An open secret in porcine acute myocardial infarction models: The relevance of anaesthetic regime and breed in ischaemic outcomes.

Large animal models of acute myocardial infarction (AMI) play a crucial role in translating novel therapeutic approaches to patients as denoted by their use in the right-before-human testing platform. At present, the porcine model of AMI is used most frequently as it mimics the human condition and its anatomopathological features accurately. We want to describe to, and share with, the translational research community our experience of how different anaesthetic protocols (sevoflurane, midazolam, ketamine+xylazine+midazolam, and propofol) and pig breeds [Large White and Landrace x Large White (LLW)] can dramatically modify the outcomes of a well-established porcine model of closed-chest AMI. Our group has extensive experience with the porcine model of reperfused AMI and, over time, we reduced the time of ischaemia used to induce the disease from 90 to 50 min to increase the salvageable myocardium for cardioprotection studies. For logistical reasons, we changed both the anaesthetic protocol and the pig breed used, but these resulted in a dramatic reduction in the size of the myocardial infarct, to almost zero in some cases (sevoflurane, 50-min ischaemia, LLW, 2.4 ± 3.9% infarct size), and the cardiac function was preserved. Therefore, we had to re-validate the model by returning to 90 min of ischaemia. Here, we report the differences in infarct size and cardiac function, measured by different modalities, for each combination of anaesthetic protocol and pig breed we have used. Furthermore, we discuss these combinations and the limited literature pertaining to how these two factors influence cardiac function and infarct size in the porcine model of AMI.This research was funded by a grant (PI18/00277) from Instituto de Salud Carlos III (ISCIII), Spain—Fondo Europeo de Desarrollo Regional (FEDER). FJ is the recipient of the Ayudas para la formación de profesorado Universitario (FPU19/04925) grant from the Spanish Ministry of Science and Innovation. IDIBAPS belongs to the CERCA Programme and receives partial funding from the Generalitat de Catalunya.S

Practical guideline for Benign paroxismal positional vertigo

Introduction and objective: Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vertigo, characterized by brief attacks of rotatory vertigo associated with nystagmus, which are elicited by specific changes in head position relative to gravity. The observation of positional nystagmus is essential for the diagnosis of BPPV. The treatment consists in maneuvers of canalith repositioning procedure to move otoconial debris from the affected semicircular canal to the utricle. These guidelines are intended for all who treat the BPPV in their work, with an intention to assist in the diagnosis and application of an appropriate therapeutic method. Method: The experience and analysis of different national and international consensus on BPPV, has allowed to a large group of ENT specialists of the Communities of Castilla y León, Cantabria and La Rioja (Spain), carry out this guide. Results: The different clinical entities are reviewed. BPPV of the posterior semicircular canal, horizontal canal and anterior canal, BPPV affecting several canals, atypical and central BPPV, subjective BPPV and the characteristics of this process in the elderly. Canalith repositioning procedures have been illustrated with explanatory drawings. Discussion and conclusions: Although the pathophysiology of BPPV is canalolithiasis comprising free-floating otoconial debris within the endolymph of a semicircular canal, or cupulolithiasis comprising otoconial debris adherent to the cupula, there are still many issues to be resolved. We think that the best way to find answers is part of using a common methodology in the diagnosis and treatment of these patients.Introducción y Objetivo: El vértigo periférico más frecuente es el Vértigo Posicional Paroxístico Benigno (VPPB), caracterizado por bruscos ataques de sensación rotatoria, que aparecen como consecuencia de determinados cambios en la posición de la cabeza con relación a la gravedad. La observación del nistagmo posicional es fundamental para el diagnóstico de VPPB. El tratamiento consiste en aplicar maniobras de reposición, para intentar trasladar los restos otoconiales libres, desde el conducto semicircular (CS) afectado hasta el utrículo. Esta guía, está orientada para quienes tratan el VPPB, con la intención práctica de ayudarles en el diagnóstico y tratamiento de esta enfermedad. Método: La experiencia y el análisis de diferentes acuerdos nacionales e internacionales sobre el VPPB, han permitido a un amplio grupo de especialistas ORL de las Comunidades de Castilla y León, Cantabria y La Rioja (España), llevar a cabo esta guía. Resultados: Se revisan las diferentes entidades clínicas. VPPB del conducto semicircular posterior (CSP), horizontal (CSA) y anterior (CSA), incluyéndose también el VPPB multicanal, VPPB atípico y central, VPPB subjetivo y las características de este proceso en el anciano. Las maniobras de reposición se han ilustrado con dibujos explicativos. Discusión y conclusiones: Aunque la fisiopatología del VPPB se explica por la presencia de restos otoconiales libres en la endolinfa de uno o varios conductos semicirculares (canalitiasis) y en algunos casos por su adherencia a la cúpula del CS (cupulolitiasis), aún quedan muchas cuestiones por resolver. Pero creemos que la mejor manera de encontrar respuestas parte de utilizar una metodología común en el diagnóstico y tratamiento de estos pacientes

