanchez-Garcia,MA] Present address: Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK. [Alvarez-Vergara,MI, Rosales-Nieves,AE] These authors contributed equally: Maria I. Alvarez-Vergara, Alicia E. Rosales-Nieves., A.E.R.-N. was the recipient of a JdlC-F fellowship from the Spanish Ministry of Economy, Industry, and Competitiveness (MINEICO) (FJCI-2015-23708), M.I.A.-V., N.L.-U., and C.O.-d.S.L. were the recipient of an FPU fellowship from Spanish Ministry of Education, Culture, and Sport (respectively, FPU15/02898, FPU14-02115, and AP2010‐1598), and R.M.-D. was the recipient of a 'Sara Borrell' fellowship from ISCIII (CD09/0007). Work was supported by grants to A.P. by the Spanish MINEICO, ISCIII, and FEDER (SAF2012‐33816, SAF2015‐64111‐R, RTI2018-096629-B-100, SAF2017-90794-REDT, and PIE13/0004), by the regional Government of Andalusia ('Proyectos de Excelencia', P12‐CTS‐2138 and P12‐CTS‐2232) co-funded by CEC and FEDER funds, and by the 'Ayuda de Biomedicina 2018', Fundación Domingo Martínez, J.Vitorica: Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union (PI18/01556) by La Marató-TV3 Foundation grant 20141431, by CIBERNED (CB06/05/0094), and by Junta de Andalucia Consejería de Economía y Conocimiento through grant US-1262734, A.G.: Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grant PI18/01557, and by Junta de Andalucia Consejería de Economía y Conocimiento through grants UMA18-FEDERJA-211 and P18-RT-2233 co-financed by Programa Operativo FEDER 2014-2020. The authors thank Maria Llorens-Martin (CBM-Severo Ochoa, Madrid, Spain) for the generous gift of the human samples, Ralf H. Adams and Jose L. de la Pompa for providing the Cdh5-Cre, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas

Subjects
0301 basic medicine, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Inbred Strains::Mice, Inbred C57BL [Medical Subject Headings], Cerebrovascular disorders, Angiogenesis, Malformaciones vasculares, Endothelial cells, General Physics and Astronomy, Plaque, Amyloid, Molecular neuroscience, Neovascularization, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Blood vessels, Péptidos beta-amiloides, Enfermedad de Alzheimer, Organisms::Eukaryota::Animals [Medical Subject Headings], Anatomy::Cells::Epithelial Cells::Endothelial Cells [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Metaplasia::Neovascularization, Pathologic [Medical Subject Headings], Mice, Knockout, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Presenilins [Medical Subject Headings], Multidisciplinary, Microglia, Neovascularization, Pathologic, Reverse Transcriptase Polymerase Chain Reaction, Placa amiloide, Presenilins, Brain, Alzheimer's disease, Cell biology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain Reaction [Medical Subject Headings], medicine.anatomical_structure, Vasos sanguíneos, Anatomy::Cardiovascular System::Blood Vessels::Microvessels [Medical Subject Headings], Encéfalo, Female, medicine.symptom, Alzheimer disease, Blood vessel, Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease [Medical Subject Headings], Phagocytosis, Science, Vascular malformations, Presenilinas, Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Skin Abnormalities [Medical Subject Headings], Mice, Transgenic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling [Medical Subject Headings], Biology, General Biochemistry, Genetics and Molecular Biology, Presenilin, Article, Plaque, amyloid, 03 medical and health sciences, Alzheimer Disease, Diseases::Pathological Conditions, Signs and Symptoms::Pathological Conditions, Anatomical::Plaque, Amyloid [Medical Subject Headings], medicine, Extracellular, Animals, Humans, ddc:610, Anatomy::Cardiovascular System::Blood Vessels [Medical Subject Headings], Amyloid beta-Peptides, Gene Expression Profiling, Células endoteliales, Endothelial Cells, General Chemistry, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Amyloid beta-Peptides [Medical Subject Headings], Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings], Diseases::Animal Diseases::Disease Models, Animal [Medical Subject Headings], Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Blood Vessels, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Transgenic [Medical Subject Headings], 030217 neurology & neurosurgery, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, Knockout [Medical Subject Headings]
Abstract

The human Alzheimer’s disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of Aß pathology. We also show that Aß plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD., A.E.R.-N. was the recipient of a JdlC-F fellowship from the Spanish Ministry of Economy, Industry, and Competitiveness (MINEICO) (FJCI-2015-23708), M.I.A.-V., N.L.-U., and C.O.-d.S.L. were the recipient of an FPU fellowship from Spanish Ministry of Education, Culture, and Sport (respectively, FPU15/02898, FPU14-02115, and AP2010‐1598), and R.M.-D. was the recipient of a “Sara Borrell” fellowship from ISCIII (CD09/0007). Work was supported by grants to A.P. by the Spanish MINEICO, ISCIII, and FEDER (SAF2012‐33816, SAF2015‐64111‐R, RTI2018-096629-B-100, SAF2017-90794-REDT, and PIE13/0004), by the regional Government of Andalusia (“Proyectos de Excelencia”, P12‐CTS‐2138 and P12‐CTS‐2232) co-funded by CEC and FEDER funds, and by the “Ayuda de Biomedicina 2018”, Fundación Domingo Martínez; J.Vitorica: Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union (PI18/01556) by La Marató-TV3 Foundation grant 20141431; by CIBERNED (CB06/05/0094); and by Junta de Andalucia Consejería de Economía y Conocimiento through grant US-1262734; A.G.: Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grant PI18/01557; and by Junta de Andalucia Consejería de Economía y Conocimiento through grants UMA18-FEDERJA-211 and P18-RT-2233 co-financed by Programa Operativo FEDER 2014-2020.

