• 【表面上健康的男性和女性的组织因子血清水平和未来冠状动脉疾病的风险: EPIC-Norfolk前瞻性人群研究。】 复制标题 收藏 收藏
    DOI:10.1111/j.1538-7836.2006.02190.x 复制DOI
    作者列表:Keller TT,Choi D,Nagel C,Te Velthuis H,Gerdes VE,Wareham NJ,Bingham SA,Luben R,Hack CE,Reitsma PH,Levi M,Khaw KT,Boekholdt SM
    BACKGROUND & AIMS: INTRODUCTION:Tissue factor (TF) has been implicated in coronary artery disease (CAD). High levels of circulating TF are found in patients with acute atherothrombotic events. Whether high serum TF levels predict risk of future CAD independent of known risk factors remains unknown. METHODS:We conducted a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Cases (n=1037) were apparently healthy men and women, aged 45-79 years, who developed fatal or non-fatal CAD during follow-up. Controls (n=2005) were matched by age, sex, and enrolment time. Serum TF levels were measured using high-affinity antibodies. RESULTS:In men, median TF levels were not significant higher in cases than in controls (59.0 pg mL-1, range: 16.7-370.4 vs. 54.9 pg mL-1, range: 16.2-452.4). In women, median TF levels were not significant higher in controls than in cases (73.4 pg mL-1, range: 16.7-492.3 vs. 50.5 pg mL-1, range: 16.5-376.7). The incidence of smoking was about double in the lowest compared with the highest TF quartile. Correcting for sex, age, body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and C-reactive protein levels, the risk of future CAD was 1.05 (95% CI: 0.81-1.36) for people in the highest TF quartile, compared with those in the lowest (P-value for linearity=0.8). CONCLUSION:High levels of serum TF were not independently associated with an increased risk of future CAD in apparently healthy individuals.
    背景与目标:
  • 【血管紧张素转换酶抑制剂与主动脉破裂: 一项基于人群的病例对照研究。】 复制标题 收藏 收藏
    DOI:10.1016/S0140-6736(06)69250-7 复制DOI
    作者列表:Hackam DG,Thiruchelvam D,Redelmeier DA
    BACKGROUND & AIMS: BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS:We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS:Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION:ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.
    背景与目标:
  • 【卵子发生: 减数分裂前期的染色质和微管动力学。】 复制标题 收藏 收藏
    DOI:10.1002/mrd.1080250411 复制DOI
    作者列表:Mattson BA,Albertini DF
    BACKGROUND & AIMS: :Changes in the organization of germinal vesicle chromatin in mouse oocytes have been analyzed by fluorescence microscopy with respect to progressive stages of follicular development and the disposition of oocyte cytoplasmic microtubules. Four discrete patterns of chromatin organization exist in germinal vesicle (GV)-stage oocytes isolated from the ovaries of 21-25-day-old gonadotropin-primed mice. Analysis of ovarian cryosections stained with the DNA-binding fluorochrome Hoechst 33258 indicates that sequential changes in GV chromatin occur during folliculogenesis that result in the formation of a continuous perinucleolar chromatin sheath at the time of antrum formation. Specific alterations in the cytoplasmic microtubule complex of GV-stage oocytes were observed that correlate with chromatin patterns. The extensive cytoplasmic microtubule complex seen in oocytes of preantral follicles initially localizes to perinuclear areas of the ooplasm. This is followed by a progressive reduction in cytoplasmic microtubules and the appearance of prominent microtubule-organizing centers at the nuclear periphery. Coordinated nuclear and microtubular alterations also occur under in vitro conditions prior to progression of meiosis to prometaphase-1. The results are discussed with respect to the ongoing differentiation of the oocyte nucleus and the microtubule cytoskeleton during folliculogenesis in preparation for the resumption of meiosis.
    背景与目标: : 已通过荧光显微镜分析了小鼠卵母细胞生发囊泡染色质组织的变化,涉及卵泡发育的进展阶段和卵母细胞细胞质微管的处置。从21-25天大的促性腺激素引发小鼠的卵巢中分离出的生发囊泡 (GV) 期卵母细胞中存在四种染色质组织的离散模式。用结合DNA的荧光染料Hoechst 33258染色的卵巢冷冻切片的分析表明,在卵泡发生过程中GV染色质发生顺序变化,导致在窦形成时形成连续的核周染色质鞘。观察到GV期卵母细胞的细胞质微管复合物的特定变化与染色质模式相关。在窦前卵泡的卵母细胞中看到的广泛的细胞质微管复合物最初位于卵质的核周区域。随后是细胞质微管的逐渐减少,并且在核周围出现了突出的微管组织中心。在减数分裂进展到prometaphase-1之前,在体外条件下也会发生协调的核和微管改变。讨论了卵泡发生过程中卵母细胞核和微管细胞骨架的持续分化,以准备恢复减数分裂。
  • 【基于人群的样本中肾脏血浆对血管紧张素II的血流反应与血压之间的关系。】 复制标题 收藏 收藏
    DOI:10.1097/00004872-199715050-00004 复制DOI
    作者列表:Turner ST,Kardia SL
    BACKGROUND & AIMS: OBJECTIVE:To assess whether interindividual variation in renal plasma flow or in its response to angiotensin II infusion is associated with interindividual differences in blood pressure in a population-based sample of 287 non-Hispanic whites (143 women and 144 men), aged 20-49.9 years.

    METHODS:After seven days of eating a high-sodium diet (260 mmol/day), the renal plasma flow was determined by measuring the clearance of p-aminohippurate before and after infusion of 3 ng/kg per min angiotensin II. Multiple linear regression methods were used to assess whether measures of the renal plasma flow and of its response to angiotensin II infusion were predictive of systolic or diastolic blood pressures measured prior to administration of the high-sodium diet, on day 6 of the high-sodium diet, or during the renal clearance procedure on day 7 prior to angiotensin II infusion.

    RESULTS:There was some evidence that measures of the renal plasma flow and of its response to angiotensin II infusion during the high-sodium diet were statistically significant predictors of measures of blood pressure in women; there was less evidence for this for blood pressures in men. Interindividual variation in measures of the renal plasma flow and of its response to angiotensin II infusion explained less than 10% of the interindividual variation in any measure of the blood pressure in both sexes.

    CONCLUSION:These results suggest that interindividual variation in renal plasma flow ad in its response to angiotensin II infusion during a high-sodium diet will be of limited utility in elucidating the basis for interindividual differences in blood pressure.

    背景与目标: 目的 : 在基于人群的287非西班牙裔白人 (143名女性和144名男性) 样本中,评估肾血浆流量或对血管紧张素II输注的反应的个体差异是否与血压的个体差异相关,年龄在20-49.9岁之间。
    方法 : 在食用高钠饮食 (260 mmol/天) 7天后,通过在每分钟输注3 ng/kg血管紧张素II之前和之后测量对氨基马尿酸盐的清除率来确定肾血浆流量。使用多元线性回归方法来评估肾血浆流量及其对血管紧张素II输注的反应的测量是否可以预测高钠饮食第6天在给予高钠饮食之前测得的收缩压或舒张压。钠饮食,或在输注血管紧张素II之前第7天的肾脏清除过程中。
    结果 : 有证据表明,高钠饮食期间肾脏血浆流量的测量及其对血管紧张素II输注的反应是女性血压测量的统计学显着预测指标; 男性血压的证据较少。肾血浆流量测量及其对血管紧张素II输注的反应的个体差异解释了男女血压测量中个体间差异的10%。
    结论 : 这些结果表明,在高钠饮食中对血管紧张素II输注的反应中,肾血浆流量ad的个体差异在阐明血压个体差异的基础方面将是有限的。
  • 【分解代谢质粒pjp4中重组事件的分子和种群分析。】 复制标题 收藏 收藏
    DOI:10.1128/JB.00869-06 复制DOI
    作者列表:Larraín-Linton J,De la Iglesia R,Melo F,González B
    BACKGROUND & AIMS: :Cupriavidus necator JMP134(pJP4) harbors a catabolic plasmid, pJP4, which confers the ability to grow on chloroaromatic compounds. Repeated growth on 3-chlorobenzoate (3-CB) results in selection of a recombinant strain, which degrades 3-CB better but no longer grows on 2,4-dichlorophenoxyacetate (2,4-D). We have previously proposed that this phenotype is due to a double homologous recombination event between inverted repeats of the multicopies of this plasmid within the cell. One recombinant form of this plasmid (pJP4-F3) explains this phenotype, since it harbors two copies of the chlorocatechol degradation tfd gene clusters, which are essential to grow on 3-CB, but