BACKGROUND & AIMS: :Adenovirus infection results in the suppression of cellular protein synthesis, but the mechanism has not been established. In this report we demonstrate that the shut-off of cellular protein synthesis by adenovirus is prevented in cells by treatment with the drug 2-aminopurine. Treatment with 2-aminopurine is shown to prevent suppression of cellular translation without disrupting the normal viral block in the transport of cellular mRNAs from the nucleus to the cytoplasm. We show that viral suppression of cellular protein synthesis occurs concomitant with activation of the interferon-induced double-stranded RNA-activated inhibitor (DAI), a protein kinase, and phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha), but that prevention of host cell shut-off by 2-aminopurine occurs without a decrease in kinase activity or a dephosphorylation of eIF-2 alpha. Results are presented that indicate that activation of DAI kinase and phosphorylation of eIF-2 alpha may be required but are not sufficient to achieve inhibition of cellular protein synthesis during adenovirus infection. We suggest that other events, in particular the modification of additional initiation factors, are likely involved in viral inhibition of cellular translation.

背景与目标： : 腺病毒感染导致细胞蛋白质合成的抑制，但机制尚未建立。在本报告中，我们证明了通过用药物2-氨基嘌呤处理可防止细胞中腺病毒对细胞蛋白质合成的切断。显示用2-氨基嘌呤处理可防止抑制细胞翻译，而不会破坏细胞mrna从细胞核到细胞质转运中的正常病毒阻滞。我们显示，细胞蛋白合成的病毒抑制与干扰素诱导的双链RNA激活抑制剂 (DAI)，蛋白激酶的激活以及真核起始因子2 (eIF-2 α) 的 α 亚基的磷酸化同时发生，但是，通过2-氨基嘌呤阻止宿主细胞关闭而不会降低激酶活性或eIF-2 α 的去磷酸化。结果表明DAI激酶的活化和eIF-2 α 的磷酸化可能是必需的，但不足以在腺病毒感染期间实现细胞蛋白合成的抑制。我们建议其他事件，尤其是其他起始因子的修饰，可能与病毒对细胞翻译的抑制有关。

BACKGROUND & AIMS: BACKGROUND:The Cardiac failure, Hypertension, Age, Diabetes, Stroke [Doubled] (CHADS(2)) score is a useful scheme for risk stratification of thromboembolism patients, but there is little information about its usefulness for the evaluation of antiarrhythmic drug (AAD) therapy. METHODS AND RESULTS:This study included 459 paroxysmal atrial fibrillation (AF) patients (309 men, mean age 66 ± 12 years, mean follow-up 50 ± 35 months) and prophylactic efficacy was analyzed on the basis of CHADS(2) score. (1) Survival rates free from AF recurrence at 1, 6, 12 and 24 months were, respectively, 89%, 74%, 63% and 47% in score-0 group (n=152); 92%, 68%, 59% and 48% in score-1 group (n=158); 86%, 64%, 56% and 46% in score-2 group (n=84); 81%, 65%, 51% and 35% in score-3 group (n=43); and 68%, 50%, 36% and 18% in ≥ score-4 group (n=22) (P<0.05; score-0, score-1 or score-2 vs. ≥ score-4 group). (2) Survival rates free from progression to chronic AF at 12, 36, 60 and 90 months were, respectively, 95%, 93%, 91% and 89% in score-0 group; 97%, 91%, 89% and 88% in score-1 group; 96%, 93%, 88% and 83% in score-2 group; 91%, 74%, 67% and 60% in score-3 group; and 91%, 82%, 68% and 55% in ≥ score-4 group (P<0.01; score-0, score-1 or score-2 vs. ≥ score-4 group). (3) In multivariate logistic regression analysis adjusted for potentially confounding variables, CHADS(2) score was associated with AF recurrence (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.16-1.81, P<0.001), and progression to chronic AF during AAD therapy (OR 1.64, 95% CI 1.04-2.69, P<0.001). CONCLUSIONS:When using a rhythm control strategy, the CHADS(2) score is a useful scheme for predicting the outcome of AAD treatment of patients with paroxysmal AF.  

