BACKGROUND & AIMS: :Menopausal hormone treatment (MHT) may limit progression of cardiovascular disease (CVD) but poses a thrombosis risk. To test targeted candidate gene variation for association with subclinical CVD defined by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC), 610 women participating in the Kronos Early Estrogen Prevention Study (KEEPS), a clinical trial of MHT to prevent progression of CVD, were genotyped for 13,229 single nucleotide polymorphisms (SNPs) within 764 genes from anticoagulant, procoagulant, fibrinolytic, or innate immunity pathways. According to linear regression, proportion of European ancestry correlated negatively, but age at enrollment and pulse pressure correlated positively with CIMT. Adjusting for these variables, two SNPs, one on chromosome 2 for MAP4K4 gene (rs2236935, β = 0.037, P value = 2.36 × 10(-06)) and one on chromosome 5 for IL5 gene (rs739318, β = 0.051, P value = 5.02 × 10(-05)), associated positively with CIMT; two SNPs on chromosome 17 for CCL5 (rs4796119, β = -0.043, P value = 3.59 × 10(-05); rs2291299, β = -0.032, P value = 5.59 × 10(-05)) correlated negatively with CIMT; only rs2236935 remained significant after correcting for multiple testing. Using logistic regression, when we adjusted for waist circumference, two SNPs (rs11465886, IRAK2, chromosome 3, OR = 3.91, P value = 1.10 × 10(-04); and rs17751769, SERPINA1, chromosome 14, OR = 1.96, P value = 2.42 × 10(-04)) associated positively with a CAC score of >0 Agatston unit; one SNP (rs630014, ABO, OR = 0.51, P value = 2.51 × 10(-04)) associated negatively; none remained significant after correcting for multiple testing. Whether these SNPs associate with CIMT and CAC in women randomized to MHT remains to be determined.

背景与目标： : 更年期激素治疗 (MHT) 可能会限制心血管疾病 (CVD) 的进展，但会带来血栓形成的风险。为了测试与颈动脉内膜中层厚度 (CIMT) 和冠状动脉钙化 (CAC) 定义的亚临床CVD相关的靶向候选基因变异，610参加Kronos早期雌激素预防研究 (KEEPS) 的妇女，MHT预防CVD进展的临床试验，在抗凝剂，促凝剂，纤溶或先天免疫途径的764基因内对13,229单核苷酸多态性 (snp) 进行基因分型。根据线性回归，欧洲血统的比例呈负相关，但入学年龄和脉压与CIMT呈正相关。调整这些变量，两个snp，一个在2号染色体上的MAP4K4基因 (rs2236935，β = 0.037，p值 = 2.36 × 10(-06))，一个在5号染色体上的IL5基因 (rs739318，β = 0.051，p值 = 5.02 × 10(-05))，与CIMT呈正相关; CCL5 17号染色体上的两个snp (rs4796119，β = -0.043，p值 = 3.59 × 10(-05); rs2291299，β = -0.032，p值 = 5.59 × 10(-05)) 与CIMT呈负相关; 校正多重测试后，只有rs2236935仍然显著。使用逻辑回归，当我们调整腰围时，两个snp (rs11465886，IRAK2，3号染色体，OR = 3.91，p值 = 1.10 × 10(-04); 和rs17751769，SERPINA1，14号染色体，OR = 1.96，p值 = 2.42 × 10(-04)) 与> 0 Agatston单位的CAC评分呈正相关; 1个SNP (rs630014，ABO，OR = 0.51，p值 = 2.51 × 10(-04)) 呈负相关; 校正多重测试后无显著。这些snp是否与CIMT和CAC相关，在随机分配到MHT的女性中仍有待确定。

