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【哪些血栓形成性基因突变是复发性流产的危险因素？】
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DOI：10.1111/j.1600-0897.2006.00419.x
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BACKGROUND & AIMS: PROBLEM:Thrombophilia has been associated with poor obstetrical outcomes. To determine the association of specific inherited thrombophilias and recurrent pregnancy loss, 10 thrombophilic genes were investigated. METHOD OF STUDY:A total of 550 women with a history of recurrent pregnancy loss had buccal swabs taken for DNA analyses of the following gene mutations: factor V G1691A, factor V H1299R (R2), factor V Y1702C, factor II prothrombin G20210A, factor XIII V34L, beta-fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C. The frequencies of these mutations were compared with controls published in the literature. RESULTS:When examined individually, PAI-1 4G/5G (P = 0.009), factor XIII V34L (P < 0.0001), and homozygous MTHFR C667T (P < 0.0001) correlated significantly with recurrent pregnancy loss compared with controls. The frequency of the factor V Y1702C mutation was extremely low in patients and controls; thus, this gene was removed from further calculations. The remaining six mutated genes, when analyzed cumulatively, also corresponded with recurrent pregnancy loss (P < 0.0001). CONCLUSION:A panel of thrombogenic gene mutations consisting of factor V G1691A, factor V H1299R (R2), factor II prothrombin G20210A, factor XIII V34L, beta-fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), MTHFR C677T, and MTHFR A1298C can identify individuals at risk for recurrent pregnancy loss.背景与目标： 问题：血友病与产科预后不良有关。为了确定特定遗传性血栓形成症与复发性流产的关联，研究了10个血栓形成性基因。
研究方法：总共550名有反复性流产史的妇女接受了口腔拭子以进行以下基因突变的DNA分析：因子V G1691A，因子V H1299R（R2），因子V Y1702C，因子II凝血酶原G20210A，因子XIII V34L，β-纤维蛋白原-455G> A，PAI-1 4G / 5G，HPA1a / b（L33P），亚甲基四氢叶酸还原酶（MTHFR）C677T，MTHFR A1298C。将这些突变的频率与文献中发表的对照进行了比较。
结果：当单独检查时，与对照组相比，PAI-1 4G / 5G（P = 0.009），XIII因子V34L（P <0.0001）和纯合MTHFR C667T（P <0.0001）与复发性流产显着相关。在患者和对照组中，V Y1702C因子突变的频率非常低。因此，该基因已从进一步的计算中删除。当进行累积分析时，剩下的六个突变基因也与复发性流产相对应（P <0.0001）。
结论：一组血栓形成基因突变，由因子V G1691A，因子V H1299R（R2），因子II凝血酶原G20210A，因子XIII V34L，β-纤维蛋白原-455G> A，PAI-1 4G / 5G，HPA1 a / b（ L33P），MTHFR C677T和MTHFR A1298C可以识别有复发性流产风险的个体。 -
【神经性贪食症的危险因素。基于社区的病例对照研究。】
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DOI：10.1001/archpsyc.1997.01830180015003
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BACKGROUND & AIMS: BACKGROUND:Many apparently disparate risk factors have been implicated as causes of eating disorders. This study was designed to test the hypothesis that 2 broad classes of risk factors exist for bulimia nervosa: those that increase the risk for development of a psychiatric disorder in general and those that increase the risk of dieting. It was predicted that the latter are especially common among persons with bulimia nervosa.
METHODS:A case-control design was used involving 2 integrated comparisons. First, 102 subjects with bulimia nervosa were compared with 204 healthy control subjects without an eating disorder. Second, the same 102 subjects with bulimia nervosa were compared with 102 subjects with other psychiatric disorders. To reduce sampling bias, the subjects were recruited directly from the community. A broad range of putative risk factors was assessed.
RESULTS:The subjects with bulimia nervosa and the healthy control subjects differed in their rates of exposure to most of the putative risk factors. Far fewer differences were evident between the subjects with bulimia nervosa and the control subjects with other psychiatric disorders, although exposure to factors that were likely to increase the risk of dieting and to negative self-evaluation and certain parental problems (including alcohol use disorder) were substantially more common among those with bulimia nervosa.
CONCLUSIONS:The findings support the hypothesis that bulimia nervosa is the result of exposure to general risk factors for psychiatric disorder and risk factors for dieting. An unexpected finding was the particularly high rates of premorbid negative self-evaluation and certain parental problems among those with bulimia nervosa.
