Expression and function of co-inhibitory receptors PD-1, TIGIT, TIM-3, and LAG-3 in systemic sclerosis

Systemic sclerosis is an autoimmune connective tissue disorder associated with fibrosis of the skin and internal organs. Co-inhibitory receptors (Co-IRs) regulate immune responses and have been shown to control autoimmune phenotypes. We explored the role of these receptors in systemic sclerosis through their expression in circulating lymphocytes and their control of lymphocyte function in vitro and in vivo. We found that individual co-IRs were increased on specific lymphocyte populations in patients. PD-1 was increased on CD4+ memory T cells, while TIGIT was increased on both CD4+ and CD8+ memory T cells. Changes in TIM-3 expression were limited to cytotoxic NK cell populations while LAG-3 remained low and unchanged on all lymphocyte populations identified. The blockade of PD-1 in vitro, in particular, had a greater effect on modulating cytokine production in systemic sclerosis PBMCs compared to the blockade of TIGIT and TIM-3 versus a similar modulation of cytokine production by PD-1, TIGIT, and TIM-3 in healthy controls. This indicates an increased level of exhaustion in PBMCs from systemic sclerosis patients that can be overcome by the blockade of PD-1, but not TIGIT or TIM-3. However, the blockade of TIM-3 in vitro had the greatest effect on modulating the production of soluble factors that regulate pro-fibrotic changes in gene expression in systemic sclerosis fibroblasts. In vivo, TIGIT and TIM-3 were unable to consistently regulate the autoimmune phenotype of sclerodermatous GvHD mice. These data indicate a potential function for lymphocyte exhaustion in regulating the autoimmune and inflammatory response in systemic sclerosis, with specific co-IRs playing defined roles in disease pathogenesis

Automated analysis of 16-color polychromatic flow cytometry data maps immune cell populations and reveals a distinct inhibitory receptor signature in systemic sclerosis

Background. The phenotypic profiles of both peripheral blood and tissue-resident immune cells have been linked to the health status of individuals with infectious and autoimmune diseases, as well as cancer. In light of the promising clinical trial results of agents that block the Inhibitory Receptor (IR) Programmed Death 1 (PD-1) axis, novel flow cytometric panels that simultaneously measure multiple IRs on several immune cell subsets could provide the distinct IR signatures to target in combinational therapies for many disease states. Also, due to the paucity of human samples, larger (14+ color) ‘1-tube’ panels for immune cell characterization ex vivo are of a high value in translational studies. Development of fluorescent-based panels offer several advantages as compared with analogous mass cytometric methods, including the ability to sort multiple populations of interest from the sample for further study. However, automated platforms of multi-dimensional single cell analysis that allow objective and comprehensive population characterization are severely underutilized on data generated from large polychromatic panels. Methods. A 16-color flow cytometry (FCM) panel was developed and optimized for the simultaneous characterization and purification of multiple human immune cell populations on a 4- laser BD FACSARIA II cell sorter. FCM data of samples obtained from healthy subjects and individuals with systemic sclerosis (SSc) were loaded into Cytobank cloud, then compensated and analyzed with SPADE clustering algorithm. The viSNE algorithm was also employed to compress the data into a 2D map of phenotypic space that was subsequently clustered using SPADE. For comparison, the FCM data were also analyzed manually using FlowJo software. Results. Our novel 16-color panel recognizes CD3, CD4, CD8, CD45RO, CD25, CD127, CD16, CD56, γδTCR, vα24, PD-1, LAG-3, CTLA-4, and TIM-3; it also contains a CD1d-tetramer and a live-dead dye (with CD19 and CD14 included as a combined dump channel). This panel allows combinational IR signatures to be determined from CD4+ T, CD8+ T, Natural Killer (NK), invariant Natural Killer (iNKT), and gamma delta (γδ) immune cell subsets within one sample. We have successfully identified all subsets of interest using automatic SPADE and viSNE algorithms integrated into Cytobank services, and demonstrated a distinctive phenotype of IR distribution on healthy versus systemic sclerosis subject groups. Conclusions. Methods of automatic analysis that were originally developed for processing multi-dimensional mass cytometry can be applied to polychromatic FCM datasets and provide robust results, including subset identification and distinct IR signatures in healthy compared to diseased subject groups

Biblioteca hospitalar : reflexões sobre conceitos, serviços e produtos

Monografia (graduação)—Universidade de Brasília, Faculdade de Ciência da Informação e Documentação, Curso de Biblioteconomia, 2019.Tendo em vista a interdisciplinaridade entre Ciência da Informação e Medicina, o reduzido número de publicações sobre bibliotecas em ambientes hospitalares e a limitada abordagem sobre tal vertente da área de Ciência da Informação como campo de atuação do bibliotecário, pesquisa-se sobre biblioteca hospitalar, a fim de analisar, com base na literatura, as características das unidades de informação e os serviços e produtos oferecidos para o corpo assistencial e para os pacientes na área de saúde. Para isto, analisa-se o conceito de biblioteca hospitalar, a literatura especializada quanto às características, serviços e produtos de tais bibliotecas, as características da biblioterapia e as redes de informação na área da medicina e saúde em nível internacional, nacional, regional e no Distrito Federal. Realiza-se, então, uma pesquisa exploratória e descritiva e se utiliza a técnica de pesquisa bibliográfica, com abordagem qualitativa. Com essa pesquisa pretende-se ampliar o conhecimento da comunidade acadêmica sobre as características, serviços e produtos das bibliotecas hospitalares e ressaltar a importância destas.In view of the interdisciplinarity between Information Science and Medicine, the reduced number of publications on libraries in hospital environments and the limited approach on such aspect of the Information Science area as the librarian's field of activity, research on the hospital library, In order to analyze, based on the literature, the characteristics of the information units and the services and products offered to the care body and to the patients in the health area. To this end, we analyze the concept of hospital library, the specialized literature on the characteristics, services and products of such libraries, the characteristics of bibliotherapy and the information networks in the area of medicine and health at the international, national, regional and District levels. Federal. Then, an exploratory and descriptive research is carried out and the bibliographic research technique is used, whose approach was qualitative. This research aims to expand the knowledge of the academic community about the characteristics, services and products of hospital libraries and highlight their importance