BACKGROUND & AIMS: :Although low-dose acetylsalicylic acid (ASA) is recommended for prevention of cardiovascular events in at-risk patients, its long-term use can be associated with the risk of peptic ulcer and upper gastrointestinal (GI) symptoms that may impact treatment compliance. This prespecified secondary analysis of the OBERON study (NCT00441727) determined the efficacy of esomeprazole for prevention/resolution of low-dose ASA-associated upper GI symptoms. A post hoc analysis of predictors of symptom prevention/resolution was also conducted. Helicobacter pylori-negative patients taking low-dose ASA (75-325 mg) for cardiovascular protection who had ≥1 upper GI risk factor were eligible. The patients were randomized to once-daily esomeprazole 40 mg, 20 mg, or placebo, for 26 weeks; 2303 patients (mean age 67.6 years; 36% aged >70 years) were evaluable for upper GI symptoms. The proportion of patients with dyspeptic or reflux symptoms (self-reported Reflux Disease Questionnaire) was significantly lower (P < 0.0001) in those treated with esomeprazole versus in those treated with placebo. Treatment with esomeprazole (P < 0.0001), age >70 years (P < 0.01), and the absence of upper GI symptoms at baseline (P < 0.0001) were all factors associated with prevention/resolution of upper GI symptoms. Together, these analyses demonstrate that esomeprazole is effective in preventing and resolving patient-reported upper GI symptoms in low-dose ASA users at increased GI risk.

背景与目标： : 尽管低剂量乙酰水杨酸 (ASA) 被推荐用于预防高危患者的心血管事件，但长期使用可能与消化性溃疡和上消化道 (GI) 症状的风险有关，这可能会影响治疗依从性。这项预先设定的OBERON研究 (NCT00441727) 的二次分析确定了埃索美拉唑预防/缓解低剂量ASA相关上消化道症状的疗效。还对症状预防/解决的预测因素进行了事后分析。幽门螺杆菌阴性患者服用低剂量ASA (75-325 mg) 进行心血管保护，且上消化道危险因素 ≥ 1。患者被随机分配至每日一次埃索美拉唑40 mg、20 mg或安慰剂，持续26周; 2303患者 (平均年龄67.6岁; 36% 年龄> 70岁) 可评估上消化道症状。与安慰剂组相比，使用埃索美拉唑治疗的患者有消化不良或反流症状 (自我报告的反流疾病问卷) 的比例显著降低 (P <0.0001)。埃索美拉唑治疗 (P < 0.0001) 、年龄> 70岁 (P < 0.01) 和基线时没有上消化道症状 (P < 0.0001) 都是与预防/缓解上消化道症状相关的因素。总之，这些分析表明，埃索美拉唑可有效预防和解决患者报告的上消化道症状，在胃肠道风险增加的低剂量ASA使用者中。

BACKGROUND & AIMS: :The regulations pertaining to the obligation of continuation of health surveillance of workers formerly exposed to asbestos are also examined from the point of view of clinical epidemiological usefulness. The outcomes of some types of campaigns of health surveillance of formerly exposed workers organized by the SSN (National Health Service) are also examined.

背景与目标： : 还从临床流行病学有用性的角度研究了与继续对以前接触石棉的工人进行健康监测的义务有关的法规。还检查了SSN (国家卫生局) 组织的某些类型的健康监测运动的结果。

BACKGROUND & AIMS: BACKGROUND:Low utilization of effective coronary heart disease (CHD) prevention strategies may be due to many factors, but chief among them is the lack of patient involvement in prevention decisions. We undertook this study to test the effectiveness of an individually-tailored, computerized decision aid about CHD on patients' discussions with their doctor and their plans for CHD prevention. METHODS:We conducted a pilot randomized trial in a convenience sample of adults with no previous history of cardiovascular disease to test the effectiveness of an individually-tailored, computerized decision aid about CHD prevention against a risk factor list that patients could present to their doctor. RESULTS:We enrolled 75 adults. Mean age was 53. 59% were female, 73% white, and 23% African-American. 66% had some college education. 43% had a 10-year CHD risk of 0-5%, 25% a risk of 6-10%, 24% a risk of 11-20%, and 5% a risk of > 20%. 78% had at least one option to reduce their CHD risk, but only 45% accurately identified the strategies best supported by evidence. 41 patients received the decision aid, 34 received usual care. In unadjusted analysis, the decision aid increased the proportion of patients who discussed CHD risk reduction with their doctor from 24% to 40% (absolute difference 16%; 95% CI -4% to +37%) and increased the proportion who had a specific plan to reduce their risk from 24% to 37% (absolute difference 13%; 95% CI -7% to +34%). In pre-post testing, the decision aid also appeared to increase the proportion of patients with plans to intervene on their CHD risk (absolute increase ranging from 21% to 47% for planned medication use and 5% to 16% for planned behavioral interventions). CONCLUSION:Our study confirms patients' limited knowledge about their CHD risk and effective risk reduction options and provides preliminary evidence that an individually-tailored decision aid about CHD prevention might be expected to increase patients' discussions about CHD prevention with their doctor and their plans for CHD risk reduction. These findings should be replicated in studies with a larger sample size and patients at overall higher risk of CHD.

