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31.
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Background

The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.

Objectives

The purpose of this study was to assess whether a diagnostic strategy based on coronary computed tomographic angiography (CTA) is superior to functional stress testing in reducing adverse cardiovascular (CV) outcomes (CV death or myocardial infarction [MI]) among symptomatic patients with diabetes.

Methods

PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) was a randomized trial evaluating an initial strategy of CTA versus functional testing in stable outpatients with symptoms suggestive of CAD. The study compared CV outcomes in patients with diabetes (n = 1,908 [21%]) and without diabetes (n = 7,058 [79%]) based on their randomization to CTA or functional testing.

Results

Patients with diabetes (vs. without) were similar in age (median 61 years vs. 60 years) and sex (female 54% vs. 52%) but had a greater burden of CV comorbidities. Patients with diabetes who underwent CTA had a lower risk of CV death/MI compared with functional stress testing (CTA: 1.1% [10 of 936] vs. stress testing: 2.6% [25 of 972]; adjusted hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.79; p = 0.01). There was no significant difference in nondiabetic patients (CTA: 1.4% [50 of 3,564] vs. stress testing: 1.3% [45 of 3,494]; adjusted hazard ratio: 1.03; 95% confidence interval: 0.69 to 1.54; p = 0.887; interaction term for diabetes p value = 0.02).

