49 research outputs found

    Pulmonary paracoccidioidomycosis in AhR deficient hosts is severe and associated with defective Treg and Th22 responses

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    © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.AhR is a ligand-activated transcription factor that plays an important role in the innate and adaptive immune responses. In infection models, it has been associated with host responses that promote or inhibit disease progression. In pulmonary paracoccidioidomycosis, a primary fungal infection endemic in Latin America, immune protection is mediated by Th1/Th17 cells and disease severity with predominant Th2/Th9/Treg responses. Because of its important role at epithelial barriers, we evaluate the role of AhR in the outcome of a pulmonary model of paracoccidioidomycosis. AhR-/- mice show increased fungal burdens, enhanced tissue pathology and mortality. During the infection, AhR-/- mice have more pulmonary myeloid cells with activated phenotype and reduced numbers expressing indoleamine 2,3 dioxygenase 1. AhR-deficient lungs have altered production of cytokines and reduced numbers of innate lymphoid cells (NK, ILC3 and NCR IL-22). The lungs of AhR-/- mice showed increased presence Th17 cells concomitant with reduced numbers of Th1, Th22 and Foxp3+ Treg cells. Furthermore, treatment of infected WT mice with an AhR-specific antagonist (CH223191) reproduced the main findings obtained in AhR-/- mice. Collectively our data demonstrate that in pulmonary paracoccidioidomycosis AhR controls fungal burden and excessive tissue inflammation and is a possible target for antifungal therapy.This work was supported by a grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-grant to VLGC 2011/51258-2 and 2016/23189-0; fellowship to EFA 2014/18668-2; grant to FVL 2018/14762-3; fellowship to NWP 2019-09278-8), European Union H2020 ERA project (No 667824 – EXCELLtoINNOV) to MV and Conselho Nacional de Pesquisas (CNPq).info:eu-repo/semantics/publishedVersio

    Circular economy, green economy and sustainability: perceptions of teachers and students at ISMU, ESCN, ISFIC and Uni-Licungo on their practices

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    Este artigo pretende analisar as perceções e as práticas diárias da economia circular, economia verde e sustentabilidade nos docentes e estudantes do ISMU, ESCN, ISFIC e Uni-Licungo. O seu argumento central é que apesar dos docentes e estudantes do ISMU, ESCN, ISFIC e Uni-Licungo terem perceção da economia circular, economia verde e sustentabilidade, eles não têm a prática diária destes elementos. Recordar que até a década de 1960 a economia era sempre linear o que levava a desperdício e que de forma rápida acabaria por levar ao esgotamento dos recursos naturais, criando de certa forma perigo para o nosso futuro comum devido a degradação do ambiente. Foi daí que se pensou na economia circular, economia verde e na sustentabilidade. O presente estudo é baseado num questionário cujas opções de respostas às perguntas obedecem uma escala de tipo likert de cinco categorias. As variáveis que foram sendo cruzadas tiveram sua seleção de acordo com a respetiva intensidade de relacionamento, tendo sido escolhidas somente aquelas cujo relacionamento (r) era forte. Também foram realizados testes de correlação e apresentadas várias formas de validade do instrumento de recolha de dados (o questionário) e a validade dos dados. O estudo conclui que a incorporação da sustentabilidade nas Instituições de Ensino Superior (IES) aquando da execução das atividades diárias tomando como base os 17 Objetivos de Desenvolvimento Sustentável (ODS) é fundamental para que haja uma educação para a sustentabilidade, contribua-se para mudanças de comportamento a nível das Instituições de Ensino Superior (IES) e que de forma mais expedita haja mais práticas sobre os domínios da economia verde, sustentabilidade e economia circular, o que vai contribuír para uma melhor educação orientada a cidadania ambiental. A prática da economia circular, economia verde e a sustentabilidade trazem consequências benéficas ao nosso planeta e à humanidade.This article intends to analyze the perceptions and daily practices of the circular economy, green economy and sustainability among teachers and students at ISMU, ESCN, ISFIC and Uni-Licungo. Its central argument is that although ISMU, ESCN, ISFIC and Uni-Licungo teachers and students have a perception of the circular economy, green economy and sustainability, they do not have the daily practice of these elements. Remember that until the 1960s, the economy was always linear, which led to waste and that would quickly end up leading to the depletion of natural resources, creating a certain danger for our common future due to the degradation of the environment. That's when we thought about the circular economy, green economy and sustainability. The present study is based on a questionnaire whose options for answering the questions follow a five-category Likerttype scale. The variables that were being crossed were selected according to the respective relationship intensity, with only those whose relationship (r) was strong being chosen. Correlation tests were also performed and various forms of validity of the data collection instrument (the questionnaire) and data validity were presented. The study concludes that the incorporation of sustainability in Higher Education Institutions (HEIs) when carrying out daily activities based on the 17 Sustainable Development Goals (SDGs) is fundamental for there to be an education for sustainability, to contribute to changes of behavior at Higher Education Institutions (HEIs) level and that there are more practices in the areas of green economy, sustainability and circular economy more quickly, which will contribute to a better education oriented to environmental citizenship. The practice of circular economy, green economy and sustainability bring beneficial consequences to our planet and humanity.info:eu-repo/semantics/publishedVersio

