Mediation effect of arterial stiffness on ideal cardiovascular health and stroke

Background and aimsIdeal cardiovascular health (CVH) metrics was associated with stroke, but the causal pathway was poorly investigated. Arterial stiffness was a major factor associated with both ideal CVH metrics and stroke. This study aimed to investigate whether the effect of ideal CVH metrics on stroke was mediated and enhanced by arterial stiffness.Methods and resultsA total of 15,297 participants were included in current study. Arterial stiffness was measured by brachial–ankle pulse wave velocity (baPWV). Causal mediation analyses were used to separate the overall effects of ideal CVH metrics on stroke into indirect effects (mediated by arterial stiffness) and direct effects (mediated through pathways other than arterial stiffness). After a median follow-up of 5.88 years, 324 total stroke events (292 ischemic stroke and 31 hemorrhagic stroke) occurred. Mediation analysis showed 23.94% of the relation between ideal CVH and total stroke was mediated by baPWV (95% confidence interval [CI] of the indirect effect: 0.93–0.95). Further analysis showed the ideal CVH < median combined with baPWV ≥1400 cm/s was associated with the highest risk of total stroke (hazard ratio: 5.62; 95% CI, 3.53–8.96), compared with CVH ≥ median combined with baPWV < 1400 cm/s. Similar results were observed for ischemic stroke, but not for hemorrhagic stroke.ConclusionsArterial stiffness played a mediating role in the associations between ideal CVH metrics and risk of total and ischemic stroke. Combined ideal CVH metrics and baPWV is a reasonable and useful tool for the assessment and prevention of stroke.     

Impact of binocular integrated visual field defects on healthy related quality of life in glaucoma

To investigate the impact of different types of binocular integrated visual field defects on the quality of life in glaucoma.Ninety-six patients with primary glaucoma were divided into 5 groups with 25, 24, 11, 15, and 21 patients according to types of the binocular integrated visual field (BVF) defects. The criteria for BVF grouping included mild visual field defect in binocular eyes, mild visual field defect in 1 eye and moderate or advanced defect in the other, moderate and non-overlapping visual field defect in both eyes, overlapping and moderate visual field defect in binocular eyes, and severe defect in both eyes, respectively. The visual field (VF) evaluation was based on H-P-A visual field grading system. Visual acuity, visual field tests and Glaucoma Quality of Life-15 Questionnaire (GQL-15) were performed for enrolled patients, and binocular visual field results were integrated. The changes and correlations of the Visual field index values and quality of life scores were compared among the 5 groups. The main factors affecting the quality of life in glaucoma were analyzed by multiple regression analysis.The best binocular integrated visual field index (BVFI) and optimal quality of life were observed in group A. The BVFI of group B was better than that of group C or group D, but the peripheral vision glare and dark adaptation were worse. No significant difference was noted between group C and group D in terms of BVFI. However, the glare and dark adaptation in group C were better than that in group D. The BVFI was the lowest and the quality of life was the worst in group E. In all, BVFI and decibels (dB) values were negatively correlated with GQL-15 scores and positively correlated with patients’ quality of life.Binocular integrated visual field accurately reflects the visual function in glaucoma. Higher binocular integrated visual field indices represent a better quality of life for patients with glaucoma. Mild to moderate synchronous or complementary binocular VF defects had a slight effect on the quality of life, while severe and non-compensated VF loss significantly impacts on quality of life in glaucoma patients.     

A Multiscale Computational Approach to Dissect Early Events in the Erb Family Receptor Mediated Activation,Differential Signaling,and Relevance to Oncogenic Transformations

