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，在pH 7时，M中间体的衰减减慢了100倍以上。在L93A突变体中，O中间体的衰减减慢了250倍。我们在这里报告说，在L93A，D96N双突变体中，M中间物的衰减以及O中间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中间体的降解来完成的。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。因为两个突变体的作用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的脑部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，以及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“较小不一致”。
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: :The study demonstrates the application of QbD based on historical data for a product at a later development stage - retrospective QbD (rQbD). More specifically, it is investigated the root-cause for the observed slower drug release in Orodispersible Films (ODFs) during storage. Risk assessment tools were used to identify parameters affecting ODFs critical quality attributes, namely percent drug release and residual water content. The parameters room temperature, room relative humidity, drying temperature and mixing equipment were used in the statistical modeling of the available data. The estimated models were then used to define the feasible working region. Statistical modeling indicates that initial residual water content of the ODFs is mainly affected by 2nd order interactions of room temperature, room relative humidity and drying temperature, while the stability of drug release profile is mostly influenced by room temperature and an interaction between room relative humidity and drying temperature. Depending on the drying temperature employed the effect of room temperature and room relative humidity change significantly. This work shows that it is possible to apply rQbD to achieve a greater understanding of the manufacturing process of ODFs and to define a proper design space.

背景与目标： ：研究证明了基于历史数据的QbD在后期产品开发中的应用-回顾性QbD（rQbD）。更具体地说，研究了在储存过程中观察到的较慢的药物在口腔分散膜（ODF）中释放的根本原因。风险评估工具用于确定影响ODF关键质量属性的参数，即药物释放百分比和残留水分。在可用数据的统计模型中，使用了室温，室内相对湿度，干燥温度和混合设备等参数。然后，将估计的模型用于定义可行的工作区域。统计模型表明，ODFs的初始残留水含量主要受室温，室温相对湿度和干燥温度的二阶相互作用影响，而药物释放曲线的稳定性主要受室温以及室温相对湿度与干燥温度之间相互作用的影响。干燥温度。取决于所采用的干燥温度，室温和室内相对湿度的影响会明显变化。这项工作表明，有可能应用rQbD来更好地理解ODF的制造过程并定义适当的设计空间。

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：报告推测的眼结核患者摄取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: OBJECTIVE:To identify early clinical factors that are correlated with death or severe disability in paediatric patients who have sustained an injury by hanging or strangulation. METHODS:A retrospective review of all patient records from January 1, 1997, to September 30, 2007, was conducted. Patient records were identified by International Classification of Diseases and Related Health Problems, Tenth Revision, Canada diagnostic codes for asphyxia, strangulation, hypoxic-ischemic encephalopathy, hanging, hypoxemia, hypoxia or anoxia. RESULTS:A total of 109 records were identified. Of these, 41 met the inclusion criteria for the study. Of 19 (46%) children who were pulse-less and received cardiopulmonary resuscitation, 16 died and the survivors were severely disabled. Of the 22 (54%) children who were found with a pulse, 18 made a full recovery. CONCLUSIONS:Children who are pulseless at discovery for hanging injuries are at high risk of death or severe disability. Early clinical and neurophysiological indicators should be applied systematically to best guide clinicians and parents in their decision making.

背景与目标： 目的：确定与因悬挂或绞死而受伤的小儿患者的死亡或严重残疾有关的早期临床因素。
方法：对1997年1月1日至2007年9月30日的所有患者记录进行回顾性回顾。通过国际疾病分类和相关健康问题分类（第十次修订版，加拿大）对窒息，窒息，缺氧缺血性脑病，悬挂，低氧血症，缺氧或缺氧的诊断代码确定了患者的记录。
结果：共鉴定到109条记录。其中有41个符合研究的纳入标准。在19名（46％）无脉搏并接受心肺复苏的儿童中，有16人死亡，幸存者严重残疾。在发现有脉搏的22名儿童中（54％），其中18名完全康复。
结论：发现悬吊伤害而无脉搏的儿童极有可能导致死亡或严重残疾。应系统地应用早期临床和神经生理指标，以最好地指导临床医生和父母进行决策。

