Factors associated with extubation failure in very low birth weight infants: a cohort study in the northeast Brazil.

OBJECTIVES: Identifying and understanding the main risk factors associated with extubation failure of very low birthweight (VLBW) infants in different populations can subsequently help in establishing better criteria while taking decision of extubation. The aim of the study was to identify factors associated with extubation failure in VLBW infants. METHODS: A cohort study of VLBW infants who underwent their first extubation between April 2018 and December 2019 in a Neonatal Intensive Care Unit, Alagoas, Brazil, were included in this study. Extubation failure was defined as reintubation within seven days of extubation. Relative risks of predictive variables different between the extubation success group (ES) and extubation failure group (EF) were estimated with a robust Poisson regression model. RESULTS: Out of the 112 infants included, 26 (23%) cases exhibited extubation failure. Extremely low birth weight (RR 2.55, 95% CI 1.07, 6.06), mechanical ventilation duration for first extubation greater than seven days (RR 2.66, 95% CI 1.10, 6.45), vaginal delivery (RR 2.07, 95% CI 1.03, 4.18) and maternal chorioamnionitis (RR 4.89, 95% CI 1.26-18.98) remained independently associated with extubation failure. EF had a significant greater need for respiratory support, longer oxygen therapy duration, more bronchopulmonary dysplasia (BPD) and longer length of hospital stay, even when adjusted for confounding variables. CONCLUSIONS: Extremely low birth weight infants needing mechanical ventilation, wherein the duration for first extubation was longer than seven days, with vaginal delivery and maternal chorioamnionitis failed more frequently at the first attempt of extubation. And this failure increased the risk of BPD and the length of hospital stay.

The toxic nature of murine amylin and the immune responsivity of pancreatic islet to conformational antibody in mice.

The human amylin is a pancreatic peptide hormone found in hyperhormonemic state along with insulin in subclinical diabetes. Amylin has been associated with the pathology of type 2 diabetes, particularly due to its ability to assembly into toxic oligomers and amyloid specimens. On the other hand, some variants such as murine amylin has been described as non-amyloidogenic, either in vitro or in vivo. Recent data have demonstrated the amyloid propensity of murine amylin and the therapeutic analogue pramlintide, suggesting a universality for amylin amyloidosis. Here, we report the amyloidogenesis of murine amylin, which showed lower responsivity to the fluorescent probe thioflavin T compared to human amylin, but presented highly organized fibrilar amyloid material. The aggregation of murine amylin also resulted in the formation of cytotoxic specimens, as evaluated in vitro in INS-1 cells. The aggregation product from murine amylin was responsive to a specific antibody raised against amyloid oligomers, the A11 oligomer antibody. Pancreatic islets of wild-type Swiss male mice have also shown responsivity for the anti-oligomer, indicating the natural abundance of such specimen in rodents. These data provide for the first time evidences for the toxic nature of oligomeric assemblies of murine amylin and its existence in wild-type, non-transgenic mice.

Effect of acute intradialytic strength physical exercise on oxidative stress and inflammatory responses in hemodialysis patients.

BACKGROUND: Oxidative stress and inflammation are common findings in chronic kidney disease (CKD) patients, and they are directly related to the increased risk of developing cardiovascular disease, which is the major cause of death in these patients, particularly for those undergoing hemodialysis (HD). Strength physical exercise is a new therapeutic approach to reduce these complications in CKD patients. Following this, the purpose of this study was to assess the effect of acute intradialytic strength physical exercise on oxidative stress and inflammatory responses in HD patients. METHODS: Sixteen HD patients were studied (11 women; 44.4±14.6 years; body mass index 23.3±4.9 kg/m(2); 61.6±43.1 months of dialysis) and served as their own controls. Acute (single session) intradialytic physical exercise were performed at 60% of the one-repetition maximum test for three sets of 10 repetitions for four exercise categories in both lower limbs during 30 minutes. Blood samples were collected on two different days at exactly the same time (30 minutes and 60 minutes after initiating the dialysis-with and without exercise). Antioxidant enzymes activity [superoxide dismutase (SOD), catalase, and glutathione peroxidase], lipid peroxidation marker levels (malondialdehyde), and inflammatory marker levels (high-sensitivity C-reactive protein) were determined. RESULTS: SOD plasma levels were significantly reduced after acute physical exercise from 244.8±40.7 U/mL to 222.4±28.9 U/mL (P=0.03) and, by contrast, increased on the day without exercise (218.2±26.5 U/mL to 239.4±38.6 U/mL, P=0.02). There was no alteration in plasma catalase, glutathione peroxidase, malondialdehyde, or high-sensitivity C-reactive protein levels in on either day (with or without exercise). Additionally, there was no association between these markers and clinical, anthropometric, or biochemical parameters. CONCLUSION: These data suggest that acute intradialytic strength physical exercise was unable to reduce oxidative stress and inflammation, and in addition, it seems to reduce plasma SOD levels, which could exacerbate the oxidative stress in HD patients.

