HCP

HCP
  • 文章类型: Journal Article
    抗肥胖药物(AOM)可能为肥胖管理提供可行的选择。然而,对SCI/D患者使用AOM的情况知之甚少。
    描述医疗保健提供者(HCP)对SCI/D患者使用AOM的障碍的看法。
    使用深度访谈进行描述性定性设计使用描述性统计数据来计算人口统计学和就业特征。访谈是录音和逐字转录的。使用Braun和Clarke\(2006)的六个主题分析阶段对成绩单进行了编码和分析。
    HCP(n=12)来自11个不同的全国性设施。大多数HCP是男性(75%),绝大多数是白人(67%),大多数年龄在26-49岁之间。参与者是营养师(75%),医生(17%),心理学家(8%)。HCP提供SCI/D护理的时间为1.5至15年。HCP描述了SCI/D患者使用AOM的四个主要主题障碍:(1)SCI/D患者特别关注的AOM副作用;(2)AOM导致不良的饮食习惯;(3)可用性,可访问性,和管理;(4)缺乏证据,临床协议,以及有关SCI/D人群中AOM使用的知识。
    在SCI/D人群中使用AOM存在若干潜在障碍。障碍包括可能导致或加剧SCI/D患者已经关注的疾病的AOM副作用,比如肠道和皮肤问题,肌肉损失。SCI/DHCP报告缺乏关于SCI/D患者使用AOM的证据,而是对获得更多知识的兴趣。
    UNASSIGNED: Anti-obesity medications (AOMs) may provide a viable option for obesity management. However, little is known about the use of AOMs in persons with SCI/D.
    UNASSIGNED: Describe health care providers\' (HCPs) views about barriers to AOM use in persons living with SCI/D.
    UNASSIGNED: Descriptive qualitative design using in-depth interviews Descriptive statistics were used to calculate demographic and employment characteristics. Interviews were audio-recorded and transcribed verbatim. Transcripts were coded and analyzed using Braun and Clarke\'s (2006) six thematic analysis phases.
    UNASSIGNED: HCPs (n = 12) were from 11 different nationwide facilities. Most HCPs were male (75%), a large majority were white (67%), and most were 26-49 years of age. Participants were dietitians (75%), physicians (17%), and psychologists (8%). HCPs ranged from 1.5 to 15 years of providing SCI/D care. HCPs described four main thematic barriers to AOM use in persons with SCI/D: (1) AOM side effects that are especially concerning in persons with SCI/D; (2) AOMs contribute to poor eating habits; (3) availability, accessibility, and administration; and (4) lack of evidence, clinical agreement, and knowledge about AOM use in the SCI/D population.
    UNASSIGNED: There are several potential barriers to AOM use in the SCI/D population. Barriers include AOM side effects which may cause or exacerbate conditions that are already concerns in persons with SCI/D, such as bowel and skin problems, and muscle loss. SCI/D HCPs reported a lack of evidence about AOM use in persons with SCI/D, but interest in obtaining more knowledge.
