BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :A major problem in the search for new cancer drug targets is that the drugs are often toxic to normal tissues and require high doses to kill tumor cells. Therefore cellular targets which appear to involve low dose responses to cancer therapy are especially interesting since they could selectively target normal tissues which are not targeted by the treatment and thus may be responsible for unpleasant side effects or may be amenable to exploitation in order to improve the therapeutic ratio. One such target, which is the subject of this review, is radiation-induced bystander effects [RIBE], which result in the observation of radiation like responses in cells which have not been irradiated. RIBE is a novel phenomenon which indicates that at low doses, cell signaling is more important than direct DNA damage. Historically, DNA has always been considered to be the target for radiation therapy. The growing realization that signaling is important opens up several important therapeutic strategies which will be discussed in this review. RIBE appears to be the result of a generalized stress response in tissues or cells which is expressed at the level of the tissue, organ or organism rather than at the level of the individual cell. The signals may be produced by all exposed cells, but the response may require a quorum of cells in order to be expressed. The major response involving low LET (x- or gamma-ray) radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but may be detected in cell lines without p53 expression, although the death response is suppressed in many tumor cell lines. While a death response in unirradiated normal cells around a tumor might appear to be adverse, it can in fact be protective and remove damaged cells from the population. If harnessed correctly, it could lead to the development of new drugs aimed not at tissue destruction but at enabling homeostatic mechanisms to control tumor expansion. In this scenario, the level of harmful or beneficial response will be related to the background damage, carried by the cell population, and the genetic programme determining response to damage. This focus may be important when attempting to predict the consequences of mixed therapies involving radiation and other cytotoxic agents. In this review, our current knowledge of the mechanisms underlying the induction of bystander effects by ionizing radiation is reviewed, and the question of how bystander effects may be harnessed to produce a new generation of anti-cancer drugs aimed at stabilization of tissue homeostasis rather than tissue destruction is considered.

背景与目标： ：寻找新的癌症药物靶标的主要问题是该药物通常对正常组织有毒性，需要高剂量才能杀死肿瘤细胞。因此，细胞靶标似乎涉及对癌症治疗的低剂量反应，因此特别令人感兴趣，因为它们可以选择性地靶向未被治疗靶标的正常组织，因此可能引起令人不快的副作用，或者可能适于利用以改善治疗效果。治疗比率。辐射诱导的旁观者效应[RIBE]是本综述的主题之一，该效应导致在未辐射的细胞中观察到辐射样反应。 RIBE是一种新现象，表明在低剂量时，细胞信号传导比直接DNA损伤更为重要。从历史上看，DNA一直被认为是放射治疗的目标。人们日益认识到信号转导很重要，这开启了几种重要的治疗策略，本文将对此进行讨论。 RIBE似乎是组织或细胞中普遍的应激反应的结果，这种应激反应是在组织，器官或生物体的水平而不是单个细胞的水平表达的。信号可能由所有暴露的细胞产生，但响应可能需要一定数量的细胞才能表达。现有文献中讨论的涉及低LET（X射线或γ射线）辐射暴露的主要反应是死亡反应。这具有许多细胞凋亡特征，但尽管在许多肿瘤细胞系中死亡反应受到抑制，但在没有p53表达的细胞系中可能检测到。虽然在肿瘤周围未照射的正常细胞中的死亡反应似乎是不利的，但实际上可以起到保护作用，并从群体中清除受损的细胞。如果利用得当，它可能会导致开发新药物，其目的不是破坏组织，而是使稳态机制能够控制肿瘤的扩展。在这种情况下，有害或有益反应的水平将与细胞群体所携带的背景损伤以及决定对损伤的反应的遗传程序有关。当试图预测涉及放射线和其他细胞毒剂的混合疗法的后果时，这一重点可能很重要。在这篇综述中，我们对电离辐射诱发旁观者效应的潜在机制的现有知识进行了综述，并探讨了如何利用旁观者效应来生产旨在稳定组织稳态而不是稳定组织的新一代抗癌药物的问题。考虑组织破坏。

BACKGROUND & AIMS: BACKGROUND:Previous studies revealed increased parietal late positive potentials (LPPs) in response to spider pictures in spider phobic individuals. This study searched for basic features of fear-relevant stimuli by investigating whether schematic spider images are sufficient to evoke differential behavioral as well as differential early and late ERP responses in spider phobic, social phobic (as a clinical control group), and non-phobic control participants. METHODS:Behavioral and electrophysiological correlates of the processing of schematic spider and flower images were investigated while participants performed a color (emotional Stroop) and an object identification task. Stimuli were schematic pictures of spiders and flowers matched with respect to constituting visual elements. RESULTS:Consistent with previous studies using photographic spider pictures, spider phobic persons showed enhanced LPPs when identifying schematic spiders compared to schematic flowers. In addition, spider phobic individuals showed generally faster responses than the control groups. This effect was interpreted as evidence for an increased general behavioral hypervigilance in this anxiety disorder group. Furthermore, both phobic groups showed enhanced P100 amplitudes compared to controls, which was interpreted as evidence for an increased (cortical) hypervigilance for incoming stimuli in phobic patients in general. Finally, all groups showed faster identification of and larger N170 amplitudes in response to schematic spider than flower pictures. This may reflect either a general advantage for fear-relevant compared to neutral stimuli, or might be due to a higher level of expertise in processing schematic spiders as compared to the more artificially looking flower stimuli. CONCLUSION:Results suggest that schematic spiders are sufficient to prompt differential responses in spider-fearful and spider-non-fearful persons in late ERP components. Early ERP components, on the other hand, seem to be modified by anxiety status per se, which is consistent with recent theories on general hypervigilance in the anxiety disorder spectrum.

