Suchergebnisse

Este trabajo busca dar respuesta a las siguientes preguntas: ¿qué se está haciendo hoy en la prisión?, ¿qué se hace hoy con la prisión?, desde la biopolítica de Foucault y el punto de vista del trabajo-valor de Marx, mediante el empleo de la metodología cualitativa (por observación y testimonio). En este orden, se pretende demostrar que la prisión funciona como un espacio donde la vida es sobreexplotada: un espacio donde la fuerza de trabajo vivo es administrada y colocada en una situación de riesgo y de lucha por la vida, en un punto en que la vida debe ser defendida en todo momento. Pero, sobre todo, la prisión es un lugar donde la vida es usada para la rentabilidad capitalista y asuntos utilitarios. Sugerimos todo esto, tomando en cuenta, como estudio de caso específico, el Centro de Reinserción Social Puebla, México, con el fin de demostrar que todos estos problemas también se consideran en América Latina.

The use of water treatment plant sludge to restore degraded soils is customary agricultural practice, but it could be dangerous from the point of view of both health and the environment. A transient increase of either pathogenic or indicator microbial populations, whose persistence in time is variable and attributed to the characteristics of the soil (types of materials in the soil), any amendments (origin and treatments it has undergone) or the weather (humidity and temperature mainly), has often been detected in soils treated with this kind of waste. Given their origin, water treatment plant sludges could lead to the transmission of a) pathogens and b) antibiotic-resistant microorganisms to human beings through the food chain and cause the spreading of antibiotic resistances as a result of their increase and persistence in the soil for variable periods of time. However, Spanish legislation regulating the use of sludges in the farming industry is based on a very restricted microbiological criterion. Thus, we believe better parameters should be established to appropriately inform of the state of health of soils treated with water treatment plant sludge, including aspects which are not presently assessed such as antibiotic resistance. ; A aplicação de lamas de estações de tratamento de águas residuais é uma prática habitual na agricultura como método de recuperação de solos degradados que pode não estar isenta de perigos quando avaliada dos pontos de vista ambiental e sanitário. Habitualmente tem-se detetado no solo tratado com este tipo de resíduos um incremento transitório das populações microbianas quer patogénicas, quer indicadoras, cuja persistência no tempo é variável e atribuída às características do solo (tipo de materiais no solo), das correções (origem e tratamento aplicado) ou o clima (principalmente a humidade e a temperatura). As lamas das estações de tratamento, pela sua origem, poderiam proporcionar a transferência para o ser humano através da cadeia alimentar de 1) microrganismo patogénicos e 2) microrganismos resistentes a antibióticos e produzir a disseminação de resistências a antibióticos, pelo aumento e manutenção destes no solo por períodos de tempo variáveis. Contudo, a legislação espanhola que regula a aplicação de lamas no setor agrário optou por um critério microbiológico muito limitado. Por essa razão, consideramos que se deveriam estabelecer melhores parâmetros que informem devidamente sobre o estado sanitário dos solos tratados com lamas e que incluam também aspetos que atualmente não se avaliam como a resistência a antibióticos. ; La aplicación de lodos de depuradora es una práctica habitual en agricultura como método de recuperación de suelos degradados que podría no estar exenta de peligrosidad cuando se evalúa desde los puntos de vista ambiental y sanitario. Habitualmente se ha detectado en el suelo tratado con estos residuos un incremento transitorio de las poblaciones microbianas bien patógenas, bien indicadoras, cuya persistencia en el tiempo es variable y atribuida a las características del suelo (tipo de materiales en el suelo), de las enmiendas (origen y tratamiento que han sufrido) o el clima (principalmente humedad y temperatura). Los lodos de depuradora, por su origen, podrían producir la transferencia al ser humano a través de la cadena tró ca de 1) microorganismos patógenos y 2) microorganismos resistentes a antibióticos y producir la diseminación de resistencias a antibióticos, por el incremento y mantenimiento de estos en el suelo por periodos variables de tiempo. Sin embargo, la legislación española que regula la aplicación de lodos en el sector agrario ha optado por un criterio microbiológico muy limitado. Por ello, estimamos que se deberían establecer mejores parámetros que informen apropiadamente del estado sanitario de los suelos tratados con lodos de depuradora que incluyeran, además, aspectos que actualmente no se evalúan como la resistencia a antibióticos.

