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Antiangiogenic agent as a novel treatment for pediatric intracranial arteriovenous malformations: case report. 抗血管生成剂作为小儿颅内动静脉畸形的新型治疗方法:病例报告。
IF 2.1 Pub Date : 2019-10-04 Print Date: 2019-12-01 DOI: 10.3171/2019.7.PEDS1976
Ken Maynard, Melissa LoPresti, Ionela Iacobas, Peter Kan, Sandi Lam

Intracerebral arteriovenous malformations (AVMs) are high-flow collections of abnormal vessels and a common cause of pediatric intracranial hemorrhage. There are few treatment options available for AVMs not amenable to surgical resection, endovascular embolization, radiosurgery, or multimodality treatment. The authors sought to review the molecular and genetic pathways that have been implicated in the formation of AVMs, focusing on the possibility of medically targeting these pathways in the treatment of AVMs. In the novel case presented here, a pediatric patient who was diagnosed with an intracranial AVM unamenable to conventional treatments underwent alternative treatment with molecular pathway inhibitors.

脑动静脉畸形(AVM)是异常血管的高流量聚集,也是小儿颅内出血的常见原因。对于无法进行手术切除、血管内栓塞、放射外科手术或多模式治疗的动静脉畸形,可供选择的治疗方法很少。作者试图回顾与动静脉畸形形成有关的分子和遗传途径,重点探讨在治疗动静脉畸形时以这些途径为药物靶点的可能性。在本文介绍的新病例中,一名被诊断出患有颅内动静脉畸形的儿童患者接受了分子通路抑制剂的替代治疗。
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引用次数: 0
Phototropism 向光性
Pub Date : 2019-01-01 DOI: 10.1007/978-1-4939-9015-3
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引用次数: 0
Sex differences of human cortical blood flow and energy metabolism. 人体皮质血流和能量代谢的性别差异。
Pub Date : 2017-07-01 Epub Date: 2016-01-01 DOI: 10.1177/0271678X16668536
Joel Aanerud, Per Borghammer, Anders Rodell, Kristjana Y Jónsdottir, Albert Gjedde

Brain energy metabolism is held to reflect energy demanding processes in neuropil related to the density and activity of synapses. There is recent evidence that men have higher density of synapses in temporal cortex than women. One consequence of these differences would be different rates of cortical energy turnover and blood flow in men and women. To test the hypotheses that rates of oxygen consumption (CMRO2) and cerebral blood flow are higher in men than in women in regions of cerebral cortex, and that the differences persist with aging, we used positron emission tomography to determine cerebral blood flow and cerebral metabolic rate of oxygen as functions of age in healthy volunteers of both sexes. Cerebral metabolic rate of oxygen did not change with age for either sex and there were no differences of mean values of cerebral metabolic rate of oxygen between men and women in cerebral cortex. Women had significant decreases of cerebral blood flow as function of age in frontal and parietal lobes. Young women had significantly higher cerebral blood flow than men in frontal and temporal lobes, but these differences had disappeared at age 65. The absent sex difference of cerebral energy turnover suggests that the known differences of synaptic density between the sexes are counteracted by opposite differences of individual synaptic activity.

脑能量代谢被认为反映了神经细胞中与突触密度和活动有关的能量需求过程。最近有证据表明,男性的颞叶皮层突触密度高于女性。这些差异的一个后果就是男性和女性大脑皮层能量转换和血液流动的速率不同。为了验证大脑皮层区域中男性的耗氧量(cro2)和脑血流量高于女性的假设,并且这种差异随着年龄的增长而持续存在,我们使用正电子发射断层扫描来确定男女健康志愿者的脑血流量和脑氧代谢率作为年龄的函数。脑氧代谢率不随年龄变化,男女大脑皮质区脑氧代谢率平均值无差异。女性在额叶和顶叶的脑血流量随年龄明显减少。年轻女性在额叶和颞叶的脑血流量明显高于男性,但这些差异在65岁时消失了。大脑能量转换的性别差异的缺失表明,已知的性别间突触密度的差异被个体突触活动的相反差异所抵消。
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引用次数: 66
Gene polymorphism linked to increased asthma and IBD risk alters gasdermin-B structure, a sulfatide and phosphoinositide binding protein. 与哮喘和 IBD 风险增加有关的基因多态性改变了 gasdermin-B 的结构,这是一种硫化物和磷脂结合蛋白。
Pub Date : 2017-02-14 Epub Date: 2017-02-01 DOI: 10.1073/pnas.1616783114
Kinlin L Chao, Liudmila Kulakova, Osnat Herzberg

