BACKGROUND & AIMS: :Cell cycle arrest in response to DNA damage involves protein stabilization and consequent upregulation of p53, which induces transcription of cyclin-dependent kinase inhibitor p21 (CDKN1A). We now show that p21 acts as a negative regulator of the cellular levels of p53. p21 knockdown by short hairpin RNA strongly increased p53 upregulation by a DNA-damaging drug doxorubicin in HT1080 fibrosarcoma cells. A protease inhibitor N-Ac-Leu-Leu-norleucinal (ALLN) drastically increased the amount of p53 in HCT116 colon carcinoma cells, but it had no effect on the already high p53 level in a p21(-/-) derivative of this cell line. Inhibition of transcription, which increases p53 levels in different cell lines due to the degradation of p53-destabilizing proteins such as Mdm2, failed to increase but instead decreased the amount of p53 in p21(-/-) cells, despite a drastic decrease in the level of Mdm2. These results indicate that p21 acts as a negative regulator of p53 stability in different cell types. p53 regulation by p21 may provide a negative regulatory loop that limits p53 induction.

背景与目标： : 响应DNA损伤的细胞周期停滞涉及蛋白质稳定和随后的p53上调，p53诱导细胞周期蛋白依赖性激酶抑制剂p21 (CDKN1A) 的转录。现在，我们显示p21充当p53细胞水平的负调节剂。短发夹RNA的p21敲除强烈增加了HT1080纤维肉瘤细胞中DNA损伤药物阿霉素的p53上调。蛋白酶抑制剂N-Ac-Leu-正常亮氨酸 (ALLN) 大大增加了HCT116结肠癌细胞中p53的含量，但对p21(-/-) 衍生物中已经很高的p53水平没有影响该细胞系。由于p53-destabilizing蛋白 (例如Mdm2) 的降解而增加了不同细胞系中p53水平的转录抑制，尽管其水平急剧下降，但未能增加，而是减少了p21(-/-) 细胞中p53的量。Mdm2。这些结果表明，p21在不同细胞类型中充当p53稳定性的负调节剂。p21对p53的调节可能会提供限制p53诱导的负调节环。

BACKGROUND & AIMS: OBJECTIVE:Inflammatory mechanisms are involved in atherosclerotic plaque rupture and subsequent thrombin formation. Thrombin not only plays a central role in thrombus formation and platelet activation, but also in the induction of inflammatory processes. We assessed the hypothesis that melagatran, a direct thrombin inhibitor, attenuates plaque progression and promotes stability of advanced atherosclerotic lesions. METHODS AND RESULTS:Melagatran (500 micromol/kg/d) or control diet was administered to apolipoprotein E-deficient mice (n=54) with advanced atherosclerotic lesions. Treatment reduced lesion progression in brachiocephalic arteries (P<0.005). Morphometric analysis confirmed that thrombin inhibition promoted plaque stability and resulted in thicker fibrous caps (28.4+/-14.2 microm versus 20.8+/-12.0 microm; P<0.05), increased media thickness (29.3+/-9.6 microm versus 24.4+/-6.7 microm; P<0.05), and smaller necrotic cores (73,537+/-41,301 microm2 versus 126,819+/-51,730 microm2; P<0.0005). Electro mobility shift assays revealed reduced binding activity of nuclear factor kappaB (P<0.05) and activator protein-1 (P<0.05) in aortas of treated mice. Furthermore, immunohistochemistry demonstrated reduced staining for matrix metalloproteinase (MMP)-9 (P<0.05). Melagatran had no significant effect on early lesion formation in C57BL/6J mice. CONCLUSIONS:The direct thrombin inhibitor melagatran reduces lesion size and may promote plaque stability in apolipoprotein E-deficient mice, possibly through reduced activation of proinflammatory transcription factors and reduced synthesis of MMP-9.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:Daytime sleepiness correlates with sleep-related accidents, but convenient tests for occupational sleepiness monitoring are scarce. The effect of daytime on balance, on posturographic measurements, and on their repeatability was investigated in 30 healthy volunteers as part of our work to develop such a test. METHODS:The daytime effect was assessed by measuring balance at 8:30 am, 10:30 am, and 1:30 pm. The repeatability was assessed with morning trials once a week for 1 month. The posturographic test was performed on a static force platform, and the balance was evaluated from a fractal dimension of sway, most common sway amplitude, and time interval for open-loop stance control. RESULTS:The balance worsened during the day, and it was possible to determine whether the measurement was performed in the morning or in the afternoon. The morning balance remained unchanged during the month-long test. CONCLUSIONS:Posturographic measurements are repeatable and have a circadian effect, which may be influenced by sleepiness.

