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Effects and Safety of Linagliptin as an Add-on Therapy in Advanced-Stage Diabetic Nephropathy Patients Taking Renin–Angiotensin–Aldosterone System Blockers 利格列汀在使用肾素-血管紧张素-醛固酮系统阻滞剂的晚期糖尿病肾病患者中的疗效和安全性
IF 2.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2016-01-01 DOI: 10.4137/DTI.S38339
Yuichiro Ueda, Hiroki Ishii, Taisuke Kitano, Mitsutoshi Shindo, Haruhisa Miyazawa, K. Ito, Keiji Hirai, Y. Kaku, H. Mori, T. Hoshino, S. Ookawara, M. Kakei, K. Tabei, Yoshiyuki Morishita
Background We investigated the effects and safety of linagliptin as an add-on therapy in patients with advanced-stage diabetic nephropathy (DMN) taking renin–angiotensin–aldosterone system (RAAS) blockers. Method Twenty advanced-stage DMN patients (estimated glomerular filtration rate (eGFR): 24.5 ± 13.4 mL/min/1.73 m2) taking RAAS blockers were administered 5 mg/day linagliptin for 52 weeks. Changes in glucose and lipid metabolism and renal function were evaluated. Results Linagliptin decreased glycosylated hemoglobin levels (from 7.32 ± 0.77% to 6.85 ± 0.87%, P < 0.05) without changing fasting blood glucose levels, and significantly decreased total cholesterol levels (from 189.6 ± 49.0 to 170.2 ± 39.2 mg/dL, P < 0.05) and low-density lipoprotein cholesterol levels (from 107.1 ± 32.4 to 90.2 ± 31.0 mg/dL, P < 0.05) without changing high-density lipoprotein cholesterol and triglyceride levels. Urine protein/creatinine ratio and annual change in eGFR remained unchanged. No adverse effects were observed. Conclusion Linagliptin as an add-on therapy had beneficial effects on glucose and lipid metabolism without impairment of renal function, and did not have any adverse effects in this population of patients with advanced-stage DMN taking RAAS blockers.
我们研究了利格列汀作为晚期糖尿病肾病(DMN)患者服用肾素-血管紧张素-醛固酮系统(RAAS)阻滞剂的附加治疗的效果和安全性。方法20例晚期DMN患者(估计肾小球滤过率(eGFR): 24.5±13.4 mL/min/1.73 m2)服用RAAS阻滞剂,给予利格列汀5mg /d,连续52周。观察糖、脂代谢及肾功能的变化。结果利格列汀降低糖化血红蛋白水平(从7.32±0.77%降至6.85±0.87%,P < 0.05),不改变空腹血糖水平;降低总胆固醇水平(从189.6±49.0降至170.2±39.2 mg/dL, P < 0.05)和低密度脂蛋白胆固醇水平(从107.1±32.4降至90.2±31.0 mg/dL, P < 0.05),不改变高密度脂蛋白胆固醇和甘油三酯水平。尿蛋白/肌酐比值和eGFR的年变化保持不变。未观察到不良反应。结论利格列汀作为辅助治疗对晚期DMN患者的糖脂代谢有良好的影响,且不损害肾功能,且在使用RAAS阻滞剂的人群中无不良反应。
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引用次数: 0
CURRENT DEVELOPMENTS IN DRUG ELUTING DEVICES: Introductory Editorial: Drug-Eluting Stents or Drug-Eluting Grafts? Insights from Proteomic Analysis 药物洗脱装置的最新进展:导论:药物洗脱支架还是药物洗脱移植物?来自蛋白质组学分析的见解
IF 2.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2016-01-01 DOI: 10.4137/DTI.S41240
C. Spadaccio, F. Nappi, N. Al-Attar, R. Coccia, M. Perluigi, F. Di Domenico
