• 【全身静磁场暴露会增加蜗牛Helix Pomatia的热伤害感受性阈值。】 复制标题 收藏 收藏
    DOI:10.1556/ABiol.63.2012.4.3 复制DOI
    作者列表:László JF,Hernádi L
    BACKGROUND & AIMS: :We investigated the effect of homogeneous and inhomogeneous static magnetic field (SMF) exposure on the thermal nociceptive threshold of snail in the hot plate test (43 °C). Both homogeneous (hSMF) and inhomogeneous (iSMF) SMF increased the thermo-nociceptive threshold: 40.2%, 29.2%, or 41.7% after an exposure of 20, 30, or 40 min hSMF by p < 0.001, p < 0.0001, or p < 0.001, and 32.7% or 46.2% after an exposure of 20 or 40 min iSMF by p < 0.05 or p < 0.0001. These results suggest that SMF has an antinociceptive effect in snail. On the other hand, naloxone as an atypical opioid antagonist in an amount of 1 μg/g was found to significantly decrease the thermo-nociceptive threshold (41.9% by p < 0.002), which could be antagonized by hSMF exposure implying that hSMF exerts its antinociceptive effect partly via opioid receptors.
    背景与目标: :我们在热板测试(43°C)中研究了均匀和不均匀的静磁场(SMF)暴露对蜗牛的热伤害感受性阈值的影响。均质(hSMF)和不均质(iSMF)SMF均可在暴露20、30或40分钟的hSMF时通过p <0.001,p <0.0001或p提高热伤害感受性阈值:40.2%,29.2%或41.7% iSMF暴露p≤0.05或p≤0.0001后,<0.001,以及32.7%或46.2%。这些结果表明,SMF对蜗牛具有镇痛作用。另一方面,发现纳洛酮作为一种非典型的阿片类药物拮抗剂,可显着降低热伤害感受性阈值(41.9%,p <0.002),可被hSMF暴露所拮抗,暗示hSMF发挥了其作用。部分通过阿片样物质受体产生抗伤害感受作用。
  • 【南非城市青少年队列中的居民流动性,社会经济背景和体重指数。】 复制标题 收藏 收藏
    DOI:10.1016/j.healthplace.2012.09.016 复制DOI
    作者列表:Ginsburg C,Griffiths PL,Richter LM,Norris SA
    BACKGROUND & AIMS: :Adolescents who are changing residence, as well as their social and economic circumstances may experience lifestyle changes that have an effect on body composition outcomes such as undernutrition, overweight or obesity. This paper uses data from Birth to Twenty, a birth cohort of South African urban children, to determine the relationship between residential mobility and body mass index (BMI) amongst Black adolescents aged 15 (n=1613), and to examine the role of changes in household socioeconomic status (SES). The prevalence of overweight and obesity in the sample was 25% in females and 8% in males. Amongst the females, a strong positive association between residential mobility and BMI was observed for those who also experienced an increase in household SES between birth and 15 years (β=0.42, SE=0.13), while no effect was identified for males. The study shows the potential for environmental change and increased resources to influence the risk for obesity. It also highlights the value in considering the range of social environmental factors and changes across the early life course that might play a part in evolving nutritional patterns in urban transitioning environments.
    背景与目标: :正在改变居住地的青少年以及他们的社会和经济状况,可能会经历生活方式的改变,这些改变会影响身体组成的结果,例如营养不良,超重或肥胖。本文使用南非城市儿童的出生队列出生至二十岁的数据来确定15岁黑人青少年(n = 1613)的居住流动性与体重指数(BMI)之间的关系,并研究变化的作用家庭社会经济地位(SES)。样本中超重和肥胖的患病率在女性中为25%,在男性中为8%。在女性中,对于那些出生至15岁之间家庭SES也有所增加的人,其居住活动性与BMI之间存在很强的正相关性(β= 0.42,SE = 0.13),而对男性没有影响。研究显示环境变化和增加资源影响肥胖风险的潜力。它还强调了考虑社会环境因素的范围和整个生命过程中的变化的价值,这些因素可能在城市过渡环境中不断演变的营养模式中发挥作用。
  • 【按年龄和性别划分的霍奇金淋巴瘤的体重和风险:康涅狄格州和马萨诸塞州的一项基于人群的病例对照研究。】 复制标题 收藏 收藏
    DOI:10.1007/s10552-012-0100-1 复制DOI
    作者列表:Li Q,Chang ET,Bassig BA,Dai M,Qin Q,Gao Y,Zhang Y,Zheng T
    BACKGROUND & AIMS: PURPOSE:Descriptive studies have indicated a rising trend in Hodgkin's lymphoma (HL) incidence in young adults, especially females. Increasing evidence has suggested that some risk factors associated with HL may vary by age or gender. Recent studies have reported an increased risk of HL associated with increasing body mass index (BMI), but the results have been inconsistent. The objectives of this study were to examine whether the associations between measures of body size (height, weight, and BMI) and HL risk vary by age and/or gender. METHODS:A population-based case-control study was conducted in Connecticut and Massachusetts. A total of 567 HL cases and 679 controls were recruited in 1997-2000. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS:Among younger women <35 years old, being overweight (25-29.9 kg/m(2)) versus normal weight (18.5-24.9 kg/m(2)) was significantly associated with an increased risk of HL (OR = 2.1, 95 % CI = 1.1-4.0). The risk increased with increasing weight and BMI (p trends <0.01). Among women ≥35 years old, by contrast, higher weight and BMI were associated with a reduced risk of HL (p trends <0.01). Conversely, there was no significant association between BMI and risk of HL in younger or older males. CONCLUSIONS:These findings show that the associations between body size and risk of HL vary by gender and age, and require confirmation in other populations.
