BACKGROUND & AIMS: CD4+ anti-tumor T cells reactive with rat adenocarcinoma 13762 kill tumor in vitro and cause regression of tumor in vivo. The role of various host immune cells in CD4+ T-cell-mediated tumor elimination in vivo was investigated by adoptive transfer of anti-tumor T cell clones to recipients that were selectively depleted of individual immune cell types. By these means, macrophages and NK cells were found to be required for tumor killing. Depletion of host CD4+ T cells, CD8+ T cells, or neutrophils was without effect on tumor elimination by anti-tumor T cells. An essential role for antigen receptor-negative NK cells is likely dependent upon secretion of IFN-gamma from NK cells since treatment of tumor recipients with anti-IFN-gamma antibody prior to adoptive transfer and tumor challenge abrogated T cell killing, resulting in progressive tumor growth. Viability of adenocarcinoma 13762 or anti-tumor T cells was unaffected by treatment with either IFN-gamma or anti-IFN-gamma antibody in vitro, but cell surface MHC class II expression was induced in tumor cells by exposure to IFN-gamma. In addition, tumor cells were isolated from tumor-bearing animals by absorption using anti-MHC class II antibody, demonstrating that 13762 tumor expresses cell surface MHC class II antigens in situ. However, if hosts were depleted of NK cells before tumor challenge, MHC class II+ tumor was not recovered. Collectively these results suggest that adenocarcinoma 13762 is eliminated by MHC class II-restricted CD4+ T cells by direct tumor killing.

背景与目标： 与大鼠腺癌13762反应的CD4抗肿瘤T细胞在体外杀死肿瘤并在体内引起肿瘤消退。通过将抗肿瘤T细胞克隆过继转移到选择性清除了个体免疫细胞类型的受体上，研究了各种宿主免疫细胞在体内CD4 T细胞介导的肿瘤消除中的作用。通过这些手段，发现杀死肿瘤需要巨噬细胞和NK细胞。宿主CD4 T细胞，CD8 T细胞或嗜中性白细胞的耗竭对抗肿瘤T细胞对肿瘤的消除没有影响。抗原受体阴性NK细胞的重要作用可能取决于NK细胞分泌的IFN-γ，因为在过继转移和肿瘤攻击之前用抗IFN-γ抗体治疗肿瘤受体可以消除T细胞杀伤，从而导致进行性肿瘤生长。体外用IFN-γ或抗IFN-γ抗体治疗不会影响腺癌13762或抗肿瘤T细胞的存活率，但通过暴露于IFN-γ诱导了肿瘤细胞的细胞表面MHC II类表达。另外，通过使用抗MHC II类抗体的吸收从荷瘤动物中分离出肿瘤细胞，表明13762肿瘤原位表达细胞表面MHC II类抗原。但是，如果宿主在肿瘤攻击前已耗尽NK细胞，则无法恢复MHC II类肿瘤。这些结果共同表明，通过直接杀死肿瘤，MHC II类限制性CD4 T细胞可消除13762腺癌。

BACKGROUND & AIMS: :Professional antigen-presenting cells (APC) are able to process and present exogenous antigen leading to the activation of T cells. Antigen-immunoglobulin (Ig)G complexes (IC) are much more efficiently processed and presented than soluble antigen. Dendritic cells (DC) are known for their ability to take up and process immune complex (IC) via FcgammaR, and they have been shown to play a crucial role in IC-processing onto major histocompatibility complex (MHC) class I as they contain a specialized cross-presenting transport system required for MHC class I antigen-processing. However, the MHC class II-antigen-processing pathway is distinct. Therefore various other professional APC, like macrophages and B cells, all displaying FcgammaR, are thought to present IC-delivered antigen in MHC class II. Nonetheless, the relative contribution of these APC in IC-facilitated antigen-presentation for MHC class II in vivo is not known. Here we show that, in mice, both macrophages and DC, but not B cells, efficiently capture IC. However, only DC, but not macrophages, efficiently activate antigen-specific MHC class II restricted CD4(+) T cells. These results indicate that mainly DC and not other professional APC, despite expressing FcgammaR and MHC class II, contribute significantly to IC-facilitated T cell activation in vivo under steady-state conditions.

