O desempenho da imunoterapia na redução de células tumorais: uma revisão integrativa / The performance of immunotherapy in reducing tumor cells: an integrative review

Ainda que já tenha sido estudada a sua causa e os mecanismos interferentes em seu desenvolvimento, o câncer contempla um alto índice de mortalidade, fato indicativo de que não há muitas expectativas de sobrevida para os indivíduos em quadros terminais. Muitos são os tratamentos, sendo os mais eficazes a retirada dos possíveis tumores por via cirúrgica e o uso de quimioterápicos, medicamentos estes que provocam até mesmo uma série de sintomas, pelos fortes efeitos colaterais. Sendo assim, esse trabalho se justifica pela importância de correlacionar as terapias convencionais contra o câncer e a imunoterapia, terapia esta que está em constante evolução nas ciências médicas, e objetiva demonstrar, através de formas alternativas e complementares, a ação da imunoterapia frente à regressão tumoral. Estes dados surgiram a partir de um levantamento bibliográfico acerca do desenvolvimento do câncer e dos métodos terapêuticos existentes. Foi realizada uma revisão integrativa da literatura analisando-se artigos de 2001 a 2021, visando apontar os questionamentos e elucidar os trabalhos feitos com a temática do câncer e da imunoterapia. Foram discorridos artigos provindos de plataformas científicas incluindo aspectos direcionados ao estudo do câncer e de seus efeitos, aos componentes imunológicos e ao emprego da imunoterapia na regressão tumoral. Este estudo procura esclarecer alguns métodos terapêuticos já existentes e, comparar os resultados provenientes destes com o possível fortalecimento do sistema imunológico frente ao câncer nas técnicas imunoterápicas. Este assunto pode contribuir, consideravelmente, para o debate de opiniões a respeito dos benefícios e malefícios da técnica, como também para o avanço da medicina e da pesquisa

Analysis of skin microbiota alteration in patients after chemotherapy treatment/Análise da alteração da microbiota epidermal de pacientes após tratamento quimioterápico

The human body is inhabited by millions of micro-organisms, which play an auxiliary role in the digestion and absorption of nutrients, as well as in the immune protection of the host. The human skin contains an immense number of micro-organisms, which vary with the local interferences and appear different according to the area where they inhabit. However, such micro-organisms are in constant modification due to some disturbances. Knowing that chemotherapy is a very aggressive treatment for human cells and based on other related researches, the work in question is an evaluation of the changes caused by the epidermal microbiota in cancer patients after the chemotherapy treatment. The methods consisted in the collection of samples by sterile swab rubbed in the patients' skin pre- and post-chemotherapy treatment, and in the analysis of the samples, which were sown in three culture media with different properties. Subsequently, the main bacteria that grew in the medium were isolated and identified by means of Gram staining and biochemical tests. Some qualitative changes were found at the species level; however, we detected the preservation of the micro-organisms Staphylococcus epidermidis, the main colonizers of the skin and that present beneficial role for the host. Therefore, the results are positive when evaluated from a collaboration point of view to improve patients' quality of life. A more complete analysis of the microbiota is now required through molecular techniques, so that quantitative results can be verified

Avaliação da capacidade antimicrobiana do óleo essencial de pereskia aculeata: interação com microrganismos encontrados em jalecos de profissionais de saúde / Evaluation of the antimicrobial capacity of pereskia aculeata essential oil: interaction with microorganisms found in the coat of health professionals

Este trabalho analisou a capacidade antimicrobiana do óleo essencial (OE) da Pereskia aculeata, popularmente conhecida como ‘Ora-pro-nobis’, frente a microrganismos encontrados nos jalecos de profissionais de saúde de um hospital de Varginha em Minas Gerais. Tal abordagem justificou-se pela hipótese de que o OE da planta tem ação inibitória contra diferentes tipos de microrganismos. Este estudo teve como propósito identificar os microrganismos encontrados no equipamento de proteção individual (EPI) dos profissionais de saúde e testar a eficácia dele sobre estes. Isto se realizou através da coleta de amostras de jalecos dos profissionais de saúde, seguido pela análise por testes qualitativos de antibiograma, testando a capacidade inibitória do óleo essencial na concentração de 100%. A pesquisa evidenciou a capacidade bacteriostática do OE frente a cepas de Staphylococcus spp, Bacilus spp, filo Actinobactéria, como também a um Bacilo Gram negativo não fermentador. Apenas duas cepas de Staphylococcus spp não foram inibidas pelo OE. Portanto, isto indica que a Pereskia aculeata possui capacidade antimicrobiana frente a microrganismos hospitalares, sendo uma proposta promissora seu uso como um agente bacteriostático, principalmente por ser uma planta acessível, de rápido crescimento e fácil cultivo na região. Contudo, faz-se necessário a realização de novos testes para evidenciar quais compostos do OE possuem esta atividade antimicrobiana

Análise da capacidade antimicrobiana da pereskia aculeata frente a microrganismos bacterianos: staphylococcus epidermidis e klebsiella pneumoniae / Analysis of the antimicrobial capacity of pereskia aculeata in front of bacterial microrganisms: staphylococcus epidermidis and klebsiella pneumoniae

