The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Extraction Process of Dibenzothiophene with New Distillable Amine-Based Protic Ionic Liquids

In this study, two kinds of amine-based protic ionic liquids (PILs), namely, 2-[2-(dimethylamino)ethoxy] ethanol propionate ([DMEE][CO2Et]) and 3-(dimethylamino)-propanenitrile propionate ([DMAPN][CO2Et]), were introduced into the desulfurization process for the first time. Some important parameters, such as stirring speed, ionic liquid (IL) dosage, initial concentration, etc., were investigated. According to the experiments, the sulfur content in the model oil can be effectively removed from 1600 to about 650 ppm by a single extraction cycle. After five cycles, the sulfur content could reach up to 19 ppm and the deep desulfurization was achieved. Most important, the recycling of PILs was realized by vacuumed distillation. The properties and extraction efficiency of PILs have no change after recycling. At the same time, the extraction mechanisms were probed. The results show that the hydrogen bond formed between the sulfur of dibenzothiophene (DBT) and the active hydrogen of PIL accounts for the high desulfurization efficiencies. This novel process would provide a new route for extraction desulfurization of diesel fuels

Transcriptome-guided target identification of the TetR-like regulator SACE_5754 and engineered overproduction of erythromycin in Saccharopolyspora erythraea

Abstract Background Erythromycin A (Er-A) produced by the actinomycete Saccharopolyspora erythraea is an important antibiotic extensively used in human medicine. Dissecting of transcriptional regulators and their target genes associated with erythromycin biosynthesis is crucial to obtain erythromycin overproducer strains through engineering of relevant regulatory elements in S. erythraea. Results Here, we identified a TetR family transcriptional regulator (TFR), SACE_5754, negatively controlling erythromycin production. SACE_5754 indirectly repressed the transcription of ery cluster and cannot regulate itself and its adjacent gene SACE_5753. RNA-seq coupled with EMSAs and qRT-PCR was performed to identify the targets of SACE_5754, and confirmed that transcription of SACE_0388 (encoding a pyruvate, water diknase), SACE_3599 (encoding an antibiotic resistance macrolide glycosyltransferase) and SACE_6149 (encoding a FAD-binding monooxygenase) were directly repressed by SACE_5754. A consensus palindromic sequence TYMAGG-n2/n4/n11-KKTKRA (Y: C/T, M: A/C, K: T/G, R: A/G) was proved to be essential for SACE_5754 binding using DNase I footprinting and EMSAs. During the three target genes of SACE_5754, SACE_0388 and SACE_6149 exhibited the positive effect on erythromycin production. Overexpression of either SACE_0388 or SACE_6149 in ∆SACE_5754 further increased the Er-A production. By engineering the industrial strain S. erythraea WB with deletion of SACE_5754 combined with overexpression of either SACE_0388 or SACE_6149, Er-A production in WB∆SACE_5754/pIB139–0388 and WB∆SACE_5754/pIB139–6149 was successively increased by 42 and 30% compared to WB. Co-overexpression of SACE_0388 and SACE_6149 in WB∆SACE_5754 resulted in enhanced Er-A production by 64% relative to WB. In a 5-L fermenter, WB∆SACE_5754/pIB139–0388-6149 produced 4998 mg/L Er-A, a 48% increase over WB. Conclusion We have identified a TFR, SACE_5754, as a negative regulator of erythromycin biosynthesis, and engineering of SACE_5754 and its target genes, SACE_0388 and SACE_6149, resulted in enhanced erythromycin production in both wild-type and industrial S. erythraea strains. The strategy demonstrated here may be valuable to facilitate the manipulation of transcriptional regulators and their targets for production improvement of antibiotics in industrial actinomycetes

Extraction Process of Dibenzothiophene with New Distillable Amine-Based Protic Ionic Liquids

In this study, two kinds of amine-based protic ionic liquids (PILs), namely, 2-[2-(dimethylamino)­ethoxy] ethanol propionate ([DMEE]­[CO₂Et]) and 3-(dimethylamino)-propanenitrile propionate ([DMAPN]­[CO₂Et]), were introduced into the desulfurization process for the first time. Some important parameters, such as stirring speed, ionic liquid (IL) dosage, initial concentration, etc., were investigated. According to the experiments, the sulfur content in the model oil can be effectively removed from 1600 to about 650 ppm by a single extraction cycle. After five cycles, the sulfur content could reach up to 19 ppm and the deep desulfurization was achieved. Most important, the recycling of PILs was realized by vacuumed distillation. The properties and extraction efficiency of PILs have no change after recycling. At the same time, the extraction mechanisms were probed. The results show that the hydrogen bond formed between the sulfur of dibenzothiophene (DBT) and the active hydrogen of PIL accounts for the high desulfurization efficiencies. This novel process would provide a new route for extraction desulfurization of diesel fuels

Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer's Disease Patients in Asia

10.3988/jcn.2021.17.3.376JOURNAL OF CLINICAL NEUROLOGY173376-38