背景与目标： ：专业抗原呈递细胞（APC）能够处理并呈递导致T细胞活化的外源性抗原。抗原-免疫球蛋白（Ig）G复合物（IC）比可溶性抗原的加工和呈递效率更高。树突状细胞（DC）以其通过FcgRR吸收和加工免疫复合物（IC）的能力而闻名，并且由于它们包含I型树突状细胞（DC），它们在I类加工主要组织相容性复合物（MHC）的过程中起着至关重要的作用。 MHC I类抗原加工所需的专业交叉展示转运系统。但是，MHC II类抗原加工途径是不同的。因此，各种其他的专业APC，如巨噬细胞和B细胞，都显示FcgR，被认为在II类MHC中呈递了IC递送的抗原。然而，尚不清楚这些APC在体内II型MHC的IC促进的抗原呈递中的相对贡献。在这里，我们表明，在小鼠中，巨噬细胞和DC都有效捕获了IC，而B细胞却没有。但是，只有DC，而不是巨噬细胞，可以有效地激活II型MHC限制性抗原特异性CD4（）T细胞。这些结果表明，尽管表达FcgammaR和II类MHC，但主要DC而非其他专业APC在稳态条件下在体内促进了IC促进的T细胞活化。

BACKGROUND & AIMS: :An immediately inducible gene by gonadotropin was isolated from rat ovaries primed with pregnant mare serum gonadotropin (PMSG) by using a subtraction cloning procedure. Homology analysis revealed that the gene is a rat homologue of scavenger receptor class B-I, which was recently identified as a specific receptor for high density lipoprotein (HDL). The structure of rat SRBI was determined by nucleotide sequence analysis of full-length cDNAs for SRBI. Northern blot analysis revealed that rat SRBI mRNA levels were rapidly and strongly increased within 3 h by the injection of PMSG. In situ hybridization study revealed that SRBI mRNA was strongly induced in theca interna cells of immature rat ovary stimulated with 30 IU of PMSG for 6 h. SRBI mRNA expression was also observed in corpora lutea of the adult rat ovary. These findings indicate that expression of SRBI mRNA is restricted to and induced in the ovarian steroidogenic cell types where cholesterol is used as a substrate for synthesis of steroid hormones. Our data strongly suggest that SRBI may play a significant role in the ovarian steroidogenesis by mediating selective uptake of cholesterol from HDL to ovarian theca interna cells or to corpus luteum.

背景与目标： ：通过减法克隆程序，从用怀孕母马血清促性腺激素（PMSG）引发的大鼠卵巢中分离出由促性腺激素立即诱导的基因。同源性分析显示该基因是清道夫受体B-I类的大鼠同源物，最近被鉴定为高密度脂蛋白（HDL）的特异性受体。通过SRBI全长cDNA的核苷酸序列分析确定大鼠SRBI的结构。 Northern印迹分析表明，通过注射PMSG，大鼠SRBI mRNA水平在3小时内迅速而强烈地增加。原位杂交研究表明，SRBI mRNA在30 IU PMSG刺激6 h的未成熟大鼠卵巢的内膜细胞中被强烈诱导。在成年大鼠卵巢的黄体中也观察到了SRBI mRNA表达。这些发现表明，SRBI mRNA的表达受限于卵巢类固醇生成细胞类型并在其中被诱导，其中胆固醇被用作类固醇激素合成的底物。我们的数据有力地表明，SRBI可能通过介导HDL对胆固醇和卵巢黄体的选择性摄取来介导胆固醇的选择性摄取，从而在卵巢类固醇生成中发挥重要作用。

BACKGROUND & AIMS: We have used 600 MHz 1H NMR spectroscopy data to determine the solution structure of a 31-residue domain of a murine class II major histocompatibility (MHC) protein. This domain, I-Ab(beta)-(60-90), binds to the superantigen staphylococcal enterotoxin A. Distance geometry and dynamical simulated annealing calculations were performed using NOESY- and COSY-deduced constraints. I-Ab(beta)-(60-90), which is mostly alpha-helical, is more similar to the corresponding region of the class II MHC protein HLA-DR1 than to the class I MHC protein HLA-A2. Arg-72 and Arg-80 lie on the same side of the helix and face away from the antigenic peptide binding groove. His-81, implicated in both superantigen and peptide binding, is located midway between the surface defined by Arg-72/Arg-80 and residues that define the inside of the peptide binding groove, allowing for its participation in both types of binding.

