BACKGROUND & AIMS: BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS:We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS:Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION:ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.

背景与目标：

BACKGROUND & AIMS: :The ovarian steroid hormone estrogen (E2) elicits a multiplicity of both systemic and uterotropic responses in vivo. For example, the administration of E2 to ovariectomized (Ovx) and sexually immature rodents leads to uterine-specific inflammatory infiltrates. In this study, we quantitated the number of eosinophils and BM8+, Ia+, and CD4+ cells in uteri obtained from adult Ovx control and E2-treated C57BL/6J, C3H/HeJ, and (C57BL/6J x C3H/HeJ) (B6C3) F1 hybrid mice. All three strains exhibited a significant increase in the number of uterine eosinophils and BM8+ macrophages after E2 treatment. However, C57BL/6J and B6C3 F1 hybrid mice responded with a greater number of infiltrating eosinophils and macrophages as compared with C3H/HeJ. A similar analysis of Ia+ and CD4+ cells showed that E2 treatment either down-regulates or does not affect the number of such cells in all three strains. Genome exclusion mapping using a (C57BL/6J x C3H/HeJ) x C3H/HeJ backcross population localized Est1, the major locus controlling the number of eosinophils infiltrating the uterus after E2 treatment, to chromosome 4. In addition, suggestive linkage to marker loci on chromosomes 10 and 16 was detected and evidence for locus interaction is presented. Our results conclusively demonstrate that E2-regulated/ dependent responses can be genetically controlled, indicating that the phenotypic variation observed in both the normal and pathological effects of E2 may, in part, be due to a genetic component.

背景与目标： : 卵巢类固醇激素雌激素 (E2) 在体内引起多种全身和子宫性反应。例如，向卵巢切除 (Ovx) 和性不成熟的啮齿动物施用E2会导致子宫特异性炎症浸润。在这项研究中，我们定量了从成年Ovx对照和E2-treated C57BL/6J，C3H/HeJ和 (C57BL/6J x C3H/HeJ) (B6C3) F1杂交小鼠获得的子宫中嗜酸性粒细胞和BM8，Ia和CD4细胞的数量。E2处理后，所有这三种菌株的子宫嗜酸性粒细胞和BM8巨噬细胞数量均显着增加。然而，与C3H/HeJ相比，C57BL/6J和B6C3 F1杂交小鼠的浸润嗜酸性粒细胞和巨噬细胞数量更多。对Ia和CD4细胞的类似分析表明，E2处理下调或不影响所有三种菌株中此类细胞的数量。使用 (C57BL/6J x C3H/HeJ) x C3H/HeJ回交群体的基因组排斥图谱将Est1定位为4号染色体，Est1是控制E2治疗后子宫浸润的嗜酸性粒细胞数量的主要基因座。此外，还检测到与10号和16号染色体上的标记基因座的暗示连锁，并提供了基因座相互作用的证据。我们的结果最终证明了E2-regulated/依赖性反应可以在遗传上控制，这表明在E2的正常和病理作用中观察到的表型变异可能部分归因于遗传成分。

BACKGROUND & AIMS: :A transcript (RNA I) from ColE1 inhibits initiation of replication of the plasmid DNA by binding to the precursor of the primer RNA (RNA II). The ability of RNA I to inhibit replication is altered by the presence of a plasmid-specified small protein, Rom. In vitro, RNA I binds to RNA II to form a very unstable complex, C*. Binding of a single molecule of Rom converts C* to a more stable complex, Cm*. Each of these complexes, C* or Cm*, transforms to a more stable complex, C** or Cm**, respectively. While formation of complex C* or Cm* is inferred from the inhibition of binding caused by a second RNA I species, that of complex C** or Cm** is detected by alteration of RNase sensitivity. Complex C* converts to complex Cm* very rapidly upon addition of Rom to the medium and complex Cm* converts to complex C* very rapidly by removal of Rom from the medium. On the other hand, complexes C** and Cm** do not rapidly interconvert, but can eventually transform to the same stable final product. Thus, Rom affects binding of RNA I to RNA II through conversion of a very unstable early intermediate to a more stable complex, creating a second pathway for their stable binding.

