BACKGROUND & AIMS: :This short article describes the results obtained in both internal and external quality assessment of point of care devices (POCD) for the monitoring of blood glucose. The results show that the use of synthetic, serum and whole blood matrices for the samples do not markedly change the inaccuracy of measurement. It is only possible to check precision of POC devices for glucose in external quality assessment (EQA) surveys for POC devices for blood glucose. The majority of devices used in point of care testing for blood glucose had acceptable (im)precision. The applications and limitations of the use of POC devices for blood glucose must be clearly defined before allowing their use in patient care programmes. Finally, the results confirm that the decision of the German Federal Medical Council (Bundesärztekammer) to exclude POC devices from accuracy checks against a reference method procedure in national EQA surveys was correct, at least at the present time.

背景与目标： : 这篇简短的文章介绍了用于监测血糖的点护理设备 (POCD) 的内部和外部质量评估中获得的结果。结果表明，对样品使用合成，血清和全血基质不会显着改变测量的不准确性。只有在血糖POC设备的外部质量评估 (EQA) 调查中，才能检查POC设备的葡萄糖精度。大多数用于血糖检测的设备具有可接受的 (im) 精确度。在允许其用于患者护理计划之前，必须明确定义用于血糖的POC设备的应用和限制。最后，结果证实，至少在目前，德国联邦医学委员会 (bundes ä rztekammer) 决定将POC设备从国家EQA调查中参考方法程序的准确性检查中排除是正确的。

BACKGROUND & AIMS: :Prolonged exposure to inhaled anesthetics may lead to postoperative cognitive dysfunction (POCD). Nevertheless, the underlying mechanisms are not known. Hypoxia-inducible factor-1α (HIF-1α) and its target gene vascular endothelial growth factor (VEGF) were shown to be activated by inhaled anesthetics. The aim of the present study was to determine the role of HIF-1α in isoflurane-induced blood-brain barrier (BBB) disruption and resultant cognitive impairment. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in vascular permeability, and disrupted BBB ultrastructure were accompanied by the degradation of tight junction proteins occludin and collagen type IV in brain blood vessels. Increases in HIF-1α and VEGF proteins and activation of MMP-2 in the hippocampus were also observed in the hippocamp of isoflurane-exposed rats compared with control rats. Pharmacological inhibition of HIF-1α activation by 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) markedly suppressed the expression of HIF-1α, VEGF and MMP-2, and mitigated the severity of BBB disruption.YC-1 pretreatment also significantly attenuated isoflurane-induced cognitive deficits in the Morris water maze task. Overall, our results demonstrate that hippocampal HIF-1α/VEGF signaling seems to be the upstream mechanism of isoflurane-induced cognitive impairment, and provides apotential preventive and therapeutic target for POCD.

背景与目标： : 长期接触吸入麻醉药可能导致术后认知功能障碍 (POCD)。然而，潜在的机制尚不清楚。低氧诱导因子-1α (HIF-1α) 及其靶基因血管内皮生长因子 (VEGF) 被吸入麻醉药激活。本研究的目的是确定HIF-1α 在异氟醚诱导的血脑屏障 (BBB) 破坏和导致的认知障碍中的作用。在20个月大的大鼠中暴露于1.5% 异氟烷4小时后，血管通透性增加和BBB超微结构破坏伴随着脑血管中紧密连接蛋白occludin和IV型胶原的降解。与对照组相比，在异氟醚暴露的大鼠海马中还观察到HIF-1α 和VEGF蛋白的增加以及海马中MMP-2的激活。3-(5 '-hydroxymethyl-2'-呋喃基)-1-苄基利达唑 (YC-1) 对HIF-1α 激活的药理抑制作用可显着抑制HIF-1α，VEGF和MMP-2的表达，并减轻BBB破坏的严重程度。YC-1预处理还可显着减轻异氟烷诱导的莫里斯水迷宫任务中的认知缺陷。总体而言，我们的结果表明，海马HIF-1α/VEGF信号似乎是异氟醚诱导的认知障碍的上游机制，并为POCD提供了潜在的预防和治疗靶点。