    A educação escolar nas prisões: uma análise a partir das representações dos presos da penitenciária de Uberlândia (MG)

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    Este artigo é fruto da dissertação de mestrado intitulada Para além das celas de aula: a educação escolar no contexto prisional à luz das representações dos presos da penitenciária de Uberlândia - Minas Gerais (MG), desenvolvida no período de 2010 a 2012, no programa de pós-graduação em educação da Universidade Federal de Uberlândia. A finalidade deste artigo é promover uma reflexão acerca da educação escolar prescrita e instituída no contexto prisional, a partir de uma análise contextualizada das representações dos presos da penitenciária de Uberlândia (MG). Objetiva-se contribuir com a compreensão dos limites e das possibilidades da educação escolar nas prisões. Com base na metodologia de pesquisa qualitativa e participante, e com fulcro em uma investigação bibliográfica, documental e de campo, o artigo pretende problematizar o discurso oficial e a realidade vivenciada pelos presos. Os sujeitos da pesquisa foram selecionados aleatoriamente, a partir de critérios de segurança da direção da penitenciária. Os dados foram coletados por meio de entrevistas semiestruturadas e grupo focal. Os resultados alcançados mostram que o panorama atual da educação escolar nas prisões tem demonstrado fragilidades, não somente por atingir um número reduzido de presos no Brasil, mas, principalmente, porque a possibilidade de uma ação efetiva de educação nas prisões é sustentada, sobretudo, no compromisso pessoal dos professores, agentes penitenciários e técnicos envolvidos na tarefa. Além disso, predomina-se, nesses espaços, uma visão pragmática da educação escolar, isolada das demais políticas setoriais e relacionada à obtenção de um emprego ou profissão

    Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis : Results from the COVID-19 Global Rheumatology Alliance physician registry