背景与目标： : 来自ColE1的转录本 (RNA I) 通过与引物RNA (RNA II) 的前体结合来抑制质粒DNA的复制启动。RNA I抑制复制的能力因质粒指定的小蛋白Rom的存在而改变。在体外，RNA I与RNA II结合形成非常不稳定的复合物C *。单个Rom分子的结合将C * 转化为更稳定的复合物Cm *。这些配合物C * 或Cm * 中的每一个分别转换为更稳定的配合物C ** 或Cm **。虽然从第二种RNA I物种引起的结合抑制推断出复合物C * 或Cm * 的形成，但通过RNase敏感性的改变来检测复合物C ** 或Cm ** 的形成。将Rom添加到介质中时，复杂C * 非常迅速地转换为复杂Cm *，而通过从介质中删除Rom，复杂Cm * 非常迅速地转换为复杂C *。另一方面，络合物C ** 和Cm ** 不会快速互转，但最终可以转化为相同的稳定最终产物。因此，Rom通过将非常不稳定的早期中间体转化为更稳定的复合物来影响RNA I与RNA II的结合，从而为它们的稳定结合创造了第二条途径。

BACKGROUND & AIMS: Environmental pollution has become a major concern for the future of life on our planet; medical care, especially in hospitals, contributes significantly to this pollution. The increasing usage of highly-developed medical devices, drugs and disposable products are a drain on natural resources as well as financial ones. In this situation, it is a major task for hospital epidemiologists to maintain high standards of hygiene while reducing environmental pollution, reducing consumption of limited natural resources, and minimizing costs. The reduction of hospital waste, the control of polluting and toxic emissions, the avoidance of unnecessary disinfection procedures and disposables, the implementation of energy and water saving technologies are practicable measures in hospital ecology. To realize a sustainable development within hospitals, it is necessary that the need to maintain a balance between effective infection control and a good ecological environment is recognized and supported by health-care workers and the hospital management.

背景与目标： 环境污染已成为地球生命未来的主要问题; 医疗保健，尤其是医院的医疗保健，对这种污染有很大影响。高度发达的医疗设备，药品和一次性产品的使用日益增加，既消耗了自然资源，也消耗了金融资源。在这种情况下，医院流行病学家的主要任务是在减少环境污染的同时保持高标准的卫生，减少对有限自然资源的消耗并最大程度地降低成本。减少医院废物，控制污染和有毒排放物，避免不必要的消毒程序和一次性用品，实施节能节水技术是医院生态中的可行措施。为了实现医院内部的可持续发展，有必要在有效的感染控制和良好的生态环境之间保持平衡的需要得到医护人员和医院管理层的认可和支持。

BACKGROUND & AIMS: :The skin as a barrier and immune organ is exposed to omnipresent environmental challenges such as irradiation or chemical and biologic hazards. Neuropeptides released from cutaneous nerves or skin and immune cells in response to noxious stimuli are mandatory for a fine-tuned regulation of cutaneous immune responses and tissue maintenance and repair. They initialize host immune responses, but are equally important for counter regulation of proinflammatory events. Interaction of the nervous and immune systems occurs both locally - at the level of neurogenic inflammation and immunocyte activation - and centrally - by controlling inflammatory pathways such as mononuclear activation or lymphocyte cytokine secretion. Consequently, a deregulated neurogenic immune control results in disease manifestation and frequently accompanies chronic development of cutaneous disorders. The current understanding, therapeutic options, and open questions of the role that neuropeptides such as substance P, calcitonin gene-related peptide, vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide, neuropeptide Y, or others play in these events are discussed. Progress in this field will likely result in novel therapies for the management of diseases characterized by deregulated inflammation, tissue remodeling, angiogenesis, and neoplasm.

