• 【患者定位对动态肺顺应性的影响。】 复制标题 收藏 收藏
    DOI:10.1111/j.1399-6576.1997.tb04750.x 复制DOI
    作者列表:Tanskanen P,Kyttä J,Randell T
    BACKGROUND & AIMS: BACKGROUND:Side-stream spirometry offers a non-invasive method to monitor continuously respiratory mechanics in intubated patients. We studied the effects of different positions on dynamic lung compliance during anaesthesia. METHODS:The study consisted of 56 patients, operated in supine, prone, kneeling or lateral park-bench position. Dynamic lung compliance and inspiratory peak pressure were recorded after induction of anaesthesia, 15 min and 1 h after posturing the patient. RESULTS:The first measured compliances were comparable in all groups. The compliance in the lateral and the prone positions was significantly lower than in the supine position at 15 min (P < 0.01) and 1 h (P < 0.001) after the posture change. The peak inspiratory pressure was significantly lower in the kneeling position than in the other groups (P < 0.01 at the first measurement, P < 0.001 at the later measurements). No correlation was found between body mass index and compliance. CONCLUSION:We found that dynamic lung compliance decreased significantly upon change of posture from supine to lateral or prone position, whereas in the kneeling position no change in compliance was observed. We suggest that the kneeling position might be preferable to the prone position.
    背景与目标:
  • 【在患有严重先兆子痫的患者中,有三倍体胎儿在20周时出现明显的异常四联筛查。】 复制标题 收藏 收藏
    DOI:10.1080/14767050600553084 复制DOI
    作者列表:Barsoom MJ,McEntaffer A,Fleming A,Nipper HC
    BACKGROUND & AIMS: :Severe preeclampsia rarely occurs prior to 20 weeks of gestation except in pregnancies with triploidy. The patient reported herein is a 29-year-old primigravida who developed severe preeclampsia at 20 weeks of gestation. Evaluation of the pregnancy demonstrated a markedly abnormal quadruple screen. Amniocentesis demonstrated a fetus with triploidy, despite a normal appearance.
    背景与目标: : 除三倍体妊娠外,妊娠20周前很少发生严重的先兆子痫。本文报道的患者是一名29岁的初产妇,在妊娠20周时出现严重的先兆子痫。对妊娠的评估显示出明显异常的四重筛查。羊膜穿刺术显示胎儿具有三倍体,尽管外观正常。
  • 【健康干预的优先级设置: 多标准决策分析的必要性。】 复制标题 收藏 收藏
    DOI:10.1186/1478-7547-4-14 复制DOI
    作者列表:Baltussen R,Niessen L
    BACKGROUND & AIMS: :Priority setting of health interventions is often ad-hoc and resources are not used to an optimal extent. Underlying problem is that multiple criteria play a role and decisions are complex. Interventions may be chosen to maximize general population health, to reduce health inequalities of disadvantaged or vulnerable groups, ad/or to respond to life-threatening situations, all with respect to practical and budgetary constraints. This is the type of problem that policy makers are typically bad at solving rationally, unaided. They tend to use heuristic or intuitive approaches to simplify complexity, and in the process, important information is ignored. Next, policy makers may select interventions for only political motives. This indicates the need for rational and transparent approaches to priority setting. Over the past decades, a number of approaches have been developed, including evidence-based medicine, burden of disease analyses, cost-effectiveness analyses, and equity analyses. However, these approaches concentrate on single criteria only, whereas in reality, policy makers need to make choices taking into account multiple criteria simultaneously. Moreover, they do not cover all criteria that are relevant to policy makers. Therefore, the development of a multi-criteria approach to priority setting is necessary, and this has indeed recently been identified as one of the most important issues in health system research. In other scientific disciplines, multi-criteria decision analysis is well developed, has gained widespread acceptance and is routinely used. This paper presents the main principles of multi-criteria decision analysis. There are only a very few applications to guide resource allocation decisions in health. We call for a shift away from present priority setting tools in health--that tend to focus on single criteria--towards transparent and systematic approaches that take into account all relevant criteria simultaneously.
