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The role of inflammation in cancer is a topic that has been investigated for many years. As established, inflammation emerges as a defining characteristic of cancer, presenting itself as a compelling target for therapeutic interventions in the realm of oncology. Controlling the tumor microenvironment (TME) has gained paramount significance, modifying not only the effectiveness of immunotherapy but also modulating the outcomes and prognoses of standard chemotherapy and other anticancer treatments. Immunotherapy has surfaced as a central focus within the domain of tumor treatments, using immune checkpoint inhibitors as cancer therapy. Immune checkpoints and their influence on the tumor microenvironment dynamic are presently under investigation, aiming to ascertain their viability as therapeutic interventions across several cancer types. Cancer presents a significant challenge in humans and cats, where female breast cancer ranks as the most prevalent malignancy and feline mammary carcinoma stands as the third most frequent. This review seeks to summarize the data about the immune checkpoints cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), programmed cell death protein-1 (PD-1), V-domain Ig suppressor of T cell activation (VISTA), and T-cell immunoglobulin and mucin domain 3 (TIM-3) respective ongoing investigations as prospective targets for therapy for human breast cancer, while also outlining findings from studies reported on feline mammary carcinoma (FMC), strengthening the rationale for employing FMC as a representative model in the exploration of human breast cancer.
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INTRODUCTION: The aim of the study was to describe trauma injuries associated with rope bullfights in the Azores, Portugal, regarding the cause of the incident, trauma mechanism, most affected anatomical areas, and injury severity. METHODS: Two-year cross-sectional study in the local hospital with prospective data collection. Patients who were consecutively admitted to the local hospital's emergency department with trauma injuries from the bull's direct impact or from falls either during the bull's escape or when handling the rope, were included. Data on general demographics, lesion characteristics, treatments, need for hospitalization and mortality were collected. RESULTS: Fifty-six incidents and 80 trauma injuries were identified. The main cause of trauma was the bull's direct impact (37; 66.07%) and the mechanism of injury was blunt trauma in all patients (100%; 56). Head and neck injuries (27; 33.75%) were the most common. The median Injury Severity Score at the emergency department admission was 4. Major trauma was noted in five patients (8.92%). Ten patients (17.85%) needed hospitalization with a median hospital stay of seven days. Three of the 10 hospitalized patients (30%) were previously admitted to the intensive care unit. Surgery was performed in six patients (10.71%). CONCLUSION: The main cause of trauma was the bull's direct impact, and the mechanism of injury was blunt trauma. The most affected anatomical areas were the head and neck. These findings are a wake-up call to the impact of these events regarding the economic costs they entail, the costs for the health of the local population, the safety measures currently implemented and the availability of the necessary means to treat these patients.
Introdução: O objetivo deste estudo foi caracterizar as lesões traumáticas tauromáquicas ocorridas nas touradas à corda nos Açores no que diz respeito à causa do incidente, mecanismo de trauma, área anatómica mais afetada e gravidade das lesões. Métodos: Estudo unicêntrico, transversal, com a colheita prospetiva de dados realizada durante dois anos. Foram incluídos os doentes que consecutivamente recorreram ao serviço de urgência do hospital local por lesões traumáticas ocorridas por trauma direto com o animal ou quedas aquando da fuga ou manuseio da corda. Foram colhidos dados demográficos gerais, características da lesão, tratamentos efetuados, necessidade de internamento hospitalar e mortalidade. Foi realizada uma análise estatística descritiva com recurso ao software estatístico SPSS. Resultados: Registaram-se 56 admissões hospitalares e 80 lesões traumáticas. A principal causa de traumatismo foi o trauma direto com o animal (37; 66,07%) e o mecanismo de lesão foi o trauma fechado (56; 100%). As áreas anatómicas mais afetadas foram a cabeça e pescoço (27; 33,75%). A mediana de Injury Severity Score foi de 4 à admissão hospitalar. Cinco doentes (8,92%) apresentaram trauma major. Dez doentes (17,85%) necessitaram de internamento hospitalar com uma mediana de dias de internamento de sete (IIQ 4,5 dias). Três (30%) dos doentes internados necessitaram de internamento em unidade de cuidados intensivos. Seis doentes (10,71%) foram submetidos a cirurgia. Conclusão: A principal causa de traumatismo foi o trauma direto com o animal e o mecanismo de lesão foi o trauma fechado. As áreas anatómicas mais afetadas foram a cabeça e pescoço. Estes dados constituem um alerta para o impacto destes eventos no que diz respeito aos custos económicos que acarretam, aos custos para a saúde da população local, às medidas de segurança atualmente implementadas e à disponibilidade dos meios necessários para tratar estes doentes.
