BACKGROUND & AIMS: INTRODUCTION:Tissue factor (TF) has been implicated in coronary artery disease (CAD). High levels of circulating TF are found in patients with acute atherothrombotic events. Whether high serum TF levels predict risk of future CAD independent of known risk factors remains unknown. METHODS:We conducted a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Cases (n=1037) were apparently healthy men and women, aged 45-79 years, who developed fatal or non-fatal CAD during follow-up. Controls (n=2005) were matched by age, sex, and enrolment time. Serum TF levels were measured using high-affinity antibodies. RESULTS:In men, median TF levels were not significant higher in cases than in controls (59.0 pg mL-1, range: 16.7-370.4 vs. 54.9 pg mL-1, range: 16.2-452.4). In women, median TF levels were not significant higher in controls than in cases (73.4 pg mL-1, range: 16.7-492.3 vs. 50.5 pg mL-1, range: 16.5-376.7). The incidence of smoking was about double in the lowest compared with the highest TF quartile. Correcting for sex, age, body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and C-reactive protein levels, the risk of future CAD was 1.05 (95% CI: 0.81-1.36) for people in the highest TF quartile, compared with those in the lowest (P-value for linearity=0.8). CONCLUSION:High levels of serum TF were not independently associated with an increased risk of future CAD in apparently healthy individuals.

背景与目标：

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：

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: 神经性贪食症存在两大类危险因素: 通常增加精神疾病发展风险的因素和增加节食风险的因素。据预测，后者在神经性贪食症患者中尤其常见。
方法 : 使用了涉及2个综合比较的病例对照设计。首先，将102名患有神经性贪食症的受试者与204名没有进食障碍的健康对照受试者进行比较。其次，将患有暴食症的相同102受试者与患有其他精神疾病的102受试者进行比较。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 : 患有神经性贪食症的受试者和健康对照受试者在暴露于大多数推定危险因素的比率上有所不同。神经性贪食症的受试者与其他精神疾病的对照受试者之间的差异要少得多，尽管暴露于可能增加节食风险的因素以及负面的自我评估和某些父母问题 (包括酒精使用障碍) 在神经性贪食症患者中更为普遍。
结论 : 研究结果支持以下假设: 神经性贪食症是暴露于精神疾病的一般危险因素和节食的危险因素的结果。一个意想不到的发现是，在神经性贪食症患者中，病前负面自我评估和某些父母问题的发生率特别高。

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一种主要的单侧左侧疾病。但是，由于只有一个健康的睾丸可以保留男性的生育能力，因此不育表现为双侧睾丸功能障碍。假设 :( i) 无法通过触诊来诊断右精索静脉曲张，因此过去没有通过传统疗法进行治疗，并且 (ii) 右精索静脉曲张会导致右睾丸微循环中的氧气供应受损，导致生殖细胞变性。这项研究在治疗840名患有精索静脉曲张的不育男性期间对左右精索内静脉进行了静脉造影，并使用流体力学工具分析了结果。右睾丸的组织病理学显示，由于所有睾丸细胞类型缺乏足够的氧合，导致血流停滞和退行性变化。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约为正常水平的五倍，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相反，导致持续的缺氧。右精索静脉曲张虽然未被发现，但在患有精索静脉曲张的不育男性中很普遍，因此只有双侧精索内静脉 (包括相关的旁路) 闭塞，消除病理性静水压将导致睾丸微循环中动脉血流的恢复。

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 : 肽生长因子是已知的角膜伤口愈合的促进剂，可能是通过细胞增殖增加介导的; 但是，缺乏有关它们对角质细胞运动的影响的信息。用以下生长因子: 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-β1 (tgf-β1)。
方法 : 将角质细胞接种在1型胶原蛋白的凝胶上，添加生长因子，细胞迁移72小时。随后，通过用倒置相差显微镜以20微米的间隔光学切片来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，EGF和bFGF为10 ng/ml，与未刺激的对照相比，在凝胶的不同水平下，所有这些都增加了角质细胞的数量 (p <0.05或p <0.01，学生t检验)。TGF-β 被证明是角质细胞迁移的强抑制剂，减少了在凝胶中每个水平观察到的角质细胞的数量 (p <0.05和p <0.01，学生t检验)，而没有发现igf-i和aFGF的作用。在迁移的72小时内，未观察到胶原蛋白凝胶的收缩。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% 胎牛血清诱导角质细胞增殖增加。
结论 :PDGF，EGF和bFGF增加角质细胞迁移，在胶原蛋白凝胶侵袭试验中独立于增殖，并且可能不仅通过增加细胞增殖，而且通过增加运动性来促进角膜伤口愈合。

