Association of peripheral and central arterial wave reflections with the CYP11B2 -344C allele and sodium excretion

OBJECTIVE: Angiotensin II and aldosterone, generated by the angiotensin-converting enzyme (ACE) and aldosterone synthase (CYP11B2), respectively, not only regulate sodium and water homeostasis, but also influence vascular remodeling in response to high blood pressure. In the European Project on Genes in Hypertension (EPOGH), we therefore investigated whether the ACE I/D and CYP11B2 C-344T polymorphisms influence early arterial wave reflections, a measure of vascular stiffness. METHODS: We measured the peripheral and central augmentation index of systolic blood pressure by applanation tonometry at the level of the radial artery in 622 subjects (160 families and 64 unrelated individuals) randomly recruited from three European populations, whose average urinary sodium excretion ranged from 196 to 245 mmol/day. In multivariate analyses, with sodium excretion analyzed as a continuous variable, we explored the phenotype-genotype associations by means of generalized estimating equations and the quantitative transmission disequilibrium test. RESULTS: The peripheral and central augmentation indexes were significantly higher in CYP11B2 -344C allele carriers than in -344T homozygotes. In offspring, early wave reflections increased with the transmission of the -344C allele. This effect of the CYP11B2 polymorphism occurred in subjects with a higher than median urinary sodium excretion (210 mmol/day). The ACE I/D polymorphism did not influence augmentation of systolic blood pressure. CONCLUSIONS: The CYP11B2 C-344T polymorphism affects arterial stiffness. However, sodium intake seems to modulate this genetic effect.     

Maternal and paternal influences on left ventricular mass of offspring

Significant intrafamilial correlations of left ventricular mass exist in first-degree relatives. However, the specific maternal and paternal influences on left ventricular mass of offspring remain unknown. We therefore evaluated familial aggregation of left ventricular mass by type of familial relation in two European populations. A random sample of 159 nuclear families (250 parents and 321 offspring) was investigated in Cracow, Poland, and Novosibirsk, Russia. The mean age of parents and offspring was 51.4 years and 25.1 years, respectively. Two-dimensionally guided M-mode echocardiography was performed, and left ventricular mass was calculated. As a measure of concordance, we computed correlation coefficients for left ventricular mass between first-degree relatives and between spouse pairs. After adjustment for center, gender, age, height, body weight, systolic blood pressure, antihypertensive treatment, smoking, alcohol intake, and physical activity, the intrafamilial correlations for left ventricular mass were 0.06 (P=0.57) in 91 spouse-spouse pairs, 0.14 (P=0.002) in 500 parent-offspring pairs, and 0.32 (P<0.001) in 179 sib-sib pairs. Across the four parent-offspring relations, the intrafamilial correlations of left ventricular mass differed. The mother-son (n=140, r=0.27, P<0.001) and mother-daughter (n=161, r=0.28, P<0.001) correlations were significant, whereas the father-son (n=101, r=0.04, P=0.69) and father-daughter (n=98, r=-0.09, P=0.38) correlations were not different from zero. Overall, the mother-offspring correlation coefficient was significantly higher than the father-offspring correlation (r=0.28 versus r=-0.04; P=0.005). Thus, maternal factors appear to have more impact on left ventricular mass of offspring than do paternal influences. Further studies are required to elucidate the genetic, epigenetic, and ecogenetic mechanisms underlying these divergent parent-offspring correlations.     

Host and environmental determinants of heart rate and heart rate variability in four European populations

OBJECTIVE: In a population-based sample of nuclear families recruited in the framework of the European Project on Genes in Hypertension (EPOGH), we investigated the association between heart rate (HR) and its variability (HRV), and gender, age, posture, breathing frequency, body mass index, systolic blood pressure, family history of hypertension and various lifestyle factors, such as smoking, alcohol and coffee consumption and physical activity. METHODS: RR interval and respiration were registered in the supine and standing positions (15 min each) in 1208 subjects in Bucharest (Romania, n= 267), Cracow (Poland, n= 323), Mirano (Italy, n= 323) and Novosibirsk (Russian Federation, n= 295). After exclusion of 199 participants on antihypertensive treatment and/or patients with diabetes mellitus (n= 40) or myocardial infarction (n= 4), 993 subjects were eligible for analysis. We evaluated 858 participants with high-quality recordings. Using fast Fourier transform, we decomposed HRV into low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF: 0.15-0.40 Hz) components, which were expressed in normalized units. RESULTS: Mean values were 35.3 years for age, 24.3 kg/m for body mass index (BMI) and 121.0/77.2 mmHg for blood pressure. The group included 462 (53.8%) women. Across four centres, HR and HRV were similarly and independently associated with gender, age and postural position (P <0.001). In the supine position, HR was higher in women than men (67.2 versus 63.7 bpm). Men had higher normalized LF power than women (48.8 versus 41.5), but lower HF power (40.6 versus 47.4). The normalized HF power decreased with age (r = -0.43), whereas LF power increased (r = 0.32). On standing, HR increased (83.3 versus 65.6 bpm), normalized HF power declined (19.2 versus 44.3) and LF power increased (67.4 versus 44.9). The independent effects of respiration frequency, systolic blood pressure, family history of hypertension, body mass index and lifestyle factors on HRV differed between populations, and explained no more than 8% of the total variance. CONCLUSIONS: Across four European populations, gender, age and posture were consistent and independent correlates of HR and HRV. Lifestyle seems to have small but varying influences on HR and/or HRV, probably depending on the environmental and cultural background of the population under study.     