背景与目标： : 皮肤作为屏障和免疫器官暴露于无所不在的环境挑战，如辐射或化学和生物危害。响应有害刺激从皮肤神经或皮肤和免疫细胞释放的神经肽对于微调皮肤免疫反应以及组织维护和修复是必不可少的。它们初始化宿主免疫反应，但对于反调节促炎事件同样重要。神经和免疫系统的相互作用通过控制炎症途径 (例如单核激活或淋巴细胞细胞因子分泌) 在局部发生-在神经源性炎症和免疫细胞激活水平上-在中枢发生。因此，放松的神经源性免疫控制会导致疾病表现，并经常伴随皮肤疾病的慢性发展。讨论了神经肽 (例如p物质，降钙素基因相关肽，血管活性肠肽/垂体腺苷酸环化酶激活多肽，神经肽Y或其他) 在这些事件中的作用的当前理解，治疗选择和开放性问题。该领域的进展可能会导致新的疗法来管理以炎症，组织重塑，血管生成和肿瘤为特征的疾病。

BACKGROUND & AIMS: Recent genome searches suggest a putative linkage of many loci to susceptibility to type I diabetes. The chromosome 2q31-35 region is reported to be linked to susceptibility to type I diabetes and is thought to contain several diabetes susceptibility loci. These candidate genes include the HOXD gene cluster, BETA2, CTLA4, CD28, IGFBP2, and IGFBP5. Association studies in populations and families are required to confirm and/or identify the actual susceptibility loci. We hereby report several previously unknown DNA polymorphisms for HOXD8, BETA2, and IGFBP5, which we have used along with previously known polymorphisms of HOXD8 and CTLA4 to test whether these candidate loci are the susceptibility genes on chromosome 2q31-35. Using a case-control design with a subsequent family-association approach to confirm associations, we find no evidence that these candidate genes are associated with susceptibility to type I diabetes.

背景与目标： 最近的基因组搜索表明，许多基因座与I型糖尿病易感性之间存在推定的联系。据报道，染色体2q31-35区域与I型糖尿病的易感性有关，并被认为包含多个糖尿病易感性位点。这些候选基因包括HOXD基因簇，BETA2，CTLA4，CD28，IGFBP2和igfbp5。需要在人群和家庭中进行关联研究，以确认和/或确定实际的易感性位点。我们在此报告了HOXD8，BETA2和IGFBP5的几个先前未知的DNA多态性，我们将其与先前已知的HOXD8和CTLA4的多态性一起使用，以测试这些候选基因座是否是染色体2q31-35上的易感基因。使用病例对照设计和随后的家庭关联方法来确认关联，我们没有发现证据表明这些候选基因与I型糖尿病的易感性有关。

BACKGROUND & AIMS: :In some randomized (drug versus placebo) clinical trials, the estimand of interest is the between-treatment difference in population means of a clinical endpoint that is free from the confounding effects of "rescue" medication (e.g., HbA1c change from baseline at 24 weeks that would be observed without rescue medication regardless of whether or when the assigned treatment was discontinued). In such settings, a missing data problem arises if some patients prematurely discontinue from the trial or initiate rescue medication while in the trial, the latter necessitating the discarding of post-rescue data. We caution that the commonly used mixed-effects model repeated measures analysis with the embedded missing at random assumption can deliver an exaggerated estimate of the aforementioned estimand of interest. This happens, in part, due to implicit imputation of an overly optimistic mean for "dropouts" (i.e., patients with missing endpoint data of interest) in the drug arm. We propose an alternative approach in which the missing mean for the drug arm dropouts is explicitly replaced with either the estimated mean of the entire endpoint distribution under placebo (primary analysis) or a sequence of increasingly more conservative means within a tipping point framework (sensitivity analysis); patient-level imputation is not required. A supplemental "dropout = failure" analysis is considered in which a common poor outcome is imputed for all dropouts followed by a between-treatment comparison using quantile regression. All analyses address the same estimand and can adjust for baseline covariates. Three examples and simulation results are used to support our recommendations.