背景与目标： 背景：许多明显不同的危险因素被认为是饮食失调的原因。这项研究旨在检验以下假设：存在2种广泛的神经性贪食症危险因素：那些通常会增加患精神病的风险，以及那些会增加节食的风险的因素。预计后者在神经性贪食症患者中尤为常见。
方法：采用病例对照设计，涉及2个综合比较。首先，将102例神经性贪食症患者与204例无饮食失调的健康对照者进行了比较。其次，将相同的102名神经性贪食症患者与102名其他精神疾病患者进行了比较。为了减少抽样偏差，直接从社区招募了受试者。评估了广泛的推定危险因素。
结果：神经性贪食症患者和健康对照组的暴露于大多数推定危险因素的比率有所不同。尽管暴露于可能会增加饮食风险和自我评估风险的因素，以及某些父母问题（包括饮酒障碍），但神经性贪食症患者与其他精神疾病对照组的差异明显较少。结论
结论：这些发现支持以下假设：神经性贪食症是暴露于精神疾病的一般危险因素和饮食风险因素的结果。一个出乎意料的发现是神经性贪食症患者的病前阴性自我评估率特别高，并且存在某些父母问题。
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【右精索静脉曲张和缺氧，是男性不育症的关键因素：睾丸引流系统受损的流体力学分析。】
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DOI：10.1016/s1472-6483(10)60638-4
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BACKGROUND & AIMS: :Varicocele is considered a predominantly unilateral left-sided disease. However, since male fertility is preserved with only one healthy testis, infertility perforce represents bilateral testicular dysfunction. It was hypothesized that: (i) right varicocele cannot be diagnosed by palpation and therefore has not been treated in the past by the traditional treatment, and (ii) right varicocele causes impaired oxygen supply in the right testicular microcirculation, leading to germ cell degeneration. This study performed venographies of both right and left internal spermatic veins during the treatment of 840 infertile men with varicocele and analysed the results using tools of fluid mechanics. Histopathology of the right testis revealed stagnation of blood flow and degenerative changes attributed to lack of adequate oxygenation in all testicular cell types. Right varicocele was found in the vast majority of the patients. We found that due to the destruction of one-way valves, pathologic hydrostatic pressure is produced in the testicular venous microcirculatory system about five times higher than normal, exceeding arteriolar pressure. The pressure gradient between the arterioles and venules in the testicular tissue is therefore reversed, leading to persistent hypoxia. Right varicocele, although undetected, is prevalent in infertile men with varicocele, hence only bilateral occlusion of the internal spermatic veins, including the associated bypasses, eliminating the pathologic hydrostatic pressure will lead to resumption of arterial blood flow in the testicular microcirculation.背景与目标： ：精索静脉曲张被认为是主要的单侧左侧疾病。但是，由于只有一个健康的睾丸才能维持男性的生育能力，因此不育症的强迫表现为双侧睾丸功能障碍。假设：（i）右精索静脉曲张不能通过触诊诊断，因此过去没有通过传统疗法进行治疗；（ii）右精索静脉曲张导致右睾丸微循环中的氧气供应受损，从而导致生殖细胞变性。这项研究在对840名不育男性精索静脉曲张的治疗过程中进行了左右精索静脉的静脉造影，并使用流体力学工具对结果进行了分析。右睾丸的组织病理学显示血流停滞和变性变化归因于所有睾丸细胞类型缺乏足够的氧合。在绝大多数患者中发现了右精索静脉曲张。我们发现，由于单向阀的破坏，睾丸静脉微循环系统中产生的病理性静水压力比正常高约五倍，超过了小动脉压力。因此，睾丸组织中小动脉和小静脉之间的压力梯度会反向，从而导致持续的缺氧。右精索静脉曲张虽然未被发现，但在精索静脉曲张的不育男性中很普遍，因此，只有双侧内精子静脉闭塞，包括相关的旁路，消除病理性静水压会导致睾丸微循环中动脉血流的恢复。
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【角质形成细胞迁移和肽生长因子：PDGF，bFGF，EGF，IGF-I，aFGF和TGF-β对胶原凝胶中人角膜细胞迁移的影响。】
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DOI：10.1076/ceyr.16.6.605.5081
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BACKGROUND & AIMS: PURPOSE:Peptide growth factors are known accelerators of corneal wound healing, probably mediated through increased proliferation of the cells; however, information about their effect on keratocyte motility is lacking. The influence of peptide growth factors on keratocyte migratory activity was investigated, using the following growth factors: platelet derived growth factor (PDGF-BB), epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I) and transforming growth factor-beta-1 (TGF-beta 1).
METHODS:Keratocytes were seeded on gels of type 1 collagen, growth factor added, and the cells left to migrate for 72 hours. Subsequently, the number of keratocytes at the different levels in the collagen gel was evaluated by optically sectioning the gel at 20 microns, intervals, with an inverted phase contrast microscope.
RESULTS:PDGF, EGF and bFGF at 10 ng/ml, all increased the number of keratocytes at the different levels of the gel as compared to a non-stimulated control (p < 0.05 or p < 0.01, students t-test). TGF-beta proved to be a strong inhibitor of keratocyte migration, decreasing the number of keratocytes observed at every level in the gel (p < 0.05 and p < 0.01, students t-test), whereas no effect of IGF-I and aFGF was found. During the 72 hours of migration, no contraction of the collagen gels was observed. Autoradiography of histological sections of the gels showed that during the 72-hour period only TGF-beta and 10% fetal bovine serum induced an increase in keratocyte proliferation.
