Mooring forces in horizontal interlaced multilayered Floating pipe breakwater with three layers

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

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

Reactions of arylaminomethylenemalonates with amines

The reaction of arylaminomethylenemalonates with amines can in some cases lead to ami-dines, e.g. reaction of diethyl N-[4-(3-methyl-4-isothiazolyl)-2-thiazolyl]aminomethylenemalonate (IV) with morpholine and pyrrolidine gives the corresponding-amidines besides 2-amino-4-(3-methyl-4-isothiazolyl) thiazole (III), the starting substrate for the preparation of (IV). The reaction of IV with N-methylpiperazine gives only III. Mechanism to explain the regeneration of III in the reaction of IV with amines has been suggested

The Intensive Dysphagia Rehabilitation Approach Applied to Patients with Neurogenic Dysphagia: A Case Series Design Study Presented in part to the American Speech Language and Hearing Association, November 20, 2014, Orlando, FL.

Objective To examine the effects of the Intensive Dysphagia Rehabilitation approach on physiological and functional swallowing outcomes in adults with neurogenic dysphagia. Design Intervention study; before-after trial with 4-week follow-up through an online survey. Setting Outpatient university clinics. Participants A consecutive sample of subjects (N=10) recruited from outpatient university clinics. All subjects were diagnosed with adult-onset neurologic injury or disease. Dysphagia diagnosis was confirmed through clinical and endoscopic swallowing evaluations. No subjects withdrew from the study. Interventions Participants completed the 4-week Intensive Dysphagia Rehabilitation protocol, including 2 oropharyngeal exercise regimens, a targeted swallowing routine using salient stimuli, and caregiver participation. Treatment included hourly sessions twice per week and home practice for approximately 45min/d. Main Outcome Measures Outcome measures assessed pre- and posttreatment included airway safety using an 8-point Penetration Aspiration Scale, lingual isometric pressures, self-reported swallowing-related quality of life (QOL), and level of oral intake. Also, patients were monitored for adverse dysphagia-related effects. QOL and adverse effects were also assessed at the 4-week follow-up (online survey). Results The Intensive Dysphagia Rehabilitation approach was effective in improving maximum and mean Penetration Aspiration Scale scores (P<.05, η2=.8146 and P<.05, η2=.799708, respectively) and level of oral intake (P<.005, Cohen d=-1.387). Of the 5 patients who were feeding tube dependent initially, 2 progressed to total oral nutrition, and 2 progressed to partial oral nutrition. One patient remained tube dependent. QOL was significantly improved at the 4-week follow-up (95% confidence interval, 6.38-14.5; P<.00), but not at the posttreatment. No adverse effects were observed/reported. Conclusions The Intensive Dysphagia Rehabilitation approach was safe and improved physiological and some functional swallowing outcomes in our sample; however, further investigation is needed before it can be widely applied. © 2016 American Congress of Rehabilitation Medicine

Synthesis of O-acylbenzohydroxamic acids and their use in peptide synthesis

The addition of N-protected amino acids to benzonitrile oxides yields activated esters, which on coupling with amino acid esters lead to peptides