背景与目标： : 在一些随机 (药物与安慰剂) 临床试验中，感兴趣的估计是临床终点的人群治疗间差异，该临床终点不受 “抢救” 药物的混杂作用 (例如，hbA1c在24周时与基线相比的变化，无论是否或何时终止分配的治疗，在没有抢救药物的情况下都会观察到).在这种情况下，如果某些患者在试验中过早退出试验或开始使用抢救药物，则会出现数据丢失的问题，后者需要丢弃抢救后的数据。我们警告说，常用的混合效应模型重复测量分析与随机假设的嵌入缺失可以提供对上述感兴趣估计的夸大估计。发生这种情况的部分原因是对药物组中 “辍学” (即缺少感兴趣的终点数据的患者) 过于乐观的均值进行了隐含的估算。我们提出了一种替代方法，其中将药物组辍学的缺失平均值明确替换为安慰剂下的整个终点分布的估计平均值 (主要分析) 或在临界点框架内的一系列越来越保守的平均值 (敏感性分析); 不需要患者水平的估算。考虑了补充的 “辍学 = 失败” 分析，其中对所有辍学进行了共同的不良结果估算，然后使用分位数回归进行治疗之间的比较。所有分析都针对相同的估计，并且可以针对基线协变量进行调整。使用了三个示例和仿真结果来支持我们的建议。

BACKGROUND & AIMS: :The purpose of this study was to compare preferred facial profiles rated by different age groups. An average profile of each gender was constructed from subjects with normal occlusions. Each average profile was located in the centre, and then the lips were protruded or retruded in six 1mm increments in each direction. 70 lay people were divided into 3 groups: young adult (20-39 years); middle-aged (40-54 years); and senior (55-70 years). They were asked to rank their 3 most preferred profiles for each gender. The distribution of the most pleasing profile was compared according to age groups by the Kruskal-Wallis test and according to the rater's gender by the Mann-Whitney U-test. There was a significant difference between the three age groups regarding the preferred male and female profiles (P<0.001). Both the middle-aged and the senior groups tended to select a slightly more retruded lip/flat profile than the young adult group. There was no gender dimorphism in the selection of the preferred profile. The young adult group preferred the straight profile while the middle-aged and senior groups favoured the slightly retruded profile. This may provide useful information for treatment planning in orthodontics and orthognathic surgery.

背景与目标： : 这项研究的目的是比较不同年龄段的首选面部特征。从正常闭塞的受试者中构建每个性别的平均特征。每个平均轮廓位于中心，然后在每个方向上以六个1毫米的增量突出或重放嘴唇。70名外行人分为3组: 年轻人 (20-39岁); 中年 (40-54岁); 和老年人 (55-70岁)。他们被要求对每个性别的3个最喜欢的个人资料进行排名。通过Kruskal-Wallis测试根据年龄组比较了最令人愉悦的个人资料的分布，并通过Mann-Whitney u- test根据评估者的性别进行了比较。三个年龄组在首选男性和女性特征方面存在显着差异 (P<0.001)。与年轻的成年组相比，中老年组和老年组都倾向于选择略胜一筹的嘴唇/扁平轮廓。在选择首选特征时没有性别二态性。年轻的成年组更喜欢直率的轮廓，而中老年组则更喜欢略微被重述的轮廓。这可能为正畸和正颌手术的治疗计划提供有用的信息。

