Safety analysis of sacubitril/valsartan in patients with heart failure in Vitória, Espírito Santo

Background: Sacubitril/valsartan has proven its efficacy to reduce cardiovascular mortality, all-cause mortality and sudden death in heart failure with reduced ejection fraction (HFrEF). Thus, it becomes important to evaluate the safety profile of the medication in clinical practice. Objectives: This study aimed to assess safety outcomes on the use of sacubitril/valsartan in patients with HFrEF attended in a Brazilian specialized service. Methods: Prospective observational study that included patients with HFrEF from a specialized ambulatory service, in functional class II-IV, initiated on sacubitril/valsartan as per clinical indication, with a four-month follow-up. Primary outcomes were the occurrence of symptomatic arterial hypotension, hyperkalemia and reduction of renal function. Serum potassium values, blood pressure and creatinine clearance were analyzed at inclusion and at the end of follow-up. A 5% significance level was considered for comparisons. Results: Twenty-six patients were analyzed, 57.7% male, mean age 57.8 ± 10 years, average left ventricle ejection fraction 29.9 ± 7.7%. Symptomatic hypotension occurred in 53.8%, hyperkalemia in 19.2% and reduction of renal function in 6.7%. There was significant difference from initial to final systolic (122 ± 24mmHg versus 109 ± 15mmHg; p=0.024) and diastolic (76 ± 18mmHg versus 66 ± 12mmHg; p=0.022) blood pressure, but no difference in serum potassium (4.8 ± 0.4mEq/L versus 5.0 ± 0.3mEq/L; p=0.07) and creatinine clearance (65 ± 23mL/min/1.73m² versus 66 ± 29mL/min/1.73m²; p=0.89). Conclusions: Symptomatic hypotension was the most frequent side-effect of sacubitril/valsartan. Reduction of blood pressure was observed at the end of follow-up, but no reduction of renal function or significant increase of serum potassium

Estimation of Tumor Size Evolution Using Particle Filters

Cancer is characterized by the uncontrolled growth of cells with the ability of invading local organs and/or tissues and of spreading to other sites. Several kinds of mathematical models have been proposed in the literature, involving different levels of refinement, for the evolution of tumors and their interactions with chemotherapy drugs. In this article, we present the solution of a state estimation problem for tumor size evolution. A system of nonlinear ordinary differential equations is used as the state evolution model, which involves as state variables the numbers of tumor, normal and angiogenic cells, as well as the masses of the chemotherapy and anti-angiogenic drugs in the body. Measurements of the numbers of tumor and normal cells are considered available for the inverse analysis. Parameters appearing in the formulation of the state evolution model are treated as Gaussian random variables and their uncertainties are taken into account in the estimation of the state variables, by using an algorithm based on the auxiliary sampling importance resampling particle filter. Test cases are examined in the article dealing with a chemotherapy protocol for pancreatic cancer.Indisponível

European grapevine moth, Lobesia botrana Part I: biology and ecology

Though the European grapevine moth, Lobesia botrana (Denis & Schiffermüller) (Lepidoptera: Tortricidae) can feed on more than forty plant species, grapevine is the preferred crop worldwide. This moth is a western palearctic species that has recently spread to Chile, Argentina, and California. The possible further expansion in other regions of the Americas is greatly feared and should be monitored carefully in the near future. In this framework, we provide an updated review of the current knowledge on its taxonomy, morphology, biology, ecology, genomics, geographic distribution, and invasiveness. Then, in the last section, we develop a research agenda pointing out significant challenges for future investigations on bio-ecology and invasion biology, which are tightly connected with the prevention and management strategie

European grapevine moth, Lobesia botrana Part II: prevention and management

Lobesia botrana (Denis & Schiffermüller) (Lepidoptera: Tortricidae), commonly known as the European grapevine moth (EGVM), is a primary pest of vineyards. This article provides an updated review of its monitoring, modelling, and management tools. EGVM management strategies analysed here include insecticide-based control, insecticide resistance, side-effects (particularly those caused by the exposure to sublethal doses of pesticides), cultural control, sterile insect technique, pheromone-mediated control strategies (with special reference to pheromone-based mating disruption), biological control, and area-wide control programs. Lastly, we outline significant challenges for future EGVM research and sustainable control implementatio