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: BACKGROUND:There are a growing number of observational studies that do not only focus on single biomarkers for predicting an outcome event, but address questions in a multivariable setting. For example, when quantifying the added value of new biomarkers in addition to established risk factors, the aim might be to rank several new markers with respect to their prediction performance. This makes it important to consider the marker correlation structure for planning such a study. Because of the complexity, a simulation approach may be required to adequately assess sample size or other aspects, such as the choice of a performance measure. METHODS:In a simulation study based on real data, we investigated how to generate covariates with realistic distributions and what generating model should be used for the outcome, aiming to determine the least amount of information and complexity needed to obtain realistic results. As a basis for the simulation a large epidemiological cohort study, the Gutenberg Health Study was used. The added value of markers was quantified and ranked in subsampling data sets of this population data, and simulation approaches were judged by the quality of the ranking. One of the evaluated approaches, the random forest, requires original data at the individual level. Therefore, also the effect of the size of a pilot study for random forest based simulation was investigated. RESULTS:We found that simple logistic regression models failed to adequately generate realistic data, even with extensions such as interaction terms or non-linear effects. The random forest approach was seen to be more appropriate for simulation of complex data structures. Pilot studies starting at about 250 observations were seen to provide a reasonable level of information for this approach. CONCLUSIONS:We advise to avoid oversimplified regression models for simulation, in particular when focusing on multivariable research questions. More generally, a simulation should be based on real data for adequately reflecting complex observational data structures, such as found in epidemiological cohort studies.

背景与目标： 背景技术：越来越多的观察性研究不仅专注于单个生物标志物来预测结果事件，而且在多变量环境中解决问题。例如，当量化除已建立的风险因素外的新生物标记物的附加值时，目标可能是就其预测性能对几种新标记物进行排名。因此，重要的是要考虑标记物相关结构以进行此类研究。由于其复杂性，可能需要一种仿真方法来充分评估样本大小或其他方面，例如性能指标的选择。
方法：在基于真实数据的模拟研究中，我们调查了如何生成具有实际分布的协变量，以及应使用哪种生成模型进行结果计算，旨在确定获得实际结果所需的最少信息量和复杂度。大型流行病学队列研究作为模拟的基础，使用了古腾堡健康研究。对标记的增加值进行量化，并在该总体数据的子采样数据集中进行排名，并根据排名的质量来判断模拟方法。评估方法之一是随机森林，它需要各个级别的原始数据。因此，还研究了基于随机森林的模拟试验研究规模的影响。
结果：我们发现简单的逻辑回归模型无法充分生成现实数据，即使具有交互项或非线性效应等扩展。人们认为，随机森林方法更适合于复杂数据结构的仿真。从大约250个观察值开始的试点研究被认为为该方法提供了合理水平的信息。
结论：我们建议避免过度简化的回归模型进行仿真，尤其是在关注多变量研究问题时。更一般而言，模拟应基于真实数据，以充分反映复杂的观察数据结构，例如流行病学队列研究中发现的结构。

