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68 results on '"Wellcome Trust. UK"'

1. Poly(caprolactone)/Lignin-based 3D-printed Dressings Loaded with a Novel Combination of Bioactive Agents for Wound-healing Applications

Author: Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica, Wellcome Trust. UK., Domínguez Robles, Juan, Cuartas Gómez, Elías, Dynes, Sean, Utomo, Emilia, Anjani, Qonita Kurnia, Detamornrat, Usanee, Donnelly, Ryan F., Moreno Castellanos, Natalia, Larrañeta, Eneko, Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica, Wellcome Trust. UK., Domínguez Robles, Juan, Cuartas Gómez, Elías, Dynes, Sean, Utomo, Emilia, Anjani, Qonita Kurnia, Detamornrat, Usanee, Donnelly, Ryan F., Moreno Castellanos, Natalia, and Larrañeta, Eneko
Abstract: Curcumin (CUR) has been shown to possess significant anti-inflammatory properties and significant wound healing potential. Additionally, lignin (LIG) is a renewable biomacromolecule with well-known antioxidant and antimicrobial properties, which makes this biomacromolecule a good candidate to be included in medical materials, such as wound dressings. Although many of the wound dressings used at present have interesting features, some are limited in terms of antibacterial properties. To address these limitations, in the present work, both CUR and LIG were combined with poly(caprolactone) (PCL), a biocompatible polymer, to obtain dressings with antioxidant and antimicrobial properties for wound healing treatment. Moreover, D-Panthenol (DPA) was included in the composite materials formulation due to its skin regenerative ability by enhancing epidermal differentiation. Semi-solid extrusion (SSE) 3D printing was used to manufacture wound dressings without the use of any solvents. 3D-printed dressings provided a sustained DPA and CUR release for periods of up to 4 and 35 days, respectively. A DPPH (2,2-diphenyl-1-picrylhydrozyl) assay was performed confirming that the presence of LIG and CUR provided antioxidant properties to the 3D-printed dressings. Additionally, these 3D-printed materials showed a marked resistance to adherence of Staphylococcus aureus when compared to the PCL control 3D-printed samples, resulting in substantial reductions of up to 89.9% and 98.9% after incubation periods of 4 h and 24 h respectively. Although, all of the 3D-printed materials were able to provide a supportive environment for cellular attachment, viability and growth, the combination of both bioactive compounds CUR and DPA exhibited the most significant values for cell viability and proliferation. In vivo wound healing study performed in Wistar rats showed that dressings containing these novel two compounds CUR and DPA exhibited marked improvement at any stage of the treatment process.
Published: 2023

2. Killing in the name of: T6SS structure and effector diversity

Author: Universidad de Sevilla. Departamento de Microbiología, Wellcome Trust. UK., Government Department of Business, Energy and Industrial Strategy. UK., Ministerio de Ciencia e Innovación (MICIN). España, Agencia Estatal de Investigación. España, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Allsopp, Luke P., Bernal Guzmán, Patricia, Universidad de Sevilla. Departamento de Microbiología, Wellcome Trust. UK., Government Department of Business, Energy and Industrial Strategy. UK., Ministerio de Ciencia e Innovación (MICIN). España, Agencia Estatal de Investigación. España, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Allsopp, Luke P., and Bernal Guzmán, Patricia
Abstract: The life of bacteria is challenging, to endure bacteria employ a range of mechanisms to optimize their environment, including deploying the type VI secretion system (T6SS). Acting as a bacterial crossbow, this system delivers effectors responsible for subverting host cells, killing competitors and facilitating general secretion to access common goods. Due to its importance, this lethal machine has been evolutionarily maintained, disseminated and specialized to fulfil these vital functions. In fact, T6SS structural clusters are present in over 25% of Gram-negative bacteria, varying in number from one to six different genetic clusters per organism. Since its discovery in 2006, research on the T6SS has rapidly progressed, yielding remarkable breakthroughs. The identification and characterization of novel components of the T6SS, combined with biochemical and structural studies, have revealed fascinating mechanisms governing its assembly, loading, firing and disassembly processes. Recent findings have also demonstrated the efficacy of this system against fungal and Gram-positive cells, expanding its scope. Ongoing research continues to uncover an extensive and expanding repertoire of T6SS effectors, the genuine mediators of T6SS function. These studies are shedding light on new aspects of the biology of prokaryotic and eukaryotic organisms. This review provides a comprehensive overview of the T6SS, highlighting recent discoveries of its structure and the diversity of its effectors. Additionally, it injects a personal perspective on avenues for future research, aiming to deepen our understanding of this combative system.
Published: 2023

3. Xpf suppresses the mutagenic consequences of phagocytosis in Dictyostelium

Author: Universidad de Sevilla. Departamento de Genética, Medical Research Council (MRC). UK, Wellcome Trust. UK, Cancer Research. UK, Pontel, Lucas B., Langenick, Judith, Valle Rosado, Iván, Zhang, Xiao-Yin, Traynor, David, Kay, Robert R., Patel, Ketan J., Universidad de Sevilla. Departamento de Genética, Medical Research Council (MRC). UK, Wellcome Trust. UK, Cancer Research. UK, Pontel, Lucas B., Langenick, Judith, Valle Rosado, Iván, Zhang, Xiao-Yin, Traynor, David, Kay, Robert R., and Patel, Ketan J.
Abstract: As time passes, mutations accumulate in the genomes of all living organisms. These changes promote genetic diversity, but also precipitate ageing and the initiation of cancer. Food is a common source of mutagens, but little is known about how nutritional factors cause lasting genetic changes in the consuming organism. Here, we describe an unusual genetic interaction between DNA repair in the unicellular amoeba Dictyostelium discoideum and its natural bacterial food source. We found that Dictyostelium deficient in the DNA repair nuclease Xpf (xpf−) display a severe and specific growth defect when feeding on bacteria. Despite being proficient in the phagocytosis and digestion of bacteria, over time, xpf− Dictyostelium feeding on bacteria cease to grow and in many instances die. The Xpf nuclease activity is required for sustained growth using a bacterial food source. Furthermore, the ingestion of this food source leads to a striking accumulation of mutations in the genome of xpf− Dictyostelium. This work therefore establishes Dictyostelium as a model genetic system to dissect nutritional genotoxicity, providing insight into how phagocytosis can induce mutagenesis and compromise survival fitness.
Published: 2016

4. Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen

Author: Universidad de Sevilla. Departamento de Genética, Medical Research Council. UK, Instituto de Salud Carlos III. España, Ministerio de Economía y Competitividad (MINECO). España, National Institute of Environmental Health Sciences (NIEHS). U.S., Texas Commission for Environmental Quality. U.S., Wellcome Trust. UK, Pontel, Lucas B., Valle Rosado, Iván, Burgos Barragán, Guillermo, Garaycoechea, Juan I., Yu, Rui, Arends, Mark J., Patel, Ketan J., Universidad de Sevilla. Departamento de Genética, Medical Research Council. UK, Instituto de Salud Carlos III. España, Ministerio de Economía y Competitividad (MINECO). España, National Institute of Environmental Health Sciences (NIEHS). U.S., Texas Commission for Environmental Quality. U.S., Wellcome Trust. UK, Pontel, Lucas B., Valle Rosado, Iván, Burgos Barragán, Guillermo, Garaycoechea, Juan I., Yu, Rui, Arends, Mark J., and Patel, Ketan J.
Abstract: Endogenous formaldehyde is produced by numerous biochemical pathways fundamental to life, and it can crosslink both DNA and proteins. However, the consequences of its accumulation are unclear. Here we show that endogenous formaldehyde is removed by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), and Adh5−/− mice therefore accumulate formaldehyde adducts in DNA. The repair of this damage is mediated by FANCD2, a DNA crosslink repair protein. Adh5−/−Fancd2−/− mice reveal an essential requirement for these protection mechanisms in hematopoietic stem cells (HSCs), leading to their depletion and precipitating bone marrow failure. More widespread formaldehyde-induced DNA damage also causes karyomegaly and dysfunction of hepatocytes and nephrons. Bone marrow transplantation not only rescued hematopoiesis but, surprisingly, also preserved nephron function. Nevertheless, all of these animals eventually developed fatal malignancies. Formaldehyde is therefore an important source of endogenous DNA damage that is counteracted in mammals by a conserved protection mechanism.
Published: 2015

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

Author: Fulvio Ricceri, Joseph A. Rothwell, Amanda J. Cross, Graham G. Giles, Elisabete Weiderpass, Tilman Kühn, Emily Sonestedt, Yi Yang, Rudolf Kaaks, Valeria Pala, Anna Karakatsani, Dallas R. English, Rosario Tumino, Pilar Amiano, Antonia Trichopoulou, John L. Hopper, Leila Lujan-Barroso, Allison M. Hodge, Bengt Wallner, Ruth C. Travis, María Dolores López, Anne Tjønneland, Hazel M. Mitchell, Kostas Tsilidis, Domenico Palli, Harindra Jayasekara, Elio Riboli, Antonio Agudo, Robin Room, Heiner Boeing, Eva Ardanaz, Bas Bueno-de-Mesquita, Torkjel M. Sandanger, Pietro Ferrari, Robert J. MacInnis, Susana Merino, Andrew Haydon, Eleni Peppa, Marie-Christine Boutron-Ruault, Salvatore Panico, María José Sánchez, Marc J. Gunter, Hanna Sternby, Roger L. Milne, Gianluca Severi, Ana Lucia Mayen-Chacon, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), VicHealth Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT Medical Research Council, MRC: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1 British Heart Foundation, BHF Department of Health and Social Care, DH Cancer Research UK, CRUK: C570/ A16491, C8221/A19170, C864/A14136 World Cancer Research Fund, WCRF Food Standards Agency, FSA Stroke Association European Commission, EC National Health and Medical Research Council, NHMRC: 1074383, 209057, 396414, GNT1163120 Cancer Council Victoria Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Stavros Niarchos Foundation, SNF Vetenskapsrådet, VR Consiglio Nazionale delle Ricerche, CNR Ministère des Affaires Sociales et de la Santé: GR‐IARC‐2003‐09‐12‐01 Instituto de Salud Carlos III, ISCIII Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Rijksinstituut voor Volksgezondheid en Milieu, RIVM Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN Ministry of Health and Social Solidarity, Greece Foundation for Alcohol Research and Education, FARE Hellenic Health Foundation, HHF, Australian National Health and Medical Research Council, Grant/Award Numbers: 1074383, 209057, 396414, GNT1163120, Cancer Council Victoria (Australia), Cancer Research UK, Grant/Award Numbers: C570/ A16491, C8221/A19170, C864/A14136, Catalan Institute of Oncology ‐ ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission (Directorate General for Health and Consumer Affairs), Foundation for Alcohol Research and Education (Australia), French Ministry of Health, Grant/Award Number: Grant GR‐IARC‐2003‐09‐12‐01, Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Santé et de la Recherche Médicale (France), Italian Association for Research on Cancer and the National Research Council (Italy), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, Medical Research Council (UK), Grant/Award Numbers: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1, Mutuelle Générale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK), Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), the Federal Ministry of Education and Research (Germany), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), the Institut Gustave Roussy Funding information, We thank Carine Biessy and Bertrand Hemon for their technical contribution to EPIC data used in this work. We are also grateful to all the EPIC participants who have been part of the project, and to the many members of the study teams who enabled this research. We thank the original MCCS investigators and the diligent team, who recruited the participants and who continue working on follow‐up, for their contribution. We also express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. This work was supported by the Direction Générale de la Santé (French Ministry of Health, Grant GR‐IARC‐2003‐09‐12‐01), by the European Commission (Directorate General for Health and Consumer Affairs) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), the Ligue Contre le Cancer, the Institut Gustave Roussy, the Mutuelle Générale de l'Education Nationale and the Institut National de la Santé et de la Recherche Médicale (France), the Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, the World Cancer Research Fund and Statistics Netherlands (the Netherlands), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study, the Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology ‐ ICO (Spain), the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), Cancer Research UK (C864/A14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/N003284/1 and MC‐UU_12015/1 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, United Kingdom), the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK). MCCS cohort recruitment was funded by Cancer Council Victoria ( https://www.cancervic.org.au/ ) and VicHealth ( https://www.vichealth.vic.gov.au/ ). The MCCS was further supported by Australian National Health and Medical Research Council (NHMRC) ( https://www.nhmrc.gov.au/ ) grants 209057, 396414 and 1074383, and ongoing follow‐up and data management has been funded by Cancer Council Victoria since 1995. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. Harindra Jayasekara is supported by NHMRC grant GNT1163120. John L. Hopper is a NHMRC Senior Principal Research Fellow. Yi Yang is supported by a Melbourne Research Scholarship from the University of Melbourne. Robin Room's position was funded by the Foundation for Alcohol Research and Education. The sponsors had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and and decision to submit the manuscript for publication.
Subjects: Male, Cancer Research, Gastroenterology, 0302 clinical medicine, Prospective Studies, Stomach cancer, Prospective cohort study, stomach cancer, biology, Stomach, Incidence, Hazard ratio, Smoking, cardia cancer, Cardia cancer, Middle Aged, Lifetime alcohol intake, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, medicine.anatomical_structure, Oncology, Drinking of alcoholic beverages, 030220 oncology & carcinogenesis, Consum d'alcohol, Female, Life Sciences & Biomedicine, Cohort study, Adult, medicine.medical_specialty, Alcohol Drinking, [SDV.CAN]Life Sciences [q-bio]/Cancer, Helicobacter Infections, noncardia cancer, 03 medical and health sciences, Stomach Neoplasms, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Aged, Science & Technology, Helicobacter pylori, EPIC, lifetime alcohol intake, MCCS, business.industry, Càncer d'estómac, Kirurgi, Australia, Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Noncardia cancer, medicine.disease, biology.organism_classification, Surgery, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences., National Health and Medical Research Council of Australia 1074383 209057 396414 GNT1163120, Canadian Institutes of Health Research (CIHR) Cancer Council Victoria, Cancer Research UK C570/A16491 C8221/A19170 C864/A14136, Catalan Institute of Oncology - ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission European Commission Joint Research Centre, Foundation for Alcohol Research and Education (Australia), French Ministry of Health GR-IARC-2003-09-12-01, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Junta de Andalucía, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Sante et de la Recherche Medicale (Inserm), Consiglio Nazionale delle Ricerche (CNR), Associazione Italiana per la Ricerca sul Cancro (AIRC), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, Netherlands Organization for Scientific Research (NWO), UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MC-UU_12015/1 MR/M012190/1 MR/N003284/, Mutuelle Generale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association (UK), British Heart Foundation, Department of Health (UK), Food Standards Agency (UK), Wellcome Trust, Swedish Cancer Society, Swedish Scientific Council (Sweden), Regional Government of Skane (Sweden), Federal Ministry of Education & Research (BMBF), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), Institut Gustave Roussy
Published: 2021

6. The estimated burden of scrub typhus in Thailand from national surveillance data (2003-2018)

Author: Tri Wangrangsimakul, Supalert Nedsuwan, Ivo Elliott, Nicholas P. J. Day, Soawapak Hinjoy, Serge Morand, Kittipong Chaisiri, Rawadee Kumlert, Mahidol Oxford Tropical Medicine Research Unit (MORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford [Oxford]-University of Oxford [Oxford], Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, Chiangrai Prachanukroh Hospital, Ministry of Public Health [Thailand], Mahidol University [Bangkok], Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Kasetsart University - KU (THAILAND), Kasetsart University (KU), TW and NPJD are funded by the Wellcome Trust, UK, as part of the MORU Tropical Health Network institutional funding support. IE is funded by the Wellcome Trust, UK, as part of a Clinical Training Fellowship (grant number 105731/Z/14/Z). SM, RK and KC are supported by the French ANR FutureHealthSEA (ANR-17-CE35-0003-02) 'Predictive scenarios of health in Southeast Asia: linking land use and climate changes to infectious diseases'., ANR-17-CE35-0003,FutureHealthSEA,Scénarios de la santé en Asie du Sud-Est: changements d'utilisation des terres, changement climatique et maladies infectieuses(2017), Department of Helminthology, Faculty of Tropical Medicine, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), ANR: ANR17-CE35-0003-01,FutureHealthSEA, University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of Oxford-University of Oxford, and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE)
Subjects: Bacterial Diseases, 0301 basic medicine, Atmospheric Science, Epidemiology, Rain, [SDV]Life Sciences [q-bio], RC955-962, Scrub typhus, Forests, Geographical Locations, 0302 clinical medicine, Cost of Illness, Risk Factors, Arctic medicine. Tropical medicine, Medicine and Health Sciences, Public and Occupational Health, Child, Aged, 80 and over, Disease surveillance, education.field_of_study, Ecology, Incidence, Population size, Incidence (epidemiology), Middle Aged, Thailand, Terrestrial Environments, 3. Good health, Professions, Infectious Diseases, Geography, Child, Preschool, Epidemiological Monitoring, Agricultural Workers, Topography, Medical, Public aspects of medicine, RA1-1270, Research Article, Adult, medicine.medical_specialty, Asia, Adolescent, 030231 tropical medicine, Population, Disease Surveillance, Ecosystems, Typhus, Young Adult, 03 medical and health sciences, Meteorology, medicine, Humans, education, Disease burden, Aged, Ecology and Environmental Sciences, Public Health, Environmental and Occupational Health, Infant, Biology and Life Sciences, Tropics, medicine.disease, bacterial infections and mycoses, 030104 developmental biology, Scrub Typhus, People and Places, Earth Sciences, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Population Groupings, Demography
Abstract: Background Scrub typhus is a major cause of acute febrile illness in the tropics and is endemic over large areas of the Asia Pacific region. The national and global burden of scrub typhus remains unclear due to limited data and difficulties surrounding diagnosis. Methodology/Principal findings Scrub typhus reporting data from 2003–2018 were collected from the Thai national disease surveillance system. Additional information including the district, sub-district and village of residence, population, geographical, meteorological and satellite imagery data were also collected for Chiangrai, the province with the highest number of reported cases from 2003–2018. From 2003–2018, 103,345 cases of scrub typhus were reported with the number of reported cases increasing substantially over the observed period. There were more men than women, with agricultural workers the main occupational group affected. The majority of cases occurred in the 15–64 year old age group (72,144/99,543, 72%). Disease burden was greatest in the northern region, accounting for 53% of the total reported cases per year (mean). In the northern region, five provinces–Chiangrai, Chiangmai, Tak, Nan and Mae Hong Son–accounted for 84% (46,927/55,872) of the total cases from the northern region or 45% (46,927/103,345) of cases nationally. The majority of cases occurred from June to November but seasonality was less marked in the southern region. In Chiangrai province, elevation, rainfall, temperature, population size, habitat complexity and diversity of land cover contributed to scrub typhus incidence. Interpretation The burden of scrub typhus in Thailand is high with disease incidence rising significantly over the last two decades. However, disease burden is not uniform with northern provinces particularly affected. Agricultural activity along with geographical, meteorological and land cover factors are likely to contribute to disease incidence. Our report, along with existing epidemiological data, suggests that scrub typhus is the most clinically important rickettsial disease globally., Author summary Scrub typhus, caused by the bacterium Orientia tsutsugamushi, is a major cause of fever in tropical and subtropical Asia. Symptoms can be similar to other common infections such as malaria, dengue, leptospirosis or typhoid, making it difficult to diagnose. Laboratory tests to diagnose scrub typhus are often unavailable, inaccurate, impractical, or too costly. Consequently, the true burden of scrub typhus disease remains unknown. Here, we collected data on the number of reported cases of scrub typhus in Thailand for 2003–2018 from the national surveillance system. There were 103,345 cases reported with incidence rising significantly over the study period. More men than women were affected, agricultural workers were the main occupational group (45%) and most cases (72%) were in adults of working age. The disease was seasonal with the cases mainly occurring during the rainy season from June to November. Five northern provinces were particularly affected with Chiangrai being the province with the highest number of cases. In Chiangrai, agricultural activity, elevation, rainfall, temperature and land cover factors contribute to disease burden. These results improve our understanding of the distribution and burden of scrub typhus in Thailand and help to identify factors that may contribute to disease incidence.
Published: 2020

7. Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort

Author: Magritt Brustad, Veronika Fedirko, Marc J. Gunter, Anja Olsen, Antonia Trichopoulou, Geneviève Nicolas, Anna Karakatsani, Veronique Chajes, Gianluca Severi, Elom K. Aglago, Eva Ardanaz, Aurora Perez-Cornago, Kim Overvad, Cristina Lasheras, Salvatore Panico, Verena Katzke, Bas Bueno-de-Mesquita, José María Huerta, Neil Murphy, Christina C. Dahm, Maria Wennberg, Teresa Norat, Bodil Ohlsson, Elisabete Weiderpass, Antonio Agudo, Heather Ward, Anne Tjønneland, Valeria Pala, Tilman Kühn, Bethany Van Guelpen, Guri Skeie, Rosario Tumino, María José Sánchez, A. M. May, Corinne Casagrande, Jeroen W.G. Derksen, Marie-Christine Boutron-Ruault, Elio Riboli, Agnès Fournier, Sophie Hellstrand, Inge Huybrechts, Georgia Martimianaki, Alessio Naccarati, Tobias Pischon, Amanda J. Cross, Pilar Amiano, Domenico Palli, 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), RD06/0020 6236 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT: C570/A16491, C8221/A19170, MR/M012190/1 National Research Council, NRC Medical Research Council, MRC British Heart Foundation, BHF Cancer Research UK, CRUK World Cancer Research Fund, WCRF: WCRF 2013/1002 Food Standards Agency, FSA Stroke Association European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Stavros Niarchos Foundation, SNF Instituto de Salud Carlos III, ISCIII Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Associazione Iblea per la Ricerca Epidemiologica, AIRE Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN Ministry of Health and Social Solidarity, Greece Fondation Gustave Roussy Hellenic Health Foundation, HHF, Funding Supported by a grant from the World Cancer Research Fund ( WCRF ) to Marc Gunter (grant number: WCRF 2013/1002 ). 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 Générale de l'Education Nationale , and Institut National de la Santé et de la Recherche Médicale ( INSERM ) (France), German Cancer Aid , German Cancer Research Center ( DKFZ ), and Federal Ministry of Education and Research ( BMBF ) (Germany), Hellenic Health Foundation , Stavros Niarchos Foundation , and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer ( AIRC ), National Research Council , and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu ( AVIS ) Ragusa, Sicilian Government (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), Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucía , Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública and Instituto de Salud Carlos II ( 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 , Stroke Association , British Heart Foundation , Department of Health , Food Standards Agency , the Wellcome Trust (UK), Cancer Research UK ( 14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)., Funding Supported by a grant from the World Cancer Research Fund (WCRF) to Marc Gunter (grant number: WCRF 2013/1002). 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 G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), and Federal Ministry of Education and Research (BMBF) (Germany), Hellenic Health Foundation, Stavros Niarchos Foundation, and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, Sicilian Government (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), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigaci?n Biom?dica en Red en Epidemiolog?a y Salud P?blica and Instituto de Salud Carlos II (ISCIII RETIC) (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (UK), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Subjects: Colorectal cancer, [SDV]Life Sciences [q-bio], Àcids grassos insaturats, Physiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Càncer colorectal, Fatty Acids, Omega-3, Medicine, Animals, Humans, Prospective Studies, 2. Zero hunger, chemistry.chemical_classification, Unsaturated fatty acids, Epidemiologic, Gastroenterology & Hepatology, Hepatology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, business.industry, Gastroenterology, Fishes, 1103 Clinical Sciences, Odds ratio, medicine.disease, Eicosapentaenoic acid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Diet, chemistry, Seafood, Docosahexaenoic acid, 030220 oncology & carcinogenesis, Omega 3, Cohort, Colonic Neoplasms, Tumorigenesis, 030211 gastroenterology & hepatology, Docosapentaenoic acid, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Polyunsaturated fatty acid
Abstract: Background & Aims There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
Published: 2020