背景与目标：

BACKGROUND & AIMS: :Doxazosin used in benign prostatic hyperplasia has the side effects of causing hypotension and the risk of heart failure. The 3 targets of α(1A)-adrenoceptors (in the prostate), α(1D)-adrenoceptors (in the aorta), and an unknown mechanism (in the heart) are involved, respectively. We hypothesized that there is a chiral recognition of doxazosin enantiomers in the 3 targets. Using isolated rat aorta (α(1D)-adrenoceptors) and rabbit prostate (α(1A)-adrenoceptors), we examined pA(2) and pK(B) values of doxazosin enantiomers. We observed chronotropic and inotropic effects of doxazosin enantiomers in isolated rat and rabbit heart tissues. (-)Doxazosin and (+)doxazosin produced a shift to the right of concentration-contraction curves for noradrenalin (aorta) and phenylephrine (prostate smooth muscle). The pA(2) value of (-)doxazosin (8.625 ± 0.053) was smaller than (+)doxazosin (9.503 ± 0.051) in rat aorta, but their pK(B) values in rabbit prostate were the same. In rat and rabbit heart tissues, (+)doxazosin (3-30 µmol·L(-1)) significantly decreased atrial rate, and produced negative inotropic effects; however, (-)doxazosin did not affect the atrial rate, and produced positive inotropic effects in the atria. Thus, the chiral carbon atom of doxazosin does not affect its activity at the therapeutic target of α(1A)-adrenoceptors in the prostate, but significantly changes its blocking activity against α(1D)-adrenoceptors in the aorta, and produces opposite inotropic effects in the atria via an α(1)-adrenoceptor-independent mechanism.

背景与目标： : 多沙唑嗪用于良性前列腺增生具有引起低血压和心力衰竭风险的副作用。分别涉及 α(1A)-肾上腺素受体 (在前列腺中)，α(1D)-肾上腺素受体 (在主动脉中) 和未知机制 (在心脏中) 的3个目标。我们假设在3个靶标中存在多沙唑嗪对映体的手性识别。使用分离的大鼠主动脉 (α(1D)-肾上腺素受体) 和兔前列腺 (α(1A)-肾上腺素受体)，我们检查了多沙唑嗪对映体的pA(2) 和pK(B) 值。我们观察到多沙唑嗪对映体在分离的大鼠和兔心脏组织中的变时性和正性肌力作用。(-) 多沙唑嗪和 () 多沙唑嗪使去甲肾上腺素 (主动脉) 和去氧肾上腺素 (前列腺平滑肌) 的浓度-收缩曲线向右移动。在大鼠主动脉中 (-) 多沙唑嗪 (8.625 ± 0.053) 的pA(2) 值小于 () 多沙唑嗪 (9.503 ± 0.051)，但它们在兔前列腺中的pK(B) 值相同。在大鼠和兔心脏组织中，() 多沙唑嗪 (3-30 µ mol·L(-1)) 显着降低了心房速率，并产生了负性肌力作用; 但是，(-) 多沙唑嗪不影响心房速率，并在心房中产生了正性肌力作用。因此，多沙唑嗪的手性碳原子不会影响其在前列腺中 α(1A)-肾上腺素受体的治疗靶标上的活性，但会显着改变其对主动脉中 α(1D)-肾上腺素受体的阻断活性，并通过不依赖 α(1)-肾上腺素受体的机制在心房中产生相反的正性肌力作用。

BACKGROUND & AIMS: :A large-scale study was carried out in order to determine the contamination level of antineoplastic drugs in pharmacies and to investigate the suitability and effects of wipe sample monitoring at regular intervals. A specific study design was developed. The 130 participating pharmacies were divided into a study and a control group, carrying out five and two wipe sampling cycles, respectively. The work practice was analyzed using questionnaires to identify factors that influence the contamination level. From 1269 wipe samples, 774 (61%) were contaminated with at least one of the analyzed cytotoxic drugs: cyclophosphamide, docetaxel, etoposide, 5-fluorouracil, gemcitabine, ifosfamide, methotrexate, and paclitaxel. A significant decrease of the contamination with cyclophosphamide and 5-fluorouracil was observed in the study group. The Monitoring-Effect Study of Wipe Sampling in Pharmacies method has proven to be a reliable and affordable tool for contamination control. Based on the 90th percentile of the contamination values, a substance-independent performance-based guidance value of 0.1ng cm(-2) has been derived.

