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1. Antibody Responses and Reactogenicity of Graded Doses of Inactivated Influenza A/New Jersey/76 Whole-Virus Vaccine in Humans

Author: The Pandemic Working Group of the Medical Research Council (United Kingdom) Committee on Influenza and Other Respiratory Virus Vaccines
Published: 1977

2. Antibody Responses and Reactogenicity of Graded Doses of Inactivated Influenza A/New Jersey/76 Whole-Virus Vaccine in Humans

Author: a, The Pandemic Working Group of the Medical Research Council (United Kingdom) Committee on Influenza
Abstract: Graded doses of inactivated whole influenza A/New Jersey/8/76 virus vaccine were injected into healthy volunteers. Presence of hemagglutination-inhibiting (HAI) antibody was uncommon before vaccination in persons younger than 45 years and most common in those older than 65 years. All vaccine doses (4–61 µg of hemagglutinin) induced HAl antibody in at least 50% of recipients, although a booster dose was required to induce high titers in those younger than 24 years of age. A tendency for HAl titers to increase with increasing age and dose was noted. A trivalent vaccine (composed of A/New Jersey/76, A/Victoria/75, and B/Hong Kong/73) given to persons 24–44 years old produced HAl antibody titers to A/New Jersey/76 similar to those produced by the same dose of A/New Jersey/76 as a monovalent vaccine and produced higher titers in subjects 65 years of age or older. Increases in neuraminidase-inhibiting antibody were small and infrequent. Local and systemic symptoms were commonly reported after vaccination but were mostly mild (11% had moderate pain and 19% had muscular aches). Reactions were less common among those with HAl antibody at the time of vaccination and were unacceptably severe (in 20% of recipients) only in seronegative recipients given the 61-µg dose of hemagglutinin.
Published: 1977
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3. Adipose tissue fatty acid chain length and mono-unsaturation increases with obesity and insulin resistance

Author: Chong Yew Tan, Samuel Virtue, Steven Murfitt, Lee D. Robert, Yi Hui Phua, Martin Dale, Julian L. Griffin, Francisco Tinahones, Philipp E. Scherer, Antonio Vidal-Puig, [Yew Tan,C, Virtue,S, Dale,M, Vidal-Puig,A] University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, MDU MRC. Addenbrooke’s Hospital, Cambridge, UK. [Murfitt,S, Robert,LD, Phua,YH, Griffin,JL] University of Cambridge Department of Biochemistry, Cambridge, UK. [Tinahones,FJ] UGC Endocrinologia y Nutrición (IBIMA), Hospital Virgen de la Victoria. CIBER of Physiopathology, Obesity and Nutrition (CIBEROBN) Málaga, Spain. [Scherer,P] Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. [Vidal-Puig,A] Wellcome Trust Sanger Institute, Hinxton, Uk. [Robert,LD, Griffin,JL] Medical Research Council – Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, Uk., BB/H002731/1, Biotechnology and Biological Sciences Research Council, United Kingdom, BB/H013539/1, Biotechnology and Biological Sciences Research Council, United Kingdom, MC_G0802535, Medical Research Council, United Kingdom, MC_PC_13030, Medical Research Council, United Kingdom, MC_UP_A090_1006, Medical Research Council, United Kingdom, MC_UU_12012/2, Medical Research Council, United Kingdom, RG/12/13/29853, British Heart Foundation, United Kingdom, Griffin, Julian [0000-0003-1336-7744], Vidal-Puig, Antonio [0000-0003-4220-9577], and Apollo - University of Cambridge Repository
Subjects: Male, Tejido adiposo, Adenosine Deaminase, Fatty Acid Elongases, Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Adipokines::Adiponectin [Medical Subject Headings], Adipose Tissue, White, Obesidad, Mice, Obese, Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Drug Resistance::Insulin Resistance [Medical Subject Headings], Grasa intra-abdominal, Severity of Illness Index, Gato, Grasa subcutánea, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mice, Acetyltransferases, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Essential [Medical Subject Headings], Organisms::Eukaryota::Animals [Medical Subject Headings], Animals, Obesity, Anatomy::Tissues::Connective Tissue::Adipose Tissue::Adipose Tissue, White::Abdominal Fat::Intra-Abdominal Fat [Medical Subject Headings], Triglycerides, Chemicals and Drugs::Lipids::Glycerides::Triglycerides [Medical Subject Headings], Mice, Knockout, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Fatty Acids, food and beverages, Anatomy::Tissues::Connective Tissue::Adipose Tissue [Medical Subject Headings], Humanos, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Chemicals and Drugs::Inorganic Chemicals::Elements::Carbon [Medical Subject Headings], Ácidos grasos monoinsaturados, Adiposidad, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Body Composition::Body Fat Distribution::Adiposity [Medical Subject Headings], Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Monounsaturated [Medical Subject Headings], Female, lipids (amino acids, peptides, and proteins), Insulin Resistance, Adiponectina, Ácidos grasos, esenciales
Abstract: Journal Article; The non-essential fatty acids, C18:1n9, C16:0, C16:1n7, C18:0 and C18:1n7 account for over 75% of fatty acids in white adipose (WAT) triacylglycerol (TAG). The relative composition of these fatty acids (FA) is influenced by the desaturases, SCD1-4 and the elongase, ELOVL6. In knock-out models, loss of SCD1 or ELOVL6 results in reduced Δ9 desaturated and reduced 18-carbon non-essential FA respectively. Both Elovl6 KO and SCD1 KO mice exhibit improved insulin sensitivity. Here we describe the relationship between WAT TAG composition in obese mouse models and obese humans stratified for insulin resistance. In mouse models with increasing obesity and insulin resistance, there was an increase in scWAT Δ9 desaturated FAs (SCD ratio) and FAs with 18-carbons (Elovl6 ratio) in mice. Data from mouse models discordant for obesity and insulin resistance (AKT2 KO, Adiponectin aP2-transgenic), suggested that scWAT TAG Elovl6 ratio was associated with insulin sensitivity, whereas SCD1 ratio was associated with fat mass. In humans, a greater SCD1 and Elovl6 ratio was found in metabolically more harmful visceral adipose tissue when compared to subcutaneous adipose tissue. Yes
Published: 2015

4. The association between serum lipids and intraocular pressure in 2 large United Kingdom cohorts

Author: Kian M. Madjedi, Kelsey V. Stuart, Sharon Y.L. Chua, Robert N. Luben, Alasdair Warwick, Louis R. Pasquale, Jae H. Kang, Janey L. Wiggs, Marleen A.H. Lentjes, Hugues Aschard, Naveed Sattar, Paul J. Foster, Anthony P. Khawaja, Mark Chia, Ron Do, Alan Kastner, Jihye Kim, Giovanni Montesano, Denize Atan, Tariq Aslam, Sarah A. Barman, Jenny H. Barrett, Paul Bishop, Peter Blows, Catey Bunce, Roxana O. Carare, Usha Chakravarthy, Michelle Chan, David P. Crabb, Philippa M. Cumberland, Alexander Day, Parul Desai, Bal Dhillon, Andrew D. Dick, Cathy Egan, Sarah Ennis, Paul Foster, Marcus Fruttiger, John E.J. Gallacher, David F. Garway-Heath, Jane Gibson, Dan Gore, Jeremy A. Guggenheim, Chris J. Hammond, Alison Hardcastle, Simon P. Harding, Ruth E. Hogg, Pirro Hysi, Pearse A. Keane, Sir Peng T. Khaw, Gerassimos Lascaratos, Andrew J. Lotery, Tom Macgillivray, Sarah Mackie, Keith Martin, Michelle McGaughey, Bernadette McGuinness, Gareth J. McKay, Martin McKibbin, Danny Mitry, Tony Moore, James E. Morgan, Zaynah A. Muthy, Eoin O’Sullivan, Chris G. Owen, Praveen Patel, Euan Paterson, Tunde Peto, Axel Petzold, Jugnoo S. Rahi, Alicja R. Rudnikca, Jay Self, Sobha Sivaprasad, David Steel, Irene Stratton, Nicholas Strouthidis, Cathie Sudlow, Dhanes Thomas, Emanuele Trucco, Adnan Tufail, Veronique Vitart, Stephen A. Vernon, Ananth C. Viswanathan, Cathy Williams, Katie Williams, Jayne V. Woodside, MaxM. Yates, Jennifer Yip, Yalin Zheng, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University of Calgary, University of Cambridge [UK] (CAM), University College of London [London] (UCL), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Harvard Medical School [Boston] (HMS), Örebro University, Institut Pasteur [Paris] (IP), University of Glasgow, Supported by UCL Overseas Research Scholarship (K.V.S.), Fight for Sight, London, United Kingdom (grant no.: 1956A [K.V.S.]), The Desmond Foundation (K.V.S.), the Wellcome Trust (grant no.: 220558/Z/20/Z [A.W.]), Alcon (P.J.F.), United Kingdom Research and Innovation Future Leaders Fellowship (A.P.K.), Moorfields Eye Charity (Springboard Award [R.N.L.] and Career Development Fellowship [A.P.K.]), the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant nos.: EY015473 [L.R.P.], EY032559 [L.R.P.], [J.L.W.]), Research to Prevent Blindness, Inc., New York, New York (Challenge Grant [L.R.P., J.L.W.]), The Glaucoma Foundation, New York, New York (L.R.P.), Astra Zeneca (N.S.), Boehringer Ingelheim (N.S.), Novartis (N.S.), Roche Diagnostics (N.S.), Association for Research in Vision and Ophthalmology Foundation (David Epstein Award [J.L.W.]), and UK Research and Innovation Future Leaders Fellowship (Medical Research Council grant no.: MR/T040912/1 [A.P.K.]). The authors acknowledge a proportion of their financial support from the United Kingdom Department of Health through an award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Biomedical Research Centre for Ophthalmology. This research used data from the UK Biobank Resource under data access request nos. 2112 and 36741. The UK Biobank Eye and Vision Consortium is supported by grants from Moorfields Eye Charity, The NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, the Alcon Research Institute, and the International Glaucoma Association (United Kingdom). The EPIC-Norfolk study was supported by the Medical Research Council, United Kingdom (grant nos.: SP2024/0201 and MR/N003284/1), and Cancer Research United Kingdom (grant nos.: G9502233 and C864/A8257)., Neurology, Ophthalmology, APH - Mental Health, APH - Methodology, and Amsterdam Neuroscience - Neuroinfection & -inflammation
Subjects: Intraocular pressure, Cholesterol, HDL, Glaucoma, Cholesterol, LDL, Middle Aged, Lipids, United Kingdom, Ophthalmology, Cross-Sectional Studies, Cholesterol, SDG 3 - Good Health and Well-being, RA0421, Risk Factors, Humans, RE, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Prospective Studies, Triglycerides, Aged
Abstract: Purpose: Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP). Design: Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts. Participants: We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and 2009. Methods: Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc). Main Outcome Measures: Corneal-compensated IOP. Results: Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06–0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08–0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05–0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07–0.31 mmHg; P = 0.001), 0.14 mmHg (95% CI, 0.03–0.25 mmHg; P = 0.016), and 0.17 mmHg (95% CI, 0.06–0.29 mmHg; P = 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (–0.05 mmHg; 95% CI, –0.08 to –0.03; P < 0.001) was not replicated in the EPIC-Norfolk cohort (P = 0.30). Conclusions: Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.
Published: 2022
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5. Parameter estimates for trends and patterns of excess mortality among persons on antiretroviral therapy in high-income European settings

Author: Juan Berenguer, Christoph Wyen, M. John Gill, Sophie Abgrall, Ard van Sighem, Matthias Cavassini, Sophie Grabar, Jordi Casabona, Margaret T May, Julia del Amo, Antonella d'Arminio Monforte, Robert Zangerle, John Stover, Niels Obel, Jonathan A C Sterne, Fabrice Bonnet, Adam Trickey, Medical Research Council (Reino Unido), Department for International Development (Reino Unido), NIH - National Institute on Alcohol Abuse and Alcoholism (NIAAA) (Estados Unidos), National Institute for Health Research (Reino Unido), Unión Europea, Agence Nationale de Recherches sur le sida et les hépatites virales (Francia), Institut National de la Santé et de la Recherche Médicale (Francia), Ministero della Salute (Italia), Ministerio de Sanidad y Consumo (España), Ministerio de Ciencia e Innovación (España), Red de Investigación Cooperativa en Investigación en Sida (España), Swiss National Science Foundation, University of Bristol [Bristol], Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), 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, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital General Universitario 'Gregorio Marañón' [Madrid], Instituto de Investigación Sanitaria Gregorio Marañón [Madrid, Spain] ( IiSGM), University Hospital of Cologne [Cologne], Centre d'Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), CIBER de Epidemiología y Salud Pública (CIBERESP), Università degli Studi di Milano = University of Milan (UNIMI), Ospedale San Paolo-Polo Universitario, ASST Santi Paolo e Carlo, Milan, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Université de Lausanne = University of Lausanne (UNIL), Instituto de Salud Carlos III [Madrid] (ISC), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University of Calgary, Department of Infectious Diseases [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Gestionnaire, Hal Sorbonne Université, Medical Research Council (United Kingdom), Department for International Development (United Kingdom), National Institute on Alcohol Abuse and Alcoholism (United States), National Institute for Health Research (United Kingdom), European Union, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), Institut National de la Santé et de la Recherche Médicale (France), and Red Española de Investigación en SIDA
Subjects: Adult, Male, 0301 basic medicine, Anti-HIV Agents, [SDV]Life Sciences [q-bio], Immunology, Population, HIV Infections, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Acquired immunodeficiency syndrome (AIDS), Risk Factors, death, cause-specific, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Mortality, education, United Nations Programme on HIV/AIDS, education.field_of_study, Models, Statistical, business.industry, Developed Countries, Mortality rate, duration, HIV, cohort, Middle Aged, medicine.disease, Confidence interval, 3. Good health, AIDS, [SDV] Life Sciences [q-bio], Europe, Anti-HIV Agents/therapeutic use, Europe/epidemiology, Female, HIV Infections/drug therapy, HIV Infections/mortality, Mortality/trends, Editorial, 030104 developmental biology, Infectious Diseases, Cohort, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, business, Developed country, Demography, Cohort study
Abstract: Supplemental Digital Content is available in the text, Introduction: HIV cohort data from high-income European countries were compared with the UNAIDS Spectrum modelling parameters for these same countries to validate mortality rates and excess mortality estimates for people living with HIV (PLHIV) on antiretroviral therapy (ART). Methods: Data from 2000 to 2015 were analysed from the Antiretroviral Therapy Cohort Collaboration (ART-CC) for Austria, Denmark, France, Italy, the Netherlands, Spain, and Switzerland. Flexible parametric models were used to compare all-cause mortality rates in the ART-CC and Spectrum. The percentage of AIDS-related deaths and excess mortality (both are the same within Spectrum) were compared, with excess mortality defined as that in excess of the general population mortality. Results: Analyses included 94 026 PLHIV with 585 784 person-years of follow-up, from which there were 5515 deaths. All-cause annual mortality rates in Spectrum for 2000–2003 were 0.0121, reducing to 0.0078 in 2012–2015, whilst the ART-CC's corresponding annual mortality rates were 0.0151 [95% confidence interval (95% CI): 0.0130–0.0171] reducing to 0.0049 (95% CI: 0.0039–0.0060). The percentage of AIDS-related deaths in Spectrum was 74.7% in 2000–2003, dropping to 43.6% in 2012–2015. In the ART-CC, AIDS-related mortality constitutes 45.3% (95% CI: 38.4–52.9%) of mortality in 2000–2003 and 26.7% (95% CI: 19–46%) between 2012 and 2015. Excess mortality in the ART-CC was broadly similar to the Spectrum estimates, dropping from 75.3% (95% CI: 60.3–95.2%) in 2000–2003 to 30.7% (95% CI: 25.5–63.7%) in 2012–2015. Conclusion: All-cause mortality assumptions for PLHIV on ART in high-income European settings should be adjusted in Spectrum to be higher in 2000–2003 and decline more quickly to levels currently captured for recent years.
Published: 2019
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6. Pilot study of a two-arm non-randomized controlled cluster trial of a psychosocial intervention to improve late life depression in socioeconomically deprived areas of São Paulo, Brazil (PROACTIVE): feasibility study of a psychosocial intervention for late life depression in São Paulo

