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。

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。

BACKGROUND & AIMS: Etoposide produces reversible inhibition of topoisomerase II, leading to cleavage of DNA, and thereby has an antitumor effect. This mechanism suggests that the longer treatment is continued, the greater the antitumor effect will be. In the present study, both therapeutic and adverse effects of long-term treatment with low-dose oral etoposide were studied in 29 patients aged > or = 65 years with non-Hodgkin's lymphoma (NHL) for whom standard chemotherapy was not effective or refractory. These patients received etoposide at a dose of 50 mg/d for as long as possible. Treatment was continued until white blood cell count decreased to < or = 2,000/microL or the platelet count decreased to < or = 5 x 10(4)/microL. According to the World Health Organization (WHO) criteria of therapeutic effects, 6 (20.7%) of the 29 patients achieved complete remission and 13 patients (44.8%) had partial remission, for a response rate of 65.5%. Adverse effects of > or = grade 3 included leukopenia in 24 patients (82.8%) and anemia in 7 (24.1%). Granulocyte colony-stimulating factor (G-CSF) was given in combination with etoposide to eight patients because of leukopenia (granulocyte count < or = 1,000/microL). In view of the excellent subjective tolerance, low incidence of serious adverse effects, and good activity, single agent oral etoposide given continuously over prolonged periods represents a useful treatment for elderly patients with NHL.

背景与目标： 依托泊苷产生拓扑异构酶II的可逆抑制，导致DNA裂解，从而具有抗肿瘤作用。这种机制表明，持续治疗的时间越长，抗肿瘤作用就越大。在本研究中，对29例年龄> 或 = 65岁的非霍奇金淋巴瘤 (NHL) 患者进行了低剂量口服依托泊苷长期治疗的治疗和不良反应的研究，这些患者的标准化疗无效或难治性。这些患者尽可能长时间地接受依托泊苷50 mg/d的剂量。继续治疗直到白细胞计数降低至 <或 = 2,000/microL或血小板计数降低至 <或 = 5 × 10(4)/microL。根据治疗效果的世卫组织标准，29例患者中有6例 (20.7% 例) 完全缓解，13例 (44.8% 例) 部分缓解，缓解率为65.5%。> or = 3级的不良反应包括白细胞减少24例 (82.8%) 和贫血7例 (24.1%)。由于白细胞减少 (粒细胞计数 <或 = 1,000/microL)，将八名患者与依托泊苷联合给予粒细胞集落刺激因子 (g-csf)。鉴于其良好的主观耐受性，低的严重不良反应发生率和良好的活性，长期连续给予单药口服依托泊苷代表了对老年NHL患者的有用治疗。

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。

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：

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。

BACKGROUND & AIMS: OBJECTIVE:To examine the analytic role of arsenic exposure on cancer mortality among the low-dose (well water arsenic level <150 μg/L) villages in the Blackfoot-disease (BFD) endemic area of southwest Taiwan and with respect to the southwest regional data. METHOD:Poisson analyses of the bladder and lung cancer deaths with respect to arsenic exposure (μg/kg/day) for the low-dose (<150 μg/L) villages with exposure defined by the village median, mean, or maximum and with or without regional data. RESULTS:Use of the village median well water arsenic level as the exposure metric introduced misclassification bias by including villages with levels >500 μg/L, but use of the village mean or the maximum did not. Poisson analyses using mean or maximum arsenic levels showed significant negative cancer slope factors for models of bladder cancers and of bladder and lung cancers combined. Inclusion of the southwest Taiwan regional data did not change the findings when the model contained an explanatory variable for non-arsenic differences. A positive slope could only be generated by including the comparison population as a separate data point with the assumption of zero arsenic exposure from drinking water and eliminating the variable for non-arsenic risk factors. CONCLUSION:The cancer rates are higher among the low-dose (<150 μg/L) villages in the BFD area than in the southwest Taiwan region. However, among the low-dose villages in the BFD area, cancer risks suggest a negative association with well water arsenic levels. Positive differences from regional data seem attributable to non-arsenic ecological factors.

