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

“Reverse McConnell's Sign”: Interpreting Interventricular Hemodynamic Dependency and Guiding the Management of Acute Heart Failure during Takotsubo Cardiomyopathy

Although most patients with Takotsubo cardiomyopathy (TTC) have benign clinical course and prognosis, TTC can induce acute heart failure and hemodynamic instability. TTC mimics the clinical features of acute anterior wall myocardial infarction (AMI). Bedside clinicians often have a diagnostic dilemma when cardiac catheterization and angiography are either contraindicated or can cause potential adverse consequences. Misdiagnosing TTC as AMI will lead to initiation of harmful pharmacological or device-based treatment, which worsens hemodynamic compromise. Therefore, understanding and interpreting the unique pathophysiological and hemodynamic features of TTC in a better manner becomes crucial to guide effective clinical management of acute heart failure/cardiogenic shock during TTC. We review recent advances in echocardiographic diagnosis of TTC and its role in guiding bedside management of acute heart failure and cardiogenic shock, with specific focus on the interpretation of discrepant, but reciprocally dependent, left and right ventricular hemodynamics during acute stages of TTC

Design and Testing of a 2-DOF Flexure-based Compliant Stage

This paper presents the mechanical design and testing of a 2-DOF flexure-based compliant stage. The prismatic joints are first discussed. To obtain high resonance frequency and decoupled property, the stage composed of four parallel chains with symmetrical configuration should be employed. Finally, an experimental platform is set up to test the cooperative tracking performance. The experimental trajectory is in good agreement with the desired trajectory under various input frequencies. It shows that the maximum tracking error exhibits an increase from 0.8% to 2.7%. The experiment results demonstrate that the proposed compliant stage possess good tracking performance under 100 Hz, which also validates the reasonability of the stage

Design and Testing of a 2-DOF Flexure-based Compliant Stage

This paper presents the mechanical design and testing of a 2-DOF flexure-based compliant stage. The prismatic joints are first discussed. To obtain high resonance frequency and decoupled property, the stage composed of four parallel chains with symmetrical configuration should be employed. Finally, an experimental platform is set up to test the cooperative tracking performance. The experimental trajectory is in good agreement with the desired trajectory under various input frequencies. It shows that the maximum tracking error exhibits an increase from 0.8% to 2.7%. The experiment results demonstrate that the proposed compliant stage possess good tracking performance under 100 Hz, which also validates the reasonability of the stage

Preparation of Perlite Reference Material for Compositional Analysis

BACKGROUND Perlite is a vitreous rock formed by rapid cooling of volcanic eruptive acidic lava. It is a very important non-metallic mineral, because of its brittleness, light weight, rapid expansion on heating, and other excellent characteristics, and is widely used in construction, water treatment, agriculture and other fields. However, according to the International Database for Certified Reference Materials (COMAR), there is no reference material for perlite composition analysis at home and abroad. So, in order to meet the research needs of perlite, it is necessary to develop one. OBJECTIVES To develop a reference material for composition analysis of perlite. The reference material can basically cover the chemical composition needed by the market. METHODS Perlite samples were collected from Shangcheng County, Henan Province. The collected samples were dried and picked out, the bulk ore was crushed and ground in a ball mill for 40h, then the samples were coarse crushed and discharged, and the debris was removed by 1mm sieve. The samples were dried at 105℃ for 24h, dehydrated and inactivated. After drying, the samples were crushed in a grinder containing high-alumina ceramic balls, and the grinding time was determined by the time required to meet the particle size requirements of the first class standard substance. The processed samples were stored temporarily in polyethylene plastic vats under constant temperature and clean conditions, then sub-packed at 70g per bottle for test. Random samples were taken for homogeneity and stability tests. Through nine collaborative laboratories, more targeted valuation methods such as the gravimetric method, volumetric method, inductively coupled plasma-mass spectrometry, and inductively coupled plasma-optical emission spectrometry were used to ensure the accuracy of the perlite valued components. RESULTS Fifteen items of 60 components were tested for uniformity and stability, including Ag, As, B, Ba, Be, Bi, Cd, Co, Cr, Cs, Cu, Ga, Hf, Hg, In, Li, Mo, Nb, Ni, Pb, Rb, Sb, Sc, Sn, Sr, Ta, Th, U, V, W, Zn, Zr, SiO2, Al2O3, TFe2O3, FeO, MgO, CaO, Na2O, K2O, MnO, TiO2, P2O5, LOI, TC, and rare earth elements. The RSD of most of the components was less than 3%, and the F value of the variance test was less than the critical value [F0.05(29, 60)=1.65], indicating that the homogeneity of the reference material was good. During the stability inspection period, there was no significant difference in the content of the 60 components, indicating that the reference material was stable. The data were processed in accordance with General and Statistical Principles for Characterization of Reference Materials and outlier tests were performed using the Grubbs and Dixon methods. According to statistics, there were 2500 original data of perlite reference material, and 68 outliers were eliminated, with an elimination rate of 2.7%. The standard value and uncertainty of the certified reference material for perlite composition analysis were determined by statistical processing of the constant value test data. The normal distribution of the mean data set was tested by the method of Shapiro-wilk, and the test results were all normal distribution. The final values were 63 components, covering major, trace, and all rare earth elements. The contents of three major components MgO, CaO and TFe2O3 were all less than 1%, which formed a gradient with the existing silicate reference material content. CONCLUSIONS The certified reference material for perlite composition analysis developed in this paper has met the requirements of Technical Norm of Primary Reference Material (JJF1006—94) by processing, crushing, homogeneity and stability test of the candidate. The test for uniformity and stability adopts the same detection technology as the fixed value method, and the selected fixed value technology is suitable and accurate, which ensures the accuracy of the fixed value data. The development of perlite composition analysis standard material has enriched the series of China geological mineral composition analysis standard material, and its chemical composition is numerous, it provides important technical support for instrument calibration, analysis method verification, quality control and quantity traceability of modern analytical technology