Author: Renato M. Franzin, Tim J Peters, Maria Clara Pinheiro de Paula Couto, Ana Vilela Mendes, Paula Carvalho Pereda, Alicia Matijasevich, Maiara Garcia Henrique, Ricardo Araya, Marcia Scazufca, Pepijn van de Ven, William Hollingworth, Antonio Carlos Seabra, CNPq-Brazil, Medical Research Council- United Kingdom, and Fundação de Amparo à Pesquisa do Estado de São Paulo
Subjects: Male, medicine.medical_specialty, Collaborative Care, Pilot Projects, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Poverty Areas, Intervention (counseling), Health care, medicine, Humans, 030212 general & internal medicine, Depression (differential diagnoses), Aged, Pilot study, Primary Health Care, business.industry, Depression, Public health, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Middle Aged, Late life depression, Primary care, Psychotherapy, Treatment Outcome, Collaborative care, Older adults, Physical therapy, Feasibility Studies, Female, business, Psychosocial, Brazil, 030217 neurology & neurosurgery, Follow-Up Studies, Research Article
Abstract: Background Depression is a common and recurrent condition among older adults and is associated with poor quality of life and increased health care utilization and costs. The purpose of this pilot study was to assess the feasibility of delivering a psychosocial intervention targeting depression, and to develop the procedures to conduct a cluster randomized controlled trial among older adults registered with primary care clinics in poor neighbourhoods of São Paulo, Brazil. Methods We conducted a pilot study of a two-arm cluster, non-randomized controlled trial. Two primary care clinics adhering to the Family Health Strategy were allocated to either the intervention or the control arm. In the control arm, patients received enhanced usual care consisting of staff training for improved recognition and management of depression. In the intervention arm, alongside the enhanced usual care, patients received a 17-week psychosocial intervention delivered by health workers assisted with an application installed in a tablet. Results We randomly selected 579 of 2020 older adults registered in the intervention clinic to participate in the study. Among these individuals, 353 were assessed for depression and 40 (11.0%) scored at least 10 on the PHQ-9 and were therefore invited to participate. The consent rate was 33/40 (82%) with a resulting yield of 33/579 (5.7%). In the control arm, we randomly selected 320 older adults among 1482 registered in the clinic, 223 were assessed for depression and 28 (12.6%) scored 10 or above on the PHQ-9. The consent rate was 25/28 (89%), with a resulting yield of 25/320 (7.8%). Of the 33 who consented in the intervention arm, 19 (59.4%) completed all sessions. The mean PHQ-9 at follow-up (approximately 30 weeks after inclusion) were 12.3 (SD = 3.7) and 3.8 (SD = 3.9) in the control and intervention arms, respectively. Follow-up rates were 92 and 94% in control and intervention arms, respectively. Conclusions Identification and engagement of clinics, randomization, recruitment of individuals, measures, and baseline and follow-up assessments all proved to be feasible in primary care clinics in São Paulo, Brazil. Results support the development of a definitive cluster randomized controlled trial. Trial registration This study was retrospectively registered with Registro Brasileiro de Ensaios Clínicos (ReBEC), number RBR-5nf6wd. Registered 06 August 2018.
Published: 2019
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7. Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis

Author: Olivier Lortholary, Síle F. Molloy, Sokoine Kivuyo, Shabbar Jaffar, Lawrence Mwenge, Louis W. Niessen, Cecilia Kanyama, Angela Loyse, Elvis Temfack, Shabir Lakhi, Joseph N Jarvis, Tinevimbo Shiri, Peter Mwaba, Robert S. Heyderman, Mina C. Hosseinipour, Charles Kouanfack, Sayoki Mfinanga, Tao Chen, Duncan Chanda, Thomas S. Harrison, Adrienne K. Chan, Liverpool School of Tropical Medicine (LSTM), St George's, University of London, Zambart Health Economics Unit Lusaka, University Teaching Hospital (UTH), Lusaka, University Teaching Hospital [Lusaka] (UTH), Institute for Medical Research and Training, University of Teaching Lusaka, Department of Internal Medicine and Directorate of Research and Post-graduate Studies, Lusaka Apex Medical University, Zambia, University of Malawi, University College of London [London] (UCL), University of North Carolina Project-Malawi (UNC Project), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Hôpital Central de Yaoundé [Yaoundé], Université de Dschang, Hôpital Général de Douala, Mycologie moléculaire - Molecular Mycology, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), National Institute for Medical Research - Muhimbili Research Centre (NIMR), Zomba Central Hospital Malawi, University of Toronto, London School of Hygiene and Tropical Medicine (LSHTM), Bostwana Harvard AIDS Institute Partneship Gaborone, Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), This work was supported by grants to the Advancing Cryptococcal Meningitis Treatment for Africa trial from the Medical Research Council, United Kingdom (grant number 100504) and the French Agency for Research on AIDS and Viral Hepatitis (ANRS, grant number ANRS12275)., The authors thank all the patients and their families, Andrew Nunn, Halima Dawood, Andrew Kitua, and William Powderly for serving on the data and safety monitoring committee, and Graeme Meintjes, Calice Talom, Newton Kumwenda, and Maryline Bonnet for serving on the trial steering committee., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Microbiology (medical), medicine.medical_specialty, Antifungal Agents, Cost effectiveness, Cost-Benefit Analysis, flucytosine, Meningitis, Cryptococcal, Flucytosine, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, cryptococcal meningitis, Internal medicine, Amphotericin B, fluconazole, medicine, Humans, 030212 general & internal medicine, Articles and Commentaries, cost-effectiveness, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, health care economics and organizations, 0303 health sciences, treatment, 030306 microbiology, business.industry, Mortality rate, virus diseases, Cost-effectiveness analysis, Confidence interval, 3. Good health, respiratory tract diseases, Infectious Diseases, Africa, business, Fluconazole, medicine.drug
Abstract: Background Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. Methods The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. Results The mean costs per patient were US $847 (95% confidence interval [CI] $776–927) for FLU+5FC, and US $628 (95% CI $557–709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9–41.7%) with FLU+5FC and 53.8% (95% CI 43.1–64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28–208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. Conclusions The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus–infected persons in Africa., The combination of flucytosine plus fluconazole (FLU) is cost-effective, compared with the commonly used regimen of FLU monotherapy, for cryptococcal meningitis treatment in Africa, with an incremental cost-effectiveness ratio of US $65 per life-year saved at the current price.
Published: 2020
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8. Cause-specific mortality after diagnosis of cancer among HIV-positive patients: a collaborative analysis of cohort studies

Author: Peter Reiss, Margaret T May, Matthias Cavassini, Sophie Grabar, Christoph Wyen, Sophie Abgrall, Fabrice Bonnet, Julia del Amo, Amy C. Justice, Antonella d'Arminio Monforte, Ferdinand W. N. M. Wit, Katharina Grabmeier-Pfistershammer, Leah Shepherd, Ramón Teira, Juan Berenguer, M. John Gill, Adam Trickey, Jodie L. Guest, Janne Vehreschild, Dominique Costagliola, Jonathan A C Sterne, Gestionnaire, Hal Sorbonne Université, University of Bristol [Bristol], University of Calgary, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Groupe hospitalier Broca, University Hospital of Cologne [Cologne], German Centre for Infection Research (DZIF), University of Amsterdam [Amsterdam] (UvA), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), Amsterdam Institute for Global Health & Development [Amsterdam, The Netherlands], VU University Medical Center [Amsterdam], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Université de Lausanne = University of Lausanne (UNIL), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Medizinische Universität Wien = Medical University of Vienna, Emory University School of Medicine, Emory University [Atlanta, GA], University College of London [London] (UCL), Università degli Studi di Milano = University of Milan (UNIMI), Institute of Health Carlos III, Yale School of Medicine [New Haven, Connecticut] (YSM), VA Connecticut Healthcare System, Department for International Development (Reino Unido), NIH - National Institute on Alcohol Abuse and Alcoholism (NIAAA) (Estados Unidos), Medical Research Council (Reino Unido), Unión Europea. Comisión Europea. 7 Programa Marco, Institut National de la Santé et de la Recherche Médicale (Francia), Swiss National Science Foundation, Ministerio de Sanidad y Consumo (España), Red de Investigación Cooperativa en Investigación en Sida (España), National Institutes of Health (Estados Unidos), Canadian Institutes of Health Research, Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne (UNIL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Università degli Studi di Milano [Milano] (UNIMI), Yale University School of Medicine, United Kingdom Department for International Development, National Institute on Alcohol Abuse and Alcoholism (United States), Medical Research Council (United Kingdom), 7º Programa Marco - Comisión Europea, Institut National de la Santé et de la Recherche Médicale, Red Española de Investigación en SIDA, and National Institutes of Health (United States)
Subjects: Cancer Research, Lung Neoplasms, ADM, Human immunodeficiency virus (HIV), Uterine Cervical Neoplasms, medicine.disease_cause, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medical diagnosis, Cancer, Lymphoma, AIDS-Related, education.field_of_study, Mortality rate, Liver Neoplasms, Cohort, cohort, Middle Aged, Prognosis, Hodgkin Disease, 3. Good health, Survival Rate, NADM, PLHIV, cancer, mortality, Infectious Causes of Cancer, Oncology, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, Cohort study, Adult, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, IDLIC, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Mortality, education, Acquired Immunodeficiency Syndrome, business.industry, medicine.disease, United Kingdom, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: People living with HIV (PLHIV) are more likely than the general population to develop AIDS‐defining malignancies (ADMs) and several non‐ADMs (NADMs). Information is lacking on survival outcomes and cause‐specific mortality after cancer diagnosis among PLHIV. We investigated causes of death within 5 years of cancer diagnosis in PLHIV enrolled in European and North American HIV cohorts starting antiretroviral therapy (ART) 1996–2015, aged ≥16 years, and subsequently diagnosed with cancer. Cancers were grouped: ADMs, viral NADMs and nonviral NADMs. We calculated cause‐specific mortality rates (MR) after diagnosis of specific cancers and compared 5‐year survival with the UK and France general populations. Among 83,856 PLHIV there were 4,436 cancer diagnoses. Of 603 deaths after ADM diagnosis, 292 (48%) were due to an ADM. There were 467/847 (55%) and 74/189 (39%) deaths that were due to an NADM after nonviral and viral NADM diagnoses, respectively. MR were higher for diagnoses between 1996 and 2005 versus 2006–2015: ADMs 102 (95% CI 92–113) per 1,000 years versus 88 (78–100), viral NADMs 134 (106–169) versus 111 (93–133) and nonviral NADMs 264 (232–300) versus 226 (206–248). Estimated 5‐year survival for PLHIV diagnosed with liver (29% [19–39%]), lung (18% [13–23%]) and cervical (75% [63–84%]) cancer was similar to general populations. Survival after Hodgkin's lymphoma diagnosis was lower in PLHIV (75% [67–81%]). Among ART‐treated PLHIV diagnosed with cancer, MR and causes of death varied by cancer type, with mortality highest for liver and lung cancers. Deaths within 5 years of NADM diagnoses were more likely to be from cancer than AIDS., What's new? People with HIV live longer than they used to, thanks to advances in antiretroviral therapy. These improvements reduced the incidence of AIDS‐defining malignancies, such as Kaposi's sarcoma, but the increased life expectancy has led to more diagnoses of cancers not traditionally associated with HIV. Here, the authors studied cause‐specific mortality among people with HIV diagnosed with cancer. For those people, within 5 years after a cancer diagnosis, cause of death was more likely to be cancer than AIDS. Survival rates after diagnosis varied by cancer type, but were similar to rates among the general population.
Published: 2020
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9. Conformational flexibility in the immunoglobulin-like domain of the Hepatitis C Virus Glycoprotein E2

Author: Dorothea Bankwitz, Steven K. H. Foung, Ieva Vasiliauskaite, Arvind H. Patel, Thomas Krey, Joseph Marcotrigiano, Sarah Cole, Patrick England, Félix A. Rey, Ania M. Owsianka, Thomas Pietschmann, Abdul Ghafoor Khan, TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany., Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), MRC - University of Glasgow Centre for Virus Research, Biophysique Moléculaire (Plate-forme), Rutgers University System (Rutgers), Centre for Experimental and Clinical Infection Research [Hanover] (TWINCORE), Department of Pathology [Stanford], Stanford Medicine, Stanford University-Stanford University, Centre for Experimental and Clinical Infection Research (TWINCORE), Helmholtz Centre for Infection Research (HZI)-Medizinische Hochschule Hannover (MHH), Hannover Medical School [Hannover] (MHH), German Center for Infection Research, Partnersite Munich (DZIF), This work was supported by an ANRS grant and recurrent funding from the Institut Pasteur to F.A.R., an ANRS grant to T.K., and funding to T.K. by the Deutsche Forschungsgemeinschaft within Project B10 of the Collaborative Research Centre SFB900 'Chronic Infections: Microbial Persistence and Its Control.' T.P. was supported by the Collaborative Research Centre SFB 900 project A6. Work in A.H.P.’s laboratory was supported by the Medical Research Council, United Kingdom (MC_UU12014/2)., and We thank Francois Bontems for critical reading of the manuscript, Ahmed Haouz and Patrick Weber from the crystallization platform for help in crystallization, and staff of the synchrotron beamline Proxima-1 at Synchrotron Soleil and PX-I at the Swiss Light Sources for help during data collection.
Subjects: 0301 basic medicine, conformational flexibility, hepatitis C virus, Immunogen, Protein Conformation, MESH: Virus Internalization, [SDV]Life Sciences [q-bio], Hepacivirus, medicine.disease_cause, Antibodies, Viral, Crystallography, X-Ray, MESH: Antibodies, Monoclonal, MESH: Antibodies, Neutralizing, MESH: Tetraspanin 28, Epitopes, MESH: Protein Conformation, Viral Envelope Proteins, MESH: Hepacivirus, Neutralizing antibody, Antibodies, Monoclonal, Hepatitis C, QR1-502, MESH: HEK293 Cells, glycoprotein E2, vaccine design, monoclonal antibodies, Antibody, Protein Binding, Research Article, Viral Hepatitis Vaccines, MESH: Epitopes, medicine.drug_class, Viral protein, Biology, CD81 binding site, Monoclonal antibody, Microbiology, Virus, Tetraspanin 28, 03 medical and health sciences, Viral entry, Virology, medicine, MESH: Protein Binding, Humans, MESH: Hepatitis C, MESH: Immunoglobulin Domains, MESH: Humans, Binding Sites, 030102 biochemistry & molecular biology, MESH: Viral Hepatitis Vaccines, Virus Internalization, MESH: Crystallography, X-Ray, Antibodies, Neutralizing, Ig-like domain, NS2-3 protease, 030104 developmental biology, HEK293 Cells, MESH: Binding Sites, MESH: Viral Envelope Proteins, biology.protein, Immunoglobulin Domains, MESH: Antibodies, Viral
Abstract: The hepatitis C virus (HCV) glycoprotein E2 is the major target of neutralizing antibodies and is therefore highly relevant for vaccine design. Its structure features a central immunoglobulin (Ig)-like β-sandwich that contributes to the binding site for the cellular receptor CD81. We show that a synthetic peptide corresponding to a β-strand of this Ig-like domain forms an α-helix in complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of hydrophobic residues and a secondary structure change in the composite CD81 binding site. A detailed interaction analysis of DAO5 and cross-competing neutralizing antibodies with soluble E2 revealed that the Ig-like domain is trapped by different antibodies in at least two distinct conformations. DAO5 specifically captures retrovirus particles bearing HCV glycoproteins (HCVpp) and infectious cell culture-derived HCV particles (HCVcc). Infection of cells by DAO5-captured HCVpp can be blocked by a cross-competing neutralizing antibody, indicating that a single virus particle simultaneously displays E2 molecules in more than one conformation on its surface. Such conformational plasticity of the HCV E2 receptor binding site has important implications for immunogen design., IMPORTANCE Recent advances in the treatment of hepatitis C virus (HCV) infection with direct-acting antiviral drugs have enabled the control of this major human pathogen. However, due to their high costs and limited accessibility in combination with the lack of awareness of the mostly asymptomatic infection, there is an unchanged urgent need for an effective vaccine. The viral glycoprotein E2 contains regions that are crucial for virus entry into the host cell, and antibodies that bind to these regions can neutralize infection. One of the major targets of neutralizing antibodies is the central immunoglobulin (Ig)-like domain within E2. We show here that this Ig-like domain is conformationally flexible at the surface of infectious HCV particles and pseudoparticles. Our study provides novel insights into the interactions of HCV E2 with the humoral immune system that should aid future vaccine development.
Published: 2017
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10. The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort

Author: María José Sánchez, Jennifer Ose, Antonia Trichopoulou, J. Ramón Quirós, Marc J. Gunter, Xavier Castellsagué, Carlotta Sacerdote, Inger T. Gram, H B As Bueno-de-Mesquita, Johanna Ekström, Ruth C. Travis, Joakim Dillner, Carmen Navarro, Silvia de Sanjosé, Annika Idahl, Renée T. Fortner, Domenico Palli, Noémie Travier, Amalia Mattiello, David Lindquist, Annika Steffen, Elisabete Weiderpass, Christian Munk, Kay-Tee Khaw, Aurelio Barricarte, Elio Riboli, Michael Pawlita, Petra H.M. Peeters, Valeria Pala, Eiliv Lund, Philippos Orfanos, Sabina Rinaldi, F. Xavier Bosch, Pagona Lagiou, Kim Overvad, Nerea Larrañaga, N. Margall, Sylvie Mesrine, Massimo Tommasino, Silvia Franceschi, Silvia Polidoro, Melissa A. Merritt, Tim Waterboer, Giovanna Masala, Agnès Fournier, Rosario Tumino, Esther Roura, Anne Tjønneland, Françoise Clavel-Chapelon, University Medical Center Utrecht, Imperial College Trust, [Roura,E, de Sanjosé,S, Bosch,FX, Castellsagué,X] Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Roura,E, Sánchez,MJ, Navarro,C, Barricarte,A, Larrañaga,N, Castellsagué,X] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Travier,N] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Waterboer,T, Pawlita,M] Division of Molecular Diagnostics of Oncogenic Infections (F020), Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.[Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Weiderpass, Dillner,J] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Weiderpass,E, Gram,IT, Lund,E] Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. [Margall,N] Microbiology Department, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain. [Dillner,J] Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. [Tjønneland,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Munk,C] Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. [Palli,D, Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute–ISPO, Florence, Italy. [Khaw,K] School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Mesrine,S, Fournier,A] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. Université Paris Sud, Villejuif, France.Institut Gustave Roussy, Villejuif, France. [Fortne,RT, Ose,J] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Steffen,A] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Lagiou,P, Orfanos,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Boston, United States of America. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic—M.P. Arezzo' Hospital, Ragusa, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, University of Turin, Turin, Italy. Centre for Cancer Epidemiology and Prevention (CPO Piemonte), Turin, Italy. [Polidoro,S] Human Genetics Foundation (HuGeF), Turin, Italy. [Mattiello,A] Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy. [Peeters,PH] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.[Bueno-de-Mesquita,HB, Merritt,MA, Gunter,MJ, Riboli,E] Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. [Bueno-de-Mesquita,HB] Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.[Quirós,JR] Public Health Directorate, Asturias, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Barricarte,A] Navarra Public Health Institute, Pamplona, Spain. Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Larrañaga,N] Public Health Division of Gipuzkoa, BIODonostia Research Institute, Basque Health Department, Bilbao, Spain. [Ekström,J] BBMRI.se Service Center for Southern Sweden, Lund University, Medicon Village, Lund, Sweden. [Lindquist,D] Department of Radiation Sciences, Umeå University, Umeå, Sweden. [Idahl,A] Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. [Rinaldi,S, Tommasino,M, Franceschi,S] International Agency for Research on Cancer, Lyon, France., Funding: The work was partially supported by grants from the Instituto de Salud Carlos III (Spanish Government) (grants FIS PI08/1308, PI13/00053, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RD12/0036/0056, RD12/0036/0018, and CIBERESP) and from the Agència de Gestió d’Ajuts Universitaris i de Recerca – Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2005SGR00695, 2009SGR939 and 2009SGR126, 2014SGR1077, 2014SGR2016). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and the Catalan Institute of Oncology, La Caixa (BM 06-130), RTICC-RD06/10091 (Spain), 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), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC) 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) and Statistics Netherlands (The Netherlands), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council (United Kingdom), and Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway).
Subjects: Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in Situ::Cervical Intraepithelial Neoplasia [Medical Subject Headings], Oncology, Replacement therapy, Pathology and Laboratory Medicine, Antibodies, Viral, Biochemistry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pregnancy, Prospective Studies, lcsh:Science, Gonadal Steroid Hormones, education.field_of_study, Hormonal Therapy, Contraceptives, Humanos, Anticonceptivos, 030220 oncology & carcinogenesis, Cohort, Carcinoma, Squamous Cell, Cohort studies, Science & Technology - Other Topics, Intreaepithelial neoplasia, Human, Cohort study, Oral, Human Papillomavirus Infection, medicine.medical_specialty, Càncer de coll uterí, Sexually Transmitted Diseases, Estudios retrospectivos, 03 medical and health sciences, Drug Therapy, Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Uterine Cervical Neoplasms [Medical Subject Headings], Neoplasias del cuello uterino, Humans, education, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Parity [Medical Subject Headings], Aged, Pharmacology, Gynecology, Cancer och onkologi, Science & Technology, Herpes Genitalis, Genitourinary Infections, Herpesvirus 2, lcsh:R, Case-control study, Biology and Life Sciences, Estrogens, medicine.disease, Hormones, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, Case-Control Studies, Cervical cancer, Medical Devices and Equipment, lcsh:Q, Intrauterine Devices, 0301 basic medicine, Glutathione-S-transferase, Viral Diseases, Human papillomavirus infection, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Herpesvirus 2, Human, lcsh:Medicine, Uterine Cervical Neoplasms, Chlamydia trachomatis, Cervical Cancer, Cohort Studies, Cervix cancer, Paridad, Medicine and Health Sciences, Viral, Non-U.S. Gov't, Prospective cohort study, Papillomaviridae, Reproductive History, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Reproductive Control Agents::Contraceptive Agents [Medical Subject Headings], Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings], Multidisciplinary, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Pharmaceutics, Research Support, Non-U.S. Gov't, Femenino, Drugs, Estudios de Casos y Controles, Middle Aged, humanities, Multidisciplinary Sciences, Infectious Diseases, Serology, Research Design, Hormonal therapy, Female, Research Article, Biotechnology, Adult, Risk, Papillomaviruses, Embarazo, General Science & Technology, Hormone Replacement Therapy, Urology, Population, Individual data, Research Support, Research and Analysis Methods, Cervical intraepithelial neoplasia, Antibodies, Contraceptives, Oral, Hormonal, Young Adult, Collaborative reanalysis, Internal medicine, Oral-contraceptives, MD Multidisciplinary, Journal Article, medicine, Multicentric case-control, Cervical Intraepithelial Neoplasia, Neoplasia Intraepitelial Cervical, Papil·lomavirus, Reproductive factors, Hormonal, business.industry, Carcinoma, Papillomavirus Infections, Cancers and Neoplasms, Chlamydia Infections, Uterine Cervical Dysplasia, Squamous Cell, Organisms::Viruses::DNA Viruses::Papillomaviridae [Medical Subject Headings], business, Gynecological Tumors, Follow-Up Studies
Abstract: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130) In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
Published: 2016

11. The Contribution of Risk Factors to the Higher Incidence of Invasive and In Situ Breast Cancers in Women With Higher Levels of Education in the European Prospective Investigation Into Cancer and Nutrition

Author: Elio Riboli, Carla H. van Gils, Gillian K Reeves, Tonje Braaten, María José Sánchez, Kim Overvad, Naomi E. Allen, Amelia Mattiello, Eric J. Duell, Anton E. Kunst, Petra H.M. Peeters, Kay-Tee Khaw, Anne-Kathrin Illner, Domenico Palli, Pagona Lagiou, Valentina Gallo, Anja Olsen, Eiliv Lund, Eva Ardanaz, José Ramón Quirós, Signe Borgquist, Manuela M. Bergmann, Paolo Vineis, Franco Berrino, Jonas Manjer, Carmen Navarro, Veronique Chajes, Rudolf Kaaks, Sabina Rinaldi, Carlotta Sacerdote, Silke Hermann, Rosario Tumino, A. M. May, Antonia Trichopoulou, Dimitrios Trichopoulos, Evelyn M. Monninkhof, Anne Tjønneland, Gwenn Menvielle, Hendriek Boshuizen, H. Bas Bueno-de-Mesquita, Nadia Slimani, Amsterdam Public Health, Public and occupational health, Department of Public Health, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Amsterdam [Amsterdam] (UvA), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Dept of Epidemiology and Public Health, Imperial College London, Department of Cardiology and Department of Clinical Epidemiology, Aarhus University Hospital, Cancer Epidemiology Institute, Danish Cancer Society, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Dept of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Epidemiology, Havard School of Public Health, Hellenic Health Foundation, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Department of Preventive & Predictive Medicine, Fondazione IRCCS-Istituto Nazionale dei Tumori, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, CPO Piemonte, Institute of Community Medicine, University of Tromsø (UiT), Public Health and Health Planning Directorate, Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Andalusian School of Public Health [Granada], CIBERESP, CIBER Epidemiologia y Salud Pública, Epidemiology Department, Murcia Health Council, Public Health Institute of Navarra, Department of Oncology, Lund University Hospital-Lund University [Lund], Department of surgery, Lund University [Lund]-Malmö University Hospital, Dept of Public Health and Primary Care, University of Cambridge [UK] (CAM)-MRC Center for Nutritional Epidemiology and Cancer Prevention and Survival, Cancer Epidemiology Unit, University of Oxford [Oxford]-Cancer Epidemiology Unit, International Agency for Cancer Research (IACR), University of Torino and CPO-Piemonte, Università degli studi di Torino (UNITO), ISI Foundation Institute for Scientific Interchange, G Menvielle received a funding from the Fondation pour la Recherche Médicale for this analysis. The project was in part funded by the European Commission, through the Eurocadet project (from the commission of the European communities research directorate-general, grant No EUROCADET:SP23-CT-2005-006528). EPIC was supported by the European Commission: Public Health and Consumer Protection Directorate 1993-2004 and the Research Directorate-General 2005-2008. European Commission FP5 project (QLG1-CT-2001-01049). The EPIC study was funded by 'Europe Against Cancer' Programme of the European Commission (SANCO), Ligue contre le Cancer (France), Société 3M (France), Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale, German Cancer Aid, German Cancer Research Center, German Federal Ministry of Education and Research, Red Temática de Investigación Cooperativa de Centros de Cáncer (C03/10), the participating regional governments and institutions of Murcia, Navarra, Asturias, Pais Vasco y Andalucia, Spain, Cancer Research UK, Medical Research Council, United Kingdom, Stroke Association, United Kingdom, British Heart Foundation, Department of Health, United Kingdom, Food Standards Agency, United Kingdom, The Wellcome Trust, United Kingdom, Greek Ministry of Health, Stavros Niarchos Foundation, Italian Association for Research on Cancer, Dutch Ministry of Public Health, Welfare and Sports, Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, Dutch Zorg Onderzoek Nederland, World Cancer Research Fund, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Vasterbotten and Skane, Sweden, Norwegian Cancer Society, and Foundation to Promote Research into Functional Vitamin B12 Deficiency, Norway. Some authors are partners of Environmental Cancer Risk, Nutrition and Individual Susceptibility, a network of excellence of the European Commission (6FP contract 513943). Antonio Agudo and Paolo Vineis were supported by ECNIS., Schmaus, Annie, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Naples Federico II = Università degli studi di Napoli Federico II, Lund University [Lund]-Lund University Hospital, University of Oxford-Cancer Epidemiology Unit, Università degli studi di Torino = University of Turin (UNITO), Public Health, and Cell biology
Subjects: MESH: Reproductive History, Epidemiology, MESH: Risk Assessment, 0302 clinical medicine, MESH: Risk Factors, Prevalence, breast neoplasms, Mass Screening, risk factors, Prospective Studies, 030212 general & internal medicine, MESH: Incidence, Prospective cohort study, reproductive history, MESH: Aged, education, MESH: Middle Aged, Obstetrics, Incidence (epidemiology), MESH: Follow-Up Studies, Middle Aged, Nutrition Surveys, Prognosis, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, 030220 oncology & carcinogenesis, Educational Status, Female, Breast disease, Risk assessment, Adult, medicine.medical_specialty, Risk Assessment, Article, MESH: Prognosis, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, MESH: Nutrition Surveys, medicine, Humans, Neoplasm Invasiveness, MESH: Mass Screening, Risk factor, MESH: Prevalence, Aged, Gynecology, MESH: Humans, business.industry, Cancer, MESH: Adult, MESH: Neoplasm Invasiveness, medicine.disease, MESH: Prospective Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, incidence, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Europe, business, MESH: Educational Status, MESH: Female, MESH: Breast Neoplasms, Follow-Up Studies
Abstract: International audience; The authors investigated the role of known risk factors in educational differences in breast cancer incidence. Analyses were based on the European Prospective Investigation Into Cancer and Nutrition and included 242,095 women, 433 cases of in situ breast cancer, and 4,469 cases of invasive breast cancer. Reproductive history (age at first full-term pregnancy and parity), exposure to endogenous and exogenous hormones, height, and health behaviors were accounted for in the analyses. Relative indices of inequality (RII) for education were estimated using Cox regression models. A higher risk of invasive breast cancer was found among women with higher levels of education (RII = 1.22, 95% confidence interval (CI): 1.09, 1.37). This association was not observed among nulliparous women (RII = 1.13, 95% CI: 0.84, 1.52). Inequalities in breast cancer incidence decreased substantially after adjusting for reproductive history (RII = 1.11, 95% CI: 0.98, 1.25), with most of the association being explained by age at first full-term pregnancy. Each other risk factor explained a small additional part of the inequalities in breast cancer incidence. Height accounted for most of the remaining differences in incidence. After adjusting for all known risk factors, the authors found no association between education level and risk of invasive breast cancer. Inequalities in incidence were more pronounced for in situ breast cancer, and those inequalities remained after adjustment for all known risk factors (RII = 1.61, 95% CI: 1.07, 2.41), especially among nulliparous women.
Published: 2011
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12. A genetic risk score combining 32 SNPs is associated with body mass index and improves obesity prediction in people with major depressive disorder

Author: Peter Vollenweider, Ian W. Craig, Stefan Kloiber, Gerome Breen, Sven Bergmann, Rudolf Uher, Tanguy Corre, Chi-Fa Hung, Ania Korszun, Gérard Waeber, Martin Preisig, Cathryn M. Lewis, Florian Holsboer, Michael John Owen, Peter McGuffin, Marcella Rietschel, Zoltán Kutalik, Bertram Müller-Myhsok, Michael Gill, Nicholas John Craddock, Lisa Jones, Wolfgang Maier, Christiane Wolf, Susanne Lucae, Anne Farmer, Ole Mors, Margarita Rivera, John P. Rice, Darina Czamara, Ian Jones, [Hung,CF, Breen,G, Uher,R, Craig,IW, Farmer,AE, Lewis,CM, McGuffin,P, Rivera,M] MRC SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London ,London, UK. [Hung,CF] Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan. [Breen,G] National Institute for Health Research Biomedical Research Centre for Mental Health at the Maudsley and Institute of Psychiatry, King’s College London, London, UK. [Czamara,D, Wolf,C, Kloiber,S, Holsboer,F, Lucae,S, Müller-Myhsok,B] Max-Planck-Institute of Psychiatry, Munich, Germany. [Corre,T, Bergmann,S, Kutalik,Z]Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier, Universitaire Vaudois (CHUV), Lausanne, Switzerland. [Bergmann,S, Kutalik,Z] Swiss Institute of Bioinformatics Lausanne, Switzerland. [Craddock,N, Jones,I] MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, UK. [Gill,M] Department of Psychiatry, Trinity Centre for Health Sciences Dublin, Ireland. [Jones,L] Department of Psychiatry, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK. [Korszun,A] Barts and The London School of Medicine and Dentistry, Queen Mary’s University of London London, UK. [Maier,W] Department of Psychiatry, University of Bonn, Bonn, Germany. [Mors,O] Research Department P, Aarhus University Hospital Skovagervej, Risskov, Denmark. [Owen,MJ] MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, UK. [Rice,J] Department of Psychiatry, Washington University School of Medicine St Louis, MO, USA. [Rietschel1,M] Central Institute of Mental Health, Mannheim, Germany. [Uher,R] Department of Psychiatry, Dalhousie University, Halifax Nova Scotia, Canada. [Vollenweider,P, d Waeber,G] Division of Internal Medicine, Lausanne, Switzerland. [Lewis,CM] Department of Medical and Molecular Genetics, School of Medicine, King’s College London, Guys Hospital, London UK. [Preisig,M ]Department of Psychiatry, Lausanne University Hospital, Prilly-Lausanne, Switzerland. [Rivera,M] CIBERSAM-University of Granada and Institute of Neurosciences Federico Olóriz, Centro de Investigación Biomédica, University of Granada, Armilla Granada, Spain. Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain., G0701420, Medical Research Council, United Kingdom, and This study was funded by the Medical Research Council, UK. GlaxoSmithKline (G0701420) funded the DeNT study and were co-funders with the Medical Research Centre for the GWAS of the whole sample. The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. This study presents independent research [part-] funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. The CoLaus/PsyCoLaus was funded by four grants from the Swiss National Science Foundation (#32003B-105993, #32003B-118308, #33CSC0-122661, and #139468), the Faculty of Biology and Medicine of Lausanne, and two grants from GlaxoSmithKline Clinical Genetics
Subjects: Male, Oncology, Gerontology, Polimorfismo de nucleótido simple, Estudio de asociación del genoma completo, LOCI, Obesidad, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Genome-wide association study, VARIANTS, Índice de masa corporal, Logistic regression, Body Mass Index, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Psychiatry and Psychology::Mental Disorders::Mood Disorders::Depressive Disorder::Depressive Disorder, Major [Medical Subject Headings], RECURRENT DEPRESSION, 10. No inequality, POPULATION, Body mass index, METABOLIC SYNDROME, Medicine(all), 2. Zero hunger, 0303 health sciences, education.field_of_study, Estudios de casos y controles, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Área bajo la curva, General Medicine, Middle Aged, Genetic risk score, Modelos logísticos, 3. Good health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models [Medical Subject Headings], Area Under Curve, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], Major depressive disorder, Female, HEALTH, Research Article, Adult, Risk, medicine.medical_specialty, Population, Check Tags::Male [Medical Subject Headings], Polymorphism, Single Nucleotide, Riesgo, 03 medical and health sciences, US ADULTS, Internal medicine, Trastorno depresivo mayor, medicine, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Genetic Predisposition to Disease, Obesity, GENOME-WIDE ASSOCIATION, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Sensitivity and Specificity::ROC Curve [Medical Subject Headings], Aged, 030304 developmental biology, Genetic association, Depressive Disorder, Major, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Receiver operating characteristic, business.industry, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies::Genome-Wide Association Study [Medical Subject Headings], Curva ROC, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Area Under Curve [Medical Subject Headings], medicine.disease, TRENDS, R1, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Logistic Models, ROC Curve, Check Tags::Female [Medical Subject Headings], Case-Control Studies, Metabolic syndrome, business, METHODOLOGY, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Background: Obesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD., Methods: Linear and logistic regression models were conducted to predict BMI and obesity, respectively, in three independent large case–control studies of major depression (Radiant, GSK-Munich, PsyCoLaus). The analyses were first performed in the whole sample and then separately in depressed cases and controls. An unweighted GRS was calculated by summation of the number of risk alleles. A weighted GRS was calculated as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver operating characteristic (ROC) analysis was used to compare the discriminatory ability of predictors of obesity., Results: In the discovery phase, a total of 2,521 participants (1,895 depressed patients and 626 controls) were included from the Radiant study. Both unweighted and weighted GRS were highly associated with BMI (P, Conclusions: A GRS proved to be a highly significant predictor of obesity in people with MDD but accounted for only modest amount of variance. Nevertheless, as more risk loci are identified, combining a GRS approach with information on non-genetic risk factors could become a useful strategy in identifying MDD patients at higher risk of developing obesity., This study was funded by the Medical Research Council, UK. GlaxoSmithKline (G0701420) funded the DeNT study and were co-funders with the Medical Research Centre for the GWAS of the whole sample. The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT- 2003-503428. This study presents independent research [part-] funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. The CoLaus/PsyCoLaus was funded by four grants from the Swiss National Science Foundation (#32003B-105993, #32003B-118308, #33CSC0-122661, and #139468), the Faculty of Biology and Medicine of Lausanne, and two grants from GlaxoSmithKline Clinical Genetics.
Published: 2015
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13. Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study