Published
2021

44. Dietary intake and plasma phospholipid concentrations of saturated, monounsaturated and trans fatty acids and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Author

Joseph A. Rothwell, Giovanna Masala, José María Huerta, Aurora Perez-Cornago, Elisabete Weiderpass, Anja Olsen, Magritt Brustad, Claudia Agnoli, Corinne Casagrande, Guri Skeie, Ulrika Ericson, Verena Katzke, Mazda Jenab, Christina C. Dahm, Anne Tjønneland, Geneviève Nicolas, Rudolf Kaaks, Inge Huybrechts, Veronika Fedirko, Carlotta Sacerdote, Neil Murphy, Maria Wennberg, Veronique Chajes, Jeroen W.G. Derksen, Matthias B. Schulze, Elom K. Aglago, Bas Bueno-de-Mesquita, Alicia K Heath, Pilar Amiano, Salvatore Panico, Paula Jakszyn, Rosario Tumino, Marc J. Gunter, Inger T. Gram, María José Sánchez, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), 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, 1000143, MR/M012190/1, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Cancer Research UK, CRUK: 14136, C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Rijksinstituut voor Volksgezondheid en Milieu, RIVM, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, World Cancer Research Fund, Grant/Award Number: WCRF 2013/1002 Funding information trans, The authors would like to thank the EPIC study participants and staff for their valuable contribution to this research. The authors would also like to thank Ms Beatrice Vozar, Mr Bertrand Hemon and Ms Carine Biessy for the analysis of plasma samples, and the preparation of the databases. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC‐Norfolk, C8221/A29017 to EPIC‐Oxford), MedicalResearch Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford). (United Kingdom), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. The EPIC‐Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1, MC‐PC_13048 and MC‐UU_12015/1). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. The authors would like to acknowledge the use of data and samples from EPIC centres in Cambridge, France, Asturias, and Navarro. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Our study was funded by a grant from the World Cancer Research Fund to Marc Gunter (Grant number: WCRF 2013/1002)., Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Health Research Fund (FIS)?Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology?ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), MedicalResearch Council (1000143 to EPIC-Norfolk, and MR/M012190/1 to EPIC-Oxford). (United Kingdom), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1, MC-PC_13048 and MC-UU_12015/1). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. The authors would like to acknowledge the use of data and samples from EPIC centres in Cambridge, France, Asturias, and Navarro. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Our study was funded by a grant from the World Cancer Research Fund to Marc Gunter (Grant number: WCRF 2013/1002).

Subjects
Cancer Research, medicine.medical_specialty, Colorectal cancer, Myristic acid, [SDV.CAN]Life Sciences [q-bio]/Cancer, colorectal cancer, Gastroenterology, fatty acids, DISEASE, Palmitic acid, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, COLON, medicine, 2 SIDES, 2. Zero hunger, chemistry.chemical_classification, business.industry, Fatty acid, Odds ratio, ASSOCIATION, medicine.disease, Elaidic acid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Oncology, chemistry, 030220 oncology & carcinogenesis, biomarker, Stearic acid, business, dietary intake, LIPIDS
Abstract

International audience; Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial-processed trans (iTFA), and ruminant-sourced trans (rTFA) fatty acids, and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Baseline fatty acid intakes were estimated in 450 112 participants (6162 developed CRC, median follow-up = 15 years). In a nested case-control study, plasma phospholipid fatty acids were determined by gas chromatography in 433 colon cancer cases and 433 matched controls. Multivariable-adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Cox and conditional logistic regression, respectively. Dietary total SFA (highest vs lowest quintile, HRQ5vsQ1 = 0.80; 95%CI:0.69-0.92), myristic acid (HRQ5vsQ1 = 0.83, 95%CI:0.74-0.93) and palmitic acid (HRQ5vsQ1 = 0.81, 95%CI:0.70-0.93) were inversely associated with CRC risk. Plasma myristic acid was also inversely associated with colon cancer risk (highest vs lowest quartile, ORQ4vsQ1 = 0.51; 95%CI:0.32-0.83), whereas a borderline positive association was found for plasma stearic acid (ORQ4vsQ1 = 1.63; 95%CI:1.00-2.64). Dietary total MUFA was inversely associated with colon cancer (per 1-SD increment, HR1-SD = 0.92, 95%CI: 0.85-0.98), but not rectal cancer (HR1-SD = 1.04, 95%CI:0.95-1.15, Pheterogeneity = 0.027). Dietary iTFA, and particularly elaidic acid, was positively associated with rectal cancer (HR1-SD = 1.07, 95%CI:1.02-1.13). Our results suggest that total and individual saturated fatty acids and fatty acids of industrial origin may be relevant to the aetiology of CRC. Both dietary and plasma myristic acid levels were inversely associated with colon cancer risk, which warrants further investigation.

Published
2021

45. A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC

Author

Ingegerd Johansson, David S. Lopez, Alicia K Heath, Amanda J. Cross, Anne Tjønneland, J. Ramón Quirós, Melissa A. Merritt, Paula Jakszyn, Bas Bueno-de-Mesquita, Pilar Amiano, Anne Kirstine Eriksen, Manuela M. Bergmann, Marc J. Gunter, Bernard Srour, David C. Muller, Piet A. van den Brandt, Matthias B. Schulze, Salvatore Panico, Claudia Agnoli, Pietro Ferrari, Marco Lukic, José María Huerta, Christina C. Dahm, Therese Haugdahl Nøst, Areti Papadopoulou, Aurelio Barricarte Gurrea, Rosario Tumino, María José Sánchez, Fulvio Ricceri, Nadia Bastide, Paolo Vineis, Ulrika Ericson, Eva Ardanaz, Gianluca Severi, Guri Skeie, Aurora Perez-Cornago, Nikos Papadimitriou, Emmanouil Bouras, Elisabete Weiderpass, Ellio Riboli, Ioanna Tzoulaki, Heiner Boeing, Stina Bodén, Giovanna Masala, Jeroen W.G. Derksen, Jonna Berntsson, Verena Katzke, Elena Critselis, Konstantinos K. Tsilidis, University of Ioannina, Maastricht University [Maastricht], Imperial College London, Biomedical Research Foundation of the Academy of Athens (BRFAA), International Agency for Cancer Research (IACR), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), 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, University of Hawai'i [Honolulu] (UH), The University of Texas Health Science Center at Houston (UTHealth), University of Oxford [Oxford], University of Potsdam, The Arctic University of Norway (UiT), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Umeå University, Università degli studi di Torino = University of Turin (UNITO), Lund University [Lund], Instituto de Salud Carlos III [Madrid] (ISC), Aarhus University [Aarhus], IRCCS Istituto Nazionale dei Tumori [Milano], University of Copenhagen = Københavns Universitet (KU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Naples Federico II, La Salle [Ramon Llull University], Utrecht University [Utrecht], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, International Council of Ophthalmology, ICO, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF: WCRF 2014/1180, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Funding This work was supported by the World Cancer Research Fund International Regular Grant Programme (WCRF 2014/1180 to Konstantinos K. Tsilidis). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the National Institute for Health Research Imperial Biomedical Research Centre. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)?Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (ICO) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford) and Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., Funding This work was supported by the World Cancer Research Fund International Regular Grant Programme ( WCRF 2014/1180 to Konstantinos K. Tsilidis). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the National Institute for Health Research Imperial Biomedical Research Centre . The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid , German Cancer Research Center ( DKFZ ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research ( BMBF ) (Germany), Dutch Ministry of Public Health , Welfare and Sports ( VWS ), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund ( WCRF ), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)– Instituto de Salud Carlos III ( ISCIII ), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology ( ICO ) (Spain), Swedish Cancer Society , Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Epidemiologie, and RS: GROW - R1 - Prevention

