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1. Online Personalized Intervention for the Prevention of Anxiety. (prevANS)

Author: Agencia Estatal de Investigación (AEI), Institute of Health Carlos III (ISCIII), Institute of Biomedical Research in Málaga (IBIMA), European Regional Development Fund (FEDER), and Patricia Moreno Peral, PhD
Published: 2023

2. Downregulation of thioredoxin-1-dependent CD95 S-nitrosation by Sorafenib reduces liver cáncer

Author: Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica, Andalusian Ministry of Economy, Innovation, Science and Employment, Andalusian Ministry of Equality, Health and Social Policies, European Development Regional Fund "A way to achieve Europe" ERDF, FPU predoctoral fellowship from Ministry of Education, Culture and Sports, Institute of Health Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, González, Raúl, Rodríguez-Hernández, María A., Negrete, María, Ranguelova, Kalina, Rossin, Aurelie, Choya-Foces, Carmen, Cruz-Ojeda, Patricia de la, Muntané Relat, Jordi, Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica, Andalusian Ministry of Economy, Innovation, Science and Employment, Andalusian Ministry of Equality, Health and Social Policies, European Development Regional Fund "A way to achieve Europe" ERDF, FPU predoctoral fellowship from Ministry of Education, Culture and Sports, Institute of Health Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, González, Raúl, Rodríguez-Hernández, María A., Negrete, María, Ranguelova, Kalina, Rossin, Aurelie, Choya-Foces, Carmen, Cruz-Ojeda, Patricia de la, and Muntané Relat, Jordi
Abstract: Hepatocellular carcinoma (HCC) represents 80% of the primary hepatic neoplasms. It is the sixth most frequent neoplasm, the fourth cause of cancer-related death, and 7% of registered malignancies. Sorafenib is the first line molecular targeted therapy for patients in advanced stage of HCC. The present study shows that Sorafenib exerts free radical scavenging properties associated with the downregulation of nuclear factor E2-related factor 2 (Nrf2)-regulated thioredoxin 1 (Trx1) expression in liver cancer cells. The experimental downregulation and/or overexpression strategies showed that Trx1 induced activation of nitric oxide synthase (NOS) type 3 (NOS3) and S-nitrosation (SNO) of CD95 receptor leading to an increase of caspase-8 activity and cell proliferation, as well as reduction of caspase-3 activity in liver cancer cells. In addition, Sorafenib transiently increased mRNA expression and activity of S-nitrosoglutathione reductase (GSNOR) in HepG2 cells. Different experimental models of hepatocarcinogenesis based on the subcutaneous implantation of HepG2 cells in nude mice, as well as the induction of HCC by diethylnitrosamine (DEN) confirmed the relevance of Trx1 downregulation during the proapoptotic and antiproliferative properties induced by Sorafenib. In conclusion, the induction of apoptosis and antiproliferative properties by Sorafenib were related to Trx1 downregulation that appeared to play a relevant role on SNO of NOS3 and CD95 in HepG2 cells. The transient increase of GSNOR might also participate in the deactivation of CD95-dependent proliferative signaling in liver cancer cells.
Published: 2020

3. Differential effectiveness of tyrosine kinase inhibitors in 2D/3D culture according to cell differentiation, p53 status and mitochondrial respiration in liver cancer cells

Author: Universidad de Sevilla. Departamento de Cirugía, Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica, Andalusian Ministry of Health, Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd), European Development Regional Fund "A way to achieve Europe" (ERDF), Institute of Health Carlos III (ISCiii), ISCiii, Valencian Ministry of Education, Culture and Sports, Rodríguez-Hernández, María A., Chapresto-Garzón, Raquel, Cadenas, Miryam, Navarro-Villarán, Elena, Negrete, María, Gómez Bravo, Miguel Ángel, Padillo Ruiz, Francisco Javier, Muntané Relat, Jordi, Universidad de Sevilla. Departamento de Cirugía, Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica, Andalusian Ministry of Health, Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd), European Development Regional Fund "A way to achieve Europe" (ERDF), Institute of Health Carlos III (ISCiii), ISCiii, Valencian Ministry of Education, Culture and Sports, Rodríguez-Hernández, María A., Chapresto-Garzón, Raquel, Cadenas, Miryam, Navarro-Villarán, Elena, Negrete, María, Gómez Bravo, Miguel Ángel, Padillo Ruiz, Francisco Javier, and Muntané Relat, Jordi
Abstract: Sorafenib and Regorafenib are the recommended first- and second-line therapies in patients with advanced hepatocellular carcinoma (HCC). Lenvatinib and Cabozantinib have shown non-inferior antitumoral activities compared with the corresponding recommended therapies. The clinical trials have established recommended doses for each treatment that lead different blood concentrations in patients for Sorafenib (10 µM), Regorafenib (1 µM), Lenvatinib (0.1 µM), and Cabozantinib (1 µM). However, very low response rates are observed in patients attributed to intrinsic resistances or upregulation of survival signaling. The aim of the study was the comparative dose-response analysis of the drugs (0-100 µM) in well-differentiated (HepG2, Hep3B, and Huh7), moderately (SNU423), and poorly (SNU449) differentiated liver cancer cells in 2D/3D cultures. Cells harbors wild-type p53 (HepG2), non-sense p53 mutation (Hep3B), inframe p53 gene deletion (SNU423), and p53 point mutation (Huh7 and SNU449). The administration of regular used in vitro dose (10 µM) in 3D and 2D cultures, as well as the dose-response analysis in 2D cultures showed Sorafenib and Regorafenib were increasingly effective in reducing cell proliferation, and inducing apoptosis in well-differentiated and expressing wild-type p53 in HCC cells. Lenvatinib and Cabozantinib were particularly effective in moderately to poorly differentiated cells with mutated or lacking p53 that have lower basal oxygen consumption rate (OCR), ATP, and maximal respiration capacity than observed in differentiated HCC cells. Sorafenib and Regorafenib downregulated, and Lenvatinib and Cabozantinib upregulated epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor receptor (c-Met) in HepG2 cells. Conclusions: Sorafenib and Regorafenib were especially active in well-differentiated cells, with wild-type p53 and increased mitochondrial respiration. By contrast, Lenvatinib and Cabozantinib appeared more effective in moder
Published: 2020

4. RNF43 mutations predict response to anti-BRAF/EGFR combinatory therapies in BRAFV600E metastatic colorectal cancer

Author: Elena Elez, Javier Ros, Jose Fernández, Guillermo Villacampa, Ana Belén Moreno-Cárdenas, Carlota Arenillas, Kinga Bernatowicz, Raquel Comas, Shanshan Li, David Philip Kodack, Roberta Fasani, Ariadna Garcia, Javier Gonzalo-Ruiz, Alejandro Piris-Gimenez, Paolo Nuciforo, Grainne Kerr, Rossana Intini, Aldo Montagna, Marco Maria Germani, Giovanni Randon, Ana Vivancos, Ron Smits, Diana Graus, Raquel Perez-Lopez, Chiara Cremolini, Sara Lonardi, Filippo Pietrantonio, Rodrigo Dienstmann, Josep Tabernero, Rodrigo A. Toledo, Institut Català de la Salut, [Elez E] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Ros J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy. [Fernández J, Villacampa G, Moreno-Cárdenas AB, Bernatowicz K, Comas R, Fasani R, Garcia A, Gonzalo-Ruiz J, Piris-Gimenez A, Nuciforo P, Vivancos A, Dienstmann R] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Arenillas C, Toledo RA] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Institute of Health Carlos III (ISCIII), Madrid, Spain. [Perez-Lopez R] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei de Radiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Tabernero J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Institute of Health Carlos III (ISCIII), Madrid, Spain. UVic-UCC, IOB-Quirón, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, and Gastroenterology & Hepatology
Subjects: Còlon - Càncer - Tractament, Anomalies cromosòmiques, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], SDG 3 - Good Health and Well-being, Recte - Càncer - Tractament, Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], General Medicine, Other subheadings::Other subheadings::/drug therapy [Other subheadings], neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], General Biochemistry, Genetics and Molecular Biology, fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS]
Abstract: Colorectal cancer; Predictive markers; Tumour biomarkers Cáncer colorrectal; Marcadores predictivos; Biomarcadores tumorales Càncer colorrectal; Marcadors predictius; Biomarcadors tumorals Anti-BRAF/EGFR therapy was recently approved for the treatment of metastatic BRAFV600E colorectal cancer (mCRCBRAF-V600E). However, a large fraction of patients do not respond, underscoring the need to identify molecular determinants of treatment response. Using whole-exome sequencing in a discovery cohort of patients with mCRCBRAF-V600E treated with anti-BRAF/EGFR therapy, we found that inactivating mutations in RNF43, a negative regulator of WNT, predict improved response rates and survival outcomes in patients with microsatellite-stable (MSS) tumors. Analysis of an independent validation cohort confirmed the relevance of RNF43 mutations to predicting clinical benefit (72.7% versus 30.8%; P = 0.03), as well as longer progression-free survival (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.12–0.75; P = 0.01) and overall survival (HR, 0.26; 95% CI, 0.10–0.71; P = 0.008), in patients with MSS-RNF43mutated versus MSS-RNF43wild-type tumors. Microsatellite-instable tumors invariably carried a wild-type-like RNF43 genotype encoding p.G659fs and presented an intermediate response profile. We found no association of RNF43 mutations with patient outcomes in a control cohort of patients with MSS-mCRCBRAF-V600E tumors not exposed to anti-BRAF targeted therapies. Overall, our findings suggest a cross-talk between the MAPK and WNT pathways that may modulate the antitumor activity of anti-BRAF/EGFR therapy and uncover predictive biomarkers to optimize the clinical management of these patients. VHIO would like to acknowledge the Cellex Foundation for providing research facilities and equipment, the FERO Foundation for their funding support, the Consorcio Centro de Investigación Biomédica en Red de Cáncer (CIBERONC, CB16/12/00259) from the Institute of Health Carlos III (ISCIII), Ministry of Science and Innovation, and the Department of Health (Generalitat de Catalunya, SLT008/18/00198 and SLT008/18/00205) for their support on this research. Authors acknowledge financial support from the State Agency for Research (Agencia Estatal de Investigación) (CEX2020-001024-S / AEI / 10.13039 /501100011033). This research is funded by the SCITRON program; Novartis funded the genomics characterization by WES of samples from 28 patients from the discovery cohort and had no influence on data analysis/interpretation or writing of the paper (3003145512 to R.A.T.). S.Li. is financially supported by a Chinese Scholarship Council PhD fellowship (201909370083 to S. Li). R.P.-L. is supported by a CRIS Foundation Talent Award (TALENT19-05), the FERO Foundation, the Instituto de Salud Carlos III-Investigación en Salud (PI18/01395 and PI21/01019 to R.P.-L.) and the Prostate Cancer Foundation (Young Investigator Award). This work was supported by the Miguel Servet-I Research Award from ISCIII of the Ministry of Economy (CP17/00199 to R.A.T.), the Olga Torres Foundation Award to emerging researchers (2601 to R.A.T.), the ISCIII-FEDER (PI17/00947 and PI20/00968 to E.E.), and the Fundación AECC (CLSEN19001ELEZ to E.E.) and Ministry of Science and Innovation (Europa Redes y Gestores, ECT2020-000827 to E.E.).
Published: 2022

5. Mechanisms Involved in the Relationship between Vitamin D and Insulin Resistance: Impact on Clinical Practice

Author: Contreras-Bolívar, Victoria, García-Fontana, Beatriz, García-Fontana, Cristina, Muñoz-Torres, Manuel, [Contreras-Bolívar,V, García-Fontana,B, García-Fontana,C, Muñoz-Torres,M] Endocrinology and Nutrition Unit, University Hospital Clínico San Cecilio, Granada, Spain. [Contreras-Bolívar,V, Muñoz-Torres,M] Instituto de Investigación Biosanitaria de Granada (Ibs. Granada), Granada, Spain. [García-Fontana,B, Muñoz-Torres,M] CIBERFES, Instituto de Salud Carlos III, Madrid, Spain. [Muñoz-Torres,M] Department of Medicine, University of Granada, Granada, Spain., This research was funded by the Institute of Health Carlos III grants (PI18-00803 and PI18-01235), co-funded by the European Regional Development Fund (FEDER) and Junta de Andalucía (PI-0268-2019). In addition, V.C.-B. and C.G.-F. are funded by postdoctoral fellowships from the Junta de Andalucía and Institute of Health Carlos III respectively (RH-0141-2020, and CD20/00022).
Subjects: Síndrome metabólico, Vitamina D, Obesidad, Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Drug Resistance::Insulin Resistance [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Malnutrition::Deficiency Diseases::Avitaminosis::Vitamin D Deficiency [Medical Subject Headings], Diabetes Mellitus Tipo 2, 25-hydroxyvitamin D-1alpha-hydroxylase, Resistencia a la insulina, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Síndrome del ovario poliquístico, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism::Insulin Resistance [Medical Subject Headings], Calcitriol, Homeostasis, Obesity, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], Vitamin D, Polycystic ovary syndrome, Calcifediol, Receptores de calcitriol, Insulin resistance, Type 2 diabetes, 25-hidroxivitamina D3 1-alfa-hidroxilasa, 25-hydroxyvitamin D, Metabolic syndrome, Homeostasis model assessment of insulin resistance, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Vitamin D receptor, Phenomena and Processes::Physiological Phenomena::Physiological Processes::Homeostasis [Medical Subject Headings]
Abstract: Recent evidence has revealed anti-inflammatory properties of vitamin D as well as extra-skeletal activity. In this context, vitamin D seems to be involved in infections, autoimmune diseases, cardiometabolic diseases, and cancer development. In recent years, the relationship between vitamin D and insulin resistance has been a topic of growing interest. Low 25-hydroxyvitamin D (25(OH)D) levels appear to be associated with most of the insulin resistance disorders described to date. In fact, vitamin D deficiency may be one of the factors accelerating the development of insulin resistance. Vitamin D deficiency is a common problem in the population and may be associated with the pathogenesis of diseases related to insulin resistance, such as obesity, diabetes, metabolic syndrome (MS) and polycystic ovary syndrome (PCOS). An important question is the identification of 25(OH)D levels capable of generating an effect on insulin resistance, glucose metabolism and to decrease the risk of developing insulin resistance related disorders. The benefits of 25(OH)D supplementation/repletion on bone health are well known, and although there is a biological plausibility linking the status of vitamin D and insulin resistance supported by basic and clinical research findings, well-designed randomized clinical trials as well as basic research are necessary to know the molecular pathways involved in this association. Yes
Published: 2021

6. Control of hyperparathyroidism with the intravenous calcimimetic etelcalcetide in dialysis patients adherent and non-adherent to oral calcimimetics

Author: M. Victoria Pendón-Ruiz de Mier, Mariano Rodriguez, Maria Dolores Arenas, Cristian Rodelo-Haad, [Arenas,MD] Nephrology Department, Vithas Perpetuo Socorro International, Alicante, Spain. [Arenas,MD] Nefrologia Clínica y Dialisis, Consorci Parc de Salut Mar, Barcelona, Spain. [Rodelo-Haad,C, Pendón-Ruiz de Mier,MV, Rodriguez,M] Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain. [Rodelo-Haad,C, Rodriguez,M] Nephrology Service, Reina Sofia University Hospital, Cordoba, Spain. [Rodelo-Haad,C, Rodriguez,M] RETICs-REDinREN (National Institute of Health Carlos III), Madrid, Spain., and M.V.P.-R.d.M. is the recipient of a research contract sup ported by the Rio Hortega Programme from the National Institute of Health Carlos III.
Subjects: Cinacalcet, Calcimimetic, medicine.medical_treatment, 030232 urology & nephrology, Parathyroid hormone, Diseases::Endocrine System Diseases::Parathyroid Diseases::Hyperparathyroidism::Hyperparathyroidism, Secondary [Medical Subject Headings], 030204 cardiovascular system & hematology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, adherence, Cumplimiento de la medicación, Etelcalcetide, etelcalcetide, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Questionnaires [Medical Subject Headings], Chemicals and Drugs::Inorganic Chemicals::Phosphorus Compounds::Phosphorus Acids::Phosphoric Acids::Phosphates [Medical Subject Headings], Chemicals and Drugs::Inorganic Chemicals::Calcium Compounds [Medical Subject Headings], Persons::Persons::Patients [Medical Subject Headings], Nephrology, Hormona paratiroidea, Pacientes, Secondary hyperparathyroidism, Hemodialysis, medicine.symptom, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Dialysis [Medical Subject Headings], PTH, medicine.drug, medicine.medical_specialty, Urology, cinacalcet, Asymptomatic, Hiperparatiroidismo secundario, Calcio, 03 medical and health sciences, medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Renal Replacement Therapy::Renal Dialysis [Medical Subject Headings], AcademicSubjects/MED00340, Transplantation, Hyperparathyroidism, calcium, business.industry, Adhesión celular, Diálisis, Original Articles, medicine.disease, Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Parathyroid Hormone [Medical Subject Headings], Adherence, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Health Behavior::Patient Compliance::Medication Adherence [Medical Subject Headings], Calcium, business
Abstract: Background In dialysis patients, non-adherence to oral cinacalcet adds complexity to the control of secondary hyperparathyroidism. The present study aims to evaluate the use of intravenous calcimimetic, etelcalcetide, in the control of secondary hyperparathyroidism in patients adherent and non-adherent to oral calcimimetics. Method The Simplified Medication Adherence Questionnaire was used to identify non-adherence. Almost half of the patients were non-adherent to the treatment with cinacalcet. Twenty-five patients (15 non-adherent) were switched from cinacalcet to etelcalcetide and were followed-up monthly for 8 months. Results Cinacalcet was discontinued for 1 week before the initiation of etelcalcetide. After this period, the serum PTH levels increased by2-fold in adherent patients, whereas it did not change in non-adherent patients suggesting that they were not taking the medication. Etelcalcetide progressively reduced serum parathyroid hormone (PTH) (mean ± standard deviation) from 818 ± 395 to 367 ± 289 pg/mL (P Conclusion The lack of adherence to cinacalcet is a possible cause of the apparent lack of response to oral calcimimetic. The use of etelcalcetide ensures compliance and control of secondary hyperparathyroidism in both non-adherent and adherent patients.
Published: 2020
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7. Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs

Author: de la Cruz-Ojeda, Patricia, Flores-Campos, Rocío, Dios-Barbeito, Sandra, Navarro-Villarán, Elena, Muntané, Jordi, [de la Cruz-Ojeda,P, Flores-Campos,R, Dios-Barbeito,S, Navarro-Villarán,E, Muntané,J] Institute of Biomedicine of Seville (IBiS), Hospital University 'Virgen del Rocío'/ CSIC/ University of Seville, Seville, Spain. [de la Cruz-Ojeda,P, Muntané,J] Networked Biomedical Research Center Hepatic and Digestive Diseases (CIBEREHD o Ciberehd), Institute of Health Carlos III, Madrid, Spain. [de la Cruz-Ojeda,P, Muntané,J] Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain. [Dios-Barbeito,S] Department of General Surgery, Hospital University 'Virgen del Rocío'/ CSIC/ University of Seville/ IBiS, Seville, Spain., and This research was funded by the Institute of Health Carlos III (ISCiii) (PI19/01266) and Andalusian Ministry of Health (PI-0216-2020). P de la C-O was supported by the FPU predoctoral fellowship (FPU17/00026) from the Ministry of Education, Culture and Sports. E N-V was supported by the predoctoral i-PFIS IIS-enterprise contract in science and technologies in health (IFI18/00014) from the ISCiii. S D-B was supported by the 'Rio Hortega' postdoctoral contract (CM19/00151) from the ISCiii. We thank the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd), founded by the ISCIII and co-financed by European Regional Development Fund 'A way to achieve Europe' ERDF for their financial support.
Subjects: ARN largo no codificante, Células madre neoplásicas, Hepatocarcinoma, MicroARNs, Cancer stem cells, Nitric oxide synthase, Tumor-associated macrophages, Chemicals and Drugs::Inorganic Chemicals::Free Radicals::Nitric Oxide [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], Macrófagos asociados a tumores, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Amino Acid Sequence::Histone Code [Medical Subject Headings], Phenomena and Processes::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment [Medical Subject Headings], Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::RNA, Long Noncoding [Medical Subject Headings], Cancer associated fibroblasts, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], lncRNA, Fibroblastos asociados al cáncer, Organisms::Eukaryota::Animals [Medical Subject Headings], Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation [Medical Subject Headings], Óxido nítrico sintasa, miRNA
Abstract: Nitric oxide (NO) has been identified and described as a dual mediator in cancer according to dose-, time- and compartment-dependent NO generation. The present review addresses the different epigenetic mechanisms, such as histone modifications and non-coding RNAs (ncRNAs), miRNA and lncRNA, which regulate directly or indirectly nitric oxide synthase (NOS) expression and NO production, impacting all hallmarks of the oncogenic process. Among lncRNA, HEIH and UCA1 develop their oncogenic functions by inhibiting their target miRNAs and consequently reversing the inhibition of NOS and promoting tumor proliferation. The connection between miRNAs and NO is also involved in two important features in cancer, such as the tumor microenvironment that includes key cellular components such as tumor-associated macrophages (TAMs), cancer associated fibroblasts (CAFs) and cancer stem cells (CSCs). Yes
Published: 2021

8. Hypophosphatasia: A Unique Disorder of Bone Mineralization

Author: Villa-Suárez, Juan Miguel, García-Fontana, Cristina, Andújar-Vera, Francisco, González-Salvatierra, Sheila, de Haro-Muñoz, Tomás, Contreras-Bolívar, Victoria, García-Fontana, Beatriz, Muñoz-Torres, Manuel, [Villa-Suárez,JM, de Haro-Muñoz,T] Clinical Analysis Unit, University Hospital Clínico San Cecilio, Granada, Spain. [Villa-Suárez,JM, García-Fontana,C, Andújar-Vera,F, González-Salvatierra,S, Contreras-Bolívar,V, García-Fontana,B, Muñoz-Torres,M] Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain. [García-Fontana,C, Muñoz-Torres,M] Endocrinology and Nutrition Unit, University Hospital Clínico San Cecilio, Granada, Spain. [García-Fontana,C, Muñoz-Torres,M] CIBERFES, Institute of Health Carlos III, Granada, Spain. [González-Salvatierra,S, Muñoz-Torres,M] Department of Medicine, University of Granada, Granada, Spain., This research was funded by the Institute of Health Carlos III grants (PI18-00803 and PI18-01235), co-funded by the European Regional Development Fund (FEDER). In addition, JM.V-S and C.G-F are funded by predoctoral and postdoctoral fellowships, respectively, from the Institute of Health Carlos III (CM19/00188, CD20/00022). The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, and in the writing of the manuscript, or in the decision to publish the results.
Subjects: Fosfato de piridoxal, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::Alkaline Phosphatase [Medical Subject Headings], Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Metal Metabolism, Inborn Errors::Hypophosphatasia [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], Mutación, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Enzyme Therapy::Enzyme Replacement Therapy [Medical Subject Headings], Pyridoxal-5′-phosphate, Hypophosphatasia, Genotype-phenotype, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Asfotase alfa, TNSALP, Hipofosfatasia, Fosfatasa alcalina, Terapia de reemplazo enzimático
Abstract: Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the ALPL gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the ALPL gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-50-phosphate (PLP). It has been observed that the prevalence of mild forms of the disease is more than 40 times the prevalence of severe forms. Patients with HPP present at least one mutation in the ALPL gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the ALPL gene. Although the phenotype can be correlated with the genotype in HPP, the prediction of the phenotype from the genotype cannot be made with complete certainty. The availability of a specific enzyme replacement therapy for HPP undoubtedly represents an advance in therapeutic strategy, especially in severe forms of the disease in pediatric patients. Yes
Published: 2021

9. Assessment of Inorganic Phosphate Intake by the Measurement of the Phosphate/Urea Nitrogen Ratio in Urine

Author: Arnold J. Felsenfeld, María Dolores López-Zamorano, Cristina Membrives-González, Francisco Caravaca, Rafael Santamaria, Noemi Vergara, Eugenio J De la Torre, Sagrario Soriano, Rodrigo López-Baltanás, Mariano Rodriguez, Maria Victoria Pendon-Ruiz de Mier, Cristian Rodelo-Haad, Juan R. Muñoz-Castañeda, Alejandro Martin-Malo, [Pendón-Ruiz de Mier,MV, Vergara,N, Rodelo-Haad,C, Membrives-González,C, López-Baltanás,R, Muñoz-Castañeda,JR, Martín-Malo,A, Soriano,S, Santamaría,R, Rodríguez,M] Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Reina Sofia University Hospital, Nephrology Service, University of Cordoba, Cordoba, Spain. [Pendón-Ruiz de Mier,MV, Santamaría,R] Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain. [López-Zamorano,MD] Nephrology Service, Reina Sofia University Hospital, Cordoba, Spain. [Muñoz-Castañeda,JR, Rodríguez,M] EUTOXandCKD-MBD groups of the ERA-EDTA, Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain. [Caravaca,F] Nephrology Service, Infanta Cristina Hospital, Badajoz, Spain. [Felsenfeld,AJ] Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System and the David Geffen School of Medicine, University of California, Los Angeles, USA. [De la Torre,EJ] General Medicine, Miguelturra Clinic, Ciudad Real, Spain., and This work was supported by a Spanish government grant from the Programa Nacional I+D+I 2013–2016 and Instituto de Salud Carlos III (ISCIII) Grants PI18/0138, PI17/01010 co-financing from European Funds (FEDER), Consejería de Salud and EUTOX and REDinREN from the ISCIII. J.R.M.-C. is senior researcher supported by the Nicolás Monardes Programme, Consejería de Salud-Servicio Andaluz de Salud (Junta de Andalucía).
Subjects: Factor de crecimiento fibroblástico 23, Male, phosphate intake, 030232 urology & nephrology, Urine, 030204 cardiovascular system & hematology, Intestinal absorption, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, Eating, 0302 clinical medicine, FGF23, Organisms::Eukaryota::Animals [Medical Subject Headings], Urea, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, Wistar [Medical Subject Headings], Insuficiencia renal crónica, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Nutrition and Dietetics, Chemicals and Drugs::Organic Chemicals::Urea [Medical Subject Headings], Urea nitrogen, Middle Aged, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], phosphaturia, Hormona paratiroidea, Female, lcsh:Nutrition. Foods and food supply, PTH, Adult, Hipofosfatemia familiar, Urinary system, Check Tags::Male [Medical Subject Headings], lcsh:TX341-641, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Article, Phosphates, 03 medical and health sciences, Inorganic phosphate, Animal science, medicine, CKD, Animals, Humans, Rats, Wistar, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Aged, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Fibroblast Growth Factors [Medical Subject Headings], medicine.disease, Phosphate, Diet, Rats, Chemicals and Drugs::Inorganic Chemicals::Acids::Acids, Noncarboxylic::Phosphorus Acids::Phosphoric Acids::Phosphates [Medical Subject Headings], Fibroblast Growth Factor-23, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings], Cross-Sectional Studies, chemistry, Check Tags::Female [Medical Subject Headings], Metabolic syndrome, Food Science, Kidney disease
Abstract: In chronic kidney disease (CKD) patients, it would be desirable to reduce the intake of inorganic phosphate (P) rather than limit the intake of P contained in proteins. Urinary excretion of P should reflect intestinal absorption of P(inorganic plus protein-derived). The aim of the present study is to determine whether the ratio of urinary P to urinary urea nitrogen (P/UUN ratio) helps identify patients with a high intake of inorganic P.A cross-sectional study was performed in 71 patients affected by metabolic syndrome with CKD (stages 2&ndash, 3) with normal serum P concentration. A 3-day dietary survey was performed to estimate the average daily amount and the source of P ingested. The daily intake of P was 1086.5 &plusmn, 361.3 mg/day, 64% contained in animal proteins, 22% in vegetable proteins, and 14% as inorganic P. The total amount of P ingested did not correlate with daily phosphaturia, but it did correlate with the P/UUN ratio (p &lt, 0.018). Patients with the highest tertile of the P/UUN ratio &gt, 71.1 mg/g presented more abundant inorganic P intake (p &lt, 0.038).The P/UUN ratio is suggested to be a marker of inorganic P intake. This finding might be useful in clinical practices to identify the source of dietary P and to make personalized dietary recommendations directed to reduce inorganic P intake.
Published: 2021
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10. Circadian Patterns of Patients with Type 2 Diabetes and Obstructive Sleep Apnea

