STAT3 Regulates Monocyte TNF-Alpha Production in Systemic Inflammation Caused by Cardiac Surgery with Cardiopulmonary Bypass

BACKGROUND: Cardiopulmonary bypass (CPB) surgery initiates a controlled systemic inflammatory response characterized by a cytokine storm, monocytosis and transient monocyte activation. However, the responsiveness of monocytes to Toll-like receptor (TLR)-mediated activation decreases throughout the postoperative course. The purpose of this study was to identify the major signaling pathway involved in plasma-mediated inhibition of LPS-induced tumor necrosis factor (TNF)-α production by monocytes. METHODOLOGY/PRINCIPAL FINDINGS: Pediatric patients that underwent CPB-assisted surgical correction of simple congenital heart defects were enrolled (n = 38). Peripheral blood mononuclear cells (PBMC) and plasma samples were isolated at consecutive time points. Patient plasma samples were added back to monocytes obtained pre-operatively for ex vivo LPS stimulations and TNF-α and IL-6 production was measured by flow cytometry. LPS-induced p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation by patient plasma was assessed by Western blotting. A cell-permeable peptide inhibitor was used to block STAT3 signaling. We found that plasma samples obtained 4 h after surgery, regardless of pre-operative dexamethasone treatment, potently inhibited LPS-induced TNF-α but not IL-6 synthesis by monocytes. This was not associated with attenuation of p38 MAPK activation or IκB-α degradation. However, abrogation of the IL-10/STAT3 pathway restored LPS-induced TNF-α production in the presence of suppressive patient plasma. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that STAT3 signaling plays a crucial role in the downregulation of TNF-α synthesis by human monocytes in the course of systemic inflammation in vivo. Thus, STAT3 might be a potential molecular target for pharmacological intervention in clinical syndromes characterized by systemic inflammation

Manufacturing considerations of the magnetic structures for the undulators for the X-FEL at TESLA

A study is presented to estimate the production effort of the magnetic structures for the undulatorsystems of the TESLA X-ray SASE FELs. The total magnetic length of the magnet structures is1405m. It is proposed to produce these huge quantity ‘turn key ready’ on an industrial scale. Thisimplies a resolute R&D effort. It should include the improvement and optimization of the materialquality of NdFeB material, the development of robustmagnetic measurement and fine tuningtechniques, which can be used in an industrial environment and an extended prototyping phase. Thesedevelopments are prerequisite for successful industrial production and are described in more detail. Anestimate is made for production capacities which are required to produce 1405m of magnetic structurewithin five years

Coronary artery bypass grafting: Part 2-optimizing outcomes and future prospects

Since first introduced in the mid-1960s, coronary artery bypass grafting (CABG) has become the standard of care for patients with coronary artery disease. Surprisingly, the fundamental surgical technique itself did not change much over time. Nevertheless, outcomes after CABG have dramatically improved over the first 50 years. Randomized trials comparing percutaneous coronary intervention (PCI) to CABG have shown converging outcomes for select patient populations, providing more evidence for wider use of PCI. It is increasingly important to focus on the optimization of the short- and long-term outcomes of CABG and to reduce the level of invasiveness of this procedure. This review provides an overview on how new techniques and widespread consideration of evolving strategies have the potential to optimize outcomes after CABG. Such developments include off-pump CABG, clampless/anaortic CABG, minimally invasive CABG with or without extending to hybrid procedures, arterial revascularization, endoscopic vein harvesting, intraprocedural epiaortic scanning, graft flow assessment, and improved secondary prevention measures. In addition, this review represents a framework for future studies by summarizing the areas that need more rigorous clinical (randomized) evaluation