8. Human plague: An old scourge that needs new answers

Author: Steven R. Belmain, Minoarisoa Rajerison, Oswaldo Cabanillas, Nils Chr. Stenseth, Peter Horby, Christian E. Demeure, Sandra Telfer, Xavier Vallès, Beza Ramasindrazana, Ratsitorahina M, Inès Vigan-Womas, Voahangy Andrianaivoarimanana, Pablo Tortosa, Yazdan Yazdanpanah, Laurence Baril, Javier Pizarro-Cerdá, David M. Wagner, Arnaud Fontanet, Eric D'Ortenzio, Jane Lynda Deuve, Romain Girod, Paul S. Mead, Holger C. Scholz, B. Joseph Hinnebusch, Guia Carrara, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Tsinghua University [Beijing] (THU), Yersinia, Institut Pasteur [Paris] (IP), University of Oxford, Centers for Disease Control and Prevention, Oficina General de Epidemiologia [Lima, Peru], Ministerio de Salud de Perú [Lima], Unité Peste - Plague Unit [Antananarivo, Madagascar], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Bundeswehr Institute of Microbiology, Unité d'Entomologie Médicale [Antananarivo, Madagascar] (IPM), Rocky Mountain Laboratories, Unité d'immunologie des maladies infectieuses [Antananarivo, Madagascar] (IPM), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Northern Arizona University [Flagstaff], University of Aberdeen, REACTing, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), Natural Resources Institute [Chatham], University of Greenwich, The workshop meeting where the contents of this article were developed was hosted by the Institut Pasteur (Paris, France) with financial and organizational support from the Department of International Affairs, the Emerging Disease Epidemiology Unit, the Mathematical Modelling of Infectious Diseases Unit and REACTing-Inserm. Oswaldo Cabanillas’s travel was financed by the Department of International Affairs at the Institut Pasteur (Paris, France). Travel costs for Laurence Baril and Maherisoa Ratsitorahina were financially supported by USAID (Grant n° AID-687-G-13-00003), and for Voahangy Andrianaivoarimanan and Minoarisoa Rajerison by Northern Arizona University (through HDTRA1-11-16-BRCWMD-BAA). Attendance of Steven Belmain was supported by the African Union (Grant AURGII/1/006/2016). Travel and accommodation for Feno Rakotoarimanana, and accommodation for Romain Girod, Beza Ramasindrazana, Voahangy Andrianaivoarimanana, and Minoarisoa Rajerison, were financially supported by the Wellcome Trust/UK Department for International Development (Grant 211309/Z/18/Z) and REACTing-Inserm. All other participants financially supported travel and accommodation through their own institutional funding. The preparation and editing of the manuscript was financially supported by Wellcome Trust/UK Department for International Development (Grant 211309/Z/18/Z)., List of the other participants to the Plague Workshop (by alphabetical order): Fabrice Biot, Institut de Recherche Biomédicale des Armées, France, Carine Brouat, IRD, France, Simon Cauchemez, Infectious Diseases Mathematical Modelling Unit, Institut Pasteur, Paris, France, Rob Cohen, USAID, Washington, DC, USA, Koussay Dellagy, Department of International Affairs, Institut Pasteur, Paris, France, Nathalie Denoyes, Institut Pasteur, Paris, France, Hebert Echenique-Rivera, Yersinia Unit, Institut Pasteur, Paris, France, Florence Fouque, TDR, WHO, Lyon, France, Stephen Francesconi, Defence Threat Reduction Agency, Washington, DC, USA, Anna Funk, Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France, Finnian Hanrahan, DG Research, European Commission, Brussels, Belgium, Mireille Harimalala, Medical Entomology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Nadia Khellef, Institut Pasteur, Paris, France, Anne-Sophie Le Guern, Yersinia Unit, Institut Pasteur, Paris, France, Nadine Lemaitre, Bacteriology Department, CHU Lille, France, Jean-Claude Manuguerra, CIBU, Institut Pasteur, Paris, France, Jodie Mac Vernon, GLoPID-R, University of Melbourne, Australia, Serge Morand, CIRAD, Bangkok, Thailand, Birgit Nikolay, Infectious Diseases Mathematical Modelling Unit, Institut Pasteur, Paris, France, Juliette Paireau, Infectious Diseases Mathematical Modelling Unit, Institut Pasteur, Paris, France, Anna Paoletti, Ministry for Higher Education and Research, Paris, France, Feno MJ Rakotoarimanana, Epidemiology and Clinical Research Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Zely Randriamanatany, Ministry of Public Health, Antananarivo, Madagascar, Laurent Raskine, Fondation Mérieux, Stéphanie Simon, CEA de Saclay, France, Cathy Roth, Department for International Development, London, UK, Alex Salam, Epidemic Diseases Research Group Oxford (ERGO), Nuffield Department of Medicine, University of Oxford, Oxford, UK, Florent Sebbane, Institut Pasteur de Lille, France, Christophe Shako, Department of Disease Control, Ministry of Health, Democratic Republic of Congo, Quirine Ten Bosch, Epidemiology and Clinical Research Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar, Kathleen Victoir, Department of International Affairs, Institut Pasteur, Paris, France., Demeure, Christian E., Institut Pasteur [Paris], University of Oxford [Oxford], Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and Centre National de la Recherche Scientifique (CNRS)-IRD-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR)
Subjects: Epidemiology, RC955-962, MESH: Rodentia, Review, Pathology and Laboratory Medicine, Disease Outbreaks, Medical Conditions, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Arctic medicine. Tropical medicine, Case fatality rate, Public and Occupational Health, MESH: Animals, media_common, Mammals, Eukaryota, Neglected Diseases, Bacterial Pathogens, 3. Good health, One Health, Geography, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Medical Microbiology, Public aspects of medicine, S1, Yersinia Pestis, media_common.quotation_subject, Immunology, MESH: Yersinia pestis, Rodentia, Microbiology, 03 medical and health sciences, Vaccine Development, Madagascar, Humans, Microbial Pathogens, MESH: Disease Reservoirs, MESH: Humans, Bacteria, Organisms, Public Health, Environmental and Occupational Health, Biology and Life Sciences, Outbreak, medicine.disease, Invertebrates, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Insect Vectors, 030104 developmental biology, Vector (epidemiology), Africa, Preventive Medicine, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Bacterial Diseases, 0301 basic medicine, Economic growth, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Geographical Locations, MESH: Madagascar, Medicine and Health Sciences, MESH: Disease Outbreaks, biology, Vaccination and Immunization, Yersinia, Insects, Infectious Diseases, Fleas, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Vertebrates, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Siphonaptera, Psychological resilience, RA1-1270, Pathogens, Pneumonic plague, Arthropoda, Pneumonic Plagues, 030231 tropical medicine, MESH: Insect Vectors, Plague (disease), Rodents, MESH: Plague, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, medicine, Animals, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Disease Reservoirs, Plague, MESH: Siphonaptera, biology.organism_classification, Plagues, Yersinia pestis, 13. Climate action, People and Places, Amniotes, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Neglected Diseases, Zoology, Entomology
Abstract: Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague’s resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a “One Health” approach., Author summary The historical aspect of plague makes for fascinating reading, due to its capacity to disrupt human society and its socioeconomic and cultural impacts throughout human history. We argue that the Madagascar outbreak in 2017 is a tipping point in human plague epidemiology and a call to elevate research priorities on plague as a matter of some urgency. In contrast with what occurred with the Ebola virus disease crisis in West Africa between 2013 and 2015 and the new coronaviruses (the emergence of severe acute respiratory syndrome coronavirus [SARS-CoV] and Middle East respiratory syndrome coronavirus [MERS-CoV] as early warnings of the current severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] pandemic), we have an opportunity to act preventively and enable evidence-based measures to avoid major health crises due to plague outbreaks in the near future.
Published: 2020

9. Poly(caprolactone)/lignin-based 3D-printed dressings loaded with a novel combination of bioactive agents for wound-healing applications

Author: Juan Domínguez-Robles, Elias Cuartas-Gómez, Sean Dynes, Emilia Utomo, Qonita Kurnia Anjani, Usanee Detamornrat, Ryan F. Donnelly, Natalia Moreno-Castellanos, Eneko Larrañeta, Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica, and Wellcome Trust. UK.
Subjects: Curcumin, Renewable Energy, Sustainability and the Environment, Antimicrobial dressings, D-Panthenol, General Materials Science, 3D printing, SDG 7 - Affordable and Clean Energy, Bioactive materials, Waste Management and Disposal, Industrial and Manufacturing Engineering, Sustained release
Abstract: Curcumin (CUR) has been shown to possess significant anti-inflammatory properties and significant wound healing potential. Additionally, lignin (LIG) is a renewable biomacromolecule with well-known antioxidant and antimicrobial properties, which makes this biomacromolecule a good candidate to be included in medical materials, such as wound dressings. Although many of the wound dressings used at present have interesting features, some are limited in terms of antibacterial properties. To address these limitations, in the present work, both CUR and LIG were combined with poly(caprolactone) (PCL), a biocompatible polymer, to obtain dressings with antioxidant and antimicrobial properties for wound healing treatment. Moreover, D-Panthenol (DPA) was included in the composite materials formulation due to its skin regenerative ability by enhancing epidermal differentiation. Semi-solid extrusion (SSE) 3D printing was used to manufacture wound dressings without the use of any solvents. 3D-printed dressings provided a sustained DPA and CUR release for periods of up to 4 and 35 days, respectively. A DPPH (2,2-diphenyl-1-picrylhydrozyl) assay was performed confirming that the presence of LIG and CUR provided antioxidant properties to the 3D-printed dressings. Additionally, these 3D-printed materials showed a marked resistance to adherence of Staphylococcus aureus when compared to the PCL control 3D-printed samples, resulting in substantial reductions of up to 89.9% and 98.9% after incubation periods of 4 h and 24 h respectively. Although, all of the 3D-printed materials were able to provide a supportive environment for cellular attachment, viability and growth, the combination of both bioactive compounds CUR and DPA exhibited the most significant values for cell viability and proliferation. In vivo wound healing study performed in Wistar rats showed that dressings containing these novel two compounds CUR and DPA exhibited marked improvement at any stage of the treatment process. Finally, histological examination revealed that dressings loaded with CUR and DPA also showed the best outcomes for all the evaluated parameters: (i) epithelisation, (ii) inflammatory reaction, (iii) proliferation rate of fibroblast and (iv) neoangiogenesis. Wellcome Trust UNS40040
Published: 2023

10. Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Author: Amanda J. Cross, Petra H.M. Peeters, Pietro Ferrari, Françoise Clavel-Chapelon, Salvatore Panico, Augustin Scalbert, Anja Olsen, José María Huerta, Paolo Vineis, Gianluca Severi, Eva Ardanaz, H. Bas Bueno-de-Mesquita, Ruth C. Travis, Bénédicte Elena-Herrmann, Nicholas J. Wareham, Pagona Lagiou, Talita Duarte-Salles, Christina Bamia, Anne Tjønneland, Rudolf Kaaks, Bodil Ohlsson, Magdalena Stepien, Antonio Agudo, Krasimira Aleksandrova, Heiner Boeing, Isabelle Romieu, Kay-Tee Khaw, Veronika Fedirko, Domenico Palli, Julie A. Schmidt, Anne Fages, Rosario Tumino, Valeria Pala, Anna Floegel, Dimitrios Trichopoulos, Miren Dorronsoro, Marc J. Gunter, Klas Sjöberg, Clément Pontoizeau, Marie-Christine Boutron-Ruault, Elisabete Weiderpass, Tilman Kühn, Elio Riboli, Mazda Jenab, Antonia Trichopoulou, Esther Molina-Montes, Fages, Anne, Duarte Salles, Talita, Stepien, Magdalena, Ferrari, Pietro, Fedirko, Veronika, Pontoizeau, Clément, Trichopoulou, Antonia, Aleksandrova, Krasimira, Tjønneland, Anne, Olsen, Anja, Clavel Chapelon, Françoise, Boutron Ruault, Marie Christine, Severi, Gianluca, Kaaks, Rudolf, Kuhn, Tilman, Floegel, Anna, Boeing, Heiner, Lagiou, Pagona, Bamia, Christina, Trichopoulos, Dimitrio, Palli, Domenico, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Bueno de Mesquita, H. Ba, Peeters, Petra H, Weiderpass, Elisabete, Agudo, Antonio, Molina Montes, Esther, Huerta, José María, Ardanaz, Eva, Dorronsoro, Miren, Sjöberg, Kla, Ohlsson, Bodil, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C, Schmidt, Julie A, Cross, Amanda, Gunter, Marc, Riboli, Elio, Scalbert, Augustin, Romieu, Isabelle, Elena Herrmann, Benedicte, Jenab, Mazda, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), ISA - Centre de RMN à très hauts champs, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), parent, International Agency for Cancer Research (IACR), Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Epidemiology, Deutsches Institut für Ernahrungsforschung Potsdam-Rehbrücke (DIFE), Institute of Cancer Epidemiology, Danish Cancer Society, Department of Food Science [Copenhagen] (UCPH FOOD), Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Gustave Roussy (IGR), Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Thermo Fisher Scientific, Thermo Fisher Scientific Inc., German Institute of Human Nutrition Potsdam-Rehbruecke, German Institute of Human Nutrition, Harvard School of Public Health, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Nutritional Epidemiology Unit, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-IRCCS Foundation, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Julius Center for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Community Medicine, University of Tromsø (UiT), Department of Research, Cancer Registry of Norway-Samfundet Folkhälsan, Helsinki, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet [Stockholm], Institut Català d'Oncologia, Spain Institute of Oncology, Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), Danish Cancer Society Research Center, Murcia Regional Health Council, Sección de Epidemiología de Enfermedades No Transmisibles, Navarre Public Health Institute, Epidemiology and Health Information, Public Health Department of Gipuzkoa, Volvo, VOLVO-VOLVO, Skane University Hospital [Lund], University of Cambridge School of Clinical Medicine, MRC epidemiology Unit, Addenbrooke's Hospital, Cancer Epidemiology Unit, University of Oxford [Oxford], Laboratoire d'informatique Fondamentale de Marseille (LIF), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Department of Chemistry, University of Cambridge [UK] (CAM), Nutrition and Metabolism Section, Biomarkers Group, Nutrition and Metabolism Section, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA, grant number 2009-139, PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. 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 Generale de l'Education Nationale, and Institut National de la Sante et de la Recherche Medicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (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), European Research Council (ERC, grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and 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, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Centre Européen de Résonance Magnétique Nucléaire à Très Hauts Champs (CERMNTHC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 'Civile M. P. Arezzo' Hospital, Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), [Fages,A, Pontoizeau,C, Elena-Herrmann,B] Institut des Sciences Analytiques, Centre de RMN à très hauts champs, CNRS/ENS Lyon/UCB Lyon-1, Université de Lyon, Villeurbanne, France. [Duarte-Salles,T, Stepien,M, Ferrari,P, Scalbert,A, Romieu,I, Jenab,M] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Aleksandrova,K, Floegel,A, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Clavel-Chapelon,F, Boutron-Ruault,M] 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. [Severi,G, Vineis,P] Human Genetics Foundation (HuGeF), Torino, Italy. [Kaaks,R, Kuhn,T] Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Lagiou,P, Bamia,C] Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Palli,D] 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, Milano, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P, Peeters,PH] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [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. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Bueno-de-Mesquita,HB, Cross,A, Gunter,M, RibolI,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Peeters,PH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Agudo,A] Unit of Nutrition and Cancer, IDIBELL, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain. [Molina-Montes,E] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Molina-Montes,E, Huerta,JM, Ardanaz, E] CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarre Public Health Institute, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Sjöberg,K] Department of Clinical Sciences, Lund University, Malmö, Sweden. Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden. [Ohlsson,B] Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,N] MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. [Travis,RC, Schmidt,JA] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., This work was supported by the French National Cancer Institute (L’Institut National du Cancer, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and 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, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication, Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), 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), Università degli studi di Torino = University of Turin (UNITO), University of Naples Federico II = Università degli studi di Napoli Federico II, and University of Oxford
Subjects: Oncology, Male, Neoplasias Hepáticas, Cirrhosis, Magnetic Resonance Spectroscopy, Epidemiology, Hepatocellular carcinoma, Nuclear magnetic resonance, Cohort Studies, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Hepatocellular [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Prospective Studies, Prospective cohort study, CIRRHOSIS, Early Detection of Cancer, Medicine(all), 0303 health sciences, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms [Medical Subject Headings], Liver Neoplasms, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics [Medical Subject Headings], Metabolómica, Estudios Prospectivos, General Medicine, Middle Aged, CANCER, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Liver Neoplasm, 030220 oncology & carcinogenesis, Female, Liver cancer, Case-Control Studie, Life Sciences & Biomedicine, Metabolomics, Carcinoma Hepatocelular, Research Article, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, 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], TISSUE METABOLOMICS, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], Metabolomic, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus [Medical Subject Headings], Càncer de fetge, 03 medical and health sciences, Medicine, General & Internal, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, IDENTIFY SERUM BIOMARKERS, Internal medicine, General & Internal Medicine, medicine, Humans, Obesity, Epidemiologia, 030304 developmental biology, FATTY LIVER-DISEASE, Aged, Hepatitis, Science & Technology, business.industry, Case-control study, METABONOMICS, Cancer, MASS-SPECTROMETRY, medicine.disease, NMR, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Prospective Studie, Case-Control Studies, DISCOVERY, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Immunology, RISK-FACTORS, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer., This work was supported by the French National Cancer Institute (L’Institut National du Cancer; INCA; grant number 2009-139; PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. 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 Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (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); European Research Council (ERC; grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and 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, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK).
Published: 2015

11. The legacy of ZikaPLAN

Author: Annelies Wilder-Smith, Elizabeth B. Brickley, Ricardo Arraes de Alencar Ximenes, Demócrito de Barros Miranda-Filho, Celina Maria Turchi Martelli, Tom Solomon, Bart C. Jacobs, Carlos A. Pardo, Lyda Osorio, Beatriz Parra, Suzannah Lant, Hugh J Willison, Sonja Leonhard, Lance Turtle, Maria Lúcia Brito Ferreira, Rafael Freitas de Oliveira Franca, Louis Lambrechts, Johan Neyts, Suzanne Kaptein, Rosanna Peeling, Deborah Boeras, James Logan, Helen Dolk, Ieda M Orioli, Andreas Neumayr, Trudie Lang, Bonny Baker, Eduardo Massad, Raman Preet, Umeå University, University of Heidelberg, Medical Faculty, London School of Hygiene and Tropical Medicine (LSHTM), Universidade Federal de Pernambuco [Recife] (UFPE), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), University of Liverpool, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Johns Hopkins University School of Medicine [Baltimore], Universidad del Valle [Cali] (Univalle), University of Glasgow, Erasmus University Rotterdam, Hospital da Restauração, Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Global Health Impact Group, University of Ulster, Federal University of Rio de Janeiro, Swiss Tropical and Public Health Institute [Basel], University of Oxford, Universidade de São Paulo = University of São Paulo (USP), This project, ZikaPLAN is funded by the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. h2020 health 734584. Some authors have received additional research funding. The Microencephaly Epidemic Research Group (MERG) has received additional funding from Wellcome Trust UK, Department for International Development UK, Medical Research Council UK, the Brazilian funding through CNPq, Secretaria de Vigilância de Saúde (SVS), and Fundação do Amparo a Ciência e Tecnologia (FACEPE). LT is supported by a Wellcome Trust fellowship [205228/Z/16/Z]. The Latin American Congenital Malformations Network (ReLAMC) group has received additional Brazilian funding through DECIT, CNPq (440614/2016-3), and CAPES (88887.130724/2016-00, 88887.130724/2016-00), and European Project: 734584,ZikaPLAN
Subjects: Adult, congenital Zika syndrome, encephalitis, birth defect, MESH: Zika Virus, MESH: Global Health, research capacity building, Global Health, MESH: Zika Virus Infection, Zika, epidemic preparedness, SDG 3 - Good Health and Well-being, MESH: Child, Humans, microcephaly, European Commission, Child, MESH: Humans, Zika Virus Infection, Health Policy, Public Health, Environmental and Occupational Health, Guillain-Barré Syndrome, MESH: Adult, Public Health, Global Health, Social Medicine and Epidemiology, Zika Virus, sustainability, Infectious Disease Transmission, Vertical, MESH: Infectious Disease Transmission, Vertical, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Brazil, Brazil
Abstract: Global health research partnerships with institutions from high-income countries and low- and middle-income countries are one of the European Commission's flagship programmes. Here, we report on the ZikaPLAN research consortium funded by the European Commission with the primary goal of addressing the urgent knowledge gaps related to the Zika epidemic and the secondary goal of building up research capacity and establishing a Latin American-European research network for emerging vector-borne diseases. Five years of collaborative research effort have led to a better understanding of the full clinical spectrum of congenital Zika syndrome in children and the neurological complications of Zika virus infections in adults and helped explore the origins and trajectory of Zika virus transmission. Individual-level data from ZikaPLAN`s cohort studies were shared for joint analyses as part of the Zika Brazilian Cohorts Consortium, the European Commission-funded Zika Cohorts Vertical Transmission Study Group, and the World Health Organization-led Zika Virus Individual Participant Data Consortium. Furthermore, the legacy of ZikaPLAN includes new tools for birth defect surveillance and a Latin American birth defect surveillance network, an enhanced Guillain-Barre Syndrome research collaboration, a de-centralized evaluation platform for diagnostic assays, a global vector control hub, and the REDe network with freely available training resources to enhance global research capacity in vector-borne diseases. ispartof: GLOBAL HEALTH ACTION vol:14 issue:sup1 ispartof: location:United States status: published
Published: 2022

12. Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study

Author: Pietro Ferrari, Fulvio Ricceri, Christina C. Dahm, Kim Overvad, Sabina Sieri, Elisabete Weiderpass, Eleni Peppa, María José Sánchez, Leila Luján Barroso, Marta Solans Margalef, Matthias B. Schulze, Federico Canzian, Giovanna Masala, Florentin Spaeth, Dagfinn Aune, Roel Vermeulen, Tilman Kühn, Delphine Casabonne, Karin Jirstom, Anna Karakatsani, José María Huerta, Yahya Mahamat-Saleh, Paul Brennan, Cecilie Kyrø, Mats Jerkeman, Caroline Besson, Pilar Amiano Exezarreta, Virginia Menéndez, Elio Riboli, Julie A. Schmidt, Rosario Tumino, Sairah L.F. Chen, Marc J. Gunter, Eva Ardanaz, Antonia Trichopoulou, Alexandra Nieters, Marie-Christine Boutron-Ruault, Anne Tjønneland, Fatemeh Saberi Hosnijeh, Sabine Naudin, Salvatore Panico, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Centre Hospitalier de Versailles André Mignot (CHV), Direction Générale de la Compétitivité, de l’Industrie et des Services, DGCIS Food Standards Agency, FSA Cancer Research UK, CRUK: C864/A14136, C8221/A19170, C570/A16491 RD06/0020 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Université Claude Bernard Lyon 1, UCBL Wellcome Trust, WT Ligue Contre le Cancer 6236 German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Department of Health, Australian Government Ministry of Health and Social Solidarity, Greece Kræftens Bekæmpelse, DCS British Heart Foundation, BHF Instituto de Salud Carlos III, ISCIII National Research Council, NRC Mutuelle Générale de l'Education Nationale, MGEN Hellenic Health Foundation, HHF Stroke Association Institut National de la Santé et de la Recherche Médicale, Inserm Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, IARC Deutsche Krebshilfe Cancerfonden World Cancer Research Fund, WCRF Stavros Niarchos Foundation, SNF Ministère des Affaires Sociales et de la Santé: GR‐IARC‐2003‐09‐12‐01 Medical Research Council, MRC: MR/M012190/1, MR/N003284/1, MC‐UU_12015/1, We thank Carine Biessy and Bertrand Hemon for their technical support and contribution to this work. We are also grateful to all the EPIC participants who have been part of the project and to the many other members of the study teams who have enabled this research. This work was supported by the Direction Générale de la Santé (French Ministry of Health, Grant GR‐IARC‐2003‐09‐12‐01), by the European Commission (Directorate General for Health and Consumer Affairs) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), the Ligue Contre le Cancer, the Institut Gustave Roussy, the Mutuelle Générale de l'Education Nationale and the Institut National de la Santé et de la Recherche Médicale (France), the Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, the World Cancer Research Fund and Statistics Netherlands (the Netherlands), the Health Research Fund, Regional Governments of Andalucýa, Asturias, Basque Country, Murcia (project 6236) and Navarra, Instituto de Salud Carlos III, Redes de Investigacion Cooperativa (RD06/0020, Spain), the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), Cancer Research UK (C864/A14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/N003284/1 and MC‐UU_12015/1 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, and United Kingdom), the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK). This work was part of Sabine Naudin's PhD at Claude Bernard Lyon I University (France), funded by Région Auvergne Rhône‐Alpes, ADR 2016 (France).
Subjects: Male, Oncology, Cancer Research, Lymphoma, Body Mass Index, 0302 clinical medicine, Risk Factors, immune system diseases, hemic and lymphatic diseases, Prospective Studies, Prospective cohort study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Incidence, non-Hodgkin lymphoma, Smoking, Hazard ratio, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, 030220 oncology & carcinogenesis, Female, EPIC, healthy lifestyle index, Hodgkin lymphoma, prospective study, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Alcohol Drinking, [SDV.CAN]Life Sciences [q-bio]/Cancer, Diet Surveys, 03 medical and health sciences, Internal medicine, REGRESSION, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Healthy Lifestyle, Exercise, Aged, Science & Technology, business.industry, Proportional hazards model, HODGKINS-LYMPHOMA, Feeding Behavior, medicine.disease, Confidence interval, Etiology, UPDATE, CIGARETTE-SMOKING, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Follow-Up Studies
Abstract: This is the peer reviewed version of the following article: Naudin, S., Margalef, M.S., Hosnijeh, F.S., Nieters, A., Kyrø, C. Tjønneland, A. ... Ferrari, P. (2020) Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study. International Journal of Cancer, 147(6):1649-1656, which has been published in final form at https://doi.org/10.1002/ijc.32977. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this work, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL) were evaluated in a large‐scale European prospective cohort. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases (132 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow‐up. The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, physical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox proportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI score. The HLI was inversely associated with HL, with HR for a 1‐standard deviation (SD) increment in the score equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly driven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1‐SD increment equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL subtypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.
Published: 2020

13. Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry

Author: Meng-Chuan Lai, Elena Maria Busuoli, Antonio M. Persico, Bonnie Auyeung, Eva Loth, Sarah Durston, Andreas Meyer-Lindenberg, Sven Bölte, Carolin Moessnang, Stavros Trakoshis, Marianne Oldehinkel, Prantik Kundu, Steve C.R. Williams, Jan K. Buitelaar, Sarah Baumeister, Tony Charman, Michael V. Lombardo, Isotta Landi, Richard A. I. Bethlehem, Rosemary Holt, Veronica Mandelli, Christine Ecker, Natasha Bertelsen, Julian Tillmann, Declan G. Murphy, Christian F. Beckmann, Jakob Seidlitz, Eleonora Satta, Mark H. Johnson, Will Spooren, Simon Baron-Cohen, Guillaume Dumas, Luke Mason, Emily J.H. Jones, Thomas Bourgeron, Istituto Italiano di Tecnologia (IIT), University of Trento [Trento], University of Cambridge [UK] (CAM), Children’s Hospital of Philadelphia (CHOP ), University of Pennsylvania, University of Cyprus [Nicosia] (UCY), University of Edinburgh, King‘s College London, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Universität Heidelberg [Heidelberg] = Heidelberg University, Radboud University Medical Center [Nijmegen], Karolinska Institutet [Stockholm], Stockholm Health Care Services (SLSO), Curtin University [Perth], Planning and Transport Research Centre (PATREC), University Medical Center [Utrecht], Goethe-Universität Frankfurt am Main, University of London [London], Monash University [Melbourne], University of Messina, Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome ( UCBM), University of Vienna [Vienna], Roche Pharma Research and Early Development [Basel] (pRED), F. Hoffmann-La Roche [Basel], Centre for Addiction and Mental Health [Toronto] (CAMH), The Hospital for sick children [Toronto] (SickKids), University of Toronto, National Taiwan University [Taiwan] (NTU), This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under grant agreement No 755816 (ERC Starting Grant to MVL). This work was also supported by EU-AIMS and EU AIMS-2-TRIALS, which both received support from the Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115300 and the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement No. 777394, the resources of which are composed of financial contributions from the European Union’s Seventh Framework Programme (Grant No. FP7/2007–2013), from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions, and from Autism Speaks, Autistica and the Simons Foundation for Autism Research Initiative. The views expressed are those of the author(s) and not necessarily those of the IMI 2JU. This work was also supported by the Netherlands Organization for Scientific Research through Vidi grants (Grant No. 864.12.003 [to CFB]), from the FP7 (Grant Nos. 602805) (AGGRESSOTYPE) (to JKB), 603016 (MATRICS), and 278948 (TACTICS), and from the European Community’s Horizon 2020 Programme (H2020/2014–2020) (Grant Nos. 643051 [MiND] and 642996 (BRAINVIEW). This work received funding from the Wellcome Trust UK Strategic Award (Award No. 098369/Z/12/Z) and from the National Institute for Health Research Maudsley Biomedical Research Centre (to DGMM). M-CL was supported by the Academic Scholars Award from the Department of Psychiatry, University of Toronto, the Slaight Family Child and Youth Mental Health Innovation Fund from the CAMH Foundation, the Ontario Brain Institute via the Province of Ontario Neurodevelopmental Disorders (POND) Network (IDS-I l-02), the Canadian Institutes of Health Research Sex and Gender Science Chair (GSB 171373), and the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario (CAM-20-004). R.A.I.B acknowledges research support by the Autism Research Trust and a British Academy Fellowship (PF2\180017). MHJ, TC, and EJHJ acknowledge support from a UK MRC Programme Grant., the EU-AIMS LEAP group : Jumana Ahmad, Sara Ambrosino, Bonnie Auyeung, Tobias Banaschewski, Simon Baron-Cohen, Sarah Baumeister, Christian F. Beckmann, Sven Bölte, Thomas Bourgeron, Carsten Bours, Michael Brammer, Daniel Brandeis, Claudia Brogna, Yvette de Bruijn, Jan K. Buitelaar, Bhismadev Chakrabarti, Tony Charman, Chris Chatham, Ineke Cornelissen, Daisy Crawley, Flavio Dell’Acqua, Guillaume Dumas, Sarah Durston, Christine Ecker, Jessica Faulkner, Vincent Frouin, Pilar Garcés, David Goyard, Lindsay Ham, Hannah Hayward, Joerg Hipp, Rosemary J. Holt, Mark H. Johnson, Emily J. H. Jones, Prantik Kundu, Meng-Chuan Lai, Xavier Liogier D’ardhuy, Michael V. Lombardo, Eva Loth, David J. Lythgoe, René Mandl, Andre Marquand, Luke Mason, Maarten Mennes, Andreas Meyer-Lindenberg, Carolin Moessnang, Nico Mueller, Declan G. M. Murphy, Bethany Oakley, Laurence O’Dwyer, Marianne Oldehinkel, Bob Oranje, Gahan Pandina, Antonio M. Persico, Barbara Ruggeri, Amber N. V. Ruigrok, Jessica Sabet, Roberto Sacco, Antonia San José Cáceres, Emily Simonoff, Will Spooren, Julian Tillmann, Roberto Toro, Heike Tost, Jack Waldman, Steve C. R. Williams, Caroline Wooldridge & Marcel P. Zwiers, European Project: 0755816(2008), European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), European Project: 602805,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,AGGRESSOTYPE(2013), European Project: 603016,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,MATRICS(2014), European Project: 278948,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,TACTICS(2012), European Project: 643051,H2020,H2020-MSCA-ITN-2014,MiND(2015), European Project: 642996,H2020,H2020-MSCA-ITN-2014,BRAINVIEW(2015), University of Pennsylvania [Philadelphia], University of Cyprus (UCY), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Universität Heidelberg [Heidelberg], Bethlehem, Richard A I [0000-0002-0714-0685], Seidlitz, Jakob [0000-0002-8164-7476], Bourgeron, Thomas [0000-0001-8164-9220], Charman, Tony [0000-0003-1993-6549], Persico, Antonio M [0000-0001-8910-4479], Lombardo, Michael V [0000-0001-6780-8619], Apollo - University of Cambridge Repository, and Bethlehem, Richard AI [0000-0002-0714-0685]
Subjects: Male, 0301 basic medicine, Autism Spectrum Disorder, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Medicine (miscellaneous), MESH: Magnetic Resonance Imaging, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, MESH: Child, Neural Pathways, Biology (General), Child, MESH: Autism Spectrum Disorder, MESH: Child Behavior Disorders, Communication, 220 Statistical Imaging Neuroscience, Hyperconnectivity, Autism spectrum disorders, Magnetic Resonance Imaging, Autism spectrum disorder, Female, MESH: Communication, General Agricultural and Biological Sciences, MESH: Stereotyped Behavior, QH301-705.5, autism spectrum disorders, Child Behavior Disorders, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Neuroimaging, mental disorders, medicine, Biological neural network, Humans, Association (psychology), MESH: Neurodevelopmental Disorders, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], MESH: Humans, Resting state fMRI, Genetic heterogeneity, MESH: Neural Pathways, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, MESH: Male, 030104 developmental biology, Neurodevelopmental Disorders, Autism, Stereotyped Behavior, Neuroscience, MESH: Female, 030217 neurology & neurosurgery
Abstract: Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97–99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry., Natasha Bertelsen et al. develop a computational model to categorize patients with autism spectrum disorder (ASD) into distinct subgroups, based on social-communicative or restricted repetitive behaviors. By integrating publicly available neuroimaging and genetic data, they report neural and molecular signatures in two of these subgroups, altogether highlighting subtle differences in neural circuitry and genomic networks that could underlie phenotypic differences among ASD patients.
Published: 2021

14. Blood Metal Levels and Amyotrophic Lateral Sclerosis Risk: A Prospective Cohort

Author: Broberg, Karin E., Kippler, Maria J., Veldink, Jan Herman, Van Den Berg, Leonard H., Middleton, Lefkos T., Travis, Ruth C., Bergmann, Manuela M., Mancini, Francesca Romana, Katzke, Verena Andrea, Agudo, Antonio T., Gómez, Jesús Humberto, Rodríguez-Barranco, Miguel A., Trichopoulou, Antonia D., Vermeulen, Roel C.H., Peters, Susan, Broberg, Karin, Gallo, Valentina, Levi, Michael, Kippler, Maria, Vineis, Paolo, Veldink, Jan, Berg, Leonard, Middleton, Lefkos, Travis, Ruth, Bergmann, Manuela, Palli, Domenico, Grioni, Sara, Tumino, Rosario, Elbaz, Alexis, Vlaar, Tim, Mancini, Francesca, Kühn, Tilman, Katzke, Verena, Agudo, Antonio, Goñi, Fernando, Gómez, Jesús‐humberto, Rodríguez‐barranco, Miguel, Merino, Susana, Barricarte, Aurelio, Trichopoulou, Antonia, Jenab, Mazda, Weiderpass, Elisabete, Vermeulen, Roel, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), FOOD‐CT‐2005‐513943 Ministry of National Education and Religious Affairs Cancer Research UK, CRUK Wellcome Trust, WT German Cancer Research Center, DKFZ Department of Health, Australian Government Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS Instituto de Salud Carlos III, ISCIII: C03/09 Stichting Diabetes Onderzoek Nederland British Heart Foundation, BHF Norges Forskningsråd QLK4CT199900927 Stroke Association European Commission, EC Deutsche Krebshilfe World Cancer Research Fund, WCRF Kreftforeningen, NCS Medical Research Council, MRC, The EPIC study is funded by a number of grants, however, no funding source had any role in the preparation of this article. The EPIC study was funded by the Europe against Cancer program of the European Commission (SANCO), Italian Association for Research on Cancer, and Italian National Research Council. In addition, the authors thank the following for their financial support: the Environmental Cancer Risk, Nutrition, and Individual Susceptibility Network of Excellence, operating within the European Union Sixth Framework Program, Priority 5: Food Quality and Safety (FOOD‐CT‐2005‐513943), European Community Fifth Framework Program (grant QLK4CT199900927), ISCIII, Red de Centros RCESP (C03/09), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia, and Navarra, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, Italian Association for Research on Cancer, Italian National Research Council, Dutch Ministry of Public Health, Welfare, and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands, Swedish Cancer, Swedish Scientific Council, Regional Government of Skåne and Västerbotten, Sweden, Norwegian Cancer Society, Research Council of Norway, French League against Cancer, INSERM, Mutuelle Generale l'Education National, and IGR. The EPIC‐Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC‐UU_12015/1) and Cancer Research UK (C864/A14136)., and 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)
Subjects: 0301 basic medicine, Adult, Male, Risk, medicine.medical_specialty, Clinical Neurology, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, LEAD-EXPOSURE, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Research Articles, POPULATION, Aged, Retrospective Studies, Science & Technology, Neurology & Neurosurgery, business.industry, Amyotrophic Lateral Sclerosis, Neurosciences, 1103 Clinical Sciences, Retrospective cohort study, Odds ratio, Environmental exposure, Environmental Exposure, Mercury, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030104 developmental biology, Neurology, Cohort, Population study, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurosciences & Neurology, Neurology (clinical), SMOKING, 1109 Neurosciences, business, Life Sciences & Biomedicine, 030217 neurology & neurosurgery, Research Article, Cohort study
Abstract: International audience; Objective: Metals have been suggested as a risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality. Methods: A nested ALS case–control study was conducted within the prospective EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium, and zinc concentrations were measured by inductively coupled plasma–mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models. Results: The study population comprised 107 cases (65% female) and 319 controls matched for age, sex, and study center. Median time between blood collection and ALS death was 8 years (range = 1–15). Comparing the highest with the lowest tertile, cadmium (odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.08–3.87) and lead (OR = 1.89, 95% CI = 0.97–3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR = 0.50, 95% CI = 0.27–0.94). Associations for cadmium and lead remained when limiting analyses to noncurrent smokers. Interpretation: This is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead, and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. ANN NEUROL 20209999:n/a–n/a.
Published: 2021

15. Fractionating autism based on neuroanatomical normative modeling

Author: Zabihi, Mariam, Floris, Dorothea L, Kia, Seyed Mostafa, Wolfers, Thomas, Tillmann, Julian, Arenas, Alberto Llera, Moessnang, Carolin, Banaschewski, Tobias, Holt, Rosemary, Baron-Cohen, Simon, Loth, Eva, Charman, Tony, Bourgeron, Thomas, Murphy, Declan, Ecker, Christine, Buitelaar, Jan K, Beckmann, Christian F, Marquand, Andre, EU-AIMS LEAP Group, Zabihi, Mariam [0000-0002-7083-2318], Kia, Seyed Mostafa [0000-0002-7128-814X], Banaschewski, Tobias [0000-0003-4595-1144], Charman, Tony [0000-0003-1993-6549], Murphy, Declan [0000-0002-6664-7451], Buitelaar, Jan K [0000-0001-8288-7757], Apollo - University of Cambridge Repository, TILT, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Radboud University Medical Center [Nijmegen], University of Oslo (UiO), Oslo University Hospital [Oslo], King‘s College London, University of Vienna [Vienna], Universität Heidelberg [Heidelberg], Medical Faculty [Mannheim], University of Cambridge [UK] (CAM), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Goethe-Universität Frankfurt am Main, Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], University of Oxford [Oxford], The work is supported by the Netherlands Organization for Scientific Research VIDI Grant Nos. 016.156.415 (to A.F.M.) and 864.12.003 (to C.F.B.), European Union Seventh Framework Program Grant Nos. 602805 (AGGRESSOTYPE) (to J.K.B.), 603016 (MATRICS) (to J.K.B.), and 278948 (TACTICS) (to J.K.B.), European Community’s Horizon 2020 Program (H2020/2014–2020) Grant Nos. 643051 (MiND) (to J.K.B.) and 642996 (BRAINVIEW) (to J.K.B.), Wellcome Trust UK Strategic Award Grant No. 098369/Z/12/Z (to C.F.B.), and EU-AIMS (European Autism Interventions), which receives support from Innovative Medicines Initiative Joint Undertaking Grant No. 115300, the resources of which are composed of financial contributions from the European Union’s Seventh Framework Program (Grant No. FP7/2007–2013), from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions and Innovative Medicines Initiative 2 Joint Undertaking Grant No. 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA and AUTISM SPEAKS, Autistica, SFARI. D.M. was also supported by the NIHR Maudsley Biomedical Research Centre. S.B.-C. was funded by the Wellcome Trust and the Autism Research Trust during the period of this work., European Project: 602805,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,AGGRESSOTYPE(2013), European Project: 603016,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,MATRICS(2014), European Project: 278948,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,TACTICS(2012), European Project: 643051,H2020,H2020-MSCA-ITN-2014,MiND(2015), European Project: 642996,H2020,H2020-MSCA-ITN-2014,BRAINVIEW(2015), European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), Radboud University [Nijmegen], Universität Heidelberg [Heidelberg] = Heidelberg University, University Hospital Mannheim | Universitätsmedizin Mannheim, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Oxford, Buitelaar, Jan K. [0000-0001-8288-7757], and Baron-Cohen, Simon [0000-0001-9217-2544]
Subjects: Autism Spectrum Disorder, Autism, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Neurobiology, MESH: Child, Psychology, Young adult, Child, EU-AIMS LEAP Group, MESH: Autism Spectrum Disorder, Cortical Thickness, 0303 health sciences, 220 Statistical Imaging Neuroscience, Cognition, Autism spectrum disorders, MESH: Case-Control Studies, 692/699/476/1373, Magnetic Resonance Imaging, Psychiatry and Mental health, MESH: Young Adult, Autism spectrum disorder, 9, Female, Neurotypical, Clinical psychology, Adult, Adolescent, MESH: Autistic Disorder, Biology, Predictive markers, Article, lcsh:RC321-571, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, All institutes and research themes of the Radboud University Medical Center, MESH: Neurobiology, 692/53/2423, Neurodevelopmental Condition, medicine, Humans, Autistic Disorder, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, 030304 developmental biology, MESH: Adolescent, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], MESH: Humans, [SCCO.NEUR]Cognitive science/Neuroscience, Case-control study, MESH: Adult, medicine.disease, Case-Control Studies, 59/57, Normative, Polygenic risk score, 631/477, MESH: Female, 030217 neurology & neurosurgery
Abstract: Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440, Funder: SBC was funded by the Wellcome Trust and the Autism Research Trust during the period of this work., Funder: DM was supported by the NIHR Maudsley Biomedical Research Centre., Autism is a complex neurodevelopmental condition with substantial phenotypic, biological, and etiologic heterogeneity. It remains a challenge to identify biomarkers to stratify autism into replicable cognitive or biological subtypes. Here, we aim to introduce a novel methodological framework for parsing neuroanatomical subtypes within a large cohort of individuals with autism. We used cortical thickness (CT) in a large and well-characterized sample of 316 participants with autism (88 female, age mean: 17.2 ± 5.7) and 206 with neurotypical development (79 female, age mean: 17.5 ± 6.1) aged 6–31 years across six sites from the EU-AIMS multi-center Longitudinal European Autism Project. Five biologically based putative subtypes were derived using normative modeling of CT and spectral clustering. Three of these clusters showed relatively widespread decreased CT and two showed relatively increased CT. These subtypes showed morphometric differences from one another, providing a potential explanation for inconsistent case–control findings in autism, and loaded differentially and more strongly onto symptoms and polygenic risk, indicating a dilution of clinical effects across heterogeneous cohorts. Our results provide an important step towards parsing the heterogeneous neurobiology of autism.
Published: 2020

16. Bioactive Indanes: Comparative In Vitro Metabolism Study of PH46A, a New Potential Anti-inflammatory Agent and biosynthesis of its primary metabolite PH132

Author: Gaia Scalabrino, Tao Zhang, Neil Frankish, Helen Sheridan, and The Wellcome Trust UK
Subjects: Bioactive indane, PH46A, PH46, Metabolism, PH132, LC-MS, Biosynthesis, 010405 organic chemistry, Metabolite, 010401 analytical chemistry, Primary metabolite, Life Sciences, Pharmacology, 01 natural sciences, 0104 chemical sciences, Hydroxylation, chemistry.chemical_compound, chemistry, Pharmacokinetics, In vivo, Microsome, Glucuronide
Abstract: PH46A is the lead of a new class of bioactive indanes with potential for the treatment of inflammatory bowel disease. A qualitative in vitro metabolism profile of PH46A was investigated in preclinical studies, and the rate of its metabolism in cryopreserved hepatocytes prepared from male Sprague Dawley rat, Beagle dog, Cynomolgus monkey and pooled mixed gender human was compared by LC-MS. The clearance order of PH46A was determined to be rat>dog>monkey>human. The species tested which exhibited the closest clearance values to the human was monkey. Following incubation of PH46A with cryopreserved hepatocytes, 5 metabolites were identified, including M1 (keto-PH46), M2 (PH46-OH, PH132), M3 (PH46-diOH), M4 (keto-glucuronide-PH46) and M5 (glucuronide conjugate-PH46). It was found that the human metabolites M2 and M5 were also present in rat, dog and monkey, while M1 was present in all species except monkey. M2 was detected in dog and monkey by LC1 conditions, but only in dog by LC2. Therefore, the metabolism in rat was most similar to human, in terms of the metabolites observed, but all putative human metabolites were present in rat and dog. We further explored the characterization of key metabolite M2 (PH46-OH). Identical PH46-OH was obtained via a bio-catalytic oxidation method from PH46 using rat liver microsomes (RLM) and the human liver P450s (Cyp 2D6, Cyp 2C19 and Cyp 4A11) following screening of selectAZyme panels of microbial P450s, recombinant human liver P450s and different microsomes. RLM was used in scale up production and PH132 was isolated and characterized as 4-(((1’S,2’S)-1’,6-dihydroxy-1’,3’-dihydro- 1H,2’H-[2,2’-biinden]-2’-yl)methyl) benzoic acid via LC-MS/MS, NMR and HRMS. The site of hydroxylation on the biindane scaffold was unexpected. The outcomes of these studies have provided valuable information for future pharmacokinetic and in vivo toxicological investigations.
Published: 2020

17. Bioactive Indanes: Proof of Concept Study for Enantioselective Synthetic Routes to PH46A, a New Potential Anti-inflammation Agent

Author: Tao Zhang, Neil Frankish, Gaia Scalabrino, Helen Sheridan, and The Wellcome Trust UK
Subjects: Ketone, Alkylation, biocatalysis, Cinchona Alkaloids, Anti-Inflammatory Agents, Pharmaceutical Science, Chemistry Techniques, Synthetic, hydrolases, 010402 general chemistry, Proof of Concept Study, 01 natural sciences, Article, Analytical Chemistry, Stereocenter, lcsh:QD241-441, chemistry.chemical_compound, lcsh:Organic chemistry, Drug Discovery, Hydrolase, Physical and Theoretical Chemistry, Bioactive indanes, Enantiomeric excess, Cinchonidine, chemistry.chemical_classification, Molecular Structure, Quinine, 010405 organic chemistry, Chemistry, Organic Chemistry, Enantioselective synthesis, Life Sciences, Stereoisomerism, PH46A, Ketones, Combinatorial chemistry, 3. Good health, 0104 chemical sciences, Kinetics, Chemistry (miscellaneous), Biocatalysis, Indans, Molecular Medicine, Enantiomer, enantioselective, phase-transfer catalyst (PTC), bioactive indanes
Abstract: PH46A is a single enantiomer and a member of the 1,2-indane dimer family. It has two contiguous stereogenic centers with S,S configurations, one of which being a quaternary center, which has been developed as a clinical candidate for the treatment of inflammatory and autoimmune conditions. The current synthetic route to PH46A involves the generation of an unwanted enantiomer (R,R)-7, thus reducing the final yield significantly. Therefore, we have investigated potential alternatives to improve the efficiency of this synthesis. The first phase of the study has demonstrated proof of principle for a chiral alkylation of ketone 3 using phase-transfer catalysis, providing a key intermediate ketone (S)-4. The parent alkaloids required for the synthesis of PH46A, quinine or cinchonidine, have also been identified. Promising enantiomeric excesses of up to 50% have been achieved to date, and the use of an alternative substrate, unsaturated ketone 9, has also opened up further avenues for optimisation in future studies. The second part of the study involved preliminary screening the effects of a panel of hydrolase enzymes on (rac)-4 in order to identify a potential chemo-enzymatic route to optimise the introduction of chirality into PH46A at early stage of the synthesis. The hydrolase module has also yielded positive results, enzyme AH-46 with MtBE providing a selectivity factor of 8.4 with enantiomeric excess of 77%. Overall, positive results were obtained in this proof of concept study described herein. It is believed that conditions of both chiral PTC alkylation and biocatalytic hydrolysis could be optimised to further enhance the selectivity and improve the overall yield. This work is currently ongoing.
Published: 2020

