A New Calibrated Bayesian Internal Goodness-of-Fit Method: Sampled Posterior p-Values as Simple and General p-Values That Allow Double Use of the Data

Background: Recent approaches mixing frequentist principles with Bayesian inference propose internal goodness-of-fit (GOF) p-values that might be valuable for critical analysis of Bayesian statistical models. However, GOF p-values developed to date only have known probability distributions under restrictive conditions. As a result, no known GOF p-value has a known probability distribution for any discrepancy function. Methodology/Principal Findings: We show mathematically that a new GOF p-value, called the sampled posterior p-value (SPP), asymptotically has a uniform probability distribution whatever the discrepancy function. In a moderate finite sample context, simulations also showed that the SPP appears stable to relatively uninformative misspecifications of the prior distribution. Conclusions/Significance: These reasons, together with its numerical simplicity, make the SPP a better canonical GOF p-value than existing GOF p-values

High OCT4 and Low p16INK4A Expressions Determine In Vitro Lifespan of Mesenchymal Stem Cells

After long-term culture, mesenchymal stem cells alter their biological properties and enter into a state of replicative senescence. Although several classical biomarkers have been used for quantitative assessment of cellular senescence, no hallmark has been proven completely unique to the senescent state in cells. We used bone marrow-derived MSCs (BM-MSCs) from different healthy young donors and an in vitro model with well-defined senescence end points to identify a set of robust markers that could potentially predict the expansion capacity of MSCs preparations before reaching senescence. For each early passage BM-MSC sample (5th or 6th passages), the normalized protein expression levels of senescence-associated markers p16INK4A, p21WAF1, SOD2, and rpS6S240/244; the concentration of IL6 and IL8 in cell culture supernatants; and the normalized gene expression levels of pluripotency markers OCT4, NANOG, and SOX2 were correlated with final population doubling (PD) number. We revealed that the low expression of p16INK4A protein and a high OCT4 gene expression, rather than other evaluated markers, might be potential hallmarks and predictors of greater in vitro lifespan and growth potential, factors that can impact the successful therapeutic use of MSCs preparations

Use of alprostadil, a stable prostaglandin E(1) analogue, for the attenuation of rat skeletal muscle ischemia and reperfusion injury

Aim. Some stable prostaglandin analogues such as alprostadil have been used to attenuate the deleterious effects of ischemia and reperfusion injury. The aim of this paper was to test if alprostadil can decrease the ischemia- reperfusion injury in rat skeletal muscle using muscular enzymes as markers, such as aspartate aminotransferase (AST), creatine kinase (CPK), lactate dehydrogenase (LDH); degeneration products of cell membrane-malondialdehyde (MDA) and muscle glycogen storage. Methods. Thirty male Wistar rats were used in a model of hind limb ischemia achieved by infrarenal aortic cross-clamping. The animals were randomized into three equal groups (N=10) submitted to 5 hours of ischemia followed by one hour of reperfusion. The first group (control) received continuous intravenous infusion of saline solution and the second group (preischemia, GPI) received continuous intravenous infusion of alprostadil throughout the experiment starting 20 minutes before the aortic cross-clamping. The third group, prereperfusion (GPR), received alprostadil only during the reperfusion period, with intravenous infusion being started 10 min before the clamp release. Results. There was no difference in CPK, LDH, AST or tissue glycogen values between groups. However, a significant elevation in MDA was observed in the GPI and GPR groups compared to the control group, with no difference between the GPI and GPR. Conclusion. Under conditions of partial skeletal muscle ischemia, alprostadil did not reduce the release of muscular enzymes, the consumption of tissue glycogen or the effects of ischemia and reperfusion on the cell membrane, characterized by lipid peroxidation.CNPq/FAEP