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Riboflavin, colorectal cancer, Lower risk, Cohort Studies, Animal science, beta-Carotene, Risk Factors, Epidemiology, medicine, cohort study, Humans, Prospective Studies, Hepatology, Gastroenterology & Hepatology, business.industry, Hazard ratio, Gastroenterology, food and beverages, 1103 Clinical Sciences, Confidence interval, European Prospective Investigation into Cancer and Nutrition, Diet, epidemiology, nutrition, business, Colorectal Neoplasms, Cohort study
Abstract

Background & Aims: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. Methods: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. Results: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04–1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04–1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93–0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90–0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90–0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92–0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93–0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. Conclusions: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.

Published
2020

46. Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer’s disease model

Author

Victoria Navarro, Javier Vitorica, Cristina Nuñez-Diaz, Sebastian Jimenez, Elisabeth Sanchez-Mejias, Angela Gomez-Arboledas, Clara Muñoz-Castro, Marisa Vizuete, Raquel Sanchez-Varo, Juan Jose Fernandez-Valenzuela, Ines Moreno-Gonzalez, Jose Carlos Davila, Antonia Gutierrez, Vanessa De Castro, Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Instituto de Salud Carlos III (ISCiii) de España, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Centro de Investigación Biomédica en Red (CIBERNED), Instituto de Salud Carlos III, European Commission, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Universidad de Málaga, Ministerio de Ciencia, Innovación y Universidades (España), [Fernandez-Valenzuela,JJ, Sanchez-Varo,R, De Castro,V, Sanchez-Mejias,E, Nuñez-Diaz,C, Gomez-Arboledas,A, Moreno-Gonzalez,I, Davila,JC, Gutierrez,A] Dpto. Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga‑IBIMA, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain. [Fernandez-Valenzuela,JJ, Muñoz-Castro,C, Navarro,V, Jimenez,S, Vizuete,M, Vitorica,J, Gutierrez,A] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. [Muñoz-Castro,C, Vitorica,J] Dpto. Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain. [Muñoz-Castro,C, Vitorica,J] Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio/CSIC, Universidad de Sevilla, Sevilla, Spain., This study was supported by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grants PI15/00796 and PI18/01557 (both to AG), PI15/00957 and PI18/01556 (both to JV), and CIBERNED (CB06/05/1116 to AG and CB06/05/0094 to JV), and by Malaga University grant PPIT.UMA.B1.2017/26 (to RSV). JJFV and CMC were supported by FPU PhD fellowships (Spanish Ministry of Science, Innovation and Universities). RSV held a postdoctoral contract from Malaga University. IMG is recipient of a senior postdoctoral contract from Ramon y Cajal Program (Spain Government).

Subjects
Male, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Interneuronas, Psychiatry and Psychology::Mental Disorders::Delirium, Dementia, Amnestic, Cognitive Disorders::Cognition Disorders [Medical Subject Headings], lcsh:Medicine, Hippocampal formation, Chemicals and Drugs::Organic Chemicals::Lactones::Macrolides::Epothilones [Medical Subject Headings], Axonal Transport, Microtubules, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mice, Enfermedad de Alzheimer, Organisms::Eukaryota::Animals [Medical Subject Headings], Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic [Medical Subject Headings], lcsh:Science, Anatomy::Nervous System::Neurons [Medical Subject Headings], Neurons, Tauopatías, Multidisciplinary, Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies [Medical Subject Headings], Neurodegeneration, Brain, Tubulin Modulators, Phenotype, Tauopathies, Encéfalo, Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Cytoskeleton::Microtubules [Medical Subject Headings], GABAergic, Female, Intracellular, Amyloid, Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease [Medical Subject Headings], Transporte axonal, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Mitosis Modulators::Antimitotic Agents::Tubulin Modulators [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Mice, Transgenic, Biology, Neuroprotection, Article, Interneurons, Alzheimer Disease, Microtubule, Extracellular, medicine, Animals, Humans, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cytoplasmic Streaming::Axonal Transport [Medical Subject Headings], Amiloide, lcsh:R, medicine.disease, Cellular neuroscience, Diseases::Animal Diseases::Disease Models, Animal [Medical Subject Headings], Disease Models, Animal, Check Tags::Female [Medical Subject Headings], Epothilones, Axoplasmic transport, Diseases of the nervous system, lcsh:Q, Cognition Disorders, Neuroscience
Abstract