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Hospitalização , Ferimentos não Penetrantes , Humanos , Masculino , Animais , Bovinos , Estudos Transversais , Açores , Tempo de Internação , Estudos RetrospectivosRESUMO
Microbial diversity profoundly influences soil ecosystem functions, making it vital to monitor community dynamics to comprehend its structure. Our study focused on six agrosystems in Madeira Archipelago, analysing bacteria, archaea, fungi and AMF through classical microbiology and molecular techniques. Despite distinct edaphoclimatic conditions and management practices, bacterial structures exhibited similarities, with Alphaproteobacteria at 18%-20%, Bacilli at 11%-18% and Clostridia at 9%-14%. The predominance of copiothrophic groups suggested that soil nutrient content was the driver of these communities. Regarding archaea, the communities changed among sites, and it was evident that agrosystems provided niches for methanogens. The Crenarchaeota varied between 15% and 29%, followed by two classes of Euryarchaeota, Methanomicrobia (17%-25%) and Methanococci (4%-32%). Fungal communities showed consistent composition at the class level but had differing diversity indices due to management practices and soil texture. Sordaryomycetes (21%-28%) and Agaricomycetes (15%-23%) were predominant. Conversely, AMF communities appeared to be also influenced by the agrosystem, with Glomus representing over 50% of the community in all agrosystems. These insights into microbial groups' susceptibilities to environmental conditions are crucial for maintaining healthy soil and predicting climate change effects on agrosystems' productivity, resilience and sustainability. Additionally, our findings enable the development of more robust prediction models for agricultural practices.
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Ecossistema , Euryarchaeota , Microbiologia do Solo , Fungos , Bactérias/genética , Archaea/genética , Solo/química , FirmicutesRESUMO
Recent findings in human breast cancer (HBC) indicate that T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3)-targeted therapies may effectively activate anticancer immune responses. Although feline mammary carcinoma (FMC) is a valuable cancer model, no studies on TIM-3 have been developed in this species. Thus, we evaluated the expression of TIM-3 by immunohistochemistry in total (t), stromal (s), and intra-tumoral (i) tumor-infiltrating lymphocytes (TILs) and in cancer cells, of 48 cats with mammary carcinoma. In parallel, serum TIM-3 levels were quantified using ELISA and the presence of somatic mutations in the TIM-3 gene was evaluated in 19 tumor samples. sTILs-TIM3+ were more frequent than iTILs-TIM-3+, with the TIM-3 ex-pression in sTILs and cancer cells being associated with more aggressive clinicopathological features. In contrast, the TIM-3 expression in iTILs and tTILs was associated with a more benign clinical course. Moreover, the serum TIM-3 levels were lower in animals with FMC when compared to healthy animals (p < 0.001). Only one somatic mutation was found in the TIM-3 gene, at intron 2, in one tumor sample. Altogether, our results suggest that the expression of TIM-3 among TILs subpopulations and cancer cells may influence the clinical outcome of cats with FMC, in line with the previous reports in HBC.
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Despite the available antibiotics, tuberculosis (TB) has made its return since the 90's of the last century as a global threat mostly due to co-infection with HIV, to the emergence of drug resistant strains and the lack of an effective vaccine. Host-directed strategies could be exploited to improve treatment efficacy, contain drug-resistant strains, improve immune responses and reduce disease severity. Macrophages in the lungs are often found infected with Mycobacterium tuberculosis (Mtb) and/or with HIV. The long-term survival of lung macrophages infected with Mtb or with HIV, together with their ability to produce viral particles, especially during TB, makes these niches major contributors to the pathogenicity of the infection. Among the available drugs to control HIV infection, protease inhibitors (PIs), acting at post-integrational stages of virus replication cycle, are the only drugs able to interfere with virus production and release from macrophages during chronic infection. For Mtb we recently found that the pathogen induces a general down-regulation of lysosomal proteases, helping bacteria to establish an intracellular niche in macrophages. Here we found that the PI saquinavir, contrary to ritonavir, is able to induce an increase of endolysosomal proteases activity especially of cathepsin S in Mtb infected macrophages and during co-infection with HIV. Our results indicate that saquinavir treatment of infected macrophages led not only to a significant intracellular killing of Mtb but also: (i) to an improved expression of the HLA class II antigen presentation machinery at the cell surface; (ii) to increased T-lymphocyte priming and proliferation; and (iii) to increased secretion of IFN-γ. All together the results indicate saquinavir as a potential host directed therapy for tuberculosis.
