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。

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关注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，目的是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: 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：二十一项研究（3777例维生素D缺乏症患者和4792例对照者）的CCA-IMT数据和6项研究（1889例维生素D缺乏症患者和2883例对照者）纳入了颈动脉斑块的患病率。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: :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保护机体免受各种外部威胁的内在机制，但同时也使组织完整性和器官特异性功能得以快速恢复。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: AIMS:To test aripiprazole for efficacy in decreasing use in methamphetamine-dependent adults, compared to placebo. DESIGN:Participants were randomized to receive 12 weeks of aripiprazole or placebo, with a 3-month follow-up and a platform of weekly 30-minute substance abuse counseling. SETTING:The trial was conducted from January 2009 to March 2012 at the San Francisco Department of Public Health. PARTICIPANTS:Ninety actively using, methamphetamine-dependent, sexually active adults were recruited from community venues. MEASUREMENTS:The primary outcome was regression estimated reductions in weekly methamphetamine-positive urines. Secondary outcomes were study medication adherence [by self-report and medication event monitoring systems (MEMS)], sexual risk behavior and abstinence from methamphetamine. FINDINGS:Participant mean age was 38.7 years, 87.8% were male, 50.0% white, 18.9% African American, and 16.7% Latino. Eighty-three per cent of follow-up visits and final visits were completed. By intent-to-treat, participants assigned to aripiprazole had similar reductions in methamphetamine-positive urines as participants assigned to placebo [risk ratio (RR) 0.88, 95% confidence interval (CI): 0.66-1.19, P = 0.41]. Urine positivity declined from 73% (33 of 45 participants) to 45% (18 of 40) in the placebo arm and from 77% (34 of 44) to 44% (20 of 35) in the aripiprazole arm. Adherence by MEMS and self-report was 42 and 74%, respectively, with no significant difference between arms (MEMS P = 0.31; self-report P = 0.17). Most sexual risk behaviors declined similarly among participants in both arms (all P > 0.05). There were no serious adverse events related to study drug, although participants randomized to aripiprazole reported more akathisia, fatigue and drowsiness (P < 0.05). CONCLUSION:Compared with placebo, aripiprazole did not reduce methamphetamine use significantly among actively using, dependent adults.

背景与目标： 目的：与安慰剂相比，测试阿立哌唑在减少依赖甲基苯丙胺的成年人中的使用效率。
设计：参与者被随机分配接受12周的阿立哌唑或安慰剂治疗，为期3个月的随访和每周30分钟的药物滥用咨询平台。
地点：该试验于2009年1月至2012年3月在旧金山公共卫生部进行。
参与者：从社区场所招募了90名积极使用甲基苯丙胺的性活跃成年人。
测量：主要结果是每周甲基苯丙胺阳性尿量的回归估计减少。次要结果是研究药物依从性[通过自我报告和药物事件监测系统（MEMS）]，性风险行为和对甲基苯丙胺的戒断。
结果：参与者的平均年龄为38.7岁，男性为87.8％，白人为50.0％，非裔美国人为18.9％，拉丁美洲人为16.7％。完成了后续访问和最后访问的83％。通过意向性治疗，与使用安慰剂的受试者相比，分配给阿立哌唑的受试者的甲基苯丙胺阳性尿液减少量相似[风险比（RR）0.88，95％的置信区间（CI）：0.66-1.19，P = 0.41]。安慰剂组的尿液阳性率从73％（45名参与者中的33名）下降到45％（40名中的18名），阿立哌唑组从77％（44名中的34名）下降到44％（35名中的20名）。 MEMS和自报告的依从性分别为42％和74％，两臂之间没有显着差异（MEMS P = 0.31；自报告P = 0.17）。两组参与者中大多数性风险行为均以类似方式下降（所有P> 0.05）。尽管随机分组使用阿立哌唑的参与者报告有更多的静坐无力，疲劳和嗜睡，但没有与研究药物相关的严重不良事件（P <0.05）。
结论：与安慰剂相比，阿立哌唑在积极使用依赖的成年人中并未显着减少甲基苯丙胺的使用。