背景与目标： 我们已经使用600 MHz 1H NMR光谱数据确定了鼠类II类主要组织相容性（MHC）蛋白的31个残基域的溶液结构。该结构域I-Abβ-（60-90）与超抗原葡萄球菌肠毒素A结合。使用NOESY和COSY推导的约束条件进行距离几何结构和动态模拟退火计算。 I-Abβ-（60-90）主要是α-螺旋，与II类MHC蛋白HLA-DR1的相应区域相比，与I类MHC蛋白HLA-A2的相应区域更为相似。 Arg-72和Arg-80位于螺旋的同一侧，背对抗原肽结合槽。 His-81涉及超抗原和肽的结合，位于Arg-72 / Arg-80定义的表面与定义肽结合槽内部的残基之间的中间位置，从而允许其参与两种结合类型。 br>

BACKGROUND & AIMS: AIMS:To assess the relationship between ambulance attendances, emergency department (ED) presentations and hospital admissions for acute alcohol intoxication and the timing of public holidays, sporting and social events. DESIGN:Time-series analysis was used to explore trends in intoxication in the context of major events. SETTING:Population of Melbourne, Victoria, Australia between 2000 and 2009. PARTICIPANTS:All patients attended by ambulance, presenting to hospital EDs, or admitted to hospital who were classified as acutely alcohol intoxicated. MEASUREMENT:Analysis of daily numbers of presentations for acute alcohol intoxication associated with major events were undertaken, including lead and lag effects. Analyses controlled for day of week and month of year to address temporal and seasonal variations. FINDINGS:Alcohol intoxication presentations were significantly elevated the day before all public holidays, with intoxication cases on the day of public holidays only higher on New Year's Day (ambulance 6.57, 95% confidence intervals (CI): 3.4-9.74; ED 3.34, 95% CI: 1.28-5.4) and ANZAC Day (ambulance 3.71, 95% CI: 0.68-6.75). The Australian Football League (AFL) Grand Final (ED 2.37, 95% CI: 0.55-4.19), Commonwealth Games (ED 2.45, 95% CI: 0.6-4.3) and Melbourne Cup Day (ambulance 6.14, 95% CI: 2.42-9.85) represented the sporting events with significant elevations in acute intoxication requiring medical attention. The last working day before Christmas was the only social event where a significant increase in acute intoxication occurred (ambulance 8.98, 95% CI: 6.8-11.15). CONCLUSIONS:Acute alcohol intoxication cases requiring ambulance, emergency department and hospital in-patient treatment increase substantially on the day preceding public holidays and other major social events.

背景与目标： 目的：评估急救酒精中毒的救护车出勤率，急诊科演示和医院住院之间的关系以及公共假日，体育和社交活动的时间。
设计：时间序列分析用于探讨重大事件中的中毒趋势。
地点：2000年至2009年之间，澳大利亚维多利亚州墨尔本市。
参加者：所有被急救，就诊急诊室急诊就诊或入院的患者均被分类为急性酒精中毒。
测量：进行与主要事件相关的急性酒精中毒的每日呈报次数分析，包括铅和滞后效应。在一周中的某天和一年中的某月进行受控分析，以解决时间和季节变化。
结果：在所有公共假日前一天，酒精中毒的症状明显增加，在公共假日的酒精中毒病例仅在元旦更高（救护车6.57，95％置信区间（CI）：3.4-9.74; ED 3.34，95 ％CI：1.28-5.4）和ANZAC Day（救护车3.71，95％CI：0.68-6.75）。澳大利亚足球联赛（AFL）总决赛（ED 2.37，95％CI：0.55-4.19），英联邦运动会（ED 2.45，95％CI：0.6-4.3）和墨尔本杯日（救护车6.14，95％CI：2.42-） 9.85）代表体育赛事，急性中毒水平明显升高，需要医疗护理。圣诞节前的最后一个工作日是唯一发生急性中毒显着增加的社交活动（救护车8.98，95％CI：6.8-11.15）。
结论：在公共假期和其他重大社会事件发生的前一天，需要救护车，急诊科和医院住院治疗的急性酒精中毒病例大量增加。

