Radiotherapy planning for glioblastoma based on a tumor growth model: Improving target volume delineation

Glioblastoma are known to infiltrate the brain parenchyma instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In clinical practice, a uniform margin is applied to account for microscopic spread of disease. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth: Anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. A retrospective study involving 10 glioblastoma patients has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most crucial model input. We conclude that the tumor growth model provides a method to account for anisotropic growth patterns of glioblastoma, and may therefore provide a tool to make target delineation more objective and automated

MDM2 prevents spontaneous tubular epithelial cell death and acute kidney injury

Murine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as a modulator of NF-kB signaling. As such it promotes proliferation and inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial cells and we hypothesized that MDM2 is necessary for their survival and homeostasis. MDM2 knockdown by siRNA or by genetic depletion resulted in demise of tubular cells in vitro. This phenotype was completely rescued by concomitant knockdown of p53, thus suggesting p53 dependency. In vivo experiments in the zebrafish model demonstrated that the tubulus cells of the larvae undergo cell death after the knockdown of mdm2. Doxycycline-induced deletion of MDM2 in tubular cell-specific MDM2-knockout mice Pax8rtTa-cre; MDM2f/f caused acute kidney injury with increased plasma creatinine and blood urea nitrogen and sharp decline of glomerular filtration rate. Histological analysis showed massive swelling of renal tubular cells and later their loss and extensive tubular dilation, markedly in proximal tubules. Ultrastructural changes of tubular epithelial cells included swelling of the cytoplasm and mitochondria with the loss of cristae and their transformation in the vacuoles. The pathological phenotype of the tubular cell-specific MDM2-knockout mouse model was completely rescued by co-deletion of p53. Tubular epithelium compensates only partially for the cell loss caused by MDM2 depletion by proliferation of surviving tubular cells, with incomplete MDM2 deletion, but rather mesenchymal healing occurs. We conclude that MDM2 is a non-redundant survival factor for proximal tubular cells by protecting them from spontaneous p53 overexpression-related cell death

Das Weidesystem beeinflusst Schlachtleistung und Fleischqualität von gesömmerten Lämmern

Die Sömmerungsbeiträge für Schafe sind in der Schweiz nach Weidesystem gestaffelt und bei Umtriebsweide höher als bei Standweide. In dieser Studie wurden in einem kontrollierten Alpweideversuch die in diesen beiden Weidesystemen erzielbare Mast- und Schlachtleistung sowie die Fleischqualität verglichen. Hierzu wurden 55 männliche kastrierte Lämmer (36,2±4,2 kg schwer und 27±3 Wochen alt) der Schweizer Rassen Engadinerschaf und Walliser Schwarznasenschaf einer fetten Milchkrautweide und einer Borstgrasweide jeweils mit Standweide- und Umtriebsweidesystem zugeteilt. Von jeder Rasse wurden auf jedem Vegetationstyp und Weidesystem sechs bis sieben Tiere gehalten. Bei Umtriebsweide waren Tageszuwachs, Schlachtausbeute und tendenziell die Fleischigkeit (CH-TAX) bei beiden Rassen höher als bei Standweide. Einen stärkeren Einfluss auf Tageszuwachs und Schlachtgewicht als das Weidesystem hatte jedoch der Vegetationstyp. Im Vergleich zur Standweide waren beim Fleisch vom Umtriebsweidesystem der Garverlust höher und die maximale Scherkraft niedriger. Dies galt aber nur für die Engadinerschafe. Bei den Walliser Schwarznasenschafen war nur die Scherkraft ansatzweise niedriger. Im Hinblick auf die Fleischqualität reagierten die beiden Rassen also unterschiedlich sensibel auf das Weidesystem. Bei den Mast- und Schlachtleistungen hingegen war für beide Rassen die Alplämmermast im Umtriebsweidesystem derjenigen im Standweidesystem vorzuziehe

The Protein Model Portal

Structural Genomics has been successful in determining the structures of many unique proteins in a high throughput manner. Still, the number of known protein sequences is much larger than the number of experimentally solved protein structures. Homology (or comparative) modeling methods make use of experimental protein structures to build models for evolutionary related proteins. Thereby, experimental structure determination efforts and homology modeling complement each other in the exploration of the protein structure space. One of the challenges in using model information effectively has been to access all models available for a specific protein in heterogeneous formats at different sites using various incompatible accession code systems. Often, structure models for hundreds of proteins can be derived from a given experimentally determined structure, using a variety of established methods. This has been done by all of the PSI centers, and by various independent modeling groups. The goal of the Protein Model Portal (PMP) is to provide a single portal which gives access to the various models that can be leveraged from PSI targets and other experimental protein structures. A single interface allows all existing pre-computed models across these various sites to be queried simultaneously, and provides links to interactive services for template selection, target-template alignment, model building, and quality assessment. The current release of the portal consists of 7.6million model structures provided by different partner resources (CSMP, JCSG, MCSG, NESG, NYSGXRC, JCMM, ModBase, SWISS-MODEL Repository). The PMP is available at http://www.proteinmodelportal.org and from the PSI Structural Genomics Knowledgebas