Putting data to work for people in Senegal

French version available in IDRC Digital Library: Données au service de la population du SénégalSpanish version available in IDRC Digital Library: Poner la información a trabajar para la gente en SenegalWhen the new mayor of Tivaouane, Senegal, took office in 2002, he was stymied by the lack of current information about his community. Thanks to city surveys, the implementation of a community-based poverty monitoring system, and the creation of an observatory of living conditions, that is no longer the case. The city’s population is the clear beneficiary

Poner la información a trabajar para la gente en Senegal

Versión en inglés disponible en la Biblioteca Digital del IDRC: Putting data to work for people in SenegalVersión en francés disponible en la Biblioteca Digital del IDRC: Données au service de la population du SénégalCuando asumió el cargo en 2002, el nuevo alcalde de Tivaouane, en Senegal, se sentía bloqueado por la falta de información actualizada sobre su comunidad. Por medio de encuestas, la implementación de un sistema de seguimiento comunitario y la creación de un observatorio de las condiciones de vida, resolvió el problema y la población de la ciudad fue claramente beneficiada

Learning how not to be poor in Burkina Faso

French version available in IDRC Digital Library: Apprendre à ne pas être pauvre au Burkina FasoSpanish version available in IDRC Digital Library: Aprendiendo a dejar de ser pobres en Burkina FasoWhen a community-based monitoring system showed Burkina Faso villagers just how poor they were, in so many ways, they did not like what they saw. They set out to take their development in hand. Community action has led to tangible improvements and new funding sources for key development projects

Apprendre à ne pas être pauvre au Burkina Faso

Version anglaise disponible dans la Bibliothèque numérique du CRDI: Learning how not to be poor in Burkina FasoVersion espagnole disponible dans la Bibliothèque numérique du CRDI: Aprendiendo a dejar de ser pobres en Burkina FasoUn système de suivi communautaire de la pauvreté a permis à des villageois du Burkina Faso d’analyser leur état de pauvreté, sous divers aspects, et les résultats ne leur ont pas plu. Aussi, ont-ils décidé d’agir. Leur action collective a entraîné des améliorations concrètes et attiré de nouvelles sources de financement destiné à des projets de développement prioritaires

Aprendiendo a dejar de ser pobres en Burkina Faso

Versión en inglés disponible en la Biblioteca Digital del IDRC: Learning how not to be poor in Burkina FasoVersión en francés disponible en la Biblioteca Digital del IDRC: Apprendre à ne pas être pauvre au Burkina FasoUn sistema de seguimiento comunitario mostró a los pobladores de Burkina Faso cuán pobres eran, en muchos sentidos. Lo que vieron no les gustó y decidieron hacerse cargo de su desarrollo. La acción de la comunidad condujo a mejoras tangibles y atrajo nuevas fuentes de financiamiento para proyectos de desarrollo fundamentales

Données au service de la population du Sénégal

Version anglaise disponible dans la Bibliothèque numérique du CRDI: Putting data to work for people in SenegalVersion espagnole disponible dans la Bibliothèque numérique du CRDI: Poner la información a trabajar para la gente en SenegalLorsque le nouveau maire de Tivaouane, au Sénégal, est entré en fonction en 2002, le manque d’information à jour sur sa collectivité l’empêchait d’agir. Mais depuis, les enquêtes menées dans la commune, l’adoption d’un système de suivi communautaire de la pauvreté et la création d’un observatoire des conditions de vie ont changé la donne, et les citoyens en bénéficient

Hemangioma hepático gigante: Giant hepatic hemangioma

Introdução: Devido à maior disponibilidade de exames de imagem, os tumores hepáticos estão cada vez mais presentes na prática clínica, tendo como o mais comum o hemangioma (5-20%) da população, com maior incidência em mulheres (5:1). Por ser comumente diagnosticado de maneira incidental, os hemangiomas gigantes podem cursar com sintomas condutores a suspeita. Apresentação do caso: MCRM, sexo feminino, 33 anos de idade, admitida no PS Ciams Urias Magalhães, com quadro de desconforto no abdome superior, sensação de plenitude. Negou comorbidades e uso de medicamentos. Estável hemodinamicamente, massa palpável em abdome. Tomografia de tórax evidenciou lesão de 7 cm em seu maior diâmetro, compatível com hemangioma. Discussão: o tratamento se mantém controverso. Atualmente, a conduta é expectante, exceto em casos de pacientes sintomáticos, tumores gigantes (>4 cm ), com complicações e desejo de engravidar. Nesses casos, o tratamento cirúrgico é indicado, sendo eles a ressecção hepática ou a hepatectomia. Conclusão: Geralmente, são tumores hepáticos benignos e assintomáticos, apesar de estarem sendo cada vez mais diagnosticados os hemangiomas gigantes. As complicações são raras, como rotura, abscesso, Síndrome de Kasabach-Merritt e icterícia por obstrução, ficando reservado o transplante hepático nesses casos mais graves