UMA PROPOSTA DIDÁTICA CONTEXTUALIZADA PARA O CURSO DE LICENCIATURA EM QUÍMICA: O CASO DO ENSINO DE QUÍMICA ANALÍTICA

Este trabalho apresenta uma proposta didática desenvolvida numa disciplina de Química Analítica do curso de Licenciatura em Química – UDESC. A proposta contém atividades embasadas em metodologia ativa, valorizando de forma integrada a formação científica e a formação para atuação na sociedade. Os estudantes trabalharam em grupo e tiveram como problema evidenciar e quantificar a migração de ésteres de ftalato (EF) de amostras cotidianas de embalagens para a alimentação humana utilizando uma técnica analítica de cromatografia a gás. A atividade propiciou desenvolver habilidades requeridas para operação de um equipamento de análise (CG-EM), desenvolver e aplicar conhecimentos químicos e vivenciar atividades próprias da ciência química tanto do ponto de vista científico como do social.Palavras chave: Formação de Professores; Contextualização; Metodologia Ativa.

Mesoderm migration in Drosophila is a multi-step process requiring FGF signaling and integrin activity

Migration is a complex, dynamic process that has largely been studied using qualitative or static approaches. As technology has improved, we can now take quantitative approaches towards understanding cell migration using in vivo imaging and tracking analyses. In this manner, we have established a four-step model of mesoderm migration during Drosophila gastrulation: (I) mesodermal tube formation, (II) collapse of the mesoderm, (III) dorsal migration and spreading and (IV) monolayer formation. Our data provide evidence that these steps are temporally distinct and that each might require different chemical inputs. To support this, we analyzed the role of fibroblast growth factor (FGF) signaling, in particular the function of two Drosophila FGF ligands, Pyramus and Thisbe, during mesoderm migration. We determined that FGF signaling through both ligands controls movements in the radial direction. Thisbe is required for the initial collapse of the mesoderm onto the ectoderm, whereas both Pyramus and Thisbe are required for monolayer formation. In addition, we uncovered that the GTPase Rap1 regulates radial movement of cells and localization of the beta-integrin subunit, Myospheroid, which is also required for monolayer formation. Our analyses suggest that distinct signals influence particular movements, as we found that FGF signaling is involved in controlling collapse and monolayer formation but not dorsal movement, whereas integrins are required to support monolayer formation only and not earlier movements. Our work demonstrates that complex cell migration is not necessarily a fluid process, but suggests instead that different types of movements are directed by distinct inputs in a stepwise manner

Identification, Expression and Target Gene Analyses of MicroRNAs in Spodoptera litura

MicroRNAs (miRNAs) are small RNAs widely present in animals and plants and involved in post-transcriptional regulation of gene transcripts. In this study we identified and validated 58 miRNAs from an EST dataset of Spodoptera litura based on the computational and experimental analysis of sequence conservation and secondary structure of miRNA by comparing the miRNA sequences in the miRbase. RT-PCR was conducted to examine the expression of these miRNAs and stem-loop RT-PCR assay was performed to examine expression of 11 mature miRNAs (out of the 58 putative miRNA) that showed significant changes in different tissues and stages of the insect development. One hundred twenty eight possible target genes against the 11 miRNAs were predicted by using computational methods. Binding of one miRNA (sli-miR-928b) with the three possible target mRNAs was confirmed by Southern blotting, implying its possible function in regulation of the target genes

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Scientific Reports / Quality of medical therapy in heart failure patients undergoing elective revascularisation: A protective effect of disease modifying therapy at discharge

The STICH(-ES) trial showed that coronary artery bypass grafting was superior to medical therapy alone in treating ischemic heart failure. However, dosages of disease modifying drugs were not reported. We included 128 (84% male, mean age 6611 years) consecutive patients with ischemic heart failure and an ejection fraction 35% undergoing isolated elective coronary artery bypass grafting. We defined optimal medical therapy (OMT) as prescription of 50% dosages of guideline recommended medications (i.e. beta-blocker (BB) and renin angiotensin system (RAS) antagonist) plus prescription of a mineralocorticoid receptor antagonist (MRA). The mean logistic EuroSCORE was 12.313.8%. The five year survival was 74%. At discharge, 111 patients (87%) were on a BB and 106 (83%) were on a RAS antagonist. Forty-nine patients (38%) received an MRA. Only 8 patients (6%) received OMT. A Cox regression analysis revealed EuroSCORE (p<0.001) and the use of MRA (p=0.003) and BB (p=0.037) at discharge as significant predictors of 5 year survival. Prescription rates of heart failure medication are comparable to those reported in the STICH trial, but rates of OMT are very low at admission and discharge. Prescription of BB and MRA was associated with improved survival, highlighting the need for disease management programs and rigorous discharge management.(VLID)486788

Polyunsaturated fatty acids supplementation impairs anti-oxidant high-density lipoprotein function in heart failure

Background The underlying reasons for the highly inconsistent clinical outcome data for omega3polyunsaturated fatty acids (n3PUFAs) supplementation in patients with cardiac disease have not been understood yet. The aim of this prospective, randomized, doubleblind, placebo controlled study was to determine the effects of oral treatment with n3PUFAs on the antioxidant capacity of HDL in heart failure (HF) patients. Methods A total of 40 patients with advanced HF of nonischaemic origin, defined by NTproBNP levels of >2000 pg/mL, NYHA class III or IV and a LVEF <35% who were on stable optimized medical therapy for 3 months, were consecutively enrolled into this prospective, doubleblind, placebocontrolled trial and randomized in a 1:1:1 fashion to receive 1 g/day or 4 g/day of n3PUFA, or placebo, respectively, for 12 weeks. Results After 12 weeks of treatment, the antioxidant function of HDL, measured by the HDL inflammatory index, was found significantly impaired in the treatment group in a dosedependent fashion with 0.67 [IQR 0.491.04] for placebo vs 0.71 [IQR 0.551.01] for 1 g/day n3PUFA vs 0.98 [IQR 0.731.16] for 4 g/day n3PUFA (P for trend = 0.018). Conclusion We provide evidence for an adverse effect of n3PUFA supplementation on antioxidant function of HDL in nonischaemic heart failure patients, establishing a potential mechanistic link for the controversial outcome data on n3PUFA supplementation.(VLID)339841