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  • 文章类型: Journal Article
    霍乱弧菌(V.霍乱),霍乱的病原体,利用各种毒力因子在水生和人类宿主环境中适应和茁壮成长。在这些因素中,VI型分泌系统(T6SS)是其致病性的关键决定因素之一。缬氨酸甘氨酸重复蛋白G1(VgrG1)和溶血素共调蛋白(HCP)被认为是T6SS的主要效应分子。先前的研究已经强调VgrG1与HCP蛋白相互作用。此外,已经显示VgrG1具有具有肌动蛋白结合活性的肌动蛋白交联结构域(ACD)。有趣的是,据报道,纯化的HCP蛋白处理增加了细胞内的应激纤维。因此,我们假设HCP可能与宿主细胞肌动蛋白相互作用,在霍乱弧菌感染期间可能在细胞骨架重排中起作用。为了检验这个假设,我们表征了霍乱弧菌O139血清型的HCP,并证明了其与肌动蛋白单体的相互作用。计算机模拟分析和实验验证揭示了HCP内肌动蛋白结合位点的存在。此外,HCP的过表达导致其与宿主细胞中的肌动蛋白应激纤维共定位。我们的发现确立了HCP作为霍乱弧菌感染期间有效宿主细胞肌动蛋白细胞骨架重塑的效应分子,为细菌致病机制提供新的见解。了解细菌效应子和宿主细胞成分之间的相互作用对于开发针对霍乱和相关传染病的靶向治疗干预措施至关重要。
    Vibrio cholerae (V. cholerae), the etiological agent of cholera, employs various virulence factors to adapt and thrive within both aquatic and human host environments. Among these factors, the type VI secretion system (T6SS) stands out as one of the crucial determinants of its pathogenicity. Valine glycine repeat protein G1 (VgrG1) and hemolysin coregulated protein (HCP) are considered major effector molecules of T6SS. Previous studies have highlighted that VgrG1 interacts with HCP proteins. Additionally, it has been shown that VgrG1 possesses an actin cross-linking domain (ACD) with actin-binding activity. Interestingly, it was reported that purified HCP protein treatment increased the stress fibers within cells. Therefore, we hypothesize that HCP may interact with host cell actin, potentially playing a role in the cytoskeletal rearrangement during V. cholerae infection. To test this hypothesis, we characterized HCP from the V. cholerae O139 serotype and demonstrated its interaction with actin monomers. In silico analysis and experimental validation revealed the presence of an actin-binding site within HCP. Furthermore, overexpression of HCP resulted in its colocalization with actin stress fibers in host cells. Our findings establish HCP as an effector molecule for potent host cell actin cytoskeleton remodeling during V. cholerae infection, providing new insights into bacterial pathogenicity mechanisms. Understanding the interplay between bacterial effectors and host cell components is crucial for developing targeted therapeutic interventions against cholera and related infectious diseases.
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  • 文章类型: Systematic Review
    背景:作为药物警戒活动的一部分,医疗保健专业人员在报告药物不良反应中起着至关重要的作用。然而,医疗保健专业人员报告的药物不良反应仍然很低。
    目的:本系统评价的目的是调查医疗保健专业人员的知识,意识,态度,药物警戒和药物不良反应报告的实践,探索漏报问题的原因,并提供改进策略。
    方法:本系统综述使用四个电子数据库进行原始论文,包括PubMed,Scopus,谷歌学者,学者ID。选择了2012年1月1日至2022年12月31日的最新出版物。搜索中使用了以下术语:“意识”,\"知识\",“药物不良反应”,“药物警戒”,“医疗保健专业人员”,和“漏报因素”。文章被选中,提取,并由两位作者审查。
    结果:选择了25项研究进行系统评价。这篇综述发现,24.8%-73.33%的医疗保健专业人员不知道国家药物警戒中心。大约20%-95.7%的医疗保健专业人员对药物警戒和药物不良反应报告持积极态度。12%-60.8%的医疗保健专业人员在其实践中有报告任何药物不良反应的经验。最常见的药物警戒障碍是缺乏对什么的认识和知识,when,向谁报告。
    结论:由于缺乏药物警戒和药物不良反应报告的认识和知识,因此需要医疗保健专业人员立即关注漏报问题。大多数研究都建议采取教育和培训计划干预措施来解决这些问题。
    BACKGROUND: Healthcare professionals play an essential role in reporting adverse drug reactions as part of pharmacovigilance activities. However, adverse drug reactions reported by healthcare professionals remain low.
    OBJECTIVE: The aim of this systematic review was to investigate healthcare professionals\' knowledge, awareness, attitude, and practice on pharmacovigilance and adverse drug reaction reporting, explore the causes of the underreporting issue, and provide improvement strategies.
    METHODS: This systematic review was conducted using four electronic databases for original papers, including PubMed, Scopus, Google Scholar, and Scholar ID. Recent publications from 1st January 2012 to 31st December 2022 were selected. The following terms were used in the search: \"awareness\", \"knowledge\", \"adverse drug reaction\", \"pharmacovigilance\", \"healthcare professional\", and \"underreporting factor\". Articles were chosen, extracted, and reviewed by the two authors.
