Wilms' Tumor with Long-delayed Recurrence: 25 Years after Initial Treatment

Wilms' tumor is one of the most frequent malignant neoplasms in childhood. Advances in treatment modalities such as the combination of chemoradiation therapy with surgery have enhanced overall survival. However, recurrence of Wilms' tumor is still a problem. In this case, a 28-year-old female had experienced intermittent abdominal pain, and the computed tomography scan showed a huge pelvic mass. The patient had a history of radical nephrectomy for Wilms' tumor with concurrent chemotherapy at the age of three. The pelvic mass was resected in February 2010 and was confirmed to be a recurrent Wilms' tumor. The recurrent tumor showed a classic triphasic Wilms' tumor growth pattern with frequent mitoses and tumor necrosis. Our case is an extraordinary case of a long-delayed recurrent Wilms' tumor after 25 years, which is the longest disease-free interval ever reported. The possible effects of chemotherapy as well as some other mechanisms of this late relapse are discussed

Unsupervised Bayesian linear unmixing of gene expression microarrays

Background: This paper introduces a new constrained model and the corresponding algorithm, called unsupervised Bayesian linear unmixing (uBLU), to identify biological signatures from high dimensional assays like gene expression microarrays. The basis for uBLU is a Bayesian model for the data samples which are represented as an additive mixture of random positive gene signatures, called factors, with random positive mixing coefficients, called factor scores, that specify the relative contribution of each signature to a specific sample. The particularity of the proposed method is that uBLU constrains the factor loadings to be non-negative and the factor scores to be probability distributions over the factors. Furthermore, it also provides estimates of the number of factors. A Gibbs sampling strategy is adopted here to generate random samples according to the posterior distribution of the factors, factor scores, and number of factors. These samples are then used to estimate all the unknown parameters. Results: Firstly, the proposed uBLU method is applied to several simulated datasets with known ground truth and compared with previous factor decomposition methods, such as principal component analysis (PCA), non negative matrix factorization (NMF), Bayesian factor regression modeling (BFRM), and the gradient-based algorithm for general matrix factorization (GB-GMF). Secondly, we illustrate the application of uBLU on a real time-evolving gene expression dataset from a recent viral challenge study in which individuals have been inoculated with influenza A/H3N2/Wisconsin. We show that the uBLU method significantly outperforms the other methods on the simulated and real data sets considered here. Conclusions: The results obtained on synthetic and real data illustrate the accuracy of the proposed uBLU method when compared to other factor decomposition methods from the literature (PCA, NMF, BFRM, and GB-GMF). The uBLU method identifies an inflammatory component closely associated with clinical symptom scores collected during the study. Using a constrained model allows recovery of all the inflammatory genes in a single factor

Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol.

INTRODUCTION: The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. METHODS AND ANALYSIS: Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. ETHICS AND DISSEMINATION: This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. TRIAL REGISTRATION NUMBER: NCT01991106

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al

Association analysis of PRNP gene region with chronic wasting disease in Rocky Mountain elk

<p>Abstract</p> <p>Background</p> <p>Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids including white-tailed (<it>Odocoileus virginianus</it>) and mule deer (<it>Odocoileus hemionus</it>), Rocky Mountain elk (<it>Cervus elaphus nelsoni</it>), and moose (<it>Alces alces</it>). A leucine variant at position 132 (132L) in prion protein of Rocky Mountain elk confers a long incubation time with CWD, but not complete resistance. However, variants in regulatory regions outside the open reading frame of <it>PRNP </it>have been associated with varying degrees of susceptibility to prion disease in other species, and some variants have been observed in similar regions of Rocky Mountain elk <it>PRNP</it>. Thus, additional genetic variants might provide increased protection, either alone or in combination with 132L.</p> <p>Findings</p> <p>This study provided genomic sequence of all exons for <it>PRNP </it>of Rocky Mountain elk. Many functional sites in and around the <it>PRNP </it>gene region were sequenced, and this report approximately doubled (to 75) the number of known variants in this region. A haplotype-tagging approach was used to reduce the number of genetic variants required to survey this variation in the <it>PRNP </it>gene region of 559 Rocky Mountain elk. Eight haplotypes were observed with frequencies over 1.0%, and one haplotype was present at 71.2% frequency, reflecting limited genetic diversity in the <it>PRNP </it>gene region.</p> <p>Conclusions</p> <p>The presence of 132L cut odds of CWD by more than half (Odds Ratio = 0.43; P = 0.0031), which was similar to a previous report. However after accounting for 132L, no association with CWD was found for any additional variants in the <it>PRNP </it>region (P > 0.05).</p