CONCLUSION:PDGF, EGF and bFGF increase keratocyte migration, independent of proliferation in a collagen gel invasion assay and might promote corneal wound healing, not only by increasing cell proliferation, but also through increased motility.
背景与目标： 目的：肽生长因子是角膜伤口愈合的已知促进剂，可能是通过细胞增殖的增加来介导的。然而，缺乏有关它们对角膜细胞运动性影响的信息。使用以下生长因子研究了肽生长因子对角膜细胞迁移活性的影响：血小板衍生生长因子（PDGF-BB），表皮生长因子（EGF），酸性成纤维细胞生长因子（aFGF），碱性成纤维细胞生长因子（bFGF） ），胰岛素样生长因子I（IGF-I）和转化生长因子β-1（TGF-beta 1）。
方法：将角质形成细胞接种在1型胶原蛋白，添加了生长因子，细胞迁移了72小时。随后，通过倒置相差显微镜以20微米的间隔对凝胶进行光学切片，评估胶原蛋白凝胶中不同水平的角质形成细胞的数量。
结果：PDGF与未刺激的对照组相比，10 ng / ml的EGF和bFGF均增加了凝胶水平不同时的角膜细胞数量（p <0.05或p <0.01，学生t检验）。 TGF-β被证明是一种强烈的角膜细胞迁移抑制剂，减少了凝胶中每个水平上观察到的角膜细胞数量（p <0.05和p <0.01，学生t检验），而IGF-I和aFGF没有作用成立。在迁移的72小时内，未观察到胶原凝胶的收缩。凝胶组织学切片的放射自显影显示，在72小时内，只有TGF-β和10％的胎牛血清诱导了角膜细胞增殖的增加。
结论：PDGF，EGF bFGF和bFGF可增加角膜细胞迁移，而不受胶原凝胶入侵试验中的增殖的影响，并且不仅可以通过增加细胞增殖，而且可以通过增加运动性来促进角膜伤口愈合。
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【B淋巴细胞群体对IgM受体连接的差异敏感性由局部因素决定。】
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DOI：10.1093/intimm/9.5.755
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BACKGROUND & AIMS: Ligation of surface IgM on B cells responding to lipopolysaccharide (LPS) suppresses terminal differentiation and high-rate Ig secretion with no effect on proliferation. As shown here, different B cell populations show characteristic mean values of ligand concentration required for 50% inhibition, with Gaussian distributions of sensitivity to IgM receptor ligation that reflect cellular heterogeneity of 'al-or-none' inhibitions in single cells. Differential sensitivity of B cell populations to IgM ligation seems to be locally determined by the cellular environment and unrelated to the 'maturity' of the responding cells. Thus, while long-lived peritoneal B cells are 3- to 5-fold more resistant than splenic B cells, there is no difference in sensitivity between short- and long-lived B cells in the spleen. Furthermore, while B cells in bone marrow and spleen differ in sensitivity by two orders of magnitude, B cells differentiated in vitro from bone marrow pre-B cells are as resistant as splenic B cells. Moreover, bone marrow cell culture supernatants restore a high level of sensitivity in such cell populations. Differential sensitivity to IgM receptor ligation is reproduced by multivalent nominal antigen, in cell populations that show identical dose-response inhibition curves to direct activation of protein kinase C by phorbol esters. We conclude that the level of sensitivity to IgM ligation is independent of the life span or maturity of the B cell, but differentially regulated in vivo by putative tissue factors.
背景与目标： 响应脂多糖（LPS）的B细胞表面IgM的连接可抑制终末分化和高速率的Ig分泌，而对增殖没有影响。如此处所示，不同的B细胞群体显示出50％抑制所需的配体浓度的特征平均值，其对IgM受体连接的敏感性的高斯分布反映了单细胞“异或无”抑制的细胞异质性。 B细胞群体对IgM连接的差异敏感性似乎是由细胞环境局部决定的，并且与响应细胞的“成熟度”无关。因此，虽然长寿腹膜B细胞的抵抗力比脾脏B细胞高3至5倍，但脾脏中短寿和长寿B细胞之间的敏感性没有差异。此外，尽管骨髓和脾脏中的B细胞在敏感性方面相差两个数量级，但体外与骨髓前B细胞分化出的B细胞与脾脏B细胞一样具有抗性。而且，骨髓细胞培养物上清液在这种细胞群体中恢复了高水平的敏感性。在表现出相同剂量反应抑制曲线以直接通过佛波醇酯激活蛋白激酶C的细胞群体中，多价名义抗原重现了对IgM受体连接的不同敏感性。我们得出的结论是，对IgM结扎的敏感性水平与B细胞的寿命或成熟度无关，但在体内受假定的组织因子的调节。
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【Tn10换位中负责靶位选择的因素：DDE基序在靶DNA捕获中的作用。】
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DOI：10.1093/emboj/16.10.2646
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BACKGROUND & AIMS: Tn10, like several other transposons, exhibits a marked preference for integration into particular target sequences. Such sequences are referred to as integration hotspots and have been used to define a consensus target site in Tn10 transposition. We demonstrate that a Tn10 hotspot called HisG1, which was identified originally in vivo, also functions as an integration hotspot in vitro in a reaction where the HisG1 sequence is present on a short DNA oligomer. We use this in vitro system to define factors which are important for the capture of the HisG1 target site. We demonstrate that although divalent metal ions are not essential for HisG1 target capture, they greatly facilitate capture of a mutated HisG1 site. Analysis of catalytic transposase mutants further demonstrates that the DDE motif plays a critical role in 'divalent metal ion-dependent' target capture. Analysis of two other classes of transposase mutants, Exc+ Int- (which carry out transposon excision but not integration) and ATS (altered target specificity), demonstrates that while a particular ATS transposase binds HisG1 mutants better than wild-type transposase, Exc+ Int- mutants are defective in HisG1 capture, further defining the properties of these classes of mutants. Possible mechanisms for the above observations are considered.
