• 【钳位上升时间对非洲爪蟾卵母细胞大鼠脑IIA钠通道的影响。】 复制标题 收藏 收藏
    DOI:10.1016/s0165-0270(96)02216-9 复制DOI
    作者列表:Ruben PC,Fleig A,Featherstone D,Starkus JG,Rayner MD
    BACKGROUND & AIMS: The kinetic properties of wild-type rat brain IIa sodium channels in excised macropatches were studied using step depolarizations and ramp depolarizations to imitate the slow settling-time of voltage in two-electrode voltage clamp. Ramp depolarizations longer than 1 ms produce an increasing suppression of peak sodium current (I[Na]). Two rates of inactivation can be seen in macroscopic sodium current records from excised patches following both step and ramp depolarizations. During slow ramp depolarizations, reduction in peak I[Na] is associated with selective loss of the fastest rate of test-pulse inactivation. This change can be interpreted as resulting from inactivation of a separate sub-population of 'fast mode' channels. The slow rate of test-pulse inactivation is relatively unaffected by changing ramp durations. These results are sufficient to explain the typically slow inactivation kinetics seen in two-electrode voltage clamp recordings of sodium channels in Xenopus oocytes. Thus, the kinetics of sodium channels expressed in Xenopus oocytes are not readily characterizable by two-electrode clamp because of the large membrane capacitance and resulting slow clamp settling time which artifactually selects for slow mode channels.

    背景与目标: 使用逐步去极化和斜坡去极化来模拟两电极电压钳位中电压的缓慢建立时间,研究了切除的大斑块中野生型大鼠脑IIa钠通道的动力学特性。长于1 ms的斜坡去极化会增加对峰值钠电流 (I[Na]) 的抑制。在阶跃和斜坡去极化之后,从切除的斑块的宏观钠电流记录中可以看到两种失活速率。在缓慢的斜坡去极化过程中,峰值I[Na] 的降低与最快的测试脉冲失活速率的选择性损失有关。此更改可以解释为由于 “快速模式” 通道的单独子种群的失活而导致。测试脉冲失活的缓慢速度相对不受斜坡持续时间变化的影响。这些结果足以解释非洲爪蟾卵母细胞中钠通道的两电极电压钳制记录中看到的典型的缓慢失活动力学。因此,非洲爪蟾卵母细胞中表达的钠通道的动力学不容易通过两电极钳来表征,因为膜电容大,并且会导致人为选择慢模式通道而产生的慢钳建立时间。
  • 【通过基质辅助激光解吸/电离飞行时间质谱法测定人呼吸道合胞病毒附着 (G) 蛋白的二硫键排列。】 复制标题 收藏 收藏
    DOI:10.1002/pro.5560060619 复制DOI
    作者列表:Gorman JJ,Ferguson BL,Speelman D,Mills J
    BACKGROUND & AIMS: The attachment protein or G protein of the A2 strain of human respiratory syncytial virus (RSV) was digested with trypsin and the resultant peptides separated by reverse-phase high-performance liquid chromatography (HPLC). One tryptic peptide produced a mass by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) corresponding to residues 152-187 with the four Cys residues of the ectodomain (residues 173, 176, 182, and 186) in disulfide linkage and absence of glycosylation. Sub-digestion of this tryptic peptide with pepsin and thermolysin produced peptides consistent with disulfide bonds between Cys173 and Cys186 and between Cys176 and Cys182. Analysis of ions produced by post-source decay of a peptic peptide during MALDI-TOF-MS revealed fragmentation of peptide bonds with minimal fission of an inter-chain disulfide bond. Ions produced by this unprecedented MALDI-induced post-source fragmentation corroborated the existence of the disulfide arrangement deduced from mass analysis of proteolysis products. These findings indicate that the ectodomain of the G protein has a non-glycosylated subdomain containing a "cystine noose."