BACKGROUND & AIMS: :Hemorrhage is the most preventable cause of posttraumatic death. Many cases are potentially anatomically salvageable, yet remain lethal without logistics or trained personnel to deliver diagnosis or resuscitative surgery in austere environments. Revolutions in technology for remote mentoring of ultrasound and surgery may enhance capabilities to utilize the skill sets of non-physicians. Thus, our research collaborative explored remote mentoring to empower non-physicians to address junctional and torso hemorrhage control in austere environments. Major studies involved using remote-telementored ultrasound (RTMUS) to identify torso and junctional exsanguination, remotely mentoring resuscitative surgery for torso hemorrhage control, understanding and mitigating physiological stress during such tasks, and the technical practicalities of conducting damage control surgery (DCS) in austere environments. Iterative projects involved randomized guiding of firefighters to identify torso (RCT) and junctional (pilot) hemorrhage using RTMUS, randomized remote mentoring of MedTechs conducting resuscitative surgery for torso exsanguination in an anatomically realistic surgical trainer ("Cut Suit") including physiological monitoring, and trained surgeons conducting a comparative randomized study for torso hemorrhage control in normal (1g) versus weightlessness (0g). This work demonstrated that firefighters could be remotely mentored to perform just-in-time torso RTMUS on a simulator. Both firefighters and mentors were confident in their abilities, the ultrasounds being 97% accurate. An ultrasound-naive firefighter in Memphis could also be remotely mentored from Hawaii to identify and subsequently tamponade an arterial junctional hemorrhage using RTMUS in a live tissue model. Thereafter, both mentored and unmentored MedTechs and trained surgeons completed resuscitative surgery for hemorrhage control on the Cut-Suit, demonstrating practicality for all involved. While remote mentoring did not decrease blood loss among MedTechs, it increased procedural confidence and decreased physiologic stress. Therefore, remote mentoring may increase the feasibility of non-physicians conducting a psychologically daunting task. Finally, DCS in weightlessness was feasible without fundamental differences from 1g. Overall, the collective evidence suggests that remote mentoring supports diagnosis, noninvasive therapy, and ultimately resuscitative surgery to potentially rescue those exsanguinating in austere environments and should be more rigorously studied.

背景与目标： : 出血是创伤后死亡最可预防的原因。许多病例在解剖学上可能是可挽救的，但如果没有后勤人员或训练有素的人员在严峻的环境中进行诊断或复苏手术，则仍然致命。超声波和外科手术远程指导技术的革命可能会增强利用非医生技能的能力。因此，我们的研究合作探索了远程指导，以使非医生能够在严峻的环境中解决交界处和躯干出血控制问题。主要研究包括使用远程远程超声 (RTMUS) 识别躯干和交界性放血，远程指导复苏手术以控制躯干出血，理解和减轻此类任务期间的生理压力，以及在严峻环境中进行损伤控制手术 (DCS) 的技术实用性。迭代项目包括随机指导消防员使用RTMUS识别躯干 (RCT) 和交界 (pilot) 出血，随机远程指导MedTechs在解剖学上逼真的外科训练器 (“切割服”) 中进行躯干放血的复苏手术，包括生理监测，和训练有素的外科医生进行了一项比较随机研究，以正常 (1g) 与失重 (0g) 的躯干出血控制。这项工作表明，可以远程指导消防员在模拟器上执行及时的躯干RTMUS。消防员和导师都对自己的能力充满信心，超声波97% 准确。孟菲斯的一名未经超声检查的消防员也可以从夏威夷进行远程指导，以识别并随后在活组织模型中使用RTMUS填塞动脉交界性出血。此后，经过指导和未经指导的MedTechs和训练有素的外科医生都完成了复苏手术，以控制剪裁服上的出血，这证明了所有参与者的实用性。虽然远程指导并没有减少MedTechs的失血，但它增加了程序信心并减少了生理压力。因此，远程指导可能会增加非医生执行心理艰巨任务的可行性。最后，失重的dc是可行的，与1g没有根本差异。总体而言，集体证据表明，远程指导支持诊断，无创治疗以及最终的复苏手术，以潜在地挽救那些在严峻环境中放血的人，因此应进行更严格的研究。

