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Neutrophil overstimulation plays a crucial role in tissue damage during severe infections. As pathogen-derived neuraminidase (NEU) stimulate neutrophils, we investigated whether host NEU can be targeted to regulate neutrophil dysregulation observed in severe infections.The effects of NEU inhibitors in lipopolysaccharide (LPS)-stimulated neutrophils from healthy donors or COVID-19 patients were determined by evaluating the shedding of surface sialic acids, cell activation, and reactive oxygen species (ROS) production. Re-analysis of single-cell RNA sequencing of respiratory tract samples from COVID-19 patients was also carried out. The effects of Oseltamivir on sepsis and betacoronavirus-induced acute lung injury were evaluated in murine models.Oseltamivir and Zanamivir constrain host NEU activity, surface sialic acid release, cell activation, and ROS production by LPS-activated human neutrophils. Mechanistically, LPS increased the interaction of NEU1 with the matrix metalloproteinase (MMP)-9. Inhibition of MMP-9 prevents LPS-induced NEU activity and neutrophil response. In vivo, treatment with Oseltamivir fine-tunes neutrophil migration and improves infection control and host survival in peritonitis and pneumonia sepsis. NEU1 is also highly expressed in neutrophils from COVID-19 patients and treatment of whole blood samples from these patients with Oseltamivir or Zanamivir reduces neutrophil overactivation. Oseltamivir treatment of intranasally infected mice with the mouse hepatitis coronavirus 3 (MHV-3) decreased lung neutrophil infiltration, viral load, and tissue damage.These findings suggest that NEU1-MMP-9 interplay induces neutrophil overactivation. In vivo, it was shown that NEU may serve as a host-directed target to dampen neutrophil dysfunction during severe infections.

OLIVEIRA, Larayne Gallo Farias et al. Desigualdades no acesso à saúde: um olhar sobre a população negra na atenção primária à saúde. Acesso à saúde no Brasil: percursos da universalização. Tradução . Curitiba: Bagai, 2023. . Disponível em: https://doi.org/10.37008/978-65-5368-205-4.18.03.23

COVID-19 has accounted for more than 6 million deaths worldwide. Bacillus Calmette–Guérin (BCG), the existing tuberculosis vaccine, is known to induce heterologous effects over other infections due to trained immunity and has been proposed to be a potential strategy against SARS-CoV-2 infection. In this report, we constructed a recombinant BCG (rBCG) expressing domains of the SARS-CoV-2 nucleocapsid and spike proteins (termed rBCG-ChD6), recognized as major candidates for vaccine development. We investigated whether rBCG-ChD6 immunization followed by a boost with the recombinant nucleocapsid and spike chimera (rChimera), together with alum, provided protection against SARS-CoV-2 infection in K18-hACE2 mice. A single dose of rBCG-ChD6 boosted with rChimera associated with alum elicited the highest anti-Chimera total IgG and IgG2c Ab titers with neutralizing activity against SARS-CoV-2 Wuhan strain when compared with control groups. Importantly, following SARS-CoV-2 challenge, this vaccination regimen induced IFN-γ and IL-6 production in spleen cells and reduced viral load in the lungs. In addition, no viable virus was detected in mice immunized with rBCG-ChD6 boosted with rChimera, which was associated with decreased lung pathology when compared with BCG WT-rChimera/alum or rChimera/alum control groups. Overall, our study demonstrates the potential of a prime-boost immunization system based on an rBCG expressing a chimeric protein derived from SARS-CoV-2 to protect mice against viral challenge.

Objective: To map the methods of dissertations and theses of technological productions of graduate professionals/students of a federal university in southern Brazil. Method: Scoping Review, which will be developed following the recommendations of the international guide Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews and the Joanna Briggs Institute Reviewers Manual, registered in the Open Science Framework platform (https://osf.io/jnfz9/). This study will be conducted in five steps: identification of the research question; identification of relevant studies; selection of studies for review; data mapping; and synthesis and reporting of results. The searches and identification of studies, will occur in May 2023 in the University Library databases. Results: The results included in this scoping review will be classified into conceptual categories from thematic categorical content analysis, following the three proposed phases: pre-analysis; exploration of the material and treatment of the results, inference and interpretation.

