BACKGROUND & AIMS: These experiments were designed to determine whether glycogenolysis was influenced by the glycogen concentration of vascular smooth muscle. Segments of hog carotid artery smooth muscle were allowed to synthesize variable amounts of 1-[13C]glucosyl units of glycogen. Artery segments were then isometrically contracted in the presence of 2-[13C]glucose. Prior to and after isometric contraction, measurements were made of tissue glycogen content and superfusate glucose and lactate concentrations. 2-[13C]Lactate and 3-[13C]lactate peak intensities in the superfusate were measured using 13C-NMR spectroscopy. The tissue glycogen content decreased exponentially during the 4.5 h of isometric contraction (R2 = 0.990), despite more than a 3-fold range of glycogen concentration prior to contraction. The extent of glycogen utilization during a 3 h isometric contraction varied linearly with the precontraction glycogen concentration (R2 = 0.727). Lactate production specifically from glycogen breakdown increased with an increase in precontraction glycogen concentration (R2 = 0.620). During a 3 h isometric contraction neither the glucose utilization (R2 = 0.007) nor lactate production specifically produced from glucose (R2 = 0.00002) varied with the precontraction glycogen concentration. It is concluded that the rate of glycogenolysis is determined by the content of glycogen during prolonged contractions. In addition, precontraction glycogen levels influence the pathway for glycogen utilization but not the pathway for glucose utilization. Therefore, glycolysis and glycogenolysis behave independently in vascular smooth muscle.

背景与目标： 这些实验旨在确定糖原分解是否受血管平滑肌糖原浓度的影响。允许猪颈动脉平滑肌段合成可变量的1-[13C] 糖原葡萄糖单元。然后在2-[13C] 葡萄糖存在下等距收缩动脉段。在等距收缩之前和之后，测量组织糖原含量和超融合物葡萄糖和乳酸浓度。使用13C-NMR光谱测量超融合物中的2-[13C] 乳酸和3-[13C] 乳酸峰强度。组织糖原含量在等距收缩的4.5小时内呈指数下降 (R2 = 0.990)，尽管收缩前糖原浓度超过3倍。在3 h等距收缩期间糖原利用的程度随收缩前糖原浓度线性变化 (R2 = 0.727)。糖原分解产生的乳酸产量随着收缩前糖原浓度的增加而增加 (R2 = 0.620)。3小时的等距收缩葡萄糖利用率 (R2 = 0.007) 和特别由葡萄糖产生的乳酸产量 (R2 = 0.00002) 都不随收缩前糖原浓度而变化。结论是糖原分解速率由长期收缩期间糖原含量决定。此外，收缩前糖原水平会影响糖原利用的途径，但不会影响葡萄糖利用的途径。因此，糖酵解和糖原分解在血管平滑肌中独立运作。

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。作者对急诊重症监护中心收治的失败自杀 (准完成自杀) 进行了回顾性研究。根据自杀方法的杀伤力，6岁以上 (1986-1991岁) 的265名受试者中有133名被归类为绝对危险 (AD; 失败的自杀) 组。作为主要诊断，AD组75% 中存在精神病，内源性抑郁症，药物滥用。诊断分布差异很大，抑郁症主要发生在老年人组 (50岁)，而精神病主要发生在年轻人组 (< 30岁)。这项研究表明，日本大多数自杀受害者也患有精神障碍，预防自杀应面对这一临床事实。

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： : 很少有精心构建的研究系统地评估了自闭症谱系障碍儿童的医学调查方案。这在很大程度上是由于人口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情况。如果要在指导治疗或更广泛的治疗方法中有用，则强调了根据特定临床表现列出可能存在的条件并使用全面的病史和检查来产生目标疾病的预测试概率的重要性。管理方法。