18. Investigation of the Stereoselective Synthesis of the Indane Dimer PH46A, a New Potential Anti-inflammatory Agent

Author: Graham Robert Cumming, Tao Zhang, Gaia Scalabrino, Neil Frankish, Helen Sheridan, and The Wellcome Trust UK, Enterprise Ireland
Subjects: chemistry.chemical_classification, Ketone, stereoselective, 010405 organic chemistry, Chemistry, Stereochemistry, phase transfer catalyst (PTC), Dimer, Organic Chemistry, Diastereomer, Indane, Life Sciences, PH46A, Alkylation, 010402 general chemistry, 01 natural sciences, Article, 0104 chemical sciences, chemistry.chemical_compound, Stereoselectivity, Physical and Theoretical Chemistry, Enantiomer, Bioactive indanes, diastereoselective reduction, Phase-transfer catalyst
Abstract: PH46A, belonging to a class of 1,2-Indane dimers, has been developed by our research group as a potential therapeutic agent for the treatment of inflammatory and autoimmune diseases. The initial synthetic route to PH46A gave a low overall yield, due in large part to the generation of undesired diastereoisomer 5 and the unwanted enantiomer (R,R)-8 during the synthesis. The aim of this work was to carry out a comprehensive investigation into the stereoselective synthesis of PH46A. Significant progress was made on the ketone reduction step, where the use of triisobutylaluminum [TiBA, Al(iBu)3] afforded high selectivity for the target diastereoisomer (rac)-6, compared to the unfavorable ratio obtained using a previous process. This enabled a multikilo scale synthesis of PH46A in a GMP environment. Further, a brief proof-of-principle investigation was carried out using an achiral phase transfer catalyst (PTC) for alkylation at the methine carbon of the parent indanone.
Published: 2020

19. Dissecting the heterogeneous cortical anatomy of autism spectrum disorder using normative models

Author: David Goyard, Tony Charman, Sarah Durston, Marianne Oldehinkel, Vincent Frouin, Sven Bölte, Andre F. Marquand, Christine Ecker, Simon Baron-Cohen, Mariam Zabihi, Christian F. Beckmann, Tobias Banaschewski, Jan K. Buitelaar, Rosemary Holt, Guillaume Dumas, Eva Loth, Declan G. Murphy, Thomas Wolfers, Julian Tillmann, Radboud University Medical Center [Nijmegen], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of Cambridge [UK] (CAM), University Medical Center [Utrecht], Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Stockholm County Council, Sackler Institute of Translational Neurodevelopment, Institute of Psychiatry, King's College London, Goethe-University Frankfurt am Main, Department of Psychiatry, The work is supported by the Netherlands Organization for Scientific Research VIDI Grant Nos. 016.156.415 (to AFM) and 864.12.003 (to CFB), European Union Seventh Framework Programme Grant Nos. 602805 (AGGRESSOTYPE) (to JKB), 603016 (MATRICS) (to JKB), and 278948 (TACTICS) (to JKB), European Community’s Horizon 2020 Programme (H2020/2014-2020) Grant Nos. 643051 (MiND) (to JKB) and 642996 (BRAINVIEW) (to JKB), Wellcome Trust UK Strategic Award Grant No. 098369/Z/12/Z (to CFB), and EU-AIMS (European Autism Interventions), which receives support from Innovative Medicines Initiative Joint Undertaking Grant No. 115300, the resources of which are composed of financial contributions from the European Union’s Seventh Framework Programme (Grant No. FP7/2007-2013), from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions., JKB has been a consultant to, advisory board member of, and a speaker for Janssen Cilag BV, Eli Lilly, Shire, Lundbeck, Roche, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents or royalties. CFB is director and shareholder in SBGNeuro Ltd. SB discloses that he has in the last 5 years acted as an author, consultant or lecturer for Shire, Medice, Roche, Eli Lilly, Prima Psychiatry, GLGroup, System Analytic, Ability Partner, Kompetento, Expo Medica, and Prophase. He receives royalties for text books and diagnostic tools from Huber/Hogrefe, Kohlhammer, and UTB. TB served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Novartis, and Shire. He received conference support or speaker’s fee by Lilly, Medice, Novartis, and Shire. He has been involved in clinical trials conducted by Shire and Vifor Pharma. He received royalities from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. The present work is unrelated to the above grants and relationships. The other authors report no biomedical financial interests or potential conflicts of interest., We gratefully acknowledge the support of the EU-AIMS (European Autism Interventions) Longitudinal European Autism Project study team for data acquisition, quality control, and preprocessing., European Project: 602805,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,AGGRESSOTYPE(2013), European Project: 603016,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,MATRICS(2014), European Project: 278948,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,TACTICS(2012), European Project: 643051,H2020,H2020-MSCA-ITN-2014,MiND(2015), European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), Radboud University [Nijmegen], Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University Hospital Mannheim | Universitätsmedizin Mannheim, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Sackler Institute of Translational Neurodevelopment [London]
Subjects: Male, 0301 basic medicine, Autism Spectrum Disorder, Autism, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Neuroimaging biomarkers, 0302 clinical medicine, Child, Cerebral Cortex, 0303 health sciences, 220 Statistical Imaging Neuroscience, Magnetic Resonance Imaging, medicine.anatomical_structure, Autism spectrum disorder, Homogeneous, Radiology Nuclear Medicine and imaging, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biological psychiatry, Psychology, Normative modeling, Cognitive psychology, Adult, Brain development, Adolescent, Cognitive Neuroscience, Models, Neurological, Clinical Neurology, Cognitive neuroscience, behavioral disciplines and activities, Article, Cortical thickness, Young Adult, 03 medical and health sciences, Clinical heterogeneity, Image Interpretation, Computer-Assisted, mental disorders, medicine, Journal Article, Outlier detection, Humans, Radiology, Nuclear Medicine and imaging, Gaussian process, Biological Psychiatry, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], cortical thickness, medicine.disease, Cross-Sectional Studies, 030104 developmental biology, Case-Control Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Multiple comparisons problem, Normative, Neurology (clinical), Heterogeneity, heterogeneity, 030217 neurology & neurosurgery, Neuroanatomy
Abstract: BackgroundThe neuroanatomical basis of autism spectrum disorder (ASD) has remained elusive, mostly due to high biological and clinical heterogeneity among diagnosed individuals. Despite considerable effort towards understanding ASD using neuroimaging biomarkers, heterogeneity remains a barrier, partly because studies mostly employ case-control approaches, which assume that the clinical group is homogeneous.MethodsHere, we used an innovative normative modelling approach to parse biological heterogeneity in ASD. We aimed to dissect the neuroanatomy of ASD by mapping the deviations from a typical pattern of neuroanatomical development at the level of the individual and to show the necessity to look beyond the case-control paradigm to understand the neurobiology of ASD. We first estimated a vertex-wise normative model of cortical thickness development using Gaussian process regression, then mapped the deviation of each participant from the typical pattern. For this we employed a heterogeneous cross-sectional sample of 206 typically developing (TD) individuals (127 male), and 321 individuals (232 male) with ASD (aged 6-31).ResultsWe found few case-control differences but the ASD cohort showed highly individualized patterns of deviations in cortical thickness that were widespread across the brain. These deviations correlated with severity of repetitive behaviors and social communicative symptoms, although only repetitive behaviors survived corrections for multiple testing.ConclusionsOur results: (i) reinforce the notion that individuals with ASD show distinct, highly individualized trajectories of brain development and (ii) show that by focusing on common effects (i.e. the ‘average ASD participant’), the case-control approach disguises considerable inter-individual variation crucial for precision medicine.
Published: 2019

20. Altered connectivity between cerebellum, visual, and sensory-motor networks in autism spectrum disorder: Results from the EU-AIMS Longitudinal European Autism Project

Author: Marianne Oldehinkel, Maarten Mennes, Andre Marquand, Tony Charman, Julian Tillmann, Christine Ecker, Flavio Dell’Acqua, Daniel Brandeis, Tobias Banaschewski, Sarah Baumeister, Carolin Moessnang, Simon Baron-Cohen, Rosemary Holt, Sven Bölte, Sarah Durston, Prantik Kundu, Michael V. Lombardo, Will Spooren, Eva Loth, Declan G.M. Murphy, Christian F. Beckmann, Jan K. Buitelaar, Jumana Ahmad, Sara Ambrosino, Bonnie Auyeung, Thomas Bourgeron, Carsten Bours, Michael Brammer, Claudia Brogna, Yvette de Bruijn, Bhismadev Chakrabarti, Ineke Cornelissen, Daisy Crawley, Guillaume Dumas, Jessica Faulkner, Vincent Frouin, Pilar Garcés, David Goyard, Lindsay Ham, Hannah Hayward, Joerg Hipp, Mark H. Johnson, Emily J.H. Jones, Meng-Chuan Lai, Xavier Liogier D’ardhuy, David J. Lythgoe, René Mandl, Luke Mason, Andreas Meyer-Lindenberg, Nico Mueller, Bethany Oakley, Laurence O’Dwyer, Bob Oranje, Gahan Pandina, Antonio M. Persico, Barbara Ruggeri, Amber Ruigrok, Jessica Sabet, Roberto Sacco, Antonia San José Cáceres, Emily Simonoff, Roberto Toro, Heike Tost, Jack Waldman, Steve C.R. Williams, Caroline Wooldridge, Marcel P. Zwiers, Radboud University Medical Center [Nijmegen], Monash University [Melbourne], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Goethe-University Frankfurt am Main, Universität Heidelberg [Heidelberg], Universität Zürich [Zürich] = University of Zurich (UZH), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], University of Cambridge [UK] (CAM), Karolinska Institutet [Stockholm], Stockholm County Council, University Medical Center [Utrecht], Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Cyprus [Nicosia], Roche Pharma Research and Early Development [Basel] (pRED), F. Hoffmann-La Roche [Basel], University of Oxford [Oxford], University of Edinburgh, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome ( UCBM), University of Reading (UOR), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), University of Nottingham, UK (UON), University of Toronto, Centre for Brain and Cognitive Development [Birkbeck College], Birkbeck College [University of London], Janssen Research & Development, This work was supported EU-AIMS, which receives support from the Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115300 and the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement No. 777394, the resources of which are composed of financial contributions from the European Union’s Seventh Framework Programme (Grant No. FP7/2007-2013), from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions, and from Autism Speaks. This work was also supported by the Netherlands Organization for Scientific Research through Vidi grants (Grant No. 864.12.003 [to CFB] and Grant No. 016.156.415 [to AFM]), from the FP7 (Grant Nos. 602805) (AGGRESSOTYPE) (to JKB), 603016 (MATRICS), and 278948 (TACTICS), and from the European Community’s Horizon 2020 Programme (H2020/2014-2020) (Grant Nos. 643051 [MiND] and 642996 (BRAINVIEW). This work received funding from the Wellcome Trust UK Strategic Award (Award No. 098369/Z/12/Z) and from the National Institute for Health Research Maudsley Biomedical Research Centre (to DM)., European Project: 602805,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,AGGRESSOTYPE(2013), European Project: 603016,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,MATRICS(2014), European Project: 278948,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,TACTICS(2012), European Project: 643051,H2020,H2020-MSCA-ITN-2014,MiND(2015), European Project: 642996,H2020,H2020-MSCA-ITN-2014,BRAINVIEW(2015), Radboud University [Nijmegen], Universität Heidelberg [Heidelberg] = Heidelberg University, University of Cyprus [Nicosia] (UCY), University of Oxford, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of Zurich, Oldehinkel, Marianne, University of Zürich [Zürich] (UZH), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Lombardo, Michael V. [0000-0001-6780-8619]
Subjects: Male, Autism Spectrum Disorder, Autism, Functional connectivity, 0302 clinical medicine, Cerebellum, Neural Pathways, Longitudinal Studies, 10064 Neuroscience Center Zurich, Child, Visual-motor integration, Visual Cortex, Brain Mapping, medicine.diagnostic_test, 05 social sciences, Sensory networks, 220 Statistical Imaging Neuroscience, 10058 Department of Child and Adolescent Psychiatry, Magnetic Resonance Imaging, 2728 Neurology (clinical), Autism spectrum disorder, Radiology Nuclear Medicine and imaging, 10076 Center for Integrative Human Physiology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sensorimotor Cortex, Biological psychiatry, Psychology, 2803 Biological Psychiatry, Adult, 2805 Cognitive Neuroscience, Autism, Cerebellum, Functional connectivity, Resting-state fMRI, Sensory networks, Visual-motor integration, Radiology, Nuclear Medicine and Imaging, Cognitive Neuroscience, Neurology (clinical), Biological Psychiatry, Adolescent, Cognitive Neuroscience, Clinical Neurology, Sensory system, 610 Medicine & health, Cognitive neuroscience, 050105 experimental psychology, 03 medical and health sciences, Young Adult, Salience (neuroscience), mental disorders, medicine, Humans, 2741 Radiology, Nuclear Medicine and Imaging, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Resting-state fMRI, Biological Psychiatry, Radiology, Nuclear Medicine and Imaging, Neurology (clinical), Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Resting state fMRI, medicine.disease, Case-Control Studies, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery
Abstract: BackgroundResting-state functional magnetic resonance imaging–based studies on functional connectivity in autism spectrum disorder (ASD) have generated inconsistent results. Interpretation of findings is further hampered by small samples and a focus on a limited number of networks, with networks underlying sensory processing being largely underexamined. We aimed to comprehensively characterize ASD-related alterations within and between 20 well-characterized resting-state networks using baseline data from the EU-AIMS (European Autism Interventions—A Multicentre Study for Developing New Medications) Longitudinal European Autism Project.MethodsResting-state functional magnetic resonance imaging data was available for 265 individuals with ASD (7.5–30.3 years; 73.2% male) and 218 typically developing individuals (6.9–29.8 years; 64.2% male), all with IQ > 70. We compared functional connectivity within 20 networks—obtained using independent component analysis—between the ASD and typically developing groups, and related functional connectivity within these networks to continuous (overall) autism trait severity scores derived from the Social Responsiveness Scale Second Edition across all participants. Furthermore, we investigated case-control differences and autism trait–related alterations in between-network connectivity.ResultsHigher autism traits were associated with increased connectivity within salience, medial motor, and orbitofrontal networks. However, we did not replicate previously reported case-control differences within these networks. The between-network analysis did reveal case-control differences showing on average 1) decreased connectivity of the visual association network with somatosensory, medial, and lateral motor networks, and 2) increased connectivity of the cerebellum with these sensory and motor networks in ASD compared with typically developing subjects.ConclusionsWe demonstrate ASD-related alterations in within- and between-network connectivity. The between-network alterations broadly affect connectivity between cerebellum, visual, and sensory-motor networks, potentially underlying impairments in multisensory and visual-motor integration frequently observed in ASD.
Published: 2019

21. Urinary metabolic profiling by 1H NMR spectroscopy in patients with cirrhosis may discriminate overt but not covert hepatic encephalopathy

Author: Sara Montagnese, Hamza El Hadi, Simon D. Taylor-Robinson, Roger Williams, Mark J. W. McPhail, I. Jane Cox, Manuela Villanova, Piero Amodio, Mary M.E. Crossey, and Wellcome Trust, UK
Subjects: 0301 basic medicine, LIVER, Cirrhosis, Hepatic encephalopathy, Hippurate, Histidine, Magnetic resonance spectroscopy, Metabolic profiling, Urinary biomarkers, Biochemistry, Neurology (clinical), Cellular and Molecular Neuroscience, Gastroenterology, DISEASE, Liver disease, chemistry.chemical_compound, 0302 clinical medicine, Model for End-Stage Liver Disease, HEPATOCELLULAR-CARCINOMA, MAGNETIC-RESONANCE, EEG, medicine.diagnostic_test, Hepatocellular carcinoma, TESTS, 030211 gastroenterology & hepatology, Life Sciences & Biomedicine, NUTRITIONAL-STATUS, medicine.medical_specialty, Urinary system, Clinical Neurology, VALIDATION, Endocrinology & Metabolism, 03 medical and health sciences, SYSTEMS, Internal medicine, medicine, Creatinine, Science & Technology, Neurology & Neurosurgery, business.industry, Neurosciences, METABONOMICS, 1103 Clinical Sciences, Magnetic resonance imaging, medicine.disease, 030104 developmental biology, Endocrinology, chemistry, Neurosciences & Neurology, 1109 Neurosciences, business
Abstract: To date urinary metabolic profiling has been applied to define a specific metabolic fingerprint of hepatocellular carcinoma on a background of cirrhosis. Its utility for the stratification of other complications of cirrhosis, such as hepatic encephalopathy (HE), remains to be established. Urinary proton nuclear magnetic resonance (1H-NMR) spectra were acquired and NMR data from 52 patients with cirrhosis (35 male; 17 female, median (range) age [60 (18–81) years]) and 17 controls were compared. A sub-set of 45 patients (33 male; 12 female, [60 (18–90) years, median model for end stage liver disease (MELD) score 11 (7–27)]) were fully characterised by West-Haven criteria, Psychometric Hepatic Encephalopathy Score (PHES) and electroencephalogram (EEG), and defined as overt HE (OHE, n = 21), covert HE (cHE, n = 7) or no HE (n = 17). Urinary proton nuclear magnetic resonance (1H-NMR) spectra were analysed by partial-least-squares discriminant analysis (PLS-DA). The results showed good discrimination between patients with cirrhosis (n = 52) and healthy controls (n = 17) (R2X = 0.66, R2Y = 0.47, Q2Y = 0.31, sensitivity-60 %, specificity-100 %) as the cirrhosis group had higher 1-methylnicotinamide with lower hippurate, acetate, phenylacetylglycine and N-methyl nicotinic acid levels. While patients with OHE could be discriminated from those with no HE, with higher histidine, citrate and creatinine levels, the best models lack robust validity (R2X = 0.65, R2Y = 0.48, Q2Y = 0.12, sensitivity-100 %, specificity-64 %) with the sample size used. Urinary 1H-NMR metabolic profiling did not discriminate patients with cHE from those without HE, nor discriminate subjects on the basis of PHES/EEG result or MELD score. In conclusion, patients with cirrhosis showed different urinary 1H-NMR metabolic profiles compared to healthy controls and those with OHE may be distinguished from those with no HE although larger studies are required. However, urinary 1H-NMR metabolic profiling did not discriminate patients with differing grades of HE or according to severity of underlying liver disease.
Published: 2016

22. Incidence and Outcomes for Patients With Cirrhosis Admitted to the United Kingdom Critical Care Units

Author: K Rowan, Francesca Parrott, William Bernal, Julia Wendon, David A Harrison, Mark J. W. McPhail, and Wellcome Trust, UK
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, MEDLINE, 1110 Nursing, Critical Care and Intensive Care Medicine, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Patient Admission, law, Liver Cirrhosis, Alcoholic, Intensive care, Epidemiology, medicine, Humans, 030212 general & internal medicine, Diagnosis-Related Groups, APACHE, Retrospective Studies, business.industry, Incidence (epidemiology), Incidence, Retrospective cohort study, 1103 Clinical Sciences, Middle Aged, medicine.disease, Intensive care unit, Emergency & Critical Care Medicine, United Kingdom, Intensive Care Units, Treatment Outcome, 1117 Public Health And Health Services, Research centre, Emergency medicine, 030211 gastroenterology & hepatology, Female, business
Abstract: OBJECTIVE: To assess the epidemiology and outcome of patients with cirrhosis following critical care unit admission.DESIGN: Retrospective cohort study.SETTING: Critical care units in England, Wales, and Northern Ireland participating in the U.K. Intensive Care National Audit and Research Centre Case Mix Programme.PATIENTS: Thirty-one thousand three hundred sixty-three patients with cirrhosis identified of 1,168,650 total critical care unit admissions (2.7%) admitted to U.K. critical care units between 1998 and 2012.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Ten thousand nine hundred thirty-six patients had alcohol-related liver disease (35%). In total, 1.6% of critical care unit admissions in 1998 had cirrhosis rising to 3.1% in 2012. The crude critical care unit mortality of patients with cirrhosis was 41% in 1998 falling to 31% in 2012 (p < 0.001). Crude hospital mortality fell from 58% to 46% over the study period (p < 0.001). Mean(SD) Acute Physiology and Chronic Health Evaluation II score in 1998 was 20.3 (8.5) and 19.5 (7.1) in 2012. Mean Acute Physiology and Chronic Health Evaluation II score for patients with alcohol-related liver disease in 2012 was 20.6 (7.0) and 19.0 (7.2) for non-alcohol-related liver disease (p < 0.001). In adjusted analysis, alcohol-related liver disease was associated with increased risk of death (odds ratio, 1.51 [95% CI, 1.42-1.62; p < 0.001]) with a year-on-year reduction in hospital mortality (adjusted odds ratio, 0.95/yr, [0.94-0.96, p < 0.001]).CONCLUSIONS: More patients with cirrhosis are being admitted to critical care units but with increasing survival rates. Patients with alcohol-related liver disease have reduced survival rates partly explained by higher levels of organ failure at admission. Patients with cirrhosis and organ failure warrant a trial of organ support and universal prognostic pessimism is not justified.
Published: 2018

23. Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen

Author: Rui Yu, Verena Broecker, Guillermo Burgos-Barragan, James A. Swenberg, Mark J. Arends, Gayathri Chandrasekaran, Ketan J. Patel, Gerry P. Crossan, Lucas B. Pontel, Wei Wei, Limin Liu, Iván V. Rosado, Juan I. Garaycoechea, Universidad de Sevilla. Departamento de Genética, Medical Research Council. UK, Instituto de Salud Carlos III. España, Ministerio de Economía y Competitividad (MINECO). España, National Institute of Environmental Health Sciences (NIEHS). U.S., Texas Commission for Environmental Quality. U.S., and Wellcome Trust. UK
Subjects: DNA damage, Endogeny, Kidney, Article, DNA Adducts, Gene Knockout Techniques, Mice, Formaldehyde, medicine, Animals, Molecular Biology, Carcinogen, Cells, Cultured, Alcohol dehydrogenase, biology, Fanconi Anemia Complementation Group D2 Protein, Alcohol Dehydrogenase, Kidney metabolism, Hematopoietic stem cell, Cell Biology, Hematopoietic Stem Cells, Molecular biology, 3. Good health, Cell biology, Haematopoiesis, medicine.anatomical_structure, Liver, biology.protein, Carcinogens, Stem cell, Mutagens
Abstract: Summary Endogenous formaldehyde is produced by numerous biochemical pathways fundamental to life, and it can crosslink both DNA and proteins. However, the consequences of its accumulation are unclear. Here we show that endogenous formaldehyde is removed by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), and Adh5−/− mice therefore accumulate formaldehyde adducts in DNA. The repair of this damage is mediated by FANCD2, a DNA crosslink repair protein. Adh5−/−Fancd2−/− mice reveal an essential requirement for these protection mechanisms in hematopoietic stem cells (HSCs), leading to their depletion and precipitating bone marrow failure. More widespread formaldehyde-induced DNA damage also causes karyomegaly and dysfunction of hepatocytes and nephrons. Bone marrow transplantation not only rescued hematopoiesis but, surprisingly, also preserved nephron function. Nevertheless, all of these animals eventually developed fatal malignancies. Formaldehyde is therefore an important source of endogenous DNA damage that is counteracted in mammals by a conserved protection mechanism., Graphical Abstract, Highlights • ADH5 removes endogenous formaldehyde to prevent DNA adducts • ADH5 and FANCD2 protect HSCs, hepatocytes, and nephrons from endogenous DNA damage • Bone marrow transplantation provides protection against formaldehyde nephrotoxicity • Endogenous formaldehyde is a potent carcinogen, Formaldehyde is a ubiquitous, highly reactive molecule that is a byproduct of metabolism; Pontel et al. now show how mammals protect themselves against this metabolic toxin and what happens if this protection is removed.
Published: 2015
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24. Molecular structure studies of (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol

Author: Krzysztof J. Paluch, Anne Marie Healy, Tao Zhang, Helen Sheridan, Neil Frankish, Gaia Scalabrino, and The Wellcome Trust UK
Subjects: Stereochemistry, Crystal structure, Nuclear magnetic resonance crystallography, XRPD, Article, Analytical Chemistry, X-ray, Inorganic Chemistry, Chemical separation, Molecule, Spectroscopy, 2S)-2-Benzyl-2, Chemistry, (1S, Organic Chemistry, Diastereomer, Life Sciences, (1S,2S)-2-Benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol, NMR, 3. Good health, 3-dihydro-2-(1H-inden- 2-yl)-1H-inden-1-ol, Single enantiomer, Enantiomer, Powder diffraction
Abstract: Highlights • Chemical separation is used for racemate resolution. • NMR analyses are used for single enantiomer structure education. • Intermolecular interactions are observed by X-ray study., The single enantiomer (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol (2), has recently been synthesized and isolated from its corresponding diastereoisomer (1). The molecular and crystal structures of this novel compound have been fully analyzed. The relative and absolute configurations have been determined by using a combination of analytical tools including X-ray crystallography, X-ray Powder Diffraction (XRPD) analysis and Nuclear Magnetic Resonance (NMR) spectroscopy.
Published: 2015
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25. Community perceptions of health and chronic disease in South Indian rural transitional communities: a qualitative study

Author: Arabella K M, Hayter, Roger, Jeffery, Chitra, Sharma, Audrey, Prost, Sanjay, Kinra, and Wellcome Trust UK
Subjects: Adult, Male, Rural Population, community environment, Adolescent, Health Status, India, Young Adult, chronic disease, urbanisation, qualitative, Residence Characteristics, Humans, Exercise, Qualitative Research, lcsh:Public aspects of medicine, Urbanization, lcsh:RA1-1270, Middle Aged, Diet, Socioeconomic Factors, Quality of Life, Female, Perception, Original Article, Environmental Pollution, Community Health, Global Health, Public Health
Abstract: Background: Chronic diseases are now the leading cause of death and disability worldwide; this epidemic has been linked to rapid economic growth and urbanisation in developing countries. Understanding how characteristics of the physical, social, and economic environment affect behaviour in the light of these changes is key to identifying successful interventions to mitigate chronic disease risk.Design: We undertook a qualitative study consisting of nine focus group discussions (FGDs) (n=57) in five villages in rural Andhra Pradesh, South India, to understand people’s perceptions of community development and urbanisation in relation to chronic disease in rural transitional communities. Specifically, we sought to understand perceptions of change linked to diet, physical activity, and pollution (because these exposures are most relevant to chronic diseases), with the aim of defining future interventions. The transcripts were analysed thematically.Results: Participants believed their communities were currently less healthy, more polluted, less physically active, and had poorer access to nutritious food and shorter life expectancies than previously. There were contradictory perceptions of the effects of urbanisation on health within and between individuals; several of the participants felt their quality of life had been reduced.Conclusions: In the present study, residents viewed change and development within their villages as an inevitable and largely positive process but with some negative health consequences. Understanding how these changes are affecting populations in transitional rural areas and how people relate to their environment may be useful to guide community planning for health. Measures to educate and empower people to make healthy choices within their community may help reduce the spread of chronic disease risk factors in future years.Keywords: chronic disease; urbanisation; community environment; qualitative; India(Published: 9 February 2015)Citation: Glob Health Action 2015, 8: 25946 - http://dx.doi.org/10.3402/gha.v8.25946
Published: 2015

26. Multi-platform metabonomics reveals a distinct metabolic phenotype of acute-on-chronic liver failure

Author: Zia, R, Patel, VC, Gray, N, Wilson, ID, Wendon, J, McPhail, M, Coen, M, Wellcome Trust, UK, Medical Research Council, and Imperial College Healthcare NHS Trust- BRC Funding
Subjects: Science & Technology, Gastroenterology & Hepatology, 1101 Medical Biochemistry And Metabolomics, 1103 Clinical Sciences, Life Sciences & Biomedicine
Published: 2017

27. Xpf suppresses the mutagenic consequences of phagocytosis in Dictyostelium

Author: Pontel, Lucas B., Langenick, Judith, Valle Rosado, Iván, Zhang, Xiao-Yin, Traynor, David, Kay, Robert R., Patel, Ketan J., [Pontel, Lucas B.] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England, [Langenick, Judith] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England, [Rosado, Ivan V.] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England, [Zhang, Xiao-Yin] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England, [Traynor, David] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England, [Kay, Robert R.] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England, [Patel, Ketan J.] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England, [Rosado, Ivan V.] Univ Seville, Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS Hosp, Seville 41013, Spain, [Zhang, Xiao-Yin] Oxford Univ Hosp NHS Fdn Trust, Dept Haematol, Oxford OX1 2HB, England, [Patel, Ketan J.] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England, Medical Research Council (MRC), Wellcome Trust, Cancer Research UK, MRC, Medical Research Council, Universidad de Sevilla. Departamento de Genética, Medical Research Council (MRC). UK, Wellcome Trust. UK, and Cancer Research. UK
Subjects: Xpf, Bacteria, DNA Repair, Methanol, fungi, Resistance, Protozoan Proteins, macromolecular substances, Growth, Discoideum, Dna-damage, Genes, Phagocytosis, Mutagenesis, Dictyostelium, Ameba, Amino Acid Sequence, Repair, Pathway
Abstract: As time passes, mutations accumulate in the genomes of all living organisms. These changes promote genetic diversity, but also precipitate ageing and the initiation of cancer. Food is a common source of mutagens, but little is known about how nutritional factors cause lasting genetic changes in the consuming organism. Here, we describe an unusual genetic interaction between DNA repair in the unicellular amoeba Dictyostelium discoideum and its natural bacterial food source. We found that Dictyostelium deficient in the DNA repair nuclease Xpf (xpf−) display a severe and specific growth defect when feeding on bacteria. Despite being proficient in the phagocytosis and digestion of bacteria, over time, xpf− Dictyostelium feeding on bacteria cease to grow and in many instances die. The Xpf nuclease activity is required for sustained growth using a bacterial food source. Furthermore, the ingestion of this food source leads to a striking accumulation of mutations in the genome of xpf− Dictyostelium. This work therefore establishes Dictyostelium as a model genetic system to dissect nutritional genotoxicity, providing insight into how phagocytosis can induce mutagenesis and compromise survival fitness. Medical Research Council (MRC) de Reino Unido. MC_U105178811 y MC_U105115237 Wellcome Trust de Reino Unido. WT106202
Published: 2016

28. Targeting CCL5 in inflammation

Author: Rodrigo Guabiraba, Remo Castro Russo, Mauro M. Teixeira, Rafael Elias Marques, Universidade Federal de Minas Gerais, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Institute of Infection, Immunity and Inflammation, University of Glasgow, Brazilian funding agency CNPq, Brazilian support agencies (CNPq, FAPEMIG, FINEP), European community, Wellcome Trust, UK, and Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT)
Subjects: CCR1, Graft Rejection, Chemokine, Clinical Biochemistry, CCR3, Helminthiasis, Reviews, Inflammation, Context (language use), CCL5, 03 medical and health sciences, RANTES, 0302 clinical medicine, Immune system, stomatognathic system, Neoplasms, parasitic diseases, Drug Discovery, medicine, Animals, Humans, Chemokine CCL5, 030304 developmental biology, Pharmacology, 0303 health sciences, disease pathogenesis, biology, Neovascularization, Pathologic, business.industry, virus diseases, hemic and immune systems, Atherosclerosis, Fibrosis, infection, Asthma, 3. Good health, Clinical trial, stomatognathic diseases, Virus Diseases, 030220 oncology & carcinogenesis, Immunology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular Medicine, medicine.symptom, business
Abstract: Marques, Rafael Elias Guabiraba, Rodrigo Russo, Remo Castro Teixeira, Mauro Martins Wellcome Trust/United Kingdom England Expert Opin Ther Targets. 2013 Dec;17(12):1439-60. doi: 10.1517/14728222.2013.837886. Epub 2013 Oct 3.; International audience; INTRODUCTION: Chemokines play important roles in inflammation and in immune responses. This article will discuss the current literature on the C-C chemokine ligand 5 (CCL5), and whether it is a therapeutic target in the context of various allergic, autoimmune or infectious diseases. AREAS COVERED: Small-molecule inhibitors, chemokine and chemokine receptor-deficient mice, antibodies and modified chemokines are the current tools available for CCL5 research, and there are several ongoing clinical trials targeting the CCL5 receptors, CCR1, CCR3 and CCR5. There are fewer studies specifically targeting the chemokine itself and clinical studies with anti-CCL5 antibodies are still to be carried out. EXPERT OPINION: Although clinical trials are strongly biased toward HIV treatment and prevention with blockers of CCR5, the therapeutic potential for CCL5 and its receptors in other diseases is relevant. Overall, it is not likely that specific targeting of CCL5 will result in new adjunct strategies for the treatment of infectious diseases with a major inflammatory component. However, targeting CCL5 could result in novel therapies for chronic inflammatory diseases, where it may decrease inflammatory responses and fibrosis, and certain solid tumors, where it may have a role in angiogenesis.
Published: 2013

29. Complex dynamic of dengue virus serotypes 2 and 3 in Cambodia following series of climate disasters

Author: Alain Viari, Chantha Ngan, Vincent Deubel, Sowath Ly, Sivuth Ong, Veasna Duong, Bunthin Y, Rekol Huy, Niall J. Lennon, Philippe Buchy, Matthew R. Henn, Bruce W. Birren, Jeremy Farrar, Laurent Gavotte, Roger Frutos, Cameron P. Simmons, Sirenda Vong, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), National Center of Parasitology (CNM), National Malaria Center [Phnom Penh], Université Montpellier 2 - Sciences et Techniques (UM2), An algorithmic view on genomes, cells, and environments (BAMBOO), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria), Interactions hôtes-vecteurs-parasites-environnement dans les maladies tropicales négligées dues aux trypanosomatides (UMR INTERTRYP), Université de Bordeaux (UB)-Institut de Recherche pour le Développement (IRD)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), This study was funded in part by the Wellcome Trust UK. Roger Frutos was supported in part by the PHC Grant 20624 VK and the FP7 Erasmus Mundus project MAHEVA. Alain Viari was supported in part by the PHC Grant 20624 VK. We are very grateful to the Doctorate School SIBAGHE (University Montpellier 2) and the French Ministry of Foreign Affairs for providing scholarships supporting in part Veasna Duong., Duong V, Henn MR, Ly S, Vong S, Birren BW, Farrar JJ, Deubel V, Frutos R, Buchy P., Simmons C, Ngan C, Y B, Gavotte L, Viari A, Ong S, Huy R, Lennon NJ, Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université de Bordeaux (UB)
Subjects: Serotype, Genes, Viral, Climate, viruses, Lineage (evolution), Dengue virus, Accident climatique, Facteur climatique, medicine.disease_cause, Dengue fever, Dengue, Disasters, 0302 clinical medicine, Lignée, Case fatality rate, Child, Phylogeny, Diversity, 0303 health sciences, education.field_of_study, biology, virus diseases, Middle Aged, 3. Good health, Flavivirus, Infectious Diseases, S50 - Santé humaine, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cambodia, épidémie, Adult, Microbiology (medical), Adolescent, Molecular Sequence Data, 030231 tropical medicine, Population, Descendance, Genome, Viral, Catastrophe naturelle, Microbiology, Open Reading Frames, Young Adult, 03 medical and health sciences, Variation génétique, Genetics, medicine, Humans, Amino Acid Sequence, Selection, Genetic, Serotyping, education, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Aged, 030304 developmental biology, Polymorphism, Genetic, Base Sequence, DENV-2, Infant, DENV-3, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, medicine.disease, Virology, Sérotype, Lineage dynamics, Vector (epidemiology), Mutation
Abstract: Lien vers le texte intégral : http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=22677620; International audience; The Dengue National Control Program was established in Cambodia in 2000 and has reported between 10,000 and 40,000 dengue cases per year with a case fatality rate ranging from 0.7 to 1.7. In this study 39 DENV-2 and 57 DENV-3 viruses isolated from patients between 2000 and were fully sequenced. Five DENV2 and four DENV3 distinct lineages with different dynamics were identified. Each lineage was characterized by the presence of specific mutations with no evidence of recombination. In both DENV-2 and DENV-3 the lineages present prior to 2003 were replaced after that date by unrelated lineages. After 2003, DENV-2 lineages D2-3 and D2-4 cocirculated until 2007 when they were almost completely replaced by a lineage D2-5 which emerged from Conversely, all DENV-3 lineages remained, diversified and cocirculated with novel lineages emerging. Years 2006 and 2007 were marked by a high prevalence of DENV-3 and 2007 with a large dengue outbreak and a high proportion of patients with severe disease. Selective sweeps in DENV-1 and DENV-2 were linked to immunological escape to a predominately DENV-3-driven immunological response. The complex dynamic of dengue in Cambodia in the last ten years has been associated with a combination of stochastic climatic events, cocirculation, coevolution, adaptation to different vector populations, and with the human population immunological landscape.
Published: 2013

30. Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change

Author: Giovanna Tagliabue, Ingegerd Johansson, José María Huerta, Domenico Palli, Anne Tjønneland, Petra H.M. Peeters, Aurelio Barricarte, Anne M. May, Göran Hallmans, Francesca L. Crowe, Madlen Schütze, Daphne L. van der A, Françoise Clavel-Chapelon, Birgit Teucher, George Makrygiannis, Thorkild I. A. Sørensen, Jonas Manjer, Isabelle Romieu, Laudina Rodríguez, H. B. Bueno-de-Mesquita, Veronique Chajes, Kim Overvad, Guy Fagherazzi, Nadia Slimani, Karen Margrete Due, Nicholas J. Wareham, Dimosthenis Zylis, Heiner Boeing, Pilar Amiano, Kay-Tee Khaw, Claus Dethlefsen, Amalia Mattiello, Marianne Uhre Jakobsen, Rudolf Kaaks, Jytte Halkjær, Marie-Christine Boutron-Ruault, Elisabet Wirfält, Esther Molina-Montes, Noémie Travier, Elio Riboli, Antonia Trichopoulou, [Jakobsen,MU] Department of Clinical Epidemiology. [Jakobsen,MU, Dethlefsen,C, Due,KM, Overvad,K] Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Aalborg. [Jakobsen,MU, Overvad,K] Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark. [Slimani,N, Chajès,V, Romieu,I] Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. [May,AM, Peeter,PHM] Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht. [May,AM, van der A,DL, Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Sørensen,TIA] Institute of Preventive Medicine, Copenhagen University Hospital. [Halkjær,J, Tjønneland,A] The Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark. [Clavel-Chapelon,F, Boutron-Ruault,M, Fagherazzi,G] Inserm, Centre for Research in Epidemiology and Population Health, Institut Gustave Roussy. Paris South University, Villejuif, France. [Teucher,B, Kaaks,R] German Cancer Research Center, Department of Cancer Epidemiology, Heidelberg. [Boeing,H, Schütze,M, Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Zylis,D] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School. [Trichopoulou,A, Zylis,D, Makrygiannis,G] Hellenic Health Foundation, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, ISPO, Florence. [Mattiello,A] Department of Clinical and Experimental Medicine, Federico II University, Naples. [Tagliabue,G] Cancer Registry and Environmental Epidemiology Division, National Cancer Institute, Milan, Italy. [Bueno-de-Mesquita,HB] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands. [Rodríguez,L] Public Health and Participation Directorate, Health and Health Care Services Council, Asturias. [Travier,N] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, IDIBELL, Barcelona. [Molina-Montes,E] Andalusian School of Public Health, Granada. [Molina-Montes,E, Huerta,JM, Barricarte,A, Amiano,P] CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia. [Barricarte,A] Public Health Institute of Navarra, Pamplona. [Amiano,P] Public Health Division of Gipuzkoa, Basque Government, Spain. [Manjer,J] Department of Surgery, Skåne University Hospital Malmö, Lund University. [Wirfält,E] Department of Clinical Sciences in Malmö/Nutrition Epidemiology, Lund University, Malmö. [Johansson,I] Department of Odontology, Umeå University. [Hallmans,G] Department of Public Health and Clinical Medicine, Umeå University, Nutritional Research, Umeå, Sweden. [Khaw,K] Clinical Gerontology Unit, Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge. [Wareham, NJ] MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge. [Crowe,F] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford. [Riboli,E, Peeters, PHM] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK., This work is part of the project Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of Home and Obesity (PANACEA), which is supported by the European Union in the framework of the Public Health Programmme (Contract 2005328). The work was further supported by the European Commission: Public Health and Consumer Protection Directorate 1993–2004, Research Directorate-General 2005, Ligue contre le Cancer, Société 3M, Mutuelle Générale de l’Education Nationale, Institut National de la Santé de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany), Danish Cancer Society (Denmark), ISCIII (RETICC RD06/0020) of the Spanish Ministry of Health, the participating regional governments and institutions (Spain), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, The Wellcome Trust (UK), Greek Ministry of Health, Greek Ministry of Education, Hellenic Ministry of Health, Stavros Niarchos Foundation, and the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer, National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports, Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, Dutch Zorg Onderzoek Nederland (ZON), World Cancer Research Fund (WCRF) (The Netherlands), and and Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane and Västerbotten (Sweden). This work is also part of the project Hepatic and Adipose Tissue and Functions in the Metabolic Syndrome (HEPADIP, www.hepadip.org), which is supported by the European Commission as an Integrated Project under the 6th Framework Programme (Contract LSHM-CT-2005-018734) and part of the research program of the Danish Obesity Research Centre (DanORC, www.danorc.dk), which is supported by the Danish Council for Strategic Research (Contract 2101-06-0005).
Subjects: Male, Health (social science), 030309 nutrition & dietetics, Obesidad, Ácidos grasos omega-3, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, 0302 clinical medicine, Estudios prospectivos, Fosfolípidos, Modelos lineales, Prospective Studies, Masculino, Prospective cohort study, Phospholipids, chemistry.chemical_classification, 0303 health sciences, education.field_of_study, Weight change, Femenino, Middle Aged, n-3 fatty acids, Humanos, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Female, Original Article, lipids (amino acids, peptides, and proteins), Cohort study, Polyunsaturated fatty acid, medicine.medical_specialty, 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, Phospholipid, Check Tags::Male [Medical Subject Headings], 030209 endocrinology & metabolism, 03 medical and health sciences, Chemicals and Drugs::Lipids::Fats::Dietary Fats::Dietary Fats, Unsaturated::Fatty Acids, Omega-3 [Medical Subject Headings], Physiology (medical), Internal medicine, Fatty Acids, Omega-3, Omega-3 fatty acids, medicine, Humans, Obesity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Linear Models [Medical Subject Headings], Chemicals and Drugs::Lipids::Phospholipids [Medical Subject Headings], education, Mediana edad, business.industry, Body Weight, Peso corporal, Body weight, Confidence interval, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Endocrinology, Check Tags::Female [Medical Subject Headings], chemistry, Linear Models, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight [Medical Subject Headings], sense organs, business
Abstract: Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVE We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. METHOD A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. RESULTS The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was -0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: -20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. CONCLUSION The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population. Yes
Published: 2016

31. Mutlivariate metabotyping of plasma accurately predicts survival in decompensated cirrhosis

Author: McPhail, MJW, Shawcross, D, Lewis, MR, Coltart, I, Want, E, Veselkov, K, Abeles, RD, Kyriakides, M, Pop, O, Triantafyllou, E, Antoniades, CG, Quaglia, A, Bernal, W, Auzinger, G, Coen, M, Nicholson, J, Wendon, JA, Holmes, E, Taylor-Robinson, SD, Jassem, W, O'Grady, J, Heaton, N, Wellcome Trust, Imperial College Healthcare Charity, Imperial College Healthcare NHS Trust- BRC Funding, and Wellcome Trust, UK
Subjects: Gastroenterology & Hepatology, Metabonomics, Acute on chronic liver failure, Metabolic profiling, Metabolomics, Personalised medicine, 1103 Clinical Sciences, Outcome prediction
Published: 2016

32. Interaction Between Hippocampus and Cerebellum Crus I in Sequence-Based but not Place-Based Navigation

Author: Anne-Lise Paradis, Christian F. Doeller, Karim Benchenane, Kinga Igloi, Neil Burgess, Alain Berthoz, Laure Rondi-Reig, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-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)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-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)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC), EU, Agence Nationale de la Recherche, Fondation pour la Recherche Medicale (France), Medical Research Council, Wellcome Trust (UK), European Research Council [ERC-StG RECONTEXT 261177], Netherlands Organisation for Scientific Research (NWO-Vidi) [452-12-009], Collège de France (CdF (institution)), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-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)-Centre National de la Recherche Scientifique (CNRS), 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)-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)-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)-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)
Subjects: Adult, Male, Cerebellum, Cognitive Neuroscience, Posterior parietal cortex, Hippocampus, Hippocampal formation, Sequence learning, Spatial memory, Functional Laterality, Virtual reality, User-Computer Interface, Young Adult, Functional connectivity, Cellular and Molecular Neuroscience, Neural Pathways, Image Processing, Computer-Assisted, medicine, Humans, Maze Learning, Prefrontal cortex, sequence learning, medicine.diagnostic_test, fMRI, functional connectivity, Parietal lobe, Articles, spatial memory, Magnetic Resonance Imaging, Oxygen, ddc:128.37, medicine.anatomical_structure, nervous system, virtual reality, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Functional magnetic resonance imaging, 120 Memory and Space, Neuroscience, Spatial Navigation
Abstract: International audience; To examine the cerebellar contribution to human spatial navigation we used functional magnetic resonance imaging and virtual reality. Our findings show that the sensory-motor requirements of navigation induce activity in cerebellar lobules and cortical areas known to be involved in the motor loop and vestibular processing. By contrast, cognitive aspects of navigation mainly induce activity in a different cerebellar lobule (VIIA Crus I). Our results demonstrate a functional link between cerebellum and hippocampus in humans and identify specific functional circuits linking lobule VIIA Crus I of the cerebellum to medial parietal, medial prefrontal, and hippocampal cortices in nonmotor aspects of navigation. They further suggest that Crus I belongs to 2 nonmotor loops, involved in different strategies: placebased navigation is supported by coherent activity between left cerebellar lobule VIIA Crus I and medial parietal cortex along with right hippocampus activity, while sequence-based navigation is supported by coherent activity between right lobule VIIA Crus I, medial prefrontal cortex, and left hippocampus. These results highlight the prominent role of the human cerebellum in both motor and cognitive aspects of navigation, and specify the cortico-cerebellar circuits by which it acts depending on the requirements of the task.
Published: 2015

33. Ability of King's College criteria and model for end-stage liver disease scores to predict mortality of patients with acute liver failure: a meta-analysis

