Morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis.

BACKGROUND: Fibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA). METHODS: FLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1ß. RESULTS: RA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well-developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1ß by CIA-FLSs than by RA-FLSs. CONCLUSION: This study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.

Morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis

Abstract Background Fibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA). Methods FLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1β. Results RA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well- developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1β by CIA-FLSs than by RA-FLSs. Conclusion This study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.

Análise da qualidade de vida de professores de educação física escolar / Analysis of quality of life of school physical education teachers / Análisis de la calidad de vida del profesorado escolar de educación física

RESUMO O objetivo do presente estudo foi verificar o índice de qualidade de vida (QV) de professores de educação física de uma rede pública municipal de ensino no estado do Rio de Janeiro através do questionário Whoqol-breef. Foram avaliados 31 professores de um total de 65 professores de educação física da rede, estratificados pelo sexo e tempo de trabalho (2-8 anos, 9-15 anos, >15 anos). Os resultados A média geral do escore de QV indicou que a qualidade de vida dos professores necessita de mais atenção e melhorias, principalmente nos domínios das relações sociais, condições ambientais e estresse. Conclui-se que os índices reduzidos de satisfação e cuidados com a QV denota necessidade de repensar as políticas públicas de saúde do trabalhador e as características do trabalho docente.

ABSTRACT The objective of the present study was to verify the quality of life (QL) index of physical education teachers from a municipal public teaching network in the state of Rio de Janeiro through the Whoqol-breef questionnaire. Thirty-one teachers from a total of 65 physical education teachers in the network were evaluated, stratified by gender and length of service (2-8 years, 9-15 years, >15 years). The results The general average of the QL score indicated that the teachers' quality of life needs more attention and improvements, mainly in the domains of social relations, environmental conditions and stress. It is concluded that the reduced rates of satisfaction and care with QoL denotes the need to rethink public policies on workers' health and the characteristics of teaching work.

RESUMEN El objetivo del presente estudio fue verificar el índice de calidad de vida (CV) de profesores de educación física de una red pública municipal de enseñanza en el estado de Río de Janeiro a través del cuestionario Whoqol-breef. Se evaluaron 31 docentes de un total de 65 docentes de educación física de la red, estratificados por género y antigüedad (2-8 años, 9-15 años, >15 años). Los resultados El promedio general de la puntuación de la CV indicó que la calidad de vida de los profesores necesita más atención y mejoras, principalmente en los dominios de relaciones sociales, condiciones ambientales y estrés. Se concluye que los reducidos índices de satisfacción y cuidado con la CV denotan la necesidad de repensar las políticas públicas sobre salud de los trabajadores y las características del trabajo docente.

Avaliação Psicométrica da Prova de Título de Especialista em Cardiologia da Sociedade Brasileira de Cardiologia / Psychometric Evaluation of the Cardiology Certification Exam of the Brazilian Society of Cardiology

Resumo Fundamento A Sociedade Brasileira de Cardiologia promove anualmente a prova para obtenção do título de especialista em Cardiologia, sendo a Comissão Julgadora do Título de Especialista em Cardiologia responsável pela sua organização e aplicação. A análise psicométrica dos itens de uma prova, por meio da Teoria de Resposta ao Item (TRI) pode fornecer informações robustas e contribuir para o aprimoramento contínuo dessa avaliação. Objetivos Avaliar as propriedades psicométricas da prova do Título de Especialista em Cardiologia no ano de 2019, em relação aos parâmetros da TRI. Métodos Estudo observacional, com a análise psicométrica das 120 questões da prova realizada por 1120 (mil cento e vinte) candidatos para a obtenção do título de especialista em Cardiologia, no ano de 2019. Resultados A análise da prova pela TRI mostrou 32,2% dos itens com poder de discriminação "alto" ou "muito alto", 49,2% dos itens categorizados como "fácil" ou "muito fácil" e 41,5% apresentavam alta probabilidade de acerto ao acaso . Foram identificados 69 itens com problemas em relação aos parâmetros da TRI e, portanto, com baixo poder de avaliar a proficiência do candidato. Conclusões A análise psicométrica da prova de título de Especialista em Cardiologia pela TRI demonstrou um alto percentual de questões fáceis, com cerca de dois terços dos itens com alta probabilidade de acerto ao acaso. Esses dados poderão desencadear uma série de discussões e propostas para a construção das futuras provas em cardiologia.