背景与目标：

BACKGROUND & AIMS: :Cholera is a substantial health burden on the developing world and is endemic in Africa, Asia, South America, and Central America. The exact scale of the problem is uncertain because of limitations in existing surveillance systems, differences in reporting procedures, and failure to report cholera to WHO; official figures are likely to greatly underestimate the true prevalence of the disease. We have identified, through extensive literature searches, additional outbreaks of cholera to those reported to WHO, many of which originated from the Indian subcontinent and southeast Asia. Such underestimation of cholera can have important implications for decisions on provision of health interventions for indigenous populations, and on risk assessments for travellers. Furthermore, until recently, it has not been possible to implement public-health interventions in low-income countries to eliminate disease, and the prevention of cholera in travellers has been limited to restrictive guidelines. However, a vaccine against cholera is now available that has proven efficacy and tolerability in mass vaccination campaigns in low-income countries, and among travellers.

背景与目标： : 霍乱是发展中国家的沉重健康负担，在非洲，亚洲，南美和中美洲很流行。由于现有监测系统的局限性，报告程序的差异以及未能向世卫组织报告霍乱，问题的确切规模尚不确定; 官方数字可能大大低估了该疾病的真实患病率。通过广泛的文献检索，我们发现了向世卫组织报告的霍乱疫情，其中许多霍乱疫情来自印度次大陆和东南亚。对霍乱的这种低估可能对决定为土著居民提供健康干预措施以及对旅行者的风险评估产生重要影响。此外，直到最近，还无法在低收入国家实施公共卫生干预措施来消除疾病，旅行者霍乱的预防仅限于限制性准则。然而，现在已经有了一种霍乱疫苗，该疫苗在低收入国家和旅行者的群体接种运动中被证明是有效和耐受性的。

BACKGROUND & AIMS: :The objective of this study was to answer the question of whether a double instead of triple embryo transfer strategy in patients over 38 years would substantially reduce the number of multiple pregnancies while maintaining the chance of a term live birth at an acceptable level. A randomized controlled two-centre trial was performed. Forty-five patients, 38 years or older, were randomized. Double embryo transfer over a maximum of four cycles (DET group) or triple embryo transfer over a maximum of three cycles (TET group) was performed. The cumulative term live birth rate was 47.3% after four cycles in the DET group and 40.5% after three cycles in the TET group. The difference between the DET and the TET group was 6.8% in favour of the DET group (95% CI -25 to 38). The multiple pregnancy rates in the DET and TET group were 0% (95% CI 0 to 24) and 30% (95% CI 7 to 65) respectively (P = 0.05). In the DET patients, the mean number of treatment cycles was 2.9 compared with 2.1 in the TET group (P = 0.01). In women of 38 years and older, double embryo transfer after IVF may result in similar cumulative term live birth rates compared with triple embryo transfer, provided that a higher number of treatment cycles is accepted.

背景与目标： : 这项研究的目的是回答以下问题: 在38岁以上的患者中采用双重而不是三重胚胎移植策略是否会大大减少多胎妊娠的数量，同时将足月活产的机会保持在可接受的水平。进行了一项随机对照的两中心试验。45名38岁或以上的患者被随机分组。进行了最多四个周期的双胚胎移植 (DET组) 或最多三个周期的三胚胎移植 (TET组)。在DET组中，在四个周期后47.3% 累积足月活产率，在TET组中，在三个周期后40.5%。DET和TET组之间的差异6.8% 有利于DET组 (95% CI -25至38)。DET组和TET组的多次妊娠率分别为0% (95% CI 0 ~ 24) 和30% (95% CI 7 ~ 65) (P = 0.05)。在DET患者中，平均治疗周期数与TET组的2.1相比2.9 (P = 0.01)。在38岁及以上的女性中，如果接受更多的治疗周期，IVF后的双胚胎移植可能会导致与三胚胎移植相似的累积足月活产率。