IntroductionUse of deep sequencing is becoming a critical tool in clinical virology, with an important impact in the HIV field for routine diagnostic purposes. Here, we present the comparison of deep and Sanger sequencing in newly diagnosed HIV patients, and the use of DeepChek v1.3 & VisibleChek for their interpretation and integration with virological and clinical data.Patients and MethodsPlasma samples from 88 newly diagnosed HIV‐1‐infected patients were included in the study. Median age (IQR) was 37 (27–47), median CD4 count (IQR) was 387 (220–554), and 85% were males. Median Viral Load (Log, IQR) was 5.03 (4.51–5.53). Deep sequencing was obtained using a GS‐Junior (Roche). Sequences were preprocessed with the 454 AVA software; aligned reads were uploaded into the DeepChek v1.3 system (ABL SA). Sanger sequences (Trugene), were uploaded in parallel. Stanford algorithm (version 7.0) resistance interpretation to first line drugs and all the mutations (score≥5) were analyzed. For deep sequencing, 1%, 5% and 10% thresholds were chosen for resistance interpretation.ResultsUsing VisibleChek for analysis, we were able to describe the detection of any mutation using Sanger in 37/88 patients, with a total number of 50 Stanford ≥5 mutations, K103N and E138A being the most prevalent (n=4). Using UDS‐1%, we found 72/88 patients with at least one mutation (total of 206 Stanford ≥5 mutations). Using Sanger data, 9/88 patients (10.22%) showed any resistance to NNRTIs, while none showed resistance to NRTIs or PIs. Using UDS‐10% increased resistance to NRTIs [3/88 (3.40%)], to NNRTIs 12/88 (13.63%), and to a lesser extent to PIs [1/88 (1.13%)]. Using UDS‐5% increased resistance to NRTIs [4/88 (4.54%)] and to NNRTIs [12/88 (13.63%)], but not to PIs. Using UDS‐1% increased resistance to all classes: NRTIs [14/88 (15.90%)], NNRTIs [26/88 (30.68%)], and PIs [6/88 (6.81].ConclusionsDeepChek and VisibleChek allow for an easy, reliable and rapid analysis of UDS data from HIV‐1. Compared to Sanger data, UDS detected a higher number of resistance mutations. UDS with a 5 &10% threshold resulted in an increase in the number of patients with any degree of resistance mainly to NRTI, NNRTIs. Going down as low as 1% increased resistance to all classes. A correct definition of clinically relevant thresholds for the interpretation of minor variant detection for different classes of ARVs is needed.

A list of morphological characters to separate Iberoformica and Formica (Serviformica) (F. fusca species group) is provided. Sexual forms of Formica gerardi Bondroit are described based on Iberian material and reinstated into the subgenus Serviformica based on genetic data and morphological characters. The status of †F.horrida Wheeler, 1915 is assessed.

AG has received support by NordForsk Nordic Trial Alliance (NTA) grant, by Academy of Finland Fellow grant N. 323116 and the Academy of Finland for PREDICT consortium N. 340541. The Richards research group is supported by the Canadian Institutes of Health Research (CIHR) (365825 and 409511), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation (CFI), the NIH Foundation, Cancer Research UK, Genome Québec, the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS). TN is supported by a research fellowship of the Japan Society for the Promotion of Science for Young Scientists. GBL is supported by a CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship. JBR is supported by an FRQS Clinical Research Scholarship. Support from Calcul Québec and Compute Canada is acknowledged. TwinsUK is funded by the Welcome Trust, the Medical Research Council, the European Union, the National Institute for Health Research-funded BioResource and the Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London. The Biobanque Québec COVID19 is funded by FRQS, Genome Québec and the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé. These funding agencies had no role in the design, implementation or interpretation of this study. The COVID19-Host(a)ge study received infrastructure support from the DFG Cluster of Excellence 2167 "Precision Medicine in Chronic Inflammation (PMI)" (DFG Grant: "EXC2167"). The COVID19-Host(a)ge study 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). Genotyping in COVID19-Host(a)ge was supported by a philantropic donation from Stein Erik Hagen. The COVID GWAs, Premed COVID-19 study (COVID19-Host(a)ge_3) was supported by "Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"and also by the Instituto de Salud Carlos III (CIBERehd and CIBERER). Funding comes from COVID-19-GWAS, COVID-PREMED initiatives. Both of them are supported by "Consejeria de Salud y Familias" of the Andalusian Government. DMM is currently funded by the the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018). The Columbia University Biobank was supported by Columbia University and the National Center for Advancing Translational Sciences, NIH, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Columbia University. The SPGRX study was supported by the Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150. The GEN-COVID study was funded by: the MIUR grant "Dipartimenti di Eccellenza 2018-2020" to the Department of Medical Biotechnologies University of Siena, Italy; the "Intesa San Paolo 2020 charity fund" dedicated to the project NB/2020/0119; and philanthropic donations to the Department of Medical Biotechnologies, University of Siena for the COVID-19 host genetics research project (D.L n.18 of March 17, 2020). Part of this research project is also funded by Tuscany Region "Bando Ricerca COVID-19 Toscana" grant to the Azienda Ospedaliero Universitaria Senese (CUP I49C20000280002). Authors are grateful to: the CINECA consortium for providing computational resources; the Network for Italian Genomes (NIG) (http://www.nig.cineca.it) for its support; the COVID-19 Host Genetics Initiative (https://www.covid19hg.org/); the Genetic Biobank of Siena, member of BBMRI-IT, Telethon Network of Genetic Biobanks (project no. GTB18001), EuroBioBank, and RD-Connect, for managing specimens. Genetics against coronavirus (GENIUS), Humanitas University (COVID19-Host(a)ge_4) was supported by Ricerca Corrente (Italian Ministry of Health), intramural funding (Fondazione Humanitas per la Ricerca). The generous contribution of Banca Intesa San Paolo and of the Dolce&Gabbana Fashion Firm is gratefully acknowledged. Data acquisition and sample processing was supported by COVID-19 Biobank, Fondazione IRCCS Cà Granda Milano; LV group was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, the European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- "Liver Investigation: Testing Marker Utility in Steatohepatitis", Programme "Photonics" under grant agreement "101016726" for the project "REVEAL: Neuronal microscopy for cell behavioural examination and manipulation", Fondazione Patrimonio Ca' Granda "Liver Bible" PR-0361. DP was supported by Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, CV PREVITAL "Strategie di prevenzione primaria nella popolazione Italiana" Ministero della Salute, and Associazione Italiana per la Prevenzione dell'Epatite Virale (COPEV). Genetic modifiers for COVID-19 related illness (BeLCovid_1) was supported by the "Fonds Erasme". The Host genetics and immune response in SARS-Cov-2 infection (BelCovid_2) study was supported by grants from Fondation Léon Fredericq and from Fonds de la Recherche Scientifique (FNRS). The INMUNGEN-CoV2 study was funded by the Consejo Superior de Investigaciones Científicas. KUL is supported by the German Research Foundation (LU 1944/3-1) SweCovid is funded by the SciLifeLab/KAW national COVID-19 research program project grant to Michael Hultström (KAW 2020.0182) and the Swedish Research Council to Robert Frithiof (2014-02569 and 2014-07606). HZ is supported by Jeansson Stiftelser, Magnus Bergvalls Stiftelse. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping for the COMRI cohort was performed and funded by the Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland. These funding agencies had no role in the design, implementation or interpretation of this study. ; Background: There is considerable variability in COVID-19 outcomes amongst younger adults—and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. Method: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. Findings: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. Interpretation: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality—and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. ; Academy of Finland Fellow grant N. 323116 ; Academy of Finland for PREDICT consortium N. 340541. ; Canadian Institutes of Health Research (CIHR) (365825 and 409511) ; Lady Davis Institute of the Jewish General Hospital ; Canadian Foundation for Innovation (CFI) ; NIH Foundation ; Cancer Research UK ; Genome Québec ; Public Health Agency of Canada ; McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS) ; Japan Society for the Promotion of Science for Young Scientists ; CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship ; FRQS Clinical Research Scholarship ; Calcul Québec ; Compute Canada ; Welcome Trust ; Medical Research Counc ; European Union ; National Institute for Health Research-funded BioResource ; Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust ; King's College London ; Genome Québec ; Public Health Agency of Canada ; McGill Interdisciplinary Initiative in Infection and Immunity ; Fonds de Recherche Québec Santé ; (DFG Grant: "EXC2167") ; (CompLS grant 031L0165) ; Stein Erik Hagen ; "Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia" ; Instituto de Salud Carlos III (CIBERehd and CIBERER) ; COVID-19-GWAS ; COVID-PREMED initiatives ; "Consejeria de Salud y Familias" of the Andalusian Government ; Andalusian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018) ; Columbia University ; National Center for Advancing Translational Sciences ; NIH Grant Number UL1TR001873 ; Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150 ; MIUR grant "Dipartimenti di Eccellenza 2018-2020" ; "Intesa San Paolo 2020 charity fund" dedicated to the project NB/2020/0119 ; Tuscany Region "Bando Ricerca COVID-19 Toscana" ; CINECA consortium ; Network for Italian Genomes (NIG) ; COVID-19 Host Genetics Initiative ; Genetic Biobank of Siena ; EuroBioBank ; RD-Connect ; Ricerca Corrente (Italian Ministry of Health) ; Fondazione Humanitas per la Ricerca ; Banca Intesa San Paolo ; Dolce&Gabbana Fashion Firm ; COVID-19 Biobank ; Fondazione IRCCS Cà Granda Milano ; MyFirst Grant AIRC n.16888 ; Ricerca Finalizzata Ministero della Salute RF-2016-02364358 ; Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico ; European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) ; "Photonics" "101016726" ; Fondazione Patrimonio Ca' Granda "Liver Bible" PR-0361 ; CV PREVITAL "Strategie di prevenzione primaria nella popolazione Italiana" Ministero della Salute, and Associazione Italiana per la Prevenzione dell'Epatite Virale (COPEV) ; "Fonds Erasme" ; Fondation Léon Fredericq ; Fonds de la Recherche Scientifique (FNRS) ; Consejo Superior de Investigaciones Científicas ; German Research Foundation (LU 1944/3-1) ; SciLifeLab/KAW national COVID-19 research program project (KAW 2020.0182) ; Swedish Research Council (2014-02569 and 2014-07606) ; Jeansson Stiftelser, Magnus Bergvalls Stiftelse ; Technical University of Munich, Munich, Germany ; Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland

The COVID-19 pandemic represents an unprecedented opportunity to exploit the advantages of personalized medicine for the prevention, diagnosis, treatment, surveillance and management of a new challenge in public health. COVID-19 infection is highly variable, ranging from asymptomatic infections to severe, life-threatening manifestations. Personalized medicine can play a key role in elucidating individual susceptibility to the infection as well as inter-individual variability in clinical course, prognosis and response to treatment. Integrating personalized medicine into clinical practice can also transform health care by enabling the design of preventive and therapeutic strategies tailored to individual profiles, improving the detection of outbreaks or defining transmission patterns at an increasingly local level. SARS-CoV2 genome sequencing, together with the assessment of specific patient genetic variants, will support clinical decision-makers and ultimately better ways to fight this disease. Additionally, it would facilitate a better stratification and selection of patients for clinical trials, thus increasing the likelihood of obtaining positive results. Lastly, defining a national strategy to implement in clinical practice all available tools of personalized medicine in COVID-19 could be challenging but linked to a positive transformation of the health care system. In this review, we provide an update of the achievements, promises, and challenges of personalized medicine in the fight against COVID-19 from susceptibility to natural history and response to therapy, as well as from surveillance to control measures and vaccination. We also discuss strategies to facilitate the adoption of this new paradigm for medical and public health measures during and after the pandemic in health care systems. ; The authors included in this review have received funding for two COVID-19 projects (COVID GWAs, Premed COVID-19) from the Consejería de Salud y Familias of the Andalusian Government. DMM's contract is supported by the Andalussian government (Proyectos Estratégicos Fondos Feder PE-0451-2018). ; Peer reviewed