Abstract Background The Cardiology Certification Exam is issued annually by the Brazilian Cardiology Society and set and applied by the Judging Committee for the Cardiologist Title (CJTEC). The psychometric analysis of the exam items using the Item Response Theory (IRT) may provide robust data that can help in the continuous improvement of this instrument. Objectives To evaluate the psychometric properties of the 2019 Cardiology Certification Exam in relation to the IR parameters. Methods This was an observational study, with psychometric analysis of the 120 questions of the exam taken by 1,120 candidates for the title of Cardiologist in 2019. Results The IRT analysis revealed that 32.2% of the items had a "high" or "very high" discriminating power, 49.2% were categorized as "easy" or "very easy", and 41.5% showed a high probability of a correct guessing. Sixty-nine deficient items in terms of the IRT parameters were identified, which were then considered poorly effective in evaluating the candidate's ability. Conclusions The psychometric analysis of the 2019 Cardiology Certification Exam by the IRT revealed a high percentage of easy questions, with nearly two thirds of the items with a high probability of correct guessing. These data may serve as a basis for a series of discussions and proposals for the elaboration of future certificate exams in Cardiology.

Mast cell-T cell axis alters development of colitis-dependent and colitis-independent colorectal tumours: potential for therapeutically targeting via mast cell inhibition.

BACKGROUND: Colorectal cancer (CRC) has a high mortality rate and can develop in either colitis-dependent (colitis-associated (CA)-CRC) or colitis-independent (sporadic (s)CRC) manner. There has been a significant debate about whether mast cells (MCs) promote or inhibit the development of CRC. Herein we investigated MC activity throughout the multistepped development of CRC in both human patients and animal models. METHODS: We analyzed human patient matched samples of healthy colon vs CRC tissue alongside conducting a The Cancer Genome Atlas-based immunogenomic analysis and multiple experiments employing genetically engineered mouse (GEM) models. RESULTS: Analyzing human CRC samples revealed that MCs can be active or inactive in this disease. An activated MC population decreased the number of tumor-residing CD8 T cells. In mice, MC deficiency decreased the development of CA-CRC lesions, while it increased the density of tumor-based CD8 infiltration. Furthermore, co-culture experiments revealed that tumor-primed MCs promote apoptosis in CRC cells. In MC-deficient mice, we found that MCs inhibited the development of sCRC lesions. Further exploration of this with several GEM models confirmed that different immune responses alter and are altered by MC activity, which directly alters colon tumorigenesis. Since rescuing MC activity with bone marrow transplantation in MC-deficient mice or pharmacologically inhibiting MC effects impacts the development of sCRC lesions, we explored its therapeutic potential against CRC. MC activity promoted CRC cell engraftment by inhibiting CD8+ cell infiltration in tumors, pharmacologically blocking it inhibits the ability of allograft tumors to develop. This therapeutic strategy potentiated the cytotoxic activity of fluorouracil chemotherapy. CONCLUSION: Therefore, we suggest that MCs have a dual role throughout CRC development and are potential druggable targets against this disease.

Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease.

Host immune responses contribute to dengue's pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, interferon (alpha and beta) receptor one knockout (KO), AnxA1 KO, and formyl peptide receptor 2 (FPR2) KO mice were infected with dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac2-26 for analysis. In addition, the effect of Ac2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. Whilst the absence of AnxA1 or its receptor FPR2 aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestationsatteanuated the symptoms of the disease. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease.

Narrative review about kip's execution on the low bar of uneven bars / Revisão narrativa sobre a execução do kip na barra baixa das paralelas assimétricas

O kip é uma habilidade fundamental amplamente utilizada nas rotinas de treinamento da ginástica artística. No entanto, faltam materiais didáticos que auxiliem o processo de ensino-aprendizagem dos alunos e dos professores iniciantes. OBJETIVO: Apresentar uma análise biomecânica qualitativa do kippe realizado na barra inferior das paralelas assimétricas. MÉTODOS: Esta foi uma revisão narrativa baseada no Google Acadêmico. Os termos utilizados para a busca dos materiais foram kippe e biomecânica, em Português e Inglês, considerando estudos experimentais e não experimentais. RESULTADOS: A literatura aponta diferentes termos para designar este mesmo movimento. Os movimentos articulares predominantes são extensão e flexão, o que justifica a maioria dos textos abordar a análise do plano sagital. O kippe tem seis instantes e três fases de movimento, Glide, Pike e Pull Up. A literatura mostra pequenas diferenças na execução em cada uma dessas fases. No entanto, alguns erros comuns de execução são apontados com algum consenso como deslizar muito curto, não alcançar o pike, abaixar as pernas muito rápido após o pike e flexionar os cotovelos na tentativa de encerrar o movimento. CONCLUSÃO: Há um número reduzido de estudos que integram a avaliação biomecânica ao processo ensino-aprendizagem na ginástica, bem como no contexto do esporte de alto rendimento. Demonstramos que essa abordagem qualitativa pode ser útil para o processo de ensino-aprendizagem desse exercício específico. A decomposição do movimento em fases permite estabelecer prioridades com base nas forças e fraquezas apresentadas pelos atletas / alunos, otimizando assim as intervenções para melhorar o seu desempenho. (AU)

