Hyperhomocysteinemia, anticardiolipin antibody status, and risk for vascular access thrombosis in hemodialysis patients

Hyperhomocysteinemia, anticardiolipin antibody status, and risk for vascular access thrombosis in hemodialysis patients.Background. Vascular access failure is an important cause of morbidity in end-stage renal failure patients on hemodialysis. Currently, little is known about risk factors that predispose certain hemodialysis patients to recurrent access thrombosis. Hyperhomocysteinemia (common in patients with renal failure) predisposes people with normal renal function to recurrent and early-onset venous thrombosis, although the effect on vascular access thrombosis is currently unknown. Previous studies have suggested that high titers of IgG anticardiolipin antibody (IgG-ACA) predispose hemodialysis patients to access thrombosis. This cross sectional study was designed to assess for an association between two predictive variables, hyperhomocysteinemia and elevated titers of IgG-ACA, and vascular access thrombosis in patients undergoing chronic hemodialysis.Methods. Risk factors for vascular access thrombosis were documented, and the number of episodes of access thrombosis was recorded for the previous three years in patients undergoing hemodialysis. Midweek predialysis total homocysteine and IgG-ACA levels were measured in all subjects.Results. Of the 118 patients who were enrolled, 75.4% had a native arteriovenous fistula. Episodes of vascular access thrombosis were recorded for the previous three years; 34 (28.8%, 95% CI 20.9 to 37.9%) patients had 72 episodes of access thrombosis over the period of risk. Mean homocysteine levels were not significantly different between these 34 patients (28.6 μmol/liter, 95% CI 24.5 to 32.7) and the patients who had no episodes of graft thrombosis (29.8 μmol/liter, 95% CI 26.7 to 32.9). Sixty-seven unselected patients had IgG-ACA levels drawn for analysis, and all assays were negative. The only variable that was associated with a higher risk for graft thrombosis was the type of vascular access placed (odds ratio 4.0, 95% CI 1.6 to 9.6 for patients with a synthetic graft compared with those with an arteriovenous fistula).Conclusions. No association was found between homocysteine levels or anticardiolipin antibody and vascular access thrombosis in our patient population

Anticancer activities of bovine and human lactoferricin-derived peptides

Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency

Active Treatment in Low-Risk Prostate Cancer: A Population-Based Study

Background: Active surveillance instead of active treatment (AT) is preferred for patients with low-risk prostate cancer (LR-PCa), but practice varies widely. We conducted a population-based study to assess the proportion of patients who underwent AT between January 2011 and December 2014, and to evaluate factors associated with AT. Methods: The provincial cancer registry was linked to administrative health datasets to identify patients with lr-pca and to acquire demographic, tumour, and treatment data. The primary outcome was receipt of AT during the first 12 months after diagnosis, defined as any receipt of external-beam radiotherapy, brachytherapy, radical prostatectomy, cryotherapy, or androgen deprivation. Univariate and multivariate logistic regression were used to analyze the correlation between patient and tumour factors and AT. Results: Of 1565 patients with LR-PCa, 554 (35.4%) underwent AT within 12 months of diagnosis. Radical prostatectomy was the most common treatment (58%), followed by brachytherapy (29.6%). Younger age [odds ratio (or) 0.92; 95% confidence interval (CI): 0.91 to 0.94], lower score (≥3) on the Charlson comorbidity index (OR: 0.36; 95% CI: 0.19 to 0.68), T2 stage (or: 3.05; 95% CI: 2.03 to 4.58), higher prostate-specific antigen (PSA) at diagnosis (or: 1.13; 95% CI: 1.06 to 1.21), radiation oncologist consultation (or: 3.35; 95% CI: 2.55 to 4.39), and earlier diagnosis year (2012 or: 0.46; 95% CI: 0.34 to 0.63; 2013 or: 0.45; 95% CI: 0.32 to 0.63; 2014 or: 0.33; 95% CI: 0.23 to 0.47) were associated with a higher probability of AT. Conclusions: This contemporary population-based study demonstrates that approximately one third of patients with lr-pca undergo AT. Patients of younger age, with less comorbidity, a higher tumour stage, higher psa, earlier year of diagnosis, and radiation oncologist consultation were more likely to undergo AT. Further investigation is needed to identify strategies that could minimize overtreatment

Competition and moral behavior: A meta-analysis of forty-five crowd-sourced experimental designs

Does competition affect moral behavior? This fundamental question has been debated among leading scholars for centuries, and more recently, it has been tested in experimental studies yielding a body of rather inconclusive empirical evidence. A potential source of ambivalent empirical results on the same hypothesis is design heterogeneity?variation in true effect sizes across various reasonable experimental research protocols. To provide further evidence on whether competition affects moral behavior and to examine whether the generalizability of a single experimental study is jeopardized by design heterogeneity, we invited independent research teams to contribute experimental designs to a crowd-sourced project. In a large-scale online data collection, 18,123 experimental participants were randomly allocated to 45 randomly selected experimental designs out of 95 submitted designs. We find a small adverse effect of competition on moral behavior in a meta-analysis of the pooled data. The crowd-sourced design of our study allows for a clean identification and estimation of the variation in effect sizes above and beyond what could be expected due to sampling variance. We find substantial design heterogeneity?estimated to be about 1.6 times as large as the average standard error of effect size estimates of the 45 research designs?indicating that the informativeness and generalizability of results based on a single experimental design are limited. Drawing strong conclusions about the underlying hypotheses in the presence of substantive design heterogeneity requires moving toward much larger data collections on various experimental designs testing the same hypothesis

Competition and moral behavior: A meta-analysis of forty-five crowd-sourced experimental designs

Does competition affect moral behavior? This fundamental question has been debated among leading scholars for centuries, and more recently, it has been tested in experimental studies yielding a body of rather inconclusive empirical evidence. A potential source of ambivalent empirical results on the same hypothesis is design heterogeneity—variation in true effect sizes across various reasonable experimental research protocols. To provide further evidence on whether competition affects moral behavior and to examine whether the generalizability of a single experimental study is jeopardized by design heterogeneity, we invited independent research teams to contribute experimental designs to a crowd-sourced project. In a large-scale online data collection, 18,123 experimental participants were randomly allocated to 45 randomly selected experimental designs out of 95 submitted designs. We find a small adverse effect of competition on moral behavior in a meta-analysis of the pooled data. The crowd-sourced design of our study allows for a clean identification and estimation of the variation in effect sizes above and beyond what could be expected due to sampling variance. We find substantial design heterogeneity—estimated to be about 1.6 times as large as the average standard error of effect size estimates of the 45 research designs—indicating that the informativeness and generalizability of results based on a single experimental design are limited. Drawing strong conclusions about the underlying hypotheses in the presence of substantive design heterogeneity requires moving toward much larger data collections on various experimental designs testing the same hypothesis