    背景与目标: 目的:描述性研究表明,霍奇金淋巴瘤(HL)的发病率在年轻人中,尤其是女性中呈上升趋势。越来越多的证据表明,与HL相关的某些危险因素可能随年龄或性别而变化。最近的研究报告了与体重指数(BMI)增加相关的HL风险增加,但结果不一致。这项研究的目的是检查身体大小(身高,体重和BMI)与HL风险之间的关系是否随年龄和/或性别而变化。
    方法:在康涅狄格州和马萨诸塞州进行了一项基于人群的病例对照研究。在1997-2000年间,共招募了567例HL病例和679例对照。使用无条件逻辑回归来计算比值比(OR)和95%置信区间(CIs)。
    结果:<35岁的年轻女性中,超重(25-29.9 kg / m(2))与正常体重(18.5-24.9 kg / m(2))与HL风险增加显着相关(OR = 2.1 ,95%CI = 1.1-4.0)。风险随着体重和BMI的增加而增加(p趋势<0.01)。相比之下,≥35岁的女性中,体重增加和BMI升高与HL风险降低相关(p趋势<0.01)。相反,年轻或老年男性的BMI与HL风险之间没有显着相关性。
    结论:这些发现表明,体型与HL风险之间的关联因性别和年龄而异,需要在其他人群中进行确认。
  • 【双足卷尾猴的地面反作用力和质量力学中心:对人类双足动物进化的启示。】 复制标题 收藏 收藏
    DOI:10.1002/ajpa.22176 复制DOI
    作者列表:Demes B,O'Neill MC
    BACKGROUND & AIMS: :Tufted capuchin monkeys are known to use both quadrupedalism and bipedalism in their natural environments. Although previous studies have investigated limb kinematics and metabolic costs, their ground reaction forces (GRFs) and center of mass (CoM) mechanics during two and four-legged locomotion are unknown. Here, we determine the hind limb GRFs and CoM energy, work, and power during bipedalism and quadrupedalism over a range of speeds and gaits to investigate the effect of differential limb number on locomotor performance. Our results indicate that capuchin monkeys use a "grounded run" during bipedalism (0.83-1.43 ms(-1)) and primarily ambling and galloping gaits during quadrupedalism (0.91-6.0 ms(-1)). CoM energy recoveries are quite low during bipedalism (2-17%), and in general higher during quadrupedalism (4-72%). Consistent with this, hind limb vertical GRFs as well as CoM work, power, and collisional losses are higher in bipedalism than quadrupedalism. The positive CoM work is 2.04 ± 0.40 Jkg(-1) m(-1) (bipedalism) and 0.70 ± 0.29 Jkg(-1) m(-1) (quadrupedalism), which is within the range of published values for two and four-legged terrestrial animals. The results of this study confirm that facultative bipedalism in capuchins and other nonhuman primates need not be restricted to a pendulum-like walking gait, but rather can include running, albeit without an aerial phase. Based on these results and similar studies of other facultative bipeds, we suggest that important transitions in the evolution of hominin locomotor performance were the emergences of an obligate, pendulum-like walking gait and a bouncy running gait that included a whole-body aerial phase.
    背景与目标: :簇绒的卷尾猴在其自然环境中同时使用四足动物和两足动物。尽管先前的研究已经研究了肢体运动学和代谢成本,但是在两腿和四腿运动过程中其地面反作用力(GRF)和质心(CoM)力学仍然未知。在这里,我们确定了双足和四足动物在各种速度和步态下的后肢GRF和CoM能量,功和功率,以研究差异肢数对运动性能的影响。我们的研究结果表明,卷尾猴在两足动物(0.83-1.43 ms(-1))期间使用“地面跑步”,在四足动物(0.91-6.0 ms(-1))期间主要使用步态和奔腾步态。在两足动物中,CoM能量回收率非常低(2-17%),而在四足动物中,CoM能量回收率通常较高(4-72%)。与此相一致,两足动物的后肢垂直GRF以及CoM功,功率和碰撞损失要比四足动物的高。 CoM的正工作为2.04±0.40 Jkg(-1)m(-1)(双足)和0.70±0.29 Jkg(-1)m(-1)(四足),这在两个和两个的已发布值范围内四足陆生动物。这项研究的结果证实,卷尾猴和其他非人类灵长类动物的兼性两足动物不必局限于像摆一样的步行步态,而可以包括奔跑,尽管没有空中阶段。根据这些结果以及对其他兼性两足动物的类似研究,我们建议,人的自发运动能力进化的重要转变是专心的,像钟摆一样的步行步态和有弹性的奔跑步态的出现,其中包括整个身体的空中阶段。
  • 【血清甲胎蛋白的半衰期:肝细胞癌肝切除术后复发和生存的早期预后指标。】 复制标题 收藏 收藏
    DOI:10.1097/SLA.0b013e318273be70 复制DOI
    作者列表:Shim JH,Han S,Lee YJ,Lee SG,Kim KM,Lim YS,Chung YH,Lee YS,Lee HC
    BACKGROUND & AIMS: OBJECTIVE:To explore the prognostic value of the postsurgical half-life (HL) of serum alpha-fetoprotein (AFP). BACKGROUND:There is still a paucity of early surrogate indicators of clinical endpoints after liver resection of hepatocellular carcinoma (HCC). METHODS:The analysis was based on cohorts of 225 (exploration set) and 117 (validation set) treatment-naïve HCC patients undergoing curative liver resection. We defined 3 categories of AFP HL: early complete resolution of AFP, normal HL, and prolonged HL if the HL exceeded 7 days. Overall, probabilities of recurrence and survival were estimated and compared across the AFP HL categories. RESULTS:In the exploration cohort, 48 patients (21.3%) achieved early AFP complete resolution, 116 (51.6%) had normal HL, and 61 (27.1%) had prolonged HL. Long AFP HL was significantly associated with early postoperative recurrence (P < 0.001), as was microvascular invasion. Early recurrence within 2 years of resection was observed in 59% of the patients with prolonged AFP HL compared with only 29.3% of those with normal AFP HL (P < 0.001). A log-rank test followed by multivariate Cox analysis identified an independent function of prolonged AFP HL in predicting shorter recurrence-free survival and overall survival time after HCC resection (hazard ratios, 2.81 and 3.58; P < 0.001). When AFP HL analysis was applied to the validation cohort, the association between prolonged AFP HL and survival endpoints (hazard ratio, 11.63 and 16.39; P < 0.001) was confirmed.
