Efeitos de um programa domiciliar de exercícios após um treinamento resistido supervisionado em pacientes com doença pulmonar obstrutiva crônica

Design of the study: clinical Trial. Objective: This study aimed to evaluate the effects of a homebased resistance exercise program with elastic tubing after supervised resistance training on peripheral muscle strength and quality of life in patients with chronic obstructive pulmonary disease (COPD). Methods: The study included 22 COPD patients, aged 55-70 years. Peripheral muscle strength and quality of life were evaluated through digital dynamometer and Chronic Respiratory Disease Questionnaire (CRDQ) respectively after supervised resistance training program, and then the patients were divided into two groups: home-based treatment (n = 10) and control (n = 12). After 16 weeks the assessments were repeated. Results: The home resistance training showed no significant increase in peripheral muscle strength and quality of life, however, was able to maintain the gains made in the previous supervised training. Conclusion: The continuity of home-based treatment did not promote additional improvements to supervised training after the protocol, since the gains were maintained in both assessed groups after 4 monthsDesenho do estudo: ensaio clínico. Objetivo: Avaliar os efeitos de um programa de exercícios resistidos em domicílio, com tubos elásticos, após o treinamento resistido supervisionado sobre a força muscular periférica e qualidade de vida de pacientes com doença pulmonar obstrutiva crônica (DPOC). Métodos: O estudo incluiu 22 pacientes com DPOC, com idade entre 55-70 anos. A força muscular periférica e a qualidade de vida foram avaliados por meio da dinamometria e do questionário Chronic Respiratory Questionare (CRQ), respectivamente, após o programa de treinamento de resistência supervisionado, e, em seguida, os pacientes foram divididos em dois grupos: tratamento domiciliar (n = 10) e controle (n = 12). Após 16 semanas, as avaliações foram repetidas. Resultados: O treinamento resistido em domicílio não mostrou aumento significativo sobre a força muscular periférica e qualidade de vida, no entanto, foi capaz de manter os ganhos obtidos após o programa de treinamento supervisionado. Conclusão: A continuidade do tratamento em domicílio não promoveu melhorias adicionais após o protocolo, uma vez que os ganhos foram mantidos nos dois grupos avaliados após 4 mese

Acute effect of aerobic exercise in different intensities in mucociliary clearance of patients with COPD

Design of the Study: Clinical Trial. Objective (s): To analyze the acute effect of aerobic exercise at different intensities in mucociliary clearance in patients with COPD, and to investigate possible associations of the autonomic nervous system in this response. Methods: 22 COPD patients underwent an initial evaluation for collecting personal data and spirometry to assess lung function. It was performed a progressive treadmill test for aerobic exercise prescription. Finally two randomized sessions of aerobic exercise with intensity of 60 % and 90 % of peak speed reached during the incremental test ( vVO2peack ) were performed with at least 24 hours of rest between them. The mucociliary clerance was assessed before and after the exercise sessions by testing the saccharin transit time (STT). Assessment of autonomic modulation was performed by heart rate variability (HRV) which continued throughout the protocol. Results: The values obtained in the STT test after aerobic exercise at 60 % of vVO2peack (9,08 minutes ± 4,96 ) was lower when compared to the STT before exercise ( 11,96 ± 6,31, p = 0,005 ) . That response also occurred after aerobic exercise at 90% of vVO2peack ( 8,90 ± 4,21 min ) compared to baseline ( 12,94 ± 7,22 , p = 0,023 ). Correlation analysis between the final values of STT test and HRV indexes did not show significant differences. Conclusions: Patients with COPD showed acceleration of mucociliary clerance right after a session of aerobic exercise. It was not possible to observe the association of autonomic modulation in this responseModelo do Estudo: Experimental. Objetivo(s) do estudo: Analisar o efeito agudo do exercício aeróbio em diferentes intensidades no transporte mucociliar de pacientes com DPOC, bem como investigar possíveis associações do sistema nervoso autônomo nesta resposta. Metodologia: Foram analisados 22 pacientes com DPOC que realizaram avaliação inicial para coleta de dados pessoais e espirometria a fim de avaliar a função pulmonar. Realizou-se um teste progressivo em esteira ergométrica para prescrição do exercício aeróbio. Por fim foram realizadas duas sessões de exercício aeróbio randomizadas em esteira ergométrica com intensidade de 60% e 90% do pico da velocidade atingida no teste incremental (vVO2pico) com pelo menos 24 horas de descanso entre elas. O transporte mucociliar foi avaliado antes e após realização do exercício por meio do teste do tempo de trânsito da sacarina (TTS). A avaliação da modulação autonômica foi realizada por meio da variabilidade da frequência cardíaca (VFC) a qual prosseguiu durante todo o protocolo. Resultados: Os valores obtidos no teste de TTS dos pacientes com DPOC após exercício aeróbio a 60% da vVO2pico (9,08 ± 4,96 minutos) foi menor comparado ao TTS antes do exercício (11,96 ± 6,31; p = 0,005). O que também ocorreu após exercício aeróbio a 90% da vVO2pico (8,90 ± 4,21 minutos) quando comparado ao momento basal (12,94 ± 7,22; p = 0,023). As análises de correlação entre os valores finais de TTS e índices da VFC não apontaram diferenças significativas. Conclusões: Pacientes com DPOC apresentaram aceleração da transportabilidade mucociliar frente a uma sessão de exercício aeróbio. Não foi possível observar associação da modulação autonômica nesta resposta após o exercíci