背景与目标：

BACKGROUND & AIMS: :Cefpodoxime proxetil is a third generation cephalosporin antibiotic demonstrates pH dependent solubility and is highly soluble only in acidic pH. The purpose of this investigation was to design and develop immediate release tablets of cefpodoxime proxetil by direct compression method and determine the effect of different solid buffers (organic acids) such as fumaric acid (formulations F1-F4), maleic acid (formulations M1-M4) and citric acid (formulations C1-C4) by using cefpodoxime and acid in the ratios of 4:1, 2:1, 1:1 and 1:2 to achieve pH-independent release of the drug. Physical parameters and assay were found to be within the acceptable range as prescribed in USP 36 / NF 31. In vitro dissolution studies of each formulation were performed in distilled water, USP dissolution medium, HCl buffer solution of pH 1.2, phosphate buffer solutions of pH 4.5 and 6.8 to observe the drug release. The formulations F3, F4, M4 were selected for film coating on the basis of better drug release profile, to protect the drug from chemical degradation through hydrolysis. Film coated formulation F3, F4 and M4 showed a remarkable in vitro release of the drug (72.88±0.43 to 92.67±0.71%) within 30min of observation in all dissolution media and further evaluated by model independent and model dependent approaches. The drug release was found to be best fit to Weibull model as highest r2adjusted (0.924-0.998) and lowest AIC (18.416-54.710) values were obtained in all dissolution media. R Gui® applied for stability studies of F3 and F4 formulations, showing shelf lives of 28 & 27months at ambient and 33 months at accelerated temperatures. Formulation F4 was chosen as best formulation on the basis of physical properties, highest dissolution rate and stability studies.

背景与目标： : 头孢泊肟酯是第三代头孢菌素抗生素，具有pH依赖性溶解度，仅在酸性pH下高度可溶。本研究的目的是通过直接压片法设计和开发头孢泊肟酯的速释片剂，并确定不同固体缓冲液 (有机酸) 如富马酸 (配方F1-F4) 的效果。马来酸 (制剂M1-M4) 和柠檬酸 (制剂C1-C4) 通过以4:1，2:1，1:1和1:2的比例使用头孢泊肟和酸来实现药物的pH独立释放。发现物理参数和测定在USP 36 / NF 31规定的可接受范围内。在蒸馏水，USP溶解介质，pH 1.2的HCl缓冲溶液，pH 4.5和6.8的磷酸盐缓冲溶液中进行每种制剂的体外溶出研究，以观察药物释放。基于更好的药物释放特性，选择F3，F4，M4制剂进行薄膜包衣，以保护药物免受水解化学降解。薄膜包衣制剂F3，F4和M4在所有溶解介质中观察30分钟内显示出显着的药物体外释放 (72.88 ± 0.43至92.67 ± 0.71%)，并通过模型独立和模型依赖方法进行进一步评估。发现药物释放最适合Weibull模型，因为在所有溶解介质中获得最高的r2调节值 (0.924-0.998) 和最低的AIC值 (18.416-54.710)。R Gui®适用于F3和F4制剂的稳定性研究，显示在环境下的保质期为28和27个月，在加速温度下的保质期为33个月。根据物理性质，最高溶解速率和稳定性研究，选择配方F4作为最佳配方。