Drug Target Insights aims to provide researchers working in this complex, quickly developing field with online, open access to highly relevant scholarly articles by leading international researchers. In a field where the literature is ever-expanding, researchers increasingly need access to up-to-date, high quality scholarly articles on areas of specific contemporary interest. This supplement aims to address this by presenting high-quality articles that allow readers to distinguish the signal from the noise. The editor in chief hopes that through this effort, practitioners and researchers will be aided in finding answers to some of the most complex and pressing issues of our time. Supplement Aims and Scope Journal name: Drug Target Insights
Drug Target Insights旨在为在这个复杂、快速发展的领域工作的研究人员提供在线、开放的、由国际领先研究人员撰写的高度相关的学术文章。在一个文献不断扩展的领域,研究人员越来越需要获得关于特定当代兴趣领域的最新、高质量的学术文章。本增刊旨在通过提供高质量的文章,让读者从噪音中区分信号来解决这个问题。总编辑希望通过这一努力,从业者和研究人员将有助于找到我们这个时代一些最复杂和最紧迫问题的答案。增刊目的与范围期刊名称:药物靶标洞察
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引用次数: 7
Immunoinformatics Approach in Designing Epitope-based Vaccine Against Meningitis-inducing Bacteria (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae Type b) 设计基于表位的抗脑膜炎诱导细菌(肺炎链球菌、脑膜炎奈瑟菌和b型流感嗜血杆菌)疫苗的免疫信息学方法
IF 2.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2016-01-01 DOI: 10.4137/DTI.S38458
H. Zahroh, Ahmad Ma’rup, U. S. Tambunan, A. A. Parikesit
Meningitis infection is one of the major threats during Hajj season in Mecca. Meningitis vaccines are available, but their uses are limited in some countries due to religious reasons. Furthermore, they only give protection to certain serogroups, not to all types of meningitis-inducing bacteria. Recently, research on epitope-based vaccines has been developed intensively. Such vaccines have potential advantages over conventional vaccines in that they are safer to use and well responded to the antibody. In this study, we developed epitope-based vaccine candidates against various meningitis-inducing bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. The epitopes were selected from their protein of polysaccharide capsule. B-cell epitopes were predicted by using BCPred, while T-cell epitope for major histocompatibility complex (MHC) class I was predicted using PAProC, TAPPred, and Immune Epitope Database. Immune Epitope Database was also used to predict T-cell epitope for MHC class II. Population coverage and molecular docking simulation were predicted against previously generated epitope vaccine candidates. The best candidates for MHC class I- and class II-restricted T-cell epitopes were MQYGDKTTF, MKEQNTLEI, ECTEGEPDY, DLSIVVPIY, YPMAMMWRNASNRAI, TLQMTLLGIVPNLNK, ETSLHHIPGISNYFI, and SLLYILEKNAEMEFD, which showed 80% population coverage. The complexes of class I T-cell epitopes-HLA-C*03:03 and class II T-cell epitopes-HLA-DRB1*11:01 showed better affinity than standards as evaluated from their δGbinding value and the binding interaction between epitopes and HLA molecules. These peptide constructs may further be undergone in vitro and in vivo testings for the development of targeted vaccine against meningitis infection.
