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Metastatic disease is the major cause of breast cancer–related death and despite many advances, current therapies are rarely curative. Tumor cell migration and invasion require actin cytoskeletal reorganization to endow cells with capacity to disseminate and initiate the formation of secondary tumors. However, it is still unclear how these migratory cells colonize distant tissues to form macrometastases. The E6-associated protein, E6AP, acts both as an E3 ubiquitin-protein ligase and as a coactivator of steroid hormone receptors. We report that E6AP suppresses breast cancer invasiveness, colonization, and metastasis in mice, and in breast cancer patients, loss of E6AP associates with poor prognosis, particularly for basal breast cancer. E6AP regulates actin cytoskeletal remodeling via regulation of Rho GTPases, acting as a negative regulator of ECT2, a GEF required for activation of Rho GTPases. E6AP promotes ubiquitination and proteasomal degradation of ECT2 for which high expression predicts poor prognosis in breast cancer patients. We conclude that E6AP suppresses breast cancer metastasis by regulating actin cytoskeleton remodeling through the control of ECT2 and Rho GTPase activity. These findings establish E6AP as a novel suppressor of metastasis and provide a compelling rationale for inhibition of ECT2 as a therapeutic approach for patients with metastatic breast cancer. Cancer Res; 76(14); 4236–48. ©2016 AACR.

The aim of this study is to estimate the relative displacement between the spindle nose and the clamping vice in a rotary transfer machine due to temperature variations. The study was focused on the relative displacements caused by temperature variations produced by two heat sources: the environment around the machine and the three-axis computer numerical control station during the duty cycle. Regarding the last point, an analytical model was developed, in order to account for different thermal sources inside the three-axis module (e.g., ball-screws, rolling bearings, and guideways friction heat, as well as heat generation in the motor). The complete numerical model was calibrated and successfully validated. A comparison was run between numerical results and experimental data in the framework of trials involving a newly developed transfer machine. Finally, the complete model, considering the combination of both the heat sources, has made it possible to estimate spindle nose-clamp relative displacement during a typical working day, highlighting that the radial displacement risks affecting seriously the accuracy of a workpiece.

Objectives Venipuncture is one of the most frequently performed painful procedures in children. The aim of this study was to investigate the effectiveness of 2 analgesic strategies for venipuncture in children in a specific setting like a blood-drawing center. Methods This was a prospective randomized controlled trial. It was conducted in the blood-drawing center of a tertiary level children's hospital in Italy, between November 2014 and February 2015. Eligible patients were children aged from 4 to 12 years referred to the blood-drawing center for venipuncture. Enrolled children were randomized to be distracted by Buzzy device or by playing with a handheld computer. The procedural pain was measured with the faces pain scale-revised by children aged from 4 to 7 years and with a numerical rating scale by children aged from 8 to 12 years. Results Two hundred children with a median age of 8 years were enrolled in the study. The self-reported procedural pain was not statistically different between the Buzzy group and the handheld computer group: median (interquartile range) = 3.0 (1.0-4.8) and 2.0 (1.0-4.8), respectively (P = 0.72). Children reported significant pain in 25% of cases with both distraction strategies. The procedural success rate at the first attempt was not significantly different in the 2 groups. Conclusions Analgesia provided by Buzzy or by a handheld computer was not significantly different in children undergoing venipuncture in a blood-drawing center, with the great proportion of them reporting no or mild pain during procedure.

PURPOSE: To evaluate the potential differences in non-target embolization and vessel microsphere filling of a reflux-control microcatheter (RCM) compared to a standard end-hole microcatheter (SEHM) in a swine model. MATERIALS AND METHODS: Radiopaque microspheres were injected with both RCM and SEHM (2.4-Fr and 2.7-Fr) in the kidneys of a preclinical swine model. Transarterial renal embolization procedures with RCM or SEHM were performed in both kidneys of 14 pigs. Renal arteries were selectively embolized with an automated injection protocol of radio-opaque microspheres. Ex-vivo X-ray microtomography images of the kidneys were utilized to evaluate the embolization by quantification of the deposition of injected microspheres in the target vs. the non-target area of injection. X-ray microtomography images were blindly analyzed by five interventional radiologists. The degree of vessel filling and the non-target embolization were quantified using a scale from 1 to 5 for each parameter. An analysis of variance was used to compare the paired scores. RESULTS: Total volumes of radio-opaque microspheres injected were similar for RCM (11.5±3.6 [SD] mL; range: 6-17mL) and SEHM (10.6±5.2 [SD] mL; range: 4-19mL) (P=0.38). The voxels enhanced ratio in the target (T) vs. non-target (NT) areas was greater with RCM (T=98.3% vs. NT=1.7%) than with SEHM (T=89% vs. NT=11%) but the difference was not significant (P=0.30). The total score blindly given by the five interventional radiologists was significantly different between RCM (12.3±2.1 [SD]; range: 6-15) and the standard catheter (11.3±2.5 [SD]; range: 4-15) (P=0.0073), with a significant decrease of non-target embolization for RCM (3.8±1.3 [SD]; range: 3.5-4.2) compared to SEHM (3.2±1.5 [SD]; range: 2.9-3.5) (P=0.014). CONCLUSION: In an animal model, RCM microcatheters reduce the risk of non-target embolization from 11% to 1.7%, increasing the delivery of microspheres of 98% to the target vessels, compared to SEHM microcatheters. ispartof: DIAGNOSTIC AND INTERVENTIONAL IMAGING vol:102 issue:10 pages:641-648 ispartof: location:France status: published