BACKGROUND & AIMS: :A moderately halophilic protease producer, Bacillus sp. strain isolated from sea water is described. The protease is purified to homogeneity by ammonium sulphate precipitation and CM cellulose chromatography. The serine protease has a molecular mass of 29 kDa. Enzymatic characterization of protease revealed K(m) 2.22 mg mL(-1), Vmax 1111.11 U mL(-1), pH optimum 9.0, t1/2 190 min at 60°C and salt optima 1% (w/v) NaCl. The protease is remarkably stable in hydrophilic and hydrophobic solvents at high concentrations. The purified preparation is unstable at room temperature. Ca(2+) ions are required for preventing this loss of activity. Interestingly, the activity and stability are modulated differentially. Whereas, divalent cation Ca(2+) are involved in maintaining stability in solution at room temperature by preventing unfolding, monovalent Na(+) and K(+) ions participate in regulating the activity and assist in refolding of the enzyme. Application of the protease is shown in efficient removal of blood stain.

背景与目标： : 中度嗜盐蛋白酶生产者，芽孢杆菌属。描述了从海水中分离的菌株。通过硫酸铵沉淀和二1212纤维素色谱法将蛋白酶纯化至均质。丝氨酸蛋白酶的分子量为29 kDa。蛋白酶的酶促表征显示K(m) 2.22 mg mL(-1)，Vmax 1111.11 U mL(-1)，pH最适9.0，60 °C下的t1/2 190分钟和盐最适1% (w/v) NaCl。蛋白酶在高浓度的亲水和疏水溶剂中非常稳定。纯化的制剂在室温下不稳定。需要Ca(2) 离子来防止这种活性损失。有趣的是，活性和稳定性受到不同的调节。鉴于二价阳离子Ca(2) 通过防止展开而参与在室温下维持溶液的稳定性，单价Na () 和K () 离子参与调节活性并协助酶的重折叠。蛋白酶的应用可有效去除血迹。

BACKGROUND & AIMS: PURPOSE:The purpose of this study was to determine the quantity and quality of DNA extracted from a dental bite impression wafer immediately after impression and after 12 months of home storage. The authors' hypothesis was that the wafer would retain sufficient DNA with appropriate genetic markers to make an identification match. METHODS:Two impression wafers (Toothprints(®) brand) were administered to 100 3- to 26-year-olds. A cotton swab was used as a control. DNA from wafers stored for 12 months at home were compared to DNA collected at time 0 and compared to swabs at specific sites to determine quality and accuracy. The amount of DNA captured and recovered was analyzed using MagAttract technology and a quantitative real-time polymerase chain reaction. Capillary gel electrophoresis was performed to determine the quality of the DNA profiles obtained from the wafers vs those generated from the swabs of each subject. RESULTS:Average DNA concentration was: 480 pg/μL (wafer at time 0); 392 pg/μL (wafer after 12 months kept by subjects); and 1,041 pg/μL (buccal swab). Sufficient DNA for human identification was recovered from all sets of wafers, producing clear DNA profiles and accurate matches to buccal swabs. No inhibitors were found that could interfere with DNA profiling. CONCLUSIONS:Toothprints® impression wafers can be useful for DNA collection and child identification. After 12 months, the wafer was still usable for DNA capture and identification match.

背景与目标：

BACKGROUND & AIMS: :In this study, the efficiency of binary ethyleneimine (BEI) in combination with formaldehyde (FA) and glutaraldehyde (GTA) in inactivating the Indian FMDV vaccine strains is compared. The acceptable safety of virus inactivation was faster and the inactivation rates were increased many-folds with combination of inactivants than BEI alone. FMDV A was inactivated rapidly than the other two serotypes with BEI + FA combination. Inactivation plots were linear for all the serotypes irrespective of inactivation process. Further, the integrity studies on 146S using serotype specific ELISA indicated no significant change in the antigenic mass of all the serotypes throughout the inactivation process. However, the loss of 146S antigen occurred in the subsequent steps of downstream processing. Further, the studies on intactness of viral RNA using real time PCR indicated the amplification of 1D gene sequences in all the preparations of timed samples irrespective of serotypes/inactivation process. Further, inactivated virus preparation (146S) was more stable at lower temperatures for all the serotypes/inactivation process. Among the combinations of inactivants, BEI + FA out performed compared to BEI + GTA and BEI in terms of inactivation rates, 146S yield and its storage stability, irrespective of the serotypes.