BACKGROUND & AIMS: :Psychosocial issues have been recognized as important factors in children's health for decades. This study documents the relation among several important psychosocial variables (e.g., mothers' depressive symptoms) and a new instrument that assesses parents' perception of their communities' social capital. Mothers were recruited from their children's primary care (PC) pediatricians' offices within the Southwestern Ohio Ambulatory Research Network or from a children's hospital developmental clinic (DC). Mothers completed a questionnaire that included the Social Capital Scale (SCS), Children with Special Health Care Needs Screener (CSHCNS), Pediatric Quality of Life Inventory, Maternal Social Support Index and the Center for Epidemiologic Studies Depression Scale (CES-D). Mothers were sorted into three subgroups based on site of recruitment (PC or DC) and results of the CSHCNS. The sample (N = 620) was also sorted into terciles based on SCS scores. Mean SCS was about 73 for each of the three subgroups. Compared to mothers in the highest SCS tercile, mothers in the lowest SCS tercile reported lower education, lower income and higher CES-D median scores. The SCS subscale "sense of belonging" had an inverse correlation with CES-D scores (r = -.248, p < 0.001). Mothers from primary care and sub-specialty clinics had similar perceptions about their communities' social capital. Compared to mothers in the highest one third of SCS scores, mothers in the lowest one third were more likely to report less education and income as well as more depressive symptoms. A decreased sense of belonging in their communities was also correlated with more depressive symptoms. The SCS is a new useful tool for investigators and clinicians who work with children and their families.

背景与目标： ：几十年来，社会心理问题已被视为影响儿童健康的重要因素。这项研究记录了几个重要的社会心理变量（例如母亲的抑郁症状）之间的关系以及一种评估父母对社区社会资本感知的新工具。母亲是从其在西南俄亥俄非卧床研究网络内的儿童初级保健（PC）儿科医生办公室或儿童医院发展诊所（DC）招募的。母亲们完成了一个问卷调查，包括社会资本量表（SCS），有特殊保健需求筛查的儿童（CSHCNS），儿科生活质量量表，孕产妇社会支持指数和流行病学研究抑郁量表（CES-D）。根据招聘地点（PC或DC）和CSHCNS的结果，将母亲分为三个亚组。样本（N = 620）也根据SCS分数分为三等分。三个亚组中的每个亚组的平均SCS约为73。与南卡罗来纳州最高的母亲相比，南卡罗来纳州最低的母亲教育程度较低，收入较低且CES-D中位数得分较高。 SCS分量表的「归属感」与CES-D分数呈反比关系（r =-。248，p <0.001）。来自初级保健和专科诊所的母亲对社区的社会资本有相似的看法。与SCS得分最高的三分之一的母亲相比，收入最低的三分之一的母亲更有可能报告较少的教育和收入，以及更多的抑郁症状。在他们的社区中归属感的下降也与抑郁症的症状有关。对于与孩子及其家庭一起工作的研究人员和临床医生，SCS是一种新的有用工具。

BACKGROUND & AIMS: :Type 2 diabetes mellitus is the most common form of diabetes that occurs in both human and nonhuman primates. Although spontaneously diabetic nonhuman primates are used extensively in diabetic related research and are a proven valuable tool for the study of the natural history of diabetes, little is known about the key factors that can cause this metabolic disorder and the preventative measures that could be employed to minimize the consequences of diabetes. Using a model of developing and untreated diabetes, this study describes the effects of housing arrangement (socially group- versus individually single-housed), exercise, diet, age, and sex on fasting plasma glucose, key lipids associated with diabetes, and bodyweight in two large cohorts of nonhuman primates. Key findings include exercise/housing arrangement's contribution to significant differences in bodyweight, levels of fasting plasma glucose, total cholesterol, and high- and low-density lipoproteins. Age also had profound effects on glucose, triglyceride and high-density lipoproteins, particularly in single-caged animals. Moreover, females had higher fasting glucose, total cholesterol and triglyceride levels than male counterparts within the same housing situations. These factors may be critical to identifying preventive measures that could eventually be used to minimize obesity and diabetes in humans.

背景与目标： 2型糖尿病是人类和非人类灵长类动物中最常见的糖尿病形式。尽管自发性糖尿病非人类灵长类动物在糖尿病相关研究中被广泛使用，并且是研究糖尿病自然史的一种被证明有价值的工具，但对于引起这种代谢紊乱的关键因素以及可以采取的预防措施知之甚少尽量减少糖尿病的后果。本研究使用发展中的糖尿病和未经治疗的糖尿病模型，描述了住房安排（集体居住与个人独居），运动，饮食，年龄和性别对空腹血糖，糖尿病相关的主要脂质和体重的影响。两个大型的非人类灵长类动物。主要发现包括运动/住房安排对体重，空腹血糖水平，总胆固醇以及高密度和低密度脂蛋白的显着差异的贡献。年龄对葡萄糖，甘油三酸酯和高密度脂蛋白也有深远的影响，特别是在单笼动物中。此外，在相同的居住环境下，女性的空腹血糖，总胆固醇和甘油三酸酯水平高于男性。这些因素对于确定预防措施至关重要，这些预防措施最终可用于最大程度地减少人类的肥胖和糖尿病。

