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。

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 : 失眠在一般实践中被广泛报道和广泛治疗，但针对初级保健机构中该病的自然史的研究相对较少。因此，目前几乎没有信息可以使临床医生评估失眠风险，或预测老年全科医生的结果。
目标 : 使用8年的纵向数据进行估计，失眠发作的风险与选定的健康和生活方式因素有关。
方法 : 1989年 (n = 690) 和1993 (n = 410) 重新评估了来自1985年最初接受采访的具有全国代表性的老年人样本 (n = 1042) 的幸存者。在第一次随访1989年，发现了84例新的失眠病例 (每人每年加权发病率，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失眠发作的风险。
结果 : 1985年评估的三个因素与失眠事件显着且独立相关: 符合抑郁情绪优势比 (OR) = 4.41; 95% CI = 3.32-5.43); 健康指数得分表明较低的身体健康状况 (OR = 1.19; 95% CI = 1.06-1.31每单位变化的量表得分); 和中等和低水平的体育活动 (OR = 1.91和2.14; 95% CI分别 = 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健康而不是精神健康不良。
结论 : 精神病学，躯体和生活方式因素显着且独立地增加了老年全科患者的失眠风险。在预测事件睡眠障碍时，这些因素的重要性超过了患者的年龄和性别。

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： 在各种人类癌症中，已发现位于癌侵袭性前沿的肿瘤细胞与其他肿瘤细胞有很大不同。目前对94例口腔鳞状细胞癌 (oscc) 的多变量生存分析显示，侵袭性肿瘤细胞的嗜银核仁组织区相关蛋白 (AgNOR) 含量和多参数组织病理学肿瘤前等级均与肿瘤相关死亡显着且独立相关，与肿瘤的常规broders等级和临床分期无关。因此，侵袭性OSCC前沿的高肿瘤前沿得分和AgNOR含量似乎反映了恶性潜能的增加。通过标准化的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。

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个月的时间内，对33位连续的肝移植受者进行了前瞻性研究，以寻找巨细胞病毒感染的证据。确定了16 (48%) 例巨细胞病毒感染; 9例为原发感染，7例为复发性感染。从患者8开始，大多数患者常规使用丙种球蛋白预防。评估了巨细胞病毒感染的十二个潜在危险因素，包括供体和受者的移植前巨细胞病毒血清学状态; 受者的年龄，性别，种族和肝脏疾病; 输血的血液制品的数量和类型; 免疫抑制的类型和强度; 和排斥的发生。Cox比例风险模型确定阳性供体巨细胞病毒血清学是随后发生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的血清学状况无关。此外，使用丙种球蛋白预防似乎可以预防弥漫性巨细胞病毒疾病的发生。

BACKGROUND & AIMS: :Many field sports involve equipment that restricts one or both arms from moving while running. Arm swing during running has been examined from a biomechanical and physiologic perspective but not from an injury perspective. Moreover, only bilateral arm swing suppression has been studied with respect to running. The purpose of this study was to determine the influence of running with one arm restrained on lower extremity mechanics associated with running or sport-related injury. Fifteen healthy participants ran at a self-selected speed with typical arm swing, with one arm restrained and with both arms restrained. Lower extremity kinematics and spatiotemporal measures were analysed for all arm swing conditions. Running with one arm restrained resulted in increased frontal plane knee and hip angles, decreased foot strike angle, and decreased centre of mass vertical displacement compared to typical arm swing or bilateral arm swing restriction. Stride length was decreased and step frequency increased when running with one or both arms restrained. Unilateral arm swing restriction induces changes in lower extremity kinematics that are not similar to running with bilateral arm swing restriction or typical arm swing motion. Running with one arm restrained increases frontal plane mechanics associated with risk of knee injury.