Gender differences and age-specific associations between Body Mass Index and other cardiovascular risk factors in CMV infected and uninfected people

Recent studies have highlighted Body Mass Index (BMI) as an important parameter associated with cardiovascular risk and cancer. Here we have explored the relationship between BMI and other cardiovascular risk factors such as white blood count (WBC) and mean arterial blood pressure (MAP) in young (20-35 years) and older (60-85 years) healthy donors stratified by gender and CMV IgG serostatus. We found a positive correlation between BMI and WBC in young women, which was significant in CMV+ women. Interestingly, there was a non-significant opposite trend in young men. In older women the positive trend was preserved in the presence of CMVinfection, but no clear trend was seen in older men. Gender differences were also observed by opposite trends regarding an association between MAP and WBC (positive in young women, negative in young men). These associations were not observed at older ages. However, in CMV+ older men, there was a significant association between MAP and WBC as well as neutrophil count (NC). CRP values were only available in older participants, and interestingly, correlated with WBC and NC only in women, and more closely in CMVwomen. This study reveals that the correlations between common inflammatory markers/cardiovascular risk factors depend on age, gender, and CMV infection status in a complex fashion. Our findings support the need to evaluate risk factors independently in men and women and to take into account CMV infection status. More focused studies will be required to shed light on these novel findings

Asymptotic normality for random simplices and convex bodies in high dimensions

Central limit theorems for the log-volume of a class of random convex bodies in $\mathbb{R}^n$ are obtained in the high-dimensional regime, that is, as $n\to \infty$. In particular, the case of random simplices pinned at the origin and simplices where all vertices are generated at random is investigated. The coordinates of the generating vectors are assumed to be independent and identically distributed with subexponential tails. In addition, asymptotic normality is also established for random convex bodies (including random simplices pinned at the origin) when the spanning vectors are distributed according to a radially symmetric probability measure on the $n$-dimensional $\ell _p$-ball. In particular, this includes the cone and the uniform probability measure

Conocimientos y prácticas tradicionales maternas en el cuidado del niño menor de cinco años con infecciones respiratorias agudas - Hospital I Florencia de Mora - 2016

El presente estudio se realizó con el propósito de determinar la relación entre el nivel de conocimientos y prácticas tradicionales maternas en el cuidado del niño menor de cinco años con infecciones respiratorias agudas en el Hospital I Florencia de Mora, 2016. Estudio descriptivo – correlacional de corte transversal, constituido por una muestra de 208 madres de niños menores de cinco años, a quienes se les aplicó el cuestionario adaptado por las autoras para medir el nivel de conocimientos y prácticas tradicionales maternas. Los resultados demuestran que el 55.29% tiene nivel de conocimiento alto y no usa prácticas tradicionales, y solo un 18.27% de las madres usa prácticas tradicionales teniendo un nivel de conocimiento alto; realizado mediante la prueba estadística Chi cuadrada a un nivel de significancia del 5% (p<0.05), concluyendo que existe relación significativa entre el conocimiento y las prácticas tradicionales maternas en el cuidado del niño menor de cinco años del Hospital I Florencia de Mora de 2016.This study was conducted in order to determine the relationship between maternal knowledge and maternal traditional practices in the care of children under five years old with acute respiratory infections in the Hospital I Florencia de Mora, 2016. Descriptive - correlational cross- section study, consisting by a sample of 208 mothers of children under five, who were administered the questionnaire adapted by the authors to measure knowledge and maternal traditional practices. The results show that 55.29% have high knowledge and do not use traditional practices, and only 18.27% of mothers use traditional practices having a high knowledge; performed by Chi statistical square test at a significance level of 5% (p <0.05), concluding that there is significant relationship between knowledge and traditional maternal practices about the care of children under five years old of the Hospital I Florencia de Mora 2016

Nanoproteomic analysis of ischemia-dependent changes in signaling protein phosphorylation in colorectal normal and cancer tissue

Additional file 1: Table S1. Clinical data for the 20 patients analyzed in the study. Presents patient clinical data including tumor stage and grade