    背景与目标: 目的:探讨血清甲胎蛋白(AFP)的术后半衰期(HL)的预后价值。
    背景:肝切除肝细胞癌(HCC)后仍缺乏临床终点的早期替代指标。
    方法:该分析基于225例(探索组)和117例(验证组)未进行过根治性肝切除的未接受治疗的HCC患者的分析。我们定义了AFP HL的3个类别:AFP的早期完全消退,正常HL和如果HL超过7天则延长HL。总体而言,估计并比较了AFP HL类别中复发和存活的可能性。
    结果:在探索队列中,有48例(21.3%)的患者达到了AFP的早期完全缓解,HL正常的116例(51.6%),HL延长的61例(27.1%)。长期AFP HL与微血管浸润与术后早期复发显着相关(P <0.001)。 AFP HL延长的患者中有59%的患者在切除的2年内出现了早期复发,而AFP HL正常的患者中只有29.3%的患者出现了早期复发(P <0.001)。对数秩检验和随后的多元Cox分析确定了AFP HL延长在预测肝癌切除术后较短的无复发生存期和总生存期方面具有独立的功能(危险比,2.81和3.58; P <0.001)。当将AFP HL分析应用于验证队列时,证实了延长的AFP HL与生存终点之间的关联(危险比:11.63和16.39; P <0.001)。
  • 【肥胖男性中大剂量白藜芦醇的补充:一项由研究人员发起,随机,安慰剂对照的底物代谢,胰岛素敏感性和身体成分的临床试验。】 复制标题 收藏 收藏
    DOI:10.2337/db12-0975 复制DOI
    作者列表:Poulsen MM,Vestergaard PF,Clasen BF,Radko Y,Christensen LP,Stødkilde-Jørgensen H,Møller N,Jessen N,Pedersen SB,Jørgensen JO
    BACKGROUND & AIMS: :Obesity, diabetes, hypertension, and hyperlipidemia constitute risk factors for morbidity and premature mortality. Based on animal and in vitro studies, resveratrol reverts these risk factors via stimulation of silent mating type information regulation 2 homolog 1 (SIRT1), but data in human subjects are scarce. The objective of this study was to examine the metabolic effects of high-dose resveratrol in obese human subjects. In a randomized, placebo-controlled, double-blinded, and parallel-group design, 24 obese but otherwise healthy men were randomly assigned to 4 weeks of resveratrol or placebo treatment. Extensive metabolic examinations including assessment of glucose turnover and insulin sensitivity (hyperinsulinemic euglycemic clamp) were performed before and after the treatment. Insulin sensitivity, the primary outcome measure, deteriorated insignificantly in both groups. Endogenous glucose production and the turnover and oxidation rates of glucose remained unchanged. Resveratrol supplementation also had no effect on blood pressure; resting energy expenditure; oxidation rates of lipid; ectopic or visceral fat content; or inflammatory and metabolic biomarkers. The lack of effect disagrees with persuasive data obtained from rodent models and raises doubt about the justification of resveratrol as a human nutritional supplement in metabolic disorders.