Author: Carla H. van Gils, E. Riboli, Christos Tsironis, Anne-Claire Vergnaud, H. Bas Bueno-de-Mesquita, Laureen Dartois, José Ramón Quirós, Veronika Fedirko, Pietro Ferrari, Teresa Norat, Pagona Lagiou, Christina C. Dahm, Giovanna Masala, Timothy J. Key, Mark J. Gunter, Maria Wennberg, Kay-Tee Khaw, Verena Katzke, Petra H.M. Peeters, Aurelio Barricarte, Heather Ward, Nicholas J. Wareham, Anne Tjønneland, Lena Maria Nilsson, Bodil Ohlsson, Valeria Pala, Laure Dossus, Antonia Trichopoulou, Tilman Kühn, Heiner Boeing, Elisabete Weiderpass, Petra A. Wark, M. Dorronsoro, Carmen Navarro, Camilla Plambeck Hansen, Genevieve Buckland, Salvatore Panico, Marie-Christine Boutron-Ruault, María José Sánchez, Paolo Vineis, Peter D. Siersema, Karin Jirström, Dora Romaguera, Rosario Tumino, Mazda Jenab, Romaguera, Dora, Ward, Heather, Wark, Petra A, Vergnaud, Anne Claire, Peeters, Petra H, van Gils, Carla H, Ferrari, Pietro, Fedirko, Veronika, Jenab, Mazda, Boutron Ruault, Marie Christine, Dossus, Laure, Dartois, Laureen, Hansen, Camilla Plambeck, Dahm, Christina Catherine, Buckland, Genevieve, Sánchez, María José, Dorronsoro, Miren, Navarro, Carmen, Barricarte, Aurelio, Key, Timothy J, Trichopoulou, Antonia, Tsironis, Christo, Lagiou, Pagona, Masala, Giovanna, Pala, Valeria, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Siersema, Peter D, Ohlsson, Bodil, Jirström, Karin, Wennberg, Maria, Nilsson, Lena M, Weiderpass, Elisabete, Kühn, Tilman, Katzke, Verena, Khaw, Kay Tee, Wareham, Nick J, Tjønneland, Anne, Boeing, Heiner, Quirós, José R, Gunter, Marc J, Riboli, Elio, Norat, Teresa, Department of Medical and Clinical Genetics, Medicum, BMC, BMC, Department of Epidemiology and Public Health, Imperial College London, Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, CIBER Fisiopatología de la Obesidad y Nutrición ( (CIBEROBN)), Instituto de Salud Carlos III [Madrid] (ISC), Department of Primary Care and Public Health, Department of Epidemiology, University Medical Center [Utrecht]-Julius Center for Health Sciences and Primary Care, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Emory University [Atlanta, GA]-Rollins School of Public Health-Winship Cancer Institute, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Section for Epidemiology, Aarhus University [Aarhus], Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL)-Cancer Epidemiology Research Programme, Granada Cancer Registry, Andalusian School of Public Health [Granada], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Murcia Regional Health Council [Murcia], Department of Health and Social Sciences, Universidad de Murcia, Navarre Public Health Institute, Cancer Epidemiology Unit, University of Oxford, Hellenic Health Foundation, Bureau of Epidemiologic Research, Academy of Athens, Department of Hygiene, Epidemiology and Medical Statistics, Harvard School of Public Health, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Cancer Registry and Histopathology Unit, Department of Oncology-Civile - M.P.Arezzo Hospital, Human Genetics Foundation (HuGeF), Università degli studi di Torino = University of Turin (UNITO), Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II = Università degli studi di Napoli Federico II, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Center [Utrecht], Division of Internal Medicine, Skane University Hospital [Malmo], Lund University [Lund]-Lund University [Lund], Division of Oncology and Pathology, Lund University [Lund], Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Arctic Research Centre, Department of Community Medicine, The Arctic University of Norway [Tromsø, Norway] (UiT), Department of Research, Cancer Registry of Norway, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Clinical Gerontology Unit, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Danish Cancer Society Research Center, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Public Health Directorate, Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Oxford [Oxford], Università degli studi di Torino (UNITO), University of Naples Federico II, University of Malaya, The Arctic University of Norway, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, [Romaguera,D, Ward,H, Vergnaud,A, Peeters,PH, Vineis,P, Bueno-de-Mesquita,HB, Gunter, MJ, Riboli,E, Norat,T] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Romaguera,D] Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. [Romaguera,D] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Wark,PA] Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK. [Peeters,PH, Gils, CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Ferrari,P, Jenab,M] International Agency for Cancer Research (IARC), Lyon CEDEX, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, USA. [Fedirko,V] Winship Cancer Institute, Emory University, Atlanta, USA. [Boutron-Ruault,M, Dossus,L, Dartois,L] Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health (CESP), Vaillant, Villejuif, Cedex, France. [Boutron-Ruault,M, Dartois,L] Univ Paris Sud, Villejuif, France. [Boutron-Ruault,M, Dartois,L] Gustave Roussy, Villejuif, France. [Hansen,CP, Dahm,CC] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Dorronsoro,M, Navarro,C, Barricarte,A] CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Basque Regional Health Department, San Sebastian, Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Campus Universitario de Espinardo, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford UK. [Trichopoulou,A, Tsironis,C] Hellenic Health Foundation, Athens, Greece . [Trichopoulou,A, Lagiou,P] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic – M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P] HuGeF Foundation, Turin, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven The Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Ohlsson,B] Division of Internal Medicine, Department of Clinical Sciences, Skane University Hospital, Malmo, Lund University, Lund, Sweden. [Jirström,K] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Wennberg,M] Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. [Nilsson,LM] Arctic Research Centre, Umeå University, Umeå, Sweden. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, ISM - Universitetet i Tromsø, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Majorstuen Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Folkhälsan Research Center, Biomedicum 1, University of Helsinki, Helsinki, Finland. [Kühn,T, Katzke,V] German Cancer Research Center (DKFZ), Division of Cancer Epidemiology Im Neuenheimer Feld 581, Heidelberg, Germany. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit Box 251, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK. [Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Quirós,JR] Public Health Directorate, Oviedo Asturias, Spain., This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economía y Competitividad, Spain and European Regional Development Fund, RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO), German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), Danish Cancer Society, Catalan Institute of Oncology, Spain, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain, Cancer Research UK, Medical Research Council, United Kingdom, The Hellenic Health Foundation, Greece, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Fondazione-Istituto Banco Napoli, Italy, Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skåne, Sweden, Helga—Nordic Center of Excellence Programme in Nutrition and Health, French League against Cancer (LNCC), National Institute for Health and Medical Research (INSERM), France, Mutuelle Générale de l'Education Romaguera et al. BMC Medicine (2015) 13:107 Page 10 of 12 Nationale (MGEN), France, 3 M Co., France, Gustave Roussy Institute (IGR), France, and and General Councils of France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Subjects: Male, physical activity, 0302 clinical medicine, estudios prospectivos, Prospective Studies, estudios de cohortes, mediana edad, Aged, 80 and over, anciano, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activity [Medical Subject Headings], dieta, Incidence, Hazard ratio, COLON-CANCER, General Medicine, adulto, 3. Good health, Näringslära, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, estilo de vida, Cohort, Dieta, Estilo de Vida, RESEARCH FUND/AMERICAN INSTITUTE, Cohort study, Human, medicine.medical_specialty, Concordance, European Continental Ancestry Group, DIAGNOSIS, incidencia, White People, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Neoplasias Colorrectales, BREAST-CANCER, Humans, Life Style, Aged, Cancer prevention, Proportional hazards model, Physical activity, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], weight, LIFE-STYLE FACTORS, Colorectal cancer, REPRODUCTIVE HISTORY, Prospective Studie, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Proportional Hazards Model, grupo de ascendencia continental europea, Estudios de Cohortes, Gerontology, cumplimiento del paciente, Survival, modelos de riesgos proporcionales, VDP::Medisinske Fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803, [SDV]Life Sciences [q-bio], humanos, Colorectal Neoplasm, Alcohol consumption, Breast cancer, Prospective study, Named Groups::Persons::Survivors [Medical Subject Headings], Cohort Studies, 030212 general & internal medicine, Prospective cohort study, Non-U.S. Gov't, 2. Zero hunger, Medicine(all), RISK, Nutrition and Dietetics, Healthy lifestyle, Diet, Weight, Research Support, Non-U.S. Gov't, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, European Prospective Investigation into Cancer and Nutrition, VDP::Medical disciplines: 700::Health sciences: 800::Epidemiology medical and dental statistics: 803, NUTRITION, Female, Colorectal Neoplasms, Research Article, Adult, neoplasias colorrectales, 3122 Cancers, RECREATIONAL PHYSICAL-ACTIVITY, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], colorectal cancer, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research Support, survival, Sobrevivientes, healthy lifestyle, Internal medicine, medicine, Journal Article, Proportional Hazards Models, Actividad Motora, business.industry, Physical fitness, BODY-MASS INDEX, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Other Clinical Medicine, 3121 General medicine, internal medicine and other clinical medicine, Patient Compliance, Cohort Studie, business, diet, Condició física
Abstract: Background: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. Methods: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Results: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend, We would like to acknowledge the contribution of all participants in the study. This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economia y Competitividad, Spain and European Regional Development Fund; RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research (BMBF); Danish Cancer Society; Catalan Institute of Oncology, Spain; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra; ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain; Cancer Research UK; Medical Research Council, United Kingdom; The Hellenic Health Foundation, Greece; Italian Association for Research on Cancer (AIRC); Italian National Research Council; Fondazione-Istituto Banco Napoli, Italy; Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Helga-Nordic Center of Excellence Programme in Nutrition and Health; French League against Cancer (LNCC); National Institute for Health and Medical Research (INSERM), France; Mutuelle Generale de l'Education Nationale (MGEN), France; 3 M Co., France; Gustave Roussy Institute (IGR), France; and General Councils of France.
Published: 2014
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14. Combined impact of healthy lifestyle factors on colorectal cancer : a large European cohort study

Author: Domenico Palli, Aurelio Barricarte, José Ramón Quirós, Laureen Dartois, Heather Ward, Salvatore Panico, Isabelle Romieu, Veronika Fedirko, Ulrika Ericson, Kim Overvad, Miren Dorronsoro, Pagona Lagiou, Krasimira Aleksandrova, Rudolf Kaaks, Kay-Tee Khaw, Anne Tjønneland, Elio Riboli, Laure Dossus, Sabina Rinaldi, Ingrid Ljuslinder, Genevieve Buckland, Marc J. Gunter, Petra H.M. Peeters, Vittorio Krogh, Alessio Naccarati, Ingegerd Johansson, Bodil Ohlsson, Peter D. Siersema, Kathryn E. Bradbury, Heiner Boeing, María José Sánchez, Mazda Jenab, Antonia Trichopoulou, H. Bas Bueno-de-Mesquita, Elisabete Weiderpass, Guri Skeie, Kristin Benjaminsen Borch, Tobias Pischon, Sven Knüppel, Teresa Norat, Nicholas J. Wareham, Joyce Kong, Dora Romaguera, Kuanrong Li, Dimitrios Trichopoulos, Rosario Tumino, Marie-Christine Boutron-Ruault, María Dolores Chirlaque, [Aleksandrova,K, Knüppe,S, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Pischon,T] Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany. [Jenab,M, Fedirko,V, Rinald,S, Romieu,I, Kong,J] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, the Netherlands. [Bueno-de-Mesquita,HB, Norat,T, Romaguera,D, Peeters,PHM, Gunter,MJ, Ward,HA, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA. [Romaguera,D] Instituto de Investigacion Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, Spain. [Boutron-Ruault,M, Dossus,L, Dartois,L] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. Univ Paris Sud, Villejuif, France. IGR, Villejuif, France. [Kaaks,R, Li,K] Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Tjønneland,K] Diet, Genes and Environment Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain. [Sánchez,MJ, Chirlaque,M] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Dorronsoro,M] Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain. [Chirlaque,M] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] Clinical Gerontology Unit, Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Bradbury,KE] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'M.P.Arezzo' Hospital, Ragusa, Italy. [Naccarati,A] HuGeF - Human Genetics Foundation – Torino, Molecular and Genetic Epidemiology Unit, Turin, Italy. [Panico,S] Department of clinical and experimental medicine-Federico II University, Naples, Italy. [Peeters,PHM] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherland. [Ljuslinder,I] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [Johansson,I] Department of Odontology, Umeå University, Umeå, Sweden. [Ericson,U] Diabetes and Cardiovascular Disease, Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden. [Ohlsson,B] Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital Malmö, Lund University, Malmö, Sweden. [Weiderpass,E, Skeie,G, Borch,KB] Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland., The coordination of the EPIC study is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. 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), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa and AVIS Ragusa (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) and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health, Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway), Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council (United Kingdom)., Aleksandrova, Krasimira, Pischon, Tobia, Jenab, Mazda, Bueno de Mesquita, H. Ba, Fedirko, Veronika, Norat, Teresa, Romaguera, Dora, Knüppel, Sven, Boutron Ruault, Marie Christine, Dossus, Laure, Dartois, Laureen, Kaaks, Rudolf, Li, Kuanrong, Tjønneland, Anne, Overvad, Kim, Quirós, José Ramón, Buckland, Genevieve, Sánchez, María José, Dorronsoro, Miren, Chirlaque, Maria Dolore, Barricarte, Aurelio, Khaw, Kay Tee, Wareham, Nicholas J, Bradbury, Kathryn E, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Naccarati, Alessio, Panico, Salvatore, Siersema, Peter D, Peeters, Petra H. M, Ljuslinder, Ingrid, Johansson, Ingegerd, Ericson, Ulrika, Ohlsson, Bodil, Weiderpass, Elisabete, Skeie, Guri, Borch, Kristin Benjaminsen, Rinaldi, Sabina, Romieu, Isabelle, Kong, Joyce, Gunter, Marc J, Ward, Heather A, Riboli, Elio, and Boeing, Heiner
Subjects: Male, consumo de alcohol, Health Behavior, 0302 clinical medicine, estudios prospectivos, European Prospective Investigation into Cancer and, Prospective Studies, estudios de cohortes, mediana edad, PROPORTION, anciano, education.field_of_study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activity [Medical Subject Headings], dieta, Incidence, COLON-CANCER, Hazard ratio, lifestyle factors, General Medicine, adulto, 3. Good health, estilo de vida, 030220 oncology & carcinogenesis, Cohort, acrylamide, Dieta, Cohort study, Human, medicine.medical_specialty, Alcohol Drinking, European Continental Ancestry Group, Lifestyles, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], European Prospective Investigation into Cancer and Nutrition (EPIC), Endocrinology and Diabetes, dietary questionnaires, haemoglobin adducts, incidencia, White People, 03 medical and health sciences, Càncer colorectal, population attributable risks, Humans, education, Life Style, METAANALYSIS, Aged, Cancer och onkologi, Science & Technology, Proportional hazards model, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, biomarkers, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], PREVENTION, Prospective Studie, MYOCARDIAL-INFARCTION, ATTRIBUTABLE RISK, Cardiovascular and Metabolic Diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], RISK-FACTORS, Proportional Hazards Model, grupo de ascendencia continental europea, measurement errors, Gerontology, colorectal cancer, combined impact, modelos de riesgos proporcionales, humanos, Colorectal Neoplasm, Cohort Studies, Risk Factors, Neoplasias colorrectales, Hábito de fumar, 030212 general & internal medicine, Prospective cohort study, conducta sanitaria, Medicine(all), Consumo de alcohol, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Europe, NUTRITION, Female, Colorectal Neoplasms, Life Sciences & Biomedicine, Research Article, Adult, Estils de vida, neoplasias colorrectales, 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], Population, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], smoking, Medicine, General & Internal, General & Internal Medicine, Internal medicine, medicine, factores de riesgo, Proportional Hazards Models, Nutrition (EPIC), RECTAL CANCERS, business.industry, Risk Factor, Diet, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, PHYSICAL-ACTIVITY, Attributable risk, Cohort Studie, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract: Background: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. Results: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend, The coordination of the EPIC study is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. 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); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa and AVIS Ragusa (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) and Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health, Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway); Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skane and Vasterbotten (Sweden); Cancer Research UK, Medical Research Council (United Kingdom).
Published: 2014
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15. Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition

Author: Veronika Fedirko, Annekatrin Lukanova, H. Bas Bueno-de-Mesquita, Salma Butt, Elio Riboli, Anne Tjønneland, Nathalie Chabbert-Buffet, Maria Plada, Valeria Pala, Domenico Palli, Isabelle Romieu, Leo J. Schouten, Kim Overvad, Roy F.P.M. Kruitwagen, George Adarakis, Marieke G.M. Braem, Inger T. Gram, Karin Jirström, Sabina Rinaldi, Rosario Tumino, Aurelio Barricarte Gurrea, Oxana Gavrilyuk, Anna Floegel, José Ramón Quirós, María José Sánchez, Konstantinos K. Tsilidis, Christina Marie Braüner, María Dolores Chirlaque, Carlotta Sacerdote, Catalina Bonet, Eiliv Lund, Eva Lundin, Birgit Teucher, Louise Hansen, Nerea Larrañaga, Rudolf Kaaks, Antonia Trichopoulou, Heiner Boeing, Petra A. Wark, Nina Ohlson, Naomi E. Allen, Rocco Galasso, Annika Idahl, Nicholas J. Wareham, Kay-Tee Khaw, N. Charlotte Onland-Moret, Petra H.M. Peeters, Françoise Clavel-Chapelon, [Braem,MGM, Onland-Moret,NC, Peeters,PHM] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Schouten,LJ] Department of Epidemiology, GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. [Kruitwagen, RFPM] Department of Obstetrics and Gynaecology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands. [Lukanova,A, Teuche,B, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. [Allen,NE, KK] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom. [Wark,PA] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St. Mary’s Campus, London, United Kingdom. [Tjønneland,A, Hansen,L] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Braü ner,MC, Overvad,K] Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F] Inserm, Centre for Research in Epidemiology and Population Health, U1018, Institut Gustave Roussy, Villejuif, France. [Chabbert-Buffet,N] Gynecology Department Hospital Tenon AP-HP, Paris, France. University Pierre and Marie Curie, Paris, France. [Floege,A, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou,A, Adarakis,G, Plada,M] Hellenic Health Foundation, Athens, Greece. [Rinaldi,S, Fedirko,V, Romieu,I] Section of Nutrition and Metabolism, Nutritional Epidemiology Group, International Agency for Research on Cancer, Lyon, France. [Pala,V] Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy. [Galasso,R] Istituto di Ricovero e Cura a Carattere Scientifico - Centro di Riferimento Oncologico di Basilicata, Unit of Clinical Epidemiolgy, Biostatistics and Cancer Registry, Rionero in Vulture, Italy. [Sacerdote,C] Center for Cancer Prevention (CPOPiemonte), Turin, Italy. Human Genetic Foundation, Torino, Italy. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civile - M.P. Arezzo' Hospital, ASP 7 Ragusa, Italy. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Gram,IT, Gavrilyuk,O, Lund,E] Institute of Community Medicine, Faculty of Health Sciences, University of Tromsø, Norway. [Sánchez,MJ] Escuela Andaluza de Salud Publica, Granada, Spain. [Sánchez,MJ, Chirlaque,MD, Larrañaga,N, Gurrea,AB] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Barcelona, Spain. [Bonet,C] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Barcelona, Spain. [Chirlaque,MD] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Barcelona, Spain. Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Larrañaga,N] Public Health Department of Gipuzkoa, Basque Government, Spain. [Gurrea,AB] Navarre Public Health Institute, Pamplona, Spain. [Quirós,JR] Public Health and Health Planning Directorate, Asturias, Spain. [Idah,A] Department of Clinical Sciences, Obstetrics and Gynecology, Umea University, Umea, Sweden. Department of Public Health and Clinical Medicine, Nutritional research, Umea University, Umea, Sweden. [Ohlson,N, Lundin,E] Department of Medical Biosciences, Pathology, Umea University, Umea, Sweden. [Jirström,K] Department of Clinical Sciences, Division of Pathology, Lund University, Skane University Hospital, Lund, Sweden. [Butt,S] Department of Surgery, Lund University, Skane University Hospital, Malmö , Sweden. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece. [Khaw,KT] University of Cambridge, Cambridge, United Kingdom. [Wareham,N] MRC Epidemiology Unit Cambridge, Cambridge, United Kingdom. [Riboli,E] School of Public Health, Imperial College London, London, United Kingdom., Funding: This study was financially supported by the Dutch Cancer Society (UU2008-4267). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Ge´ne´rale de l’Education Nationale, Institut National de la Sante´ et de la Recherche Me´dicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and 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), Italian Association for Research on Cancer (AIRC) 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), Regional Governments of Andalucı´a, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Ska°ne and Va¨sterbotten (Sweden), Cancer Research United Kingdom, Medical Research Council (United Kingdom)., Epidemiologie, and Obstetrie & Gynaecologie
Subjects: Questionnaires, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Proportional Hazards Models [Medical Subject Headings], Epidemiology, lcsh:Medicine, Abortion, Miscarriage, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Pregnancy, Surveys and Questionnaires, Clinical Epidemiology, Neoplasms, Glandular and Epithelial, Prospective Studies, Prospective cohort study, lcsh:Science, Reproductive History, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings], Ovarian Neoplasms, Multidisciplinary, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Cancer Risk Factors, Femenino, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Questionnaires [Medical Subject Headings], Obstetrics and Gynecology, Geographicals::Geographic Locations::Europe [Medical Subject Headings], European Prospective Investigation into Cancer and Nutrition, Ovarian Cancer, Humanos, Diseases::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [Medical Subject Headings], Europe, Oncology, Observational Studies, Hormonal therapy, Medicine, Female, Europa, Cancer Prevention, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial [Medical Subject Headings], Cancer Epidemiology, Cohort study, Research Article, medicine.medical_specialty, Abortion, Habitual, 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], Clinical Research Design, Diseases::Female Urogenital Diseases and Pregnancy Complications::Pregnancy Complications::Abortion, Spontaneous::Abortion, Habitual [Medical Subject Headings], Reproduktionsmedicin och gynekologi, Risk Assessment, Obstetrics, Gynecology and Reproductive Medicine, medicine, Humans, Proportional Hazards Models, Gynecology, Cancer och onkologi, business.industry, lcsh:R, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Assessment [Medical Subject Headings], Cancers and Neoplasms, medicine.disease, Neoplasias Glandulares y Epiteliales, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Medical History Taking::Reproductive History [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Other Clinical Medicine, Cancer and Oncology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Miscarriage and Stillbirth, lcsh:Q, Neoplasias Ováricas, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Ovarian cancer, business, Estudios de Cohortes, Gynecological Tumors
Abstract: While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR >= 4vs.0: 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR >= 4vs.0: 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR >= 4vs.0: 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.
Published: 2012
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16. Combined effect of hypothermia and caspase-2 gene deficiency on neonatal hypoxic-ischemic brain injury

Author: Leslie Schwendimann, Henrik Hagberg, Ylva Carlsson, Pierre Gressens, Carina Mallard, Etienne Jacotot, Xiaoyang Wang, Marianne Thoresen, Catherine I. Rousset, Neuronal Stress and Aging (NSA), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Medical Research Council (United Kingdom) [P19381], Medical Research Council (Sweden) [2009-2642, K2009-54X-21119-01-4, 20092630], foundation for the memory of Anna Brita och Bo Castegren, ALF-LUA (Sweden) [ALFGBG2863, ALFGBG-142881], Leducq Foundation, Wellcome Trust [WT094823MA], European Union [HEALTH-F2-2009-241778], Ahlens Foundation, Martina and Wilhelm Lundberg Foundation, SU-Foundation, Goteborg Medical Society, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Pathology, Caspase 2, Ischemia, Hypoxic ischemic brain injury, Central nervous system disease, Mice, 03 medical and health sciences, 0302 clinical medicine, Hypothermia, Induced, Internal medicine, medicine, Animals, Gene, 030304 developmental biology, Mice, Knockout, 0303 health sciences, biology, Hypothermia, Hypoxia (medical), medicine.disease, 3. Good health, Endocrinology, Animals, Newborn, Recien nacido, Hypoxia-Ischemia, Brain, Pediatrics, Perinatology and Child Health, biology.protein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, 030217 neurology & neurosurgery
Abstract: International audience; INTODUCTION: Hypoxia-ischemia (HI) injury in term infants develops with a delay during the recovery phase, opening up a therapeutic window after the insult. Hypothermia is currently an established neuroprotective treatment in newborns with neonatal encephalopathy (NE), saving one in nine infants from developing neurological deficits. Caspase-2 is an initiator caspase, a key enzyme in the route to destruction and, therefore, theoretically a potential target for a pharmaceutical strategy to prevent HI brain damage. METHODS: The aim of this study was to explore the neuroprotective efficacy of hypothermia in combination with caspase-2 gene deficiency using the neonatal Rice-Vannucci model of HI injury in mice. RESULTS: HI brain injury was moderately reduced in caspase-2-imice as compared with wild-type (WT) mice. Five hours of hypothermia (33 degrees C) vs. normothermia (36 degrees C) directly after HI provided additive protection overall (temperature P = 0.0004, caspase-2 genotype P = 0.0029), in the hippocampus and thalamus, but not in other gray matter regions or white matter. Delayed hypothermia initiated 2 h after HI in combination with caspase-2 gene deficiency reduced injury in the hippocampus, but not in other brain areas. DISCUSSION: In conclusion, caspase-2 gene deficiency combined with hypothermia provided enhanced neuroprotection as compared with hypothermia alone.
Published: 2012
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17. Social Inequalities and Mortality in Europe - Results from a Large Multi-National Cohort

Author: Larraitz Arriola, Eiliv Lund, Anne Tjønneland, Johan P. Mackenbach, Gwenn Menvielle, Nicholas J. Wareham, Anton E. Kunst, Rudolf Kaaks, Manuela M. Bergmann, Sabine Rohrmann, Kay-Tee Khaw, Göran Hallmans, Petra P.H. Peeters, Antonio Agudo, Aurelio Barricante Gurrea, Antonia Trichopoulou, Valentina Gallo, Majid Ezzati, Androniki Naska, Birgit Teucher, Sophia Zackrisson, Martin Almquist, H. Bas Bueno-de-Mesquita, Dimitrios Trichopoulos, Traci Mouw, Timothy J. Key, Elio Riboli, Peter D. Siersema, Heiner Boeing, Kim Overvad, Susanne Oksbjerg Dalton, Rosario Tumino, Carmen Navarro, María-Luisa Redondo, Tonje Braaten, Giovanna Masala, Salvatore Panico, Guri Skeie, Anne-Kathrin Illner, Paolo Vineis, Sture Eriksson, Paolo Contiero, Antonio Daponte, APH - Amsterdam Public Health, Public and occupational health, University of Zurich, Vineis, Paolo, [Gallo,V, Ezzati,M, Mouw,T, Riboli,E, Vineis,P] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. [Gallo,V] Social and Environmental Health Research,London School of Hygiene and Tropical Medicine, London, United Kingdom. [Mackenbach,JP] Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands. [Menvielle,G] Epidemiology of Occupational and Social Determinants of Health, INSERM, Villejuif, France. [Menvielle,G] Universite of Versailles Saint Quentin, Versailles, France. [Kunst,AE] Department of Public Health, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. [Rohrmann,S] Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland. [Kaaks,R, Teucher,B] Division of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Boeing,H, Bergmann,MM] Institute of Human Nutrition, Potsdam-Rehbrücke, Germany. [Tjønneland,A, Dalton,SO] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Overvad,K] Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. [Redondo,M] Public Health and Participation Directorate, Health and Health Care Services Council, Oviedo, Asturias, Spain. [Agudo,A] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain. [Daponte,A, Arriola,L, Navarro,C, Barricante Gurrea,A] CIBER Epidemiologia y Salud Publica, Barcelona, Spain. [Daponte,A] Andalusian School of Public Health, Granada, Spain. [Arriola,L] Public Health Division of Gipuzkoa, Basque Government, Spain. [Navarro,C] Department of Epidemiology, Regional Health Authority, Murcia, Spain. [Navarro,C] Departamento de Ciencias Sociosanitarias, University of Murcia School of Medicine, Murcia, Spain. [Barricante Gurrea,A] Navarra Public Health Institute, Pamplona, Spain. [Khaw,KT] University of Cambridge, Cambridge, United Kingdom. [Wareham,N] Medical Research Council – Epidemiology Unit, Cambridge, United Kingdom. [Key,T] Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. [Naska,A, Trichopoulou,A] World Health Organisation Collaborating Centre for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, United States of America. [Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Greece. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy. [Panico,S] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Contiero,T] Cancer Registry and Environmental Epidemiology, Istituto Nazionale Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathological Unit, Civile M. P. Arezzo Hospital, Ragusa, Italy. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands. [Peeters,PP] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands. [Zackrisson,S] Department of Clinical Sciences in Malmö , Diagnostic Radiology, Lund University, Sweden. [Almquist,M] Department of Surgery, University Hospital Lund and Lund University, Lund, Sweden. [Eriksson,S, Hallmans,G] Department of Community Medicine and Rehabilitation, Umea University, Umea, Sweden. [Skeie,G, Braaten,T, Lund,E] Institutt for samfunnsmedisin, Universitetet i Tromsø, Tromsø, Norway. [Illner,A] Dietary Exposure Assessment Group, Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France., This research has been made possible thanks to a grant of the European Community (5th Framework Programme) to PV (grant QLK4CT199900927), and a grant of the Compagnia di San Paolo to the ISI Foundation. All authors are independent form founders. Mortality data from the Netherlands were obtained from 'Statistics Netherlands'. In addition we would like to thank for their financial support: Europe Against cancer Program of the European Commission (SANCO), ISCIII, Red de Centros RCESP, C03/09, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Cancer Research U.K., Medical Research Council, United Kingdom, Stroke Association, United Kingdom, British Heart Foundation, Department of Health, United Kingdom, Food Standards Agency, United Kingdom, Wellcome Trust, United Kingdom, Greek Ministry of Health and Social Solidarity, Stavros Niacrchos Foundation, Hellenic Health Foundation, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Dutch Ministry of Public Health, Welfare and Sports, World Cancer Research Fund, Swedish Cancer, Swedish Scientific Council, Regional Government of Skane, Sweden, Norwegian Cancer Society, Research Council of Norway, French League against Cancer, Inserm, Mutuelle Generale l’Education National and IGR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Gallo, V, Mackenbach, Jp, Ezzati, M, Menvielle, G, Kunst, Ae, Rohrmann, S, Kaaks, R, Teucher, B, Boeing, H, Bergmann, Mm, Tj?nneland, A, Dalton, So, Overvad, K, Redondo, Ml, Agudo, A, Daponte, A, Arriola, L, Navarro, C, Gurrea, Ab, Khaw, Kt, Wareham, N, Key, T, Naska, A, Trichopoulou, A, Trichopoulos, D, Masala, G, Panico, Salvatore, Contiero, P, Tumino, R, Bueno de Mesquita, Hb, Siersema, Pd, Peeters, Pp, Zackrisson, S, Almquist, M, Eriksson, S, Hallmans, G, Skeie, G, Braaten, T, Lund, E, Illner, Ak, Mouw, T, Riboli, E, Vineis, P., Public Health, Epidemiology, and Gastroenterology & Hepatology
Subjects: Gerontology, Male, Survival, Epidemiology, lcsh:Medicine, Poison control, Educational inequalities, DETERMINANTS, 0302 clinical medicine, SOCIOECONOMIC INEQUALITIES, Medicine, Socioeconomic inequalities, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, lcsh:Science, Determinants, media_common, Multidisciplinary, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Lung-cancer incidence, Relative index of inequality, Mortality rate, CARDIOVASCULAR RISK, Geographicals::Geographic Locations::Europe [Medical Subject Headings], WOMEN, Epidemiology of Aging, Public Health, Global Health, Social Medicine and Epidemiology, SDG 10 - Reduced Inequalities, ASSOCIATION, Middle Aged, Socioeconomic Aspects of Health, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Health Care::Health Services Administration::Patient Care Management::Delivery of Health Care::Healthcare Disparities [Medical Subject Headings], Health, 030220 oncology & carcinogenesis, Cohort, SURVIVAL, Science & Technology - Other Topics, Female, NUTRITION, Public Health, HEALTH, Europa, Behavioral and Social Aspects of Health, Cancer Epidemiology, Research Article, Adult, Clinical Research Design, 610 Medicine & health, Social epidemiology, 1100 General Agricultural and Biological Sciences, Association, 03 medical and health sciences, Sex Factors, SDG 3 - Good Health and Well-being, 1300 General Biochemistry, Genetics and Molecular Biology, media_common.cataloged_instance, Humans, Women, European Union, European union, Mortality, Socioeconomic status, Biology, EDUCATIONAL INEQUALITIES, Cardiovascular Disease Epidemiology, Nutrition, 1000 Multidisciplinary, Science & Technology, Population Biology, business.industry, MULTIDISCIPLINARY SCIENCES, lcsh:R, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality [Medical Subject Headings], 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Cardiovascular risk, Social Epidemiology, LUNG-CANCER INCIDENCE, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Social Class, Socioeconomic Factors, Mortalidad, lcsh:Q, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Disparidades en atención de salud, business, Demography, Follow-Up Studies
Abstract: Journal Article; Research Support, Non-U.S. Gov't; BACKGROUND Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. METHODS A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socio-economic status (SES). Cox proportional hazard model's with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. RESULTS Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. DISCUSSION In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported. Yes
Published: 2012
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18. Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study