Neutrophil overstimulation plays a crucial role in tissue damage during severe infections. Neuraminidase (NEU)-mediated cleavage of surface sialic acid has been demonstrated to regulate leukocyte responses. Here, we report that antiviral NEU inhibitors constrain host NEU activity, surface sialic acid release, ROS production, and NETs released by microbial-activated human neutrophils.In vivo, treatment with Oseltamivir results in infection control and host survival in peritonitis and pneumonia models of sepsis. Single-cell RNA sequencing re-analysis of publicly data sets of respiratory tract samples from critical COVID-19 patients revealed an overexpression of NEU1 in infiltrated neutrophils. Moreover, Oseltamivir or Zanamivir treatment of whole blood cells from severe COVID-19 patients reduces host NEU-mediated shedding of cell surface sialic acid and neutrophil overactivation. These findings suggest that neuraminidase inhibitors can serve as host-directed interventions to dampen neutrophil dysfunction in severe infections.At a GlanceIn a severe systemic inflammatory response, such as sepsis and COVID-19, neutrophils play a central role in organ damage. Thus, finding new ways to inhibit the exacerbated response of these cells is greatly needed. Here, we demonstrate thatin vitrotreatment of whole blood with the viral neuraminidase inhibitors Oseltamivir or Zanamivir, inhibits the activity of human neuraminidases as well as the exacerbated response of neutrophils. In experimental models of severe sepsis, oseltamivir decreased neutrophil activation and increased the survival rate of mice. Moreover, Oseltamivir or Zanamivirex vivotreatment of whole blood cells from severe COVID-19 patients rewire neutrophil function.

Peer reviewed: True, Zika virus (ZIKV) is a single-strand RNA mosquito-borne flavivirus with significant public health impact. ZIKV infection induces double-strand DNA breaks (DSBs) in human neural progenitor cells that may contribute to severe neuronal manifestations in newborns. The DNA-PK complex plays a critical role in repairing DSBs and in the innate immune response to infection. It is unknown, however, whether DNA-PK regulates ZIKV infection. Here we investigated the role of DNA-PKcs, the catalytic subunit of DNA-PK, during ZIKV infection. We demonstrate that DNA-PKcs restricts the spread of ZIKV infection in human epithelial cells. Increased ZIKV replication and spread in DNA-PKcs deficient cells is related to a notable decrease in transcription of type I and III interferons as well as IFIT1, IFIT2, and IL6. This was shown to be independent of IRF1, IRF3, or p65, canonical transcription factors necessary for activation of both type I and III interferon promoters. The mechanism of DNA-PKcs to restrict ZIKV infection is independent of DSB. Thus, these data suggest a non-canonical role for DNA-PK during Zika virus infection, acting downstream of IFNs transcription factors for an efficient antiviral immune response.

