BACKGROUND & AIMS: :In Japan, there has not yet been a complete psychological autopsy study. The author conducted a retrospective study of failed suicides (quasi-completed suicides) admitted to an emergency critical care center. According to the lethality of suicide methods, 133 out of 265 subjects over 6 years (1986-1991) were classified as the absolutely dangerous (AD; the failed suicides) group. As a principal diagnosis, psychoses, endogenous depression, substance abuse were present in 75% of the AD group. The diagnostic distribution largely differed with depressive disorders being mainly in the older group (50+ years), and psychoses predominating in the younger group (< 30 years). This study suggested that the majority of suicide victims in Japan also had mental disorders, and suicide prevention should be confronted with this clinical fact.

背景与目标： ：在日本，尚未进行完整的心理尸检研究。作者对入院急救中心的失败自杀（准完全自杀）进行了回顾性研究。根据自杀方法的致死性，在6年内（1986-1991年）的265名受试者中，有133名被归为绝对危险（AD；失败的自杀）组。作为主要诊断，在AD组中有75％患有精神病，内源性抑郁症和药物滥用。诊断分布存在很大差异，其中抑郁症主要发生在老年组（50岁），而精神病在年轻组（<30岁）占主导。这项研究表明，日本大多数自杀受害者也患有精神疾病，因此自杀预防应面对这一临床事实。

BACKGROUND & AIMS: :Varieties of neuropathological disorders are caused by a perturbation of normal developmental processes, resulting from insults by heterogeneous etiologic factors. These factors trigger the sequence of molecular, biochemical, and morphologic alterations of the brain, resulting morphologically and/or functionally abnormal brain. The resulting brain contains basic components of the normal brain but is assembled in an abnormal way. The developmental stage when the insults occur appears to largely dictate the outcome of the pathological processes. Depending on the developmental stage involved, the morphology of the brain may be grossly abnormal or is apparently normal but functionally abnormal. The brain development progresses in an orderly fashion and can be divided into several major developmental stages; the neurulation (neural tube formation), ventral induction (formation of prosencephalon), neuroepithelial cell proliferation and migration, neuroglial differentiation and establishment of neuronal circuits. The perturbation of these developmental stages results in uniquely specific pathological outcome, regardless of the etiologic factors/agents. In this review, I will briefly discuss the normal pattern of brain development and neuropathology of the representative disorders resulting from the deviation of normal developmental processes in the individual developmental stage.

背景与目标： 神经病理性疾病的各种变化是由于正常的发育过程受到扰动引起的，这种扰动是由各种病因引起的。这些因素触发了大脑的分子，生化和形态改变的顺序，从而导致了形态和/或功能异常的大脑。生成的大脑包含正常大脑的基本组件，但以异常方式组装。侮辱发生的发育阶段似乎在很大程度上决定了病理过程的结果。根据所涉及的发育阶段，大脑的形态可能是严重异常，或者显然是正常的但功能异常。大脑发育以有序的方式进行，可以分为几个主要的发育阶段。神经（神经管形成），腹腔诱导（前脑形成），神经上皮细胞增殖和迁移，神经胶质细胞分化和神经回路的建立。这些发展阶段的扰动导致独特的特定病理结果，而与病因/因素无关。在这篇综述中，我将简要讨论由于个体发育阶段正常发育过程的偏离而导致的代表性疾病的大脑发育和神经病理学的正常模式。

BACKGROUND & AIMS: PURPOSE:Consistent condom use is critical to efforts to prevent sexually transmitted infections among adolescents, but condom use may decline as relationships and contraceptive needs change. The purpose of this research is to assess changes in condom non-use longitudinally in the context of changes in relationship quality, coital frequency and hormonal contraceptive choice. METHODS:Participants were women (aged 14-17 years at enrollment) recruited from three urban adolescent medicine clinics. Data were collected at three-month intervals using a face-to-face structured interview. Participants were able to contribute up to 10 interviews, but on average contributed 4.2 interviews over the 27-month period. Independent variables assessed partner-specific relationship quality (five items; scale range 5-25; alpha = .92, e.g., this partner is a very important person to me); and, number of coital events with a specific partner. Additional items assessed experience with oral contraceptive pills (OCP) use and injected depo medroxy-progesterone acetate (DMPA). The outcome variable was number of coital events without condom use during the past three months. Analyses were conducted as a three-level hierarchical linear growth curve model using HLM 6. The Level 1 predictor was time, to test the hypothesis that condom non-use increases over time. Level 2 predictors assessed relationship quality and coital frequency across all partners to assess hypotheses that participants' condom non-use increases over time as a function of relationship quality and coital frequency. Level 3 predictors assessed the participant-level influence of OCP or DMPA experience on time-related changes in condom non-use. RESULTS:A total of 176 women reported 279 sex partners and contributed 478 visits. Both average coital frequency and average condom non-use linearly increased during the 27-month follow-up. At any given follow-up, about 35% reported recent OCP use, and 65% reported DMPA use. HLM analyses showed that condom non-use increased as a function of time (beta = .12; p = .03, Level 1 analysis). Increased condom non-use over time was primarily a function of increased coital frequency (beta = .01; p = .00), although higher levels of relationship quality were associated with increased condom non-use at enrollment (beta = .44; p = .00, Level 2 analysis). The temporal rise in condom non-use significantly increased among DMPA users (beta = .06; p = .00) but not OCP users (Level 3 analysis) (beta = -.04; p = .06). CONCLUSIONS:Developmentally, relationship characteristics and coital frequency appear to have increasing weight in decisions about condom use. Hormonal contraceptive methods are not equivalently associated with the overall temporal decline in condom use. Future research associated with dual contraceptive/condom use should address differential factors associated condom use in combination with different hormonal methods.