背景与目标：

BACKGROUND & AIMS: :The Z-Scan (ZS) technique in the thermal regime has been used to measure the nonlinear optical response of low-density lipoprotein (LDL). The ZS technique is carried out in LDL from 40 patients with chronic periodontitis before and after three, six, and 12 months of periodontal treatment. Clinical parameters such as probing depths, bleeding on probing, total and differential white blood cells counts, lipid profiles, cytokine levels, and antibodies against oxidized LDL are also determined and compared over time. Before the treatment, the ZS experimental results reveal that the LDL particles of these patients are heavily modified. Only after 12 months of the periodontal treatment, the ZS results obtained reveal behavioral characteristics of healthy particles. This conclusion is also supported by complementary laboratorial analysis showing that the periodontal treatment induces systemic changes in several inflammatory markers.

背景与目标： : 热状态下的Z扫描 (ZS) 技术已用于测量低密度脂蛋白 (LDL) 的非线性光学响应。ZS技术是在牙周治疗3、6和12个月之前和之后对40例慢性牙周炎患者的LDL进行的。还可以确定临床参数，例如探测深度，探测出血，白细胞总数和差异计数，脂质分布，细胞因子水平以及针对氧化LDL的抗体，并随时间进行比较。治疗前，ZS实验结果表明，这些患者的LDL颗粒已被严重修饰。仅在牙周治疗12个月后，获得的ZS结果才显示出健康颗粒的行为特征。该结论也得到补充实验室分析的支持，该分析表明牙周治疗可引起几种炎症标志物的全身变化。

BACKGROUND & AIMS: :Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma. Immunohistochemistry was used to measure the effect of low intensity rTMS (LI-rTMS) on GFAP (astrocyte), IBA1 (microglial), and CS56 (proteoglycan) expression in a unilateral penetrating cortical stab injury model of glial scarring in young adult and aged male and female C57BL6/J mice. Mice received contralateral low frequency, ipsilateral low frequency, ipsilateral high frequency or sham LI-rTMS (4-5mT intensity), for two weeks following injury. There was no significant difference in the overall volume of tissue containing GFAP positive (+) astrocytes, IBA1+ microglia, or proteoglycan expression, between sham and LI-rTMS-treated mice of all ages and sex. Importantly however, the density of GFAP+ astrocytes and IBA1+ microglia immediately adjacent to the injury was significantly reduced following ipsilateral low and high frequency stimulation in adult and aged females (p≤0.05), but was significantly increased in adult and aged males (p≤0.05). LI-rTMS effects were generally of greater magnitude in aged mice compared to young adult mice. These results suggest that sex differences need to be factored into therapeutic rTMS protocols. In particular, more work analyzing frequency and intensity specific effects, especially in relation to age and sex, is required to determine how rTMS can best be used to modify glial reactivity and phenotype following neurotrauma.

背景与目标： 重复经颅磁刺激 (rTMS) 是一种非侵入性的脑刺激形式，即使在低强度 (即动作电位产生的亚阈值) 下，也已在一系列神经调节模型中显示出实验和临床功效。中枢神经系统 (CNS) 损伤后，研究表明反应性星形胶质细胞和小胶质细胞可能具有有害但有益的作用; 因此，例如通过应用rTMS调节神经胶质活性，可能是神经创伤后有用的治疗工具。免疫组织化学用于测量低强度rTMS (LI-rTMS) 对年轻成年和老年C57BL6/J小鼠单侧穿透性皮质瘢痕损伤模型中GFAP (星形胶质细胞)，IBA1 (小胶质细胞) 和CS56 (蛋白聚糖) 表达的影响。损伤后两周，小鼠接受对侧低频，同侧低频，同侧高频或假LI-rTMS (4-5mT强度)。在所有年龄和性别的sham和LI-rTMS治疗的小鼠之间，含有GFAP阳性 () 星形胶质细胞，IBA1小胶质细胞或蛋白聚糖表达的组织的总体积均无显着差异。然而，重要的是，在同侧低频和高频刺激后，与损伤紧邻的GFAP + 星形胶质细胞和IBA1 + 小胶质细胞的密度在成年和老年女性中显著降低 (p ≤ 0.05)，但在成年和老年男性中显著增加 (p ≤ 0.05)。与年轻的成年小鼠相比，老年小鼠的LI-rTMS效应通常更大。这些结果表明，需要将性别差异纳入治疗性rTMS方案。特别是，需要更多的工作来分析频率和强度的特定影响，尤其是与年龄和性别有关的影响，以确定rTMS如何最好地用于改变神经创伤后的神经胶质反应性和表型。

BACKGROUND & AIMS: :In order to understand the effect of pH on the formation of electrostatic complexes between lysozyme and low methoxyl (LM) pectin, mixtures were prepared at a fixed lysozyme concentration (0.714g.L-1) by progressive addition of LM pectin (from 0 to 4g.L-1). Turbidity analysis allowed to determine specific conditions of pH and lysozyme/LM pectin ratio for optimal complex aggregation. The intrinsic fluorescence enhancement observed upon binding of LM pectin to lysozyme was correlated with the formation of intermolecular aggregates. Conversely, the intrinsic fluorescence decrease observed at higher LM pectin amounts was correlated with the dissociation of intermolecular aggregates. UV absorption spectroscopy showed modifications in lysozyme conformation during both the aggregation phase and the dissociation phase. The role of electrostatic interactions in the formation of lysozyme/LM pectin complexes is discussed in relation to the overall structure and the charge density profile of the two biopolymers.

背景与目标： 为了了解pH对溶菌酶和低甲氧基 (LM) 果胶之间静电复合物形成的影响，通过逐渐加入LM果胶 (0至4g.L-1)，在固定的溶菌酶浓度 (0.714g.L-1) 下制备混合物。浊度分析可以确定pH和溶菌酶/LM果胶比率的特定条件，以实现最佳的复合聚集。LM果胶与溶菌酶结合后观察到的固有荧光增强与分子间聚集体的形成有关。相反，在较高的LM果胶量下观察到的固有荧光降低与分子间聚集体的解离有关。紫外吸收光谱显示，在聚集相和解离相中，溶菌酶构象都发生了变化。讨论了静电相互作用在溶菌酶/LM果胶复合物形成中的作用，涉及两种生物聚合物的整体结构和电荷密度分布。

BACKGROUND & AIMS: BACKGROUND:The aim of the present study was to evaluate the effects of low-level laser therapy (LLLT) on the healing of bone defects in rats with streptozotocin (STZ)-induced DM. METHODS:28 male Sprague-Dawley rats were used in this study. 14 animals received a single dose of STZ intraperitoneally (65 mg/kg) to induce Type I DM, whereas others were injected only with sterile saline solution. Four weeks later, standard bone defects were created in the tibiae of rats. Surgical wounds in one group from each of the diabetic and non-diabetic animals were irradiated with diode laser for every other day for 4 weeks and they were described as DM + LLLT and CONT + LLLT groups, respectively. Remaining two groups received no laser treatment. New bone formation, osteoblast and blood vessel counts were calculated in histologic sections. RESULTS:DM group had significantly smaller bone area and lower blood vessel count when compared to DM + LLLT, CONT and CONT + LLLT groups (p < 0.05 for each). CONT and CONT + LLLT groups had significantly larger bone area than DM + LLLT group (p < 0.05 for both). CONCLUSIONS:LLLT application promoted vascularization and new bone formation in animals with DM to a limited extent, since it was unable to support the healing process up to the level of non-diabetic animals.

背景与目标：

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.

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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。

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.

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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.

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