Consenso da Sociedade Brasileira de Cefaleia sobre o tratamento da migrânea crônica

Chronic migraine poses a significant personal, social and economic burden and is characterized by headache present on 15 or more days per month for at least three months, with at least eight days of migrainous headache per month. It is frequently associated with analgesic or acute migraine medication overuse and this should not be overlooked. The present consensus was elaborated upon by a group of members of the Brazilian Headache Society in order to describe current evidence and to provide recommendations related to chronic migraine pharmacological and nonpharmacological treatment. Withdrawal strategies in medication overuse headache are also described, as well as treatment risks during pregnancy and breastfeeding. Oral topiramate and onabotulinum toxin A injections are the only treatments granted Class A recommendation, while valproate, gabapentin, and tizanidine received Class B recommendation, along with acupuncture. biofeedback, and mindfulness. The anti-CGRP or anti-CGRPr monoclonal antibodies, still unavailable in Brazil, are promising new drugs already approved elsewhere for migraine prophylactic treatment, the efficacy of which in chronic migraine is still to be definitively proven777509520A migrânea (enxaqueca) crônica determina uma carga pessoal, social e econômica significativa e é caracterizada por dor de cabeça presente em quinze ou mais dias por mês por ao menos três meses, com no mínimo oito dias de cefaleia migranosa a cada mês. É frequentemente associada ao uso excessivo de medicação analgésica ou antimigranosa aguda e isso não deve ser negligenciado. Este consenso foi elaborado por um grupo de membros da Sociedade Brasileira de Cefaleia, para descrever as evidências atualmente disponíveis e fornecer recomendações relacionadas ao tratamento farmacológico e não farmacológico da migrânea crônica. Estratégias de retirada na cefaleia por uso excessivo de medicamentos também são descritas, assim como os riscos dos tratamentos durante a gravidez e a amamentação. O topiramato oral e as injeções de toxina onabotulínica A são os únicos tratamentos que receberam a recomendação classe A, enquanto que o valproato, a gabapentina e a tizanidina receberam recomendação classe B, juntamente com acupuntura, biofeedback e mindfulness. Os anticorpos monoclonais anti-CGRP ou anti-CGRPr, ainda não disponíveis no Brasil, são novos fármacos promissores, já aprovados em outros países para o tratamento profilático da migrânea, cuja eficácia na migrânea crônica ainda está por ser definitivamente comprovad

Updated cardiovascular prevention guideline of the Brazilian Society of Cardiology: 2019

Sem informação113478788

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Amenability of Reduced Iron Ore Pellets to Mechanical Degradation

The mechanical properties of iron ore pellets are of central importance to guarantee good productivity in direct reduction plants. Besides the generation of fines during handling, mechanical degradation resulting from forces produced inside the furnace are detrimental to the performance of these reactors, since they can lead to the generation of clusters, and also because they impact negatively the permeability of the charge to the flow of reducing gases. The present work analyzed the effect of different degrees of reduction on the mechanical properties of direct reduction iron ore pellets so as to estimate the proportion of fines generated inside a direct reduction furnace. As such, tests have been performed with unreduced, as well as iron ore pellets that were subjected to different degrees of reduction, with the aim of analyzing their mechanical properties, including microhardness, cold compression strength, mass loss in drop tests as well as pore size distributions. From these results, a parameter of a model of mass loss due to surface breakage was estimated, which demonstrated their greater amenability to breakage as reduction progressed. A combination of these results to simulations using the Discrete Element Method of a direct reduction furnace made it possible to estimate in 5.7% the percentage of fines generated in the furnace.11Ysciescopu