BACKGROUND & AIMS: :The aim of the study was to use in silico and in vitro techniques to evaluate whether a triple formulation of antiretroviral drugs (tenofovir, darunavir, and dapivirine) interacted with P-glycoprotein (P-gp) or exhibited any other permeability-altering drug-drug interactions in the colorectal mucosa. Potential drug interactions with P-gp were screened initially using molecular docking, followed by molecular dynamics simulations to analyze the identified drug-transporter interaction more mechanistically. The transport of tenofovir, darunavir, and dapivirine was investigated in the Caco-2 cell models and colorectal tissue, and their apparent permeability coefficient (Papp), efflux ratio (ER), and the effect of transporter inhibitors were evaluated. In silico, dapivirine and darunavir showed strong affinity for P-gp with similar free energy of binding; dapivirine exhibiting a ΔGPB value -38.24 kcal/mol, darunavir a ΔGPB value -36.84 kcal/mol. The rank order of permeability of the compounds in vitro was tenofovir < darunavir < dapivirine. The Papp for tenofovir in Caco-2 cell monolayers was 0.10 ± 0.02 × 10-6 cm/s, ER = 1. For dapivirine, Papp was 32.2 ± 3.7 × 10-6 cm/s, but the ER = 1.3 was lower than anticipated based on the in silico findings. Neither tenofovir nor dapivirine transport was influenced by P-gp inhibitors. The absorptive permeability of darunavir (Papp = 6.4 ± 0.9 × 10-6 cm/s) was concentration dependent with ER = 6.3, which was reduced by verapamil to 1.2. Administration of the drugs in combination did not alter their permeability compared to administration as single agents. In conclusion, in silico modeling, cell culture, and tissue-based assays showed that tenofovir does not interact with P-gp and is poorly permeable, consistent with a paracellular transport mechanism. In silico modeling predicted that darunavir and dapivirine were P-gp substrates, but only darunavir showed P-gp-dependent permeability in the biological models, illustrating that in silico modeling requires experimental validation. When administered in combination, the disposition of the proposed triple-therapy antiretroviral drugs in the colorectal mucosa will depend on their distinctly different permeability, but was not interdependent.

背景与目标： : 该研究的目的是使用计算机和体外技术来评估抗逆转录病毒药物的三重制剂 (替诺福韦，达罗纳韦和达比韦林) 是否与P-糖蛋白 (P-gp) 相互作用或表现出任何其他渗透性改变的药物-大肠粘膜中的药物相互作用。最初使用分子对接筛选与P-gp的潜在药物相互作用，然后进行分子动力学模拟，以更机械地分析已鉴定的药物-转运蛋白相互作用。在Caco-2细胞模型和结直肠组织中研究了替诺福韦，达鲁纳韦和达比韦林的转运，并评估了它们的表观渗透系数 (Papp)，流出比 (ER) 和转运蛋白抑制剂的作用。在计算机中，达皮韦林和达卢纳韦对P-gp表现出很强的亲和力，具有相似的结合自由能; 达皮韦林表现出 Δ gpb值-38.24 kcal/mol，达卢纳韦a Δ gpb值-36.84 kcal/mol。化合物体外通透性的等级顺序为替诺福韦 <达瑞那韦 <达瑞韦林。替诺福韦在Caco-2细胞单层中的Papp为0.10 ± 0.02 × 10-6厘米/s，ER = 1。对于dapivirine，Papp为32.2 ± 3.7 × 10-6厘米/s，但ER = 1.3低于基于计算机研究结果的预期。替诺福韦和达比韦林的转运均不受P-gp抑制剂的影响。darunavir的吸收渗透率 (Papp = 6.4 ± 0.9 × 10-6厘米/s) 与ER = 6.3有关，维拉帕米将其降低至1.2。与作为单一药物施用相比，联合施用药物不会改变其渗透性。总之，在计算机模拟，细胞培养和基于组织的测定中，替诺福韦不与P-gp相互作用，渗透性差，与细胞旁转运机制一致。在计算机模拟中预测darunavir和dapivirine是P-gp底物，但只有darunavir在生物模型中显示出P-gp依赖性渗透性，这说明在计算机模拟中需要实验验证。当联合给药时，拟议的三联疗法抗逆转录病毒药物在大肠粘膜中的配置将取决于它们明显不同的渗透性，但不是相互依存的。