BACKGROUND & AIMS: PURPOSE:To evaluate the indications and outcomes of amniotic membrane transplantation (AMT) performed within the first 2 weeks of presentation in the management of patients with acute Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS:A retrospective chart review from January 1998 to May 2011 identified 128 SJS/TEN patients admitted to Loyola University Medical Center Burn intensive care unit. The degree of initial ocular surface inflammation was graded as mild, moderate, or severe within the first 2 weeks of admission. Patients were managed either medically or with amniotic membrane (AM). Outcomes were graded as good [best-corrected visual acuity (BCVA)>20/40], fair (BCVA 20/40 to 20/200 or with ocular surface discomfort, requiring contact lens or reconstructive surgeries), or poor (BCVA<20/200). RESULTS:Of the 182 eyes (91 patients) with documented inpatient eye examinations, 108 eyes (59.4%) had mild or no initial ocular involvement, 37 eyes (20.3%) had moderate, and 37 eyes (20.3%) had severe inflammation. Of the 29 patients (58 eyes) with greater than 1 month of follow-up, 17 patients (33 eyes) were treated with medical management and 13 patients (25 eyes) were treated with early AM. One of the 23 eyes with moderate or severe presentation treated with early AMT (4.3%) resulted in a poor outcome within 3 months compared with 8 of 23 eyes (34.8%) that were medically managed (P=0.022). CONCLUSIONS:We present the first case-control study of the use of AM in the management of acute SJS/TEN. Early use of AMT prevents severe vision loss in SJS/TEN patients with initial moderate or severe ocular surface inflammation.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:To evaluate temperament and character traits using the Junior Temperament and Character Inventory (JTCI) in children and adolescents with major depressive disorder (MDD) in comparison with healthy control subjects (HC), and to verify if comorbidity with disruptive behavioral disorders and being currently depressed influence JTCI scores. METHODS:A case-control study comprising 41 MDD children/adolescents matched to 40 HC by gender and age (8-17years). All participants were assessed diagnostically with the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime (K-SADS-PL). Temperament and character traits were measured with the parent and child versions of JTCI, and depression was evaluated with the Children's Depression Rating Scale (CDRS). RESULTS:According to child and parent data, MDD subjects had significantly higher scores on harm avoidance and novelty seeking, and lower scores on reward dependence, persistence, self-directedness and cooperativeness compared with HC. According to parent data only, MDD subjects significantly differed from HC on self-transcendence (lower spirituality scores and higher fantasy scores). Comorbidity with disruptive behavioral disorders exerted influence on almost all dimensions, in general increasing the mean differences between MDD and HC subjects. Also, being currently depressed did not influence the results, except for reward dependence according to parent data. LIMITATIONS:The cross-sectional nature of the study and its limited sample size. CONCLUSIONS:MDD children/adolescents have a different temperament and character profile compared to HC subjects. This study supports previous findings of trait-like characteristics of harm avoidance and self-directedness.

背景与目标：

BACKGROUND & AIMS: :Previous studies have shown that drugs which block the reuptake of catecholamine neurotransmitters improve impulse control in diseases such as attention deficit hyperactivity disorder (ADHD). Serotonin-specific reuptake inhibitors (SSRI) lack efficacy in ADHD and have been linked to increased suicide risk. The present study investigated drugs with affinity for one or more of the monoamine reuptake transporters using the 5-choice serial reaction time task, a model of attention and impulsivity in rodents. We also tested the effects of the alpha(2)-adreoceptor antagonist, idazoxan and novel antidepressant, agomelatine, which both increase cortical noradrenaline concentrations through non-reuptake mechanisms. Improvements in impulse control were observed with venlafaxine, a serotonin and noradrenaline re-uptake inhibitor (SNRI) but not bupropion (dopamine and noradrenaline re-uptake inhibitor). Sibutramine (SNRI) reduced premature responses by ~50% at the highest dose tested but this was not significant. All three of the SSRIs tested reduced premature responding in a dose-dependent manner, although also slowed response and collection latencies. Neither idazoxan nor agomelatine significantly reduced premature responding, suggesting a lack of efficacy at the doses tested. None of the drugs tested improved attention in this task but sibutramine (SNRI), fluoxetine (SSRI) and paroxetine (SSRI) all increased omissions at the highest dose tested. These data suggest that the SNRIs and SSRIs reduce premature responding but tend to be less specific than noradrenaline specific reuptake inhibitors in this model. SSRIs did not induce any specific impairment in impulse control in this model.