背景与目标： 目的：持续使用避孕套对于预防青少年性传播感染至关重要，但是随着人际关系和避孕需求的变化，避孕套的使用可能会减少。这项研究的目的是在关系质量，性交频率和激素避孕选择的变化的背景下，纵向评估未使用安全套的变化。
方法：参与者是从三个城市青少年医学诊所招募的女性（入学年龄14-17岁）。使用面对面的结构化访谈，每三个月收集一次数据。参加者最多可以贡献10个访谈，但在27个月内平均贡献了4.2个访谈。自变量评估了特定于伴侣的关系质量（五个项目；等级范围5-25；α= 0.92，例如，这个伴侣对我来说是非常重要的人）；以及与特定伴侣发生性行为的次数。其他项目评估了口服避孕药（OCP）的使用经验和注射醋酸去甲羟孕酮（DMPA）的经验。结果变量是在过去三个月中未使用安全套的性交事件的数量。使用HLM 6作为三级分层线性增长曲线模型进行了分析。1级预测因子是时间，以检验安全套不使用随时间增加的假设。 2级预测变量评估了所有伴侣之间的关系质量和性交频率，以评估以下假设：参与者不使用安全套会随着时间的推移而增加，这是关系质量和性交频率的函数。 3级预测变量评估了OCP或DMPA经验对安全套不使用时间相关变化的参与者水平影响。
结果：总共176名妇女报告了279个性伴侣，并贡献了478次探视。在27个月的随访中，平均性交频率和平均不使用安全套均呈线性增加。在任何给定的随访中，约35％的患者报告了最近的OCP使用，而65％的患者报告了DMPA的使用。 HLM分析表明，不使用安全套随时间增加（β= .12； p = .03，1级分析）。随着时间的流逝，不使用安全套的增加主要是性交频率增加的函数（β= .01； p = .00），尽管较高的关系质量与入学时不使用安全套的增加相关（β= .44； p = .00，第2级分析）。在DMPA用户中，未使用安全套的时间增加显着增加（β= .06； p = .00），但在OCP用户中则没有（第三级分析）（β= -.04； p = .06）。
结论：在发展上，关系特征和性交频率似乎在有关使用安全套的决策中具有越来越大的重要性。激素避孕方法与使用避孕套的总体时间下降没有同等的联系。与双重避孕/避孕套使用相关的未来研究应解决与不同激素方法结合使用避孕套相关的差异因素。

BACKGROUND & AIMS: :Few well-constructed studies have systematically evaluated medical investigation protocols for children with autistic spectrum disorders. This is in large part due to the heterogeneous nature of the population and changing diagnostic frameworks. This review outlines the studies that have directed investigation strategies to date, and discusses how these might be applied in the clinical situation. The importance of listing the conditions that may be present on the basis of the specific clinical presentation, and using a thorough history and examination to generate a pre-test probability of the target disorders is emphasized if tests are to be useful in directing therapy or broader management approaches.

背景与目标： ：很少有结构完善的研究能够系统地评估自闭症谱系障碍儿童的医学研究方案。这在很大程度上是由于人群的异质性和不断变化的诊断框架。这篇综述概述了迄今为止指导研究策略的研究，并讨论了如何将这些策略应用于临床。如果测试对指导治疗或更广泛有用，则强调列出根据具体临床表现可能出现的疾病，并使用详尽的病史和检查以产生目标疾病的预测试概率的重要性。管理方法。

BACKGROUND & AIMS: :In the last few years, our knowledge of genetically determined causes of short stature has greatly increased by reports of challenging patients, who offered the opportunity to study genes that play a role in growth. Since the first paper that showed the etiology of Laron syndrome [Godowski PJ, et al: Proc Natl Acad Sci USA 1989;86:8083-8087], many mutations in the growth hormone (GH) receptor have been identified. Recently, new mutations or deletions have been found in several components of the GH-insulin-like growth factor-I (IGF-I) axis: a homozygous mutation of the GH1 gene, resulting in a bio-inactive GH; mutations in the STAT5b gene, which plays a major role in the GH signal transduction; a homozygous missense mutation in the IGF-I gene; heterozygous mutations in the IGF-I receptor gene and a homozygous deletion of the acid-labile subunit gene. In this mini review, we describe the clinical and biochemical features of these genetic defects. Genetic analysis has become essential in the diagnostic workup of a patient with short stature. However, regarding the time consuming nature of molecular analysis, it is important to carefully select the patient for specific genetic evaluation. To help in this selection process, we developed flowcharts, based on the recently described patients, that can be used as guidelines in the diagnostic process of patients with severe short stature of unknown origin.