We describe a hierarchical multiscale computational approach based on molecular dynamics simulations, free energy-based molecular docking simulations, deterministic network-based kinetic modeling, and hybrid discrete/continuum stochastic dynamics protocols to study the dimer-mediated receptor activation characteristics of the Erb family receptors, specifically the epidermal growth factor receptor (EGFR). Through these modeling approaches, we are able to extend the prior modeling of EGF-mediated signal transduction by considering specific EGFR tyrosine kinase (EGFRTK) docking interactions mediated by differential binding and phosphorylation of different C-terminal peptide tyrosines on the RTK tail. By modeling signal flows through branching pathways of the EGFRTK resolved on a molecular basis, we are able to transcribe the effects of molecular alterations in the receptor (e.g., mutant forms of the receptor) to differing kinetic behavior and downstream signaling response. Our molecular dynamics simulations show that the drug sensitizing mutation (L834R) of EGFR stabilizes the active conformation to make the system constitutively active. Docking simulations show preferential characteristics (for wildtype vs. mutant receptors) in inhibitor binding as well as preferential enhancement of phosphorylation of particular substrate tyrosines over others. We find that in comparison to the wildtype system, the L834R mutant RTK preferentially binds the inhibitor erlotinib, as well as preferentially phosphorylates the substrate tyrosine Y1068 but not Y1173. We predict that these molecular level changes result in preferential activation of the Akt signaling pathway in comparison to the Erk signaling pathway for cells with normal EGFR expression. For cells with EGFR over expression, the mutant over activates both Erk and Akt pathways, in comparison to wildtype. These results are consistent with qualitative experimental measurements reported in the literature. We discuss these consequences in light of how the network topology and signaling characteristics of altered (mutant) cell lines are shaped differently in relationship to native cell lines. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. These authors contributed equally     

HPLC-ELSD法测定复胃散胶囊中黄芪甲苷的含量

目的 建立高效液相色谱-蒸发光散射检测器法测定复胃散胶囊中黄芪甲苷的含量。方法 采用Agilent 1200高效液相色谱仪和Waters XSELECT C₁₈色谱柱（4.6 mm×250 mm,5 μm）,流动相为乙腈-水（32:68）,流速为1.0 mL·min^-1,进样量为20 μL,蒸发光散射检测器（漂移管温度为70 ℃,载气流速为2.0 L·min^-1）。结果 黄芪甲苷在0.050 5～1.011 mg·mL^-1的范围内呈良好的线性关系,标准曲线为lgA=1.3555lgC+3.277 6,（r=0.999）;精密度和重复性的RSD分别为1.2%和1.6%;平均回收率为96.1%,RSD为1.7%。结论 该方法简便准确、快速、方便、精密度高、重复性好,可用于复胃散胶囊中黄芪甲苷的含量测定。     

Associations between Dietary Patterns and Cardiometabolic Risk Factors—A Longitudinal Analysis among High-Risk Individuals for Diabetes in Kerala,India

The association between dietary patterns and cardiometabolic risk factors is not well understood among adults in India, particularly among those at high risk for diabetes. For this study, we analyzed the data of 1007 participants (age 30–60 years) from baseline and year one and two follow-ups from the Kerala Diabetes Prevention Program using multi-level mixed effects modelling. Dietary intake was measured using a quantitative food frequency questionnaire, and dietary patterns were identified using principal component analysis. Two dietary patterns were identified: a “snack-fruit” pattern (highly loaded with fats and oils, snacks, and fruits) and a “rice-meat-refined wheat” pattern (highly loaded with meat, rice, and refined wheat). The “snack-fruit” pattern was associated with increased triglycerides (mg/dL) (β = 6.76, 95% CI 2.63–10.89), while the “rice-meat-refined wheat” pattern was associated with elevated Hb1Ac (percentage) (β = 0.04, 95% CI 0.01, 0.07) and central obesity (OR 1.16, 95% CI 1.01, 1.34). These findings may help inform designing dietary interventions for the prevention of diabetes and improving cardiometabolic risk factors in high-diabetes-risk individuals in the Indian setting.     

以发热为首要症状的巨细胞动脉炎一例报道

<正>患者,女性,78岁,汉族,因"发热1个月余"于2018年8月14日入四川大学华西医院治疗。入院前1个多月,患者出现无明显诱因发热,每日下午体温升高,服用解热镇痛药后可缓解。自诉体温大多波动在37～38℃之间,最高体温38.1℃,伴有轻度咳嗽,咳少量白色黏痰,有夜间出汗、心慌等不适症状。无胸闷、胸痛,无腹痛、腹泻,无尿频、尿急、尿痛,无全身关节疼痛等症状。半个月前于外院住院,多次查血常规均提示血象正常,但红细胞及血红蛋白进行性下降,红细胞沉降率(erythrocyte sedimentation rate,ESR)明显高于正常,给予抗感染、对症支持等治疗后患者病情无好转,进一步行胸部CT、骨髓