    背景与目标: : 卫生干预措施的优先级设定通常是临时性的,资源的使用没有达到最佳程度。潜在的问题是,多个标准发挥作用,决策很复杂。可以选择干预措施,以最大程度地提高总体人口健康水平,减少弱势或弱势群体的健康不平等,ad/或应对威胁生命的情况,所有这些都涉及实际和预算方面的限制。这是政策制定者通常不善于理性地、没有帮助地解决的问题。他们倾向于使用启发式或直观的方法来简化复杂性,在此过程中,重要的信息被忽略。接下来,政策制定者可能只出于政治动机选择干预措施。这表明需要合理和透明的方法来确定优先级。在过去的几十年中,已经开发了许多方法,包括循证医学,疾病负担分析,成本效益分析和公平性分析。但是,这些方法仅集中在单个标准上,而实际上,决策者需要同时考虑多个标准来做出选择。此外,它们并未涵盖与决策者相关的所有标准。因此,有必要开发一种多标准方法来确定优先级,并且最近确实已将其确定为卫生系统研究中最重要的问题之一。在其他科学学科中,多准则决策分析得到了很好的发展,得到了广泛的认可,并被常规使用。本文介绍了多准则决策分析的主要原理。只有很少的应用程序来指导健康中的资源分配决策。我们呼吁从目前的卫生优先事项设定工具 (往往侧重于单一标准) 转向透明和系统的方法,同时考虑到所有相关标准。
  • 【[胎儿纤连蛋白作为高危患者样本中早产的标志物]。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Surbek D,Bösiger H,Pavic N,Huber P,Almendral AC,Holzgreve W
    BACKGROUND & AIMS: The accuracy of cervicovaginal fetal fibronectin as a predictor of preterm birth was studied in patients with increased risk for preterm delivery (according to the Creasy-score). In a prospective blind observational study the smear from the posterior fornix vaginae of 56 pregnant patients without PROM was examined using a quantitative immunoassay for the detection of fetal fibronectin. The patients who tested positively for fetal fibronectin had significantly more preterm deliveries than those with a negative result (CHI square-test, p < 0.01, RR 5.1). Overall, sensitivity, specificity, positive and negative predictive values were 56%, 87%, 45% and 91%, respectively. In patients with preterm labor these values were 75%, 87%, 60%, and 93%, respectively. No patient with a negative result delivered preterm during the following two weeks. It is concluded that performing the fetal fibronectin test in patients with preterm labor is useful for the prediction of preterm birth. Routine testing in patients at increased risk (asymptomatic patients) is not recommended for lack of effectiveness.

    背景与目标: 在早产风险增加的患者中研究了宫颈阴道胎儿纤维连接蛋白作为早产预测指标的准确性 (根据Creasy评分)。在一项前瞻性盲观察研究中,使用定量免疫测定法检查了56例无胎膜早破的孕妇的后穹窿阴道涂片,以检测胎儿纤连蛋白。胎儿纤连蛋白检测呈阳性的患者的早产明显多于阴性结果的患者 (卡方检验,p <0.01,RR 5.1)。总体而言,敏感性、特异性、阳性和阴性预测值分别为56% 、87% 、45% 和91%。在早产患者中,这些值分别为75%,87%,60% 和93%。在接下来的两周内,没有阴性结果的患者早产。结论对早产患者进行胎儿纤连蛋白试验对预测早产有一定的帮助。不建议对风险增加的患者 (无症状患者) 进行常规测试,因为缺乏有效性。
  • 【保护患者和环境-医院感染控制的新方面和挑战。】 复制标题 收藏 收藏
    DOI:10.1016/s0195-6701(97)90086-4 复制DOI
    作者列表:Daschner FD,Dettenkofer M
    BACKGROUND & AIMS: Environmental pollution has become a major concern for the future of life on our planet; medical care, especially in hospitals, contributes significantly to this pollution. The increasing usage of highly-developed medical devices, drugs and disposable products are a drain on natural resources as well as financial ones. In this situation, it is a major task for hospital epidemiologists to maintain high standards of hygiene while reducing environmental pollution, reducing consumption of limited natural resources, and minimizing costs. The reduction of hospital waste, the control of polluting and toxic emissions, the avoidance of unnecessary disinfection procedures and disposables, the implementation of energy and water saving technologies are practicable measures in hospital ecology. To realize a sustainable development within hospitals, it is necessary that the need to maintain a balance between effective infection control and a good ecological environment is recognized and supported by health-care workers and the hospital management.

