393 research outputs found
Systematic evaluation of pleiotropy identifies 6 further loci associated with coronary artery disease
Nicht-manuelle Immobilisierung von biologischen Erkennungselementen durch pH-induzierte Deposition von Polymerfilmen als Basis fĂŒr die reproduzierbare Herstellung amperometrischer Biosensoren
Die reproduzierbare, parallele und nicht-manuelle Fixierung von molekularen Erkennungselementen auf OberflĂ€chen hat eine erhebliche Bedeutung fĂŒr die Entwicklung von spezifischen Sensoren fĂŒr Anwendungen im Bereich der Biotechnologie, der klinischen Analytik, der medizinischen Diagnostik sowie in der kombinatorischen Chemie und dem Hochdurchsatzscreening. Insbesondere bei der Miniaturisierung von Biosensoren sowie der Herstellung höher integrierter Sensor-Aktuator-Systeme besteht dabei die Notwendigkeit fĂŒr eine lokale Abscheidungstechnik mit hoher Auflösung bei gleichzeitig geringem Verbrauch an biologischen Erkennungskomponenten. Eine Methode, die diese Anforderungen erfĂŒllen kann, ist die elektrochemisch induzierte Abscheidung von Polymeren in Gegenwart unterschiedlicher Erkennungselemente. Dabei erfolgt bei den herkömmlich verwendeten Polymerabscheidungen[1] die Kettenwachstumsreaktion durch Oxidation des entsprechenden Monomers ĂŒber intermediĂ€re radikalische Zwischenstufen in der Diffusionsschicht vor der Elektrode. Aufgrund des Radikalmechanismus sind solche Reaktionen sensitiv gegenĂŒber der Anwesenheit von molekularem Sauerstoff und nukleophilen Reagenzien, so daĂ die Konzentration von Proteinen (z.B. Enzymen) in der Abscheidungslösung wegen der nukleophilen Seitenketten gering gehalten werden muĂ.
DemgegenĂŒber erfolgt die Bildung des Polymerfilms bei der von uns auf Basis eines industriell gebrĂ€uchlichen Verfahrens fĂŒr den Korrosionsschutz entwickelten Methode, durch eine elektrochemisch oder photochemisch induzierte lokale Ănderung des pH-Wertes, welche die Löslichkeit von emulgierten Polymeren verĂ€ndert und somit zu dessen Koagulation auf der ElektrodenoberflĂ€che fĂŒhrt. Die elektrochemische Abscheidung kann dabei je nach verwendetem Polymer entweder an der Anode oder der Kathode erfolgen
Association of common polymorphisms in known susceptibility genes with rheumatoid arthritis in a Slovak population using osteoarthritis patients as controls
Treatment Satisfaction and Convenience for Patients With Atrial Fibrillation on Edoxaban or Vitamin K Antagonists After Transcatheter Aortic Valve Replacement:A Post Hoc Analysis from the ENVISAGE-TAVI AF Trial
ENVISAGE-TAVI AF (Edoxaban versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve ImplantationâAtrial Fibrillation; NCT02943785) was a prospective, randomized, open-label trial comparing nonâvitamin K oral anticoagulant (NOAC) edoxaban with vitamin K antagonists (VKAs) in patients with atrial fibrillation after successful transcatheter aortic valve replacement (TAVR). The effect of edoxaban- or VKA-based therapy on patient-reported outcomes remains unknown, as most studies focus on efficacy and safety. Pre-TAVR patient-reported expectations and post-TAVR Treatment Satisfaction and Convenience with edoxaban or VKA treatment (at months 3 and 12) were analyzed using the Perception of Anticoagulation Treatment Questionnaire (PACT-Q). This analysis included randomized and dosed patients with an evaluable PACT-Q1 assessment at baseline and â„1 postbaseline assessment (PACT-Q2). Subanalyses included patients stratified by pre-TAVR anticoagulant (NOAC, VKA, no NOAC/VKA). Edoxaban- (n = 585) and VKA-treated (n = 522) patients had similar baseline characteristics and treatment expectations. Pre-TAVR anticoagulant use did not affect treatment expectations. After TAVR, edoxaban-treated patients had significantly higher Treatment Satisfaction and Convenience scores compared with VKA-treated patients at all time points (p <0.001 for all). Among edoxaban-treated patients, those who received VKAs pre-TAVR were significantly more satisfied with treatment than those who received NOACs (p <0.001) or no NOACs/VKAs (p = 0.003); however, there was no significant difference in the perception of convenience (p = 0.927 and p = 0.092, respectively). Conversely, among VKA-treated patients, the type of anticoagulant used pre-TAVR did not affect Treatment Satisfaction or Convenience scores post-TAVR. In conclusion, patients with atrial fibrillation who received edoxaban post-TAVR reported significantly higher Treatment Satisfaction and Convenience scores compared with those who received VKAs, resulting in a clinically meaningful difference between treatment groups.</p
Outcomes after TAVI in patients with atrial fibrillation and a history of recent PCI:Results from the ENVISAGE-TAVI AF trial
Background: Patients with atrial fibrillation (AF) and a recent (†90 days) percutaneous coronary intervention (PCI) undergoing transcatheter aortic valve implantation (TAVI) are at high bleeding risk due to the addition of oral antiplatelet (OAP) agents on top of oral anticoagulants. Data on outcomes of these patients are needed to optimize antithrombotic treatment. Methods: This analysis compared annualized clinical event rates in patients with and without a recent PCI enrolled in ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban and vitamin K antagonists in AF patients after TAVI. The primary efficacy and safety outcomes were net adverse clinical events (NACE) and major bleeding. Results: Overall, 132 (94.3%) patients with a recent PCI (n = 140) received OAP after TAVI, compared with 692 (55.9%) patients without a recent PCI (n = 1237). Among patients with a recent PCI on OAP agents, use of dual antiplatelet therapy decreased to 5.5%, and use of single antiplatelet therapy (SAPT) increased to 78.0% over 3 months post-randomization. Conversely, use of SAPT predominated at all time points in patients without a recent PCI history. There were no significant differences in the incidence of NACE or other outcomes assessed, except for major bleeding events, which were more frequent in patients with vs without a recent PCI history (hazard ratio [95% confidence interval]: 2.17 [1.27, 3.73]; P = 0.005). Conclusions: Patients with AF undergoing TAVI with a recent PCI have a similar risk of ischemic events and mortality, but an increased risk of major bleeding compared with patients without a recent PCI. Graphical abstract: [Figure not available: see fulltext.].</p
Circulating brainâderived neurotrophic factor concentrations and the risk of cardiovascular disease in the community
BACKGROUND: Brainâderived neurotrophic factor (BDNF) is a pleiotropic peptide involved in maintaining endothelial integrity. It is unknown if circulating BDNF levels are associated with risk of cardiovascular disease (CVD). METHODS AND RESULTS: We prospectively investigated the association of circulating BDNF levels with cardiovascular events and mortality in 3687 participants (mean age 65 years, 2068 women) from the Framingham Heart Study (FHS). Using a common nonsynonomous single nucleotide polymorphism (SNP) in the BDNF gene (rs6265), we then performed a Mendelian randomization experiment in the CARDIoGRAM (Coronary ARtery DIsease GenomeâWide Replication And MetaâAnalysis) consortium (>22 000 coronary artery disease [CAD] cases, >60 000 controls) to investigate whether SNP rs6265 was associated with CAD in CARDIoGRAM and, if so, whether the effect estimate differed from that predicted based on FHS data. On followâup (median 8.9 years), 467 individuals (261 women) in FHS experienced a CVD event, and 835 (430 women) died. In multivariableâadjusted Cox regression, serum BDNF was associated inversely with CVD risk (hazard ratio [HR] per 1âSD increase 0.88, 95% CI 0.80 to 0.97, P=0.01) and with mortality (HR 0.87, 95% CI 0.80 to 0.93, P=0.0002). SNP rs6265 was associated with BDNF concentrations (0.772 ng/mL increase per minor allele copy) in FHS. In CARDIoGRAM, SNP rs6265 was associated with CAD (odds ratio 0.957, 95% CI 0.923 to 0.992), a magnitude consistent with the predicted effect (HR per minor allele copy 0.99, 95% CI 0.98 to 1.0; P=0.06 for difference between predicted and observed effect). CONCLUSION: Higher serum BDNF is associated with a decreased risk of CVD and mortality. Mendelian randomization suggests a causal protective role of BDNF in the pathogenesis of CVD