The exact function of human gasdermin-B (GSDMB), which regulates differentiation and growth of epithelial cells, is yet to be elucidated. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, GSDMB gene amplification and protein overexpression indicate a poor response to HER2-targeted therapy. Genome-wide association studies revealed a correlation between GSDMB SNPs and an increased susceptibility to Crohn's disease, ulcerative colitis, and asthma. The N- and C-terminal domains of all gasdermins possess lipid-binding and regulatory activities, respectively. Inflammatory caspases cleave gasdermin-D in the interdomain linker but not GSDMB. The cleaved N-terminal domain binds phosphoinositides and cardiolipin, forms membrane-disrupting pores, and executes pyroptosis. We show that both full-length GSDMB and the N-terminal domain bind to nitrocellulose membranes immobilized with phosphoinositides or sulfatide, but not with cardiolipin. In addition, the GSDMB N-terminal domain binds liposomes containing sulfatide. The crystal structure of the GSDMB C-terminal domain reveals the structural impact of the amino acids encoded by SNPs that are linked to asthma and inflammatory bowel disease (IBD). A loop that carries the polymorphism amino acids corresponding to healthy individuals (Gly299:Pro306) exhibits high conformational flexibility, whereas the loop carrying amino acids found in individuals with increased disease risk (Arg299:Ser306) exhibits a well-defined conformation and higher positive surface charge. Apoptotic executioner caspase-3, -6, and -7, but not the inflammatory caspases, cleave GSDMB at 88DNVD91 within the N-terminal domain. Selective sulfatide binding may indicate possible function for GSDMB in the cellular sulfatide transport.

人gasdermin-B(GSDMB)调节上皮细胞的分化和生长,其确切功能尚待阐明。在人类表皮生长因子受体 2(HER2)阳性乳腺癌中,GSDMB 基因扩增和蛋白过表达表明对 HER2 靶向治疗的反应不佳。全基因组关联研究显示,GSDMB SNPs 与克罗恩病、溃疡性结肠炎和哮喘的易感性增加有关。所有 gasdermins 的 N 端和 C 端结构域分别具有脂质结合活性和调节活性。炎症性 caspases 可裂解 gasdermin-D 的结构域间连接器,但不能裂解 GSDMB。被裂解的 N 端结构域可结合磷脂和心磷脂,形成膜破坏孔,并执行热昏迷。我们的研究表明,全长 GSDMB 和 N 端结构域都能与固定了磷脂或硫酸盐的硝酸纤维素膜结合,但不能与心磷脂结合。此外,GSDMB N 端结构域还能与含有硫化物的脂质体结合。GSDMB C 端结构域的晶体结构揭示了与哮喘和炎症性肠病(IBD)有关的 SNP 编码的氨基酸对结构的影响。携带与健康个体相对应的多态性氨基酸(Gly299:Pro306)的环路表现出高度的构象灵活性,而携带在疾病风险增加的个体中发现的氨基酸(Arg299:Ser306)的环路则表现出明确的构象和较高的正表面电荷。凋亡刽子手 caspase-3、-6 和 -7(而非炎症性 caspases)会在 N 端结构域的 88DNVD91 处裂解 GSDMB。选择性硫化物结合可能表明 GSDMB 在细胞硫化物转运中可能具有功能。
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引用次数: 0
Pharmacokinetics of calycopterin and xanthmicrol, two polymethoxylated hydroxyflavones with anti-angiogenic activities from Dracocephalum kotschyi Bioss. 具有抗血管生成活性的两种多甲氧基羟基黄酮--钙鞘氨醇和黄曲霉毒素的药代动力学
IF 3.6 Pub Date : 2016-10-04 DOI: 10.1186/s40199-016-0161-x
Seyedeh-Somayeh Zamani, Mohsen Hossieni, Mahmoud Etebari, Pirooz Salehian, Soltan Ahmad Ebrahimi

Background: Recently flavonoids have attracted the attention of researchers in the fight against cancer. Calycopterin and xanthomicrol, are two polymethoxylated flavonoids found in the aerial parts of Dracocephalum kotschyi Bioss.. We have recently shown that these compounds possess antiangiogenic activity and may be of value as potential anticancer agents. In order to demonstrate putative in vivo antitumor effect of these compounds we needed preliminary information on both pharmacokinetics and toxicological properties of these two agents.

Method: A new online SPE HPLC method for measurement of calycopterin and xanthomicrol in rat plasma was developed. Pharmacokinetic parameters of calycopterin and xanthomicrol, after i.v. administration in rats, were determined.

Results: The plasma half-life for both agents was around 4 h, however, the volume of distribution of calycopterin appeared to be about 8 times greater than xanthomicrol. This was probably due the greater hydrophobicity of the former which had other consequences such as much smaller maximum plasma concentration of calycopterin compared to its less methoxylated congener. Preliminary toxicological study of xanthomicrol failed to show any behavioral, histological and biochemical adverse effects after repeated administrations of high doses. Pharmacokinetics of xanthomicrol in rats.