    背景与目标: 环境污染已成为地球生命未来的主要问题; 医疗保健,尤其是医院的医疗保健,对这种污染有很大影响。高度发达的医疗设备,药品和一次性产品的使用日益增加,既消耗了自然资源,也消耗了金融资源。在这种情况下,医院流行病学家的主要任务是在减少环境污染的同时保持高标准的卫生,减少对有限自然资源的消耗并最大程度地降低成本。减少医院废物,控制污染和有毒排放物,避免不必要的消毒程序和一次性用品,实施节能节水技术是医院生态中的可行措施。为了实现医院内部的可持续发展,有必要在有效的感染控制和良好的生态环境之间保持平衡的需要得到医护人员和医院管理层的认可和支持。
  • 【基于放射性核素确定的肿瘤患者射血分数的临床决策。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Peng NJ,Advani R,Kopiwoda S,Fisher G,Strauss HW
    BACKGROUND & AIMS: UNLABELLED:Decreased left ventricular ejection fraction (LVEF) is a relative contraindication for the use of potentially cardiotoxic chemotherapy. A resting LVEF of 50% is usually used as the lower limit of normal values. The decision to change chemotherapy, however, is complex and is affected by many factors, including ejection fraction.

    METHODS:To determine how LVEF data were used by clinical oncologists in clinical decision making, we performed a retrospective analysis of patients referred for ejection fraction measurements from the hematology/oncology divisionS of Stanford University from March 1992 through March 1995. The records of 565 patients treated with potentially cardiotoxic chemotherapy were evaluated.

    RESULTS:LVEFs < 50% were found in 153 patients. The charts of patients with reduced ejection fractions were reviewed to determine if the radionuclide measurement resulted in either discontinuation of the cardiotoxic agent or substitution of a less cardiotoxic drug or mode of administration. These specific changes in therapy occurred in only 43 of the 153 (28%) patients with ejection fractions below 50%; 24 of the 43 (57%) had ejection fractions < or = 40%. Patients with lower ejection fraction values were more likely to have their therapy changed than those with LVEFs close to normal. Patients with ejection fractions < or = 30 generally had cardiotoxic agents discontinued. Of patients who had a resting LVEF < 50% and whose therapy was not changed, 81% had a normal increase in LVEF with exercise.

    CONCLUSION:In clinical practice at our institution, ejection fraction < 50% is not used as an absolute contraindication to cardiotoxic chemotherapy. When the LVEF is less than 40%, potentially cardiotoxic therapy is most often discontinued or omitted. Radionuclide evidence of cardiac reserve may account for decisions to continue cardiotoxic agents despite ejection fractions < 50% in the majority of patients. Further study will be needed to establish standard criteria. Reserve function, as measured by the change in ejection fraction from rest to stress may be an important parameter used by oncologists to help select patients for continued therapy in spite of a reduced ejection fraction. Our results argue that use of fixed criteria may be too restrictive.

    背景与目标: 未标记 : 左心室射血分数 (LVEF) 降低是使用潜在心脏毒性化学疗法的相对禁忌症。50% 的静息LVEF通常用作正常值的下限。然而,改变化疗的决定是复杂的,并且受到许多因素的影响,包括射血分数。
    方法 : 为了确定临床肿瘤学家如何在临床决策中使用LVEF数据,我们对1992年3月至1995年3月期间接受斯坦福大学血液学/肿瘤学部门射血分数测量的患者进行了回顾性分析。评估了565例接受潜在心脏毒性化学疗法治疗的患者的记录。
    结果 : 在153例患者中发现LVEFs <50%。回顾了射血分数降低的患者的图表,以确定放射性核素测量是否导致停用心脏毒性药物或替代心脏毒性较小的药物或给药方式。这些特定的治疗变化仅发生在射血分数低于50% 的153 (28%) 患者中; 43 (57%) 中的24的射血分数 <或 = 40%。射血分数值较低的患者比LVEFs接近正常的患者更有可能改变治疗。射血分数 <或 = 30的患者通常停用心脏毒性药物。在静息LVEF <50% 且治疗未改变的患者中,81% 的LVEF随运动而正常增加。
    结论 : 在我们机构的临床实践中,射血分数 <50% 不作为心脏毒性化疗的绝对禁忌症。当LVEF小于40% 时,潜在的心脏毒性治疗通常被停止或省略。尽管大多数患者的射血分数 <50%,但心脏储备的放射性核素证据可能解释了继续服用心脏毒性药物的决定。需要进一步研究以建立标准。储备功能 (通过从静息到压力的射血分数变化来衡量) 可能是肿瘤学家使用的重要参数,尽管射血分数降低,但可以帮助选择患者继续治疗。我们的结果认为,使用固定标准可能过于严格。
  • 【杂合蛋白缺乏患者的皮肤肝素坏死。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Libow LF,DiPreta EA,Dyksterhouse DL
    BACKGROUND & AIMS: A patient with heterozygous protein S deficiency experienced cutaneous necrosis following subcutaneous heparin administration. Deficiencies of both protein C and protein S, known risk factors for the more frequently encountered coumarin necrosis, may predispose patients to this complication of heparin therapy as well. The putative association of protein S deficiency with cutaneous heparin necrosis could not be proven, however, since attempts to reproduce the heparin necrosis were unsuccessful.

