Educational intervention improves anticoagulation control in atrial fibrillation patients:the TREAT randomised trial

Background: Stroke prevention in atrial fibrillation (AF), most commonly with warfarin, requires maintenance of a narrow therapeutic target (INR 2.0 to 3.0) and is often poorly controlled in practice. Poor patient-understanding surrounding AF and its’ treatment may contribute to patient’s willingness to adhere to recommendations. Method: A theory-driven intervention, developed using patient interviews and focus groups, consisting of a one-off group session (1-6 patients) utilising an ‘expert-patient’ focussed DVD, educational booklet, self-monitoring diary and worksheet, was compared in a randomised controlled trial (ISRCTN93952605) against usual care, with patient postal follow-ups at 1, 2, 6, and 12-months. Ninety-seven warfarin-naïve AF patients were randomised to intervention (n=46, mean age (SD) 72.0 (8.2), 67.4% men), or usual care (n=51, mean age (SD) 73.7 (8.1), 62.7% men), stratified by age, sex, and recruitment centre. Primary endpoint was time within therapeutic range (TTR); secondary endpoints included knowledge, quality of life, anxiety/depression, beliefs about medication, and illness perceptions. Main findings: Intervention patients had significantly higher TTR than usual care at 6-months (76.2% vs. 71.3%; p=0.035); at 12-months these differences were not significant (76.0% vs. 70.0%; p=0.44). Knowledge increased significantly across time (F (3, 47) = 6.4; p<0.01), but there were no differences between groups (F (1, 47) = 3.3; p = 0.07). At 6-months, knowledge scores predicted TTR (r=0.245; p=0.04). Patients’ scores on subscales representing their perception of the general harm and overuse of medication, as well as the perceived necessity of their AF specific medications predicted TTR at 6- and 12-months. Conclusions: A theory-driven educational intervention significantly improves TTR in AF patients initiating warfarin during the first 6-months. Adverse clinical outcomes may potentially be reduced by improving patients’ understanding of the necessity of warfarin and reducing their perception of treatment harm. Improving education provision for AF patients is essential to ensure efficacious and safe treatment

Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

BACKGROUND: Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure. METHODS AND RESULTS: MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3. CONCLUSIONS: This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation

Guanylate-binding protein 1 expression from embryonal endothelial progenitor cells reduces blood vessel density and cellular apoptosis in an axially vascularised tissue-engineered construct

BACKGROUND: Guanylate binding protein-1 (GBP-1) is a large GTPase which is actively secreted by endothelial cells. It is a marker and intracellular inhibitor of endothelial cell proliferation, migration, and invasion. We previously demonstrated that stable expression of GBP-1 in murine endothelial progenitor cells (EPC) induces their premature differentiation and decreases their migration capacity in vitro and in vivo. The goal of the present study was to assess the antiangiogenic capacity of EPC expressing GBP-1 (GBP-1-EPC) and their impact on blood vessel formation in an axially vascularized 3-D bioartificial construct in vivo. RESULTS: Functional in vitro testing demonstrated a significant increase in VEGF secretion by GBP-1-EPC after induction of cell differentiation. Undifferentiated GBP-1-EPC, however, did not secrete increased levels of VEGF compared to undifferentiated control EPC expressing an empty vector (EV-EPC). In our In vivo experiments, we generated axially vascularized tissue-engineered 3-D constructs. The new vascular network arises from an arterio-venous loop (AVL) embedded in a fibrin matrix inside a separation chamber. Total surface area of the construct as calculated from cross sections was larger after transplantation of GBP-1-EPC compared to control EV-EPC. This indicated reduced formation of fibrovascular tissue and less resorption of fibrin matrix compared to constructs containing EV-EPC. Most notably, the ratio of blood vessel surface area over total construct surface area in construct cross sections was significantly reduced in the presence of GBP-1-EPC. This indicates a significant reduction of blood vessel density and thereby inhibition of blood vessel formation from the AVL constructs caused by GBP-1. In addition, GBP-1 expressed from EPC significantly reduced cell apoptosis compared to GBP-1-negative controls. CONCLUSION: Transgenic EPC expressing the proinflammatory antiangiogenic GTPase GBP-1 can reduce blood vessel density and inhibit apoptosis in a developing bioartificial vascular network and may become a new powerful tool to manipulate angiogenetic processes in tissue engineering and other pathological conditions such as tumour angiogenesis

Evolution of sex determination and heterogamety changes in section Otites of the genus Silene

Abstract Switches in heterogamety are known to occur in both animals and plants. Although plant sex determination systems probably often evolved more recently than those in several well-studied animals, including mammals, and have had less time for switches to occur, we previously detected a switch in heterogamety in the plant genus Silene: section Otites has both female and male heterogamety, whereas S. latifolia and its close relatives, in a different section of the genus, Melandrium (subgenus Behenantha), all have male heterogamety. Here we analyse the evolution of sex chromosomes in section Otites, which is estimated to have evolved only about 0.55 MYA. Our study confirms female heterogamety in S. otites and newly reveals female heterogamety in S. borysthenica. Sequence analyses and genetic mapping show that the sex-linked regions of these two species are the same, but the region in S. colpophylla, a close relative with male heterogamety, is different. The sex chromosome pairs of S. colpophylla and S. otites each correspond to an autosome of the other species, and both differ from the XY pair in S. latifolia. Silene section Otites species are suitable for detailed studies of the events involved in such changes, and our phylogenetic analysis suggests a possible change from female to male heterogamety within this section. Our analyses suggest a possibility that has so far not been considered, change in heterogamety through hybridization, in which a male-determining chromosome from one species is introgressed into another one, and over-rides its previous sex-determining system

Fibrinolytic status in acute coronary syndromes: Evidence of differences in relation to clinical features and pathophysiological pathways.

SummaryLimited data are available on the role of innate fibrinolysis in acute coronary syndromes (ACS). In the present study we evaluated the dynamic alterations of fibrinolytic markers in patients presenting with ACS. Tissue-type-(tPA) and urokinase type-(uPA) plasminogen activators, plasminogen activator inhibitor (PAI-1) antigen and activity and thrombin activatable fibrinolysis inhibitor (TAFI) were analysed in 50 patients with ST elevation myocardial infarction (STEMI), 47 non-STEMI patients (NSTEMI), 40 patients with stable coronary artery disease (CAD) and 39 controls. The parameters were measured on day 1 and days 3, 7 and 30. Counts of monocyte subsets, monocyte-platelet aggregates and plasma inflammatory cytokines were assessed on admission. On day 1, TAFI was higher in NSTEMI vs. STEMI (p&lt;0.001) while PAI-1 activity was higher in STEMI (p&lt;0.001). In STEMI, uPA activity levels was low on day 1 but significantly increased on day 30 (p&lt;0.001). TAFI levels were increased in NSTEMI on day 1 and gradually reduced by day 30 (p&lt;0.05). In STEMI, TAFI levels peaked at day 7 (p&lt;0.05) and dropped significantly by day 30 (p&lt;0.05). CD14++CD16+ monocytes were independently associated with PAI-1 activity in ACS (p=0.03). Monocyte-platelet aggregates rather than platelet-free monocytes were an independent determinant of tPA, PAI-1 antigen and TAFI on a multivariate analysis (p&lt;0.05). There are significant differences in fibrinolytic activity between patients with STEMI and NSTEMI. These changes could reflect the role of these factors in post-MI myocardial healing. Monocyteplatelet interactions are independently associated with the regulation of the fibrinolytic status in ACS.Note: The editorial process for this article was fully handled by Prof. Christian Weber, Editor-in-Chief.</jats:p