Author: Antoni Díez-Noguera, Trinitat Cambras, Gabriel Sampol, Odile Romero, Albert Lecube, Institut Català de la Salut, [Cambras T, Díez-Noguera A] Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, Universitat de Barcelonan, 08028 Barcelona, Spain. [Romero O, Sampol G] Unitat del Son, Servei de Neurofisiologia Clínica i Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III (ISCIII), 28029 Madrid, Spain. [Lecube A] Department of Endocrinology and Nutrition, University Hospital Arnau de Vilanova, 25198 Lleida, Spain. Obesity, Diabetes and Metabolism Research Group (ODIM), Biomedical Research Institute of Lleida, (IRBLleida), Universitat de Lleida, 25198 Lleida, Spain. CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Institute of Health Carlos III (ISCIII), 28029 Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: medicine.medical_specialty, Apnea, lcsh:Medicine, 030209 endocrinology & metabolism, Type 2 diabetes, Diabetis no-insulinodependent, Article, enfermedades del sistema endocrino::diabetes mellitus::diabetes mellitus tipo II [ENFERMEDADES], 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Respiratory Tract Diseases::Respiration Disorders::Apnea::Sleep Apnea Syndromes::Sleep Apnea, Obstructive [DISEASES], Glycated hemoglobin, Internal medicine, Medicine, Circadian rhythm, Physiological Phenomena::Chronobiology Phenomena::Periodicity::Circadian Rhythm [PHENOMENA AND PROCESSES], Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2 [DISEASES], Ritmes circadiaris, Glycemic, business.industry, lcsh:R, Circadian, Sleep apnea, General Medicine, medicine.disease, respiratory tract diseases, Obstructive sleep apnea, circadian, chemistry, fenómenos fisiológicos::fenómenos cronobiológicos::periodicidad::ritmo circadiano [FENÓMENOS Y PROCESOS], Cardiology, enfermedades respiratorias::trastornos respiratorios::apnea::síndromes de apnea del sueño::apnea obstructiva del sueño [ENFERMEDADES], Apnea-hypoapnea index, medicine.symptom, apnea-hypoapnea index, business, Body mass index, 030217 neurology & neurosurgery, glycated hemoglobin
Abstract: Sleep apnea, a condition that modifies sleep and circadian rhythms, is highly prevalent in patients with diabetes. However, it is not known if there is an association between sleep apnea, circadian alterations and glycemic regulation in this type of patient. Here, a polysomnographic study was carried out on 21 women and 25 men (mean age = 64.3 &plusmn, 1.46 years) with diagnoses of type 2 diabetes to detect the presence of sleep apnea. Moreover, patients wore an actigraph and a temperature sensor on the wrist for one week, to study the manifestation of the circadian rhythms. The correlations of circadian and polysomnographic variables with the severity of apnea, measured by the apnea-hypopnea index, and with glycemic dysregulation, measured by the percentage of glycated hemoglobin, were analyzed. The mean apnea-hypoapnea index of all the participants was 39.6 &plusmn, 4.3. Apnea-hypoapnea index correlated with % N1, negatively with % N3, and also the stability of the active circadian rhythm. However, no significant correlation was found between the apnea-hypopnea index and wrist temperature rhythm and glycated hemoglobin. Glycated hemoglobin levels were negatively associated with the percentage of variance explained by the wrist temperature circadian rhythm (calculated via 24 and 12 h rhythms). This association was independent of body mass index and was strongest in patients with severe apnea. In conclusion, patients with diabetes showed altered circadian rhythms associated with a poor glycemic control and this association could partially be related to the coexistence of sleep apnea.
Published: 2021
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11. Biochemical Validation of a Self-Administered Food Frequency Questionnaire to Assess Diet Using Carotenoids and Vitamins E and D in Male Adolescents in Spain

Author: Manuela García-de-la-Hera, Carmen Freire, Elena Hernandez-Alvarez, Leyre Notario-Barandiaran, Sandra González-Palacios, Encarnación Donoso-Navarro, Mariana F. Fernandez, Desirée Valera-Gran, Eva-María Navarrete-Muñoz, Jesús Vioque, [Notario-Barandiaran,L, Navarrete-Muñoz,EM, González-Palacios,S, García-de-la-Hera,M, Vioque,J] Alicante Institute for Health and Biomedical Research, ISABIAL-UMH, Alicante, Spain. [Notario-Barandiaran,L, Vioque,J] Nutritional Epidemiology Unit, University Miguel Hernandez, Alicante, Spain. [Navarrete-Muñoz,EM, Valera-Gran,D] InTeO Research Group, Department of Pathology and Surgery, Miguel Hernández University, Alicante, Spain. [Hernández-Álvarez,E, Donoso-Navarro,E] Department of Clinical Biochemistry, Puerta de Hierro University Hospital Majadahonda, Madrid, Spain. [González-Palacios,S, Fernández,MF, Freire,C, Vioque,J] Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Institute of Health Carlos III, Madrid, Spain. [Fernández,MF] Biosanitary Research Institute of Granada (ibs.GRANADA), Granada, Spain. [Fernández,MF] Department of Radiology, School of Medicine and Center for Biomedical Research, University of Granada, Granada, Spain., This study was funded by grants from the Institute of Health Carlos III (ISCIII), the Spanish Ministry of Health (FIS 07/0314, and PI11/01007), the 'Fondo Europeo de Desarrollo Regional' (ISCIII/FEDER) for the Miguel Servet Type I Program granted to C. Freire (grant no. CP16/00085) and the 'Instituto de Salud Carlos III/Agencia Estatal de Investigación', grant number PI18/00825 Project: Dieta y actividad física en embarazo y tras el nacimiento y longitud del telómero en niños y adolescentes: Proyecto TeloDiPA' and Unión Europea (FEDER) 'Una manera de hacer Europa'.
Subjects: 0301 basic medicine, Carotenoid intake, Dietary assessment, Physiology, medicine.medical_treatment, food frequency questionnaire, Clinical Biochemistry, fruit and vegetable intake, vitamin D, vitamin E, Biochemistry, biochemical validity, Nutrición del adolescente, chemistry.chemical_compound, 0302 clinical medicine, Phenomena and Processes::Digestive System and Oral Physiological Phenomena::Digestive System Physiological Phenomena::Digestive System Processes::Eating [Medical Subject Headings], Medicine, Vitamin E, Technology and Food and Beverages::Food and Beverages::Food::Fruit [Medical Subject Headings], 030212 general & internal medicine, Vitamin D, Carotenoid, chemistry.chemical_classification, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Questionnaires [Medical Subject Headings], Food frequency questionnaire, food and beverages, carotenoid intake, Lycopene, Adolescence, Verduras, Biochemical validity, Dieta, Birth cohort, Chemicals and Drugs::Biological Factors::Pigments, Biological::Carotenoids::Xanthophylls::Lutein [Medical Subject Headings], Frutas, Correlation coefficient, Vitamina E, Conducta alimentaria, Vitamina D, Carotenoides, Check Tags::Male [Medical Subject Headings], Chemicals and Drugs::Polycyclic Compounds::Steroids::Secosteroids::Vitamin D [Medical Subject Headings], RM1-950, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Fruit and vegetable intake, Article, Persons::Persons::Age Groups::Adolescent [Medical Subject Headings], Ingestión de alimentos, 03 medical and health sciences, Animal science, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Nutrition Assessment [Medical Subject Headings], Vitamin D and neurology, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Benzopyrans::Vitamin E [Medical Subject Headings], Nutritional biomarker, Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development [Medical Subject Headings], Molecular Biology, nutritional biomarker, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], 030109 nutrition & dietetics, business.industry, Technology and Food and Beverages::Food and Beverages::Food::Vegetables [Medical Subject Headings], Cell Biology, Diet, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Requirements::Recommended Dietary Allowances [Medical Subject Headings], chemistry, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Food Frequency Questionnaire (FFQ), adolescence, Therapeutics. Pharmacology, business
Abstract: Reliable tools to evaluate diet are needed, particularly in life periods such as adolescence in which a rapid rate of growth and development occurs. We assessed the biochemical validity of a self-administered food frequency questionnaire (FFQ) in a sample of Spanish male adolescents using carotenoids and vitamin E and D data. We analyzed data from 122 male adolescents aged 15–17 years of the INMA-Granada birth cohort study. Adolescents answered a 104-item FFQ and provided a non-fasting blood sample. Mean daily nutrient intakes and serum concentration were estimated for main carotenoids (lutein-zeaxanthin, β-cryptoxanthin, lycopene, α-carotene and β-carotene), vitamins E and D and also for fruit and vegetable intake. Pearson correlation coefficients (r) and the percentage of agreement (same or adjacent quintiles) between serum vitamin concentrations and energy-adjusted intakes were estimated. Statistically significant correlation coefficients were observed for the total carotenoids (r = 0.40) and specific carotenoids, with the highest correlation observed for lutein–zeaxanthin (r = 0.42) and the lowest for β-carotene (0.23). The correlation coefficient between fruit and vegetable intake and serum carotenoids was 0.29 (higher for vegetable intake, r = 0.33 than for fruit intake, r = 0.19). Low correlations were observed for vitamin E and D. The average percentage of agreement for carotenoids was 55.8%, and lower for vitamin E and D (50% and 41%, respectively). The FFQ may be an acceptable tool for dietary assessment among male adolescents in Spain., Institute of Health Carlos III (ISCIII), Spanish Ministry of Health (FIS 07/0314; PI11/01007), “Fondo Europeo de Desarrollo Regional” (ISCIII/FEDER) for the Miguel Servet Type I Program granted to C. Freire (grant no. CP16/00085), “Instituto de Salud Carlos III/Agencia Estatal de Investigación”, grant number PI18/00825 Project: Dieta y actividad física en embarazo y tras el nacimiento y longitud del telómero en niños y adolescentes: Proyecto TeloDiPA”, Unión Europea (FEDER) “Una manera de hacer Europa”
Published: 2021
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12. Urinary concentrations of (+)-catechin and (-)-epicatechin as biomarkers of dietary intake of flavan-3-ols in the european prospective investigation into cancer and nutrition (epic) study

Author: Matthias B. Schulze, David Achaintre, Enrique Almanza-Aguilera, Rosario Tumino, Joseph A. Rothwell, Theron Johnson, Verena Katzke, Gianluca Severi, Carlotta Sacerdote, Nasser Laouali, Domenico Palli, Maria Santucci de Magistris, Augustin Scalbert, Raul Zamora-Ros, Daniela Ceballos-Sánchez, Giuliana Gargano, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Universität Potsdam, Università degli studi di Napoli Federico II, Instituto de Salud Carlos III, ISCIII: PI18/00191, European Regional Development Fund, ERDF, Funding: This research was funded by the by the Institute of Health Carlos III through the grant PI18/00191 (co-funded by European Regional Development Fund. ERDF, a way to build Europe), and from the 553/C/2019 project, funded by La Marató de TV-3. The national EPIC cohorts are supported by the French National Cancer Institute (L’Institut National du Cancer, INCA Grant No. 2009-139), Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer, and Compagnia San Paolo (Italy). IDIBELL acknowledges support from the Generalitat de Catalunya through the CERCA Program. E.A.-A. and R.Z.-R. wish to thank the 'Sara Borrell' (CD20/00071) and the 'Miguel Servet' (CP CPII20/00009) programs from the Institute of Health Carlos III (co-funded by the European Social Fund (ESF)—ESF investing in your future).
Subjects: Male, Questionnaires, 030309 nutrition & dietetics, Urine, Catechin, chemistry.chemical_compound, Eating, Medicine, TX341-641, Food science, Prospective Studies, Epicatechin, 0303 health sciences, Nutrition and Dietetics, Biochemical markers, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Proanthocyanidin, Marcadors bioquímics, Intake, Female, Adult, Urinary system, Qüestionaris, Diet Surveys, Article, Statistics, Nonparametric, Flavan-3-ols, 03 medical and health sciences, Herbal tea, Flavan, Biflavonoids, Humans, Proanthocyanidins, 030304 developmental biology, Aged, Wine, Flavonoids, business.industry, Nutrition. Foods and food supply, Orina, Diet, Nutrition Assessment, chemistry, Food, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Aliments, business, EPIC, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers, Food Science
Abstract: This study examines the correlation of acute and habitual dietary intake of flavan-3-ol monomers, proanthocyanidins, theaflavins, and their main food sources with the urinary concentrations of (+)-catechin and (-)-epicatechin in the European Prospective Investigation into Cancer and Nutrition study (EPIC). Participants (N = 419, men and women) provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day. Acute and habitual dietary data were collected using a standardized 24-HDR software and a validated dietary questionnaire, respectively. Intake of flavan-3-ols was estimated using the Phenol-Explorer database. Concentrations of (+)-catechin and (-)-epicatechin in 24-h urine were analyzed using tandem mass spectrometry after enzymatic deconjugation. Simple and partial Spearman’s correlations showed that urinary concentrations of (+)-catechin, (-)-epicatechin and their sum were more strongly correlated with acute than with habitual intake of individual and total monomers (acute rpartial = 0.13–0.54, p &lt, 0.05, and habitual rpartial = 0.14–0.28, p &lt, 0.01), proanthocyanidins (acute rpartial = 0.24–0.49, p &lt, 0.001, and habitual rpartial = 0.10–0.15, p &lt, 0.05), theaflavins (acute rpartial = 0.22–0.31, p &lt, and habitual rpartial = 0.20–0.26, p &lt, 0.01), and total flavan-3-ols (acute rpartial = 0.40–0.48, p &lt, and habitual rpartial = 0.23–0.33, p &lt, 0.001). Similarly, urinary concentrations of flavan-3-ols were weakly correlated with both acute (rpartial = 0.12–0.30, p &lt, 0.05) and habitual intake (rpartial = 0.10–0.27, p &lt, 0.05) of apple and pear, stone fruits, berries, chocolate and chocolate products, cakes and pastries, tea, herbal tea, wine, red wine, and beer and cider. Moreover, all comparable correlations were stronger for urinary (-)-epicatechin than for (+)-catechin. In conclusion, our data support the use of urinary concentrations of (+)-catechin and (-)-epicatechin, especially as short-term nutritional biomarkers of dietary catechin, epicatechin and total flavan-3-ol monomers.
Published: 2021
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13. V-shaped pyranylidene/triphenylamine-based chromophores with enhanced photophysical, electrochemical and nonlinear optical properties

Author: Rocío Ponce Ortiz, Carlos Benitez-Martin, Carlos Moreno-Yruela, Raquel Andreu, David Neusser, M. Carmen Ruiz Delgado, Sergio Gámez-Valenzuela, Belén Villacampa, Francisco Najera, Juan Antonio Guadix, Sabine Ludwigs, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Junta de Andalucía, Gobierno de Aragón, German Research Foundation, [Gámez-Valenzuela,S, Ponce Ortíz,R, Ruiz Delgado,MC] Department of Physical Chemistry, University of Malaga, Malaga, Spain. [Neusser,D, Ludwigs,S] IPOC – Functional Polymers, Institute of Polymer Chemistry, University of Stuttgart, Stuttgart, Germany. [Benitez-Martín,C, Najera,F] Departamento de Química Orgánica, Universidad de Málaga-IBIMA, Málaga, Spain. [Benitez-Martín,C, Najera,F, Guadix,JA] Centro Andaluz de Nanomedicina y Biotecnología-BIONAND, Parque Tecnológico de Andalucía, Campanillas, Málaga, Spain. [Guadix,JA] Departamento de Biología Animal, Facultad de Ciencias, Universidad de Málaga-IBIMA, Málaga, Spain. [Moreno-Yruela,C, Andreu,R] Instituto de Nanociencia y Materiales de Aragón (INMA)-Departamento de Química Orgánica, CSIC-Universidad de Zaragoza, Zaragoza, Spain. [Moreno-Yruela,C] Center for Biopharmaceuticals & Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [Villacampa,B] Instituto de Nanociencia y Materiales de Arago´n (INMA)-Departamento de Física de la Materia Condensada, CSIC-Universidad de Zaragoza, Zaragoza, Spain., The work at the University of Málaga was funded by the MICINN (PID2019-110305GB-I00, PID2019-104293GB-I00, RTI2018-095410-B-I00, EuroNanoMed 2019 PCI2019-111825-2), the Institute of Health Carlos III (ISCIII) RETIC ARADYAL (RD16/0006/0012) and by the Junta de Andalucıa (P09-FQM-4708, UMA18-FEDERJA-080, UMA18-FEDERJA-007, PIER-0084-2019). The work at the University of Zaragoza was funded by the MICINN (PID2019-104307GB-I00/AEI/10.13039/501100011033) and Gobierno de Aragón (E47_20R). The work at the University of Stuttgart was funded by the German Science Foundation (DFG) through the project 'LU 1445/7-1, project number 416982273' on electrooptical hybrid modulators, C. Malacrida is acknowledged for discussions. S. G.-V. thanks the MINECO for a FPU predoctoral fellowship (FPU17/04908) and CB-M for FPU fellowship (FPU16/02516). Computer resources, technical expertise and assistance provided by the SCBI (Supercomputing and Bioinformatics) centre of the University of Málaga are gratefully acknowledged. We thank the Vibrational spectroscopy lab (EVI) of the Research Central Services (SCAI) of the University of Málaga and John Pearson (BIONAND) for help with laser confocal microscopy analysis. We gratefully acknowledge the ICTS 'NANBIOSIS' facilities, more specifically the U28 Unit of the Andalusian Centre for Nanomedicine & Biotechnology (BIONAND), for their help with the 2PA characterization and the microscopy studies., [Gamez-Valenzuela, Sergio] Univ Malaga, Dept Phys Chem, Campus Teatinos S-N, Malaga 29071, Spain, [Ponce Ortiz, Rocio] Univ Malaga, Dept Phys Chem, Campus Teatinos S-N, Malaga 29071, Spain, [Ruiz Delgado, M. Carmen] Univ Malaga, Dept Phys Chem, Campus Teatinos S-N, Malaga 29071, Spain, [Neusser, David] Univ Stuttgart, Inst Polymer Chem, IPOC Funct Polymers, Pfaffenwaldring 55, D-70569 Stuttgart, Germany, [Ludwigs, Sabine] Univ Stuttgart, Inst Polymer Chem, IPOC Funct Polymers, Pfaffenwaldring 55, D-70569 Stuttgart, Germany, [Benitez-Martin, Carlos] Univ Malaga IBIMA, Dept Quim Organ, Campus Teatinos S-N, Malaga 29071, Spain, [Najera, Francisco] Univ Malaga IBIMA, Dept Quim Organ, Campus Teatinos S-N, Malaga 29071, Spain, [Benitez-Martin, Carlos] Ctr Andaluz Nanomed & Biotecnol BIONAND, Parque Tecnol Andaluci,C Severo Ochoa 35, Malaga 29071, Spain, [Najera, Francisco] Ctr Andaluz Nanomed & Biotecnol BIONAND, Parque Tecnol Andaluci,C Severo Ochoa 35, Malaga 29071, Spain, [Guadix, Juan A.] Ctr Andaluz Nanomed & Biotecnol BIONAND, Parque Tecnol Andaluci,C Severo Ochoa 35, Malaga 29071, Spain, [Guadix, Juan A.] Univ Malaga IBIMA, Fac Ciencias, Dept Biol Anim, Campus Teatinos S-N, Malaga 29071, Spain, [Moreno-Yruela, Carlos] CSIC Univ Zaragoza, Inst Nanociencia & Mat Aragon INMA, Dept Quim Organ, Zaragoza 50009, Spain, [Andreu, Raquel] CSIC Univ Zaragoza, Inst Nanociencia & Mat Aragon INMA, Dept Quim Organ, Zaragoza 50009, Spain, [Moreno-Yruela, Carlos] Univ Copenhagen, Ctr Biopharmaceut, Fac Hlth & Med Sci, Univ Pk 2, DK-2100 Copenhagen, Denmark, [Moreno-Yruela, Carlos] Univ Copenhagen, Dept Drug Design & Pharmacol, Fac Hlth & Med Sci, Univ Pk 2, DK-2100 Copenhagen, Denmark, [Villacampa, Belen] CSIC Univ Zaragoza, Inst Nanociencia & Mat Aragon INMA, Dept Fis Mat Condensada, Zaragoza 50009, Spain, MICINN, Institute of Health Carlos III (ISCIII) RETIC ARADYAL, Junta de Andalucia, Gobierno de Aragon, German Science Foundation (DFG), and MINECO
Subjects: Inactivación por luz asistida por cromóforos, 02 engineering and technology, Photochemistry, Electrochemistry, Triphenylamine, 01 natural sciences, chemistry.chemical_compound, DESIGN, Chemical oxidation, 4-Butirolactona, Moiety, General Materials Science, REDOX, DERIVATIVES, TRIPHENYLAMINE, 021001 nanoscience & nanotechnology, Fluorescence, Phenomena and Processes::Physical Phenomena::Elementary Particles::Electrons [Medical Subject Headings], Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Furans [Medical Subject Headings], Chromophore-Assisted Light Inactivation, Tetrahydrofuran, EMITTERS, Chemistry (miscellaneous), Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Dimerization [Medical Subject Headings], Fluorescencia, symbols, Phenomena and Processes::Physical Phenomena::Optical Phenomena::Light::Luminescence::Fluorescence [Medical Subject Headings], 0210 nano-technology, Dimerization, Materials science, Electrons, Electrones, 010402 general chemistry, AGGREGATION-INDUCED EMISSION, symbols.namesake, OLIGOTHIOPHENES, FUTURE, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chromophore-Assisted Light Inactivation [Medical Subject Headings], Stokes shift, SPECTRA, Dimerización, Chemicals and Drugs::Inorganic Chemicals::Hydroxides::Water [Medical Subject Headings], Chromophore, Acceptor, 0104 chemical sciences, 2-PHOTON ABSORPTION, Oxidación química, chemistry
Abstract: We report the synthesis and comprehensive study of two chromophores based on 4H-pyranylidene moiety as a part of the π-conjugated spacer. Triphenylamine (TPA) acts as donor and tricarbonitrile-based electron-accepting groups complete these V-shaped D–A–D architectures (A, acceptor; D, donor). Their electrochemical, photophysical and nonlinear optical properties are analyzed in detail by using a joint experimental and theoretical approach. The two chromophores exhibit near-infrared fluorescence, large Stokes shift, enhanced emission in tetrahydrofuran/water mixtures and good photostability. Additionally, the dimerization of triphenylamine groups to tetraphenylbenzidine (TPB) takes place upon electrochemical and chemical oxidation showing their peculiar electrochemical behavior and film formation capabilities. Interestingly, high molecular first hyperpolarizabilities and two-photon absorption cross-sections were found, highlighting their potential applications in electro-optical devices. Overall, our work demonstrates that these near-infrared (NIR) fluorescent chromophores are versatile materials with a myriad of applications ranging from optoelectronics to biological applications., The work at the University of Málaga was funded by the MICINN (PID2019-110305GB-I00, PID2019-104293GB-I00, RTI2018-095410-B-I00, EuroNanoMed 2019 PCI2019-111825-2), the Institute of Health Carlos III (ISCIII) RETIC ARADYAL (RD16/0006/0012) and by the Junta de Andalucıa (P09-FQM-4708, UMA18-FEDERJA-080, UMA18-FEDERJA-007, PIER-0084-2019). The work at the University of Zaragoza was funded by the MICINN (PID2019-104307GB-I00/AEI/10.13039/501100011033) and Gobierno de Aragón (E47_20R). The work at the University of Stuttgart was funded by the German Science Foundation (DFG) through the project “LU 1445/7-1, project number 416982273” on electrooptical hybrid modulators, C. Malacrida is acknowledged for discussions. S. G.-V. thanks the MINECO for a FPU predoctoral fellowship (FPU17/04908) and CB-M for FPU fellowship (FPU16/02516). Computer resources, technical expertise and assistance provided by the SCBI (Supercomputing and Bioinformatics) centre of the University of Málaga are gratefully acknowledged. We thank the Vibrational spectroscopy lab (EVI) of the Research Central Services (SCAI) of the University of Málaga and John Pearson (BIONAND) for help with laser confocal microscopy analysis. We gratefully acknowledge the ICTS “NANBIOSIS” facilities, more specifically the U28 Unit of the Andalusian Centre for Nanomedicine & Biotechnology (BIONAND), for their help with the 2PA characterization and the microscopy studies.
Published: 2021
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14. Physiopathology of Lifestyle Interventions in Non-Alcoholic Fatty Liver Disease (NAFLD)

Author: Carneros, David, López-Lluch, Guillermo, Bustos, Matilde, [Carneros,D, Bustos,M] Institute of Biomedicine of Seville (IBIS), Spanish National Research Council (CSIC), University of Seville, Virgen del Rocio University Hospital, Seville, Spain. [López-Lluch,G] Centro Andaluz de Biología del Desarrollo (CABD/CSIC/JA), Institute of Health Carlos III (CIBERER), University of Pablo de Olavide, Sevilla, Spain., and This research was funded by MINECO/AEI/FEDER, UE PID2019-110587RB-I00 from the Ministry of Economy and Competitiveness (co-funded by European Social Fund) to G.L.-L and M.B. and Andalusian Ministry of Economy, Innovation, Science and Employment (P18-RT-4775) to G.L.-L. and M.B. D.C. is supported by a pre-doctoral iPFIS, (IFI 19/00048) funded by the Spanish Institute of Health Carlos III (co-funded by European Social Fund).
Subjects: Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Nutrition Therapy::Diet Therapy::Diet, Reducing [Medical Subject Headings], Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise [Medical Subject Headings], NAFLD, Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Growth::Body Size::Body Weight::Body Weight Changes::Weight Loss [Medical Subject Headings], Physical exercise, Diseases::Digestive System Diseases::Liver Diseases::Fatty Liver [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], Fasting, Enfermedad del hígado graso no alcohólico, Ejercicio físico, Ayuno
Abstract: Non-alcoholic fatty liver disease (NAFLD) is a major health problem, and its prevalence has increased in recent years. Diet and exercise interventions are the first-line treatment options, with weight loss via a hypocaloric diet being the most important therapeutic target in NAFLD. However, most NAFLD patients are not able to achieve such weight loss. Therefore, the requisite is the investigation of other effective therapeutic approaches. This review summarizes research on understanding complex pathophysiology underlying dietary approaches and exercise interventions with the potential to prevent and treat NAFLD. Yes
Published: 2020

15. The Role of Disturbed Mg Homeostasis in Chronic Kidney Disease Comorbidities

Author: Rodelo-Haad, Cristian, Pendón-Ruiz de Mier, M. Victoria, Díaz-Tocados, Juan Miguel, Martin-Malo, Alejandro, Santamaria, Rafael, Muñoz-Castañeda, Juan Rafael, Rodríguez, Mariano, [Rodelo-Haad,C, Pendón-Ruiz de Mier,MV, Díaz-Tocados,JM, Martin-Malo,A, Santamaria,R, Muñoz-Castañeda,JR, Rodríguez,M] Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain. [Rodelo-Haad,C, Rodríguez,M] University of Córdoba, Córdoba, Spain. [Rodelo-Haad,C, Rodríguez,M] Nephrology Service, Reina Sofia University Hospital, Córdoba, Spain. [Rodelo-Haad,C, Rodríguez,M] Spanish Renal Research Network (REDinREN), Institute of Health Carlos III, Madrid, Spain., and JRM-C is a senior researcher supported by the Nicolás Monardes Program from Consejeria de Salud-SAS (Junta de Andalucía). This study was supported by grants from the National Institute of Health Carlos III (FIS 17/01010, and FIS 18/0138), the Consejeria de Salud of Junta de Andalucía (PI-0136-2016), the REDinREN from the National Institute of Health Carlos III, the EUTox Workgroup, and the EDTA CKD-MBD group. The sponsors had no influence in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
Subjects: Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Calcium Metabolism Disorders::Calcinosis::Vascular Calcification [Medical Subject Headings], Diseases::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Renal Insufficiency, Chronic [Medical Subject Headings], Diseases::Endocrine System Diseases::Diabetes Mellitus [Medical Subject Headings], Enfermedades óseas, Mineral metabolism and bone disease, Chemicals and Drugs::Inorganic Chemicals::Minerals [Medical Subject Headings], Cardiovascular disease, Anatomy::Cardiovascular System::Blood Vessels::Arteries::Coronary Vessels [Medical Subject Headings], Chemicals and Drugs::Inorganic Chemicals::Elements::Metals, Alkaline Earth::Magnesium [Medical Subject Headings], Diseases::Female Urogenital Diseases and Pregnancy Complications::Female Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Renal Insufficiency, Chronic [Medical Subject Headings], Magnesio, Diseases::Cardiovascular Diseases::Vascular Diseases::Hypertension [Medical Subject Headings], Chronic kidney disease, Technology and Food and Beverages::Food and Beverages::Food::Dietary Supplements [Medical Subject Headings], Hypomagnesemia, Magnesium, Diseases::Musculoskeletal Diseases::Bone Diseases [Medical Subject Headings], Enfermedades cardiovasculares, Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress [Medical Subject Headings], Diseases::Cardiovascular Diseases [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Physiological Processes::Homeostasis [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings]
Abstract: Some of the critical mechanisms that mediate chronic kidney disease (CKD) progression are associated with vascular calcifications, disbalance of mineral metabolism, increased oxidative and metabolic stress, inflammation, coagulation abnormalities, endothelial dysfunction, or accumulation of uremic toxins. Also, it is widely accepted that pathologies with a strong influence in CKD progression are diabetes, hypertension, and cardiovascular disease (CVD). A disbalance in magnesium (Mg) homeostasis, more specifically hypomagnesemia, is associated with the development and progression of the comorbidities mentioned above, and some mechanisms might explain why low serum Mg is associated with negative clinical outcomes such as major adverse cardiovascular and renal events. Furthermore, it is likely that hypomagnesemia causes the release of inflammatory cytokines and C-reactive protein and promotes insulin resistance. Animal models have shown that Mg supplementation reverses vascular calcifications; thus, clinicians have focused on the potential benefits that Mg supplementation may have in humans. Recent evidence suggests that Mg reduces coronary artery calcifications and facilitates peripheral vasodilation. Mg may reduce vascular calcification by direct inhibition of the Wnt/β-catenin signaling pathway. Furthermore, Mg deficiency worsens kidney injury induced by an increased tubular load of phosphate. One important consequence of excessive tubular load of phosphate is the reduction of renal tubule expression of α-Klotho in moderate CKD. Low Mg levels worsen the reduction of Klotho induced by the tubular load of phosphate. Evidence to support clinical translation is yet insufficient, and more clinical studies are required to claim enough evidence for decision-making in daily practice. Meanwhile, it seems reasonable to prevent and treat Mg deficiency. This review aims to summarize the current understanding of Mg homeostasis, the potential mechanisms that may mediate the effect of Mg deficiency on CKD progression, CVD, and mortality. Yes
Published: 2020