    背景与目标: 杂合蛋白S缺乏症患者在皮下注射肝素后出现皮肤坏死。蛋白C和蛋白S的缺乏是香豆素坏死较常见的已知危险因素,也可能使患者易患肝素治疗的这种并发症。然而,由于试图重现肝素坏死的尝试均未成功,因此无法证明蛋白质S缺乏症与皮肤肝素坏死的关系。
  • 【具有cblJ先天性维生素B12代谢错误的非典型患者的症状迟发: 通过外显子组测序揭示的诊断和新突变。】 复制标题 收藏 收藏
    DOI:10.1016/j.ymgme.2012.10.005 复制DOI
    作者列表:Kim JC,Lee NC,Hwu PW,Chien YH,Fahiminiya S,Majewski J,Watkins D,Rosenblatt DS
    BACKGROUND & AIMS: :Inborn errors of vitamin B(12) (cobalamin) metabolism are characterized by decreased production of active cobalamin cofactors and subsequent deficiencies in the activities of methionine synthase and methylmalonyl-CoA mutase. With the recent discovery of the cblJ defect in two patients with phenotypes mimicking the cblF defect, there are nine genes known to be involved in cobalamin metabolism. The new defect is caused by mutations in the ABCD4 gene, encoding an ABC transporter. At the moment, there is no clear distinction between the cblJ and cblF defects either clinically or biochemically, and both defects result in blocks in the transport of cobalamin from the lysosome to the cytoplasm. A patient was diagnosed with hyperhomocysteinemia and methylmalonic aciduria at the age of 8 years. Incorporations of both [(14)C]propionate and [(14)C]methyltetrahydrofolate in cultured fibroblasts were within reference ranges and thus too high to allow for complementation analysis. We observed decreased synthesis of both adenosylcobalamin and methylcobalamin and accumulation of unmetabolized cyanocobalamin. Exome sequencing was performed to identify causative mutation(s) and Sanger re-sequencing was performed to validate segregation of mutation in the family. By this approach, a homozygous mutation, c.423C>G, in the ABCD4 gene was identified. Here, we report the successful application of exome sequencing for diagnosis of a rare inborn error of vitamin B(12) metabolism in a patient whose unusual presentation precluded diagnosis using standard biochemical and genetic approaches. The patient represents only the third known patient with the cblJ disorder.