Kip is a fundamental skill widely used in artistic gymnastics trai-ning routines. However, there is a lack of didactic material that helps students' tea-ching-learning process and beginning teachers. OBJECTIVE: To present a qualitative biomechanical analysis of the kippe performed on the lower bar of the asymmetric parallel bars. METHODS: This was an narrative review based on Google Scholar. The terms used to search for materials were kippe and biomechanics, in Portuguese and English, considering experimental and nonexperimental studies. RESULTS: The lite-rature points out different terms to designate this same movement. The predominant articular movements are extension and flexion, which justifies the majority of the texts to approach the sagittal plane analysis. The kippe has six instants and three phases of movement, Glide, Pike, and Pull Up. The literature show small differences in executi-on in each of these phases. However, some common execution errors are pointed out with consensus as glide too short, do no reach the pike, lower the legs too fast after the pike, and flexing the elbows in an attempt to end the movement. CONCLUSION: The-re is a low number of studies that integrate biomechanical assessment with the tea-ching-learning process in gymnastics, as well as in the context of high-performance sport. We have demonstrated that this qualitative approach might be useful to the tea-ching-learning process of this specific exercise. The decomposition of the movement in critical phases allows establishing priorities based on the strengths and weaknesses exhibited by the athletes/students, thereby optimizing the interventions to improve their performance. (AU)

Performance of High Mobility Protein Group 1 and Interleukin-6 as Predictors of Outcomes Resulting from Variceal Bleeding in Patients with Advanced Chronic Liver Disease.

Variceal bleeding is a serious complication in cirrhotic patients and is related to increased expression of inflammatory mediators that accentuate circulatory dysfunction. The study aims to evaluate the performance of high mobility protein group 1 (HMG1) and interleukin-6 (IL-6) as predictors of acute kidney injury (AKI), infection and death in these patients. Fifty patients who were diagnosed with advanced chronic liver disease with variceal bleeding were included. The mean age was 52.8 ± 10.8 years, and 33 (66%) were male. Twenty-one (42%) patients were classified as Child-Pugh C, 21 (42%) Child-Pugh B and 8 (16%) Child-Pugh A. The mean HMG1 serum level was 2872.36 pg/mL ± 2491.94, and the median IL-6 serum level was 47.26 pg/mL (0-1102.4). In AKI, the serum level of HMG1 that performed best on the ROC curve was 3317.9 pg/mL. The IL-6 serum level was not associated with AKI. HMG1 and IL-6 cut-off values that better predicted infection were 3317.9 pg/mL and 72.9 pg/mL, and for mortality, the values were 2668 pg/mL and 84.5 pg/mL, respectively. In multivariate analysis, the variables that were associated with AKI and infection outcomes were model for end-stage liver disease and HMG1. Infections were related to the risk of death. Clinical and laboratory variables related to the outcomes were identified. Serum levels of HMG1 were associated with AKI and infection and had good performance in the ROC curve. IL-6 levels were not maintained in logistic regression outcomes but had good performance in infection and death outcomes. Such data will be useful for comparisons and possible future validations.

Clinical Frailty Scale em idosos atendidos no Serviço Hospitalar de Emergência: a fragilidade basal é um bom preditor de mortalidade em 90 dias? / Clinical Frailty Scale in older adults admitted at Emergency Department: is baseline frailty a good predictor of Ninety-Day Mortality?

Resumo Objetivo Avaliar a capacidade da Clinical Frailty Scale (CFS) em predizer a mortalidade em até 90 dias e outros desfechos desfavoráveis em idosos admitidos em um Serviço Hospitalar de Emergência (SHE). Método Estudo de coorte prospectivo que incluiu idosos admitidos e que permaneceram por pelo menos uma noite no SHE de um hospital público terciário. O grau de fragilidade basal foi avaliado através da CFS e sua pontuação, o preditor estudado, por meio da curva Receiver Operator Characteristics (ROC). Analisou-se como desfecho primário a mortalidade em 90 dias. Considerou-se como desfechos secundários: mortalidade em 180 dias, declínio funcional, readmissão no SHE, reinternação e necessidade de atenção domiciliar. Resultados 206 participantes foram incluídos. Dos 127 idosos frágeis, 40 (31,5%) faleceram até o 90º dia comparado a 5 (6,3%) do grupo não frágil (p<0,001). Após ajuste para variáveis demográficas e clínicas, a fragilidade manteve-se no modelo como um preditor independente de mortalidade em 90 dias da admissão. A acurácia obtida pela curva ROC (AUROC) para predição de mortalidade em 90 dias foi de 0,81. Para mortalidade em 180 dias foi 0,80; para necessidade de atenção domiciliar, 0,77; e para reinternação, 0,65. Para os demais desfechos estudados, a acurácia não foi significativa. Conclusão A fragilidade basal medida pela CFS é um bom preditor de mortalidade em 90 e 180 dias e de necessidade de atenção domiciliar em idosos admitidos no SHE. Sua aplicação nesse cenário pode auxiliar na tomada de decisões clínicas.