has lost the tfdA gene, encoding the first step in degradation of 2,4-D. The other recombinant plasmid (pJP4-FM) should harbor two copies of the tfdA gene but no copies of the tfd gene clusters. A molecular analysis using a multiplex PCR approach to distinguish the wild-type plasmid pJP4 from its two recombinant forms, was carried out. Expected PCR products confirming this recombination model were found and sequenced. Few recombinant plasmid forms in cultures grown in several carbon sources were detected. Kinetic studies indicated that cells containing the recombinant plasmid pJP4-FM were not selectable by sole carbon source growth pressure, whereas those cells harboring recombinant plasmid pJP4-F3 were selected upon growth on 3-CB. After 12 days of repeated growth on 3-CB, the complete plasmid population in C. necator JMP134 apparently corresponds to this form. However, wild-type plasmid forms could be recovered after growing this culture on 2,4-D, indicating that different plasmid forms can be found in C. necator JMP134 at the population level.
    背景与目标: : Cupriavidus necatator JMP134(pJP4) 具有分解代谢质粒pJP4,该质粒赋予了在氯芳族化合物上生长的能力。在3-氯苯甲酸酯 (3-CB) 上重复生长导致选择重组菌株,该菌株可以更好地降解3-CB,但不再在2,4-二氯苯氧乙酸 (2,4-d) 上生长。我们先前已经提出,这种表型是由于该质粒在细胞内的多胞菌的反向重复之间发生了双重同源重组事件。这种质粒的一种重组形式 (pJP4-F3) 解释了这种表型,因为它包含两个拷贝的氯邻苯二酚降解tfd基因簇,这两个拷贝对于在3-CB上生长是必不可少的,但是已经失去了tfdA基因,编码2,4-d降解的第一步。另一个重组质粒 (pJP4-FM) 应该包含两个拷贝的tfdA基因,但没有拷贝的tfd基因簇。进行了分子分析,使用多重PCR方法将野生型质粒pJP4与其两种重组形式区分开。发现并测序了证实该重组模型的预期PCR产物。在几种碳源中生长的培养物中,几乎没有检测到重组质粒形式。动力学研究表明,含有重组质粒pJP4-FM的细胞不能通过唯一的碳源生长压力来选择,而那些具有重组质粒pJP4-F3的细胞在3-CB上生长时被选择。在3-CB上重复生长12天后,C. necator JMP134中的完整质粒群体显然对应于这种形式。但是,在2,4-d上生长该培养物后,可以恢复野生型质粒形式,这表明在种群水平上在C. necator JMP134中可以发现不同的质粒形式。
  • 【通过分子动力学模拟研究了水对螺旋肽展开动力学的作用。】 复制标题 收藏 收藏
    DOI:10.1016/S0006-3495(97)78889-1 复制DOI
    作者列表:Doruker P,Bahar I
    BACKGROUND & AIMS: Molecular dynamics simulations have been carried out with four polypeptides, Ala13, Val(13), Ser13, and Ala4Gly5Ala4, in vacuo and with explicit hydration. The unfolding of the polypeptides, which are initially fully alpha-helix in conformation, has been monitored during trajectories of 0.3 ns at 350 K. A rank of Ala < Val < Ser < Gly is found in the order of increasing rate of unwinding. The unfolding of Ala13 and Val(13) is completed in hundreds of picoseconds, while that of Ser13 is about one order of magnitude faster. The helix content of the peptide containing glycine residues falls to zero within a few picoseconds. Ramachandran plots indicate quite distinct equilibrium distributions and time evolution of dihedral angles in water and in vacuum for each residue type. The unfolding of polyalanine and polyvaline helices is accelerated due to solvation. In contrast, polyserine is more stable in water compared to vacuum, because its side chains can form intramolecular hydrogen bonds with the backbone more readily in vacuum, which disrupts the helix. Distribution functions of the spatial and angular position of water molecules in the proximity of the polypeptide backbone polar groups reveal the stabilization of the coiled structures by hydration. The transition from helix to coil is characterized by the appearance of a new peak in the probability distribution at a specific location characteristic of hydrogen bond formation between water and backbone polar groups. No significant insertion of water molecules is observed at the precise onset of unwinding, while (i, i+3) hydrogen bond formation is frequently detected at the initiation of alpha-helix unwinding.