BACKGROUND & AIMS: :Epilepsy prevention is one of the great unmet needs in epilepsy. Approximately 15% of all epilepsy is caused by an acute acquired CNS insult such as traumatic brain injury (TBI), stroke or encephalitis. There is a latent period between the insult and epilepsy onset that presents an opportunity to intervene with preventive treatment that is unique in neurology. Yet no phase 3 epilepsy prevention studies, and only 2 phase 2 studies have been initiated in the last 16years. Current prevailing opinion is that the research community is not ready for clinical preventive epilepsy studies, and that animal models should first be refined and biomarkers of epileptogenesis and of epilepsy discovered before clinical studies are embarked upon. We review data to suggest that there is basis to do epilepsy prevention studies now with the current knowledge and available drugs, and that those studies are feasible with currently available tools. We suggest that a different approach is needed from the past in order to maximize chances of success, minimize the cost, and set up platform for future preventive treatment development. That approach should include close coordination of preclinical and clinical development programs in a combined PTE prevention strategy, consideration of polytherapy, and simultaneous, combined clinical development of preventive treatment and of biomarker discovery. We argue that the currently favored approach of eschewing clinical studies until biomarkers are available will delay the discovery of epilepsy prevention treatment by at least 10 years and significantly increase the cost of such discovery.

背景与目标： : 癫痫预防是癫痫病中巨大的未满足的需求之一。大约15% 的癫痫是由急性获得性CNS损伤引起的，例如创伤性脑损伤 (TBI)，中风或脑炎。在侮辱和癫痫发作之间有一个潜伏期，这为干预神经科独特的预防性治疗提供了机会。然而，在过去的16年中，尚未进行3期癫痫预防研究，并且仅启动了2期研究。目前的普遍观点是，研究界还没有准备好进行临床预防性癫痫研究，应该首先完善动物模型，并在开始临床研究之前发现癫痫发生和癫痫的生物标志物。我们回顾了数据，以表明现在有基础可以利用当前的知识和可用的药物进行癫痫预防研究，并且使用当前可用的工具进行这些研究是可行的。我们建议需要一种与过去不同的方法，以最大程度地提高成功机会，最大程度地降低成本，并为将来的预防性治疗开发建立平台。该方法应包括在联合PTE预防策略中密切协调临床前和临床开发计划，考虑多治疗以及预防性治疗和生物标志物发现的同时，联合临床开发。我们认为，在生物标志物可用之前，目前最受欢迎的避免临床研究的方法将使癫痫预防治疗的发现延迟至少10年，并显着增加这种发现的成本。

BACKGROUND & AIMS: :The recognition that human papillomavirus (HPV) infection is the central, necessary cause of cervical cancer paved the way to new fronts of prevention via improved screening methods and HPV vaccination. Much has been learned in all fronts, from the molecular basis of our understanding of how HPV causes disease to the health economics of preventive strategies at the individual and population levels. Progress in other areas of cancer control has yet to show the same multi- and trans-disciplinary gains seen in research on HPV-associated malignancies, which is one of the unequivocal success stories in disease prevention. Yet, as an embarrassment of riches, much more research is needed to fill the gaps in knowledge that remain before we are able to reap the benefits from the knowledge translation from all fronts. Public health research on setting-specific implementation of HPV-based preventive strategies and more concerted advocacy to counter barriers facing the adoption of these strategies are likely to yield major dividends in reducing the burden of HPV-associated diseases. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

背景与目标： : 认识到人乳头瘤病毒 (HPV) 感染是宫颈癌的主要必要原因，通过改进筛查方法和HPV疫苗接种，为预防的新领域铺平了道路。从我们对HPV如何引起疾病的理解的分子基础到个人和人群水平的预防策略的健康经济学，在各个方面都学到了很多东西。癌症控制的其他领域的进展尚未显示出与HPV相关的恶性肿瘤研究中相同的多学科和跨学科收益，这是疾病预防中明确的成功案例之一。然而，作为财富的尴尬，需要更多的研究来填补知识的空白，这些空白在我们能够从各个方面获得知识翻译的好处之前仍然存在。针对特定环境实施基于HPV的预防策略的公共卫生研究以及采取这些策略所面临的障碍的更协调一致的倡导，可能会在减轻HPV相关疾病的负担方面产生重大好处。本文是2012年《HPV感染及相关疾病的综合控制》疫苗第30卷第5期补充的部分内容。

BACKGROUND & AIMS: :Hirschsprung-associated enterocolitis (HAEC) is a common and sometimes life-threatening complication of Hirschsprung disease (HD). Presenting either before or after definitive surgery for HD, HAEC may manifest clinically as abdominal distension and explosive diarrhea, along with emesis, fever, lethargy, and even shock. The pathogenesis of HAEC, the subject of ongoing research, likely involves a complex interplay between a dysfunctional enteric nervous system, abnormal mucin production, insufficient immunoglobulin secretion, and unbalanced intestinal microflora. Early recognition of HAEC and preventative practices, such as rectal washouts following a pull-through, can lead to improved outcomes. Treatment strategies for acute HAEC include timely resuscitation, colonic decompression, and antibiotics. Recurrent or persistent HAEC requires evaluation for mechanical obstruction or residual aganglionosis, and may require surgical treatment with posterior myotomy/myectomy or redo pull-through. This chapter describes the incidence, pathogenesis, treatment, and preventative strategies in management of HAEC.

背景与目标： : Hirschsprung相关性小肠结肠炎 (HAEC) 是Hirschsprung病 (HD) 的常见且有时危及生命的并发症。在HD明确手术之前或之后，HAEC可能在临床上表现为腹胀和爆炸性腹泻，以及呕吐，发热，嗜睡甚至休克。正在进行的研究主题HAEC的发病机理可能涉及功能失调的肠道神经系统，异常的粘蛋白产生，免疫球蛋白分泌不足和肠道菌群不平衡之间的复杂相互作用。早期认识到HAEC和预防性做法，例如拉通后的直肠冲洗，可以改善预后。急性HAEC的治疗策略包括及时复苏，结肠减压和抗生素。复发性或持续性HAEC需要评估机械阻塞或残留的神经节病，并且可能需要通过后路肌切开术/肌切除术或重做拉通手术治疗。本章介绍了HAEC的发病率，发病机制，治疗和预防策略。

BACKGROUND & AIMS: :Alloreactive donor T cells against host minor histocompatibility antigens (mHAs) cause graft-versus-host disease (GVHD) after marrow transplantation from HLA-identical siblings. We sought to identify and expand regulatory CD4 T cells (Tregs) specific for human mHAs in numbers and potency adequate for clinical testing. Purified Tregs from normal donors were stimulated by dendritic cells (DCs) from their HLA-matched siblings in the presence of interleukin 2, interleukin 15, and rapamycin. Male-specific Treg clones against H-Y antigens DBY, UTY, or DFFRY-2 suppressed conventional CD4 T cell (Tconv) response to the specific antigen. In the blood of 16 donors, we found a 24-fold (range, 8-fold to 39-fold) excess Tconvs over Tregs reactive against sibling mHAs. We expanded mHA-specific Tregs from 4 blood samples and 4 leukaphereses by 155- to 405-fold. Cultured Tregs produced allospecific suppression, maintained demethylation of the Treg-specific Foxp3 gene promoter, Foxp3 expression, and transforming growth factor β production. The rare CD4 T conv and CD8 T cells in the end product were anergic. This is the first report of detection and expansion of potent mHA-specific Tregs from HLA-matched siblings in sufficient numbers for application in human transplant trials.

