Conformational control of integrin subtype selectivity in isoDGR peptide motifs: A biological switch

Thumbnail image of graphical abstract The rearrangement of asparagine to isoaspartate (isoD) is responsible for the deactivation of many functional proteins. However, the isoDGR motif, which is optimally presented as a conformationally controlled cyclic pentapeptide, binds selectively to a5ß1 integrin (see the docking model) with an affinity comparable to that of the peptidic antitumor agent CilengitidePeer ReviewedPostprint (published version

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Conformational control of integrin-subtype selectivity in isodgr peptide motifs: A biological switch

The rearrangement of asparagine to isoaspartate (isoD) is responsible for the deactivation of many functional proteins. However, the isoDGR motif, which is optimally presented as a conformationally controlled cyclic pentapeptide, binds selectively to α5β 1 integrin (see the docking model) with an affinity comparable to that of the peptidic antitumor agent Cilengitide. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Evaluation of the single cervical skin test and interferon gamma responses to detect Mycobacterium bovis infected cattle in a herd co-infected with Mycobacterium avium subsp. paratuberculosis

This study reports the performance of the single intradermal tuberculin (SIT) test and the interferon-gamma (IFN-γ) assay for Mycobacterium bovis in a cattle herd with high prevalence of paratuberculosis (PTB). A total of 58/350 animals were selected for necropsy based on one or more of the following criteria: positive to SIT, IFN-γ, a breeding cow that seroconverted to PTB and showed signs compatible with a wasting disease. Infection status was determined by post mortem diagnostic tests that included histopathology examination, mycobacterial cultures and PCR identification for M. bovis and Mycobacterium avium subsp. paratuberculosis (MAP). In 7/58 animals primary tuberculosis (TB) lesions, affecting only the retropharyngeal and/or mediastinal lymph nodes, were found; 3/7 animals were found SIT positive. PTB was confirmed in 35/58 animals, of which 30 had seroconverted and 14 had typical clinical signs. 45/58 animals were IFN-γ+ using the most stringent criterion (cut-off point≥0.05); however, IFN-γ test was only positive in 33 animals when using a higher threshold (cut-off point≥0.1). Three animals co-infected also showed extensive TB and diffuse PTB lesions. These results show that the combined use of SIT and IFN-γ, as interpreted using official guidelines, detected all confirmed cases of TB. Individually, the sensitivity of the SIT was inadequate to diagnose TB-positive animals with an advanced stage of PTB. The large number of IFN-γ+ animals with no visible TB lesion could be due, in part, to some protection conferred by prior infection with MAP.</p

Fourteen years of hydro-biogeochemical monitoring in a Mediterranean catchment

8 páginas, 8 figuras[EN]Fluvial systems in Mediterranean areas are subject to strong precipitation seasonality, characterized by a low flow period, and, in severe conditions, the complete disruption of surface flow continuum. The Fuirosos is a Mediterranean intermittent stream that has been monitored since 1998. It is located near Barcelona (Spain) in a catchment almost untouched by anthropic activity. Thus it has become a target for many studies on biogeochemistry and fluvial ecology. Some of these studies especially emphasize the role of the dry-wet cycling and its influence on other aspects of fluvial processes. This text provides a wide overview of the research conducted in Fuirosos catchment and highlights the relevance of the alternation of hydrological periods in Mediterranean systems. [DE]Die Abflusssysteme mediterraner Einzugsgebiete sind in starkem Maße von der Saisonalität der Niederschläge beeinflusst und zeigen daher Perioden mit Niederwasserführung bzw. gänzlich fehlendem Oberflächenabfluss. Der Fuirosos- Fluss zeigt intermittierende Verhältnisse, die seit 1998 beobachtet werden. Er liegt nahe Barcelona (Spanien) und ist nahezu anthropogen unbeeinflusst. Daher wird er oft als Testgebiet für biogeochemische und flussökologische Untersuchungen herangezogen. Diese konzentrieren sich oft auf den Einfluss von Trocken-Feuchte-Zyklen auf andere fluviatile Prozesse. Der Beitrag bietet einen Überblick über die Forschungsaktivitäten am Fuirosos-Fluss und unterstreicht die Wichtigkeit der Unterscheidung zwischen Feucht- und Trockenperioden in mediterranen Einzugsgebieten.This contribution has been partially founded by Ministerio de Economia y Competitividad (project CGL2011-30151- C02).Peer reviewe

Serial measurements of serum NT-proBNP as markers of left ventricular systolic function and remodeling in children with heart failure

BACKGROUND: Increasing serum levels of N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) are associated with worsening heart failure (HF) in adults. We determined whether changes in NT-proBNP level are associated with changes in symptoms and left ventricular (LV) systolic function and remodeling in children with HF secondary to dilated cardiomyopathy. METHODS: We retrospectively examined associations between serum NT-proBNP levels and NYHA/Ross functional class, LV systolic and diastolic diameter (LVSD-z and LVDD-z), LV ejection fraction (LVEF), and LV shortening fraction (LVSF-z) using generalized linear mixed models. Fluctuation in functional class of subjects was also modeled using logistic regression and receiver operating characteristic (ROC) curves. RESULTS: In 36 children (14 males), a 10-fold increase in NT-proBNP serum levels was associated (P<0.001) with a 9.8% decrease in LVEF, a 3.25-unit drop in LVSF-z, a 1.53-unit increase in LVDD-z, a 2.64-unit increase in LVSD-z, and an increased odds of being in functional class III/IV (OR 85.5; 95% CI, 10.9 to 671.0). An NT-proBNP level greater than 1000 pg/mL identified children constantly or intermittently in functional class III-IV with 95% sensitivity and 80% specificity. The reliability of a single NT-proBNP value was 0.61, but the means for two and three NT-proBNP values were 0.76 and 0.82, respectively. CONCLUSIONS: In children with HF, NT-proBNP is associated with cardiac symptoms and indices of LV systolic dysfunction and remodeling. NT-proBNP >1000 pg/mL identifies highly symptomatic children. Within subject serial measurements of NT-proBNP are needed for a reliable and accurate determination of disease status and/or course