背景与目标： : 进行了大规模研究，以确定药房中抗肿瘤药物的污染水平，并调查定期擦拭样品监测的适用性和效果。开发了一个特定的研究设计。将130家参与的药房分为研究组和对照组，分别进行了五个和两个擦拭采样周期。使用问卷调查对工作实践进行了分析，以确定影响污染水平的因素。从1269擦拭样品中，774 (61%) 被至少一种分析的细胞毒性药物污染: 环磷酰胺，多西他赛，依托泊苷，5-氟尿嘧啶，吉西他滨，异环磷酰胺，甲氨蝶呤和紫杉醇。在研究组中观察到环磷酰胺和5-氟尿嘧啶的污染显着减少。药房擦拭采样方法的监测效果研究已被证明是控制污染的可靠且负担得起的工具。根据污染值的第90个百分位数，得出了与物质无关的基于性能的指导值0.1ng cm(-2)。

BACKGROUND & AIMS: :The objective of this study was to prepare a 72 h-release formulation of silybin (72 h-SLB) using a combination of solid dispersion, gel matrix and porous silica nanoparticles (PSNs) and to investigate the in vitro/in vivo correlations (IVIVCs). The results of scanning electron microscopy and N(2) adsorption demonstrated that empty PSNs possessed a spherical shape, a highly porous structure, a large specific surface area (385.89 ± 1.12 m(2)/g) and a small pore size (2.74 nm on average). The in vitro dissolution profiles of both 72 h-SLB and silybin-loaded PSNs in different concentrations (0.01, 0.06 and 0.08M) of Na(2)CO(3) solutions revealed that 0.06 M Na(2)CO(3) solution was the optimal medium in which silybin could be released from 72 h-SLB with first-order release kinetics and from PSNs with Higuchi kinetics. Furthermore, the IVIVCs of 72 h-SLB and silybin-loaded PSNs in beagle dogs were also established. Using 0.06 M Na(2)CO(3) solution as the in vitro dissolution medium, a good linear relationship could be achieved for both 72 h-SLB and silybin-loaded PSNs. The findings support the fact that the 72 h-SLB (consisting of solid dispersion, regular gel matrix and PSNs) together with Na(2)CO(3) solution as an in vitro dissolution medium can be developed into a promising formulation for poorly soluble drugs, which enjoys a good IVIVC.

背景与目标： : 本研究的目的是使用固体分散体，凝胶基质和多孔二氧化硅纳米颗粒 (psn) 的组合制备水飞蓟宾 (72 h-SLB) 的72 h释放制剂，并研究体外/体内相关性 (IVIVCs)。扫描电子显微镜和N(2) 吸附结果表明，空psn具有球形，高度多孔结构，大的比表面积 (385.89 ± 1.12 m(2)/g) 和小的孔径 (平均2.74 nm)。72 h-SLB和水飞蓟宾负载的psn在不同浓度 (0.01，0.06和0.08M) 的Na(2)CO(3) 溶液表明，0.06 M Na(2)CO(3) 溶液是最佳介质，其中水飞蓟宾可以从72 h-SLB中释放，具有一级释放动力学和psn。具有Higuchi动力学。此外，还建立了beagle犬中72 h-SLB和水飞蓟宾psn的ivvc。使用0.06 M Na(2)CO(3) 溶液作为体外溶出介质，对于72 h-SLB和水飞蓟宾负载的psn都可以实现良好的线性关系。研究结果支持以下事实: 72 h-SLB (由固体分散体，规则凝胶基质和psn组成) 与Na(2)CO(3) 溶液一起作为体外溶出介质，可以开发为具有良好的IVIVC可溶性药物的有希望的制剂。

BACKGROUND & AIMS: BACKGROUND:Major advances in our understanding of the underlying biology of prostate cancer have helped to herald a new era in the treatment of castration-resistant prostate cancer (CRPC), with 5 new agents having shown a survival advantage in the last 3 years and an impressive number of promising novel agents now entering the clinic. CONTENT:We discuss the challenges facing drug development for CRPC and strategies to meet these challenges, with a focus not only on the development of predictive and intermediate endpoint biomarkers, but also on novel hypothesis-testing, biomarker-driven clinical trial designs. SUMMARY:With several promising agents now entering the clinic, there is increasing pressure to rethink drug development for CRPC to ensure that novel agents are appropriately evaluated and that patients and resources are appropriately allocated. We envision that biomarker-driven, reiterative clinical trials will have a major impact on CRPC treatment through the testing of robust scientific hypotheses with rationally designed drugs and drug combinations administered to selected patients.

