Promising role of preoperative neutrophil-to-lymphocyte ratio in patients treated with radical nephroureterectomy.

Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort. Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models. Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease (p < 0.001). Within a median follow-up of 40 months (IQR 20-76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS (p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS (p = 0.03). In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy

Participation of the endoplasmic reticulum protein chaperone thio-oxidoreductase in gonadotropin-releasing hormone receptor expression at the plasma membrane

Chaperone members of the protein disulfide isomerase family can catalyze the thiol-disulfide exchange reaction with pairs of cysteines. There are 14 protein disulfide isomerase family members, but the ability to catalyze a thiol disulfide exchange reaction has not been demonstrated for all of them. Human endoplasmic reticulum protein chaperone thio-oxidoreductase (ERp18) shows partial oxidative activity as a protein disulfide isomerase. The aim of the present study was to evaluate the participation of ERp18 in gonadotropin-releasing hormone receptor (GnRHR) expression at the plasma membrane. Cos-7 cells were cultured, plated, and transfected with 25 ng (unless indicated) wild-type human GnRHR (hGnRHR) or mutant GnRHR (Cys14Ala and Cys200Ala) and pcDNA3.1 without insert (empty vector) or ERp18 cDNA (75 ng/well), pre-loaded for 18 h with 1 µCi myo-[2-3H(N)]-inositol in 0.25 mL DMEM and treated for 2 h with buserelin. We observed a decrease in maximal inositol phosphate (IP) production in response to buserelin in the cells co-transfected with hGnRHR, and a decrease from 20 to 75 ng of ERp18 compared with cells co-transfected with hGnRHR and empty vector. The decrease in maximal IP was proportional to the amount of ERp18 DNA over the range examined. Mutants (Cys14Ala and Cys200Ala) that could not form the Cys14-Cys200 bridge essential for plasma membrane routing of the hGnRHR did not modify maximal IP production when they were co-transfected with ERp18. These results suggest that ERp18 has a reduction role on disulfide bonds in wild-type hGnRHR folding

Características morfológicas de cultivares de soja convencionais e Roundup ReadyTM em função da época e densidade de semeadura Morphologic characteristic of the conventional soybean genotype and Roundup ReadyTM according to the sowing season and seed densities

O trabalho tem como objetivo verificar a influência de diferentes densidades e épocas de semeadura em genótipos convencionais e Roundup ReadyTM (RR), nas características morfológicas de plantas de soja. O experimento foi conduzido em Jari, Rio Grande do Sul (RS). A primeira semeadura foi realizada dentro da época indicada para a cultura (novembro), e a segunda, após a época indicada (janeiro), com as cultivares 'CEP/CD 41', 'CD 201', 'Fundacep 39',' Fundacep 44', 'CD 205', 'BRS 133', 'Fundacep 45', 'A 6001 RG', 'Mágica', 'AL72' e 'A 8100 RG', nas densidades de 250, 400 e 550 mil sementes aptas ha-1, na safra 2005/2006. O delineamento experimental utilizado foi blocos ao acaso, com parcelas subsubdivididas e quatro repetições. Foram avaliados o ciclo das cultivares, a altura de plantas, a altura de inserção do primeiro legume, o número de ramos planta-1 e de ramos m-2, o número de nós na haste principal planta-1 e na haste principal m-2, o rendimento biológico (RB) e o índice de colheita (IC). A semeadura em janeiro ocasiona redução no ciclo da cultura, na altura de plantas, na altura de inserção do primeiro legume, no número de nós planta-1 e de RB e no atraso da semeadura. O aumento da densidade de sementes não proporcionou aumento na estatura de plantas e altura de inserção do primeiro legume, nas cultivares RR. O período do ciclo que é mais afetado com atraso da semeadura é o vegetativo. O IC foi menor na semeadura em novembro; no entanto, o RB foi maior.<br>This paper has the objective to evaluate the influence of seed densities and sowing season in conventional soybean genotype and Roundup ReadyTM (RR), in the morphological characteristic of soybean plant. The experiments were conducted in Jari-RS, Brazil. The first seeding was done within the time prescribed for the crop(November), and the second, after the time indicated (January), with the cultivars 'CEP/CD 41', 'CD 201', 'Fundacep 39', 'Fundacep 44', 'CD 205', 'BRS 133', 'Fundacep 45', 'A 6001 RG', 'Mágica, AL72' and A '8100 RG', at densities of 250, 400 and 550 thousand seed seeds suitable ha-1 in the 2005/2006 harvest. The experiment design was randomized blocks with split plots, with four replications. The cultivars cycle, plant height, height of first pod insertion, number of branches plant-1, branches m-2, nodes' number of the main stem plant-1, nodes main stem m-2, biological yield (RB) and harvest index (IC). Sowing in January causes reduction in the crop cycle, plant height, height of first pod insertion, number of nodes plant-1 and RB and the increase in seed density not increased the height of first pod insertion in RR cultivars. The period cycle that is most affected by the delayed sowing is the vegetative. The IC sowing in November was lower, but the RB was larger

Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.

International audienceStatin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.)