BACKGROUND & AIMS: :Arthrofibrosis is a fibrotic joint disorder that begins with an inflammatory reaction to insults such as injury, surgery and infection. Excessive extracellular matrix and adhesions contract pouches, bursae and tendons, cause pain and prevent a normal range of joint motion, with devastating consequences for patient quality of life. Arthrofibrosis affects people of all ages, with published rates varying. The risk factors and best management strategies are largely unknown due to a poor understanding of the pathology and lack of diagnostic biomarkers. However, current research into the pathogenesis of fibrosis in organs now informs the understanding of arthrofibrosis. The process begins when stress signals stimulate immune cells. The resulting cascade of cytokines and mediators drives fibroblasts to differentiate into myofibroblasts, which secrete fibrillar collagens and transforming growth factor-β (TGF-β). Positive feedback networks then dysregulate processes that normally terminate healing processes. We propose two subtypes of arthrofibrosis occur: active arthrofibrosis and residual arthrofibrosis. In the latter the fibrogenic processes have resolved but the joint remains stiff. The best therapeutic approach for each subtype may differ significantly. Treatment typically involves surgery, however, a pharmacological approach to correct dysregulated cell signalling could be more effective. Recent research shows that myofibroblasts are capable of reversing differentiation, and understanding the mechanisms of pathogenesis and resolution will be essential for the development of cell-based treatments. Therapies with significant promise are currently available, with more in development, including those that inhibit TGF-β signalling and epigenetic modifications. This review focuses on pathogenesis of sterile arthrofibrosis and therapeutic treatments.

背景与目标： : 关节纤维化是一种纤维化的关节疾病，始于对损伤，手术和感染等侮辱的炎症反应。过多的细胞外基质和粘连会收缩袋，滑囊和肌腱，引起疼痛并阻止关节运动的正常范围，对患者的生活质量造成毁灭性后果。关节纤维化影响所有年龄段的人，其公布的比率各不相同。由于对病理的了解不足和缺乏诊断生物标志物，因此风险因素和最佳管理策略在很大程度上是未知的。然而，目前对器官纤维化发病机理的研究现在有助于理解关节纤维化。当压力信号刺激免疫细胞时，这个过程就开始了。由此产生的细胞因子和介体级联驱动成纤维细胞分化为肌成纤维细胞，从而分泌原纤维胶原蛋白和转化生长因子-β (TGF-β)。然后，正反馈网络会失调通常终止愈合过程的过程。我们提出发生关节纤维化的两种亚型: 活动性关节纤维化和残余关节纤维化。在后者中，纤维化过程已经解决，但关节仍然僵硬。每种亚型的最佳治疗方法可能存在显着差异。治疗通常涉及手术，但是，纠正失调的细胞信号传导的药理学方法可能更有效。最近的研究表明，肌成纤维细胞能够逆转分化，了解发病机理和解决机制对于开发基于细胞的治疗至关重要。目前，具有重大前景的疗法正在开发中，包括抑制TGF-β 信号传导和表观遗传修饰的疗法。这篇综述着重于无菌关节纤维化的发病机理和治疗方法。

BACKGROUND & AIMS: :Agrobacterium-mediated genetic transformation not only represents a technology of choice to genetically manipulate plants, but it also serves as a model system to study mechanisms employed by invading pathogens to counter the myriad defenses mounted against them by the host cell. Here, we uncover a new layer of plant defenses that is targeted by A. tumefaciens to facilitate infection. We show that the Agrobacterium F-box effector VirF, which is exported into the host cell, recognizes an Arabidopsis transcription factor VFP4 and targets it for proteasomal degradation. We hypothesize that VFP4 resists Agrobacterium infection and that the bacterium utilizes its VirF effector to degrade VFP4 and thereby mitigate the VFP4-based defense. Indeed, loss-of-function mutations in VFP4 resulted in differential expression of numerous biotic stress-response genes, suggesting that one of the functions of VFP4 is to control a spectrum of plant defenses, including those against Agrobacterium tumefaciens. We identified one such gene, ATL31, known to mediate resistance to bacterial pathogens. ATL31 was transcriptionally repressed in VFP4 loss-of-function plants and activated in VFP4 gain-of-function plants. Gain-of-function lines of VFP4 and ATL31 exhibited recalcitrance to Agrobacterium tumorigenicity, suggesting that A. tumefaciens may utilize the host ubiquitin/proteasome system to destabilize transcriptional regulators of the host disease response machinery.

背景与目标： : 农杆菌介导的遗传转化不仅代表了一种遗传操纵植物的选择技术，而且还作为一个模型系统来研究入侵病原体所采用的机制，以对抗宿主细胞对其进行的无数防御。在这里，我们发现了一种新的植物防御层，该防御层是由a.tumefaciens靶向的，以促进感染。我们表明，输出到宿主细胞中的农杆菌F-box效应子病毒可识别拟南芥转录因子VFP4，并将其靶向蛋白酶体降解。我们假设VFP4抵抗农杆菌感染，并且该细菌利用其VirF效应物降解VFP4，从而减轻VFP4-based防御。实际上，VFP4中的功能丧失突变导致许多生物胁迫反应基因的差异表达，这表明VFP4的功能之一是控制一系列植物防御，包括针对根癌农杆菌的防御。我们鉴定了一个这样的基因，ATL31，已知介导对细菌病原体的抗性。ATL31在VFP4功能丧失植物中被转录抑制，在VFP4功能获得植物中被激活。VFP4和ATL31的功能获得系表现出对农杆菌致瘤性的顽抗性，这表明根癌A可能利用宿主泛素/蛋白酶体系统来破坏宿主疾病反应机制的转录调节剂。