背景与目标： ：在过去的几年中，由于挑战性患者的报道，我们对遗传决定的矮小身高原因的了解大大增加了，这些患者为研究在生长中起作用的基因提供了机会。自从第一篇显示Laron综合征病因的论文以来[Godowski PJ等人：Proc Natl Acad Sci USA 1989; 86：8083-8087]，已经确定了生长激素（GH）受体的许多突变。最近，在GH-胰岛素样生长因子-I（IGF-I）轴的几个组成部分中发现了新的突变或缺失：GH1基因的纯合突变，导致了生物失活的GH； STAT5b基因的突变，在GH信号转导中起主要作用； IGF-I基因的纯合错义突变； IGF-1受体基因中的杂合突变和对酸不稳定的亚基基因的纯合缺失。在这个小型综述中，我们描述了这些遗传缺陷的临床和生化特征。遗传分析已成为身材矮小的患者的诊断检查中必不可少的。但是，考虑到分子分析的耗时性质，重要的是要仔细选择患者进行特定的基因评估。为了帮助选择过程，我们根据最近描述的患者制定了流程图，可以将其用作诊断患有严重身材矮小，来源不明的患者的诊断过程中的指导原则。

BACKGROUND & AIMS: :Native chromatin IP assays were used to define changes in core histone acetylation at the lysozyme locus during developmental maturation of chicken macrophages and stimulation to high-level expression by lipo-polysaccharide. In pluripotent precursors the lysozyme gene (Lys) is inactive and there is no acetylation of core histones at the gene, its promoter or at the upstream cis-control elements. In myeloblasts, where there is a very low level of Lys expression, H4 acetylation appears at the cis-control elements but not at the Lys gene or its promoter: neither H3 nor H2B become significantly acetylated in myeloblasts. In mature macrophages, Lys expression increases 5-fold: H4, H2B and H2A.Z are all acetylated at the cis-control elements but H3 remains unacetylated except at the -2.4 S silencer. Stimulation with LPS increases Lys expression a further 10-fold: this is accompanied by a rise in H3 acetylation throughout the cis-control elements; H4 and H2B acetylation remain substantial but acetylation at the Lys gene and its promoter remains low. Acetylation is thus concentrated at the cis-control elements, not at the Lys gene or its immediate promoter. H4 acetylation precedes H3 acetylation during development and H3 acetylation is most directly linked to high-level Lys expression.

背景与目标： ：天然染色质IP分析用于确定鸡巨噬细胞发育成熟和脂多糖刺激高水平表达期间溶菌酶基因座核心组蛋白乙酰化的变化。在多能的前体中，溶菌酶基因（Lys）是无活性的，并且在该基因，其启动子或上游顺式控制元件上没有核心组蛋白的乙酰化。在成纤维细胞中，Lys表达水平非常低，H4乙酰化出现在顺式控制元件上，而没有出现在Lys基因或其启动子上：H3和H2B在成纤维细胞中都没有被显着乙酰化。在成熟的巨噬细胞中，Lys表达增加5倍：H4，H2B和H2A.Z在顺式控制元件上均被乙酰化，但H3除外-2.4 S沉默子上保持未乙酰化。用LPS刺激可将Lys表达进一步提高10倍：伴随着整个顺式控制元件中H3乙酰化的增加； H4和H2B的乙酰化作用仍然很强，但Lys基因及其启动子的乙酰化作用仍然很低。因此，乙酰化作用集中在顺式控制元件上，而不是Lys基因或其直接启动子上。在发育过程中，H4乙酰化先于H3乙酰化，而H3乙酰化与高水平Lys表达最直接相关。

BACKGROUND & AIMS: BACKGROUND:Diabetes mellitus (DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles, currently the extracts from leaves of cynara scolymus has been discovered to treat metabolic disorders and has been stated by multitudinous scientists according to a good source of polyphenols compounds. The present study aimed to evaluate the protective effect of the ethanol leaves extract of C. scolymus in alloxan induced stress oxidant, hepatic-kidney dysfunction and histological changes in liver, kidney and pancreas of different experimental groups of rats. METHODS:We determinate the antioxidant activity by ABTS .+ and antioxidant total capacity (TAC) of all extracts of C. scolymus leaves, the inhibition of α-amylase activity in vitro was also investigated. Forty male Wistar rats were induced to diabetes with a single dose intraperitoneal injection (i.p.) of alloxan (150 mg/kg body weight (b.w.)). Diabetic rats were orally and daily administrated of ethanol extract from C. scolymus at two doses (200-400 mg/kg, b.w) or (12 mg/kg, b.w) with anti-diabetic reference drug, Acarbose for one month. Ethanol extract of C. scolymus effect was confirmed by biochemical analysis, antioxidant activity and histological study. RESULTS:The results indicated that the ethanol extract from leaves of C. scolymus showed the highest antioxidant activity by ABTS .+ (499.43g± 39.72 Trolox/g dry extract) and (128.75 ± 8.45 mg VC /g dry extract) for TAC and endowed the powerful inhibition in vitro of α-amylase activity with IC50=72,22 ug/uL. In vivo, the results showed that ethanol extract from the leaves of C. scolymus (200-400 mg/kg) decreased significantly (p < 0.001) the α-amylase levels in serum of diabetic rats, respectively associated with significant reduction (p < 0.001) in blood glucose rate of 42,84% and 37,91% compared to diabetic groups after 28 days of treatment, a significant lowered of plasma total cholesterol (T-Ch) by 18,11% and triglyceride (TG) by 60,47%, significantly and low-density lipoproteins (LDL-C) by 37,77%, compared to diabetic rats, moreover, the administration of ethanol extract appears to exert anti-oxidative activity demonstrated by the increase of CAT, SOD and GSH activities in liver, kidney and pancreas of diabetic rats. This positive effect of the ethanol extract from C. scolymus was confirmed by histological study. CONCLUSION:These observed strongly suggest that ethanol extract from the leaves of C. scolymus has anti-hyperglycemic properties, at least partly mediated by antioxidant and hypolipidemic effects.

背景与目标： 背景：糖尿病（DM）与高血糖，炎性疾病和异常脂质状况相关，目前已发现粘虫c叶片的提取物可治疗代谢紊乱，许多科学家已经根据多酚化合物的良好来源进行了陈述。本研究旨在评价鳞球菌乙醇叶提取物对四氧嘧啶诱导的应激氧化剂，肝肾功能障碍以及不同实验组大鼠肝，肾和胰腺组织学变化的保护作用。
方法：我们通过ABTS测定抗氧化活性。鼠尾草叶片的所有提取物的抗氧化剂和总抗氧化剂（TAC），还研究了其对α-淀粉酶活性的体外抑制作用。通过单剂量腹膜内注射（i.p.）四氧嘧啶（150 mg / kg体重（b.w.））将40只雄性Wistar大鼠诱发为糖尿病。糖尿病大鼠口服和每天服用两种剂量（200-400 mg / kg，b.w）或（12 mg / kg，b.w）的鼠尾草乙醇提取物和抗糖尿病参考药物阿卡波糖（acarbose）。通过生化分析，抗氧化活性和组织学研究证实了粘液梭状芽胞杆菌的乙醇提取物作用。
结果：结果表明，ABTS从粘枝sco叶片中提取的乙醇具有最高的抗氧化活性。 （499.43g±39.72 Trolox / g干提取物）和（128.75±8.45 mg VC / g干提取物）用于TAC，并在体外有效抑制α-淀粉酶活性，IC50 = 72.22 ug / uL。在体内，结果显示，从粘液梭菌的叶子中提取乙醇（200-400 mg / kg）显着降低（p <0.001）糖尿病大鼠血清中的α-淀粉酶水平，分别与显着降低有关（p <0.001）。在治疗28天后，与糖尿病组相比，血糖比率分别为0.001、42.84％和37.91％，血浆总胆固醇（T-Ch）显着降低了18.11％，甘油三酸酯（TG）显着降低了60与糖尿病大鼠相比，低密度脂蛋白（LDL-C）降低了47.7％，低密度脂蛋白（LDL-C）降低了37.77％，此外，乙醇提取物的给药似乎表现出抗氧化活性，这是由于CAT，SOD和GSH的增加所证明的在糖尿病大鼠肝，肾和胰腺中的活性。组织学研究证实了粘液梭菌乙醇提取物的这种积极作用。
结论：这些观察结果强烈表明，从粘液梭菌的叶子中提取乙醇具有抗降血糖作用，至少部分是由抗氧化剂和降血脂作用介导的。

BACKGROUND & AIMS: :The revisions proposed for the DSM-5 would greatly alter how personality pathology is conceptualized, assessed, and diagnosed. One aspect of the proposed changes, elimination of four current personality disorders, has raised considerable controversy. The present study attempts to inform this debate by exploring clinicians' views of the structure of Personality Disorders using the current diagnostic system, the DSM-IV. An exploratory factor analysis was conducted on the DSM-IV Personality Disorder criteria using clinician ratings for 280 patients. The factor analysis revealed eight clear and meaningful factors. The eight factors contained all six personality disorders proposed for retention in DSM-5 but also contained clear representations of two disorders (Paranoid and Schizoid) identified for removal from the system. These conditions appear to have clinical utility and their removal may have unintended negative consequences in clinical practice. Dependent and Avoidant criteria also merged to form a new construct with interesting clinical implications. These findings provide new insights into the complex typologies clinicians employ when applying the DSM-IV system to personality disordered patients. Lastly we argue that successful refinement of clinically significant constructs, like diagnostic systems, requires a balanced appraisal of evidence for clinical utility as well as external and internal validity.