BACKGROUND & AIMS: :Go/Gi coupled G-protein receptor mediated transactivation is critical in the activation of receptor tyrosine kinases (RTK). Here we show that mu opioid receptor (MOR) transactivates Flk1 and platelet-derived growth factor-beta (PDGF-beta) receptors and its agonist morphine stimulates pro-angiogenic and survival-promoting signaling in mouse retinal endothelial cells (mREC). Morphine stimulates mREC proliferation in a dose dependent fashion and promotes survival to the same extent as vascular endothelial growth factor164 (VEGF164). Morphine stimulates mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and Akt phosphorylation in a time dependent manner like VEGF in mREC. Moreover, analogous to VEGF, morphine stimulates oncogenic signal transducer and activator of transcription 3 (STAT3) signaling. Morphine as well as VEGF-induced phospho-STAT3 and phospho-Flk1 immunoprecipitated with MOR-associated proteins. In addition morphine also stimulated MOR associated PDGF-beta receptor phosphorylation. Consistent with the relationship between VEGF and MOR we found that VEGF upregulates MOR protein and RNA expression in mREC. These data suggest that MOR associates and transactivates RTKs for Flk1 and PDGF-beta, which may have a compounding effect on angiogenic signaling in endothelium. Therefore, G-Protein coupled receptors including MOR provide novel targets to develop anti-angiogenic agents.

背景与目标： : Go/Gi偶联的g蛋白受体介导的反式激活在受体酪氨酸激酶 (RTK) 的激活中至关重要。在这里，我们显示mu阿片受体 (MOR) 反式激活Flk1和血小板衍生的生长因子-β (pdgf-β) 受体及其激动剂吗啡刺激小鼠视网膜内皮细胞 (mREC) 中的促血管生成和促进存活的信号。吗啡以剂量依赖性方式刺激mREC增殖，并以与血管内皮生长因子164 (VEGF164) 相同的程度促进存活。吗啡以时间依赖性方式刺激丝裂原激活的蛋白激酶/细胞外信号调节激酶 (MAPK/ERK) 和Akt磷酸化，如mREC中的VEGF。此外，与VEGF类似，吗啡刺激致癌信号转导和转录激活因子3 (STAT3) 信号传导。吗啡以及VEGF诱导的phospho-STAT3和phospho-Flk1用MOR相关蛋白免疫沉淀。此外，吗啡还刺激MOR相关的PDGF-β 受体磷酸化。与VEGF和MOR之间的关系一致，我们发现VEGF上调了MOR蛋白和RNA在mREC中的表达。这些数据表明，MOR关联并反式激活了Flk1和PDGF-β 的RTKs，这可能对内皮中的血管生成信号传导具有复合作用。因此，包括MOR在内的g蛋白偶联受体为开发抗血管生成剂提供了新的靶标。

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，由于有挑战性的患者的报道，我们对基因确定的矮小原因的了解大大增加了，他们提供了研究在生长中起作用的基因的机会。自从第一篇显示拉隆综合征病因的论文 [Godowski PJ等人: Proc Natl Acad Sci USA 1989;86:8083-8087] 以来，已经鉴定出生长激素 (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，导致了具有生物活性的GH; STAT5b基因的突变，在GH信号转导中起主要作用; Igf-i基因中的纯合错义突变; Igf-i受体基因中的杂合突变和酸不稳定亚基基因的纯合缺失。在这篇小型综述中，我们描述了这些遗传缺陷的临床和生化特征。基因分析在身材矮小的患者的诊断检查中已变得至关重要。但是，关于分子分析的耗时性质，重要的是要仔细选择患者以进行特定的遗传评估。为了帮助这一选择过程，我们根据最近描述的患者开发了流程图，该流程图可作为不明原因严重矮小患者诊断过程的指南。

BACKGROUND & AIMS: OBJECTIVE:To compare prostate carcinoma, with and with no lymph node metastasis, to benign prostatic hyperplasia (BPH) tissue for lymphatic vessel density (LVD) and the expression of the lymph-endothelial specific growth factor, vascular endothelial growth factor C (VEGF-C), to determine their role in lymphogenic metastasis. PATIENTS, MATERIALS AND METHODS:Lymphatic vessels were stained using lymphatic vessel endothelial hyaluronan receptor 1 and assessed in standard areas. The expression of VEGF-C was assessed by the number of positive epithelial cells. The data were compared with the clinical staging. RESULTS:The lowest LVD was found in tumorous areas as opposed to periphery and nontumorous tissue (P = 0.007; P < 0.001). The highest LVD was in BPH tissue (P < 0.001). There was no correlation with clinical staging. There was more VEGF-C staining in pN1 than in pN0 and in BPH specimens (P = 0.002). CONCLUSION:LVD is not a prognostic variable for the process of lymphogenic metastasis in prostate cancer. VEGF-C is up-regulated in prostate cancer and its correlation with lymph node status suggests a role for the development of lymph node metastasis, e.g. via an increased permeability of lymphatic vessels.