    背景与目标: 肥胖,糖尿病,高血压和高脂血症是发病率和过早死亡的危险因素。根据动物和体外研究,白藜芦醇通过刺激无声交配类型信息调节2同源物1(SIRT1)来逆转这些危险因素,但人类受试者的数据却很少。这项研究的目的是检查高剂量白藜芦醇在肥胖人类受试者中的代谢作用。在随机,安慰剂对照,双盲和平行组设计中,将24名肥胖但其他方面健康的男性随机分配到白藜芦醇或安慰剂治疗4周。在治疗之前和之后进行了广泛的代谢检查,包括评估葡萄糖更新和胰岛素敏感性(高胰岛素正常血糖钳夹)。两组的主要结果指标胰岛素敏感性均无显着性恶化。内源性葡萄糖的产生以及葡萄糖的周转率和氧化率保持不变。补充白藜芦醇对血压也没有影响。静息能量消耗;脂质的氧化速率;异位或内脏脂肪含量;或炎症和代谢生物标志物。缺乏效果与从啮齿动物模型获得的有说服力的数据不同,并引起人们对白藜芦醇作为代谢障碍中人类营养补充剂的合理性的怀疑。
  • 【大型草食动物的纤维消化率与消化类型和体重有关-一种体外方法。】 复制标题 收藏 收藏
    DOI:10.1016/j.cbpa.2012.10.026 复制DOI
    作者列表:Steuer P,Südekum KH,Müller DW,Kaandorp J,Clauss M,Hummel J
    BACKGROUND & AIMS: :The coexistence of different ungulate species in a given ecosystem has been the focus of many studies. Differences between ruminant foregut fermenters and hindgut fermenters were remarkable for example in the way they ingest and digest high fibre diets. Digestion trials based on total collections are difficult to conduct or are sometimes even not possible for wild animals in the field or in zoos. To gain information on the fibre digestion achieved by these animals and the influence of body mass (BM) thereon, a method using spot sampling is desirable. In this study, in vitro fermentation of faecal neutral detergent fibre (NDF) was used as a measure of fibre digestion in large ungulates. Food and faecal samples of 10 ruminant foregut fermenting and 7 hindgut fermenting species/breeds were collected. All animals received 100% grass hay with ad libitum access. The NDF of food and faeces was fermented in vitro in a Hohenheim gas test (HGT) for 96 h. The digestion type generally had an effect on the gas production (GP) of faecal NDF in the HGT with hindgut fermenters showing higher values than ruminant foregut fermenters. At any time interval of incubation, BM had no influence on GP. The results are in accordance with both findings that ruminant foregut fermenters have longer mean retention times and more comprehensive particle reduction and findings of a lack of influence of BM on digesta mean retention time. It can be stated that the HGT (96 h) is a useful and quick method to show also small differences within groups in fibre digestion.
    背景与目标: 在一个给定的生态系统中,有蹄类动物的共存一直是许多研究的重点。反刍动物前肠发酵罐和后肠发酵罐之间的差异非常明显,例如,它们摄取和消化高纤维饮食的方式不同。基于总收集物的消化试验很难进行,有时甚至对于野外或动物园中的野生动物也无法进行。为了获得有关这些动物实现的纤维消化及其体重(BM)的影响的信息,需要一种使用点采样的方法。在这项研究中,粪便中性洗涤剂纤维(NDF)的体外发酵被用作大有蹄类动物中纤维消化的量度。收集了10种反刍动物前肠发酵食品和7种后肠发酵物种/品种的食物和粪便样本。所有动物均自由采食100%干草。食物和粪便的NDF在Hohenheim气体试验(HGT)中进行了96 h的体外发酵。消化类型通常会对HGT中粪便NDF的产气量(GP)产生影响,其中后肠发酵罐的值要高于反刍动物前肠发酵罐的值。在任何孵育时间间隔,BM对GP均无影响。结果与两个发现均一致:反刍动物前肠发酵罐具有更长的平均保留时间和更全面的颗粒减少,并且发现BM对消化物的平均保留时间缺乏影响。可以说,HGT(96 h)是一种有用且快速的方法,可以显示纤维消化组内的细微差异。
  • 【血液透析患者的踝臂指数随时间下降和心血管结局。】 复制标题 收藏 收藏
    DOI:10.1097/MAJ.0b013e31825141bf 复制DOI
    作者列表:Chen SC,Chang JM,Liu WC,Huang JC,Chen YY,Yang TK,Su HM,Chen HC
    BACKGROUND & AIMS: INTRODUCTION:Abnormal ankle-brachial index (ABI) is associated with increased morbidity and mortality in hemodialysis patients. However, whether the decrease in ABI over time carries the prognostic value is unknown. The aim of this study was to assess whether the decrease in ABI over time was a good predictor of poor cardiovascular (CV) prognosis in hemodialysis patients. METHODS:This study enrolled 234 routine hemodialysis patients and 173 patients completed the follow-up. The ABI was measured by an ABI-form device at baseline and at the first year follow-up. The ΔABI was defined as ABI measured at the first year follow-up minus ABI measured at baseline. Progressors of ABI were defined as patients with ΔABI < -0.3. CV events were defined as CV death, hospitalization for unstable angina, nonfatal myocardial infarction, hospitalization for arrhythmia, hospitalization for congestive heart failure and stroke. RESULTS:The follow-up period was 37.8 ± 11.1 months. In the multivariate analysis, progressors of ABI (hazard ratio, 2.71; 95% confidence interval, 1.10-6.68, P = 0.03), decreased albumin and increased high-sensitivity C-reactive protein were associated with increased CV events. CONCLUSIONS:This longitudinal study showed ΔABI < -0.3 was independently associated with an increase in CV events. Hence, a great decrease in ABI over time might be a useful indicator of poor CV prognosis in hemodialysis patients.