    背景与目标: 已在真空中并在显式水合作用下使用四种多肽Ala13,Val(13),Ser13和Ala4Gly5Ala4进行了分子动力学模拟。在350 K处0.3 ns的轨迹期间,已经监测了最初在构象上完全为 α-螺旋的多肽的展开。Ala
  • 【来自 “进化峡谷” 的酿酒酵母自然种群中的分子遗传生物多样性: 微卫星多态性,倍性和有争议的性状态。】 复制标题 收藏 收藏
    DOI:10.1534/genetics.106.062745 复制DOI
    作者列表:Ezov TK,Boger-Nadjar E,Frenkel Z,Katsperovski I,Kemeny S,Nevo E,Korol A,Kashi Y
    BACKGROUND & AIMS: :The yeast S. cerevisiae is a central model organism in eukaryotic cell studies and a major component in many food and biotechnological industrial processes. However, the wide knowledge regarding genetics and molecular biology of S. cerevisiae is based on an extremely narrow range of strains. Studies of natural populations of S. cerevisiae, not associated with human activities or industrial fermentation environments, are very few. We isolated a panel of S. cerevisiae strains from a natural microsite, "Evolution Canyon" at Mount Carmel, Israel, and studied their genomic biodiversity. Analysis of 19 microsatellite loci revealed high allelic diversity and variation in ploidy level across the panel, from diploids to tetraploids, confirmed by flow cytometry. No significant differences were found in the level of microsatellite variation between strains derived from the major localities or microniches, whereas strains of different ploidy showed low similarity in allele content. Maximum genetic diversity was observed among diploids and minimum among triploids. Phylogenetic analysis revealed clonal, rather than sexual, structure of the triploid and tetraploid subpopulations. Viability tests in tetrad analysis also suggest that clonal reproduction may predominate in the polyploid subpopulations.
    背景与目标: : 酵母酿酒酵母是真核细胞研究中的中心模式生物,也是许多食品和生物技术工业过程中的主要组成部分。然而,关于酿酒酵母的遗传学和分子生物学的广泛知识是基于极其狭窄的菌株范围。与人类活动或工业发酵环境无关的酿酒酵母自然种群研究很少。我们从以色列卡梅尔山的自然微位点 “进化峡谷” 中分离了一组酿酒酵母菌株,并研究了它们的基因组生物多样性。对19个微卫星基因座的分析显示,从二倍体到四倍体,整个面板的等位基因多样性和倍性水平变化很高,通过流式细胞术证实。在来自主要地区或微型物种的菌株之间的微卫星变异水平上没有发现显着差异,而不同倍性的菌株在等位基因含量上显示出较低的相似性。在二倍体中观察到最大的遗传多样性,在三倍体中观察到最小。系统发育分析显示,三倍体和四倍体亚群的克隆而非性结构。tetrad分析中的生存力测试还表明,克隆繁殖可能在多倍体亚群中占主导地位。
  • 【水痘短缺对社区人口中18和24个月大的儿童的近期和长期影响。】 复制标题 收藏 收藏
    DOI:10.1186/1471-2296-7-51 复制DOI
    作者列表:Yawn BP,Schroeder C,Wollan P,Rocca L,Zimmerman R,Bardenheier B
    BACKGROUND & AIMS: BACKGROUND:Little is known about the impact of the recent varicella vaccine shortage. To assess the temporal trend in varicella vaccine administration before 18 and 24 months of age in a community cohort of children prior to, during and after the recent varicella vaccine shortage. And to compare the temporal trends in varicella vaccinations to trends of an older, more widely accepted vaccine, the MMR. METHODS:Community population-based birth cohorts were identified who were eligible for the varicella vaccination before, during and after the 2001 to 2002 varicella