RESUMO
Humanity did surprisingly well so far, considering how unprepared it was to respond to the coronavirus disease 2019 (COVID-19) threat. By blending old and ingenious new technology in the context of the accumulated knowledge on other human coronaviruses, several vaccine candidates were produced and tested in clinical trials in record time. Today, five vaccines account for the bulk of the more than 13 billion doses administered worldwide. The ability to elicit biding and neutralizing antibodies most often against the spike protein is a major component of the protection conferred by immunization but alone it is not enough to limit virus transmission. Thus, the surge in numbers of infected individuals by newer variants of concern (VOCs) was not accompanied by a proportional increase in severe disease and death rate. This is likely due to antiviral T-cell responses, whose evasion is more difficult to achieve. The present review helps navigating the very large literature on T cell immunity induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination. We examine the successes and shortcomings of the vaccinal protection in the light of the emergence of VOCs with breakthrough potential. SARS-CoV-2 and human beings will likely coexist for a long while: it will be necessary to update existing vaccines to improve T-cell responses and attain better protection against COVID-19.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Linfócitos T , Ciências Humanas , VacinaçãoRESUMO
BACKGROUND: CrossFit® is usually composed of high intensity workout routines and is executed quickly, repetitively and with limited rest time. Previous studies have identified a high prevalence of injuries in CrossFit®. This study aimed to determine the prevalence of CrossFit-related musculoskeletal injuries and to identify potential associated factors. METHODS: A cross-sectional study was conducted with 413 CrossFitters. Participants completed a questionnaire containing personal data, training characteristics and injury history in the last 12 months. Data were analyzed by descriptive statistics and logistic regression models. RESULTS: The prevalence of CrossFit-related musculoskeletal injuries was 24.0%; and the injury rate was of 0.80 injuries per 1,000 hours of exposure. The regions of the body most affected were the lumbar spine (33.3%), shoulders (31.3%) and knees (14.1%). The majority of CrossFitters participated in competitions (74.6%), had more than 12 months of experience in CrossFit® (62.7%), and trained up to 90 minutes a day (82.3%) for more than 4 days a week (76.8%). The variables that showed a significant association with CrossFit®-related musculoskeletal injuries were weekly training frequency (OR=2.25; 95% CI: 1.13-4.48) and regular physiotherapeutic care (OR=1.85; 95% CI: 1.11-3.07). CONCLUSIONS: The prevalence of musculoskeletal injury was 24.0%, and the most affected regions of the body were the lumbar spine, shoulders and knees. Training more than four days a week and do not receive regular physiotherapeutic care were associated with CrossFit-related musculoskeletal injuries.
Assuntos
Traumatismos em Atletas/epidemiologia , Sistema Musculoesquelético/lesões , Adulto , Traumatismos em Atletas/fisiopatologia , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Sistema Musculoesquelético/fisiopatologia , Condicionamento Físico Humano/efeitos adversos , Condicionamento Físico Humano/métodos , Prevalência , Inquéritos e Questionários , Adulto JovemRESUMO
Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of cancer is now an approved treatment for B cell malignancies. However, the use of viral vectors to provide long-term CAR expression is associated with high production costs and cumbersome quality controls, impacting the final cost of CAR T cell therapies. Nonviral integrative vectors, such as Sleeping Beauty (SB) transposons, provide an alternative to modify primary T cells. Therefore, we developed a protocol to expand SB-transfected 19BBζ CAR T cells using a lymphoblastoid cell line, and evaluated T cell phenotype as well as function along the T cell expansion. Electroporation of PBMCs with transposon plasmid decreased cell viability on day 1 but had a minor impact on the frequency of memory subpopulations when compared to mock condition. CAR+ lymphocytes showed increased proliferation compared to mock control and high cytotoxic activity towards CD19+ cells without significant differences in exhaustion markers expression. Moreover, CAR+ lymphocytes showed an increased frequency by the end of the stimulation cycle compared with day 1, suggesting that CAR expression confers a selective proliferation advantage. Immunodeficient NOD scid gamma chain knockout (NSG) mice engrafted with the human pre-B leukemic cell line RS4;11 and treated with 19BBζ CAR T cells showed improved overall survival when compared to mock T cells treated animals. The results showed that electroporation using the SB system is a simple and affordable method for inducing long-term CAR expression in T lymphocytes. Expansion of gene-modified T cells with the lymphoblastoid cell line provided up to 2 cycles of stimulations, generating effective T cells against leukemia in vitro and in vivo.