16. Predicting mortality in hemodialysis patients using machine learning analysis

Author: Ignacio R Molina, Mariano Rodriguez, V. García-Montemayor, Francesco Bellocchio, Pedro Aljama, Carlo Barbieri, Victoria Pendon-Ruiz de Mier, Sagrario Soriano, Alejandro Martin-Malo, [Garcia-Montemayor,V, Martin-Malo,A, Soriano,S, Pendon-Ruiz de Mier,V, Molina,IR, Aljama,P, Rodriguez,M] Department of Nephrology, Reina Sofia University Hospital, Cordoba, Spain. [Martin-Malo,A, Rodriguez,M] Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Spain. [Martin-Malo,A, Rodriguez,M] RETICs-REDinREN (National Institute of Health Carlos III), Madrid, Spain. [Barbieri,C, Bellocchio,F] Fresenius Medical Care Italia, Vaiano Cremasco, Cremona, Italy., and This study was supported by grants from the National Institute of Health Carlos III (FIS 17/01785, FIS 17/01010), RETICs Red Renal RD06/0016/0007, the Consejeria de Salud of Junta de Andalucia (PI-0311-2014), the REDinREN from the National Institute of Health Carlos III (RD16/0009/0034) and the European group EUTox and CKD-MBD group.
Subjects: Anatomy::Urogenital System::Urinary Tract::Kidney [Medical Subject Headings], medicine.medical_treatment, 030232 urology & nephrology, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Forecasting [Medical Subject Headings], 030204 cardiovascular system & hematology, Logistic regression, Machine learning, computer.software_genre, Predictive models, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 03 medical and health sciences, 0302 clinical medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Statistical::Logistic Models [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Comorbidity [Medical Subject Headings], medicine, Predicción, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Renal Replacement Therapy::Renal Dialysis [Medical Subject Headings], Mortality prediction, Mortality, AcademicSubjects/MED00340, Diálisis renal, Transplantation, business.industry, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Area Under Curve [Medical Subject Headings], Area under the curve, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality [Medical Subject Headings], Mean age, Baseline data, Original Articles, predictive models, mortality, Aprendizaje automático, Random forest, haemodialysis, Haemodialysis, machine learning, Nephrology, Charlson comorbidity index, Mortalidad, Hemodialysis, Artificial intelligence, business, computer, random forest
Abstract: Background Besides the classic logistic regression analysis, non-parametric methods based on machine learning techniques such as random forest are presently used to generate predictive models. The aim of this study was to evaluate random forest mortality prediction models in haemodialysis patients. Methods Data were acquired from incident haemodialysis patients between 1995 and 2015. Prediction of mortality at 6 months, 1 year and 2 years of haemodialysis was calculated using random forest and the accuracy was compared with logistic regression. Baseline data were constructed with the information obtained during the initial period of regular haemodialysis. Aiming to increase accuracy concerning baseline information of each patient, the period of time used to collect data was set at 30, 60 and 90 days after the first haemodialysis session. Results There were 1571 incident haemodialysis patients included. The mean age was 62.3 years and the average Charlson comorbidity index was 5.99. The mortality prediction models obtained by random forest appear to be adequate in terms of accuracy [area under the curve (AUC) 0.68–0.73] and superior to logistic regression models (ΔAUC 0.007–0.046). Results indicate that both random forest and logistic regression develop mortality prediction models using different variables. Conclusions Random forest is an adequate method, and superior to logistic regression, to generate mortality prediction models in haemodialysis patients.
Published: 2020

17. Assessing autophagy in archived tissue or how to capture autophagic flux from a tissue snapshot

Author: Guillermo Velasco, Jordi Muntané, Magali Humbert, Eva Žerovnik, María Morán, Walter Balduini, Sharon L. McKenna, Paula Ludovico, Tabea Wiedmer, Leopold Eckhart, Bassam Janji, Nikolai Engedal, Aurel Perren, Patricia de la Cruz-Ojeda, Mario P. Tschan, Rupert Langer, Nadezda Apostolova, Belém Sampaio-Marques, Universidade do Minho, Bernese Cancer League, Stiftung für klinisch-experimentelle Tumorforschung, Werner and Hedy Berger-Janser Foundation for Cancer Research, Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Junta de Andalucía, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Breakthrough Cancer Research (Ireland), Fonds National de la Recherche Luxembourg, Fundação para a Ciência e a Tecnologia (Portugal), Slovenian Research Agency, Recherche Suisse contre le Cancer, Swiss National Science Foundation, Universidad de Sevilla. Departamento de Cirugía, [Humbert,M, Morán,M, Muntané,J, Apostolova,N, McKenna,SL, Velasco,G, Balduini,W, Eckhart,L, Janji,B, Sampaio-Marques,B, Ludovico,P, Zerovnik,E, Engedal,N, Tschan,MP] TRANSAUTOPHAGY: European Network for Multidisciplinary Research and Translation of Autophagy Knowledge, COST Action CA15138, Barcelona, Spain. [Humbert,M, Wiedmer,T, Langer,R, Perren,A, Tschan,MP] Institute of Pathology, University of Bern, Bern, Switzerland. [Morán,M] Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigación Sanitaria Hospital ‘12 de Octubre’ (‘imas12’), Madrid, Spain. [Morán,M] Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Institute of Health Carlos III (ISCIII), Madrid, Spain. [de la Cruz-Ojeda,P, Muntané,J] Institute of Biomedicine of Seville (IBiS), Hospital University 'Virgen del Rocío'/CSIC/University of Seville, Seville, Spain. [de la Cruz-Ojeda,P, Muntané,J] Department of Surgery, School of Medicine, University of Seville, Seville, Spain. [Muntané,J, Apostolova,N] Spanish Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III (ISCIII), Madrid, Spain. [Apostolova,N] Department of Pharmacology, University of Valencia, Valencia, Spain. [McKenna,SL] Cancer Research at UCC,Western Gateway Building, University College Cork, Cork, Ireland. [Velasco,G] Department of Biochemistry and Molecular Biology, School of Biology, Complutense University, and Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain. [Balduini,W] Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy. [Eckhart,L] Department of Dermatology, Medical University of Vienna, Vienna, Austria. [Janji,B] Tumor Immunotherapy and Microenvironment (TIME) Group, Department of Oncology—Luxembourg. Institute of Health, Luxembourg City, Luxembourg. [Sampaio-Marques,B, Ludovico,P] Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. [Sampaio-Marques,B, Ludovico,P] ICVS/3B’s—PT Government Associate Laboratory, Braga/Guimarães, Portugal. [Zerovnik,E] Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana, Slovenia. [Engedal,N] Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., This work was supported by grants fromthe Bernese Cancer League, 'Stiftung für klinisch-experimentelle Tumorforschung', and theWerner and Hedy Berger-Janser Foundation for Cancer Research (to M.H.), by Institute of Health Carlos III (ISCIII) and FEDER funds from the EU (PI14/01085 and PI17/00093) and supported by Miguel Servet contract by ISCIII and FSE funds (CPII16/00023) (to M.M.), from the Spanish Ministry of Science, Innovation and Universities (RTI2018-096748-B-100 to N.A.), from the University Professor Training Fellowship, Ministry of Science, Innovation and University, Government of Spain (FPU17/00026) (to P.C.O), from the ISCIII (PI16/00090 and PI19/01266) and the Andalusian Government (Consejería de Igualdad, Salud y Políticas Sociales, PI-0198-2016) for their financial support, and from the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd) founded by the ISCIII and co-financed by European Development Regional Fund (EDRF) 'A way to achieve Europe' for their financial support (to J.M.), from Breakthrough Cancer Research, Ireland funding (to S.L.M), from the PI18/00442 grant integrated into the State Plan for R & D + I2013-2016 and funded by the ISCIII and the ERDF, a way to make Europe (to G.V.), from the Luxembourg National Research Fund (C18/BM/12670304/COMBATIC to B.J.), from the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, by the European Regional Development Fund (FEDER), through the Competitiveness Factors Operational Programme (COMPETE) (NORTE-01-0145-FEDER-000013) and from the projects POCI-01-0145-FEDER-028159 and POCI-01-0145-FEDER-030782 by FEDER, through the COMPETE (to P.L.), from National funds, through the Foundation for Science and Technology (FCT) (to P.L.), from ARRS—the Slovenian research agency, programme P1-0140: Proteolysis and its regulation (led by B. Turk) (to E.Ž.), and from the Swiss Cancer Research (KFS-3360-02-2014) (to A.P, and M.P.T.) (KFS-3409-02-2014), and the Swiss National Science Foundation (31003A_173219) (to M.P.T.).
Subjects: Bioquímica, autophagy, Ciências da Saúde [Ciências Médicas], Ciências Médicas::Ciências da Saúde, Cellular homeostasis, Autofagia, 610 Medicine & health, Biology, General Biochemistry, Genetics and Molecular Biology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 03 medical and health sciences, 0302 clinical medicine, Human disease, Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings], Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Autophagy [Medical Subject Headings], lcsh:QH301-705.5, 030304 developmental biology, 0303 health sciences, disease, Biología molecular, Science & Technology, General Immunology and Microbiology, Mechanism (biology), Communication, Autophagy, biomarkers, pathology, Patología, 3. Good health, Cell biology, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Research Design::Reproducibility of Results [Medical Subject Headings], Biomarcadores, Tejidos, lcsh:Biology (General), 030220 oncology & carcinogenesis, 570 Life sciences, biology, General Agricultural and Biological Sciences, Flux (metabolism), Enfermedad, Phenomena and Processes::Physiological Phenomena::Physiological Processes::Homeostasis [Medical Subject Headings]
Abstract: This article belongs to the Special Issue Autophagy in Cancer., Autophagy is a highly conserved degradation mechanism that is essential for maintaining cellular homeostasis. In human disease, autophagy pathways are frequently deregulated and there is immense interest in targeting autophagy for therapeutic approaches. Accordingly, there is a need to determine autophagic activity in human tissues, an endeavor that is hampered by the fact that autophagy is characterized by the flux of substrates whereas histology informs only about amounts and localization of substrates and regulators at a single timepoint. Despite this challenging task, considerable progress in establishing markers of autophagy has been made in recent years. The importance of establishing clear-cut autophagy markers that can be used for tissue analysis cannot be underestimated. In this review, we attempt to summarize known techniques to quantify autophagy in human tissue and their drawbacks. Furthermore, we provide some recommendations that should be taken into consideration to improve the reliability and the interpretation of autophagy biomarkers in human tissue samples., This work was supported by grants from the Bernese Cancer League, “Stiftung für klinisch-experimentelle Tumorforschung”, and the Werner and Hedy Berger-Janser Foundation for Cancer Research (to M.H.); by Institute of Health Carlos III (ISCIII) and FEDER funds from the EU (PI14/01085 and PI17/00093) and supported by Miguel Servet contract by ISCIII and FSE funds (CPII16/00023) (to M.M.); from the Spanish Ministry of Science, Innovation and Universities (RTI2018-096748-B-100 to N.A.); from the University Professor Training Fellowship, Ministry of Science, Innovation and University, Government of Spain (FPU17/00026) (to P.C.O); from the ISCIII (PI16/00090 and PI19/01266) and the Andalusian Government (Consejería de Igualdad, Salud y Políticas Sociales, PI-0198-2016) for their financial support, and from the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd) founded by the ISCIII and co-financed by European Development Regional Fund (EDRF) “A way to achieve Europe” for their financial support (to J.M.), from Breakthrough Cancer Research, Ireland funding (to S.L.M); from the PI18/00442 grant integrated into the State Plan for R & D + I2013-2016 and funded by the ISCIII and the ERDF, a way to make Europe (to G.V.); from the Luxembourg National Research Fund (C18/BM/12670304/COMBATIC to B.J.); from the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, by the European Regional Development Fund (FEDER), through the Competitiveness Factors Operational Programme (COMPETE) (NORTE-01-0145-FEDER-000013) and from the projects POCI-01-0145-FEDER-028159 and POCI-01-0145-FEDER-030782 by FEDER, through the COMPETE (to P.L.); from National funds, through the Foundation for Science and Technology (FCT) (to P.L.); from ARRS—the Slovenian research agency, programme P1-0140: Proteolysis and its regulation (led by B. Turk) (to E.Ž.); from the Swiss Cancer Research (KFS-3360-02-2014) (to A.P, and M.P.T.) (KFS-3409-02-2014), and the Swiss National Science Foundation (31003A_173219) (to M.P.T.).
Published: 2020
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18. Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy

Author: Hmadcha, Abdelkrim, Martin-Montalvo, Alejandro, Gauthier, Benoit R., Soria, Bernat, Capilla-Gonzalez, Vivian, [Hmadcha,A, Martin-Montalvo,A, Gauthier,BR, Capilla-Gonzalez,V] Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Pablo de Olavide University, University of Seville, CSIC, Seville, Spain. [Hmadcha,A, Soria,B] Biomedical Research Network on Diabetes and Related Metabolic Diseases (CIBERDEM), Institute of Health Carlos III, Madrid, Spain. [Soria,B] School of Medicine, Miguel Hernández University, Alicante, Spain. [Soria,B] Pablo de Olavide University, Seville, Spain., and The authors received financial support from the Andalusian Regional Ministry of Health (PI-0272-2017), the Institute of Health Carlos III, and the Spanish Ministry of Science, Innovation and University, co-funded by Fondos FEDER (CD16/00118, CP19/00046, PI16/00259, BFU2017-83588-P, CP14/00105, PI18/01590, PI17/02104, PIC18/0010, and IC19/0052), the JDRF (2-SRA-2019-837-S-B), and the crowdfunding platform PRECIPITA of the Spanish Foundation for Science and Technology (2018-000237).
Subjects: Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Reconstructive Surgical Procedures::Guided Tissue Regeneration [Medical Subject Headings], Therapeutic agents, Terapéutica, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics [Medical Subject Headings], Células madre mesenquimatosas, Anatomy::Cells::Stem Cells::Neoplastic Stem Cells [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Mesenchymal Stem Cell Transplantation [Medical Subject Headings], Diseases::Neoplasms [Medical Subject Headings], Cell therapy, Anti-tumor activity, Neoplasias, Disciplines and Occupations::Health Occupations::Medicine::Regenerative Medicine [Medical Subject Headings], Tratamiento basado en trasplante de células y tejidos, Anatomy::Cells::Stem Cells [Medical Subject Headings], Mesenchymal stem cells, Cancer
Abstract: Mesenchymal stem cells (MSCs) are among the most frequently used cell type for regenerative medicine. A large number of studies have shown the beneficial effects of MSC-based therapies to treat different pathologies, including neurological disorders, cardiac ischemia, diabetes, and bone and cartilage diseases. However, the therapeutic potential of MSCs in cancer is still controversial. While some studies indicate that MSCs may contribute to cancer pathogenesis, emerging data reported the suppressive effects of MSCs on cancer cells. Because of this reality, a sustained effort to understand when MSCs promote or suppress tumor development is needed before planning a MSC-based therapy for cancer. Herein, we provide an overview on the therapeutic application of MSCs for regenerative medicine and the processes that orchestrates tissue repair, with a special emphasis placed on cancer, including central nervous system tumors. Furthermore, we will discuss the current evidence regarding the double-edged sword of MSCs in oncological treatment and the latest advances in MSC-based anti-cancer agent delivery systems. Yes
Published: 2020

19. Association between Polyphenol Intake and Gastric Cancer Risk by Anatomic and Histologic Subtypes: MCC-Spain

Author: Nuria Aragonés, Facundo Vitelli-Storelli, Inés Gómez-Acebo, Gemma Castaño-Vinyals, Eva Adarnaz, Marina Pollán, Raul Zamora-Ros, Juan Alguacil, Estefanía Toledo, Manolis Kogevinas, Antonio J. Molina, José Juan Jiménez-Moleón, Vicente Martín, Ana Molina-Barceló, María Rubín-García, Guillermo Fernández-Tardón, María Dolores Chirlaque, Beatriz Pérez-Gómez, Mireia Obón-Santacana, Instituto de Salud Carlos III, Fundación Marqués de Valdecilla, Ministerio de Economía y Competitividad (España), Red Temática de Investigación Cooperativa en Cáncer (España), Junta de Castilla y León (España), Regional Government of Andalusia (España), Generalitat Valenciana (España), Fundación La Caixa, Basque Government (España), Gobierno de la Región de Murcia (España), Unión Europea. Comisión Europea, Asociación Española Contra el Cáncer, Government of Catalonia (España), Fundación Caja de Ahorros de Asturias, University of Oviedo (España), Ministerio de Educación (España), University of Leon (España), Ministerio de Ciencia e Innovación (España), Junta de Castilla y León, Gobierno de Andalucía, Generalitat Valenciana, Recercaixa, Gobierno Vasco, Gobierno de Murcia, European Commission, Fundación Científica AECC, Generalitat de Catalunya, Universidad de Oviedo, Universidad de León, Universidad de Cantabria, [Rubín-García,M, Vitelli-Storelli,F, Molina,AJ, Martín,V] Group of Investigation in Interactions Gene-Environment and Health (GIIGAS), Institute of Biomedicine (IBIOMED), University of León, León, Spain. [Zamora-Ros,R] Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet del Llobregat, Barcelona, Spain. [Aragonés,N] Department of Health of Madrid, Epidemiology Section, Public Health Division, Madrid, Spain. [Aragonés,N, Adarnaz,E, Castaño-Vinyals,G, Gómez-Acebo,I, Fernández-Tardón,G, Jiménez-Moleón,JJ, Alguacil,J, Dolores Chirlaque,MD, Pérez-Gómez,B, Pollán,M, Kogevinas,M, Martín,V] Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Madrid, Spain. [Adarnaz,E, Toledo,E] Institute for Health Research (IdiSNA), Pamplona, Spain. [Castaño-Vinyals,G, Kogevinas,M] Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. [Castaño-Vinyals,G, Kogevinas,M] Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. [Castaño-Vinyals,G, Kogevinas,M] Department of Public Health, Universitat Pompeu Fabra (UPF), Campus del Mar, Barcelona, Spain. [Obón-Santacana,M] ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet De Llobregat, Barcelona, Spain. [Obón-Santacana,M] Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet Del Llobregat, Barcelona, Spain. [Gómez-Acebo,I] Facultad de Medicina, Universidad de Cantabria, IDIVAL, Santander, Spain. [Molina-Barceló,A] Cancer and Public Health Area, FISABIO-Public Health, Valencia, Spain. [Fernández-Tardón,G] Health Research Institute of the Principality of Asturias (ISPA), Oncology Institute, University of Oviedo, Oviedo, Asturias. [Jiménez-Moleón,JJ] Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Hospitales Universitarios de Granada, Universidad de Granada, Granada, Spain. [Alguacil,J] Centro de Investigación en Recursos Naturales, Salud y Medio Ambiente (RENSMA), Universidad de Huelva, Campus Universitario de El Carmen, Huelva, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Campus de Ciencias de la Salud, El Palmar, Murcia, Spain. [Toledo,E] Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Institute of Health Carlos III, Madrid, Spain. [Toledo,E] Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain. [Pérez-Gómez,B, Pollán,M] Cancer and Environmental Epidemiology Unit, Department of Epidemiology and Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain. [Pérez-Gómez,B] Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro, IDIPHIM, Madrid, Spain., and The study was partially funded by the 'Accion Transversal del Cancer', approved by the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17CIII/00034), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)), by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 and 2014SGR850, by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. IDIBELL is a member of the CERCA Programme, Generalitat de Catalunya. R.Z.-R. was supported by the 'Miguel Servet' program (CP15/00100) from the Institute of Health Carlos III (Co-funded by the European Social Fund (ESF)-ESF investing in your future). M.R.-G., is supported by the Ministry of Education of Spain (FPU17/06488) and by University of León. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the 'Centro de Excelencia Severo Ochoa 2019–2023' Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program.
Subjects: 0301 basic medicine, Male, stilbenes, Logistic regression, Gastroenterology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, Eating, 0302 clinical medicine, Estilbenos, Risk Factors, Epidemiology, histologic, Odds Ratio, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], Prospective cohort study, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Nutrition and Dietetics, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Stomach, lignans, MCC-Spain, Middle Aged, anatomic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models [Medical Subject Headings], Quartile, 030220 oncology & carcinogenesis, Dieta, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys::Diet Surveys [Medical Subject Headings], Female, epidemiology, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Benzyl Compounds::Lignans [Medical Subject Headings], lcsh:Nutrition. Foods and food supply, medicine.medical_specialty, Neoplasias gástricas, Polifenoles, Stomach cancer, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols::Polyphenols [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Anatomy::Digestive System::Gastrointestinal Tract::Upper Gastrointestinal Tract::Stomach [Medical Subject Headings], lcsh:TX341-641, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Diet Surveys, Article, 03 medical and health sciences, Stomach Neoplasms, Internal medicine, medicine, Epidemiología, Humans, Compuestos fenólicos, Epidemiologia, Nutrició, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutrition Processes::Eating [Medical Subject Headings], polyphenols, Nutrition, Aged, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Stomach Neoplasms [Medical Subject Headings], Càncer d'estómac, gastric cancer, Cancer, Lignanos, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, Phenolic acid, medicine.disease, Diet, 030104 developmental biology, Logistic Models, Check Tags::Female [Medical Subject Headings], chemistry, Polyphenol, Spain, Case-Control Studies, business, diet, phenolic acids, Food Science
Abstract: Several anticancer properties have been largely attributed to phenolics in in vivo and in vitro studies, but epidemiologic evidence is still scarce. Furthermore, some classes have not been studied in relation to gastric cancer (GC). The aim of this study was to assess the relationship between the intake of phenolic acids, stilbenes, and other phenolics and the risk of developing GC and its anatomical and histological subtypes. We used data from a multi-case-control study (MCC-Spain) obtained from di erent regions of Spain. We included 2700 controls and 329 GC cases. Odds ratios (ORs) were calculated using mixed e ects logistic regression considering quartiles of phenolic intake. Our results showed an inverse association between stilbene and lignan intake and GC risk (ORQ4 vs. Q1 = 0.47; 95% CI: 0.32–0.69 and ORQ4 vs. Q1 = 0.53; 95% CI: 0.36–0.77, respectively). We found no overall association between total phenolic acid and other polyphenol class intake and GC risk. However, hydroxybenzaldehydes (ORQ4 vs. Q1 = 0.41; 95% CI: 0.28–0.61), hydroxycoumarins (ORQ4 vs. Q1 = 0.49; 95% CI: 0.34–0.71), and tyrosols (ORQ4 vs. Q1 = 0.56; 95% CI: 0.39–0.80) were inversely associated with GC risk. No di erences were found in the analysis by anatomical or histological subtypes. In conclusion, a diet high in stilbenes, lignans, hydroxybenzaldehydes, hydroxycoumarins, and tyrosols was associated with a lower GC risk. Further prospective studies are needed to confirm our results., Instituto de Salud Carlos III, Instituto de Salud Carlos III European Union (EU) PI08/1770 PI08/0533 PI08/1359 PS09/00773-Cantabria PS09/01286-Leon PS09/01903-Valencia PS09/02078-Huelva PS09/01662-Granada PI11/01403 PI11/01889-FEDER PI11/00226 PI11/01810 PI11/02213 PI12/00488, Instituto de Salud Carlos III API 10/09, ICGC International Cancer Genome Consortium CLL (Spanish Ministerio de Economia y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)), ICGC International Cancer Genome Consortium CLL (Spanish Ministerio de Economia y Competitividad (MINECO) through Red Tematica de Investigacion del Cancer (RTICC) del ISCIII) RD12/0036/0036, Junta de Castilla y León LE22A10-2, Junta de Andalucía PI-0571-200 PI-0306-2011 salud201200057018tra, Conselleria de Sanitat of the Generalitat Valenciana AP_061/10, La Caixa Foundation 2010ACUP 00310, Regional Government of the Basque Country, Consejería de Sanidad de la Región de Murcia, European Commission European Commission Joint Research Centre FOOD-CT-2006-036224-HIWATE, Spanish Association Against Cancer (AECC) Scientific Foundation, Catalan Government Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 2014SGR850, Fundación Caja de Ahorros de Asturias, University of Oviedo, "Miguel Servet" program from the Institute of Health Carlos III (European Social Fund (ESF)-ESF investing in your future) CP15/00100, Ministry of Education of Spain FPU17/06488, University of Leon, Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019-2023" Program CEX2018-000806-S, Generalitat de Catalunya through the CERCA Program, The Instituto de Salud Carlos III-FEDER PI12/00265 PI12/01270 PI12/00715 PI12/00150 PI14/01219 PI14/0613 PI15/00069 PI15/00914 PI15/01032 PI17CIII/00034
Published: 2020

20. The Global Meningococcal Initiative meeting on prevention of meningococcal disease worldwide: Epidemiology, surveillance, hypervirulent strains, antibiotic resistance and high-risk populations

Author: Hajime Kamiya, Mehmet Ceyhan, Konstantin Mironov, Gabriela Echániz-Aviles, Jay Lucidarme, Susan Meiring, Yanet Climent, Muhamed-Kheir Taha, Philippe De Wals, Bianca Stenmark, Dominique A. Caugant, Xilian Bai, Marco Aurélio Palazzi Sáfadi, Josefina Carlos, Caroline Trotter, Ener Cagri Dinleyici, Vinny Smith, Reinaldo Acevedo, Bingqing Zhu, Hannah Christensen, Zhujun Shao, Ray Borrow, Andromachi Karachaliou, Julio A. Vázquez, Ahmed Hakawi, Robert Steffen, Finlay Institute of Vaccines, Public Health England [London], Norwegian Institute of Public Health [Oslo] (NIPH), University of the East – Ramon Magsaysay Memorial Medical Center [Philippines], Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, University of Bristol [Bristol], Université Laval [Québec] (ULaval), Eskisehir Osmangazi University, National Institute of Public Health = Instituto Nacional de Salud Pública [Cuernavaca, Mexique] (INSP), Ministry of Health [Riyadh], National Institute of Infectious Diseases [Tokyo], University of Cambridge [UK] (CAM), National Institute for Communicable Diseases [Johannesburg] (NICD), Central Research Institute of Epidemiology [Moscow], FCM Santa Casa de São Paulo School of Medical Sciences [São Paulo], Chinese Centre for Disease Control and Prevention, Meningitis Research Foundation [Bristol], Universität Zürich [Zürich] = University of Zurich (UZH), Örebro University Hospital [Örebro, Sweden], Centre National de Référence des Méningocoques et Haemophilus influenzae - National Reference Center Meningococci and Haemophilus influenzae (CNR), Institut Pasteur [Paris], Institute of Health Carlos III, R. Borrow, J. Lucidarme and X. Bai perform contract work for Public Health England on behalf of GSK, PATH, Sanofi Pasteur and Pfizer. M.K. Taha performs contract work for the Institut Pasteur funded by GSK, Pfizer and Sanofi Pasteur. S. Meiring has received grant funding for a meningococcal carriage study by Sanofi Pasteur. G. Enchaniz-Aviles has received support for research projects from GSK and Pfizer. J.A. Vázquez performs contract work for the Institute of Health Carlos III funded by GSK and Pfizer. P. De Wals has received research grants, and reimbursements of travel expenses from vaccine manufacturers including GSK, Novartis, Sanofi Pasteur, and Pfizer, as well as from governmental agencies including the Quebec Ministry of Health and Social Services, Health Canada, and the Public Health Agency of Canada. M.A.P. Sáfadi has received grants to support research projects and consultancy fees from GSK, Pfizer and Sanofi Pasteur. C. Trotter has received consulting fees from GSK and an honorarium from Sanofi-Pasteur for developing and delivering a modeling workshop at a previous GMI meeting. H. Christensen has received reimbursements of travel expenses and, for previous GMI meetings, honoraria, from Sanofi-Pasteur, consultancy fees from IMS Health and AstraZeneca all paid to her employer. She is supported by the NIHR Health Protection Research Unit in Evaluation of Interventions at the University of Bristol. The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care., Institut Pasteur [Paris] (IP), and Sanofi Pasteur
Subjects: 0301 basic medicine, Antibiotic resistance, MESH: Anti-Bacterial Agents/administration & dosage, MESH: Anti-Bacterial Agents/pharmacology, MESH: Global Health, Neisseria meningitidis, medicine.disease_cause, Global Health, Disease Outbreaks, MESH: Meningococcal Infections/epidemiology, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, vaccine, Drug Discovery, Epidemiology, 030212 general & internal medicine, MESH: Disease Outbreaks, immunization program, Vaccination, 3. Good health, Anti-Bacterial Agents, conjugate vaccine, surveillance, Molecular Medicine, Epidemiology / Surveillance, epidemiology, bacterial meningitis, serogroup, medicine.medical_specialty, Immunology, MESH: Meningococcal Infections/microbiology, Meningococcal Vaccines, Polysaccharide Vaccine, Meningococcal disease, 03 medical and health sciences, Conjugate vaccine, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, medicine, Humans, MESH: Meningococcal Vaccines/administration & dosage, Pharmacology, meningococcal disease, High risk populations, MESH: Humans, business.industry, MESH: Vaccination, medicine.disease, Virology, polysaccharide vaccine, Meningococcal Infections, 030104 developmental biology, MESH: Meningococcal Infections/prevention & control, business
Abstract: Introduction: The 2018 Global Meningococcal Initiative (GMI) meeting focused on evolving invasive meningococcal disease (IMD) epidemiology, surveillance, and protection strategies worldwide, with emphasis on emerging antibiotic resistance and protection of high-risk populations. The GMI is comprised of a multidisciplinary group of scientists and clinicians representing institutions from several continents. Areas covered: that the incidence and prevalence of IMD continually varies both geographically and temporally, and surveillance systems differ worldwide, the true burden of IMD remains unknown. Genomic alterations may increase the epidemic potential of meningococcal strains. Vaccination and (to a lesser extent) antimicrobial prophylaxis are the mainstays of IMD prevention. Experiences from across the globe advocate the use of conjugate vaccines, with promising evidence growing for protein vaccines. Multivalent vaccines can broaden protection against IMD. Application of protection strategies to high-risk groups, including individuals with asplenia, complement deficiencies and human immunodeficiency virus, laboratory workers, persons receiving eculizumab, and men who have sex with men, as well as attendees at mass gatherings, may prevent outbreaks. There was, however, evidence that reduced susceptibility to antibiotics was increasing worldwide. Expert commentary: The current GMI global recommendations were reinforced, with several other global initiatives underway to support IMD protection and prevention. This paper was in part supported by Sanofi Pasteur. Sí
Published: 2018
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21. The Global Meningococcal Initiative: global epidemiology, the impact of vaccines on meningococcal disease and the importance of herd protection

Author: Hannah Christensen, Caroline Trotter, Hajime Kamiya, Sergey Sidorenko, Josefina Carlos, Dominique A. Caugant, Roberto Debbag, Ray Borrow, Marco Aurélio Palazzi Sáfadi, Muhamed-Kheir Taha, Chris Head, Philippe De Wals, Jamie Findlow, Daphne Holt, Anne von Gottberg, Gabriela Echániz-Aviles, Pedro Alarcón, Samir K. Saha, Julio A. Vázquez Moreno, Manchester Royal Infirmary, University of Manchester [Manchester], Instituto de Salud Pública de Chile (ISP), University of the East – Ramon Magsaysay Memorial Medical Center [Philippines], Norwegian Institute of Public Health [Oslo] (NIPH), University of the West of England [Bristol] (UWE Bristol), Malvinas Children's Hospital [Buenos Aires], Université Laval [Québec] (ULaval), National Institute of Public Health = Instituto Nacional de Salud Pública [Cuernavaca, Mexique] (INSP), Meningitis Research Foundation [Bristol], Confederation of Meningitis Organisations [Bristol] (CoMO), National Institute of Infectious Diseases [Tokyo], Dhaka Shishu Hospital [Bangladesh], Scientific Research Institute of Children's Infections [Saint-Petersburg, Russia], Centre National de Référence des Méningocoques et Haemophilus influenzae - National Reference Center Meningococci and Haemophilus influenzae (CNR), Institut Pasteur [Paris], University of Cambridge [UK] (CAM), Institute of Health Carlos III, National Institute for Communicable Diseases [Johannesburg] (NICD), FCM Santa Casa de São Paulo School of Medical Sciences [São Paulo], The GMI is funded by an educational grant from Sanofi Pasteur, however, the group is not led in any way by the company. GMI members determine meeting agenda items and lead the discussions and outputs. Medical writing support was provided by Shelley Lindley, PhD, of PAREXEL, which was funded by Sanofi Pasteur. R Borrow and J Findlow perform contract research on behalf of Public Health England for Baxter Biosciences, GlaxoSmithKline, Novartis, Pfizer, Sanofi Pasteur, and Sanofi Pasteur MSD. DA Caugant has performed in the past contract research on behalf of the Norwegian Institute of Public Health for Novartis, Pfizer, and Sanofi Pasteur. H Christensen has received an honorarium from Sanofi Pasteur for running a GMI modeling workshop paid to her employer. Furthermore, H Christensen is supported by the National Institute for Health Research [PDF-2012-05-245] and is a member of the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Evaluation of Interventions at the University of Bristol, UK. S Sidorenko has received grants from Pfizer, outside the submitted work. P De Wals has received research grants and reimbursements of travel expenses from vaccine manufacturers including GlaxoSmithKline, Novartis, Sanofi Pasteur, and Pfizer, as well as from governmental agencies including the Quebec Ministry of Health and Social Services, Health Canada, and the Public Health Agency of Canada. J Carlos has received research grant support from GlaxoSmithKline, Novartis, and Sanofi Pasteur, however, no conflict of interest relevant to this manuscript is reported. M-K Taha performs contract research on behalf of Institut Pasteur for GlaxoSmithKline, Novartis, Pfizer, and Sanofi Pasteur. C Trotter received a consulting payment from GlaxoSmithKline in 2013 for critical review of a health economic model of meningococcal vaccines and an honorarium from Sanofi Pasteur in 2015 for running a GMI modeling workshop. JA Vázquez Moreno performed contract research on behalf of Institute of Health Carlos III for Baxter Biosciences, GlaxoSmithKline, Novartis, Pfizer, and Sanofi Pasteur. A von Gottberg received research funding from Pfizer. MAP Sáfadi has received grants to support research projects from GlaxoSmithKline, Novartis, Pfizer, and Sanofi Pasteur. This work is produced by the authors under the terms of the research training fellowships issued by the NIHR. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, NIHR, the Department of Health, or Public Health England. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., Global Meningococcal Initiative, and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, Epidemiology, MESH: Meningococcal Vaccines/immunology, MESH: Global Health, Neisseria meningitidis, medicine.disease_cause, Global Health, MESH: Immunization Programs, Disease Outbreaks, MESH: Neisseria meningitidis/immunology, MESH: Meningococcal Infections/prevention & control, MESH: Meningococcal Infections/epidemiology, 0302 clinical medicine, prevention, MESH: Meningococcal Vaccines/therapeutic use, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Discovery, Global health, 030212 general & internal medicine, MESH: Incidence, Global Meningococcal Initiative, MESH: Vaccines, Conjugate/immunology, Incidence, MESH: Meningitis, Meningococcal/immunology, MESH: Disease Outbreaks/prevention & control, 3. Good health, Vaccination, outbreaks, surveillance, Molecular Medicine, African meningitis belt, serogroups, 030106 microbiology, Immunology, Meningococcal Vaccines, Meningococcal vaccine, MESH: Meningitis, Meningococcal/epidemiology, Meningitis, Meningococcal, Meningococcal disease, 03 medical and health sciences, Environmental health, MESH: Meningitis, Meningococcal/prevention & control, Epidemiology, Global Meningococcal Initiative, meningococcal disease, MenW, Neisseria meningitidis, outbreaks, prevention, serogroups, surveillance, vaccination, medicine, Humans, MESH: Vaccines, Conjugate/therapeutic use, MenW, Pharmacology, meningococcal disease, Vaccines, Conjugate, MESH: Humans, business.industry, Immunization Programs, Outbreak, medicine.disease, vaccination, Meningococcal Infections, Carriage, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Neisseria meningitidis/classification, business, MESH: Meningococcal Infections/immunology
Abstract: Introduction: The 2015 Global Meningococcal Initiative (GMI) meeting discussed the global importance of meningococcal disease (MD) and its continually changing epidemiology.Areas covered: Although recent vaccination programs have been successful in reducing incidence in many countries (e.g. Neisseria meningitidis serogroup [Men]C in Brazil, MenA in the African meningitis belt), new clones have emerged, causing outbreaks (e.g. MenW in South America, MenC in Nigeria and Niger). The importance of herd protection was highlighted, emphasizing the need for high vaccination uptake among those with the highest carriage rates, as was the need for boosters to maintain individual and herd protection following decline of immune response after primary immunization.Expert commentary: The GMI Global Recommendations for Meningococcal Disease were updated to include a recommendation to enable access to whole-genome sequencing as for surveillance, guidance on strain typing to guide use of subcapsular vaccines, and recognition of the importance of advocacy and awareness campaigns.
Published: 2017
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22. A machine learning derived echocardiographic algorithm identifies people at risk of heart failure with distinct cardiac structure, function, and response to spironolactone: findings from the HOMAGE trial

Author: Kobayashi, Masatake, Huttin, Olivier, Ferreira, João Pedro, Duarte, Kevin, González, Arantxa, Heymans, Stephane, Verdonschot, Job A.J., Rocca, Hans‐peter Brunner‐la, Pellicori, Pierpaolo, Clark, Andrew, Petutschnigg, Johannes, Edelmann, Frank, Cleland, John, Rossignol, Patrick, Zannad, Faiez, Girerd, Nicolas, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA)-Universidad de Navarra [Pamplona] (UNAV)-Clínica Universidad de Navarra [Pamplona], Institute of Health Carlos III, Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Glasgow, University of Hull [United Kingdom], Castle Hill Hospital, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), and European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013)
Subjects: collagen, spironolactone, [SDV]Life Sciences [q-bio], biomarkers, Heart failure, Heart failure echocardiogram collagen spironolactone biomarkers, echocardiogram
Abstract: International audience; Background: An echocardiographic algorithm derived by machine learning (e'VM) characterizes preclinical individuals with different cardiac structure and function, biomarkers, and long-term risk of heart failure (HF). Our aim was the external validation of the e'VM algorithm and to explore whether it may identify subgroups who benefit from spironolactone.Methods: The HOMAGE (Heart OMics in Aging) trial enrolled participants at high risk of developing HF randomly assigned to spironolactone or placebo over 9 months. The e'VM algorithm was applied to 416 participants (mean age 74±7years, 25% women) with available echocardiographic variables (i.e., e' mean, left ventricular [LV] end-diastolic volume and mass indexed by body surface area [LVMi]). The effects of spironolactone on changes in echocardiographic and biomarker variables were assessed across e'VM phenotypes.Results: A majority (>80%) had either "diastolic changes (D)", or "diastolic changes with structural remodeling (D/S)" phenotype. D/S phenotype had the highest LVMi, left atrial volume, E/e', natriuretic peptide and troponin levels (all p0.10; Pinteraction
Published: 2023
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23. Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma

Author: Bruna Calsina, Elena Piñeiro-Yáñez, Ángel M. Martínez-Montes, Eduardo Caleiras, Ángel Fernández-Sanromán, María Monteagudo, Rafael Torres-Pérez, Coral Fustero-Torre, Marta Pulgarín-Alfaro, Eduardo Gil, Rocío Letón, Scherezade Jiménez, Santiago García-Martín, Maria Carmen Martin, Juan María Roldán-Romero, Javier Lanillos, Sara Mellid, María Santos, Alberto Díaz-Talavera, Ángeles Rubio, Patricia González, Barbara Hernando, Nicole Bechmann, Margo Dona, María Calatayud, Sonsoles Guadalix, Cristina Álvarez-Escolá, Rita M. Regojo, Javier Aller, Maria Isabel Del Olmo-Garcia, Adrià López-Fernández, Stephanie M. J. Fliedner, Elena Rapizzi, Martin Fassnacht, Felix Beuschlein, Marcus Quinkler, Rodrigo A. Toledo, Massimo Mannelli, Henri J. Timmers, Graeme Eisenhofer, Sandra Rodríguez-Perales, Orlando Domínguez, Geoffrey Macintyre, Maria Currás-Freixes, Cristina Rodríguez-Antona, Alberto Cascón, Luis J. Leandro-García, Cristina Montero-Conde, Giovanna Roncador, Juan Fernando García-García, Karel Pacak, Fátima Al-Shahrour, Mercedes Robledo, Institut Català de la Salut, [Calsina B, Martínez-Montes ÁM, Fernández-Sanromán Á, Monteagudo M] Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. [Piñeiro-Yáñez E] Bioinformatics Unit, Structural Biology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. [Caleiras E] Histopathology Core Unit, Biotechnology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. [López-Fernández A] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Toledo RA] Gastrointestinal and Endocrine Tumors, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Institute of Health Carlos III (ISCIII), Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors::Paraganglioma::Pheochromocytoma [DISEASES], Natural Science Disciplines::Biological Science Disciplines::Biology::Computational Biology::Genomics [DISCIPLINES AND OCCUPATIONS], Multidisciplinary, Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment [PHENOMENA AND PROCESSES], fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral [FENÓMENOS Y PROCESOS], neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::tumores neuroendocrinos::paraganglioma [ENFERMEDADES], Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors::Paraganglioma [DISEASES], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology, Genòmica, neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::tumores neuroendocrinos::paraganglioma::feocromocitoma [ENFERMEDADES], All institutes and research themes of the Radboud University Medical Center, Metàstasi, disciplinas de las ciencias naturales::disciplinas de las ciencias biológicas::biología::biología computacional::genómica [DISCIPLINAS Y OCUPACIONES], Tumors neuroendocrins - Aspectes genètics
Abstract: Adrenal gland diseases; Cancer genomics; Prognostic markers Malalties de les glàndules suprarenals; Genòmica del càncer; Marcadors pronòstics Enfermedades de las glándulas suprarrenales; Genómica del cáncer; Marcadores pronósticos The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy. This work was supported by Project PI17/01796 and PI20/01169 to M.R. [Instituto de Salud Carlos III (ISCIII), Acción Estratégica en Salud, cofinanciado a través del Fondo Europeo de Desarrollo Regional (FEDER)], Paradifference Foundation [no grant number applicable to M.R.], Pheipas Association [no grant number applicable to M.R.], the Clinical Research Priority Program of the University of Zurich for the CRPP HYRENE to F.B., the Deutsche Forschungsgemeinschaft (DFG) within the CRC/Transregio 205/1 (Project No. 314061271-TRR205 to to F.B., M.F., N.B., and G.E.) and the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation (Project No. PID2019-111356RA-I00 to G.M.). B.C. was supported by the Rafael del Pino Foundation (Becas de Excelencia Rafael del Pino 2017). A.M.M.-M. was supported by CAM (S2017/BMD-3724; TIRONET2-CM). A.F.-S. and J.L. received the support of a fellowship from La Caixa Foundation (ID 100010434; LCF/BQ/DR21/11880009 and LCF/BQ/DR19/11740015, respectively). M.M., S.M., and M.S. were supported by the Spanish Ministry of Science, Innovation and Universities “Formación del Profesorado Universitario— FPU” fellowship with ID number FPU18/00064, FPU19/04940 and FPU16/05527. A.D.-T. is supported by the Centro de Investigacion Biomédica en Red de Enfermedades Raras (CIBERER). L.J.L.-G. was supported both by the Banco Santander Foundation and La Caixa Postdoctoral Junior Leader Fellowship (LCF/BQ/PI20/11760011). C.M.-C. was supported by a grant from the AECC Foundation (AIO15152858 MONT). We thank the Spanish National Tumor Bank Network (RD09/0076/00047) for the support in obtaining tumorsamples and all patients, physicians and tumor biobanks involved in the study.
Published: 2023
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24. A difficult to treat Leishmania infantum relapse after allogeneic stem cell transplantation

Author: Rob J.W. Arts, Geneviève I.C.G. Ector, Pau Bosch-Nicolau, Isreal Molina, Matthew B.B. McCall, Walter J.F.M. van der Velden, Arjan van Laarhoven, Quirijn de Mast, Suzanne van Dorp, Institut Català de la Salut, [Arts RJW] Department of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboudumc Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands. [Ector GICG, van der Velden WJFM] Department of Hematology, Radboud University Medical Center, Radboud Institute of Molecular Life Sciences (RIMLS), Nijmegen, the Netherlands. [Bosch-Nicolau P, Molina I] Servei de Malalties Infeccioses, Centre de Salut Internacional i Malalties Transmissibles Drassanes-Vall d'Hebron Hospital Universitari, Barcelona, Spain. PROSICS Barcelona, CSUR Imported Tropical Diseases, Center for Biomedical Research in Infectious Diseases Network (CIBERINFEC), Institute of Health Carlos III, Madrid, Spain. [McCall MBB] Department of Medical Microbiology, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboudumc Center for Infectious Diseases (RCI), Radboud University Medical Center, GA Nijmegen, the Netherlands, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Malalties parasitàries - Recaiguda, afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::recurrencia [ENFERMEDADES], Parasitic Diseases [DISEASES], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Case Report, enfermedades parasitarias [ENFERMEDADES], Leishmaniosi - Recaiguda, Eukaryota::Euglenozoa::Kinetoplastida::Trypanosomatina::Leishmania::Leishmania infantum [ORGANISMOS], Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence [DISEASES], Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], Infectious Diseases, All institutes and research themes of the Radboud University Medical Center, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Eukaryota::Euglenozoa::Kinetoplastida::Trypanosomatina::Leishmania::Leishmania infantum [ORGANISMS], Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5]
Abstract: Amphotericin B; Leishmania; Pancytopenia Amfotericina B; Leishmania; Pancitopènia Anfotericina B; Leishmania; Pancitopenia Here we describe a complicated case of a relapsed Leishmania infantum infection after an allogeneic stem cell transplantation (allo-SCT) for primary myelofibrosis. Three years earlier the patient had been diagnosed with a hemophagocytic lymphohistiocytosis secondary to a visceral Leishmania infantum infection, for which he was effectively treated with a cumulative dose of 40 mg/kg liposomal amphotericin B. During the first disease episode he was also diagnosed with primary myelofibrosis for which he received medical follow-up. One year later ruxolitinib was started due to progressive disease. No Leishmania relapse occurred. Nevertheless, the marrow fibrosis progressed, and an allo-SCT was performed. Two months after allo-SCT prolonged fever and a persistent pancytopenia occurred, which was due to a relapse of visceral Leishmaniasis. The infection was refractory to a prolonged treatment with liposomal amphotericin B with a cumulative dose up to 100 mg/kg. Salvage treatment with miltefosine led to reduction of fever within a few days and was followed by a slow recovery of pancytopenia over the following months. The Leishmania parasite load by PCR started to decline and after 3.5 months no Leishmania DNA could be detected anymore and follow-up until ten months afterwards did not show a relapse.
Published: 2023

25. A versatile and interoperable computational framework for the analysis and modeling of COVID-19 disease mechanisms

Author: Niarakis, Anna, Ostaszewski, Marek, Mazein, Alexander, Kuperstein, Inna, Kutmon, Martina, Gillespie, Marc, Funahashi, Akira, Acencio, Marcio, Hemedan, Ahmed, Aichem, Michael, Klein, Karsten, Czauderna, Tobias, Burtscher, Felicia, Yamada, Takahiro, Hiki, Yusuke, Hiroi, Noriko, Hu, Finterly, Pham, Nhung, Ehrhart, Friederike, Willighagen, Egon, Valdeolivas, Alberto, Dugourd, Aurelien, Messina, Francesco, Esteban-Medina, Marina, Pena-Chilet, Maria, Rian, Kinza, Soliman, Sylvain, Aghamiri, Sara, Puniya, Bhanwar, Naldi, Aurelien, Helikar, Tomas, Singh, Vidisha, Farinas Fernandez, Marco, Bermudez, Viviam, Tsirvouli, Eirini, Montagud, Arnau, Noel, Vincent, Ponce de Leon, Miguel, Maier, Dieter, Bauch, Angela, Gyori, Benjamin, Bachman, John, Luna, Agustin, Pinero, Janet, Furlong, Laura, Balaur, Irina, Rougny, Adrien, Jarosz, Yohan, Overall, Rupert, Phair, Robert, Perfetto, Livia, Matthews, Lisa, Rex, Devasahayam, Orlic-Milacic, Marija, Monraz Gomez, Luis, de Meulder, Bertrand, Ravel, Jean, Jassal, Bijay, Satagopam, Venkata, Wu, Guanming, Golebiewski, Martin, Gawron, Piotr, Calzone, Laurence, Beckmann, Jacques, Evelo, Chris, d'Eustachio, Peter, Schreiber, Falk, Saez-Rodriguez, Julio, Dopazo, Joaquin, Kuiper, Martin, Valencia, Alfonso, Wolkenhauer, Olaf, Kitano, Hiroaki, Barillot, Emmanuel, Auffray, Charles, Balling, Rudi, Schneider, Reinhard, Computational systems biology and optimization (Lifeware), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire de recherche européen pour la polyarthrite rhumatoïde (GenHotel), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay, University of Luxembourg [Luxembourg], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Maastricht Centre for Systems Biology [Maastricht] (MaCSBio), Maastricht University [Maastricht], Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Keio University, Luxembourg Centre For Systems Biomedicine (LCSB), University of Konstanz, Hochschule Mittweida - University of Applied Sciences, Kanagawa Institute of Technology, Heidelberg University Hospital [Heidelberg], National Institute for Infectious Diseases 'Lazzaro Spallanzani', Hospital Universitario Virgen del Rocío [Sevilla], Biomedicine Institute of Sevilla [Seville, Spain], University of Nebraska–Lincoln, University of Nebraska System, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Harvard Medical School [Boston] (HMS), Universitat Pompeu Fabra [Barcelona] (UPF), National Institute of Advanced Industrial Science and Technology (AIST), Humboldt University Of Berlin, Integrative Bioinformatics Inc [Mountain View], Department of Informatics and System Sciences (Sapienza University of Rome), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Yenepoya University, Janet Piñero, Laura I. Furlong: IMI2-JU grants, resources which are composed of financial contributions from the European Union’s Horizon 2020 Research and Innovation Programme and EFPIA [GA: 777365 eTRANSAFE], and the EU H2020 Programme [GA:964537 RISKHUNT3R], Project 001-P-001647—Valorisation of EGA for Industry and Society funded by the European Regional Development Fund (ERDF) and Generalitat de Catalunya, and Institute of Health Carlos III (project IMPaCT-Data, exp. IMP/00019), co-funded by the European Union, European Regional Development Fund (ERDF, 'A way to make Europe').
Subjects: SARS-CoV-2, disease maps, systems biology, dynamic models, systems medicine, large-scale community effort, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], mechanistic models
Abstract: The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Community-driven and highly interdisciplinary, the project is collaborative and supports community standards, open access, and the FAIR data principles. The coordination of community work allowed for an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework links key molecules highlighted from broad omics data analysis and computational modeling to dysregulated pathways in a cell-, tissue- or patient-specific manner. We also employ text mining and AI-assisted analysis to identify potential drugs and drug targets and use topological analysis to reveal interesting structural features of the map. The proposed framework is versatile and expandable, offering a significant upgrade in the arsenal used to understand virus-host interactions and other complex pathologies.
Published: 2022

26. Two distinct lipid transporters together regulate invasive filamentous growth in the human fungal pathogen Candida albicans

Author: Miguel A. Basante-Bedoya, Stéphanie Bogliolo, Rocio Garcia-Rodas, Oscar Zaragoza, Robert A. Arkowitz, Martine Bassilana, Université Côte d'Azur (Francia), French National Centre for Scientific Research (Francia), Institut National de la Santé et de la Recherche Médicale (Francia), Agence Nationale de la Recherche (Francia), Ministerio de Ciencia e Innovación (España), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institute of Health Carlos III, and BASSILANA, Martine
Subjects: Adenosine Triphosphatases, Cancer Research, Saccharomyces cerevisiae Proteins, [SDV]Life Sciences [q-bio], Membrane Transport Proteins, Saccharomyces cerevisiae, [SDV] Life Sciences [q-bio], Fungal Proteins, Candida albicans, Genetics, Humans, Molecular Biology, Fluconazole, Genetics (clinical), Ecology, Evolution, Behavior and Systematics
Abstract: Flippases transport lipids across the membrane bilayer to generate and maintain asymmetry. The human fungal pathogen Candida albicans has 5 flippases, including Drs2, which is critical for filamentous growth and phosphatidylserine (PS) distribution. Furthermore, a drs2 deletion mutant is hypersensitive to the antifungal drug fluconazole and copper ions. We show here that such a flippase mutant also has an altered distribution of phosphatidylinositol 4-phosphate [PI(4)P] and ergosterol. Analyses of additional lipid transporters, i.e. the flippases Dnf1-3, and all the oxysterol binding protein (Osh) family lipid transfer proteins, i.e. Osh2-4 and Osh7, indicate that they are not critical for filamentous growth. However, deletion of Osh4 alone, which exchanges PI(4)P for sterol, in a drs2 mutant can bypass the requirement for this flippase in invasive filamentous growth. In addition, deletion of the lipid phosphatase Sac1, which dephosphorylates PI(4)P, in a drs2 mutant results in a synthetic growth defect, suggesting that Drs2 and Sac1 function in parallel pathways. Together, our results indicate that a balance between the activities of two putative lipid transporters regulates invasive filamentous growth, via PI(4)P. In contrast, deletion of OSH4 in drs2 does not restore growth on fluconazole, nor on papuamide A, a toxin that binds PS in the outer leaflet of the plasma membrane, suggesting that Drs2 has additional role(s) in plasma membrane organization, independent of Osh4. As we show that C. albicans Drs2 localizes to different structures, including the Spitzenkörper, we investigated if a specific localization of Drs2 is critical for different functions, using a synthetic physical interaction approach to restrict/stabilize Drs2 at the Spitzenkörper. Our results suggest that the localization of Drs2 at the plasma membrane is critical for C. albicans growth on fluconazole and papuamide A, but not for invasive filamentous growth.
Published: 2022

27. Oleoylethanolamide enhances β-adrenergic-mediated thermogenesis and white-to-brown adipocyte phenotype in epididymal white adipose tissue in rat