背景与目标： 背景：以前的研究表明，在恐惧蜘蛛的个体中，对蜘蛛图片的顶壁晚期正电位（LPPs）增加。这项研究通过调查示意性蜘蛛图像是否足以引起蜘蛛恐惧症，社交恐惧症（作为临床对照组）和非恐惧症中的差异行为以及差异化的早期和晚期ERP反应，从而寻找与恐惧相关的刺激的基本特征。控制参与者。
方法：在参与者执行颜色（情绪化的Stroop）和对象识别任务的过程中，研究了示意性蜘蛛和花朵图像处理的行为和电生理相关性。刺激是与构成视觉元素相匹配的蜘蛛和花朵的示意图。
结果：与以前使用摄影蜘蛛图片进行的研究一致，与原理图花朵相比，畏惧蜘蛛的人在识别原理图蜘蛛时显示出增强的LPP。另外，蜘蛛恐惧症个体通常显示出比对照组更快的反应。该效应被解释为该焦虑症组中一般行为过度警觉性增加的证据。此外，与对照组相比，两个恐惧组均显示出增强的P100振幅，这可以解释为总体而言，恐惧患者传入刺激的（皮质）超警觉性增加的证据。最后，所有组均显示出对蜘蛛网的响应比花卉图片更快地识别N170振幅，并具有更大的N170振幅。与中性刺激相比，这可能反映与恐惧相关的一般优势，或者可能是由于与较人为看似的花刺激相比，在处理示意性蜘蛛上的专业知识水平更高。
结论：结果表明，原理图蜘蛛足以在ERP后期的恐惧蜘蛛和非恐惧蜘蛛患者中引起差异反应。另一方面，早期的ERP组件似乎已被焦虑状态本身所改变，这与最近关于焦虑症谱系的一般超警觉的理论相一致。

BACKGROUND & AIMS: :The alkenyldiarylmethanes (ADAMs) are a unique class of non-nucleoside reverse transcriptase inhibitors that have potential value in the treatment of HIV/AIDS. However, the potential usefulness of the ADAMs is limited by the presence of metabolically labile methyl ester moieties. A series of novel ADAMs were therefore designed and synthesized in order to replace the metabolically labile methyl ester moieties of the existing ADAM lead compounds with hydrolytically stable, fused isoxazolone, isoxazole, oxazolone, or cyano substituents on the aromatic rings. The methyl ester and methoxy substituents on both of the aromatic rings in the parent compound 1 were successfully replaced with metabolically stable moieties with retention of anti-HIV activity and a general decrease in cytotoxicity.

背景与目标： ：烯基二芳基甲烷（ADAM）是一类独特的非核苷类逆转录酶抑制剂，在治疗HIV / AIDS中具有潜在价值。然而，ADAM的潜在用途受到代谢不稳定的甲基酯部分的存在的限制。因此，设计并合成了一系列新颖的ADAM，以在芳香环上用水解稳定的稠合异恶唑酮，异恶唑，恶唑酮或氰基取代基取代现有ADAM铅化合物的代谢不稳定的甲基部分。母体化合物1的两个芳香环上的甲酯和甲氧基取代基均成功地被代谢稳定的部分所取代，并保留了抗HIV活性并普遍降低了细胞毒性。

BACKGROUND & AIMS: Etoposide produces reversible inhibition of topoisomerase II, leading to cleavage of DNA, and thereby has an antitumor effect. This mechanism suggests that the longer treatment is continued, the greater the antitumor effect will be. In the present study, both therapeutic and adverse effects of long-term treatment with low-dose oral etoposide were studied in 29 patients aged > or = 65 years with non-Hodgkin's lymphoma (NHL) for whom standard chemotherapy was not effective or refractory. These patients received etoposide at a dose of 50 mg/d for as long as possible. Treatment was continued until white blood cell count decreased to < or = 2,000/microL or the platelet count decreased to < or = 5 x 10(4)/microL. According to the World Health Organization (WHO) criteria of therapeutic effects, 6 (20.7%) of the 29 patients achieved complete remission and 13 patients (44.8%) had partial remission, for a response rate of 65.5%. Adverse effects of > or = grade 3 included leukopenia in 24 patients (82.8%) and anemia in 7 (24.1%). Granulocyte colony-stimulating factor (G-CSF) was given in combination with etoposide to eight patients because of leukopenia (granulocyte count < or = 1,000/microL). In view of the excellent subjective tolerance, low incidence of serious adverse effects, and good activity, single agent oral etoposide given continuously over prolonged periods represents a useful treatment for elderly patients with NHL.