背景与目标：

BACKGROUND & AIMS: :Amyotrophic lateral sclerosis (ALS) is an unrelenting progressive neurodegenerative disease causing progressive weakness, ultimately leading to death. Despite aggressive research, the pathways leading to neuronal death are incompletely understood. Riluzole is the only drug clinically proven to enhance survival of ALS patients, but its mechanism of action is not clearly understood. In this article, the proposed pathophysiology of ALS is reviewed including glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, autoimmune mechanisms, protein aggregation, SOD1 accumulation, and neuronal death. Based on these mechanisms, past major ALS drug studies will be reviewed as well as promising current ALS drug studies, focusing on the advancement of these studies from the bench to the patient's bedside.

背景与目标： 肌萎缩性侧索硬化症 (ALS) 是一种持续的进行性神经退行性疾病，导致进行性虚弱，最终导致死亡。尽管进行了积极的研究，但导致神经元死亡的途径尚不完全清楚。利鲁唑是唯一经临床证实可提高ALS患者生存率的药物，但其作用机制尚不清楚。在本文中，对ALS的拟议病理生理学进行了综述，包括谷氨酸兴奋性毒性，氧化应激，线粒体功能障碍，自身免疫机制，蛋白质聚集，SOD1积累和神经元死亡。基于这些机制，将回顾过去的主要ALS药物研究以及有希望的当前ALS药物研究，重点是从替补席到患者床边的这些研究的进展。

BACKGROUND & AIMS: :Entecavir, a drug approved by the Food and Drug Administration for the treatment of chronic hepatitis B virus (HBV) infection, is not believed to inhibit replication of human immunodeficiency virus type 1 (HIV-1) at clinically relevant doses. We observed that entecavir led to a consistent 1-log(10) decrease in HIV-1 RNA in three persons with HIV-1 and HBV coinfection, and we obtained supportive in vitro evidence that entecavir is a potent partial inhibitor of HIV-1 replication. Detailed analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V. In vitro experiments showed that M184V confers resistance to entecavir. Until more is known about HIV-1-resistance patterns and their selection by entecavir, caution is needed with the use of entecavir in persons with HIV-1 and HBV coinfection who are not receiving fully suppressive antiretroviral regimens.

背景与目标： : 恩替卡韦是美国食品药品监督管理局批准的用于治疗慢性乙型肝炎病毒 (HBV) 感染的药物，据信不抑制临床相关剂量的人类免疫缺陷病毒1型 (HIV-1) 的复制。我们观察到恩替卡韦导致HIV-1 RNA在三个HIV-1和HBV共感染的人一致的1-log(10) 减少，我们获得了支持的体外证据，恩替卡韦是HIV-1复制的有效部分抑制剂。详细分析显示，在其中一名患者中，恩替卡韦单药治疗导致拉米夫定耐药突变M184V的HIV-1变异体积累。体外实验表明，M184V具有对恩替卡韦的抗性。直到更多关于HIV-1-resistance模式及其恩替卡韦的选择，需要谨慎使用恩替卡韦与HIV-1和HBV合并感染谁没有接受完全抑制抗逆转录病毒方案的人。

BACKGROUND & AIMS: :Patients taking tricyclic antidepressants (TCA) can experience toxicity or severe side effects. As a rapid and less technically demanding alternative to quantitative serum analysis, most laboratories offer qualitative immunoassays to assist in the evaluation of a suspected TCA overdose. However, the relationship between quantitative serum and qualitative urine levels of TCA-related compounds and their metabolites has not been comprehensively studied. Serum high-performance liquid chromatography results were compared to the qualitative urine results using the Syva Rapid Test and the Biosite Triage. Serum concentrations of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline ranging from subtherapeutic to toxic triggered a positive response on both urine immunoassay devices. On the other hand, neither immunoassay uniformly detected clomipramine, even at serum levels greater than the therapeutic range. False positives due to cyclobenzaprine were more common with the Biosite assay. For virtually all positive urine TCA findings, it was not possible to determine whether the positive results corresponded to subtherapeutic, therapeutic, supratherapeutic, or toxic serum concentrations. Because urine immunoassays are the only option for many laboratories analyzing specimens for TCAs (especially in an emergency setting), clinicians must understand the limitations and interpret results in conjunction with clinical findings and/or quantitation of serum levels.