BACKGROUND & AIMS: OBJECTIVE:The mechanism behind the epidemiologically evident inverse relation between Helicobacter pylori seropositivity and risk of oesophageal adenocarcinoma (OAC) remains obscure. Severe corpus gastritis is unlikely to be in the causal pathway. With the hypothesis of a uniformly low risk, the associations of OAC with duodenal ulcer and gastric ulcer were explored, both linked to H pylori infection but with different patterns of bacterial colonisation and intragastric acidity. Possible associations of oesophageal squamous cell carcinoma (OSCC) with these ulcer types were also addressed. DESIGN AND PATIENTS:Retrospective cohorts of 61,548 and 81,379 unoperated patients with duodenal ulcer and gastric ulcer, respectively, recorded in the Swedish Inpatient Register since 1965, were followed from the first hospitalisation until the date of any cancer, death, emigration, definitive surgery, or 31 December 2003. Standardised incidence ratios (SIRs), with 95% CIs, expressed relative risk of oesophageal cancer, compared with the Swedish population matched for age, sex and calendar period. RESULTS:Contrary to expectation, patients with duodenal ulcer had a significant 70% excess risk of OAC (SIR 1.7, 95% CI 1.1 to 2.5). Gastric ulcer was unrelated to OAC (SIR 1.1, 95% CI 0.6 to 1.7). Although duodenal ulcer was non-significantly associated with a small excess of OSCC (SIR 1.3, 95% CI 0.96 to 1.8), gastric ulcer was linked to 80% increased risk (SIR 1.8, 95% CI 1.4 to 2.3). CONCLUSION:The inverse association between H pylori and OAC does not pertain to all infections. The pattern of gastric colonisation and/or impact on acidity may be important. With the reservation for the possibility of confounding, this study also provides some support for the importance of intragastric environment in the aetiology of OSCC.

背景与目标：

BACKGROUND & AIMS: To determine the efficacy of endoscopic variceal ligation (EVL) in prophylaxis on the rate of first esophageal variceal bleeding, we conducted a prospective, randomized trial in 126 cirrhotic patients with no history of previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage. The end-points of the study were bleeding and death. Life-table curves showed that prophylactic EVL significantly diminished the rate of variceal hemorrhage (12/62 [19%] vs. 38/64 [60%]; P = .0001) and overall mortality (17/62 [28%] vs. 37/64 [58%]; P = .0011). The 2-year cumulative bleeding rate was 19% (12/ 62) in the EVL group and 60% (38/64) in the control group. The 2-year cumulative mortality rate was 28% (17/62) in the EVL group and 58% (37/64) in the control group. Comparison of Kaplan-Meier estimates of the time to death of both groups showed significantly lower mortality in the ligation group (P = .001). Patients undergoing EVL had few treatment failures and died mainly of hepatic failure. The lower risk in the EVL group was attributed to a rapid reduction of variceal size. Prophylactic EVL was more efficient in preventing first bleeding in patients with good condition (Child A) than in those with decompensated disease (Child B and C). We conclude that prophylactic EVL can decrease the incidence of first variceal bleeding and death over a period of 2 years in cirrhotic patients with high-risk esophageal varices.

背景与目标： 为了确定内镜下静脉曲张结扎术 (EVL) 预防首次食管静脉曲张出血的疗效，我们对126例无上消化道出血史且经内镜下食管静脉曲张出血风险高的肝硬化患者进行了一项前瞻性随机试验。研究的终点是出血和死亡。生命表曲线显示，预防性EVL显著降低了静脉曲张出血的发生率 (12/62 [19%] vs. 38/64 [60%]; P = .0001) 和总死亡率 (17/62 [28%] vs. 37/64 [58%]; P = .0011)。EVL组2年累积出血率为19% (12/ 62)，对照组为60% (38/64)。2年累积死亡率在EVL组为28% (17/62)，在对照组为58% (37/64)。两组死亡时间的Kaplan-Meier估计值的比较显示，结扎组的死亡率显着降低 (P = .001)。接受EVL的患者几乎没有治疗失败，主要死于肝衰竭。EVL组的较低风险归因于静脉曲张大小的快速减小。与患有失代偿期疾病 (儿童B和C) 的患者相比，预防性EVL在预防状况良好的患者 (儿童A) 的首次出血方面更有效。我们得出的结论是，预防性EVL可以降低肝硬化高危食管静脉曲张患者在2年内首次静脉曲张出血和死亡的发生率。