Este trabalho analisou a capacidade antimicrobiana do óleo essencial (OE) da planta Pereskia aculeata frente aos microrganismos Staphylococcus epidermidis e Klebsiella pneumoniae. Tal abordagem justificou-se pela hipótese de que o OE da planta Pereskia aculeata possui substâncias ativas com alta capacidade antimicrobiana e que as cepas destes patógenos são sensíveis ao OE. O objetivo deste trabalho foi avaliar o potencial bacteriostático do OE e se este poderá a vir ser utilizado como opção de tratamento às infecções causadas pelos microrganismos Staphylococcus epidermidis e Klebsiella pneumoniae. Este intento foi conseguido mediante a uma pesquisa qualitativa de avaliação dos halos de inibição, utilizando a técnica de disco-difusão, verificando a capacidade inibitória mínima. A análise evidenciou a capacidade antimicrobiana do OE puro ou em concentrações até 90% por meio da medição dos halos de inibição, comprovando a hipótese de que o OE da cactácea Peresekia aculeata possui capacidade antimicrobiana frente a bactérias com composição de parede celular distintas. Contudo, em concentrações menores, o halo de inibição foi inexistente, sugerindo que o consumo do OE pela população no combate ou auxílio do tratamento de infecções provocadas por estes patógenos é prescindível

Studies of inclusive four-jet production with two b-tagged jets in proton-proton collisions at 7 TeV

Peer reviewe

Search for new physics in final states with two opposite-sign, same-flavor leptons, jets, and missing transverse momentum in pp collisions at TeV

A search is presented for physics beyond the standard model in final states with two opposite-sign, same-flavor leptons, jets, and missing transverse momentum. The data sample corresponds to an integrated luminosity of 2.3 fb−1 of proton-proton collisions at s√=13s=13 TeV collected with the CMS detector at the LHC in 2015. The analysis uses the invariant mass of the lepton pair, searching for a kinematic edge or a resonant-like excess compatible with the Z boson mass. Both search modes use several event categories in order to increase the sensitivity to new physics. These categories are based on the rapidity of the leptons, the multiplicity of jets and b jets, the scalar sum of jet transverse momenta, and missing transverse momentum. The observations in all signal regions are consistent with the expectations from the standard model, and the results are interpreted in the context of simplified models of supersymmetry

Resistance to P. brasiliensis Experimental Infection of Inbred Mice Is Associated with an Efficient Neutrophil Mobilization and Activation by Mediators of Inflammation

Paracoccidioidomycosis (PCM) is a systemic fungal infection, endemic in Brazil, that leads to severe morbidity and even mortality if not correctly treated. Patients may respond differently to PCM depending on the pattern of the acquired immune response developed. The onset of protective immune response is notably mediated by neutrophils (PMN) that play an important role through directly killing the fungi and also by interacting with other cell types to modulate the acquired protective immune response that may follow. In that way, this study aimed to present and compare different experimental models of PCM (intraperitoneal and subcutaneous) regarding PMN production and maturation inside femoral bone marrow and also PMN infiltration in peritoneal and subcutaneous exudates of resistant and susceptible mice. We also assessed the fungal colony forming units and the levels of soluble inflammatory mediators (LTB4, KC, IFN-γ, GM-CSF, and IL-10) inside subcutaneous air-pouches to compare the efficiency of the PMN present at this site in relation to the two main neutrophil functions: initial lysis of the invading pathogen and modulation of the acquired immune response. P. brasiliensis inoculated intraperitoneally was able to disseminate to the bone marrow of susceptible mice, causing a more marked alteration of PMN production and maturation than that observed after resistant mice infection by the same route. Subcutaneous air-pouch inoculation of P. brasiliensis elicited a controlled and limited infection that produced a PMN-rich exudate, thus favoring the study of the interaction between the fungus and the neutrophils. Susceptible mice produced higher numbers of PMN; however, these cells were less effective in killing the fungi. Inflammatory cytokines were more pronounced in resistant mice, which supports their PCM raised resistance

Impact of Paracoccidioides brasiliensis Coinfection on the Evolution of Schistosoma mansoni-Induced Granulomatous Liver Injury in Mice

The pathogens Schistosoma mansoni and Paracoccidioides brasiliensis share common geographic areas, determining infectious diseases with high mortality rates worldwide. Histopathological and immunological changes induced by each pathogen are well understood; however, the host responses to S. mansoni and P. brasiliensis coinfection are still unknown. Thus, we investigated liver damage and cytokines production in a murine model acutely and chronically coinfected with these pathogens. Fourty male Swiss mice were infected with S. mansoni and P. brasiliensis alone or coinfected. The animals were euthanized with 50 (acute infection) and 120 (chronic infection) days of infection. All infected animals exhibited liver inflammation. Intense granulomatous inflammation was detected in animals infected with S. mansoni alone and those coinfected. Productive and involutive granulomas were clearly observed in acute and chronic infections, respectively. Granuloma size was reduced in the acute phase and increased in the chronic phase of S. mansoni and P. brasiliensis coinfection, compared with animals infected only with S. mansoni. In the chronic phase of infection, the granulomatous inflammation in coinfected animals was characterized by intense neutrophils accumulation and reduced eosinophils number. IFN-γ, IL-2, IL-4, and IL-5 circulating levels were increased in all infected groups. Coinfected animals presented attenuated IFN-γ and IL-4 production in the acute and chronic infections. Taken together, our findings indicate that coinfected animals exhibited a differential modulation of granulomatous inflammation during the acute and chronic phases of infection, which was potentially associated with a divergent profile of cytokines production and migration of neutrophils and eosinophils in response to S. mansoni and P. brasiliensis antigenic stimulation

Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohortResearch in context

Summary: Background: Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs. Methods: This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677. Findings: Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively). Interpretation: Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials. Funding: The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch &amp; ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424