Hebron University

About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.

Proteomic Identification of Desmoglein 2 and Activated Leukocyte Cell Adhesion Molecule as Substrates of ADAM17 and ADAM10 by Difference Gel Electrophoresis

Abstract: In contrast with the early view of metalloproteases as simple extracellular matrix-degrading entities, recent findings show that they are highly specific modulators of different signaling pathways involved, positively or negatively, in tumor development. Thus, before considering a given metalloprotease a therapeutic target, it seems advisable to characterize its function by identifying its repertoire of substrates. Here, we present a proteomic approach to identify ADAM17 substrates by difference gel electrophoresis. We found that the shedding of the extracellular domain of the transferrin receptor and those of two cell-cell adhesion molecules, activated leukocyte cell adhesion molecule (ALCAM) and desmoglein 2 (Dsg-2), is increased in cells overexpressing ADAM17. Genetic evidence shows that while ADAM17 is responsible for the shedding of ALCAM, both ADAM17 and ADAM10 can act on Dsg-2. Activation of the epidermal growth factor receptor leads to the upregulation of the shedding of Dsg-2 and to the concomitant upregulation of ADAM17, but not ADAM10, supporting the ability of overexpressed ADAM17 to shed Dsg-2. These results unveil a role of ADAM10 and ADAM17 in the shedding of cell-cell adhesion molecules. Since loss of cell adhesion is an early event in tumor development, these results suggest that ADAM17 is a useful target in anticancer therapy.

Is a planned caesarean section in women with cardiac disease beneficial

Abstract: Objectives In the general population, planned caesarean section is thought to be safer in high-risk situations as it avoids the greater risk of an emergency caesarean section. Only limited data exist on the optimal mode of delivery in women with structural heart disease. We investigated the relationship between mode of delivery and pregnancy outcome in women with preexisting heart disease. Methods The Registry on Pregnancy and Cardiac Disease is an on-going, global, prospective observational registry of women with structural heart disease. We report on 1262 deliveries, between January 2007 and June 2011. Results The caesarean section was planned in 393 women (31%): 172 (44%) for cardiac and 221 (56%) for obstetric reasons of whom 53 delivered by emergency caesarean section. Vaginal delivery was planned in 869 (69%) women, of whom 726 (84%) actually delivered vaginally and 143 (16%) had an emergency caesarean section. Perinatal mortality(1.1 vs 2.7, p=0.14) and low apgar score (11.9 vs 10.1, p=0.45) were not significantly different in women who had a caesarean section or vaginal delivery; gestational age(37 vs 38 weeks p=0.003) and birth weight (3073 vs 2870 g p<0.001) were lower in women delivered by caesarean section compared with women delivered by vaginal delivery. In those delivered by elective or emergency caesarean section, there was no difference in maternal mortality (1.8% vs 1.5%, p=1.0), postpartum heart failure (8.8% vs 8.2% p=0.79) or haemorrhage (6.2% vs 5.1% p=0.61). Conclusions These data suggest that planned caesarean section does not confer any advantage over planned vaginal delivery, in terms of maternal outcome, but is associated with an adverse fetal outcome.

Predicting responders to therapies for multiple sclerosis

Abstract: Therapies for relapsing-remitting multiple sclerosis (RRMS) are only partially effective, and, in most patients receiving such treatment, clinical activity persists. Accurately assessing the treatment response to disease-modifying agents enables non-responder patients to be identified at an early stage into therapy. Patients can then be switched to another, potentially more effective, therapy before too much neurological damage has occurred. Several criteria based on relapses, disability progression or both have been proposed for clinical evaluation of the treatment response to disease-modifying agents. These criteria have not been independently validated, however, and no consensus over which are the best to use currently exists among investigators. MRI can also be employed to detect disease activity in patients treated with disease-modifying agents. Changes on MRI can provide subclinical data relating to disease activity that can be of great benefit in patients monitoring, as inflammatory events occur more often than clinical events. Pharmacogenomic approaches are in the early stages of development for MS, but hold great promise for the eventual development of individually tailored therapies. In this Review, we discuss the proposed approaches for monitoring and predicting treatment responses to disease-modifying agents in patients with RRMS. We evaluate the roles of clinical measures, MRI and pharmacogenomics in these processes.

Clinical impact and evolution of mitral regurgitation following transcatheter aortic valve replacement: a meta-analysis

Abstract: Objectives Mitral regurgitation (MR) is a common entity in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), but its influence on outcomes remains controversial. The purpose of this meta-analysis was to assess the clinical impact of and changes in significant (moderate–severe) MR in patients undergoing TAVR, overall and according to valve design (self-expandable (SEV) vs balloon-expandable (BEV)). Methods All national registries and randomised trials were pooled using meta-analytical guidelines to establish the impact of moderate–severe MR on mortality after TAVR. Studies reporting changes in MR after TAVR on an individual level were electronically searched and used for the analysis. Results Eight studies including 8015 patients (SEV: 3474 patients; BEV: 4492 patients) were included in the analysis. The overall 30-day and 1-year mortality was increased in patients with significant MR (OR 1.49, 95% CI 1.16 to 1.92; HR 1.32, 95% CI 1.12 to 1.55, respectively), but a significant heterogeneity across studies was observed (p Conclusions Concomitant moderate–severe MR was associated with increased early and late mortality following TAVR. A significant improvement in MR severity was detected in half of the patients following TAVR, and the degree of improvement was greater in those patients who had received a BEV.