背景与目标： : 在这项研究中，比较了二元乙烯亚胺 (BEI) 与甲醛 (FA) 和戊二醛 (GTA) 联合灭活印度FMDV疫苗株的效率。与单独使用灭活剂相比，灭活剂的可接受安全性更快，灭活率提高了许多倍。FMDV A比BEI FA组合的其他两种血清型迅速失活。与灭活过程无关，所有血清型的灭活图都是线性的。此外，使用血清型特异性ELISA对146S的完整性研究表明，在整个灭活过程中，所有血清型的抗原质量没有显著变化。然而，146S抗原的损失发生在下游处理的后续步骤中。此外，使用实时PCR对病毒RNA的完整性进行的研究表明，无论血清型/失活过程如何，在所有定时样品的制剂中都扩增了1D基因序列。此外，对于所有血清型/灭活过程，灭活病毒制剂 (146S) 在较低温度下更稳定。在灭活剂的组合中，与BEI GTA和BEI相比，BEI + FA在灭活率，146S产率及其储存稳定性方面进行了比较，而与血清型无关。

BACKGROUND & AIMS: :Catalysing the reduction of oxygen in acidic media is a standing challenge. Although activity of platinum, the most active metal, can be substantially improved by alloying, alloy stability remains a concern. Here we report that platinum nanoparticles supported on graphite-rich boron carbide show a 50-100% increase in activity in acidic media and improved cycle stability compared to commercial carbon supported platinum nanoparticles. Transmission electron microscopy and x-ray absorption fine structure analysis confirm similar platinum nanoparticle shapes, sizes, lattice parameters, and cluster packing on both supports, while x-ray photoelectron and absorption spectroscopy demonstrate a change in electronic structure. This shows that purely electronic metal-support interactions can significantly improve oxygen reduction activity without inducing shape, alloying or strain effects and without compromising stability. Optimizing the electronic interaction between the catalyst and support is, therefore, a promising approach for advanced electrocatalysts where optimizing the catalytic nanoparticles themselves is constrained by other concerns.

背景与目标： : 催化酸性介质中氧的还原是一个长期的挑战。尽管通过合金化可以大大提高铂 (最具活性的金属) 的活性，但合金的稳定性仍然令人担忧。在这里，我们报告，与商业碳负载的铂纳米颗粒相比，负载在富含石墨的碳化硼上的铂纳米颗粒在酸性介质中显示出50-100% 的活性增加和改进的循环稳定性。透射电子显微镜和x射线吸收精细结构分析证实了两种载体上相似的铂纳米颗粒形状，大小，晶格参数和团簇堆积，而x射线光电子和吸收光谱表明电子结构发生了变化。这表明，纯电子金属-载体相互作用可以显着提高氧还原活性，而不会引起形状，合金化或应变效应，并且不会损害稳定性。因此，优化催化剂和载体之间的电子相互作用是先进的电催化剂的一种有前途的方法，其中优化催化纳米颗粒本身受到其他问题的限制。

BACKGROUND & AIMS: BACKGROUND:Psychopathological heterogeneity in manic syndromes may in part reflect underlying latent classes with characteristic outcome patterns. Differential treatment course and outcome after 12 weeks of treatment were examined for three distinct classes of patients with acute mania in bipolar disorder. SUBJECTS AND METHODS:Three thousand four hundred and twenty-five patients with acute mania were divided into three distinct mania classes: 'Typical', 'Psychotic' and 'Dual' (i.e. comorbid substance use) mania. Persistence of class differences and social outcomes were examined, using multilevel regression analyses and odds ratios. RESULTS:The three classes showed substantial stability post-baseline in the pattern of associations with class-characteristic variables. Psychotic and Dual mania predicted poorer outcome in terms of psychosis comorbidity and overall bipolar and mania severity, while Dual mania additionally predicted poorer outcome of alcohol and substance abuse. Worse social outcomes were observed for both Dual and Psychotic mania. CONCLUSION:The identified distinct classes are stable and associated with differential treatment outcome. Overall, Dual and Psychotic mania show less favourable outcomes compared to Typical mania. These findings additionally give rise to concern on the generalisability of randomized clinical trials RCTs.