Saneamento rural no Brasil: impacto da fossa séptica biodigestora / Rural sanitation in Brazil: impact analysis of the septic tank digester

O Brasil tem mais de 23 milhões de pessoas na zona rural sem coleta ou tratamento de esgoto, o que corresponde a 75% da população rural. Este estudo teve como objetivo mensurar os impactos social, ambiental e econômico decorrente da atual falta de saneamento rural no país em relação à implementação de uma proposta tecnológica de tratamento do esgoto, a fossa séptica biodigestora. Foi observado que, ao ano, a construção desse sistema de saneamento poderia evitar cerca de 250 mortes e 5,5 milhões de infecções causados por doenças diarreicas; reduzir a poluição dos cursos d'água em cerca de 129 mil toneladas de resíduos; e que cada R$ 1,00 investido na implementação da alternativa tecnológica avaliada poderia causar um retorno para a sociedade de R$ 1,6 em renda interna bruta. Além disto, a construção da fossa séptica biodigestora promoveria a geração de cerca de 39 mil empregos.

Brazil has more than 23 million rural people with unimproved sanitation, which corresponds to about 75% of rural population. This study aimed to measure the social, environmental and economic impacts caused by the implementation of a technological proposal for sanitation, the septic cesspool biodigester. It was observed that, per year, the implementation of this technology in rural homes with unimproved sanitation could reduce about 250 deaths and 5.5 million infections caused by diarrheal diseases; reduce pollution of waterways by about 129 thousand tons of sediment; and that every R$ 1.00 invested in the implementation of the alternative technology evaluated could cause a return to the society of R$ 1.6 in gross domestic product. Moreover, the implementation of septic cesspool biodigesters would promote the creation of 39 thousand jobs.

Fatores associados à qualidade de vida de criançasasmáticas atendidas em ambulatório públicoespecializado da cidade de Maceió/AL / Factors associated with quality of life of asthmatic children treated in a specialized public outpatient service at Maceió/AL

A asma é a doença crônica mais comum da infância,caracterizada pela hiper-responsividade das vias aéreas inferiorese pela limitação variável ao fluxo aéreo. Objetivo: Determinar osfatores associados à qualidade de vida de crianças asmáticas em umambulatório público especializado. Métodos: Foram coletados dadossocioeconômicos familiares e biológicos de 77 crianças asmáticasentre 7 e 12 anos, no período de agosto e setembro de 2010, emum ambulatório público especializado em Maceió/AL. A avaliaçãoda qualidade de vida foi realizada através do Paedriatric AsthmaQuality of Life Questionnaire – adaptado (PAQLQ-A). Para análiseestatística utilizaram-se os testes do qui-quadrado e exato de Fisher(p ≤ 5%). Resultados: A idade média das crianças em anos foi de 9,31(± 1,7). A maioria (60,8%) tinha uma renda familiar total de 1 a 2salários mínimos, 67,5% possuíam asma do tipo leve. A qualidadede vida foi considerada ruim em 24,7%. A idade das crianças entre7 e 9 anos e o sexo feminino apresentaram uma associação significativacom uma melhor qualidade de vida. A baixa renda familiarfoi associada a uma pior qualidade de vida. Conclusão: Criançasasmáticas de níveis socioeconômicos mais baixos apresentam maisfrequentemente uma pior qualidade de vida...