背景与目标： : 先前的研究表明，阻断儿茶酚胺神经递质再摄取的药物可改善注意力缺陷多动障碍 (ADHD) 等疾病的冲动控制。血清素特异性再摄取抑制剂 (SSRI) 在ADHD中缺乏疗效，并与自杀风险增加有关。本研究使用5选择系列反应时间任务 (啮齿动物的注意力和冲动性模型) 研究了对一种或多种单胺再摄取转运蛋白具有亲和力的药物。我们还测试了 α (2)-受体拮抗剂咪唑嗪和新型抗抑郁药阿戈米拉汀的作用，它们均通过非再摄取机制增加皮质去甲肾上腺素浓度。使用文拉法辛 (一种5-羟色胺和去甲肾上腺素再摄取抑制剂 (SNRI)) 但未使用安非他酮 (多巴胺和去甲肾上腺素再摄取抑制剂) 观察到冲动控制的改善。在测试的最高剂量下，西布曲明 (SNRI) 将过早反应降低约50%，但这并不显著。测试的所有三个ssri均以剂量依赖性方式减少了过早反应，尽管也减慢了反应和收集延迟。依达唑烷和阿戈米拉汀均未显着降低过早反应，表明在测试剂量下缺乏疗效。测试的药物均未提高此任务中的注意力，但西布曲明 (SNRI)，氟西汀 (SSRI) 和帕罗西汀 (SSRI) 在测试的最高剂量下均增加了遗漏。这些数据表明，在该模型中，snri和SSRIs减少了过早反应，但特异性不如去甲肾上腺素特异性再摄取抑制剂。在该模型中，SSRIs不会在冲动控制中引起任何特定的损害。

BACKGROUND & AIMS: :Mitochondrial dysfunction is the most prominent source of oxidative stress in acute and chronic kidney disease. NLRX1 is a receptor of the innate immune system that is ubiquitously expressed and localized in mitochondria. We investigated whether NLRX1 may act at the interface of metabolism and innate immunity in a model of oxidative stress. Using a chimeric mouse model for renal ischemia-reperfusion injury, we found that NLRX1 protects against mortality, mitochondrial damage, and epithelial cell apoptosis in an oxidative stress-dependent fashion. We found that NLRX1 regulates oxidative phosphorylation and cell integrity, whereas loss of NLRX1 results in increased oxygen consumption, oxidative stress, and subsequently apoptosis in epithelial cells during ischemia-reperfusion injury. In line, we found that NLRX1 expression in human kidneys decreased during acute renal ischemic injury and acute cellular rejection. Although first implicated in immune regulation, we propose that NLRX1 function extends to the control of mitochondrial activity and prevention of oxidative stress and apoptosis in tissue injury.

背景与目标： : 线粒体功能障碍是急性和慢性肾脏疾病中氧化应激的最突出来源。NLRX1是先天免疫系统的受体，广泛表达并定位在线粒体中。我们研究了NLRX1是否可能在氧化应激模型中作用于代谢和先天免疫的界面。使用嵌合小鼠肾缺血再灌注损伤模型，我们发现NLRX1以氧化应激依赖性方式保护死亡率，线粒体损伤和上皮细胞凋亡。我们发现NLRX1调节氧化磷酸化和细胞完整性，而NLRX1的丢失会导致缺血再灌注损伤期间的耗氧量增加，氧化应激以及上皮细胞的凋亡。我们发现，在急性肾缺血损伤和急性细胞排斥反应期间，人肾脏中NLRX1的表达降低。尽管首先涉及免疫调节，但我们建议NLRX1功能扩展到控制线粒体活性以及预防组织损伤中的氧化应激和凋亡。