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design

Introduction: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Methods: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. Discussion: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.The study was partially funded by the “Accion Transversal del Cancer”, approved on 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, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), 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 European Commission grants FOOD-CT- 2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the The Catalan Government DURSI grant 2009SGR1489

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Detailed stratified GWAS analysis for severe COVID-19 in four European populations

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.S.E.H. and C.A.S. partially supported genotyping through a philanthropic donation. A.F. and D.E. were supported by a grant from the German Federal Ministry of Education and COVID-19 grant Research (BMBF; ID:01KI20197); A.F., D.E. and F.D. were supported by the Deutsche Forschungsgemeinschaft Cluster of Excellence ‘Precision Medicine in Chronic Inflammation’ (EXC2167). D.E. was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences funding concept (CompLS grant 031L0165). D.E., K.B. and S.B. acknowledge the Novo Nordisk Foundation (NNF14CC0001 and NNF17OC0027594). T.L.L., A.T. and O.Ö. were funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project numbers 279645989; 433116033; 437857095. M.W. and H.E. are supported by the German Research Foundation (DFG) through the Research Training Group 1743, ‘Genes, Environment and Inflammation’. L.V. received funding from: Ricerca Finalizzata Ministero della Salute (RF-2016-02364358), Italian Ministry of Health ‘CV PREVITAL’—strategie di prevenzione primaria cardiovascolare primaria nella popolazione italiana; The European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- and for the project ‘REVEAL’; Fondazione IRCCS Ca’ Granda ‘Ricerca corrente’, Fondazione Sviluppo Ca’ Granda ‘Liver-BIBLE’ (PR-0391), Fondazione IRCCS Ca’ Granda ‘5permille’ ‘COVID-19 Biobank’ (RC100017A). A.B. was supported by a grant from Fondazione Cariplo to Fondazione Tettamanti: ‘Bio-banking of Covid-19 patient samples to support national and international research (Covid-Bank). This research was partly funded by an MIUR grant to the Department of Medical Sciences, under the program ‘Dipartimenti di Eccellenza 2018–2022’. This study makes use of data generated by the GCAT-Genomes for Life. Cohort study of the Genomes of Catalonia, Fundació IGTP (The Institute for Health Science Research Germans Trias i Pujol) IGTP is part of the CERCA Program/Generalitat de Catalunya. GCAT is supported by Acción de Dinamización del ISCIII-MINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026); the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529). M.M. received research funding from grant PI19/00335 Acción Estratégica en Salud, integrated in the Spanish National RDI Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (European Regional Development Fund (FEDER)-Una manera de hacer Europa’). B.C. is supported by national grants PI18/01512. X.F. is supported by the VEIS project (001-P-001647) (co-funded by the European Regional Development Fund (ERDF), ‘A way to build Europe’). Additional data included in this study were obtained in part by the COVICAT Study Group (Cohort Covid de Catalunya) supported by IsGlobal and IGTP, European Institute of