    RESULTS: Twenty-five studies were selected for systematic review. This review found that 24.8%-73.33% of healthcare professionals were unaware of the National Pharmacovigilance Center. Around 20%-95.7% of healthcare professionals have a positive attitude toward pharmacovigilance and adverse drug reaction reporting, while 12%-60.8% of healthcare professionals have experience reporting any adverse drug reaction in their practice. The most frequently highlighted barriers to pharmacovigilance were a lack of awareness and knowledge regarding what, when, and to whom to report.
    CONCLUSIONS: Underreporting issues require immediate attention among healthcare professionals due to a lack of awareness and knowledge of pharmacovigilance and adverse drug reaction reporting. Educational and training program interventions have been suggested by most studies to address these issues.
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  • 文章类型: Journal Article
    背景:使用人工智能(AI)进行疼痛评估有可能解决婴儿疼痛评估中的历史挑战。从卫生保健专业人员(HCP)和父母的角度来看,在新生儿重症监护病房(NICU)中实施AI进行新生儿疼痛监测的益处和障碍的信息缺乏。这种定性分析提供了从加拿大和英国的2家大型三级保健医院获得的新数据。
    目的:本研究的目的是探讨HCPs和父母在NICU中使用AI进行疼痛评估方面的观点。
    方法:总共,招募了20名HCP和20名早产儿父母,并同意从2020年2月至2022年10月参加访谈,询问在NICU中使用AI进行疼痛评估。该技术的潜在好处,和使用的潜在障碍。
    结果:40名参与者包括20名HCP(17名女性和3名男性),在NICU平均有19.4(SD10.69)年的经验,以及20名父母(平均年龄34.4,SD5.42岁)平均43天(SD30.34)的早产儿。从HCPs的角度确定了六个主题:在NICU中定期使用技术,关于人工智能集成的担忧,改善病人护理的潜力,实施要求,AI作为疼痛评估的工具,和道德考虑。七个家长主题包括改善护理的潜力,增加父母的痛苦,对父母关于人工智能的支持,对父母参与的影响,人类关怀的重要性,集成的要求,以及对其使用选择的渴望。一个一致的主题是人工智能作为一种为临床决策提供信息而不是取代它的工具的重要性。
    结论:HCP和父母对NICU中AI用于疼痛评估的潜在用途普遍表示积极态度。与HCP强调重要的道德考虑。这项研究确定了关键利益相关者的关键方法和道德观点,任何考虑在NICU中创建和实施AI进行疼痛监测的团队都应注意到这一点。
    BACKGROUND: The use of artificial intelligence (AI) for pain assessment has the potential to address historical challenges in infant pain assessment. There is a dearth of information on the perceived benefits and barriers to the implementation of AI for neonatal pain monitoring in the neonatal intensive care unit (NICU) from the perspective of health care professionals (HCPs) and parents. This qualitative analysis provides novel data obtained from 2 large tertiary care hospitals in Canada and the United Kingdom.
    OBJECTIVE: The aim of the study is to explore the perspectives of HCPs and parents regarding the use of AI for pain assessment in the NICU.
    METHODS: In total, 20 HCPs and 20 parents of preterm infants were recruited and consented to participate from February 2020 to October 2022 in interviews asking about AI use for pain assessment in the NICU, potential benefits of the technology, and potential barriers to use.
    RESULTS: The 40 participants included 20 HCPs (17 women and 3 men) with an average of 19.4 (SD 10.69) years of experience in the NICU and 20 parents (mean age 34.4, SD 5.42 years) of preterm infants who were on average 43 (SD 30.34) days old. Six themes from the perspective of HCPs were identified: regular use of technology in the NICU, concerns with regard to AI integration, the potential to improve patient care, requirements for implementation, AI as a tool for pain assessment, and ethical considerations. Seven parent themes included the potential for improved care, increased parental distress, support for parents regarding AI, the impact on parent engagement, the importance of human care, requirements for integration, and the desire for choice in its use. A consistent theme was the importance of AI as a tool to inform clinical decision-making and not replace it.