Les torsades de pointes correspondent à un type particulier de tachycardie ventriculaire, associée à un allongement de l’intervalle QT. C’est un événement indésirable grave, mettant en péril la vie du patient. Des facteurs, tels que l’hypokaliémie, la bradycardie et certains médicaments, amplifient le risque de survenue de TDP. Or, plus d’une centaine de molécules commercialisées en France sont concernées.Malgré une fréquence d’apparition de torsades de pointes iatrogènes a priori mineures, ces dernières sont la plupart du temps contre-indiquées et leur impact clinique potentiel reste majeur. L’étude des médicaments fréquemment impliqués et la mise en place d’outils pratiques peut permettre au pharmacien de proposer des alternatives adaptées, contribuant ainsi à la prévention de ce risque iatrogène.

Depuis plusieurs années, les associations de consommateurs lancent régulièrement des alertes concernant la présence d’ingrédients potentiellement nocifs dans les produits cosmétiques, ce qui pousse les consommateurs à se soucier de plus en plus de la composition de ces produits.Les particularités de la peau du nourrisson, qui le rendent plus vulnérable aux toxicités potentielles de ces ingrédients, entraînent une vigilance accrue de la part des parents, soucieux du bien-être de leur enfant.A travers une étude analytique de la composition de différents produits cosmétiques destinés aux nourrissons ainsi que des résultats obtenus par ces produits sur différentes applications qui analysent la composition des produits cosmétiques, cet ouvrage permet de mettre en lumière les différences considérables de notation entre les différentes applications, dues notamment à une différence sur les critères pris en compte dans cette notation.

Nanodispersions of pristine single-wall carbon nanohorns (i.e., p-SWCNHs) and oxidized-SWCNHs (i.e.; o-SWCNHs) were used to modify screen printed electrode (SPE). p-SWCNHs and o-SWCNHs were fully characterized by using several analytical techniques, as: HR-TEM (High Resolution-Transmission Electron Microscopy), FE-SEM/EDX (Field Emission-Scanning Electron Microscopy/Energy Dispersive X-ray Analysis), Raman spectroscopy, thermogravimetric analysis, differential thermal analysis (DTA), and the Brunauer-Emmett-Teller (BET) method. The chemically modified SPEs were also characterized with Cyclic Voltammetry (CV), using several different electro-active targets. In all cases, p-SWCNHs showed better performances than those obtained for o-SWCNHs as well as with respect to conventional Glassy Carbon (GC) electrodes, in terms of peak currents, significant shift at lower redox-potential ranges and enhanced heterogeneous apparent kinetic constants.

In this study, we discuss the portfolio, also known as learning folder. It exist several types among different supports. Its principal objective is to trace the learnings and the students’ progress by the successive addition of their production in one or more disciplines. In this research waged in PE on 3rd grade students, we measure the impact that can have the presentation portfolio and the assessment portfolio on the learnings. Regarding on the results achieved, we can admit the students who keep a portfolio have a better awareness of progress achieved in PE. But, it is the students who profit of an assessment portfolio who have a progress rate superior to them who keep a presentation portfolio and well superior to them who don’t keep it. With the assessment portfolio, the student may therefore become aware of his progress and better integrate the criteria which make him succeed.; Nous traitons dans cet écrit du portfolio, également appelé dossier d’apprentissage. Il en existe plusieurs types selon différents supports. Il a pour objectif principal de retracer les apprentissages et les progressions des élèves par l’ajout successif de leurs productions dans une ou plusieurs disciplines. Dans cette recherche menée en EPS sur des élèves de 3e, nous mesurons l’impact que peuvent avoir le portfolio de présentation et le portfolio d’évaluation sur les apprentissages. Au regard des résultats obtenus, nous pouvons admettre que les élèves disposant d’un portfolio ont une meilleure conscience des progrès réalisés en EPS. Mais ce sont les élèves bénéficiant d’un portfolio d’évaluation qui ont un taux de progression supérieur à ceux disposant d’un portfolio de présentation et bien supérieur à ceux n’en disposant pas. Avec le portfolio d’évaluation, l’élève prend donc conscience de ses progrès et intègre mieux les critères lui permettant d’être en réussite.