BACKGROUND & AIMS: INTRODUCTION:The goal of burn care is that 'the quality of the outcome must be worth the pain of survival'. More research is needed to understand how best to deliver care for patients with burns to achieve this aim. Loss of independence, function as well as loss of income for patients with burns and carers cause a significant burden at both individual and societal levels. Much is being done to advance knowledge in the clinical care field; however, there has been a paucity of research exploring psychosocial outcomes. This paper describes the study background and methods, as implemented in an Australian cohort study of psychosocial outcomes after major burn injuries. METHODS AND ANALYSIS:In this inception cohort study, a target sample of 230 participants, aged 18 years or over, admitted to a single statewide burns centre with a burn injury are identified by hospital staff for inclusion. Baseline survey data are collected either in person or by telephone within 28 days of the injury and participants then followed up with telephone interviews at 3, 6 and 12 months postburn. Injury and burns treatment information is collected from medical records. Social support is measured as a predictor variable using the Multidimensional Scale of Perceived Social Support. Outcome data are collected via standardised measures in the domains of Quality of Life (SF-12, EQ-5D, BSHS-B), depression (PHQ-9), post-traumatic stress disorder (PCL-C, PAS), community integration (CIQ-R) and Quality-Adjusted Life Years (EQ-5D). Additional survey questions measure life satisfaction, return to work and public services utilisation at 12 months postinjury. Data analysis methods will include analysis of variance, Pearson correlation and hierarchical multiple regression analyses. ETHICS AND DISSEMINATION:Hospital-based and University of Queensland Human Research Ethics Committees have approved the protocol. Results from the study will be disseminated at national and international conferences, in peer-reviewed journals and in a doctoral thesis. TRIAL REGISTRATION NUMBER:Australia New Zealand Clinical Trials Registry (ACTRN12616000828426). Retrospectively registered on 23 June 2016; pre-results.

背景与目标： 简介：烧伤护理的目标是“结果的质量必须值得生存之苦”。需要更多的研究来了解如何最好地为烧伤患者提供护理以实现该目标。烧伤和照顾者患者失去独立性，功能以及收入损失，在个人和社会层面都造成了沉重的负担。为了提高临床护理领域的知识水平，正在做很多工作。然而，很少有研究探讨社会心理结果。本文描述了一项研究背景和方法，该方法在澳大利亚严重烧伤后心理社会结局队列研究中实施。
方法和分析：在这项队列研究中，由医院工作人员确定了230名年龄在18岁或以上，被纳入一个州范围内烧伤中心的烧伤中心的参与者的目标样本。基线调查数据在受伤后28天内亲自或通过电话收集，参与者在烧伤后3、6和12个月进行电话访谈。受伤和烧伤的治疗信息是从医疗记录中收集的。使用“感知社会支持的多维量表”将社会支持作为预测变量进行衡量。通过生活质量（SF-12，EQ-5D，BSHS-B），抑郁症（PHQ-9），创伤后应激障碍（PCL-C，PAS），社区整合等领域的标准化措施收集结果数据（CIQ-R）和质量调整寿命年（EQ-5D）。额外的调查问题可衡量受伤后12个月的生活满意度，重返工作岗位和使用公共服务的情况。数据分析方法将包括方差分析，Pearson相关性和分层多元回归分析。
道德与传播：医院和昆士兰大学人类研究伦理委员会已批准该协议。该研究的结果将在国家和国际会议，同行评审期刊和博士学位论文中进行传播。
试验注册号：澳大利亚新西兰临床试验注册（ACTRN12616000828426）。追溯注册于2016年6月23日;结果。