In Alzheimer’s disease (AD), and other tauopathies, microtubule destabilization compromises axonal and synaptic integrity contributing to neurodegeneration. These diseases are characterized by the intracellular accumulation of hyperphosphorylated tau leading to neurofibrillary pathology. AD brains also accumulate amyloid-beta (Aβ) deposits. However, the effect of microtubule stabilizing agents on Aβ pathology has not been assessed so far. Here we have evaluated the impact of the brain-penetrant microtubule-stabilizing agent Epothilone D (EpoD) in an amyloidogenic model of AD. Three-month-old APP/PS1 mice, before the pathology onset, were weekly injected with EpoD for 3 months. Treated mice showed significant decrease in the phospho-tau levels and, more interesting, in the intracellular and extracellular hippocampal Aβ accumulation, including the soluble oligomeric forms. Moreover, a significant cognitive improvement and amelioration of the synaptic and neuritic pathology was found. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation. Therefore, our results suggested that EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Aβ levels and promoting neuronal and cognitive protection. These results underline the existence of a crosstalk between cytoskeleton pathology and the two major AD protein lesions. Therefore, microtubule stabilizers could be considered therapeutic agents to slow the progression of both tau and Aβ pathology., This study was supported by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grants PI15/00796 and PI18/01557 (both to AG), PI15/00957 and PI18/01556 (both to JV), and CIBERNED (CB06/05/1116 to AG and CB06/05/0094 to JV); by Malaga University grant PPIT.UMA.B1.2017/26 (to RSV). JJFV and CMC were supported by FPU PhD fellowships (Spanish Ministry of Science, Innovation and Universities). RSV held a postdoctoral contract from Malaga University. IMG is recipient of a senior postdoctoral contract from Ramon y Cajal Program (Spain Government).

Published
2020

47. Interpreting molecular similarity between patients as a determinant of disease comorbidity relationships

Author

Sánchez-Valle, Jon, Tejero-Cicuéndez, Héctor, Fernández, José María, Juan, David, Urda-García, Beatriz, Capella-Gutiérrez, Salvador, Al-Shahrour, Fátima, Tabarés-Seisdedos, Rafael, Baudot, Anaïs, Pancaldi, Vera, Valencia, Alfonso, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, Aix-Marseille Université, Instituto Nacional de Bioinformática (España), Generalitat Valenciana, Barcelona Supercomputing Center, Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Spanish National Cancer Research Center (CNIO), Spanish National Bioinformatics Institute [Madrid, Espagne], Institute of Evolutionary Biology [Barcelone, Espagne], Universitat de València (UV), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Université de Toulouse (UT), Institució Catalana de Recerca i Estudis Avançats (ICREA), This work was supported by a Ph.D. Fellowship (BES-2016-077403) and funded by the Spanish Ministry of Economics and Competitiveness (BFU2015-71241-R, RTI2018-096653-B-I00). The Coordination Node led by A.V. at the Barcelona Supercomputing Center (BSC) is a member of the Spanish National Bioinformatics Institute (INB), ISCIII-Bioinformatics platform and is supported by grant PT17/0009/0001 of the Acción Estratégica en Salud 2013-2016 of the Programa Estatal de Investigación Orientada a los Retos de la Sociedad, funded by the Instituto de Salud Carlos III (ISCIII) and European Regional Development Fund (ERDF). V.P. is supported by INSERM, the Fondation Toulouse Cancer Santé and Pierre Fabre Research Institute as part of the Chair of Bioinformatics in Oncology of the CRCT. A.B. has received funding from the Excellence Initiative of Aix-Marseille University—A*Midex, a French 'Investissements d’Avenir' program. D.J. was supported by Juan de la Cierva fellowship (FJCI-2016-29558) from the Ministerio de Ciencia, Innovación y Universidades. H.T. and F.A.-S. were supported by the Instituto de Salud Carlos III (ISCIII), Spanish National Bioinformatics Institute (INB) Grant (PT17/0009/0011—ISCIII-SGEFI/ERDF) and Marie-Curie Career Integration Grant (CIG334361). J.M.F. and S.C.-G. were supported by the Instituto de Salud Carlos III (ISCIII), Spanish National Bioinformatics Institute (INB) Grant (PT17/0009/0001— ISCIII-SGEFI/ERDF). R.T.-S. was supported in part by grant number PROMETEOII/2015/021 from Generalitat Valenciana and the national grant PI17/00719 from ISCIIIFEDER., ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), 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), Université Fédérale Toulouse Midi-Pyrénées, Bodescot, Myriam, and INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE - - Amidex2011 - ANR-11-IDEX-0001 - IDEX - VALID

Subjects
Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC], Disease PERCEPTION portal, Science, Datasets as Topic, Diseases, Comorbidity, Protein−protein interaction, Article, Genètica molecular, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Humans, Genetic Predisposition to Disease, Biomedical research, Molecular genetics, lcsh:Science, Cancer, Gene Expression Profiling, Healthcare, Computational Biology, Computational biology and bioinformatics, Phenotypes, Gene expression profiles, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Molecular similarity, Case-Control Studies, Malalties, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Enginyeria biomèdica, Gene expression, Biomedical engineering, Medical care, Biomarkers
Abstract

Comorbidity is a medical condition attracting increasing attention in healthcare and biomedical research. Little is known about the involvement of potential molecular factors leading to the emergence of a specific disease in patients affected by other conditions. We present here a disease interaction network inferred from similarities between patients’ molecular profiles, which significantly recapitulates epidemiologically documented comorbidities. Furthermore, we identify disease patient-subgroups that present different molecular similarities with other diseases, some of them opposing the general tendencies observed at the disease level. Analyzing the generated patient-subgroup network, we identify genes involved in such relations, together with drugs whose effects are potentially associated with the observed comorbidities. All the obtained associations are available at the disease PERCEPTION portal (http://disease-perception.bsc.es)., This work was supported by a Ph.D. Fellowship (BES-2016-077403) and funded by the Spanish Ministry of Economics and Competitiveness (BFU2015-71241-R, RTI2018-096653-B-I00). The Coordination Node led by A.V. at the Barcelona Supercomputing Center (BSC) is a member of the Spanish National Bioinformatics Institute (INB), ISCIII-Bioinformatics platform and is supported by grant PT17/0009/0001 of the Acción Estratégica en Salud 2013-2016 of the Programa Estatal de Investigación Orientada a los Retos de la Sociedad, funded by the Instituto de Salud Carlos III (ISCIII) and European Regional Development Fund (ERDF). V.P. is supported by INSERM, the Fondation Toulouse Cancer Santé and Pierre Fabre Research Institute as part of the Chair of Bioinformatics in Oncology of the CRCT. A.B. has received funding from the Excellence Initiative of Aix-Marseille University—A*Midex, a French “Investissements d’Avenir” program. D.J. was supported by Juan de la Cierva fellowship (FJCI-2016-29558) from the Ministerio de Ciencia, Innovación y Universidades. H.T. and F.A.-S. were supported by the Instituto de Salud Carlos III (ISCIII), Spanish National Bioinformatic