The beneficial effects of probiotics on immune-based pathologies such as inflammatory bowel disease (IBD) have been well reported. However, their exact mechanisms have not been fully elucidated. Few studies have focused on the impact of probiotics on the composition of the colonic microbiota. The aim of the present study was to correlate the intestinal anti-inflammatory activity of the probiotic Escherichia coli Nissle 1917 (EcN) in the dextran sodium sulfate (DSS) model of mouse colitis with the changes induced in colonic microbiota populations. EcN prevented the DSSinduced colonic damage, as evidenced by lower disease activity index (DAI) values and colonic weight/length ratio, when compared with untreated control mice. The beneficial effects were confirmed biochemically, since the probiotic treatment improved the colonic expression of different cytokines and proteins involved in epithelial integrity. In addition, it restored the expression of different micro-RNAs (miR-143, miR-150, miR-155, miR- 223, and miR-375) involved in the inflammatory response that occurs in colitic mice. Finally, the characterization of the colonic microbiota by pyrosequencing showed that the probiotic administration was able to counteract the dysbiosis associated with the intestinal inflammatory process. This effect was evidenced by an increase in bacterial diversity in comparison with untreated colitic mice. The intestinal anti-inflammatory effects of the probiotic EcN were associated with an amelioration of the altered gut microbiome in mouse experimental colitis, especially when considering bacterial diversity, which is reduced in these intestinal conditions. Moreover, this probiotic has shown an ability to modulate expression levels of miRNAs and different mediators of the immune response involved in gut inflammation. This modulation could also be of great interest to understand the mechanism of action of this probiotic in the treatment of IBD. ; This work was supported by the Junta de Andalucía (CTS 164) and by the Spanish Ministry of Economy and Competitiveness (SAF2011-29648 and AGL2015-67995-C3-3-R) with funds from the European Union. The funders had no role in the study design, data collection, and analysis.

Nowadays, there is an increasing interest in alternative therapies in the treatment of metabolic syndrome that combine efficacy and safety profiles. Therefore, this study aimed to evaluate the effect of an extract of Thymus serpyllum, containing rosmarinic acid, on high-fat diet (HFD)- induced obesity mice, highlighting the impact of its antioxidant activity on the inflammatory status and gut dysbiosis. The extract was administered daily (50, 100 and 150 mg/kg) in HFD-fed mice. The treatment reduced body weight gain, glucose and lipid metabolic profiles. Moreover, the extract ameliorated the inflammatory status, with the c-Jun N-terminal kinases (JUNK) pathway being involved, and showed a significant antioxidant effect by the reduction of radical scavenging activity and the mitigation of lipid peroxidation. Moreover, the extract was able to modulate the altered gut microbiota, restoring microbial richness and diversity, and augmenting the counts of short-chain fatty acid producing bacteria, which have been associated with the maintenance of gut permeability and weight regulation. In conclusion, the antioxidant activity of Thymus serpyllum extract displayed a positive impact on obesity and its metabolic alterations, also reducing systemic inflammation. These effects may be mediated by modulation of the gut microbiota. ; Junta de Andalucia CTS 164 ; Instituto de Salud Carlos III European Commission PI19.01058 ; Spanish Government AGL201567995-C3-3-R ; European Commission ; Instituto de Salud Carlos III