脑膜炎感染是麦加朝觐期间的主要威胁之一。脑膜炎疫苗是可以获得的,但由于宗教原因,它们的使用在一些国家受到限制。此外,它们只对某些血清群提供保护,而不是对所有类型的脑膜炎诱导细菌提供保护。近年来,基于表位的疫苗研究得到了深入的发展。与传统疫苗相比,这种疫苗具有潜在的优势,因为它们使用起来更安全,而且对抗体反应良好。在这项研究中,我们开发了基于表位的候选疫苗,以对抗多种脑膜炎诱导细菌,包括肺炎链球菌、脑膜炎奈瑟菌和b型流感嗜血杆菌。表位是从多糖胶囊的蛋白质中选择的。使用BCPred预测b细胞表位,使用PAProC、TAPPred和Immune epitope Database预测t细胞主要组织相容性复合体(MHC) I类表位。免疫表位数据库也用于预测MHC II类t细胞表位。针对先前生成的表位候选疫苗进行了人群覆盖率和分子对接模拟预测。MHC I类和ii类限制性t细胞表位的最佳候选是MQYGDKTTF、MKEQNTLEI、ECTEGEPDY、DLSIVVPIY、YPMAMMWRNASNRAI、TLQMTLLGIVPNLNK、etslhipgisnyfi和SLLYILEKNAEMEFD,其种群覆盖率为80%。I类t细胞表位-HLA- c *03:03和II类t细胞表位-HLA- drb1 *11:01复合物的δ g结合值和表位与HLA分子的结合相互作用均显示出较好的亲和力。这些肽结构可以进一步在体外和体内进行测试,以开发针对脑膜炎感染的靶向疫苗。
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引用次数: 36
Brain Histamine N-Methyltransferase As a Possible Target of Treatment for Methamphetamine Overdose 脑组胺n -甲基转移酶作为甲基苯丙胺过量治疗的可能靶点
IF 2.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2016-01-01 DOI: 10.4137/DTI.S38342
J. Kitanaka, N. Kitanaka, F. Hall, G. Uhl, M. Takemura
Stereotypical behaviors induced by methamphetamine (METH) overdose are one of the overt symptoms of METH abuse, which can be easily assessed in animal models. Currently, there is no successful treatment for METH overdose. There is increasing evidence that elevated levels of brain histamine can attenuate METH-induced behavioral abnormalities, which might therefore constitute a novel therapeutic treatment for METH abuse and METH overdose. In mammals, histamine N-methyltransferase (HMT) is the sole enzyme responsible for degrading histamine in the brain. Metoprine, one of the most potent HMT inhibitors, can cross the blood-brain barrier and increase brain histamine levels by inhibiting HMT. Consequently, this compound can be a candidate for a prototype of drugs for the treatment of METH overdose.
过量甲基苯丙胺引起的刻板行为是甲基苯丙胺滥用的明显症状之一,可以很容易地在动物模型中进行评估。目前,对过量服用冰毒没有成功的治疗方法。越来越多的证据表明,高水平的脑组胺可以减轻冰毒引起的行为异常,因此这可能成为冰毒滥用和冰毒过量的一种新的治疗方法。在哺乳动物中,组胺n -甲基转移酶(HMT)是大脑中唯一负责降解组胺的酶。甲托林是最有效的HMT抑制剂之一,可以通过血脑屏障,通过抑制HMT而增加脑组胺水平。因此,该化合物可作为治疗甲基苯丙胺过量的药物原型的候选物。
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引用次数: 9
Preliminary In Vivo Evaluation of a Hybrid Armored Vascular Graft Combining Electrospinning and Additive Manufacturing Techniques 结合静电纺丝和增材制造技术的混合装甲血管移植物的初步体内评价
IF 2.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2016-01-01 DOI: 10.4137/DTI.S35202
C. Spadaccio, F. Nappi, F. De Marco, P. Sedati, Fraser W. H. Sutherland, M. Chello, M. Trombetta, A. Rainer
In this study, we tested in vivo effectiveness of a previously developed poly-L-lactide/poly-8-caprolactone armored vascular graft releasing heparin. This bioprosthesis was designed in order to overcome the main drawbacks of tissue-engineered vascular grafts, mainly concerning poor mechanical properties, thrombogenicity, and endothelialization. The bioprosthesis was successfully implanted in an aortic vascular reconstruction model in rabbits. All grafts implanted were patent at four weeks postoperatively and have been adequately populated by endogenous cells without signs of thrombosis or structural failure and with no need of antiplatelet therapy. The results of this preliminary study might warrant for further larger controlled in vivo studies to further confirm these findings.
