Convergence towards a European strategic culture? A constructivist framework for explaining changing norms.

The article contributes to the debate about the emergence of a European strategic culture to underpin a European Security and Defence Policy. Noting both conceptual and empirical weaknesses in the literature, the article disaggregates the concept of strategic culture and focuses on four types of norms concerning the means and ends for the use of force. The study argues that national strategic cultures are less resistant to change than commonly thought and that they have been subject to three types of learning pressures since 1989: changing threat perceptions, institutional socialization, and mediatized crisis learning. The combined effect of these mechanisms would be a process of convergence with regard to strategic norms prevalent in current EU countries. If the outlined hypotheses can be substantiated by further research the implications for ESDP are positive, especially if the EU acts cautiously in those cases which involve norms that are not yet sufficiently shared across countries

Epstein-Barr virus–associated lymphoproliferative disorders

Epstein-Barr virus (EBV) is a member of the human herpesvirus family that was initially isolated from a cultured Burkitt lymphoma cell line by Epstein et al in 1964. Subsequent studies have proven that it is the causative agent in most cases of infectious mononucleosis. Primary infection is usually asymptomatic in childhood; but in adulthood, it is associated with a self-limiting infectious mononucleosis syndrome in approximately one third of the cases. EBV has been linked to many human neoplasms including hematopoietic, epithelial, and mesenchymal tumors. In this review, we will only discuss the EBV-associated lymphoproliferative disorders, dividing them into B-cell, T/NK-cell, and HIV-related lymphoproliferative disorders

Pleiotropic effect of the proton pump inhibitor esomeprazole leading to suppression of lung inflammation and fibrosis

Background: The beneficial outcome associated with the use of proton pump inhibitors (PPIs) in idiopathic pulmonary fibrosis (IPF) has been reported in retrospective studies. To date, no prospective study has been conducted to confirm these outcomes. In addition, the potential mechanism by which PPIs improve measures of lung function and/or transplant-free survival in IPF has not been elucidated. Methods: Here, we used biochemical, cell biological and preclinical studies to evaluate regulation of markers associated with inflammation and fibrosis. In our in vitro studies, we exposed primary lung fibroblasts, epithelial and endothelial cells to ionizing radiation or bleomycin; stimuli typically used to induce inflammation and fibrosis. In addition, we cultured lung fibroblasts from IPF patients and studied the effect of esomeprazole on collagen release. Our preclinical study tested efficacy of esomeprazole in a rat model of bleomycin-induced lung injury. Furthermore, we performed retrospective analysis of interstitial lung disease (ILD) databases to examine the effect of PPIs on transplant-free survival. Results: The cell culture studies revealed that esomeprazole controls inflammation by suppressing the expression of pro-inflammatory molecules including vascular cell adhesion molecule-1, inducible nitric oxide synthase, tumor necrosis factor-alpha (TNF-alpha) and interleukins (IL-1 beta and IL-6). The antioxidant effect is associated with strong induction of the stress-inducible cytoprotective protein heme oxygenase-1 (HO1) and the antifibrotic effect is associated with potent inhibition of fibroblast proliferation as well as downregulation of profibrotic proteins including receptors for transforming growth factor beta (TGF beta), fibronectin and matrix metalloproteinases (MMPs). Furthermore, esomeprazole showed robust effect in mitigating the inflammatory and fibrotic responses in a murine model of acute lung injury. Finally, retrospective analysis of two ILD databases was performed to assess the effect of PPIs on transplant-free survival in IPF patients. Intriguingly, this data demonstrated that IPF patients on PPIs had prolonged survival over controls (median survival of 3.4 vs 2 years). Conclusions: Overall, these data indicate the possibility that PPIs may have protective function in IPF by directly modulating the disease process and suggest that they may have other clinical utility in the treatment of extra-intestinal diseases characterized by inflammatory and/or fibrotic phases.Stanford School of Medicine [1049528-149- KAVFB]; Tobacco-Related Disease Research Program of the University of California [20FT-0090]; National Institutes of Health National Heart, Lung, and Blood Institute [5K01HL118683, P01HL114470]; Houston Methodist Research Institute [25150001]; Stanford SPARK Translational Research ProgramSCI(E)[email protected]