Experimental and computational study of trace element distribution between orthopyroxene and anhydrous silicate melts: substitution mechanisms and the effect of iron

Although orthopyroxene (Opx) is present during a wide range of magmatic differentiation processes in the terrestrial and lunar mantle, its effect on melt trace element contents is not well quantified. We present results of a combined experimental and computational study of trace element partitioning between Opx and anhydrous silicate melts. Experiments were performed in air at atmospheric pressure and temperatures ranging from 1,326 to 1,420°C in the system CaO-MgO-A

A Comparison of Administrative and Physiologic Predictive Models in Determining Risk Adjusted Mortality Rates in Critically Ill Patients

Hospitals are increasingly compared based on clinical outcomes adjusted for severity of illness. Multiple methods exist to adjust for differences between patients. The challenge for consumers of this information, both the public and healthcare providers, is interpreting differences in risk adjustment models particularly when models differ in their use of administrative and physiologic data. We set to examine how administrative and physiologic models compare to each when applied to critically ill patients.We prospectively abstracted variables for a physiologic and administrative model of mortality from two intensive care units in the United States. Predicted mortality was compared through the Pearsons Product coefficient and Bland-Altman analysis. A subgroup of patients admitted directly from the emergency department was analyzed to remove potential confounding changes in condition prior to ICU admission.We included 556 patients from two academic medical centers in this analysis. The administrative model and physiologic models predicted mortalities for the combined cohort were 15.3% (95% CI 13.7%, 16.8%) and 24.6% (95% CI 22.7%, 26.5%) (t-test p-value<0.001). The r(2) for these models was 0.297. The Bland-Atlman plot suggests that at low predicted mortality there was good agreement; however, as mortality increased the models diverged. Similar results were found when analyzing a subgroup of patients admitted directly from the emergency department. When comparing the two hospitals, there was a statistical difference when using the administrative model but not the physiologic model. Unexplained mortality, defined as those patients who died who had a predicted mortality less than 10%, was a rare event by either model.In conclusion, while it has been shown that administrative models provide estimates of mortality that are similar to physiologic models in non-critically ill patients with pneumonia, our results suggest this finding can not be applied globally to patients admitted to intensive care units. As patients and providers increasingly use publicly reported information in making health care decisions and referrals, it is critical that the provided information be understood. Our results suggest that severity of illness may influence the mortality index in administrative models. We suggest that when interpreting "report cards" or metrics, health care providers determine how the risk adjustment was made and compares to other risk adjustment models

Comparative study on the use of specific and heterologous microsatellite primers in the stingless bees Melipona rufiventris and M. mondury (Hymenoptera, Apidae)

Due to their high degree of polymorphism, microsatellites are considered useful tools for studying population genetics. Nevertheless, studies of genetic diversity in stingless bees by means of these primers have revealed a low level of polymorphism, possibly the consequence of the heterologous primers used, since in most cases these were not specifically designed for the species under consideration. Herein we compared the number of polymorphic loci and alleles per locus, as well as observed heterozygosity in Melipona rufiventris and M. mondury populations, using specific and heterologous primers. The use of specific primers placed in evidence the greater frequency of polymorphic loci and alleles per locus, besides an expressive increase in observed heterozygosity in M. rufiventris and M. mondury, thereby reinforcing the idea that populational studies should be undertaken by preferably using species-specific microsatellite primers