Assuntos
Elementos de DNA Transponíveis , Vetores Genéticos/genética , Imunoterapia Adotiva , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Linhagem Celular Transformada , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Expressão Gênica , Vetores Genéticos/administração & dosagem , Humanos , Memória Imunológica , Camundongos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: This study aimed to assess the intraexaminer and interexaminer reproducibility of the Downing test in sacroiliac joint evaluation in symptomatic and asymptomatic individuals. METHODS: A reliability study was conducted with a test-retest design in 54 college students of both sexes. To assess the intraexaminer reproducibility, each participant was evaluated twice by the same examiner with a 7-day interval, and to assess the interexaminer reproducibility, each participant was evaluated by 2 examiners. RESULTS: Of the 54 participants included in the study, 18 (33.3%) were asymptomatic and 36 (66.7%) were symptomatic; a total of 108 sacroiliac joints were evaluated. Sacroiliac joint diagnosis based on the Downing test presented low intraexaminer reproducibility in all participants (κ = 0.12, 95% confidence interval [CI] 0.03-0.22), in asymptomatic individuals (κ = 0.18, 95% CI 0.02-0.34), and in symptomatic individuals (κ = 0.28, 95% CI 0.17-0.39). The interexaminer reproducibility also was low in all participants (κ = 0.18, 95% CI 0.09-0.27), in asymptomatic individuals (κ = 0.22, 95% CI 0.15-0.37), and in symptomatic individuals (κ = 0.16, 95% CI 0.05-0.27). The standard error of the measurement values were not lower than smallest detectable change values considering a CI of 95% for all participants. CONCLUSION: For this group of asymptomatic and symptomatic participants, the reproducibility of the Downing test was poor. The clinical utility of this test used in isolation is not supported by the present study.
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BACKGROUND: The Pressure biofeedback unit (PBU) is an assessment tool used in clinical practice and research aimed to indirectly analyze the transversus abdominis (TrA) muscle activity. The concurrent validity of the PBU in a clinically relevant sample is still unclear. OBJECTIVE: The purpose of this study was to evaluate the concurrent validity and diagnostic accuracy of the PBU in measuring TrA muscle activity in patients with chronic nonspecific low back pain. METHOD: This study was performed using a validation, cross-sectional design. Fifty patients with chronic nonspecific low back pain were recruited for this study. To test the concurrent validity both PBU measures (index test) and superficial electromyographic measures (reference-standard test) were compared and collected by a physical therapist in a series of voluntary contraction maneuvers of TrA muscle. RESULTS: Participants were on average 22 years old, weighed 63.7 kilos, 1.70 meters height and mean low back pain duration was 1.9 years. It was observed a weak and non-significant Phi coefficient (r=0.2, p<0.20). With regards to diagnostic accuracy tests, our results suggest a low sensitivity (60%) and specificity (60%) of the PBU. The positive predictive value was high (0.8) and negative predictive value was low (0.2). Conclusions: Concurrent validity of the PBU in measuring TrA muscle activity in patients with chronic nonspecific low back pain is poor given the low correlation and diagnostic accuracy with superficial EMG.
CONTEXTUALIZAÇÃO: A Unidade de Biofeedback Pressórico (UBP) é uma ferramenta de avaliação usada na prática clínica e pesquisa científica para analisar indiretamente a atividade muscular do transverso abdominal (TrA). A validade concorrente da UBP em uma amostra clinicamente relevante ainda não está esclarecida. OBJETIVO: Avaliar a validade concorrente e acurácia diagnóstica da UBP em mensurar a atividade muscular do TrA em pacientes com dor lombar crônica inespecífica. MÉTODO: Este estudo foi realizado usando um delineamento de validação. Cinquenta pacientes com dor lombar crônica inespecífica foram recrutados. Para testar a validade concorrente, ambas as medidas pressóricas (teste índice) e eletromiográficas superficiais (teste padrão de referência) foram comparadas e coletadas por um fisioterapeuta a partir de uma manobra de contração voluntária do músculo TrA. RESULTADOS: Os participantes tinham em média 22 anos, 63,7 kg, 1,70 m de altura, e a duração média de dor lombar era de 1,9 ano. Observou-se um coeficiente Phi fraco e não significativo (r=0,2; p<0,20). Com relação aos testes de acurácia diagnóstica, os resultados sugerem uma baixa sensibilidade (60%) e especificidade (60%) da UBP. O valor preditivo positivo foi elevado (0,8), e o valor preditivo negativo foi baixo (0,2). Conclusões: A validade concorrente da UBP em mensurar a atividade muscular do TrA em pacientes com dor lombar crônica inespecífica é pobre, considerando a baixa correlação e acurácia diagnóstica com a EMG de superfície.