Published
2020

48. Peroxisome Proliferator-Activated Receptors: Experimental Targeting for the Treatment of Inflammatory Bowel Diseases

Author

Decara, Juan, Rivera, Patricia, López-Gambero, Antonio Jesús, Serrano, Antonia, Pavón, Francisco Javier, Baixeras, Elena, Rodríguez de Fonseca, Fernando, Suárez, Juan, [Decara,J, López-Gambero,AJ, Serrano,A, Pavón,FJ, Rodríguez de Fonseca,F, Suárez,J] UGC Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Rivera,P] Departamento de Endocrinología, Fundación Investigación Biomédica del Hospital Infantil Universitario Niño Jesús, Madrid, Spain. [Pavón,FJ] Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV) and UGC del Corazón, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain. [Baixeras,E] Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Málaga, IBIMA, Málaga, Spain., This study was supported by the following research projects and programs: Proyecto de Investigación en Salud 'PI-0139-2018' funded by Consejerı́a de Salud y Familias, Junta de Andalucı́a, 'DTS19/00125' funded by Instituto de Salud Carlos III (ISCIII) and co-funded by European Regional Development Fund (ERDF) 'A way to make Europe', Proyecto de Investigación en Salud 'PI19/01577' funded by Instituto de Salud Carlos III (ISCIII) and co-funded by European Regional Development Fund (ERDF) 'A way to make Europe', and AS and JS hold 'Miguel Servet' research contracts (CP14/00173 and CPII17/00024 respectively) from the ISCIII and co-funded by European Social Fund 'Investing in your future' PR holds a 'Sara Borrell' research contract (CD16/00067) from the ISCIII and co-funded by European Social Fund 'Investing in your future' FP holds a 'Programa Nicolás Monardes' contract (C1-0049-2019) from Servicio Andaluz de Salud, Junta de Andalucía.

Subjects
Enfermedades inflamatorias del intestino, Chemicals and Drugs::Pharmaceutical Preparations [Medical Subject Headings], Inflammatory bowel diseases, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Peroxisome Proliferator-Activated Receptors [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::Ligands [Medical Subject Headings], Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases [Medical Subject Headings], Crohn's disease, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Peroxisome Proliferator-Activated Receptors::PPAR gamma [Medical Subject Headings], Ulcerative colitis, Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid Metabolism [Medical Subject Headings], Colitis ulcerosa, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::NF-kappa B [Medical Subject Headings], Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Colitis, Ulcerative [Medical Subject Headings], PPARg, Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Crohn Disease [Medical Subject Headings], Enfermedad de Crohn, Receptores activados del proliferador del peroxisoma, PPARa, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Physiological Processes::Homeostasis [Medical Subject Headings], PPARb/d
Abstract

The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that promote ligand-dependent transcription of target genes that regulate energy production, lipid metabolism, and inflammation. The PPAR superfamily comprises three subtypes, PPARα, PPARγ, and PPARβ/δ, with differential tissue distributions. In addition to their different roles in the regulation of energy balance and carbohydrate and lipid metabolism, an emerging function of PPARs includes normal homeostasis of intestinal tissue. PPARα activation represses NF-κB signaling, which decreases the inflammatory cytokine production by different cell types, while PPARγ ligands can inhibit activation of macrophages and the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Il-1β. In this regard, the anti-inflammatory responses induced by PPAR activation might restore physiopathological imbalances associated with inflammatory bowel diseases (IBD). Thus, PPARs and their ligands have important therapeutic potential. This review briefly discusses the roles of PPARs in the physiopathology and therapies of the most important IBDs, ulcerative colitis (UC), and Crohn's disease (CD), as well some new experimental compounds with PPAR activity as promising drugs for IBD treatment. Yes

Published
2020

49. Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions

Author

Pol Cuscó, Demian Burguera, Salvatore D'Aniello, Cristina Vicente-García, Bru Cormand, Enrique Navas-Perez, José Luis Ferran, Jordi Garcia-Fernàndez, Carlos Herrera-Úbeda, Marta Alaiz-Noya, Rafael Falcón-Moya, Angel M. Carrión, Serena Mirra, Irene Suárez-Pereira, Gemma Marfany, Fausto Ulloa, Eduardo Soriano, Noèlia Fernàndez-Castillo, Ester Antón-Galindo, Jaime J. Carvajal, Antonio Rodríguez-Moreno, Macarena López-Mayorga, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Junta de Andalucía, Centro de Investigación Biomédica en Red Enfermedades Raras (España), [Navas-Pérez,E, Mirra,S, Burguera,D, Fernàndez-Castillo,N, Antón-Galindo,E, Herrera-Úbeda,C, Cormand,B, Marfany,G, Garcia-Fernàndez,J] Department of Genetics, Microbiology and Statistics, Faculty of Biology, and Institut de Biomedicina (IBUB), University of Barcelona, Barcelona, Spain. [Vicente-García,C, López-Mayorga,M, Carvajal,JJ] Centro Andaluz de Biología del Desarrollo, CSIC-UPO-JA, Universidad Pablo de Olavide, Sevilla, Spain. [Mirra,S, Ulloa,F, Soriano,E] Department of Cell Biology, Physiology and Immunology, and Institute of Neurosciences, University of Barcelona, Barcelona, Spain. [Mirra,S, Marfany,G] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Mirra,S, Soriano,E] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Burguera,D] Department of Zoology, Charles University, Prague, Czech Republic. [Fernàndez-Castillo,N, Marfany,G] Institut de Recerca Sant Joan de Déu (IR-SJD), Esplugues de Llobregat, Barcelona, Spain. [Ferrán,JL] Department of Human Anatomy, School of Medicine, University of Murcia and IMIB-Arrixaca Institute, Murcia, Spain. [Alaiz-Noya,M, Suárez-Pereira,I, Falcón-Moya,R, Rodríguez-Moreno,A, Carrión,AM] Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, Sevilla, Spain. [Alaiz-Noya,M] Present Address: Instituto de Neurociencias de Alicante (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas), Alicante, Spain. [Suárez-Pereira,I] Present Address: Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Neuropsychopharmacology and psychobiology research group, UCA, INiBICA, Cádiz, Spain. [Cuscó,P] Genome Architecture, Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), the Barcelona Institute of Science and Technology, Barcelona, Spain. [Cuscó,P] Universitat Pompeu Fabra (UPF), Barcelona, Spain. [D'Aniello,S] Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Naples, Italy. [Soriano,E] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain., and Major financial support for this research was received from Spanish 'Ministerio de Ciencia, Innovación y Universidades.' Grants BFU2015-68655-P and BFU2017-861152-P to J.G.F., RTI2018-100968-B-I00, 2017-SGR-738, H2020/2014-2020 under grant agreements n°667302, n°643051, and n°728018 to B.C., PGC2018-098229-B-I00 to J.L.F., BES-2016-077374 to E.A.-G., CVI-7290 Junta de Andalucía to A.R.M., SAF2016-80937-R (Ministerio de Economía y Competitividad/FEDER) to G.M., Institutional Grant MDM-2016-0687 (Maria de Maeztu Excellence Unit, Department of Gene Regulation and Morphogenesis at CABD) and BFU2017-83150-P to J.J.C, BFU2017-89780-R and P12-CTS-2257 to A.M.C. and SAF2016-76340-R and María de Maeztu Excellence Unit, Institute of Neurosciences to E.S.. E.N.P. held an FPI pre-doctoral fellowship (Spanish 'Ministerio de Ciencia, Innovación y Universidades'). S.M. was first supported by a contract with the 'Centro de Investigación Biomédica en Enfermedades Neurodegenerativas,' and later by 'Centro de Investigación Biomédica en Red de Enfermedades Raras' (CIBERER). N.F.C. is also under contract by CIBERER. This study makes use of data generated by the DECIPHER community. A full list of centres who contributed to the generation of the data is available at http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Funding for the project was provided by the Wellcome Trust.