Conclusions

In diabetic patients presenting with stable chest pain, a CTA strategy resulted in fewer adverse CV outcomes than a functional testing strategy. CTA may be considered as the initial diagnostic strategy in this subgroup. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550)  相似文献   
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目的:观察稀土化合物硝酸钇[Y(NO33]亚慢性(90 d)暴露对大鼠学习记忆能力的影响,并探究其可能的机制,为全面评估稀土元素钇的健康风险提供科学依据。方法:选用刚离乳(PND21)SD雌性大鼠,根据质量随机分为4组,分别为对照组(ddH2O),Y(NO33低剂量组[10 mg/(kg·d)]、中剂量组[40 mg/(kg·d)]和高剂量组[160 mg/(kg·d)],每组15只。连续灌胃受试物90 d后进行旷场实验、高架十字迷宫实验、转棒实验、Morris水迷宫实验。水迷宫检测后,每组取5只雌鼠心脏原位灌注,进行脑组织病理学检查。每组剩余10只雌鼠摘取脑组织,紫外分光光度计检测雌鼠大脑皮质和海马中谷氨酸(Glu)的含量;Western blot检测海马组织中N-甲基-D-天冬氨酸(NMDA)受体蛋白表达情况。结果:与对照组相比,硝酸钇90 d暴露后,转棒实验中160 mg/(kg·d)剂量组大鼠在棒时间、在棒圈数、掉落速度明显升高(P<0.05)。在Morris水迷宫定位航向实验第4天时,40、160 mg/(kg·d)剂量组大鼠逃避潜伏期明显降低(P<0.05);Morris水迷宫空间探索实验中,40 mg/(kg·d)剂量组大鼠穿越平台次数、目标象限游泳时间明显增加(P<0.05);160 mg/(kg·d)剂量组穿越平台次数、进入目标象限次数、目标象限游泳时间明显增加(P<0.05);160 mg/(kg·d)剂量组大鼠东北、东南、西南象限的逃避潜伏期明显低于西北象限的逃避潜伏期(P<0.05)。160 mg/(kg·d)剂量组大鼠海马中Glu含量和NMDA受体NR1含量均明显低于对照组(P<0.05)。40和160 mg/(kg·d)剂量组大鼠海马中NMDA受体NR2A含量明显低于对照组(P<0.05)。结论:硝酸钇亚慢性(90 d)暴露可以引起雌性大鼠空间学习记忆能力增强;硝酸钇可能通过降低海马组织神经元细胞外Glu含量,抑制NMDA受体激活,增强雌性大鼠的空间学习记忆能力。  相似文献   
34.
目的建立单抗N糖分析方法的系统适用性对照品,并设定相应的系统适用性要求。方法利用液质联用(LC-MS)仪对N糖系统适用性对照品进行N糖型的表征鉴别,并对对照品进行稳定性评价。结合方法特点和验证数据,对系统适用性要求进行设定。结果建立的系统适用性对照品具有良好的稳定性,其糖型涵盖了单抗主要的N糖型种类。针对3种药典拟收录的单抗N糖分析方法,设定了以下系统适用性要求,包括:图谱与典型图谱相似、G1F(1,6)和G1F(1,3)的分离度应满足具体要求、G0F%应在规定的范围内、G0F保留时间的RSD应≤4%。结论建立了单抗N糖系统适用性对照品,可配合3种2020年版《中国药典》拟收录的N糖分析方法使用。  相似文献   
35.
ObjectivesGrowing evidence of the importance of motor competence for developing a healthy lifestyle has been established in the last decade. Nonetheless, no single instrument or observation tool have been able to fully measure this construct, particularly because most were built for the diagnosis of children in risk for motor impairment; are limited to a few years of the developmental span; lack objectivity in the assessment protocols; or do not include the locomotor, stability, and manipulative components. This led to the difficulty of comparing researches, and longitudinally follow children into adulthood. Recently, a novel proposal to assess motor competence was presented - the Motor Competence Assessment (MCA) - and this study aims to present the MCA normative data from 3-to-23 years.Design and methodsTwo thousand and eighty-seven participants (1102 boys) between 3 and 23 years of age were evaluated in the MCA (standing long jump, 10 m shuttle run, throwing velocity, kicking velocity, lateral jumps, shifting platforms). Results for each test were introduced in the LMS Chartmaker 2.3. The best model for test and sex was used, resulting in normative curves and percentile values.ResultsFinal norms showed a good fit to the instrument developmental expectations, allowing to differentiate and classify performances along the age interval.ConclusionsThe MCA age- and sex- normative values allow to assess motor competence from childhood to early adulthood. Future directions will include obtaining a total MCA score and the normative scores for the MCA components (stability, locomotion, object control), and to expand the norms to adulthood and old age.  相似文献   
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Mesoporous silica nanoparticles (MSNs) can provide a structural foundation for a new generation of nanocarriers with a broad range of functionalities. Multifunctional MSNs can serve as all-in-one diagnostic and therapeutic tools that can be used to simultaneously visualize and treat various diseases, such as cancer. This research study is the first time that two lanthanide-based imaging systems have been combined to incorporate controlled drug release and targeted tracing into a single MSN-based nano-platform for a novel theranostic drug delivery system. Doping lanthanide ions, i.e., europium (Eu) and gadolinium (Gd) ions, into an MSN structure (EuGd-MSNs) imparts fluorescence and magnetism to the nanostructure that can be used to develop magnetic resonance imaging (MRI) and biological fluorescence tools. Current cancer research has revealed that most human cancer cells express a large number of folate receptors on their surface. Grafting folic acid (FA) onto the EuGd-MSN surface (EuGd-FA-MSNs) imparts a targeting function to the MSN because of the specificity of the binding of FA to cell surface receptors. Furthermore, grafting anticancer drugs, such as camptothecin (CPT), onto the surface of these MSNs by forming disulfide bonds (EuGd-SS-CPT-FA-MSNs) enables intracellular controlled drug release. A high concentration of intracellular glutathione cleaves the disulfide bond to release the drug and treat the disease. The results of in vitro and in vivo studies show that the functionalized MSNs can be successfully used as a platform to integrate dual-imaging, targeting, and therapeutic treatment in multifunctional diagnosis drug delivery systems.  相似文献   
40.
The main of this study was to evaluate the mutagenic and carcinogenic potential of (+) – usnic acid (UA), using Somatic Mutation and Recombination Test (SMART) and the test for detecting epithelial tumor clones (wts) in Drosophila melanogaster. Larvae from 72 ± 4 h from Drosophila were fed with UA (5.0, 10.0 or 20.0 mM); urethane (10.0 mM) (positive control); and solvent (Milli-Q water, 1% Tween-80 and 3% ethanol) (negative control). ST cross produced increase in total mutant spots in the individuals treated with 5.0, 10.0 or 20.0 mM of UA. HB cross produced spot frequencies in the concentration of 5.0 mM that were higher than the frequency for the same concentration in the ST cross. In the highest concentrations the result was negative, which means that the difference observed can be attributed, in part, to the high levels of P450, suggesting that increasing the metabolic capacity maximized the toxic effect of these doses. In the evaluation of carcinogenesis using the wts test, the results obtained for the same concentrations of UA show a positive result for the presence of tumors when compared to the negative control. We conclude that UA has recombinogenic, mutagenic and carcinogenic effects on somatic cells in D. melanogaster.  相似文献   
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