背景与目标： 依托泊苷产生对拓扑异构酶II的可逆抑制，导致DNA裂解，因此具有抗肿瘤作用。该机制表明持续的治疗时间越长，抗肿瘤作用越大。在本研究中，对29岁年龄≥65岁的非霍奇金淋巴瘤（NHL）患者进行了长期低剂量口服依托泊苷的治疗，并对其不良反应进行了研究，这些患者对于标准化疗均无效或难治。这些患者尽可能长时间接受依托泊苷50 mg / d的剂量。继续治疗直至白细胞计数降低至<或= 2,000 / microL或血小板计数降低至<或= 5 x 10（4）/ microL。根据世界卫生组织（WHO）的疗效标准，在29例患者中有6例（20.7％）完全缓解，13例（44.8％）部分缓解，缓解率为65.5％。 ≥3级的不良反应包括24例白细胞减少症（82.8％）和7例贫血（24.1％）。由于白细胞减少症（粒细胞计数<或= 1,000 / microL），与依托泊苷联合给予了粒细胞集落刺激因子（G-CSF）与依托泊苷。鉴于出色的主观耐受性，严重不良反应的发生率低和良好的活动性，长时间连续给予单剂口服依托泊苷代表了对老年NHL患者的一种有效治疗方法。

BACKGROUND & AIMS: BACKGROUND:Several case reports have raised serious concerns about the safety of shoulder surgery in the beach-chair position, related to global cerebral hypoperfusion. We summarize our experiences with 15,014 cases of shoulder arthroscopy over an 11-year period. Our primary aim was to evaluate the incidence of intraoperative or immediate postoperative neurologic events and secondarily to relate other perioperative complications. METHODS:We searched our online deidentified departmental quality improvement and patient safety database for adverse outcomes associated with arthroscopic shoulder surgery performed in the beach-chair position for the 11-year period between April 2001 and November 2011, as well as our hospital-system database and a statewide database. This was compared with the total number of such cases, available from our department billing database. RESULTS:The total rate of adverse events was 0.37%. Neurologic abnormalities suggestive of acute cerebral ischemia or hemorrhage did not occur in the immediate perioperative period. One new neurologic deficit was reported, secondary to ischemic stroke, which occurred 24 hours after the surgery. The most frequent complications detected were unplanned return to care (0.067%), local anesthetic systemic toxicity (0.053%), and airway compromise requiring unplanned intubation (0.033%). Complications were infrequent and did not vary in incidence over the course of the study. CONCLUSIONS:This retrospective study suggests that intraoperative or immediate postoperative stroke is rare when surgery is conducted in beach-chair position in conjunction with regional anesthesia, propofol sedation, and spontaneous respiration via natural airway.

背景与目标： 背景：几例病例报告引起了人们对与全脑低灌注相关的沙滩椅位置肩部手术安全性的严重关注。我们总结了我们在11年中共15014例肩关节镜检查的经验。我们的主要目的是评估术中或术后立即发生的神经系统事件的发生率，其次是与其他围手术期并发症相关。
方法：我们在2001年4月至2011年11月的11年期间，通过在线不确定的部门质量改善和患者安全性数据库搜索了在沙滩椅位置进行的关节镜肩部手术相关的不良结局，以及医院系统数据库和全州数据库。将其与此类案件的总数进行了比较，可从我们的部门账单数据库中获得该数目。
结果：不良反应总发生率为0.37％。围手术期未发生提示急性脑缺血或出血的神经系统异常。据报道，缺血性中风继发于术后24小时，出现了一种新的神经功能缺损。发现的最常见并发症是计划外恢复治疗（0.067％），局麻药全身毒性（0.053％）和需要计划外插管的气道损害（0.033％）。在研究过程中，并发症很少见，发生率也没有变化。
结论：这项回顾性研究表明，当在沙滩椅位置进行手术并伴有区域麻醉，异丙酚镇静和通过自然气道自发呼吸时，很少发生术中或术后中风。

BACKGROUND & AIMS: PROBLEM:Nurses are crucial members of the team caring for the acutely injured trauma patient. Until recently, nurses and physicians gained an understanding of leadership and supportive roles separately. With the advent of a multidisciplinary team approach to trauma care, formal team training and simulation has transpired. METHODS:Since 2007, our Level I trauma system has integrated TeamSTEPPS (Team Strategies & Tools to Enhance Performance & Patient Safety; Agency for Healthcare Research and Quality, Rockville, MD) into our clinical care, joint training of nurses and physicians, using simulations with participation of all health care providers. With the increased expectations of a well-orchestrated team and larger number of emergency nurses, our program created the Trauma Nurse Academy. This academy provides a core of experienced nurses with an advanced level of training while decreasing the variability of personnel in the trauma bay. Components of the academy include multidisciplinary didactic education, the Essentials of TeamSTEPPS, and interactive trauma bay learning, to include both equipment and drug use. Once completed, academy graduates participate in the orientation and training of General Surgery and Emergency Medicine residents' trauma bay experience and injury prevention activities. RESULTS:Internal and published data have demonstrated growing evidence linking trauma teamwork training to knowledge and self-confidence in clinical judgment to team performance, patient outcomes, and quality of care. IMPLICATIONS FOR PRACTICE:Although trauma resuscitations are stressful, high risk, dynamic, and a prime environment for error, new methods of teamwork training and collaboration among trauma team members have become essential.