    背景与目标: 简介:踝臂指数异常(ABI)与血液透析患者的发病率和死亡率增加相关。但是,随着时间的推移,ABI的降低是否具有预后价值尚不清楚。这项研究的目的是评估ABI随时间的下降是否是血液透析患者不良心血管(CV)预后的良好预测指标。
    方法:本研究招募了234例常规血液透析患者,其中173例患者完成了随访。在基线和第一年随访时,通过ABI形式的设备对ABI进行测量。 ΔABI定义为在第一年随访中测得的ABI减去在基线时测得的ABI。 ABI的进展者定义为ΔABI<-0.3的患者。 CV事件的定义为CV死亡,不稳定型心绞痛的住院治疗,非致命性心肌梗死,心律不齐的住院治疗,充血性心力衰竭和中风的住院治疗。
    结果:随访时间为37.8±11.1个月。在多变量分析中,ABI的进展(危险比,2.71; 95%置信区间,1.10-6.68,P = 0.03),白蛋白降低和高敏感性C反应蛋白升高与CV事件增加相关。
    结论:这项纵向研究表明ΔABI<-0.3与CV事件的增加独立相关。因此,随着时间的推移,ABI的大幅下降可能是血液透析患者CV预后不良的有用指标。
  • 【液相色谱-串联质谱测定法用于测定环孢菌素A,他克莫司,西罗莫司和依维莫司的新型商业测定方法的评估。】 复制标题 收藏 收藏
    DOI:10.1097/FTD.0b013e318274827d 复制DOI
    作者列表:Becker S,Thiery J,Ceglarek U
    BACKGROUND & AIMS: OBJECTIVE:The aim of this study was the evaluation of the first commercially available in-vitro diagnostic (IVD)- mass spectrometric immunosuppressant assay from Chromsystems (MassTox Immunosuppressants ONEMINUTE Test) and the comparison to a routinely used online solid phase extraction liquid chromatography-tandem mass spectrometric assay method for the measurement of cyclosporine A, everolimus, sirolimus, and tacrolimus in patient whole blood samples. METHODS:An API 4000 [tandem mass spectrometer (AB SCIEX)] combined with a CTC Pal autosampler (CTC Analytics AG) and a Shimadzu ultra-fast liquid chromatography (UFLC) system were applied for the direct liquid chromatography-tandem mass spectrometric assay analysis using electrospray ionization in positive ion mode. Isotope-labeled internal standards were used for the commercial assay. Within- and between-day variation, accuracy, and limits of quantification were determined. Samples from external international proficiency testing schemes were measured to assess the accuracy of the commercial assay. About 100 patient samples were reanalyzed with the commercial test kit, and the results were compared with our in-house results. RESULTS:The limit of quantification for the commercial assay was 0.5 ng/mL for everolimus, sirolimus, and tacrolimus and 5 ng/mL for cyclosporine A. The coefficient of variation for all immunosuppressants was lower than 7% (within day) and 12% (between days) for all 5 concentration levels. Accuracy ranged between 82% and 111% for quality control samples and between 89% and 112% for samples from the external quality assurance program. Both methods showed a very good agreement (r > 0.91) in patient samples over the whole concentration range for all immunosuppressants. CONCLUSION:The commercial immunosuppressant assay from Chromsystems represents a standardized IVD-certified alternative to our in-house developed assay.
    背景与目标: 目的:本研究的目的是评估Chromsystems的第一个可商购的体外诊断(IVD)-质谱免疫抑制试验(MassTox免疫抑制剂ONEMINUTE测试),并将其与常规使用的在线固相萃取液相色谱串联进行比较质谱法测定患者全血样品中的环孢素A,依维莫司,西罗莫司和他克莫司。
    方法:将API 4000 [串联质谱仪(AB SCIEX)]结合CTC Pal自动进样器(CTC Analytics AG)和Shimadzu超快速液相色谱(UFLC)系统用于直接液相色谱-串联质谱分析在正离子模式下使用电喷雾电离。同位素标记的内标用于商业检测。确定日内和日间变化,准确性和定量限。对来自外部国际能力验证计划的样本进行了测量,以评估商业化验的准确性。使用商业测试套件对大约100个患者样品进行了重新分析,并将结果与​​我们的内部结果进行了比较。
    结果:商业化验的定量限为依维莫司,西罗莫司和他克莫司为0.5 ng / mL,环孢霉素A为5 ng / mL。所有免疫抑制剂的变异系数均低于7%(日内)和12% (介于两天之间)所有5种浓度水平。对于质量控制样品,其准确性介于82%至111%之间,对于来自外部质量保证计划的样品,其准确性介于89%至112%之间。两种方法在所有免疫抑制剂的整个浓度范围内的患者样品中均显示出很好的一致性(r> 0.91)。
    结论:Chromsystems的商业免疫抑制剂测定法是我们内部开发测定法的标准化IVD认证替代品。
  • 【抗逆转录病毒方案复杂性指数。一种量化方案复杂性的新颖方法。】 复制标题 收藏 收藏
    DOI:10.1097/QAI.0b013e31811ed1f1 复制DOI
    作者列表:Martin S,Wolters PL,Calabrese SK,Toledo-Tamula MA,Wood LV,Roby G,Elliott-DeSorbo DK
    BACKGROUND & AIMS: BACKGROUND:Individuals with HIV disease often must adhere to complex medication regimens. To date, regimen complexity has not been examined in the literature using standardized procedures incorporating all important elements of antiretroviral (ARV) regimens. OBJECTIVE:This article presents a novel method of quantifying regimen complexity using objective criteria addressing the factors that may complicate adherence to ARV regimens. METHODS:Part 1 of this article describes the development of the Antiretroviral Regimen Complexity (ARC) Index scoring system. Based on input from pediatric and adult patients, caregivers of pediatric patients, and health care professionals, this comprehensive system includes the number of medications, dosing schedules, administration methods, special instructions, and required preparations associated with ARV regimens. Weights are applied for each of these factors to produce an overall score representing the regimen's level of complexity. Part 2 of this article presents reliability and validity data for the system. RESULTS:The ARC Index demonstrates excellent test-retest and interrater reliability as well as strong construct and discriminant validity. An on-line version of this system minimizes computation errors. CONCLUSIONS:Although modifications may be necessary for patients requiring nonstandard dosing instructions, preliminary evidence supports the utility of this measure as a reliable and valid indicator of the complexity of antiretroviral treatment regimens.