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： 对脂多糖 (LPS) 响应的b细胞上的表面IgM连接抑制了终末分化和高速度Ig分泌，而对增殖没有影响。如这里所示，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中 “al-or-none” 抑制的细胞异质性。B细胞群体对IgM连接的不同敏感性似乎是由细胞环境局部决定的，与响应细胞的 “成熟度” 无关。因此，尽管长寿命的腹膜b细胞的抵抗力比脾b细胞高3至5倍，但脾脏中短寿命b细胞和长寿命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细胞的敏感性相差两个数量级，但从骨髓前b细胞体外分化的b细胞与脾b细胞一样具有抵抗力。此外，骨髓细胞培养上清液在此类细胞群体中恢复了高水平的敏感性。在显示出与佛波酯直接激活蛋白激酶C相同的剂量反应抑制曲线的细胞群体中，多价名义抗原再现了对IgM受体连接的不同敏感性。我们得出的结论是，对IgM连接的敏感性水平与b细胞的寿命或成熟度无关，但在体内受假定的组织因素的差异调节。

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： Tn10与其他几个转座子一样，表现出对整合到特定靶序列的明显偏好。此类序列被称为整合热点，并已用于定义Tn10转座中的共有靶位点。我们证明了最初在体内鉴定的称为HisG1的Tn10热点在HisG1序列存在于短DNA寡聚物上的反应中也起着体外整合热点的作用。我们使用此体外系统来定义对于捕获HisG1靶位点很重要的因素。我们证明，尽管二价金属离子对于HisG1靶捕获不是必需的，但它们极大地促进了突变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” 靶捕获中起关键作用。对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 (改变靶特异性) 的分析表明，尽管特定的ATS转座酶比野生型转座酶更好地结合HisG1突变体，但Exc Int-突变体在HisG1捕获中存在缺陷，进一步定义这些类别的突变体的属性。考虑了上述观察的可能机制。

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支持其选择的最佳环境。在这里，我们提供了证据，表明紧密连接 (TJs) 广泛地连接了人胸腺的髓质基质细胞。TJ相关分子的Occludin (OCLN) 和claudin-1 (CLDN-1) 在髓样胸腺上皮细胞 (mtec) 中主要表达，CLDN-4和CLDN-7也位于Hassall小体附近的一些mtec中。有趣的是，正如最近在mTEC功能的调节中所建议的那样，发现p53-like转录因子上调人TEC系中的OCLN和CLDN-1。此外，对胸腺细胞的选择具有主要作用的髓质树突状细胞 (dc) 也表达CLDN-1和OCLN，这意味着DCs在mTEC支架内的插入也受到TJs的帮助。胸腺的冷冻断裂复制品分析显示，TJ链结构位于缝隙连接斑块附近，小分子可能会穿过缝隙连接斑块移动，如髓质细胞系的染料转移分析所暗示的那样。因此，人们认为p53-like分子调节延髓基质细胞的TJ相关相互作用，并且该机制可能与细胞间通信网络有关，可能用于保护延髓壁。

BACKGROUND & AIMS: :With currently available combination chemotherapy regimens, the outcome of the patients newly diagnosed with aggressive non-Hodgkin's lymphoma (NHL) identified as 'high' and 'high-intermediate' risk groups according to the international prognostic index (IPI) is still unsatisfactory and a more innovative therapy is urgently required to improve the survival of the patients. The purpose of this study was to compare the efficacy of rituximab given in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and ESHAP (etoposide, methylprednisolone, high-dose Ara-C, cisplatin) vs CHOP-ESHAP and upfront high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) vs standard CHOP in patients aged < or = 65 years old newly diagnosed with 'high' and 'high-intermediate' risk aggressive lymphoma enrolled onto two consecutive treatment trials at the institute. Between May 1995 - July 2002, 84 patients, aged 15 - 65 years old, with newly diagnosed aggressive NHL and an age-adjusted IPI of 2 or 3 were enrolled. The median age of the patients was 38 years (range 15 - 65). The baseline demographic features, in particular the major prognostic variables, were similar between the treatment groups. Patients treated with rituximab-CHOP-ESHAP received eight cycles of rituximab (375 mg m(-2) on day 1 of cycles 1 - 6 and days 21 and 28 of cycle 7) plus CHOP (day 3 of cycles 1, 3 and 5) and ESHAP (day 3 of cycles 2, 4 and 6 and day 1 of cycle 7) at 21-day intervals. Patients enrolled onto the CHOP-ESHAP-HDT arm (n = 23) were treated with three courses of CHOP and then switched to two or four cycles of ESHAP followed by HDT. Patients treated with CHOP alone (n = 25) were treated with the standard eight cycles of CHOP. The rate of complete remission was significantly improved with rituximab-CHOP-ESHAP compared with either CHOP-ESHAP-HDT or CHOP alone (67% compared with 44% and 36%, respectively; p = 0.043). With a median follow-up time of 53 months, the 5-year overall survival (OS) was improved by the addition of rituximab-61% with rituximab-CHOP-ESHAP, compared with 43% for CHOP-ESHAP-HDT and 24% for CHOP alone (p = 0.088). Significant increases in failure-free survival (FFS) and disease-free survival (DFS) (61% and 96%), compared with CHOP-ESHAP-HDT (34% and 90%) and CHOP (16% and 44%; p = 0.002 and p < 0.001, respectively) were observed. Compared to CHOP, rituximab-CHOP-ESHAP yielded significantly superior OS (p = 0.014), FFS (p < 0.001) and DFS (p < 0.001). The survivals, however, were not significantly different from patients treated with CHOP-ESHAP-HDT. It is concluded that rituximab-ESHAP-CHOP is superior over standard CHOP and fares comparably to upfront HDT/ASCT in previously untreated patients with aggressive lymphoma. A prospective randomized controlled trial is warranted to confirm these results.

背景与目标： : 根据目前可用的联合化疗方案，根据国际预后指数 (IPI)，新诊断为侵袭性非霍奇金淋巴瘤 (NHL) 的患者的预后仍不令人满意，迫切需要一种更具创新性的疗法来改善患者的生存。本研究的目的是比较利妥昔单抗与CHOP (环磷酰胺，阿霉素，长春新碱，泼尼松) 和ESHAP (依托泊苷，甲基强的松龙，大剂量Ara-C，顺铂与CHOP-ESHAP以及前期大剂量治疗 (HDT) 和自体干细胞移植 (ASCT) 与标准CHOP在新诊断为 “高” 和 “高中间” 风险侵袭性淋巴瘤的年龄 <或 = 65岁的患者中加入了该研究所的两项连续治疗试验。在1995年5月2002年7月之间，纳入了84例年龄在15-65岁之间的新诊断为侵袭性NHL且年龄校正后的IPI为2或3的患者。患者的中位年龄为38岁 (范围15-65岁)。治疗组之间的基线人口统计学特征，特别是主要预后变量相似。利妥昔单抗-CHOP-ESHAP治疗的患者接受8个周期的利妥昔单抗 (第1-6周期的第1天和第7周期的第21天和第28天的375 mg m(-2)) 加CHOP (第1、3和5周期的第3天) 和ESHAP (第2周期的第3天，第4和第6周期以及第7周期的第1天) 间隔21天。纳入CHOP-ESHAP-HDT臂 (n = 23) 的患者接受了三个疗程的CHOP治疗，然后切换到两个或四个周期的ESHAP，然后进行HDT。仅接受CHOP治疗的患者 (n = 25) 接受标准的8个CHOP周期治疗。与单独使用CHOP-ESHAP-HDT或单独使用CHOP相比，利妥昔单抗-CHOP-ESHAP显著提高了完全缓解率 (分别与44% 和36% 相比67%; p = 0.043)。中位随访时间为53个月，通过添加利妥昔单抗-CHOP-ESHAP的rituximab-61 %，改善了5年总生存率 (OS)，而CHOP-ESHAP-HDT为43%，CHOP单独为24% (p = 0.088)。与CHOP-ESHAP-HDT (34% 和90%) 和CHOP (16% 和44%; 分别为p = 0.002和p <0.001) 相比，无失败生存率 (FFS) 和无病生存率 (DFS) 显著增加 (61% 和96%)。与CHOP相比，利妥昔单抗-CHOP-ESHAP产生显著优越的OS (p = 0.014) 、FFS (p < 0.001) 和DFS (p <0.001)。然而，生存率与接受CHOP-ESHAP-HDT治疗的患者没有显着差异。结论是，在先前未经治疗的侵袭性淋巴瘤患者中，利妥昔单抗-ESHAP-CHOP优于标准CHOP，与前期HDT/ASCT相比。需要进行前瞻性随机对照试验来证实这些结果。