背景与目标： 问题：护士是护理严重受伤的创伤患者的团队的关键成员。直到最近，护士和医师还分别了解领导和支持角色。随着多学科团队创伤治疗方法的问世，正式的团队培训和模拟已经出现。
方法：自2007年以来，我们的I级创伤系统已将TeamSTEPPS（提高绩效和患者安全的团队策略和工具；医疗研究与质量局，马里兰州罗克维尔）集成到我们的临床护理中，使用模拟对护士和医生进行联合培训在所有医疗保健提供者的参与下。随着团队的精心安排和急诊护士人数的增加，我们的计划创建了创伤护士学院。该学院为经验丰富的护士提供了高级培训，同时又减少了外伤部位人员的变异性。该学院的组成部分包括多学科的教学教育，TeamSTEPPS的基础知识以及交互式创伤学，包括设备和药物使用。完成后，学院的毕业生将参加普通外科和急诊科住院医师的创伤湾经验和伤害预防活动的指导和培训。
结果：内部和公开的数据表明，越来越多的证据将创伤团队合作训练与临床判断的知识和自信心与团队绩效，患者结果和护理质量联系起来。
实践的意义：尽管创伤复苏具有压力，高风险，动态且是错误的主要环境，但创伤团队成员之间进行团队合作培训和协作的新方法已变得至关重要。

BACKGROUND & AIMS: BACKGROUND:Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Recent studies demonstrated that microRNA-330-3p (miR-330-3p) was involved in NSCLC brain metastasis (BM). However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC. METHODS:Stable over-expression and knockdown of miR-330-3p in NSCLC cells was constructed with lentivirus. Expression levels of miR-330-3p in NSCLC cells were quantified by quantitive real-time PCR (qRT-PCR). The effects of miR-330-3p on NSCLC cells were investigated using assays of cell viability, migration, invasion, cell cycle, apoptosis, western blotting, immunohistochemical, and immunofluorescence staining. A xenograft nude mouse model and in situ brain metastasis model were used to observe tumor growth and brain metastasis. The potential target of miR-330-3p in NSCLC cells was explored using the luciferase reporter assay, qRT-PCR, and western blotting. The miR-330-3p targets were identified using bioinformatics analysis and verified by luciferase reporter assay. The correlation between GRIA3 and DNA methyltransferase (DNMT) 1 and DNMT3A was tested by RT-PCR, western blotting, and co-immunoprecipitation (IP). RESULTS:miR-330-3p was significantly up-regulated in NSCLC cell lines. MTT assay, transwell migration, and invasion assays showed that miR-330-3p promoted the growth, migration, and invasion of NSCLC cells in vitro and induced tumor growth and metastasis in vivo. Luciferase reporter assays showed that GRIA3 was a target of miR-330-3p. qRT-PCR and western blotting exhibited that miR-330-3p promoted the growth, invasion, and migration of NSCLC cells by activating mitogen-activated protein kinase (MAPK)/extracellular-regulated protein kinases (ERK) signaling pathway. Furthermore, miR-330-3p up-regulated the total DNA methylation in NSCLC cells, and co-IP-demonstrated GRIA3 was directly related with DNMT1 and DNMT3A. CONCLUSIONS:miR-330-3p promoted the progression of NSCLC and might be a potential target for the further research of NSCLC brain metastasis.

背景与目标： 背景：脑转移（BM）与非小细胞肺癌（NSCLC）患者预后差有关。最近的研究表明，microRNA-330-3p（miR-330-3p）参与了NSCLC脑转移（BM）。但是，miR-330-3p在NSCLC的BM中所起的确切作用仍然未知。发现和开发生物标志物以及阐明NSCLC中BM的潜在机制对于有效的预防性干预至关重要。在这里，我们评估了miR-330-3p在NSCLC细胞中的表达和生物学效应，并探讨了miR-330-3p在促进NSCLC细胞迁移和侵袭中的潜在机制。
方法：用慢病毒构建稳定表达miR-330-3p的NSCLC细胞。通过定量实时PCR（qRT-PCR）定量检测NSCLC细胞中miR-330-3p的表达水平。使用细胞活力，迁移，侵袭，细胞周期，凋亡，蛋白质印迹，免疫组织化学和免疫荧光染色的方法研究了miR-330-3p对NSCLC细胞的影响。用异种移植裸鼠模型和原位脑转移模型观察肿瘤的生长和脑转移。使用荧光素酶报告基因检测，qRT-PCR和Western印迹探索了NSCLC细胞中miR-330-3p的潜在靶标。使用生物信息学分析鉴定了miR-330-3p靶标，并通过萤光素酶报告基因检测法对其进行了验证。通过RT-PCR，蛋白质印迹和免疫共沉淀（IP）测试了GRIA3与DNA甲基转移酶（DNMT）1和DNMT3A之间的相关性。
结果：miR-330-3p在NSCLC细胞系中显着上调。 MTT测定，穿孔迁移和侵袭测定显示，miR-330-3p在体外促进NSCLC细胞的生长，迁移和侵袭，并在体内诱导肿瘤生长和转移。萤光素酶报告基因检测表明GRIA3是miR-330-3p的靶标。 qRT-PCR和western blotting显示，miR-330-3p通过激活有丝分裂原激活的蛋白激酶（MAPK）/细胞外调节的蛋白激酶（ERK）信号通路，促进了NSCLC细胞的生长，侵袭和迁移。此外，miR-330-3p上调了NSCLC细胞中的总DNA甲基化，并且共同IP展示的GRIA3与DNMT1和DNMT3A直接相关。
结论：miR-330-3p促进了非小细胞肺癌的发展，可能是进一步研究非小细胞肺癌脑转移的潜在靶标。