Subjects
Bex3, Tceal, Placenta, Autism, Genome, Neurodevelopmental disorders, Familia de multigenes, Domestication, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mice, 0302 clinical medicine, Human genetics, Pregnancy, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue Proteins [Medical Subject Headings], Gene duplication, Gene cluster, Organisms::Eukaryota::Animals [Medical Subject Headings], Autism spectrum disorder, Genetic novelty, lcsh:QH301-705.5, Serina-treonina quinasas TOR, Phylogeny, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings], Mice, Knockout, 0303 health sciences, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins [Medical Subject Headings], Genètica humana, Eutheria, TOR Serine-Threonine Kinases, Brain, Nuclear Proteins, DNA-Binding Proteins, Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic::Mice, Knockout [Medical Subject Headings], Multigene Family, Placental mammals, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins [Medical Subject Headings], mTOR, Female, Transposon domestication, Transposable element, lcsh:QH426-470, Psychiatry and Psychology::Mental Disorders::Mental Disorders Diagnosed in Childhood::Child Development Disorders, Pervasive::Autistic Disorder [Medical Subject Headings], Nerve Tissue Proteins, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins [Medical Subject Headings], Biology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors [Medical Subject Headings], Evolution, Molecular, 03 medical and health sciences, Trastornos del neurodesarrollo, Animals, Humans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::TOR Serine-Threonine Kinases [Medical Subject Headings], Allele, Gene, 030304 developmental biology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Research, Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings], Anatomy::Embryonic Structures::Placenta [Medical Subject Headings], Phenomena and Processes::Biological Phenomena::Biological Processes::Biological Evolution::Evolution, Molecular [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic::Gene Silencing::CRISPR-Cas Systems [Medical Subject Headings], Mice, Inbred C57BL, lcsh:Genetics, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Interspersed Repetitive Sequences::DNA Transposable Elements [Medical Subject Headings], lcsh:Biology (General), Check Tags::Female [Medical Subject Headings], Evolutionary biology, DNA Transposable Elements, Euterios, Phenomena and Processes::Genetic Phenomena::Phylogeny [Medical Subject Headings], Trastorno del espectro autista, CRISPR-Cas Systems, Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BL [Medical Subject Headings], Autisme, Apoptosis Regulatory Proteins, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Multigene Family [Medical Subject Headings], 030217 neurology & neurosurgery, Transcription Factors
Abstract

[Background]: One of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes at the core of key macroevolutionary changes, their origin and organismal function are generally poorly understood., [Results]: Here, we identify several previously unreported transposable element domestication events in the human and mouse genomes. Among them, we find a remarkable molecular domestication that gave rise to a multigenic family in placental mammals, the Bex/Tceal gene cluster. These genes, which act as hub proteins within diverse signaling pathways, have been associated with neurological features of human patients carrying genomic microdeletions in chromosome X. The Bex/Tceal genes display neural-enriched patterns and are differentially expressed in human neurological disorders, such as autism and schizophrenia. Two different murine alleles of the cluster member Bex3 display morphological and physiopathological brain modifications, such as reduced interneuron number and hippocampal electrophysiological imbalance, alterations that translate into distinct behavioral phenotypes., [Conclusions]: We provide an in-depth understanding of the emergence of a gene cluster that originated by transposon domestication and gene duplication at the origin of placental mammals, an evolutionary process that transformed a non-functional transposon sequence into novel components of the eutherian genome. These genes were integrated into existing signaling pathways involved in the development, maintenance, and function of the CNS in eutherians. At least one of its members, Bex3, is relevant for higher brain functions in placental mammals and may be involved in human neurological disorders., Major financial support for this research was received from Spanish “Ministerio de Ciencia, Innovación y Universidades.” Grants BFU2015-68655-P and BFU2017-861152-P to J.G.F., RTI2018-100968-B-I00, 2017-SGR-738, H2020/2014-2020 under grant agreements n°667302, n°643051, and n°728018 to B.C., PGC2018-098229-B-I00 to J.L.F., BES-2016-077374 to E.A.-G., CVI-7290 Junta de Andalucía to A.R.M., SAF2016-80937-R (Ministerio de Economía y Competitividad/FEDER) to G.M., Institutional Grant MDM-2016-0687 (Maria de Maeztu Excellence Unit, Department of Gene Regulation and Morphogenesis at CABD) and BFU2017-83150-P to J.J.C, BFU2017-89780-R and P12-CTS-2257 to A.M.C. and SAF2016-76340-R and María de Maeztu Excellence Unit, Institute of Neurosciences to E.S.. E.N.P. held an FPI pre-doctoral fellowship (Spanish “Ministerio de Ciencia, Innovación y Universidades”). S.M. was first supported by a contract with the “Centro de Investigación Biomédica en Enfermedades Neurodegenerativas,” and later by “Centro de Investigación Biomédica en Red de Enfermedades Raras” (CIBERER). N.F.C. is also under contract by CIBERER.