Abstract Objective To evaluate the ability of the Clinical Frailty Scale (CFS) to predict 90-day mortality and other poor outcomes in older adults admitted at a Hospital Emergency Department (ED). Method This is a prospective cohort study including older adults admitted at ED of a Public Hospital who spent at least one night in it. The degree of baseline frailty was assessed through the CFS, and its score was the predictor studied, through the Receiver Operator Characteristics (ROC) curve analysis. We analyzed 90-day mortality as a primary outcome. The following outcomes were considered as secondary ones: mortality, functional decline, readmittance to ED, readmission and need for home care. Results 206 participants were included. Of the 127 frail older adults, 40 (31.5%) died before the 90th day compared to 5 (6.3%) in the non-frail group (p<0.001). After adjustment for demographic and clinical variables, frailty remained in the model as an independent predictor of 90-day mortality. The accuracy obtained by the ROC curve (AUROC) for predicting 90-day mortality was 0.81. For 180-day mortality, 0.80, for the need for home care, 0.77 for readmission, 0.65. For the other outcomes studied, the accuracy was not significant. Conclusion Baseline frailty measured by the CFS is a good predictor of 90 and 180-day mortality and needing for home care in older adults admitted to ED. Its application in this setting might help clinical decision-making.

Implications for clinical practice from a multicenter survey of heart failure management centers

OBJECTIVES: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil. METHODS: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment. RESULTS: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment. CONCLUSION: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.

A autoliberação miofascial sobre o desempenho de potência muscular em atletas de futebol sub-13 / The myofascial self-liberation on muscular power performance in sub-13 soccer athletes

Este estudo investiga o efeito da autoliberação miofascial sobre o desempenho de potência muscular no salto vertical, salto horizontal e agilidade uniplanar em atletas de futebol sub-13, cuja amostra foi composta por 22 adolescentes do sexo masculino, praticantes de uma escolinha de futebol da cidade de Juiz de Fora, MG. Ao todo, realizaram-se três dias de testes de cada variável, assim como o protocolo de autoliberação, com intervalo de 48 horas entre as sessões. Para o protocolo controle, os participantes foram orientados a realizar três tentativas de salto horizontal, vertical e agilidade uniplanar, com intervalo de dois minutos para cada tentativa e uma pausa de cinco minutos entre os testes. Os mesmos procedimentos foram repetidos para a realização do protocolo experimental de autoliberação, porém executou-se, nos pré-testes de membros inferiores, um minuto de autoliberação miofascial, com ordem aleatória dos grupos musculares (quadríceps, isquiostibiais e gastrocnêmio), com o total de seis minutos de autoliberação, validando-se os melhores resultados de cada teste dos protocolos controle e experimental, em que utilizou-se o Foam Rolling. Observou-se uma média de 2,8 (±0,8) para os estágios de desenvolvimento dos participantes, considerando a Escala de Tanner. Quanto ao protocolo de autoliberação, o desempenho no salto vertical foi significativamente superior após a utilização do Foam Rolling, comparado ao controle. Não houve diferença significativa no desempenho de salto horizontal e agilidade uniplanar ao comparar o protocolo controle com o experimental, todavia, efeitos adversos não foram observados na utilização deste método.(AU)

This study investigates the effect of myofascial self-liberation on the performance of muscle power in the variables of vertical jump, horizontal jump and uniplanar agility in under-13 soccer athletes, whose sample was composed of 22 male adolescents, practitioners of a soccer school from the city of Juiz de Fora, MG. In all, three days of tests were performed for each variable, as well as the self-release protocol, with an interval of 48 hours between sessions. For the control protocol, participants were instructed to make three attempts to jump horizontally, vertically and uniplanar agility, with an interval of two minutes for each attempt and a five-minute pause between tests. The same procedures were repeated for the experimental self-liberation protocol, however, in the lower limb pre-tests, a minute of myofascial self-liberation was performed, with a random order of the muscle groups (quadriceps, hamstrings and gastrocnemius), with the total of six minutes of self-liberation, validating the best results of each test of the control and experimental protocols, in which Foam Rolling was used. An average of 2.8 (± 0.8) was observed for the participants' developmental stages, considering the Tanner Scale. As for the selfliberation protocol, the performance in the vertical jump was significantly higher after using Foam Rolling, compared to the control. There was no significant difference in the performance of horizontal jump and uniplanar agility when comparing the control protocol with the experimental one, however, adverse effects were not observed in the use of this method.(AU)