背景与目标： : 许多野外运动都涉及限制一只或两只手臂在跑步时移动的设备。从生物力学和生理角度检查了跑步过程中的手臂摆动，但没有从损伤的角度进行检查。此外，仅研究了关于跑步的双侧臂摆动抑制。这项研究的目的是确定限制一只手臂的跑步对与跑步或运动相关的损伤相关的下肢力学的影响。15名健康的参与者以典型的手臂摆动以自我选择的速度奔跑，一只手臂受到约束，而两只手臂受到约束。分析了所有手臂摆动条件下的下肢运动学和时空测量。与典型的手臂摆动或双侧手臂摆动限制相比，用一只手臂约束跑步会导致额面膝关节和髋关节角度增加，脚的打击角度减小，并且质量中心垂直位移减小。在一只或两只手臂受约束的情况下跑步时，步幅减少，步频增加。单侧手臂摆动限制会引起下肢运动学的变化，与双侧手臂摆动限制或典型手臂摆动运动的跑步不相似。一只手臂约束跑步会增加与膝盖受伤风险相关的正面平面力学。

BACKGROUND & AIMS: BACKGROUND:Trabecular bone strength diminishes as a result of osteoporosis and altered biomechanical loading at the vertebral and spinal levels. The spine consists of the anterior, middle and posterior columns and the load supported by the anterior and middle columns will differ across different regions of the spine. Stress shielding of the anterior column can contribute to bone loss and increase the risk of wedge fracture. There is a lack of quantitative data related to regional spinal bone mineral density distribution over time. We hypothesize that there is an increase in the posterior-to-anterior vertebral body bone mineral density ratio and a decrease in whole-body bone mineral density over time. METHODS:Bone mineral density was measured in 33 subjects using quantitative computed tomography scans for L1-L3 vertebrae, region (anterior and posterior vertebral body), and time (baseline and 6 years after). FINDINGS:Lumbar bone mineral density decreased significantly (Δ: ~15%) from baseline to the 6th year visit. Individual vertebra differences over time (L1: ~14%, L2: ~14%, L3: ~17%) showed statistical significance. Anterior bone mineral density change was significantly greater than in the posterior vertebral body region (Δ anterior: ~18%; Δ posterior: ~13%). Posterior-to-anterior bone mineral density ratio was significantly greater in the 6th year compared to baseline values (mean (SD), 1.33 (0.2) vs. 1.23 (0.1)). INTERPRETATION:This study provides longitudinal quantitative measurement of bone mineral density in vertebrae as well as regional changes in the anterior and posterior regions. Understanding bone mineral density distribution over time may help to decrease the risk of wedge fractures if interventions can be developed to bring spine loading to its normal state.

背景与目标：

BACKGROUND & AIMS: :We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10-7; OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.

背景与目标： : 我们使用严格定义的表型对神经性厌食症 (AN) 进行了全基因组关联研究 (gwa)。表型变异性的分析导致鉴定出一种特定的遗传危险因素，该因素具有全基因组意义 (EBF1中的rs929626 (早期b细胞因子1); P   =   2.04  ×   10-7; Or   =   0.7; 95% 置信区间 (CI)  =   0.61-0.8) 与独立复制 (p   =   0.04)，提示一个变异介导的瘦素信号失调可能在AN中起作用。具有变体的LD中的多个snp支持名义上的关联。这表明，尽管AN的临床和病因学异质性已得到普遍认可，但对病例的进一步仔细分类可能会提供更精确的基因组信号。在这项研究中，通过改进AN的表型谱，我们提出了名义上与AN相关的可复制gwa信号，突出了潜在的重要候选基因座，以供进一步研究。

BACKGROUND & AIMS: AIMS:We aimed to determine whether there is an association between dietary zinc intake (DZI) and prevalent kidney stone disease defined as self-report of any previous episode of kidney stone. METHODS:We examined The Third National Health and Nutrition Examination Survey (NHANES III), a large US population-based cross-sectional study, and used logistic regression analyses to determine the independent association between DZI and prevalent kidney stone disease. RESULTS:A total of 15,444 men and women over 18 years of age were eligible for analysis. Among them, 710 participants reported a history of kidney stones. Stone formers tended to have higher DZI than non-stone formers among NHANES III participants, though this difference did not reach statistical significance (p = 0.1). Multivariate adjusted logistic regression analysis revealed that higher DZI (log transformed) was associated with a significantly increased risk of kidney stone disease (odds ratio, OR = 1.41, 95% confidence interval, CI: 1.10-1.81, p = 0.01). After categorizing zinc intake into three groups, those with highest DZI (>15 mg/day) were also associated with a significantly increased risk of kidney stone disease, compared to those with lower DZI (<7 mg/day; OR = 1.70, 95% CI: 1.13-2.57, p = 0.01). CONCLUSIONS:Our study suggests that higher DZI is associated with increased risk of kidney stone disease. Future prospective studies are needed to clarify the causal relationship between zinc intake and kidney stone formation.

背景与目标：