BACKGROUND & AIMS: OBJECTIVES:To estimate the agreement between prenatal ultrasonography observations at 16 - 21 gestational weeks and fetal autopsy findings in pregnancies terminated because of fetal anomalies. STUDY DESIGN:This 4½ year retrospective study includes consecutive fetuses that were terminated because of fetal malformation and/or chromosomal anomaly diagnosed in the second trimester. Only fetuses that had undergone fetal anatomy scanning by an obstetrician trained in fetal ultrasound before the termination and with available fetal autopsy reports were included. The cases were identified through the malformation registry database of our ultrasound unit. The sensitivity and specificity of ultrasound were calculated per organ system. When estimating the agreement between ultrasound results and autopsy findings, the cases were allocated to one of four categories according to the degree of concordance between ultrasound and autopsy findings: full agreement, near match, partial agreement and unconfirmed ultrasound findings. RESULTS:71 of 95 pregnancy terminations due to fetal malformations met the inclusion criteria and constitute our study population. The sensitivity of ultrasonography with regard to malformations in the brain and spine was 100 % (27/27) and with regard to malformations in the internal organ system (including malformations in the urogenital and gastrointestinal systems and in the abdominal wall and diaphragm) was 91 % (30/33). The corresponding figures for malformations in the cardiovascular and skeletal organ systems were 63 % (17/27) and 71 % (25/35), respectively. The specificity was lowest for malformations in the central nervous system and internal organ system (33/38, 87 % and 39/44, 89 %, respectively). There was full agreement between the ultrasound and autopsy findings in 44 % (31/71) of all cases and a near match in 46 % (33/71) of cases. In almost 10 % (7/71) of the pregnancies, the ultrasound findings were only partially confirmed or not confirmed by autopsy. In one case the discrepancy between the ultrasound and autopsy findings suggests that the pregnant woman might have decided to terminate the pregnancy on the basis of incorrect interpretation of ultrasound findings. CONCLUSION:Even though the agreement between ultrasound and autopsy findings was acceptable from a clinical point of view, agreement with regard to the detailed description of malformations was far from perfect. The detection rates were suboptimal for the cardiovascular and skeletal organ systems. :ZIEL:: Bewertung, inwieweit bei Schwangerschaftsabbrüchen aufgrund fetaler Anomalien die Befunde der pränatalen Ultraschalluntersuchung in der 16.–21. SSW mit dem Autopsiebefund des Feten übereinstimmen. METHODEN:Diese 4½ jährige retrospektive Studie schließt fortlaufend Feten ein, bei denen im 2. Trimenon ein Schwangerschaftsabbruch (TOP) aufgrund fetaler Fehlbildungen und/oder aufgrund von diagnostizierten Chromosomenanomalien erfolgt ist. Es wurden nur Feten einbezogen, bei denen vor dem Abbruch eine anatomische Untersuchung durch einen in der Fetalsonografie geübten Geburtshelfer durchgeführt wurde und bei denen fetale Autopsiebefunde vorlagen. Die Fälle wurden durch die Datenbank unserer Sonografieabteilung zur „Registrierung von Fehlbildungen“ ermittelt. Die Sensitivität und Spezifität der Sonografie wurde für jedes Organsystem berechnet. Zur Abschätzung der Übereinstimmung von Ultraschall- und Autopsiebefunden wurden die Fälle einer der vier Kategorien zugewiesen, je nach Grad der Übereinstimmung der Befunde: Solche mit völliger, sich fast entsprechender und nur teilweiser Übereinstimmung sowie nicht bestätigte Ultraschallbefunde. ERGEBNISSE:Die Einschlusskriterien erfüllten 71 von 95 Schwangerschaftsabbrüchen aufgrund fetaler Anomalien und bildeten somit unsere Studienpopulation. Die Sensitivität der Sonografie in Bezug auf Malformationen des Gehirns und Wirbelsäule betrug 100 % (27/27) und in Bezug auf Anomalien der inneren Organe (einschließlich der Fehlbildungen des Urogenital- und Magen-Darm-Systems, der Bauchdecke und des Diaphragmas) 91 % (31/33). Die entsprechende Rate für Anomalien des Herz-Kreislauf-Systems betrug 63 % (17/27) und für die des Skelettsystems 71 % (25/35). Die niedrigste Spezifität wurde für Malformationen des zentralen Nervensystems (33/38, 87 %) und der inneren Organe (39/44, 89 %) ermittelt. Eine völlige Übereinstimmung von Ultraschall- und Autopsiebefunden wurde in 44 % (31/71) und eine sich fast entsprechende Übereinstimmung in 46 % (33/71) aller Fälle gefunden. Bei beinahe 10 % (7/71) der Schwangerschaften konnten die Ultraschallbefunde nur teilweise beziehungsweise gar nicht durch die Autopsie bestätigt werden. In einem Fall mit diskrepanten Ultraschall- und Autopsiebefunden kann angenommen werden, dass die Schwangere die Entscheidung für einen Abbruch vermutlich aufgrund der fehlerhaften Interpretation des Ultraschallbefundes fällte. SCHLUSSFOLGERUNG:Obwohl die Übereinstimmung von Ultraschall- und Autopsiebefunden vom klinischen Standpunkt betrachtet akzeptierbar schien, war sie bezüglich der genauen Beschreibung der Fehlbildungen bei weitem nicht perfekt. Die Trefferquoten beim Herz-Kreislauf- und Skelettsystem waren suboptimal.