背景与目标： : 服用三环类抗抑郁药 (TCA) 的患者会出现毒性或严重的副作用。作为定量血清分析的快速且技术要求较低的替代方法，大多数实验室提供定性免疫测定，以帮助评估可疑的TCA过量。然而，尚未全面研究TCA相关化合物及其代谢产物的定量血清和定性尿液水平之间的关系。使用Syva快速测试和Biosite分诊将血清高效液相色谱结果与定性尿液结果进行比较。阿米替林，地昔帕明，多塞平，丙咪嗪和去甲替林的血清浓度从亚治疗性到毒性，在两种尿液免疫测定设备上都产生了阳性反应。另一方面，即使在血清水平大于治疗范围的情况下，也没有免疫测定方法能均匀检测到氯米帕明。由于环苯扎林引起的假阳性在生物矿测定中更为常见。对于几乎所有尿液TCA阳性结果，无法确定阳性结果是否对应于亚治疗，治疗，超治疗或毒性血清浓度。由于尿液免疫测定是许多实验室分析TCAs标本的唯一选择 (尤其是在紧急情况下)，因此临床医生必须了解局限性并结合临床发现和/或血清水平定量来解释结果。

BACKGROUND & AIMS: BACKGROUND:Recent studies show that patients with multiple nonsteroidal anti-inflammatory drug (NSAID) intolerance are frequently characterized by autoreactivity; this can be detected by autologous serum skin test (ASST). OBJECTIVE:To assess whether the autologous plasma skin test (APST), a test that was recently shown to be more sensitive than ASST, may be usefully employed as a predictive test for multiple NSAID intolerance in patients with a history of single NSAID intolerance. METHODS:Thirty otherwise normal adults with a history of acute urticaria following the ingestion of one single NSAID underwent an APST before being challenged with a COX-1-inhibiting NSAID other than the offending drug. RESULTS:Sixteen patients experienced urticaria following the ingestion of the alternative NSAID and were therefore classified as multiple NSAID reactors; all 16 (100%) scored positive on APST. In contrast only 3/14 patients finally classified as single NSAID reactors were positive on APST (p < 0.001). The positive and negative predictive value of APST for multiple NSAID intolerance were 86 and 100%, respectively. CONCLUSION:In patients with a history of acute urticaria induced by a single NSAID APST can be usefully employed to detect patients that are prone to react to NSAID other than the original offending one.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Pentavalent antimony (Sb(v)) is the mainstay therapy for mucosal leishmaniasis (ML), but it is toxic, and relapses are common. Immunotherapy using a mixture of killed parasites, with or without bacille Calmette-Guerin, is an alternative but is used sporadically because of inconsistent results. METHODS:We developed a defined immunotherapeutic antigen preparation for use in an observational, open-label trial to treat 6 patients with ML with a history of Sb(v) therapy failure. All patients were treated with the antigens thiol-specific antioxidant, Leishmania major stress inducible protein 1, Leishmania elongation initiation factor, and Leishmania heat shock protein 83, plus granulocyte-macrophage colony-stimulating factor. Patients underwent clinical and pathological evaluations before the initiation of immunotherapy and at 3, 6, 9, 12, 18, 24, and 60 months after. RESULTS:One month after the third injection, 1 patient showed complete clinical remission (CC) and remained disease free for the duration of the study. At the 9-month follow-up examination, 5 patients showed CC, and all patients were asymptomatic at a subsequent 5-year follow-up examination. CONCLUSIONS:These data support the concept that vaccine therapy with a defined antigen combination, used with standard chemotherapy, is a safe and effective approach to treat drug-refractory ML.