Cerebral microbleeds are associated with blood pressure levels in individuals with hypertension

Objective: Cerebral microbleeds (CMBs), which appear as small dot-like hypointense lesions, are strongly associated with cerebrovascular disease. Recently, numerous investigations have suggested that hypertension and age are risk factors for CMBs; however, whether blood pressure grade and age rank are related to the severity of CMBs remains unclear. The purpose of this research was to assess the association between cerebral microbleeds and blood pressure levels. Methods: In total, 460 consecutive hypertension patients (214 males and 246 females; aged 44–96 years, mean age 60.95 ± 6.82 years) from Lishui Central Hospital were enrolled and classified as CMB or non-CMB patients according to magnetic resonance imaging (MRI). Gradient echo T2*-weighted MRI was used to detect CMBs. Differences in blood pressure, CMB severity, and other patient characteristics were compared between the two groups. Multifactorial logistic regression was used to analyze the correlation between blood pressure and microbleeds. Results: In our study, CMB lesions were identified in 123 patients (26.7%), including 39 patients with CMB lesions located deep in the brain. In the hypertensive population, smoking is an independent risk factor for CMBs. Additionally, systolic blood pressure (SBP), diastolic blood pressure (DBP) and age are also independent risk factors for CMBs. Furthermore, a modest correlation was noted between the number of microbleeds and grade of hypertension. Conclusions: This study provides novel evidence that microbleed severity is associated with hypertension grade. This conclusion emphasizes the importance of antihypertensive therapy in hypertension patients to avoid an increase in CMBs

Synthesis and Cytotoxic Evaluation of Novel N-Methyl-4-phenoxypicolinamide Derivatives

molecule

Design and Stereochemical Research (DFT, ECD and Crystal Structure) of Novel Bedaquiline Analogs as Potent Antituberculosis Agents

A series of bedaquiline analogs containing H-bond donors were designed as anti-Mycobacterium tuberculosis drugs. A pair of diastereoisomers (R/S- and S/S-isomers) was selected from these designed compounds for synthetic and stereochemical research. The title compounds were synthesized from chiral precursors for the first time and the absolute configurations (ACs) were determined by electronic circular dichroism (ECD) with quantum chemical calculations. Moreover, a single crystal of the S/S compound was obtained for X-ray diffraction analysis, and the crystal structure showed high consistency with the geometry, confirming the reliability of ACs obtained by ECD analyses and theoretical simulation. Furthermore, the effect of stereochemistry on the anti-tuberculosis activity was investigated. The MICs of the R/S- and S/S-isomers against Mycobacterium phlei 1180 are 9.6 and 32.1 μg·mL−1, respectively. Finally, molecular docking was carried out to evaluate the inhibitory nature and binding mode differences between diastereoisomers

Association of serum cystatin C level with coronary atherosclerotic plaque burden: a comprehensive analysis of observational studies and genetic study

Abstract Background and Aims Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden. Methods This study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk. Results A total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59–3.91; P < 0.001) and medium-level cystatin C levels (OR: 1.86; 95% Cl: 1.21–2.88; P = 0.005) were significantly higher after fulled adjusted confounders compared with the lowest levels of serum cystatin C by SSS. The MR analysis showed that genetic predicted cystatin C levels was associated with an increased risk of coronary atherosclerosis (OR, 1.004; 95% CI, 1.002–1.006, P < 0.001) . Conclusion Elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. Cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level. What is already known on this topic? Coronary artery disease is currently the most common cardiovascular disease and the leading global cause of mortality. Previous studies reported that higher serum cystatin C levels were associated with an increased risk for future cardiovascular events, independent of the normal creatinine levels or estimated glomerular filtration rate (eGFR) values. The presence of high-risk coronary atherosclerotic plaque burden is associated with increased risk of cardiovascular events. However, the association between serum cystatin C and coronary atherosclerotic plaque burden is not very clear. What this study adds? Our study demonstrated that the elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. In addition, we found that serum cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level. How this study might affect research, practice or policy? Current research finds that serum cystatin C levels were associated with coronary atherosclerosis. The metabolic pathway of cystatin C could be a target for new therapies against CAD