背景与目标： 目的：估计在妊娠16〜-21周的产前超声检查结果与因胎儿异常而终止妊娠的胎儿尸检结果之间的一致性。
研究设计：这项为期4½年的回顾性研究包括由于胎儿畸形和/或在妊娠中期诊断为染色体异常而终止的连续胎儿。仅包括终止前接受过胎儿超声培训的产科医生进行的胎儿解剖学扫描的胎儿，并提供胎儿尸检报告。这些病例是通过我们超声科的畸形登记数据库确定的。超声的灵敏度和特异性是根据每个器官系统计算的。在估计超声结果与尸检结果之间的一致性时，根据超声与尸检结果之间的一致性程度，将病例分为以下四类之一：完全一致，接近匹配，部分一致和未经证实的超声发现。
结果：因胎儿畸形而终止的95例妊娠中有71例符合纳入标准，构成了我们的研究人群。超声检查对脑和脊柱畸形的敏感性为100％（27/27），对内脏器官系统的畸形（包括泌尿生殖系统和胃肠系统以及腹壁和and肌的畸形）的敏感性为91 ％（30/33）。心血管和骨骼器官系统畸形的相应数字分别为63％（17/27）和71％（25/35）。中枢神经系统和内脏器官系统畸形的特异性最低（分别为33 / 38、87％和39 / 44、89％）。在所有病例中，超声检查和尸检结果完全吻合（44％）（31/71），接近匹配率在46％（33/71）中。在几乎10％（7/71）的怀孕中，超声检查结果仅部分被证实或尸检未得到证实。在一种情况下，超声检查与尸检结果之间的差异表明，孕妇可能已基于对超声检查结果的错误解释而决定终止妊娠。
结论：即使从临床角度来看，超声检查与尸检结果之间的一致性是可以接受的，但就畸形的详细描述而言，一致性还远非完美。对于心血管和骨骼器官系统，检出率不是最理想的。
：ZIEL :: Bewertung，来自Schwangerschaftsabbrüchen的胎儿异常胎儿在16到21日间因超自然现象丧生。 SSW mit dem Autopsiebefund des Fetenübereinstimmen。
Methoden：Diese4½jährige具有追溯力的Studieschließtfortlaufend Feten ein，bei denen im 2。 Es wurden nur Feten einbezogen，bei denen vor dem Abbruch eine anatomische Untersuchung durch einen der FetalsonografiegeübtenGeburtshelferdurchgeführtwurde und bei denen fetale Autopsiebefunde vorlagen。 DateFällewurden durch和Datenbank取消注册„ Registrierung von Fehlbildungen“ ermittelt。器官系统的敏感度和敏感度。 ZülAbschätzungderÜbereinstimmungvon Ultraschall- and AutopsiebefundenWädendieFälleeiner der vier Kategorien zugewiesen，je nach Grad derÜbereinstimmungder Befunde：Solche mitvölligenics und undtüstenchästen
急诊室：死于脑卒中71到95Schwangerschaftsabbrüchenaufgrund胎儿异常和二等体不育的研究人群。百事可乐和Wirbelsäule投注在100％（27/27）和内部器官异常（Einschließlichder Fehlbildungen des Urogenital- und Magen-Darm-Duch-System）中， （31/33）。赫兹-克劳斯劳夫系统异常率达到63％（17/27），而斯凯莱特系统异常率达到71％（25/35）。神经系统神经网络（33/38，87％）和内部有机体（39/44，89％）。 EinevölligeÜbereinstimmungvon Ultraschall- and Autopsiebefunden wurde患病率为44％（31/71），eine sich fast entsprechendeÜbereinstimmung患病率为46％（33/71）。贝纳赫河（Bei beinahe）10％（7/71）从施万格啤酒厂（Ultraschallbefunde nur teilweise beziehungsweise gar nicht durch）进行尸检。在《超常的世界》和《超常的世界》中，施瓦格大帝和德国的企业家之间的关系得到了解释。
SCHLUSSFOLGERUNG：Obwohl死于Ultraschall-and Autopsiebefunden vom klinischen Standpunkt betrachtet akzeptierbar schien，战胜了beschüglichder genauen Beschreibung der Fehlbildungen bei weitem nicht。 Die Trefferquoten认为Herz-Kreislauf-和Skelettsystem警告不理想。

