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

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

The inventory of geological heritage of the state of São Paulo, Brazil: Methodological basis, results and perspectives

An inventory of geological sites based on solid and clear criteria is a first step for any geoconservation strategy. This paper describes the method used in the geoheritage inventory of the State of São Paulo, Brazil, and presents its main results. This inventory developed by the geoscientific community aimed to identify geosites with scientific value in the whole state, using a systematic approach. All 142 geosites representative of 11 geological frameworks were characterised and quantitatively evaluated according to their scientific value and risk of degradation, in order to establish priorities for their future management. An online database of the inventory is under construction, which will be available to be easily consulted and updated by the geoscientific community. All data were made available to the State Geological Institute as the backbone for the implementation of a future state geoconservation strategy.The authors acknowledge the Science Without Borders Programme, Process 075/2012, which supported this study and the São Paulo Research Foundation (FAPESP), Process 2011/17261-6. We also thanks C. Mazoca for his help with maps and figures.info:eu-repo/semantics/acceptedVersio

Factors influencing terrestriality in primates of the Americas and Madagascar

Among mammals, the order Primates is exceptional in having a high taxonomic richness in which the taxa are arboreal, semiterrestrial, or terrestrial. Although habitual terrestriality is pervasive among the apes and African and Asian monkeys (catarrhines), it is largely absent among monkeys of the Americas (platyrrhines), as well as galagos, lemurs, and lorises (strepsirrhines), which are mostly arboreal. Numerous ecological drivers and species-specific factors are suggested to set the conditions for an evolutionary shift from arboreality to terrestriality, and current environmental conditions may provide analogous scenarios to those transitional periods. Therefore, we investigated predominantly arboreal, diurnal primate genera from the Americas and Madagascar that lack fully terrestrial taxa, to determine whether ecological drivers (habitat canopy cover, predation risk, maximum temperature, precipitation, primate species richness, human population density, and distance to roads) or species-specific traits (bodymass, group size, and degree of frugivory) associate with increased terrestriality. We collated 150,961 observation hours across 2,227 months from 47 species at 20 sites in Madagascar and 48 sites in the Americas. Multiple factors were associated with ground use in these otherwise arboreal species, including increased temperature, a decrease in canopy cover, a dietary shift away from frugivory, and larger group size. These factors mostly explain intraspecific differences in terrestriality. As humanity modifies habitats and causes climate change, our results suggest that species already inhabiting hot, sparsely canopied sites, and exhibiting more generalized diets, are more likely to shift toward greater ground use