在这项研究中,我们测试了先前开发的聚l -丙交酯/聚8-己内酯装甲血管移植物释放肝素的体内有效性。这种生物假体的设计是为了克服组织工程血管移植物的主要缺点,主要是机械性能差,血栓形成性和内皮化。该生物假体成功植入家兔主动脉血管重建模型。所有移植的移植物在术后四周通畅,内源性细胞充分填充,无血栓形成或结构衰竭迹象,不需要抗血小板治疗。这项初步研究的结果可能需要进一步进行更大规模的体内对照研究,以进一步证实这些发现。
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引用次数: 32
Basal Plasma Levels of Copeptin are Elevated in Inactive Inflammatory Bowel Disease after Bowel Resection. 非活动性炎性肠病患者肠切除术后基础血浆Copeptin水平升高
IF 2.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2015-07-13 eCollection Date: 2015-01-01 DOI: 10.4137/DTI.S26589
Bodil Ohlsson, Olle Melander

Evidence of interactions between the enteric nervous system, neuropeptides, and the immune system is growing. The aim of this study was to examine basal plasma levels of a variety of peptide precursors in patients with inflammatory bowel disease (IBD). In two middle-aged cohorts, Malmö Preventive Medicine (n = 5,415) and Malmö Diet and Cost Study (n = 6,103), individuals with the diagnosis of IBD were identified. Medical records were scrutinized. Three controls were matched for each patient. Copeptin, midregional fragments of adrenomedullin, pro-atrial natriuretic peptide, and proenkephalin A, as well as N-terminal protachykinin A and proneurotensin were analyzed in the plasma. Sixty-two IBD patients were identified. The only difference between patients and controls was higher copeptin levels in the patients compared with controls (P = 0.006), with higher copeptin levels in resected than unresected patients (P = 0.020). There was no difference in any precursor levels between Crohn's disease and ulcerative colitis, between different distributions of disease lesions, or between different treatments.

肠道神经系统、神经肽和免疫系统之间相互作用的证据越来越多。本研究的目的是检测炎症性肠病(IBD)患者多种肽前体的基础血浆水平。在两个中年队列中,Malmö预防医学(n = 5415)和Malmö饮食和成本研究(n = 6103),确定了诊断为IBD的个体。他们仔细检查了医疗记录。每个病人有三个对照。分析血浆中Copeptin、肾上腺髓质素中部片段、前房利钠肽、前脑啡肽A,以及n端原激肽A和前神经紧张素。确定了62例IBD患者。患者与对照组之间唯一的差异是患者的copeptin水平高于对照组(P = 0.006),切除患者的copeptin水平高于未切除患者(P = 0.020)。在克罗恩病和溃疡性结肠炎之间,在疾病病变的不同分布之间,或在不同的治疗方法之间,没有任何前体水平的差异。
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引用次数: 1
Medicinal Plants: A Potential Source of Compounds for Targeting Cell Division. 药用植物:靶向细胞分裂化合物的潜在来源。
IF 2.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2015-06-15 eCollection Date: 2015-01-01 DOI: 10.4137/DTI.S24946
Ihsan N Zulkipli, Sheba R David, Rajan Rajabalaya, Adi Idris

Modern medicinal plant drug discovery has provided pharmacologically active compounds targeted against a multitude of conditions and diseases, such as infection, inflammation, and cancer. To date, natural products from medicinal plants remain a solid niche as a source from which cancer therapies can be derived. Among other properties, one favorable characteristic of an anticancer drug is its ability to block the uncontrollable process of cell division, as cancer cells are notorious for their abnormal cell division. There are numerous other documented works on the potential anticancer activity of drugs derived from medicinal plants, and their effects on cell division are an attractive and growing therapeutic target. Despite this, there remains a vast number of unidentified natural products that are potentially promising sources for medical applications. This mini review aims to revise the current knowledge of the effects of natural plant products on cell division.