Este artículo tuvo como objetivo analizar cómo la red pública municipal de Canavieiras - BA garantizó el derecho a la educación en el contexto de la pandemia de COVID-19. El problema cuestiona: cual es el dominio de estos docentes para la enseñanza a través de la intermediación tecnológica? ¿Cuál es la calidad de acceso de docentes y estudiantes para realizar la docencia en línea? A través de una investigación cualitativa, a partir de los resultados del cuestionario aplicado a los docentes del Municipio de Canavieiras-BA, donde se cuestionó el uso de la mediación tecnológica durante la pandemia, así, se buscó describir cómo docentes y alumnos del Sistema Municipal de Educación - SME desarrolló actividades educativas en el período de distanciamiento social y aislamiento. En este sentido, se puede ver que los datos de la investigación indican que parte de los docentes optó por utilizar sólo la actividad impresa, en el período remoto, como era la forma encontrada para garantizar la enseñanza a los estudiantes, y, por lo tanto, este tipo de artificio hizo que la enseñanza de los estudiantes fuera responsabilidad de las familias, lo que comprometía el Derecho a la Educación de los estudiantes de familias sin los conocimientos básicos para ayudar a los estudiantes durante este proceso., This article aimed to analyze how the municipal public network of Canavieiras - BA ensured the right to education in the context of the COVID-19 pandemic. Its problem questions: what is the domain of these teachers for teaching through technological intermediation? What is the quality of access for teachers and students to carry out online teaching? Through a qualitative research, based on the results of the questionnaire applied to teachers in the Municipality of Canavieiras-BA, where the use of technological mediation during the pandemic was questioned, thus, it sought to describe how teachers and students of the Municipal Education System - SME developed educational activities in the period of social distancing and isolation. In this sense, it can be seen that the research data indicate that parts of the teachers chose to use only the printed activity, in the remote period, as it was the way found to ensure teaching to students, and, thus, this type of artifice made the teaching of students the responsibility of families, which compromised the Right to Education for students from families without the basic knowledge to help students during this process., O presente artigo objetivou analisar como a rede pública municipal de Canavieiras – BA assegurou o direito à educação no contexto da pandemia de COVID-19. Sua problemática questiona qual o domínio desses professores para o ensino por intermediação tecnológica? Qual a qualidade de acesso dos professores e alunos para a realização do ensino online? Por meio de uma pesquisa qualitativa, a partir dos resultados do questionário aplicado aos professores do Município de Canavieiras-BA, onde foi questionado o uso de mediação tecnológica durante a pandemia, assim, buscou descrever como os professores e alunos do Sistema Municipal de Educação – SME desenvolveram as atividades educativas no período de distanciamento e isolamento social. Neste sentido, pode-se constatar que os dados da pesquisa apontam que partes dos professores optaram por utilizar apenas a atividade impressa, no período remoto, pois foi a forma encontrada de assegurar o ensino aos estudantes, e, deste modo, esse tipo de artifício tornou o ensino dos alunos responsabilidade das famílias, o que comprometeu o Direito à Educação para os alunos oriundos de famílias sem o conhecimento básico para ajudar os estudantes durante este processo.

Ultrasensitive electroanalytical monitoring of interleukin-6 levels in serum samples has emerged as a valuable tool for the early diagnosis of inflammatory diseases. Despite its advantages, there is a lack of strategies for the label-free voltammetric determination of cytokines. Here, a novel chitosan/genipin modified fluorine tin oxide electrode was developed providing an in-situ hydrogel formation (FTO/CSG). This platform was applied for the detection of interleukin-6, a major pro-inflammatory cytokine. Transmission electron microscopy (TEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) indicated genipin serves as an efficient green cross-linker to build the immunosensing platform (FTO/CSG/anti-IL-6). EIS showed an increase in charge transfer resistance from 326 to 1360 kΩ after the immobilization of anti-IL-6 antibodies. By square wave voltammetry, this method achieved a detection limit of 0.03 pg mL

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children under 1 year. RSV vaccines are currently unavailable, and children suffering from multiple reinfections by the same viral strain fail to develop protective responses. Although RSV-specific antibodies can be detected upon infection, these have limited neutralizing capacity. Follicular helper T (Tfh) cells are specialized in providing signals to B cells and help the production and affinity maturation of antibodies, mainly via interleukin (IL) 21 secretion. In this study, we evaluated whether RSV could inhibit Tfh responses. We observed that Tfh cells fail to upregulate IL-21 production upon RSV infection. In the lungs, RSV infection downregulated the expression of IL-21/interleukin-21 receptor (IL-21R) in Tfh cells and upregulated programmed death-ligand 1 (PD-L1) expression in dendritic cells (DCs) and B cells. PD-L1 blockade during infection recovered IL-21R expression in Tfh cells and increased the secretion of IL-21 in a DC-dependent manner. IL-21 treatment decreased RSV viral load and lung inflammation, inducing the formation of tertiary lymphoid organs in the lung. It also decreased regulatory follicular T cells, and increased Tfh cells, B cells, antibody avidity and neutralization capacity, leading to an overall improved anti-RSV humoral response in infected mice. Passive immunization with purified immunoglobulin G from IL-21-treated RSV-infected mice protected against RSV infection. Our results unveil a pathway by which RSV affects Tfh cells by increasing PD-L1 expression on antigen-presenting cells, highlighting the importance of an IL-21-PD-L1 axis for the generation of protective responses to RSV infection.