Innovation & Technology (EIT), a body of the European Union, COVID-19 Rapid Response activity 73A and SR20-01024 La Caixa Foundation. A.J. and S.M. were supported by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36). A.J. was also supported by national grant PI17/00019 from the Acción Estratégica en Salud (ISCIII) and the European Regional Development Fund (FEDER). The Basque Biobank, a hospital-related platform that also involves all Osakidetza health centres, the Basque government’s Department of Health and Onkologikoa, is operated by the Basque Foundation for Health Innovation and Research-BIOEF. M.C. received Grants BFU2016-77244-R and PID2019-107836RB-I00 funded by the Agencia Estatal de Investigación (AEI, Spain) and the European Regional Development Fund (FEDER, EU). M.R.G., J.A.H., R.G.D. and D.M.M. are supported by the ‘Spanish Ministry of Economy, Innovation and Competition, the Instituto de Salud Carlos III’ (PI19/01404, PI16/01842, PI19/00589, PI17/00535 and GLD19/00100) and by the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018, COVID-Premed, COVID GWAs). The position held by Itziar de Rojas Salarich is funded by grant FI20/00215, PFIS Contratos Predoctorales de Formación en Investigación en Salud. Enrique Calderón’s team is supported by CIBER of Epidemiology and Public Health (CIBERESP), ‘Instituto de Salud Carlos III’. J.C.H. reports grants from Research Council of Norway grant no 312780 during the conduct of the study. E.S. reports grants from Research Council of Norway grant no. 312769. The BioMaterialBank Nord is supported by the German Center for Lung Research (DZL), Airway Research Center North (ARCN). The BioMaterialBank Nord is member of popgen 2.0 network (P2N). P.K. Bergisch Gladbach, Germany and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany. He is supported by the German Federal Ministry of Education and Research (BMBF). O.A.C. is supported by the German Federal Ministry of Research and Education and is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—CECAD, EXC 2030–390661388. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. This work was supported by grants of the Rolf M. Schwiete Stiftung, the Saarland University, BMBF and The States of Saarland and Lower Saxony. K.U.L. is supported by the German Research Foundation (DFG, LU-1944/3-1). Genotyping for the BoSCO study is funded by the Institute of Human Genetics, University Hospital Bonn. F.H. was supported by the Bavarian State Ministry for Science and Arts. Part of the genotyping was supported by a grant to A.R. from the German Federal Ministry of Education and Research (BMBF, grant: 01ED1619A, European Alzheimer DNA BioBank, EADB) within the context of the EU Joint Programme—Neurodegenerative Disease Research (JPND). Additional funding was derived from the German Research Foundation (DFG) grant: RA 1971/6-1 to A.R. P.R. is supported by the DFG (CCGA Sequencing Centre and DFG ExC2167 PMI and by SH state funds for COVID19 research). F.T. is supported by the Clinician Scientist Program of the Deutsche Forschungsgemeinschaft Cluster of Excellence ‘Precision Medicine in Chronic Inflammation’ (EXC2167). C.L. and J.H. are supported by the German Center for Infection Research (DZIF). T.B., M.M.B., O.W. und A.H. are supported by the Stiftung Universitätsmedizin Essen. M.A.-H. was supported by Juan de la Cierva Incorporacion program, grant IJC2018-035131-I funded by MCIN/AEI/10.13039/501100011033. E.C.S. is supported by the Deutsche Forschungsgemeinschaft (DFG; SCHU 2419/2-1).Peer reviewe