    背景与目标: : 维生素b (12) (钴胺素) 代谢的先天性错误的特征是活性钴胺素辅因子的产生减少,随后蛋氨酸合酶和甲基丙二酰辅酶a变位酶的活性不足。随着最近在两名表型模仿cblF缺陷的患者中发现cblJ缺陷,已知有9个基因与钴胺素代谢有关。新的缺陷是由编码ABC转运蛋白的ABCD4基因突变引起的。目前,无论是在临床上还是在生化上,cblJ和cblF缺陷之间都没有明确的区别,这两个缺陷都会导致钴胺素从溶酶体到细胞质的转运受到阻碍。一名患者在8岁时被诊断出患有高同型半胱氨酸血症和甲基丙二酸尿症。培养的成纤维细胞中 [(14)C] 丙酸酯和 [(14)C] 甲基四氢叶酸的加入都在参考范围内,因此太高,无法进行互补分析。我们观察到腺苷钴胺和甲钴胺的合成减少以及未代谢的氰钴胺的积累。进行外显子组测序以鉴定致病突变 (s),并进行了Sanger重新测序以验证家族中突变的分离。通过这种方法,在ABCD4基因中发现了一个纯合突变,c.423C>G。在这里,我们报告了外显子组测序在诊断罕见的先天性维生素b (12) 代谢错误中的成功应用,该患者的异常表现无法使用标准的生化和遗传学方法进行诊断。该患者仅代表第三位已知的cblJ疾病患者。
  • 【术中电子加速部分乳房照射: 使用GEC-ESTRO推荐作为患者选择的指导。】 复制标题 收藏 收藏
    DOI:10.1016/j.radonc.2012.10.018 复制DOI
    作者列表:Leonardi MC,Maisonneuve P,Mastropasqua MG,Morra A,Lazzari R,Dell'Acqua V,Ferrari A,Rotmensz N,Sangalli C,Luini A,Veronesi U,Orecchia R
    BACKGROUND & AIMS: PURPOSE:To evaluate outcomes among early-stage breast cancer patients after conservative surgery and full-dose intraoperative radiotherapy electrons (ELIOT) by applying the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations for partial breast irradiation (APBI). MATERIALS AND METHODS:One-thousand eight-hundred and twenty-two patients were stratified into the three GEC-ESTRO categories of "good candidates", "possible candidates" and "contraindication" in order to assess outcomes. RESULTS:All the 1822 cases except 7 could be classified according to GEC-ESTRO groups: 573 patients met the criteria to be included in the "good candidates" group, 468 patients in the "possible candidates" group and 767 patients in the "contraindication" group. Median and mean follow-up length was 3.5 years (range 0-10.5 years) and 3.8 years (SD 2.2), respectively. The 5-year rate of in-breast tumor reappearances for "good candidates", "possible candidates" and "contraindication" groups were 1.9%, 7.4% and 7.7%, respectively (p 0.001). While the regional node relapse showed no difference, the rate of distant metastases was significantly different in the "contraindication" group compared to the other two categories, having a significant impact on survival. CONCLUSIONS:Among the ELIOT population, the GEC-ESTRO recommendations enabled the selection of the good candidates with a low rate of local recurrence, but failed to differentiate the "possible candidates" and the "contraindication" groups.
    背景与目标:
  • 【在急诊科新发癫痫发作患者中进行实验室研究的实用性。】 复制标题 收藏 收藏
    DOI:10.1016/s0196-0644(05)82337-6 复制DOI
    作者列表:Turnbull TL,Vanden Hoek TL,Howes DS,Eisner RF
    BACKGROUND & AIMS: :Extensive laboratory testing is often performed in the emergency department evaluation of the new-onset seizure patient. To determine the utility of such testing, a prospective study of patients with a new-onset seizure presenting to the ED of an inner-city, university-affiliated teaching hospital was done. One hundred thirty-six patients were entered into the study between October 1984 and January 1988. All patients had uniform data collection performed. Pertinent historical information and physical examination findings were recorded on a standardized form before laboratory abnormality was a sole or contributory cause of the seizure disorder. These included four patients with hypoglycemia, four with hyperglycemia, two with hypocalcemia, and one with hypomagnesemia. Only two cases (hypoglycemia) were not suspected on the basis of findings on the history or physical examination. In ED patients, the incidence of a new-onset seizure due to a correctable metabolic disturbance is low. We conclude that, with the exception of the serum glucose, the extensive ED laboratory workup often done for the evaluation of a new-onset seizure is unnecessary. Further test ordering should be directed by the medical history and physical examination.