Land Reform in NE Brazil: a stochastic frontier production efficiency evaluation

The aim of this paper is to address the sources of technical and allocative inefficiency from a cross section sample of 308 beneficiaries of a market assisted land reform program, called “Cédula da Terra” from five states in Northeastern region of Brazil. In spite of some differences on governance of the “Cédula da Terra” in comparison with traditional expropriation land reform program, studies carried by Buainain et al. (2002) have shown small differences between then, regarding their social and economic characteristics. We believe that our results could be useful to identify the main problems of Brazilian land reform settlements. We estimated a potential production frontier following the methodology of Battese and Coelli (1995), Coelli et al. (1998) and applied econometric techniques to explain inefficiency. The results indicate the existence of technical and allocative inefficiency, which is identified mostly in situations where the presence of production for consumption is high. This is a result that shows how immature the agriculture activity is in most of Cédula da Terra Program settlements and the difficulty to overcome the limitations imposed by the initial condition of formation of agrarian reform, primarily in Northeastern region of Brazil

SAR, QSAR and Docking of Anticancer Flavonoids and Variants: A Review

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-04T13:34:32Z No. of bitstreams: 1 Scotti L SAR, QSAR and Docking of Anticancer Flavonoids....pdf: 545154 bytes, checksum: 71393247ab290fc268c1fd811528fcff (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-04T13:45:16Z (GMT) No. of bitstreams: 1 Scotti L SAR, QSAR and Docking of Anticancer Flavonoids....pdf: 545154 bytes, checksum: 71393247ab290fc268c1fd811528fcff (MD5)Made available in DSpace on 2018-04-04T13:45:16Z (GMT). No. of bitstreams: 1 Scotti L SAR, QSAR and Docking of Anticancer Flavonoids....pdf: 545154 bytes, checksum: 71393247ab290fc268c1fd811528fcff (MD5) Previous issue date: 2012CNPq, CAPES and FAPESQ. I. R. P. is thankful to the INCT_if; D.R.M.M. holds a FAPESBFederal University of Paraíba. Centre for Biotechnology. João Pessoa, PB, BrazilState University of Paraiba. Laboratory of Synthesis and Drug Delivery. Biological Science Department. João Pessoa, PB, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFederal University of Paraíba. Centre for Biotechnology. João Pessoa, PB, BrazilFederal University of Pernambuco. Departamento de Antibióticos. Recife, PE, BrazilFederal University of Paraíba. Department of Engineering and the Environment. Rio Tinto, PB, BrazilFlavonoids are phenolic compounds, secondary metabolites of plants that cause several benefits to our health, including helping the treatment against cancer. These pharmacological properties are associated with the ability of flavonoids in attenuating the generation of reactive oxygen species, acting as chelate compounds or affecting the oxi-redox cycle. In spite of the large number of information in term of SAR and QSAR, no recent review has tabulated and discussed in detail these data. In view of this, we bring here a detailed discussion of the structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) models. We have also analyzed the correlation between the chemical structure of flavonoids and analogues to their anticancer activities. A large number of methodologies have been used to identify the characteristics of these compounds with their potential anticancer: multiple linear regression, principal components analysis, comparative molecular field analysis, comparative molecular similarity indices analysis, partial least squares, neural networks, configuration of classification and regression trees, Free-Wilson, docking; using topological, structural and enthalpies’ descriptors. We also discussed the use of docking models, together with QSAR models, for the virtual screening of anticancer flavonoids. The importance of docking models to the medicinal chemistry of anticancer flavonoids has increased in the last decade, especially to help in identifying the structural determinants responsible for the activity. We tabulated here the most important examples of virtual screening determined for anticancer flavonoids and we highlighted the structural determinants. The mode of action, the most potent anticancer flavonoids and hints for the structural design of anticancer flavonoids are revised in details and provided here

Evaluation of DNA damage and lipoperoxidation of propofol in patients undergoing elective surgery