Asthma is the most common childhood chronic diseasecharacterized by lower airway hyperresponsiveness and variableairflow limitation. Objective: To determine factors associated withasthmatic children’s quality of life in a specialized public outpatientservice. Methods: Socioeconomic and biological data of 77 asthmaticchildren, from 7 to 12 years, between August and September 2010,in a specialized public outpatient service in Maceió, Alagoas werecollected. The quality of life evaluation was performed using the PaedriatricAsthma Quality of Life Questionnaire - adapted (PAQLQ--A). To statistical analysis the chi-square and Fisher exact tests (p ≤5%) were used. Results: The average age of children’s was 9.31 years(± 1.7). The majority (60.8%) had a total household income of 1 to2 minimum wages, and 67.5% had mild asthma. The quality of lifewas considered poor in 24.7%. The children’s age from 7 to 9 yearsand female showed a meaningful association with a better qualityof life. Low family income was associated with a poorer quality oflife. Conclusion: Asthmatic children of lower socioeconomic statushave more often a poorer quality of life...

Broncoprovocação com solução salina hipertônica em crianças asmáticas / Bronchoprovocation with hypertonic saline solution in asthmatic children / Brocoprovocación con solución salina hipertónica en niños asmáticos

OBJETIVO: Verificar se o teste de broncoprovocação, com solução salina hipertônica a 4,5%, permite detectar o gradiente de resposta em crianças e adolescentes com asma, segundo a gravidade da enfermidade. MÉTODOS: Estudo transversal composto por 75 pacientes asmáticos com idades entre seis e 18 anos. Os pacientes foram classificados pela gravidade (intermitente associada à persistente leve - IL, e persistente moderada associada à grave - MG) e segundo a presença de sensibilização a aeroalérgenos (testes cutâneos de hipersensibilidade imediata a Dermatophagoides pteronyssinus, D. farinae e Blomia tropicalis) ou não (atópicos versus não atópicos). Todos foram submetidos ao teste de broncoprovocação com solução salina hipertônica a 4,5%, considerando-se o resultado positivo se havia redução do volume expiratório forçado no primeiro segundo (VEF1) ≥20%. RESULTADOS: 60 indivíduos eram atópicos. A frequência de positividade do teste de broncoprovocação foi maior no Grupo MG do que no IL (93 versus 65%). O tempo necessário para a queda de 20% do VEF1 para o grupo de atópicos foi menor no MG quando comparado ao IL: 90 (30 - 330) versus 210 (30 - 690) segundos, com p<0,05. A porcentagem de queda do VEF1 foi mais acentuada no subgrupo MG do que no IL [26,4% (14 - 63) versus 20% (0 - 60), p<0,05]. CONCLUSÕES: O teste de broncoprovocação com solução salina hipertônica a 4,5% é de fácil realização e seguro, permitindo detectar gradiente de resposta em crianças e adolescentes com asma segundo a gravidade da mesma. A maior frequência de positividade e a queda mais rápida do VEF1 foram observadas nos pacientes com asma moderada ou grave.

OBJECTIVE: To verify if the bronchoprovocation test with 4.5% hypertonic saline solution allows to detect the gradient of response in asthmatic children and adolescents, according to asthma severity. METHODS: 75 asthmatic patients aged six to 18 years-old were evaluated in this cross-sectional study. They were classified according to asthma severity in: intermittent or mild persistent (IM) and moderate or severe persistent (MS). They were also classified according to sensitization to inhaled allergens in atopics: positive skin prick test to Dermatophagoides pteronyssinus, D. farinae and Blomia tropicalis; or non- atopic with negative skin prick tests. All patients underwent a bronchoprovocation test with 4.5% hypertonic saline solution. The result of the bronchoprovocation test was considerd positive if at least a reduction of 20% in the forced expiratory volume in one second (FEV1) was noted. RESULTS: 60 individuals were atopic. The bronchoprovocation test was positive more frequently in the MS group than in the IM one (93 versus 65%). Less time was needed for a 20% fall of FEV1 in the MG compared to the IL group [90 (30 - 330) versus 210 (30 - 690) seconds; p<0.05]. The percentage of FEV1 fall was higher in the MG group than in the IL one [26,4% (14 - 63) versus 20% (0 - 60); p<0.05]. CONCLUSIONS: The 4.5% hypertonic saline solution bronchoprovocation test is safe and easy to perform. It detects a gradient of response in asthmatic children and adolescents regarding asthma severity. Higher frequency of positive tests, shorter time for FEV1 fall, and higher percentage of FEV1 fall were observed in moderate and severe asthmatic patients.