BACKGROUND & AIMS: :Objective To evaluate the etiologies for dense vitreous hemorrhage in adults with non-traumatic and reveal management of early vitrectomy for the disease. Methods Study included 105 eyes from 105 patients. Outcome measures were etiologies of vitreous hemorrhage, formation of retinal and/or disk neovascular membrane (NVM), incidence of retinal tear and detachment, visual acuity (VA) and postoperative complications. Results Mean time between presentation and surgery was 7.1 days. The most common etiologies were retinal vein occlusion (RVO) (58.1%), retinal tear (22.9%) and retinal vasculitis (10.4%). Most RVO (77.0%) and retinal vasculitis (72.7%) eyes were associated with retinal and/or disk NVM. Retinal tear and retinal detachment was found in 24 and 48 eyes, respectively. VA improved significantly from 1/70 to 0.6 following vitrectomy. The most common postoperative complication was cataract (28.6%). Conclusion RVO, retinal tear and retinal vasculitis were the most common causes of dense vitreous hemorrhage. Early vitrectomy has a good outcome with acceptable complication rates in this setting.

背景与目标： ：目的评估非创伤成人玻璃体大出血的病因，并揭示该疾病的早期玻璃体切除术的治疗方法。方法研究包括来自105名患者的105只眼睛。结果的措施是玻璃体出血，视网膜和/或盘状新血管膜（NVM）形成，视网膜撕裂和脱离的发生率，视力（VA）和术后并发症的病因。结果从就诊到手术的平均时间为7.1天。最常见的病因是视网膜静脉阻塞（RVO）（58.1％），视网膜撕裂（22.9％）和视网膜血管炎（10.4％）。大多数RVO（77.0％）和视网膜血管炎（72.7％）眼睛与视网膜和/或椎间盘NVM相关。分别在24和48只眼中发现了视网膜撕裂和视网膜脱离。玻璃体切除术后VA从1/70显着提高至0.6。最常见的术后并发症是白内障（28.6％）。结论RVO，视网膜撕裂和视网膜血管炎是玻璃体致密性出血的最常见原因。在这种情况下，早期玻璃体切除术的结果良好，并发症发生率可以接受。

BACKGROUND & AIMS: OBJECTIVE:Polyarteritis nodosa (PAN) is a necrotizing vasculitis of medium/small arteries. We aimed to examine the characteristics of adult- and childhood-onset PAN. METHODS:Fifteen pediatric (˂ 18 years) and 22 adult PAN patients who fulfilled the Ankara 2008 and American College of Rheumatology 1990 criteria, respectively, were included in the study. RESULTS:Five children had cutaneous and all the rest of the patients had systemic PAN. Weight loss was more common (59.1% vs. 20%, P = 0.041) and presence of an angiography at diagnosis was more frequent (81.8% vs. 33.3%, P = 0.003) in adults than children. Arthralgia/arthritis and skin involvement were more common in children (86.7% vs. 59.1%; 93.3% vs. 72.7%, respectively) while renal and neurologic involvement were more frequently observed in adult patients (50% vs. 20%; 59.1% vs. 40%, respectively) (P > 0.05 for all). Cutaneous PAN patients were treated with corticosteroids only. All but one adult patient received cyclophosphamide while mycophenolate mofetil was used in five and cyclophosphamide was used in four children as induction treatment. The median duration of induction treatment was longer in adults than children (12 vs. 3 months, respectively; P = 0.004). The most common maintenance drug was mycophenolate mofetil in children and azathioprine in adults. The mortality rate was 13.6% (n = 3) and 0% in adults and children, respectively. CONCLUSION:To our knowledge, this is the first study comparing characteristics of adult and childhood onset PAN. Our results have suggested that juvenile PAN had a more benign course (with less renal and neurologic involvement, shorter duration of induction treatment) than adult onset PAN.