vaccine shortage. Only children (84% of all) who remained in the community through their second birthday were included. For each child in the cohort, the medical records and immunization registry records from both medical facilities in the county were reviewed to identify the dates and sites for all varicella immunizations given. In addition to varicella immunizations, the dates of all MMR vaccinations were recorded. Additional data abstracted included the child's birth date, gender and dates of any recognized cases of chickenpox up through age 24 months. RESULTS:Of the 2,512 children in the birth cohorts, 50.8% were boys. In the three cohorts combined, 81.1% of the boys and 79.3% of the girls (p = 0.30) received the varicella vaccine by age 24 months. The pre-shortage community rate of varicella immunization was 79.7% by 24 months of age. During the varicella vaccine shortage, the rate of varicella immunization by 24 months fell to 77.2%. Only 6 additional children received a "catch-up" immunization by 36 months of age. In the post shortage period the community 24-month immunization rate rebounded to a level higher than the pre-shortage rate 84.0%. During the almost three years of observation, the MMR immunization rate by age 24 months was constant (87%). CONCLUSION:The varicella shortage was associated with an immediate drop in the 24-month varicella immunizations rate but rebounded quickly to above pre-shortage rates. In this community the only long term impact of the varicella vaccine shortage may be on the small number of children who still had not received catch-up varicella immunizations by 36 months of age.
    背景与目标:
  • 【百草枯在小肠,肝脏和肾脏中的免疫组织化学定位和动力学。】 复制标题 收藏 收藏
    DOI:10.1016/0300-483x(90)90040-n 复制DOI
    作者列表:Nagao M,Takatori T,Inoue K,Shimizu M,Terazawa K,Akabane H
    BACKGROUND & AIMS: :Immunohistochemical techniques were used to observe the localization of paraquat in the small intestine, liver and kidney, organs that absorb and eliminate chemicals. Paraquat-poisoned rats were killed 3 h, 12 h, 24 h, 3 days, 7 days and 10 days after intravenous administration of paraquat. Three hours after injection, paraquat was localized in hepatocytes and in the kidney in the epithelial cells of the distal tubule. The amount of paraquat in the liver and kidney increased by 24 h after the administration and thereafter decreased with time, suggesting that paraquat is secreted into bile and urine. In the intestine, 3 h after injection, paraquat was localized in the epithelial cells. The same finding was also made in rats with a cannulated bile duct. Therefore, it is likely that paraquat is secreted into the gut lumen from epithelial cells and that paraquat secreted from liver into the duodenum is reabsorbed into the epithelial cells of the intestine.