Background and objectives Inhaled anaesthetics have been studied regarding their genotoxic and mutagenic potential in vivo. Propofol differs from volatile anaesthetics because it does not show mutagenic effects and it has been reported to be an antioxidant However, there are no studies with propofol and genotoxicity in vivo. The study aimed to evaluate the hypothesis that propofol is not genotoxic and it inhibits lipid peroxidation [malondialdehyde (MDA)] in patients undergoing propofol anaesthesia.Methods ASA physical status I patients scheduled for elective surgery, lasting at least 90 min, were enrolled in this study. Initially, the estimated plasma concentration of propofol was targeted at 4 mu g ml(-1) and then maintained at 2-4 mu g ml(-1) until the end of surgery. Haemodynamic data were determined at baseline (before premedication) and in conjunction with target-controlled infusion of propofol: after tracheal intubation, 30, 60 and 90 min after anaesthesia induction and at the end of the surgery. Venous blood samples were collected at baseline, after tracheal intubation, at the end of the surgery and on the postoperative first day for evaluating DNA damage in white blood cells (WBCs), by comet assay, and MDA levels.Results Haemodynamic data did not differ among times. No statistically significant differences were observed for the levels of DNA damage in WBCs, nor in plasma MDA, among the four times.Conclusion Propofol does not induce DNA damage in WBCs and does not alter MDA in plasma of patients. Eur J Anaesthesiol 26:654-660 (C) 2009 European Society of Anaesthesiology.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Identification of the MYST3-CREBBP fusion gene in infants with acute myeloid leukemia and hemophagocytosis

ABSTRACT Background: Acute myeloid leukemia presenting the MYST3-CREBBP fusion gene is a rare subgroup associated with hemophagocytosis in early infancy and monocytic differentiation. The aim of this study was to define the relevant molecular cytogenetic characteristics of a unique series of early infancy acute myeloid leukemia cases (≤24 months old), based on the presence of hemophagocytosis by blast cells at diagnosis. Methods: A series of 266 infant cases of acute myeloid leukemia was the reference cohort for the present analysis. Acute myeloid leukemia cases with hemophagocytosis by blast cells were reviewed to investigate the presence of the MYST3-CREBBP fusion gene by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Results: Eleven cases with hemophagocytosis were identified with hemophagocytic lymphohistiocytosis being ruled out. Six cases were classified as myelomonocytic leukemia, three as AML-M7 and two as AML-M2. In five cases, the presence of the MYST3-CREBBP fusion gene identified by molecular cytogenetics was confirmed by fluorescence in situ hybridization. All patients received treatment according to the Berlin-Frankfürt-Münster acute myeloid leukemia protocols and only one out of the five patients with the MYST3-CREBBP fusion gene is still alive. Conclusions: Our findings demonstrate that the presence of hemophagocytosis in acute myeloid leukemia was not exclusively associated to the MYST3-CREBBP fusion gene. Improvements in molecular cytogenetics may help to elucidate more complex chromosomal rearrangements in infants with acute myeloid leukemia and hemophagocytosis

Structural Investigation of Anti-Trypanosoma cruzi 2-Iminothiazolidin-4-ones Allows the Identification of Agents with Efficacy in Infected Mice

We modified the thiazolidinic ring at positions N3, C4, and C5, yielding compounds 6-24. Compounds with a phenyl at position N3, 15-19, 22-24, exhibited better inhibitory properties for cruzain and against the parasite than 2-iminothiazolidin-4-one S. We were able to identify one high-efficacy trypanocidal compound, 2-minothiazolidin-4-one 18, which inhibited the activity of cruzain and the proliferation of epirnastigotes and was cidal for trypomastigotes but was not toxic for splenocytes. Having located some of the structural determinants of the trypanocidal properties, we subsequently wished to determine if the exchange of the thiazolidine for a thiazole ring leaves the functional properties unaffected. We therefore tested thiazoles 26-45 and observed that they did not inhibit cruzain, but they exhibited trypanocidal effects. Parasite development was severely impaired when treated with 18, thus reinforcing the notion that this class of heterocycles can lead to useful cidal agents for Chagas disease.CNPq [471461/2011-3]CAPES [23038.003155/2011-37]FAPESB (PRONEX grant)European Union ChemBioFight [269301]CAPES-Fulbright Foundatio