BACKGROUND & AIMS: :Coordination is a vital component in healthcare provision and teamwork. Relational coordination (RC) represents a type of informal coordination reinforced by communication and supportive relationships. It is an important concept in the study of interprofessional team performance and is associated with improved patient care outcomes. However, little is known about the specific relational characteristics that contribute to higher levels of RC. This study examined the association between social capital (resources embedded within relationships) and RC in outpatient clinics. RC was hypothesized to be predicted by social capital. In addition, social capital was hypothesized to be predicted by team tenure, and RC was hypothesized to be predicted by formal coordination mechanisms. A cross-sectional design was used to survey a random sample of 342 physicians and nurses from outpatient clinics. Study variables were measured using previously validated instruments with acceptable levels of reliability and validity. Structural equation modeling was used for hypothesis testing. Final analysis revealed a good fit of data to the hypothesized model (comparative fit index = 0.966; standardized root mean square residual = 0.0316). Results suggested that social capital predicted both factors of RC (b = 0.70 and 0.81, p < 0.001) and team tenure predicted social capital (b = 0.13, p < 0.05). Also, the association between team tenure and RC (b = 0.09, p < 0.05) was found to be partially mediated by social capital. Findings of this study suggest that characteristics within relational ties are predictive of informal coordination. The strength and pattern of these associations provide a better understanding in how relationships may facilitate interprofessional teamwork.

背景与目标： ：协调是提供医疗保健和团队合作的重要组成部分。关系协调（RC）代表一种非正式的协调，通过沟通和支持性关系得到加强。这是研究跨专业团队绩效的重要概念，并且与改善的患者护理结果相关。但是，对于导致较高RC的特定关系特性知之甚少。这项研究检查了门诊诊所社会资本（关系中嵌入的资源）与RC之间的关联。假设RC是由社会资本预测的。另外，假设社会资本是由团队任期预测的，而RC是假设是由正式协调机制预测的。使用横断面设计对来自门诊诊所的342名医生和护士进行随机抽样调查。研究变量是使用先前验证过的，具有可接受水平的信度和效度进行测量的。结构方程模型用于假设检验。最终分析显示，数据与假设的模型拟合良好（比较拟合指数= 0.966；标准均方根残差= 0.0316）。结果表明，社会资本既可以预测RC的因素（b = 0.70和0.81，p <0.001），也可以预测球队任期对社会资本的预测（b = 0.13，p <0.05）。此外，还发现团队任期与RC之间的关联（b = 0.09，p <0.05）部分地由社会资本介导。这项研究的结果表明，在关系中的特征预示着非正式的协调。这些协会的实力和模式可以更好地理解人际关系如何促进专业间的团队合作。

BACKGROUND & AIMS: :Humans have two glutaminase genes, GLS (GLS1) and GLS2, each of which has two alternative transcripts: the kidney isoform (KGA) and glutaminase C (GAC) for GLS, and the liver isoform (LGA) and glutaminase B (GAB) for GLS2. Initial hit compound (Z)-5-((1-(4-bromophenyl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)thiazolidine-2,4-dione (2), a thiazolidine-2,4-dione, was obtained from a high throughput screening of 40 000 compounds against KGA. Subsequently, a series of thiazolidine-2,4-dione derivatives was synthesized. Most of these were found to inhibit KGA and GAC with comparable activities, were less potent inhibitors of GAB, and were moderately selective for GLS1 over GLS2. The relationships between chemical structure, activity, and selectivity were investigated. The lead compounds obtained were found to (1) offer in vitro cellular activities for inhibiting cell growth, clonogenicity, and cellular glutamate production, (2) exhibit high concentrations of exposure in plasma by a pharmacokinetic study, and (3) reduce the tumor size of xenografted human pancreatic AsPC-1 carcinoma cells in mice.

背景与目标： ：人类有两个谷氨酰胺酶基因，GLS（GLS1）和GLS2，每个都有两个替代转录物：GLS的肾脏同种型（KGA）和谷氨酰胺酶C（GAC），肝脏同种型（LGA）和谷氨酰胺酶B（GAB）适用于GLS2。初始命中化合物（Z）-5-（（（1-（4-溴苯基）-2,5-二甲基-1H-吡咯-3-基）亚甲基）噻唑烷-2,4-二酮（2），噻唑烷-2通过对KGA筛选40000种化合物的高通量筛选获得了4-4-二酮。随后，合成了一系列噻唑烷-2,4-二酮衍生物。发现其中大多数可抑制KGA和GAC的活性相当，对GAB的抑制作用较弱，并且对GLS1的选择性比对GLS2的中等。研究了化学结构，活性和选择性之间的关系。发现获得的先导化合物具有（1）提供体外细胞活性以抑制细胞生长，克隆形成和细胞谷氨酸的产生；（2）通过药代动力学研究显示血浆中的高浓度暴露；以及（3）减小肿瘤大小小鼠体内异种移植人胰腺AsPC-1癌细胞的表达。

BACKGROUND & AIMS: :This case report describes the orthodontic treatment of an 18-year-old woman with a skeletal Class III malocclusion and a midline deviation. The treatment plan consisted of distalizing the mandibular dentition asymmetrically and producing space for retraction of the mandibular anterior teeth. Short Class III elastics, an open-coil spring, and the mulitloop edgewise archwire technique were used, combining the entire maxillary dentition as integrated anchorage. The active treatment period was 26 months. Normal overbite and overjet were obtained, and facial balance was improved.