背景与目标：

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：

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： : 为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。拟议更改的一个方面，即消除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一辩论提供信息。使用280名患者的临床医生评分，对dsm-iv人格障碍标准进行了探索性因素分析。因子分析揭示了八个明确而有意义的因子。这八个因素包含建议保留在DSM-5中的所有六种人格障碍，但也包含明确表示要从系统中删除的两种障碍 (偏执狂和精神分裂症)。这些疾病似乎具有临床实用性，并且在临床实践中可能会产生意想不到的负面后果。依赖和回避标准也合并形成了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所采用的复杂类型提供了新的见解。最后，我们认为，成功完善具有临床意义的结构，例如诊断系统，需要对临床实用性以及外部和内部有效性的证据进行平衡评估。

BACKGROUND & AIMS: :Thrombosis is the main cause of failure of small-diameter synthetic vascular grafts when used for by-pass procedures. The development of bioresorbable vascular scaffolds with localized and sustained intra-luminal antithrombotic drug release could be considered a desirable improvement towards a valuable solution for this relevant clinical need. For this aim, we present the fabrication and characterization of aspirin-loaded electrospun poly(ε-caprolactone) tubular scaffolds as a vascular drug-delivery graft. Three different drug concentrations were considered (i.e., 1, 5 or 10 % w/w). Although a fibrous structure was clearly observed for all the collected scaffolds, aspirin content was directly implied in the final microstructure leading to a bimodal fiber diameter distribution and fused fibers at crossing-points (5 or 10 % w/w). Mechanical response highlighted a direct relationship for modulus and stress at break with the aspirin content, while the elongation at break was not remarkably different for the investigated cases. The temporal drug release was strongly dependent from the amount of loaded aspirin, reaching a steady state release after about 50 h. Finally, the adhesion assay confirmed the capability of the electrospun scaffolds to reduce platelet adhesion/aggregation onto aspirin loaded polymeric fibers. Aspirin-loaded electrospun tubular scaffold could represent a feasible candidate to develop a novel bioresorbable drug-releasing graft for small-diameter vessel replacements.

背景与目标： : 血栓形成是用于旁路手术时小直径合成血管移植物失败的主要原因。开发具有局部和持续的腔内抗血栓药物释放的生物可吸收血管支架可被认为是针对此相关临床需求的有价值解决方案的理想改进。为此，我们介绍了负载阿司匹林的电纺聚 (ε-己内酯) 管状支架作为血管药物递送移植物的制备和表征。考虑三种不同的药物浓度 (即1、5或10% w/w)。尽管对于所有收集的支架都清楚地观察到纤维结构，但在最终微结构中直接隐含阿司匹林含量，导致双峰纤维直径分布和在交叉点处的融合纤维 (5或10% w/w)。机械响应强调了模量和断裂应力与阿司匹林含量的直接关系，而断裂伸长率在所研究的情况下没有显着差异。暂时的药物释放强烈依赖于阿司匹林的载量，约50小时后达到稳定状态释放。最后，粘附试验证实了电纺支架减少血小板粘附/聚集在阿司匹林负载的聚合物纤维上的能力。阿司匹林负载的电纺管状支架可能是开发用于小直径血管置换的新型生物可吸收药物释放移植物的可行候选者。

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绪状态的临床异质性，我们使用相同的工具开发了用于评估所有情绪发作 (抑郁，躁狂，躁狂，混合状态) 的维度量表。胸腺状态的多维评估 (MATHYS) (Henry等人，2008) 提供两个分数，测量激活水平的总分和情绪反应性的子分数。这项研究的目的是在双相情感障碍的总激活与抑制以及情绪反应性子评分中建立适当的临界值。急性发作期间的患者 (n = 187) 和对照组 (n = 89) 填充了MATHYS。获得受试者工作特征 (ROC) 曲线，以估计MATHYS的整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曲线对情绪反应性的总评分和子评分均显示出非常令人满意的敏感性和特异性水平，从而提供了适当的临界值。关于总得分在0和200之间，得分低于91的患者具有显着的整体抑制，而得分高于109的患者具有显着的整体激活。关于0到40之间的情绪反应性子评分，得分低于16的患者具有显着的情绪低反应性，而得分高于24的患者具有显着的情绪高反应性。我们的结果为MATHYS识别急性期患者提供了截止日期。