    背景与目标: 背景:艾滋病毒感染者通常必须遵守复杂的药物治疗方案。迄今为止,文献中尚未使用纳入抗逆转录病毒(ARV)方案所有重要要素的标准化程序来检查方案的复杂性。
    目的:本文提出了一种新的量化方案复杂性的方法,该方法使用客观标准解决了可能使遵守ARV方案复杂化的因素。
    方法:本文的第1部分描述了抗逆转录病毒药物复杂性(ARC)指数评分系统的开发。基于小儿和成年患者,小儿患者的看护者以及医疗保健专业人员的输入,此综合系统包括药物数量,给药方案,给药方法,特殊说明以及与ARV疗法相关的所需制剂。将权重应用于这些因素中的每一个,以产生代表方案复杂程度的总分。本文的第2部分介绍了系统的可靠性和有效性数据。
    结果:ARC指数显示出优异的重测性和跨度可靠性,以及强大的构造和判别效度。该系统的在线版本最大程度地减少了计算错误。
    结论:尽管对于需要非标准剂量指导的患者可能需要进行修改,但初步证据支持该措施可作为抗逆转录病毒治疗方案复杂性的可靠且有效的指标。
  • 【使用电喷雾电离质谱法直接观察在淀粉样蛋白原纤维形成的早期阶段形成的寡聚物种。】 复制标题 收藏 收藏
    DOI:10.1016/j.jmb.2006.08.081 复制DOI
    作者列表:Smith AM,Jahn TR,Ashcroft AE,Radford SE
    BACKGROUND & AIMS: :Numerous debilitating human disorders result from protein misfolding and amyloid formation. Despite the grave nature of these maladies, our understanding of the structural mechanism of fibril assembly is limited. Of paramount importance is the need to identify and characterize oligomeric species formed early during fibril assembly, so that the nature of the initiating assembly mechanism can be revealed and species that may be toxic to cells identified. However, the transient nature of early oligomeric species, combined with their heterogeneity and instability, has precluded detailed analysis to date. Here, we have used electrospray ionisation mass spectrometry (ESI-MS), complemented by analytical ultracentrifugation (AUC) and measurements of thioflavin-T fluorescence, to monitor the early stages of assembly of amyloid-like fibrils formed from human beta-2-microglobulin (beta2m) in vitro. We show that worm-like fibrils that form with nucleation-independent kinetics assemble by a mechanism consistent with monomer addition, with species ranging from monomer to > or = 13-mer being identified directly and uniquely as transient assembly intermediates. By contrast, only monomers, dimers, trimers and tetramers are observed during nucleated growth, which leads to the formation of long straight fibrils. The results highlight the unique power of non-covalent ESI-MS to identify protein assembly intermediates in complex heterogeneous systems and demonstrate its great potential to identify and characterise individual species formed early during amyloid assembly.
    背景与目标: :许多使人衰弱的疾病源于蛋白质错误折叠和淀粉样蛋白形成。尽管这些疾病具有严重的性质,但是我们对原纤维组装的结构机理的理解是有限的。最重要的是需要鉴定和表征在原纤维组装过程中早期形成的寡聚物种,以便可以揭示起始组装机制的性质并鉴定可能对细胞有毒的物种。然而,迄今为止,早期寡聚物种的短暂性质,加上其异质性和不稳定性,已使详细分析无法进行。在这里,我们使用了电喷雾电离质谱(ESI-MS),并通过分析超速离心(AUC)和硫代黄素-T荧光的测量,来监测由人β-2-微球蛋白形成的淀粉样蛋白原纤维组装的早期阶段。 (beta2m)体外。我们显示,与成核无关的动力学形式形成的蠕虫状原纤维通过与单体加成一致的机制组装,从单体到>或= 13-mer的物质被直接和唯一地识别为瞬态组装中间体。相反,在成核生长期间仅观察到单体,二聚体,三聚体和四聚体,这导致长直原纤维的形成。结果突出了非共价ESI-MS识别复杂异质系统中蛋白质装配中间体的独特能力,并证明了其鉴定和表征淀粉样蛋白装配早期形成的单个物种的巨大潜力。
  • 【由带状孢子间体连接的形成子囊孢子的两种新的哈萨克斯坦菌种:Kazachstania zonata和Kazachstania gamospora。】 复制标题 收藏 收藏
    DOI:10.1111/j.1567-1364.2006.00163.x 复制DOI
    作者列表:Imanishi Y,Ueda-Nishimura K,Mikata K
    BACKGROUND & AIMS: :Four strains of ascomycetous yeasts were isolated from samples collected at two locations in southern Japan. The strains formed two warty ascospores that were joined together by an intersporal body appearing as a belt. Phylogenetic analysis of rRNA gene nucleotide sequences indicated that the strains represented two new and closely related species of the genus Kazachstania. Isolates of one of the species were from Miyazaki Prefecture and those of the other species were from the Iriomote Islands. Genetic separation of the two species was further confirmed by DNA-DNA reassociation, which gave values of 63.3-78.1%, and from interspecific crosses, which gave nonviable ascospores. On the basis of these data, the isolates from Miyazaki Prefecture are described as Kazachstania zonata sp. nov. [type strain NBRC 100504=CBS 10326, mating types NBRC 101821 (+), NBRC 101822 (-)], and the isolates from the Iriomote Islands are described as Kazachstania gamospora sp. nov. [type strain NBRC 11056=CBS 10328, mating types NBRC 101825 (+), NBRC 101826 (-)].