Author: Mark J. W. McPhail, Hugo Farne, William Bernal, Julia Wendon, Naz Senvar, and Wellcome Trust, UK
Subjects: medicine.medical_specialty, Survival, medicine.medical_treatment, Clinical Sciences, Liver transplantation, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Model for End-Stage Liver Disease, Internal medicine, medicine, Mortality, Hepatology, Receiver operating characteristic, Gastroenterology & Hepatology, business.industry, Gastroenterology, Odds ratio, medicine.disease, Prognosis, King's College Criteria, Confidence interval, Surgery, 030220 oncology & carcinogenesis, Diagnostic odds ratio, 030211 gastroenterology & hepatology, business, Prediction
Abstract: Background & Aims Several prognostic factors are used to identify patients with acute liver failure (ALF) who require emergency liver transplantation. We performed a meta-analysis to determine the accuracy of King's College criteria (KCC) versus the model for end-stage liver disease (MELD) scores in predicting hospital mortality among patients with ALF. Methods We performed a systematic search of the literature for articles published from 2001 through 2015 that compared the accuracy of the KCC with MELD scores in predicting hospital mortality in patients with ALF. We identified 23 studies (comprising 2153 patients) and assessed the quality of data, and then performed a meta-analysis of pooled sensitivity and specificity values, diagnostic odds ratios (DORs), and summary receiver operating characteristic curves. Subgroups analyzed included study quality, era, location (Europe vs non-Europe), and size; ALF etiology (acetaminophen-associated ALF [AALF] vs nonassociated [NAALF]); and whether or not the study included patients who underwent liver transplantation and if the study center was also a transplant center. Results The DOR for the KCC was 5.3 (95% confidence interval [CI], 3.7–7.6; 57% heterogeneity) and the DOR for MELD score was 7.0 (95% CI, 5.1–9.7; 48% heterogeneity), so the MELD score and KCC are comparable in overall accuracy. The summary area under the receiver operating characteristic curve values was 0.76 for the KCC and 0.78 for MELD scores. The KCC identified patients with AALF who died with 58% sensitivity (95% CI, 51%–65%) and 89% specificity (95% CI, 85%–93%), whereas MELD scores identified patients with AALF who died with 80% sensitivity (95% CI, 74%–86%) and 53% specificity (95% CI, 47%–59%). The KCC predicted hospital mortality in patients with NAALF with 58% sensitivity (95% CI, 54%–63%) and 74% specificity (95% CI, 69%–78%), whereas MELD scores predicted hospital mortality in patients with NAALF with 76% sensitivity (95% CI, 72%–80%) and 73% specificity (95% CI, 69%–78%). In patients with AALF, the KCC's DOR was 10.4 (95% CI, 4.9–22.1) and the MELD score's DOR was 6.6 (95% CI, 2.1–20.2). In patients with NAALF, the KCC's DOR was 4.16 (95% CI, 2.34–7.40) and the MELD score's DOR was 8.42 (95% CI, 5.98–11.88). Conclusions Based on a meta-analysis of studies, the KCC more accurately predicts hospital mortality among patients with AALF, whereas MELD scores more accurately predict mortality among patients with NAALF. However, there is significant heterogeneity among studies and neither system is optimal for all patients. Given the importance of specificity in decision making for listing for emergency liver transplantation, MELD scores should not replace the KCC in predicting hospital mortality of patients with AALF, but could have a role for NAALF.
Published: 2015

34. Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Author: Stéphane Duquerroy, Christine Girard-Blanc, William Shepard, Wiyada Wongwiwat, Giovanna Barba-Spaeth, Stéphane Petres, Félix A. Rey, Pablo Guardado-Calvo, Ahmed Haouz, Juthathip Mongkolsapaya, M. Erika Navarro Sanchez, Carlos M. Kikuti, Wanwisa Dejnirattisai, Philippe Dussart, Fernando Arenzana-Seisdedos, Alexander Rouvinski, Marie-Christine Vaney, Philippe Desprès, Gavin R. Screaton, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11), Imperial College London, Protéopole, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur [Paris] (IP), Pathogénie Virale - Viral Pathogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Mahidol University [Bangkok], his work was made possible by a Pediatrics Dengue Vaccine Initiative grant to F.A.R., allowing the set up of a production facility of recombinant DENV sE. The co-crystallization with the bnAbs was done with European Union funding (DenFree consortium) to F.A.R. and G.R.S./J.M. F.A.R. acknowledges support from Insitut Pasteur, from the French Government’s ‘Investissements d’Avenir’ program: Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant number ANR-10-LABX-62-IBEID) and the CNRS. G.S.R. and J.M. were supported by the Medical Research Council, UK, the Wellcome Trust, UK, the National Institute for Health Research Biomedical Research Centre, Funding Scheme. G.R.S. is a Wellcome Trust Senior investigator. We thank staffs at beam lines PROXIMA-1 and PROXIMA-2 at the SOLEIL synchrotron (St Aubin, France) and ID23-2 and ID29 at the European Synchrotron Radiation Facility (Grenoble, France)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Tortosa, Pablo, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Pathogénie Virale, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical Research Council (MRC), Wellcome Trust, Commission of the European Communities, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]
Subjects: Serotype, MECHANISM, Models, Molecular, MONOCLONAL-ANTIBODY, FAB FRAGMENTS, Protein Conformation, viruses, DROSOPHILA S2 CELLS, Dengue virus, medicine.disease_cause, Antibodies, Viral, Crystallography, X-Ray, Epitope, Dengue fever, Epitopes, FUSION, Viral Envelope Proteins, Virus maturation, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Multidisciplinary, REFINEMENT, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], BORNE ENCEPHALITIS-VIRUS, ENVELOPE GLYCOPROTEIN, 3. Good health, Multidisciplinary Sciences, Flavivirus, IMMATURE FLAVIVIRUS PARTICLES, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Science & Technology - Other Topics, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.IMM] Life Sciences [q-bio]/Immunology, General Science & Technology, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Molecular Sequence Data, Biology, Cross Reactions, Virus, MATURATION, 03 medical and health sciences, Species Specificity, MD Multidisciplinary, medicine, Humans, Antibody-dependent enhancement, 030304 developmental biology, Science & Technology, 030306 microbiology, Dengue Virus, medicine.disease, biology.organism_classification, Virology, Antibodies, Neutralizing, Solubility, Mutation, Protein Multimerization
Abstract: International audience; Dengue disease is caused by four different flavivirus serotypes, which infect 390 million people yearly with 25% symptomatic cases and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (refs 3, 4). Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies. We recently isolated human antibodies potently neutralizing all four dengue virus serotypes. Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop and the two conserved glycan chains. This 'E-dimer-dependent epitope' is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell, explaining its conservation across serotypes and highlighting an Achilles' heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus.
Published: 2015

35. Two distinct cytoplasmic regions of the beta2 integrin chain regulate RhoA function during phagocytosis

Author: Agnès Wiedemann, Andy Tsun, Jenson Lim, Jayesh C Patel, Yvette van Kooyk, Emmanuelle Caron, Molecular cell biology and Immunology, Imperial College London, and Wellcome Trust, UK (068556/Z/02/Z), Biotechnology and Biological Sciences Research Council (28/C18637)
Subjects: Threonine, rac1 GTP-Binding Protein, RHOA, Erythrocytes, Phagocytosis, Integrin, Molecular Sequence Data, Macrophage-1 Antigen, GTPase, Biology, Transfection, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Cell Line, Tumor, Phagosomes, Chlorocebus aethiops, Animals, Amino Acid Sequence, Rho-associated protein kinase, Research Articles, 030304 developmental biology, Phagosome, 0303 health sciences, [SDV.BA]Life Sciences [q-bio]/Animal biology, Macrophages, Cell Biology, Actins, Cell biology, 030220 oncology & carcinogenesis, Macrophage-1 antigen, CD18 Antigens, COS Cells, Complement C3b, Mutation, biology.protein, Tetradecanoylphorbol Acetate, MDia1, Guanosine Triphosphate, rhoA GTP-Binding Protein
Abstract: AlphaMbeta2 integrins mediate phagocytosis of opsonized particles in a process controlled by RhoA, Rho kinase, myosin II, Arp2/3, and actin polymerization. AlphaMbeta2, Rho, Arp2/3, and F-actin accumulate underneath bound particles; however, the mechanism regulating Rho function during alphaMbeta2-mediated phagocytosis is poorly understood. We report that the binding of C3bi-opsonized sheep red blood cells (RBCs) to alphaMbeta2 increases Rho-GTP, but not Rac-GTP, levels. Deletion of the cytoplasmic domain of beta2, but not of alphaM, abolished Rho recruitment and activation, as well as phagocytic uptake. Interestingly, a 16-amino acid (aa) region in the membrane-proximal half of the beta2 cytoplasmic domain was necessary for activating Rho. Three COOH-terminal residues (aa 758-760) were essential for beta2-induced accumulation of Rho at complement receptor 3 (CR3) phagosomes. Activation of Rho was necessary, but not sufficient, for its stable recruitment underneath bound particles or for uptake. However, recruitment of active Rho was sufficient for phagocytosis. Our data shed light on the mechanism of outside-in signaling, from ligated integrins to the activation of Rho GTPase signaling.
Published: 2006

36. Low health-related quality of life in school-aged children in Tonga, a lower-middle income country in the South Pacific

Author: Boyd Swinburn, Helen Mavoa, Marjory Moodie, Gavin Faeamani, Caroline Tupoulahi-Fusimalohi, Solveig Petersen, Kalesita Fotu, and the Wellcome Trust (UK), the National Health and Medical Research Council (Australia), the Health Research Council (New Zealand), the current paper also by the Swedish Council for Working Life and Social Research and the Olle Engkvist Foundation (Sweden)
Subjects: Male, Economic growth, Epidemiology, Health Status, Distribution (economics), Quality of life, Surveys and Questionnaires, Child, community health, Psychiatry, education.field_of_study, Health Policy, lcsh:Public aspects of medicine, Tonga, 1. No poverty, Public Health, Global Health, Preventive Medicine, Community Health, Population Health, Gender Studies, Public Health, Global Health, Social Medicine and Epidemiology, adolescent health, humanities, 3. Good health, Mental Health, Community health, Income, child health, Original Article, Female, low-income population, mental health, quality of life, Adolescent health, medicine.medical_specialty, Adolescent, Population, Developing country, Psykiatri, RA1-1270, RA407-409.5, RA421-790.95, RA790-790.95, RC49-52, RJ101-103, medicine, Humans, education, Developing Countries, business.industry, Public health, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Mental health, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Cross-Sectional Studies, business, Demography, New Zealand
Abstract: Background : Ensuring a good life for all parts of the population, including children, is high on the public health agenda in most countries around the world. Information about children’s perception of their health-related quality of life (HRQoL) and its socio-demographic distribution is, however, limited and almost exclusively reliant on data from Western higher income countries. Objectives : To investigate HRQoL in schoolchildren in Tonga, a lower income South Pacific Island country, and to compare this to HRQoL of children in other countries, including Tongan children living in New Zealand, a high-income country in the same region. Design : A cross-sectional study from Tonga addressing all secondary schoolchildren (11–18 years old) on the outer island of Vava’u and in three districts of the main island of Tongatapu (2,164 participants). A comparison group drawn from the literature comprised children in 18 higher income and one lower income country (Fiji). A specific New Zealand comparison group involved all children of Tongan descendent at six South Auckland secondary schools (830 participants). HRQoL was assessed by the self-report Pediatric Quality of Life Inventory 4.0. Results : HRQoL in Tonga was overall similar in girls and boys, but somewhat lower in children below 15 years of age. The children in Tonga experienced lower HRQoL than the children in all of the 19 comparison countries, with a large difference between children in Tonga and the higher income countries (Cohen’s d 1.0) and a small difference between Tonga and the lower income country Fiji (Cohen’s d 0.3). The children in Tonga also experienced lower HRQoL than Tongan children living in New Zealand (Cohen’s d 0.6). Conclusion : The results reveal worrisome low HRQoL in children in Tonga and point towards a potential general pattern of low HRQoL in children living in lower income countries, or, alternatively, in the South Pacific Island countries. Keywords : adolescent health; child health; community health; Epidemiology; low-income population; mental health; quality of life (Published: 20 August 2014) Citation : Glob Health Action 2014, 7 : 24896 - http://dx.doi.org/10.3402/gha.v7.24896
Published: 2014

37. Dietary intakes and food sources of phenolic acids in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author: Sabina Sieri, Elio Riboli, Konstantinos Tsiotas, Fulvio Ricceri, Raul Zamora-Ros, Florence Perquier, Pilar Amiano, Domenico Palli, Kim Overvad, José María Huerta, Marina Touillaud, H. Bas Bueno-de-Mesquita, Anne Tjønneland, Petra H.M. Peeters, Guy Fagherazzi, Peter Wallström, Dagrun Engeset, Joseph A. Rothwell, Rosario Tumino, Carlos González, Ingegerd Johansson, Kay Thee Khaw, Vassiliki Benetou, Francesca L. Crowe, Aurelio Barricarte, Isabelle Romieu, Rikard Landberg, Jana Förster, Nadia Slimani, Augustin Scalbert, Martine M. Ros, Ulrika Ericson, Jytte Halkjær, Viktoria Knaze, Nicholas J. Wareham, Verena A. Grote, Heiner Boeing, Petra A. Wark, Elisabete Weiderpass, Esther Molina-Montes, Kuanrong Li, Guri Skeie, Virginia Menéndez, Maria Santucci de Magistris, Antonia Trichopoulou, Catalan Institute of Oncology, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Centre International de Recherche contre le Cancer (CIRC), 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), Escuela Andaluza de Salud Pública, CIBER de Epidemiología y Salud Pública (CIBERESP), Consejo de Salud de la Región de Murcia, Partenaires INRAE, Instituto Navarro de Salud Publica, Instituto de Investigación Sanitaria Biodonostia (Tissue Engineering Laboratory, Bioengineering Area), Dirección General de Salud Pública, Civile - M.P.Arezzo Hospital, Università degli studi di Napoli Federico II, Istituto per lo Studio e la Prevezione Oncologica, Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), Istituto Nazionale dei Tumori, University of Oxford [Oxford], Department of Public Health and Primary Care, University of Cambridge [UK] (CAM)-Institute of Public Health, Epidemiology Unit, Medical Research Council, Department of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, German Institute of Human Nutrition, Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens., Hellenic Health Foundation, 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, University Medical Center [Utrecht], Imperial College London, Danish Cancer Society, Aarhus University [Aarhus], Lund University [Lund], Department of Odontology, Umeå University, Swedish University of Agricultural Sciences (SLU), University of Tromsø (UiT), European Commission: Public Health and Consumer Protection Directorate, Research Directorate-General, 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), Institut National du Cancer (France), German Cancer Aid, German Cancer Research Center, German Federal Ministry of Education and Research, Danish Cancer Society: Health Research Fund (FIS) of the Spanish Ministry of Health (RTICC) [DR06/0020], Catalan Institute of Oncology of Spain, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Hellenic Ministry of Health, Stavros Niarchos Foundation, Italian Association for Research on Cancer, Compagnia San Paolo, Italy, Dutch Ministry of Public Health, Welfare and Sports, Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane, Sweden, Nordforsk - Centre of Excellence programme, Spanish Ministry of Science and Innovation [CD09/00133], Universitat de Barcelona, 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, Università degli studi di Torino = University of Turin (UNITO), University of Oxford, ProdInra, Migration, and IRCCS Istituto Nazionale dei Tumori [Milano]
Subjects: Male, Nutritional Sciences, 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Coffee, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Neoplasms, Surveys and Questionnaires, Hydroxybenzoates, Prospective Studies, Food science, Food sources, Prospective cohort study, Càncer, Investigation into Cancer and Nutrition, Cancer, 2. Zero hunger, chemistry.chemical_classification, 0303 health sciences, Nutrition and Dietetics, Anthropometry, Geography, European Prospective, dietary intakes, Middle Aged, Hydroxycinnamic acid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, [SDV] Life Sciences [q-bio], Cohort, Female, Epic study, Dieta, Dietary intakes, Cohort study, Adult, Hydroxybenzoic acid, Coumaric Acids, Phenolic acids, food sources, 030209 endocrinology & metabolism, Diet Surveys, 03 medical and health sciences, Humans, Life Style, Nutrició, Aged, Nutrition, Inflammation, Phenolic acid, Diet, Oxidative Stress, Social Class, chemistry, european prospective investigation into cancer and nutrition, phenolic acids
Abstract: International audience; Phenolic acids are secondary plant metabolites that may have protective effects against oxidative stress, inflammation and cancer in experimental studies. To date, limited data exist on the quantitative intake of phenolic acids. We estimated the intake of phenolic acids and their food sources and associated lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Phenolic acid intakes were estimated for 36 037 subjects aged 35-74 years and recruited between 1992 and 2000 in ten European countries using a standardised 24 h recall software (EPIC-Soft), and their food sources were identified. Dietary data were linked to the Phenol-Explorer database, which contains data on forty-five aglycones of phenolic acids in 452 foods. The total phenolic acid intake was highest in Aarhus, Denmark (1265.5 and 980.7 mg/d in men and women, respectively), while the intake was lowest in Greece (213.2 and 158.6 mg/d in men and women, respectively). The hydroxycinnamic acid subclass was the main contributor to the total phenolic acid intake, accounting for 84.6-95.3% of intake depending on the region. Hydroxybenzoic acids accounted for 4.6-14.4%, hydroxyphenylacetic acids 0.1-0.8% and hydroxyphenylpropanoic acids
Published: 2013

38. Interleukin-33 exacerbates acute colitis via interleukin-4 in mice

Author: James Alexander, Peter Natesan Pushparaj, Damo Xu, Rodrigo Guabiraba, Mousa Komai-Koma, Dong Li, Charles McSharry, Institute of Infection, Immunity and Inflammation, University of Glasgow, King Abdulaziz University, Umm Al-Qura University, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde [Glasgow], Arthritis Research UK, Medical Research Council UK, Wellcome Trust, UK, and Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT)
Subjects: Chemokine, Exacerbation, colitis, Immunology, Gene Expression, 03 medical and health sciences, Mice, 0302 clinical medicine, Immunology and Allergy, Medicine, Animals, Colitis, interleukin-4 deficiency, Interleukin 4, Acute colitis, 030304 developmental biology, ST2 deficiency, Mice, Knockout, 0303 health sciences, Mice, Inbred BALB C, biology, business.industry, Interleukins, Receptors, Interleukin, Original Articles, medicine.disease, Interleukin-33, Ulcerative colitis, Interleukin-1 Receptor-Like 1 Protein, early interleukin-33 expression, 3. Good health, Receptors, Interleukin-4, Interleukin 33, 030220 oncology & carcinogenesis, Acute Disease, biology.protein, CXCL9, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, Colitis, Ulcerative, Female, Interleukin-4, Chemokines, Inflammation Mediators, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract: Pushparaj, Peter N Li, Dong Komai-Koma, Mousa Guabiraba, Rodrigo Alexander, James McSharry, Charles Xu, Damo Arthritis Research UK/United Kingdom Medical Research Council/United Kingdom Wellcome Trust/United Kingdom England Immunology. 2013 Sep;140(1):70-7. doi: 10.1111/imm.12111.; International audience; Interleukin-33 (IL-33) and its receptor ST2 are over-expressed in clinical colitis tissue. However, the significance of these observations is at present unknown. Significantly, we demonstrate here that IL33 and ST2 are the primary early genes induced in the inflamed colon of BALB/c mice following dextran sulphate sodium (DSS)-induced experimental ulcerative colitis. Accordingly diarrhoea and DSS-induced colon inflammation were impaired in ST2(-/-) BALB/c mice and exacerbated in wild-type mice by treatment with exogenous recombinant IL-33, associated respectively with reduced and enhanced expression of chemokines (CXCL9 and CXCL10), and inflammatory (IL-4, IL-13, IL-1, IL-6, IL-17) and angiogenic (vascular endothelial growth factor) cytokines in vivo. The exacerbation effect of treatment with recombinant IL-33 on DSS-induced acute colitis was abolished in IL-4(-/-) BALB/c mice. Hence, IL-33 signalling via ST2, by inducing an IL-4-dependent immune response, may be a major pathogenic factor in the exacerbation of ulcerative colitis.
Published: 2013

39. Myeloid related protein induces muscle derived inflammatory mediators in juvenile dermatomyositis

Author: Helmut Wittkowski, Johannes Roth, Vanita Shah, Lucy R. Wedderburn, Thomas Vogl, Kiran Nistala, Kamel Mamchaoui, Petra Krol, Paul A. Brogan, Hemlata Varsani, Rheumatology Unit, UCL Institute of Child Health, Department of General Pediatrics, Münster University Children Hospital, Interdisciplinary Centre for Clinical Research (IZKF), Westfälische Wilhelms-Universität Münster (WWU)-Institute of Immunology, Charles University [Prague] (CU), Thérapie des maladies du muscle strié, 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), University Children's Hospital Muenster, Institute of Immunology-Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Department of Pediatrics and Adolescent Medicine, Charles University [Prague] (CU)-First Faculty of Medicine-General University Hospital in Prague, 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), The JDM Cohort Study and this work have been supported by generous grants from the Wellcome Trust UK (085860), Action Medical Research UK, (SP4252), and The Henry Smith Charity. LW is supported in part by the Great Ormond Street Hospital Children's Charity. KN is a Wellcome Trust Intermediate Clinical Fellow (097259). TV and JR were supported by grants from the Interdisciplinary Centre for Clinical Research at the University of Muenster (Vo2/014/09 to T.V. as well as grant Ro2/004/10 to J.R) and the Deutsche Forschungsgemeinschaft (DFG project RO 1190/9-1)., BMC, Ed., and HAL UPMC, Gestionnaire
Subjects: Male, Myeloid, Biopsy, Gene Expression, 0302 clinical medicine, Interferon, Immunology and Allergy, Myocyte, Child, Chemokine CCL2, Juvenile dermatomyositis, 0303 health sciences, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, biology, Reverse Transcriptase Polymerase Chain Reaction, Muscles, Endoplasmic Reticulum Stress, Immunohistochemistry, 3. Good health, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Child, Preschool, Cytokines, Female, Inflammation Mediators, Research Article, medicine.drug, Muscle tissue, Adolescent, Myoblasts, Skeletal, Immunology, Antigens, Differentiation, Myelomonocytic, Dermatomyositis, Cell Line, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Rheumatology, Downregulation and upregulation, Antigens, CD, medicine, Calgranulin B, Humans, Calgranulin A, Muscle Strength, Interleukin 6, 030304 developmental biology, 030203 arthritis & rheumatology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Interleukin-6, business.industry, Macrophages, medicine.disease, Microscopy, Fluorescence, biology.protein, business
Abstract: International audience; IntroductionThe aetiopathogenesis of juvenile dermatomyositis (JDM) remains poorly understood. In particular the contribution of monocytes or macrophages, which are frequently observed to be an infiltrate within muscle tissue very early in the disease process, is unknown. We hypothesised that these cells secrete the pro-inflammatory myeloid related protein (MRP) 8/14 which may then contribute to muscle pathology in JDM.MethodsIn this study of 56 JDM patients, serum MRP8/14 levels were compared with clinical measures of disease activity. Muscle biopsies taken early in disease were assessed by immunohistochemistry to determine the frequency and identity of MRP-expressing cells. The effects of MRP stimulation and endoplasmic reticulum (ER) stress on muscle were tested in vitro. Serum or supernatant levels of cytokines were analyzed by multiplex immunoassay.ResultsSerum MRP8/14 correlated with physician's global assessment of disease activity in JDM (R = 0.65, p = 0.0003) and muscle strength/endurance, childhood myositis assessment score (CMAS, R = −0.55, p = 0.004). MRP8/14 was widely expressed by CD68+ macrophages in JDM muscle tissue. When cultured with human myoblasts, MRP8 led to the secretion of MCP-1 and IL-6, which was enhanced by ER stress. Both inflammatory mediators were detected in significantly higher levels in the serum of JDM patients compared to healthy controls.ConclusionsThis study is the first to identify serum MRP8/14 as a potential biomarker for disease activity in JDM. We propose that tissue infiltrating macrophages secreting MRP8/14 may contribute to myositis, by driving the local production of cytokines directly from muscle.
Published: 2013

40. An interferon signature is associated with HAM/TSP but not viral containment in HTLV-1 infection

Author: Matthew Berry, Damien Chaussabel, Jason A. Skinner, Graham P. Taylor, Jacques Banchereau, Sonja Tattermusch, Anne O'Garra, Charles R. M. Bangham, BMC, Ed., Departments of Immunology and GU Medicine and Communicable Diseases, Imperial College London, Développement de nouveaux vaccins pour le traitement de maladies virales chroniques, Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Immunoregulation, MRC National Institute for Medical Research, and This study is funded by the Wellcome Trust (UK).
Subjects: lcsh:Immunologic diseases. Allergy, Pathogenesis, 03 medical and health sciences, Immune system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, immune system diseases, Interferon, hemic and lymphatic diseases, Virology, medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Whole blood, 0303 health sciences, biology, 030306 microbiology, business.industry, Multiple sclerosis, virus diseases, medicine.disease, 3. Good health, Real-time polymerase chain reaction, Infectious Diseases, Meeting Abstract, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, biology.protein, Antibody, business, lcsh:RC581-607, Asymptomatic carrier, medicine.drug
Abstract: Most people infected with Human T-cell Lymphotropic Virus Type 1 (HTLV-1) remain clinically asymptomatic; however, a minority develops the debilitating myelopathy HAM/TSP. Current treatment of HAM/TSP is limited by our partial understanding of the protective immune response to HTLV-1 and the pathogenesis of HAM/TSP. We wished to test the hypothesis that a gene expression signature in peripheral blood distinguishes between patients with HAM/TSP and ACs. We investigated genome-wide transcription patterns in whole blood from HTLV-1 asymptomatic carriers (AC; n=37), patients with HAM/TSP (n=20) and uninfected control subjects (n=17). We identified a 542-gene signature that was deregulated in all HTLV-1+ individuals and predominantly comprised transcripts involved in p53-mediated DNA damage responses (p=0.00489). An 80-gene signature distinguished patients with HAM/TSP from those with the clinically similar disease multiple sclerosis. Paradoxically, at a given proviral load patients with HAM/TSP, but not ACs, over-expressed antiviral interferon-stimulated genes (ISGs; p=0.00859). Expression of these ISGs (assessed by quantitative PCR and flow cytometry) was not limited to HTLV-1infected CD4+ T cells, suggesting that all peripheral blood immune cells were exposed to interferons (IFN) in vivo. Neither elevated IFN plasma levels nor an abnormal capacity for IFN production was detected in patients with HAM/TSP. However, peripheral immune cells in patients with HAM/TSP were more sensitive to IFN-alpha and IFN-gamma stimulation. These findings suggest that chronic over-expression of a specific subset of ISGs is ineffective in containing HTLV-1 and may instead contribute to the pathogenesis of HTLV-1-associated myelopathy.
Published: 2011

41. Crohn disease–associated adherent-invasive E. coli bacteria target mouse and human Peyer’s patches via long polar fimbriae

Author: Amélie de Vallée, Arlette Darfeuille-Michaud, Benoit Chassaing, Maelle Prorok-Hamon, Sa’ad Y. Salim, Christel Neut, Johan D. Söderholm, Jean-Pierre Hugot, Jean-Frederic Colombel, Barry J. Campbell, Nathalie Rolhion, Institut National de la Recherche Agronomique (INRA), Institut Universitaire de Technologie de Clermont Ferrand, Linköping University (LIU), University of Liverpool, Université de Lille, Droit et Santé, Université Paris Diderot - Paris 7 (UPD7), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Ministere de la Recherche et de la Technologie [JE2526], INRA [USC-2018], Association F. Aupetit (AFA), European Commission, Swedish Research Council [VR-M 2005-7013], National Institute of Health Research Specialist Biomedical Research Centre in Microbial Disease [01CD1], Wellcome Trust UK [074949/Z/04/Z], and National Association for Colitis and Crohn's Disease UK [M/08/1]
Subjects: [SDV]Life Sciences [q-bio], Fimbria, Nod2 Signaling Adaptor Protein, medicine.disease_cause, Bacterial Adhesion, Epithelium, Mice, Peyer's Patches, 0302 clinical medicine, Crohn Disease, Intestine, Small, health care economics and organizations, Microfold cell, 0303 health sciences, Microscopy, Confocal, General Medicine, 3. Good health, medicine.anatomical_structure, ESCHERICHIA-COLI, 030211 gastroenterology & hepatology, Research Article, EXPRESSION, education, Virulence, Ileum, Mice, Transgenic, Biology, PATIENT, Microbiology, 03 medical and health sciences, Immune system, TYPE-1 PILI, medicine, Escherichia coli, Animals, Humans, FOLLICLE-ASSOCIATED EPITHELIUM, M-CELL MODEL, 030304 developmental biology, Inflammation, ILEAL MUCOSA, STRAIN LF82, SALMONELLA-TYPHIMURIUM, Small intestine, Fimbriae, Bacterial, Immune System, Mutation, INFLAMMATORY-BOWEL-DISEASE
Abstract: International audience; Crohn disease (CD) is a multifactorial disease in which an abnormal immune response in the gastrointestinal (GI) tract leads to chronic inflammation. The small intestine, particularly the ileum, of patients with CD is colonized by adherent-invasive E. coil (AIEC) a pathogenic group of E. coil able to adhere to and invade intestinal epithelial cells. As the earliest inflammatory lesions are microscopic erosions of the epithelium lining the Peyer's patches (PPs), we investigated the ability of AIEC bacteria to interact with PPs and the virulence factors involved. We found that AIEC bacteria could interact with mouse and human PPs via long polar fimbriae (LPF). An LPF-negative AIEC mutant was highly impaired in its ability to interact with mouse and human PPs and to translocate across monolayers of M cells, specialized epithelial cells at the surface of PPs. The prevalence of AIEC strains harboring the lpf operon was markedly higher in CD patients compared with controls. In addition, increased numbers of AIEC, but not LPF-deficient AIEC, bacteria were found interacting with PPs from Nod2(-/-) mice compared with WT mice. In conclusion, we have identified LPF as a key factor for AIEC to target PPs. This could be the missing link between AIEC colonization and the presence of early lesions in the PPs of CD patients.
Published: 2011

42. Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study

Author: Antonio Agudo, Carla H. van Gils, Naomi E. Allen, Miren Dorronsoro, Tobias Pischon, Christina C. Dahm, Antonia Trichopoulou, Madlen Schütze, Sabine Rohrmann, Tara Kehoe, Nadia Slimani, Nicholas J. Wareham, Aurelio Barricarte, Paolo Boffetta, Kim Overvad, Rudolf Kaaks, Petra H.M. Peeters, María José Sánchez, Jürgen Rehm, Anja Olsen, Gerrit Gmel, Laudina Rodríguez, Manuela M. Bergmann, Françoise Clavel-Chapelon, Heiner Boeing, Franco Berrino, Petra A. Wark, Mazda Jenab, Elio Riboli, María Dolores Chirlaque, Vasiliki Benetou, Anne Tjønneland, Dora Romaguera, Kay-Tee Khaw, Rosario Tumino, Paolo Vineis, Marie-Christine Boutron-Ruault, Dimosthenis Zylis, Domenico Palli, Timothy J. Key, Schütze, M., Boeing, H., Pischon, T., Rehm, J., Kehoe, T., Gmel, G., Olsen, A., Tjønneland, A.M., Dahm, C.C., Overvad, K., Clavel-Chapelon, F., Boutron-Ruault, M.C., Trichopoulou, A., Benetou, V., Zylis, D., Kaaks, R., Rohrmann, S., Palli, D., Berrino, F., Tumino, R., Vineis, P., Rodríguez, L., Agudo, A., Sánchez, M.J., Dorronsoro, M., Chirlaque, M.D., Barricarte, A., Peeters, P.H., van Gils, C.H., Khaw, K.T., Wareham, N., Allen, N.E., Key, T.J., Boffetta, P., Slimani, N., Jenab, M., Romaguera, D., Wark, P.A., Riboli, E., Bergmann, M.M., [Schuetze,M, Boeing,H, Pischon,T, Bergmann,MM.] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany. [Rehm,J, Kehoe,T, Gmel,G] CAMH, Toronto, ON, Canada. [Rehm, J] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, Dresden, Germany. [Olsen,A, Tjonneland,AM.] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Dahm,CC] Aarhus Univ Hosp, Dept Clin Epidemiol, Aalborg, Denmark. [Overvad,K] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aarhus, Denmark. [Clavel-Chapelon,F, Boutron-Ruault,M-C] Inst Gustave Roussy, Ctr Res Epidemiol & Populat Hlth,Villejuif, France. [Clavel-Chapelon,F, Boutron-Ruault,MC] Paris S Univ, UMRS 1018, Villejuif, France. [Trichopoulou, A, Benetou,V, Zylis,D] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Food & Nutr Policies, Athens, Greece. [Kaaks,R, Rohrmann,S] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Palli,D] Canc Res & Prevent Inst, Mol & Nutr Epidemiol Unit, Florence, Italy. [Berrino, Franco] Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Epidemiol Unit, Milan, Italy. [Tumino,R] Civile MP Arezzo Hosp, Canc Registry, Ragusa, Italy. [Vineis, Paolo] Inst Sci Interchange Fdn, Turin, Italy. [Rodriguez,L] Hlth & Hlth Care Serv Council, Publ Hlth & Participat Directorate, Asturias, Spain. [Tumino,R] Civile MP Arezzo Hosp, Histopathol Unit, Ragusa, Italy. [Agudo,A] Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Programme, Unit Nutr Environm & Canc, Barcelona, Spain. [Sanchez,MJ] Andalusian Sch Publ Hlth, Granada, Spain. [Sanchez,MJ, Dorronsoro,M, Chirlaque,MD, Barricarte,A] CIBERESP, San Sebastian, Spain. [Dorronsoro, Miren] Publ Hlth Dept Gipuzkoa, San Sebastian, Spain. [Chirlaque,MD] Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain. [Peeters,PH., van Gils,CH.] Univ Med Ctr, Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Khaw,K_T] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Wareham,N] MRC, Epidemiol Unit, Cambridge, England. [Allen,NE., Key,TJ.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, England. [Boffetta, P, Slimani,N, Jenab,M] Int Agcy Res Canc, Lyon, France. [Boffetta,P] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Vineis,P, Romaguera,D, Wark,PA., Riboli,E] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England., The work was performed (partly) within the coordinated action EPIC (SP23-CT-2005-006438), which has received research funding from the Community’s Sixth Framework Programme, as well as by the 'Europe Against Cancer' Programme of the European Commission (SANCO), Deutsche Krebshilfe, German Cancer Research Center, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health (grant No: Network RCESP C03/09), Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII, Red de Centros RETIC(RD06/0020) (grant No: C03/09), Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Italian Association for Research on Cancer (AIRC), Compagnia di San Paolo, Progetto Integrato Oncologia-PIO, Regione Toscana, Dutch Ministry of Public Health, Welfare and Sports, National Cancer Registry of the Netherlands, Greek Ministry of Health and Social Solidarity, and Hellenic Health Foundation and Stavros Niarchos Foundation
Subjects: Male, Alcohol drinking, Alcohol use disorder, burden, 0302 clinical medicine, Breast cancer, Cost of Illness, Neoplasms, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Health Education, General Environmental Science, Colon Cancer, Incidence (epidemiology), Hazard ratio, General Engineering, General Medicine, cohort, Middle Aged, Diseases::Neoplasms [Medical Subject Headings], Consumo de bebidas alcohólicas, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Colon cancer, Europe, Oncology, 030220 oncology & carcinogenesis, Female, Incidencia, Alcohol, Cohort study, Adult, medicine.medical_specialty, Alcohol Drinking, Health Promotion, 03 medical and health sciences, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Breast Cancer, Humans, cancer, Sex Distribution, Aged, Health Care::Health Care Facilities, Manpower, and Services::Health Services::Preventive Health Services::Health Education [Medical Subject Headings], business.industry, Research, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques [Medical Subject Headings], prospective, medicine.disease, Surgery, Epidemiologic Studies, Cardiovascular and Metabolic Diseases, Relative risk, attributable, Attributable risk, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], incidence, General Earth and Planetary Sciences, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], business, Quantitative research, Demography
Abstract: Objective To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study. Design Combination of prospective cohort study with representative population based data on alcohol exposure. Setting Eight countries (France, Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Denmark) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Participants 109 118 men and 254 870 women, mainly aged 37-70. Main outcome measures Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants. Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex. Partial alcohol attributable fractions for consumption higher than the recommended upper limit (two drinks a day for men with about 24 g alcohol, one for women with about 12 g alcohol) and the estimated total annual number of cases of alcohol attributable cancer. Results If we assume causality, among men and women, 10% (95% confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries. For selected cancers the figures were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive tract, 33% (11 to 54%) and 18% (−3 to 38%) for liver, 17% (10 to 25%) and 4% (−1 to 10%) for colorectal cancer for men and women, respectively, and 5.0% (2 to 8%) for female breast cancer. A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit: 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women. Conclusions In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits. These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer.
Published: 2011

43. The health and well-being of older people in Nairobi’s slums

Author: Catherine Kyobutungi, Alex Ezeh, Thaddaeus Egondi, and National Institutes of Health, Wellcome Trust UK, Flora and William Hewlett foundation
Subjects: Population, Developing country, INDEPTH WHO-SAGE Supplement, older people, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Quality of life, well-being, Global health, Medicine, 030212 general & internal medicine, education, education.field_of_study, business.industry, 030503 health policy & services, Health Policy, 1. No poverty, Public Health, Environmental and Occupational Health, Nairobi, Slum settlements, wellbeing, quality of life, medicine.disease, 3. Good health, Supplement 2, 2010, ageing, slum settlements, Marital status, Residence, INDEPTH WHO-SAGE, 0305 other medical science, business, Slum, Demography
Abstract: Background: Globally, it is estimated that people aged 60 and over constitute more than 11% of the population, with the corresponding proportion in developing countries being 8%. Rapid urbanisation in sub- Saharan Africa (SSA), fuelled in part by ruralurban migration and a devastating HIV/AIDS epidemic, has altered the status of older people in many SSA societies. Few studies have, however, looked at the health of older people in SSA. This study aims to describe the health and well-being of older people in two Nairobi slums. Methods: Data were collected from residents of the areas covered by the Nairobi Urban Health and Demographic Surveillance System (NUHDSS) aged 50 years and over by 1 October 2006. Health status was assessed using the short SAGE (Study on Global AGEing and Adult Health) form. Mean WHO Quality of Life (WHOQoL) and a composite health score were computed and binary variables generated using the median as the cut-off. Logistic regression was used to determine factors associated with poor quality of life (QoL) and poor health status. Results: Out of 2,696 older people resident in the NUHDSS surveillance area during the study period, data were collected on 2,072. The majority of respondents were male, aged 50-60 years. The mean WHOQoL score was 71.3 (SD 6.7) and mean composite health score was 70.6 (SD 13.9). Males had significantly better QoL and health status than females and older respondents had worse outcomes than younger ones. Sex, age, education level and marital status were significantly associated with QoL, while slum of residence was significantly associated with health status. Conclusion: The study adds to the literature on health and well-being of older people in SSA, especially those in urban informal settlements. Further studies are needed to validate the methods used for assessing health status and to provide comparisons from other settings. Health and Demographic Surveillance Systems have the potential to conduct such studies and to evaluate health and well-being over time. Keywords: Nairobi; slum settlements; older people; ageing; well-being; quality of life; INDEPTH WHO-SAGE (Published: 27 September 2010) Citation: Global Health Action Supplement 2, 2010. DOI: 10.3402/gha.v3i0.2138 Access the supplementary material to this article: INDEPTH WHO-SAGE questionnaire (including variants of vignettes), a data dictionary and a password-protected dataset (see Supplementary files under Reading Tools online). To obtain a password for the dataset, please send a request with ‘SAGE data’ as its subject, detailing how you propose to use the data, to global.health@epiph.umu.se
Published: 2010

44. Striving against adversity: the dynamics of migration, health and poverty in rural South Africa

Author: Mark A. Collinson, Wellcome Trust, UK, Medical Research Council, South Africa, and Andrew W. Mellon Foundation, USA
Subjects: Economic growth, Refugee, socio-economic status, permanent migration, migration, child mortality, adult mortality, 03 medical and health sciences, 0302 clinical medicine, temporary migration, refugee settlement, socioeconomic status, HIV transmission, Global health, 030212 general & internal medicine, Sociology, 10. No inequality, Socioeconomics, Socioeconomic status, PhD REVIEW, Government, 030505 public health, Poverty, Human migration, business.industry, lcsh:Public aspects of medicine, Health Policy, 1. No poverty, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, social sciences, Public Health, Population, Migration, 3. Good health, Child mortality, RA410-410.9, RA771-771.7, Rural area, 0305 other medical science, business
Abstract: This article is a review of the PhD thesis of Mark Collinson, titled, ‘Striving against adversity: the dynamics of migration, health and poverty in rural South Africa’. The findings show that in rural South Africa, temporary migration has a major impact on household well-being and health. Remittances from migrants make a significant difference to socioeconomic status (SES) in households left behind by the migrant. For the poorest households the key factors improving SES are government grants and female temporary migration, while for the less poor it is male temporary migration and local employment. Migration is associated with HIV but not in straightforward ways. Migrants that return more frequently may be less exposed to outside partners and therefore less implicated in the HIV epidemic. There are links between migration and mortality patterns, including a higher risk of dying for returnee migrants compared with permanent residents. A mother’s migration impacts significantly on child survival for South African and former refugee parents, but there is an additional mortality risk for children of Mozambican former refugees. It is recommended that national censuses and surveys account for temporary migration when collecting information on household membership, because different migration types have different outcomes. Without discriminating between different migration types, the implications for sending and receiving communities will remain lost to policy-makers. Keywords: migration; temporary migration; permanent migration; refugee settlement; socio-economic status; HIV transmission; adult mortality; child mortality (Published: 3 June 2010) Citation: Global Health Action 2010, 3: 5080 - DOI: 10.3402/gha.v3i0.5080 Access the supplementary material to this article: a video showing the author's official defense of his thesis, and a PDF presenting the Agincourt Health and Demographic Surveillance Systems (see Supplementary files under Reading Tools online). This article has been commented on by Peter Mark Streatfield. Please follow this link http://www.globalhealthaction.net/index.php/gha/article/view/5301 - to read his Commentary.
Published: 2010

45. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study

Author: Jakob Linseisen, Pierre Hainaut, Antonia Trichopoulou, Eiliv Lund, Pietro Ferrari, Sophie Morois, Kay-Tee Khaw, Kim Overvad, Philippe Autier, Gesthimani Misirli, Dimitrios Trichopoulos, Timothy J. Key, Andrew W. Roddam, Carla H. van Gils, Salvatore Panico, María J. Tormo, Paolo Vineis, Graham Byrnes, Eugene Jansen, Fränzel J.B. Van Duijnhoven, María José Sánchez, Martine M. Ros, Teresa Norat, Anja Olsen, Anne Tjønneland, Rudolf Kaaks, H. Bas Bueno-de-Mesquita, Tobias Pischon, Göran Hallmans, R. Palmqvist, Domenico Palli, Rosario Tumino, Sabina Rinaldi, Manuela M. Bergmann, Franco Berrino, Magritt Brustad, Eva Ardanaz, Heiner Boeing, Miren Dorronsoro, Nadia Slimani, Françoise Clavel-Chapelon, Petra H.M. Peeters, Elio Riboli, Mazda Jenab, Laudina Rodríguez, Marie-Christine Boutron-Ruault, Carlos A. González, [Jenab M, Ferrari P, Slimani N, Byrnes G, Rinaldi S, Autier P, Hainaut P] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Bueno-de-Mesquita HB, van Duijnhoven FJB, Jansen EHJM, Ros MM] National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands. [Ferrari P] Data Collection and Exposure Unit, European Food Safety Authority (EFSA), Parma, Italy. [van Duijnhoven FJB, van Gils CH, Peeters PH] Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht, Netherlands. [Norat T, Vineis P, Riboli E] School of Public Health, Imperial College, London, UK. [Pischon T, Boeing H, Bergmann MM] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Tjonneland A, Olsen A] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Overvad K] Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark. [Boutron-Ruault M-C, Clavel-Chapelon F, Morois S] Inserm (Institut National de la Santé et de la Recherche Médicale) ERI 20, EA. [Kaaks R, Linseisen J] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Trichopoulou A, Misirli G] Department of Hygiene and Epidemiology, University of Athens Medical School, Greece. [Trichopoulou A] Hellenic Health Foundation, Greece. [Trichopoulos D] Department of Epidemiology, Harvard School of Public Health, USA and Bureau of Epidemiologic Research, Academy of Athens, Greece. [Berrino F] Department of Preventive and Predictive Medicine, Etiologic Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Milan, Italy. [Vineis P] ISI Foundation, Turin, Italy. [Panico S] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Palli D] Molecular and Nutritional Epidemiology Unit, ISPO (Cancer Research and Prevention Institute), Florence, Italy. [Tumino R] Ragusa Cancer Registry and Histopathology Unit, 'Civile M.P.Arezzo' Hospital, ASP 7 Ragusa, Italy. [Ros MM] Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. [Brustad M, Lund E] Centre for Sami Health Research, Institute of Community Medicine, University of Tromsø, Tromsø, Norway. [Tormo MJ] Epidemiology Service, Murcia Regional Health Authority, Spain. [Ardanaz E] Public Health Institute of Navarra, Pamplona, Spain. [Ardanaz E, Sánchez MJ] CIBER Epidemiología y Salud Pública (CIBERESP), Spain. [Rodríguez L] Health Information Section, Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain. [Sánchez MJ] Andalusian School of Public Health-Granada (Spain). [Dorronsoro M] Epidemiology Unit, Public Health Division of Guipuzkoa, San Sebastian, Spain. [Gonzalez CA] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Hallmans G] Department of Public Health and Clinical Medicine, Nutritional Research, Umeå, Sweden. [Palmqvist R] Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. [Roddam A, Key TJ] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. [Khaw KT] Clinical Gerontology Unit, University of Cambridge, Cambridge, UK. [Bueno-de-Mesquita HB] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands. [Linseisen J] Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany, We thank the World Cancer Research Fund (WCRF, London, UK, grant number 2005/12) for grant funding for the present study. The EPIC study was supported by the Europe Against Cancer Programme of the European Commission (SANCO), Ligue contre le Cancer (France), Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM), German Cancer Aid, German Cancer Research Center, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health (RETIC-RD06/0020), the participating regional governments and institutions of Spain, The ISCIII Red de Centro RCESP (C03/09), Cancer Research UK, Medical Research Council, UK, the Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, the Wellcome Trust, UK, Greek Ministry of Health and Social Solidarity, Hellenic Health Foundation and Stavros Niarchos Foundation, Greek Ministry of Education, Italian Association for Research on Cancer, Italian National Research Council, Compagnia di San Paolo, Dutch Ministry of Public Health, Welfare and Sports, Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), Swedish Cancer Society, Swedish Scientific Council, Regional Governments of Skane and Vasterbotten, Sweden, and Norwegian Cancer Society., Jenab, M, Bueno de Mesquita, Hb, Ferrari, P, van Duijnhoven, Fj, Norat, T, Pischon, T, Jansen, Eh, Slimani, N, Byrnes, G, Rinaldi, S, Tjønneland, A, Olsen, A, Overvad, K, Boutron Ruault, Mc, Clavel Chapelon, F, Morois, S, Kaaks, R, Linseisen, J, Boeing, H, Bergmann, Mm, Trichopoulou, A, Misirli, G, Trichopoulos, D, Berrino, F, Vineis, P, Panico, Salvatore, Palli, D, Tumino, R, Ros, Mm, van Gils, Ch, Peeters, Ph, Brustad, M, Lund, E, Tormo, Mj, Ardanaz, E, Rodríguez, L, Sánchez, Mj, Dorronsoro, M, Gonzalez, Ca, Hallmans, G, Palmqvist, R, Roddam, A, Key, Tj, Khaw, Kt, Autier, P, Hainaut, P, Riboli, E., and University of Groningen
Subjects: Oncology, Male, Colorectal cancer, 0302 clinical medicine, Risk Factors, Neoplasias colorrectales, SERUM 25-HYDROXYVITAMIN-D, DIETARY-INTAKE, Epidemiology, 030212 general & internal medicine, Vitamin D, General Environmental Science, 2. Zero hunger, Colon Cancer, COLON-CANCER, Confounding, General Engineering, Estudios de Casos y Controles, Geographicals::Geographic Locations::Europe [Medical Subject Headings], General Medicine, Middle Aged, META-ANALYSIS, 3. Good health, Europe, 030220 oncology & carcinogenesis, Cohort, Female, Risk assessment, Colorectal Neoplasms, Europa, Life Sciences & Biomedicine, D SUPPLEMENTATION, medicine.medical_specialty, CALCIUM INTAKE, Vitamina D, Chemicals and Drugs::Polycyclic Compounds::Steroids::Secosteroids::Vitamin D [Medical Subject Headings], Enzyme-Linked Immunosorbent Assay, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Medicine, General & Internal, D-RECEPTOR, General & Internal Medicine, Internal medicine, Vitamin D and neurology, medicine, Humans, ddc:610, Life Style, Immunology (Including Allergy), Science & Technology, Dose-Response Relationship, Drug, 25-HYDROXYVITAMIN-D LEVELS, business.industry, Research, Case-control study, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], medicine.disease, RANDOMIZED-CONTROLLED-TRIALS, Diet, Epidemiologic Studies, Endocrinology, Cardiovascular and Metabolic Diseases, Case-Control Studies, Nested case-control study, General Earth and Planetary Sciences, Calcium, D METABOLITES, business
Abstract: Contains fulltext : 88351.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. DESIGN: Nested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. PARTICIPANTS: 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls MAIN OUTCOME MEASURES: Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. RESULTS: 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend or=100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P
Published: 2010