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    Funding Information: Competing interests JAS is supported by the National Institute of Arthritis and Funding Information: Musculoskeletal and Skin Diseases (grant numbers K23 AR069688, R03 AR075886, L30 AR066953, P30 AR070253 and P30 AR072577), the Rheumatology Research Foundation (K Supplement Award and R Bridge Award), the Brigham Research Institute, and the R Bruce and Joan M Mickey Research Scholar Fund. JAS has received research support from Amgen and Bristol-Myers Squibb and performed consultancy for Bristol-Myers Squibb, Gilead, Inova, Janssen and Optum, unrelated to this work. ZSW reports grant support from Bristol-Myers Squibb and Principia/ Sanofi and performed consultancy for Viela Bio and MedPace, outside the submitted work. His work is supported by grants from the National Institutes of Health. MG is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K01 AR070585 and K24 AR074534; JY). KLH reports she has received speaker’s fees from AbbVie and grant income from BMS, UCB and Pfizer, all unrelated to this study. KLH is also supported by the NIHR Manchester Biomedical Research Centre. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories such as, among other institutions, AbbVie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal and UCB Pharma. LG reports research grants from Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz and Sanofi; consulting fees from AbbVie, Amgen, BMS, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi Aventis and UCB, all unrelated to this study. EFM reports that LPCDR received support for specific activities: grants from AbbVie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal, MSD, Celgene, Medac, Pharma Kern and GAfPA; grants and non-financial support from Pfizer; and non-financial support from Grünenthal, outside the submitted work. AS reports grants from a consortium of 13 companies (among them AbbVie, BMS, Celltrion, Fresenius Kabi, Lilly, Mylan, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi Aventis and UCB) supporting the German RABBIT register, and personal fees from lectures for AbbVie, MSD, Roche, BMS and Pfizer, outside the submitted work. AD-G has no disclosures relevant to this study. His work is supported by grants from the Centers for Disease Control and Prevention and the Rheumatology Research Foundation. KMD is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258) and the Rheumatology Research Foundation. NJP is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258). PD has received research support from Bristol-Myers Squibb, Chugai and Pfizer, and performed consultancy for Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Sanofi, Pfizer, Chugai, Roche and Janssen, unrelated to this work. NS is supported by the RRF Investigator Award and the American Heart Association. MFU-G reports grant support from Janssen and Pfizer. SB reports no competing interests related to this work. He reports non-branded consulting fees for AbbVie, Horizon, Novartis and Pfizer (all <10000).RGreportsnocompetinginterestsrelatedtothiswork.Outsideofthisworkshereportspersonaland/orspeakingfeesfromAbbVie,Janssen,Novartis,PfizerandCornerstones,andtravelassistancefromPfizer(all<10 000). RG reports no competing interests related to this work. Outside of this work she reports personal and/or speaking fees from AbbVie, Janssen, Novartis, Pfizer and Cornerstones, and travel assistance from Pfizer (all <10 000). JH reports no competing interests related to this work. He is supported by grants from the Rheumatology Research Foundation and the Childhood Arthritis and Rheumatology Research Alliance. He has performed consulting for Novartis, Sobi and Biogen, all unrelated to this work (<10000).JLhasreceivedresearchfundingfromPfizer,outsidethesubmittedwork.ESisaBoardMemberoftheCanadianArthritisPatientAlliance,apatientrun,volunteerbasedorganisationwhoseactivitiesarelargelysupportedbyindependentgrantsfrompharmaceuticalcompanies.PSreportsnocompetinginterestsrelatedtothiswork.HereportshonorariumfordoingsocialmediaforAmericanCollegeofRheumatologyjournals(<10 000). JL has received research funding from Pfizer, outside the submitted work. ES is a Board Member of the Canadian Arthritis Patient Alliance, a patient-run, volunteer-based organisation whose activities are largely supported by independent grants from pharmaceutical companies. PS reports no competing interests related to this work. He reports honorarium for doing social media for American College of Rheumatology journals (<10 000). PMM has received consulting/speaker’s fees from AbbVie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this study (all <10000).PMMissupportedbytheNationalInstituteforHealthResearch(NIHR)UniversityCollegeLondonHospitals(UCLH)BiomedicalResearchCentre(BRC).PCRreportsnocompetinginterestsrelatedtothiswork.Outsideofthisworkhereportspersonalconsultingand/orspeakingfeesfromAbbVie,EliLilly,Janssen,Novartis,PfizerandUCB,andtravelassistancefromRoche(all<10 000). PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). PCR reports no competing interests related to this work. Outside of this work he reports personal consulting and/or speaking fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and UCB, and travel assistance from Roche (all <10 000). JY reports no competing interests related to this work. Her work is supported by grants from the National Institutes of Health, Centers for Disease Control, and the Agency for Healthcare Research and Quality. She has performed consulting for Eli Lilly and AstraZeneca, unrelated to this project. Publisher Copyright: © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.Objective To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). Methods We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. Results Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. Conclusions People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.publishersversionPeer reviewe

    The limits of fiction: politics and absent scenes in Susumu Hani’s Bad Boys (Furyōshōnen, 1960). A film re-reading through its script

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    This text proposes an updated analysis of Susumu Hani’s Bad Boys (1960) through the director’s theoretical contribution and the re-reading of his script. This film, made within the limits of reality and fiction, was instrumental in the cinematic language of the sixties in Japan. Hani implemented herein a style that he developed during his earlier decade as a documentary maker for Iwanami Eiga studios. Hani based his filmmaking method on a philosophical pragmatism extracted from the practices of an amateur writing called seikatsu kiroku (life document) that appeared in the early 1950s. In fact, Bad Boys is a loose adaptation of Tobenai Tsubasa (Wings that Cannot Fly) an example of seikatsu kiroku consisting of a compilation of experiences written by inmates from the Kurihama reformatory. Hani responded to the demands for a new realism of the time with this film, which he made collectively with the former inmates of that reformatory. Additionally, a close analysis of the script reveals significant ‘absent scenes’ of student demonstrations, which are similar to those Oshima and Yoshida used in 1960. This fact evidences Hani’s shared concern with other filmmakers of the time about the necessities of bringing cinema closer to topical issues