    背景与目标: : 免疫组织化学技术用于观察百草枯在小肠,肝脏和肾脏,吸收和消除化学物质的器官中的定位。静脉注射百草枯后3 h,12 h,24 h,3天,7天和10天杀死百草枯中毒的大鼠。注射三小时后,百草枯位于肝细胞和远端小管上皮细胞的肾脏中。给药后24小时,肝脏和肾脏中的百草枯量增加,此后随时间减少,这表明百草枯分泌到胆汁和尿液中。在肠中,注射后3小时,百草枯位于上皮细胞中。在具有插管胆管的大鼠中也有相同的发现。因此,百草枯很可能从上皮细胞分泌到肠腔中,而百草枯从肝脏分泌到十二指肠被重新吸收到肠的上皮细胞中。
  • 【自我收集的宫颈阴道采样,用于基于HPV的初级宫颈癌筛查的护理地点: 在服务不足的希腊农村人群中的一项初步研究。】 复制标题 收藏 收藏
    DOI:10.1080/01443615.2017.1323197 复制DOI
    作者列表:Chatzistamatiou K,Chatzaki Ε,Constantinidis Τ,Nena E,Tsertanidou A,Agorastos T
    BACKGROUND & AIMS: :In the present pilot study, the feasibility of a site-of-care cervicovaginal self-sampling methodology for HPV-based screening was tested in 346 women residing in underserved rural areas of Northern Greece. These women provided self-collected cervicovaginal sample along with a study questionnaire. Following molecular testing, using the cobas® HPV Test, Roche®, HPV positive women, were referred to colposcopy and upon abnormal findings, to biopsy and treatment. Participation rate was 100%. Regular pap-test examination was reported for 17.1%. Among hrHPV testing, 11.9% were positive and colposcopy/biopsy revealed 2 CIN3 cases. Non-compliance was the most prevalent reason for no previous attendance. Most women reported non-difficulty and non-discomfort in self-sampling (77.6% and 82.4%, respectively). They would choose self-sampling over clinician-sampling (86.2%), and should self-sampling being available, they would test themselves more regularly (92.3%). In conclusion, self-sampling is feasible and well-accepted for HPV-based screening, and could increase population coverage in underserved areas, helping towards successful prevention.
    背景与目标: : 在本试点研究中,对居住在希腊北部服务不足的农村地区的346名妇女进行了基于HPV筛查的护理现场宫颈阴道自采样方法的可行性进行了测试。这些妇女提供了自我收集的宫颈阴道样本以及研究问卷。在分子测试之后,使用cobas®罗氏HPV检测®HPV阳性女性被转诊至阴道镜检查和异常发现后,进行活检和治疗。参与率为100%。报告定期进行17.1% 巴氏试验检查。在hrHPV检测中,11.9% 例为阳性,阴道镜/活检显示2例CIN3。不遵守是以前没有出席的最普遍原因。大多数妇女报告说,自我取样没有困难,也没有不适 (分别为77.6% 和82.4%)。他们将选择自采样而不是临床医生采样 (86.2%),并且如果自采样可用,他们将更定期地测试自己 (92.3%)。总之,自我采样对于基于HPV的筛查是可行的且被广泛接受,并且可以增加服务不足地区的人口覆盖率,从而有助于成功预防。
  • 【挪威乳腺癌患者术后放疗后乏力过程-与普通人群的比较。】 复制标题 收藏 收藏
    DOI:10.3109/0284186X.2012.742563 复制DOI
    作者列表:Reidunsdatter RJ,Albrektsen G,Hjermstad MJ,Rannestad T,Oldervoll LM,Lundgren S
    BACKGROUND & AIMS: INTRODUCTION:Fatigue after treatment for breast cancer (BC) is common, but poorly understood. We examined the fatigue levels during first year after radiotherapy (RT) according to the extent of RT (local or locoregional), hormonal therapy (HT) and chemotherapy (CT). The impact of comorbidity was also explored. Moreover, we compared fatigue levels in patients with the general population (GenPop) data. MATERIAL AND METHODS:BC patients (n = 250) referred for post-operative RT at St. Olavs Hospital, Trondheim, Norway, were enrolled. Fatigue was measured by the EORTC QLQ-C30-fatigue subscale, ranging from 0 to 100, before RT (baseline), after RT, and at three, six, and 12 months. Clinical and treatment-related factors were recorded at baseline. GenPop data was available from a previous survey (n = 652). Linear mixed models and analysis of covariance were applied. RESULTS:Compliance ranged from 87% to 98%. At baseline, mean value (SD) of fatigue in BC patients was 26.8 (23.4). The level increased during RT (mean change 8.3, 95% CI 5.5-11.1), but declined thereafter and did not differ significantly from pre-treatment levels at subsequent time points. In age-adjusted analyses, locoregional RT accounted for more overall fatigue than local RT (mean difference 6.6, 95% CI 1.2-12.0), but the association was weakened and not statistical significant when adjusting for CT and HT. Similar pattern was seen for CT and HT. The course of fatigue differed significantly by CT (p < 0.001, interaction test). At baseline, fatigue levels were higher in patients with than without CT, but at subsequent time points similar levels were evident, indicating a temporary adverse effect of CT. Comorbidity was significantly associated with increased level of fatigue, independent of other factors (mean difference 8.1, 95% CI 2.2-14.1). BC-patients were not significantly more fatigued than GenPop, except for immediately after ending RT, and then only among those without comorbidity (mean 35.9 vs. 25.8, p < 0.001). CONCLUSION:Comorbidity seems to be a more important determinant for fatigue levels than the cancer treatment.