BACKGROUND & AIMS: :In 2018, a cluster of pediatric human parechovirus (HPeV) infections in 2 neighboring German hospitals was detected. Viral protein 1 sequence analysis demonstrated co-circulation of different HPeV-3 sublineages and of HPeV-1 and -5 strains, thereby excluding a nosocomial outbreak. Our findings underline the need for HPeV diagnostics and sequence analysis for outbreak investigations.

背景与目标： : 2018年，在德国邻近的2家医院中检测到一群小儿人类parechovirus (HPeV) 感染。病毒蛋白1序列分析证明了不同HPeV-3亚群以及HPeV-1和-5菌株的共循环，从而排除了院内暴发。我们的发现强调了HPeV诊断和序列分析用于暴发调查的必要性。

BACKGROUND & AIMS: :Anthracyclines are anti-neoplastic drugs presenting cardiotoxicity as a side effect. Cardiac troponins (cTn) and echocardiography are currently used to assess cardiac damage and dysfunction, but early biomarkers identifying patients in need of preventive treatments remain a partially met need. Circulating microRNAs (miRNAs) represent good candidates, so we investigated their possible roles as predictors of troponin elevation upon anthracycline treatment. Eighty-eight female breast cancer patients administered with doxorubicin (DOX) or epirubicin (EPI) were divided into four groups basing on drug type and cTn positive (cTn+) or negative (cTn-) levels: DOX cTn-, DOX cTn+, EPI cTn- and EPI cTn+. Blood was collected at baseline, during treatment, and at follow-up. We identified plasma miRNAs of interest by OpenArray screening and single assay validation. Our results showed miR-122-5p, miR-499a-5p and miR-885-5p dysregulation in DOX patients at T0, identifying a signature separating, with good accuracy, DOX cTn- from DOX cTn+. No miRNAs showed differential expression in EPI subjects. Conversely, an anthracycline-mediated modulation (regardless of cTn) was observed for miR-34a-5p, -122-5p and -885-5p. Our study indicates specific circulating miRNAs as possible prediction markers for cardiac troponin perturbation upon anthracycline treatment. Indeed, our findings hint at the possible future use of plasma miRNAs to predict the cardiac responsiveness of patients to different anticancer agents.

背景与目标： : 蒽环类药物是抗肿瘤药物，具有心脏毒性作为副作用。心肌肌钙蛋白 (cTn) 和超声心动图目前用于评估心脏损伤和功能障碍，但早期识别需要预防性治疗的患者的生物标志物仍然是部分满足的需求。循环microrna (mirna) 代表了良好的候选者，因此我们研究了它们作为蒽环类药物治疗后肌钙蛋白升高的预测因子的可能作用。根据药物类型和cTn阳性 (cTn) 或阴性 (cTn-) 水平将88例接受阿霉素 (DOX) 或表柔比星 (EPI) 的女性乳腺癌患者分为四组: DOX cTn-，DOX cTn，EPI cTn-和EPI cTn。在基线，治疗期间和随访时收集血液。我们通过开放阵列筛选和单分析验证鉴定了目标血浆miRNAs。我们的结果显示，在T0时，DOX患者的miR-122-5p，miR-499a-5p和miR-885-5p失调，从而确定了将DOX cTn-与DOX cTn分离的准确性良好的特征。在EPI受试者中没有mirna显示差异表达。相反，对于miR-34a-5p，-122-5p和-885-5p观察到蒽环类药物介导的调节 (与cTn无关)。我们的研究表明，特定的循环mirna可能是蒽环类药物治疗后心肌肌钙蛋白扰动的预测标志物。实际上，我们的发现暗示了将来可能使用血浆mirna来预测患者对不同抗癌药物的心脏反应性。

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BACKGROUND & AIMS: :The original version of this article unfortunately contained a mistake. The given names and family names of all authors were interchanged.