Evaluation of the Biomarkers HMGB1 and IL-6 as Predictors of Mortality in Cirrhotic Patients with Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) affects from 20% to 50% of cirrhotic patients, and the one-month mortality rate is 60%. The main cause of AKI is bacterial infection, which worsens circulatory dysfunction through the release of HMGB1 and IL-6. OBJECTIVES: To evaluate HMGB1 and IL-6 as biomarkers of morbidity/mortality. METHODS: Prospective, observational study of 25 hospitalised cirrhotic patients with AKI. Clinical and laboratory data were collected at the time of diagnosis of AKI, including serum HMGB1 and IL-6. RESULTS: The mean age was 55 years; 70% were male. Infections accounted for 13 cases. The 30-day and three-month mortality rates were 17.4% and 30.4%, respectively. HMGB1 levels were lower in survivors than in nonsurvivors at 30 days (1174.2 pg/mL versus 3338.5 pg/mL, p = 0.035), but not at three months (1540 pg/mL versus 2352 pg/mL, p = 0.243). Serum IL-6 levels were 43.3 pg/mL versus 153.3 pg/mL (p = 0.061) at 30 days and 35.8 pg/mL versus 87.9 pg/mL (p = 0.071) at three months, respectively. The area under the ROC curve for HMGB1 was 0.842 and 0.657, and that for IL-6 was 0.803 and 0.743 for discriminating nonsurvivors at 30 days and three months, respectively. In multivariate analysis, no biomarker was independently associated with mortality. CONCLUSION: HMGB1 levels were associated with decreased survival in cirrhotics. Larger studies are needed to confirm our results.

Fibroblast-like synoviocytes from fluid and synovial membrane from primary osteoarthritis demonstrate similar production of interleukin 6, and metalloproteinases 1 and 3.

OBJECTIVES: The objective of the study was to compare the production of metalloproteinases (MMP)-1, -3 and interleukin (IL)-6 by fibroblast-like synoviocytes (FLS) derived from synovial fluid (FD-FLS), and FLS derived from synovial tissue (TD-FLS) of patients with primary osteoarthritis (OA). The more accessible FD-FLS could facilitate the study of the role of these cells in OA pathophysiology. METHODS: MMP-1, MMP-3, and IL-6 levels were measured in the supernatant culture at baseline and 22 hours after stimulation with TNF-α and IL-1 ß. RESULTS: There was no difference at baseline between MMP-1, MMP-3 and IL-6 production by FD-FLS and TDFLS. Analogous to baseline, stimulation of FD-FLS and TD-FLS with IL-1ß and TNF-α did not result in difference on MMP-3 and IL-6 production. However, TD-FLS produced more MMP-1 than FD-FLS after stimulation with IL-1ß (p=0.01). Additionally, there was a positive correlation for production of MMP-1, MMP-3 and IL-6 between FD-FLS and TD-FLS (r=0.40 and p<0.0008; r=0.66 and p<0.0001; r=0.76 and p<0.0001, respectively). Supporting this statistical significant positive correlation, the Bland-Altman plotting, showed a homogeneous distribution of the values and low mean disagreement rates between all results of FD-FLS and TD-FLS (23.1%, 56.8% and 48.1%, respectively). CONCLUSIONS: Our data demonstrated functional similarity between FD-FLS and TD-FLS and support the use of a more accessible source of FLS for the study of the pathogenesis of joint destruction and therapeutic targets in primary OA.

Methotrexate use, not interleukin 33, is associated with lower carotid intima-media thickness in patients with rheumatoid arthritis

Abstract Background: Rheumatoid arthritis is a risk factor for early mortality due to cardiovascular disease. Interleukin-33 appears to protect against the development of atherosclerosis. The purpose of this study was to investigate the relationship between serum levels of interleukin-33 and its soluble receptor with the presence of subclinical carotid atherosclerosis in rheumatoid arthritis patients. Methods: Rheumatoid arthritis patients without atherosclerotic disease were subjected to clinical and laboratory assessments, including carotid ultrasound. Interleukin-33 and its soluble receptor serum levels were measured by ELISA. Results: 102 patients were included. The prevalence of carotid plaques was 23.5% and the median intima-media thickness was 0.7 mm. The median interleukin-33 and its soluble receptor concentration was 69.1 and 469.8 pg/ml. No association was found between serum interleukin-33 or its soluble receptor and intima-media thickness or plaque occurrence. Each 0.1 mm increase of intima-media thickness raised the odds of plaque occurrence by 5.3-fold, and each additional year of rheumatoid arthritis duration increased the odds of plaque occurrence by 6%. Each additional year in patients age and each one-point increase in the Framingham Risk Score were associated with a 0.004 mm and 0.012 mm increase in intima-media thickness. Methotrexate use was associated with a 0.07 mm reduction in intima-media thickness. Conclusions: Interleukin-33 and its soluble receptor were not associated with subclinical atherosclerosis. Traditional risk factors for atherosclerosis and rheumatoid arthritis duration were associated with intima-media thickness and plaque occurrence; methotrexate use was associated with a lower intima-media thickness.