Author: Fernando Rodríguez de Fonseca, Juan Suárez, Ana Crespillo, Sergio Arrabal, Antonia Serrano, Patricia Rivera, Joan Ballesteros, Francisco Javier Pavón, Carlos Dieguez, Elena Baixeras, Rubén Nogueiras, Manuel Cifuentes, [Suárez,J, Rivera, P, Arrabal,S, Crespillo,A, Serrano,A, Baixeras,E, Pavón, FJ, Rodríguez de Fonseca,F] Laboratorio de Medicina Regenerativa, Hospital Carlos Haya-IBIMA, Málaga, Spain. [Suárez,J, Nogueiras,R, Dieguez,C, Rodríguez de Fonseca,F] Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. [Cifuentes,M] Departamento de Biología Celular, Genética y Fisiología, Universidad de Málaga, Málaga, Spain. Centro de Investigaciones Biomédicas en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain. [Nogueiras,R] Department of Physiology, School of Medicine-CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain. [Ballesteros,J] ViviaBiotech S.L., Campanillas, Spain., This work was supported by the seventh Framework Programme of European Union (grant number HEALTH-F2-2008-223713, REPROBESITY, and 245009, NEUROFAST). The following grants from the Spanish Ministry of Science and Innovation also supported our work: SAF2010-20521, MINECO co-funded by the FEDER Program of EU (R.N.: RyC-2008-02219 and BFU2012-35255, and C.D.: BFU2011-29102), Xunta de Galicia (R.N.: EM 2012/039 and 2012-CP069), National Institute of Health ‘Carlos III’ Red de Trastornos Adictivos EU-ERDF (RD06/0001/0000 and RD06/0001/0014), and CIBER-OBN EU-ERDF (CB06/03/1008). Finally, we are supported by the EU-ERDF grants (CTS-433, CTS-8221 and PI45403) from the Andalusian Ministry of Economy, Innovation and Science. J.S. is recipient of a ‘Miguel Servet’ research contract from the National Institute of Health ‘Carlos III’ (CP12/03109).
Subjects: Male, FGF21, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxygenases::Mixed Function Oxygenases::Fatty Acid Desaturases::Stearoyl-CoA Desaturase [Medical Subject Headings], Adipocytes, White, Medicine (miscellaneous), Adipose tissue, lcsh:Medicine, Oleic Acids, Ácidos Oléicos, White adipose tissue, PPAR alfa, Phenomena and Processes::Physiological Phenomena::Physiological Processes::Body Temperature Regulation::Thermogenesis [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Anthropometry::Body Weights and Measures::Body Size::Body Weight [Medical Subject Headings], Rats, Sprague-Dawley, chemistry.chemical_compound, Oleoylethanolamide, Eating, 0302 clinical medicine, Immunology and Microbiology (miscellaneous), Adipocyte, Brown adipose tissue, Homeostasis, Phosphorylation, Regulación del apetito, 2. Zero hunger, PRDM16, Epididymis, Termogénesis, 0303 health sciences, Adipocitos Marrones, Temperature, β3-adrenergic receptor, Thermogenesis, Receptores Adrenérgicos beta, Lipids, 3. Good health, Mitochondria, medicine.anatomical_structure, Cholesterol, Phenotype, Adipocytes, Brown, Liver, Epidídimo, Anatomy::Cells::Connective Tissue Cells::Adipocytes [Medical Subject Headings], Body Composition, Research Article, lcsh:RB1-214, medicine.medical_specialty, Neuroscience (miscellaneous), Adrenergic beta-3 Receptor Agonists, Dioxoles, Biology, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Hunger::Appetite::Appetite Regulation [Medical Subject Headings], General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Ratas, Adipokines, Internal medicine, Receptors, Adrenergic, beta, medicine, lcsh:Pathology, Animals, PPAR alpha, Obesity, 030304 developmental biology, Body Weight, lcsh:R, Peso corporal, Rats, Oxygen, Endocrinology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings], chemistry, β-oxidation, Peroxisome proliferator-activated receptor alpha, 030217 neurology & neurosurgery, Endocannabinoids
Abstract: Journal Article; Research Support, Non-U.S. Gov't; β-adrenergic receptor activation promotes brown adipose tissue (BAT) β-oxidation and thermogenesis by burning fatty acids during uncoupling respiration. Oleoylethanolamide (OEA) can inhibit feeding and stimulate lipolysis by activating peroxisome proliferator-activating receptor-α (PPARα) in white adipose tissue (WAT). Here we explore whether PPARα activation potentiates the effect of β3-adrenergic stimulation on energy balance mediated by the respective agonists OEA and CL316243. The effect of this pharmacological association on feeding, thermogenesis, β-oxidation, and lipid and cholesterol metabolism in epididymal (e)WAT was monitored. CL316243 (1 mg/kg) and OEA (5 mg/kg) co-administration over 6 days enhanced the reduction of both food intake and body weight gain, increased the energy expenditure and reduced the respiratory quotient (VCO2/VO2). This negative energy balance agreed with decreased fat mass and increased BAT weight and temperature, as well as with lowered plasma levels of triglycerides, cholesterol, nonessential fatty acids (NEFAs), and the adipokines leptin and TNF-α. Regarding eWAT, CL316243 and OEA treatment elevated levels of the thermogenic factors PPARα and UCP1, reduced p38-MAPK phosphorylation, and promoted brown-like features in the white adipocytes: the mitochondrial (Cox4i1, Cox4i2) and BAT (Fgf21, Prdm16) genes were overexpressed in eWAT. The enhancement of the fatty-acid β-oxidation factors Cpt1b and Acox1 in eWAT was accompanied by an upregulation of de novo lipogenesis and reduced expression of the unsaturated-fatty-acid-synthesis enzyme gene, Scd1. We propose that the combination of β-adrenergic and PPARα receptor agonists promotes therapeutic adipocyte remodelling in eWAT, and therefore has a potential clinical utility in the treatment of obesity. Yes
Published: 2014

28. Early estimates of the effectiveness of the 2011/12 influenza vaccine in the population targeted for vaccination in Spain, 25 December 2011 to 19 February 2012

Author: Jimenez-Jorge S, de Mateo S, Pozo F, Casas I, Garcia Cenoz M, Jesus Castilla, Gallardo V, Perez E, Vega T, Rodriguez C, Quinones C, Martinez E, Gimenez J, Vanrell J, Castrillejo D, Serrano M, Ramos J, Larrauri A, [Jiménez-Jorge,S, Mateo,S de, Larrauri,A] National Centre of Epidemiology, Institute of Health Carlos III, Madrid, Spain. [Jiménez-Jorge,S, García Cenoz,M, Castilla,J, Larrauri,A] Ciber Epidemiología y Salud Pública (CIBERESP), Ministry of Economy and Competitiveness, Institute of Health Carlos III, Madrid, Spain. [Pozo,F, Casas,I] National Centre for Microbiology, World Health Organization National Influenza Centre, Institute of Health Carlos III, Madrid, Spain. [García Cenoz,M, Castilla,J] Instituto de Salud Pública de Navarra, Navarra, Spain. [Gallardo,V, Pérez,E] Servicio de Epidemiología y Salud Laboral. Secretaría General de Salud Pública y Participación. Consejería de Salud de Andalucía, Seville, Spain. [Vega,T, Rodriguez,C] Dirección General de Salud Pública, Consejería de Sanidad de Castilla y León, Valladolid, Spain. [Quinones,C, Martínez,E] Servicio de Epidemiología, Subdirección de Salud Pública de La Rioja, La Rioja, Spain. [Giménez,J, Vanrell,JM] Servicio de Epidemiología, Dirección General de Salut Pública, Mallorca, Baleares, Spain. [Castrillejo,D] Servicio de Epidemiología, Dirección General de Sanidad y Consumo, Consejería de Bienestar Social y Sanidad, Ciudad Autónoma de Melilla, Spain. [Serrano,MC, and Ramos,JM] Dirección General de Salud Pública, Servicio Extremeño de Salud, Badajoz, Junta de Extremadura, Spain
Subjects: Adult, Male, Named Groups::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings], Adolescent, Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Named Groups::Persons::Age Groups::Infant::Infant, Newborn [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Young Adult, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Statistical::Logistic Models [Medical Subject Headings], Efectividad, Influenza, Human, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Vacunas contra la Influenza, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Child, Named Groups::Persons::Age Groups::Child [Medical Subject Headings], Aged, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Aged, 80 and over, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Named Groups::Persons::Age Groups::Child::Child, Preschool [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunotherapy, Active::Vaccination [Medical Subject Headings], Influenza A Virus, H3N2 Subtype, Vaccination, Infant, Newborn, virus diseases, Infant, Middle Aged, Logistic Models, Check Tags::Female [Medical Subject Headings], Chemicals and Drugs::Complex Mixtures::Biological Agents::Vaccines::Viral Vaccines::Influenza Vaccines [Medical Subject Headings], Influenza Vaccines, Spain, Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings], Case-Control Studies, Child, Preschool, Female, Named Groups::Persons::Age Groups::Infant [Medical Subject Headings], Organisms::Viruses::Vertebrate Viruses::RNA Viruses::Orthomyxoviridae::Influenzavirus A::Influenza A virus::Influenza A Virus, H3N2 Subtype [Medical Subject Headings], Diseases::Virus Diseases::RNA Virus Infections::Orthomyxoviridae Infections::Influenza, Human [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Sentinel Surveillance [Medical Subject Headings], Sentinel Surveillance
Abstract: Journal Article; Research Support, Non-U.S. Gov't; We present early estimates of influenza vaccine effectiveness (VE) in the population targeted for vaccination, during 25 December 2011 to 19 February 2012. The adjusted VE was 55% (95% CI: 3 to 79) against any type of influenza virus and 54% (95% CI: 1 to 79) against influenza A(H3N2) virus. This suggests a moderate protective effect of the vaccine in the targeted population in a late influenza epidemic with limited match between vaccine and circulating strains. Yes
Published: 2012

29. Ulcerative colitis impairs the acylethanolamide-based anti-inflammatory system reversal by 5-aminosalicylic acid and glucocorticoids

Author: Yanina Romero-Zerbo, Francisco Javier Bermúdez-Silva, Fernando Rodríguez de Fonseca, Juan Suárez, Montserrat Andreu, Lucía Márquez, Patricia Rivera, Mar Iglesias, [Suárez,J, Romero-Zerbo,Y, Rivera,P, Bermúdez-Silva,FJ, Rodríguez de Fonseca,F] Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Mediterranean Institute for the Advance of Biotechnology and Health Research Fundación, Málaga, Spain. [Márquez,L, Andreu,M] Department of Gastroenterology, Parc de Salut Mar, Universidad Autónoma, Barcelona, Spain. [Suárez,J, Rodríguez de Fonseca,F] El Centro de Investigación Biomédica en Red de Fisiopatología de Obesidad y Nutrición, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain. [Iglesias,M] Department of Pathology, Parc de Salut Mar, Universidad Autónoma, Barcelona, Spain., This study was supported by grants to FRdF from the European Union’s 7th Framework Programme (Health-F2-2008-223713, REPROBESITY), the following grants from the Spanish Ministry of Science and Innovation (SAF2010-20521), National Institute of Health ‘‘Carlos III’’ (PI07/1226, PI07/0880 and PI 07/0953), Red de Trastornos Adictivos-UE-ERDF (RD06/0001/0000) and El Centro de Investigación Biomédica en Red de Fisiopatología de Obesidad y Nutrición, grants from the Consejería de Economía, Innovación y Ciencia de la Junta de Andalucía, UE/ERDF (CTS-433 and PI45403), and and a grant from the Consejería de Salud de la Junta de Andalucía (PI0232/2008), Spain. FJBS holds a Miguel Servet research contracts CD07/00283, and JS holds a Sara Borrell postdoctoral contract CD08/00203, both from the National Institute of Health ‘‘Carlos III’’, Madrid, Spain.
Subjects: Male, Amidohidrolasas, Anti-Inflammatory Agents, Anatomy::Digestive System::Gastrointestinal Tract::Lower Gastrointestinal Tract::Intestine, Large::Colon [Medical Subject Headings], Gene Expression, Nitric Oxide Synthase Type II, Peroxisome proliferator-activated receptor, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], PPAR alfa, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, 0302 clinical medicine, Intestinal mucosa, Molecular Cell Biology, Intestinal Mucosa, Mesalamine, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Peroxisome Proliferator-Activated Receptors::PPAR alpha [Medical Subject Headings], Receptor, Colitis Ulcerosa, Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Benzoates::Hydroxybenzoates::Salicylates::Aminosalicylic Acids::Aminosalicylic Acid::Mesalamine [Medical Subject Headings], chemistry.chemical_classification, 0303 health sciences, Multidisciplinary, Middle Aged, 3. Good health, medicine.anatomical_structure, Ethanolamines, Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings], 030220 oncology & carcinogenesis, Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Colitis, Ulcerative [Medical Subject Headings], Medicine, Female, medicine.symptom, Research Article, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-NH2 Group Donors::Amino Acid Oxidoreductases::Nitric Oxide Synthase::Nitric Oxide Synthase Type II [Medical Subject Headings], Adult, Chemicals and Drugs::Organic Chemicals::Alcohols::Amino Alcohols::Ethanolamines [Medical Subject Headings], medicine.medical_specialty, Aminosalicylic acid, Adolescent, Expresión Génica, Named Groups::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings], Colon, Science, Antiinflamatorios, Check Tags::Male [Medical Subject Headings], Inflammation, Gastroenterology and Hepatology, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents [Medical Subject Headings], Biology, Amidohydrolases, Molecular Genetics, Young Adult, 03 medical and health sciences, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Glucocorticoids [Medical Subject Headings], Immune system, Internal medicine, Genetics, Phospholipase D, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Ulcerative Colitis, Humans, Gene Regulation, PPAR alpha, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Peroxisome Proliferator-Activated Receptors::PPAR gamma [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Colitis, Glucocorticoides, Glucocorticoids, Aged, 030304 developmental biology, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Diester Hydrolases::Phospholipases::Phospholipase D [Medical Subject Headings], Lamina propria, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases [Medical Subject Headings], Inflammatory Bowel Disease, Immunity, medicine.disease, PPAR gamma, Endocrinology, Check Tags::Female [Medical Subject Headings], chemistry, Clinical Immunology, Colitis, Ulcerative, Anatomy::Digestive System::Gastrointestinal Tract::Intestines::Intestinal Mucosa [Medical Subject Headings]
Abstract: Journal Article; Research Support, Non-U.S. Gov't; Studies in animal models and humans suggest anti-inflammatory roles on the N acylethanolamide (NAE)-peroxisome proliferators activated receptor alpha (PPARα) system in inflammatory bowel diseases. However, the presence and function of NAE-PPARα signaling system in the ulcerative colitis (UC) of humans remain unknown as well as its response to active anti-inflammatory therapies such as 5-aminosalicylic acid (5-ASA) and glucocorticoids. Expression of PPARα receptor and PPARα ligands-biosynthetic (NAPE-PLD) and -degrading (FAAH and NAAA) enzymes were analyzed in untreated active and 5-ASA/glucocorticoids/immunomodulators-treated quiescent UC patients compared to healthy human colonic tissue by RT-PCR and immunohistochemical analyses. PPARα, NAAA, NAPE-PLD and FAAH showed differential distributions in the colonic epithelium, lamina propria, smooth muscle and enteric plexus. Gene expression analysis indicated a decrease of PPARα, PPARγ and NAAA, and an increase of FAAH and iNOS in the active colitis mucosa. Immunohistochemical expression in active colitis epithelium confirmed a PPARα decrease, but showed a sharp NAAA increase and a NAPE-PLD decrease, which were partially restored to control levels after treatment. We also characterized the immune cells of the UC mucosa infiltrate. We detected a decreased number of NAAA-positive and an increased number of FAAH-positive immune cells in active UC, which were partially restored to control levels after treatment. NAE-PPARα signaling system is impaired during active UC and 5-ASA/glucocorticoids treatment restored its normal expression. Since 5-ASA actions may work through PPARα and glucocorticoids through NAE-producing/degrading enzymes, the use of PPARα agonists or FAAH/NAAA blockers that increases endogenous PPARα ligands may yield similar therapeutics advantages. Yes
Published: 2012

30. Common variants of the liver fatty acid binding protein gene influence the risk of type 2 diabetes and insulin resistance in Spanish population

Author: Fernando Martinez, Sonsoles Morcillo, Juan Carlos Martín-Escudero, Gemma Rojo, María Teresa Martínez-Larrad, Federico Soriguer, Josep Redon, Manuel Serrano-Ríos, Felipe J. Chaves, Maria L. Mansego, Carina Zabena, [Mansego,ML, Chaves,FJ] Genotyping and Genetic Diagnosis Unit, Fundación de Investigación del Hospital Clínico de Valencia-INCLIVA, Valencia, Spain [Martínez,F, Redon,J] Fundación de Investigación del Hospital Clínico de Valencia- INCLIVA, Hypertension Clinic, Hospital Clínico Universitario, University of Valencia, Valencia, Spain. [Martínez-Larrad,MT, Zabena,C, Serrano-Ríos,M] Hospital Clínico San Carlos, Department of Internal Medicine II, Madrid, Spain. [Rojo,G, Morcillo,S, Soriguer,F] Endocrinology and Nutrition Department, Carlos Haya University Hospital, Málaga, Spain. [Martín-Escudero,JC] Internal Medicine department. Hospital Rio Hortega, University of Valladolid, Valladolid, Spain. [Mansego,ML, Chaves,FJ] Centro de Investigación Biomédica en Red (CIBER) de Diabetes y Enfermedades Metabólicas Asociadas ‘‘CIBERDEM’’, Institute of Health Carlos III, Ministry of Health, Madrid, Spain. [Martínez,F, Redon,J] Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología, Obesidad y Nutrición [CIBEROB (CIBER 03/06)], Institute of Health Carlos III, Ministry of Health, Madrid, Spain. [Martínez-Larrad,MT, Serrano-Ríos,M, Rojo,G, Soriguer,F] Centro de Investigación Biomédica en Red (CIBER) de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institute of Health Carlos III, Ministry of Health, Madrid, Spain., Funding: This study was supported by grants SAF2005-02883 from the Interministry Commission of Science and Technology (CICYT), Biomedical Research Centers (CIBER) of Physiopathology, Obesity and Nutrition (CIBEROB), CIBER of Diabetes and Metabolic Diseases (CIBERDEM), Carlos III Health Institute Madrid, the Spanish Health Ministry, GRUPOS 03/101 and 2005/027 from the Valencian Government and European Network of Excellence Ingenious Hypercare (EPSS-037093) from the European Commission, and and Biobank grant from the National Health Institute Carlos III FEDER RD09/0076/00132 (Madrid, Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Subjects: Male, Anatomy and Physiology, España, Diabetes Mellitus Tipo 2, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Type 2 diabetes, Resistencia a la Insulina, Variación Genética, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Endocrinology, Polymorphism (computer science), Risk Factors, Análisis de Regresión, Factores de Riesgo, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Genetics, education.field_of_study, Multidisciplinary, Adulto, Middle Aged, Cardiovascular Diseases, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2 [Medical Subject Headings], Regression Analysis, Medicine, Female, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation [Medical Subject Headings], Fatty Acid Binding Protein 3, Research Article, Adult, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], Genotype, Science, Population, Check Tags::Male [Medical Subject Headings], Single-nucleotide polymorphism, Endocrine System, Biology, Fatty Acid-Binding Proteins, Polymorphism, Single Nucleotide, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism::Insulin Resistance [Medical Subject Headings], Insulin resistance, Genetic variation, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Humans, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education, Diseases::Cardiovascular Diseases [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings], Alleles, Aged, Diabetic Endocrinology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Regression Analysis [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Polymorphism, Genetic, Endocrine Physiology, Haplotype, Genetic Variation, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings], medicine.disease, Obesity, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Fatty Acid-Binding Proteins [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Diabetes Mellitus, Type 2, Haplotypes, Spain, Metabolic Disorders, Mutation, Insulin Resistance, Population Genetics
Abstract: Journal Article; Research Support, Non-U.S. Gov't; SUMMARY The main objective was to evaluate the association between SNPs and haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction with fat intake, in one general Spanish population. The association was replicated in a second population in which HOMA index was also evaluated. METHODS 1217 unrelated individuals were selected from a population-based study [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The replication population included 805 subjects from Segovia, a neighboring region of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes). DM2 mellitus was defined in a similar way in both studies. Fifteen SNPs previously associated with metabolic traits or with potential influence in the gene expression within the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were used as covariates in the logistic regression model. RESULTS One polymorphism (rs2197076) and two haplotypes of the FABP-1 showed a strong association with the risk of DM2 in the original population. This association was further confirmed in the second population as well as in the pooled sample. None of the other analyzed variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal interaction between rs2197076 and fat intake. A significant association between the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the replication population. CONCLUSIONS The study supports the role of common variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians. Yes
Published: 2011

31. The Global Meningococcal Initiative: Recommendations for reducing the global burden of meningococcal disease

Author: Marco Aurélio Palazzi Sáfadi, Johan Holst, Muhamed-Kheir Taha, Anne von Gottberg, Lee H. Harrison, Annelies Wilder-Smith, Stanley A. Plotkin, Ray Borrow, Julio A. Vázquez, Stephen I. Pelton, F. Marc LaForce, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), National University of Singapore (NUS), Norwegian Institute of Public Health [Oslo] (NIPH), FCM Santa Casa de São Paulo School of Medical Sciences [São Paulo], Meningococcal Reference Laboratory [Madrid], Institute of Health Carlos III, PATH Europe [Ferney Voltaire], National Institute for Communicable Diseases [Johannesburg] (NICD), Manchester Royal Infirmary, University of Manchester [Manchester], University of Pennsylvania, Members of the GMI Chairman: Stanley Plotkin, MD (University of Pennsylvania, Doylestown, PA, USA). Steering Committee: Carl Frasch, PhD (Frasch Biologics Consulting, Martinsburg, WV, USA), Sunil Gupta, MBBS, MD (National Institute of Communicable Diseases, Delhi, India), Lee H. Harrison, MD (University of Pittsburgh, Pittsburgh, PA, USA), Ziad Memish, MD (Ministry of Health, Riyadh, Saudi Arabia), Andrew J. Pollard, FRCPCH, PhD (University of Oxford, Oxford, UK), Muhamed-Kheir Taha, MD, PhD (Institut Pasteur, Paris, France), Julio Vazquez, PhD (Institute of Health Carlos III, Madrid, Spain), Anne von Gottberg, MBBCh (National Institute for Communicable Diseases, Johannesburg, South Africa). Summit Members: Richard Adegbola, MSc, PhD (Bill and Melinda Gates Foundation, Seattle, WA, USA), Colin Block, MBBCh, PhD (Hadassah-Hebrew University Medical Centre, Jerusalem, Israel), Ray Borrow, PhD, FRCPath (Health Protection Agency, Manchester, UK), Tom Clark, MD, MPH (Centers for Disease Control and Prevention, Atlanta, GA, USA), Benoit Dervaux, PhD (Faculty of Medicine, University 'Droit et Santé', Lille, France), Johan Holst, PhD, MSc (Norwegian Institute of Public Health, Oslo, Norway), Sheldon Kaplan, MD (Baylor College of Medicine, Houston, TX, USA), Marc LaForce, MD (Meningitis Vaccine Project, Ferney, France), Xiaofeng Liang, MD (National Immunization Program, China CDC, Beijing, China), Diana Martin, PhD (Institute of Environmental Science and Research, Poriru, New Zealand), Stephen Pelton, MD (Boston University Schools of Medicine and Public Health, Boston, MA, USA), Marco Safadi, MD (FCM Da Santa Casa de São Paulo, São Paulo, Brazil), Samir Saha, PhD (Bangladesh Institute of Child Health, Dhaka, Bangladesh), Franklin Sotolongo, MD (Finlay Institute, Havana, Cuba), Irina Stanislavovna Koroleva, MD, PhD (Central Research Institute of Epidemiology, Moscow, Russia), Annelies Wilder-Smith, MD, PhD, MIH (National University of Singapore, Singapore)., and University of Pennsylvania [Philadelphia]
Subjects: medicine.medical_specialty, MESH: Vaccines, Conjugate, Meningococcal Vaccines, Meningococcal vaccine, Meningococcal disease, MESH: Immunization Programs, MESH: Meningococcal Infections, MESH: Meningococcal Vaccines, MESH: Population Surveillance, Epidemiology, medicine, Humans, Disease burden, Vaccines, Conjugate, MESH: Humans, General Veterinary, General Immunology and Microbiology, business.industry, Immunization Programs, Public health, Public Health, Environmental and Occupational Health, medicine.disease, Vaccination, Meningococcal Infections, Infectious Diseases, Immunization, Vaccination policy, Family medicine, Population Surveillance, Immunology, Molecular Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Public Health, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business, MESH: Public Health
Abstract: International audience; The Global Meningococcal Initiative (GMI) is composed of an international group of scientists, clinicians and public health officials with expertise in meningococcal immunology, epidemiology and prevention. The primary goal of the GMI is the promotion of the global prevention of invasive meningococcal disease through education and research. The GMI members reviewed global meningococcal disease epidemiology, immunization strategies, and research needs. Over the past decade, substantial advances in meningococcal vaccine development have occurred and much has been learned about prevention from countries that have incorporated meningococcal vaccines into their immunization programs. The burden of meningococcal disease is unknown for many parts of the world because of inadequate surveillance, which severely hampers evidence-based immunization policy. As the field of meningococcal vaccine development advances, global surveillance for meningococcal disease needs to be strengthened in many regions of the world. For countries with meningococcal vaccination policies, research on vaccine effectiveness and impact, including indirect effects, is crucial for informing policy decisions. Each country needs to tailor meningococcal vaccination policy according to individual country needs and knowledge of disease burden. Innovative approaches are needed to introduce and sustain meningococcal vaccination programs in resource-poor settings with a high incidence of meningococcal disease.
Published: 2011
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32. Granada Virus: a Natural Phlebovirus Reassortant of the Sandfly Fever Naples Serocomplex with Low Seroprevalence in Humans

Author: María Paz Sánchez-Seco, Mercedes Pérez-Ruiz, Ximena Collao, Ian W. Lipkin, Ricardo Molina, Antonio Tenorio, Stephen K. Hutchison, Fernando de Ory, Navarro Jm, Sara Sanbonmatsu, Gustavo Palacios, [Collao,X, Tenorio,A, Sánchez-Seco,MP] Laboratory of Arbovirus and Imported Viral Diseases, National Center of Microbiology, Institute of Health CarlosIII, Madrid, Spain. [Palacios,G, Lipkin,WI] Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York. [de Ory,F] Serology Section, National Center of Microbiology, Institute of Health Carlos III, Madrid, Spain.[Sanbonmatsu,S, Pérez-Ruiz,M, Navarro,JM] Service of Microbiology, Universitary Hospital Virgen de las Nieves, Granada, Spain. [Molina,R] Service of Parasitology, National Center of Microbiology, Institute of Health Carlos III, Madrid, Spain. [Hutchison,S] 454 Life Sciences, Branford, CT. [Collao,X] Virology, Medicine School, Universidad de Valparaíso, Valparaiso, Chile., and The authors thank all members of the Red de Enfermedades Víricas Transmitidas por Artrópodos y Roedores, a multidisciplinary group founded by the Fondo de Investigaciones Sanitarias (FIS), Spanish Ministry of Health (G03/059). This work was founded also by Instituto de Salud 'Carlos III' and is part of the work carriedout within the Red de Investigación Cooperativa en Enfermedades Tropicales (RICET) network (FIS C03/04 and RD06/0021). Workthe Center for Infection and Immunity in the Mailman School of Public Health of Columbia University is supported by National Institutes of Health Grants AI051292 and AI57158 (Northeast Biodefense Center– Lipkin), the US Department of Defense, and Google.org. Finally, wealso thank Alla Tashmukhamedova for her help in sequencing
Subjects: Male, Organisms::Viruses::Reassortant Viruses [Medical Subject Headings], viruses, Antibodies, Viral, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Virus de Nápoles de la Fiebre de la Mosca de los Arenales, Seroepidemiologic Studies, Phlebotomus Fever, Chlorocebus aethiops, Organisms::Eukaryota::Animals [Medical Subject Headings], Diseases::Virus Diseases::Arbovirus Infections::Phlebotomus Fever [Medical Subject Headings], Masculino, Phylogeny, Estudios Seroepidemiológicos, Insectos Vectores, biology, Anticuerpos Antivirales, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome, Viral [Medical Subject Headings], Femenino, Anatomy::Cells::Cells, Cultured::Cell Line::Vero Cells [Medical Subject Headings], Articles, Organisms::Viruses::Vertebrate Viruses::RNA Viruses::Bunyaviridae::Phlebovirus::Sandfly fever Naples virus [Medical Subject Headings], Humanos, Organisms::Eukaryota::Animals::Invertebrates::Arthropods::Insects::Diptera::Psychodidae [Medical Subject Headings], Infectious Diseases, Células Vero, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Cercopithecidae::Cercopithecinae::Cercopithecus::Cercopithecus aethiops [Medical Subject Headings], Female, Bunyaviridae, Reassortant Viruses, Health Care::Environment and Public Health::Public Health::Disease Transmission, Infectious::Disease Vectors::Arthropod Vectors::Insect Vectors [Medical Subject Headings], Molecular Sequence Data, Secuencia Molecular, Genome, Viral, Virus, Cercopithecus aethiops, Phenomena and Processes::Biological Phenomena::Biological Processes::Biological Evolution::Phylogeny [Medical Subject Headings], Virology, Genoma Viral, Seroprevalence, Animals, Humans, Virus Reordenados, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Serum Globulins::Immunoglobulins::Antibodies::Antibodies, Viral [Medical Subject Headings], Vero Cells, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Seroepidemiologic Studies [Medical Subject Headings], Febre por Flebótomos, Base Sequence, Sandfly fever Naples virus, biology.organism_classification, Sandfly, Insect Vectors, Filogenia, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Base Sequence [Medical Subject Headings], Information Science::Information Science::Information Services::Documentation::Molecular Sequence Data [Medical Subject Headings], Phlebovirus, Animales, Parasitology, Psychodidae, Secuencia de Bases
Abstract: A new member of the phlebovirus genus, tentatively named Granada virus, was detected in sandflies collected in Spain. By showing the presence of specific neutralizing antibodies in human serum collected in Granada, we show that Granada virus infects humans. The analysis of the complete genome of Granada virus revealed that this agent is likely to be a natural reassortant of the recently described Massilia virus (donor of the long and short segments) with ayet unidentified phlebovirus (donor of the medium segment) Yes
Published: 2010