    背景与目标: 用胰蛋白酶消化人呼吸道合胞病毒 (RSV) 的A2菌株的附着蛋白或g蛋白,并通过反相高效液相色谱 (HPLC) 分离所得肽。一种胰蛋白酶肽通过基质辅助激光解吸/电离 (MALDI) 飞行时间 (TOF) 质谱 (MS) 产生了与胞外域的四个Cys残基152-187的残基 (残基173,176,182,和186) 在二硫键连接和不存在糖基化。用胃蛋白酶和嗜热菌素对这种胰蛋白酶进行亚消化,产生的肽与Cys173和Cys186之间以及Cys176和cys182之间的二硫键一致。对maldi-tof-MS期间消化肽的源后衰变产生的离子的分析表明,肽键断裂,链间二硫键的裂变最小。这种前所未有的MALDI诱导的后源断裂产生的离子证实了从蛋白水解产物的质量分析得出的二硫键排列的存在。这些发现表明g蛋白的外结构域具有包含 “胱氨酸套索” 的非糖基化亚域。
  • 【膜联蛋白V与脂质体结合后的构象适应性: 时间分辨荧光研究。】 复制标题 收藏 收藏
    DOI:10.1006/bbrc.1997.6596 复制DOI
    作者列表:Follenius-Wund A,Piémont E,Freyssinet JM,Gérard D,Pigault C
    BACKGROUND & AIMS: The fluorescence intensity decay of the single tryptophan residue, Trp-187, of free annexin V is described by the sum of three lifetime components (5.4, 1.3, and 0.4 ns), which may be correlated to three ground-state classes of Trp conformers. The two major classes (44 and 48%) are embedded in the protein matrix. When annexin V binds to calcium and liposomes made of dioleoylphosphatidylcholine and dioleoylphosphatidylserine, similar results are obtained whatever the (10-200) lipid ratio. The Trp fluorescence decay is fitted with only two components (6.9-7.2 and 2.0-2.2 ns). Decay-associated spectra reveal that the longest lifetime of bound annexin V can be related to Trp residues (60%) located in a partially polar environment, which could correspond to the protein-membrane interface. The shortest lifetime is attributed to Trp residues (40%) which reside in a hydrophobic surroundingthese Trp residues would penetrate into the phospholipid membrane and contribute to the stabilization of the 2D-array of annexin V molecules.

    背景与目标: Trp-187,游离膜联蛋白V的单个色氨酸残基的荧光强度衰减由三个寿命分量 (5.4、1.3和0.4 ns) 的总和描述,这可能与Trp构象的三个基态类别相关。两个主要类别 (44和48%) 嵌入蛋白质基质中。当膜联蛋白V与钙和由二油酰基磷脂酰胆碱和二油酰基磷脂酰丝氨酸制成的脂质体结合时,无论 (10-200) 脂质比率如何,都获得相似的结果。Trp荧光衰减仅适合两种组分 (6.9-7.2和2.0-2.2 ns)。衰变相关光谱表明,结合膜联蛋白V的最长寿命可能与位于部分极性环境中的Trp残基 (60%) 有关,这可能对应于蛋白质-膜界面。最短的寿命归因于存在于疏水性周围的Trp残基 (40%),这些Trp残基会渗透到磷脂膜中,并有助于膜联蛋白V分子的2d阵列的稳定。
  • 【2种用于检测北京地区甲型H1N1 2009病毒的商业实时PCR试剂盒的评价。】 复制标题 收藏 收藏
    DOI:10.1016/j.jviromet.2012.11.042 复制DOI
    作者列表:Lu G,Yan H,Yang Y,Cui S,Lü Y,Zhang X,Zhang D,Yang P,Huang F,Wang J,Wang Q
    BACKGROUND & AIMS: :Active surveillance and diagnosis of the influenza pandemic (H1N1) 2009 (pH1N1) have played a critical role in the effective control and prevention of the pandemic in China. Although several commercially available real-time PCR kits for pH1N1 virus have been used in diagnostic laboratories in Beijing, little has been known about the performance of these kits for detecting pH1N1 virus. In this study, the performance of two commercial real-time PCR kits in Beijing was evaluated. Analysis of clinical samples showed that the positive detection rate for the AgPath-ID™ kit (38.2%) was significantly higher than that for the Da An H1N1 kit (30.0%) (McNemar's chi-square test, P=0.000). The limit of detection (LOD) of the AgPath-ID™ kit was 10(2), 10(2), and 10(3) copies/reaction for the Influenza A (set 1), H1N1 Influenza A (set 2) and H1N1 Influenza A Sub H1 (set 3) genes, respectively, whereas the LOD of the Da An kit was 10(3) copies/reaction for both H1 and N1 genes. Although the AgPath-ID™ kit exhibited a significantly higher detection rate for pH1N1 than the Da An kit, cross-reactivity to A/PR8/34 was found for the AgPath-ID™ kit for H1N1 Influenza A (set 2).
    背景与目标: : 对流感大流行 (H1N1) 2009 (pH1N1) 的积极监测和诊断在有效控制和预防中国大流行方面发挥了关键作用。尽管北京的诊断实验室已经使用了几种市售的pH1N1病毒实时PCR试剂盒,但对这些试剂盒检测pH1N1病毒的性能知之甚少。在这项研究中,评估了北京两种商用实时PCR试剂盒的性能。临床样本分析表明,AgPath-ID的阳性检出率™试剂盒 (38.2%) 显着高于Da H1N1试剂盒 (30.0%) (McNemar卡方检验,P = 0.000)。AgPath-ID的检测极限 (LOD)™试剂盒分别为甲型流感 (第1组) 、甲型H1N1流感 (第2组) 和甲型H1N1流感亚H1 (第3组) 基因的10(2) 、10(2) 和10(3) 拷贝/反应,而Da An试剂盒的LOD对于H1和N1基因均为10(3) 个拷贝/反应。虽然AgPath-ID™试剂盒对pH1N1的检出率明显高于Da一试剂盒,发现AgPath-ID对a/PR8/34的交叉反应性™甲型H1N1流感试剂盒 (第2套)。
  • 【严峻环境中的损伤控制手术研究小组 (DCSAERG): 一个动态程序,可促进实时远程监护/远程诊断,以解决极端和严峻环境中的失血问题。】 复制标题 收藏 收藏
    DOI:10.1097/TA.0000000000001483 复制DOI
    作者列表:Kirkpatrick AW,McKee JL,McBeth PB,Ball CG,LaPorta A,Broderick T,Leslie T,King D,Wright Beatty HE,Keillor J,Tien H
    BACKGROUND & AIMS: :Hemorrhage is the most preventable cause of posttraumatic death. Many cases are potentially anatomically salvageable, yet remain lethal without logistics or trained personnel to deliver diagnosis or resuscitative surgery in austere environments. Revolutions in technology for remote mentoring of ultrasound and surgery may enhance capabilities to utilize the skill sets of non-physicians. Thus, our research collaborative explored remote mentoring to empower non-physicians to address junctional and torso hemorrhage control in austere environments. Major studies involved using remote-telementored ultrasound (RTMUS) to identify torso and junctional exsanguination, remotely mentoring resuscitative surgery for torso hemorrhage control, understanding and mitigating physiological stress during such tasks, and the technical practicalities of conducting damage control surgery (DCS) in austere environments. Iterative projects involved randomized guiding of firefighters to identify torso (RCT) and junctional (pilot) hemorrhage using RTMUS, randomized remote mentoring of MedTechs conducting resuscitative surgery for torso exsanguination in an anatomically realistic surgical trainer ("Cut Suit") including physiological monitoring, and trained surgeons conducting a comparative randomized study for torso hemorrhage control in normal (1g) versus weightlessness (0g). This work demonstrated that firefighters could be remotely mentored to perform just-in-time torso RTMUS on a simulator. Both firefighters and mentors were confident in their abilities, the ultrasounds being 97% accurate. An ultrasound-naive firefighter in Memphis could also be remotely mentored from Hawaii to identify and subsequently tamponade an arterial junctional hemorrhage using RTMUS in a live tissue model. Thereafter, both mentored and unmentored MedTechs and trained surgeons completed resuscitative surgery for hemorrhage control on the Cut-Suit, demonstrating practicality for all involved. While remote mentoring did not decrease blood loss among MedTechs, it increased procedural confidence and decreased physiologic stress. Therefore, remote mentoring may increase the feasibility of non-physicians conducting a psychologically daunting task. Finally, DCS in weightlessness was feasible without fundamental differences from 1g. Overall, the collective evidence suggests that remote mentoring supports diagnosis, noninvasive therapy, and ultimately resuscitative surgery to potentially rescue those exsanguinating in austere environments and should be more rigorously studied.
    背景与目标: : 出血是创伤后死亡最可预防的原因。许多病例在解剖学上可能是可挽救的,但如果没有后勤人员或训练有素的人员在严峻的环境中进行诊断或复苏手术,则仍然致命。超声波和外科手术远程指导技术的革命可能会增强利用非医生技能的能力。因此,我们的研究合作探索了远程指导,以使非医生能够在严峻的环境中解决交界处和躯干出血控制问题。主要研究包括使用远程远程超声 (RTMUS) 识别躯干和交界性放血,远程指导复苏手术以控制躯干出血,理解和减轻此类任务期间的生理压力,以及在严峻环境中进行损伤控制手术 (DCS) 的技术实用性。迭代项目包括随机指导消防员使用RTMUS识别躯干 (RCT) 和交界 (pilot) 出血,随机远程指导MedTechs在解剖学上逼真的外科训练器 (“切割服”) 中进行躯干放血的复苏手术,包括生理监测,和训练有素的外科医生进行了一项比较随机研究,以正常 (1g) 与失重 (0g) 的躯干出血控制。这项工作表明,可以远程指导消防员在模拟器上执行及时的躯干RTMUS。消防员和导师都对自己的能力充满信心,超声波97% 准确。孟菲斯的一名未经超声检查的消防员也可以从夏威夷进行远程指导,以识别并随后在活组织模型中使用RTMUS填塞动脉交界性出血。此后,经过指导和未经指导的MedTechs和训练有素的外科医生都完成了复苏手术,以控制剪裁服上的出血,这证明了所有参与者的实用性。虽然远程指导并没有减少MedTechs的失血,但它增加了程序信心并减少了生理压力。因此,远程指导可能会增加非医生执行心理艰巨任务的可行性。最后,失重的dc是可行的,与1g没有根本差异。总体而言,集体证据表明,远程指导支持诊断,无创治疗以及最终的复苏手术,以潜在地挽救那些在严峻环境中放血的人,因此应进行更严格的研究。
  • 【使用5选择系列反应时间任务研究不同单胺递质和冲动控制的作用。】 复制标题 收藏 收藏
    DOI:10.1177/0269881112466182 复制DOI
    作者列表:Humpston CS,Wood CM,Robinson ES
    BACKGROUND & AIMS: :Previous studies have shown that drugs which block the reuptake of catecholamine neurotransmitters improve impulse control in diseases such as attention deficit hyperactivity disorder (ADHD). Serotonin-specific reuptake inhibitors (SSRI) lack efficacy in ADHD and have been linked to increased suicide risk. The present study investigated drugs with affinity for one or more of the monoamine reuptake transporters using the 5-choice serial reaction time task, a model of attention and impulsivity in rodents. We also tested the effects of the alpha(2)-adreoceptor antagonist, idazoxan and novel antidepressant, agomelatine, which both increase cortical noradrenaline concentrations through non-reuptake mechanisms. Improvements in impulse control were observed with venlafaxine, a serotonin and noradrenaline re-uptake inhibitor (SNRI) but not bupropion (dopamine and noradrenaline re-uptake inhibitor). Sibutramine (SNRI) reduced premature responses by ~50% at the highest dose tested but this was not significant. All three of the SSRIs tested reduced premature responding in a dose-dependent manner, although also slowed response and collection latencies. Neither idazoxan nor agomelatine significantly reduced premature responding, suggesting a lack of efficacy at the doses tested. None of the drugs tested improved attention in this task but sibutramine (SNRI), fluoxetine (SSRI) and paroxetine (SSRI) all increased omissions at the highest dose tested. These data suggest that the SNRIs and SSRIs reduce premature responding but tend to be less specific than noradrenaline specific reuptake inhibitors in this model. SSRIs did not induce any specific impairment in impulse control in this model.
    背景与目标: : 先前的研究表明,阻断儿茶酚胺神经递质再摄取的药物可改善注意力缺陷多动障碍 (ADHD) 等疾病的冲动控制。血清素特异性再摄取抑制剂 (SSRI) 在ADHD中缺乏疗效,并与自杀风险增加有关。本研究使用5选择系列反应时间任务 (啮齿动物的注意力和冲动性模型) 研究了对一种或多种单胺再摄取转运蛋白具有亲和力的药物。我们还测试了 α (2)-受体拮抗剂咪唑嗪和新型抗抑郁药阿戈米拉汀的作用,它们均通过非再摄取机制增加皮质去甲肾上腺素浓度。使用文拉法辛 (一种5-羟色胺和去甲肾上腺素再摄取抑制剂 (SNRI)) 但未使用安非他酮 (多巴胺和去甲肾上腺素再摄取抑制剂) 观察到冲动控制的改善。在测试的最高剂量下,西布曲明 (SNRI) 将过早反应降低约50%,但这并不显著。测试的所有三个ssri均以剂量依赖性方式减少了过早反应,尽管也减慢了反应和收集延迟。依达唑烷和阿戈米拉汀均未显着降低过早反应,表明在测试剂量下缺乏疗效。测试的药物均未提高此任务中的注意力,但西布曲明 (SNRI),氟西汀 (SSRI) 和帕罗西汀 (SSRI) 在测试的最高剂量下均增加了遗漏。这些数据表明,在该模型中,snri和SSRIs减少了过早反应,但特异性不如去甲肾上腺素特异性再摄取抑制剂。在该模型中,SSRIs不会在冲动控制中引起任何特定的损害。
  • 【重大公共假期,体育和社交活动中的酒精中毒: 2000-2009年澳大利亚墨尔本的时间序列分析。】 复制标题 收藏 收藏
    DOI:10.1111/add.12041 复制DOI
    作者列表:Lloyd B,Matthews S,Livingston M,Jayasekara H,Smith K
    BACKGROUND & AIMS: AIMS:To assess the relationship between ambulance attendances, emergency department (ED) presentations and hospital admissions for acute alcohol intoxication and the timing of public holidays, sporting and social events. DESIGN:Time-series analysis was used to explore trends in intoxication in the context of major events. SETTING:Population of Melbourne, Victoria, Australia between 2000 and 2009. PARTICIPANTS:All patients attended by ambulance, presenting to hospital EDs, or admitted to hospital who were classified as acutely alcohol intoxicated. MEASUREMENT:Analysis of daily numbers of presentations for acute alcohol intoxication associated with major events were undertaken, including lead and lag effects. Analyses controlled for day of week and month of year to address temporal and seasonal variations. FINDINGS:Alcohol intoxication presentations were significantly elevated the day before all public holidays, with intoxication cases on the day of public holidays only higher on New Year's Day (ambulance 6.57, 95% confidence intervals (CI): 3.4-9.74; ED 3.34, 95% CI: 1.28-5.4) and ANZAC Day (ambulance 3.71, 95% CI: 0.68-6.75). The Australian Football League (AFL) Grand Final (ED 2.37, 95% CI: 0.55-4.19), Commonwealth Games (ED 2.45, 95% CI: 0.6-4.3) and Melbourne Cup Day (ambulance 6.14, 95% CI: 2.42-9.85) represented the sporting events with significant elevations in acute intoxication requiring medical attention. The last working day before Christmas was the only social event where a significant increase in acute intoxication occurred (ambulance 8.98, 95% CI: 6.8-11.15). CONCLUSIONS:Acute alcohol intoxication cases requiring ambulance, emergency department and hospital in-patient treatment increase substantially on the day preceding public holidays and other major social events.
    背景与目标:
  • 【12,390神经外科患者的 “团队时间” 和手术安全经验。】 复制标题 收藏 收藏
    DOI:10.3171/2012.8.FOCUS12261 复制DOI
    作者列表:Oszvald Á,Vatter H,Byhahn C,Seifert V,Güresir E
    BACKGROUND & AIMS: OBJECT:Quality and safety are basic concerns in any medical practice. Especially in daily surgical practice, with increasing turnover and shortened procedure times, attention to these topics needs to be assured. Starting in 2007, the authors used a perioperative checklist in all elective procedures and extended the checklist in January 2011 according to the so-called team time-out principles, with additional assessment of patient identity and the planned surgical procedure performed immediately before skin incision, including the emergency cases. METHODS:The advanced perioperative checklist includes parts for patient identification, preoperative assessments, team time-out, postoperative treatment, and imaging controls. All parts are signed by the responsible physician except for the team time-out, which is performed and signed by the theater nurse on behalf of the surgeon immediately before skin incision. RESULTS:Between January 2007 and December 2010, 1 wrong-sided bur hole in an emergency case and 1 wrong-sided lumbar approach in an elective case (of 8795 surgical procedures) occurred in the authors' department. Using the advanced perioperative checklist including the team time-out principles, no error occurred in 3595 surgical procedures (January 2011-June 2012). In the authors' department all team members appreciate the chance to focus on the patient, the surgical procedure, and expected difficulties. The number of incomplete checklists and of patients not being transferred into the operating room was lowered significantly (p = 0.002) after implementing the advanced perioperative checklist. CONCLUSIONS:In the authors' daily experience, the advanced perioperative checklist developed according to the team time-out principles improves preoperative workup and the focus of the entire team. The focus is drawn to the procedure, expected difficulties of the surgery, and special needs in the treatment of the particular patient. Especially in emergency situations, the team time-out synchronizes the involved team members and helps to improve patient safety.
    背景与目标:
  • 【[进食障碍患者综合治疗的训练模型]。】 复制标题 收藏 收藏
    DOI:10.3305/nh.2012.27.3.5690 复制DOI
    作者列表:Calvo Sagardoy R,Gallego Morales LT,García de Lorenzo y Mateos A
    BACKGROUND & AIMS: :The need to find effective treatments for patients with Anorexia or Bulimia nervosa has led to the professionals who care for them to develop new forms of treatment that take into account the variables that cause resistance to change. Patients in this study (2006-2009) have the following characteristics: 340 patients who have 7 or more years of evolution and/or have tried numerous previous treatments without having succeeded in starting and / or maintaining the desired changes, that allowed them to recover steadily. As the proposed treatment, the patient-treatment team is based on the principles of the training model. It considers the patient holistically, it informs and provides him with resources to increase its commitment to change. Teaches the patient to take care physically and mentally as a way to regain their health and leave the disorder in a stable way. Includes family members as essential support in the recovery of their closest. Therapists require extensive experience in the treatment of ED, flexibility, ability to integrate with other team members even if they use different theoretical models, skills for group sessions, ability to handle negative emotions and frustration tolerance. Finally, the model presented below has been implemented, recovered patients whose stay in the disorder exceeded 15 years of development and led to permanent occupational disability.
    背景与目标: : 需要为厌食症或神经性贪食症患者找到有效的治疗方法,这导致了照顾他们的专业人员开发新的治疗方法,其中考虑了导致耐药性变化的变量。该研究中的患者 (2006-2009) 具有以下特征: 340具有7年或更长时间的进化和/或尝试了许多先前治疗而没有成功开始和/或维持期望的变化的患者,这使他们能够稳定地恢复。作为建议的治疗方法,患者治疗团队基于培训模型的原理。它从整体上考虑患者,告知并为他提供资源,以增加其对变革的承诺。教导患者在身体和精神上保持谨慎,以恢复健康并以稳定的方式离开疾病。包括家庭成员作为他们最亲近的恢复的基本支持。治疗师需要在治疗ED方面的丰富经验,灵活性,与其他团队成员整合的能力,即使他们使用不同的理论模型,小组会议的技能,处理负面情绪和挫折承受能力。最后,下面介绍的模型已经实施,康复的患者在疾病中的停留时间超过15年,并导致永久性职业残疾。
  • 【放射治疗使用的特征和充分性及其时间趋势。】 复制标题 收藏 收藏
    DOI:10.1016/j.radonc.2012.10.008 复制DOI
    作者列表:Palacios Eito A,Cabezas SG,Ugalde PF,del Campo ER,Romero AO,Martín Mdel M,Arjona JM,Paredes MM
    BACKGROUND & AIMS: BACKGROUND AND PURPOSE:Characterization of radiotherapy activity and its trend over time. Gathering of parameters for future planning of our resources, applicable to similar population areas. Performing a clinical audit of appropriate use of radiotherapy. MATERIAL AND METHODS:Analysis of 9782 patients treated between 1998 and 2008. Descriptive statistics of pathologies and social/demographic characteristics. Intention of treatment. The rate of radiotherapy utilization was estimated and compared with those considered optimal. Rate of reirradiation. RESULTS:The average global rate of radiotherapy utilization for the period was 32.7%. It increased by 23% between 1998 and 2008, while the population of the area rose by 1.04%, equaling an average 1.13 irradiations/1000 inhabitants/year. Radiation treatment has increased by 13.6, 2.3, 1.6 and 1.06 times in patients with prostate, breast, rectal and lung cancer, respectively. Eight percent of radiotherapy treatments involve concurrent chemotherapy. The proportion of treatments with palliative intent was 18.2%. The overall underutilization of radiation therapy in our environment was an estimated 13.4%. CONCLUSIONS:The grade of adequacy of radiation rates in relation with scientific evidence was globally considered suboptimal, especially in lung cancer. There was an upward trend of irradiation in breast and prostate cancer, tending toward rates considered optimal.
    背景与目标:
  • 【作为评估抗结核药物活性的临床前建模框架的一部分,时间终止动力学测定法的作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.tube.2017.04.010 复制DOI
    作者列表:Bax HI,Bakker-Woudenberg IAJM,de Vogel CP,van der Meijden A,Verbon A,de Steenwinkel JEM
    BACKGROUND & AIMS: :Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework.
    背景与目标: 迫切需要新的结核病治疗策略。有许多不同的评估抗结核药物活性的临床前模型,但尚不清楚哪种模型组合最能预测临床治疗效果。这项研究的目的是确定我们的体外时间杀伤动力学测定法作为评估抗结核药物活性的预测性临床前建模框架的资产的作用。在暴露于结核分枝杆菌北京基因型菌株的过程中,确定了六种抗结核药物的浓度和时间依赖性的分枝杆菌杀伤能力,并评估了耐药性。链霉素,利福平和异烟肼对快速生长的结核分枝杆菌最有效。异烟肼与利福平或高剂量乙胺丁醇是唯一的协同药物组合。在异烟肼中添加利福平或链霉素可防止异烟肼耐药性。体外排名显示,对于某些 (但不是所有) 抗结核药物,结核病患者的早期杀菌活性一致。时间杀伤动力学测定法提供了有关药物暴露早期抗结核药物的分枝杆菌杀伤动力学的重要信息。因此,该测定是临床前建模框架的有价值的组成部分。
  • 【受伤前残疾的回忆会随着时间的推移而改变吗?】 复制标题 收藏 收藏
    DOI:10.1136/injuryprev-2012-040457 复制DOI
    作者列表:Williamson OD,Gabbe BJ,Sutherland AM,Hart MJ,Victorian Orthopaedic Trauma Outcome Registry Project Group.
    BACKGROUND & AIMS: BACKGROUND:Pre-injury disability must be determined when assessing whether treatment programs return people to pre-injury status, however there is little empirical evidence to support recommendations that this be done as soon as possible after injury to prevent recall bias. OBJECTIVES:To determine disagreement between recall of pre-injury disability at different time points post-injury and bias towards under- or overestimating pre-injury disability. METHODS:Self-reported pre-injury global disability was assessed within days, 6 months and 12 months post-injury in patients admitted to two level 1 adult trauma centres. Kappa statistics and multiple logistic regression models identified predictors of disagreement between time-points. RESULTS:Pre-injury disability was measured at all time-points in 801 patients. Pre-injury disability at baseline was rated as none, mild, moderate, marked and severe in 80%, 12%, 5.1%, 1.9% and 1.0% respectively. Absolute agreement between baseline and 6 and 12 months respectively, was 79% and 80%. Corresponding kappa values (95% confidence intervals) were 0.33 (0.26-0.40) and 0.32 (0-25-0.38). Patients over 65 years or not completing high school were more likely to report less pre-injury disability at 6 and 12 months than at baseline with adjusted odds ratios (95% confidence intervals) for these groups being 8.24 (4.32-15.72) and 1.93 (1.03-3.64) respectively. CONCLUSIONS:There was little evidence of recall bias in an adult trauma population if self-reported global pre-injury disability was assessed 6 months post-injury. The recall of pre-injury disability up to 6 months post-injury can be used to determine return to pre-injury status, if assessment is not feasible shortly after injury.
    背景与目标:
  • 【出生时间是围产期不良结局的预测指标吗?坦桑尼亚资源匮乏的医院横断面研究。】 复制标题 收藏 收藏
    DOI:10.1186/s12884-017-1358-9 复制DOI
    作者列表:Mgaya A,Hinju J,Kidanto H
    BACKGROUND & AIMS: BACKGROUND:Inconsistent evidence of a higher risk of adverse perinatal outcomes during off-hours compared to office hours necessitated a search for clear evidence of an association between time of birth and adverse perinatal outcomes. METHODS:A cross-sectional study conducted at a tertiary referral hospital compared perinatal outcomes across three working shifts over 24 h. A checklist and a questionnaire were used to record parturients' socio-demographic and obstetric characteristics, mode of delivery and perinatal outcomes, including 5th minute Apgar score, and early neonatal mortality. Risks of adverse outcomes included maternal age, parity, referral status and mode of delivery, and were assessed for their association with time of delivery and prevalence of fresh stillbirth as a proxy for poor perinatal outcome at a significance level of p = 0.05. RESULTS:Off-hour deliveries were nearly twice as likely to occur during the night shift (odds ratio (OR), 1.62; 95% confidence interval (CI), 1.50-1.72), but were unlikely during the evening shift (OR, 0.58; 95% CI, 0.45-0.71) (all p < 0.001). Neonatal distress (O.R, 1.48, 95% CI; 1.07-2.04, p = 0.02), early neonatal deaths (OR, 1.70; 95% CI, 1.07-2.72, p = 0.03) and fresh stillbirths (OR, 1.95; 95% CI, 1.31-2.90, p = 0.001) were more significantly associated with deliveries occurring during night shifts compared to evening and morning shifts. However, fresh stillbirths occurring during the night shift were independently associated with antenatal admission from clinics or wards, referral from another hospital, and abnormal breech delivery (OR 1.9; 95% CI, 1.3-2.9, p = 0.001, for fresh stillbirths; OR, 5.0; 95% CI 1.7-8.3, p < 0.001, for antenatal admission; OR, 95% CI, 1.1-2.9, p < 0.001, for referral form another hospital; and OR 1.6; 95% CI 1.02-2.6, p = 0.004, for abnormal breech deliveries). CONCLUSION:Off-hours deliveries, particularly during the night shift, were significantly associated with higher proportions of adverse perinatal outcomes, including low Apgar score, early neonatal death and fresh stillbirth, compared to morning and evening shifts. Labour room admissions from antenatal wards, referrals from another hospital and abnormal breech delivery were independent risk factors for poor perinatal outcome, particularly fresh stillbirths.
    背景与目标:
  • 【血液透析患者踝臂指数随时间的下降和心血管结局。】 复制标题 收藏 收藏
    DOI:10.1097/MAJ.0b013e31825141bf 复制DOI
    作者列表:Chen SC,Chang JM,Liu WC,Huang JC,Chen YY,Yang TK,Su HM,Chen HC
    BACKGROUND & AIMS: INTRODUCTION:Abnormal ankle-brachial index (ABI) is associated with increased morbidity and mortality in hemodialysis patients. However, whether the decrease in ABI over time carries the prognostic value is unknown. The aim of this study was to assess whether the decrease in ABI over time was a good predictor of poor cardiovascular (CV) prognosis in hemodialysis patients. METHODS:This study enrolled 234 routine hemodialysis patients and 173 patients completed the follow-up. The ABI was measured by an ABI-form device at baseline and at the first year follow-up. The ΔABI was defined as ABI measured at the first year follow-up minus ABI measured at baseline. Progressors of ABI were defined as patients with ΔABI < -0.3. CV events were defined as CV death, hospitalization for unstable angina, nonfatal myocardial infarction, hospitalization for arrhythmia, hospitalization for congestive heart failure and stroke. RESULTS:The follow-up period was 37.8 ± 11.1 months. In the multivariate analysis, progressors of ABI (hazard ratio, 2.71; 95% confidence interval, 1.10-6.68, P = 0.03), decreased albumin and increased high-sensitivity C-reactive protein were associated with increased CV events. CONCLUSIONS:This longitudinal study showed ΔABI < -0.3 was independently associated with an increase in CV events. Hence, a great decrease in ABI over time might be a useful indicator of poor CV prognosis in hemodialysis patients.
    背景与目标:
  • 【缺血性卒中后残疾和病因特异性死亡率演变的时程: 对试验设计的启示.】 复制标题 收藏 收藏
    DOI:10.1161/JAHA.117.005788 复制DOI
    作者列表:Ganesh A,Luengo-Fernandez R,Wharton RM,Gutnikov SA,Silver LE,Mehta Z,Rothwell PM,Oxford Vascular Study.
    BACKGROUND & AIMS: BACKGROUND:Outcome in stroke trials is often based on a 3-month modified Rankin scale (mRS). How 3-month mRS relates to longer-term outcomes will depend on late recovery, delayed stroke-related deaths, recurrent strokes, and nonstroke deaths. We evaluated 3-month mRS and death/disability at 1 and 5 years in a population-based cohort study. METHODS AND RESULTS:In 3-month survivors of ischemic stroke (Oxford Vascular Study; 2002-2014), we related 3-month mRS to disability (defined as mRS >2) at 1 and 5 years and/or death rates (age/sex adjusted). Accrual of disability and index-stroke-related and nonstroke deaths in each poststroke year was categorized according to 3-month mRS. Among 1606 patients with acute ischemic stroke, 181 died within 3 months, but 126 index-stroke-related deaths and 320 other deaths occurred during the subsequent 4866 patient-years of follow-up up to 5 years. Although 69/126 (54.8%) post-3-month index-stroke-related deaths occurred after 1 year, mRS>2 at 1 year strongly predicted these deaths (adjusted hazard ratio=21.94, 95%CI 7.88-61.09, P<0.0001). Consequently, a 3-month mRS >2 was a strong independent predictor of death at both 1 year (adjusted hazard ratio=6.67, 95%CI 4.16-10.69, P<0.0001) and 5 years (adjusted hazard ratio=2.93, 95%CI 2.38-3.60, P<0.0001). Although mRS improved by ≥1 point from 3 months to 1 year in 317/1266 (25.0%) patients with 3-month mRS ≥1, improvement in mRS after 1 year was limited (improvement by ≥1 point: 91/858 [10.6%]; improvement to mRS ≤2: 13/353 [3.7%]). CONCLUSIONS:Our results reaffirm use of the 3-month mRS outcome in stroke trials. Although later recovery does occur, extending follow-up to 1 year would capture most long-term stroke-related disability. However, administrative mortality follow-up beyond 1 year has the potential to demonstrate translation of early disability gains into additional reductions in long-term mortality without much erosion by non-stroke-related deaths.
    背景与目标:

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