    CONCLUSIONS: HCPs and parents expressed generally positive sentiments about the potential use of AI for pain assessment in the NICU, with HCPs highlighting important ethical considerations. This study identifies critical methodological and ethical perspectives from key stakeholders that should be noted by any team considering the creation and implementation of AI for pain monitoring in the NICU.
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  • 文章类型: Preprint
    皮层网络的警惕性和兴奋性对大脑动力学产生了广泛的影响,唤醒涌动可以迅速改变。我们先前报道了基于3TMR静息状态脑图像的脑觉醒上升网络(AAN)和丘脑核中自发眨眼与BOLD激活之间的关联。在这里,我们旨在使用7TMR图像在从HumanConnectomeProject(HCP)收集的更大的参与者队列中复制我们的分析。其中还包含同时的眼球追踪记录,并评估眨眼相关的觉醒和警觉状态之间的相互作用。为此,我们比较了警觉和昏昏欲睡状态下眨眼相关的BOLD活动,根据fMRI扫描期间获得的瞳孔数据进行分类。我们进行了两个主要分析:i)BOLD信号和眨眼事件之间的互相关分析(眨眼时间序列与血液动力学响应函数的规范和时间导数进行了卷积,HRF)在预选的兴趣区域(ROI)内(即,脑干AAN,丘脑和小脑核)以及探索性体素分析以评估全脑,和ii)BOLD信号的闪烁事件分析,以揭示预选ROI中的闪烁开始的信号变化。与我们之前在3TMRI上的发现一致,我们在脑干和丘脑核中的BOLD峰之间显示出显著的正相关,这些峰在眨眼时刻之前或与眨眼时刻重叠,并且眨眼后急剧下降.全脑分析显示与眨眼相关的激活在小脑中最强,脑岛,外侧膝状核(LGN)和视觉皮层。困倦影响HRFBOLD(增强它),达到峰值的时间(延迟它)和眨眼后的BOLD活动(强调减少)。昏昏欲睡状态下的反应可能与皮质兴奋性的差异有关,皮质下和小脑组织,这样,参与视觉注意力处理的小脑和丘脑区域对警觉状态反应更灵敏,但是AANROIs,以及连接到前马达的小脑和丘脑ROI,额叶,时间区和DMN区反应较少。与眨眼相关的BOLD信号变化的这种定性和定量差异可以反映出在困倦状态下皮质处理的延迟和唤醒浪涌的无效性。需要进行操纵唤醒的未来研究,以证实唤醒激增与警觉状态和皮质兴奋性之间的机械相互作用。
    The vigilance state and the excitability of cortical networks impose wide-range effects on brain dynamics that arousal surges could promptly modify. We previously reported an association between spontaneous eye-blinks and BOLD activation in the brain arousal ascending network (AAN) and in thalamic nuclei based on 3T MR resting state brain images. Here we aimed to replicate our analyses using 7T MR images in a larger cohort of participants collected from the Human Connectome Project (HCP), which also contained simultaneous eye-tracking recordings, and to assess the interaction between the blink-associated arousal surges and the vigilance states. For this purpose, we compared blink associated BOLD activity under a vigilant versus a drowsy state, a classification made based on the pupillary data obtained during the fMRI scans. We conducted two main analyses: i) Cross-correlation analysis between the BOLD signal and blink events (eye blink time-series were convolved with the canonical and also with the temporal derivative of the Hemodynamic Response Function, HRF) within preselected regions of interests (ROIs) (i.e., brainstem AAN, thalamic and cerebellar nuclei) together with an exploratory voxel-wise analyses to assess the whole-brain, and ii) blink-event analysis of the BOLD signals to reveal the signal changes onset to the blinks in the preselected ROIs. Consistent with our prior findings on 3T MRI, we showed significant positive cross correlations between BOLD peaks in brainstem and thalamic nuclei that preceded or were overlapping with blink moments and that sharply decreased post-blink. Whole brain analysis revealed blink-related activation that was strongest in cerebellum, insula, lateral geniculate nucleus (LGN) and visual cortex. Drowsiness impacted HRF BOLD (enhancing it), time-to-peak (delaying it) and post-blink BOLD activity (accentuating decreases). Responses in the drowsy state could be related to the differences in the excitability of cortical, subcortical and cerebellar tissue, such that cerebellar and thalamic regions involved in visual attention processing were more responsive for the vigilant state, but AAN ROIs, as well as cerebellar and thalamic ROIs connected to pre-motor, frontal, temporal and DMN regions were less responsive. Such qualitative and quantitative differences in the blink related BOLD signal changes could reflect delayed cortical processing and the ineffectiveness of arousal surges during states of drowsiness. Future studies that manipulate arousal are needed to corroborate a mechanistic interaction of arousal surges with vigilance states and cortical excitability.
