Handling protest responses in contingent valuation surveys

OBJECTIVES: Protest responses, whereby respondents refuse to state the value they place on the health gain, are commonly encountered in contingent valuation (CV) studies, and they tend to be excluded from analyses. Such an approach will be biased if protesters differ from non-protesters on characteristics that predict their responses. The Heckman selection model has been commonly used to adjust for protesters, but its underlying assumptions may be implausible in this context. We present a multiple imputation (MI) approach to appropriately address protest responses in CV studies, and compare it with the Heckman selection model. METHODS: This study exploits data from the multinational EuroVaQ study, which surveyed respondents' willingness-to-pay (WTP) for a Quality Adjusted Life Year (QALY). Here, our simulation study assesses the relative performance of MI and Heckman selection models across different realistic settings grounded in the EuroVaQ study, including scenarios with different proportions of missing data and non-response mechanisms. We then illustrate the methods in the EuroVaQ study for estimating mean WTP for a QALY gain. RESULTS: We find that MI provides lower bias and mean squared error compared with the Heckman approach across all considered scenarios. The simulations suggest that the Heckman approach can lead to considerable underestimation or overestimation of mean WTP due to violations in the normality assumption, even after log-transforming the WTP responses. The case study illustrates that protesters are associated with a lower mean WTP for a QALY gain compared with non-protesters, but that the results differ according to method for handling protesters. CONCLUSIONS: MI is an appropriate method for addressing protest responses in CV studies

Novos «critérios refinados» eletrocardiográficos na avaliação de atletas

info:eu-repo/semantics/publishedVersio

Potent hepatoprotective effect in CCl4-induced hepatic injury in mice of phloroacetophenone from Myrcia multiflora

Background: This study investigated the hepatoprotective effect and antioxidant properties of phloroacetophenone (2',4',6'-trihydroxyacetophenone - THA), an acetophenone derived from the plant Myrcia multiflora. Material & Method: The free radical scavenging activity in vitro and induction of oxidative hepatic damage by carbon tetrachloride (CCl4) (0.5 ml/kg, i.p.) were tested in male Swiss mice (2595 g). Results: This compound exhibited in vitro antioxidant effects on FeCl2-ascorbate-induced lipid peroxidation (LPO) in mouse liver homogenate, scavenging hydroxyl and superoxide radicals, and 2,2-diphenyl-1-picrylhydrazyl. The in vivo assays showed that THA significantly (p<0.01) prevented the increases of hepatic LPO as measured by the levels of thiobarbituric acid-reactive substances, mitochondrial swelling. It also protected hepatocytes against protein carbonylation and oxidative DNA damage. Consistent with these observations, THA pre-treatment normalized the activities of antioxidant enzymes, such as catalase, glutathione peroxidase, and superoxide dismutase, and increased the levels of reduced glutathione (GSH) in CCl4-treated mice. In addition, THA treatment significantly prevented the elevation of serum enzymatic activities of alanine amino transferase, aspartate amino transferase, and lactate dehydrogenase, as well as histological alterations induced by CCl4. Silymarin (SIL) (24 mg/kg), a known hepatoprotective drug used for comparison, led to a significant decrease (p<0.01) in activities of theses enzymes in way very similar to that observed in pre-treatment with THA. Conclusion: These results suggest that the protective effects are due to reduction of oxidative damage induced by CCl4 resulting from the antioxidant properties of THA.Keywords: antioxidant; hepatoprotective; 2',4',6'-trihydroxyacetophenone; Myrcia multiflora; CCl4; Silymari

Brazilian Bidens pilosa Linne´ yields fraction containing quercetin-derived flavonoid with free radical scavenger activity and hepatoprotective effects

