Stimulation of immature lung macrophages with intranasal interferon gamma in a novel neonatal mouse model of respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral death in infants. Reduced CD8 T-cells and negligible interferon gamma (IFNγ) in the airway are associated with severe infant RSV disease, yet there is an abundance of alveolar macrophages (AM) and neutrophils. However, it is unclear, based on our current understanding of macrophage functional heterogeneity, if immature AM improve viral clearance or contribute to inflammation and airway obstruction in the IFNγ-deficient neonatal lung environment. The aim of the current study was to define the age-dependent AM phenotype during neonatal RSV infection and investigate their differentiation to classically activated macrophages (CAM) using i.n. IFNγ in the context of improving viral clearance. Neonatal and adult BALB/cJ mice were infected with 1×106 plaque forming units (PFU)/gram (g) RSV line 19 and their AM responses compared. Adult mice showed a rapid and robust CAM response, indicated by increases in major histocompatibility complex class II (MHC II), CD86, CCR7, and a reduction in mannose receptor (MR). Neonatal mice showed a delayed and reduced CAM response, likely due to undetectable IFNγ production. Intranasal (i.n.) treatment with recombinant mouse IFNγ (rIFNγ) increased the expression of CAM markers on neonatal AM, reduced viral lung titers, and improved weight gain compared to untreated controls with no detectable increase in CD4 or CD8 T-cell infiltration. In vitro infection of J774A.1 macrophages with RSV induced an alternatively activated macrophage (AAM) phenotype however, when macrophages were first primed with IFNγ, a CAM phenotype was induced and RSV spread to adjacent Hep-2 cells was reduced. These studies demonstrate that the neonatal AM response to RSV infection is abundant and immature, but can be exogenously stimulated to express the antimicrobial phenotype, CAM, with i.n. rIFNγ. © 2012 Empey et al

War and peace in The Law of Peoples: Rawls, Kant and the use of force

Where Rawls’s The Law of Peoples addresses war and the use of force then his position has often been identified closely with Walzer’s restatement of just war theory, as both positions appear to take nation-states, and the conflicts between them, to be the bedrock of the international system. On the other hand, Kant’s notion of a peaceful federation of states presents us with the notion of a world without war and where the international system is transformed. This article argues that Rawls’s account of the use of force is better understood if we read it with an eye to its resonances with Kant rather than with Walzer. Doing so rewards us with a clearer understanding of central aspects of Rawls’s account of just war and vision of international politic

Laminin α5 guides tissue patterning and organogenesis

Laminins (LM) are extracellular matrix molecules that contribute to and are required for the formation of basement membranes. They participate in the modulation of epithelial/mesenchymal interactions and are implicated in organogenesis and maintenance of organ homeostasis. Among the LM molecules, the LM α5 chain (LMα5) is one of the most widely distributed LM in the developing and mature organism. Its presence in some basement membranes during embryogenesis is absolutely required for maintenance of basement membrane integrity and thus for proper organogenesis. LMα5 also regulates the expression of genes important for major biological processes, in part by repressing or activating signaling pathways, depending upon the physiological context

Just cyber war?: Casus belli, information ethics, and the human perspective

Does the advent of cyber-war require us to abandon the traditional ethical framework for thinking about the morality of warfare - just war theory - and develop principles specific to the unique nature of cyber-attacks? Or can just war theory still provide an appropriate basis for thinking through the ethical issues raised by cyber-weapons? This article explores these questions via the issue of whether a cyber-attack can constitute a casus belli. The first half of the paper critically engages with recent attempts to provide a new theory of just information warfare (JIW) that is supposedly better suited to the unique character of cyber war insofar as it is grounded the broader meta-ethical framework of information ethics (IE). Yet the paper argues that not only is JIW fundamentally unsuitable as a way of thinking about cyber-war, but (in the second half) that it is possible to develop a different account of how we can understand a cyber-attack as constituting a casus belli in a way that is in keeping with traditional just war theory. In short, there is no need to reinvent just war theory for the digital age

Technical and clinical success after endovascular therapy for chronic type B aortic dissections

ObjectiveTo analyze early technical success and late clinical success after endovascular entry sealing for chronic type B dissection with special emphasis on reintervention, false lumen thrombosis, and aortic remodeling.MethodsRetrospective analysis of a prospective database. From September 1999 to January 2011, 19 patients with chronic type B dissections were treated by endovascular entry sealing. Median age was 60 years. Median time between onset of acute dissection and surgical intervention was 36 (1 to 60) months. Median follow-up was 13 months (1 to 124).ResultsThe endografts used were: Medtronic Captivia (5), Medtronic Valiant (5), Gore TAG (6), Gore C-TAG (2), and Cook Zenith (1). In four patients, revascularization of the left subclavian artery was performed prior to entry sealing. Primary technical success rate (entry sealing, absence of type I leak) was 18/19 (94.7%). In-hospital mortality was 0%. Spinal cord injury with persistent paraplegia occurred in 1/19 (5.2%) patients. After a maximal follow-up of 124 months, reinterventions in 9/19 (47.3%) were necessary: distal/proximal extension of stent graft (8), replacement of the aortic arch due to retrograde dissection (1), and open infrarenal aneurysm repair (1). During follow-up, none of the patients died due to stent-related complications.ConclusionEndovascular treatment (EVT) in chronic type B dissections has a high technical success rate and low mortality/morbidity. However reintervention rates are not negligible which might reduce the clinical success of EVT. Future investigations should aim at identifying patients who benefit from EVT at better defining the timing of EVT and at determining if entry sealing alone is sufficient

Effect of statin therapy on serum activity of proteinases and cytokines in patients with abdominal aortic aneurysm

Bernd Muehling1, Alexander Oberhuber1, Hubert Schelzig1, Gisela Bischoff1, Nikolaus Marx2, Ludger Sunder-Plassmann1, Karl H Orend11Department of Thoracic and Vascular surgery; 2Department of Internal Medicine, University of Ulm, Ulm, GermanyBackground and aims: Metalloproteinases (MMPs) are considered to be key enzymes in the pathogenesis of abdominal aortic aneurysms (AAA), with elevated levels in diseased aorta and in patient sera. Statins seem to exert an inhibitory effect on MMP activity in the aortic wall. No data exist on the effect of statins on serum activity of MMPs and inflammatory cytokines (interleukins, IL).Methods: The serum activities of MMP2 and MMP9, osteoprotegerin (OPG), and IL6 and IL10 in 63 patients undergoing elective infrarenal aneurysm repair were measured on the day before surgery. Levels were correlated to statin therapy and aneurysm diameter.Results: There was no significant difference between the two groups in the activity of circulating levels of MMP2/9, OPG, and IL6/10 in patients with infrarenal aortic aneurysm. IL6 levels in patients with AAA larger than 6 cm were significantly elevated; differences in serum activities of MMP2/9, OPG, and IL10 were not related to AAA diameter.Conclusion: Serum activities of MMP2/9, OPG, and IL6/10 are not correlated to statin therapy; IL6 levels are higher in patients with large aneurysms. Hence the effect of statin therapy in the treatment of aneurismal disease remains to be elucidated.Keywords: biomarkers, aneurismal disease, statin therap