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  • 文章类型: Journal Article
    阻燃剂可以改善锂电池(LB)的安全性,同时由于寄生反应而牺牲电化学性能。为了同意这一点,我们通过微胶囊技术设计了以脲甲醛(UF)树脂为外壳的六氯膦腈(HCP)添加剂的热响应衣服。HCP@UF通过氢键与聚丙烯腈(PAN)成功结合,形成了PAN-HCP@UF作为阻燃固体聚合物电解质。氢键确保了聚合物电解质的优异的机械性能。多尺度自由基湮灭剂HCP在高温下有效消除电解质的氢自由基,表现出优异的阻燃性。在电池运行期间,UF树脂上的官能团充当促进锂离子迁移的活性位点,同时保护内部HCP免受电化学反应。增加25%的HCP@UF,PAN-HCP@UF的极限氧指数增加到28%,Li转移数增加到0.80。通过UF保护,与PAN-HCP@UF组装的Li||LFP电池在0.5C下循环500次后的初始容量保持率为88.8%。因此,微胶囊包封的方法被认为提供了制备具有稳定长循环寿命的高安全性固态LB的创新策略。
    Flame retardants could improve the safety properties of lithium batteries (LBs) with the sacrifice of electrochemical performance due to parasitic reactions. To concur with this, we designed thermal-response clothes for hexachlorophosphazene (HCP) additives by the microcapsule technique with urea-formaldehyde (UF) resin as the shell. HCP@UF combines with polyacrylonitrile (PAN) by hydrogen bonds successfully to form PAN-HCP@UF as the flame-retardant solid polymer electrolyte. The hydrogen bonds ensure excellent mechanical properties of the polymer electrolyte. The multiscale free radical-annihilating agent HCP effectively eliminates hydrogen free radicals of electrolytes under high temperature, showing excellent flame retardation. During the operation of the battery, functional groups on the UF resin act as active sites to promote the migration of lithium ions, while the internal HCP is protected from electrochemical reaction. With 25% HCP@UF addition, the limiting oxygen index of the PAN-HCP@UF increases to 28% and the Li+ transfer number up to 0.80. By UF protection, the initial capacity retention rate of the Li||LFP battery that assembles with PAN-HCP@UF is 88.8% after 500 cycles at 0.5 C. Thus, the microcapsule-encapsulated approach is deemed to provide an innovative strategy to prepare high-safety solid-state LB with a stable long cycle life.
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  • 文章类型: Journal Article
    自1970年代以来,营养在囊性纤维化(pwCF)患者的管理和结果中发挥了核心作用。近几十年来,治疗和实践的进步导致患者景观发生了重大变化,预期寿命显着提高。以及生活质量,带来新的问题。历史上,囊性纤维化是一种与儿童和营养不良有关的疾病;然而,患者人口统计学的变化,营养评估和基本营养管理已经发展,它已经成为一种越来越普遍的成人疾病,面临着新的营养挑战,包括肥胖.本文旨在描述这些变化以及它们为该领域的工作人员带来的影响和挑战。营养专业人员需要进化,适应并保持敏捷适应新一代pwCF所需的更广泛的情况和支持。将继续需要专门的营养支持,此外,改善和优化生活质量和长期健康也很重要。
    Nutrition has played a central role in the management and outcomes of people with cystic fibrosis (pwCF) since the 1970s. Advances in therapies and practices in recent decades have led to a significant change in the patient landscape with dramatic improvements in life expectancy, as well as quality of life, bringing with it new issues. Historically, cystic fibrosis was a condition associated with childhood and malnutrition; however, changes in patient demographics, nutritional assessment and fundamental nutritional management have evolved, and it has become an increasingly prevalent adult disease with new nutritional challenges, including obesity. This paper aims to describe these changes and the impact and challenges they bring for those working in this field. Nutritional professionals will need to evolve, adapt and remain agile to the wider range of situations and support required for a new generation of pwCF. Specialised nutrition support will continue to be required, and it will be additionally important to improve and optimise quality of life and long-term health.