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Coinfecção/imunologia , Reposicionamento de Medicamentos/métodos , Infecções por HIV/imunologia , Inibidores da Protease de HIV/farmacologia , HIV-1/genética , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/virologia , Mycobacterium tuberculosis/efeitos dos fármacos , Saquinavir/farmacologia , Tuberculose/imunologia , Doadores de Sangue , Linfócitos T CD4-Positivos/imunologia , Catepsinas/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Coinfecção/virologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Interferon gama/metabolismo , Macrófagos Alveolares/enzimologia , Transdução de Sinais/efeitos dos fármacos , Tuberculose/microbiologiaRESUMO
Dies1/VISTA induces embryonic stem-cell differentiation, via BMP-pathway, but also acts as inflammation regulator and immune-response modulator. Dies1 inhibition in a melanoma-mouse model led to increased tumour-infiltrating T-cells and decreased tumour growth, emphasizing Dies1 relevance in tumour-microenvironment. Dies1 is involved in cell de/differentiation, inflammation and cancer processes, which mimic those associated with Epithelial-to-Mesenchymal-Transition (EMT). Despite this axis linking Dies1 with EMT and cancer, its expression, modulation and relevance in these contexts is unknown. To address this, we analysed Dies1 expression, its regulation by promoter-methylation and miR-125a-5p overexpression, and its association with BMP-pathway downstream-effectors, in a TGFß1-induced EMT-model, cancer cell-lines and primary samples. We detected promoter-methylation as a mechanism controlling Dies1 expression in our EMT-model and in several cancer cell-lines. We showed that the relationship between Dies1 expression and BMP-pathway effectors observed in the EMT-model, was not present in all cell-lines, suggesting that Dies1 has other cell-specific effectors, beyond the BMP-pathway. We further demonstrated that: Dies1 expression loss is a recurrent event in GC, caused by promoter methylation and/or miR-125a-5p overexpression and; GC-microenvironment myofibroblasts overexpress Dies1. Our findings highlight Dies1 as a novel player in GC, with distinct roles within tumour cells and in the tumour-microenvironment.
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Antígenos B7/genética , Epigênese Genética , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Metilação de DNA , Regulação para Baixo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína 2 Inibidora de Diferenciação/genética , Proteínas Inibidoras de Diferenciação/genética , Proteínas de Neoplasias/genética , Regiões Promotoras Genéticas , Neoplasias Gástricas/patologia , Fator de Crescimento Transformador beta1/farmacologia , Microambiente Tumoral/genéticaRESUMO
O trabalho é um estudo experimental sobre procedimentos utilizados na colheita de urina para exame bacteriológico em mulheres. Foi comparado o procedimento que vem sendo utilizado, na sala de colheita de urina para urocultura do Laboratório Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, denominado de procedimento controle e um alternativo, proposto pela pesquisadora, denominado de experimental. O método experimental apresenta uma cadeira especialmente construída para a colheita de amostra de urina para cultura em mulheres. Foram colhidas amostras de urina de 93 pacientes externas, portadoras de requisição de cultura de urina, por ambos os métodos, num toral de 472 amostras. As análises bacteriológicas foram realizadas em dois serviços bacteriológicos: no Setor de Bacteriologia do Laboratório Central do HC-FMUSP, 186 amostras e na Seção de Bacteriologia do Instituto Adolfo Lutz Central - São paulo, 100 amostras. No Setor de Bioquímica do HC-FMUSP foram analisados os sedimentos urinários de 186 amostras. Os resultados encontrados e analisados, estatisticamente, permitiram concluir que o procedimento experimental minimizou as contaminações do jato urinário, proporcionando uma colheita de amostra de urina mais próxima da realidade, diminuindo as inconveniências de contaminações paralelas. Além disso, segundo a opinião da maioria das pacientes, a cadeira especialmente construída proporcionou conforto e uma posição adequada para o ato da micção e para a pesquisadora, tornou o procedimento mais técnico e uma posição adequada para a paciente, que permaneceu com o meato urinário externo exposto durante todo o procedimento.