背景与目标：

BACKGROUND & AIMS: :Silymarin, a known standardized extract obtained from seeds of Silybum marianum is used in treatment of liver diseases of varying origins. Aiming at improving its poor bioavailability from oral products, silymarin hybrid liposomes are introduced in this work for buccal administration after investigating their stability and in vivo hepatoprotective efficiency. Silymarin loaded hybrid liposomes composed of lecithin (L), cholesterol (Ch), stearyl amine (SA) and Tween 20 (T20) in molar ratio of (9:1:1:0.5) were prepared. Their stability upon storage was studied at 4 degrees C and at ambient conditions. Stored samples were analyzed for percent encapsulation, drug release, particle size, turbidity measurement and visual changes. Characterization of the blend between phospholipid and silymarin was done using FT-IR and DSC which indicated a possible interaction. The stabilized formula of silymarin hybrid liposomes was evaluated upon buccal administration regarding its hepatoprotective activity against carbon tetrachloride-induced oxidative stress in albino rats. The degree of protection was measured using biochemical parameters like serum glutamic oxalacetate transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT). The introduced silymarin hybrid liposomes produced a significant decrease in both transaminase levels when challenged with CCl(4) (intraperitonially) in comparison with orally administered silymarin suspension. This improvement was also confirmed histopathologically.

背景与目标： 水飞蓟素，从水飞蓟素种子中获得的已知标准化提取物，用于治疗不同来源的肝脏疾病。为了改善口服产品的生物利用度，在研究其稳定性和体内保肝效率后，将水飞蓟素杂交脂质体引入口腔给药。制备了由卵磷脂 (L)，胆固醇 (Ch)，硬脂胺 (SA) 和吐温20 (T20) 组成的水飞蓟素杂化脂质体，摩尔比为 (9:1:1:0.5)。在4摄氏度和环境条件下研究了它们在储存时的稳定性。分析存储的样品的包封百分比，药物释放，粒径，浊度测量和视觉变化。使用ft-ir和DSC对磷脂和水飞蓟素之间的混合物进行表征，这表明可能存在相互作用。在颊给药后评估了水飞蓟素混合脂质体的稳定配方，以评估其对白化病大鼠四氯化碳诱导的氧化应激的保肝活性。使用生化参数 (例如血清谷草转氨酶 (SGOT) 和血清谷丙酮酸转氨酶 (SGPT)) 测量保护程度。与口服水飞蓟素混悬液相比，引入的水飞蓟素混合脂质体在用CCl(4) 攻击时 (腹膜内) 使两种转氨酶水平均显着降低。这种改善也在组织病理学上得到证实。

BACKGROUND & AIMS: :The purpose of this study was to determine how two different types of concurrent tasks affect gait stability in patients with concussion and how balance is maintained. Fourteen individuals suffering from a grade II concussion and 14 matched controls performed a single task of level walking and two types of concurrent tasks during level walking: a discrete reaction time task and a continuous sequential question and answer task. Common gait spatial/temporal measurements, whole-body center of mass motion, and the center of pressure trajectory were recorded. Concussed individuals demonstrated differences in gait while performing single-task level walking and while being challenged with a more difficult secondary task compared to normal controls. Concussed individuals adopted a slower, more conservative gait strategy to maintain stability, but still exhibited signs of instability with center of mass deviations in the coronal plane increasing by 13% during the question and answer dual-task and 26% more than control subjects. Trends of attentional deficits were present with the question and answer task, while the reaction time task seemed to help concussed individuals be more alert to their gait and stability. Recommendations for a sensitive testing protocol of deficits following concussion are explained.