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  • 文章类型: Journal Article
    大脑功能不是从孤立的活动中出现的,而是来自形成称为连接体的网络的神经元素之间的相互作用和交换。人类连接体由结构和功能方面组成。结构连接体(SC)代表解剖连接,功能性连接体代表了从这种结构排列中产生的动力学。因为有不同的加权方式这些连接,重要的是要考虑这些不同的方法如何影响研究结论。这里,我们认为不同的加权连接体会导致不同的网络属性,虽然两者都不优越,选择可能会影响不同研究案例中的解释和结论。我们提出了三种不同的加权模型,即,流线数(NOS),分数各向异性(FA),和轴突直径分布(ADD),来证明这些差异。后来,使用最近发布的AxSI方法提取,并首先与常用的加权方法进行比较。此外,我们探索每个加权SC的功能相关性,使用HumanConnectomeProject(HCP)数据库。通过分析与情报相关的数据,我们基于图形属性和美国国立卫生研究院(NIH)工具箱开发了认知表现的预测模型。结果表明,ADDSC,结合功能子网模型,在估计认知表现方面优于其他模型。
    Brain function does not emerge from isolated activity, but rather from the interactions and exchanges between neural elements that form a network known as the connectome. The human connectome consists of structural and functional aspects. The structural connectome (SC) represents the anatomical connections, and the functional connectome represents the resulting dynamics that emerge from this arrangement of structures. As there are different ways of weighting these connections, it is important to consider how such different approaches impact study conclusions. Here, we propose that different weighted connectomes result in varied network properties, and while neither superior the other, selection might affect interpretation and conclusions in different study cases. We present three different weighting models, namely, number of streamlines (NOS), fractional anisotropy (FA), and axon diameter distribution (ADD), to demonstrate these differences. The later, is extracted using recently published AxSI method and is first compared to commonly used weighting methods. Moreover, we explore the functional relevance of each weighted SC, using the Human Connectome Project (HCP) database. By analyzing intelligence-related data, we develop a predictive model for cognitive performance based on graph properties and the National Institutes of Health (NIH) toolbox. Results demonstrate that the ADD SC, combined with a functional subnetwork model, outperforms other models in estimating cognitive performance.
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    文章类型: Journal Article
    斑块型银屑病是一种慢性、炎症,免疫介导的皮肤病。生物治疗可显着改善中度至重度斑块型银屑病患者的皮肤病严重程度和健康相关生活质量。在美国批准的用于中度至重度斑块状银屑病的生物制剂中,除两种外,其他所有生物制剂均可由成年患者通过皮下注射自行施用。这篇综述讨论了为斑块状银屑病患者选择医疗保健提供者(HCP)给药而不是自我给药生物制剂的理由。包括治疗依从性,患者偏好,和实际考虑。
    搜索PubMed的“牛皮癣和生物学和管理和(办公室或提供者或专业)”。“从参考文献中确定的最相关的结果和其他论文都包含在审查中。
    尽管许多患者更喜欢自我给药,其他人可能受益于HCP管理。在HCP与HCP之间进行选择时的关键考虑因素用于斑块状银屑病治疗的生物制剂的自我给药包括依从性,患者偏好,和实际问题。讨论了可能使HCP给予治疗斑块状银屑病的生物疗法优于在家自我给药的患者特征。
    关于HCP给予生物制剂治疗牛皮癣的特异性研究很少。
    在选定的斑块状银屑病患者中,与自我给药相比,HCP给予生物制剂可以改善治疗依从性和临床结果。
    UNASSIGNED: Plaque psoriasis is a chronic, inflammatory, immune-mediated skin disease. Biologic therapies markedly improve skin disease severity and health-related quality of life for patients with moderate-to-severe plaque psoriasis. All but two of the biologics approved in the United States for moderate-to-severe plaque psoriasis may be self-administered by adult patients via subcutaneous injection. This review discusses rationales for choosing healthcare provider (HCP) administration over self-administration of biologics for patients with plaque psoriasis, including treatment adherence, patient preference, and practical considerations.