This research was funded by the FEDER-INNTERCONECTA-CDTI program (CDTI, Centre for the Development of Industrial Technology; NATURPICK Project ITC-20181038), by the Junta de Andalucia (CTS 164) and by Instituto de Salud Carlos III (PI19/01058) with funds from the European Union. T.V. is a postdoctoral fellow from Instituto de Investigacion Biosanitaria de Granada; A.J.R.-M. and L.H.-G. are predoctoral fellows from University of Granada ("Programa de Doctorado: Medicina Clinica y Salud Publica"); P.D.-E. is a postdoctoral fellow from University of Granada. The CIBER-EHD and CIBERCV are funded by the Instituto de Salud Carlos III. ; Background: Propyl propane thiosulfonate (PTSO) is an organosulfur compound from Allium spp. that has shown interesting antimicrobial properties and immunomodulatory effects in different experimental models. In this sense, our aim was to evaluate its effect on an experimental model of obesity, focusing on inflammatory and metabolic markers and the gut microbiota. Methods and results: Mice were fed a high-fat diet and orally treated with different doses of PTSO (0.1, 0.5 and 1 mg/kg/day) for 5 weeks. PTSO lessened the weight gain and improved the plasma markers associated with glucose and lipid metabolisms. PTSO also attenuated obesityassociated systemic inflammation, reducing the immune cell infiltration and, thus, the expression of pro-inflammatory cytokines in adipose and hepatic tissues (Il-1ß, Il-6, Tnf-a, Mcp-1, Jnk-1, Jnk-2, Leptin, Leptin R, Adiponectin, Ampk, Ppar-a, Ppar-g, Glut-4 and Tlr-4) and improving the expression of different key elements for gut barrier integrity (Muc-2, Muc-3, Occludin, Zo-1 and Tff-3). Additionally, these effects were connected to a regulation of the gut microbiome, which was altered by the high-fat diet. Conclusion: Allium-derived PTSO can be considered a potential new tool for the treatment of metabolic syndrome. ; FEDER-INNTERCONECTA-CDTI program (CDTI, Centre for the Development of Industrial Technology) ITC-20181038 ; Junta de Andalucia CTS 164 ; Instituto de Salud Carlos III European Commission PI19/01058 European Commission Instituto de Salud Carlos III ; European Commission

[Background] Reducing the burden of the hepatitis C virus (HCV) requires large-scale deployment of intervention programmes, which can be informed by the dynamic pattern of HCV spread. In Spain, ongoing transmission of HCV is mostly fuelled by people who inject drugs (PWID) infected with subtype 1a (HCV1a). ; [Aim] Our aim was to map how infections spread within and between populations, which could help formulate more effective intervention programmes to halt the HCV1a epidemic in Spain. ; [Methods] Epidemiological links between HCV1a viruses from a convenience sample of 283 patients in Spain, mostly PWID, collected between 2014 and 2016, and 1,317, 1,291 and 1,009 samples collected abroad between 1989 and 2016 were reconstructed using sequences covering the NS3, NS5A and NS5B genes. To efficiently do so, fast maximum likelihood-based tree estimation was coupled to a flexible Bayesian discrete phylogeographic inference method. ; [Results] The transmission network structure of the Spanish HCV1a epidemic was shaped by continuous seeding of HCV1a into Spain, almost exclusively from North America and European countries. The latter became increasingly relevant and have dominated in recent times. Export from Spain to other countries in Europe was also strongly supported, although Spain was a net sink for European HCV1a lineages. Spatial reconstructions showed that the epidemic in Spain is diffuse, without large, dominant within-country networks. ; [Conclusion] To boost the effectiveness of local intervention efforts, concerted supra-national strategies to control HCV1a transmission are needed, with a strong focus on the most important drivers of ongoing transmission, i.e. PWID and other high-risk populations. ; Bram Vrancken is a postdoctoral research fellow funded by the Research Foundation Flanders - Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO, Flanders, Belgium). Part of this research was sponsored by FWO grants G.0E84.16N, G.0B23.17N, G.0662.15N, G.0D51.17N and G.0B93.17N. Funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422-ReservoirDOCS) has been used for this study. A part of the computational resources and services used in this work were provided by the Hercules Foundation and the Flemish Government - department EWI-FWO Krediet aan Navorsers (Theys, KAN2012 1.2.249.12). This work was supported in part by grants from Fondo de Investigación Sanitaria (www.isciii.es) (PI15/00713), Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (www.red.es/redes/inicio) (RD16/0025/0040), Fundación Progreso y salud, Junta de Andalucía (www.fps2.junta-andalucia.es/fundacionprogresoysalud/es/home) (PI-0411-2014), and GEHEP-SEIMC (GEHEP-004 and GEHEP-005).