33. Targeting cholesteryl ester accumulation in the heart improves cardiac insulin response

Author: Actis Dato, Virginia, Benitez-Amaro, Aleyda, García Rodríguez, Jesús Eduardo, Claudi, Lene, La Chica, María Teresa, Iborra, A., Escolà-Gil, Joan Carles, Guerra, José M., Samouillan, V., Enrich, C., Chiabrando, G., Llorente-Cortés, Vicenta, Universitat Autònoma de Barcelona, Institute of Health Carlos III - CIBERCV (SPAIN), Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut d′Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS (SPAIN), Institute of Biomedical Research of Barcelona of the Spanish National Research Council - IIBB-CSIC (SPAIN), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Universidad Nacional de Cordoba - UNC (ARGENTINA), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Universitat Autònoma de Barcelona - UAB (SPAIN), Universitat de Barcelona - UB (SPAIN), Consejo Nacional de Investigaciones Científicas y Técnicas - CONICET (ARGENTINA), Hospital de la Santa Creu i Sant Pau (SPAIN), Centre Interuniversitaire de Recherche et d'Ingénierie des Matériaux - CIRIMAT (Toulouse, France), Fundació La Marató de TV3, Instituto de Salud Carlos III, Fundación BBVA, and Fondo para la Investigación Científica y Tecnológica (Argentina)
Subjects: Pharmacology, Matériaux, LRP1, nutritional and metabolic diseases, Heart, LipoproteinInsulin, General Medicine, Diet, High-Fat, Lipid droplets, Cholesteryl esters, Glucose, High-fat diet, Physique Médicale, Animals, Insulin, Cholesterol Esters, Rabbits, Lipoprotein, Low Density Lipoprotein Receptor-Related Protein-1, hormones, hormone substitutes, and hormone antagonists
Abstract: Background: Antibodies against the P3 sequence (Gly1127-Cys1140) of LRP1 (anti-P3 Abs) specifically block cholesteryl ester (CE) accumulation in vascular cells. LRP1 is a key regulator of insulin receptor (InsR) trafficking in different cell types. The link between CE accumulation and the insulin response are largely unknown. Here, the effects of P3 peptide immunization on the alterations induced by a high-fat diet (HFD) in cardiac insulin response were evaluated. Methods: Irrelevant (IrP)- or P3 peptide-immunized rabbits were randomized into groups fed either HFD or normal chow. Cardiac lipid content was characterized by thin-layer chromatography, confocal microscopy, and electron microscopy. LRP1, InsR and glucose transporter type 4 (GLUT4) levels were determined in membranes and total lysates from rabbit heart. The interaction between InsR and LRP1 was analyzed by immunoprecipitation and confocal microscopy. Insulin signaling activity and glucose uptake were evaluated in HL-1 cells exposed to rabbit serum from the different groups. Findings: HFD reduces cardiac InsR and GLUT4 membrane levels and the interactions between LRP1/InsR. Targeting the P3 sequence on LRP1 through anti-P3 Abs specifically reduces CE accumulation in the heart independently of changes in the circulating lipid profile. This restores InsR and GLUT4 levels in cardiac membranes as well as the LRP1/InsR interactions of HFD-fed rabbits. In addition, anti-P3 Abs restores the insulin signaling cascade and glucose uptake in HL-1 cells exposed to hypercholesterolemic rabbit serum. Interpretation: LRP1-immunotargeting can block CE accumulation within the heart with specificity, selectivity, and efficacy, thereby improving the cardiac insulin response; this has important therapeutic implications for a wide range of cardiac diseases., Fundació MARATÓ TV3: grant 101521-10, Instiuto de Salud Carlos III (ISCIII) and ERDF PI18/01584, Fundación BBVA Ayudas a Equipos de Investigación 2019. SECyT-UNC grants PROYECTOS CONSOLIDAR 2018-2021; FONCyT, Préstamo BID PICT grant 2015-0807 and grant 2017-4497.
Published: 2022

34. Comprehensive molecular analysis of immortalization hallmarks in thyroid cancer reveals new prognostic markers

Author: Cristina Montero‐Conde, Luis Javier Leandro‐García, Ángel M. Martínez‐Montes, Paula Martínez, Francisco J. Moya, Rocío Letón, Eduardo Gil, Natalia Martínez‐Puente, Sonsoles Guadalix, Maria Currás‐Freixes, Laura García‐Tobar, Carles Zafon, Mireia Jordà, Garcilaso Riesco‐Eizaguirre, Patricia González‐García, María Monteagudo, Rafael Torres‐Pérez, Veronika Mancikova, Sergio Ruiz‐Llorente, Manuel Pérez‐Martínez, Guillermo Pita, Juan Carlos Galofré, Anna Gonzalez‐Neira, Alberto Cascón, Cristina Rodríguez‐Antona, Diego Megías, María A. Blasco, Eduardo Caleiras, Sandra Rodríguez‐Perales, Mercedes Robledo, Institut Català de la Salut, [Montero-Conde C] Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Madrid, Spain. [Leandro-García LJ, Martínez-Montes ÁM, Letón R] Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. [Martínez P] Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. [Moya FJ] Molecular Cytogenetics Unit, Human Cancer Genetics Program, Spanish National Cancer Research Center (CNIO), Madrid, Spain. [Zafon C] Servei d’Endocrinologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 5p-end FISH, Telòmer, Otros calificadores::Otros calificadores::/genética [Otros calificadores], Genetic Phenomena::Genetic Structures::Chromosome Structures::Telomere [PHENOMENA AND PROCESSES], Medicine (miscellaneous), TERT promoter methylation, Telomere, Prognosis, Tiroide - Càncer - Prognosi, TERC, telomere shortening, Tiroide - Càncer - Aspectes genètics, Other subheadings::Other subheadings::/genetics [Other subheadings], fenómenos genéticos::estructuras genéticas::estructuras cromosómicas::telómero [FENÓMENOS Y PROCESOS], Molecular Medicine, Humans, subtelomeric gene expression, Thyroid Neoplasms, TERT promoter mutation, Diagnosis::Prognosis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Telomerase, Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Thyroid Neoplasms [DISEASES], diagnóstico::pronóstico [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], In Situ Hybridization, Fluorescence, neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias de la tiroides [ENFERMEDADES]
Abstract: TERT promoter mutation; Subtelomeric gene expression; Telomere shortening Mutació del promotor TERT; Expressió gènica subtelomèrica; Escurçament dels telòmers Mutación del promotor TERT; Expresión génica subtelomérica; Acortamiento de los telómeros Background Comprehensive molecular studies on tumours are needed to delineate immortalization process steps and identify sensitive prognostic biomarkers in thyroid cancer. Methods and Results In this study, we extensively characterize telomere-related alterations in a series of 106 thyroid tumours with heterogeneous clinical outcomes. Using a custom-designed RNA-seq panel, we identified five telomerase holoenzyme-complex genes upregulated in clinically aggressive tumours compared to tumours from long-term disease-free patients, being TERT and TERC denoted as independent prognostic markers by multivariate regression model analysis. Characterization of alterations related to TERT re-expression revealed that promoter mutations, methylation and/or copy gains exclusively co-occurred in clinically aggressive tumours. Quantitative-FISH (fluorescence in situ hybridization) analysis of telomere lengths showed a significant shortening in these carcinomas, which matched with a high proliferative rate measured by Ki-67 immunohistochemistry. RNA-seq data analysis indicated that short-telomere tumours exhibit an increased transcriptional activity in the 5-Mb-subtelomeric regions, site of several telomerase-complex genes. Gene upregulation enrichment was significant for specific chromosome-ends such as the 5p, where TERT is located. Co-FISH analysis of 5p-end and TERT loci showed a more relaxed chromatin configuration in short telomere-length tumours compared to normal telomere-length tumours. Conclusions Overall, our findings support that telomere shortening leads to a 5p subtelomeric region reorganization, facilitating the transcription and accumulation of alterations at TERT-locus. This work was supported by Projects PI17/01796 and PI20/01169 [Instituto de Salud Carlos III (ISCIII), Acción Estratégica en Salud, cofinanciado a través del Fondo Europeo de Desarrollo Regional (FEDER)] and Comunidad de Madrid (S2017/BMD-3724; TIRONET2-CM) to MR. CM-C was partially supported by a grant from the Fundación Científica Asociación Española Contra el Cáncer (AIO15152858 MONT). LJL-G was supported both by the Banco Santander Foundation – CNIO Fellowship and by ‘la Caixa’ Foundation (ID 100010434), under agreement LCF/BQ/PI20/11760011. AMM-M was supported by CAM (S2017/BMD-3724; TIRONET2-CM). MM was supported by the Ministerio de Ciencia, Innovación y Universidades (Spain; ‘Formación del Profesorado Universitario – FPU’ fellowship (FPU18/00064)). We thank CNIO Biobank for their support with the frozen specimens processing. We thank the Spanish National Tumor Bank Network (RD09/0076/00047) for the support in obtaining tumour samples, and all patients, physicians and tumour biobanks involved in the study.
Published: 2022

35. Feasibility of a brief mindfulness-based program for burnout in pain healthcare professionals

Author: Server, Anna, Suso-Ribera, Carlos, Pérez-Carrasco, Marcos, Medel, Javier, Mesas, Ángela, Ayora, Alfonso, Gracia, Rosa Maria, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Server A, Medel J, Mesas Á] Servei d’Anestesiologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Suso-Ribera C] Department of Personality, Assessment and Psychological Treatments, Universitat Jaume I, Castelló, Spain. Institute of Health Carlos III, CIBERObn CB06 03/0052, Madrid, Spain. [Pérez-Carrasco M, Gracia RM] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Medicina Intensiva, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Ayora A] Unitat Bàsica de Prevenció de Riscos Laborals, Vall d'Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Síndrome d'esgotament professional, Pain clinic, Persons::Occupational Groups::Health Personnel [NAMED GROUPS], Stress, Personal sanitari, Behavioral Disciplines and Activities::Psychotherapy::Behavior Therapy::Cognitive Behavioral Therapy::Mindfulness [PSYCHIATRY AND PSYCHOLOGY], enfermedades profesionales::estrés laboral::desgaste profesional [ENFERMEDADES], disciplinas y actividades conductuales::psicoterapia::terapia conductista::terapia cognitivo-conductual::atención plena [PSIQUIATRÍA Y PSICOLOGÍA], Burnout, Health professionals, Occupational Diseases::Occupational Stress::Burnout, Professional [DISEASES], Atenció plena, Mindfulness, personas::grupos profesionales::personal sanitario [DENOMINACIONES DE GRUPOS], General Psychology
Abstract: IntroductionStress inherent to health care, which is characterized by work overload and shortage of specialized staff, is associated with decreased quality of life and suboptimal patient care. Mindfulness-based programs have proved to be effective in reducing stress in healthcare providers. This study aims to assess the feasibility of an 8-week mindfulness program to reduce the burnout levels of the staff of a pain clinic in a tertiary public hospital.Materials and methodsA longitudinal study with a within subject pre/post-intervention design, consisting of daily face-to-face 10-min sessions and the creation of a virtual group using a social media platform. Variables measured: burnout, mindfulness, empathy, self-compassion, and demographic characteristics.ResultsProgram feasibility (i.e., reach, adherence, acceptability, and preliminary effectiveness) was evaluated in 10 participants (6 physicians, 2 nurse practitioners, 1 nursing assistant, and 1 administrative). The results revealed a high reach (i.e., participation rate of 90%), excellent adherence to the program (daily practice 95% of times), and very good acceptability of the group format and satisfaction with most treatment components. Regarding potential effectiveness, we report the results of the Wilcoxon signed-rank tests and its associated effect size (r). We observed improvements in mindfulness and all its subscales (−2.077 ≤ Z ≤ −2.703, 0.69 ≤ r ≤ 0.90, all p Z ≤ −2.611, 0.83 ≤ r ≤ 0.87, all p Z = −2.201, p = 0.028, r = 0.73).DiscussionWe believe that the 8-week mindfulness-based program described in the present investigation might be a feasible and potentially effective method that can be easily implemented to reduce burnout and promote mindfulness in specialized pain clinics.
Published: 2022

36. Rapidly adapting primary care sentinel surveillance across seven countries in Europe for COVID-19 in the first half of 2020: strengths, challenges, and lessons learned

Author: Bagaria, Jayshree, Jansen, Tessa, Marques, Diogo Fp, Hooiveld, Mariette, McMenamin, Jim, de Lusignan, Simon, Vilcu, Ana-Maria, Meijer, Adam, Rodrigues, Ana-Paula, Brytting, Mia, Mazagatos, Clara, Cogdale, Jade, van der Werf, Sylvie, Dijkstra, Frederika, Guiomar, Raquel, Enkirch, Theresa, Valenciano, Marta, I-MOVE-COVID-19 study team, Larrauri, Amparo, Pozo Sanchez, Francisco, Casas Flecha, Inmaculada, Unión Europea. Comisión Europea. H2020, Public Health Scotland [Glasgow], Netherlands Institute for Health Services Research [Utrecht] (NIVEL), EpiConcept [Paris], University of Oxford, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Public Health Agency of Sweden, Institute of Health Carlos III, UK Health Security Agency (UKHSA), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003673., MOVE-COVID-19 study team: Esther Kissling, Lisa Domegan, Joan O'Donnell, Josephine Murray, Virginia Sandonis Martín, Iván Martínez-Baz, Ausenda Machado, Itziar Casado, Sylvie Behillil, Amparo Larrauri, Ruby Tsang, Marit de Lange, Maximilian Riess, Jesús Castilla, Mark Hamilton, Alessandra Falchi, Francisco Pozo, Linda Dunford, Cristina Burgui, Debbie Sigerson, Thierry Blanchon, Eva María Martínez Ochoa, Jeff Connell, Joanna Ellis, Rianne van Gageldonk-Lafeber, Irina Kislaya, Angela Mc Rose, Jamie Lopez Bernal, Nick Andrews, Inmaculada Casas Flecha, Janine Thoulass, Baltazar Nunes, Verónica Gomez, Rita Sa Machado, Vincent Enouf, Pedro Licinio Pinto Leite, Anna Molesworth, Adele McKenna, Janine Thoulass, European Project: 101003673,H2020-SC1-PHE-CORONAVIRUS-2020,I-MOVE-COVID-19(2020), HAL-SU, Gestionnaire, Multidisciplinary European network for research, prevention and control of the COVID-19 Pandemic - I-MOVE-COVID-19 - - H2020-SC1-PHE-CORONAVIRUS-20202020-03-16 - 2022-06-15 - 101003673 - VALID, UK Health Security Agency [London] (UKHSA), and Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur)
Subjects: Epidemiology, Sentinel surveillance, primary care, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Influenza, Human, Humans, Influenza-Like Illness, Pandemics, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Primary Health Care, SARS-CoV-2, Cuidados de Saúde, Public Health, Environmental and Occupational Health, Influenza-Like Illness (ILI), COVID-19, Estados de Saúde e de Doença, Primary care, Europe, Vigilância Epidemiológica, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Influenza Vaccines, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sentinel Surveillance
Abstract: I-MOVE-COVID-19 study team: Esther Kissling, Lisa Domegan, Joan O’Donnell, Josephine Murray, Virginia Sandonis Martín, Iván Martínez-Baz, Ausenda Machado, Itziar Casado, Sylvie Behillil, Amparo Larrauri, Ruby Tsang, Marit de Lange, Maximilian Riess, Jesús Castilla, Mark Hamilton, Alessandra Falchi, Francisco Pozo, Linda Dunford, Cristina Burgui, Debbie Sigerson, Thierry Blanchon, Eva María Martínez Ochoa, Jeff Connell, Joanna Ellis, Rianne van Gageldonk-Lafeber, Irina Kislaya, Angela MC Rose, Jamie Lopez Bernal, Nick Andrews, Inmaculada Casas Flecha, Janine Thoulass, Baltazar Nunes, Verónica Gomez, Rita Sa Machado, Vincent Enouf, Pedro Licinio Pinto Leite, Anna Molesworth, Adele McKenna, Janine Thoulass As the COVID-19 pandemic began in early 2020, primary care influenza sentinel surveillance networks within the Influenza - Monitoring Vaccine Effectiveness in Europe (I-MOVE) consortium rapidly adapted to COVID-19 surveillance. This study maps system adaptations and lessons learned about aligning influenza and COVID-19 surveillance following ECDC / WHO/Europe recommendations and preparing for other diseases possibly emerging in the future. Using a qualitative approach, we describe the adaptations of seven sentinel sites in five European Union countries and the United Kingdom during the first pandemic phase (March–September 2020). Adaptations to sentinel systems were substantial (2/7 sites), moderate (2/7) or minor (3/7 sites). Most adaptations encompassed patient referral and sample collection pathways, laboratory testing and data collection. Strengths included established networks of primary care providers, highly qualified testing laboratories and stakeholder commitments. One challenge was the decreasing number of samples due to altered patient pathways. Lessons learned included flexibility establishing new routines and new laboratory testing. To enable simultaneous sentinel surveillance of influenza and COVID-19, experiences of the sentinel sites and testing infrastructure should be considered. The contradicting aims of rapid case finding and contact tracing, which are needed for control during a pandemic and regular surveillance, should be carefully balanced. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003673. info:eu-repo/semantics/publishedVersion
Published: 2022
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37. The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart ‘OMics’ in AGEing (HOMAGE) randomized clinical trial

Author: Cleland, John, Ferreira, João Pedro, Mariottoni, Beatrice, Pellicori, Pierpaolo, Cuthbert, Joe, Verdonschot, Job, Petutschnigg, Johannes, Ahmed, Fozia, COSMI, FRANCO, Brunner La Rocca, Hans-Peter, Mamas, Mamas, Clark, Andrew, Edelmann, Frank, Pieske, Burkert, Khan, Javed, McDonald, Ken, Rouet, Philippe, Staessen, Jan, Mujaj, Blerim, González, Arantxa, Diez, Javier, Hazebroek, Mark, Heymans, Stephane, Latini, Roberto, Grojean, Stéphanie, Pizard, Anne, Girerd, Nicolas, Rossignol, Patrick, Collier, Tim, Zannad, Faiez, Atar, Dan, Kober, Lars, Dickstein, Kenneth, Lange, Theis, RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), MUMC+: MA Med Staf Artsass Cardiologie (9), University of Glasgow, Robertson Centre for Biostatistics, University of Glasgow, Institute of Health and Wellbeing, University of Glasgow-Gartnavel General Hospital, Glasgow, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Cortona Hospital, Castle Hill Hospital, University of Hull [United Kingdom], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Keele University [Keele], University College Dublin [Dublin] (UCD), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Universitäts Klinikum Freiburg, Universidad de Navarra [Pamplona] (UNAV), Institute of Health Carlos III, Instituto de Investigación Sanitaria de Navarra [Pamplona, Spain] (IdiSNA), IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Fondation Force, Research and Consulting Department, EDDH, Centre de Médecine Préventive, and London School of Hygiene and Tropical Medicine (LSHTM)
Subjects: Male, Aging, Cardiac & Cardiovascular Systems, Spironolactone, 030204 cardiovascular system & hematology, Q1, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Fibrosis, Clinical endpoint, AcademicSubjects/MED00200, 030212 general & internal medicine, Mineralocorticoid Receptor Antagonists, Collagen markers, R735, Heart failure prevention, RC666, 16. Peace & justice, 3. Good health, Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Procollagen, Cardiac function curve, medicine.medical_specialty, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, N-terminal telopeptide, Clinical Research, Internal medicine, medicine, Humans, Heart Failure and Cardiomyopathies, Aged, Heart Failure, Science & Technology, business.industry, medicine.disease, R1, Peptide Fragments, Procollagen peptidase, Blood pressure, chemistry, Heart failure, Cardiovascular System & Cardiology, ras Proteins, business, RA, Biomarkers
Abstract: Importance: Cardiovascular accumulation of collagen (fibrosis) may contribute to the progression from ventricular dysfunction to heart failure. Galectin-3, a potential marker of pro-fibrotic activity, might identify those at greater risk.\ud Objective: To investigate the effects of spironolactone, according to serum galectin-3 concentration, on serum markers of fibrosis and on cardiac structure and function, in people at increased risk of developing heart failure.\ud Design: Prospective, randomized, open-label, blinded endpoint (PROBE) trial.\ud Setting: Clinical research facilities in ten European hospitals.\ud Participants: People with, or at high-risk of, coronary disease with increased plasma concentrations of B-type natriuretic peptides (BNP or NT-proBNP).\ud Interventions: spironolactone (up to 50 mg/day) or control for up to nine months.\ud Main Outcomes and Measures: The primary outcome was the interaction between baseline serum galectin-3 and change in serum procollagen type-III N-terminal pro-peptide (PIIINP), a by-product of type-III collagen synthesis. Serum procollagen type-I C-terminal pro-peptide (PICP) and collagen type-1 C-terminal telopeptide (CITP), respectively reflecting synthesis and degradation of type-I collagen, were also measured.\ud Results: Of 527 participants, the median age was 73 years and 26% were women. Median follow-up was 267 days. Changes in PIIINP were similar for those assigned to spironolactone and control (mean difference -0.15; 95% confidence interval [CI] -0.44 to 0.15 μg/L; p=0.32) and did not differ when serum galectin-3 was above or below median. Those assigned to spironolactone had greater declines in PICP (mean difference -8.1; -95% CI -11.9 to -4.3 μg/L; p
Published: 2020
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38. Universal scaling laws rule explosive growth in human cancers

Author: Ángel Acosta Rojas, Esther Hernández-San Miguel, María Pérez-Cano, Gabriel F. Calvo, Lucía Zhu, Ana María García Vicente, Juan Belmonte-Beitia, Juan J. Jiménez, David Albillo, Philippe Schucht, Víctor M. Pérez-García, Pedro García-Gómez, Antonio Francisco Honguero Martínez, François M. Vallette, Manuel Valiente, Jesús J. Bosque, Álvaro Martínez, Julián Pérez-Beteta, David Molina-García, Youness Azimzade, Odelaisy León-Triana, Michael Murek, Pilar Sánchez-Gómez, Ana Ortiz de Mendivil, Rafael Hortigüela, Germán Andrés Jiménez Londoño, Estanislao Arana, Universidad de Castilla-La Mancha (UCLM), Spanish National Cancer Research Center (CNIO), Institute of Health Carlos III, University of Tehran, Sanchinarro University Hospita [HM Hospitales, Madrid], Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Bern University Hospital [Berne] (Inselspital), MD Anderson Cancer Center [Madrid, Spain], Hospital General Universitario de Albacete, Hospital General Universitario de Ciudad Real [Ciudad Real, Spain], Fundación Instituto Valenciano de Oncología [Valencia, Spain], James S. McDonnell Foundation 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer, European Regional Development Fund (ERDF/FEDER), Junta de Comunidades de Castilla-La Mancha, Ministerio de Economia y Competividad (MINECO), Bristol-Myers Squibb, Beug Foundation's Prize for Metastasis Research 2017, Fundacion Ramon Areces, Worldwide Cancer Research, H2020-FETOPEN, Fundacio La Marato de TV3, Clinic and Laboratory Integration Program CRI Award 2018, AECC Coordinated Translational Groups 2017, LAB AECC 2019, La Caixa INPhINIT Fellowship, La Caixa-Severo Ochoa International PhD Program Fellowship, European Molecular Biology Organization Young Investigators programme, Bernardo, Elizabeth, Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Scaling law, Explosive material, Computer science, General Physics and Astronomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, 01 natural sciences, Measure (mathematics), Article, 010305 fluids & plasmas, [SDV.CAN] Life Sciences [q-bio]/Cancer, GENERAL-MODEL, 0103 physical sciences, RATES, Statistical physics, Tissues and Organs (q-bio.TO), 010306 general physics, Set (psychology), Evolutionary dynamics, Mathematical model, TUMOR-GROWTH, Quantitative Biology - Tissues and Organs, Observable, EVOLUTION, PREDICTS, 3. Good health, PET, Oncología matemática, FOS: Biological sciences, SURVIVAL, Biomedicina, Value (mathematics)
Abstract: Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings. This research has been supported by the James S. McDonnell Foundation 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer (collaborative awards 220020560 and 220020450), Ministerio de Economia y Competitividad/FEDER, Spain (grant no. MTM2015-71200-R), Junta de Comunidades de Castilla-La Mancha (grant no. SBPLY/17/180501/000154). Research in the Brain Metastasis Group is supported by MINECO grant MINECO-Retos SAF2017-89643-R (M.V.), Bristol-Myers Squibb Melanoma Research Alliance Young Investigator Award 2017 (498103) (M.V.), Beug Foundation's Prize for Metastasis Research 2017 (M.V.), Fundacion Ramon Areces (CIVP19S8163) (M.V.), Worldwide Cancer Research (19-0177) (M.V.), H2020-FETOPEN (828972) (M.V.), Fundacio La Marato de tv3 (141), Clinic and Laboratory Integration Program CRI Award 2018 (54545) (M.V.), AECC Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002VALI) (M.V.), La Caixa INPhINIT Fellowship (LCF/BQ/IN17/11620028) (P.G.-G.), La Caixa-Severo Ochoa International PhD Program Fellowship (LCF/BQ/SO16/52270014) (L.Z.). M.V. is a member of the European Molecular Biology Organization Young Investigators programme (4053). We would like to acknowledge J. Cervera and J. C. Penalver from the IVO Foundation (Valencia, Spain). No
Published: 2020
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39. Prediction model for short-term mortality after palliative radiotherapy for patients having advanced cancer: a cohort study from routine electronic medical data

Author: Chuk Kwan Ng, Hollis Luk, Aray Wong, Shing Fung Lee, Miguel Angel Luque-Fernandez, Frank Chi Sing Wong, [Lee,SF, Luk,H, Wong,A, Ng,CK, Wong,FCS] Department of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, Hong Kong. [Luque-Fernandez,MA] Department of Non-Communicable Disease and Cancer Epidemiology, Institute de Investigacion Biosanitaria de Granada (ibs.GRANADA), University of Granada, Granada, Spain. [Luque-Fernandez,MA] Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK., and There was no explicit funding for the development of this project. MALF is supported by a Miguel Servet I Investigator Award (grant CP17/00206 EU-FEDER) from the National Institute of Health, Carlos III (ISCIII), Madrid, Spain. His funders had no role in the study design, data collection, dataanalysis, data interpretation, or writing of the report.
Subjects: Male, medicine.medical_treatment, lcsh:Medicine, Logistic regression, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Palliative Care [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Palliative radiotherapy, Risk Factors, Neoplasms, Odds Ratio, Electronic Health Records, 030212 general & internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], lcsh:Science, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Cancer, Multidisciplinary, Palliative Care, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Prognosis, Cuidados paliativos, Neoplasias, Oncology, Outcomes research, 030220 oncology & carcinogenesis, Female, Cohort study, medicine.medical_specialty, Estudios de cohortes, Check Tags::Male [Medical Subject Headings], Article, 03 medical and health sciences, Radioterapia, Prediction model, Internal medicine, medicine, Humans, Mortality, Lung cancer, Aged, Radiotherapy, business.industry, lcsh:R, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, medicine.disease, Confidence interval, Radiation therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Records as Topic::Medical Records::Medical Records Systems, Computerized::Electronic Health Records [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Mortalidad, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], lcsh:Q, business
Abstract: We developed a predictive score system for 30-day mortality after palliative radiotherapy by using predictors from routine electronic medical record. Patients with metastatic cancer receiving first course palliative radiotherapy from 1 July, 2007 to 31 December, 2017 were identified. 30-day mortality odds ratios and probabilities of the death predictive score were obtained using multivariable logistic regression model. Overall, 5,795 patients participated. Median follow-up was 39.6 months (range, 24.5–69.3) for all surviving patients. 5,290 patients died over a median 110 days, of whom 995 (17.2%) died within 30 days of radiotherapy commencement. The most important mortality predictors were primary lung cancer (odds ratio: 1.73, 95% confidence interval: 1.47–2.04) and log peripheral blood neutrophil lymphocyte ratio (odds ratio: 1.71, 95% confidence interval: 1.52–1.92). The developed predictive scoring system had 10 predictor variables and 20 points. The cross-validated area under curve was 0.81 (95% confidence interval: 0.79–0.82). The calibration suggested a reasonably good fit for the model (likelihood-ratio statistic: 2.81, P = 0.094), providing an accurate prediction for almost all 30-day mortality probabilities. The predictive scoring system accurately predicted 30-day mortality among patients with stage IV cancer. Oncologists may use this to tailor palliative therapy for patients.
Published: 2020
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40. Effectiveness of complete primary vaccination against COVID-19 at primary care and community level during predominant Delta circulation in Europe: multicentre analysis, I-MOVE-COVID-19 and ECDC networks, July to August 2021