背景与目标： : 这项研究的目的是确定两种不同类型的并发任务如何影响脑震荡患者的步态稳定性以及如何保持平衡。14名患有II级脑震荡的人和14名匹配的对照者在水平行走过程中执行了单一的水平行走任务和两种并发任务: 离散的反应时间任务和连续的连续问答任务。记录了常见的步态空间/时间测量，全身质心运动和压力中心轨迹。与正常对照组相比，脑震荡的个体在执行单任务水平行走时表现出步态差异，并且面临着更困难的次要任务。脑震荡的个体采取了较慢，更保守的步态策略来维持稳定，但仍表现出不稳定的迹象，在问答过程中，冠状平面的质心偏差增加了13%，并且比对照受试者26% 更多。问答任务中存在注意缺陷的趋势，而反应时间任务似乎有助于脑震荡的个体对步态和稳定性更加警惕。解释了脑震荡后缺陷的敏感测试方案的建议。

BACKGROUND & AIMS: :We employed random mutagenesis to determine the region of the initial unfolding of hyper-alkaline-sensitive subtilisin, ALP I, that precedes the denaturation of the entire protein under highly alkaline conditions. This region comprises two alpha-helices and a calcium-binding loop. Stabilization of the region caused the stabilization of the entire protein at a high alkaline pH 12. The alkaline stability of this region was most effectively improved by hydrophobic interactions, followed by ionic interactions with Arg residues. The effect of mutations on the improvement was different with regard to the alkaline stability and thermostability. This indicated that different strategies were necessary to improve the alkaline stability and thermostability of the protein.

背景与目标： : 我们采用随机诱变来确定高碱性敏感枯草杆菌蛋白酶ALP I的初始展开区域，该区域在高度碱性条件下整个蛋白质变性之前。该区域包括两个 α 螺旋和一个钙结合环。该区域的稳定导致整个蛋白质在高碱性pH 12下的稳定。通过疏水相互作用，其次是与Arg残基的离子相互作用，可以最有效地改善该区域的碱性稳定性。突变对改善的影响在碱性稳定性和热稳定性方面有所不同。这表明需要不同的策略来提高蛋白质的碱性稳定性和热稳定性。

BACKGROUND & AIMS: :An important stabilizing mechanism in most diversity stability models is the insurance hypothesis, which involves correlation/covariance relationships among species. These models require that species do not fluctuate synchronously over time: that is, the correlation between pairs of species does not equal 1.0. However, the strength of this stabilizing mechanism increases as correlations decline away from 1.0, especially as they become more negative and also as the summed covariance across all species pairs becomes more negative. We evaluated the importance of the insurance hypothesis as a stabilizing mechanism by examining a variety of terrestrial assemblages using long-term data from the Global Population Dynamics Database, the Breeding Bird Survey, and a long-term site in southeastern Arizona, USA. We identified co-occurring assemblages of species and calculated the Spearman rank correlations of all pairs of species and the summed covariance of the entire assemblage. We found that, in most assemblages, positive correlations were two to three times more common than negative and that the magnitude of the positive correlations tended to be stronger than the negative correlations. For all but three assemblages, the summed covariance was positive. Data from larger spatial scales tended to exhibit more positive correlations, but even at the smallest spatial scales, positive correlations outnumbered negative. We suggest that species often covary positively because coexisting species respond similarly to fluctuations in their resource base driven by climatic fluctuations. As such, our review suggests that the insurance hypothesis may not be a strong mechanism stabilizing fluctuations in natural terrestrial communities.

背景与目标： : 在大多数多样性稳定性模型中，一个重要的稳定机制是保险假说，它涉及物种之间的相关性/协方差关系。这些模型要求物种不会随时间同步波动: 也就是说，成对物种之间的相关性不等于1.0。然而，这种稳定机制的强度随着相关性远离1.0的下降而增加，尤其是当它们变得更负并且所有物种对的总协方差变得更负时。我们使用全球人口动态数据库，繁殖鸟类调查和美国亚利桑那州东南部的长期站点的长期数据，通过检查各种陆生组合，评估了保险假说作为稳定机制的重要性。我们确定了同时发生的物种组合，并计算了所有物种对的Spearman等级相关性以及整个组合的总协方差。我们发现，在大多数组合中，正相关是负相关的两到三倍，正相关的幅度往往强于负相关。对于除三个组合外的所有组合，总协方差均为正值。来自较大空间尺度的数据往往表现出更多的正相关性，但是即使在最小的空间尺度上，正相关性也超过了负相关性。我们建议物种通常呈正相关，因为共存物种对气候波动驱动的资源基础波动的反应相似。因此，我们的评论表明，保险假说可能不是稳定自然陆地社区波动的强大机制。