Author: Elio Riboli, Sabina Sieri, Sabina Rinaldi, Birgit Teucher, Petra H.M. Peeters, José Ramón Quirós, Rudolf Kaaks, Rebecca Ritte, María José Sánchez, Kim Overvad, Isabelle Romieu, Sanda Krum-Hansen, Franco Berrino, Naomi E. Allen, Françoise Clavel-Chapelon, Genevieve Buckland, Salvatore Panico, Anja Olsen, Afshan Siddiq, Heiner Boeing, David Cox, Eiliv Lund, Krasimira Aleksandrova, Malin Sund, Per Lenner, Rosario Tumino, Nicholas J. Wareham, Agnès Fournier, Annekatrin Lukanova, Eva Ardanaz, Carla H. van Gils, Pagona Lagiou, Inger T. Gram, Bas Bueno-de-Mesquita, Paolo Vineis, Sabine Rohrmann, Guy Fagherazzi, Thure Filskov Overvad, Antonia Trichopoulou, María Dolores Chirlaque, Pilar Amiano, Kay-Tee Khaw, Domenico Palli, Dimitrios Trichopoulos, Timothy J. Key, Anne Tjønneland, Laure Dossus, Ritte, R, Lukanova, A, Berrino, F, Dossus, L, Tj?nneland, A, Olsen, A, Overvad, Tf, Overvad, K, Clavel Chapelon, F, Fournier, A, Fagherazzi, G, Rohrmann, S, Teucher, B, Boeing, H, Aleksandrova, K, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Palli, D, Sieri, S, Panico, Salvatore, Tumino, R, Vineis, P, Quir?s, Jr, Buckland, G, S?nchez, Mj, Amiano, P, Chirlaque, Md, Ardanaz, E, Sund, M, Lenner, P, Bueno de Mesquita, B, van Gils, Ch, Peeters, Ph, Krum Hansen, S, Gram, It, Lund, E, Khaw, Kt, Wareham, N, Allen, Ne, Key, Tj, Romieu, I, Rinaldi, S, Siddiq, A, Cox, D, Riboli, E, Kaaks, R., Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Preventive and Predictive Medicine, Fondazione IRCCS Instituto Nazionale dei Tumori, Cancer Epidemiology Institute, Danish Cancer Society, Department of Cardiology, Aarhus University [Aarhus], Department of Epidemiology, Aarhus University [Aarhus]-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, German Institute of Human Nutrition, Hellenic Health Foundation, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene-Epidemiology and Medical Statistics-Athens Medical School, Harvard School of Public Health, Bureau of Epidemiologic Research, Academy of Athens, Molecular and Nutritional Epidemiology Unit, Scientific Institute of Tuscany-Cancer Research and Prevention Institute (ISPO), Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II-Medical School, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Centre for Environment and Health, Imperial College London-School of public health, Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), Public Health and Health Planning Directorate, Universidad de Oviedo, Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL)-Cancer Epidemiology Research Programme, Granada Cancer Registry, Andalusian School of Public Health [Granada], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Public Health Division of Gipuzkoa, Institute BIO Donostia-Health Department, Murcia Regional Health Authority, Navarra Public Health Institute, Leyre 15, Department of Surgery and Perioperative Sciences, Umea University Hospital, Department of Oncology and Radiation Sciences, Oncology, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Centre, Julius Center for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Department of Epidemiology and Biostatistics, Imperial College London-Faculty of Medicine-School of public health, Institute of Community Medicine, University of Tromsø (UiT), School of Clinical Medicine, University of Cambridge [UK] (CAM), Medical Research Council, Addenbrooke's Hospital-Epidemiology Unit, Cancer Epidemiology Unit, University of Oxford [Oxford], Unité d'épidémiologie nutritionnelle, Section Nutrition et Métabolisme-Centre Internationale de la recherche sur le cancer (CIRC), Department of Genomics of Common Disease, This work was (partly) supported by a grant from the German Research Foundation, Graduiertenkolleg 793: Epidemiology of communicable and chronic noncommunicable diseases and their interrelationships. The coordination of EPIC is financially supported by the European Commission Directorate General for Health and Consumer Protection (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue contre le Cancer, Mutuelle Générale de l'Education Nationale, and the Institut National de la Santé et de la Recherche Médicale (France), Deutsche Krebshilfe, 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, the Italian Association for Research on Cancer (AIRC) and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sport (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, the Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway), the Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (number 6236) and Navarra, and ISCIII RTICC Red Temática de Investigación Cooperativa en Cáncer (R06/0020) (Spain), the Swedish Cancer Society, Swedish Scientific Council and the Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, and the Medical Research Council, (United Kingdom)., [Ritte,R, Lukanova,A, Dossus,L, Rohrmann,S, Teucher,B, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Berrino,F] Department of Ritte et al. Breast Cancer Research Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tjønneland,A, Olsen,A] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Overvad,TF] Department of Cardiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Overvad,K] Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Fournier,A, Fagherazzi,G] Centre for Research in Epidemiology and Population Health, INSERM, Institut Gustave Roussy, Villejuif, France. Paris South University, Villejuif, France. [Rohrmann,S] Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, Zurich, Switzerland. [Boeing,H, Aleksandrova,K] Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Lagiou,P] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Trichopoulou, A] Hellenic Health Foundation, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Scientific Institute of Tuscany, Florence, Italy. [Sieri,S] Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Panico,S] Department of Clinical and Experimental Medicine Medical School Federico II University, Naples, Italy. [Tumino, R] Cancer Registry and Histopathology Unit, ‘Civile M.P. Arezzo’ Hospital ASP 7, Ragusa, Italy. [Vineis,P, Riboli,E] Centre for Environment and Health School of Public Health, Imperial College London, London, UK. [Vineis,P] Human Genetics Foundation (HuGeF), Torino, Italy. [Quirós,JR] Public Health and Health Planning Directorate, Asturias, Spain. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Andalusian School of Public Health, Granada, Spain. [Sánchez,MJ, Amiano,P, Chirlaque,MD, Ardanaz,E] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Amiano,P] Public Health Division of Gipuzkoa, Institute BIO Donostia, Health Department, Basque Region, Gipuzkoa, Spain. [Chirlaque,MD] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Sund,M] Department of Surgery and Perioperative Sciences, Umeå University Hospital, Umeå, Sweden. [Lenner,P] Department of Oncology and Radiation Sciences, Oncology, Umeå University Hospital, Umeå, Sweden. [Bueno-de-Mesquita,B] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [van Gils,CH, Peeters,PHM] Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. [Peeters,PHM, Siddiq,A, Cox,D] Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College, London, London, UK. [Krum-Hansen,S, Gram,IT, Lund,E] Institute of Community Medicine, University of Tromsø, Tromsø, Norway. [Khaw,KT] School of Clinical Medicine, University of Cambridge, The Old Schools, Trinity Lane, Cambridge, UK. [Wareham,N] Medical Research Council, Epidemiology Unit, Addenbrooke’s Hospital, Cambridge, UK. [Allen,NE, Key,TJ] Cancer Epidemiology Unit, University of Oxford, Oxford, UK. [Romieu,I, Rinaldi,S] Nutritional Epidemiology Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France. [Siddiq,A] Department of Genomics of Common Disease, School of Public Health, Imperial College London, London UK., University of Zurich, Kaaks, Rudolf, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical School-University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli studi di Torino = University of Turin (UNITO), Universidad de Oviedo [Oviedo], University of Oxford, and BMC, Ed.
Subjects: Oncology, medicine.medical_treatment, body-mass index, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Body Mass Index, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Medicine, 1306 Cancer Research, Prospective Studies, Adiposity, estrogen-receptor, Aged, 80 and over, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Age Factors [Medical Subject Headings], 3. Good health, Postmenopause, nutrition, Receptors, Estrogen, PREMENOPAUSAL WOMEN, Adiposidad, premenopausal omen, fat distribution, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], 030220 oncology & carcinogenesis, Cohort, 2730 Oncology, Receptors, Progesterone, Factores de riesgo, Cohort study, medicine.medical_specialty, Named Groups::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings], Estudios de cohortes, united-states, 03 medical and health sciences, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Aged, Gynecology, Cancer och onkologi, Science & Technology, Proportional hazards model, weight, ONCOLOGY, medicine.disease, Check Tags::Female [Medical Subject Headings], Premenopause, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Surgery, Body mass index, Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], postmenopausal women, Overweight, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Fat Distribution::Adiposity [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, Risk Factors, 030212 general & internal medicine, Prospective cohort study, physical-activity, 2. Zero hunger, Medicine(all), Estrogen Replacement Therapy, Age Factors, Hormone replacement therapy (menopause), Estudios Prospectivos, Middle Aged, POSTMENOPAUSAL WOMEN, Neoplasias de la mama, NUTRITION, Female, medicine.symptom, Life Sciences & Biomedicine, Research Article, Factores de Edad, Adult, Risk, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Premenopause [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::Prospective Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Hormone Replacement Therapy::Estrogen Replacement Therapy [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], UNITED-STATES, 610 Medicine & health, 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], [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, size, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Young Adult, Internal medicine, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Receptores de Progesterona, business.industry, Kirurgi, FAT DISTRIBUTION, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Receptores Estrogénicos, BODY-MASS INDEX, ESTROGEN-RECEPTOR, PHYSICAL-ACTIVITY, SIZE, WEIGHT, business
Abstract: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; INTRODUCTION Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. METHODS Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. RESULTS For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. CONCLUSIONS An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors. Yes
Published: 2012
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19. Distinct contributions of nicotinic acetylcholine receptor subunit 4 and subunit 6 to the reinforcing effects of nicotine

Author: J. Michael McIntosh, Sarah Threlfell, Alexis Evrard, Stephanie J. Cragg, Vincent David, Uwe Maskos, Raphaël Eddine, Richard Exley, Nicolas Maubourguet, Pierre Cazala, Philippe Faure, Fabio Marti, Stéphanie Pons, Jean-Pierre Changeux, Department of Physiology, Anatomy and Genetics [Oxford], University of Oxford, Neurobiologie Intégrative des Systèmes Cholinergiques (NISC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de neurosciences intégratives et cognitives (CNIC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Utah, This research was supported by the Institut Pasteur, Centre National de la Recherche Scientifique Unité de Recherche Associée 2182, Unité Mixte de Recherche 7102, and Unité Mixte de Recherche 5228, the Agence Nationale de Recherches programme Neuroscience, Neurology and Psychiatry (2005 and 2009), the Agence Nationale de Recherches Programme BLANC 2009, Medical Research Council (United Kingdom) Grant G0700932, Parkinson's Disease Society (United Kingdom) Grant G0808, and by the European Union Seventh Framework Programme under grant agreement HEALTH-F2-2008-202088 (NeuroCypres project). We also acknowledge financial support from the Network of European Neuroscience Institutes (ENI-NET), the Pierre Fabre Laboratories, and the Fondation Gilbert Lagrue (to N.M.) and the Bettencourt Foundation (to P.F.)., ANR-09-BLAN-0104,VHSMOD-2009,Variétés holomorphiquement symplectiques, leurs espaces de modules et formes automorphes(2009), European Project: 202088,EC:FP7:HEALTH,FP7-HEALTH-2007-A,NEUROCYPRES(2008), University of Oxford [Oxford], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS)
Subjects: Dopamine, MESH: Neurons, Pharmacology, Receptors, Nicotinic, MESH: Mice, Knockout, MESH: Nicotine, Nicotine, Mice, [SCCO]Cognitive science, 0302 clinical medicine, Ganglion type nicotinic receptor, MESH: Autoradiography, lentivirus, MESH: Genetic Vectors, MESH: Animals, MESH: Lentivirus, Mice, Knockout, Neurons, 0303 health sciences, voltammetry, Multidisciplinary, MESH: Electrophysiology, Chemistry, musculoskeletal, neural, and ocular physiology, Biological Sciences, Cell biology, Ventral tegmental area, Nicotinic acetylcholine receptor, medicine.anatomical_structure, Nicotinic agonist, MESH: Receptors, Nicotinic, medicine.drug, Protein subunit, Genetic Vectors, MESH: Dopamine, Nucleus accumbens, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: Analysis of Variance, mental disorders, medicine, ventral striatum, Animals, MESH: Mice, 030304 developmental biology, Acetylcholine receptor, Analysis of Variance, Ventral Tegmental Area, electrophysiology, Mice, Inbred C57BL, nervous system, MESH: Ventral Tegmental Area, Autoradiography, nicotinic receptor, 030217 neurology & neurosurgery
Abstract: International audience; Nicotine is the primary psychoactive component of tobacco. Its reinforcing and addictive properties depend on nicotinic acetylcholine receptors (nAChRs) located within the mesolimbic axis originating in the ventral tegmental area (VTA). The roles and oligomeric assembly of subunit α4- and subunit α6-containing nAChRs in dopaminergic (DAergic) neurons are much debated. Using subunit-specific knockout mice and targeted lentiviral re-expression, we have determined the subunit dependence of intracranial nicotine self-administration (ICSA) into the VTA and the effects of nicotine on dopamine (DA) neuron excitability in the VTA and on DA transmission in the nucleus accumbens (NAc). We show that the α4 subunit, but not the α6 subunit, is necessary for ICSA and nicotine-induced bursting of VTA DAergic neurons, whereas subunits α4 and α6 together regulate the activity dependence of DA transmission in the NAc. These data suggest that α4-dominated enhancement of burst firing in DA neurons, relayed by DA transmission in NAc that is gated by nAChRs containing α4 and α6 subunits, underlies nicotine self-administration and its long-term maintenance.
Published: 2011
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20. New marker of colon cancer risk associated with heme intake: 1,4-dihydroxynonane mercapturic acid

Author: Amanda J. Cross, Sylviane Taché, Fabrice Pierre, Nicole Gasc, Françoise Guéraud, Gaëlle Gottardi, Sheila Bingham, Denis E. Corpet, Géraldine Peiro, Institut National de la Recherche Agronomique - INRA (FRANCE), National Cancer Institute (USA), Medical Research Council (UNITED KINGDOM), Ecole Nationale Vétérinaire de Toulouse - ENVT (FRANCE), Guéraud, Françoise, Xénobiotiques, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), and Medical Research Council
Subjects: Male, Epidemiology, Colorectal cancer, [SDV]Life Sciences [q-bio], Lipid peroxidation, chemistry.chemical_compound, 0302 clinical medicine, Neoplasms, Mercapturic acid, Heme, Cancer, 2. Zero hunger, 0303 health sciences, Middle Aged, 3. Good health, Animal models, Oncology, Biochemistry, Red Meat Consumption, 030220 oncology & carcinogenesis, Colonic Neoplasms, Red meat, Female, Adult, Risk, medicine.medical_specialty, Colon, Iron, Excretion, 03 medical and health sciences, Internal medicine, medicine, Biomarkers, Tumor, Animals, Humans, 030304 developmental biology, Aged, Laboratory animals, Azoxymethane, business.industry, medicine.disease, Animal Feed, Rats, Inbred F344, Acetylcysteine, Diet, Rats, Oxidative Stress, Endocrinology, chemistry, Prostaglandins, 1,4 dihydroxynonane mercapturic acid, business, Haem
Abstract: Background: Red meat consumption is associated with an increased risk of colon cancer. Animal studies show that heme, found in red meat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8-iso-prostaglandin-F2α (8-iso-PGF2α), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake. Methods: We measured urinary excretion of 8-iso-PGF2α and 1,4-dihydroxynonane mercapturic acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat baseline diet, 120 g/d red meat, baseline diet supplemented with heme iron, and baseline diet supplemented with non-heme iron). Results: DHN-MA excretion increased dramatically in rats fed high heme diets, and the excretion paralleled the number of preneoplastic lesions in azoxymethane initiated rats (P < 0.0001). In the human study, the heme supplemented diet resulted in a 2-fold increase in DHN-MA (P < 0.001). Urinary 8-iso-PGF2α increased moderately in rats fed a high heme diet (P < 0.0001), but not in humans. Conclusion: Urinary DHN-MA is a useful noninvasive biomarker for determining the risk of preneoplastic lesions associated with heme iron consumption and should be further investigated as a potential biomarker of colon cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2274–9)
Published: 2006
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21. Neurogliaform Neurons Form a Novel Inhibitory Network in the Hippocampal CA1 Area

Author: Ryuichi Shigemoto, Christopher J. Price, Bertrand Lambolez, Endre R. Kovacs, Bruno Cauli, Marco Capogna, Akos Kulik, Anatomical Neuropharmacology Unit, Medical Research Council, Neurobiologie et diversité cellulaire (NDC), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Department of Anatomy and Cell Biology, University of Freiburg [Freiburg], Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Division of Cerebral Structure, National Institute for Physiological Sciences, Solution Oriented Research for Science and Technology, Japan Science and Technology Corporation, and This work was supported by the Medical Research Council (United Kingdom).
Subjects: Patch-Clamp Techniques, Hippocampus, Polymerase Chain Reaction, Rats, Sprague-Dawley, perforant path, 0302 clinical medicine, Postsynaptic potential, Entorhinal Cortex, Perforant Pathway/cytology, Dendrites/physiology, 0303 health sciences, Neuronal Plasticity, Chemistry, electrical synapses, General Neuroscience, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Receptors, GABA-B/genetics, Nerve Net/cytology, medicine.anatomical_structure, Hippocampus/cytology, Excitatory postsynaptic potential, GABAergic, short-term plasticity, Cellular/Molecular, Interneuron, Perforant Pathway, interneuron, Neurotransmission, Inhibitory postsynaptic potential, 03 medical and health sciences, Organ Culture Techniques, Interneurons, GABAB, medicine, Animals, Electrical synapse, 030304 developmental biology, unitary IPSCs, Neural Inhibition/physiology, ACM, Neural Inhibition, Dendrites, Neuronal Plasticity/physiology, Perforant path, Interneurons/physiology, Axons, Electric Stimulation, Rats, nervous system, Receptors, GABA-B, Axons/physiology, Entorhinal Cortex/cytology, Nerve Net, Neuroscience, 030217 neurology & neurosurgery, Biomarkers
Abstract: We studied neurogliaform neurons in the stratum lacunosum moleculare of the CA1 hippocampal area. These interneurons have short stellate dendrites and an extensive axonal arbor mainly located in the stratum lacunosum moleculare. Single-cell reverse transcription-PCR showed that these neurons were GABAergic and that the majority expressed mRNA for neuropeptide Y. Most neurogliaform neurons tested were immunoreactive for α-actinin-2, and many stratum lacunosum moleculare interneurons coexpressed α-actinin-2 and neuropeptide Y. Neurogliaform neurons received monosynaptic, DNQX-sensitive excitatory input from the perforant path, and 40 Hz stimulation of this input evoked EPSCs displaying either depression or initial facilitation, followed by depression. Paired recordings performed between neurogliaform neurons showed that 85% of pairs were electrically connected and 70% were also connected via GABAergic synapses. Injection of sine waveforms into neurons during paired recordings resulted in transmission of the waveforms through the electrical synapse. Unitary IPSCs recorded from neurogliaform pairs readily fatigued, had a slow decay, and had a strong depression of the synaptic response at a 5 Hz stimulation frequency that was antagonized by the GABABantagonist (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl) phosphinic acid (CGP55845). The amplitude of the first IPSC during the 5 Hz stimulation was also increased byCGP55845, suggesting a tonic inhibition of synaptic transmission. A small unitary GABAB-mediated IPSC could also be detected, providing the first evidence for such a component between GABAergic interneurons. Electron microscopic localization of the GABAB1subunit at neurogliaform synapses revealed the protein in both presynaptic and postsynaptic membranes. Our data disclose a novel interneuronal network well suited for modulating the flow of information between the entorhinal cortex and CA1 hippocampus.
Published: 2005
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22. Tat HIV-1 Primary and Tertiary Structures Critical to Immune Response Against Non-homologous Variants

Author: Sandrine Opi, Erwann Loret, David L. Yirrell, Jean-Marie Peloponese, Didier Esquieu, Emmanuelle Bouveret, Anne Walburger, Murielle Solomiac, Jean de Mareuil, Catherine Grégoire, Grant R. Campbell, Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Laboratory of Molecular Microbiology [Bethesda, MD, USA], National Institutes of Health [Bethesda] (NIH), Centre for HIV Research [Edinburgh, UK] (Waddington Building), University of Edinburgh, Medical Research Council (United Kingdom) [Entebbe, Uganda] (Programme on AIDS), Uganda Virus Research Institute, This work was supported by the Agence National pour la Recherche contre le SIDA (ANRS), Agence Nationale pour la Valorisation de la Recherche (ANVAR), and the Centre National pour la Recherche Scientifique (CNRS)., Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and PELOPONESE, Jean-Marie
Subjects: Transcriptional Activation, Protein Conformation, Blotting, Western, Molecular Sequence Data, Heterologous, Enzyme-Linked Immunosorbent Assay, HIV Antibodies, Biology, Transfection, medicine.disease_cause, Biochemistry, Protein Structure, Secondary, Epitope, Epitopes, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Animals, Humans, Amino Acid Sequence, 030212 general & internal medicine, Molecular Biology, 030304 developmental biology, AIDS Vaccines, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Mutation, Dose-Response Relationship, Drug, Sequence Homology, Amino Acid, Antibody titer, Cell Biology, Virology, Protein Structure, Tertiary, 3. Good health, Blot, Gene Products, tat, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Rabbits, Antibody, HeLa Cells
Abstract: International audience; Clinical studies show that in the absence of anti-retroviral therapy an immune response against the human immunodeficiency virus type 1 (HIV-1), transacting transcriptional activator (Tat) protein correlates with long term non-progression. The purpose of this study is to try to understand what can trigger an effective immune response against Tat. We used five Tat variants from HIV strains identified in different parts of the world and showed that mutations of as much as 38% exist without any change in activity. Rabbit sera were raised against Tat variants identified in rapid-progressor patients (Tat HXB2, a European variant and Tat Eli, an African variant) and a long term non-progressor patient (Tat Oyi, an inactive African variant). Enzyme-linked immunosorbent assay (ELISA) results showed that anti-Tat Oyi serum had the highest antibody titer and was the only one to have a broad antibody response against heterologous Tat variants. Surprisingly, Tat HXB2 was better recognized by anti-Tat Oyi serum compared with anti-Tat HXB2 serum. Western blots showed that non-homologous Tat variants were recognized by antibodies directed against conformational epitopes. This study suggests that the primary and tertiary structures of the Tat variant from the long term non-progressor patient are critical to the induction of a broad and effective antibody response against Tat.
Published: 2002
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23. UIAA Medical Commission Recommendations for Mountaineers, Hillwalkers, Trekkers, and Rock and Ice Climbers with Diabetes.

Author: Hillebrandt D, Gurtoo A, Kupper T, Richards P, Schöffl V, Shah P, van der Spek R, Wallis N, and Milledge J
Subjects: Humans, Male, Female, Ice, Mountaineering, Diabetes Mellitus therapy
Abstract: Hillebrandt, David, Anil Gurtoo, Thomas Kupper, Paul Richards, Volker Schöffl, Pankaj Shah, Rianne van der Spek, Nikki Wallis, and Jim Milledge. UIAA Medical Commission recommendations for mountaineers, hillwalkers, trekkers, and rock and ice climbers with diabetes. High Alt Med Biol . 24: 110-126.-The object of this advice article is not only to give the diabetic mountaineer general guidance but also to inform his or her medical team of practical aspects of care that may not be standard for nonmountaineers. The guidelines are produced in seven sections. The first is an introduction to the guidelines, and the second is an introduction to this medical problem and is designed to be read and understood by diabetic patients and their companions. The third section is for use in an emergency in mountains. The fourth is for rock, ice, and competition climbers operating in a less remote environment. These initial sections are deliberately written in simple language. The fifth and sixth sections are written for clinicians and those with skills to read more technical information, and the seventh looks at modern technology and its pros and cons in diabetes management in a remote area. Sections One and Two could be laminated and carried when in the mountains, giving practical advice.
Published: 2023
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24. Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS).

Author: Vidal RM, Muhsen K, Tennant SM, Svennerholm AM, Sow SO, Sur D, Zaidi AKM, Faruque ASG, Saha D, Adegbola R, Hossain MJ, Alonso PL, Breiman RF, Bassat Q, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ahmed S, Qureshi S, Quadri F, Hossain A, Das SK, Antonio M, Mandomando I, Nhampossa T, Acácio S, Omore R, Ochieng JB, Oundo JO, Mintz ED, O'Reilly CE, Berkeley LY, Livio S, Panchalingam S, Nasrin D, Farag TH, Wu Y, Sommerfelt H, Robins-Browne RM, Del Canto F, Hazen TH, Rasko DA, Kotloff KL, Nataro JP, and Levine MM
Subjects: Africa epidemiology, Asia epidemiology, Case-Control Studies, Child, Preschool, Female, Genotype, Humans, Infant, Infant, Newborn, Male, Polymerase Chain Reaction, Prevalence, Enterotoxigenic Escherichia coli genetics, Enterotoxigenic Escherichia coli isolation & purification, Escherichia coli Infections epidemiology, Escherichia coli Infections microbiology, Fimbriae Proteins genetics, Virulence Factors genetics
Abstract: Background: Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites. We also assessed strength of association of specific CFs with MSD., Methodology/principal Findings: MSD cases enrolled at healthcare facilities over three years and matched controls were tested in a standardized manner for many enteropathogens. To identify ETEC, three E. coli colonies per child were tested by polymerase chain reaction (PCR) to detect genes encoding LT, ST; confirmed ETEC were examined by PCR for major CFs (Colonization Factor Antigen I [CFA/I] or Coli Surface [CS] antigens CS1-CS6) and minor CFs (CS7, CS12, CS13, CS14, CS17, CS18, CS19, CS20, CS21, CS30). ETEC from 806 cases had a single toxin/CF profile in three tested strains per child. Major CFs, components of multiple ETEC vaccine candidates, were detected in 66.0% of LT/ST and ST-only cases and were associated with MSD versus matched controls by conditional logistic regression (p≤0.006); major CFs detected in only 25.0% of LT-only cases weren't associated with MSD. ETEC encoding exclusively CS14, identified among 19.9% of 291 ST-only and 1.5% of 259 LT/ST strains, were associated with MSD (p = 0.0011). No other minor CF exhibited prevalence ≥5% and significant association with MSD., Conclusions/significance: Major CF-based efficacious ETEC vaccines could potentially prevent up to 66% of pediatric MSD cases due to ST-encoding ETEC in developing countries; adding CS14 extends coverage to ~77%., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests. We note that the following authors are involved in the development of vaccines to prevent diarrhea caused by enterotoxigenic Escherichia coli: James P. Nataro: Has been named in patents for technology that may have relevance for ETEC vaccine technology; JPN is also a co-investigator on grants from non-profit agencies that support ETEC vaccine development. Halvor Sommerfelt: Has been named in patents for technology that may have relevance for ETEC vaccine technology including: INT Application Number PCT/IB2014/000267; INT Publication Number WO2014128555 A2 “ETEC Vaccine”. European Patent Application No. 14711297.3 United States Patent Application No. 14/769,342. China Patent Application No. 201480022329.6. Puntervoll P, Sommerfelt H, Clements J, Nataro JP, Zhang W, Taxt A. HS is also a co-investigator on grants from non-profit agencies that support ETEC vaccine development Ann-Mari Svennerholm: Has shares in the University of Göteborg spin-out biotech company Gotovax AB which is entitled to royalty from Scandinavian Biopharma on sales in travelers of the ETEC vaccine Etvax if it becomes a commercial product. A-MS is a co-inventor on ETEC vaccine patent application owned by Scandinavian Biopharma and has a research grant from the Swedish Foundation for Strategic Research for infection biology research. Myron M. Levine: Is a co-inventor of patents for ETEC vaccine technology including US patent #6,902,736 B2. “Isolation and characterization of the CSA operon (ETEC-CS4 pili) and methods of using same.” He is a member of the Scientific Advisory Board of the PaxVax Corporation. MML is also the recipient for grants relevant to ETEC vaccine development including the Enteric Center of Excellence for Translational Research (Enteric-CETR) “Immunoprophylactic Strategies to Control Emerging Enteric Infections” (NIAID U19AI109776; MML, PI)
Published: 2019
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25. The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS).

Author: Sow SO, Muhsen K, Nasrin D, Blackwelder WC, Wu Y, Farag TH, Panchalingam S, Sur D, Zaidi AK, Faruque AS, Saha D, Adegbola R, Alonso PL, Breiman RF, Bassat Q, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ahmed S, Qureshi S, Quadri F, Hossain A, Das SK, Antonio M, Hossain MJ, Mandomando I, Nhampossa T, Acácio S, Omore R, Oundo JO, Ochieng JB, Mintz ED, O'Reilly CE, Berkeley LY, Livio S, Tennant SM, Sommerfelt H, Nataro JP, Ziv-Baran T, Robins-Browne RM, Mishcherkin V, Zhang J, Liu J, Houpt ER, Kotloff KL, and Levine MM
Subjects: Afghanistan epidemiology, Africa South of the Sahara epidemiology, Asia epidemiology, Case-Control Studies, Child, Preschool, Cryptosporidiosis parasitology, Cryptosporidium classification, Cryptosporidium genetics, Cryptosporidium immunology, Cryptosporidium isolation & purification, Data Mining methods, Developing Countries economics, Developing Countries statistics & numerical data, Diarrhea epidemiology, Diarrhea parasitology, Female, Gastrointestinal Diseases mortality, Gastrointestinal Diseases parasitology, Humans, Immunoassay, Incidence, India epidemiology, Infant, Infant, Newborn, Male, Polymerase Chain Reaction, Cost of Illness, Cryptosporidiosis epidemiology, Cryptosporidiosis mortality, Diarrhea mortality, Feces parasitology, Gastrointestinal Diseases epidemiology
Abstract: Background: The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized., Methods: Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated., Findings: Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27-4.67) and 3.18 (95% CI, 1.85-4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73-2.08) and 1.36 (95% CI, 0.66-2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33-5.01) and 4.88 (95% CI, 0.82-8.92) in infants and 4.04 (95% CI, 0.56-7.51) and 4.71 (95% CI, 0.24-9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative., Conclusions: The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies.
Published: 2016
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26. Sanitation and Hygiene-Specific Risk Factors for Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study, 2007-2011: Case-Control Study.

Author: Baker KK, O'Reilly CE, Levine MM, Kotloff KL, Nataro JP, Ayers TL, Farag TH, Nasrin D, Blackwelder WC, Wu Y, Alonso PL, Breiman RF, Omore R, Faruque AS, Das SK, Ahmed S, Saha D, Sow SO, Sur D, Zaidi AK, Quadri F, and Mintz ED
Subjects: Africa epidemiology, Asia epidemiology, Case-Control Studies, Child, Preschool, Diarrhea etiology, Female, Humans, Infant, Infant, Newborn, Male, Risk Factors, Diarrhea epidemiology, Hygiene, Sanitation statistics & numerical data
Abstract: Background: Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age., Methods/findings: The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged <5 y old experiencing MSD and for 12,390 asymptomatic age, gender, and neighborhood-matched controls. An MSD case was defined as a child with a diarrheal illness <7 d duration comprising ≥3 loose stools in 24 h and ≥1 of the following: sunken eyes, skin tenting, dysentery, intravenous (IV) rehydration, or hospitalization. Site-specific conditional logistic regression models were used to explore the association between sanitation and hygiene exposures and MSD. Most households at six sites (>93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1-2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India., Conclusions: This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved.
Published: 2016
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27. Correlates of T-cell-mediated viral control and phenotype of CD8(+) T cells in HIV-2, a naturally contained human retroviral infection.

Author: de Silva TI, Peng Y, Leligdowicz A, Zaidi I, Li L, Griffin H, Blais ME, Vincent T, Saraiva M, Yindom LM, van Tienen C, Easterbrook P, Jaye A, Whittle H, Dong T, and Rowland-Jones SL
Subjects: Adult, Aged, Aged, 80 and over, Anti-Retroviral Agents therapeutic use, Antigens, CD metabolism, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes metabolism, Cell Differentiation immunology, Cell Proliferation, Female, Flow Cytometry, GPI-Linked Proteins metabolism, HIV Infections drug therapy, Humans, Immunophenotyping, Male, Middle Aged, Programmed Cell Death 1 Receptor metabolism, Receptors, Immunologic metabolism, Signaling Lymphocytic Activation Molecule Family, Viremia drug therapy, Viremia immunology, gag Gene Products, Human Immunodeficiency Virus immunology, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes virology, HIV Infections immunology, HIV-2 immunology
Abstract: While a significant proportion of HIV-2-infected individuals are asymptomatic and maintain undetectable viral loads (controllers), 15% to 20% progress to AIDS and are predicted by detectable viremia. Identifying immune correlates that distinguish these 2 groups should provide insights into how a potentially pathogenic retrovirus can be naturally controlled. We performed a detailed study of HIV-2-specific cellular responses in a unique community cohort in Guinea-Bissau followed for over 2 decades. T-cell responses were compared between controllers (n = 33) and viremic subjects (n = 27) using overlapping peptides, major histocompatibility complex class I tetramers, and multiparameter flow cytometry. HIV-2 viral control was significantly associated with a high-magnitude, polyfunctional Gag-specific CD8(+) T-cell response but not with greater perforin upregulation. This potentially protective HIV-2-specific response is surprisingly narrow. HIV-2 Gag-specific CD8(+) T cells are at an earlier stage of differentiation than cytomegalovirus-specific CD8(+) T-cells, do not contain high levels of cytolytic markers, and exhibit low levels of activation and proliferation, representing distinct properties from CD8(+) T cells associated with HIV-1 control. These data reveal the potential T-cell correlates of HIV-2 control and the detailed phenotype of virus-specific CD8(+) T cells in a naturally contained retroviral infection.
Published: 2013
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28. Potent autologous and heterologous neutralizing antibody responses occur in HIV-2 infection across a broad range of infection outcomes.