背景与目标：

BACKGROUND & AIMS: :Our previous studies have suggested a role for AMP-activated protein kinase (AMPK) in the induction of CYP2B6 by phenobarbital (PB) in hepatoma-derived cells (Rencurel et al., 2005). In this study, we showed in primary human hepatocytes that: 1) 5'-phosphoribosyl-5-aminoimidazol-4-carboxamide 1-beta-d-ribofuranoside and the biguanide metformin, known activators of AMPK, dose-dependently increase the expression of CYP2B6 and CYP3A4 to an extent similar to that of PB. 2) PB, but not the human nuclear receptor constitutive active/androstane receptor (CAR) ligand 6-(4-chlorophenyl)imidazol[2,1-6][1,3]thiazole-5-carbaldehyde, dose-dependently increase AMPK activity. 3) Pharmacological inhibition of AMPK activity with compound C or dominant-negative forms of AMPK blunt the inductive response to phenobarbital. Furthermore, in transgenic mice with a liver-specific deletion of both the alpha1 and alpha2 AMPK catalytic subunits, basal levels of Cyp2b10 and Cyp3a11 mRNA were increased but not in primary culture of mouse hepatocytes. However, phenobarbital or 1,4 bis[2-(3,5-dichloropyridyloxy)]benzene, a mouse CAR ligand, failed to induce the expression of these genes in the liver or cultured hepatocytes from mice lacking hepatic expression of the alpha1 and alpha2 subunits of AMPK. The distribution of CAR between the nucleus and cytosol was not altered in hepatocytes from mice lacking both AMPK catalytic subunits. These data highlight the essential role of AMPK in the CAR-mediated signal transduction pathway.

背景与目标： : 我们先前的研究表明，AMP激活的蛋白激酶 (AMPK) 在苯巴比妥 (PB) 在肝癌衍生细胞中诱导CYP2B6中的作用 (rencorel等人，2005)。在这项研究中，我们在原代人类肝细胞中显示: 1) 5 '-phosphoribosyl-5-aminoimidazol-4-carboxamide 1-β-d-呋喃核苷和双胍二甲双胍 (已知的AMPK激活剂) 剂量依赖性地增加CYP2B6和CYP3A4的表达与PB相似的程度。2) PB，但不是人核受体组成型活性/雄甾烷受体 (CAR) 配体6-(4-氯苯基) 咪唑 [2,1-6][1,3]thiazole-5-carbaldehyde，剂量依赖性地增加AMPK活性。3) 用化合物C或AMPK的显性阴性形式对AMPK活性的药理抑制钝化对苯巴比妥的诱导反应。此外，在具有肝脏特异性的 α1和 α2 AMPK催化亚基缺失的转基因小鼠中，Cyp2b10和Cyp3a11 mRNA的基础水平增加，但在小鼠肝细胞的原代培养中却没有。然而，苯巴比妥或1,4双 [2-(3,5-二氯吡啶基氧基)] 苯 (一种小鼠CAR配体) 未能诱导这些基因在肝脏或培养的肝细胞中的表达，这些基因来自缺乏AMPK的 α1和 α2亚基的肝表达的小鼠。缺乏两个AMPK催化亚基的小鼠的肝细胞中，核与胞质之间的CAR分布没有改变。这些数据强调了AMPK在CAR介导的信号转导途径中的重要作用。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Results are presented comparing Monte Carlo (MC) calculations for dynamic IMRT treatments of tumors in the sinus region with Eclipse treatment planning system dose calculations, and ion chamber measurements. The EGS4nrc MC code, BEAMnrc, was commissioned to simulate a Varian 21Ex Linac for both open and IMRT fields. The accuracy of the simulation for IMRT plans was evaluated using a head phantom by comparing MC, Eclipse, TLD results, and ion chamber in solid water phantom measurements. The MC code was then used to simulate dose distributions for five patients who were treated using dynamic IMRT for tumors in the sinus region. The results were compared with absolute and relative dose distributions calculated using Eclipse (pencil beam, modified-Batho inhomogeneity correction). Absolute dose differences were also compared with ion chamber results. Comparison of the doses calculated on the head phantom using MC, compared with Eclipse, ion chamber, and TLD measurements showed differences of -3.9%, -1.4%, and -2.0%, respectively (MC is colder). Relative dose distributions for the patient plans calculated using MC agreed well with those calculated using Eclipse with respect to targets and critical organs, indicating the modified-Batho correction is adequate. Average agreement for mean absolute target doses between MC and Eclipse was -3.0 +/-; 2.3% (1 s.d.). Agreement between ion chamber and Eclipse for these patients was -2.2 +/- 1.9%, compared with 0.2 +/- 2.0% for all head and neck IMRT patients. When Eclipse doses were corrected based on ion chamber results, agreement between MC and Eclipse was -0.7 +/- 2.0%, indicating a small systematic uncertainty in the doses calculated using the treatment planning system for this subset of patients.