OBJETIVO: Verificar si la prueba de broncoprovocación, con solución salina hipertónica a 4,5%, permite detectar el gradiente de respuesta en niños y adolescentes con asma, según la gravedad de la enfermedad. MÉTODOS: Estudio transversal, compuesto por 75 pacientes asmáticos, con edades entre seis y 18 años. Los pacientes fueron clasificados por la gravedad (intermitente asociada a persistente liviana - IL - y persistente moderada asociada a grave - MG) y según la presencia de sensibilización a aeroalérgenos (pruebas cutáneas de hipersensibilidad inmediata a Dermatophagoides pteronyssinus, D. farinae y Blomita tropicalis) o no (atópicos versus no atópicos). Todos fueron sometidos a la prueba de broncoprovocación con solución salina hipertónica a 4,5%, considerándose el resultado positivo como la reducción del volumen espiratorio forzado en el primer segundo (VEF1) ≥20%. RESULTADOS: Sesenta individuos eran atópicos. La frecuencia de positividad de la prueba de broncoprovocación fue mayor en el Grupo MG que en el IL (93 versus 65%). El tiempo necesario para la reducción de 20% del VEF1 para el grupo de atópicos fue menor en el MG cuando comparado al IL, 90 (30 a 330) versus 210 (30 a 690) segundos, con p<0,05. El porcentaje de reducción del VEF1 fue más acentuada en el subgrupo MG que en el IL, 26,4 (14 a 63%) versus 20% (0 a 60%), p<0,05. CONCLUSIONES: La prueba de broncoprovocación con solución salina hipertónica a 4,5% es de fácil realización y segura, permitiendo detectar el gradiente de respuesta en niños y adolescentes con asma, según la gravedad de la enfermedad. La mayor frecuencia de positividad y la reducción más rápida del VEF1 fueron observadas en los pacientes con asma moderada o grave.

Teias escola Manguinhos: o desafio da ação conjunta / School website Manguinhos: the challenge of joint action

(...) Esta pesquisa descreve e analisa o período inicial de debates sobre a construção do projeto TEIAS Escola Manguinhos na AP 3.1, que ocorreu entre os meses de junho a dezembro de 2009. A pesquisa foi desenvolvida através do acompanhamento das reuniões de planejamento do TEIAS Escola Manguinhos e da análise das atas referentes a essas reuniões, levando em consideração três focos de análises: Modelagem de Atenção à Saúde, Participação Social, Organizações Sociais de Saúde. Foi analisada também uma entrevista semi estruturada com ator chave envolvido na construção do TEIAS Escola Manguinhos, leitura e análise de documentos sobre o tema; além da revisão de literatura selecionada sobre integralidade, redes de atenção à saúde e implementação de políticas sociais. (...)

Conditioning the heart induces formation of signalosomes that interact with mitochondria to open mitoKATP channels.

