Real-World Evaluation of Anticoagulant Treatment Patterns in Patients with Atrial Fibrillation: Data from Multicenter ROTA Study.

OBJECTIVE: Oral anticoagulant therapy is the cornerstone of atrial fibrillation management to prevent stroke and systemic embolism. However, there is limited real-world information regarding stroke and systemic embolism prevention strategies in patients with atrial fibrillation. The aim of the ROTA study is to obtain the real-world data of anticoagulant treatment patterns in patients with atrial fibrillation. METHODS: The ROTA study is a prospective, multicenter, and observational study that included 2597 patients with atrial fibrillation. The study population was recruited from 41 cardiology outpatient clinics between January 2021 and May 2021. RESULTS: The median age of the study population was 72 years (range: 22-98 years) and 57.4% were female. The median CHA2DS2-VASc and HAS-BLED scores were 4 (range: 0-9) and 1 (range: 0-6), respectively. Vitamin K antagonists and direct oral anticoagulants were used in 15.9% and 79.4% of patients, respectively. The mean time in therapeutic range was 52.9% for patients receiving vitamin K antagonists, and 76% of those patients had an inadequate time in therapeutic range with <70%. The most common prescribed direct oral anticoagulants were rivaroxaban (38.1%), apixaban (25.5%), and edoxaban (11.2%). The rate of overuse of vitamin K antagonists and direct oral anticoagulants was high (76.1%) in patients with low stroke risk, and more than one-fourth of patients on direct oral anticoagulant therapy were receiving a reduced dose of direct oral anticoagulants. Among patients who were on direct oral anticoagulant treatment, patients with apixaban treatment were older, had higher CHA2DS2-VASc and HAS-BLED scores, and had lower creatinine clearance than the patients receiving other direct oral anticoagulants. CONCLUSIONS: The ROTA study provides important real-world information about anticoagulant treatment patterns in patients with atrial fibrillation.time in therapeutic range with <70%.

Tissue-specific gene expression and protein abundance patterns are associated with fractionation bias in maize.

BACKGROUND: Maize experienced a whole-genome duplication event approximately 5 to 12 million years ago. Because this event occurred after speciation from sorghum, the pre-duplication subgenomes can be partially reconstructed by mapping syntenic regions to the sorghum chromosomes. During evolution, maize has had uneven gene loss between each ancient subgenome. Fractionation and divergence between these genomes continue today, constantly changing genetic make-up and phenotypes and influencing agronomic traits. RESULTS: Here we regenerate the subgenome reconstructions for the most recent maize reference genome assembly. Based on both expression and abundance data for homeologous gene pairs across multiple tissues, we observed functional divergence of genes across subgenomes. Although the genes in the larger maize subgenome are often expressing more highly than their homeologs in the smaller subgenome, we observed cases where homeolog expression dominance switches in different tissues. We demonstrate for the first time that protein abundances are higher in the larger subgenome, but they also show tissue-specific dominance, a pattern similar to RNA expression dominance. We also find that pollen expression is uniquely decoupled from protein abundance. CONCLUSION: Our study shows that the larger subgenome has a greater range of functional assignments and that there is a relative lack of overlap between the subgenomes in terms of gene functions than would be suggested by similar patterns of gene expression and protein abundance. Our study also revealed that some reactions are catalyzed uniquely by the larger and smaller subgenomes. The tissue-specific, nonequivalent expression-level dominance pattern observed here implies a change in regulatory control which favors differentiated selective pressure on the retained duplicates leading to eventual change in gene functions.

Molecular simulation of fibronectin adsorption onto polyurethane surfaces.

Poly(ethylene glycol)-based polyurethanes have been widely used in biomedical applications; however, they are prone to swelling. A natural polyol, castor oil, can be incorporated into these polyurethanes to control the degree of the swelling, which alters mechanical properties and protein adsorption characteristic of the polymers. In this work, we modeled poly(ethylene glycol) and castor oil copolymers of hexamethylene diisocyanate-based polyurethanes (PEG-HDI and CO-HDI, respectively) and compared their mechanisms for fibronectin adsorption using molecular mechanics and molecular dynamics simulations. Results showed that the interplay between the hydrophobic residues concentrated at the N-terminal end of the protein, the surface roughness, and the hydrophilicity of the polymer surface determine the overall protein adsorption affinity. Incorporating explicit water molecules in the simulations results in higher affinity for fibronectin adsorption to more hydrophobic surface of CO-HDI surfaces, emphasizing the role that water molecules play during adsorption. We also observed that the strain energies that are indicative of flexibility and consequently entropy are significantly affected by the changes in the patterns of ß-sheet formation/breaking. Our study lends supports to the view that while castor oil controls the degree of swelling, it increases the adsorption of fibronectin to a limited extent due to the interplay between its hydrophobicity and its surface roughness, which needs to be taken into account during the design of polyurethane-based biomaterials.