Detailed stratified GWAS analysis for severe COVID-19 in four European populations

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic ∼0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.Andre Franke and David Ellinghaus were supported by a grant from the German Federal Ministry of Education and Research (01KI20197), Andre Franke, David Ellinghaus and Frauke Degenhardt were supported by the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). David Ellinghaus was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences funding concept (CompLS grant 031L0165). David Ellinghaus, Karina Banasik and Søren Brunak acknowledge the Novo Nordisk Foundation (grant NNF14CC0001 and NNF17OC0027594). Tobias L. Lenz, Ana Teles and Onur Özer were funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project numbers 279645989; 433116033; 437857095. Mareike Wendorff and Hesham ElAbd are supported by the German Research Foundation (DFG) through the Research Training Group 1743, "Genes, Environment and Inflammation". This project was supported by a Covid-19 grant from the German Federal Ministry of Education and Research (BMBF; ID: 01KI20197). Luca Valenti received funding from: Ricerca Finalizzata Ministero della Salute RF2016-02364358, Italian Ministry of Health ""CV PREVITAL – strategie di prevenzione primaria cardiovascolare primaria nella popolazione italiana; The European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- and for the project ""REVEAL""; Fondazione IRCCS Ca' Granda ""Ricerca corrente"", Fondazione Sviluppo Ca' Granda ""Liver-BIBLE"" (PR-0391), Fondazione IRCCS Ca' Granda ""5permille"" ""COVID-19 Biobank"" (RC100017A). Andrea Biondi was supported by the grant from Fondazione Cariplo to Fondazione Tettamanti: "Biobanking of Covid-19 patient samples to support national and international research (Covid-Bank). This research was partly funded by a MIUR grant to the Department of Medical Sciences, under the program "Dipartimenti di Eccellenza 2018–2022". This study makes use of data generated by the GCAT-Genomes for Life. Cohort study of the Genomes of Catalonia, Fundació IGTP. IGTP is part of the CERCA Program / Generalitat de Catalunya. GCAT is supported by Acción de Dinamización del ISCIIIMINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026); the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529). Marta Marquié received research funding from ant PI19/00335 Acción Estratégica en Salud, integrated in the Spanish National RDI Plan and financed by ISCIIISubdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa").Beatriz Cortes is supported by national grants PI18/01512. Xavier Farre is supported by VEIS project (001-P-001647) (cofunded by European Regional Development Fund (ERDF), “A way to build Europe”). Additional data included in this study was obtained in part by the COVICAT Study Group (Cohort Covid de Catalunya) supported by IsGlobal and IGTP, EIT COVID-19 Rapid Response activity 73A and SR20-01024 La Caixa Foundation. Antonio Julià and Sara Marsal were supported by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36). Antonio Julià was also supported the by national grant PI17/00019 from the Acción Estratégica en Salud (ISCIII) and the FEDER. The Basque Biobank is a hospitalrelated platform that also involves all Osakidetza health centres, the Basque government's Department of Health and Onkologikoa, is operated by the Basque Foundation for Health Innovation and Research-BIOEF. Mario Cáceres received Grants BFU2016-77244-R and PID2019-107836RB-I00 funded by the Agencia Estatal de Investigación (AEI, Spain) and the European Regional Development Fund (FEDER, EU). Manuel Romero Gómez, Javier Ampuero Herrojo, Rocío Gallego Durán and Douglas Maya Miles are supported by the “Spanish Ministry of Economy, Innovation and Competition, the Instituto de Salud Carlos III” (PI19/01404, PI16/01842, PI19/00589, PI17/00535 and GLD19/00100), and by the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018, COVID-Premed, COVID GWAs). The position held by Itziar de Rojas Salarich is funded by grant FI20/00215, PFIS Contratos Predoctorales de Formación en Investigación en Salud. Enrique Calderón's team is supported by CIBER of Epidemiology and Public Health (CIBERESP), "Instituto de Salud Carlos III". Jan Cato Holter reports grants from Research Council of Norway grant no 312780 during the conduct of the study. Dr. Solligård: reports grants from Research Council of Norway grant no 312769. The BioMaterialBank Nord is supported by the German Center for Lung Research (DZL), Airway Research Center North (ARCN). The BioMaterialBank Nord is member of popgen 2.0 network (P2N). Philipp Koehler has received non-financial scientific grants from Miltenyi Biotec GmbH, Bergisch Gladbach, Germany, and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany. He is supported by the German Federal Ministry of Education and Research (BMBF).Oliver A. Cornely is supported by the German Federal Ministry of Research and Education and is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – CECAD, EXC 2030 – 390661388. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping was performed by the Genotyping laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki. This work was supported by grants of the Rolf M. Schwiete Stiftung, the Saarland University, BMBF and The States of Saarland and Lower Saxony. Kerstin U. Ludwig is supported by the German Research Foundation (DFG, LU-1944/3-1). Genotyping for the BoSCO study is funded by the Institute of Human Genetics, University Hospital Bonn. Frank Hanses was supported by the Bavarian State Ministry for Science and Arts. Part of the genotyping was supported by a grant to Alfredo Ramirez from the German Federal Ministry of Education and Research (BMBF, grant: 01ED1619A, European Alzheimer DNA BioBank, EADB) within the context of the EU Joint Programme – Neurodegenerative Disease Research (JPND). Additional funding was derived from the German Research Foundation (DFG) grant: RA 1971/6-1 to Alfredo Ramirez. Philip Rosenstiel is supported by the DFG (CCGA Sequencing Centre and DFG ExC2167 PMI and by SH state funds for COVID19 research). Florian Tran is supported by the Clinician Scientist Program of the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). Christoph Lange and Jan Heyckendorf are supported by the German Center for Infection Research (DZIF). Thorsen Brenner, Marc M Berger, Oliver Witzke und Anke Hinney are supported by the Stiftung Universitätsmedizin Essen. Marialbert Acosta-Herrera was supported by Juan de la Cierva Incorporacion program, grant IJC2018-035131-I funded by MCIN/AEI/10.13039/501100011033. Eva C Schulte is supported by the Deutsche Forschungsgemeinschaft (DFG; SCHU 2419/2-1).N