背景与目标： 像其他几种转座子一样，Tn10表现出明显的整合特定靶序列的偏好。此类序列称为整合热点，已用于定义Tn10转座中的共有靶位点。我们证明了一个称为HisG1的Tn10热点，最初在体内被发现，在一个短DNA低聚物上存在HisG1序列的反应中，它在体外还起着整合热点的作用。我们使用这个体外系统来定义对于捕获HisG1目标位点很重要的因素。我们证明，尽管二价金属离子对于HisG1目标捕获不是必需的，但它们极大地促进了突变的HisG1位点的捕获。催化转座酶突变体的分析进一步表明，DDE基序在“二价金属离子依赖性”靶标捕获中起关键作用。分析另外两类转座酶突变体Exc Int-（进行转座子切除但不整合）和ATS（改变的靶标特异性）表明，虽然特定的ATS转座酶与HisG1突变体的结合比野生型转座酶Exc Int-突变体在HisG1捕获中存在缺陷，进一步定义了这类突变体的特性。考虑了上述观察的可能机制。
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【在西西里岛东部卡塔尼亚居住的哥伦比亚和多米尼加女性性工作者中，艾滋病毒和其他性传播疾病的流行。】
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DOI：10.1007/s10903-006-9002-1
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BACKGROUND & AIMS: INTRODUCTION:STDs are a significant cause of illness throughout the world. Female sex workers (FSWs) are commonly perceived as belonging to a social group which may engage in high-risk behaviour for acquiring or transmitting HIV and other STDs. The number of immigrant women engaged in sex work has increased in Catania, Sicily, over the last 10 years. This study aims to estimate the prevalence of HIV, HBV, HCV and syphilis among Colombian and Dominican FSWs. METHODS:In total 118 (63.78%) of the FSWs contacted in the course of the project agreed to participate in the study. All women enrolled were counselled on STDs/HIV, safer sex practices and the use of condoms. Blood samples were taken and tested for HIV, HBV, HCV and syphilis. RESULTS:Of the 118 FSWs enrolled, all were negative for both HIV and HCV infection. Two women (1.6%) were positive for hepatitis B (HbsAg). Syphilis testing by VDRL showed three positive results (2.5%), which was confirmed by TPHA. DISCUSSION:This study showed that HIV, HBV, HCV and syphilis seroprevalence among Colombian and Dominican FSWs remains low or very rare. It also indicates that these women were healthy when they arrived in Italy and that condom use with clients is high.背景与目标： 简介：性病是世界范围内引起疾病的重要原因。女性性工作者（FSWs）通常被认为属于一个社会群体，该群体可能会为获取或传播艾滋病毒和其他性传播疾病而从事高风险行为。在过去的十年中，西西里岛卡塔尼亚从事性工作的移民妇女人数有所增加。这项研究的目的是估计哥伦比亚和多米尼加的FSW中HIV，HBV，HCV和梅毒的患病率。
方法：在该项目过程中，总共有118名（63.78％）的FSW同意参与研究。为所有入选妇女提供性传播疾病/艾滋病毒，更安全的性行为和使用安全套方面的咨询。抽取血样并测试HIV，HBV，HCV和梅毒。
结果：在118个FSW中，所有的HIV和HCV感染均为阴性。两名女性（1.6％）的乙型肝炎（HbsAg）阳性。 VDRL进行的梅毒测试显示三项阳性结果（2.5％），这已被TPHA证实。
讨论：这项研究表明，哥伦比亚和多米尼加地区FSW中的HIV，HBV，HCV和梅毒血清阳性率仍然很低或非常罕见。这也表明，这些妇女抵达意大利后就很健康，而且与客人一起使用避孕套的比例很高。 -
【人类胸腺髓质基质的细胞网络由p53相关的转录因子协调。】
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DOI：10.1369/jhc.6A7028.2006
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BACKGROUND & AIMS: :The final elimination step of self-reactive T cells occurs in the medulla of the thymus where a complex framework provided by stromal cells supports an optimal milieu for their selection. Here we present evidence that tight junctions (TJs) widely join medullary stromal cells of the human thymus. Occludin (OCLN) and claudin-1 (CLDN-1) of TJ-associated molecules were dominantly expressed in medullary thymic epithelial cells (mTECs), and CLDN-4 and CLDN-7 were also localized in some mTECs near Hassall's corpuscles. Interestingly, p53-like transcription factors were found to upregulate OCLN and CLDN-1 in human TEC lines, as recently suggested in the regulation of mTEC function. Furthermore, dendritic cells (DCs) of the medulla, with a major role for selection of thymocytes, expressed CLDN-1 and OCLN as well, implying that the interposition of DCs within the mTEC scaffold is also helped by TJs. Analysis of freeze-fracture replicas of the thymus revealed TJ strand structures in the vicinity of gap junction plaques through which small molecules might move, as implied by dye-transfer analysis of a medullary cell line. Thus, it is thought that p53-like molecules regulate TJ-associated interactions of medullary stromal cells and that this mechanism might be associated with an intercellular communication network, probably for preserving the medullary niches.