BACKGROUND & AIMS: PURPOSE:Descriptive studies have indicated a rising trend in Hodgkin's lymphoma (HL) incidence in young adults, especially females. Increasing evidence has suggested that some risk factors associated with HL may vary by age or gender. Recent studies have reported an increased risk of HL associated with increasing body mass index (BMI), but the results have been inconsistent. The objectives of this study were to examine whether the associations between measures of body size (height, weight, and BMI) and HL risk vary by age and/or gender. METHODS:A population-based case-control study was conducted in Connecticut and Massachusetts. A total of 567 HL cases and 679 controls were recruited in 1997-2000. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS:Among younger women <35 years old, being overweight (25-29.9 kg/m(2)) versus normal weight (18.5-24.9 kg/m(2)) was significantly associated with an increased risk of HL (OR = 2.1, 95 % CI = 1.1-4.0). The risk increased with increasing weight and BMI (p trends <0.01). Among women ≥35 years old, by contrast, higher weight and BMI were associated with a reduced risk of HL (p trends <0.01). Conversely, there was no significant association between BMI and risk of HL in younger or older males. CONCLUSIONS:These findings show that the associations between body size and risk of HL vary by gender and age, and require confirmation in other populations.

背景与目标：

BACKGROUND & AIMS: :Over the course of its long history, Armenia has acted as both a source of numerous indigenous cultures and as a recipient of foreign invasions. As a result of this complex history among populations, the gene pool of the Armenian population may contain traces of historically well-documented ancient migrations. Furthermore, the regions within the historical boundaries of Armenia possess unique demographic histories, having hosted both autochthonous and specific exogenous genetic influences. In the present study, we analyze the Armenian population sub-structure utilizing 17 Y-chromosome short tandem repeat (Y-STR) loci of 412 Armenians from four geographically and anthropologically well-defined groups (Ararat Valley, Gardman, Lake Van and Sasun). To place the genetic composition of Armenia in a regional and historic context, we have compared the Y-STR profiles from these four Armenian collections to 18 current-day Eurasian populations and two ancient DNA collections. Our results illustrate regional trends in Armenian paternal lineages and locale-specific patterns of affinities with neighboring regions. Additionally, we observe a phylogenetic relationship between the Northern Caucasus and the group from Sasun, which offers an explanation for the genetic divergence of this group from other three Armenian collections. These findings highlight the importance of analyzing both general populations as well as geographically defined sub-populations when utilizing Y-STRs for forensic analyses and population genetics studies.

背景与目标： : 在其漫长的历史过程中，亚美尼亚既是众多土著文化的来源，也是外国入侵的接受者。由于人口之间的这种复杂历史，亚美尼亚人口的基因库可能包含历史上有据可查的古代迁徙的痕迹。此外，亚美尼亚历史边界内的地区拥有独特的人口统计学历史，既具有本土遗传影响，也具有特定的外源遗传影响。在本研究中，我们利用来自四个地理和人类学上明确定义的群体 (Ararat Valley，Gardman，Lake Van和Sasun) 的412名亚美尼亚人的17个Y染色体短串联重复序列 (y-str) 基因座来分析亚美尼亚人口亚结构)。为了将亚美尼亚的遗传组成放在区域和历史背景下，我们将这四个亚美尼亚收藏的y-str概况与18个当今的欧亚种群和两个古代DNA收藏进行了比较。我们的结果说明了亚美尼亚父系血统的区域趋势以及与邻近地区的特定区域亲和力模式。此外，我们观察到北高加索地区与Sasun组之间的系统发育关系，这为该组与其他三个亚美尼亚收藏的遗传差异提供了解释。这些发现突显了在利用y-str进行法医分析和群体遗传学研究时分析普通人群以及地理上定义的亚人群的重要性。