Perfusion of the heart with bradykinin triggers cellular signaling events that ultimately cause opening of mitochondrial ATP-sensitive K+ (mitoKATP) channels, increased H2O2 production, inhibition of the mitochondrial permeability transition (MPT), and cardioprotection. We hypothesized that the interaction of bradykinin with its receptor induces the assembly of a caveolar signaling platform (signalosome) that contains the enzymes of the signaling pathway and that migrates to mitochondria to induce mitoKATP channel opening. We developed a novel method for isolating and purifying signalosomes from Langendorff-perfused rat hearts treated with bradykinin. Fractions containing the signalosomes were found to open mitoKATP channels in mitochondria isolated from untreated hearts via the activation of mitochondrial PKC-epsilon. mitoKATP channel opening required signalosome-dependent phosphorylation of an outer membrane protein. Immunodetection analysis revealed the presence of the bradykinin B2 receptor only in the fraction isolated from bradykinin-treated hearts. Immunodetection and immunogold labeling of caveolin-3, as well as sensitivity to cholesterol depletion and resistance to Triton X-100, attested to the caveolar nature of the signalosomes. Ischemic preconditioning, ischemic postconditioning, and perfusion with ouabain also led to active signalosome fractions that opened mitoKATP channels in mitochondria from untreated hearts. These results provide initial support for a novel mechanism for signal transmission from a plasma membrane receptor to mitoKATP channels.

Mitochondrial PKC epsilon and mitochondrial ATP-sensitive K+ channel copurify and coreconstitute to form a functioning signaling module in proteoliposomes.

Mitochondria are key mediators of the cardioprotective signal and the mitochondrial ATP-sensitive K+ channel (mitoK(ATP)) plays a crucial role in originating and transmitting that signal. Recently, protein kinase C epsilon (PKC epsilon) has been identified as a component of the mitoK(ATP) signaling cascade. We hypothesized that PKC epsilon and mitoK(ATP) interact directly to form functional signaling modules in the inner mitochondria membrane. To examine this possibility, we studied K+ flux in liposomes containing partially purified mitoK(ATP). The reconstituted proteins were obtained after detergent extraction of isolated mitochondria, 200-fold purification by ion exchange chromatography, and reconstitution into lipid vesicles. Immunoblot analysis revealed the presence of PKC epsilon in the reconstitutively active fraction. Addition of the PKC activators 12-phorbol 13-myristate acetate, hydrogen peroxide, and the specific PKC epsilon peptide agonist, psi epsilonRACK, each activated mitoK(ATP)-dependent K+ flux in the reconstituted system. This effect of PKC epsilon was prevented by chelerythrine, by the specific PKC epsilon peptide antagonist, epsilonV(1-2), and by the specific mitoK(ATP) inhibitor 5-hydroxydecanoate. In addition, the activating effect of PKC agonists was reversed by exogenous protein phosphatase 2A. These results demonstrate persistent, functional association of mitochondrial PKC epsilon and mitoK(ATP).

The mechanism by which the mitochondrial ATP-sensitive K+ channel opening and H2O2 inhibit the mitochondrial permeability transition.

Myocardial infarction is a manifestation of necrotic cell death as a result of opening of the mitochondrial permeability transition (MPT). Receptor-mediated cardioprotection is triggered by an intracellular signaling pathway that includes phosphatidylinositol 3-kinase, endothelial nitric-oxide synthase, guanylyl cyclase, protein kinase G (PKG), and the mitochondrial K(ATP) channel (mitoK(ATP)). In this study, we explored the pathway that links mitoK(ATP) with the MPT. We confirmed previous findings that diazoxide and activators of PKG or protein kinase C (PKC) inhibited MPT opening. We extended these results and showed that other K(+) channel openers as well as the K(+) ionophore valinomycin also inhibited MPT opening and that this inhibition required reactive oxygen species. By using isoform-specific peptides, we found that the effects of K(ATP) channel openers, PKG, or valinomycin were mediated by a PKCepsilon. Activation of PKCepsilon by phorbol 12-myristate 13-acetate or H(2)O(2) resulted in mitoK(ATP)-independent inhibition of MPT opening, whereas activation of PKCepsilon by PKG or the specific PKCepsilon agonist psiepsilon receptor for activated C kinase caused mitoK(ATP)-dependent inhibition of MPT opening. Exogenous H(2)O(2) inhibited MPT, because of its activation of PKCepsilon, with an IC(50) of 0.4 (+/-0.1) microm. On the basis of these results, we propose that two different PKCepsilon pools regulate this signaling pathway, one in association with mitoK(ATP) and the other in association with MPT.