BACKGROUND & AIMS: PURPOSE:To understand the prospective relationship between depressive symptoms and sexual risk behavior among a community sample of African American adolescents. METHODS:African American adolescents (n = 415) who participated in a larger multi-site human immunodeficiency virus (HIV) prevention program provided baseline data on demographics, psychosocial context and depressive symptoms. At six-month follow-up, data were collected regarding sexual activity in the past 90 days. Multivariate logistic regression was conducted to determine the prospective relationship between depressive symptoms and proportion of condom use while controlling for relevant demographic and contextual factors. RESULTS:The odds that African American adolescents who reported depressive symptoms at baseline would report inconsistent condom use at six-month follow-up was approximately four times greater than that of their peers who did not report depressive symptoms. Older adolescents and females were less likely to use condoms consistently and certain contextual factors, such as less pleasurable expectations about condom use, and living with a partner also heightened HIV/STI risk. CONCLUSIONS:Clinicians should assess for depression symptoms in African American adolescent patients as an indicator of future sexual risk. Prevention interventions that address depressed mood could have a significant impact on later HIV/STI sexual risk behaviors. Further research is needed to understand the effect of depressive symptoms on sexual risk among adolescents of other race/ethnicities and to examine the potential cultural forces that affect this relationship.

背景与目标：

BACKGROUND & AIMS: The accuracy of cervicovaginal fetal fibronectin as a predictor of preterm birth was studied in patients with increased risk for preterm delivery (according to the Creasy-score). In a prospective blind observational study the smear from the posterior fornix vaginae of 56 pregnant patients without PROM was examined using a quantitative immunoassay for the detection of fetal fibronectin. The patients who tested positively for fetal fibronectin had significantly more preterm deliveries than those with a negative result (CHI square-test, p < 0.01, RR 5.1). Overall, sensitivity, specificity, positive and negative predictive values were 56%, 87%, 45% and 91%, respectively. In patients with preterm labor these values were 75%, 87%, 60%, and 93%, respectively. No patient with a negative result delivered preterm during the following two weeks. It is concluded that performing the fetal fibronectin test in patients with preterm labor is useful for the prediction of preterm birth. Routine testing in patients at increased risk (asymptomatic patients) is not recommended for lack of effectiveness.

背景与目标： 在早产风险增加的患者中研究了宫颈阴道胎儿纤维连接蛋白作为早产预测指标的准确性 (根据Creasy评分)。在一项前瞻性盲观察研究中，使用定量免疫测定法检查了56例无胎膜早破的孕妇的后穹窿阴道涂片，以检测胎儿纤连蛋白。胎儿纤连蛋白检测呈阳性的患者的早产明显多于阴性结果的患者 (卡方检验，p <0.01，RR 5.1)。总体而言，敏感性、特异性、阳性和阴性预测值分别为56% 、87% 、45% 和91%。在早产患者中，这些值分别为75%，87%，60% 和93%。在接下来的两周内，没有阴性结果的患者早产。结论对早产患者进行胎儿纤连蛋白试验对预测早产有一定的帮助。不建议对风险增加的患者 (无症状患者) 进行常规测试，因为缺乏有效性。

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，鼠疫杆菌合成具有低Toll样受体4 (TLR4) 刺激活性的脂多糖 (LPS)-脂质A。为了解决弱TLR4刺激对毒力的影响，我们对鼠疫耶尔森氏菌进行了修饰，以产生有效的TLR4-stimulating LPS。即使在高攻击剂量下，改良的鼠疫耶尔森氏菌在皮下感染后也完全无毒。对疾病的抵抗力需要TLR4，衔接子蛋白MyD88和共受体MD-2，并且CD14和衔接子Mal显着增强。对于针对改良菌株的免疫灭菌，需要先天和适应性反应，并且可以保护恢复期小鼠免受野生型鼠疫耶尔森氏菌的皮下和呼吸攻击。尽管存在其他已建立的免疫逃避机制，但改良的鼠疫耶尔森氏菌无法引起全身性疾病，这表明逃避LPS诱导的炎症反应的能力对于鼠疫耶尔森氏菌的毒力至关重要。通过脂质A改变逃避TLR4激活可能有助于各种革兰氏阴性细菌的毒力。

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由公共卫生学院和北卡罗来纳大学教堂山分校的Kenan-Flagler商学院联合提供的基于团队的培训计划。这个为期9个月的计划教公共卫生经理如何更好地管理人员，信息和财务。参与者将学习如何与社区合作伙伴一起团队合作，以及如何作为社会企业家进行思考和行为。为了实践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。本文介绍了该计划并解释了过程评估的结果，该评估研究了如何最好地构建和部署基于团队的方法，以创建更有效，更具企业家精神的公共卫生经理。研究结果表明，招聘和保留能力很强，课程要素与学习者的需求相关，并且学习者对课程感到满意并重视。确定了计划模型的几个特定好处，以及支持业务计划成功和技能在工作中的应用的几个要素。根据这些发现，确定了开发类似计划的四个成功因素。