BACKGROUND & AIMS: BACKGROUND:Recently, we reported that sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a), the pump responsible for reuptake of cytosolic calcium during diastole, plays a central role in the molecular mechanism of cardiac alternans. Heart failure (HF) is associated with impaired myocardial calcium handling, deficient SERCA2a, and increased susceptibility to cardiac alternans. Therefore, we hypothesized that restoring deficient SERCA2a by gene transfer will significantly reduce arrhythmogenic cardiac alternans in the failing heart. METHODS AND RESULTS:Adult guinea pigs were divided into 3 groups: control, HF, and HF+AAV9.SERCA2a gene transfer. HF resulted in a decrease in left ventricular fractional shortening compared with controls (P<0.001). As expected, isolated HF myocytes demonstrated slower sarcoplasmic reticulum calcium uptake, decreased Ca(2+) release, and increased diastolic Ca(2+) (P<0.05) compared with controls. Moreover, SERCA2a, cardiac ryanodine receptor 2, and sodium-calcium exchanger protein expression was decreased in HF compared with control (P<0.05). As predicted, HF increased susceptibility to cardiac alternans, as evidenced by decreased heart rate thresholds for both V(m) alternans and Ca alternans compared with controls (P<0.01). Interestingly, in vivo gene transfer of AAV9.SERCA2a in the failing heart improved left ventricular contractile function (P<0.01), suppressed cardiac alternans (P<0.01), and reduced ryanodine receptor 2 P(o) secondary to reduction of ryanodine receptor 2-P(S2814) (P<0.01). This ultimately resulted in a decreased incidence of inducible ventricular arrhythmias (P=0.05). CONCLUSIONS:These data show that SERCA2a gene transfer in the failing heart not only improves contractile function but also directly restores electric stability through the amelioration of key arrhythmogenic substrate (ie, cardiac alternans) and triggers (ie, sarcoplasmic reticulum Ca(2+) leak).

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:The authors examined the temporal stability and predictive utility of bulimic symptoms and related variables over the course of 10 years, from 1982 to 1992.

METHOD:The subjects were 459 women who were aged 18-22 years in 1982 and were surveyed in both 1982 and 1992. Each respondent completed five subscales of the Eating Disorders Inventory (bulimia, drive for thinness, maturity fears, perfectionism, and interpersonal distrust) and answered questions based on the DSM-III criteria for bulimia nervosa.

RESULTS:The temporal stability of bulimic symptoms and related variables was relatively high. Bulimic status in 1982 conferred an approximately 15-fold increase in risk 10 years later. Drive for thinness and, to lesser degrees, maturity fears and perfectionism received support as long-term predictors of bulimic symptoms.

CONCLUSIONS:Bulimic symptoms display high temporal stability and thus may affect long-term functioning and well-being. Later symptoms are related to scores on specific subscales of the Eating Disorders Inventory administered 10 years earlier. Assessment and therapy should be conducted accordingly.

背景与目标： 目的 : 作者研究了在10年的时间过程中，暴食症症状和相关变量的时间稳定性和预测效用，1982年1992年。
方法 : 受试者为459名年龄在18-22岁1982年的女性，并在1982和1992中接受了调查。每个受访者都完成了饮食失调量表的五个分量表 (贪食症，瘦弱，成熟恐惧，完美主义和人际不信任)，并根据dsm-iii神经性贪食症标准回答了问题。
结果 : 暴食症症状和相关变量的时间稳定性相对较高。10年后，暴食者状态1982年使风险增加了约15倍。瘦弱的动力，以及在较小程度上的成熟恐惧和完美主义作为贪食症症状的长期预测指标得到了支持。
结论 : 贪食症症状显示出很高的时间稳定性，因此可能会影响长期的功能和健康。后期症状与10年前管理的饮食失调量表的特定分量表得分有关。应进行相应的评估和治疗。