背景:最近,黄酮类化合物在抗癌方面引起了研究人员的关注。萼片蝶呤(Calycopterin)和黄腐霉醇(xanthomicrol)是在Dracocephalum kotschyi Bioss.的气生部分中发现的两种多甲氧基黄酮类化合物。我们最近研究发现,这两种化合物具有抗血管生成活性,可作为潜在的抗癌药物。为了证明这些化合物的体内抗肿瘤作用,我们需要这两种药物的药代动力学和毒理学特性的初步信息:方法:开发了一种新的在线 SPE HPLC 方法,用于测定大鼠血浆中的钙蝶呤和黄腐霉醇。测定了大鼠静脉注射钙蝶呤和黄腐霉醇后的药代动力学参数:结果:两种药剂的血浆半衰期都在4小时左右,但钙蝶呤的分布容积似乎比黄霉素大8倍。这可能是由于前者的疏水性更强,而疏水性强还会产生其他后果,如与甲氧基化程度较低的同系物相比,钙蝶呤的最大血浆浓度要小得多。对黄腐霉醇的初步毒理学研究显示,在重复施用高剂量后,黄腐霉醇未对行为、组织学和生化产生任何不良影响。黄腐霉醇在大鼠体内的药代动力学。
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引用次数: 0
Parity of esteem for mental and physical healthcare in England: a hundred years war? 英格兰精神和身体医疗保健的对等:百年战争?
IF 17.3 Pub Date : 2016-04-01 Epub Date: 2015-11-25 DOI: 10.1177/0141076815616089
Claire Hilton
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引用次数: 0
Cost Analysis of Selected Patient Categories Within A Dermatology Department Using an ABC Approach. 采用 ABC 法对皮肤科选定病人类别进行成本分析。
Pub Date : 2015-11-17 DOI: 10.5539/gjhs.v8n6p234
Šárka Papadaki, Boris Popesko

Background: Present trends in hospital management are facilitating the utilization of more accurate costing methods, which potentially results in superior cost-related information and improved managerial decision-making. However, the Activity-Based Costing method (ABC), which was designed for cost allocation purposes in the 1980s, is not widely used by healthcare organizations. This study analyzes costs related to selected categories of patients, those suffering from psoriasis, varicose ulcers, eczema and other conditions, within a dermatology department at a Czech regional hospital.

Methods: The study was conducted in a hospital department where both inpatient and outpatient care are offered. Firstly, the diseases treated at the department were identified. Further costs were determined for each activity using ABC. The study utilized data from managerial and financial accounting, as well as data obtained through interviews with departmental staff. Using a defined cost-allocation procedure makes it possible to determine the cost of an individual patient with a given disease more accurately than via traditional costing procedures.

Results: The cost analysis focused on the differences between the costs related to individual patients within the selected diagnoses, variations between inpatient and outpatient treatments and the costs of activities performed by the dermatology department. Furthermore, comparing the costs identified through this approach and the revenue stemming from the health insurance system is an option.

Conclusions: Activity-Based Costing is more accurate and relevant than the traditional costing method. The outputs of ABC provide an abundance of additional information for managers. The benefits of this research lie in its practically-tested outputs, resulting from calculating the costs of hospitalization, which could prove invaluable to persons involved in hospital management and decision-making. The study also defines the managerial implications of the performed cost analysis for the hospital management. Based on the analysis results, it is possible to standardize activities and performance appraisal (Benchmarking), and provide all necessary information for hospital budgeting practices, especially Activity-Based Budgeting (ABB).

背景:当前医院管理的趋势是促进使用更精确的成本计算方法,这有可能带来更优越的成本相关信息和更好的管理决策。然而,20 世纪 80 年代为成本分配而设计的活动成本法(ABC)并未被医疗机构广泛使用。本研究分析了捷克一家地区医院皮肤科选定类别患者(银屑病、静脉曲张性溃疡、湿疹和其他疾病患者)的相关成本:研究在一家既提供住院治疗又提供门诊治疗的医院皮肤科进行。首先,确定了在该科室治疗的疾病。然后使用 ABC 法确定每项活动的成本。研究利用了管理和财务会计数据,以及通过与科室员工访谈获得的数据。与传统的成本核算程序相比,使用确定的成本分配程序可以更准确地确定每个特定疾病患者的成本:成本分析的重点是与选定诊断中的个别病人有关的成本差异、住院和门诊治疗之间的差异以及皮肤科开展的活动的成本。此外,还可将通过这种方法确定的成本与来自医疗保险系统的收入进行比较:结论:与传统的成本计算方法相比,以活动为基础的成本计算方法更准确、更实用。活动成本法的产出为管理者提供了大量额外信息。这项研究的益处在于其经过实践检验的成果,即通过计算住院成本得出的结果,这对参与医院管理和决策的人员来说是非常宝贵的。本研究还确定了所进行的成本分析对医院管理层的管理影响。根据分析结果,可以对活动和绩效评估(基准)进行标准化,并为医院预算编制实践,特别是基于活动的预算编制(ABB)提供所有必要的信息。
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引用次数: 0
Soil Moisture 土壤水分
Pub Date : 2014-01-01 DOI: 10.1007/978-0-387-36699-9_173
Y. Kerr
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引用次数: 0
Phototropism 向光性
Pub Date : 2008-01-01 DOI: 10.1007/BF02871651
J. Overbeek
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引用次数: 1
Weeds 杂草
Pub Date : 2007-07-19 DOI: 10.1353/cal.2007.0131
L. Goodison
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引用次数: 0
期刊
Botanical Gazette
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