    A database of freshwater fish species of the Amazon Basin

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    The Amazon Basin is an unquestionable biodiversity hotspot, containing the highest freshwater biodiversity on earth and facing off a recent increase in anthropogenic threats. The current knowledge on the spatial distribution of the freshwater fish species is greatly deficient in this basin, preventing a comprehensive understanding of this hyper-diverse ecosystem as a whole. Filling this gap was the priority of a transnational collaborative project, i.e. the AmazonFish project - https://www.amazon-fish.com/. Relying on the outputs of this project, we provide the most complete fish species distribution records covering the whole Amazon drainage. The database, including 2,406 validated freshwater native fish species, 232,936 georeferenced records, results from an extensive survey of species distribution including 590 different sources (e.g. published articles, grey literature, online biodiversity databases and scientific collections from museums and universities worldwide) and field expeditions conducted during the project. This database, delivered at both georeferenced localities (21,500 localities) and sub-drainages grains (144 units), represents a highly valuable source of information for further studies on freshwater fish biodiversity, biogeography and conservation

    Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

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    Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

    Assessment of human cytomegalovirus (HCMV) -specific memory T and B cell responses as predictors of HCMV infection after kidney transplantion.

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    [cat] El treball que constitueix aquesta tesi doctoral, investiga més a fons com avaluar cèl·lules T IB de memòria CMVh específiques, utilitzant una tècnica altament sensible, com l'assaig ELISPOT, que permet una enumeració precisa de respostes immunes antigen específiques a nivell individual cel·lular, pot ajudar a identificar millor els pacients cel.lulars i humorals immunitzat contra la CMVh i, per tant, en última instància, ajudar a la identificació de receptors d'al·loempelts renals amb alt risc d'infecció per CMVh després del trasplantament renal. És important destacar que un coneixement exacte i fiable del nivell de protecció immunitària contra CMVh dels pacients trasplantats permetria individualització per a la presa de decisions anti-viral, personalitzant així aquesta teràpia. A la primera part d'aquesta tesi, es demostra que les altes freqüències de les respostes de cèl·lules T CMVh específics, en particular contra l'antigen CMVh dominant IE-l, pot millorar significativament l'actual identificació serològica dels receptors de al·loempelts renals d'alt risc per infecció per CMVh. És important destacar que aquest enfocament era capaç de discriminar aquests pacients abans del trasplantament amb una alta sensibilitat, sense importar el tipus d'estratègia antiviral preventiva utilitzada està basada en els factors de risc clàssics per a l'estimació del risc de CMV després del trasplantament. D'altra banda, l'alt valor predictiu negatiu de la prova posa de manifest la utilitat d'aquesta eina de diagnòstic entre la població trasplantament de ronyó. Ala segona part d'aquest estudi, es proporcionarà més informació sobre la diafonia entre la resposta immune adaptativa memòria humoral i cel·lular contra de HCMV, mitjançant el control de la memòria T i de cèl·lules 8 respostes HCMV específics de la línia de base, el que augmenta significativament la capacitat de discriminar "veritable" immunitzat receptors de trasplantament renal en contra CMVh en comparació amb l'avaluació actual dels títols d'anticossos CMVh específics en els sèrums. En els punts d'estudi a l'adreça que el monitoratge-l IE freqüències de cèl.lules T específiques de CMVh abans del trasplantament seria ajudar els metges de trasplantament, per una banda per discriminar millor els pacients sense necessitat de CMVh tractament profilàctic d'aquells a qui la profilaxi preferentment s'han d'indicar i en l'altra, per predir millor els pacients en els quals amb seguretat podria interrompre la profilaxi tractament.[eng] Despite the outstanding progress made in the understanding of the immune response against viral pathogens as well as on the care-management of transplant patients since the beginning of organ transplantation, hCMV infection still represents a major adverse complication among solid organ and hematopoietic cell transplant patients directly threatening both allograft and patient survival. While the advent of new and more potent anti-viral therapies used either as anti-viral treatments during active infection or as part of a preventive strategy, has lead to a significant reduction of the incidence of hCMV infection and its related complications, the occurrence of viral infection after transplantation is still considered as a rather unpredictable event. Certainly, this is the reflection of the considerably poor clinical monitoring of the viral immune susceptibility of each individual, which is merely based on the serological immune status combination between recipient and donor IgGantibody levels in sera and the direct assessment of the virus itself replicating in peripheral blood. The work constituting this doctoral thesis, researches further into how assessing hCMV-specific memory T and B-cell subsets, using a highly sensitive technique such as the ELiSPOT assay, which allows an accurate enumeration of antigen-specific immune responses at the single cell level, may help to better identify cellular and humoral immunized patients against the hCMV and thus, ultimately helping identifying kidney allograft recipients at high risk of hCMV infection after kidney transplantation. Importantly, an accurate and reliable knowledge of the immune-protection level against hCMV of transplant patients would allow individualization for anti-viral decision-making, thus personalizing this therapy. To date, an important body of evidence has been generated within the transplant scientific community, demonstrating the key role of the adaptive immunity, and particularly the cellular immune response in preventing, controlling and restricting viral replication. In contrast to previous reported data, in which have analyzed different types of organ transplant patients, receiving distinct type of anti-viral therapies and have fundamentally focused on the post-transplant setting, we here focused for the first time on the evaluation of hCMV-specific memory T and B cells against different immunogenic hCMV antigens prior to kidney transplantation in very clean and homogenous cohorts of kidney transplant recipients. In the first part of this thesis, it is shown that high frequencies of hCMV-specific T-cell responses, particularly against the IE-1 dominant hCMV antigen, may significantly improve the current serological identification of those kidney allograft recipients at high-risk for hCMV infection. Importantly, this approach was capable to discriminate such patients before transplantation with high sensitivity, regardless the type of preventive anti-viral strategy used based on the classical risk factors for the estimation of CMV risk after transplantation. Furthermore, the high negative predictive value of the test highlights the usefulness of such diagnostic tool among the kidney transplant population. In the second part of this study, we provide further insight about the cross-talk between the humoral and cellular memory adaptive immune response against hCMV, by monitoring baseline hCMV-specific memory T and B-cell responses, which significantly increases the capacity to discriminate "true" immunized kidney transplant recipients against hCMV as compared to current evaluation of hCMV-specific antibody titers in the sera. Our study points to the direction that monitoring IE-1 hCMV-specific T-cell frequencies before transplantation would help transplant physicians on the one hand to better discriminate patients with no need of hCMV prophylactic treatment from those in whom prophylaxis should preferentially be indicated and on the other, to better predict those patients in whom prophylaxis treatment could safely be discontinued