BACKGROUND & AIMS: Context:Vitamin D deficiency patients have an increased cardiovascular (CV) morbidity and mortality. Carotid intima-media thickness (IMT) and carotid plaques are markers of subclinical atherosclerosis and predictors of CV events. Objective:To perform a meta-analysis of studies evaluating the impact of Vitamin D deficiency on common carotid artery IMT (CCA-IMT) and on the prevalence of carotid plaques. Data Sources:Studies were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results:Twenty-one studies (3,777 Vitamin D deficiency patients and 4,792 controls) with data on CCA-IMT and 6 studies (1,889 Vitamin D deficiency patients and 2,883 controls) on the prevalence of carotid plaques were included. Compared to controls, Vitamin D deficiency patients showed a significantly higher CCA-IMT (mean difference [MD]: 0.043 mm; 95%CI: 0.030, 0.056; P<0.001), and an increased prevalence of carotid plaques (Odds Ratio [OR]: 2.29, 95%CI: 1.03-5.11; P=0.043) with an attributable risk of 35.9%. When selecting studies specifically including patients with diabetes, the prevalence of carotid plaques in Vitamin D deficiency patients than in controls resulted higher (OR: 3.27; 95%CI: 1,62-6.62; P=0.001). A significant difference in CCA-IMT was confirmed when comparing patients with Vitamin D insufficiency to controls (MD: 0.011; 95%CI: 0.010-0.012, P<0.001). Sensitivity analyses substantially confirmed results and regression models showed that with the exception of LDL-cholesterol, HDL-cholesterol, triglycerides and the prevalence of hypercholesterolemia, all the other clinical and demographic co-variates significantly impacted on the difference in CCA-IMT between Vitamin D deficiency patients and controls. Conclusions:Both Vitamin D deficiency and Vitamin D insufficiency are associated with subclinical atherosclerosis, potentially suggesting an increased CV risk in these clinical settings.

背景与目标： 背景：维生素D缺乏症患者的心血管（CV）发病率和死亡率增加。颈动脉内膜中层厚度（IMT）和颈动脉斑块是亚临床动脉粥样硬化的标志物和CV事件的预测因子。
目的：进行荟萃分析，评估维生素D缺乏对颈总动脉IMT（CCA-IMT）和颈动脉斑块患病率的影响。
数据来源：在PubMed，Web of Science，Scopus和EMBASE数据库中系统地搜索了研究。
结果：包括21项研究（3,777例维生素D缺乏症患者和4,792例对照者）的CCA-IMT数据和6项研究（1,889例D维生素D缺乏症患者和2,883例对照者）的颈动脉斑块患病率。与对照组相比，维生素D缺乏症患者的CCA-IMT显着更高（平均差异[MD]：0.043毫米； 95％CI：0.030，0.056； P <0.001），并且颈动脉斑块的患病率增加（几率[OR] ]：2.29，95％CI：1.03-5.11； P = 0.043），归因风险为35.9％。在选择专门针对糖尿病患者的研究时，维生素D缺乏症患者的颈动脉斑块患病率高于对照组（OR：3.27； 95％CI：1,62-6.62； P = 0.001）。当将维生素D功能不足的患者与对照组进行比较时，证实了CCA-IMT的显着差异（MD：0.011； 95％CI：0.010-0.012，P <0.001）。敏感性分析基本证实了结果，回归模型显示，除了低密度脂蛋白胆固醇，高密度脂蛋白胆固醇，甘油三酸酯和高胆固醇血症的患病率外，所有其他临床和人口统计学共同变量均显着影响维生素D之间CCA-IMT的差异缺乏患者和对照。
结论：维生素D缺乏症和维生素D缺乏症均与亚临床动脉粥样硬化有关，可能提示在这些临床情况下CV风险增加。