Author: Kissling, Esther, Hooiveld, Mariëtte, Martínez-Baz, Iván, Mazagatos, Clara, William, Naoma, Vilcu, Ana-Maria, Kooijman, Marjolein N, Ilić, Maja, Domegan, Lisa, Machado, Ausenda, de Lusignan, Simon, Lazar, Mihaela, Meijer, Adam, Brytting, Mia, Casado, Itziar, Larrauri, Amparo, Murray, Josephine-L K, Behillil, Sylvie, de Gier, Brechje, Mlinarić, Ivan, O'Donnell, Joan, Rodrigues, Ana Paula, Tsang, Ruby, Timnea, Olivia, de Lange, Marit, Riess, Maximilian, Castilla, Jesús, Pozo Sanchez, Francisco, Hamilton, Mark, Falchi, Alessandra, Knol, Mirjam J, Kurečić Filipović, Sanja, Dunford, Linda, Guiomar, Raquel, Cogdale, Jade, Cherciu, Carmen, Jansen, Tessa, Enkirch, Theresa, Basile, Luca, Connell, Jeff, Gomez, Verónica, Sandonis-Martin, Virginia, Bacci, Sabrina, Rose, Angela Mc, Pastore Celentano, Lucia, Valenciano, Marta, I-MOVE-COVID-19, ECDC primary care study teams, Conde-San Román, Patricia, Casas Flecha, Inmaculada, Oliva Dominguez, Jesus Angel, Delgado-Sanz, Concepcion, EpiConcept [Paris], Netherlands Institute for Health Services Research [Utrecht] (NIVEL), Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA)-Universidad de Navarra [Pamplona] (UNAV)-Clínica Universidad de Navarra [Pamplona], CIBER de Epidemiología y Salud Pública (CIBERESP), Institute of Health Carlos III, Public Health Scotland [Glasgow], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Croatian Institute of Public Health [Zagreb] (CIPH), Health Service Executive [Dublin] (HSE), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), University of Oxford, Cantacuzino Institute [Romania], Réseau International des Instituts Pasteur (RIIP), Public Health Agency of Sweden, Instituto de Salud Carlos III [Madrid] (ISC), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biologie des ARN et virus influenza - RNA Biology of Influenza Virus (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University College Dublin [Dublin] (UCD), UK Health Security Agency [London] (UKHSA), European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), I-MOVE-COVID-19 and ECDC primary care study team Katica Čusek Adamić, Ivana Ferenčak, Bernard Kaić, Mirjana Lana Kosanović Ličina, Danijela Lakošeljac, Ivana Mihin Huskić, Diana Nonković, Nick Andrews, Jamie Lopez Bernal, Joanna Ellis, Heather Whitaker, Thierry Blanchon, Caroline Guerrisi, Titouan Launay, Shirley Masse, Sylvie van der Werf, Vincent Enouf, John Cuddihy, Lois O'Connor, Adele McKenna, Michael Joyce, Cillian de Gascun, Joanne Moran, Rianne van Gageldonk-Lafeber, Susan J Hahné, Hester E de Melker, Ewout B Fanoy, Stijn Raven, Marit Middeldorp, Irina Kislaya, Baltazar Nunes, Rita Roquete, Adriana Silva, Aryse Melo, Inês Costa, Nuno Verdasca, Patrícia Conde, Amélia Soeiro, Maria Elena Mihai, Iulia Bistriceanu, Alina Ivanciuc, Diana Dintoi, Catalina Pascu, Adrian Jidovu, Debbie Sigerson, Diogo Fp Marques, Anna Molesworth, Leanne Quinn, Miranda Leyton, Selin Campbell, Janine Thoulass, Jim McMenamin, Inmaculada Casas Flecha, Ana Martínez Mateo, Daniel Castrillejo, Eva María Martínez Ochoa, Carmen Quiñones Rubio, Concepción Delgado-Sanz, Jesús Oliva, Ana Miqueleiz, Ana Navascués, Camino Trobajo-Sanmartín, Carmen Ezpeleta, Paula López Moreno, Javier Gorricho, Eva Ardanaz, Fernando Baigorria, Aurelio Barricarte, Cristina Burgui, Enrique de la Cruz, Nerea Egüés, Manuel García Cenoz, Marcela Guevara, Conchi Moreno-Iribas, Carmen Sayón, Pasi Penttinen, Christiana Carstairs, University of St Andrews. School of Medicine, Unión Europea. Comisión Europea. H2020, and European Centre for Disease Prevention and Control
Subjects: Test-negative design, RM, Delta variant, COVID-19 Vaccines, Epidemiology, [SDV]Life Sciences [q-bio], Multicentre study, Influenza, Human/prevention & control, MESH: Primary Health Care, Europe/epidemiology, MESH: Influenza Vaccines, SDG 3 - Good Health and Well-being, RA0421, RA0421 Public health. Hygiene. Preventive Medicine, Virology, Influenza, Human, Humans, MESH: COVID-19, MESH: SARS-CoV-2, COVID-19/epidemiology, Vaccine effectiveness, QR355, MESH: Humans, Primary Health Care, vaccine effectiveness, SARS-CoV-2, MESH: Influenza, Human, Vaccination, test-negative design, Public Health, Environmental and Occupational Health, COVID-19, 3rd-DAS, MESH: Vaccination, NIS, multicentre study, RM Therapeutics. Pharmacology, Europe, Influenza Vaccines, MESH: COVID-19 Vaccines, SARS-COV-2, vaccine efffectiveness, MESH: Europe, QR355 Virology
Abstract: Introduction In July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe. Aim Using a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection. Methods Individuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination. Results Overall VE was 74% (95% CI: 69–79), 76% (95% CI: 71–80), 63% (95% CI: 48–75) and 63% (95% CI: 16–83) among those aged 30–44, 45–59, 60–74 and ≥ 75 years, respectively. VE among those aged 30–59 years was 78% (95% CI: 75–81), 66% (95% CI: 58–73), 91% (95% CI: 87–94) and 52% (95% CI: 40–61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52–77), 65% (95% CI: 48–76) and 83% (95% CI: 64–92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30–59 years was 87% (95% CI: 83–89) at 14–29 days and 65% (95% CI: 56–71%) at ≥ 90 days between vaccination and onset of symptoms. Conclusions VE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.
Published: 2022
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41. Assessment of exposure to pesticide mixtures in five European countries by a harmonized urinary suspect screening approach

Author: Ottenbros, Ilse, Lebret, Erik, Huber, Carolin, Lommen, Arjen, Antignac, Jean-Philippe, Čupr, Pavel, Šulc, Libor, Mikeš, Ondřej, Szigeti, Tamás, Középesy, Szilvia, Martinsone, Inese, Martinsone, Zanna, Akulova, Lasma, Pardo, Olga, Fernández, Sandra F, Coscollá, Clara, Pedraza-Diaz, Susana, Krauss, Martin, Debrauwer, Laurent, Wagner, Kévin, Nijssen, Rosalie, Mol, Hans, Vitale, Chiara Maria, Klanova, Jana, Molina, Borja Garlito, León, Nuria, Vermeulen, Roel, Luijten, Mirjam, Vlaanderen, Jelle, IRAS OH Epidemiology Chemical Agents, IRAS OH Epidemiology Microbial Agents, Unión Europea. Comisión Europea. H2020, Ministry of Education, Youth and Sports (República Checa), IRAS OH Epidemiology Chemical Agents, IRAS OH Epidemiology Microbial Agents, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institute for Risk Assessment Sciences [Utrecht, The Netherlands] (IRAS), Utrecht University [Utrecht], Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Goethe-University Frankfurt am Main, Wageningen University and Research [Wageningen] (WUR), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Research Centre for Toxic Compounds in the Environment [Brno] (RECETOX / MUNI), Faculty of Science [Brno] (SCI / MUNI), Masaryk University [Brno] (MUNI)-Masaryk University [Brno] (MUNI), National center for public health [Hungary], Riga Stradins University (RSU), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Institute of Health Carlos III, Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ToxAlim (ToxAlim), Universitat Jaume I, Tuberculosis Reference Laboratory [RIVM], This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032 HBM4EU, No 857560and No 857340. P.Č. O.M. & L.Š. acknowledge the RECETOX research infrastructure supported by the Ministry of Education, Youth and Sports of the Czech Republic (LM2018121) and the Ministry of Education, Youth and Sports of the Czech Republic (CZ.02.1.01/0.0/0.0/17_043/0009632)., and European Project: 733032,H2020,HBM4EU(2017)
Subjects: Adult, HBM4EU, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, Agriculture, Chlorpropham, Environmental Exposure, Suspect screening, Correlation patterns, Team Pesticides 2, Pesticide exposure, Europe, Mixtures, Co-occurrence, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pesticides, Biomarkers, VLAG
Abstract: Humans are exposed to a mixture of pesticides through diet as well as through the environment. We conducted a suspect-screening based study to describe the probability of (concomitant) exposure to a set of pesticide profiles in five European countries (Latvia, Hungary, Czech Republic, Spain and the Netherlands). We explored whether living in an agricultural area (compared to living in a peri-urban area), being a a child (compared to being an adult), and the season in which the urine sample was collected had an impact on the probability of detection of pesticides (-metabolites). In total 2088 urine samples were collected from 1050 participants (525 parent-child pairs) and analyzed through harmonized suspect screening by five different laboratories. Fourty pesticide biomarkers (either pesticide metabolites or the parent pesticides as such) relating to 29 pesticides were identified at high levels of confidence in samples across all study sites. Most frequently detected were biomarkers related to the parent pesticides acetamiprid and chlorpropham. Other biomarkers with high detection rates in at least four countries related to the parent pesticides boscalid, fludioxonil, pirimiphos-methyl, pyrimethanil, clothianidin, fluazifop and propamocarb. In 84% of the samples at least two different pesticides were detected. The median number of detected pesticides in the urine samples was 3, and the maximum was 13 pesticides detected in a single sample. The most frequently co-occurring substances were acetamiprid with chlorpropham (in 62 urine samples), and acetamiprid with tebuconazole (30 samples). Some variation in the probability of detection of pesticides (-metabolites) was observed with living in an agricultural area or season of urine sampling, though no consistent patterns were observed. We did observe differences in the probability of detection of a pesticide (metabolite) among children compared to adults, suggesting a different exposure and/or elimination patterns between adults and children. This survey demonstrates the feasibility of conducting a harmonized pan-European sample collection, combined with suspect screening to provide insight in the presence of exposure to pesticide mixtures in the European population, including agricultural areas. Future improvements could come from improved (harmonized) quantification of pesticide levels. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 HBM4EU, No 857560 and No 857340. P.C., O.M. & L.S. acknowledge the RECETOX research infrastructure supported by the Ministry of Education, Youth and Sports of the Czech Republic (LM2018121) and the Ministry of Education, Youth and Sports of the Czech Republic (CZ.02.1.01/0.0/0.0/17_043/0009632). This publication reflects only the author’s view and the European Commission is not responsible for any use that may be made of the information it contains. BG was supported by the Margarita Salas postdoctoral contract MGS/2021/25 (UP2021-021) financed by the European UnionNextGenerationEU. Sí
Published: 2023
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42. Influence of ejection fraction on biomarker expression and response to spironolactone in people at risk of heart failure: findings from the HOMAGE trial

Author: João Pedro Ferreira, Job A.J. Verdonschot, Nicolas Girerd, Erwan Bozec, Pierpaolo Pellicori, Timothy Collier, Beatrice Mariottoni, Franco Cosmi, Mark Hazebroek, Joe Cuthbert, Johannes Petutschnigg, Stephane Heymans, Jan A. Staessen, Burkert Pieske, Frank Edelman, Andrew L. Clark, Javier Díez, Arantxa González, Patrick Rossignol, John G. Cleland, Faiez Zannad, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Glasgow, London School of Hygiene and Tropical Medicine (LSHTM), Cortona Hospital, University of Hull [United Kingdom], Charité Campus Virchow-Klinikum (CVK), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Studies Coordinating Centre [Louvain, Belgique], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institute of Health Carlos III, Universidad de Navarra [Pamplona] (UNAV), European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013), MUMC+: DA KG Lab Centraal Lab (9), RS: Carim - H02 Cardiomyopathy, MUMC+: MA Med Staf Artsass Cardiologie (9), Cardiologie, and MUMC+: MA Med Staf Spec Cardiologie (9)
Subjects: Heart Failure, Inflammation, Ejection fraction, INTERLEUKIN-8, IMPACT, PROGNOSTIC IMPORTANCE, Stroke Volume, Spironolactone, Fibrosis, Ventricular Function, Left, DISEASE, EVENTS, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, S100A12, Tissue Plasminogen Activator, Natriuretic Peptide, Brain, cardiovascular system, Humans, cardiovascular diseases, Cardiology and Cardiovascular Medicine, Biomarkers, Mineralocorticoid Receptor Antagonists, circulatory and respiratory physiology
Abstract: Aims: \ud Left ventricular ejection fraction (LVEF) can provide haemodynamic information and may influence the response to spironolactone and other heart failure (HF) therapies. We aimed to study patient characteristics and circulating protein associations with LVEF, and whether LVEF influenced the response to spironolactone.\ud \ud Methods and results: \ud HOMAGE enrolled patients aged >60 years at high risk of developing HF with a LVEF ≥45%. Overall, 527 patients were randomized to either spironolactone or standard of care for ≈9 months, and 276 circulating proteins were measured using Olink® technology. A total of 364 patients had available LVEF determined by the Simpson's biplane method. The respective LVEF tertiles were: tertile 1: 65% (n = 121). Patients with a LVEF >65% had smaller left ventricular chamber size and volumes, and lower natriuretic peptide levels. Compared to patients with a LVEF 65% had higher levels of circulating c-c motif chemokine ligand-23 and interleukin-8, and lower levels of tissue plasminogen activator, brain natriuretic peptide (BNP), S100 calcium binding protein A12, and collagen type I alpha 1 chain (COL1A1). Spironolactone significantly reduced the circulating levels of BNP and COL1A1 without significant treatment-by-LVEF heterogeneity: BNP change β = −0.36 log2 and COL1A1 change β = −0.16 log2 (p 0.1 for both). Spironolactone increased LVEF from baseline to month 9 by 1.1% (p = 0.007).\ud \ud Conclusion: \ud Patients with higher LVEF had higher circulating levels of chemokines and inflammatory markers and lower levels of stretch, injury, and fibrosis markers. Spironolactone reduced the circulating levels of natriuretic peptides and type 1 collagen, and increased LVEF.
Published: 2022
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43. Editorial: The Non-Coding Transcriptome as a New Player in Intercellular Communication

Author: Yvan Devaux, Florence Pinet, David de Gonzalo-Calvo, Luxembourg Institute of Health (LIH), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Arnau de Vilanova University Hospital [Lleida, Spain], Institute of Health Carlos III, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), and ANR-16-RHUS-0003,STOP-AS,STOP-AS(2016)
Subjects: microRNA, communication, [SDV]Life Sciences [q-bio], hormone, signal, Biochemistry, Genetics and Molecular Biology (miscellaneous), Molecular Biology, Biochemistry, ncRNA
Abstract: No abstract available
Published: 2022
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44. Benzotriazole-based multidonor-acceptor systems as attractive two-photon absorption dye platforms

Author: Carlos Benitez-Martin, Beatriz Donoso, Iván Torres-Moya, Jesús Herrera, Ángel Díaz-Ortiz, Francisco Najera, Pilar Prieto, Ezequiel Perez-Inestrosa, [Benitez-Martin, Carlos] Univ Malaga, Dept Quim Organ, IBIMA, Malaga 29071, Spain, [Najera, Francisco] Univ Malaga, Dept Quim Organ, IBIMA, Malaga 29071, Spain, [Perez-Inestrosa, Ezequiel] Univ Malaga, Dept Quim Organ, IBIMA, Malaga 29071, Spain, [Benitez-Martin, Carlos] Ctr Andaluz Nanomed & Biotecnol BIONAND, Parque Tecnol Andalucia, Malaga 29590, Spain, [Perez-Inestrosa, Ezequiel] Ctr Andaluz Nanomed & Biotecnol BIONAND, Parque Tecnol Andalucia, Malaga 29590, Spain, [Donoso, Beatriz] Univ Castilla La Mancha, Fac Chem & Technol Sci IRICA, Dept Organ Inorgan Chem & Biochem, Ciudad Real 13071, Spain, [Torres-Moya, Ivan] Univ Castilla La Mancha, Fac Chem & Technol Sci IRICA, Dept Organ Inorgan Chem & Biochem, Ciudad Real 13071, Spain, [Herrera, Jesus] Univ Castilla La Mancha, Fac Chem & Technol Sci IRICA, Dept Organ Inorgan Chem & Biochem, Ciudad Real 13071, Spain, [Diaz-Ortiz, Angel] Univ Castilla La Mancha, Fac Chem & Technol Sci IRICA, Dept Organ Inorgan Chem & Biochem, Ciudad Real 13071, Spain, [Prieto, Pilar] Univ Castilla La Mancha, Fac Chem & Technol Sci IRICA, Dept Organ Inorgan Chem & Biochem, Ciudad Real 13071, Spain, Spanish Ministry for Science, Innovation, and Universities, Institute of Health Carlos III (ISCIII) RETIC ARADYAL, Junta de Andalucia, MCIN/AEI, MCIN, FEDER Una manera de hacer Europa, Junta de Comunidades de Castilla-La Mancha (JCCM-FEDER), FPU predoctoral contract, Junta de Comunidades de Castilla-La Mancha, predoctoral Junta de Comunidades de Castilla-La Mancha contract, and Universidad de Malaga / CBUA
Subjects: Design, Benzotriazole dyes, Process Chemistry and Technology, General Chemical Engineering, Compuestos heterocíclicos, Benzothiadiazole, Red-fluorescent, DFT calculations, Fluorescence, Fluorescent-probe, Emission, Initiators, Interacciones fotón-fotón, Fluorescencia, Two-photon absorption, Optical-data storage, Funcionales de densidad, Wave-guide, Thiadiazoloquinoxaline, Absorbing chromophores
Abstract: Pyrazine-decorated benzotriazole cores allow the orthogonal combination of two dipolar systems within a single molecule. A series of this type of derivatives was synthesized and their photophysical features were studied. The properties of these compounds showed remarkable differences in function depending on the substitution in the pyrazine ring of the benzotriazole core. Furthermore, the two-photon absorption property (2PA) was studied to determine the structure-properties relationship for the reported compounds. The best dye achieved a crosssection of 1532 GM, which was higher than values previously obtained for similar D-π-A-π-D benzotriazole derivatives. TD-DFT calculations, which supported the experimental observations, indicating the interaction between the two dipolar systems was responsible for enhancing the 2 PA properties and favoring bathochromic shifts. PCI2019-111825-2, PID2019-104293GB-I00, UMA18-FEDERJA-007, SBPLY/17/180501/000189, PID2020-119636GB-I00 , RED2018-102331-T, Universidad de Málaga / CBUA
Published: 2022

45. The EASL–Lancet Liver Commission:protecting the next generation of Europeans against liver disease complications and premature mortality

Author: Tom H Karlsen, Nick Sheron, Shira Zelber-Sagi, Patrizia Carrieri, Geoffrey Dusheiko, Elisabetta Bugianesi, Rachel Pryke, Sharon J Hutchinson, Bruno Sangro, Natasha K Martin, Michele Cecchini, Mae Ashworth Dirac, Annalisa Belloni, Miquel Serra-Burriel, Cyriel Y Ponsioen, Brittney Sheena, Alienor Lerouge, Marion Devaux, Nick Scott, Margaret Hellard, Henkjan J Verkade, Ekkehard Sturm, Giulio Marchesini, Hannele Yki-Järvinen, Chris D Byrne, Giovanni Targher, Aviad Tur-Sinai, Damon Barrett, Michael Ninburg, Tatjana Reic, Alison Taylor, Tim Rhodes, Carla Treloar, Claus Petersen, Christoph Schramm, Robert Flisiak, Marieta Y Simonova, Albert Pares, Philip Johnson, Alessandro Cucchetti, Isabel Graupera, Christos Lionis, Elisa Pose, Núria Fabrellas, Ann T Ma, Juan M Mendive, Vincenzo Mazzaferro, Harry Rutter, Helena Cortez-Pinto, Deirdre Kelly, Robyn Burton, Jeffrey V Lazarus, Pere Ginès, Maria Buti, Philip N Newsome, Patrizia Burra, Michael P Manns, Karlsen T.H., Sheron N., Zelber-Sagi S., Carrieri P., Dusheiko G., Bugianesi E., Pryke R., Hutchinson S.J., Sangro B., Martin N.K., Cecchini M., Dirac M.A., Belloni A., Serra-Burriel M., Ponsioen C.Y., Sheena B., Lerouge A., Devaux M., Scott N., Hellard M., Verkade H.J., Sturm E., Marchesini G., Yki-Jarvinen H., Byrne C.D., Targher G., Tur-Sinai A., Barrett D., Ninburg M., Reic T., Taylor A., Rhodes T., Treloar C., Petersen C., Schramm C., Flisiak R., Simonova M.Y., Pares A., Johnson P., Cucchetti A., Graupera I., Lionis C., Pose E., Fabrellas N., Ma A.T., Mendive J.M., Mazzaferro V., Rutter H., Cortez-Pinto H., Kelly D., Burton R., Lazarus J.V., Gines P., Buti M., Newsome P.N., Burra P., Manns M.P., Repositório da Universidade de Lisboa, University of Oslo (UiO), King‘s College London, Tel Aviv Sourasky Medical Center [Te Aviv], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), University College of London [London] (UCL), Università degli studi di Torino = University of Turin (UNITO), Bewdley Medical Centre [Bewdley, UK] (BMC), Glasgow Caledonian University (GCU), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, University of Bristol [Bristol], Organisation de Coopération et de Développement Economiques = Organisation for Economic Co-operation and Development (OCDE), University of Washington [Seattle], Public Health England [London], Universität Zürich [Zürich] = University of Zurich (UZH), Amsterdam UMC - Amsterdam University Medical Center, Burnet Institute [Melbourne, Victoria], Royal Prince Alfred Hospital [Sydney, Australia], University of Melbourne, University of Groningen [Groningen], University Children's Hospital of Tübingen, Partenaires INRAE, University hospital - Policlinico S.Orsola-Malpighi [Bologna, Italy], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University Hospital Southampton NHS Foundation Trust, Università degli studi di Verona = University of Verona (UNIVR), Max Stern Yezreel Valley college (YVC), University of Gothenburg (GU), World Hepatitis Alliance [London, UK] (WHA), European Liver Patients Organization [Brussels, Belgium] (ELPO), Croatian Society for Liver Diseases-Hepatos [Split, Croatia] (CSLDH), Children's Liver Disease Foundation [Birmingham, UK] (CLDF), London School of Hygiene and Tropical Medicine (LSHTM), University of New South Wales [Sydney] (UNSW), Hannover Medical School [Hannover] (MHH), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Medical University of Białystok (MUB), Medical Military Academy [Sofia, Bulgaria] (2MA), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Liverpool, University of Bologna/Università di Bologna, University of Crete [Heraklion] (UOC), University of Barcelona, Institute of Health Carlos III, Università degli Studi di Milano = University of Milan (UNIMI), University of Bath [Bath], Universidade de Lisboa = University of Lisbon (ULISBOA), University of Birmingham [Birmingham], Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Instituto de Salud Carlos III [Madrid] (ISC), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), and Malbec, Odile
Subjects: Medicine(all), Mortality, Premature, [SDV]Life Sciences [q-bio], Liver Diseases, Health Policy, Liver Disease, Alcoholic liver diseases, General Medicine, Lancet commission, [SDV] Life Sciences [q-bio], Europe, SDG 3 - Good Health and Well-being, NAFLD, Liver diseases, NAFLD, Alcoholic liver diseases, Liver hepatitis, Lancet commission, Humans, Liver hepatitis, ComputingMilieux_MISCELLANEOUS, Human
Abstract: © 2021 Elsevier Ltd. All rights reserved., Liver diseases have become a major health threat across Europe, and the face of European hepatology is changing due to the cure of viral hepatitis C and the control of chronic viral hepatitis B, the increasingly widespread unhealthy use of alcohol, the epidemic of obesity, and undiagnosed or untreated liver disease in migrant populations. Consequently, Europe is facing a looming syndemic, in which socioeconomic and health inequities combine to adversely affect liver disease prevalence, outcomes, and opportunities to receive care. In addition, the COVID-19 pandemic has magnified pre-existing challenges to uniform implementation of policies and equity of access to care in Europe, arising from national borders and the cultural and historical heterogeneity of European societies. In following up on work from the Lancet Commission on liver disease in the UK and epidemiological studies led by the European Association for the Study of the Liver (EASL), our multidisciplinary Commission, comprising a wide range of public health, medical, and nursing specialty groups, along with patient representatives, set out to provide a snapshot of the European landscape on liver diseases and to propose a framework for the principal actions required to improve liver health in Europe. We believe that a joint European process of thinking, and construction of uniform policies and action, implementation, and evaluation can serve as a powerful mechanism to improve liver care in Europe and set the way for similar changes globally., The SHARE data collection has been funded by the European Commission through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193; COMPARE: CIT5-CT-2005-028857; SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N°211909; SHARE-LEAP: GA N°227822; SHARE M4: GA N°261982; DASISH: GA N°283646), and Horizon 2020 (SHARE-DEV3: GA N°676536; SHARE-COHESION: GA N°870628; SERISS: GA N°654221; SSHOC: GA N°823782) and by DG Employment, Social Affairs & Inclusion. Additional funding from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, the US National Institute on Aging (U01_AG09740-13S2; P01_AG005842; P01_AG08291; P30_AG12815; R21_AG025169; Y1-AG-4553-01; IAG_BSR06-11; OGHA_04-064; HHSN271201300071C), and from various national funding sources is gratefully acknowledged. PC acknowledges support by the French National Agency for HIV, hepatitis and emerging infectious diseases research (ANRS / EMERGING INFECTIOUS DISEASES).
Published: 2022
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46. Plasma Membrane Phosphatidylinositol-4-Phosphate Is Not Necessary for Candida albicans Viability yet Is Key for Cell Wall Integrity and Systemic Infection