    背景与目标: : 在急诊科对新发癫痫患者的评估中,经常进行广泛的实验室测试。为了确定这种测试的实用性,对向市中心大学附属教学医院的ED呈递的新发癫痫发作患者进行了前瞻性研究。在1984年10月和1988年1月之间,有136名患者进入了研究。所有患者均进行了统一的数据收集。在实验室异常是癫痫发作的唯一或促成原因之前,将相关的历史信息和体格检查结果记录在标准化表格上。其中包括4名低血糖患者,4名高血糖患者,2名低钙血症患者和1名低镁血症患者。根据病史或体格检查发现,仅怀疑有2例 (低血糖)。在ED患者中,由于可纠正的代谢紊乱而引起的新发癫痫发作的发生率较低。我们得出的结论是,除血清葡萄糖外,通常不需要进行广泛的ED实验室检查以评估新发癫痫发作。进一步的检查顺序应由病史和体格检查指示。
  • 【患者咨询课程对一年级药学专业学生的沟通理解,结果期望和自我效能感的影响。】 复制标题 收藏 收藏
    DOI:10.5688/ajpe768152 复制DOI
    作者列表:Rogers ER,King SR
    BACKGROUND & AIMS: OBJECTIVES:To evaluate first-year doctor of pharmacy (PharmD) students' communication apprehension, outcome expectations, and self-efficacy for communication over the duration of a 15-week patient-counseling course. DESIGN:First-year PharmD students (n=94) were asked to complete a 47-item, self-administered questionnaire on 3 occasions over the duration of the Nonprescription Drugs/Patient-Counseling course during the fall 2009 and 2010 semesters. ASSESSMENT:Eighty-seven of 94 students completed the survey instrument across data collection periods. There were significant reductions in total communication apprehension scores and in the communication apprehension subscores for meetings and public speaking, and significant increases in self-efficacy over time. No differences were found for outcome expectations of communication scores or the subscores for interpersonal conversations and group discussion. CONCLUSIONS:Communication apprehension may be decreased and self-efficacy for communication increased in first-year PharmD students through a 15-week Nonprescription Drugs/Patient-Counseling course using small-group practice sessions, case studies, and role-play exercises in conjunction with classroom lectures.
    背景与目标:
  • 【来自右室流出道的良性室性早搏复合物触发了2型LQTS患者的多形性室性心动过速。】 复制标题 收藏 收藏
    DOI:10.2169/internalmedicine.51.8565 复制DOI
    作者列表:Sato A,Chinushi M,Sonoda K,Abe A,Izumi D,Furushima H
    BACKGROUND & AIMS: :A 57-year-old woman showed frequent premature ventricular complexes (PVCs) originating from the right ventricular outflow tract (RVOT), and some of the PVCs triggered polymorphic ventricular tachycardia (PVT). Structural heart diseases were ruled out by conventional cardiac examinations. Radiofrequency catheter ablation was successful in eliminating the PVCs and subsequent PVT. However, epinephrine infusion unmasked her prolonged QT interval, and a genetic analysis revealed a KCNH2 mutation (R694H) as the cause of latent type-2 long QT syndrome (LQTS). This case suggests that latent LQTS may work as an arrhythmogenic substrate of PVT triggered by a benign form of RVOT-PVCs in patients with a structurally normal heart.
    背景与目标: : 一名57岁的女性表现出频繁的源自右心室流出道 (RVOT) 的室性早搏 (pvc),其中一些pvc触发了多形性室性心动过速 (PVT)。常规心脏检查排除了结构性心脏病。射频导管消融成功消除了pvc和随后的PVT。然而,肾上腺素输注揭示了她延长的QT间期,基因分析显示KCNH2突变 (R694H) 是潜伏性2型长QT综合征 (LQTS) 的原因。这种情况表明,在结构正常的心脏患者中,潜在的LQTS可能是由良性形式的rvot-pvc触发的PVT的致心律失常底物。
  • 【DAPK1通过使CaMKII/GluN2B结合LTP特异性来介导有限公司。】 复制标题 收藏 收藏
    DOI:10.1016/j.celrep.2017.05.068 复制DOI
    作者列表:Goodell DJ,Zaegel V,Coultrap SJ,Hell JW,Bayer KU
    BACKGROUND & AIMS: :The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP. We find that the LTP specificity of CaMKII synaptic accumulation is due to its LTD-specific suppression by calcineurin (CaN)-dependent DAPK1 activation, which in turn blocks CaMKII binding to GluN2B. This suppression is enabled by competitive DAPK1 versus CaMKII binding to GluN2B. Negative regulation of DAPK1/GluN2B binding by Ca2+/CaM results in synaptic DAPK1 removal during LTP but retention during LTD. A pharmacogenetic approach showed that suppression of CaMKII/GluN2B binding is a DAPK1 function required for LTD.