背景与目标： ：针对DSM-5提出的修订将极大地改变人格病理学的概念化，评估和诊断方式。所提议的改变的一方面，消除了当前的四种人格障碍，引起了相当大的争议。本研究试图通过使用当前的诊断系统DSM-IV探索临床医生对人格障碍结构的看法来为这场辩论提供信息。使用临床医师评估的280名患者，对DSM-IV人格障碍标准进行了探索性因素分析。因素分析揭示了八个明确而有意义的因素。八个因素既包含提议保留在DSM-5中的所有六个人格障碍，也包含明确识别出的两种人格障碍（Paranoid和Schizoid），可以从系统中移除。这些情况似乎具有临床用途，将其清除可能会在临床实践中产生意想不到的负面影响。受抚养者和回避者的标准也合并在一起，形成了一种具有有趣临床意义的新结构。这些发现为临床医生在将DSM-IV系统应用于人格障碍患者时采用的复杂类型提供了新的见解。最后，我们认为要成功地完善具有临床意义的结构（如诊断系统），需要对临床实用性以及内部和外部有效性的证据进行均衡的评估。

BACKGROUND & AIMS: :To better explore the clinical heterogeneity of bipolar mood states, we developed a dimensional scale for assessing all mood episodes (depressive, hypomanic, manic, mixed states) using the same tool. The Multidimensional Assessment of Thymic States (MATHYS) (Henry et al., 2008) provides two scores, a total score measuring a level of activation and a sub-score of emotional reactivity. The aim of this study was to establish the appropriate cut-off in total activation versus inhibition and in the emotional reactivity sub-score in bipolar disorders. Patients (n=187) during an acute episode and controls (n=89) filled in the MATHYS. Receiver Operating Characteristic (ROC) curves were obtained to estimate the sensitivity and specificity of the global score and the emotional reactivity sub-score of the MATHYS, in order to differentiate patients from controls. ROC curves showed very satisfactory sensitivity and specificity levels both for the total score and the sub-score of emotional reactivity, thus providing an appropriate cut-off. Concerning the total score between 0 and 200, patients with a score lower than 91 had significant global inhibition and those with a score higher than 109 had significant global activation. Regarding the emotional reactivity sub-score between 0 and 40, patients with a score lower than 16 had significant emotional hyporeactivity and those with a score higher than 24 had significant emotional hyperreactivity. Our results provide cut-offs for the MATHYS to identify patients in an acute phase.

背景与目标： ：为了更好地探索双相情感状态的临床异质性，我们开发了一种用于使用同一工具评估所有情绪事件（抑郁，躁狂，躁狂，混合状态）的量表。胸腺状态的多维评估（MATHYS）（Henry等，2008）提供了两个评分，一个总评分用于衡量激活水平，另一个是情感反应分数。这项研究的目的是确定双相情感障碍的总激活与抑制以及情绪反应性亚评分的适当分界。急性发作期间的患者（n = 187）和对照组（n = 89）填写了MATHYS。获得接收者操作特征（ROC）曲线以估计MATHYS总体评分和情绪反应性子评分的敏感性和特异性，以区分患者与对照组。 ROC曲线在总分和情绪反应的亚评分中均显示出非常令人满意的敏感性和特异性水平，因此提供了适当的临界值。关于总分在0到200之间，得分低于91的患者具有显着的总体抑制作用，得分高于109的患者具有显着的全局抑制作用。关于0至40之间的情绪反应分数，得分低于16的患者有明显的情绪低反应性，而得分高于24的患者则有明显的情绪高反应性。我们的结果为MATHYS识别急性期患者提供了界限。

BACKGROUND & AIMS: :Activating KIR-HLA-C ligand complexes and HLA-G∗14bp insertion/deletion (+/-) polymorphism were associated to Autism Spectrum Disorders (ASD) and were suggested to correlate with inflammation during fetal development. We evaluated whether HLA-G∗14bp(+/-) and KIR-HLA-C complexes are associated with cognitive and behavioral scores and EEG profile in 119 ASD children (58 from Sardinia, 61 from Peninsular Italy). KIR2DS1-C2; KIR2DS2-C1; KIR2DL1-C2; KIR2DL2-C1; KIR2DL3-C1 and HLA-G∗14bp(+/-) were molecularly genotyped by Single Specific Primer PCR and gel electrophoresis. Univariate linear model analysis adjusted for age, gender and provenience showed statistically higher scores of Childhood Autism Rating Scale (CARS) and Autistic Core Behavior in KIR2DS1-C2+/HLA-G∗14bp+ASD children (43.7±1.5, p=0.03; 3.3±0.1, p=0.03, respectively). These results suggested a synergistic polygenic association of KIR2DS1-HLAC2+/HLA-G∗14bp+ pattern with behavioral impairment in ASD children.