背景与目标： ：自我反应性T细胞的最终消除步骤发生在胸腺的髓质中，其中基质细胞提供的复杂框架为它们的选择提供了最佳环境。在这里，我们提供证据表明紧密连接（TJs）广泛加入人类胸腺的髓质基质细胞。 TJ相关分子的Occludin（OCLN）和claudin-1（CLDN-1）主要在髓样胸腺上皮细胞（mTECs）中表达，CLDN-4和CLDN-7也位于Hassall小体附近的某些mTECs中。有趣的是，正如最近在调控mTEC功能中所建议的那样，发现p53样转录因子可上调人TEC细胞系中的OCLN和CLDN-1。此外，在选择胸腺细胞中起主要作用的髓质树突状细胞（DC）也表达CLDN-1和OCLN，这暗示TJ也有助于mTEC支架内DC的插入。胸腺的冷冻断裂复制品的分析显示，在间隙连接斑块附近的TJ链结构中，小分子可能会通过间隙连接斑块移动，正如髓细胞系的染料转移分析所暗示的那样。因此，认为p53样分子调节髓质基质细胞的TJ相关相互作用，并且该机制可能与细胞间通讯网络有关，可能是为了保留髓ni。
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【肥胖和糖尿病突变小鼠胰腺和垂体中神经肽的含量：品系和性别差异。】
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DOI：10.1016/0026-0495(90)90252-8
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BACKGROUND & AIMS: :The nature of the primary genetic defects in ob/ob and db/db mice are unknown. Both the obese (ob) and diabetes (db) mutations produce similar, multicomponent obese-hyperinsulinemic syndromes when maintained in the same strain of mouse. In an attempt to find differences between these mutations in neuroendocrine function affecting the islets of Langerhans or the pituitary, tissue content of four neuropeptides that are known to be capable of influencing the rate of insulin secretion was examined in obese (ob/ob) and diabetes (db/db) mice. In the first study, C57BL/6Job/ob and control males were studied at 3, 4, and 11 weeks of age. In the second study, db/db mice of both sexes and two inbred strains (C57BL/6J and C57BL/KsJ), which differ markedly in the severity of expression of the diabetes phenotype, were studied at 3 weeks of age, before the development of hyperglycemia and secondary consequences thereof. Immunoreactive peptides were measured in acetic acid extracts of pancreas and pituitary. No differences between male ob/ob and db/db mice of the C57BL/6J strain were found. Marked sex differences in lean control mice were found at 3 weeks of age in pancreatic Met-enkephalin-LI and galanin-LI (with two- to threefold higher content in males). Low pancreatic content (50% to 70% lower than in control mice) of galanin-LI, Met-enkephalin-LI and Leu-enkephalin-LI was associated with hyperinsulinemia in male B6 ob/ob and db/db mice at 3 weeks of age, though not in B6 db/db females and not in BKs db/db mice of either sex.(ABSTRACT TRUNCATED AT 250 WORDS)背景与目标： ：ob / ob和db / db小鼠的主要遗传缺陷的性质尚不清楚。肥胖（ob）和糖尿病（db）突变在同一小鼠品系中均会产生相似的多成分肥胖-高胰岛素血症综合征。为了发现影响兰格罕氏岛或垂体的胰岛的神经内分泌功能的这些突变之间的差异，在肥胖（ob / ob）和糖尿病患者中检查了四种已知能够影响胰岛素分泌速率的神经肽的组织含量（db / db）小鼠。在第一个研究中，研究了C57BL / 6Job / ob和对照男性在3、4和11周的年龄。在第二项研究中，在发育前的3周龄研究了具有性别和两种近交系（C57BL / 6J和C57BL / KsJ）的db / db小鼠，它们在糖尿病表型的表达严重程度上有显着差异。高血糖及其继发后果。在胰腺和垂体的乙酸提取物中测量了免疫反应性肽。在C57BL / 6J株的雄性ob / ob和db / db小鼠之间未发现差异。在瘦瘦对照小鼠中，在3周龄的胰腺Met-脑啡肽-LI和甘丙肽-LI中发现明显的性别差异（雄性含量高2至3倍）。在3周龄的雄性B6 ob / ob和db / db小鼠中，甘丙肽-LI，Met-脑啡肽-LI和亮-脑啡肽-LI的胰腺含量低（比对照小鼠低50％至70％）与高胰岛素血症相关。年龄，但不是在B6 db / db雌性中，也不是在BK s db / db两种性别的小鼠中。（摘要以250字截断）
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10 Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response.