Effect of sildenafil on right ventricular performance in an experimental large-animal model of postcapillary pulmonary hypertension

Right ventricle (RV) dysfunction is a main determinant of morbidity and mortality in postcapillary pulmonary hypertension (PH). However, currently there are not available therapies. Since reduced nitric oxide (NO) availability and cyclic guanylate monophosphate (cGMP) levels are central in this disease, therapies targeting the NO pathway might have a beneficial effect on RV performance. In this regard, sildenafil has shown contradictory results. Our objective was to evaluate the effect of sildenafil on RV performance in an experimental pig model of postcapillary PH induced by a fixed banding of the venous pulmonary confluent. Animals were evaluated by right heart catheterization and cardiac magnetic resonance before randomization and after 8 weeks on sildenafil (n = 8) or placebo (n = 8), and myocardial tissues were analyzed with histology and molecular biology. At the end of the study, animals receiving sildenafil showed better RV performance as compared with those on placebo (improvement in RV ejection fraction of 7.3% ± 5.8% versus -0.6% ± 5.0%, P= 0.021) associated with less apoptotic cells and gene expression related with reduced oxidative stress and increased anti-inflammatory activity in the myocardium. No differences were observed in pulmonary hemodynamics. In conclusion, in a translational large animal model of chronic postcapillary PH, sildenafil improved RV systolic function independently of afterload. Further research with pharmacological approaches able to manipulate the NO-cGMP axis are needed to confirm this potential cardioprotective effect.Sin financiación7.012 JCR (2020) Q1, 2/29 Medical Laboratory Technology2.174 SJR (2021) Q1, 3/60 Biochemistry (medical)No data IDR 2020UE

Diet and environment in South-Eastern Iberia during the bronze age, based on isotope analysis of human remains

A large sample of human bones from a series of archaeological sites in the south‐eastern Iberian Peninsula was selected for δ13C and δ15N stable isotope analysis. Except for some contrast samples, the remains date from the first half of the second millennium cal BC and are ascribed to the Argar Culture, which developed during the Bronze Age in south‐eastern Iberia. Most authors have considered that this region reached a high degree of social hierarchical organization at this time, as demonstrated by the funerary record, both with regard to the grave goods and to the evidence of physical effort and diseases on the human remains. Results of the isotope analysis revealed the existence of differences among the settlements studied, as well as differences over time within every settlement and among the various individuals tested. Some variances can be assigned to social classes/status and others are linked to chronological factors. In particular, changes in δ13C can be explained by the increasing aridity of the first half of the second millennium cal BC, although other causes can be put forward too.This work was supported by the Consejería de Innovación y Empresa de la Junta de Andalucía (project HUM-061658) and by the Spanish Ministerio de Ciencia e Innovación (project HAR2016-80057-P)

Diet and environment in southeastern Iberia during the Bronze Age based on isotope analysis of human remains