    背景与目标:
  • 【缺铁性贫血是台湾骨质疏松症的危险因素: 一项基于全国人群的研究。】 复制标题 收藏 收藏
    DOI:10.3390/nu9060616 复制DOI
    作者列表:Pan ML,Chen LR,Tsao HM,Chen KH
    BACKGROUND & AIMS: :The cause-effect relationship between iron deficiency anemia (IDA) and osteoporosis has not been established in the general population. Thus, the current longitudinal study determined the role of IDA as a risk factor for osteoporosis by analyzing a large nationwide population-based sample. In a sample of 1,000,000 randomly sampled individuals from the 1998-2012. Taiwan National Health Insurance Research Database, patients with IDA (case group (n = 35,751)) and individuals without IDA (control group (n = 178,755)) were compared. Patients who were <20 years of age and who had pre-existing osteoporosis prior to the diagnosis of IDA were excluded. Each patient with IDA was age- and gender-matched to five individuals without IDA. The diagnoses of IDA and osteoporosis (coded using ICD-9CM) were further confirmed with blood test results and X-ray bone densitometry to ensure the accuracy of the diagnoses. Osteoporosis occurred more often among patients with IDA compared to individuals without IDA (2.27% vs. 1.32%, p < 0.001). Cox proportional hazard analysis revealed that the risk for osteoporosis was significantly higher in the case than the control group (hazard ratio (HR) = 1.74; 95% CI = 1.61-1.88) and remained similar after adjustment for covariates (adjusted HR = 1.81; 95% CI = 1.67-1.97). Compared with individuals without IDA, the risk for osteoporosis was even higher for patients with IDA who received intravenous ferrum therapy (adjusted HR = 2.21; 95% CI = 1.85-2.63). In contrast, the risk for osteoporosis was reduced for patients with IDA who received a blood transfusion (adjusted HR = 1.47; 95% CI = 1.20-1.80). As a predictor, prior IDA is a significant and independent risk factor for development of osteoporosis.
    背景与目标: : 在普通人群中,缺铁性贫血 (IDA) 与骨质疏松症之间的因果关系尚未建立。因此,当前的纵向研究通过分析大量全国基于人群的样本来确定IDA作为骨质疏松症危险因素的作用。在从1998-2012中随机抽取的1,000,000个样本中。对台湾全民健康保险研究数据库、IDA患者 (病例组 (n = 35,751)) 和无IDA患者 (对照组 (n = 178,755)) 进行比较。年龄 <20岁且在诊断IDA之前已有骨质疏松症的患者被排除。每位IDA患者的年龄和性别与五名没有IDA的患者相匹配。通过血液检查结果和x射线骨密度法进一步确认IDA和骨质疏松症 (使用ICD-9CM编码) 的诊断,以确保诊断的准确性。与没有IDA的个体相比,IDA患者中更经常发生骨质疏松症 (2.27% vs. 1.32%,p <0.001)。Cox比例风险分析显示,该病例的骨质疏松症风险显着高于对照组 (风险比 (HR) = 1.74; 95% CI = 1.61-1.88),并且在校正协变量后保持相似 (调整后HR = 1.81; 95% CI = 1.67-1.97)。与没有IDA的个体相比,接受静脉铁治疗的IDA患者的骨质疏松症风险更高 (调整后的HR = 2.21; 95% CI = 1.85-2.63)。相比之下,接受输血的IDA患者的骨质疏松症风险降低 (调整后的HR = 1.47; 95% CI = 1.20-1.80)。作为预测因素,先前的IDA是骨质疏松症发生的重要且独立的危险因素。
  • 【抗pdgfr α 人单克隆抗体Olaratumab在晚期和/或转移性癌症患者中的群体药代动力学模型。】 复制标题 收藏 收藏
    DOI:10.1007/s40262-017-0562-0 复制DOI
    作者列表:Mo G,Baldwin JR,Luffer-Atlas D,Ilaria RL Jr,Conti I,Heathman M,Cronier DM