Published
2020

50. Adherence to the Mediterranean Lifestyle and Desired Body Weight Loss in a Mediterranean Adult Population with Overweight: A PREDIMED-Plus Study

Author

Josep A. Tur, Itziar Abete, José J. Gaforio, Jordi Salas-Salvadó, Nerea Becerra-Tomás, Francisco J. Tinahones, Albert Goday, Xavier Pintó, Maria Dolors Zomeño, Julia Wärnberg, Alejandro Oncina-Canovas, Carmen Saiz, Jessica Pérez-López, Dolores Corella, Clotilde Vázquez, Lucas Tojal-Sierra, Leyre Notario-Barandiaran, Marga Morey, Lidia Daimiel, Aurora Bueno-Cavanillas, José Manuel Santos-Lozano, José Lapetra, F. Javier Basterra-Gortari, Julia Muñoz, Alicia Julibert, Marian Martín, M. Rosa Bernal-Lopez, Sara Castro-Barquero, Ana Galera, Josep Vidal, Vicente Martín-Sánchez, Miguel Ruiz-Canela, Maria C Belló-Mora, Emilio Ros, Ignacio M. Gimenez-Alba, Antonio García Ríos, Tamara Casañas-Quintana, Ángel M. Alonso-Gómez, Jesús García-Gavilán, Josep Basora, Jesús Vioque, Ramon Estruch, Dora Romaguera, Luis Serra-Majem, Cesar I Fernandez-Lazaro, Pilar Matía-Martín, Escarlata Angullo-Martinez, Cristina Bouzas, Carmen Sayón-Orea, J. Alfredo Martínez, Olga Castañer, Maria del Mar Bibiloni, [Bouzas,C, Bibiloni,MM, Julibert,A, Ruiz-Canela,M, Salas-Salvadó,J, Corella,D, Zomeño,MD, Romaguera,D, Alonso-Gómez,ÁM, Wärnberg,J, Martínez,JA, Serra-Majem,L, Estruch,R, Tinahones,FJ, Lapetra,J, Pintó,X, García Ríos,A, Vázquez,C, Ros,E, Fernandez-Lázaro,CI, Becerra-Tomás,N, Gimenez-Alba,IM, Muñoz,J, Morey,M, Pérez-López,J, Abete,I, Casañas-Quintana,T, Castro-Barquero,S, Bernal-López,MR, Santos-Lozano,JM, Galera,A, Angullo-Martinez,E, Basterra-Gortari,FJ, Basora,J, Saiz,C, Castañer,O, Martín,M, Belló-Mora,MC, Sayón-Orea,C, García-Gavilán,J, Goday,A, Tur,JA] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Bouzas,C, Tojal-Sierra,L, Tur,JA] Research Group on Community Nutrition & Oxidative Stress, University of Balearic Islands, Guillem Colom Bldg, Campus, Palma de Mallorca, Spain. [Bouzas,C, Tur,JA] Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, Spain. [Ruiz-Canela,M, Sayón-Orea,C] Department of Preventive Medicine and Public Health, IdISNA, University of Navarra, Pamplona, Spain. [Salas-Salvadó,J, García-Gavilán,J] Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, Human Nutrition Unit, Reus, Spain. [Salas-Salvadó,J] Institut d’Investigació Sanitària Pere Virgili (IISPV), Reus, Spain. [Corella,D, Saiz,C] Department of Preventive Medicine, University of Valencia, Valencia, Spain. [Zomeño,MD, Goday,A] Unit of Cardiovascular Risk and Nutrition, Institut Hospital del Mar de Investigaciones Médicas Municipal d’Investigació Mèdica (IMIM), Barcelona, Spain. [Zomeño,MD] Blanquerna School of Health Sciences, Universitat Ramon Llull, Barcelona, Spain. [Vioque,J, Oncina-Canovas,A, Notario-Barandiarán,L] Unit of Nutritional Epidemiology, Miguel Hernández University, ISABIAL-UMH, Alicante, Spain. [Vioque,J, Bueno-Cavanillas,A, Gaforio,JJ, Notario-Barandiarán,L] CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Alonso-Gómez,ÁM, Belló-Mora,MC] Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba University Hospital, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain. [Wärnberg,J, Pérez-López,J] Department of Nursing, School of Health Sciences, University of Málaga-IBIMA, Málaga, Spain. [Martínez,JA] Precision Nutrition Program, IMDEA Food, CEI UAM + CSIC, Madrid, Spain. [Martínez,JA, Abete,I] Department of Nutrition, Food Sciences, and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain. [Serra-Majem,L, Casañas-Quintana,T] Institute for Biomedical Research, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. [Estruch,R, Castro-Barquero,S] Department of Internal Medicine, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain. [Tinahones,FJ, Bernal-López,MR] Virgen de la Victoria Hospital, Department of Endocrinology, Biomedical Research Institute of Málaga (IBIMA), University of Málaga, Málaga, Spain. [Lapetra,J, Santos-Lozano,JM] Department of Family Medicine, Research Unit, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain. [Pintó,X, Galera,A] Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain. [García Ríos,A] Lipids and Atherosclerosis Unit, Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. [Bueno-Cavanillas,A] Department of Preventive Medicine, University of Granada, Granada, Spain. [Gaforio,JJ] Department of Health Sciences, Centro de Estudios Avanzados en Olivar y Aceites de Oliva, University of Jaen, Jaen, Spain. [Matía-Martín,P] Department of Endocrinology and Nutrition, Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), Madrid, Spain. [Daimiel,L] Nutritional Genomics and Epigenomics Group, IMDEA Food, CEI UAM + CSIC, Madrid, Spain. [Martín-Sánchez,V] CIBER Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Martín-Sánchez,V] Institute of Biomedicine (IBIOMED), University of León, León, Spain. [Vidal,J] Department of Endocrinology, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain. [Vázquez,C] Department of Endocrinology, Fundación Jiménez-Díaz, Madrid, Spain. [Ros,E] Lipid Clinic, Department of Endocrinology and Nutrition, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain. [Angullo-Martinez,E] Escola Graduada Primary Health Care Center, IBSalut, Palma de Mallorca, Spain. [Basterra-Gortari,FJ, Sayón-Orea,C] Servicio Navarro de Salud, Osasunbidea, Pamplona, Spain., The PREDIMED-Plus trial was supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (five coordinated FIS projects led by J.S.-S. and J.Vidal, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, and PI19/01332, the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S., the European Research Council (Advanced Research Grant 2013–2018, 340918) to Miguel Ángel Martínez-González, the Recercaixa Grant to J.S.-S. (2013ACUP00194), Grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a Grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN Grant, EU-COST Action CA16112, a Grant of support to research groups no. 35/2011 from the Balearic Islands Government, Grants from Balearic Islands Health Research Institute (IDISBA), funds from the European Regional Development Fund (CIBEROBN CB06/03 and CB12/03) and from the European Commission (EAT2BENICE_H2020_SFS2016). M. Rosa Bernal-López was supported by 'Miguel Servet Type I' program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the European Regional Development Fund. Jordi Salas-Salvadó is partially supported by ICREA under the ICREA Academia programme. Cristina Bouzas received a Fernando Tarongí Bauzà PhD Grant. I.M Gimenez-Alba received a grant FPU from the Ministry of Science, Innovation and Univesities (reference FPU 18/01703). The funding sponsors had no role in the design of the study, in the collection, analyses, or interpretation of the data, and in the writing of the manuscript, and in the decision to publish the results.

