Immune tumor microenvironment in ovarian cancer ascites

Ovarian cancer (OC) has a specific type of metastasis, via transcoelomic, and most of the patients are diagnosed at advanced stages with multiple tumors spread within the peritoneal cavity. The role of Malignant Ascites (MA) is to serve as a transporter of tumor cells from the primary location to the peritoneal wall or to the surface of the peritoneal organs. MA comprise cellular components with tumor and non-tumor cells and acellular components, creating a unique microenvironment capable of modifying the tumor behavior. These microenvironment factors influence tumor cell proliferation, progression, chemoresistance, and immune evasion, suggesting that MA play an active role in OC progression. Tumor cells induce a complex immune suppression that neutralizes antitumor immunity, leading to disease progression and treatment failure, provoking a tumor-promoting environment. In this review, we will focus on the High-Grade Serous Carcinoma (HGSC) microenvironment with special attention to the tumor microenvironment immunology.This work was supported by Fundacão para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior and European Union through a PhD fellowship (2021.05081.BD) cosponsored by Fundo Social Europeu (FSE) through Programa Operacional Regional Norte (Norte 2020)

Analysis of salivary levels of IL-1β, IL17A, OPG and RANK-L in periodontitis using the 2017 Classification of Periodontal Diseases - an exploratory observational study

Periodontitis is a chronic disease with a high overall prevalence. It involves a complex interplay between the immune-inflammatory pathways and biofilm changes, leading to periodontal attachment loss. The aims of this study were (i) to assess whether the salivary IL-1β, IL-17A, RANK-L and OPG levels have the potential to discriminate between the mild and severe periodontitis conditions; and (ii) to enable diagnostic/prognostic actions to differentiate between distinct levels of the disease. The analysis of the clinical parameters and the evaluation of the salivary immunomediators levels by means of a multiplex flow assay revealed a statistically significantly higher level of IL-1β in the periodontitis III/IV patients, as well as a higher level of RANK-L in the periodontitis III/IV and I/II patients, when compared to the healthy controls. Furthermore, the grade C periodontitis patients presented a significantly higher level of RANK-L compared to the grade B and grade A patients. In the grade C patients, IL-1β had a positive correlation with the PPD and CAL indices and RANK_L had a positive correlation with CAL. The evidence emerging from this study associates the salivary IL-1β and RANK-L levels with an advanced stage of periodontitis, stage III/IV, and with grade C, suggesting the possible cooperative action of both in the inflammatory and bone loss events. In addition to IL-1β, RANK-L could be considered a combined diagnostic biomarker for periodontitis.This research was funded by the University Institute of Health Sciences (IUCS-CESPU). The participation of Marta Relvas was funded by the project grants AMDNCPD_PI2RL_IINFACTS_2021 and ADMT1PD_GI2-CESPU_2022, while the participation of Luis Monteiro was funded by the project grant mTORORAL_GI2-CESPU_2022 from CESPU University, by the Foundation for Science and Technology (FCT)–project UIDB/50026/2020 and UIDP/50026/2020, by the NORTE-01-0145- FEDER-000013 and NORTE-01-0145-FEDER-000023 projects, and by the Norte Portugal Regional Operational Program (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF), the FCT contracts 2021.07836.BD to AMF and CEECIND/00185/2020 to RS

ACCESIBILIDAD Y ATENCIÓN PRIMARIA DE SALUD – LA REVISIÓN DE LOS USUARIOS

Objective: to evaluate the accessibility, based on the opinion of users of three health centers of the Regional Health Administration of the Alentejo (ARSA) where they have introduced organizational changes. Method: a descriptive study with quantitative approach, resorting to the use of a questionnaire. The sample consisted of users of three health centers. Data collection was carried out in two months. The data were analyzed with the Statistical Package for Social Sciences (SPSS ®). Consent was obtained from ARSA (No. 11/2007), with the ethical component of data collection with human beings. Results: mostly female users who are over 60 years responded. The majority has a family doctor for over 15 years, the waiting time for a routine visit ranges from one to four weeks and get an emergency appointment the same day. Conclusion: the users are satisfied with the changes in the physical structure and functioning of health centers, translating into improvements in accessibility to care. However, they mentioned the need for changes at the level of human resources, customer assistance, physical environment and utilities

Dysregulation of glycerophospholipid metabolism during Behçet's disease contributes to a pro-inflammatory phenotype of circulating monocytes