Emergency Department Information System Implementation and Process Redesign Result in Rapid and Sustained Financial Enhancement at a Large Academic Center

Objectives: The objectives were to measure the financial impact of implementing a fully integrated emergency department information system (EDIS) and determine the length of time to “break even” on the initial investment. Methods: A before‐and‐after study design was performed using a framework of analysis consisting of four 15‐month phases: 1) preimplementation, 2) peri‐implementation, 3) postimplementation, and 4) sustained effects. Registration and financial data were reviewed. Costs and rates of professional and facility charges and receipts were calculated for the phases in question and compared against monthly averages for covariates such as volume, collections rates, acuity, age, admission rate, and insurance status with an autoregressive time series analysis using a segmented model. The break‐even point was calculated by measuring cumulative monthly receipts for the last three study phases in excess of the average monthly receipts from the preimplementation phase, corrected for change in volume, and then plotting this against cumulative overall cost. Results: Time to break even on the initial EDIS investment was less than 8 months. Total revenue enhancement at the end of the 5‐year study period was $16,138,953 with an increase of 69.40% in charges and 70.06% in receipts. This corresponds to an increase in receipts per patient from $50 to $90 for professional services and $131 to $183 for facilities charges. Other than volume, there were no significant changes in trends for covariates between the preimplementation and sustained‐effects periods. Conclusions: A comprehensive EDIS implementation with process redesign resulted in sustained increases in professional and facility revenues and a rapid initial break‐even point. ACADEMIC EMERGENCY MEDICINE 2010; 17:527–535 © 2010 by the Society for Academic Emergency Medicine     

质膜相关的SNAREs syntaxin/UNC-64与SNAP-25/RIC-4蛋白调控秀丽线虫的脂肪积累(英文)

目的研究神经突触组装与功能调控相关基因是否参与秀丽线虫的脂肪积累调节。方法分析神经突触组装与功能调控相关基因突变体的脂肪积累变化,进而观察SNAREs syntaxin/unc-64和SNAP-25/ric-4基因与daf-2、daf-7、nhr-49、sbp-1及mdt-15所介导的信号通路在调控脂肪积累上的遗传关系。对unc-64与ric-4基因进行组织特异性活性分析,以确定它们在神经系统与肠道内对脂肪积累的影响。结果突触前为神经突触组装所必需的基因的突变并未明显影响脂肪积累。对调控神经突触功能的基因进行分析的结果显示,SNAREssyntaxin/unc-64与SNAP-25/ric-4基因均参与了脂肪积累的调节。利用苏丹黑染色与尼罗红标记法观察到unc-64与ric-4突变体肠道中脂肪积累显著增加,而unc-64与ric-4突变体中积累的脂肪颗粒并未出现尺寸的显著变化。在神经系统与肠道中,unc-64基因的表达均能显著降低unc-64突变体动物的脂肪积累,而基因ric-4在神经系统的表达则可以完全恢复ric-4突变体动物的脂肪积累。遗传分析表明,unc-64与ric-4对脂肪积累的调控独立于daf-2...     

靶向于胰岛素样生长因子受体的基因导入系统

目的：建立一种新的以细胞表面受体为靶向的基因导入系统。方法：根据胰岛素样生长因子Ⅰ号及Ⅱ号受体（IGFIR,IGFⅡR）在人原发性肝癌中过量表达,设计并合成了针对IGFIR及IGFⅡR的14肽E5,同时合成了流感病毒血凝素功能域20肽HA20作为内吞小体释放寡肽（Endosome releasing loigopeptide,EROP),将它们分别与多聚阳离子多肽（Polycatiomic polypeptide,PCP)－多聚赖氨酸（Polylysine,PL)共价连接,通过静电效应与DNA形成受体介导的靶向性非病毒性基因导入系统（E5－PCP,PCP－HA20）。结果：体内、外实验证实此基因导入系统能高效且 相对靶向地将外源基因导入人肝癌细胞并表达。应用此系统将细胞周期素依赖的蛋白激酶抑制物基因p15,p16,p21导入肝癌细胞,明显抑制肝癌细胞生长。体内将p21导入荷瘤裸鼠,显著抑制裸鼠皮下肿瘤的生长。结论：受体介导的非病毒型基因导入系统高效具有相对靶向性,有可能成为新的肝癌基因治疗途径。