现代药用植物药物的发现已经提供了针对多种病症和疾病的药理活性化合物,如感染、炎症和癌症。迄今为止,药用植物的天然产物仍然是癌症治疗的坚实来源。在其他特性中,抗癌药物的一个有利特性是它能够阻止不可控的细胞分裂过程,因为癌细胞以其异常的细胞分裂而臭名昭著。从药用植物中提取的药物具有潜在的抗癌活性,它们对细胞分裂的影响是一个有吸引力的和不断增长的治疗靶点。尽管如此,仍有大量未经鉴定的天然产物具有潜在的医学应用前景。这篇综述的目的是修订目前对天然植物产品对细胞分裂的影响的认识。
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引用次数: 32
7-NI and ODQ Disturbs Memory in the Elevated Plus Maze, Morris Water Maze, and Radial Arm Maze Tests in Mice. 7-NI和ODQ对高架迷宫、Morris水迷宫和桡臂迷宫小鼠记忆的干扰
IF 2.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2015-03-04 eCollection Date: 2015-01-01 DOI: 10.4137/DTI.S23378
Oguz Mutlu, Furuzan Akar, Ipek Komsuoglu Celikyurt, Pelin Tanyeri, Guner Ulak, Faruk Erden

Nitric oxide (NO) is an atypical neurotransmitter that causes changes in cognition. Nitric oxide synthase (NOS) and guanylate cyclase (GC) inhibitors have been shown to exert some effects on cognition in previous studies; however, the findings have been controversial. This study was aimed at understanding the effects of an NOS inhibitor, 7-nitroindazole (7-NI), and a guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on spatial memory in modified elevated plus maze (mEPM), Morris water maze (MWM), and radial arm maze (RAM) tests. Male Balb-c mice were treated via intraperitoneal injections with 7-NI (15 mg/kg), ODQ (3, 10 mg/kg), L-arginine (100 mg/kg) + 7-NI (15 mg/kg), or physiological saline. ODQ (3 mg/kg) and 7-NI (15 mg/kg) significantly increased the second-day latency in the mEPM test. 7-NI (15 mg/kg) and ODQ (10 mg/kg) significantly increased the escape latency in second, third, and fourth sessions, decreased the time spent in the escape platform's quadrant, and increased the mean distance to the platform in the probe trial of the MWM test. ODQ (3, 10 mg/kg) and 7-NI (15 mg/kg) significantly increased the number of errors, whereas only 7-NI increased the latency in the RAM test. The administration of L-arginine (100 mg/kg) prior to 7-NI inverted the effects of 7-NI, which supports the role of NO on cognition. Our study shows that the NO/cGMP/GS pathway can regulate spatial memory in mice.

一氧化氮(NO)是一种引起认知变化的非典型神经递质。一氧化氮合酶(NOS)和鸟苷酸环化酶(GC)抑制剂已被证明对认知有一定影响;然而,这些发现一直存在争议。本研究旨在了解NOS抑制剂7-硝基indazole (7-NI)和鸟苷酸环化酶抑制剂1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ)对改良上调迷宫(mEPM)、Morris水迷宫(MWM)和径向臂迷宫(RAM)空间记忆的影响。雄性Balb-c小鼠分别腹腔注射7-NI (15 mg/kg)、ODQ (3,10 mg/kg)、l -精氨酸(100 mg/kg) + 7-NI (15 mg/kg)或生理盐水。ODQ (3 mg/kg)和7-NI (15 mg/kg)显著增加mEPM试验的第2天潜伏期。7-NI (15 mg/kg)和ODQ (10 mg/kg)显著增加了第二、第三和第四阶段的逃避潜伏期,减少了在逃避平台象限的时间,增加了MWM试验探针试验中到平台的平均距离。ODQ (3,10 mg/kg)和7-NI (15 mg/kg)显著增加了错误数量,而只有7-NI增加了RAM测试中的延迟。在7-NI之前给予l -精氨酸(100 mg/kg)逆转了7-NI的作用,支持NO对认知的作用。我们的研究表明NO/cGMP/GS通路可以调节小鼠的空间记忆。
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引用次数: 27
Screening Analogs of β-OG Pocket Binder as Fusion Inhibitor of Dengue Virus 2 登革病毒2型融合抑制剂β-OG口袋结合物的筛选
IF 2.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2015-01-01 DOI: 10.4137/DTI.S31566
Usman SF Tambunan, H. Zahroh, A. A. Parikesit, Syarifuddin Idrus, D. Kerami