BACKGROUND & AIMS: :Menyanthes trifoliata L. is used in Swedish traditional medicine for the treatment of inflammatory diseases of the kidney, e.g. glomerulonephritis. Earlier studies have shown that MtL increases glomerular filtration rate after renal reperfusion ischemia. This activity was suggested to be PAF-inhibitory since MtL also inhibited PAF-induced exocytosis in vitro on human neutrophils (IC(50) = 0.16 mg/ml). The present study further characterizes the anti-inflammatory properties of a rhizome decoction of this plant. MtL inhibited carrageenan-induced rat paw edema (ID(50) ≈ 1.7 g/kg p.o.) and ethyl phenylpropiolate-induced rat ear edema (32% at 2.0 g/kg p.o.) in a dose-dependent manner. Further studies revealed that MtL inhibited both fMLP-induced exocytosis (IC(50) = 0.16 mg/ml) and elastase activity (IC(50) = 0.16 mg/ml). According to these results it is likely that the activity shown in the PAF-test is at least partly due to an inhibition of elastase. MtL showed only minor hemolytic properties at the concentrations used in the PAF- and fMLP-tests, suggesting that the cells in these tests are undamaged. The decoction also inhibited the biosynthesis of LTB(4) (IC(50) ≈ 0.73 mg/ml) and prostaglandins (IC(50) = 0.37 mg/ml) in vitro in a concentration-dependent way. However, at concentrations where the decoction is active in the LTB(4)-test, it also possesses hemolytic properties.

背景与目标： ：Menyanthes trifoliata L.在瑞典传统医学中用于治疗肾脏的炎症性疾病，例如肾小球肾炎。较早的研究表明，肾脏缺血再灌注后MtL可提高肾小球滤过率。该活性被认为是抑制PAF的，因为MtL还可以在体外抑制人嗜中性粒细胞的PAF诱导的胞吐作用（IC（50）= 0.16 mg / ml）。本研究进一步表征了该植物的根茎煎剂的抗炎特性。 MtL以剂量依赖性方式抑制角叉菜胶诱导的大鼠爪水肿（ID（50）≈1.7 g / kg p.o.）和苯丙酸乙酯诱导的大鼠耳水肿（2.0 g / kg p.o.时32％）。进一步的研究表明，MtL抑制fMLP诱导的胞吐作用（IC（50）= 0.16 mg / ml）和弹性蛋白酶活性（IC（50）= 0.16 mg / ml）。根据这些结果，PAF-测试中显示的活性可能至少部分是由于弹性蛋白酶的抑制。在PAF和fMLP测试中使用的浓度下，MtL仅显示出较小的溶血特性，表明这些测试中的细胞未受损。该汤还以浓度依赖的方式抑制了LTB（4）（IC（50）≈0.73 mg / ml）和前列腺素（IC（50）= 0.37 mg / ml）的生物合成。但是，在LTB（4）测试中该汤具有活性的浓度下，它也具有溶血作用。

BACKGROUND & AIMS: PURPOSE:Also called acute febrile neutrophilic dermatosis, Sweet's syndrome is an inflammatory disorder with a prominent cutaneous expression. It is characterized by a variety of manifestations, clinical and histological findings. The objective of this study was to describe their clinical, pathological and therapeutic characteristics. METHODS:We report on a series of 47 patients who presented a Sweet's syndrome, collected in our institution in Tunis between 1997 and 2011. RESULTS:The patient population consisted of 11 men and 36 women. The mean age was 47 years with extreme ranging from 28 to 74 years. An associated disorder was observed in ten patients: inflammatory disease (three cases), inflammatory bowel disease (two cases), tuberculosis (three cases) and diabetes (three cases). One case of pregnancy was observed. Cutaneous lesions consisted of erythematous plaques or nodules. Lesions were located mainly on the upper or lower extremities. All biopsy specimens demonstrated a dermal infiltrate composed predominantly of neutrophils. Fibrinoid necrosis and intramural inflammation were observed in eight cases. CONCLUSION:The skin disorder can precede, follow, or appear concurrent with the diagnosis of an associated disease which requires careful surveillance.