背景与目标： : 从HLA相同的兄弟姐妹进行骨髓移植后，针对宿主次要组织相容性抗原 (mha) 的同种反应性供体T细胞会引起移植物抗宿主病 (GVHD)。我们试图鉴定和扩大人类mhs特异性调节性CD4 T细胞 (Tregs) 的数量和效力，足以进行临床测试。在白介素2，白介素15和雷帕霉素的存在下，来自正常供体的纯化treg被其HLA匹配的兄弟姐妹的树突状细胞 (dc) 刺激。针对h-y抗原DBY、UTY或DFFRY-2的男性特异性Treg克隆抑制了对特异性抗原的常规cd4t细胞 (Tconv) 反应。在16位献血者的血液中，我们发现对同胞mh反应的treg的tconv过量为24倍 (范围为8倍至39倍)。我们将来自4个血液样本和4个白细胞的mHA特异性treg扩大了155至405倍。培养的Tregs产生同种特异性抑制，维持Treg特异性Foxp3基因启动子的去甲基化，Foxp3表达和转化生长因子 β 的产生。终产物中罕见的CD4 T conv和CD8 T细胞是无能的。这是从HLA匹配的兄弟姐妹中检测和扩展有效的mHA特异性treg的第一份报告，其数量足以应用于人类移植试验。

BACKGROUND & AIMS: :High blood pressure (BP) is the most important modifiable risk factor for stroke and other vascular diseases. Evidence from randomized controlled trials supports the use of antihypertensive drugs to lower blood pressure for stroke prevention. There is some evidence that specific classes of antihypertensive drugs have different effects and/or their pharmacological actions differ in patient subgroups. This review evaluates the development of antihypertensive therapies and the latest studies of arterial hypertension and stroke prevention: HOPE trial (ramipril versus placebo), ALLHAT trial (CCB or/ and Angiotensin-Conventing enzyme Inhibitors (ACE-Is) versus diuretic), LIFE trial (losartan versus atenolol), and PROGRESS trial (perindopril or/and indapamide versus placebo). Despite the results of these relevant clinical trails, some aspects still remain unresolved. Future clinical trials on hypertension and stroke prevention should answer the following questions: Does lowering BP reduce stroke risk due to specific drug effect or class effect? Are angiotensin II receptor blockers (ARBs) better than ACE-Is? Should ACE-Is and ARBs be considered routinely for either high-risk stroke patients or patients with history of stroke or transient ischemic attack, irrespective of blood pressure? What is the role of lifestyle in BP control?

背景与目标： : 高血压 (BP) 是中风和其他血管疾病最重要的可改变的危险因素。来自随机对照试验的证据支持使用抗高血压药物来降低血压以预防中风。有证据表明，特定类别的抗高血压药物在患者亚组中具有不同的作用和/或其药理作用不同。这篇综述评估了抗高血压疗法的发展以及动脉高血压和中风预防的最新研究: HOPE试验 (雷米普利与安慰剂)，ALLHAT试验 (CCB或/和血管紧张素转换酶抑制剂 (ACE-Is) 与利尿剂)，生命试验 (氯沙坦与阿替洛尔)，和进展试验 (培哚普利或/和吲达帕胺与安慰剂)。尽管有这些相关临床试验的结果，但某些方面仍未解决。未来关于高血压和中风预防的临床试验应回答以下问题: 降低血压是否会因特定的药物效应或类别效应而降低中风风险？血管紧张素II受体阻滞剂 (arb) 比ACE-Is好吗？对于高危卒中患者或有卒中史或短暂性脑缺血发作史的患者，无论血压如何，是否应该常规考虑ACE-Is和arb？生活方式在控制血压中的作用是什么？