背景与目标： : 这篇文章的原始版本不幸地包含了一个错误。所有作者的给定姓名和姓氏均已互换。

BACKGROUND & AIMS: INTRODUCTION:Post-operative cognitive dysfunction (POCD) is frequent in patients older than 60 years undergoing major non-cardiac surgery, and increases both morbidity and mortality. Anesthetic drugs may exert neurotoxic effects and contribute to the genesis of POCD. The hypothesis of the POCD-ELA trial was that closed-loop target-controlled infusion of propofol and remifentanil could reduce the occurrence of POCD by decreasing the risk of excessive depth of anesthesia and the dose of anesthetic drugs. METHODS AND ANALYSIS:We designed a single-center, single-blind, randomized, controlled, parallel trial and aim to include 204 patients aged >60 years undergoing elective major non-cardiac surgery. Patients will be randomized to receive closed-loop versus manual target-controlled infusion of propofol and remifentanil guided by bispectral index monitoring. Cognitive assessment will be performed the day before surgery (baseline) and within 72 hours after surgery, using a battery of validated neuropsychological tests. The primary outcome is the incidence of POCD within 72 hours after surgery. POCD is defined as a Z-score value > 1.96 for at least 2 different tests or a Z-score composite value >1.96. The calculation of the Z-score is based on data from an age-matched control population who did not undergo surgery or general anesthesia. ETHICS AND DISSEMINATION:This study was approved by the Ethics Committee (Comité de Protection des Personnes Est-II) and authorized by the French Health Products Agency (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses. REGISTRATION:The trial is registered with ClinicalTrials.gov (Identifier: NCT02841423, principal investigator: Prof Emmanuel Samain, date of registration: July 22, 2016). Last amendment of protocol: version 8.0 April 2018.

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BACKGROUND & AIMS: BACKGROUND:There are a variety of techniques to handle missing data, such as removing observations with missing data from the analyses or estimating the missing values using various imputation algorithms. Dropping subjects from standard regression models and analyzing only completers, however, may bias results from the true value of reality. Likewise, 'last-observation-carried-forward' may not be an appropriate technique for studies measuring a particular variable over time. METHODS:This dataset was part of a larger prospective cohort study that examined postoperative cognitive decline (POCD) after surgery in older adults. Data collectors had provided the reasons for data being missing using adjectives including 'confused', 'incapable', 'stuporous', 'comatose', and 'intubated'. Data having these qualitative notations were re-coded as 'incapable' and trial scores of zero were recorded. This value of '0' indicated that the patient was cognitively incapable of performing the neuropsychological test. RESULTS:Missing data varied by cognitive test and postoperative day. Re-coding word list scores from missing to zero when a patient was too cognitively impaired to complete the tests improved sample size by 13.5% of postoperative day (POD) 1 and 12.8% on POD 2. Recoding missing data to zero for the digit symbol test resulted in 29.3% larger sample size on POD 1 and 22.7% on POD 2. Verbal fluency gained 15.7% sample size with re-coding for POD 1 and 13.7% for POD 2. Re-coding of each cognitive test reduced missing data sample size to 20-32% in all cognitive tests for each day. DISCUSSION:Our data suggest that using a scoring system that enters a value of '0' when patients are unable to perform cognitive testing did significantly increase the number of patients that met the diagnosis of postoperative cognitive decline using the criteria that were determined a priori and may lessen chances of type II error (failure to detect a difference).

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BACKGROUND & AIMS: Objectives:Clinical observation, as well as randomized controlled trials, indicated an increasing rate of postoperative cognitive dysfunction (POCD) with increasing depth of general anesthesia. However, the findings are subject to bias due to varying degree of analgesia. In this trial, we compared the rate of POCD between patients receiving light versus high anesthesia while holding analgesia comparable using nerve block. Methods:Elderly patients (≧60 years) receiving elective total knee replacement were randomized to receive the surgery under general anesthesia at BIS 40-50 (LOBIS group) or BIS 55-65 (HIBIS group). The femoral nerve and the sciatic nerve were blocked under ultrasonic guidance in all patients before induction. Cognitive performance was assessed with Montreal cognitive assessment (MoCA) at the baseline and 1d, 3d, and 7d after the surgery. POCD was defined by Z score of >1.96 using cross-reference. The extubation time and recovery time were also compared. Results:A total of 66 patients were randomized; 60 (n = 30 per group) completed trial as the protocol specified. POCD occurred in six patients (20%) in the LOBIS group vs. in one patient (3.3%) in the HIBIS group (Figure 3, p = .04). In all seven cases, the diagnosis of POCD was based on MoCA assessment on 1d after the surgery. Assessment in 3d and 7d after surgery did not reveal POCD in any case. Extubation time was longer in the LOBIS group (12.16 ± 2.58 vs. 5.77 ± 3.01 min in the HIBIS group (p < .001)). The time of comeback of directional ability was 13.47 ± 3.14 and 6.17 ± 3.23 min in the LOBIS and HIBIS groups, respectively (p < .001). Conclusions:In elderly patients receiving a total knee replacement, lighter anesthesia could reduce the rate of POCD with complete analgesia during surgery.

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