    UNASSIGNED: PubMed was searched for \"psoriasisAND biologic AND administration AND (office OR provider OR profession).\" The most relevant results and additional papers identified from the references were included in the review.
    UNASSIGNED: Although many patients prefer self-administration, others may benefit from HCP administration. Key considerations in the choice between HCP vs. self-administration of biologics for plaque psoriasis treatment include adherence, patient preferences, and practical concerns. Patient characteristics that may make HCP administration of biologic therapies for treatment of plaque psoriasis preferable to at-home self-administration are discussed.
    UNASSIGNED: There are few published studies specific to HCP administration of biologics for treatment of psoriasis.
    UNASSIGNED: Administration of biologics by an HCP may improve treatment adherence and clinical outcomes compared to self-administration in selected patients with plaque psoriasis.
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  • 文章类型: Journal Article
    禽致病性大肠杆菌(APEC)的VI型分泌系统(T6SS)可以通过分泌或注射效应子影响真核细胞的功能。溶血素共调节蛋白(Hcp),T6SS的标志之一,是T6SS的结构蛋白和效应蛋白。根据以前的研究,真核细胞中的线粒体是致病细菌的目标。然而,关于APEC的T6SS效应蛋白Hcp对真核宿主细胞线粒体的调节知之甚少。在我们的研究中,DF-1细胞与Hcp2a蛋白共孵育6小时显示线粒体膜电位降低,Ca2+浓度增加,和增加的细胞活性氧(ROS)水平。因此,我们得出结论,Hcp2a蛋白会导致DF-1细胞线粒体功能障碍。为了解释导致线粒体功能障碍的机制,我们重新分析了DF-1细胞中的Hcp2a相互作用蛋白数据集,和亮氨酸拉链EF手含跨膜蛋白1(LETM1),它与线粒体有关,被筛选。蛋白和分子对接结果显示Hcp2a蛋白与LETM1蛋白有较好的结合性。最后,亚细胞定位结果显示Hcp2a定位于线粒体。总之,Hcp2a效应蛋白导致DF-1细胞线粒体功能障碍,我们假设Hcp2a蛋白与LETM1蛋白的相互作用诱导线粒体功能障碍并促进DF-1细胞中Hcp2a的线粒体定位。
    The type VI secretion system (T6SS) of avian pathogenic Escherichia coli (APEC) can affect the functions of eukaryotic cells by secreting or injecting effectors. Hemolysin co-regulatory protein (Hcp), one of the markers of the T6SS, is both a structural protein and an effector protein of the T6SS. According to previous studies, mitochondria in eukaryotic cells are targeted by pathogenic bacteria. However, little is known about the regulation of mitochondria in eukaryotic host cells by the T6SS effector protein Hcp of APEC. In our study, DF-1 cells co-incubated with Hcp2a protein for 6 h showed decreased mitochondrial membrane potential, increased Ca2+ concentration, and increased cellular reactive oxygen species (ROS) levels. We therefore conclude that Hcp2a protein causes dysfunction to mitochondria in DF-1 cells. To explain the mechanism that causes mitochondrial dysfunction, we reanalyzed the Hcp2a interaction protein dataset in DF-1 cells, and the Leucine zipper EF-hand-containing transmembrane protein 1 (LETM1), which is associated with mitochondria, was screened. The protein and molecular docking results showed that Hcp2a protein and LETM1 protein have better binding. Finally, subcellular localization results showed that Hcp2a was localized to mitochondria. In summary, Hcp2a effector proteins caused dysfunction to DF-1 cellular mitochondria, and we hypothesize that the interaction of Hcp2a protein with LETM1 protein induces mitochondrial dysfunction and promotes mitochondrial localization of Hcp2a in DF-1 cells.
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