背景与目标： ：本病例报告描述了一名18岁女性的骨骼正畸III类错牙合畸形的正畸治疗方法。治疗计划包括不对称地使下颌牙列远侧，并为下颌前牙的回缩提供空间。使用了短的III类松紧带，开卷弹簧和mulitloop边向弓丝技术，将整个上颌齿列结合在一起作为整体锚固。积极治疗期为26个月。获得正常的咬合和过喷射，并改善了面部平衡。

BACKGROUND & AIMS: OBJECTIVE:Within exercise class settings, group cohesion has consistently been found to predict adherence behaviors, and has been identified as a salient target for intervention-based initiatives. Drawing upon theorizing from the field of group dynamics, exercise class cohesion is often conceptualized as a dynamic construct that requires several classes to form and once it is formed, continues to change over time. Despite the salience of this "dynamic" contention for informing physical activity interventions, this theorizing has yet to be empirically tested. METHOD:In this study a multilevel modeling framework was used to examine changes in exercise class cohesion over time. Exercisers (N = 395) completed measures of cohesion following the second, fifth, and eighth classes of their respective programs (N = 46). RESULTS:Mean levels of social cohesion changed significantly over time whereas mean levels of task cohesion did not. These patterns were largely consistent across persons and groups. CONCLUSIONS:These findings suggest that within group-based exercise programs social and task cohesion possesses different levels of dynamism, and that this dynamism (or lack thereof) might have important implications for future research and interventions involving physical activity groups.

背景与目标： 目的：在锻炼班级设置中，始终发现小组凝聚力可以​​预测依从行为，并已被确定为基于干预措施的重要目标。借鉴团体动力学领域的理论，运动课的凝聚力通常被概念化为一种动态的构造，需要形成多个班级，一旦形成，它就会随着时间的推移而不断变化。尽管这种“动态”竞争可为体育活动的干预提供依据，但这种理论化尚待实证检验。
方法：在这项研究中，使用了一个多层次的建模框架来检验运动课内聚力随时间的变化。锻炼者（N = 395）在各自程序的第二，第五和第八类（N = 46）之后完成了对内聚力的测量。
结果：社交凝聚力的平均水平随时间变化显着，而任务凝聚力的平均水平没有变化。这些模式在个人和群体之间基本保持一致。
结论：这些发现表明，在基于小组的锻炼计划中，社交和任务的凝聚力具有不同程度的活力，这种活力（或缺乏这种活力）可能对涉及体育活动群体的未来研究和干预措施具有重要意义。

BACKGROUND & AIMS: OBJECTIVE:The study sought to quantify coordination of epilepsy care, over time, between neurologists and other health care providers using social network analysis (SNA). METHODS:The Veterans Health Administration (VA) instituted an Epilepsy Center of Excellence (ECOE) model in 2008 to enhance care coordination between neurologists and other health care providers. Provider networks in the 16 VA ECOE facilities (hub sites) were compared to a subset of 33 VA facilities formally affiliated (consortium sites) and 14 unaffiliated VA facilities. The number of connections between neurologists and each provider (node degree) was measured by shared epilepsy patients and tallied to generate estimates at the facility level separately within and across facilities. Mixed models were used to compare change of facility-level node degree over time across the three facility types, adjusted for number of providers per facility. RESULTS:Over the time period 2000-2013, epilepsy care coordination both within and across facilities significantly increased. These increases were seen in all three types of facilities namely hub, consortium, and unaffiliated site, relatively equally. The increase in connectivity was more dramatic with providers across facilities compared to providers within the same facilities. CONCLUSION:Establishment of the ECOE hub and spoke model contributed to an increase in epilepsy care coordination both within and across facilities from 2000 to 2013, but there was substantial variation across different facilities. SNA is a tool that may help measure coordination of specialty care.

