Cytotoxicity of the mycotoxins deoxynivalenol and ochratoxin A on Caco-2 cell line in presence of resveratrol

Exposure to mycotoxins through dietary food intake involves a highly complex scenario where co-contamination of different mycotoxins has been frequently demonstrated. On the other hand, the effect of the interaction of mycotoxins with other generally considered beneficial food components, as the antioxidants, has been scarcely studied. The main goal of the present work was to assess the cytotoxic effects on Caco-2 cells of the mycotoxins deoxynivalenol (DON) and ochratoxin A (OTA), alone or combined, and to explore potential protective effects of resveratrol (RES), an antioxidant frequently found in wine. In parallel, reactive oxygen species (ROS) production has also been studied as a first approach to understand the underlying mechanism of cytotoxicity. Results indicate a higher toxic effect of the mycotoxins when they are co-exposed. This increase in cytotoxicity was not accompanied by an increase in ROS production. The co-exposure of OTA or DON with RES did not result in a decrease in cytotoxicity; on the contrary, it resulted in increased cytotoxicity not associated with an increase in ROS production.The authors are grateful to the CYTED Action 109AC0371, to the INIA project (RTA 2012-00053-00-00) as well as the Spanish (Project AGL2011-24862) and Catalonian (XaRTA-Reference Network on Food Technology) Governments for their financial support. C.A. González-Arias thanks the Secretaria de Universitats i Recerca del Departament de Economia i Coneixement of the Generalitat de Catalunya for the pre-doctoral grant

Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.

Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40-60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities

Impact of Age on Treatment and Outcomes After Acute Myocardial Infarction, Particularly in Very Elderly Patients

INTRODUCTION: The elderly population admitted for acute myocardial infarction is increasing. This group is not well studied in international trials and is probably treated with a more conservative approach. OBJECTIVES: To evaluate the presentation and treatment of myocardial infarction according to age, particularly in very elderly patients. METHODS: We studied 1242 consecutive patients admitted with acute myocardial infarction, assessing in-hospital, 30-day and one-year mortality during follow-up for each age-group. Patients were divided into four groups according to age: <45 years (7.6%); 45-64 years (43.3%); 65-74 years (23.4%); and ≥75 years (25.7%). RESULTS: Elderly patients had a worse risk profile (except for smoking), more previous history of coronary disease and a worse profile on admission, with the exception of lipid profile, which was more favorable. With regard to treatment of the elderly, although less optimized than in other age-groups, it was significantly better compared to other registries, including for percutaneous coronary angioplasty. Both complications and mortality were worse in the older groups. In elderly patients (≥75 years), adjusted risk of mortality was 4.9-6.3 times higher (p<0.001) than patients in the reference age-group (45-64 years). In these patients, the independent predictors of death were left ventricular function and renal function, use of beta-blockers being a predictor of survival. CONCLUSIONS: Elderly patients represent a substantial proportion of the population admitted with myocardial infarction, and receive less evidenced-based therapy. Age is an independent predictor of short- and medium-term mortality

Impact of Obesity on Results after Primary Angioplasty in Patients with ST Segment Elevation Acute Myocardial Infarction