Background and purpose The entire kallikrein-kinin system is present in the skin, and it is thought to exert a relevant role in cutaneous diseases, including psoriasis. The present study was designed to evaluate the relevance of kinin receptors in the development and progression of a model of psoriasis in mice. Experimental approach The effects of kinin B1 and B2 receptor knockout and of kinin receptor antagonists (SSR240612C or FR173657) were assessed in a model of psoriasis induced by imiquimod in C57BL/6 mice. Severity of psoriasis was assessed by histological and immunohistochemical assays of skin, along with objective scores based on the clinical psoriasis area and severity index. Key results Both kinin receptors were up-regulated following 6 days of imiquimod treatment. Kinin B1 and B2 receptor deficiency and the use of selective antagonists show morphological and histological improvement of the psoriasis hallmarks. This protective effect was associated with a decrease in undifferentiated and proliferating keratinocytes, decreased cellularity (neutrophils, macrophages, and CD4+ T lymphocytes), reduced γδ T cells, and lower accumulation of IL-17. The lack of B2 receptors resulted in reduced CD8+ T cells in the psoriatic skin. Relevantly, blocking kinin receptors reflected the improvement of psoriasis disease in the well-being behaviour of the mice. Conclusions and implications Kinins exerted critical roles in imiquimod-induced psoriasis. Both B1 and B2 kinin receptors exacerbated the disease, influencing keratinocyte proliferation and immunopathology. Antagonists of one or even both kinin receptors might constitute a new strategy for the clinical treatment of psoriasis.

Objetivo: contextualizar a vivência profissional de enfermeiros na perspectiva da Sistematização da Assistência de Enfermagem, com foco no fortalecimento da Atenção Primária à Saúde e na ampliação do acesso resolutivo e de qualidade. Método: trata-se de estudo descritivo, com abordagem qualitativa, do tipo relato de experiência, sobre vivência de enfermeiros na implantação participativa dos protocolos de enfermagem no município de Florianópolis – Santa Catarina, Brasil. Resultados: a experiência profissional compreendeu as seguintes fases: Definição de Stakeholders, Alinhamento Conceitual, Aplicação de Questionário - levantamento da expertise dos profissionais, Estabelecimento de Premissas Gerais, Validação dos Protocolos, Monitoramento e Avaliação do Processo, e Disposições Gerais. Trata-se de uma prática com possibilidade de replicação, sustentável na medida em que a Comissão Permanente de Enfermagem se fortalece e agrega profissionais com visão de rede e com foco no cuidado ao paciente. Conclusão: observou-se o avanço da atuação do enfermeiro e a ampliação do acesso ao serviço de saúde. Além disso, o uso dos protocolos auxilia na tomada de decisão, com foco na segurança do paciente e respaldo ao profissional com base em princípios éticos da profissão.Descritores: Enfermagem; Atenção Primária à Saúde; Acesso aos Serviços de Saúde;Protocolos Clínicos; Prática Avançada de Enfermagem.

Objetivo: descrever a experiência da implantação de protocolos de Enfermagem para a ampliação do acesso na atenção primária à saúde, mediante a qualificação da prática clínica do Enfermeiro. Método: estudo descritivo em formato de relato de experiência. O cenário de estudo é o Estado Santa Catarina, tendo como população alvo as Secretarias Municipais de Saúde do Estado. O Coren/SC firmou parceria com a Secretaria Municipal de Saúde de Florianópolis para utilização dos Protocolos de Enfermagem, criando um Programa de Adesão para os municípios. Resultados: Desde a implantação, o programa recebeu 225 solicitações de adesão dentre os 295 municípios catarinenses. Atingiu um total de 135 municípios com os protocolos de enfermagem implantados e 1.708 Enfermeiros capacitados. A oferta de Consultas de Enfermagem onde não havia atendimento do Enfermeiro, ampliação do acesso dos pacientes, com redução significativa de filas de espera, além do aumento das consultas de Enfermagem e resolutividade das mesmas. Conclusão: Os Protocolos de Enfermagem constituem-se como ferramenta primordial para a efetivação do modelo de Atenção Primária no Estado e como inovação e diferencial para as pessoas atendidas. A adesão aos protocolos permite a valorização e o protagonismo da Enfermagem na Atenção Primária.