Author: Rocio Garcia-Rodas, Hayet Labbaoui, François Orange, Norma Solis, Oscar Zaragoza, Scott G. Filler, Martine Bassilana, Robert A. Arkowitz, Ministerio de Ciencia e Innovación (España), Université Côte d'Azur (Francia), Agence Nationale de la Recherche (Francia), National Institutes of Health (Estados Unidos), Institut Curie, Institut National de la Santé et de la Recherche Médicale (Francia), Centre National de la Recherche Scientifique (Francia), Heitman, Joseph, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Commun de Microscopie Appliquée (CCMA), Université de Nice Sophia-Antipolis (UNSA), Harbor UCLA Medical Center [Torrance, Ca.], Institute of Health Carlos III, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), and Arkowitz, Robert
Subjects: [SDV]Life Sciences [q-bio], Hyphae, filamentous growth, Microbiology, Fungal Proteins, Vaccine Related, opportunistic fungi, Mice, Virology, Biodefense, Candida albicans, Animals, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, phosphatidylinositol phosphates, Dental/Oral and Craniofacial Disease, Aetiology, phospholipids, Phospholipids, Filamentous growth, Virulence, Animal, Prevention, Cell wall, Opportunistic fungi, Phosphatidylinositol phosphates, Cell Membrane, Candidiasis, virulence, [SDV] Life Sciences [q-bio], Infectious Diseases, Emerging Infectious Diseases, Disease Models, cell wall, Infection
Abstract: Phosphatidylinositol phosphates are key phospholipids with a range of regulatory roles, including membrane trafficking and cell polarity. Phosphatidylinositol-4-phosphate [PI(4)P] at the Golgi is required for the budding to filamentous growth transition in the human pathogenic fungus Candida albicans, however the role of plasma membrane PI(4)P is unclear. We have investigated the importance of this phospholipid in C. albicans growth, stress response, and virulence by generating mutant strains with decreased levels of plasma membrane PI(4)P, via deletion of components of the PI-4-kinase complex, i.e. Efr3, Ypp1 and Stt4. The amount of plasma membrane PI(4)P in the efr3Δ/Δ and ypp1Δ/Δ mutant was ∼60% and ∼40% of the wild-type strain, respectively, whereas it was nearly undetectable in the stt4Δ/Δ mutant. All three mutants had reduced plasma membrane phosphatidylserine (PS). Although these mutants had normal yeast phase growth, they were defective in filamentous growth, exhibited defects in cell wall integrity and had an increased exposure of cell wall β(1,3)-glucan, yet they induced a range of hyphal specific genes. In a mouse model of hematogenously disseminated candidiasis, fungal plasma membrane PI(4)P levels directly correlated with virulence; the efr3Δ/Δ had wild-type virulence, the ypp1Δ/Δ mutant had attenuated virulence and the stt4Δ/Δ mutant caused no lethality. In the mouse model of orpharyngeal candidiasis, only the ypp1Δ/Δ mutant had reduced virulence, indicating that plasma membrane PI(4)P is less important for proliferation in the oropharynx. Collectively, these results demonstrate that plasma membrane PI(4)P levels play a central role in filamentation, cell wall integrity and virulence in C. albicans.ImportanceWhile the PI-4-kinases Pik1 and Stt4 both produce PI(4)P, the former generates PI(4)P at the Golgi and the latter at the plasma membrane and these two pools are functionally distinct. To address the importance of plasma membrane PI(4)P in Candida albicans, we have generated deletion mutants of the three putative plasma membrane PI-4-kinase complex components and quantified the levels of plasma membrane PI(4)P in each of these strains. Our work reveals that this phosphatidylinositol phosphate is specifically critical for the yeast-to-hyphal transition, cell wall integrity and virulence in a mouse systemic infection model. The significance of this work is in identifying a plasma membrane phospholipid that has an infection specific role, which is attributed to the loss of plasma membrane PI(4)P resulting in β(1,3)-glucan unmasking.
Published: 2022
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47. Influenza vaccine effectiveness against influenza A subtypes in Europe: Results from the 2021–2022 I‐MOVE primary care multicentre study

Author: Kissling, Esther, Pozo, Francisco, Martínez‐Baz, Iván, Buda, Silke, Vilcu, Ana‐Maria, Domegan, Lisa, Mazagatos, Clara, Dijkstra, Frederika, Latorre‐Margalef, Neus, Kurečić Filipović, Sanja, Machado, Ausenda, Lazar, Mihaela, Casado, Itziar, Dürrwald, Ralf, van der Werf, Sylvie, O'Donnell, Joan, Linares Dopido, Juan Antonio, Meijer, Adam, Riess, Maximilian, Višekruna Vučina, Vesna, Rodrigues, Ana Paula, Mihai, Maria Elena, Castilla, Jesús, Goerlitz, Luise, Falchi, Alessandra, Connell, Jeff, Castrillejo, Daniel, Hooiveld, Mariette, Carnahan, Annasara, Ilić, Maja, Guiomar, Raquel, Ivanciuc, Alina, Maurel, Marine, Omokanye, Ajibola, Valenciano, Marta, I‐MOVE study team, European Centre for Disease Prevention and Control, EpiConcept [Paris], Institute of Health Carlos III, CIBER de Epidemiología y Salud Pública (CIBERESP), Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA)-Universidad de Navarra [Pamplona] (UNAV)-Clínica Universidad de Navarra [Pamplona], Robert Koch Institute [Berlin] (RKI), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Health Service Executive [Dublin] (HSE), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Kalmar, Croatian Institute of Public Health [Zagreb] (CIPH), Cantacuzino Institute [Romania], Réseau International des Instituts Pasteur (RIIP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Dirección General de Salud Pública, Public Health Agency of Sweden, Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Cantacuzino National Medico-Military Institute for Research Development [Bucharest], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Università di Corsica Pasquale Paoli [Université de Corse Pascal Paoli], Partenaires INRAE, University College Dublin [Dublin] (UCD), School of Social Sciences. Campus de Melilla. Univeristy of Granada, Netherlands Institute for Health Services Research [Utrecht] (NIVEL), European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), and tudy teams are very grateful to all patients, general practitioners, paediatricians, laboratory teams, and regional epidemiologists who have contributed to the studies. Participating laboratories submitted their sequences to GISAID (www.gisaid.org) for easy sharing with the central laboratory in Madrid. We would like to acknowledge Mia Brytting, who sadly passed away before publication. She is deeply missed.
Subjects: Pulmonary and Respiratory Medicine, Male, Adult, Adolescent, Epidemiology, [SDV]Life Sciences [q-bio], Vaccine Efficacy, Multicentre study, Young Adult, Influenza A Virus, H1N1 Subtype, Influenza, Human, Humans, Europe, influenza, influenza vaccine, multicentre study, vaccine effectiveness, Child, Aged, Vaccine effectiveness, Primary Health Care, Influenza vaccine, Influenza A Virus, H3N2 Subtype, Vaccination, Public Health, Environmental and Occupational Health, Infant, Newborn, Infant, Middle Aged, vaccine effectiveness, multicentre study, Influenza, Europe, Infectious Diseases, Influenza Vaccines, Case-Control Studies, Child, Preschool, Female, influenza vaccine, influenza
Abstract: Background: In 2021-2022, influenza A viruses dominated in Europe. The I-MOVE primary care network conducted a multicentre test-negative study to measure influenza vaccine effectiveness (VE). Methods: Primary care practitioners collected information on patients presenting with acute respiratory infection. Cases were influenza A(H3N2) or A(H1N1)pdm09 RT-PCR positive, and controls were influenza virus negative. We calculated VE using logistic regression, adjusting for study site, age, sex, onset date, and presence of chronic conditions. Results: Between week 40 2021 and week 20 2022, we included over 11 000 patients of whom 253 and 1595 were positive for influenza A(H1N1)pdm09 and A(H3N2), respectively. Overall VE against influenza A(H1N1)pdm09 was 75% (95% CI: 43-89) and 81% (95% CI: 45-93) among those aged 15-64 years. Overall VE against influenza A(H3N2) was 29% (95% CI: 12-42) and 25% (95% CI: -41 to 61), 33% (95% CI: 14-49), and 26% (95% CI: -22 to 55) among those aged 0-14, 15-64, and over 65 years, respectively. The A(H3N2) VE among the influenza vaccination target group was 20% (95% CI: -6 to 39). All 53 sequenced A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.1. Among 410 sequenced influenza A(H3N2) viruses, all but eight belonged to clade 3C.2a1b.2a.2. Discussion: Despite antigenic mismatch between vaccine and circulating strains for influenza A(H3N2) and A(H1N1)pdm09, 2021-2022 VE estimates against circulating influenza A(H1N1)pdm09 were the highest within the I-MOVE network since the 2009 influenza pandemic. VE against A(H3N2) was lower than A(H1N1)pdm09, but at least one in five individuals vaccinated against influenza were protected against presentation to primary care with laboratory-confirmed influenza. This project has received funding from the European Centre for Disease Prevention and Control with in the framework contract ECDC/2018/029. Sí
Published: 2022
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48. Cardiac remodelling - Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology

Author: Arantxa González, A. Mark Richards, Rudolf A. de Boer, Thomas Thum, Henrike Arfsten, Martin Hülsmann, Inês Falcao‐Pires, Javier Díez, Roger S.Y. Foo, Mark Y. Chan, Alberto Aimo, Chukwuemeka G. Anene‐Nzelu, Magdy Abdelhamid, Stamatis Adamopoulos, Stefan D. Anker, Yuri Belenkov, Tuvia Ben Gal, Alain Cohen‐Solal, Michael Böhm, Ovidiu Chioncel, Victoria Delgado, Michele Emdin, Ewa A. Jankowska, Finn Gustafsson, Loreena Hill, Tiny Jaarsma, James L. Januzzi, Pardeep S. Jhund, Yuri Lopatin, Lars H. Lund, Marco Metra, Davor Milicic, Brenda Moura, Christian Mueller, Wilfried Mullens, Julio Núñez, Massimo F. Piepoli, Amina Rakisheva, Arsen D. Ristić, Patrick Rossignol, Gianluigi Savarese, Carlo G. Tocchetti, Sophie Van Linthout, Maurizio Volterrani, Petar Seferovic, Giuseppe Rosano, Andrew J.S. Coats, Antoni Bayés‐Genís, Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV), Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA)-Universidad de Navarra [Pamplona] (UNAV)-Clínica Universidad de Navarra [Pamplona], Instituto de Salud Carlos III [Madrid] (ISC), Yong Loo Lin School of Medicine [Singapore], National University of Singapore (NUS), University of Otago [Dunedin, Nouvelle-Zélande], University Medical Center Groningen [Groningen] (UMCG), Hannover Medical School [Hannover] (MHH), Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM), Fraunhofer (Fraunhofer-Gesellschaft), Medizinische Universität Wien = Medical University of Vienna, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Departments of Cardiology and Cardiac Surgery, and Nephrology, Clínica Universidad de Navarra, Clínica Universidad de Navarra [Pamplona], Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP), Fondazione Toscana Gabriele Monasterio, Montreal Heart Institute - Institut de Cardiologie de Montréal, Cairo University - Faculty of Medicine, Onassis Cardiac Surgery Center [Athens] (OCSC), Charité Campus Virchow-Klinikum (CVK), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Université d'État Lomonossov de Moscou = Lomonosov Moscow State University (MSU), Cardiology Department, Rabin Medical Center, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Saarland University Hospital (UKS), Emergency Institute for Cardiovascular Diseases 'Prof. Dr. C.C. Iliescu' [Bucharest, Romania], Leiden University Medical Center (LUMC), Wrocław Medical University, Hôpital national = Rigshospitalet [Copenhagen, Denmark] (HNC), Queen's University [Belfast] (QUB), Linköping University (LIU), Massachusetts General Hospital [Boston], Baim Institute for Clinical Research Boston MA, British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Volgograd State Medical University [Russian Federation] (VSMU), Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Università degli Studi di Brescia = University of Brescia (UniBs), University of Zagreb, Cardiology Department, Porto Armed Forces Hospital, University Hospital Basel [Basel], Ziekenhuis Oost-Limburg (ZOL), Universitat de València (UV), Hospital Clínico Universitario de Valencia, Cardiology Division, Castelsangiovanni Hospital, Scientific Research Institute of Cardiology and Internal Medicine [Almaty, Kazakhstan], University Clinical Centre of Serbia, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Naples Federico II = Università degli studi di Napoli Federico II, IRCCS Ospedale San Raffaele [Milan, Italy], Serbian Academy of Sciences and Arts (SASA), University of Belgrade [Belgrade], St George’s University Hospitals, University of Warwick [Coventry], Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Universitat Autònoma de Barcelona (UAB), This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities Institute of Health Carlos III (ISCIII) (PI18/01469 and PI21/00946 to A.G., CB16/11/00403 to A.B.-G and CB16/11/00483 to J.D. projects co-funded by the European Regional Development Funds), the European Commission (H2020 CRUCIAL project 2019–848109-2 to A.G.), the European Research Council (ERC CoG 818715 to R.A.d.B., ERC-PoC Megfib to T.T.), the National Medical Research Council of Singapore (NMRC, NMRC/STaR/0022/2014 to A.M.R. and MOH-000280 to M.Y.C.), the Health Research Council of New Zealand (02/152, 08/070, 11/1070), National Heart Foundation of New Zealand, New Zealand Lotteries Grant Board, Foundation for Research, Science and Technology and the Christchurch Heart Institute Trust to A.M.R., the Netherlands Heart Foundation (2017-21, 2017-11, 2018-30, 2020B005) to R.A.d.B., the leDucq Foundation (Cure-PLaN) to R.A.d.B., the Deutsche Forschungsgemeinschaft (KFO311 and TRR267 to T.T., TTR 219 to M.B., and TRR 1470 to S.V.L.), the Karolinska Institutet, the Swedish Research Council (523–2014-2336), the Swedish Heart Lung Foundation (20150557, 20190310), and the Stockholm County Council (20170112, 20190525) to L.H.L., European Project, BOZEC, Erwan, H2020 CRUCIAL project 2019–848109-2 - INCOMING, and Universiteit Leiden
Subjects: Heart Failure, Tissue, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Biomarkers, Cells, Remodeling, Endothelial Cells, Humans, Ventricular Remodeling, Cardiology, Cardiology and Cardiovascular Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.
Published: 2022
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49. Resilience of people with chronic medical conditions during the COVID-19 pandemic: a 1-year longitudinal prospective survey

Author: Lorenzo Tarsitani, Irene Pinucci, Federico Tedeschi, Martina Patanè, Davide Papola, Christina Palantza, Ceren Acarturk, Emma Björkenstam, Richard Bryant, Sebastian Burchert, Camille Davisse-Paturet, Amanda Díaz-García, Rachel Farrel, Daniela C. Fuhr, Brian J. Hall, Anja C. Huizink, Agnes Iok Fong Lam, Gülşah Kurt, Ingmar Leijen, Ellenor Mittendorfer-Rutz, Naser Morina, Catherine Panter-Brick, Fredrick Dermawan Purba, Soledad Quero, Soraya Seedat, Hari Setyowibowo, Judith van der Waerden, Massimo Pasquini, Marit Sijbrandij, Corrado Barbui, Clinical Psychology, World Health Organization (WHO) Collaborating Center, Clinical, Neuro- & Developmental Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Marketing, Acartürk, Zeynep Ceren (ORCID 0000-0001-7093-1554 & YÖK ID 39271), Kurt, Gülşah, Tarsitani, L., Pinucci, Irenea, Tedeschi, Federico, Patanè, Martina, Papola, Davide, Palantza, Christina, Björkenstam, Emma, Bryant, Richard, Burchert, Sebastian, Davisse-Paturet, Camilleh, Díaz-García, Amandai Farrel, Rachel, Fuhr, Daniela C., Hall, Brian J.l, Huizink, Anja C., Lam, Agnes Iok Fongo, Leijen, Ingmar, Mittendorfer-Rutz, Ellenor, Morina, Naser, Panter-Brick, Catherine, Purba, Fredrick Dermawan, Quero, Soledad, Seedat, Soraya, Setyowibowo, Hari, van der Waerden, Judith, Pasquini, Massimo, Sijbrandij, Marit, Barbui, Corrado, College of Social Sciences and Humanities, Department of Psychology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Vrije Universiteit Amsterdam [Amsterdam] (VU), Università degli studi di Verona = University of Verona (UNIVR), Koç University, Karolinska Institutet [Stockholm], University of New South Wales [Sydney] (UNSW), Freie Universität Berlin, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Yale University [New Haven], London School of Hygiene and Tropical Medicine (LSHTM), New York University [Shanghai], NYU System (NYU), New York University [New York] (NYU), University of Macau (UMac), Universität Zürich [Zürich] = University of Zurich (UZH), Universitas Padjadjaran (UnPad), Universitat Jaume I, Institute of Health Carlos III, Stellenbosch University, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Male, MESH: Pandemics, MESH: Loneliness, SDG 16 - Peace, MESH: Depression, COVID-19 pandemic, Anxiety, Stress, Chronic medical conditions, MESH: COVID-19, Humans, Prospective Studies, 100 Philosophie und Psychologie::150 Psychologie::150 Psychologie, Pandemics, Psychiatry, MESH: Humans, MESH: Anxiety, Resilience, Depression, MESH: Chronic Disease, Loneliness, SDG 16 - Peace, Justice and Strong Institutions, COVID-19, MESH: Male, MESH: Prospective Studies, Justice and Strong Institutions, Psychiatry and Mental health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SCCO.PSYC]Cognitive science/Psychology, [SCCO.PSYC] Cognitive science/Psychology, Chronic Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Backgrounds: individuals with chronic medical conditions are considered highly exposed to COVID-19 pandemic stress, but emerging evidence is demonstrating that resilience is common even among them. We aimed at identifying sustained resilient outcomes and their predictors in chronically ill people during the first year of the pandemic. Methods: this international 4-wave 1-year longitudinal online survey included items on socio-demographic characteristics, economic and living situation, lifestyle and habits, pandemic-related issues, and history of mental disorders. Adherence to and approval of imposed restrictions, trust in governments and in scientific community during the pandemic were also investigated. The following tools were administered: the Patient Health Questionnaire, the Generalized Anxiety Disorder scale, the PTSD Checklist DSM-5, the Oslo Social Support Scale, the Padua Inventory, and the Portrait Values Questionnaire. Results: one thousand fifty-two individuals reporting a chronic condition out of 8011 total participants from 13 countries were included in the study, and 965 had data available for the final model. The estimated probability of being "sustained-resilient" was 34%. Older male individuals, participants employed before and during the pandemic or with perceived social support were more likely to belong to the sustained-resilience group. Loneliness, a previous mental disorder, high hedonism, fear of COVID-19 contamination, concern for the health of loved ones, and non-approving pandemic restrictions were predictors of not-resilient outcomes in our sample. Conclusions: we found similarities and differences from established predictors of resilience and identified some new ones specific to pandemics. Further investigation is warranted and could inform the design of resilience-building interventions in people with chronic diseases., NA
Published: 2022
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50. Dietary fatty acids, macronutrient substitutions, food sources and incidence of coronary heart disease: Findings from the EPIC-CVD case-cohort study across nine european countries

Author: Matthias B. Schulze, Vittorio Krogh, Rosario Tumino, Nita G. Forouhi, Christina C. Dahm, Kim Overvad, Marie-Christine Boutron-Ruault, Angela M. Wood, Yvonne T. van der Schouw, Guri Skeie, Laura Johnson, Fumiaki Imamura, Ivonne Sluijs, José R Quirós, Elisabete Weiderpass, Nicholas J. Wareham, Timothy J. Key, Adam S. Butterworth, Giovanna Masala, Alicia K Heath, Albert Koulman, Conchi Moreno-Iribas, Inge Huybrechts, John Danesh, Stephen J. Sharp, Salvatore Panico, Carlotta Sacerdote, Aurora Perez-Cornago, Olle Melander, Rudolf Kaaks, Elio Riboli, Tammy Y.N. Tong, María José Sánchez, Rajiv Chowdhury, Ju-Sheng Zheng, Miguel Rodríguez-Barranco, W M Monique Verschuren, Marinka Steur, Ingegerd Johansson, Heiner Boeing, Anne Tjønneland, Carmen Santiuste, Antonia Trichopoulou, Maria Wennberg, Jolanda M. A. Boer, Marcela Guevara, Cecilie Kyrø, Raul Zamora-Ros, Liher Imaz, Tilman Kühn, Marianne Uhre Jakobsen, Ulrika Ericson, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, G0800270, MR/L003120/1, Pfizer, AstraZeneca, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, Merck Sharp and Dohme, MSD, Seventh Framework Programme, FP7: HEALTH-F2-2012-279233, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MC_UU_00006/1, National Institute for Health Research, NIHR, British Heart Foundation, BHF: RG/18/13/33946, RG13/13/30194, SP/09/002, Cancer Research UK, CRUK: C8221/A29017, MR/M012190/1, World Cancer Research Fund, WCRF, Imperial College London, European Research Council, ERC: 268834, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, European Social Fund, ESF, Sixth Framework Programme, FP6: LSHM_CT_2006_037197, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Akademi Sains Malaysia, ASM: MR/P013880/1, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, UCLH Biomedical Research Centre, NIHR BRC: BRC-1215-20014, NIHR Imperial Biomedical Research Centre, BRC, Hellenic Health Foundation, HHF: CP15/00100, IS-BRC-1215-20014, MC_UU_00006/3, Dr Danesh reports grants, personal fees and non-financial support from Merck Sharp & Dohme, grants, personal fees, and nonfinancial support from Novartis, grants from Pfizer, and grants from AstraZeneca outside the submitted work. He is member of the International Cardiovascular and Metabolic Advisory Board for Novartis (since 2010), the Steering Committee of UK Biobank (since 2011), the MRC International Advisory Group (ING) member, London (since 2013), the MRC High Throughput Science ‘Omics Panel Member, London (since 2013), the Scientific Advisory Committee for Sanofi (since 2013), the International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis, and the Astra Zeneca Genomics Advisory Board (2018). Dr Butterworth reports grants outside of this work from AstraZeneca, Biogen, BioMarin, Bioverativ, Merck, Novartis, Pfizer, and Sanofi and personal fees from Novartis. The remaining authors have no disclosures to report., EPIC-CVD was supported by the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the European Research Council (268834). The coordinating center was supported by core funding from the: United Kingdom MRC (G0800270, MR/L003120/1), British Heart Foundation (BHF) (SP/09/002, RG13/13/30194, RG/18/13/33946), and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) (BRC-1215-20014).* The establishment of the study subcohort was supported by the European Union Sixth Framework Programme (grant LSHM_CT_2006_037197 to the InterAct project) and the MRC Epidemiology Unit (grant MC_UU_00006/1). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by NIHR Imperial BRC. The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands), Health Research Fund– Instituto de Salud Carlos III, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), MRC (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). EPIC-Greece was supported by the Hellenic Health Foundation (Greece). M.S., N.J.W., N.G.F., and F.I. acknowledge support from MRC Epidemiology Unit (MC_UU_00006/1 and MC_UU_00006/3). N.J.W. and N.G.F. acknowledge support from NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014) and NGF is a NIHR Senior Investigator Award holder. M.S. was also supported by BHF for part of this work while working in the BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. R.Z.-R. thanks the 'Miguel Servet' program (CP15/00100) from the Institute of Health Carlos III (co-funded by the European Social Fund–European Social Fund Investing in Your Future). A.W. was supported by a BHF-Turing Cardiovascular Data Science Award and by the European Commission-Innovative Medicines Initiative (BigData@Heart). R.C. was funded by a MRC-Newton project grant to study genetic risk factors of cardiovascular disease among Southeast Asian people and the Academy of Sciences Malaysia (grant no. MR/P013880/1) and a United Kingdom Research and Innovation-Global Challenges Research Fund Project Grant to study risk factors of noncommunicable diseases in Bangladesh. J.D. holds a BHF Professorship and a NIHR Senior Investigator Award., Steur, Marinka [0000-0002-9028-0290], Imamura, Fumiaki [0000-0002-6841-8396], Key, Timothy J [0000-0003-2294-307X], Chowdhury, Rajiv [0000-0003-4881-5690], Guevara, Marcela [0000-0001-9242-6364], Jakobsen, Marianne U [0000-0001-6518-4136], Johansson, Ingegerd [0000-0002-9227-8434], Weiderpass, Elisabete [0000-0003-2237-0128], Boer, Jolanda MA [0000-0002-9714-4304], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Heath, Alicia K [0000-0001-6517-1300], Huybrechts, Inge [0000-0003-3838-855X], Imaz, Liher [0000-0002-3777-4953], Masala, Giovanna [0000-0002-5758-9069], Zamora-Ros, Raul [0000-0002-6236-6804], Perez-Cornago, Aurora [0000-0002-5652-356X], Tong, Tammy YN [0000-0002-0284-8959], Wareham, Nicholas J [0000-0003-1422-2993], Forouhi, Nita G [0000-0002-5041-248X], and Apollo - University of Cambridge Repository
Subjects: Saturated fat, Physiology, Coronary Disease, 030204 cardiovascular system & hematology, EPIC, Cohort Studies, 0302 clinical medicine, Medicine, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, 1102 Cardiorespiratory Medicine and Haematology, 2. Zero hunger, chemistry.chemical_classification, Nutrition and Dietetics, Kardiologi, Primary prevention, Incidence, Incidence (epidemiology), Fatty Acids, Fatty acids in human nutrition, 3. Good health, Europe, Näringslära, Coronary heart disease, Dietary guidelines, Cardiology and Cardiovascular Medicine, Polyunsaturated fatty acid, Cohort study, Malalties coronàries, 03 medical and health sciences, SDG 3 - Good Health and Well-being, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Àcids grassos en la nutrició, Diseases of the circulatory (Cardiovascular) system, Humans, Nutritional epidemiology, business.industry, Nutrients, Dietary Fats, chemistry, Food, RC666-701, SPS Exercise, Nutrition and Health Sciences, business
Abstract: EPIC-CVD was supported by the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the European Research Council (268834). The coordinating center was supported by core funding from the: United Kingdom MRC (G0800270; MR/L003120/1), British Heart Foundation (BHF) (SP/09/002; RG13/13/30194; RG/18/13/33946), and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) (BRC-1215-20014).* The establishment of the study subcohort was supported by the European Union Sixth Framework Programme (grant LSHM_CT_ 2006_037197 to the InterAct project) and the MRC Epidemiology Unit (grant MC_UU_00006/1). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by NIHR Imperial BRC. The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France); German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany); Associazione Italiana per la Ricerca sul Cancro--AIRC--Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands); Health Research Fund-Instituto de Salud Carlos III, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), MRC (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). EPIC-Greece was supported by the Hellenic Health Foundation (Greece). M.S., N.J.W., N.G.F., and F.I. acknowledge support from MRC Epidemiology Unit (MC_UU_ 00006/1 and MC_UU_00006/3). N.J.W. and N.G.F. acknowledge support from NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215--20014) and NGF is a NIHR Senior Investigator Award holder. M.S. was also supported by BHF for part of this work while working in the BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. R. Z.-R. thanks the "Miguel Servet" program (CP15/00100) from the Institute of Health Carlos III (co-funded by the European Social Fund--European Social Fund Investing in Your Future). A.W. was supported by a BHF-Turing Cardiovascular Data Science Award and by the European Commission-Innovative Medicines Initiative (BigData@Heart).R.C.was funded by a MRC-Newton project grant to study genetic risk factors of cardiovascular disease among Southeast Asian people and the Academy of Sciences Malaysia (grant no. MR/P013880/1) and a United Kingdom Research and Innovation-Global Challenges Research Fund Project Grant to study risk factors of noncommunicable diseases in Bangladesh. J.D. holds a BHF Professorship and a NIHR Senior Investigator Award. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization. The funders of the study had no role in study design, data collection, analysis, data interpretation, or writing of the article, or in the decision to submit for publication. M.S. had full access to all the data in the study, and M.S. and N.G.F. had final responsibility for the decision to submit for publication., BACKGROUND: There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. METHODS AND RESULTS: We conducted a case-cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country-specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice-weighted Cox regression models and pooled results using random-effects meta-analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88–0.99]), cheese (HR, 0.98 [95% CI, 0.96–1.00]), and fish (HR, 0.87 [95% CI, 0.75–1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02–1.12]) and butter (HR, 1.02 [95% CI, 1.00–1.04]). CONCLUSIONS: This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix., European Commission Framework Programme 7 HEALTH-F2-2012-279233, European Research Council (ERC), European Commission 268834, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) G0800270 MR/L003120/1, British Heart Foundation SP/09/002 RG13/13/30194 RG/18/13/33946, National Institute for Health Research (NIHR) BRC-1215-20014, European Commission LSHM_CT_ 2006_037197, Medical Research Council UK (MRC) MC_UU_ 00006/1 MC_UU_00006/3, International Agency for Research on Cancer, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam, Rehbruecke, Federal Ministry of Education and Research (Germany), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund International (WCRF), Netherlands Government, Instituto de Salud Carlos III, Junta de Andalucia, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Catalan Institute of Oncology (Spain), Swedish Cancer Society, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, Medical Research Council UK (MRC) 1000143 MR/M012190/1, Hellenic Health Foundation (Greece), NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme IS-BRC-1215-20014, British Heart Foundation, Institute of Health Carlos III (European Social Fund-European Social Fund Investing in Your Future) CP15/00100, BHF-Turing Cardiovascular Data Science Award, European Commission-Innovative Medicines Initiative (BigData@Heart), MRC-Newton project grant MR/P013880/1, United Kingdom Research and Innovation-Global Challenges Research Fund, NIHR Senior Investigator Award
Published: 2021
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