Nuclear factor B (NF-B) activation has been observed in human atherosclerotic plaques and is enhanced in unstable coronary plaques, but whether such activation has a protective or pathophysiological role remains to be determined. We addressed this question by developing a short-term culture system of cells isolated from human atherosclerotic tissue, allowing efficient gene transfer to directly investigate signaling pathways in human atherosclerosis. We found that NF-B is activated in these cells and that this activity involves p65, p50, and c-Rel but not p52 or RelB. This NF-B activation can be blocked by overexpression of IB␣ or dominant-negative IB kinase (IKK)-2 but not dominant-negative IKK-1 or NF-B-inducing kinase, resulting in selective inhibition of inflammatory cytokines (tumor necrosis factor ␣, IL-6, and IL-8), tissue factor, and matrix metalloproteinases without affecting the antiinflammatory cytokine IL-10 or tissue inhibitor of matrix metalloproteinases. Our results demonstrate that the canonical pathway of NF-B activation that involves p65, p50, c-Rel, and IKK-2 is activated in human atherosclerosis and results in selective upregulation of major proinflammatory and prothrombotic mediators of the disease.

Background: Healthcare professionals can be seriously affected when they are involved in major clinical incidents. The impact of such incidents on staff is of particular relevance to surgery, as the operating room is one of the highest-risk areas for serious complications. This qualitative study aimed to assess the personal and professional impact of surgical complications on surgeons.Methods: This single time point study involved semistructured, individual interviews with general and vascular surgeons, consultants and senior registrars from two National Health Service organizations in London, UK.Results: Twenty-seven surgeons participated. Many were seriously affected by major surgical complications. Surgeons' practice was also often affected, not always in the best interest of their patients. The surgeons' reactions depended on the preventability of the complications, their personality and experience, patient outcomes and patients' reactions, as well as colleagues' reactions and the culture of the institution. Discussing complications, deconstructing the incidents and rationalizing were the most commonly quoted coping mechanisms. Institutional support was generally described as inadequate, and the participants often reported the existence of strong institutional blame cultures. Suggestions for supporting surgeons in managing the personal impact of complications included better mentoring, teamwork approaches, blame-free opportunities for the discussion of complications, and structures aimed at the human aspects of complications. Conclusion:Those involved in the management of surgical services need to consider how to improve support for surgeons in the aftermath of major surgical incidents.

Aortic dissection is the most common acute catastrophic event affecting the thoracic aorta. The majority of patients presenting with an uncomplicated type B dissection are treated medically, but 25% of these patients develop subsequent aneurysmal dilatation of the thoracic aorta. This study aimed at gaining more detailed knowledge of the flow phenomena associated with this condition. Morphological features and flow patterns in a dissected aortic segment of a presurgery type B dissection patient were analyzed based on computed tomography images acquired from the patient. Computational simulations of blood flow in the patient-specific model were performed by employing a correlation-based transitional version of Menter's hybrid k-epsilon/k-omega shear stress transport turbulence model implemented in ANSYS CFX 11. Our results show that the dissected aorta is dominated by locally highly disturbed, and possibly turbulent, flow with strong recirculation. A significant proportion (about 80%) of the aortic flow enters the false lumen, which may further increase the dilatation of the aorta. High values of wall shear stress have been found around the tear on the true lumen wall, perhaps increasing the likelihood of expanding the tear. Turbulence intensity in the tear region reaches a maximum of 70% at midsystolic deceleration phase. Incorporating the non-Newtonian behavior of blood into the same transitional flow model has yielded a slightly lower peak wall shear stress and higher maximum turbulence intensity without causing discernible changes to the distribution patterns. Comparisons between the laminar and turbulent flow simulations show a qualitatively similar distribution of wall shear stress but a significantly higher magnitude with the transitional turbulence model.