    背景与目标: :从日本南部两个地方收集的样品中分离出四株子囊酵母。这些菌株形成了两个疣状的子囊孢子,它们通过一个呈带状的孢子间体连接在一起。 rRNA基因核苷酸序列的系统发育分析表明,该菌株代表了哈萨克斯坦属的两个新的且密切相关的物种。其中一个物种的分离物来自宫崎县,而其他物种的分离物则来自西表岛。这两个物种的遗传分离进一步通过DNA-DNA重新关联(其值为63.3-78.1%)以及种间杂交获得了无生命的子囊孢子而得到证实。基于这些数据,来自宫崎县的分离株被描述为Kazachstania zonata sp.。十一月[类型菌株NBRC 100504 = CBS 10326,交配类型NBRC 101821(),NBRC 101822(-)]和来自西表岛的分离物被描述为Kazachstania gamospora sp.。十一月[类型菌株NBRC 11056 = CBS 10328,配合类型NBRC 101825(),NBRC 101826(-)]。
  • 【质谱分析法测定血清尿素。】 复制标题 收藏 收藏
    DOI:10.1016/0009-8981(76)90531-3 复制DOI
    作者列表:Björkhem I,Blomstrand R,Ohman G
    BACKGROUND & AIMS: A mass fragmentographic method of high accuracy for determination of serum urea is described. A fixed amount of [15N2]urea is added to a fixed amount of serum, then the urea is converted into 5,5-diallyl barbituric acid by coupling with diallyl malonic acid diethyl ester. The barbiturate is then transferred from an alkaline water phase into an organic phase containing methyl iodine by ion-pair extraction using tetrabutyl ammonium as the positive counterion. The amount of urea is determined from the ratio between the recordings at m/e 236 and m/e 238 obtained after analysis with a combined gas chromatograph-mass spectrometer equipped with an MID-unit (multiple-ion detector). The two ions used correspond to the molecular peak in the mass spectrum of the methyl derivative of unlabeled and labeled 5,5-diallyl barbituric acid, respectively. The relative standard deviation of the method was 3.6%. A comparison between the mass fragmentographic method and a routine method for determination of serum urea based on the urease-Berthelot reaction gave a high correlation (r = 0.99) and a regression coefficient of 0.95.

    背景与目标: 描述了用于测定血清尿素的高精度的质量碎片法。将固定量的[15N2]尿素添加到固定量的血清中,然后通过与二烯丙基丙二酸二乙酯偶合,将尿素转化为5,5-二烯丙基巴比妥酸。然后使用四丁基铵作为正抗衡离子,通过离子对萃取将巴比妥酸酯从碱性水相转移到含有甲基碘的有机相中。尿素的量由m / e 236和m / e 238的记录之间的比值确定,该记录是通过配备有MID单元的复合气相色谱-质谱仪(多离子检测器)进行分析后获得的。所使用的两个离子分别对应于未标记和标记的5,5-二烯丙基巴比妥酸的甲基衍生物的质谱中的分子峰。该方法的相对标准偏差为3.6%。质谱分析法与常规方法之间的比较(基于尿素酶-贝塞洛特反应测定血清尿素)具有较高的相关性(r = 0.99),回归系数为0.95。

  • 【体重指数对青春期延迟男孩生长的影响。】 复制标题 收藏 收藏
    DOI:10.1515/jpem.2006.19.8.971 复制DOI
    作者列表:Nathan BM,Sedlmeyer IL,Palmert MR
    BACKGROUND & AIMS: :It is unclear whether overweight but otherwise healthy boys with delayed puberty have a variation of constitutional delay of growth and maturation (CDGM) or a different etiology for their pubertal delay. To characterize better this group of boys and investigate whether their growth pattern distinguishes them from boys with typical CDGM, growth data were analyzed in eight overweight (BMI SDS > or = 85th percentile) and 37 non-overweight (BMI SDS <85th percentile) boys with delayed puberty. Primary outcome measures included predicted height (PH) and adult height (AH). At diagnosis of delayed puberty, the overweight boys had less delayed bone ages (chronological age [CA] - bone age [BA] = 1.2 +/- 1.0 vs 2.5 +/- 1.1 years, p <0.01), greater height SDS for CA (-0.5 +/- 0.7 vs -2.4 +/- 0.8, p <0.001), and greater height SDS for BA (0.6 +/- 0.9 vs -0.4 +/- 1.1, p <0.05). PH for the overweight boys exceeded their mid-parental height (MPH) by 5.0 +/- 7.2 cm while non-overweight boys were predicted to fall below their MPH by 2.8 +/- 6.3 cm (p <0.01). Available AH data corroborated the differences in PH, with a trend for overweight boys to have greater height relative to their MPH than the non-overweight boys. These observations suggest that in the context of delayed puberty, being overweight may modulate adult height and/or that the etiology of delayed puberty in overweight boys may differ from typical CDGM.