46. Space and time clustering of mortality in rural South Africa (Agincourt HDSS), 1992-2007

Author: Kathleen Kahn, Benn Sartorius, Mark A. Collinson, Penelope Vounatsou, Stephen Tollman, INDEPTH, SACEMA, and MRC/Wits Rural Public Health and Health Transitions Research Unit(Agincourt) through the Wellcome Trust, UK
Subjects: medicine.medical_specialty, Sanitation, 030231 tropical medicine, Distribution (economics), spatial–temporal, demographic surveillance, 03 medical and health sciences, 0302 clinical medicine, spatial-temporal, Human settlement, Supplement 1, 2010, Global health, medicine, 030212 general & internal medicine, all-cause mortality, demographic surveillance, clustering, spatial-temporal, business.industry, Health Policy, Mortality rate, Public health, 1. No poverty, Public Health, Environmental and Occupational Health, Public Health, Global Health, Social Medicine and Epidemiology, INDEPTH Mortality Clustering Supplement, 3. Good health, Child mortality, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, all-cause mortality, Rural area, business, Demography, clustering
Abstract: Background: Detailed information regarding the spatial and/or spatial-temporal distribution of mortality is required for the efficient implementation and targeting of public health interventions. Objectives: Identify high risk clusters of mortality within the Agincourt subdistrict for targeting of public health interventions, and highlight areas for further research. Design: Mortality data were extracted from the Agincourt health and socio-demographic surveillance system (HDSS) for the period 1992-2007. Mortality rates by age group and time were calculated assuming a Poisson distribution and using precise person-time contribution estimates. A spatial scan statistic (Kulldorff) was used to test for clusters of age group specific all-cause and cause-specific mortality both in space and time. Results: Many statistically significant clusters of higher all-cause and cause-specific mortality were identified both in space and time. Specific areas were consistently identified as high risk areas; namely, the east/southeast and upper east central regions. This corresponds to areas with higher mortality due to communicable causes (especially HIV/TB and diarrheal disease) and indicates a non-random element to the distribution of potential underlying causative factors e.g. settlements comprising former Mozambican refugees in east/southeast of the site, corresponding higher poverty areas, South African villages with higher HIV prevalence, etc. Clusters of older adult mortality were also observed indicating potential non-random distribution of noncommunicable disease mortality. Conclusion: This study has highlighted distinct clusters of all-cause and cause-specific mortality within the Agincourt subdistrict. It is a first step in prioritizing areas for further, more detailed research as well as for future public health follow-on efforts such as targeting of vertical prevention of HIV/TB and antiretroviral rollout in significant child and adult mortality clusters; and assessment and provision of adequate water and sanitation in the child mortality clusters particularly in the south-east where diarrheal mortality appears high. Underlying causative factors need to be identified and accurately quantified. Other questions for more detailed research are discussed. Keywords: all-cause mortality; demographic surveillance; clustering; spatial-temporal (Published: 30 August 2010) Citation: Global Health Action Supplement 1, 2010. DOI: 10.3402/gha.v3i0.5225
Published: 2010

47. Innate immunity in ocular Chlamydia trachomatis infection: contribution of IL8 and CSF2 gene variants to risk of trachomatous scarring in Gambians

Author: David Mabey, Dominic P. Kwiatkowski, Gaia Luoni, Matthew J. Burton, Hassan Joof, Kirk A. Rockett, Robin L. Bailey, Martin J. Holland, Jeremy Hull, Angels Natividad, BMC, Ed., London School of Hygiene and Tropical Medicine (LSHTM), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, Medical Research Council Laboratories, This work was supported by the Medical Research Council, UK and The Wellcome Trust, UK., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), University of Oxford [Oxford], London School of Hygiene and Tropical Medicine ( LSHTM ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), and Wellcome Trust Centre for Human Genetics
Subjects: Male, MESH : Aged, MESH: Base Sequence, Blindness, Linkage Disequilibrium, MESH: Blindness, MESH : Child, MESH : Gambia, MESH: Child, MESH: Epistasis, Genetic, Genetics(clinical), MESH: Genetic Variation, Child, Aged, 80 and over, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH : Trachoma, MESH: Granulocyte-Macrophage Colony-Stimulating Factor, MESH : Granulocyte-Macrophage Colony-Stimulating Factor, MESH: Case-Control Studies, 3. Good health, MESH: Linkage Disequilibrium, MESH: Young Adult, Child, Preschool, Chromosomes, Human, Pair 5, Gambia, Chromosomes, Human, Pair 4, MESH: Trachoma, MESH : Case-Control Studies, MESH : Young Adult, Locus (genetics), 03 medical and health sciences, Cicatrix, MESH : Adolescent, Genetics, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, education, lcsh:RC31-1245, MESH : Haplotypes, Trichiasis, Alleles, Aged, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, 030306 microbiology, MESH : Humans, MESH: Child, Preschool, Genetic Variation, Epistasis, Genetic, MESH: Adult, MESH: Matrix Metalloproteinase 9, MESH: Haplotypes, MESH : Cicatrix, medicine.disease, Immunity, Innate, MESH: Interleukin-8, Case-Control Studies, MESH : Blindness, Immunology, MESH : Alleles, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Chlamydia trachomatis, MESH: Female, Linkage disequilibrium, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Child, Preschool, medicine.disease_cause, MESH : Chromosomes, Human, Pair 5, MESH: Aged, 80 and over, MESH : Chromosomes, Human, Pair 4, Risk Factors, MESH: Risk Factors, MESH : Female, MESH : Matrix Metalloproteinase 9, Genetics (clinical), Keratoconjunctivitis, MESH : Epistasis, Genetic, MESH: Aged, MESH : Linkage Disequilibrium, MESH : Polymorphism, Single Nucleotide, MESH : Adult, MESH : Immunity, Innate, Middle Aged, MESH : Risk Factors, Trachoma, Matrix Metalloproteinase 9, Female, MESH: Immunity, Innate, Adult, MESH: Chromosomes, Human, Pair 5, MESH : Interleukin-8, lcsh:Internal medicine, MESH: Chromosomes, Human, Pair 4, Adolescent, lcsh:QH426-470, MESH : Male, Population, Biology, Polymorphism, Single Nucleotide, Young Adult, MESH : Genetic Variation, Research article, medicine, Allele, 030304 developmental biology, MESH: Cicatrix, Base Sequence, MESH: Alleles, Interleukin-8, Granulocyte-Macrophage Colony-Stimulating Factor, MESH: Male, lcsh:Genetics, MESH: Gambia, Haplotypes, MESH : Base Sequence
Abstract: Background: Trachoma, a chronic keratoconjunctivitis caused by Chlamydia trachomatis, is the world's commonest infectious cause of blindness. Blindness is due to progressive scarring of the conjunctiva (trachomatous scarring) leading to in-turning of eyelashes (trichiasis) and corneal opacification. We evaluated the contribution of genetic variation across the chemokine and cytokine clusters in chromosomes 4q and 5q31 respectively to risk of scarring trachoma and trichiasis in a large case-control association study in a Gambian population. Methods: Linkage disequilibrium (LD) mapping was used to investigate risk effects across the 4q and 5q31 cytokine clusters in relation to the risk of scarring sequelae of ocular Ct infection. Disease association and epistatic effects were assessed in a population based study of 651 case-control pairs by conditional logistic regression (CLR) analyses. Results: LD mapping suggested that genetic effects on risk within these regions mapped to the pro-inflammatory innate immune genes interleukin 8 (IL8) and granulocyte-macrophage colony stimulatory factor (CSF2) loci. The IL8-251 rare allele (IL8-251 TT) was associated with protection from scarring trachoma (OR = 0.29 p = 0.027). The intronic CSF2_27348 A allele in chromosome 5q31 was associated with dose dependent protection from trichiasis, with each copy of the allele reducing risk by 37% (p = 0.005). There was evidence of epistasis, with effects at IL8 and CSF2 loci interacting with those previously reported at the MMP9 locus, a gene acting downstream to IL8 and CSF2 in the inflammatory cascade. Conclusion: innate immune response SNP-haplotypes are linked to ocular Ct sequelae. This work illustrates the first example of epistatic effects of two genes on trachoma.
Published: 2009

48. Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the European Prospective Investigation into Cancer and Nutrition (EPIC) prospective study

Author: Carmen Martinez, Petra H.M. Peeters, Merethe Kumle, Paolo Vineis, Armelle Munnia, Seymour Garte, Bas Bueno-de-Mesquita, Emmanuelle Gormally, Ole Raaschou-Nielsen, Antonio Agudo, Giuseppe Matullo, Bengt Järvholm, Françoise Clavel-Chapelon, José Ramón Quirós, Göran Berglund, Marco Peluso, Alison M. Dunning, Rosario Tumino, Alessandro Colombi, Salvatore Panico, Timothy J. Key, Luisa Airoldi, Elio Riboli, S Bingham, Fabrizio Veglia, Rudolf Kaaks, Antonia Trichopoulou, Aurelio Barricarte, Vittorio Krogh, Christian Malaveille, Nicholas E. Day, Kim Overvad, Rodolfo Saracci, Herman Autrup, María José Tormo, Domenico Palli, J. Linseisen, Heiner Boeing, Miren Dorronsoro, Faculteit Medische Wetenschappen/UMCG, Peluso, M, Airoldi, L, Munnia, A, Colombi, A, Veglia, F, Autrup, H, Dunning, A, Garte, S, Gormally, E, Malaveille, C, Matullo, G, Overvad, K, Raaschou Nielsen, O, Clavel Chapelon, F, Linseisen, J, Boeing, H, Trichopoulou, A, Palli, D, Krogh, V, Tumino, R, Panico, Salvatore, Bueno De Mesquita, Bh, Peeters, Ph, Kumle, M, Agudo, A, Martinez, C, Dorronsoro, M, Barricarte, A, Tormo, Mj, Quiros, Jr, Berglund, G, Jarvholm, B, Day, Ne, Key, Tj, Saracci, R, Kaaks, R, Riboli, E, Bingham, S, Vineis, P., [Peluso,M, Munnia, A] Cancer Risk Factor Branch, Analytical and Biomolecular Cytology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy. [Airoldi,L, Colombi,A] Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. [Veglia, F, Matullo,G] ISI Foundation, Turin, Italy. [Autrup,H] Department of Environmental and Occupational Medicine, Aarhus, Denmark. [Dunning, A] Department of Oncology, University of Cambridge, Cambridge, UK. [Garte,S] Genetics Research Institute, Milan, Italy. [Gormally,E, Malaveille,C] International Agency for Research on Cancer, Lyon, France. [Overhad,K] Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Raaschou-Nielsen,O] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Clavel-Chapelon,F] INSERM (Institut National de la Sante´ et de la Recherche Me´dicale), ERI 20, EA 4045, and Institut Gustave Roussy, Villejuif, F-94805, France. [Linseisen,J] Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, German. [Boeing,H] German Institute of Human Nutrition, Potsdam-Rehbu¨cke, Germany. [Trichopoulou,A] Department of Hygiene and Epidemiology, Medical School, University of Athens, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, CSPO-Scientiﬁc Institute of Cancer Prevention Tuscany Region, Florence, Italy. [Krogh,V] Department of Epidemiology, National Cancer Institute, Milan, Italy. [Tumino,R] Cancer Registry, Azienda Ospedaliera ‘Civile MP Arezzo’, Ragusa, Ital. [Panico,S] Dipartimento di Medicina Clinica e Sperimentale, Universita` Federico II, Naples, Italy. [Bueno-De-Mesquita,BH] Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherland. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. [Kumle,M] Institute of Community Medicine, University of Tromso, Tromso, Norway. [Agudo,A] Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain. [Martinez,C] Andalusian School of Public Health, Granada, Spain. [Dorronsoro,M] Department of Public Health of Guipuzkoa, San Sebastian, Spain. [Barricarte,A] Public Health Institute, Navarra, Spain. [Tormo,MJ] Epidemiology Department, Murcia Health Council, Murcia, Spain. Quiros, JR] Direccio´n General de Salud Pu´blica, Consejerı´a de Salud y Servicios Sanitarios Asturias, Oviedo, Spain. [Berglund,G] Malmo¨ Diet and Cancer Study, Lund University, Malmo¨, Sweden. [Jarvholm,G] Department of Nutritional Research, University of Umea˚, Umea˚ , Sweden. [Day,ND, Bingham,S] MRC Dunn Human Nutrition Unit, Cambridge University, UK. [Key,TJ].Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, UK. [Saracci,R] IFC National Research Council, Pisa, Italy. [Kaas,R] Division of Epidemiology, DKFZ Heidelberg, Germany. [Riboli,E] Imperial College London, London, UK. [Vineis,P] University of Turin, Turin, Italy. Department of Epidemiology and Public Health, Imperial College of Science, Technology and Medicine, Norfolk Place, London W2 1PG, UK, This paper was made possible by a grant of the European Community (5th Framework Programme) to P. V. (grant QLK4–CT–1999–00 927) and a grant of the Compagnia di San Paolo to the ISI Foundation. All authors are independent from funders. Mortality data for the Netherlands were obtained from Statistics Netherlands. Also, the work described in the paper was carried out with the financial support of: 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 UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, 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 Society, Swedish Scientific Council, Regional Government of Ska°ne, Sweden, Norwegian Cancer Society, and Research Council of Norway.
Subjects: Dietary Fiber, Male, Aflatoxin, Erythrocytes, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Hemoglobins [Medical Subject Headings], medicine.medical_treatment, air pollution, RESISTANT STARCH, Medicine (miscellaneous), GUIDELINES, Carcinógenos, Body Mass Index, COLORECTAL-CANCER, Food group, chemistry.chemical_compound, Hemoglobins, Vegetables, Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants::Air Pollutants [Medical Subject Headings], Leukocytes, Aductos de ADN, Nutritional Physiological Phenomena, Food science, Prospective Studies, RISK, DNA adducts, Haemoglobin adducts, Non-smokers, Fibre intake, Air pollution, Publication Characteristics::Study Characteristics::Multicenter Study [Medical Subject Headings], Air Pollutants, Nutrition and Dietetics, Chemistry, Technology, Industry, Agriculture::Food and Beverages::Food::Dietary Fiber [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Noxae::Carcinogens [Medical Subject Headings], COLON-CANCER, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage::DNA Adducts [Medical Subject Headings], Fabaceae, Middle Aged, fibre intake, European Prospective Investigation into Cancer and Nutrition, Europe, Biochemistry, 4-Aminobiphenyl, Colonic Neoplasms, Hemoglobinas, Female, SMOKERS, Alcohol Drinking, BLADDER-CANCER, European Prospective Investigation into Cancer and Nutrition (EPIC), haemoglobin adducts, non-smokers, RATS, POLYCYCLIC AROMATIC-HYDROCARBONS, Ozone, LUNG-CANCER, DNA adduct, medicine, Humans, Contaminantes del aire, ddc:610, Carcinogen, Aged, Estudio multicéntrico, Vitamin E, Fruit, Multivariate Analysis, Fibras en la dieta, Carcinogens, Biomarkers, Food contaminant
Abstract: Udgivelsesdato: 2008-Feb-14 In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse, statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P = 0.02), vitamin E (P = 0.04) and alcohol (P = 0.03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P = 0.03, 0.04, and 0.03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances.
Published: 2008

49. Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus

Author: Henning Urlaub, Oliver Bischof, Anne Dejean, Prabhat Kumar Purbey, Sanjeev Galande, P. Pavan Kumar, Dimple Notani, National Centre for Cell Science [Pune, India] (NCCS), Organisation Nucléaire et Oncogenèse, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Max-Planck-Institut für Biophysikalische Chemie - Max Planck Institute for Biophysical Chemistry [Göttingen], Max-Planck-Gesellschaft, Work was supported by grants from the Department of Biotechnology, Government of India, the Wellcome Trust, UK, the Ligue Nationale Contre le Cancer, the Fondation de France, the European Economic Community 'Intact', and the Association Laurette Fugain. O.B. is a senior research fellow from the Centre National de la Recherche Scientifique. P.K., D.N. and P.K.P are supported by fellowships from the Council of Scientific and Industrial Research, India. S.G. is an international senior research fellow of the Wellcome Trust., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Cheriet Rauline, Samia
Subjects: Models, Molecular, MESH: Cell Nucleus, Transcription, Genetic, MESH: Interferon-gamma, [SDV]Life Sciences [q-bio], MESH: RNA Interference, Genes, MHC Class I, Biology, MESH: Protein Isoforms, Transfection, Major histocompatibility complex, MESH: Matrix Attachment Regions, Cell Line, MESH: Chromatin, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Leukemia, Promyelocytic, Acute, MHC class I, Humans, Protein Isoforms, Scaffold/matrix attachment region, 030304 developmental biology, Cell Nucleus, Regulation of gene expression, 0303 health sciences, MESH: Humans, MESH: Transcription, Genetic, MESH: Transfection, MHC Class I Gene, Matrix Attachment Region Binding Proteins, Cell Biology, SATB1, Matrix Attachment Regions, MESH: Genes, MHC Class I, MESH: Gene Expression Regulation, Chromatin, Cell biology, MESH: Cell Line, [SDV] Life Sciences [q-bio], Gene Expression Regulation, MESH: Matrix Attachment Region Binding Proteins, 030220 oncology & carcinogenesis, biology.protein, RNA Interference, Chromatin Loop, MESH: Leukemia, Promyelocytic, Acute, MESH: Models, Molecular
Abstract: International audience; The function of the subnuclear structure the promyelocytic leukaemia (PML) body is unclear largely because of the functional heterogeneity of its constituents. Here, we provide the evidence for a direct link between PML, higher-order chromatin organization and gene regulation. We show that PML physically and functionally interacts with the matrix attachment region (MAR)-binding protein, special AT-rich sequence binding protein 1 (SATB1) to organize the major histocompatibility complex (MHC) class I locus into distinct higher-order chromatin-loop structures. Interferon gamma (IFNgamma) treatment and silencing of either SATB1 or PML dynamically alter chromatin architecture, thus affecting the expression profile of a subset of MHC class I genes. Our studies identify PML and SATB1 as a regulatory complex that governs transcription by orchestrating dynamic chromatin-loop architecture.
Published: 2006

50. Trends in self-reported past alcoholic beverage consumption and ethanol intake from 1950 to 1995 observed in eight European countries participating in the European Investigation into Cancer and Nutrition (EPIC)

Author: J. Linseisen, Françoise Clavel-Chapelon, Calogero Saieva, Heiner Boeing, Magritt Brustad, Aurelio Barricarte, Fabrizio Veglia, Matthias B. Schulze, P. H. M. Peeters, Nadia Slimani, C. Martínez Garcia, Göran Berglund, Ulrich Keil, Elio Riboli, Merethe Kumle, A. Papadimitrou, Kim Overvad, Pagona Lagiou, H. B. Bueno-De-Mesquita, Naomi E. Allen, Lars Weinehall, Kerstin Klipstein-Grobusch, Anne Tjønneland, Pietro Ferrari, Angela A. Mulligan, Vittorio Krogh, Anne C. M. Thiébaut, [Klipstein-Grobusch,K, Boeing,H, Schulze,MB] Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany. [Slimani,N, Ferrari,P, Riboli,E] Unit of Nutrition and Cancer, International Agency for Cancer Research, Lyon, France. [Krogh,V] Epidemiology Unit, National Cancer Institute, Milan, Italy. [Keil,U] Department of Epidemiology and Social Medicine, University of Münster, German. [Overvad,K] Department of Epidemiology, University of Aarhus, Denmark. [Tjønneland,A] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Clavel-Chapelon,F, Thiébaut,A] INSERM, E3N–EPIC Group, Institute Gustave Roussy, Villejuif, France. [Linseisen,J] Department of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Lagiou,P, Papadimitrou,A] Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Greece. [Saieva,C] Molecular and Nutritional Epidemiology Unit, CSPO, Scientific Institute of Tuscany, Florence, Italy. [Veglia,F] Institute for Scientific Interchange Foundation, Turin, Italy. [Bueno-de-Mesquita,HB] Department for Chronic Disease Epidemiology, National Institute for Public Health and Environmental Protection, Bilthoven, The Netherlands. [Peeters,PHM] Julius Center for General Practice and Patient Oriented Research, University of Utrecht, The Netherland. [Kumle,M, Brustad,M] Institute of Community Medicine, University of Tromsø, Norway. [Martínez García,C] Andalusian School of Public Health, Granada, Spain. [Barricarte,A] Department of Epidemiology, Institute of Public Health of Navarra, Spain. [Berglund,G] Department of Medicine, Lund University, Malmö, Sweden. [Weinehal,G] Epidemiology, Public Health and Clinical Medicine, Umea University, Sweden. [Mulligan,A] Department of Public Health and Primary Care, University of Cambridge, UK. [Allen,N] Cancer Research UK, Cancer Epidemiology Unit, University of Oxford, UK., The work described in this paper was carried out with financial support of the ‘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 (INSERM), Institute Gustave Roussy, German Cancer Aid, German Cancer Research Centre, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, the Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, Italian Association for Research on Cancer, Italian National Research Council, Dutch Ministry of Public Health,Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane, Sweden, Norwegian Cancer Society, and Norwegian Research Council. Partial support for the publication of this supplement was provided by the Centre de Recherche et d’Information Nutritionnelles (CERIN).
Subjects: Male, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Medicine (miscellaneous), Wine, Distribución por Edad, Estudios Retrospectivos, EPIC, Consumo de Bebidas Alcohólicas, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Recuerdo Mental, Technology, Industry, Agriculture::Food and Beverages::Beverages::Alcoholic Beverages::Beer [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Population Surveillance [Medical Subject Headings], Medicine, Masculino, 24-Hour dietary recall, Nutrition and Dietetics, Adulto, Femenino, Vino, Beer, Geographicals::Geographic Locations::Europe [Medical Subject Headings], Time trends, European Prospective Investigation into Cancer and Nutrition, Humanos, Europe, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Disciplines and Occupations::Social Sciences::Demography::Sex Distribution [Medical Subject Headings], Population Surveillance, Cerveza, Female, Distribución por Sexo, Adult, Alcohol Drinking, Estudios Transversales, Check Tags::Male [Medical Subject Headings], Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Memory::Mental Recall [Medical Subject Headings], Spirits, Age Distribution, Environmental health, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Europa (Continente), ddc:610, Disciplines and Occupations::Social Sciences::Demography::Age Distribution [Medical Subject Headings], Sex Distribution, Retrospective Studies, Consumption (economics), Ethanol, business.industry, Public Health, Environmental and Occupational Health, Alcoholic beverage consumption, Vigilancia de la Población, Technology, Industry, Agriculture::Food and Beverages::Beverages::Alcoholic Beverages::Wine [Medical Subject Headings], EPIC study, Cross-Sectional Studies, Check Tags::Female [Medical Subject Headings], Mental Recall, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Alcoholic beverages, Ethanol intake, business, Cross-sectional analyses
Abstract: Objective:To describe the trends of self-reported past consumption of alcoholic beverages and ethanol intake from 1950 to 1995 within the European Prospective Investigation into Cancer and Nutrition (EPIC).Design:Data on consumption of beer/cider, wine and liqueur/spirits were obtained retrospectively at age 20, 30 and 40 years to calculate average consumption and ethanol intake for the time periods 1950–1975 (at age 20), 1960–1985 (at age 30) and 1970–1995 (at age 40). Regression analysis was conducted with the time period data to assess trends in past alcoholic beverage consumption and ethanol intake with time.Setting:The EPIC project.Subjects:In total, 392 064 EPIC participants (275 249 women and 116 815 men) from 21 study centres in eight European countries.Results:Generally, increases in beer/cider consumption were observed for most EPIC centres for 1950–1975, 1960–1985 and 1970–1995. Trends in wine consumption differed according to geographical location: downward trends with time were observed for men in southern European EPIC centres, upward trends for those in middle/northern European study centres. For women, similar but less pronounced trends were observed. Because wine consumption was the major contributor to ethanol intake for both men and women in most study centres, time trends for ethanol intake showed a similar geographical pattern to that of wine consumption.Conclusion:The different trends in alcoholic beverage consumption and ethanol intake suggest that information depicting lifetime history of ethanol intake should be included in analyses of the relationship between ethanol and chronic diseases, particularly in multi-centre studies such as EPIC.
Published: 2002

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