Quantitative fluid overload in severe aortic stenosis refines cardiac damage and associates with worse outcomes
Aims: Cardiac decompensation in aortic stenosis (AS) involves extra-valvular cardiac damage and progressive fluid overload (FO). FO can be objectively quantified using bioimpedance spectroscopy. We aimed to assess the prognostic value of FO beyond established damage markers to guide risk stratification. Methods and results: Consecutive patients with severe AS scheduled for transcatheter aortic valve implantation (TAVI) underwent prospective risk assessment with bioimpedance spectroscopy (BIS) and echocardiography. FO by BIS was defined as â„1.0 L (0.0 L = euvolaemia). The extent of cardiac damage was assessed by echocardiography according to an established staging classification. Right-sided cardiac damage (rCD) was defined as pulmonary vasculature/tricuspid/right ventricular damage. Hospitalization for heart failure (HHF) and/or death served as primary endpoint. In total, 880 patients (81 ± 7 years, 47% female) undergoing TAVI were included and 360 (41%) had FO. Clinical examination in patients with FO was unremarkable for congestion signs in >50%. A quarter had FO but no rCD (FO+/rCDâ). FO+/rCD+ had the highest damage markers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. After 2.4 ± 1.0 years of follow-up, 236 patients (27%) had reached the primary endpoint (29 HHF, 194 deaths, 13 both). Quantitatively, every 1.0 L increase in bioimpedance was associated with a 13% increase in event hazard (adjusted hazard ratio 1.13, 95% confidence interval 1.06â1.22, p < 0.001). FO provided incremental prognostic value to traditional risk markers (NT-proBNP, EuroSCORE II, damage on echocardiography). Stratification according to FO and rCD yielded worse outcomes for FO+/rCD+ and FO+/rCDâ, but not FOâ/rCD+, compared to FOâ/rCDâ. Conclusion: Quantitative FO in patients with severe AS improves risk prediction of worse post-interventional outcomes compared to traditional risk assessment
Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression
We aimed to assess whether pri-miRNA SNPs (miSNPs) could influence monocyte gene expression, either through marginal association or by interacting with polymorphisms located in 3'UTR regions (3utrSNPs). We then conducted a genome-wide search for marginal miSNPs effects and pairwise miSNPs Ă 3utrSNPs interactions in a sample of 1,467 individuals for which genome-wide monocyte expression and genotype data were available. Statistical associations that survived multiple testing correction were tested for replication in an independent sample of 758 individuals with both monocyte gene expression and genotype data. In both studies, the hsa-mir-1279 rs1463335 was found to modulate in cis the expression of LYZ and in trans the expression of CNTN6, CTRC, COPZ2, KRT9, LRRFIP1, NOD1, PCDHA6, ST5 and TRAF3IP2 genes, supporting the role of hsa-mir-1279 as a regulator of several genes in monocytes. In addition, we identified two robust miSNPs Ă 3utrSNPs interactions, one involving HLA-DPB1 rs1042448 and hsa-mir-219-1 rs107822, the second the H1F0 rs1894644 and hsa-mir-659 rs5750504, modulating the expression of the associated genes. As some of the aforementioned genes have previously been reported to reside at disease-associated loci, our findings provide novel arguments supporting the hypothesis that the genetic variability of miRNAs could also contribute to the susceptibility to human diseases
Recommendations for extracorporeal membrane oxygenation (ECMO) in COVID-19 patients: consensus paper of the Medical University of Vienna
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