背景与目标： ：激活的KIR-HLA-C配体复合物和HLA-G * 14bp插入/缺失（/-）多态性与自闭症谱系障碍（ASD）相关，并被认为与胎儿发育过程中的炎症相关。我们评估了119名ASD儿童（58名来自撒丁岛，61名来自意大利半岛）的HLA-G * 14bp（/-）和KIR-HLA-C复合物是否与认知和行为评分以及脑电图谱相关。 KIR2DS1-C2; KIR2DS2-C1; KIR2DL1-C2; KIR2DL2-C1;通过单特异性引物PCR和凝胶电泳对KIR2DL3-C1和HLA-G * 14bp（/-）进行分子基因分型。根据年龄，性别和出身水平进行的单变量线性模型分析显示，在KIR2DS1-C2 / HLA-G * 14bp ASD儿童中，儿童自闭症评分量表（CARS）和自闭症核心行为的统计学得分较高（43.7±1.5，p = 0.03; 3.3±分别为0.1，p = 0.03）。这些结果表明，KIR2DS1-HLAC2 / HLA-G * 14bp模式与ASD儿童的行为障碍存在协同的多基因关联。

BACKGROUND & AIMS: :Spontaneous intracranial hemorrhage is a debilitating form of stroke, often leading to death or permanent cognitive impairment. Many of the causative genes and the underlying mechanisms implicated in developmental cerebral-vascular malformations are unknown. Recent in vitro and in vivo studies in mice have shown inhibition of the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) pathway to be effective in stabilizing cranial vessels. Using a combination of pharmacological and genetic approaches to specifically inhibit the HMGCR pathway in zebrafish (Danio rerio), we demonstrate a requirement for this metabolic pathway in developmental vascular stability. Here we report that inhibition of HMGCR function perturbs cerebral-vascular stability, resulting in progressive dilation of blood vessels, followed by vessel rupture, mimicking cerebral cavernous malformation (CCM)-like lesions in humans and murine models. The hemorrhages in the brain are rescued by prior exogenous supplementation with geranylgeranyl pyrophosphate (GGPP), a 20-carbon metabolite of the HMGCR pathway, required for the membrane localization and activation of Rho GTPases. Consistent with this observation, morpholino-induced depletion of the β-subunit of geranylgeranyltransferase I (GGTase I), an enzyme that facilitates the post-translational transfer of the GGPP moiety to the C-terminus of Rho family of GTPases, mimics the cerebral hemorrhaging induced by the pharmacological and genetic ablation of HMGCR. In embryos with cerebral hemorrhage, the endothelial-specific expression of cdc42, a Rho GTPase involved in the regulation of vascular permeability, was significantly reduced. Taken together, our data reveal a metabolic contribution to the stabilization of nascent cranial vessels, requiring protein geranylgeranylation acting downstream of the HMGCR pathway.

背景与目标： ：自发性颅内出血是中风的一种虚弱形式，通常会导致死亡或永久性认知障碍。涉及发展性脑血管畸形的许​​多致病基因和潜在机制尚不清楚。最近在小鼠中进行的体外和体内研究表明，抑制3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）途径可有效稳定颅骨血管。使用药理和遗传学方法的组合来特异性抑制斑马鱼（Danio rerio）中的HMGCR途径，我们证明了这种代谢途径在发育性血管稳定性中的需求。在这里我们报道抑制HMGCR功能扰乱脑血管稳定性，导致血管进行性扩张，继而血管破裂，在人和鼠模型中模仿脑海绵状畸形（CCM）样病变。可以通过事先外源补充geranylgeranyl焦磷酸（GGPP）（HMGCR途径的20个碳代谢物）进行膜定位和激活Rho GTPases来挽救脑部出血。与该观察结果一致，吗啉代诱导的香叶基香叶基转移酶I（GGTase I）的β亚基耗竭，该酶有助于将GGPP部分翻译后转移至GTPases Rho家族的C末端，从而模拟脑出血由HMGCR的药理和遗传消融诱导。在患有脑出血的胚胎中，参与血管通透性调节的Rho GTPase cdc42的内皮特异性表达显着降低。综上所述，我们的数据揭示了新陈代谢对稳定新生颅血管的作用，需要在HMGCR途径下游作用的蛋白香叶基香叶基化作用。