Assuntos
Feminino , Humanos , Masculino , Adulto Jovem , Músculos Abdominais/fisiopatologia , Biorretroalimentação Psicológica/métodos , Dor Crônica/fisiopatologia , Eletromiografia , Dor Lombar/fisiopatologia , Biorretroalimentação Psicológica/instrumentação , Estudos Transversais , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The Pressure biofeedback unit (PBU) is an assessment tool used in clinical practice and research aimed to indirectly analyze the transversus abdominis (TrA) muscle activity. The concurrent validity of the PBU in a clinically relevant sample is still unclear. OBJECTIVE: The purpose of this study was to evaluate the concurrent validity and diagnostic accuracy of the PBU in measuring TrA muscle activity in patients with chronic nonspecific low back pain. METHOD: This study was performed using a validation, cross-sectional design. Fifty patients with chronic nonspecific low back pain were recruited for this study. To test the concurrent validity both PBU measures (index test) and superficial electromyographic measures (reference-standard test) were compared and collected by a physical therapist in a series of voluntary contraction maneuvers of TrA muscle. RESULTS: Participants were on average 22 years old, weighed 63.7 kilos, 1.70 meters height and mean low back pain duration was 1.9 years. It was observed a weak and non-significant Phi coefficient (r=0.2, p<0.20). With regards to diagnostic accuracy tests, our results suggest a low sensitivity (60%) and specificity (60%) of the PBU. The positive predictive value was high (0.8) and negative predictive value was low (0.2). CONCLUSIONS: Concurrent validity of the PBU in measuring TrA muscle activity in patients with chronic nonspecific low back pain is poor given the low correlation and diagnostic accuracy with superficial EMG.
Assuntos
Músculos Abdominais/fisiopatologia , Biorretroalimentação Psicológica/métodos , Dor Crônica/fisiopatologia , Eletromiografia , Dor Lombar/fisiopatologia , Biorretroalimentação Psicológica/instrumentação , Estudos Transversais , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Gangliosides have been considered as potential targets for immunotherapy because they are overexpressed on the surface of melanoma cells. However, immunization with purified gangliosides results in a very poor immune response, usually mediated by IgM antibodies. To overcome this limitation, we immunized mice with R24, a monoclonal antibody (mAb) that recognizes the most tumor-restricted ganglioside (GD3); our goal was to obtain anti-idiotype (Id) antibodies bearing the internal image of GD3. Animals produced anti-Id and anti-anti-Id antibodies. Both anti-Id and anti-anti-Id antibodies were able to inhibit mAb R24 binding to GD3. In addition, the anti-anti-Id antibodies were shown to recognize GD3 directly. Anti-Id and anti-anti-Id mAb were then selected from two fusion experiments for evaluation. The most interesting finding emerged from the characterization of the anti-anti-Id mAb 5.G8. It was shown to recognize two different GD3-expressing human melanoma cell lines in vitro and to mediate tumor cell cytotoxicity by complement activation and antibody-dependent cellular cytotoxicity. The biological activity of the anti-anti-Id mAb was also tested in a mouse tumor model, in which it was shown to be a powerful growth inhibitor of melanoma cells. Thus, activity of the anti-anti-Id mAb 5.G8 matched that of the prototypic anti-GD3 mAb R24 both in vitro and in vivo. Altogether, our results indicate that the idiotype approach might produce high affinity, specific and very efficient antitumor immune responses.