Author: de Silva TI, Aasa-Chapman M, Cotten M, Hué S, Robinson J, Bibollet-Ruche F, Sarge-Njie R, Berry N, Jaye A, Aaby P, Whittle H, Rowland-Jones S, and Weiss R
Subjects: Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Antibody Formation, Cell Line, Cohort Studies, Female, HIV Infections virology, HIV-1 genetics, HIV-1 immunology, HIV-1 isolation & purification, HIV-1 physiology, HIV-2 genetics, HIV-2 isolation & purification, HIV-2 physiology, Humans, Male, Middle Aged, Molecular Sequence Data, Sequence Alignment, env Gene Products, Human Immunodeficiency Virus genetics, env Gene Products, Human Immunodeficiency Virus immunology, Antibodies, Neutralizing immunology, HIV Antibodies immunology, HIV Infections immunology, HIV-2 immunology
Abstract: Few studies have explored the role of neutralizing antibody (NAb) responses in controlling HIV-2 viremia and disease progression. Using a TZM-bl neutralization assay, we assessed heterologous and autologous NAb responses from a community cohort of HIV-2-infected individuals with a broad range of disease outcomes in rural Guinea-Bissau. All subjects (n = 40) displayed exceptionally high heterologous NAb titers (50% inhibitory plasma dilution or 50% inhibitory concentration [IC(50)], 1:7,000 to 1:1,000,000) against 5 novel primary HIV-2 envelopes and HIV-2 7312A, whereas ROD A and 3 primary envelopes were relatively resistant to neutralization. Most individuals also showed high autologous NAb against contemporaneous envelopes (78% of plasma-envelope combinations in 69 envelopes from 21 subjects), with IC(50)s above 1:10,000. No association between heterologous or autologous NAb titer and greater control of HIV-2 was found. A subset of envelopes was found to be more resistant to neutralization (by plasma and HIV-2 monoclonal antibodies). These envelopes were isolated from individuals with greater intrapatient sequence diversity and were associated with changes in potential N-linked glycosylation sites but not CD4 independence or CXCR4 use. Plasma collected from up to 15 years previously was able to potently neutralize recent autologous envelopes, suggesting a lack of escape from NAb and the persistence of neutralization-sensitive variants over time, despite significant NAb pressure. We conclude that despite the presence of broad and potent NAb responses in HIV-2-infected individuals, these are not the primary forces behind the dichotomous outcomes observed but reveal a limited capacity for adaptive selection and escape from host immunity in HIV-2 infection.
Published: 2012
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29. Decay kinetics of an interferon gamma release assay with anti-tuberculosis therapy in newly diagnosed tuberculosis cases.

Author: Adetifa IM, Ota MO, Walther B, Hammond AS, Lugos MD, Jeffries DJ, Donkor SA, Adegbola RA, and Hill PC
Subjects: Adolescent, Adult, Aged, Antitubercular Agents therapeutic use, Female, Humans, Interferon-gamma immunology, Male, Middle Aged, Tuberculosis blood, Tuberculosis diagnosis, Tuberculosis drug therapy, Young Adult, Interferon-gamma blood, Tuberculosis immunology
Abstract: Background: Qualitative and quantitative changes in IGRA response offer promise as biomarkers to monitor Tuberculosis (TB) drug therapy, and for the comparison of new interventions. We studied the decay kinetics of TB-specific antigen T-cell responses measured with an in-house ELISPOT assay during the course of therapy., Methods: Newly diagnosed sputum smear positive TB cases with typical TB chest radiographs were recruited. All patients were given standard anti-TB treatment. Each subject was followed up for 6 months and treatment outcomes were documented. Blood samples were obtained for the ESAT-6 and CFP-10 (EC) ELISPOT at diagnosis, 1-, 2-, 4- and 6-months. Qualitative and quantitative reversion of the ELISPOT results were assessed with McNemar test, conditional logistic regression and mixed-effects hierarchical Poisson models., Results: A total of 116 cases were recruited and EC ELISPOT was positive for 87% (95 of 109) at recruitment. There was a significant decrease in the proportion of EC ELISPOT positive cases over the treatment period (p<0.001). Most of the reversion occurred between the start and first month of treatment and at completion at 6 months. ESAT-6 had higher median counts compared to CFP-10 at all time points. Counts for each antigen declined significantly with therapy (p<0.001). Reverters had lower median SFUs at the start of treatment compared to non-Reverters for both antigens. Apart from the higher median counts for non-Reverters, no other risk factors for non-reversion were found., Conclusions: TB treatment induces qualitative and quantitative reversion of a positive in-house IGRA in newly diagnosed cases of active TB disease. As this does not occur reliably in the majority of cured individuals, qualitative and quantitative reversion of an IGRA ELISPOT has limited clinical utility as a surrogate marker of treatment efficacy.
Published: 2010
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30. Delaying bacillus Calmette-Guérin vaccination from birth to 4 1/2 months of age reduces postvaccination Th1 and IL-17 responses but leads to comparable mycobacterial responses at 9 months of age.

Author: Burl S, Adetifa UJ, Cox M, Touray E, Ota MO, Marchant A, Whittle H, McShane H, Rowland-Jones SL, and Flanagan KL
Subjects: Adolescent, Age Factors, BCG Vaccine administration & dosage, Child, Female, Flow Cytometry, Gambia, Humans, Immunophenotyping, Infant, Infant, Newborn, Interferon-gamma immunology, Interferon-gamma metabolism, Interleukin-10 immunology, Interleukin-10 metabolism, Interleukin-17 metabolism, Interleukin-6 immunology, Interleukin-6 metabolism, Male, Prospective Studies, T-Lymphocytes immunology, T-Lymphocytes metabolism, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Th1 Cells metabolism, Time Factors, Tuberculosis microbiology, Tuberculosis prevention & control, Vaccination methods, BCG Vaccine immunology, Interleukin-17 immunology, Mycobacterium immunology, Th1 Cells immunology, Tuberculosis immunology
Abstract: Bacillus Camette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis, yet its protective efficacy is highly variable between different geographical regions. We hypothesized that exposure to nontuberculous mycobacteria attenuates BCG immunogenicity by inducing mycobacterial-specific regulatory T cells (Tregs). Gambian neonates were recruited at birth and randomized to receive BCG vaccination either at birth or at 4 1/2 mo. Mycobacterial immune responses were assessed at birth, 4 1/2, and 9 mo of age. At 4 1/2 mo of age the BCG naive individuals had detectable mycobacterial responses, including increased IL-10 production suggesting environmental priming. Vaccination at birth significantly enhanced Th1, Th2, IL-6, IL-17, and Treg responses in mycobacterial cultures at 4 1/2 mo compared with the BCG naive group. Analyzing results at 4 1/2 mo postvaccination revealed lower IFN-gamma, IL-6, and IL-17 responses in the delayed BCG vaccine group compared with those vaccinated at birth, but this did not relate to Treg levels prevaccination. When comparing responses pre- and post-BCG vaccination in the delayed vaccine group, there was no priming of mycobacterial IL-17. Mycobacterial responses waned over 9 mo in those vaccinated at birth, leading to comparable mycobacterial immunity in both groups at 9 mo of age. Overall, these data suggest that vaccination at birth induces a broad Th1/Th2/IL-17/Treg mycobacterial response but the Th1/Th-17 response was reduced when delaying the vaccine. The evidence did not suggest that mycobacterial specific naturally occurring Tregs accounted for this attenuated immunogenicity.
Published: 2010
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31. A decline in the incidence of invasive non-typhoidal Salmonella infection in The Gambia temporally associated with a decline in malaria infection.

Author: Mackenzie G, Ceesay SJ, Hill PC, Walther M, Bojang KA, Satoguina J, Enwere G, D'Alessandro U, Saha D, Ikumapayi UN, O'Dempsey T, Mabey DC, Corrah T, Conway DJ, Adegbola RA, and Greenwood BM
Subjects: Bacteremia complications, Bacteremia epidemiology, Child, Gambia epidemiology, Humans, Incidence, Pneumococcal Infections complications, Pneumococcal Infections epidemiology, Pneumococcal Infections microbiology, Salmonella Infections microbiology, Time Factors, Typhoid Fever complications, Typhoid Fever epidemiology, Typhoid Fever microbiology, Malaria complications, Malaria epidemiology, Salmonella Infections complications, Salmonella Infections epidemiology
Abstract: Background: Malaria is a risk factor for invasive non-typhoidal Salmonella (NTS) infection in children. In the last 10 years, indices of malaria infection in The Gambia have fallen substantially., Methods: We compared temporal trends of childhood malaria and NTS infection in two Gambian locations. In Fajara, on the coast, the incidence of NTS infection at three time points between 1979 and 2005 was compared to the percentage of malaria positive outpatient thick blood films and the percentage of admissions associated with malaria over time. In Basse, in the eastern part of the country, the incidence of NTS infection at three time points between 1989 and 2008 was compared to the prevalence of malaria parasitaemia at four time points between 1992 and 2008., Results: The estimated incidence of NTS infection in Fajara fell from 60 (1979-1984) to 10 (2003-05) cases per 100,000 person years. The proportion of outpatients in Fajara with suspected malaria who were parasitaemic fell from 33% (1999) to 6% (2007) while the proportion of admissions associated with malaria fell from 14.5% (1999) to 5% (2007). In Basse, the estimated incidence of NTS infection fell from 105 (1989-1991) to 29 (2008) cases per 100,000 person years while the prevalence of malaria parasitaemia fell from 45% (1992) to 10% (2008). The incidence of pneumococcal bacteraemia in Fajara and Basse did not fall over the study period., Conclusions: These data support an association between malaria and NTS infection. Reductions in malaria infection may be associated with reduced rates of invasive childhood NTS infection.
Published: 2010
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32. Quantitative detection of Plasmodium falciparum DNA in saliva, blood, and urine.

Author: Nwakanma DC, Gomez-Escobar N, Walther M, Crozier S, Dubovsky F, Malkin E, Locke E, and Conway DJ
Subjects: Adolescent, Adult, Animals, Child, DNA Primers, DNA, Protozoan analysis, DNA, Protozoan urine, Humans, Malaria blood, Malaria urine, Microscopy standards, Middle Aged, Plasmodium falciparum cytology, Polymerase Chain Reaction methods, Polymerase Chain Reaction standards, Reproducibility of Results, DNA, Protozoan blood, Malaria diagnosis, Plasmodium falciparum genetics
Abstract: Background: Current methods for detecting malaria parasites are invasive and associated with poor compliance when repeated sampling is required. New methods to detect and quantify parasites in a less-invasive manner would greatly enhance the potential for longitudinal surveillance in clinical trials., Methods: Saliva, urine, and blood samples from 386 Gambian outpatients with suspected malaria infections were analyzed by nested polymerase chain reaction (nPCR) to detect infection and to evaluate diagnostic accuracy in comparison to expert microscopy. The amount of parasite DNA in malaria-positive samples was estimated using real-time quantitative PCR (qPCR)., Results: Blood parasite density as estimated by qPCR correlated well with parasite counts established by microscopy (p = 0.94; P < .001). qPCR results for saliva had a significant correlation with microscopy counts (p = 0.58; P < .001), whereas qPCR results for urine had a positive but poor correlation with microscopy counts (p = 0.20; P = .117). The mean amounts of parasite DNA quantified in blood were greater than the mean amounts quantified in saliva and urine samples obtained concurrently from the same individual, by approximately 600-fold and approximately 2500-fold, respectively. When nPCR results were compared with microscopy results, nPCR of saliva had a sensitivity of 73% and a specificity of 97%; its sensitivity increased to 82% in samples with a parasite density of > or = 1000 parasites/microL. nPCR of urine had a sensitivity of 32% and a specificity of 98%., Conclusion: Saliva sampling is a promising less-invasive approach for detecting malaria infection.
Published: 2009
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33. Control of Japanese encephalitis--within our grasp?

Author: Solomon T
Subjects: Animals, Culicidae, Disease Outbreaks prevention & control, Encephalitis, Japanese history, Encephalitis, Japanese transmission, History, 20th Century, Humans, Insect Vectors, Insecticides, Urticaria etiology, Encephalitis Virus, Japanese genetics, Encephalitis, Japanese prevention & control, Japanese Encephalitis Vaccines adverse effects, Japanese Encephalitis Vaccines history
Published: 2006
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34. G6b, a novel immunoglobulin superfamily member encoded in the human major histocompatibility complex, interacts with SHP-1 and SHP-2.

Author: de Vet EC, Aguado B, and Campbell RD
Subjects: Amino Acid Sequence, Animals, COS Cells, Glycosylation, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Receptors, Immunologic genetics, Reverse Transcriptase Polymerase Chain Reaction, Vanadates pharmacology, Genes, Immunoglobulin, Major Histocompatibility Complex, Protein Tyrosine Phosphatases metabolism, Receptors, Immunologic metabolism
Abstract: The G6b gene, located in the class III region of the human major histocompatibility complex, has been suggested to encode a putative receptor of the immunoglobulin superfamily. Genomic sequence information was used as a starting point to clone the corresponding cDNA. Reverse transcriptase polymerase chain reaction showed that expression of the gene is restricted to certain hematopoietic cell lines including K562, Molt 4, and Jurkat. Several splice variants were detected, varying only in their C-terminal parts. One of the potential membrane-bound isoforms contained two immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail. Four of the isoforms were expressed as epitope-tagged proteins in the cell lines K562 and COS-7. The two splice isoforms lacking the hydrophobic transmembrane segment were secreted from the cell. Glycosidase treatment of the four recombinant proteins provided evidence for N- and O-glycosylation. Immunofluorescence studies indicated that the spliced isoforms having a transmembrane segment were directed to the cell membrane. The G6b isoform containing two immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail was found to be phosphorylated on tyrosine residues after pervanadate treatment of cells and, subsequently, interacts with the SH2-containing protein-tyrosine phosphatases SHP-1 and SHP-2. Mutagenesis studies showed that phosphorylation of tyrosine 211 is critical for the interaction of G6b with SHP-1 and SHP-2.
Published: 2001
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35. Contrasting cortical and subcortical activations produced by attentional-set shifting and reversal learning in humans.

Author: Rogers RD, Andrews TC, Grasby PM, Brooks DJ, and Robbins TW
Subjects: Adult, Cerebral Cortex blood supply, Cerebrovascular Circulation physiology, Cognition physiology, Humans, Memory physiology, Neuropsychological Tests, Photic Stimulation, Psychomotor Performance physiology, Reversal Learning physiology, Reward, Tomography, Emission-Computed, Attention physiology, Cerebral Cortex physiology, Discrimination Learning physiology
Abstract: Much evidence suggests that lesions of the prefrontal cortex (PFC) produce marked impairments in the ability of subjects to shift cognitive set, as exemplified by performance of the Wisconsin Card Sorting Test (WCST). However, studies with humans and experimental primates have suggested that damage to different regions of PFC induce dissociable impairments in two forms of shift learning implicit in the WCST (that is, extradimensional (ED) shift learning and reversal shift learning), with similar deficits also being apparent after damage to basal ganglia structures, especially the caudate nucleus. In this study, we used the same visual discrimination learning paradigm over multidimensional stimuli, and the H215O positron emission tomography (PET) technique, to examine regional cerebral blood flow (rCBF) changes associated with these subcomponent processes of the WCST. In three conditions, subjects were scanned while acquiring visual discriminations involving either (i) the same stimulus dimension as preceding discriminations (intradimensional (ID) shifts); (ii) different stimulus dimensions from previous discriminations (ED shifts) or (iii) reversed stimulus-reward contingencies (reversal shifts). Additionally, subjects were scanned while responding to already learnt discriminations ('performance baseline'). ED shift learning, relative to ID shift learning, produced activations in prefrontal regions, including left anterior PFC and right dorsolateral PFC (BA 10 and 9&frasl;46). By contrast, reversal learning, relative to ID shift learning, produced activations of the left caudate nucleus. Additionally, compared to reversal and ID shift learning, ED shift learning was associated with relative deactivations in occipito-temporal pathways (for example, BA 17 and 37). These results confirm that, in the context of visual discrimination learning over multidimensional stimuli, the control of an acquired attentional bias or'set', and the control of previously acquired stimulus-reinforcement associations, activate distinct cortical and subcortical neural stations. Moreover, we propose that the PFC may contribute to the control of attentional-set by modulating attentional processes mediated by occipito-temporal pathways.
Published: 2000
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36. Internet information on ion channels: issues of access and organization.

Author: Conley EC
Subjects: Computational Biology, Databases, Factual, Information Storage and Retrieval, Internet, Ion Channels genetics
Published: 1999
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