背景与目标： 目的：结节性多发性动脉炎（PAN）是一种中/小动脉的坏死性血管炎。我们旨在检查成人和儿童期PAN的特征。
方法：本研究纳入了分别符合Ankara 2008年和1990年美国风湿病学会标准的15例儿科（˂18岁）和22例成年PAN患者。
结果：5名儿童皮肤皮肤，其余患者均患有全身性PAN。与儿童相比，成人的体重减轻更为普遍（59.1％vs. 20％，P = 0.041），并且在诊断时出现血管造影的频率更高（81.8％vs. 33.3％，P = 0.003）。儿童的关节痛/关节炎和皮肤受累更为常见（分别为86.7％和59.1％； 93.3％和72.7％），而成年患者更经常观察到肾脏和神经系统受累（50％和20％； 59.1％）分别为40％）（所有P均> 0.05）。皮肤PAN患者仅接受皮质类固醇激素治疗。除一名成年患者外，其余所有患者均接受环磷酰胺治疗，其中5例使用了麦考酚酸酯，四例儿童使用了环磷酰胺作为诱导治疗。成人的中位诱导治疗时间比儿童长（分别为12个月和3个月； P = 0.004）。最常见的维持性药物是儿童用霉酚酸酯和成人用硫唑嘌呤。成人和儿童的死亡率分别为13.6％（n = 3）和0％。
结论：据我们所知，这是第一项比较成人和儿童发病PAN的特征的研究。我们的结果表明，与成人发作的PAN相比，未成年人的PAN具有更好的病程（肾脏和神经系统受累较少，诱导治疗时间更短）。

BACKGROUND & AIMS: :We recently showed that non-small cell lung carcinomas (NSCLCs) are of dismal prognosis when encompassing accelerated autophagic activity. The regulation of this abnormally functioning degradation system and its association with hypoxia and apoptosis in lung carcinoma patients is unexplored. In this study we used 115 NSCLC tissues to examine the immunohistochemical expression of four distinct molecules - the major regulator of autophagy Beclin 1, the anti-apoptotic and anti-autophagic protein Bcl-2, the pro-apoptotic and pro-autophagic protein BNIP3, and a marker of hypoxia and glucolysis, the glucose transporter Glut 1. Most cases showed reduced reactivity for Beclin 1 (62%) and Bcl-2 (82%) proteins, almost half of our sample revealed strong BNIP3 expression (57%), whereas most of the carcinomas strongly expressed Glut 1 antigen (71%). Beclin 1 expression showed no association with survival. Bcl-2 positivity was a marker of good prognosis (p = 0.04), whereas BNIP3 (p = 0.0004) and Glut 1 (p = 0.03) expression correlated with poor outcome in Stage I disease. Autophagic status was negatively associated with Bcl-2 (p = 0.0006), but positively with Glut 1 expression (p = 0.001). In conclusion, the accelerated autophagic status in NSCLC is unrelated to Beclin 1 and BNIP3 expression, but does show significant association with Bcl-2 reactivity. Furthermore, we showed important correlations between glucolysis and autophagy, guiding new pathways in future lung carcinoma research.

背景与目标： ：我们最近发现，非小细胞肺癌（NSCLC）包含加速自噬活性时预后不良。肺癌患者中这种功能异常的降解系统的调节及其与缺氧和细胞凋亡的关系尚待探索。在这项研究中，我们使用了115个非小细胞肺癌组织来检查四种不同分子的免疫组织化学表达-自噬Beclin 1的主要调节剂，抗凋亡和抗自噬蛋白Bcl-2，促凋亡和自噬蛋白BNIP3，葡萄糖转运蛋白Glut 1是缺氧和糖酵解的标志。大多数病例显示Beclin 1（62％）和Bcl-2（82％）蛋白的反应性降低，几乎一半的样本显示BNIP3表达强（57％），而大多数癌症强烈表达Glut 1抗原（71％）。 Beclin 1的表达与存活率无关。 Bcl-2阳性是预后良好的标志（p = 0.04），而BNIP3（p = 0.0004）和Glut 1（p = 0.03）的表达与I期疾病的不良预后相关。自噬状态与Bcl-2呈负相关（p = 0.0006），但与Glut 1表达呈正相关（p = 0.001）。总之，NSCLC中自噬状态的加速与Beclin 1和BNIP3的表达无关，但确实与Bcl-2的反应性显着相关。此外，我们显示了糖酵解与自噬之间的重要关联，为未来肺癌研究的新途径提供了指导。

BACKGROUND & AIMS: :The sensorimotor cortical system undergoes structural and functional changes across its lifespan. Some of these changes are physiological and parallel the normal aging process, while others might represent pathophysiological mechanisms underlying neurodegenerative disorders. In the last years, the study of possible age-related modifications in brain sensorimotor functional characteristics has been the focus of several research projects. Here we have used the transcranial magnetic stimulation (TMS)-electroencephalography (EEG) navigated co-registration to investigate the influence of physiological aging on the excitability and connectivity of the human sensorimotor cortical system. To this end, we compared the TMS-evoked EEG potentials (TEPs) collected after stimulating the dominant primary motor cortex (M1) in healthy young subjects (mean age 24.5years) with those collected in healthy older adults (mean age 67.6years). We have shown that, after stimulation of the left motor cortex, TEPs are significantly affected by physiological aging. This phenomenon has a clear spatio-temporal specificity and we speculate that normal aging per se leads to some changes in the excitability of specific cortical neural assemblies whereas other alterations could reflect compensatory mechanisms to such changes.