Avaliação da interleucina 3 como marcador prognóstico na sepse / Role of interleukin-3 as a prognostic marker in septic patients

RESUMO Objetivo: Avaliar a acurácia dos níveis de interleucina 3 para predizer prognóstico em pacientes sépticos. Métodos: Conduzimos uma coorte prospectiva que incluiu pacientes adultos internados em unidade de terapia intensiva, que apresentassem sepse ou choque séptico iniciados há até 48 horas. Mediram-se os níveis séricos de interleucina 3 quando da inclusão (dia 1) e nos dias 3 e 7. O desfecho primário analisado foi a mortalidade hospitalar por qualquer causa. Resultados: Foram incluídos 120 pacientes. Os níveis séricos de interleucina 3 dosados à inclusão foram significativamente mais elevados em pacientes que faleceram em comparação aos que sobreviveram à internação hospitalar (91,2pg/mL versus 36pg/mL; p = 0,024). Em modelo de sobrevivência de Cox com inclusão de idade e valores sequenciais de SOFA, os níveis de interleucina 3 mensurados na inclusão mantiveram-se independentemente associados à mortalidade hospitalar (HR 1,032; IC95% 1,010 - 1,055; p = 0,005). Em curva Característica de Operação do Receptor construída para investigação adicional da acurácia da interleucina 3 na predição do prognóstico, encontrou-se área sob a curva de 0,62 (IC95% 0,51 - 0,73; p = 0,024) para mortalidade hospitalar. Valores iniciais de interleucina 3 acima de 127,5pg/mL mostraram-se significativamente associados à mortalidade hospitalar (p = 0,019; OR = 2,97; IC95% 1,27 - 6,97; p = 0,019), entretanto com baixo desempenho (especificidade de 82%, sensibilidade de 39%, valor preditivo positivo de 53%, valor preditivo negativo de 72%, razão de verossimilhança negativa de 0,73 e razão de verossimilhança positiva de 2,16). Conclusão: Níveis elevados de interleucina 3 mostraram-se independentemente associados à mortalidade hospitalar em pacientes sépticos, entretanto com baixo desempenho clínico.

ABSTRACT Objective: To evaluate the accuracy of IL-3 to predict the outcome of septic patients. Methods: Prospective cohort study with adult patients in an intensive care unit with sepsis or septic shock diagnosed within the previous 48 hours. Circulating IL-3 levels were measured upon inclusion (day 1) and on days 3 and 7. The primary outcome was hospital mortality. Results: One hundred and twenty patients were included. Serum levels of IL-3 on day 1 were significantly higher among patients who died than among patients who survived the hospital stay (91.2pg/mL versus 36pg/mL, p = 0.024). In a Cox survival model considering the IL-3 levels at inclusion, age and sequential SOFA, IL-3 values remained independently associated with mortality (HR 1.032; 95%CI 1.010 - 1.055; p = 0.005). An receiver operating characteristic curve was built to further investigate the accuracy of IL-3, with an area under the curve of 0.62 (95%CI 0.51 - 0.73; p = 0.024) for hospital mortality. A cutoff initial IL-3 value above 127.5pg/mL was associated with hospital mortality (OR 2.97; 95%CI: 1.27 - 6.97; p = 0.0019) but with a low performance (82% for specificity, 39% for sensibility, 53% for the positive predictive value, 72% for the negative predictive value, 0.73 for the negative likelihood and 2.16 for the positive likelihood ratio). Conclusion: Higher levels of IL-3 are shown to be independently associated with hospital mortality in septic patients but with poor clinical performance.

Evaluation of the Bleeding Intensity of Patients Anticoagulated with Warfarin or Dabigatran Undergoing Dental Procedures / Avaliação da Intensidade de Sangramento de Procedimentos Odontológicos em Pacientes Anticoagulados com Varfarina ou Dabigatrana

Abstract Background: Thrombotic disorders remain one of the leading causes of death in the Western world. Dabigatran appeared as an alternative to warfarin for anticoagulation in the treatment of atrial fibrillation (AF). The risk associated with bleeding due to its use has been documented in several randomized clinical trials, but no large study has examined in detail the risk of bleeding during dental extraction and other dental procedures involving bleeding. Objective: To compare the intensity of bleeding in individuals taking dabigatran or vitamin K antagonist (warfarin) and undergoing dental procedures. Methods: Prospective, single-center, controlled study with one single observer. Patients diagnosed with nonvalvular AF, on warfarin or dabigatran, cared for at a cardiology referral center, and requiring single or multiple dental extractions, were evaluated up to seven days post-extraction. The following outcomes were assessed: bleeding time between the beginning and the end of suture and complete hemostasis; bleeding before the procedure, after 24 hours, 48 hours, 7 days, during and after suture removal (late); p<0.05 was defined as of statistical relevance. Results: We evaluated 37 individuals, 25 in the warfarin group and 12 in the dabigatran group. Age, sex, weight, height, blood pressure, color, schooling, family income and comorbidities were similar between the two groups. Regarding bleeding after 24 hours of the procedure, no one in the dabigatran group had bleeding, whereas 32% in the warfarin group had documented bleeding (p = 0.028). The other variables analyzed did not differ between the groups. Conclusions: This study suggests that, regarding dental extraction, there is no statistically significant difference in the intensity of bleeding of patients taking dabigatran as compared to those taking warfarin. Bleeding 24 hours after the procedure was less frequent among patients on dabigatran.