Objetivo: relatar a vivência de enfermeiros da Atenção Primária à Saúde, na implantação do Protocolo de ampliação da clínica para o enfrentamento da sífilis. Método: estudo descritivo, do tipo relato de experiência, desenvolvido junto aos Centros de Saúde da Secretaria Municipal de Saúde de Florianópolis - Santa Catarina, Brasil. Resultados: a vivência profissional no processo de implantação do Protocolo de Enfermagem no enfrentamento da sífilis – Volume II – seguiu as seguintes etapas: revisão das evidências científicas sobre a aplicação da penicilina na Atenção Primária à Saúde; capacitação dos enfermeiros da rede municipal de saúde; acompanhamento e educação permanente dos profissionais; e monitoramento e avaliação de todo o processo. Conclusão: observou-se que no período de três anos desde a publicação do Protocolo Clínico de Enfermagem houve importante aumento na participação clínica do enfermeiro em atendimentos individuais. Tal documento representou um marco na assistência de enfermagem do município, não só pela autonomia proporcionada, mas também pelo importante papel desempenhado na segurança profissional e do paciente.Descritores: Enfermagem em Saúde Pública; Sífilis; Atenção Primária à Saúde; Sistema Único de Saúde.

Objetivo: relatar a vivência profissional de enfermeiros na implantação do apoio matricial de enfermagem no cuidado à pessoa com ferida na Atenção Primária à Saúde. Método: relato de experiência acerca da implantação do Apoio Matricial como modelo de atendimento à pessoa com ferida no município de Florianópolis – entre junho de 2019 a junho de 2020. Resultados: a implantação trouxe como resultado a ampliação do acesso ao serviço de saúde e o fortalecimento do vínculo entre a equipe da Estratégia Saúde da Família e a pessoa com ferida e seus familiares. Além disso, propiciou a adequada avaliação das lesões, o cuidado compartilhado, o registro clínico das consultas, o monitoramento dos dados, e o devido faturamento dos curativos efetuados. Considerações finais: esse modelo de atendimento trouxe maior resolutividade da Atenção Primária à Saúde a partir da qualificação do atendimento, e melhor gerenciamento das informações em saúde. Este relato busca contribuir para evolução da ciência e estimular a replicabilidade do modelo em outras realidades.

Silva et al. describe and characterize a population of adipose tissue macrophages (VAMs) that are in close contact with the vasculature and powerfully uptake blood-borne macromolecules. VAMs harbor a repair/detoxifying gene signature and adapt quickly to infections and fasting., Tissue-resident macrophages are the most abundant immune cell population in healthy adipose tissue. Adipose tissue macrophages (ATMs) change during metabolic stress and are thought to contribute to metabolic syndrome. Here, we studied ATM subpopulations in steady state and in response to nutritional and infectious challenges. We found that tissue-resident macrophages from healthy epididymal white adipose tissue (eWAT) tightly associate with blood vessels, displaying very high endocytic capacity. We refer to these cells as vasculature-associated ATMs (VAMs). Chronic high-fat diet (HFD) results in the accumulation of a monocyte-derived CD11c+CD64+ double-positive (DP) macrophage eWAT population with a predominant anti-inflammatory/detoxifying gene profile, but reduced endocytic function. In contrast, fasting rapidly and reversibly leads to VAM depletion, while acute inflammatory stress induced by pathogens transiently depletes VAMs and simultaneously boosts DP macrophage accumulation. Our results indicate that ATM populations dynamically adapt to metabolic stress and inflammation, suggesting an important role for these cells in maintaining tissue homeostasis.

O objetivo é mostrar o uso do TU como um dos traços linguísticos que está se solidificando como marca de identidade local brasiliense. A partir do modelo teórico-metodológico e dos parâmetros da sociolinguística variacionista de LABOV (2008), houve o controle de quatro variáveis sociais – sexo, faixa etária, nível de escolaridade e origem das mães. Por meio do programa Goldvarb-X, foram feitas uma rodada ternária/eneária – da qual foram selecionadas todas as variáveis sociais – e duas rodadas binárias: TU X CÊ – faixa etária e nível de escolaridade – e TU X VOCÊ – origem das mães. A situação histórica e linguística do DF, desde a época da migração dos candangos até o resultado do processo de difusão e focalização dialetal, demonstra que está em crescimento o uso do pronome TU.