A large sample of human bones from a series of archaeological sites in the south-eastern Iberian Peninsula was selected for δ13C and δ15N stable isotope analysis. Except for some contrast samples, the remains date from the first half of the second millennium cal BC and are ascribed to the Argar Culture, which developed during the Bronze Age in south-eastern Iberia. Most authors have considered that this region reached a high degree of social hierarchical organization at this time, as demonstrated by the funerary record, both with regard to the grave goods and to the evidence of physical effort and diseases on the human remains. Results of the isotope analysis revealed the existence of differences among the settlements studied, as well as differences over time within every settlement and among the various individuals tested. Some variances can be assigned to social classes/status and others are linked to chronological factors. In particular, changes in δ13C can be explained by the increasing aridity of the first half of the second millennium cal BC, although other causes can be put forward too.Una amplia muestra de huesos humanos de una serie de yacimientos arqueológicos del sureste de la Península Ibérica fue seleccionada para análisis de isótopos etables δ13C y δ15N. Salvo algunas muestras de contrastación, los restos datan de la primera mitad del segundo milenio cal A.C. y se adscriben a la Cultura del Argar, que desarrollado durante la Edad del Bronce en el sureste de Iberia. Los resultados del análisis de isótopos revelaron la existencia de diferencias entre los asentamientos estudiados, así como diferencias en el tiempo dentro de cada asentamiento y entre los diversos individuos. A nivel general los cambios en δ13C pueden explicarse por la creciente aridez de la primera mitad del segundo milenio cal A.C., aunque están presentes otras causas como diferencias de consumo entre clases y sexos, factores vinculados a la lactancia en los individuos infantiles y cierta movilidad con la presencia de sujetos que no nacieron y/o crecieron en los yacimientos en que fueron enterrados. El trabajo confirma los planteamientos que consideran las sociedades argáricas como comunidades profundamente jerarquizadas y además avanza en la consideración de la existencia al interior de la cultura de profundas diferencias territoriales que, en parte, derivan de la oposición entre diferentes formaciones sociales.Impacto ambiental y cambio social en el sur de la Península Ibérica durante la Prehistoria Reciente (P06-HUM-1658). Consejería de Economía, Innovación y Ciencia de la Junta de AndalucíaEstrategias agropecuarias y consumo en la Edad del Bronce del sur de la Península Ibérica. Análisis de plantas, animales y restos humanos (HAR2016-80057-P). Ministerio de Economía y Competitivida

Effect of Chitosan and Naringin on Enteric Methane Emissions in Crossbred Heifers Fed Tropical Grass

Simple Summary The increase in human population and the concomitant rise in demand for animal protein have contributed to augment enteric methane emissions. It is imperative to reduce methane, increase sustainable production, avoid the use of chemical compounds, and guarantee quality products for the consumer. Chitosan and naringin possess antimicrobial properties, and they have shown their capacity to reduce methane in in vitro trials. This study investigated their effects as feed additives given to improve ruminal fermentation and nutrient utilization and decrease methane in crossbred heifers fed tropical grass. In in vitro experiments, chitosan and naringin at three levels (0, 1.5, 3.0 g/kg) showed significant methane reductions when 1.5 g/kg of chitosan was included. The in situ study did not reveal changes in rumen degradability with the inclusion of the additives. However, in in vivo assays, chitosan and naringin at 1.5 or 3.0 g/kg dry matter intake or the combination of both compounds (1.5 and 1.5 g/kg) given directly into the rumen did not induce changes in rumen fermentation, methane production, or nutrient utilization. However, given the promising evidence from other studies, more research needs to be conducted to clarify the potential effects of chitosan and naringin in animal production. Abstract In order to meet consumer needs, the livestock industry is increasingly seeking natural feed additives with the ability to improve the efficiency of nutrient utilization, alternatives to antibiotics, and mitigate methane emissions in ruminants. Chitosan (CHI) is a polysaccharide with antimicrobial capability against protozoa and Gram-positive and -negative bacteria, fungi, and yeasts while naringin (NA) is a flavonoid with antimicrobial and antioxidant properties. First, an in vitro gas production experiment was performed adding 0, 1.5, 3.0 g/kg of CHI and NA under a completely randomized design. The substrate containing forage and concentrate in a 70:30 ratio on a dry matter (DM) basis. Compounds increased the concentration of propionic acid, and a significant reduction in methane production was observed with the inclusion of CHI at 1.5 g/kg in in vitro experiments (p 0.05), DM intake and digestibility of (p > 0.05), and enteric methane emissions (p > 0.05). CHI at a concentration of 1.5 g/kg DM in in vitro experiments had a positive effect on fermentation pattern increasing propionate and reduced methane production. In contrast, in the in vivo studies, there was not a positive effect on rumen fermentation, nor in enteric methane production in crossbred heifers fed a basal ration of tropical grass. Keywords: additive; flavonoid; chitin; antimicrobial action; greenhouse gase