INTRODUCTION: Obesity is an important risk factor for the development of diabetes, hypertension, coronary disease, left ventricular dysfunction, stroke and cardiac arrhythmias. Paradoxically, previous studies in patients undergoing elective coronary angioplasty showed a reduction in hospital and long-term mortality in obese patients. The relation with body mass index (BMI) has been less studied in the context of primary angioplasty. OBJECTIVES: To evaluate the impact of obesity on the results of ST-segment elevation acute myocardial infarction treated by primary angioplasty. METHODS: This was a study of 464 consecutive patients with ST-segment elevation acute myocardial infarction undergoing primary angioplasty, 78% male, mean age 61 +/- 13 years. We assessed in-hospital, 30-day and one-year mortality according to BMI. Patients were divided into three groups according to BMI: normal--18-24.9 kg/m2 (n = 171); overweight--25-29.9 kg/m2 (n = 204); and obese-- > 30 kg/m2 (n = 89). RESULTS: Obese patients were younger (ANOVA, p < 0.001) and more frequently male (p = 0.014), with more hypertension (p = 0.001) and dyslipidemia (p = 0.006). There were no differences in the prevalence of diabetes, previous cardiac history, heart failure on admission, anterior location, multivessel disease, peak total CK or medication prescribed, except that obese patients received more beta-blockers (p = 0.049). In-hospital mortality was 9.9% for patients with normal BMI, 3.4% for overweight patients and 6.7% for obese patients (p = 0.038). Mortality at 30 days was 11 4.4% and 7.8% (p = 0.032) and at one year 12.9%, 4.9% and 9% (p = 0.023), respectively. On univariate analysis, overweight was the only BMI category with a protective effect; however, after multivariate logistic regression analysis, adjusted for confounding variables, none of the BMI categories could independently predict outcome. CONCLUSIONS: Overweight patients had a better prognosis after primary angioplasty for ST-segment elevation acute myocardial infarction compared with other BMI categories, but this was dependent on other potentially confounding variables

Does Admission NT-ProBNP Increase the Prognostic Accuracy of GRACE Risk Score in the Prediction of Short-Term Mortality After Acute Coronary Syndromes?

BACKGROUND: NT-proBNP has prognostic implications in heart failure. In acute coronary syndromes (ACS) setting, the prognostic significance of NT-proBNP is being sought. We studied short-term prognostic impact of admission NT-proBNP in patients admitted for ACS and in association with GRACE risk score (GRS). METHODS AND RESULTS: We studied 1035 patients admitted with ACS. Patients were divided in quartiles according to NT-proBNP levels on admission: Q1 <180 pg/ml; Q2 180-691 pg/ml; Q3 696-2664 pg/ml; Q4 2698-35 000 pg/ml. Groups were compared in terms of short-term all-cause mortality. Patients with higher NT-proBNP had worst GRS on admission. They also received less aggressive treatment. In-hospital mortality was 0.8%, 3.0%, 5.8% and 12.8% (P<0.001) and 30-day mortality 1.6%, 4.6%, 6.5% and 16.7% (P<0.001) respectively. In multivariate logistic regression analysis, NT-proBNP is an independent predictor of in-hospital (OR 2.35; 95% CI: 1.12-4.93, P=0.022) and 30-day mortality (OR 2.20; 95% CI: 1.17-4.12, P=0.014). However, NT-proBNP does not add any incremental benefit to GRS for prediction of outcome by ROC curve analysis. CONCLUSIONS: NT-proBNP is an independent predictor of in-hospital and 30-day mortality after ACS, independently of left ventricular function, but does not increase the prognostic accuracy of GRS.info:eu-repo/semantics/publishedVersio

Prognostic Value of a New Cardiopulmonary Exercise Testing Parameter in Chronic Heart Failure: Oxygen Uptake Efficiency at Peak Exercise - Comparison with Oxygen Uptake Efficiency Slope