背景与目标： 用途：又称急性发热性中性粒细胞性皮肤病，Sweet's综合征是一种具有明显皮肤表达的炎症性疾病。它的特征是多种表现，临床和组织学发现。这项研究的目的是描述其临床，病理和治疗特征。
方法：我们报道了1997年至2011年间在我们突尼斯机构中收集的47例患有Sweet's综合征的患者。
结果：该患者包括11名男性和36名女性。平均年龄为47岁，极端年龄为28至74岁。在十名患者中观察到相关疾病：炎性疾病（三例），炎性肠病（两例），结核病（三例）和糖尿病（三例）。观察到一例怀孕。皮肤病变由红斑或结节组成。病变主要位于上肢或下肢。所有活检标本均显示主要由中性粒细胞组成的皮肤浸润。八例观察到纤维蛋白样坏死和壁内炎症。
结论：皮肤疾病可以在相关疾病的诊断之前，之后或同时出现，需要仔细监测。

BACKGROUND & AIMS: :The cornea and the skin are both organs that provide the outer barrier of the body. Both tissues have developed intrinsic mechanisms that protect the organism from a wide range of external threats, but at the same time also enable rapid restoration of tissue integrity and organ-specific function. The easy accessibility makes the skin an attractive model system to study tissue damage and repair. Findings from skin research have contributed to unravelling novel fundamental principles in regenerative biology and the repair of other epithelial-mesenchymal tissues, such as the cornea. Following barrier disruption, the influx of inflammatory cells, myofibroblast differentiation, extracellular matrix synthesis and scar formation present parallel repair mechanisms in cornea and skin wound healing. Yet, capillary sprouting, while pivotal in proper skin wound healing, is a process that is rather associated with pathological repair of the cornea. Understanding the parallels and differences of the cellular and molecular networks that coordinate the wound healing response in skin and cornea are likely of mutual importance for both organs with regard to the development of regenerative therapies and understanding of the disease pathologies that affect epithelial-mesenchymal interactions. Here, we review the principal events in corneal wound healing and the mechanisms to restore corneal transparency and barrier function. We also refer to skin repair mechanisms and their potential implications for regenerative processes in the cornea.

背景与目标： ：角膜和皮肤都是提供身体外部屏障的器官。两种组织都已开发出内在机制，可以保护生物体免受各种外部威胁的侵害，但同时也可以快速恢复组织的完整性和器官特异性功能。易于访问使皮肤成为研究组织损伤和修复的有吸引力的模型系统。皮肤研究的发现有助于揭示再生生物学的新基本原理，并修复了其他上皮-间质组织，例如角膜。屏障破坏后，炎症细胞的涌入，成肌纤维细胞的分化，细胞外基质的合成和疤痕的形成在角膜和皮肤伤口愈合中呈现出平行的修复机制。然而，毛细血管发芽虽然在适当的皮肤伤口愈合中起关键作用，但它是与角膜的病理修复相关的过程。对于再生疗法的发展以及对影响上皮-间质相互作用的疾病病理学的理解，了解协调皮肤和角膜伤口愈合反应的细胞和分子网络的相似性和差异性可能对两个器官都具有共同的重要性。在这里，我们回顾了角膜伤口愈合中的主要事件以及恢复角膜透明性和屏障功能的机制。我们还提到皮肤修复机制及其对角膜再生过程的潜在影响。

BACKGROUND & AIMS: OBJECTIVE:To summarise our experience with porcine urinary bladder matrix extracellular matrix (UBM) for the treatment of diabetic, venous, ischaemic or decubitus ulcerations and to outline appropriate protocol for its application. METHOD:A retrospective review was also conducted on all patients who received UBM (MatriStem; A Cell, Inc.) from January to December 201 I. Information regarding patient demographics, wound aetiology and location, as well as any prior treatments and follow-up data,were collected and reviewed from patients' medical records. RESULTS:Thirty-four patients were evaluated for this study. Mean patient age was 62.4 + 13.4 years (range 29-88 years) and 76% (n = 26) were male.The most common comorbidities were peripheral neuropathy (n = 20), diabetes mellitus type 2 (n = 19) and hypertension (n= 13). Mean wound duration prior to UBM application was 25.5 43.5 weeks, and mean time to healing following initial application was 9.8 9.3 weeks. All patients treated with UBM progressed to full healing. CONCLUSION:After addressing modifiable risk factors, our study suggests UBM is effective in the treatment of acute and recalcitrant diabetic or venous ulcerations when applied correctly with an appropriate dressing. DECLARATION OF INTEREST:There were no external sources of funding for this study.The authors have no conflicts of interest to declare.

背景与目标： 目的：总结我们在猪膀胱基质细胞外基质（UBM）上治疗糖尿病，静脉，缺血性或褥疮性溃疡的经验，并概述其应用的适当方案。
方法：还对所有201月份（201年1月至12月）接受UBM（MatriStem; A Cell，Inc.）的患者进行了回顾性研究。有关患者人口统计学，伤口病因和位置以及任何先前治疗和随访的信息从患者的病历中收集并审查数据。
结果：本研究评估了34例患者。平均患者年龄为62.4岁13.4岁（范围29-88岁），男性占76％（n = 26），最常见的合并症是周围神经病变（n = 20），2型糖尿病（n = 19）和高血压（ n = 13）。 UBM施用前的平均伤口持续时间为25.5 43.5周，初次施用后的平均愈合时间为9.8 9.3周。所有接受UBM治疗的患者均已完全康复。
结论：在解决了可改变的危险因素后，我们的研究表明，正确使用适当的敷料，UBM可有效治疗急性和顽固性糖尿病或静脉溃疡。
利益声明：这项研究没有外部资金来源。作者没有利益冲突的声明。

BACKGROUND & AIMS: BACKGROUND:The management of neuropsychiatric symptoms, including psychosis, in Parkinson's Disease (PD) is complicated by the fact that treatment with antipsychotics can worsen the movement disorder, which may necessitate changes to antiparkinsonian medications. OBJECTIVES:The objectives of this study were to determine what antipsychotics are prescribed to residents in long-term care with PD and document subsequent changes in levodopa dosage. METHODS:A retrospective cohort study using administrative health database information from Ontario, Canada, was conducted. PD diagnostic codes were obtained from the Ontario Health Insurance Plan (physician diagnostic codes) and the Canadian Institute of Health Information (hospitalization discharge diagnoses). The Ontario Drug Benefit database provided information on the use of antiparkinsonian medications and antipsychotics. Residents diagnosed with PD in long-term care were included if they were treated with stable doses of levodopa monotherapy and received a new prescription for an antipsychotic. The type of antipsychotic and the changes in levodopa dosage were determined. RESULTS:There were 479 residents who met inclusion criteria. The prescribed antipsychotics were quetiapine (n = 192; 40 %), risperidone (n = 185; 39 %) and olanzapine (n = 81; 17 %), and only 21 (4 %) received a prescription for a typical antipsychotic. The first levodopa dosage change was a dose reduction in 469 (98 %) patients, and a dose increase in ten (2 %) patients. CONCLUSIONS:Many PD patients in long-term care are treated with potentially inappropriate antipsychotic medications. However, there is no evidence that this treatment results in a prescribing cascade that leads to inappropriate increases in levodopa dosage.

背景与目标： 背景：帕金森氏病（PD）中的神经精神症状（包括精神病）的管理因以下事实而变得复杂：使用抗精神病药治疗可加重运动障碍，这可能需要更换抗帕金森病药物。
目的：本研究的目的是确定对长期接受PD治疗的居民开具哪些抗精神病药，并记录随后左旋多巴剂量的变化。
方法：使用来自加拿大安大略省的行政健康数据库信息进行了一项回顾性队列研究。 PD诊断代码是从安大略省健康保险计划（医师诊断代码）和加拿大健康信息研究所（住院出院诊断）获得的。安大略省药品福利数据库提供了有关使用抗帕金森病药物和抗精神病药的信息。如果他们接受了稳定剂量的左旋多巴单药治疗并接受了抗精神病药的新处方，则包括长期诊断为PD的居民。确定抗精神病药的类型和左旋多巴剂量的变化。
结果：有479位居民符合入选标准。处方的抗精神病药物为喹硫平（n = 192； 40％），利培酮（n = 185； 39％）和奥氮平（n = 81； 17％），只有21（4％）接受了典型抗精神病药的处方。左旋多巴的第一个剂量变化是469名患者（98％）的剂量减少，十名患者（2％）的剂量增加。
结论：许多长期护理的PD患者接受了可能不合适的抗精神病药物治疗。但是，没有证据表明这种治疗会导致处方级联反应，从而导致左旋多巴剂量的不适当增加。