    背景与目标: :目前尚不清楚超重但健康的青春期延迟男孩是否具有体质发育和成熟延迟(CDGM)的变化或青春期延迟的病因有所不同。为了更好地表征这组男孩并研究他们的生长方式是否与典型CDGM的男孩区分开来,分析了8个超重(BMI SDS>或= 85%百分位数)和37个非超重(BMI SDS <85th百分位数)的男孩的生长数据青春期延迟。主要结局指标包括预测身高(PH)和成人身高(AH)。在诊断为青春期延迟时,超重男孩的延迟骨龄较少(先后年​​龄[CA]-骨龄[BA] = 1.2 /-1.0与2.5 /-1.1岁,p <0.01),CA的身高SDS较高(- 0.5 /-0.7 vs -2.4 /-0.8,p <0.001)和更高的BA SDS高度(0.6 /-0.9 vs -0.4 /-1.1,p <0.05)。超重男孩的PH值超出其父母中间高度(MPH)5.0 /-7.2 cm,而非超重男孩的PH值则低于其MPH 2.8 /-6.3 cm(p <0.01)。现有的AH数据证实了PH值的差异,超重男孩相对于其MPH的身高趋势要高于非超重男孩。这些观察结果表明,在青春期延迟的背景下,超重可能会调节成年人的身高,和/或在超重男孩中青春期延迟的病因可能与典型的CDGM不同。
  • 【自愿性轮转减少了Osborne-Mendel大鼠的脂肪组织质量和瘦素mRNA的表达。】 复制标题 收藏 收藏
    DOI:10.2337/diab.46.7.1159 复制DOI
    作者列表:Zachwieja JJ,Hendry SL,Smith SR,Harris RB
    BACKGROUND & AIMS: The purpose of this study was to assess the effects of voluntary wheel running on the expression of leptin mRNA in rats that are either sensitive (OM) or resistant (S5B/Pl) to diet-induced obesity. Male OM and S5B/Pl rats had ad libitum access to standard rodent diet and water. At 3-5 weeks of age, animals of both strains were randomly assigned to either an exercise or sedentary control group. The exercise groups had 24-h access to a running wheel, and they trained for 7 weeks. During weeks 1-4, animals in both OM and S5B/Pl exercise groups progressively increased their running. During weeks 5-7, S5B/Pl exercisers tended to run more than did OM (approximately 60 vs. 45 km/week), but by the end of the study both groups had an equally greater heart weight (mg/g body weight) and planteris citrate synthase activity than their sedentary controls. Oral glucose tolerance tests performed during the last week of training revealed that compared with their appropriate controls, insulin sensitivity was enhanced (P < 0.05) in OM but not in the S5B/Pl wheel-running groups. Inguinal, epididymal, and retroperitoneal fat pads weighed less in the running than in the nonrunning groups of both strains (P < 0.01). Additionally, exercised animals had an increased percentage of smaller cells (40-60 microm; P < 0.05) and a decreased percentage of larger cells (120-160 microm; P < 0.05) in the epididymal fat depot. Epididymal leptin mRNA measured by Northern blot analysis was reduced in the exercise-trained rats of both strains (P < 0.05). Furthermore, serum leptin was reduced in exercise-trained compared with the control animals of both strains. In comparison to S5B/Pl, control OM animals exhibited both a higher expression and higher circulating levels of leptin (P < 0.05). While serum leptin levels were decreased and food intake was increased in the exercise-trained animals of both strains (P < 0.05), the exact relationship between exercise, leptin, and food intake in this rat model of dietary obesity remains to be determined. Nonetheless, these results suggest that the expression and secretion of leptin can be influenced by exercise training and that these changes (i.e., reduced expression and secretion of protein) can occur independently of changes in whole-body insulin sensitivity and susceptibility to diet-induced obesity.

    背景与目标: 这项研究的目的是评估对饮食诱导的肥胖症敏感(OM)或有抵抗力(S5B / P1)的大鼠中自愿轮转运动对瘦素mRNA表达的影响。雄性OM和S5B / P1大鼠可自由获得标准啮齿动物饮食和水。在3-5周龄时,将两种品系的动物随机分为运动组或久坐对照组。锻炼组可以在24小时内使用跑轮,他们接受了7周的训练。在1-4周中,OM和S5B / P1运动组中的动物逐渐增加其奔跑。在5-7周内,S5B / P1锻炼者的奔跑倾向要比OM多(大约60 vs. 45 km /周),但是到研究结束时,两组的心脏重量(mg / g体重)均相同。和柠檬酸合酶活性比久坐对照者高。在训练的最后一周进行的口服葡萄糖耐量测试显示,与适当的对照组相比,OM组的胰岛素敏感性增强(P <0.05),而S5B / P1滚轮组则没有。两种菌株的腹股沟,附睾和腹膜后脂肪垫的重量均比非跑步组轻(P <0.01)。另外,运动的动物在附睾脂肪贮存库中具有较小百分比的较小细胞(40-60微米; P <0.05),而具有较大百分比的较小细胞(120〜160微米; P <0.05)。通过Northern印迹分析测量的附睾瘦素mRNA在两种品系的运动训练大鼠中均降低(P <0.05)。此外,与两种品系的对照动物相比,在运动训练中血清瘦素降低。与S5B / P1相比,对照OM动物表现出瘦素的更高表达和更高循环水平(P <0.05)。虽然两种品系的运动训练后动物的血清瘦素水平均下降且食物摄入量增加(P <0.05),但在该大鼠饮食肥胖模型中,运动,瘦素和食物摄入量之间的确切关系仍有待确定。尽管如此,这些结果表明,瘦素的表达和分泌会受到运动训练的影响,并且这些变化(即蛋白质的表达和分泌减少)可以独立于全身胰岛素敏感性的变化和对饮食性肥胖症的易感性而发生。 。

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