Behcet's disease (BD) is a relapsing, multisystem and inflammatory condition characterized by systemic vasculitis of small and large vessels. Although the etiopathogenesis of BD remains unknown, immune-mediated mechanisms play a major role in the development of the disease. BD patients present leukocyte infiltration in the mucocutaneous lesions as well as neutrophil hyperactivation. In contrast to neutrophils, whose involvement in the pathogenesis of BD has been extensively studied, the biology of monocytes during BD is less well known. In this study, we analyzed the phenotype and function of circulating monocytes of 38 BD patients from Hospital of Braga. In addition, we evaluated the impact of inflammatory and metabolomic plasma environment on monocyte biology. We observed a worsening of mitochondrial function, with lower mitochondrial mass and increased ROS production, on circulating monocytes of BD patients. Incubation of monocytes from healthy donors with the plasma of BD patients mimicked the observed phenotype, strongly suggesting the involvement of serum mediators. BD patients, regardless of their symptoms, had higher serum pro-inflammatory TNF-alpha and IP-10 levels and IL-1 beta/IL-1RA ratio. Untargeted metabolomic analysis identified a dysregulation of glycerophospholipid metabolism on BD patients, where a significant reduction of phospholipids was observed concomitantly with an increase of lysophospholipids and fatty acids. These observations converged to an enhanced phospholipase A2 (PLA(2)) activation. Indeed, inhibition of PLA(2) with dexamethasone or the downstream cyclooxygenase (COX) enzyme with ibuprofen was able to significantly revert the mitochondrial dysfunction observed on monocytes of BD patients. Our results show that the plasma inflammatory environment coupled with a dysregulation of glycerophospholipid metabolism in BD patients contribute to a dysfunction of circulating monocytes

Lutas coletivas por moradia na região metropolitana do Rio de Janeiro: mapeando conflitos / Collective struggles for housing in the metropolitan region of Rio de Janeiro: mapping conflicts

A luta pelo direito à cidade e à moradia digna tem sido muitas vezes invisibilizada, tanto pela sociedade quanto pela mídia hegemônica. Essa situação de ocultamento de justas e dignas demandas sociais tem resultado em iniciativas voltadas a respaldar a ação e o protagonismo de comunidades e ocupações na Região Metropolitana do Rio de Janeiro. Dessa maneira, a pesquisa “Acompanhando e Mapeando Conflitos” nasceu com o intuito de caracterizar o conceito de conflito assim como a sua identificação no território. O trabalho iniciado no ano de 2018 partiu do entendimento da necessária identificação desses conflitos, realizando um levantamento de dados históricos e transformando-os em uma cartografia social. Para isso, a equipe realizou o acompanhamento de lideranças comunitárias participantes do Fórum de Luta pela Moradia (Niterói) e do Conselho Popular (Rio de Janeiro), tendo como premissa contribuir para o empoderamento dos moradores envolvidos no processo. Ao final desse primeiro ano de pesquisa, todo o material reunido foi publicado no site do NEPHU-UFF, visando justamente oferecer acesso ao mesmo, democratizando o conhecimento produzido dentro de uma universidade pública, a Universidade Federal Fluminense, cumprindo assim sua função social que deve ir além dos muros da própria instituição

Perivascular-like cells contribute to the stability of the vascular network of osteogenic tissue formed from cell sheet-based constructs

In recent years several studies have been supporting the existence of a close relationship in terms of function and progeny between Mesenchymal Stem Cells (MSCs) and Pericytes. This concept has opened new perspectives for the application of MSCs in Tissue Engineering (TE), with special interest for the pre-vascularization of cell dense constructs. In this work, cell sheet technology was used to create a scaffold-free construct composed of osteogenic, endothelial and perivascular-like (CD146+) cells for improved in vivo vessel formation, maturation and stability. The CD146 pericyte-associated phenotype was induced from human bone marrow mesenchymal stem cells (hBMSCs) by the supplementation of standard culture medium with TGF-b1. Co-cultured cell sheets were obtained by culturing perivascular-like (CD146+) cells and human umbilical vein endothelial cells (HUVECs) on an hBMSCs monolayer maintained in osteogenic medium for 7 days. The perivascular-like (CD146+) cells and the HUVECs migrated and organized over the collagen-rich osteogenic cell sheet, suggesting the existence of cross-talk involving the co-cultured cell types. Furthermore the presence of that particular ECM produced by the osteoblastic cells was shown to be the key regulator for the singular observed organization. The osteogenic and angiogenic character of the proposed constructs was assessed in vivo. Immunohistochemistry analysis of the explants revealed the integration of HUVECs with the host vasculature as well as the osteogenic potential of the created construct, by the expression of osteocalcin. Additionally, the analysis of the diameter of human CD146 positive blood vessels showed a higher mean vessel diameter for the co-cultured cell sheet condition, reinforcing the advantage of the proposed model regarding blood vessels maturation and stability and for the in vitro pre-vascularization of TE constructs.Funding provided by Fundacao para a Ciencia e a Tecnologia project Skingineering (PTDC/SAU-OSM/099422/2008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Relatório de estágio : mestrado em análises clínicas