背景与目标： : 给出了将鼻窦区域肿瘤的动态IMRT治疗的蒙特卡洛 (MC) 计算与Eclipse治疗计划系统剂量计算和离子室测量进行比较的结果。EGS4nrc MC代码BEAMnrc被委托为开放和IMRT字段模拟Varian 21Ex直线加速器。通过比较固体水体模测量中的MC，Eclipse，TLD结果和离子室，使用头体模评估了IMRT计划模拟的准确性。然后使用MC代码模拟五名患者的剂量分布，这些患者使用动态IMRT治疗窦区肿瘤。将结果与使用Eclipse计算的绝对剂量和相对剂量分布进行比较 (笔形光束，改进的-Batho不均匀性校正)。绝对剂量差异也与离子室结果进行了比较。与Eclipse，离子室和TLD测量相比，使用MC在头部模上计算的剂量的比较分别显示出-3.9%，-1.4% 和-2.0% 的差异 (MC较冷)。使用MC计算的患者计划的相对剂量分布与使用Eclipse计算的目标和关键器官的相对剂量分布非常吻合，表明改良的-Batho校正是足够的。MC和Eclipse之间平均绝对目标剂量的平均一致性为-3.0 +/-; 2.3% (1 s.d.)。这些患者的离子室与Eclipse之间的一致性为-2.2/- 1.9%，而所有头颈部IMRT患者的0.2/- 2.0%。当基于离子室结果校正Eclipse剂量时，MC和Eclipse之间的一致性为-0.7 +/- 2.0%，表明使用治疗计划系统为该患者子集计算的剂量中的小的系统不确定性。

BACKGROUND & AIMS: :Atomoxetine improves inhibitory control and visual processing in healthy volunteers and adults with attention-deficit/hyperactivity disorder (ADHD). However, little is known about the neural correlates of these two functions after chronic treatment with atomoxetine. This study aimed to use the counting Stroop task with functional magnetic resonance imaging (fMRI) and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to investigate the changes related to inhibitory control and visual processing in adults with ADHD. This study is an 8-week, placebo-controlled, double-blind, randomized clinical trial of atomoxetine in 24 drug-naïve adults with ADHD. We investigated the changes of treatment with atomoxetine compared to placebo-treated counterparts using the counting Stroop fMRI and two CANTAB tests: rapid visual information processing (RVP) for inhibitory control and delayed matching to sample (DMS) for visual processing. Atomoxetine decreased activations in the right inferior frontal gyrus and anterior cingulate cortex, which were correlated with the improvement in inhibitory control assessed by the RVP. Also, atomoxetine increased activation in the left precuneus, which was correlated with the improvement in the mean latency of correct responses assessed by the DMS. Moreover, anterior cingulate activation in the pre-treatment was able to predict the improvements of clinical symptoms. Treatment with atomoxetine may improve inhibitory control to suppress interference and may enhance the visual processing to process numbers. In addition, the anterior cingulate cortex might play an important role as a biological marker for the treatment effectiveness of atomoxetine. Hum Brain Mapp 38:4850-4864, 2017. © 2017 Wiley Periodicals, Inc.

背景与目标： : 阿托莫西汀改善健康志愿者和患有注意力缺陷/多动障碍 (ADHD) 的成年人的抑制控制和视觉处理。然而，对于长期使用阿托莫西汀治疗后这两种功能的神经相关性知之甚少。这项研究旨在使用功能磁共振成像 (fMRI) 和剑桥神经心理测试自动电池 (CANTAB) 的计数Stroop任务来研究ADHD成人与抑制性控制和视觉处理相关的变化。这项研究是一项为期8周，安慰剂对照，双盲，随机临床试验的阿托莫西汀在24名未用药的ADHD成人中进行的试验。我们使用Stroop fMRI计数和两种CANTAB测试研究了与安慰剂治疗的对应物相比，托莫西汀治疗的变化: 用于抑制控制的快速视觉信息处理 (RVP) 和用于视觉处理的延迟匹配 (DMS)。阿托莫西汀降低了右下额回和前扣带回皮层的激活，这与RVP评估的抑制性控制的改善有关。此外，阿托莫西汀增加了左前肌的激活，这与DMS评估的正确反应的平均潜伏期的改善有关。此外，治疗前的扣带回激活能够预测临床症状的改善。用阿托莫西汀治疗可以改善抑制控制以抑制干扰，并可以增强视觉处理以处理数字。此外，前扣带回皮层可能是阿托莫西汀治疗效果的生物学标记。Hum Brain Mapp 38:4850-4864，2017。©2017威利期刊公司