    BACKGROUND & AIMS: BACKGROUND AND OBJECTIVES:Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-α (PDGFRα). In a randomized phase II study, olaratumab plus doxorubicin met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement in overall survival versus doxorubicin alone in patients with advanced or metastatic soft tissue sarcoma (STS). In this study, we characterize the pharmacokinetics (PKs) of olaratumab in a cancer patient population. METHODS:Olaratumab was tested at 15 or 20 mg/kg in four phase II studies (in patients with nonsmall cell lung cancer, glioblastoma multiforme, STS, and gastrointestinal stromal tumors) as a single agent or in combination with chemotherapy. PK sampling was performed to measure olaratumab serum levels. PK data were analyzed by nonlinear mixed-effect modeling techniques using NONMEM®. RESULTS:The PKs of olaratumab were best described by a two-compartment PK model with linear clearance (CL). Patient body weight was found to have a significant effect on both CL and central volume of distribution (V 1), whereas tumor size significantly affected CL. A small subset of patients developed treatment-emergent anti-drug antibodies (TE-ADAs); however, TE-ADAs did not have any effect on CL or PK time course of olaratumab. There was no difference in the PKs of olaratumab between patients who received olaratumab as a single agent or in combination with chemotherapy. CONCLUSION:The PKs of olaratumab were best described by a model with linear disposition. Patient body weight and tumor size were found to be significant covariates. The PKs of olaratumab were not affected by immunogenicity or chemotherapeutic agents.
    背景与目标:
  • 【海地地震后的精神病理学: 一项基于人群的创伤后应激障碍和严重抑郁症研究。】 复制标题 收藏 收藏
    DOI:10.1002/da.22007 复制DOI
    作者列表:Cerdá M,Paczkowski M,Galea S,Nemethy K,Péan C,Desvarieux M
    BACKGROUND & AIMS: BACKGROUND:In the first population-based study of psychopathology conducted in Haiti, we documented earthquake-related experiences associated with risk for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) 2-4 months following the 2010 Haiti earthquake. METHODS:A population-based survey was conducted of 1,323 survivors randomly selected from the general nondisplaced community, internally displaced persons camps, and a community clinic. Respondents were from the Nazon area of Port-au-Prince, ∼20 miles from the epicenter. RESULTS:Respondents (90.5%) reported at least one relative/close friend injured/killed, 93% saw dead bodies, and 20.9% lost their job post-earthquake. The prevalence of PTSD (24.6%) and MDD (28.3%) was high. History of violent trauma was associated with risk of PTSD and MDD (adjusted odds ratio [AOR] 1.4, 95% confidence interval [CI], 1.0-1.9; AOR, 1.7, 95% CI 1.3, 2.2, respectively). Low social support (AOR, 1.7, 95% CI 1.2, 2.3; AOR 1.4, 95% CI 1.0, 1.9, respectively) increased risk of PTSD and MDD among women. Suffering damage to the home increased risk of MDD in males (AOR 2.8, 95% CI 1.5, 5.5). Associations between being trapped in rubble, major damage to house, job loss, and PTSD; and participation in rescue/recovery, friends/family injured/killed, and MDD varied based on prior history of violent trauma. CONCLUSIONS:Addressing mental health in a post-earthquake setting such as Haiti will require focusing resources on screening and treatment of identified vulnerable groups while targeting improvement of post-earthquake living conditions. Investment in sources of social support for women may make help mitigate the vulnerability of women to PTSD and MDD.
    背景与目标:
  • 【按年龄和性别划分的霍奇金淋巴瘤的体型和风险: 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:

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