    背景与目标: 死亡相关蛋白激酶1 (DAPK1) 是神经元细胞死亡的有效介质。在这里,我们发现DAPK1还通过调节Ca2/钙调蛋白 (CaM) 依赖性蛋白激酶II (CaMKII) 在突触可塑性中起作用。长期增强 (LTP) 和抑郁 (LTD) 都需要CaMKII和T286自磷酸化,这是学习,记忆和认知基础的突触可塑性的两种相反形式。T286-autophosphorylation诱导CaMKII与NMDA受体 (NMDAR) 亚基GluN2B结合,后者在LTP期间介导CaMKII突触积累。我们发现CaMKII突触积累的LTP特异性是由于钙调神经磷酸酶 (CaN) 依赖性DAPK1激活对其LTD特异性的抑制,这反过来又阻止了CaMKII与GluN2B的结合。通过竞争性DAPK1与CaMKII结合GluN2B来实现这种抑制。Ca2 +/CaM对DAPK1/GluN2B结合的负调节导致LTP期间突触DAPK1去除,但在LTD.期间保留。药物遗传学方法表明,抑制CaMKII/GluN2B结合是LTD所需的DAPK1功能。
  • 【验证同种异体BMT中院内非专业护理伙伴支持对患者生存的积极影响: 一项前瞻性研究。】 复制标题 收藏 收藏
    DOI:10.1038/bmt.2012.208 复制DOI
    作者列表:Foster LW,McLellan L,Rybicki L,Dabney J,Copelan E,Bolwell B
    BACKGROUND & AIMS: :This prospective study validates the finding from retrospective research that having an inpatient lay care-partner (CP) is associated with better survival following allogeneic BMT. Compared with patients without a CP (n=76), patients with a CP (n=88) have significantly better OS (P=0.017) and relapse-free survival (RFS) (P=0.020). Four-year and median survivals were 42% and 36 months among patients with CPs, compared with 26% and 10 months among those without CPs. Four-year survival and median RFS were 39% and 25 months among those with CPs, compared with 23% and 7 months among those without CPs. Further, better survival and RFS were associated with CP visit duration of >3 h per day (P=0.005 and P=0.007, respectively) and with CP frequency of visits >75% of inpatient days (P=0.004 and P=0.010, respectively). A CP support program should encourage not only presence of a CP but also duration and frequency of CP visits associated with better patient survival.
    背景与目标: : 这项前瞻性研究证实了回顾性研究的发现,即拥有住院非专业护理伴侣 (CP) 与同种异体BMT后更好的生存率相关。与没有CP的患者 (n = 76) 相比,具有CP的患者 (n = 88) 具有明显更好的OS (P = 0.017) 和无复发生存率 (RFS) (P = 0.020)。CPs患者的4年和中位生存期分别为42% 和36个月,而无CPs的患者为26% 和10个月。患有CPs的患者的四年生存率和中位RFS分别为39% 和25个月,而没有CPs的患者为23% 和7个月。此外,更好的生存率和RFS与每天> 3 h的CP访视时间 (分别为P = 0.005和P = 0.007) 和CP访视频率> 住院天数的75% (分别为P = 0.004和P = 0.010) 相关。CP支持计划不仅应鼓励CP的存在,而且还应鼓励CP就诊的持续时间和频率与更好的患者生存率相关。
  • 【虚拟现实暴露疗法和催眠治疗难治性患者的飞行恐惧症: 一例报告。】 复制标题 收藏 收藏
    DOI:10.1080/00029157.2011.639587 复制DOI
    作者列表:Hirsch JA
    BACKGROUND & AIMS: :Flying phobia is a problem that affects a significant portion of the population. There are a number of therapeutic approaches but no one is universally accepted as the gold standard. One therapy is hypnosis. A recent addition to the armamentarium is virtual reality exposure (VRE) therapy. Both therapies are short-term and compare favorably to in vivo desensitization. Heretofore a combination of both approaches has not been reported. This article presents a case of a 50-year phobia to flying that was refractory to traditional methods including pharmacotherapy, systematic desensitization, and cognitive behavioral therapy but was successfully treated using VRE therapy and hypnosis as the primary modalities. This treatment was supplemented by other approaches. The rationale for this multimodal therapy and possible mechanisms involved are discussed.
    背景与目标: : 飞行恐惧症是一个影响很大一部分人口的问题。有许多治疗方法,但没有人被普遍接受为黄金标准。一种疗法是催眠。最近在aramentarium中添加的是虚拟现实暴露 (VRE) 疗法。两种疗法都是短期的,与体内脱敏相比是有利的。迄今为止,尚未报道两种方法的组合。本文介绍了一个50年的飞行恐惧症案例,该案例对传统方法 (包括药物疗法,系统脱敏和认知行为疗法) 难以治疗,但已成功使用VRE疗法和催眠作为主要方式进行治疗。这种治疗得到了其他方法的补充。讨论了这种多模式疗法的原理和可能的机制。

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