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【鼠疫耶尔森氏菌的毒性因子可通过强大的脂多糖反应来克服。】
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DOI：10.1038/ni1386
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BACKGROUND & AIMS: :At mammalian body temperature, the plague bacillus Yersinia pestis synthesizes lipopolysaccharide (LPS)-lipid A with poor Toll-like receptor 4 (TLR4)-stimulating activity. To address the effect of weak TLR4 stimulation on virulence, we modified Y. pestis to produce a potent TLR4-stimulating LPS. Modified Y. pestis was completely avirulent after subcutaneous infection even at high challenge doses. Resistance to disease required TLR4, the adaptor protein MyD88 and coreceptor MD-2 and was considerably enhanced by CD14 and the adaptor Mal. Both innate and adaptive responses were required for sterilizing immunity against the modified strain, and convalescent mice were protected from both subcutaneous and respiratory challenge with wild-type Y. pestis. Despite the presence of other established immune evasion mechanisms, the modified Y. pestis was unable to cause systemic disease, demonstrating that the ability to evade the LPS-induced inflammatory response is critical for Y. pestis virulence. Evading TLR4 activation by lipid A alteration may contribute to the virulence of various Gram-negative bacteria.背景与目标： ：在哺乳动物体温下，鼠疫耶尔森菌鼠疫杆菌合成脂多糖（LPS）-脂质A，其Toll样受体4（TLR4）刺激活性较弱。为了解决弱TLR4刺激对毒力的影响，我们修饰了鼠疫耶尔森氏菌以产生有效的TLR4刺激LPS。即使在高激发剂量下，改良的鼠疫耶尔森氏菌在皮下感染后也完全无毒。对疾病的抗性需要TLR4，衔接蛋白MyD88和共受体MD-2，并且CD14和衔接蛋白Mal大大增强了抗病性。对修饰菌株的免疫力需要先天性和适应性应答，野生型鼠疫耶尔森氏菌可以保护恢复期的小鼠免受皮下和呼吸道攻击。尽管存在其他已建立的免疫逃逸机制，但经过修饰的鼠疫耶尔森氏菌不能引起全身性疾病，这表明逃避脂多糖诱导的炎症反应的能力对鼠疫耶尔森氏菌的毒力至关重要。通过脂质A改变而避免TLR4激活可能会导致多种革兰氏阴性细菌的致病性。 -
【公共卫生管理学院：程序设计和成功的关键因素。】
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DOI：10.1097/00124784-200609000-00002
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BACKGROUND & AIMS: :The Management Academy for Public Health is a team-based training program jointly offered by the School of Public Health and the Kenan-Flagler Business School at the University of North Carolina at Chapel Hill. This 9-month program teaches public health managers how to better manage people, information, and finances. Participants learn how to work in teams with community partners, and how to think and behave as social entrepreneurs. To practice and blend their new skills, teams develop a business plan that addresses a local public health issue. This article describes the program and explains the findings of the process evaluation, which has examined how best to structure and deploy a team-based method to create more effective, more entrepreneurial public health managers. Findings indicate that recruitment and retention are strong, program elements are relevant to learners' needs, and learners are satisfied with and value the program. Several specific benefits of the program model are identified, as well as several elements that support business plan success and skills' application on the job. On the basis of these findings, four success factors critical for developing similar programs are identified.背景与目标： ：公共卫生管理学院是一项基于团队的培训计划，由北卡罗来纳大学教堂山分校的公共卫生学院和Kenan-Flagler商学院联合提供。这个为期9个月的课程向公共卫生经理讲授如何更好地管理人员，信息和财务。参与者学习如何与社区合作伙伴一起工作，以及如何思考和表现为社会企业家。为了练习和融合他们的新技能，团队制定了解决当地公共卫生问题的商业计划。本文介绍了该程序，并说明了过程评估的结果，该过程评估了如何最好地构建和部署基于团队的方法来创建更有效，更具创业精神的公共卫生经理。调查结果表明，招聘和留住人才的能力很强，计划要素与学习者的需求相关，学习者对计划感到满意和重视。确定了计划模型的几个特定优点，以及支持业务计划成功和技能在工作中应用的几个要素。根据这些发现，确定了开发类似程序的四个成功因素。
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【代表性的全科医学样本中晚期失眠的危险因素。】
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BACKGROUND & AIMS: BACKGROUND:Insomnia is widely reported and widely treated in general practice, yet relatively little research has focused on the natural history of the condition in primary care settings. As a result, there is at present little information to enable clinicians to assess insomnia risk, or anticipate outcomes in older general practice populations.