背景与目标： 目的：本研究试图通过社交网络分析（SNA）量化神经科医师与其他医疗保健提供者之间随着时间的推移癫痫治疗的协调性。
方法：退伍军人卫生管理局（VA）在2008年建立了癫痫病卓越中心（ECOE）模型，以加强神经科医生与其他卫生保健提供者之间的护理协调。将16个VA ECOE设施（集线器站点）中的提供商网络与33个正式关联的VA设施（财团站点）和14个未关联的VA设施的子集进行了比较。由共享的癫痫患者测量神经科医师与每个提供者之间的联系数（节点度），并计算以在设施级别内部和设施之间分别在设施级别生成估计值。混合模型用于比较三种设施类型上设施级别节点度随时间的变化，并针对每个设施的提供者数量进行了调整。
结果：在2000年至2013年期间，设施内和设施间的癫痫护理协调性显着提高。这些增加在三种类型的设施中都可以看到，即枢纽，财团和非附属场所，相对均等。与同一设施内的提供商相比，跨设施的提供商的连接性增长更为显着。
结论：从2000年到2013年，建立ECOE枢纽和轮辐模型有助于增加设施内和设施之间的癫痫护理协调，但不同设施之间存在很大差异。 SNA是一种工具，可以帮助评估专科护理的协调性。

BACKGROUND & AIMS: OBJECTIVES:To evaluate and assess the impact of pharmacy students' electronic device (e-device) use during a lecture-based pharmacotherapeutics sequence. METHODS:A validated survey instrument to assess e-device use was e-mailed to 238 second- (P2) and third-year (P3) pharmacy students. Grades were reviewed retrospectively and correlated with e-device use to determine its impact on academic performance. RESULTS:Of 140 responding students (59% response rate), 106 reported using e-devices during class for course-related (91.5%) and non-course-related (81.1%) activities. When P2 and P3 students were combined, e-device use was not associated with academic performance (p = 0.70). Academic performance was not impacted among P3 students (p = 0.86), but P2 students performed better academically if they refrained from using e-devices during class (mean grade = 88.5% vs. 83.3%; p=0.019). CONCLUSIONS:The impact of e-device use on overall academic performance was negligible. Use of e-devices by students enrolled in their first pharmacotherapeutics course may negatively impact academics.

背景与目标： 目的：评估和评估在以讲座为基础的药物治疗过程中，药房学生使用电子设备（电子设备）的影响。
方法：通过电子邮件将有效的调查工具评估电子设备的使用情况，并通过电子邮件发送给238名二（P2）和三年级（P3）药房学生。对成绩进行回顾性审查，并将其与电子设备的使用相关联，以确定其对学习成绩的影响。
结果：在140名回应学生中（59％的回应率），有106名学生报告说在课堂上使用电子设备进行与课程相关的活动（91.5％）和与课程无关的活动（81.1％）。当P2和P3学生合并时，电子设备的使用与学习成绩无关（p = 0.70）。 P3学生的学业成绩并未受到影响（p = 0.86），但如果P2学生在上课时避免使用电子设备，则他们的学业成绩会更好（平均成绩分别为88.5％和83.3％； p = 0.019）。
结论：电子设备使用对整体学业成绩的影响可以忽略不计。首次参加药物治疗课程的学生使用电子设备可能会对学术产生负面影响。

BACKGROUND & AIMS: Despite numerous legal interventions, minors continue to purchase and consume alcohol. Prior research had suggested that the decision to request identification to prove legal age was susceptible to various judgement and decision heuristics. This research examined whether the physical attractiveness of the potential consumer and the presence or absence of others were significant predictors of alcohol accessibility. Bartenders (n = 130) rated a target individual who was either high or low in attractiveness. Results indicated that attractiveness was a significant predictor of "proofing likelihood". High levels of attractiveness were associated with a decrease in the likelihood of being asked to provide proof of legal age for the purchase of alcohol. Individuals presented alone were seen as significantly older than when grouped with others. Implications of these findings for the restriction of alcohol availability among minors are considered.

背景与目标： 尽管采取了许多法律干预措施，未成年人仍继续购买和消费酒精。先前的研究表明，要求证明身份以证明合法年龄的决定容易受到各种判断和决定启发法的影响。这项研究检查了潜在消费者的身体吸引力以及是否存在其他人是否是酒精可及性的重要预测指标。调酒师（n = 130）对吸引力高或低的目标个人进行了评分。结果表明，吸引力是“打样可能性”的重要预测指标。高水平的吸引力与被要求提供购买酒精饮料的法定年龄证据的可能性降低有关。单独出现的个体被认为比与他人分组时显着年龄大。考虑了这些发现对限制未成年人饮酒的影响。