Chronic intranasal administration of mould spores or extracts to unsensitized mice leads to lung allergic inflammation, hyper-reactivity and remodelling

Allergic asthma is a serious multifaceted disease characterized by eosinophil-rich airway inflammation, airway hyperreactivity and airway wall modifications known as remodelling. We previously demonstrated that the spores of two allergenic moulds, Alternaria alternata and Cladosporium herbarum, were potent inducers of immunoglobulin E (IgE) production. Moreover, mice sensitized by two intraperitoneal injections before intranasal challenge with A. alternata or C. herbarum spores developed an allergic lung inflammation and hyperreactivity. Here we report on the effect of chronic intranasal administration of C. herbarum spores or A. alternata extracts to unsensitized BALB/c mice. Our results demonstrate that this chronic treatment led to an increase of total serum IgE and the appearance of specific IgE and IgG1. Total cell number in bronchoalveolar lavage fluid from treated mice was highly increased compared to phosphate-buffered-saline-treated mice because of the accumulation of macrophages, neutrophils, lymphocytes and eosinophils. Airway hyperreactivity appeared after 3 weeks (extract) and 7 weeks (spores) and was maintained during the whole treatment. Increased interleukin-13 mRNA expression in the lungs and T helper type 2 cytokines (interleukin-4, -5, -6 and -13) and transforming growth factor-beta secretion in bronchoalveolar lavage fluid were also observed. Lung hydroxyproline and fibronectin contents indicated increased fibrosis in mice treated with mould allergen. These observations were confirmed by histological analysis demonstrating airway wall remodelling and strong mucus production. These observations show that this model, using chronic intranasal administration of relevant particulate allergens, is an interesting tool for the study of mechanisms leading to allergic pulmonary diseases and lung remodelling.     

Polymer gel dosimetry for synchrotron stereotactic radiotherapy and iodine dose-enhancement measurements

Synchrotron stereotactic radiotherapy (SSR) is a radiotherapy technique that makes use of the interactions of monochromatic low energy x-rays with high atomic number (Z) elements. An important dose-enhancement can be obtained if the target volume has been loaded with a sufficient amount of a high-Z element, such as iodine. In this study, we compare experimental dose measurements, obtained with normoxic polymer gel (nPAG), with Monte Carlo computations. Gels were irradiated within an anthropomorphic head phantom and were read out by magnetic resonance imaging. The dose-enhancement due to the presence of iodine in the gel (iodine concentration: 5 and 10 mg ml(-1)) was measured at two radiation energies (35 and 80 keV) and was compared to the calculated factors. nPAG dosimetry was shown to be efficient for measuring the sharp dose gradients produced by SSR. The agreement between 3D gel dosimetry and calculated dose distributions was found to be within 4% of the dose difference criterion and a distance to agreement of 2.1 mm for 80% of the voxels. Polymer gel doped with iodine exhibited higher sensitivity, in good agreement with the calculated iodine-dose enhancement. We demonstrate in this preliminary study that iodine-doped nPAG could be used for measuring in situ dose distributions for iodine-enhanced SSR treatment.     

Study of mutual influence between trait anxiety and risk of depression among older couples facing cancer

IntroductionThe present study aims to examine the process of mutual influence in older couples with cancer diagnosis by studying their risk of depression.Materials and methods282 couples with one spouse diagnosed with cancer were selected from the Three-City cohort study. Dyadic analyses were used to determine whether trait anxiety affects the risk of depression and whether a mutual influence process occurs prior and post cancer diagnosis. Cross-sectional analyses were performed at two time-points: before and after receiving the diagnosis.ResultsA higher level of anxiety among cancer patients resulted in a decreased risk of depression among spousal caregivers. Moreover, a higher anxiety among spousal caregivers increased their own risk of depression, but it didn't influence depression risk among cancer patients. While there is an intra-individual relationship between a higher level of trait anxiety and a greater risk of depression prior to cancer diagnosis, there is no cross-influence between spouses.DiscussionThe study findings indicate that a dyadic psychological adjustment process might help older adults to cope with cancer by limiting the risk of depression among spousal caregivers.     

Scale-adaptive supervoxel-based random forests for liver tumor segmentation in dynamic contrast-enhanced CT scans

Purpose

Toward an efficient clinical management of hepatocellular carcinoma (HCC), we propose a classification framework dedicated to tumor necrosis rate estimation from dynamic contrast-enhanced CT scans. Based on machine learning, it requires weak interaction efforts to segment healthy, active and necrotic liver tissues.

Methods

Our contributions are two-fold. First, we apply random forest (RF) on supervoxels using multi-phase supervoxel-based features that discriminate tissues based on their dynamic in response to contrast agent injection. Second, we extend this technique in a hierarchical multi-scale fashion to deal with multiple spatial extents and appearance heterogeneity. It translates in an adaptive data sampling scheme combining RF and hierarchical multi-scale tree resulting from recursive supervoxel decomposition. By concatenating multi-phase features across the hierarchical multi-scale tree to describe leaf supervoxels, we enable RF to automatically infer the most informative scales without defining any explicit rules on how to combine them.

Results

Assessment on clinical data confirms the benefits of multi-phase information embedded in a multi-scale supervoxel representation for HCC tumor segmentation.

Conclusion

Dedicated but not limited only to HCC management, both contributions reach further steps toward more accurate multi-label tissue classification.

     

Destruction of nonimmunogenic mammary tumor cells by a fusogenic oncolytic herpes simplex virus induces potent antitumor immunity.

In principle, destruction of tumor cells in vivo by oncolytic agents would release the entire repertoire of tumor antigens in their natural forms, leading to effective antitumor immunity. This goal has been elusive despite extensive testing of numerous strategies. We developed a doubly fusogenic oncolytic herpes simplex virus (Synco-2D) that kills tumor cells by a unique dual mechanism combining direct cytolysis with syncytial formation induced by cell membrane fusion. A single intratumor injection of Synco-2D induced strong antitumor immunity against an otherwise nonimmunogenic murine mammary tumor growing in immune-competent mice. CD8+ T cells were the primary mediators of immunity, contributing to the destruction of both primary and metastatic tumors. We conclude that the fusogenic capacity of Synco-2D enables it to elicit antitumor immunity exceeding that induced by more conventional oncolytic viruses.     

Thoracic skeletal anomalies following surgical treatment of esophageal atresia. Lessons from a national cohort

Introduction

Thoracotomy as surgical approach for esophageal atresia treatment entails the risk of deformation of the rib cage and consequently secondary thoracogenic scoliosis. The aim of our study was to assess these thoracic wall anomalies on a large national cohort and search for factors influencing this morbidity.

Solitary fibrous tumours and haemangiopericytoma of the meninges. A retrospective study for outcome and prognostic factor assessment

Background

To report on the outcome of patients diagnosed with central nervous system haemangiopericytoma (HPC) or solitary fibrous tumours (SFT) and identify factors that may influence recurrence and survival.