AIM:To estimate, using 8-year longitudinal data, the risk of insomnia onset associated with selected health and lifestyle factors.
METHOD:Survivors from a nationally representative sample (n = 1042) of elderly people originally interviewed in 1985 were reassessed in 1989 (n = 690) and 1993 (n = 410). At the first follow up in 1989, 84 new cases of insomnia were identified (a weighted incidence rate per person per year at a risk of 3.1%; 95% CI = 2.7-3.5). In logistic regression analyses controlling for age and sex, the risk of insomnia onset was then assessed in relation to the selected factors.
RESULTS:Three factors assessed in 1985 were significantly and independently related to incident insomnia: psychometric ratings consistent with depressed mood odds ratio (OR) = 4.41; 95% CI = 3.32-5.43); health index scores indicating lower physical health status (OR = 1.19; 95% CI = 1.06-1.31 per unit change in scale score); and moderate and low levels of physical activity (OR = 1.91 and 2.14; 95% CI = 1.91-3.62 and 2.14-3.64 respectively). However, although depressed mood represented a major risk factor, the most likely source of risk was physical rather than mental ill-health.
CONCLUSIONS:Psychiatric, somatic and lifestyle factors significantly and independently increase the risk of insomnia in older general practice patients. In predicting incident sleep disturbance, these factors exceed in importance the age and sex of patients.
背景与目标： 背景：失眠已被广泛报道并在一般实践中得到了广泛的治疗，但是相对较少的研究集中在初级保健机构中病情的自然史上。因此，目前尚无足够的信息可帮助临床医生评估失眠风险或预测老年全科人群的结局。
AIM ：使用8年纵向评估数据，与选定的健康和生活方式因素相关的失眠风险。
方法：对来自全国代表性样本（n = 1042）的老年人的幸存者进行了重新评估，该样本最初于1985年接受采访。在1989年（n = 690）和1993（n = 410）。在1989年的首次随访中，发现了84例新的失眠病例（加权平均每人每年的发病率，风险为3.1％； 95％CI = 2.7-3.5）。在控制年龄和性别的逻辑回归分析中，然后根据所选因素评估了失眠的风险。
结果：1985年评估的三个因素具有显着性和独立性发生失眠：心理测验评分与沮丧的情绪几率之比（OR）= 4.41； 95％CI = 3.32-5.43）；健康指数得分，表明身体健康状况较低（OR = 1.19； 95％CI =单位得分变化每单位1.06-1.31）；中度和低度的体育活动（OR分别为1.91和2.14； 95％CI分别为1.91-3.62和2.14-3.64）。但是，尽管情绪低落是主要的危险因素，但最可能的危险来源是身体而不是精神疾病。
结论：精神，躯体和生活方式因素显着且独立增加老年全科患者失眠的风险。在预测事件性睡眠障碍时，这些因素的重要性超过了患者的年龄和性别。
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【在口腔鳞状细胞癌的浸润性肿瘤前评估组织生物学因素（恶性分级和AgNOR含量）的预后价值。】
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DOI：10.1038/bjc.1997.263
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BACKGROUND & AIMS: Tumour cells at the invasive front of carcinomas have been found to differ substantially from the rest of tumour cells in a variety of human cancers. The present multivariate survival analysis of 94 oral squamous cell carcinomas (OSCCs) revealed that both the argyrophilic nucleolar organizer regions-associated protein (AgNOR) content of invading tumour cells and a multiparametric histopathological tumour front grade were significantly and independently associated with tumour-related death, irrespective of conventional Broders' grade and clinical stage of the tumours. High tumour front scores and AgNOR content at the invasive OSCC front thus seem to reflect increased malignant potential. Proliferative activity, assessed by standardized AgNOR analysis, most probably represents one of the biological features underlying the usefulness of evaluating the invasive tumour front.