Relatório de estágio no âmbito do Mestrado em Análises Clínicas, apresentado à Faculdade de Farmácia da Universidade de CoimbraAs Análises Clínicas representam uma importante ferramenta para o diagnóstico e seguimento de muitas patologias. Vários estudos internacionais apontam que setenta por cento (70%) da tomada da decisão clínica médica está dependente de, ou é confirmada por, resultados de testes médicos laboratoriais. Apesar de toda a componente teórica inerente a este tema, a aplicação dos conceitos a nível prático tem extrema importância. O objetivo deste relatório é documentar o estágio curricular do Mestrado em Análises Clínicas. Este estágio foi realizado no Laboratório S. José, durante um período de seis meses. Os objetivos do estágio curricular são não só aprofundar os conceitos teóricos adquiridos ao longo do primeiro ano do mestrado como também adquirir novas competências a nível prático. As Análises Clínicas podem ser divididas em quatro valências major: Hematologia, Imunologia, Bioquímica e Microbiologia. Durante o estágio, tomei contacto com todas as quatro, ainda que se tenham evidenciado os trabalhos realizados na Hematologia e na Imunologia durante a elaboração deste relatório. As principais partes constituintes deste documento são uma breve introdução, a descrição do funcionamento do Laboratório S. José, a apresentação das duas valências escolhidas e uma breve conclusão.Clinical Analysis represent an important tool to diagnose and follow-up many diseases. Several international studies indicate that seventy percent (70%) of medical decision is dependente or confirmed by laboratory results. Although all the theorical inherent to this topic, the application of concepts at pratical level have extreme importance. The purpose of this report is document the traineeship of the Master degree in Clinical Analysis. This traineeship was performed in Laboratório S. José, during six months. The traineeship’s aims were not only deepen the theorical concepts acquired at the first year of the Master degree, but also acquire new skills at pratical level. Clinical Analysis can be divided into four general valences: Hemathology, Immunology, Biochemistry and Microbiology. During the traineeship, they were worked all the four, even if only the work realized on Hemathology and Immunology has been discussed in this report. The main parts constituents of this document are a brief introduction, the description of the operation of the Laboratório S. José, the presentation of the two chosen valences and a brief conclusion

Relatório de estágio : mestrado em análises clínicas

Relatório de estágio no âmbito do Mestrado em Análises Clínicas, apresentado à Faculdade de Farmácia da Universidade de CoimbraAs Análises Clínicas representam uma importante ferramenta para o diagnóstico e seguimento de muitas patologias. Vários estudos internacionais apontam que setenta por cento (70%) da tomada da decisão clínica médica está dependente de, ou é confirmada por, resultados de testes médicos laboratoriais. Apesar de toda a componente teórica inerente a este tema, a aplicação dos conceitos a nível prático tem extrema importância. O objetivo deste relatório é documentar o estágio curricular do Mestrado em Análises Clínicas. Este estágio foi realizado no Laboratório S. José, durante um período de seis meses. Os objetivos do estágio curricular são não só aprofundar os conceitos teóricos adquiridos ao longo do primeiro ano do mestrado como também adquirir novas competências a nível prático. As Análises Clínicas podem ser divididas em quatro valências major: Hematologia, Imunologia, Bioquímica e Microbiologia. Durante o estágio, tomei contacto com todas as quatro, ainda que se tenham evidenciado os trabalhos realizados na Hematologia e na Imunologia durante a elaboração deste relatório. As principais partes constituintes deste documento são uma breve introdução, a descrição do funcionamento do Laboratório S. José, a apresentação das duas valências escolhidas e uma breve conclusão.Clinical Analysis represent an important tool to diagnose and follow-up many diseases. Several international studies indicate that seventy percent (70%) of medical decision is dependente or confirmed by laboratory results. Although all the theorical inherent to this topic, the application of concepts at pratical level have extreme importance. The purpose of this report is document the traineeship of the Master degree in Clinical Analysis. This traineeship was performed in Laboratório S. José, during six months. The traineeship’s aims were not only deepen the theorical concepts acquired at the first year of the Master degree, but also acquire new skills at pratical level. Clinical Analysis can be divided into four general valences: Hemathology, Immunology, Biochemistry and Microbiology. During the traineeship, they were worked all the four, even if only the work realized on Hemathology and Immunology has been discussed in this report. The main parts constituents of this document are a brief introduction, the description of the operation of the Laboratório S. José, the presentation of the two chosen valences and a brief conclusion