Dengue is an infectious disease caused by dengue virus (DENV) and transmitted between human hosts by mosquitoes. Recently, Indonesia was listed as a country with the highest cases of dengue by the Association of Southeast Asian Nations. The current treatment for dengue disease is supportive therapy; there is no antiviral drug available in the market against dengue. Therefore, a research on antiviral drug against dengue is very important, especially to prevent outbreak explosion. In this research, the development of dengue antiviral is performed through the inhibition of n-octyl-β-D-glucoside (β-OG) binding pocket on envelope protein of DENV by using analogs of β-OG pocket binder. There are 828 compounds used in this study, and all of them were screened based on the analysis of molecular docking, pharmacological character prediction of the compounds, and molecular dynamics simulation. The result of these analyses revealed that the compound that can be used as an antiviral candidate against DENV is 5-(3,4-dichlorophenyl)-N-[2-(p-tolyl) benzotriazol-5-yl]furan-2-carboxamide.
登革热是一种由登革热病毒(DENV)引起的传染病,通过蚊子在人类宿主之间传播。最近,印尼被东南亚国家联盟(Association of Southeast Asian Nations)列为登革热病例最高的国家。目前对登革热的治疗是支持疗法;市场上没有针对登革热的抗病毒药物。因此,研究登革热的抗病毒药物,特别是预防登革热的爆发具有重要意义。本研究通过β-OG口袋粘合剂的类似物抑制DENV包膜蛋白上的正辛基-β- d -葡萄糖苷(β-OG)结合口袋来开发登革热抗病毒药物。本研究共使用了828个化合物,所有化合物均通过分子对接分析、药理特性预测、分子动力学模拟进行筛选。这些分析结果表明,可以作为DENV抗病毒候选化合物的是5-(3,4-二氯苯基)- n-[2-(对甲苯基)苯并三唑-5-基]呋喃-2-羧酰胺。
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引用次数: 19
Management of Diabetes Associated with Nephrotic Syndrome: Therapeutic Potential of Dapagliflozin for Protracted Volume Retention 糖尿病肾病综合征的管理:达格列净治疗持续性容量潴留的潜力
IF 2.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2015-01-01 DOI: 10.4137/DTI.S31710
T. Imai, T. Akimoto, C. Ito, Takahiro Masuda, D. Nagata
A 48-year-old female was admitted to our hospital presenting with a chief complaint of progressive swelling because of diabetic nephrotic syndrome. Dapagliflozin seemed to play a role in accelerating the patient's urinary sodium excretion as well as reducing gross fluid retention despite the fact that her nephrotic condition was resistant to furosemide. Our experience emphasizes a potential novel approach to overcoming loop diuretic resistance using this agent among some subsets of type 2 diabetic subjects complicated with severe volume accumulation. We believe that combination treatment consisting of dapagliflozin and furosemide may produce diuretic synergy via sequential nephron blockade. The accumulation of more experience with additional cases similar to ours requires continuous and careful attention.
一名48岁女性入院,主诉为糖尿病肾病综合征的进行性肿胀。达格列净似乎在加速患者尿钠排泄和减少总液体潴留方面发挥作用,尽管她的肾病对速尿胺有耐药性。我们的经验强调了一种潜在的新方法来克服循环利尿剂抵抗,在一些2型糖尿病患者亚群中使用这种药物并伴有严重的体积积累。我们认为,由达格列净和速尿组成的联合治疗可能通过序贯肾素阻断产生利尿协同作用。在与我们类似的其他案件中积累更多的经验需要持续和仔细的关注。
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引用次数: 12
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