Deflected Jet Experiments in a Turbulent Combustor Flowfield

Mechanical Engineerin

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Differences in depression, anxiety, and quality of life between women with and without breast pain prior to breast cancer surgery

PURPOSE OF THE RESEARCH: Little is known about the relationships between pain, anxiety, and depression in women prior to breast cancer surgery. The purpose of this study was to evaluate for differences in anxiety, depression, and quality of life (QOL) in women who did and did not report the occurrence of breast pain prior to breast cancer surgery. We hypothesized that women with pain would report higher levels of anxiety and depression as well as poorer QOL than women without pain. METHODS AND SAMPLE: A total of 390 women completed self-report measures of pain, anxiety depression, and QOL prior to surgery. KEY RESULTS: Women with preoperative breast pain (28%) were significantly younger, had a lower functional status score, were more likely to be Non-white and to have gone through menopause. Over 37% of the sample reported clinically meaningful levels of depressive symptoms. Almost 70% of the sample reported clinically meaningful levels of anxiety. Patients with preoperative breast pain reported significantly higher depression scores and significantly lower physical well-being scores. No between group differences were found for patients' ratings of state and trait anxiety or total QOL scores. CONCLUSIONS: Findings from this study suggest that, regardless of pain status, anxiety and depression are common problems in women prior to breast cancer surgery

Identification of patient subgroups and risk factors for persistent arm/shoulder pain following breast cancer surgery

PURPOSE: In this prospective, longitudinal study, we extend our findings on persistent breast pain in patients (n=398) following breast cancer surgery and evaluate the prevalence and characteristics of persistent pain in the arm/shoulder In addition, differences in the severity of common symptoms and quality of life outcomes measured prior to surgery, among the arm pain classes, were evaluated. METHODS AND SAMPLE: Patients were recruited from Breast Care Centers located in a Comprehensive Cancer Center, two public hospitals, and four community practices. Patients were assessed prior to and monthly for six months following breast cancer surgery. RESULTS: Using growth mixture modeling, patients were classified into no (41.6%), mild (23.6%), and moderate (34.8%) arm pain classes based on ratings of worst arm/shoulder pain. Compared to the no pain class, patients in the moderate pain class were significantly younger, had a higher body mass index, and were more likely to report preoperative breast pain and swelling in the affected breast. In addition, patients in the moderate pain class reported higher levels of depression, anxiety, and sleep disturbance than the no pain class. CONCLUSIONS: Findings suggest that approximately 35% of women experience persistent levels of moderate arm/shoulder pain in the first six months following breast cancer surgery. Moderate arm/shoulder pain is associated with clinically meaningful decrements in functional status and quality of life

Identification of patient subgroups and risk factors for persistent breast pain following breast cancer surgery.

UnlabelledStudy purposes were to determine the prevalence of persistent pain in the breast; characterize distinct persistent pain classes using growth mixture modeling; and evaluate for differences among these pain classes in demographic, preoperative, intraoperative, and postoperative characteristics. In addition, differences in the severity of common symptoms and quality of life outcomes measured prior to surgery, among the pain classes, were evaluated. Patients (n = 398) were recruited prior to surgery and followed for 6 months. Using growth mixture modeling, patients were classified into no (31.7%), mild (43.4%), moderate (13.3%), and severe (11.6%) pain groups based on ratings of worst breast pain. Differences in a number of demographic, preoperative, intraoperative, and postoperative characteristics differentiated among the pain classes. In addition, patients in the moderate and severe pain classes reported higher preoperative levels of depression, anxiety, and sleep disturbance than the no pain class. Findings suggest that approximately 25% of women experience significant and persistent levels of breast pain in the first 6 months following breast cancer surgery.PerspectivePersistent pain is a significant problem for 25% of women following surgery for breast cancer. Severe breast pain is associated with clinically meaningful decrements in functional status and quality of life

The emergence of proteinase-activated receptor-2 as a novel target for the treatment of inflammation-related CNS disorders

The signalling molecules that are involved in inflammatory pathways are now thought to play a part in many disorders of the central nervous system (CNS). In common with peripheral chronic inflammatory diseases such a rheumatoid arthritis and ulcerative colitis, evidence now exists for the involvement of inflammatory cytokines, for example tumour necrosis factor (TNF) and interleukins (IL), in neurological disorders. A common factor observed with the up-regulation of these cytokines in peripheral inflammatory diseases, is the increased expression of the proteinase-activated receptor (PAR) subtype PAR-2. Indeed, recent evidence suggests that targeting PAR-2 helps reduce joint swelling observed in animal models of arthritis. So could targeting this receptor prove to be useful in treating those CNS disorders where inflammatory processes are thought to play an intrinsic role? The aim of this review is to summarize the emerging data regarding the role of PAR-2 in neuroinflammation and ischaemic injury and discuss its potential as an exciting new target for the prevention and/or treatment of CNS disorders

Lymphatic and Angiogenic Candidate Genes Predict the Development of Secondary Lymphedema following Breast Cancer Surgery

The purposes of this study were to evaluate for differences in phenotypic and genotypic characteristics in women who did and did not develop lymphedema (LE) following breast cancer treatment. Breast cancer patients completed a number of self-report questionnaires. LE was evaluated using bioimpedance spectroscopy. Genotyping was done using a custom genotyping array. No differences were found between patients with (n = 155) and without LE (n = 387) for the majority of the demographic and clinical characteristics. Patients with LE had a significantly higher body mass index, more advanced disease and a higher number of lymph nodes removed. Genetic associations were identified for four genes (i.e., lymphocyte cytosolic protein 2 (rs315721), neuropilin-2 (rs849530), protein tyrosine kinase (rs158689), vascular cell adhesion molecule 1 (rs3176861)) and three haplotypes (i.e., Forkhead box protein C2 (haplotype A03), neuropilin-2 (haplotype F03), vascular endothelial growth factor-C (haplotype B03)) involved in lymphangiogensis and angiogenesis. These genetic associations suggest a role for a number of lymphatic and angiogenic genes in the development of LE following breast cancer treatment