We thank the entire COVID-19 HGI community for their contributions and continued collaboration. The work of the contributing studies was supported by numerous grants from governmental and charitable bodies. Acknowledgements specific to contributing studies are provided in Supplementary Table 13. We thank G. Butler-Laporte, G. Wojcik, M.-G. Hollm-Delgado, C. Willer and G. Davey Smith for their extensive feedback and discussion. ; The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

Background There is considerable variability in COVID-19 outcomes amongst younger adults—and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. Method The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. Findings We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. Interpretation The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality—and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. ; AG has received support by NordForsk Nordic Trial Alliance (NTA) grant, by Academy of Finland Fellow grant N. 323116 and the Academy of Finland for PREDICT consortium N. 340541. The Richards research group is supported by the Canadian Institutes of Health Research (CIHR) (365825 and 409511), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation (CFI), the NIH Foundation, Cancer Research UK, Genome Quebec, the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Quebec Sante (FRQS). TN is supported by a research fellowship of the Japan Society for the Promotion of Science for Young Scientists. GBL is supported by a CIHR scholarship and a joint FRQS and Quebec Ministry of Health and Social Services scholarship. JBR is supported by an FRQS Clinical Research Scholarship. Support from Calcul Quebec and Compute Canada is acknowledged. TwinsUK is funded by the Welcome Trust, the Medical Research Council, the European Union, the National Institute for Health Research-funded BioResource and the Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London. The Biobanque Quebec COVID19 is funded by FRQS, Genome Quebec and the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Quebec Sante. These funding agencies had no role in the design, implementation or interpretation of this study. The COVID19-Host(a)ge study received infrastructure support from the DFG Cluster of Excellence 2167 Precision Medicine in Chronic Inflammation (PMI) (DFG Grant: EXC2167). The COVID19-Host(a)ge study 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). Genotyping in COVID19-Host(a)ge was supported by a philantropic donation from Stein Erik Hagen. The COVID GWAs, Premed COVID-19 study (COVID19-Host(a)ge_3) was supported by Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia and also by the Instituto de Salud Carlos III (CIBERehd and CIBERER). Funding comes from COVID-19-GWAS, COVID-PREMED initiatives. Both of them are supported by Consejeria de Salud y Familias of the Andalusian Government. DMM is currently funded by the the Andalussian government (Proyectos Estrategicos-Fondos Feder PE-0451-2018). The Columbia University Biobank was supported by Columbia University and the National Center for Advancing Translational Sciences, NIH, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Columbia University. The SPGRX study was supported by the Consejeria de Economia, Conocimiento, Empresas y Universidad #CV20-10150. The GEN-COVID study was funded by: the MIUR grant Dipartimenti di Eccellenza 2018-2020 to the Department of Medical Biotechnologies University of Siena, Italy; the Intesa San Paolo 2020 charity fund dedicated to the project NB/2020/0119; and philanthropic donations to the Department of Medical Biotechnologies, University of Siena for the COVID-19 host genetics research project (D.L n.18 of March 17, 2020). Part of this research project is also funded by Tuscany Region Bando Ricerca COVID-19 Toscana grant to the Azienda Ospedaliero Universitaria Senese (CUP I49C20000280002). Authors are grateful to: the CINECA consortium for providing computational resources; the Network for Italian Genomes (NIG) (http://www.nig.cineca.it) for its support; the COVID-19 Host Genetics Initiative (https://www.covid19hg.org/); the Genetic Biobank of Siena, member of BBMRI-IT, Telethon Network of Genetic Biobanks (project no. GTB18001), EuroBioBank, and RD-Connect, for managing specimens. Genetics against coronavirus (GENIUS), Humanitas University (COVID19-Host(a)ge_4) was supported by Ricerca Corrente (Italian Ministry of Health), intramural funding (Fondazione Humanitas per la Ricerca). The generous contribution of Banca Intesa San Paolo and of the Dolce&Gabbana Fashion Firm is gratefully acknowledged. Data acquisition and sample processing was supported by COVID-19 Biobank, Fondazione IRCCS Ca Granda Milano; LV group was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, the European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- Liver Investigation: Testing Marker Utility in Steatohepatitis, Programme Photonics under grant agreement 101016726 for the project REVEAL: Neuronal microscopy for cell behavioural examination and manipulation, Fondazione Patrimonio Ca' Granda Liver Bible PR-0361. DP was supported by Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, CV PREVITAL Strategie di prevenzione primaria nella popolazione Italiana Ministero della Salute, and Associazione Italiana per la Prevenzione dell'Epatite Virale (COPEV). Genetic modifiers for COVID-19 related illness (BeLCovid_1) was supported by the Fonds Erasme. The Host genetics and immune response in SARS-Cov-2 infection (BelCovid_2) study was supported by grants from Fondation Leon Fredericq and from Fonds de la Recherche Scientifique (FNRS). The INMUNGEN-CoV2 study was funded by the Consejo Superior de Investigaciones Cientificas. KUL is supported by the German Research Foundation (LU 1944/3-1) SweCovid is funded by the SciLifeLab/KAW national COVID-19 research program project grant to Michael Hultstrom (KAW 2020.0182) and the Swedish Research Council to Robert Frithiof (2014-02569 and 2014-07606). HZ is supported by Jeansson Stiftelser, Magnus Bergvalls Stiftelse. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping for the COMRI cohort was performed and funded by the Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland. ; No