Resumo Fundamento: Distúrbios trombóticos permanecem como uma das principais causas de morte no mundo ocidental. A dabigatrana surgiu como alternativa à varfarina para a anticoagulação no tratamento da fibrilação atrial (FA). O risco associado a eventos hemorrágicos com a sua utilização foi documentado em vários ensaios clínicos randomizados, mas nenhum grande estudo analisou detalhadamente o risco de hemorragia durante a extração dentária e em outros procedimentos odontológicos que envolvam sangramentos. Objetivo: Em indivíduos submetidos a procedimentos odontológicos, avaliar a intensidade de sangramento com o uso de dabigatrana em comparação ao uso de anticoagulante oral antagonista da vitamina K (varfarina). Métodos: Estudo prospectivo, controlado, unicêntrico, observador único. Pacientes com diagnóstico de FA não valvar atendidos em um centro de referência em cardiologia e com indicação de anticoagulação que necessitavam de tratamento odontológico para exodontia única ou múltipla, estando em uso de varfarina ou dabigatrana e avaliados até sete dias pós-exodontia. Foram avaliados os efeitos sobre: tempo de sangramento entre o início e o fim da sutura e hemostasia completa; sangramento antes do procedimento, após 24 e 48 horas, 7 dias, durante e após a remoção da sutura (tardio), sendo considerado como estatisticamente significativo valor de p < 0,05. Resultados: Foram avaliados 37 indivíduos, sendo 25 no grupo varfarina e 12 no dabigatrana. Idade, sexo, peso, altura, pressão arterial, cor, escolaridade, renda familiar e comorbidades foram semelhantes nos dois grupos. Em relação ao sangramento 24 horas após o procedimento, ninguém do grupo dabigatrana apresentou sangramento, que esteve presente em 32% do grupo varfarina (p = 0,028). Não houve diferenças entre os grupos em relação às outras variáveis analisadas. Conclusões: Os dados deste estudo permitem sugerir que, em indivíduos submetidos a procedimento odontológico de exodontia, não há diferença estatisticamente significante na intensidade de sangramento em uso de dabigatrana em comparação ao uso de varfarina. Há uma menor frequência de sangramento 24 horas após o procedimento nos indivíduos em uso de dabigatrana.

Mast Cells and Serotonin Synthesis Modulate Chagas Disease in the Colon: Clinical and Experimental Evidence.

BACKGROUND: Trypanosoma cruzi (T. cruzi) infects millions of Latin Americans each year and can induce chagasic megacolon. Little is known about how serotonin (5-HT) modulates this condition. Aim We investigated whether 5-HT synthesis alters T. cruzi infection in the colon. MATERIALS AND METHODS: Forty-eight paraffin-embedded samples from normal colon and chagasic megacolon were histopathologically analyzed (173/2009). Tryptophan hydroxylase 1 (Tph1) knockout (KO) mice and c-KitW-sh mice underwent T. cruzi infection together with their wild-type counterparts. Also, mice underwent different drug treatments (16.1.1064.60.3). RESULTS: In both humans and experimental mouse models, the serotonergic system was activated by T. cruzi infection (p < 0.05). While treating Tph1KO mice with 5-HT did not significantly increase parasitemia in the colon (p > 0.05), rescuing its synthesis promoted trypanosomiasis (p < 0.01). T. cruzi-related 5-HT release (p < 0.05) seemed not only to increase inflammatory signaling, but also to enlarge the pericryptal macrophage and mast cell populations (p < 0.01). Knocking out mast cells reduced trypanosomiasis (p < 0.01), although it did not further alter the neuroendocrine cell number and Tph1 expression (p > 0.05). Further experimentation revealed that pharmacologically inhibiting mast cell activity reduced colonic infection (p < 0.01). A similar finding was achieved when 5-HT synthesis was blocked in c-KitW-sh mice (p > 0.05). However, inhibiting mast cell activity in Tph1KO mice increased colonic trypanosomiasis (p < 0.01). CONCLUSION: We show that mast cells may modulate the T. cruzi-related increase of 5-HT synthesis in the intestinal colon.