Subjects
Male, Mediterranean diet, Obesidad, ejercicio físico, Body Mass Index, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Surveys and Questionnaires, Antineoplastic Combined Chemotherapy Protocols, Medicine, mediana edad, education.field_of_study, anciano, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Age Factors [Medical Subject Headings], dieta, protocolos de quimioterapia antineoplásica combinada, 3. Good health, Older adults, metotrexato, programas de reducción de peso, Obesitat, lcsh:Nutrition. Foods and food supply, Personas mayores frágiles, Ideal weight, Lifestyles, Check Tags::Male [Medical Subject Headings], lcsh:TX341-641, Article, Estilo de vida, 03 medical and health sciences, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Overweight [Medical Subject Headings], Anthropology, Education, Sociology and Social Phenomena::Human Activities::Exercise [Medical Subject Headings], ifosfamida, Humans, cisplatino, Ifosfamide, education, Exercise, Aged, conducta alimentaria, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Metabolic Syndrome X [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], PREDIMED-Plus, medicine.disease, Obesity, Methotrexate, Check Tags::Female [Medical Subject Headings], Desired weight loss, Metabolic syndrome, Cisplatin, Body mass index, Demography, obesity, cumplimiento del paciente, humanos, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Ideal Body Weight, desired weight loss, Health Care::Health Care Facilities, Manpower, and Services::Health Promotion::Weight Reduction Programs [Medical Subject Headings], Overweight, Diet, Mediterranean, Mediterranean lifestyle, Health Care::Health Care Facilities, Manpower, and Services::Health Services::Preventive Health Services::Health Promotion::Healthy People Programs [Medical Subject Headings], Weight loss, 030212 general & internal medicine, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Health Behavior::Patient Compliance [Medical Subject Headings], Abdominal obesity, older adults, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], 2. Zero hunger, Nutrition and Dietetics, mediterranean lifestyle, sobrepeso, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Nutrition Therapy::Diet Therapy::Diet, Mediterranean [Medical Subject Headings], Age Factors, ideal weight, Middle Aged, Peso corporal ideal, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Ideal Body Weight [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Weight Reduction Programs, Body image, Female, medicine.symptom, peso corporal ideal, Estils de vida, doxorrubicina, body image, Population, Imagen corporal, 030209 endocrinology & metabolism, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding Behavior [Medical Subject Headings], overweight, Healthy Lifestyle, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, índice de masa corporal, Feeding Behavior, Dieta mediterránea, Diet, Doxorubicin, Sobrepeso, Patient Compliance, Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Perception::Body Image [Medical Subject Headings], business, Food Science
Abstract

Background. Body weight dissatisfaction is a hindrance to following a healthy lifestyle and it has been associated with weight concerns. Objectives. The aim of this study was to assess the association between the adherence to the Mediterranean lifestyle (diet and exercise) and the desired body weight loss in an adult Mediterranean population with overweight. Methods. Cross-sectional analysis in 6355 participants (3268 men; 3087 women) with metabolic syndrome and BMI (Body mass index) between 27.0 and 40.0 kg/m2 (55–75 years old) from the PREDIMED-Plus trial. Desired weight loss was the percentage of weight that participants wished to lose. It was categorized into four cut-offs of this percentage (Q1, European Research Council (ERC) 340918, Recercaixa Grant 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Generalitat Valenciana PROMETEO/2017/017, SEMERGEN Grant, European Union (EU) European Cooperation in Science and Technology (COST) CA16112, Balearic Islands Government 35/2011, Balearic Islands Health Research Institute (IDISBA), European Union (EU) CIBEROBN CB06/03 CB12/03 PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056, European Commission Joint Research Centre EAT2BENICE_H2020_SFS2016, "Miguel Servet Type I" program from the ISCIII-Madrid (Spain) CP15/00028, ICREA under the ICREA Academia programme, Fernando Tarongi Bauza PhD Grant, FPU from the Ministry of Science, Innovation and Univesities FPU 18/01703, Spanish government, ISCIII, through the Fondo de Investigacion para la Salud (FIS), Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332

Published
2020

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