背景与目标： ：感觉运动皮质系统在其整个生命周期中都会发生结构和功能的变化。这些变化中的一些是生理上的并且与正常衰老过程平行，而其他一些则可能代表了神经退行性疾病的病理生理机制。近年来，对大脑感觉运动功能特征可能与年龄有关的修饰的研究一直是数个研究项目的重点。在这里，我们已使用经颅磁刺激（TMS）-脑电图（EEG）导航的共同注册，以研究生理老化对人类感觉运动皮层系统的兴奋性和连通性的影响。为此，我们比较了健康年轻受试者（平均年龄24.5岁）和健康老年人（平均年龄67.6岁）在刺激主要运动皮层（M1）后所采集的TMS诱发的脑电势（TEP）。我们已经表明，刺激左运动皮层后，TEP受生理老化的影响很大。这种现象具有明显的时空特异性，我们推测正常衰老本身会导致特定皮层神经组件兴奋性发生某些变化，而其他变化可能反映出这种变化的补偿机制。

BACKGROUND & AIMS: OBJECTIVE:Provoked deep venous thrombosis (DVT) is precipitated by a specific event. This paper compares the characteristics of provoked DVT in patients with transient risk (TR) factors and patients with continuous risk (CR) factors. METHODS:A retrospective review of records of all consecutive patients diagnosed with DVT between January 2013 and August 2014 was performed. Patients with provoked DVT were included in the TR group if the provoking event resolved in 2 weeks and they did not have ongoing risk of thrombosis. Patients in the CR group had a provoked DVT with ongoing risk of thrombosis due to individual factors deemed to be ongoing risks of thrombosis, such as cancer, hypercoagulable disorder, and prolonged immobilization. Demographics, risk factors, association with pulmonary embolism (PE) and its severity, risk of recurrent venous thromboembolism (VTE), and mortality were compared between the two groups. RESULTS:A total of 838 patients were diagnosed with DVT, and 50.7% (425) were provoked. There were 127 (29.9%) patients with TR and 298 (70.1%) with CR. TR patients were younger (60.4 ± 16.3 vs 65.9 ± 16.0; P = .001). TR was more likely to be provoked by surgery (70.9% vs 55.4%; P = .003), whereas CR was more likely to be provoked by immobilization (21.5% vs 12.6%; P = .032). CR patients were affected by cancer (48.7%) and hypercoagulable disorders (4.4%). TR patients were more likely to have calf DVTs (36.2% vs 26.2%; P = .047). There was a trend toward lower association with PE on presentation in TR (17.3% vs 21.1%; P = .072), but that did not reach statistical significance. However, TR factors were more likely to be associated with low-risk PE compared with CR factors (30.2% vs 54.6%; P = .040). After mean follow-up of 7.2 months, CR had higher risk of recurrent VTE (14.0% vs 6.8%; P = .045) and mortality (23.5% vs 7.1%; P < .0001). CONCLUSIONS:Provoked DVT with CR factors affects older patients and is associated with high recurrence of VTE and mortality compared with provoked DVT with TR factors.

背景与目标： 目的：诱发深静脉血栓形成（DVT）是由特定事件引起的。本文比较了短暂风险（TR）因子和持续风险（CR）因子引起的DVT的特征。
方法：回顾性分析2013年1月至2014年8月间所有诊断为DVT的连续患者的病历。如果挑衅事件在2周内解决并且他们没有持续的血栓形成风险，则将挑衅性DVT的患者纳入TR组。 CR组的患者患有诱发性DVT，具有持续的血栓形成风险，原因是被认为是持续的血栓形成风险的个体因素，例如癌症，高凝性疾病和长时间的固定。比较了两组的人口统计学，危险因素，与肺栓塞（PE）的关联及其严重性，复发性静脉血栓栓塞（VTE）的风险和死亡率。
结果：总共诊断为DVT的838例患者，引起了50.7％（425）的挑衅。有127名（29.9％）的TR患者和298名（70.1％）的CR患者。 TR患者较年轻（60.4±16.3 vs 65.9±16.0; P = .001）。 TR更有可能由手术引起（70.9％vs 55.4％; P = .003），而CR更有可能由固定引起（21.5％vs 12.6％; P = .032）。 CR患者受癌症（48.7％）和高凝性疾病（4.4％）的影响。 TR患者更有可能患有小腿深静脉血栓（36.2％vs 26.2％; P = .047）。在TR中出现与PE的关联性较低的趋势（17.3％对21.1％; P = .072），但这没有统计学意义。然而，与CR因子相比，TR因子更可能与低风险PE相关（30.2％vs 54.6％; P = .040）。平均随访7.2个月后，CR复发VTE（14.0％vs 6.8％; P = .045）和死亡率（23.5％vs 7.1％; P <.0001）的风险更高。
结论：诱发性DVT伴CR因素会影响老年患者，与诱发性DVT伴TR因素相比具有较高的VTE复发率和死亡率。