背景与目标： 已经发现，在多种人类癌症中，处于癌症侵袭性前沿的肿瘤细胞与其余肿瘤细胞有很大的不同。目前对94例口腔鳞状细胞癌（OSCC）的多因素生存分析表明，侵袭性肿瘤细胞的嗜银性核仁组织者区域相关蛋白（AgNOR）含量和多参数组织病理学肿瘤前沿均与肿瘤相关死亡显着且独立相关，与常规Broders的肿瘤分级和临床分期无关。因此，在侵袭性OSCC前沿，较高的肿瘤前沿评分和AgNOR含量似乎反映出恶性潜能的增加。通过标准化AgNOR分析评估的增殖活性很可能代表了评估侵袭性肿瘤前沿有用性的生物学特征之一。
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【肝移植受者巨细胞病毒感染危险因素的多因素分析。】
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DOI：10.1016/0016-5085(90)90352-2
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BACKGROUND & AIMS: :Thirty-three consecutive liver-transplant recipients were prospectively studied over a 37-mo period for evidence of cytomegalovirus infection. Sixteen (48%) episodes of cytomegalovirus infection were identified; 9 were primary infections and 7 were recurrent infections. Beginning with patient 8, gamma-globulin prophylaxis was routinely administered to most patients. Twelve potential risk factors for cytomegalovirus infection were evaluated and included pretransplant cytomegalovirus serological status of donor and recipient; recipient's age, sex, race, and liver disease; number and type of blood products transfused; type and intensity of immunosuppression; and occurrence of rejection. The Cox proportional hazards model identified positive donor cytomegalovirus serology as the single most important risk factor for subsequent development of cytomegalovirus infection, regardless of recipient cytomegalovirus serological status. In addition, use of gamma-globulin prophylaxis seemed to be protective against the occurrence of disseminated cytomegalovirus disease.背景与目标： ：在37个月内对33例连续肝移植接受者进行了前瞻性研究，以发现巨细胞病毒感染的迹象。鉴定出十六例（48％）巨细胞病毒感染； 9例是原发性感染，7例是复发性感染。从患者8开始，常规对大多数患者进行了γ-球蛋白的预防。评价了十二种巨细胞病毒感染的潜在危险因素，包括供体和受体移植前巨细胞病毒的血清学状况；接受者的年龄，性别，种族和肝脏疾病；输血产品的数量和类型；免疫抑制的类型和强度；和拒绝的发生。 Cox比例风险模型将阳性供体巨细胞病毒血清学确定为随后发展成巨细胞病毒感染的唯一最重要的危险因素，而与受体巨细胞病毒血清学状况无关。另外，使用γ-球蛋白预防似乎可以预防弥漫性巨细胞病毒病的发生。
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【中国昆明市女性青少年性工作者的脆弱性，健康需求和高风险性行为的预测因素。】
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DOI：10.1136/sextrans-2012-050690
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BACKGROUND & AIMS: OBJECTIVES:This study assessed social and behavioural predictors for sexual risk taking and sexually transmitted infections (STIs) including HIV among adolescent female sex workers (FSWs) from Kunming, China. Additionally, health services needs and use were assessed. METHODS:A cross-sectional survey was conducted in 2010. Using snowball and convenience sampling, self-identified FSWs were recruited from four urban areas in Kunming. Women consenting to participate were administered a semi-structured questionnaire by trained interviewers identified from local peer-support organisations. Following interview, a gynaecological examination and biological sampling to identify potential STIs were undertaken. Descriptive and multivariable logistic regression analyses were performed. RESULTS:Adolescent FSWs had a mean age of 18.2 years and reported numerous non-paying sexual partners with very low rate of consistent condom use (22.2%). Half (50.3%) the respondents had sex while feeling drunk at least once in the past week, of whom 56.4% did not use condom protection. STI prevalence was high overall (30.4%) among this group. Younger age, early sexual debut, being isolated from schools and family, short duration in sex work, and use of illicit drugs were found to be strong predictors for unprotected sex and presence of an STI. Conversely, having access to condom promotion, free HIV counselling and testing, and peer education were associated with less unprotected sex. The majority reported a need for health knowledge, free condoms and low-cost STI diagnosis and treatment. CONCLUSIONS:There is an urgent need to improve coverage, accessibility and efficiency of existing interventions targeting adolescent FSWs.背景与目标： 目的：本研究评估了来自中国昆明市的青春期女性性工作者（FSW）的性行为冒险和性传播感染（STI）（包括HIV）的社会和行为预测因素。此外，还评估了卫生服务的需求和使用。
方法：2010年进行了横断面调查。通过滚雪球和便利抽样，从昆明的四个市区招募了自我识别的FSW。从当地同支持组织确定的训练有素的访调员对同意参加的妇女进行半结构化问卷调查。采访之后，进行了妇科检查和生物采样以识别潜在的性传播感染。进行了描述性和多变量logistic回归分析。
结果：青少年FSW的平均年龄为18.2岁，并报告了许多无偿性伴侣，一致使用避孕套的比例很低（22.2％）。在过去的一周中，有一半（50.3％）的被调查者曾发生过至少一次醉酒的性行为，其中56.4％的人未使用安全套保护措施。在这一组中，性传播感染的患病率总体较高（30.4％）。人们发现，年龄较小，性行为初次出现，与学校和家庭隔离，性工作时间短以及使用非法药物是无保护性行为和性传播感染存在的强烈预测因素。相反，获得安全套宣传，免费的艾滋病毒咨询和检测以及同伴教育的机会与较少受到保护的性行为有关。大多数人报告需要健康知识，免费避孕套和低成本的STI诊断和治疗。
结论：迫切需要提高针对青少年FSW的现有干预措施的覆盖面，可及性和效率。
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