INTRODUCTION: A growing body of evidence shows the prognostic value of oxygen uptake efficiency slope (OUES), a cardiopulmonary exercise test (CPET) parameter derived from the logarithmic relationship between O(2) consumption (VO(2)) and minute ventilation (VE) in patients with chronic heart failure (CHF). OBJECTIVE: To evaluate the prognostic value of a new CPET parameter - peak oxygen uptake efficiency (POUE) - and to compare it with OUES in patients with CHF. METHODS: We prospectively studied 206 consecutive patients with stable CHF due to dilated cardiomyopathy - 153 male, aged 53.3±13.0 years, 35.4% of ischemic etiology, left ventricular ejection fraction 27.7±8.0%, 81.1% in sinus rhythm, 97.1% receiving ACE-Is or ARBs, 78.2% beta-blockers and 60.2% spironolactone - who performed a first maximal symptom-limited treadmill CPET, using the modified Bruce protocol. In 33% of patients an cardioverter-defibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) was implanted during follow-up. Peak VO(2), percentage of predicted peak VO(2), VE/VCO(2) slope, OUES and POUE were analyzed. OUES was calculated using the formula VO(2) (l/min) = OUES (log(10)VE) + b. POUE was calculated as pVO(2) (l/min) / log(10)peakVE (l/min). Correlation coefficients between the studied parameters were obtained. The prognosis of each variable adjusted for age was evaluated through Cox proportional hazard models and R2 percent (R2%) and V index (V6) were used as measures of the predictive accuracy of events of each of these variables. Receiver operating characteristic (ROC) curves from logistic regression models were used to determine the cut-offs for OUES and POUE. RESULTS: pVO(2): 20.5±5.9; percentage of predicted peak VO(2): 68.6±18.2; VE/VCO(2) slope: 30.6±8.3; OUES: 1.85±0.61; POUE: 0.88±0.27. During a mean follow-up of 33.1±14.8 months, 45 (21.8%) patients died, 10 (4.9%) underwent urgent heart transplantation and in three patients (1.5%) a left ventricular assist device was implanted. All variables proved to be independent predictors of this combined event; however, VE/VCO2 slope was most strongly associated with events (HR 11.14). In this population, POUE was associated with a higher risk of events than OUES (HR 9.61 vs. 7.01), and was also a better predictor of events (R2: 28.91 vs. 22.37). CONCLUSION: POUE was more strongly associated with death, urgent heart transplantation and implantation of a left ventricular assist device and proved to be a better predictor of events than OUES. These results suggest that this new parameter can increase the prognostic value of CPET in patients with CHF

Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process

Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Vranych, Cecilia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

Results of Primary Angioplasty in a Reference Center: in-Hospital Outcomes

INTRODUCTION: Primary angioplasty is accepted as the preferred treatment for acute myocardial infarction in the first 12 hours. However, outcomes depend to a large extent on the volume of activity and experience of the center. Continuous monitoring of methods and results obtained is therefore crucial to quality control. OBJECTIVE: To describe the demographic, clinical and angiographic characteristics as well as in-hospital outcomes of patients undergoing primary PCI in a high-volume Portuguese center. We also aimed to identify variables associated with in-hospital mortality in this population. METHODS: This was a retrospective registry of consecutive primary PCIs performed at Santa Marta Hospital between January 2001 and August 2007. Demographic, clinical, and angiographic characteristics and in-hospital outcomes were analyzed. Independent predictors of in-hospital mortality were identified by multivariate logistic regression analysis. RESULTS: A total of 1157 patients were identified, mean age 61+/-12 years, 76% male. Mean pain-to-balloon time was 7.6 hours and primary angiographic success was 88%. Overall in-hospital mortality was 6.9%, or 5.5% if patients presenting in cardiogenic shock were excluded from the analysis. Previous history of heart failure, cardiogenic shock on admission, invasive ventilatory support, major hemorrhage, and age over 75 years were found to be associated with increased risk of in-hospital death. Conclusions: In this center primary PCI is effective and safe. Angiographic success rates and in-hospital mortality and morbidity are similar to other international registries. Patients at increased risk for adverse outcome can be identified by simple clinical characteristics such as advanced age, cardiogenic shock on admission, mechanical ventilation and major hemorrhage during hospitalization

Poor youths and ‘pacification’:dilemmas between discourse and practice from the perspective of young people about policing in Rio de Janeiro’s favelas

This article explores the social representations of youngsters from favelas in Rio de Janeiro on police practices in the context of the implementation of ‘Pacifying Police Units’. Drawing from fieldwork, participant observation and interviews, the authors analyse the narratives and practices which influence relations between young people and the police in the Complexo do Alemão area of the city. The interviewees expressed a demand for further public security and social services. Young people noted some progress in police practices, although these changes appear to be unstable. The permanence of violent practices and prejudice by the police was verified in youngsters’ narratives. Any change in this scenario should be based on the replacement of the war logic of ‘pacification’ for another logic, that of participation.2030-01-0

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry