BACKGROUND & AIMS: :The distributed genome hypothesis (DGH) states that each strain within a bacterial species receives a unique distribution of genes from a population-based supragenome that is many times larger than the genome of any given strain. The observations that natural infecting populations are often polyclonal and that most chronic bacterial pathogens have highly developed mechanisms for horizontal gene transfer suggested the DGH and provided the means and the mechanisms to explain how chronic infections persist in the face of a mammalian host's adaptive defense mechanisms. Having previously established the validity of the DGH for obligate pathogens, we wished to evaluate its applicability to an opportunistic bacterial pathogen. This was accomplished by construction and analysis of a highly redundant pooled genomic library containing approximately 216,000 functional clones that was constructed from 12 low-passage clinical isolates of Pseudomonas aeruginosa, 6 otorrheic isolates and 6 from other body sites. Sequence analysis of 3,214 randomly picked clones (mean insert size, approximately 1.4 kb) from this library demonstrated that 348 (10.8%) of the clones were unique with respect to all genomic sequences of the P. aeruginosa prototype strain, PAO1. Hypothetical translations of the open reading frames within these unique sequences demonstrated protein homologies to a number of bacterial virulence factors and other proteins not previously identified in P. aeruginosa. PCR and reverse transcription-PCR-based assays were performed to analyze the distribution and expression patterns of a 70-open reading frame subset of these sequences among 11 of the clinical strains. These sequences were unevenly distributed among the clinical isolates, with nearly half (34/70) of the novel sequences being present in only one or two of the individual strains. Expression profiling revealed that a vast majority of these sequences are expressed, strongly suggesting they encode functional proteins.

背景与目标： ：分布式基因组假设（DGH）指出，细菌物种中的每个菌株都从基于种群的超基因组中获得独特的基因分布，其比任何给定菌株的基因组都要大很多倍。自然感染人群通常是多克隆的，大多数慢性细菌病原体具有水平基因转移的高度发达的机制的观点提示了DGH，并提供了解释慢性感染如何面对哺乳动物宿主的适应性防御机制而持续存在的手段和机制。先前已确定DGH对专性病原体的有效性，我们希望评估其对机会细菌病原体的适用性。这是通过构建和分析包含约216,000个功能性克隆的高度冗余的集合基因组文库完成的，该文库由铜绿假单胞菌的12种低通道临床分离株，6种耳泻分离株和6个来自其他身体部位的分离株构建而成。对来自该文库的3,214个随机挑选的克隆（平均插入片段大小，约1.4 kb）进行序列分析，结果表明，对于铜绿假单胞菌原型菌株PAO1的所有基因组序列，其中348个（10.8％）克隆是唯一的。在这些独特序列内的开放阅读框的假想翻译证明了与许多细菌毒力因子和以前在铜绿假单胞菌中未鉴定出的其他蛋白质的蛋白质同源性。进行了基于PCR和逆转录PCR的分析，以分析这些序列的70个开放阅读框子集在11种临床菌株中的分布和表达模式。这些序列在临床分离株中分布不均，只有一半或34个新序列出现在一个或两个单独的菌株中。表达谱分析表明这些序列中的绝大多数都被表达，强烈暗示它们编码功能蛋白。

BACKGROUND & AIMS: AIM:This paper reviews how the interpreter's role is described in empirically based, qualitative cross-cultural interview studies and how trustworthiness is determined. BACKGROUND:Increased immigration during the past decades has created a multiethnic society in many countries. This development poses a challenge to healthcare staff, in that they need to understand how people from different cultures experience health and illness. One way to assess immigrants' experiences is through cross-cultural interview studies, involving an interpreter. Thorough knowledge of the interpreter's role is needed in order to increase the trustworthiness of this kind of nursing research. METHOD:Literature searches were conducted from October to November 2004 using PubMed, CINAHL, Psycinfo, Sociological abstract, Your Journals@ovid, and Eric databases. Qualitative interview studies written in English and performed with an interpreter were included. The Matrix Method was used to review the literature. FINDINGS:In almost all of the 13 relevant papers found, the role of the interpreter(s) in the research process was only sparsely described. In addition, all studies except one employed different techniques to established trustworthiness. The most common techniques were prolonged engagement, member check or triangulation, the latter performed either on the data, investigators or methods. CONCLUSION:Methodological issues with respect to interpreters have received only limited attention in cross-cultural interview studies. Researchers in the field of nursing need to consider (1) the interpreter's role/involvement in the research process; (2) the interpreter's competence and the style of interpreting; (3) the interpreter's impact on the findings. This information is a prerequisite when trying to determine the trustworthiness of a cross-cultural study.

背景与目标： 目的：本文回顾了如何在基于经验的定性跨文化访谈研究中描述口译员的角色，以及如何确定信任度。
背景：过去几十年来移民的增加在许多国家创建了一个多种族的社会。这种发展对医护人员提出了挑战，因为他们需要了解来自不同文化背景的人们如何经历健康和疾病。评估移民经验的一种方法是通过跨文化访谈研究，其中包括一名口译员。为了增加这种护理研究的可信度，需要对口译员的作用有透彻的了解。
方法：从2004年10月至2004年11月使用PubMed，CINAHL，Psycinfo，Sociological abstract，Your Journals @ ovid和Eric数据库进行文献检索。包括用英语撰写并由口译员进行的定性访谈研究。矩阵法用于回顾文献。
结果：在发现的所有13篇相关论文中，几乎都很少描述口译员在研究过程中的作用。此外，除一项研究外，所有研究均采用不同的技术来建立可信度。最常见的技术是长时间的接触，成员检查或三角剖分，后者根据数据，研究人员或方法进行。
结论：关于口译员的方法论问题在跨文化访谈研究中仅受到了有限的关注。护理领域的研究人员需要考虑（1）口译员在研究过程中的角色/参与程度； （二）口译人员的能力和口译风格； （3）口译员对调查结果的影响。在尝试确定跨文化研究的可信赖性时，此信息是前提条件。

BACKGROUND & AIMS: BACKGROUND:Current genomic research methods provide researchers with enormous amounts of data. Combining data from different high-throughput research technologies commonly available in biological databases can lead to novel findings and increase research efficiency. However, combining data from different heterogeneous sources is often a very arduous task. These sources can be different microarray technology platforms, genomic databases, or experiments performed on various species. Our aim was to develop a software program that could facilitate the combining of data from heterogeneous sources, and thus allow researchers to perform genomic cross-platform/cross-species studies and to use existing experimental data for compendium studies. RESULTS:We have developed a web-based software resource, called CROPPER that uses the latest genomic information concerning different data identifiers and orthologous genes from the Ensembl database. CROPPER can be used to combine genomic data from different heterogeneous sources, allowing researchers to perform cross-platform/cross-species compendium studies without the need for complex computational tools or the requirement of setting up one's own in-house database. We also present an example of a simple cross-platform/cross-species compendium study based on publicly available Parkinson's disease data derived from different sources. CONCLUSION:CROPPER is a user-friendly and freely available web-based software resource that can be successfully used for cross-species/cross-platform compendium studies.

背景与目标： 背景：目前的基因组研究方法为研究人员提供了大量数据。结合生物学数据库中常用的不同高通量研究技术的数据，可以得出新颖的发现并提高研究效率。但是，合并来自不同异构源的数据通常是一项艰巨的任务。这些来源可以是不同的微阵列技术平台，基因组数据库或对各种物种进行的实验。我们的目标是开发一个软件程序，以方便来自不同来源的数据的合并，从而使研究人员能够进行基因组跨平台/跨物种的研究，并将现有的实验数据用于纲要研究。
结果：我们开发了一个基于Web的软件资源，称为CROPPER，该资源使用有关Ensembl数据库中不同数据标识符和直系同源基因的最新基因组信息。 CROPPER可用于组合来自不同异构来源的基因组数据，从而使研究人员无需复杂的计算工具或建立自己的内部数据库即可进行跨平台/跨物种纲要研究。我们还提供了一个简单的跨平台/跨物种纲要研究的例子，该研究基于从不同来源获得的公开可用的帕金森氏病数据。
结论：CROPPER是一种用户友好且免费提供的基于Web的软件资源，可以成功地用于跨物种/跨平台纲要研究。

BACKGROUND & AIMS: Previous mutagenesis studies with bacteriorhodopsin have shown that reprotonation of the Schiff's base is the rate-limiting step in the photocycle of the D96N mutant, whereas retinal re-isomerization and return of the protein to the initial state constitute the rate-limiting events in the photocycle of the L93A mutant. Thus, in the D96N mutant, decay of the M intermediate is slowed down by more than 100-fold at pH 7. In the L93A mutant, decay of the O intermediate is slowed down by 250-fold. We report here that in the L93A, D96N double mutant, decay of the M intermediate, as well as the formation and decay of the O intermediate, are slowed down dramatically. The photocycle is completed by the decay of a long-lived O intermediate, as in the L93A mutant. The decay of the M and O intermediates in the double mutant parallels the behavior seen in the single mutants over a wide temperature and pH range, arguing that the observed independence is an intrinsic property of the mutant. The slow decay of the M and O intermediates can be selectively and independently reversed under conditions identical to those used for the corresponding intermediates in the D96N and L93A single mutants. Because the effects of the two individual mutations are preserved in the double mutant and can be independently reversed, we conclude that residues Asp 96 and Leu 93 act independently and at different stages of the bacteriorhodopsin photocycle. These results also show that formation of the O intermediate only requires protonation of the Schiff's base and is independent of the protonation of Asp 96 from the aqueous medium.

背景与目标： 先前使用细菌视紫红质的诱变研究表明，席夫氏碱的质子化是D96N突变体光循环中的限速步骤，而视网膜重新异构化和蛋白质返回到初始状态构成了光循环中的限速事件L93A突变体的序列。因此，在D96N突变体中，pH值为7时，M中间体的衰减被减慢了100倍以上。在L93A突变体中，O中间体的衰减被减慢了250倍。我们在此报告，在L93A，D96N双重突变体中，M中间产物的衰减以及O中间产物的形成和衰减都大大减慢了。像L93A突变体一样，光循环是通过长寿命的O中间体的衰变完成的。双重突变体中M和O中间体的衰变与单个突变体在较宽的温度和pH范围内观察到的行为相似，认为观察到的独立性是突变体的固有特性。 M和O中间体的缓慢衰变可以在与D96N和L93A单个突变体中相应中间体相同的条件下有选择地独立逆转。因为两个单独的突变的影响保留在双突变体中，并且可以独立逆转，所以我们得出结论，残基Asp 96和Leu 93分别在细菌视紫红质光循环的不同阶段起作用。这些结果还表明，O中间体的形成仅需要席夫碱的质子化，而与来自水性介质的Asp 96的质子化无关。

BACKGROUND & AIMS: PURPOSE:To determine the clinical importance and relative value of reinterpreting brain CT imaging studies by subspecialty experts regarding changes in clinical management. METHODS:Computerized records were queried at two institutions during the years 2002-2003 for both primary interpretation by board-certified nonneuroradiologists and secondary interpretation by three neuroradiologists. A total of 1,081 cases were reviewed. Each case was initially interpreted as an emergent or urgent study. The reinterpreted studies were scored as concordant or discordant by the subspecialty experts. The discordant studies were then categorized as a "major discordance" if there was a change in clinical management, or as a "minor discordance" if there was no impact or change in clinical management. RESULTS:Of the 1,081 studies reviewed, 14 studies were identified as discordant (1.3%). Of those discordant studies, four were categorized as major discrepancies necessitating a change in clinical management (0.4 %). Ten were categorized as minor discrepancies (0.9%). There were no permanent adverse outcomes with respect to morbidity and mortality as a result of any discrepancy. CONCLUSION:The vast majority of interpreted head CT cases read by board-certified general radiologists do not result in discordant interpretations as verified by subspecialty experts. Discordant interpretations did not result in changes in clinical management in most cases. Double reading of head CTs by subspecialty experts appears to be an inefficient method of substantially improving imaging health quality outcomes.

背景与目标： 目的：确定亚专业专家对临床管理变化进行重新解释脑CT成像研究的临床重要性和相对价值。
方法：在2002年至2003年期间，在两家机构中查询了计算机记录，以获取由董事会认证的非神经放射科医生进行的主要解释和由三位神经放射科医生进行的次要解释。总共审查了1,081例。最初，每个案例都被解释为紧急研究。重新解释的研究被专业专家评定为一致或不一致。如果临床管理发生变化，则将不一致的研究分类为“重大不一致”，如果临床管理没有影响或发生变化，则将其分类为“轻微不一致”。
结果：在所审查的1,081项研究中，有14项研究被确定为不一致（1.3％）。在这些不一致的研究中，有四项被归类为需要改变临床管理的主要差异（0.4％）。十个分类为轻微差异（0.9％）。任何差异都不会在发病率和死亡率方面带来永久性的不良后果。
结论：经董事会认证的一般放射科医生阅读的绝大多数解释性头部CT病例，经专科专家验证，并不会导致不一致的解释。在大多数情况下，不一致的解释并不会导致临床管理的改变。专科专家对头颅CT进行双重读取似乎是一种实质上改善影像健康质量结果的无效方法。

BACKGROUND & AIMS: BACKGROUND:Choline is essential for fetal brain development, and it is not known whether a typical American diet contains enough choline to ensure optimal brain development. OBJECTIVE:The study was undertaken to determine whether supplementing pregnant women with phosphatidylcholine (the main dietary source of choline) improves the cognitive abilities of their offspring. DESIGN:In a double-blind, randomized controlled trial, 140 pregnant women were randomly assigned to receive supplemental phosphatidylcholine (750 mg) or a placebo (corn oil) from 18 wk gestation through 90 d postpartum. Their infants (n = 99) were tested for short-term visuospatial memory, long-term episodic memory, language development, and global development at 10 and 12 mo of age. RESULTS:The women studied ate diets that delivered ∼360 mg choline/d in foods (∼80% of the recommended intake for pregnant women, 65% of the recommended intake for lactating women). The phosphatidylcholine supplements were well tolerated. Groups did not differ significantly in global development, language development, short-term visuospatial memory, or long-term episodic memory. CONCLUSIONS:Phosphatidylcholine supplementation of pregnant women eating diets containing moderate amounts of choline did not enhance their infants' brain function. It is possible that a longer follow-up period would reveal late-emerging effects. Moreover, future studies should determine whether supplementing mothers eating diets much lower in choline content, such as those consumed in several low-income countries, would enhance infant brain development.

背景与目标： 背景：胆碱对胎儿的大脑发育至关重要，目前尚不清楚典型的美国饮食中是否含有足够的胆碱以确保最佳的大脑发育。
目的：本研究旨在确定孕妇补充磷脂酰胆碱（胆碱的主要饮食来源）是否能改善其后代的认知能力。
设计：在一项双盲，随机对照试验中，从怀孕18周到产后90天，随机分配了140名孕妇接受补充磷脂酰胆碱（750毫克）或安慰剂（玉米油）。他们的婴儿（n = 99）在10和12个月大时接受了短期视觉空间记忆，长期情境记忆，语言发展和整体发展的测试。
结果：这些妇女所研究的饮食中食物中的胆碱/日摄入量约为360毫克/天（孕妇的推荐摄入量约为80％，哺乳期妇女的推荐摄入量约为65％）。磷脂酰胆碱补充剂的耐受性良好。在全球发展，语言发展，短期视觉空间记忆或长期情境记忆方面，各组没有显着差异。
结论：孕妇食用含适量胆碱饮食的磷脂酰胆碱不能增强婴儿的脑功能。较长的随访期可能会显示出较晚出现的影响。此外，未来的研究应确定补充食用胆碱含量低得多的饮食的母亲（如在几个低收入国家食用的饮食）是否会增强婴儿的大脑发育。

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： ：急诊科通常会对新发作的癫痫患者进行广泛的实验室检查。为了确定此类测试的实用性，对在市内大学附属教学医院急诊室就诊的新发癫痫患者进行了一项前瞻性研究。在1984年10月至1988年1月之间，共有136例患者进入研究。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共同原因之前，以标准化的形式记录相关的历史信息和体格检查结果。这些患者包括四名低血糖患者，四名高血糖患者，两名低钙血症患者和一名低镁血症患者。根据病史或体格检查的结果，仅怀疑2例（低血糖）。在ED患者中，由于可纠正的代谢紊乱引起的新发作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，不必要进行广泛的ED实验室检查以评估新发癫痫发作。进一步的测试顺序应由病史和体格检查指示。

BACKGROUND & AIMS: AIM:To report the patterns and sites of 18-FDG uptake in patients of presumed ocular tuberculosis. MATERIALS AND METHODS:The clinical and investigational findings of 11 patients were reviewed retrospectively. These included 6 males and 5 females with a mean age of 46.2 years. 21 eyes were included in the data analysis. Clinical presentations include 15 eyes with anterior uveitis, 2 eyes with retinal vasculitis, 2 eyes with panuveitis and 2 eyes with multifocal choroidopathy. RESULTS:Two distinct patterns of systemic uptake emerged. Pattern 1: No detectable systemic uptake (4 patients). Pattern 2: Detectable systemic uptake. a. Chest disease only (2 patients). b. Disseminated pattern, uptake seen at multiple sites (4 patients). c. Extrapulmonary only (1 patient). CONCLUSIONS:Ocular tuberculosis may often be part of a wider disseminated disease.

背景与目标： 目的：报道假定的眼结核患者摄取18-FDG的方式和部位。
材料与方法：回顾性分析11例患者的临床和研究结果。其中包括6名男性和5名女性，平均年龄为46.2岁。数据分析包括21只眼睛。临床表现包括前葡萄膜炎15眼，视网膜血管炎2眼，胰腺炎2眼和多灶性脉络膜病变2眼。
结果：出现了两种不同的全身吸收模式。模式1：未检测到全身吸收（4例患者）。模式2：可检测到的全身吸收。一种。仅胸部疾病（2例）。 b。分布模式，在多个部位可见吸收（4例）。 C。仅肺外（1例患者）。
结论：眼结核通常可能是更广泛传播的疾病的一部分。

BACKGROUND & AIMS: :Novel double-capped triplet drugs, which have one pharmacophore unit and two epoxymethano or dimethylepoxymethano structures (termed cap or diMe-cap structures, respectively) were synthesized. Key intermediate oxazoline 16 derived from acetone enabled the effective synthesis of double-capped triplets. SYK-134 (7a) and SYK-135 (8a) with N-cyclopropylmethyl substituent and cap structures showed selectivities for the κ opioid receptor. On the other hand, the N-Me series exhibited selectivities for the μ opioid receptor. The double-capped triplet drugs with diMe-cap structures preferred the μ receptor independently of their N-substituents. SYK-385 (19b), one of the μ-selective double-capped triplet drugs, showed the highest selectivity for the μ receptor among the reported μ-selective nonpeptide ligands.

背景与目标： 合成了具有一个药效团单元和两个环氧亚甲基或二甲基环氧亚甲基结构（分别称为帽或二甲基-帽结构）的新型双封端三联体药物。源自丙酮的关键中间体恶唑啉16能够有效合成双封三胞胎。具有N-环丙基甲基取代基和帽结构的SYK-134（7a）和SYK-135（8a）对κ阿片受体具有选择性。另一方面，N-Me系列对μ阿片受体具有选择性。具有diMe-cap结构的双封端三联体药物优选μ受体，而与它们的N取代基无关。微米选择性双封端三联体药物之一SYK-385（19b）在已报道的微米选择性非肽配体中显示出对微米受体的最高选择性。

BACKGROUND & AIMS: :Two-hundred and ninety-three patients without a previous vaginal delivery were randomized to intracervical/extra-amniotic application of 0.5 mg prostaglandin E2 (PGE2) or to gel only. Of the patients who received PGE2, 18.7% were admitted before the next morning due to spontaneous abortion, bleeding or pains. No other side-effect was observed. A statistically significant dilatation of the cervical canal was found in the prostaglandin group. Thirty percent of the treated patients did not need further dilatation of the cervix 25.4% were non-responders to PGE2 and 7.7% were hyper-responders. The number of uterine perforations, pelvic inflammatory disease (PID) or retained pregnancy products were not influenced by the pretreatment with PGE2.

背景与目标： ：293例以前没有阴道分娩的患者被随机分配至0.5 mg前列腺素E2（PGE2）的脑内/羊膜外给药或仅凝胶化。在接受PGE2的患者中，由于自然流产，出血或疼痛，第二天早晨收治了18.7％的患者。没有观察到其他副作用。在前列腺素组中发现了颈管的统计学上显着的扩张。接受治疗的患者中有30％不需要进一步扩张子宫颈，PGE2无反应者为25.4％，高反应者为7.7％。子宫穿孔，盆腔炎（PID）或保留的妊娠产物的数量不受PGE2预处理的影响。

BACKGROUND & AIMS: BACKGROUND:The aim of this study was to evaluate the role of flexible cystoscopy in preventing malpositioning of the ureteral stent after laparoscopic ureterolithotomy in male patients. METHODS:From April 2009 to June 2015, 97 male patients with stones >1.8 cm in the upper ureter underwent intracorporeal double-J stenting of the ureter after laparoscopic ureterolithotomy performed by four different surgeons. In the last 50 patients who underwent laparoscopic ureterolithotomy flexible cystoscopy was performed through the urethral route to confirm the position of the double-J stent, while in the first 47 correct positioning of the stent was confirmed through postoperative KUB. The demographic data and perioperative outcomes were reviewed retrospectively. Penalized logistic regression analysis was used to evaluate the effects of flexible cystoscopy. RESULTS:Upward malpositioning of the ureteral stent was found in 9 of the 47 (19.1%) patients who underwent surgery without flexible cystoscopy. Among the 50 most recent patients who underwent surgery with flexible cystoscopy through the urethral route, upward malpositioning was observed in 10 (20%) patients. The factors preventing upward malpositioning of the double-J catheter in multivariate analysis were surgeon (p = 0.039) and use of flexible cystoscopy (p = 0.008). CONCLUSION:Flexible cystoscopy is a simple, safe, quick, and effective method to identify and correct malpositioning of double-J stents, especially in male patients. TRIAL REGISTRATION:This study was registered with ClinicalTrials.gov Registry on May 11, 2017 (retrospective registration) with a trial registration number of NCT03150446 .

背景与目标： 摘要背景：本研究的目的是评估柔性膀胱镜在预防男性患者腹腔镜输尿管结石术后输尿管支架位置不正中的作用。
方法：2009年4月至2015年6月，由四位不同的医生进行了腹腔镜输尿管结石切除术后，对97例输尿管上段结石> 1.8 cm的男性男性患者进行了输尿管的体内双J支架置入术。在最近的50例中，通过尿道路线进行了腹腔镜输尿管结石术的柔性膀胱镜检查以确认double-J支架的位置，而在最初的47例中，通过术后KUB确认了支架的正确位置。回顾性地回顾了人口统计学数据和围手术期结局。惩罚逻辑回归分析用于评估柔性膀胱镜检查的效果。
结果：47例（19.1％）患者中，有9例（19.1％）接受了无膀胱镜检查，输尿管支架向上定位不良。在最近通过尿道经膀胱膀胱镜手术的50例患者中，有10例（20％）患者出现错位。在多因素分析中，防止双J导管向上错位的因素是外科医生（p = 0.039）和使用柔性膀胱镜检查（p = 0.008）。
结论：柔性膀胱镜检查是一种简单，安全，快速，有效的方法，可以识别和纠正双J支架的位置不正确，特别是在男性患者中。
试验注册：本研究于2017年5月11日在ClinicalTrials.gov注册中心进行了注册（回顾性注册），试验注册号为NCT03150446。

BACKGROUND & AIMS: BACKGROUND:Injectable daxibotulinumtoxinA (RT002) is an investigational botulinum toxin Type A in clinical development. It is formulated with a proprietary peptide and offers the potential of a longer acting neurotoxin therapy. OBJECTIVE:To compare the safety, efficacy, and duration of response of daxibotulinumtoxinA with onabotulinumtoxinA and placebo [www.clinicaltrials.gov NCT02303002]. METHODS:In this Phase 2, randomized, dose-ranging, parallel-group, double-blind, multicenter study, subjects with moderate or severe glabellar lines at maximum frown were randomly assigned to 20U, 40U, or 60U daxibotulinumtoxinA, 20U onabotulinumtoxinA, or placebo. Glabellar line severity was evaluated by investigators and subjects at least every 4 weeks, for at least 24 weeks. RESULTS:Overall, 268 subjects enrolled. Statistical and clinical superiority were observed for 40U and 60U daxibotulinumtoxinA over 20U onabotulinumtoxinA for a range of efficacy outcomes despite the study not being powered to detect statistically significant differences between these active treatment groups. CONCLUSION:The 40U dose of daxibotulinumtoxinA was well tolerated (e.g., absence of ptosis) and had the most favorable risk: benefit profile. Compared with 20U onabotulinumtoxinA, it exhibited a significantly greater response rate and a significantly longer duration of response (median of 24 weeks vs 19 weeks; p = .030).

背景与目标： 背景：可注射的daxibotulinumtoxinA（RT002）是临床开发中的一种研究型A型肉毒毒素。它由专有肽配制而成，具有长效神经毒素治疗的潜力。
目的：比较daxibotulinumtoxinA，onabotulinumtoxinA和安慰剂的安全性，疗效和反应持续时间[www.clinicaltrials.gov NCT02303002]。
方法：在该阶段2中，随机，剂量范围，平行分组，双盲，多中心研究将具有最大皱眉的中度或重度纹眉系的受试者随机分配至20U，40U或60U daxibotulinumtoxinA，20U onabotulinumtoxinA或安慰剂。研究者和受试者至少每4周，至少24周评估眉毛线的严重程度。
结果：总体上，招募了268名受试者。尽管该研究未能检测出这些活跃治疗组之间的统计学显着差异，但观察到40U和60U daxibotulinumtoxinA优于20U onabotulinumtoxinA在一系列功效方面的统计学和临床​​优势。
结论：40U剂量的daxibotulinumtoxinA具有良好的耐受性（例如，没有上睑下垂），并且具有最有利的风险：获益特征。与20U的肉毒杆菌毒素A相比，它显示出显着更高的应答率和显着更长的应答持续时间（中位24周vs 19周； p = .030）。

BACKGROUND & AIMS: :T cell regulation of the generation of thyroglobulin plaque-forming cells (Tg PFC) and protein A plaque-forming cells (Prot A PFC) was investigated using lymphocytes from patients with autoimmune thyroid disease. T and B cell mixed cultures (T-B MC) were carried out without mitogenic or antigenic stimulation to identify physiological T cell effects in the system. Tg PFC were found in 8 (44%) of 18 patients who had high titers of thyroglobulin antibody in their sera. Tg-specific and nonspecific immunoregulation by T cells from patients and normal subjects was studied using B cells from these eight patients in the T-B MC system. Remarkably lower values of Tg PFC induction compared to Prot A PFC induction were found after T cell addition. Normal T cells inhibited Tg PFC induction, but patient T cells did not, while the same extent of helper effects were found on Prot A PFC induction by the addition of patient and normal T cells. Irradiation (1500 rads) of T cells from patients and normal subjects significantly enhanced both TgPFC and Prot A PFC induction. Thus, Tg-specific suppressor T cells are present in all normal subjects as part of the radiosensitive suppressor T cell subset. The increase in Tg-PFC caused by irradiation-induced inhibition of Tg-specific suppressor T cell function was significantly greater in normal subjects than in patients. Histamine type 2 receptor-bearing T cells inhibited Prot A PFC induction, but not Tg PFC induction, in the autologous T-B MC system. No Tg PFC were induced from normal B cells in any combination with untreated T cells, irradiated T cells, or histamine type 2 receptor-negative T cells from patients or normal subjects. These data indicate that in vitro Tg-specific T cell regulation can be studied in the T-B MC system by using B cells from patients with autoimmune thyroid disease with high Tg antibody titers in their sera. Tg-specific suppressor T cells appear to be present in all individuals and to be involved in the regulation of Tg antibody production. The lower activity of Tg-specific suppressor T cells in patients compared to that in normal subjects may be related to Tg antibody production in vivo. This abnormality, however, is heterogeneous and is not a complete but, rather, is a relative defect of Tg-specific suppressor T cells.

背景与目标： ：使用自身免疫性甲状腺疾病患者的淋巴细胞研究了甲状腺球蛋白斑块形成细胞（Tg PFC）和蛋白A斑块形成细胞（Prot A PFC）生成的T细胞调节。在无有丝分裂或抗原刺激的情况下进行T细胞和B细胞混合培养（T-B MC），以鉴定系统中的生理性T细胞效应。在血清中滴度高的甲状腺球蛋白抗体的18例患者中，有8例（44％）发现了Tg PFC。使用来自这八名患者的B细胞在T-B MC系统中研究了来自患者和正常受试者的T细胞的Tg特异性和非特异性免疫调节。在添加T细胞后，发现Tg PFC诱导的值比Prot A PFC诱导的低得多。正常T细胞抑制Tg PFC诱导，但对患者T细胞没有抑制作用，而通过添加患者和正常T细胞对Prot A PFC诱导发现了相同程度的辅助作用。患者和正常受试者的T细胞辐射（1500 rads）显着增强了TgPFC和Prot A PFC的诱导作用。因此，Tg特异性抑制T细胞作为放射抑制性T细胞亚群的一部分存在于所有正常受试者中。由辐射诱导的Tg特异性抑制T细胞功能的抑制引起的Tg-PFC的增加在正常受试者中比在患者中显着更大。在自体T-B MC系统中，带有组胺2型受体的T细胞抑制Prot A PFC诱导，但不抑制Tg PFC诱导。正常B细胞​​与未经治疗的T细胞，经辐照的T细胞或来自患者或正常受试者的组胺2型受体阴性T细胞的任何组合均未诱导Tg PFC。这些数据表明，可以通过使用来自自身免疫性甲状腺疾病患者血清中Tg抗体滴度高的患者的B细胞，在T-B MC系统中研究体外Tg特异性T细胞调节。 Tg特异性抑制性T细胞似乎存在于所有个体中，并参与Tg抗体产生的调节。与正常受试者相比，患者中Tg特异性抑制性T细胞的活性较低可能与体内Tg抗体的产生有关。然而，这种异常是异质的，不是完全的，而是Tg特异性抑制性T细胞的相对缺陷。

BACKGROUND & AIMS: :Our experience with the subcutaneous absorbable bridge for constructing a temporary loop ileostomy and loop colostomy is described. The use of this subcutaneous absorbable bridge in 15 patients - 6 with loop ileostomy and 9 with loop colostomy - was almost without complications. The absorbable bridge is a progress for maturation of the stoma and for immediate postoperative as prospective fitting of a watertight appliance. The actual trend substituting the temporary loop colostomy by the loop ileostomy may be advanced by the unlimited use of the subcutaneous absorbable bridge for constructing a temporary loop ileostomy.

背景与目标： ：我们描述了使用皮下可吸收桥构建临时loop回肠造口术和loop结肠造瘘术的经验。这种皮下可吸收桥在15例患者中使用-6回肠造口术6例，loop肠造瘘术9例-几乎没有并发症。可吸收桥是造口成熟和作为水密器具的前瞻性装配后立即手术的进步。通过无限地使用皮下可吸收桥来构造临时性回肠造口术，可以促进用by回肠造口术代替临时性loop回结肠造瘘术的实际趋势。

BACKGROUND & AIMS: :Antitubercular therapy (ATT) induced hepatotoxicity, although well known to clinicians, is often over looked and underrated. Given the low threshold of starting ATT, especially empirically, the adverse manifestations can take a considerable toll. A variety of associated risk factors compound the morbidity. We throw light on one such a case where ATT was detrimental to the patient and review the literature and possible preventive strategies.

背景与目标： ：抗结核疗法（ATT）诱导的肝毒性，尽管是临床医生所熟知的，但经常被忽视和低估。鉴于启动ATT的门槛很低，尤其是凭经验，不利的表现可能会造成巨大的损失。各种相关的危险因素加重了发病率。我们对ATT对患者有害的一种情况进行了阐述，并回顾了文献和可能的预防策略。