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; KIR2DL3-C1和hla-g * 14bp(+/-) 通过单特异性引物PCR和凝胶电泳进行分子分型。调整年龄，性别和出处的单变量线性模型分析显示，KIR2DS1-C2/hla-g * 14bp ASD儿童的儿童自闭症评分量表 (CARS) 和自闭症核心行为得分在统计学上更高 (43.7 ± 1.5，p = 0.03; 3.3 ± 0.1，p = 0.03)。这些结果表明，ASD儿童的KIR2DS1-HLAC2/hla-g ∗ 14bp模式与行为障碍具有协同的多基因关联。

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衰弱形式，通常导致死亡或永久性认知障碍。与发育性脑血管畸形有关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-coa还原酶 (HMGCR) 途径可有效稳定颅骨血管。使用药理学和遗传学方法相结合的方法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血管稳定性中的需求。在这里，我们报告了HMGCR功能的抑制会干扰脑血管的稳定性，导致血管进行性扩张，然后血管破裂，模仿人和鼠模型中的脑海绵状畸形 (CCM) 样病变。通过事先补充香叶基焦磷酸 (GGPP) (HMGCR途径的20碳代谢产物) 来挽救脑部出血，这是Rho GTPases膜定位和激活所必需的。与该观察结果一致，吗啉代诱导的香叶基转移酶I (GGTase I) 的 β 亚基耗竭，该酶促进了GGPP部分翻译后转移到Rho gtp酶家族的C末端，模拟了HMGCR的药理和遗传消融引起的脑出血。在脑出血的胚胎中，参与调节血管通透性的Rho GTPase cdc42的内皮特异性表达显着降低。总之，我们的数据揭示了对新生颅骨血管稳定的代谢贡献，需要在HMGCR途径下游起作用的蛋白质香叶基。

BACKGROUND & AIMS: INTRODUCTION:Databases are useful tools in clinical settings. The authors review the benefits and challenges associated with the development and implementation of an efficient electronic database for the multidisciplinary Vascular Birthmark Clinic at the Alberta Children's Hospital, Calgary, Alberta. METHODS:The content and structure of the database were designed using the technical expertise of a data analyst from the Calgary Health Region. Relevant clinical and demographic data fields were included with the goal of documenting ongoing care of individual patients, and facilitating future epidemiological studies of this patient population. After completion of this database, 10 challenges encountered during development were retrospectively identified. Practical solutions for these challenges are presented. RESULTS:THE CHALLENGES IDENTIFIED DURING THE DATABASE DEVELOPMENT PROCESS INCLUDED: identification of relevant data fields; balancing simplicity and user-friendliness with complexity and comprehensive data storage; database expertise versus clinical expertise; software platform selection; linkage of data from the previous spreadsheet to a new data management system; ethics approval for the development of the database and its utilization for research studies; ensuring privacy and limited access to the database; integration of digital photographs into the database; adoption of the database by support staff in the clinic; and maintaining up-to-date entries in the database. CONCLUSIONS:There are several challenges involved in the development of a useful and efficient clinical database. Awareness of these potential obstacles, in advance, may simplify the development of clinical databases by others in various surgical settings.

背景与目标：

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： : 需要为厌食症或神经性贪食症患者找到有效的治疗方法，这导致了照顾他们的专业人员开发新的治疗方法，其中考虑了导致耐药性变化的变量。该研究中的患者 (2006-2009) 具有以下特征: 340具有7年或更长时间的进化和/或尝试了许多先前治疗而没有成功开始和/或维持期望的变化的患者，这使他们能够稳定地恢复。作为建议的治疗方法，患者治疗团队基于培训模型的原理。它从整体上考虑患者，告知并为他提供资源，以增加其对变革的承诺。教导患者在身体和精神上保持谨慎，以恢复健康并以稳定的方式离开疾病。包括家庭成员作为他们最亲近的恢复的基本支持。治疗师需要在治疗ED方面的丰富经验，灵活性，与其他团队成员整合的能力，即使他们使用不同的理论模型，小组会议的技能，处理负面情绪和挫折承受能力。最后，下面介绍的模型已经实施，康复的患者在疾病中的停留时间超过15年，并导致永久性职业残疾。

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：