Azo Dye Mineralization by Phanerochaete Chysosporium in a Sequencing Bath Reactor

ABSTRACT The mineralization of the azo dye congo red by the fungi Phanerochaete chrysosporium was studied in two sequential batch bioreactors (R1 and R2), operated in cycles of 48 h (step I) and 24 h (step II). In step I, glucose concentration was 1 g.L-1 in both reactors and in step II, 1 g.L-1 of glucose was maintained in R1, but R2 received no addition of glucose. In step I, the average dye removal efficiencies were 76 ± 29 % (R1) and 53 ± 15% (R2), while in step II the averages recorded for dye removal for R1 and R2 were 84 ± 15 and 70 ± 28%, respectively. The rates of dye removal were 0.04 h-1 in R1 and 0.03 h-1 in R2 in step I. Higher rates were obtained in step II, 0,07 h-1 and 0,02 h-1 for R1 and R2, respectively. The highest dye removal occurred in R1 and, in R2, the residual dye was further removed. Laccase was the oxidised at higher amount, in step I was 54 μmol.min-1 for R1 and 38 μmolmin-1 for R2. The proposed treatment system was very effective in removing the azo dye, however the mineralization may not be complete and some by-products may have been formed, according to spectrofotometric analysis, were the peak corresponding to benzene, 220 nm, persisted.

Omega-3 fatty acids, inflammatory status and biochemical markers of patients with systemic lupus erythematosus: a pilot study / Ácidos graxos ômega-3, estado inflamatório e marcadores bioquímicos de pacientes com lúpus eritematoso sistêmico: estudo piloto

Abstract Background: Studies have shown that omega-3 fatty acids reduce the concentrations of eicosanoids, cytokines, chemokines, C-reactive protein (CRP) and other inflammatory mediators. Objective: To investigate the effects of omega-3 fatty acids on circulating levels of inflammatory mediators and biochemical markers in women with systemic lupus erythematosus (SLE). Methods: Experimental clinical study (clinical trial: NCT02524795); 49 women with SLE (ACR1982/1997) were randomized: 22 to the omega-3 group (daily intake of 1080 mg EPA + 200 mg DHA, for 12 weeks) and 27 to the control group. The inflammatory mediators and biochemical markers at T0 and T1 in omega-3 group were compared using Wilcoxon test. U-Mann-Whitney test was used to compare variations of measured variables [ΔV = pre-treatment (T0) − post-treatment (T1) concentrations] between groups. p < 0.05 was considered significant. Results: The median (interquartile range - IQR) of age was 37 (29-48) years old, of disease duration was 7 (4-13) years, and of SLEDAI-2K was 1 (0-2). The median (IQR) of variation in CRP levels between the two groups showed a decrease in omega-3 group while there was an increase in control group (p = 0.008). The serum concentrations of IL-6 and IL-10, leptin and adiponectin did not change after a 12 week treatment. Conclusions: Supplementation with omega-3 had no impact on serum concentrations of IL-6, IL-10, leptin and adiponectin in women with SLE and low disease activity. There was a significant decrease of CRP levels as well as evidence that omega-3 may impact total and LDL-cholesterol.

Resumo Introdução: Estudos têm mostrado que os ácidos graxos ômega-3 reduzem as concentrações de eicosanoides, citocinas, quimiocinas, proteína C-reativa (PCR) e outros mediadores inflamatórios. Objetivo: Investigar os efeitos dos ácidos graxos ômega-3 sobre os níveis circulantes de mediadores inflamatórios e marcadores bioquímicos em mulheres com lúpus eritematoso sistêmico (LES). Métodos: Ensaio clínico randomizado (ensaio clínico: NCT02524795); randomizaram-se 49 mulheres com LES (ACR1982/1997): 22 para o grupo ômega-3 (dose diária de 1.080 mg de EPA + 200 mg de DHA durante 12 semanas) e 27 para o grupo controle. Os mediadores inflamatórios e marcadores bioquímicos em T0 e T1 no grupo ômega-3 foram comparados pelo teste de Wilcoxon. O teste U de Mann-Whitney foi usado para comparar variações das variáveis mensuradas [ΔV = concentrações pré-tratamento (T0) menos concentrações pós-tratamento (T1)] entre os grupos. Um p < 0,05 foi considerado significativo. Resultados: A mediana (intervalo interquartil-IIQ) da idade foi de 37 anos (29-48), a duração da doença foi de sete anos (4-13) anos e o Systemic Lupus Disease Activity Index (Sledai-2 K) foi de 1 (0-2). A mediana (IIQ) da variação nos níveis de PCR entre os dois grupos mostrou um decréscimo no grupo ômega-3, enquanto houve um aumento no grupo controle (p = 0,008). As concentrações séricas de IL-6 e IL-10, leptina e adiponectina não se alteraram após um tratamento de 12 semanas. Conclusões: A suplementação de ômega-3 não teve impacto sobre as concentrações séricas de IL-6, IL-10, leptina e adiponectina em mulheres com LES e baixa atividade da doença. Houve uma diminuição significativa nos níveis de PCR, bem como evidências de que o ômega-3 pode impactar sobre o colesterol total e LDL.