    In situ and genetic characterization of Gossypium barbadense populations from the states of Pará and Amapá, Brazil Caracterização in situ e genética de Gossypium barbadense dos Estados do Pará e do Amapá

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    The objective of this work was to characterize the populations of Gossypium barbadense in the states of Amapá and Pará, Brazil. In situ characterization was conducted through interviews with the owners of the plants and environmental observations. Leaf or petal tissue as well as seed samples were collected for genetic characterization by single sequence repeats markers and for storage in germplasm banks, respectively. The plants were maintained in dooryards and used mainly for medical purposes. The genetic analysis showed no heterozygous plants at the loci tested (f = 1), indicating that reproduction occurs mainly through selfing. The total genetic diversity was high (He = 0.39); and a high level of differentiation was observed between cotton plants from the two states (F ST = 0.36). Conventional methods of in situ maintenance of G. barbadense populations are not applicable. The conservation of the genetic variability of populations present in the two states could be achieved through germplasm collection and establishing of ex situ seed banks.O objetivo deste trabalho foi caracterizar populações de Gossypium barbadense dos estados do Amapá e Pará. A caracterização in situ foi conduzida por meio de entrevistas com os proprietários das plantas e por observações sobre o ambiente. Tecidos de folhas ou de pétalas, além de sementes, foram coletados para a caracterização genética com marcadores SSR ("single sequence repeats") e para o armazenamento em bancos de germoplasma, respectivamente. As plantas eram mantidas em fundos de quintal e usadas, principalmente, para fins medicinais. As análises genéticas não mostraram plantas heterozigotas nos locos testados (f = 1), o que indica que a reprodução ocorre principalmente por meio de autofecundação. A diversidade genética total foi alta (He = 0,39), e um alto nível de diferenciação foi observado entre as plantas de algodoeiro dos dois estados (F ST = 0,36). Métodos convencionais para a manutenção in situ das populações de G. barbadense não são aplicáveis. A conservação da variabilidade genética das populações presentes nos dois estados deve ser realizada pela coleta de germoplasma e pela constituição de bancos de sementes ex situ
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