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVE:Results from the VALVACE (VALsartan Versus ACE inhibition after bare metal stent implantation) trial suggest that prevention of in-stent restenosis after implantation of bare-metal stents in type B2/C coronary artery lesions is possible after administration of valsartan 80 mg/day. However, the restenosis rate in patients with stable angina was relatively high (27%) with this dosage and no different from patients taking ACE inhibitors. Therefore, a 1 : 1 matched comparison on a case-control basis was initiated in a prospective controlled registry using a higher dose of valsartan, 160-320 mg/day. METHODS:A total of 450 patients (241 men, mean age 62.7 +/- 9.1 years) with matched demographic and angiographic characteristics to patients in the VALVACE trial were treated with high-dose oral valsartan 160-320 mg/day over 6 months until control angiography. Angiographic restenosis rate, target lesion revascularization (TLR) and target vessel revascularization (TVR) rates, major adverse cardiac event (MACE) rate (death, myocardial infarction, and stent thrombosis) and mean late lumen loss were analysed after 6 months. Results were compared with the results of the VALVACE trial. Analysis of the combined results of the current study together with the VALVACE trial data enabled calculation of the gender- and dose-dependent effects of valsartan. RESULTS:In the high-dose valsartan group, the angiographic restenosis rate in 368 patients with control angiography was 7.3% compared with 19.5% in the low-dose group (VALVACE) [p < 0.0001]. Mean late lumen loss was 0.37 +/- 0.3 mm in the high-dose group compared with 0.53 +/- 0.31 mm in the VALVACE trial (p < 0.01). TLR and TVR rates were 4.3% in the high-dose group compared with 9% in the VALVACE trial (p < 0.01). The MACE rate was 0% in the high-dose group compared with 1.5% in the VALVACE trial (p < 0.01). Summarizing the data for valsartan, the in-stent restenosis rates in men were 22.7%, 13.3%, 6.7%, and 5.4% in patients receiving 80, 160, 240, and 320 mg/day, respectively. In women, the in-stent restenosis rates were 13.3% and 6.3% in patients receiving 80 and 160 mg/day, respectively; no restenosis occurred in patients receiving higher doses. CONCLUSION:Administration of high-dose oral valsartan 160-320 mg/day after implantation of bare-metal stent in type B2/C coronary artery lesions reduces angiographic in-stent restenosis, TLR, TVR, late lumen loss, and MACE rates more effectively than low-dose valsartan 80 mg/day.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Annually, about 30% of the persons of 65 years and older falls at least once and 15% falls at least twice. Falls often result in serious injuries, such as fractures. Therefore, the prevention of accidental falls is necessary. The aim is to describe the design of a study that evaluates the efficacy and cost-effectiveness of a multidisciplinary assessment and treatment of multiple fall risk factors in independently living older persons with a high risk of falling. METHODS/DESIGN:The study is designed as a randomised controlled trial (RCT) with an economic evaluation. Independently living persons of 65 years and older who recently experienced a fall are interviewed in their homes and screened for risk of recurrent falling using a validated fall risk profile. Persons at low risk of recurrent falling are excluded from the RCT. Persons who have a high risk of recurrent falling are blindly randomised into an intervention (n = 100) or usual care (n = 100) group. The intervention consists of a multidisciplinary assessment and treatment of multifactorial fall risk factors. The transmural multidisciplinary approach entails close cooperation between geriatrician, primary care physician, physical therapist and occupational therapist and can be extended with other specialists if relevant. A fall calendar is used to record falls during one year of follow-up. Primary outcomes are time to first and second falls. Three, six and twelve months after the home visit, questionnaires for economic evaluation are completed. After one year, during a second home visit, the secondary outcome measures are reassessed and the adherence to the interventions is evaluated. Data will be analysed according to the intention-to-treat principle and also an on-treatment analysis will be performed. DISCUSSION:Strengths of this study are the selection of persons at high risk of recurrent falling followed by a multidisciplinary intervention, its transmural character and the evaluation of adherence. If proven effective, implementation of our multidisciplinary assessment followed by treatment of fall risk factors will reduce the incidence of falls. TRIAL REGISTRATION:Current Controlled Trials ISRCTN11546541.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Among the most serious sequelae to an initial episode of Major Depressive Disorder (MDD) during adolescence is the significant increase in the probability of recurrence. This study reports on an integrated CBT/IPT program, provided in a group format, that was developed to decrease the rate of MDD recurrence in emerging adults. METHODS:Participants were 89 young adults who were not depressed at study entry but had experienced MDD during adolescence. Participants were assigned to a CBT/IPT prevention program or to an assessment only control condition and were followed through the first 2 years of college. RESULTS:Risk for MDD recurrence was reduced more than 50% for the prevention program participants compared to assessment only controls. The intervention also conferred beneficial effects on academic performance for those students who completed the majority of the group sessions. LIMITATIONS:The study included a self-selected sample of emerging adults who were aware of their history of depression. Due to the small sample size, it will be important to evaluate similar interventions in adequately-powered trials to determine if this is a replicable finding. CONCLUSIONS:With 51% of the assessment only participants experiencing a MDD recurrence during the first 2 years of college, these findings support the need for programs designed to prevent MDD recurrence in young adults. The current program, based on IPT and CBT principles, appears to reduce the rate of MDD recurrence among previously depressed emerging adults.

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