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Feminino , Urina , Exames MédicosRESUMO
Neste trabalho relata-se a experiência das docentes da disciplina Enfermagem Médico-Cirúrgica sobre o ensino da prescrição de enfermagem, e são abordados os princípios básicos, as formas de elaboração e as estratégias utilizadas.
The authors refer the orientation given by the instructors of Medical-Surgical Nursing to undergraduate students on the nursing prescription, its basic principles and the strategies employed.
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Humanos , Educação em Enfermagem/métodos , Prescrições/enfermagem , Estágio Clínico , Cuidados de Enfermagem/métodos , Processo de EnfermagemRESUMO
The authors refer the orientation given by the instructors of Medical-Surgical Nursing to undergraduate students on the nursing prescription, its basic principles and the strategies employed.
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O trabalho aborda aspectos de um sistema educacional iniciado na Inglaterra,em 1963, denominado Universidade Aberta. Discorre sobre sua estrutura, organizaçäo, avaliaçäo e mostra as tentativas de implantar aquela metodología no Brasil. As autoras sugerem que a idéia principal da Universidade Aberta - a disseminaçäo do saber deve ser aproveitada pela enfermagem para encorajar os profissionais a assumirem o compromisso da auto-educaçäo e apontam alguns órgäos, por meio dos quais seria possível divulgar e estender programas a todo país
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Educação em Enfermagem/tendências , BrasilRESUMO
O presente estudo foi realizado em 30 hospitais do Município de SO Paulo e teve como objetivos: identificar e categorizar os procedimentos pertinentes a colheita de urina para cultura bacteriológica. A amostragem foi estratificada e a coleta de dados realizada por meio de um instrumento, preparado para observaçäo sistemática, ligado diretamente a um sistema interpretativo das categorias "Bom", "Regular" e "Deficiente", que atende a todos os procedimentos. Os resultados foram distribuidos em freqüências absolutas e relativas e as conclusöes foram categorizadas segundo o sistema interpretativo das categorias previamente defindo e destinado ao tema abordado
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Humanos , Urina/análise , Técnicas Bacteriológicas , Brasil , Hospitais GeraisRESUMO
Abordagem dos elementos ambientais, materiais e humanos, com ênfase na responsabilidade da enfermeira no atendimento às necessidades humanas básicas de ambiente e espaço do paciente hospitalizado.
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Ambiente de Instituições de Saúde , Pacientes InternadosRESUMO
The article covers aspects of a educational system, called Open University, which began in England in 1963. Its structure, organization and evaluation are presented, as well as some attempts to implement the methodology in Brazil. The authors suggest that the idea behind the Open University - dissemination of knowledge - should be incorporated by nurses, in order to encourage them towards continuing education, and indicate some organizations through which such programs could be known and extended throughout the country.
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This study was made in the City of São Paulo, in 30 hospitals with the objective of to identify and classify the procedures of collecting urine for bacteriologic study. The data's collect has been realized based on a record prepared for a systematic observation directly connected to a system interpretative of categories ("Good", "Fair" and "Poor") applied to all procedures. The results obtained have been presented in the tables distributed in the absolute end relative frequencies, grouped and classified by categories. The conclusions where in accordance to the specific objectives initially proposed and has been classified under the interpretative systems of the categories previously defined and adressed to the research.
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Neste estudo fizemos um levantamento de fatores relacionados á colheita de urina para cultura bacteriológica, com os objetivos de identificar e categorizar os procedimentos pertinentes á esta técnica. Foi realizado no Município de São Paulo, em 30 hospitais, previamente selecionados em relação à assistência prestada, capacidade de leitos, atendimento ambulatorial e recursos laboratoriais. A amostragem foi estratificada, com os estratos definidos em 4 regiões do município: Norte, Sul, Leste e Oeste. A coleta de dados foi realizada por meio de um instrumento preparado para uma observação sistemática, ligada diretamente a um sistema interpretativo das categorias (Bom, Regular e Deficiente), que atende a todos os procedimentos. Os resultados obtidos foram apresentados em tabelas que distribuem as frequências absolutas e relativas, agrupadas e categorizadas. As conclusões apresentadas responderam aos objetivos específicos inicialmente propostos e foram categorizadas segundo o sistema interpretativo das categorias, previamente definido e destinado ao tema abordado.
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Exames Médicos , Enfermagem Médico-CirúrgicaRESUMO
As autoras discorrem sobre os princípios fundamentais e as características da homeopatia. Abordam a semelhança em certos aspectos filosóficos da homeopatia e da enfermagem, que visualizam o indivíduo de forma global.