Punica granatum L. protects mice against hexavalent chromium-induced genotoxicity

This study investigated the chemoprotective effects of Punica granatum L. (Punicaceae) fruits alcoholic extract (PGE) on mice exposed to hexavalent chromium [Cr(VI)]. Animals were pretreated with PGE (25, 50 or 75 mg/kg/day) for 10 days and subsequently exposed to a sub-lethal dose of Cr(VI) (30 mg/kg). The frequency of micronucleated polychromatic erythrocytes in the bone marrow was investigated and the Cr(VI) levels were measured in the kidneys, liver and plasm. For the survival analysis, mice were previously treated with PGE for 10 days and exposed to a single lethal dose of Cr(VI) (50 mg/kg). Exposure to a sub-lethal dose of Cr(VI) induced a significant increase in the frequency of micronucleated cells. However, the prophylactic treatment with PGE led to a reduction of 44.5% (25 mg/kg), 86.3% (50 mg/kg) and 64.2% (75 mg/kg) in the incidence of micronuclei. In addition, the 50 mg/kg dose of PGE produced a higher chemoprotective effect, since the survival rate was 90%, when compared to that of the non-treated group. In these animals, reduced amounts of chromium were detected in the biological materials, in comparison with the other groups. Taken together, the results demonstrated that PGE exerts a protective effect against Cr(VI)-induced genotoxicity

Poly (A)+ Transcriptome Assessment of ERBB2-Induced Alterations in Breast Cell Lines

We report the first quantitative and qualitative analysis of the poly (A)+ transcriptome of two human mammary cell lines, differentially expressing (human epidermal growth factor receptor) an oncogene over-expressed in approximately 25% of human breast tumors. Full-length cDNA populations from the two cell lines were digested enzymatically, individually tagged according to a customized method for library construction, and simultaneously sequenced by the use of the Titanium 454-Roche-platform. Comprehensive bioinformatics analysis followed by experimental validation confirmed novel genes, splicing variants, single nucleotide polymorphisms, and gene fusions indicated by RNA-seq data from both samples. Moreover, comparative analysis showed enrichment in alternative events, especially in the exon usage category, in ERBB2 over-expressing cells, data indicating regulation of alternative splicing mediated by the oncogene. Alterations in expression levels of genes, such as LOX, ATP5L, GALNT3, and MME revealed by large-scale sequencing were confirmed between cell lines as well as in tumor specimens with different ERBB2 backgrounds. This approach was shown to be suitable for structural, quantitative, and qualitative assessment of complex transcriptomes and revealed new events mediated by ERBB2 overexpression, in addition to potential molecular targets for breast cancer that are driven by this oncogene

Análise do conhecimento de professores de Educação Infantil sobre saúde bucal

A figura do professor exerce grande influência sobre o comportamento dos alunos, pelo contato diário durante longo tempo. O objetivo do presente trabalho foi analisar o conhecimento dos professores de escolas estaduais e municipais de educação infantil no que diz respeito à saúde bucal. Foi realizado um estudo exploratório descritivo, com abordagem quanti-qualitativa com 164 professores, utilizando-se um questionário, autoaplicável, com perguntas sobre o tema. Os mesmos foram digitados e analisados pelo programa Epi Info, 3.5.1. Entre os resultados obtidos, pode-se observar que 94,5% relataram atuar em escolas que possuem atividades de educação em saúde bucal. Sobre as informações a respeito dos cuidados necessários para a manutenção da saúde bucal, 85,4% relataram ter recebido em algum momento. Segundo eles, a informação foi fornecida principalmente pelo cirurgião dentista (64,3%), alunos FOA-UNESP (16,4%), família (5,7%). 95,7% responderam saber o que é cárie dentária. Dentre esses indivíduos, 12,2% relacionaram-na a resíduos acumulados no dente. No que se refere à função do flúor em relação à cárie dentária, 88,4% indicaram conhecê-la. Destes, 50,3% atribuíram ao mesmo a função de proteção da estrutura dental. Pode-se concluir que embora a escola seja um espaço importante de informação, esta é ainda muito pouco aproveitada, os professores possuem pouco conhecimento a respeito dos cuidados necessários para a manutenção da saúde bucal e necessitam de maiores informações para abordarem com segurança estes temas em sala de aula