BACKGROUND & AIMS: :Tufted capuchin monkeys are known to use both quadrupedalism and bipedalism in their natural environments. Although previous studies have investigated limb kinematics and metabolic costs, their ground reaction forces (GRFs) and center of mass (CoM) mechanics during two and four-legged locomotion are unknown. Here, we determine the hind limb GRFs and CoM energy, work, and power during bipedalism and quadrupedalism over a range of speeds and gaits to investigate the effect of differential limb number on locomotor performance. Our results indicate that capuchin monkeys use a "grounded run" during bipedalism (0.83-1.43 ms(-1)) and primarily ambling and galloping gaits during quadrupedalism (0.91-6.0 ms(-1)). CoM energy recoveries are quite low during bipedalism (2-17%), and in general higher during quadrupedalism (4-72%). Consistent with this, hind limb vertical GRFs as well as CoM work, power, and collisional losses are higher in bipedalism than quadrupedalism. The positive CoM work is 2.04 ± 0.40 Jkg(-1) m(-1) (bipedalism) and 0.70 ± 0.29 Jkg(-1) m(-1) (quadrupedalism), which is within the range of published values for two and four-legged terrestrial animals. The results of this study confirm that facultative bipedalism in capuchins and other nonhuman primates need not be restricted to a pendulum-like walking gait, but rather can include running, albeit without an aerial phase. Based on these results and similar studies of other facultative bipeds, we suggest that important transitions in the evolution of hominin locomotor performance were the emergences of an obligate, pendulum-like walking gait and a bouncy running gait that included a whole-body aerial phase.

背景与目标： ：簇绒的卷尾猴在其自然环境中同时使用四足动物和两足动物。尽管先前的研究已经研究了肢体运动学和代谢成本，但是在两腿和四腿运动过程中其地面反作用力（GRF）和质心（CoM）力学仍然未知。在这里，我们确定了双足和四足动物在各种速度和步态下的后肢GRF和CoM能量，功和功率，以研究差异肢数对运动性能的影响。我们的研究结果表明，卷尾猴在两足动物（0.83-1.43 ms（-1））期间使用“地面跑步”，在四足动物（0.91-6.0 ms（-1））期间主要使用步态和奔腾步态。在两足动物中，CoM能量回收率非常低（2-17％），而在四足动物中，CoM能量回收率通常较高（4-72％）。与此相一致，两足动物的后肢垂直GRF以及CoM功，功率和碰撞损失要比四足动物的高。 CoM的正工作为2.04±0.40 Jkg（-1）m（-1）（双足）和0.70±0.29 Jkg（-1）m（-1）（四足），这在两个和两个的已发布值范围内四足陆生动物。这项研究的结果证实，卷尾猴和其他非人类灵长类动物的兼性两足动物不必局限于像摆一样的步行步态，而可以包括奔跑，尽管没有空中阶段。基于这些结果以及对其他兼性两足动物的类似研究，我们建议，人的自发运动能力进化的重要转变是专心的，像摆的步行步态和有弹性的奔跑步态的出现，其中包括整个身体的空中阶段。

BACKGROUND & AIMS: OBJECTIVE:Echocardiography is used for the detection of cardiac sarcoid involvement in patients with non-cardiac sarcoidosis. Little information is available regarding temporal changes in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic dimension (LVDd) in non-cardiac sarcoidosis patients. METHODS AND RESULTS:Fifty-four sarcoidosis patients who received periodic follow-up with echocardiography at our institute were enrolled in this study. At the time of initial ultrasonography, 13 patients were diagnosed with cardiac sarcoid involvement. All of the remaining 41 patients with extra-cardiac sarcoidosis only had a LVEF of >50%. During the median follow-up period of 39 months, two (4.9%) of the non-cardiac sarcoidosis patients were diagnosed with cardiac sarcoid involvement; one patient showed a progressive decline in the LVEF over a short period of time. It was also found that two of 41 non-cardiac sarcoidosis patients showed declines in the LVEF of >10% per year; however, they were not diagnosed with cardiac sarcoidosis during the follow-up period. CONCLUSION:Rapid deterioration of left ventricular function may increase the suspicion of sarcoid involvement of the heart in non-cardiac sarcoidosis patients; however, we must be aware that a certain subfraction of patients may not demonstrate significant abnormalities in LVEF or LVDd on periodic echocardiographic follow-up.

背景与目标： 目的：超声心动图用于检测非心脏结节病患者的心脏结节样病变。关于非心脏结节病患者左心室射血分数（LVEF）和左心室舒张末期尺寸（LVDd）随时间变化的信息很少。
方法与结果：54例结节病患者在我院接受了定期超声心动图随访。在初次超声检查时，有13例患者被诊断出患有心脏结节样病变。其余所有41例心外结节病患者的LVEF均仅> 50％。在39个月的中位随访期内，有2名（4.9％）非心脏结节病患者被诊断出患有心脏结节病。一名患者在短时间内LVEF逐渐下降。还发现41例非心脏结节病患者中有2例的LVEF下降每年> 10％。但是，在随访期间并未诊断出他们患有心脏结节病。
结论：非心脏结节病患者左心功能的迅速恶化可能增加对心脏结节累及的怀疑。但是，我们必须意识到，在定期超声心动图随访中，患者的某些亚分类可能未显示LVEF或LVDd的明显异常。