BACKGROUND & AIMS: :The need to find effective treatments for patients with Anorexia or Bulimia nervosa has led to the professionals who care for them to develop new forms of treatment that take into account the variables that cause resistance to change. Patients in this study (2006-2009) have the following characteristics: 340 patients who have 7 or more years of evolution and/or have tried numerous previous treatments without having succeeded in starting and / or maintaining the desired changes, that allowed them to recover steadily. As the proposed treatment, the patient-treatment team is based on the principles of the training model. It considers the patient holistically, it informs and provides him with resources to increase its commitment to change. Teaches the patient to take care physically and mentally as a way to regain their health and leave the disorder in a stable way. Includes family members as essential support in the recovery of their closest. Therapists require extensive experience in the treatment of ED, flexibility, ability to integrate with other team members even if they use different theoretical models, skills for group sessions, ability to handle negative emotions and frustration tolerance. Finally, the model presented below has been implemented, recovered patients whose stay in the disorder exceeded 15 years of development and led to permanent occupational disability.

背景与目标： 由于需要为患有厌食症或神经性贪食症的患者找到有效的治疗方法，因此引起了专业人士的关注，他们开发出了新的治疗形式，并考虑到了引起抗药性变化的因素。本研究（2006-2009年）的患者具有以下特征：340位患者经历了7年或更长时间的进化和/或尝试过许多先前的治疗而未成功开始和/或维持所需的改变，从而使他们得以康复稳步。作为建议的治疗方法，患者治疗团队基于培训模型的原则。它从整体上考虑患者，为患者提供信息并为其提供资源，以增加其对变化的承诺。教给病人身心上的照顾，以恢复健康并稳定地摆脱疾病。包括家庭成员，以帮助他们恢复最亲密的关系。治疗师需要在ED的治疗方面具有丰富的经验，灵活性，与其他团队成员融为一体的能力，即使他们使用不同的理论模型，小组会议的技能，应对负面情绪的能力和挫败感的容忍度也是如此。最终，实施了以下模型，恢复了在该疾病中停留超过15年并导致永久性职业残疾的患者。

BACKGROUND & AIMS: BACKGROUND:The majority of patients with depressive disorders are treated by general practitioners (GPs) and are prescribed antidepressant medication. Patients prefer psychological treatments but they are under-used, mainly due to time constraints and limited accessibility. A promising approach to deliver psychological treatment is blended care, i.e. guided online treatment. However, the cost-effectiveness of blended care formatted as an online psychological treatment supported by the patients' own GP or general practice mental health worker (MHW) in routine primary care is unknown. We aim to demonstrate non-inferiority of blended care compared with usual care in patients with depressive symptoms or a depressive disorder in general practice. Additionally, we will explore the real-time course over the day of emotions and affect, and events within individuals during treatment. METHODS:This is a pragmatic non-inferiority trial including 300 patients with depressive symptoms, recruited by collaborating GPs and MHWs. After inclusion, participants are randomized to either blended care or usual care in routine general practice. Blended care consists of the 'Act and Feel' treatment: an eight-week web-based program based on behavioral activation with integrated monitoring of depressive symptomatology and automatized feedback. GPs or their MHWs coach the participants through regular face-to-face or telephonic consultations with at least three sessions. Depressive symptomatology, health status, functional impairment, treatment satisfaction, daily activities and resource use are assessed during a follow-up period of 12 months. During treatment, real-time fluctuations in emotions and affect, and daily events will be rated using ecological momentary assessment. The primary outcome is the reduction of depressive symptoms from baseline to three months follow-up. We will conduct intention-to-treat analyses and supplementary per-protocol analyses. DISCUSSION:This trial will show whether blended care might be an appropriate treatment strategy for patients with depressive symptoms and depressive disorder in general practice. TRIAL REGISTRATION:Netherlands Trial Register: NTR4757; 25 August 2014. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4757 . (Archived by WebCite® at http://www.webcitation.org/6mnXNMGef ).

背景与目标： 背景：大多数抑郁症患者均由全科医生（GPs）进行治疗，并开了抗抑郁药。患者偏爱心理治疗，但由于时间紧迫且可及性有限，因此未得到充分利用。提供心理治疗的一种有前途的方法是混合护理，即指导性在线治疗。但是，由患者自己的全科医生或全科医生精神保健工作者（MHW）支持的在线初级心理保健形式的混合保健在常规初级保健中的成本效益尚不清楚。我们的目标是证明在一般情况下，患有抑郁症症状或抑郁症患者的混合护理与常规护理相比不劣于常规护理。此外，我们将探讨情绪，情感和治疗过程中个体内部事件的全天实时过程。
方法：这是一项务实的非自卑性试验，包括GP和MHW的协作招募的300例抑郁症患者。纳入后，将参与者随机分为常规常规护理中的混合护理或常规护理。混合护理由“行为与感觉”治疗组成：这是一个基于行为激活的八周基于网络的计划，具有对抑郁症状和自动反馈的集成监控。 GP或他们的MHW通过至少三节的定期面对面或电话咨询来指导参与者。在12个月的随访期内评估抑郁症状，健康状况，功能障碍，治疗满意度，日常活动和资源使用情况。在治疗过程中，情绪和情感的实时波动以及日常事件将使用生态瞬时评估进行评估。主要结果是抑郁症状从基线减少到三个月的随访。我们将进行意向性治疗分析和补充的按方案分析。
讨论：该试验将表明在一般实践中，混合护理是否可能是抑郁症和抑郁症患者的合适治疗策略。
试用注册：荷兰试用注册：NTR4757； 2014年8月25日。http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4757。 （由WebCite®存档，网址为http://www.webcitation.org/6mnXNMGef）。

BACKGROUND & AIMS: :The present investigation describes the effect on the isolated rat ileum of methanolic extracts derived from Conyza filaginoides (D. C.) Hieron (Asteraceae), Croton fragilis HBK. (Euphorbiaceae), Dodonaea viscosa Jacq. (Sapindaceae), Gymnosperma glutinosum (Spreng) Less. (Asteraceae), Parthenium tomentosum DC. var. stramonium (Greene) Rollins (Asteraceae), Potentilla thurberi A. Gray (Rosaceae), Pterogonum atrorubens (Englem.) H. Gross (Polygonaceae), Zornia venosa Mohlenbr. (Fabaceae) and Datura lanosa Barclay ex Bye (Solanaceae). In all the cases the extracts inhibited, in a concentration-dependent manner, the spontaneous contraction of the intestinal smooth muscle. The most active extract was that of D. viscosa. These findings tend to support the ethnomedical use of the selected species as spasmolytic agents in Mexican traditional medicine. Additionally, the potential antimicrobial activity of the extracts against pathogenic enterobacteria was investigated. Seven of the nine plants evaluated displayed antibacterial effects.

背景与目标： ：本研究描述了从Conyza filaginoides（D. C.）Hieron（Asteraceae），脆弱的巴豆HBK提取的甲醇提取物对离体大鼠回肠的作用。 （大戟科），Dodonaea viscosa Jacq。 （无患子科），裸子植物（Gymnosperma glutinosum）（Spreng）少。 （菊科），Parthenium tomentosum DC。变种amo（Greene）罗林斯（菊科），委陵菜A. Gray（蔷薇科），翼龙（Pterogonum atrorubens）（英）H. Gross（Po科），百日草（Zornia venosa Mohlenbr）。 （Fabaceae）和Datura lanosa Barclay ex Bye（Solanaceae）。在所有情况下，提取物均以浓度依赖性方式抑制肠平滑肌的自发收缩。活性最高的提取物是粘枝梭状芽胞杆菌。这些发现倾向于支持在种族学上将所选物种用作墨西哥传统医学中的解痉剂。此外，还研究了提取物对病原性肠杆菌的潜在抗菌活性。评估的9株植物中有7株显示出抗菌作用。

BACKGROUND & AIMS: OBJECTIVES:There is paucity of data on Primary immunodeficiency disorders (PID) from India. Here we describe the frequency of different primary immunodeficiency disorders, their clinical features and disease complications of 159 patients with PID diagnosed in a tertiary care center from India over the last 3 years. METHODS:We retrospectively reviewed the records of all the patients identified to have specific PID from 2008 to 2011. The diagnosed patients were classified according to guidelines of International Union of Immunological Society (IUIS) into eight different sub groups. RESULTS:The distribution pattern was as follows: diseases of immune dysregulation (29 %), phagocytic defects (29 %), predominant antibody deficiency (13 %), combined T and B cell deficiency (19 %) and other well defined diseases (10 %). CONCLUSION:The distribution pattern of PID varied significantly from those reported by western studies. This study highlights the need for development of more advanced facilities for diagnosis and management of PID in India and also the need for establishing population and hospital based registries.

背景与目标： 目的：印度缺乏有关原发性免疫缺陷疾病（PID）的数据。在这里，我们描述了过去3年间在印度三级护理中心诊断的159例PID的不同原发性免疫缺陷疾病的发生率，其临床特征和疾病并发症。
方法：我们回顾性回顾了2008年至2011年所有被鉴定为具有特定PID的患者的记录。根据国际免疫学会联合会（IUIS）的指南，将诊断出的患者分为八个不同的亚组。
结果：分布模式如下：免疫失调疾病（29％），吞噬缺陷（29％），主要抗体缺乏症（13％），T和B细胞联合缺乏症（19％）和其他明确疾病（10） ％）。
结论：PID的分布模式与西方研究报道的存在显着差异。这项研究强调了在印度开发用于PID诊断和管理的更先进设施的需求，以及建立以人口和医院为基础的注册表的需求。