Bidens pilosa is a plant used by Amazonian and Asian folks for some hepatopathies. The hydroethanol crude extract and three fractions were assessed for antioxidant and hepatoprotective effects. Higher levels of scavenger activity on the 1,1-diphenyl-2-picrylhydrazyl radical, inhibition of deoxyribose oxidation and lipid peroxidation in vitro were detected for the ethyl acetate fraction (IC50∼4.3-32.3 mg/ml) followed by the crude extract (IC50∼14.2-98.0 mg/ml). The ethyl acetate fraction, again followed by the crude extract, showed high contents of total soluble polyphenols (3.6±0.2 and 2.1±0.2 GAE/mg, respectively) and presence of a quercetin-derived flavonoid identified as quercetin 3,3′-dimethyl ether 7-Ο-β-D-glycopyranoside. Both products were assayed for hepatoprotector effects against CCl4-induced liver injury in mice. Markers of oxidative stress and hepatic injury were evaluated. The results showed that the 10-day pretreatments (15 mg/kg, p.o.) protected the livers against injury by blocking CCl4-induced lipid peroxidation and protein carbonylation and the DNA fragmentation was decreased (∼60%). The pretreatments avoided the loss of the plasma ferric reducing/antioxidant power and the elevation of serum transaminases and lactate dehydrogenase activities. The results suggest that the main constituents responsible for the hepatoprotective effects with free radical scavenger power associated are well extracted by performing fractionation with ethyl acetate. The findings support the Brazilian traditional use of this plant and justify further evaluations for the therapeutic efficacy and safety of the constituents of the ethyl acetate fraction to treat some liver diseases.Keywords: Bidens pilosa L.; hydroethanol maceration; ethyl acetate fractionation; free radical scavenger; hepatoprotection; CCl4 toxicit

Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance

FOXM1 has been implicated in taxane resistance, but the molecular mechanism involved remains elusive. In here, we show that FOXM1 depletion can sensitize breast cancer cells and mouse embryonic fibroblasts into entering paclitaxel-induced senescence, with the loss of clonogenic ability, and the induction of senescence-associated beta-galactosidase activity and flat cell morphology. We also demonstrate that FOXM1 regulates the expression of the microtubulin-associated kinesin KIF20A at the transcriptional level directly through a Forkhead response element (FHRE) in its promoter. Similar to FOXM1, KIF20A expression is downregulated by paclitaxel in the sensitive MCF-7 breast cancer cells and deregulated in the paclitaxel-resistant MCF-7TaxR cells. KIF20A depletion also renders MCF-7 and MCF-7TaxR cells more sensitive to paclitaxel-induced cellular senescence. Crucially, resembling paclitaxel treatment, silencing of FOXM1 and KIF20A similarly promotes abnormal mitotic spindle morphology and chromosome alignment, which have been shown to induce mitotic catastrophe-dependent senescence. The physiological relevance of the regulation of KIF20A by FOXM1 is further highlighted by the strong and significant correlations between FOXM1 and KIF20A expression in breast cancer patient samples. Statistical analysis reveals that both FOXM1 and KIF20A protein and mRNA expression significantly associates with poor survival, consistent with a role of FOXM1 and KIF20A in paclitaxel action and resistance. Collectively, our findings suggest that paclitaxel targets the FOXM1-KIF20A axis to drive abnormal mitotic spindle formation and mitotic catastrophe and that deregulated FOXM1 and KIF20A expression may confer paclitaxel resistance. These findings provide insights into the underlying mechanisms of paclitaxel resistance and have implications for the development of predictive biomarkers and novel chemotherapeutic strategies for paclitaxel resistance.Oncogene advance online publication, 11 May 2015; doi:10.1038/onc.2015.152.published_or_final_versio

Severe hereditary spherocytosis and distal renal tubular acidosis associated with the total absence of band 3

Absence of band 3, associated with the mutation Coimbra (V488M) in the homozygous state, caused severe hereditary spherocytosis in a young child. Although prenatal testing was made available to the parents, it was declined. Because the fetus stopped moving near term, an emergency cesarean section was performed and a severely anemic, hydropic female baby was delivered. She was resuscitated and initially kept alive with respiratory assistance and hypertransfusion therapy. Cord blood smears revealed erythroblastosis, poikilocytosis, and red cells with stalk-like elongations. Band 3 and protein 4.2 were absent; spectrin, ankyrin, and glycophorin A were significantly reduced. Renal tubular acidosis was detected by the age of 3 months. Nephrocalcinosis appeared soon thereafter. After 3 years of follow-up the child is doing reasonably well on a regimen that includes regular blood transfusions and daily bicarbonate supplements. The long-term prognosis remains uncertain given the potential for hematologic and renal complications