Subdominant/Cryptic CD8 T Cell Epitopes Contribute to Resistance against Experimental Infection with a Human Protozoan Parasite

During adaptive immune response, pathogen-specific CD8+ T cells recognize preferentially a small number of epitopes, a phenomenon known as immunodominance. Its biological implications during natural or vaccine-induced immune responses are still unclear. Earlier, we have shown that during experimental infection, the human intracellular pathogen Trypanosoma cruzi restricts the repertoire of CD8+ T cells generating strong immunodominance. We hypothesized that this phenomenon could be a mechanism used by the parasite to reduce the breath and magnitude of the immune response, favoring parasitism, and thus that artificially broadening the T cell repertoire could favor the host. Here, we confirmed our previous observation by showing that CD8+ T cells of H-2a infected mice recognized a single epitope of an immunodominant antigen of the trans-sialidase super-family. In sharp contrast, CD8+ T cells from mice immunized with recombinant genetic vaccines (plasmid DNA and adenovirus) expressing this same T. cruzi antigen recognized, in addition to the immunodominant epitope, two other subdominant epitopes. This unexpected observation allowed us to test the protective role of the immune response to subdominant epitopes. This was accomplished by genetic vaccination of mice with mutated genes that did not express a functional immunodominant epitope. We found that these mice developed immune responses directed solely to the subdominant/cryptic CD8 T cell epitopes and a significant degree of protective immunity against infection mediated by CD8+ T cells. We concluded that artificially broadening the T cell repertoire contributes to host resistance against infection, a finding that has implications for the host-parasite relationship and vaccine development

Impaired Innate Immunity in Tlr4−/− Mice but Preserved CD8+ T Cell Responses against Trypanosoma cruzi in Tlr4-, Tlr2-, Tlr9- or Myd88-Deficient Mice

The murine model of T. cruzi infection has provided compelling evidence that development of host resistance against intracellular protozoans critically depends on the activation of members of the Toll-like receptor (TLR) family via the MyD88 adaptor molecule. However, the possibility that TLR/MyD88 signaling pathways also control the induction of immunoprotective CD8+ T cell-mediated effector functions has not been investigated to date. We addressed this question by measuring the frequencies of IFN-γ secreting CD8+ T cells specific for H-2Kb-restricted immunodominant peptides as well as the in vivo Ag-specific cytotoxic response in infected animals that are deficient either in TLR2, TLR4, TLR9 or MyD88 signaling pathways. Strikingly, we found that T. cruzi-infected Tlr2−/−, Tlr4−/−, Tlr9−/− or Myd88−/− mice generated both specific cytotoxic responses and IFN-γ secreting CD8+ T cells at levels comparable to WT mice, although the frequency of IFN-γ+CD4+ cells was diminished in infected Myd88−/− mice. We also analyzed the efficiency of TLR4-driven immune responses against T. cruzi using TLR4-deficient mice on the C57BL genetic background (B6 and B10). Our studies demonstrated that TLR4 signaling is required for optimal production of IFN-γ, TNF-α and nitric oxide (NO) in the spleen of infected animals and, as a consequence, Tlr4−/− mice display higher parasitemia levels. Collectively, our results indicate that TLR4, as well as previously shown for TLR2, TLR9 and MyD88, contributes to the innate immune response and, consequently, resistance in the acute phase of infection, although each of these pathways is not individually essential for the generation of class I-restricted responses against T. cruzi

Pathogen-Induced Proapoptotic Phenotype and High CD95 (Fas) Expression Accompany a Suboptimal CD8+ T-Cell Response: Reversal by Adenoviral Vaccine

MHC class Ia-restricted CD8+ T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8+ T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8+ T cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8+ T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8+ T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8+ cells expanded during infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8+ T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost