BACKGROUND & AIMS: OBJECTIVE:The objective of our study was to evaluate the outcome of lobular neoplasia diagnosed at 11-gauge stereotactic vacuum-assisted biopsy (SVAB). MATERIALS AND METHODS:Retrospective review of 1,819 lesions sampled with 11-gauge SVAB yielded 27 patients with lobular neoplasia as the most severe pathologic entity diagnosed. Patients with lobular neoplasia associated with atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or infiltrating carcinoma were excluded. Twenty patients underwent surgical excisional biopsy, and seven patients were followed mammographically for a mean of 52 months (range, 14-67 months). Mammographic lesion type, number of specimens obtained per lesion, and specific histologic features related to lobular carcinoma in situ (LCIS) were assessed. Results were compared with histologic findings at surgery or mammographic follow-up. RESULTS:Nineteen lesions presented mammographically as microcalcifications, four as masses, three as masses with associated microcalcifications, and one as architectural distortion. A mean of 13 specimens were obtained per lesion. Carcinoma was found at surgical excision in 19% of the lesions (5/27). Lesions were upgraded to DCIS (n = 2), invasive lobular carcinoma (n = 2), and mixed invasive ductal and lobular carcinoma (n = 1). In addition to the diagnosis of lobular neoplasia at SVAB, one patient presented with synchronous infiltrating ductal carcinoma in the contralateral breast, and two patients developed metachronous infiltrating ductal carcinoma in a different quadrant of the ipsilateral breast. Twelve of the 27 lesions included LCIS. These lesions were evaluated pathologically to distinguish the classic (10/12) from the pleomorphic (2/12) form of this entity. Ten of the 12 LCIS cases underwent surgical excisional biopsy with four of the five upgrades occurring in these patients. Only one of these patients was shown to have the pleomorphic type of LCIS. Lesions in seven patients who underwent mammographic follow-up remained stable. CONCLUSION:The known association of lobular neoplasia with high-risk and malignant lesions at surgical biopsy requires careful consideration when lobular neoplasia is diagnosed as the most severe histologic entity at SVAB. The diagnosis of lobular neoplasia at 11-gauge SVAB is not reliable in view of the 19% upgrade rate at the time of surgical excisional biopsy in our study. No predictive mammographic features allowed distinction between the patients with lesions that were upgraded at the time of surgery from those whose lesions were not upgraded.

背景与目标： 目的：本研究的目的是评估在11号立体定向真空辅助活检（SVAB）下诊断出的小叶肿瘤的结果。
材料与方法：回顾性分析以11规格SVAB取样的1,819处病灶，共诊断出27例小叶赘生性病变，被诊断为最严重的病理学实体。患有非典型性导管增生（ADH），原位导管癌（DCIS）或浸润性癌的小叶性肿瘤患者被排除在外。 20例患者接受了手术切除活检，其中7例患者接受了X线钼靶摄影，平均52个月（14-67个月）。评估了乳腺X线照相术的病变类型，每个病变获得的标本数量以及与小叶原位癌（LCIS）相关的特定组织学特征。将结果与手术或乳腺X线摄影随访中的组织学结果进行比较。
结果：十九个病灶在乳腺X线表现为微钙化，四个为肿块，三个为伴有相关微钙化的肿块，一个为建筑畸变。每个病变平均获得13个标本。手术切除后发现19％的病变为癌（5/27）。病变升级为DCIS（n = 2），浸润性小叶癌（n = 2）以及混合浸润性导管和小叶癌（n = 1）。除了诊断为SVAB的小叶肿瘤外，一名患者在对侧乳腺中出现同步性浸润性导管癌，另外两名患者在同侧乳腺的不同象限中出现了异时性浸润性导管癌。 27个病变中有12个包含LCIS。对这些病变进行了病理学评估，以区分该实体的多形性（2/12）形式与经典形式（10/12）。在12例LCIS病例中，有10例接受了手术切除活检，其中5例升级中有4例发生在这些患者中。这些患者中只有一名显示出LCIS的多形类型。接受乳房X光检查的7例患者病灶保持稳定。
结论：在手术活检中，小叶肿瘤与高危恶性病变的相关性需要在诊断为SVAB时最严重的组织学实体时仔细考虑。鉴于我们研究中的手术切除活检时19％的升级率，在11号SVAB下诊断小叶赘生物是不可靠的。没有可预测的乳腺X线摄影特征不能区分在手术时病变已升级的患者与未病变的患者。

BACKGROUND & AIMS: INTRODUCTION:Impulsivity is a symptom of several disorders such as personality disorder, bipolar disorder, suicidal behaviour, substance use disorders, schizophrenia...Forensic psychiatry is particularly concerned with impulsivity. It increases the risk of violence among clinical populations and figures in various instruments such as the HCR-20, the VRAG and the PCL-R to assess violence risk. It is one of many dimensions that can lead to aggressive behaviour among psychiatric patients. The Barratt Impulsiveness Scale (BIS), in its 11th version, is a 30-item self-report instrument that helps assessing impulsivity trait among normal and clinical populations. The BIS is the most commonly administered self-assessment of impulsiveness. As of March 2009, there have been 551 citations of the BIS-11 among many publications. The purpose of the present study is to examine the psychometric properties of the Arabic translation of the BIS-11th version in a sample of the general population and to identify an eventual correlation between impulsivity and socio-demographic characteristics. PATIENTS AND METHODS:This is a prospective study conducted over a five-month period, from June to October 2010, and including 134 persons from the general population having provided their informed consent. The dialectal Arabic version was carried out by translation from English to dialectal Arabic followed by a back translation to English. Some questions were modified to be understood by a population with low education. After giving their verbal informed consent, the participants filled in the Arabic version of the BIS-11. For the illiterate, responses and quotations were performed by the interviewer. The persons were also asked to fill in socio-demographic data. Cronbach's coefficient was calculated, and then we assessed impulsivity prevalence and a correlation between demographic features and impulsivity scores. For the analyses, the statistical software SPSS 11 was used. RESULTS:The sex ratio is 1.02. Most of the interviewed persons were 20 to 49 years old. Around 25.4% of the sample were analphabets, 32.1% had primary education, 29.1% had secondary education and 13.4% were undergraduates. The Cronbach's alpha was respectively 0.66 for attention, 0.72 for motor impulsivity, 0.61 for lack of planning and 0.78 for total impulsivity. Factor analysis identified three factors explaining the total variance of 32.6%. Impulsivity prevalence was 9%. We did not find significant correlation between demographic features and impulsivity scores. DISCUSSION:Limits of the study: scale stability over time was not verified. This was due to the difficulty in re-inviting the same persons to fulfil the scale a second time. Because no instrument for assessing exists in Arabic, comparison was not possible between the translated Barratt's scale and the reference. Our sample represents the general population. This choice was justified in order to study an eventual correlation between impulsiveness and socio-demographic characteristics. We must mention difficulties when asking persons with low education to complete the scale, what may have caused a poorer performance of the scale due to difficulties in understanding some questions. Moreover, we had chosen a non-clinical sample. The validation of the scale could be performed in a clinical population. The measure of internal consistency (Cronbach's alpha) fell within an acceptable range (0.61-0.78), suggesting that the Arabic version of the BIS-11 is reliable. Exploratory factor analysis of the current version identified three factors, but these factors differed from those of other translated versions. CONCLUSION:There is growing interest in the impulsivity concept. Forensic psychiatry is particularly concerned by impulsivity. In fact, it is related to psychiatric patients' violence. Impulsivity also reveals the problem of responsibility assessment in psychiatric expertise and the dangerousness of psychiatric patients. The Arabic version of the BIS-11 has a good apparent and internal consistency. This version could be useful in assessing psychiatric patient's dangerousness.

背景与目标： 简介：冲动性是几种疾病的症状，例如人格障碍，躁郁症，自杀行为，药物滥用，精神分裂症……法医精神病学特别关注冲动性。它增加了临床人群中的暴力风险，并增加了各种工具（例如HCR-20，VRAG和PCL-R）中的数字，以评估暴力风险。它是可导致精神病患者攻击行为的众多维度之一。第11版的Barratt冲动量表（BIS）是一项30项自我报告工具，可帮助评估正常人群和临床人群的冲动性状。 BIS是最常用的冲动自我评估。截至2009年3月，许多出版物中已有BIS-11的引用551次。本研究的目的是检查普通人群样本中BIS-11th版本的阿拉伯语翻译的心理计量学特性，并确定冲动性与社会人口统计学特征之间的最终关联。
病人和方法：这是一项为期五个月的前瞻性研究，时间为2010年6月至2010年10月，包括来自134个普通人群的知情同意书。方言阿拉伯语版本是通过将英语翻译为方言阿拉伯语，然后再翻译回英语来实现的。修改了一些问题，使低学历的人群可以理解。在获得口头知情同意后，与会人员填写了BIS-11的阿拉伯文版本。对于不识字的人，访调员进行了答复和报价。还要求这些人填写社会人口统计数据。计算Cronbach系数，然后评估冲动患病率以及人口统计学特征与冲动得分之间的相关性。为了进行分析，使用了统计软件SPSS 11。
结果：性别比为1.02。大多数受访者年龄在20至49岁之间。样本中约有25.4％为字母表，初等教育为32.1％，中等教育为29.1％，本科生为13.4％。克朗巴赫（Cronbach）的α值分别为：注意力的0.66，运动冲动的0.72，缺乏计划的0.61和总冲动的0.78。因子分析确定了三个因素，这些因素解释了总方差为32.6％。冲动患病率为9％。我们没有发现人口统计学特征与冲动得分之间存在显着相关性。
讨论：研究的局限性：没有验证随时间推移的水垢稳定性。这是由于很难再次邀请同一个人再次满足这一需求。由于没有阿拉伯文的评估工具，因此无法将翻译后的Barratt量表与参考文献进行比较。我们的样本代表了总人口。为了研究冲动性与社会人口统计学特征之间的最终相关性，此选择是合理的。当要求低学历者完成量表时，我们必须提到困难，是由于难以理解某些问题而导致量表性能下降的原因。此外，我们选择了非临床样本。量表的验证可以在临床人群中进行。内部一致性的度量（克伦巴赫α）落在可接受的范围内（0.61-0.78），这表明阿拉伯文版本的BIS-11是可靠的。当前版本的探索性因素分析确定了三个因素，但是这些因素与其他翻译版本的因素有所不同。
结论：人们对冲动概念的兴趣与日俱增。法医精神病学特别关注冲动性。实际上，这与精神病患者的暴力行为有关。冲动性还揭示了精神病专长中责任评估的问题以及精神病患者的危险性。 BIS-11的阿拉伯文版本具有良好的外观和内部一致性。该版本可能有助于评估精神病患者的危险性。

BACKGROUND & AIMS: :Vitamin D hormone (1,25-dihydroxyvitamin D) is involved in innate immunity and induces host defense peptides in epithelial cells, suggesting its involvement in mucosal defense against infections. Chlamydia trachomatis is a major cause of bacterial sexually transmitted disease worldwide. We tested the hypothesis that the vitamin D endocrine system would attenuate chlamydial infection. Vitamin D receptor knock-out mice (VDR(-/-)) and wild-type mice (VDR(+/+)) were infected with 10(3) inclusion forming units of Chlamydia muridarum and cervical epithelial cells (HeLa cells) were infected with C. muridarum at multiplicity of infection 5:1 in the presence and absence of 1,25-dihydroxyvitamin D3. VDR(-/-) mice exhibited significantly higher bacterial loading than wild-type VDR(+/+) mice (P<0.01) and cleared the chlamydial infection in 39 days, compared with 18 days for VDR(+/+) mice. Monocytes and neutrophils were more numerous in the uterus and oviduct of VDR(-/-) mice than in VDR(+/+) mice (P<0.05) at d 45 after infection. Pre-treatment of HeLa cells with 10nM or 100nM 1,25-dihydroxyvitamin D3 decreased the infectivity of C. muridarum (P<0.001). Several differentially expressed protein spots were detected by proteomic analysis of chlamydial-infected HeLa cells pre-treated with 1,25-dihydroxyvitamin D3. Leukocyte elastase inhibitor (LEI), an anti-inflammatory protein, was up-regulated. Expression of LEI in the ovary and oviduct of infected VDR(+/+) mice was greater than that of infected VDR(-/-) mice. We conclude that the vitamin D endocrine system reduces the risk for prolonged chlamydial infections through regulation of several proteins and that LEI is involved in its anti-inflammatory activity.

背景与目标： ：维生素D激素（1,25-二羟基维生素D）参与先天免疫，并诱导上皮细胞中的宿主防御肽，表明其参与了粘膜防御感染。沙眼衣原体是全世界细菌性传播疾病的主要原因。我们检验了维生素D内分泌系统会减轻衣原体感染的假设。维生素D受体敲除小鼠（VDR（-/-））和野生型小鼠（VDR（/））感染了衣原体衣原体的10（3）个包涵体形成单位，并感染了宫颈上皮细胞（HeLa细胞）在存在和不存在1,25-二羟基维生素D3的情况下，感染C. muridarum的感染复数为5：1。 VDR（-/-）小鼠比野生型VDR（/）小鼠表现出明显更高的细菌载量（P <0.01），并且在39天后清除了衣原体感染，而VDR（/）小鼠为18天。感染后第45天，VDR（-/-）小鼠的子宫和输卵管中的单核细胞和中性粒细胞比VDR（/）小鼠中的多（P <0.05）。用10nM或100nM 1,25-二羟基维生素D3预处理HeLa细胞可降低muridarum的感染性（P <0.001）。通过蛋白质组学分析衣原体感染的HeLa细胞经1,25-二羟基维生素D3预处理后，检测到了几个差异表达的蛋白斑点。白细胞弹性蛋白酶抑制剂（LEI），一种抗炎蛋白，被上调。 LEI在受感染的VDR（/）小鼠的卵巢和输卵管中的表达大于受感染的VDR（-/-）小鼠的表达。我们得出的结论是，维生素D内分泌系统通过调节几种蛋白质降低了衣原体长时间感染的风险，并且LEI参与了其抗炎活性。

BACKGROUND & AIMS: :In a previous study it was shown that lower factor XI (FXI) levels in women with heavy menstrual bleeding (HMB). Our aim was to determine the single-nucleotide variants (SNVs) in the F11 gene in women with HMB. In addition, an extensive literature search was performed to determine the clinical significance of each SNV. Patients referred for HMB (PBAC-score >100) were included. With direct sequencing analysis of all 15 exons and flanking introns of the F11 gene, 29 different non-structural SNVs were detected in 49 patients with HMB. Interestingly, most of these SNVs have previously been associated with venous thrombosis instead of bleeding. These findings have not helped to elucidate the molecular basis of HMB. They also question the specificity of previously reported F11 variations in patients with thrombosis. More studies are needed to explain the lower FXI levels seen in patients with HMB. IMPACT STATEMENT Women with mild deficiencies of factor XI (FXI) (< 70%) are prone to excessive bleeding during menstruation. Bleeding manifestations are not well correlated with plasma FXI levels and bleeding episodes can vary widely among patients with similar low FXI levels. In a previous study we showed that women with heavy menstrual bleeding (HMB) had normal, but on average, lower levels of FXI than controls. In light of these findings, we performed F11 gene analysis to determine the single-nucleotide variants (SNVs) in women with HMB and performed an extensive literature search to determine the clinical significance of each SNV. By direct sequencing analysis of the F11 gene we found 29 different non-structural SNVs in 49 women with heavy menstrual bleeding. Remarkably, a number of these SNVs have previously been implicated in thrombosis. These findings have not helped to elucidate the molecular basis of lower FXI levels in HMB. They also question the specificity of previously reported F11 variations in patients with thrombosis. More studies are needed to explain the lower FXI levels seen in patients with HMB.

背景与目标： ：以前的研究表明，月经量大出血（HMB）的女性中的XI因子（FXI）水平较低。我们的目的是确定患有HMB的女性F11基因中的单核苷酸变异体（SNV）。另外，进行了广泛的文献检索以确定每个SNV的临床意义。包括接受HMB转诊的患者（PBAC评分> 100）。通过对F11基因的所有15个外显子和侧翼内含子进行直接测序分析，在49例HMB患者中检测到29种不同的非结构性SNV。有趣的是，大多数这些SNV以前都与静脉血栓形成有关，而不是与出血有关。这些发现无助于阐明HMB的分子基础。他们还质疑先前报道的F11变异在血栓形成患者中的特异性。需要更多的研究来解释HMB患者中较低的FXI水平。影响力陈述轻度缺乏XI因子（FXI）（<70％）的女性在月经期间容易流血过多。出血表现与血浆FXI水平没有很好的相关性，并且在FXI水平低的患者中出血事件可能差异很大。在先前的研究中，我们显示月经出血严重（HMB）的妇女的FXI水平正常，但平均水平低于对照组。根据这些发现，我们进行了F11基因分析，以确定HMB妇女的单核苷酸变异（SNV），并进行了广泛的文献检索以确定每种SNV的临床意义。通过对F11基因的直接测序分析，我们在49名经期出血严重的女性中发现了29种不同的非结构性SNV。值得注意的是，这些SNV中有许多以前都与血栓形成有关。这些发现无助于阐明HMB中较低的FXI水平的分子基础。他们还质疑先前报道的F11变异在血栓形成患者中的特异性。需要更多的研究来解释HMB患者中较低的FXI水平。

BACKGROUND & AIMS: :The Slc5a6 gene expresses a plasma membrane protein involved in the transport of the water-soluble vitamin biotin; the transporter is commonly referred to as the sodium-dependent multivitamin transporter (SMVT) because it also transports pantothenic acid and lipoic acid. The relative contribution of the SMVT system toward carrier-mediated biotin uptake in the native intestine in vivo has not been established. We used a Cre/lox technology to generate an intestine-specific (conditional) SMVT knockout (KO) mouse model to address this issue. The KO mice exhibited absence of expression of SMVT in the intestine compared with sex-matched littermates as well as the expected normal SMVT expression in other tissues. About two-thirds of the KO mice died prematurely between the age of 6 and 10 wk. Growth retardation, decreased bone density, decreased bone length, and decreased biotin status were observed in the KO mice. Microscopic analysis showed histological abnormalities in the small bowel (shortened villi, dysplasia) and cecum (chronic active inflammation, dysplasia) of the KO mice. In vivo (and in vitro) transport studies showed complete inhibition in carrier-mediated biotin uptake in the intestine of the KO mice compared with their control littermates. These studies provide the first in vivo confirmation in native intestine that SMVT is solely responsible for intestinal biotin uptake. These studies also provide evidence for a casual association between SMVT function and normal intestinal health.

背景与目标： ：Slc5a6基因表达参与水溶性维生素生物素运输的质膜蛋白；该转运蛋白通常也称为钠依赖性多种维生素转运蛋白（SMVT），因为它也可以转运泛酸和硫辛酸。 SMVT系统对体内天然肠道中载体介导的生物素摄取的相对贡献尚未确定。我们使用Cre / lox技术来生成特定于肠道的（条件性）SMVT敲除（KO）小鼠模型，以解决此问题。与性别匹配的同窝幼仔相比，KO小鼠在肠道中不存在SMVT表达，在其他组织中也表现出预期的正常SMVT表达。大约三分之二的KO小鼠在6至10周龄之间过早死亡。在KO小鼠中观察到生长迟缓，骨密度降低，骨长度降低和生物素状态降低。显微镜分析显示KO小鼠的小肠（绒毛缩短，发育不良）和盲肠（慢性活动性炎症，发育不良）的组织学异常。体内（和体外）转运研究表明，与对照组的同窝仔猪相比，KO小鼠肠道中的载体介导的生物素摄取被完全抑制。这些研究首次证实了天然肠中SMVT负责肠道生物素的摄取。这些研究还为SMVT功能与正常肠道健康之间的偶然关联提供了证据。

BACKGROUND & AIMS: :Syntaxin-11 (Stx11), an atypical member of the SNARE protein family, is part of the cytolytic machinery of T and NK cells and involved in the fusion of lytic granules with the plasmamembrane. Functional loss of syntaxin-11 in humans causes defective degranulation and impaired cytolytic activity of T and NK cells. Furthermore, patients with STX11 deficiency develop familial hemophagocytic lymphohistiocytosis type 4 (FHL4), a life-threatening disease of severe hyperinflammation. We established Stx11-deficient mice as an animal model for FHL4. Stx11-deficient mice exhibited severely reduced degranulation and cytolytic activity of CTL and NK cells and developed all clinical symptoms of hemophagocytic lymphohistiocytosis (HLH) after infection with lymphocytic choriomeningitis virus (LCMV). The HLH phenotype was further characterized by hyperactive CD8 T cells and continuous IFN-γ production. However, in contrast to perforin-deficient mice, which represent a model for FHL2, progression of HLH was not fatal. Survival of Stx11-deficient mice was determined by exhaustion of antigen-specific T cells, characterized by expression of inhibitory receptors, sequential loss of effector functions, and finally T-cell deletion. Blockade of inhibitory receptors on T cells in Stx11-deficient mice converted nonfatal disease course into fatal HLH, identifying T-cell exhaustion as an important factor for determination of disease severity in HLH.

背景与目标： ：Syntaxin-11（Stx11）是SNARE蛋白家族的非典型成员，是T细胞和NK细胞溶细胞机制的一部分，并参与溶菌颗粒与质膜的融合。人类syntaxin-11的功能丧失会导致脱颗粒不足，并损害T细胞和NK细胞的细胞溶解活性。此外，STX11缺乏症患者会发生家族性吞噬性淋巴细胞组织细胞增多症4型（FHL4），这是一种严重威胁生命的严重高炎症性疾病。我们建立了Stx11缺陷小鼠作为FHL4的动物模型。缺乏Stx11的小鼠在感染了淋巴细胞性脉络膜脑膜炎病毒（LCMV）后表现出严重降低了CTL和NK细胞的脱粒和细胞溶解活性，并出现了所有噬血细胞性淋巴组织细胞增生症（HLH）的临床症状。 HLH表型的特征还在于CD8 T细胞过度活跃，并持续产生IFN-γ。但是，与代表FHL2模型的穿孔素缺陷型小鼠相反，HLH的进展并非致命。 Stx11缺陷型小鼠的存活率是通过耗尽抗原特异性T细胞来确定的，其特征在于抑制性受体的表达，效应子功能的顺序丧失以及最后T细胞的缺失。在Stx11缺陷型小鼠中，T细胞上抑制性受体的阻断将非致死性疾病病程转化为致命的HLH，从而确定T细胞衰竭是确定HLH疾病严重程度的重要因素。

BACKGROUND & AIMS: :Candida parapsilosis is an important cause of candidiasis, yet few molecular tools are available. We adapted a recyclable nourseothricin resistance marker gene (SAT1) originally developed for use with C. albicans in order to generate gene knockouts from C. parapsilosis. We first replaced the promoters driving expression of the FLP recombinase and the SAT1 genes with the equivalent sequences from C. parapsilosis. We then used the cassette to generate a homozygous knockout of C. parapsilosis URA3. The ura3 knockouts have altered colony morphologies. We also knocked out both alleles of an ortholog of BCR1, a gene encoding a transcription factor known to be required for biofilm development in C. albicans. We show that C. parapsilosis BCR1 is necessary for biofilm development in C. parapsilosis and for expression of the cell wall protein encoded by RBT1. Our results suggest that there are significant similarities in the regulation of biofilms between the two species, despite the fact that C. parapsilosis does not generate true hyphae and that BCR1 regulates the expression of many hypha-specific adhesins in C. albicans.

背景与目标： 念珠菌：念珠菌是念珠菌病的重要病因，但分子工具很少。我们调整了最初为白念珠菌而开发的可回收的神经丝菌素抗性标记基因（SAT1），以便从副念珠菌中产生基因敲除。我们首先用来自C. parapsilosis的等效序列替换了驱动FLP重组酶和SAT1基因表达的启动子。然后，我们使用盒式磁带产生了C. parapsilosis URA3的纯合敲除。 ura3基因敲除改变了菌落的形态。我们还敲除了BCR1直系同源基因的两个等位基因，BCR1是编码白色念珠菌生物膜发育所需的转录因子的基因。我们表明，C。parapsilosis BCR1是必要的生物膜发育在C. parapsilosis和由RBT1编码的细胞壁蛋白的表达。我们的研究结果表明，尽管事实上副寄生念珠菌并没有产生真正的菌丝，而BCR1调节了白色念珠菌中许多菌丝特异性粘附素的表达，但两种物种在生物膜的调控上却存在着显着的相似之处。

BACKGROUND & AIMS: OBJECTIVES:To investigate which characteristics of women and healthcare professionals (HCPs) were associated with changing to another combined hormonal contraceptive (CHC) method after contraceptive counselling. METHODS:CHOICE was a cross-sectional survey in which 18,787 women were counselled about combined hormonal contraceptives, during which their contraceptive methods preferred both prior to and after counselling were recorded. In this subanalysis, characteristics associated with changing the method after counselling were determined using logistic regression models. RESULTS:The probability of intending to change from the pill to another method was associated with being older; university-educated; being in a steady relationship; a prior unintended pregnancy; a younger HCP or one who recommended methods other than the pill. Changing to the patch was associated with a female HCP or a HCP who recommended the patch or an injectable. Changing to the ring was associated with being over 21 years; university-educated; being in a relationship; previous hormonal method use; and counselling by a female HCP, a HCP < 60 years old, or a HCP who recommended the ring or an implant. The country of residence influenced these changes in a complex pattern. CONCLUSIONS:Women's choice of CHC methods after contraceptive counselling are influenced by their age, educational background, relationship status, prior unplanned pregnancies and country of residence, as well as age, gender and preferences of their HCP.

背景与目标： 目的：调查在避孕咨询后，女性和医护人员（HCP）的哪些特征与改用另一种联合激素避孕（CHC）方法有关。
方法：选择是一项横断面调查，其中向18,787名妇女提供了有关联合激素避孕药的咨询，在此期间，记录了她们在咨询之前和之后首选的避孕方法。在此子分析中，使用逻辑回归模型确定与咨询后更改方法有关的特征。
结果：打算从药丸换成另一种方法的可能性与年纪大有关。受过大学教育；保持稳定的关系；先前的意外怀孕；较年轻的HCP或建议使用除药丸以外的方法的人。更换贴剂与女性HCP或推荐贴剂或注射剂的HCP有关。更换戒指的年龄超过21岁。受过大学教育；处于恋爱关系中；以前使用过的荷尔蒙方法；并由女性HCP，小于60岁的HCP或推荐环或植入物的HCP进行咨询。居住国以复杂的方式影响了这些变化。
结论：避孕咨询后，妇女选择慢性丙型肝炎的方法受到其年龄，教育背景，人际关系，先前计划外的怀孕和居住国家，年龄，性别和他们的HCP偏好的影响。

BACKGROUND & AIMS: BACKGROUND:We previously demonstrated angiotensin converting enzymes (ACE) over-expression in a dextran-sodium sulfate colitis model; ACE inhibitor (ACE-I) treatment reduced colitis severity in this model. However, ACE-I has not been tested in more immunologically relevant colitis models. AIM:We hypothesized that ACE-I would decrease disease severity in an IL-10 knockout (-/-) colitis model. METHODS:Colitis was induced by giving 10-week old IL-10-/- mice piroxicam (P.O.) for 14 days. The ACE-I enalaprilat was given transanally at a dose of 6.25 mg/kg for 21 days. Prednisolone (PSL) with or without enalaprilat were used as therapeutic, comparative groups. All groups were compared to a placebo treated group. Outcome measures were clinical course, histology, abundance of pro-inflammatory cytokines/chemokines, and epithelial barrier function. RESULTS:Enalaprilat exhibited better survival (91 %) versus other treatment groups (PSL: 85.7 %, PSL + ACE-I: 71.4 %, placebo: 66.6 %). The ACE-I and PSL + ACE-I groups showed significantly better histological scores versus placebo mice. ACE-I and the PSL groups significantly reduced several pro-inflammatory cytokines versus placebo mice. FITC-dextran permeability was reduced in the ACE-I and PSL + ACE-I groups. Blood pressure was not affected in ACE-I treated mice compared to placebo mice. CONCLUSIONS:ACE-I was effective in reducing severity of colitis in an IL-10-/- model. The addition of prednisolone minimally augmented this effect. The findings suggest that appropriately dosed ACE-I with or without steroids may be a new therapeutic agent for colitis.

背景与目标： 背景：我们先前证明了在葡聚糖-硫酸钠结肠炎模型中血管紧张素转化酶（ACE）的过度表达。在该模型中，ACEI（ACE-I）抑制剂治疗可降低结肠炎的严重程度。但是，尚未在更具免疫学意义的结肠炎模型中测试ACE-1。
目的：我们假设ACE-1可以降低IL-10基因敲除（-/-）结肠炎模型中的疾病严重程度。
方法：通过给予10周龄的IL-10-/-小鼠吡罗昔康（P.O.）14天来诱发结肠炎。 ACE-1依那普利拉经鼻给药，剂量为6.25 mg / kg，持续21天。泼尼松龙（PSL）有或没有恩那普利拉被用作治疗性比较组。将所有组与安慰剂治疗组进行比较。结果指标包括临床病程，组织学，促炎细胞因子/趋化因子的含量以及上皮屏障功能。
结果：依那普利拉的生存率（91％）优于其他治疗组（PSL：85.7％，PSL ACE-1：71.4％，安慰剂：66.6％）。与安慰剂小鼠相比，ACE-1和PSL ACE-1组的组织学评分明显更高。与安慰剂小鼠相比，ACE-1和PSL组显着减少了几种促炎性细胞因子。在ACE-I和PSL ACE-I组中，FITC-葡聚糖的通透性降低。与安慰剂小鼠相比，ACE-1治疗的小鼠的血压没有受到影响。
结论：ACE-1在降低IL-10-/-模型中结肠炎的严重程度方面有效。泼尼松龙的添加最小程度地增强了这种作用。研究结果表明，适当剂量的ACE-I与或不与类固醇激素可能是结肠炎的一种新的治疗剂。

BACKGROUND & AIMS: BACKGROUND:An impairment of the intestinal barrier function is one of the major characteristics of Crohn's disease (CD). This study aimed to evaluate the impact of autophagy induction by rapamycin on the intestinal epithelial barrier function in CD model mice. METHODS:IL-10 knockout (IL-10 KO) mice were used as the human CD models in this study. All the mice were randomly assigned into four groups, (a) wild-type (WT) group; (b) IL-10 KO group; (c) IL-10 KO + rapamycin group and (d) IL-10 KO + 3-methyladenine (3-MA), containing 6 mice in each group. The disease activity index (DAI), histology, pro-inflammatory cytokines and chemotactic factors in colon tissues, intestinal and colonic permeability, distributions and expressions of tight junction (TJ) proteins, epithelial apoptosis of mice in four groups were evaluated and compared. RESULTS:Autophagy induction by rapamycin treatment ameliorated DAI and histological colitis, decreased pro-inflammatory cytokines (TNF-α, IFN-γ and IL-17) and chemotactic factors (CXCL-1 and CXCL-2), decreased intestinal and colonic permeability, improved the distribution and expression of TJ proteins in IL-10 KO mice. CONCLUSION:Autophagy induction by rapamycin significantly improved intestinal barrier function and protected IL-10 KO mice from the experimental chronic colitis.

背景与目标： 背景：肠道屏障功能的损害是克罗恩病（CD）的主要特征之一。这项研究旨在评估雷帕霉素诱导的自噬对CD模型小鼠肠上皮屏障功能的影响。
方法：以IL-10基因敲除小鼠（IL-10 KO）作为人类CD模型。将所有小鼠随机分为四组，（a）野生型（WT）组；（b）野生型（WT）组。 （b）IL-10 KO组； （c）IL-10 KO雷帕霉素组和（d）IL-10 KO 3-甲基腺嘌呤（3-MA），每组6只小鼠。评估并比较了四组小鼠的疾病活动指数（DAI），组织学，结肠组织中的促炎细胞因子和趋化因子，肠和结肠通透性，紧密连接（TJ）蛋白的分布和表达，小鼠上皮细胞凋亡。
结果：雷帕霉素诱导的自噬改善了DAI和组织性结肠炎，降低了促炎细胞因子（TNF-α，IFN-γ和IL-17）和趋化因子（CXCL-1和CXCL-2），降低了肠道和结肠的通透性，改善了IL-10 KO小鼠中TJ蛋白的分布和表达。
结论：雷帕霉素自噬诱导显着改善肠屏障功能，并保护IL-10 KO小鼠免受实验性慢性结肠炎的侵害。

BACKGROUND & AIMS: :Classically, it has been thought that high-affinity nicotinic receptors-containing beta2 subunits are the most important receptor subtypes for nicotinic involvement in cognitive function and nicotine self-administration, while low affinity alpha7-containing nicotinic receptors have not been thought to be important. In the current study, we found that knockout of either beta2 or alpha7 subunits caused significant deficits in spatial discrimination in mice. The character of the impairment in the two knockouts was different. The beta2 knockout preferentially impaired cognition in males while the alpha7 caused impairment regardless of sex. Both beta2- and alpha7-containing nicotinic receptors also are important for nicotine self-administration, also in different ways. Most animal model studies of nicotine self-administration are relatively short-term whereas the problem of tobacco addiction is considerably longer-term. To better model the impact of nicotinic receptor subtypes on nicotine self-administration over the long-term, we studied the impact of genetic knockout of low affinity alpha7 receptors vs. high-affinity beta2-containing nicotinic receptors. Mice with knockouts of either of these receptors and their wildtype counter parts were given free access to a choice of nicotine-containing and nicotine-free solution in their home cages on a continuous basis over a period of 5 months. During the first few weeks, the beta2-containing nicotinic receptor knockout mice showed a significant decrease in nicotine consumption relative to wildtype mice, whereas the alpha7 knockout mice did not significantly differ from wildtype controls at the beginning of their access to nicotine. Interestingly, in the longer-term after the first few weeks of nicotine access, the beta2 knockout mice returned to wildtype mouse levels of nicotine consumption, whereas the alpha7 knockout mice developed an emergent decrease in nicotine consumption. The alpha7 receptor knockout-induced decrease in nicotine consumption persisted for the 5-month period of the study. Both alpha7- and beta2-containing nicotinic receptors play critical roles in cognitive function and nicotine self-administration. Regarding cognitive function, beta2-containing receptors are important for maintaining normal sex differences in spatial learning and memory, whereas alpha7 receptors are important for cognitive function regardless of sex. Regarding nicotine self-administration high-affinity beta2-containing nicotinic receptors are important for consumption during the initial phase of nicotine access, but it is the alpha7 nicotinic receptors that are important for the longer-term regulation of nicotine consumption.

背景与目标： ：通常，人们一直认为，含有高亲和力烟碱受体的β2亚基是烟碱参与认知功能和尼古丁自我给药的最重要的受体亚型，而低亲和力的含α7烟碱受体尚未被认为是重要的。在当前的研究中，我们发现敲除beta2或alpha7亚基会导致小鼠的空间分辨力明显不足。两种基因敲除的损伤特征是不同的。 beta2基因敲除优先削弱男性的认知能力，而alpha7则不论性别如何均引起损害。含β2和α7的烟碱样受体对于尼古丁的自我给药也很重要，也有不同的用法。尼古丁自我管理的大多数动物模型研究都是相对短期的，而烟草成瘾的问题则是相当长期的。为了更好地模拟烟碱样受体亚型对尼古丁自我给药的长期影响，我们研究了基因敲除低亲和力α7受体与高亲和力的含β2烟碱样受体的影响。敲除这些受体及其野生型对应部分中的任一个的小鼠可在其笼子中连续5个月自由接触选择的含尼古丁和不含尼古丁的溶液。在最初的几周内，相对于野生型小鼠，含β2的烟碱样受体敲除小鼠的尼古丁消耗量显着减少，而α7敲除小鼠在接触尼古丁的初期与野生型对照无显着差异。有趣的是，在进入尼古丁的最初几周后，长期而言，β2敲除小鼠恢复了野生型小鼠的尼古丁消耗水平，而alpha7敲除小鼠出现了尼古丁消耗的突然下降。在研究的5个月中，α7受体基因敲除引起的尼古丁消耗减少一直持续。含α7和β2的烟碱样受体在认知功能和尼古丁自我给药中都起着关键作用。关于认知功能，含β2受体对于维持空间学习和记忆中的正常性别差异很重要，而alpha7受体对于无论性别如何的认知功能都很重要。关于尼古丁的自我给药，含高亲和力的含β2的尼古丁受体对于尼古丁进入初期的消耗很重要，但是α7尼古丁受体对于长期调节尼古丁的消耗很重要。

BACKGROUND & AIMS: :Metallo-β-lactamases (MBL) producing Pseudomonas aeruginosa isolates have been well characterized. Quinolones are commonly used in the treatment of carbapenem-resistant P. aeruginosa infections; however, data about PMQR in this species are scarce. The objective of this study was to report the simultaneous presence of qnrS and blaVIM-11 in P. aeruginosa, and to characterize the qnrS-harboring plasmid. Thirty-eight carbapenem-resistant P. aeruginosa isolates were recovered from a hospital in Buenos Aires during 2012. Screening for MBL was assessed by the double disk synergy test using EDTA and carbapenem discs. Plasmid DNA extraction was performed by a method using phenol-chloroform. PCR followed by sequencing was carried out to determine each MBL and PMQR allele. PCR-BseGI-RFLP was performed to detect aac-(6')-Ib-cr. The gyrA-QRDR was sequenced in those PMQR-harboring isolates. Plasmid incompatibility groups and addiction systems were characterized by PCR. The PMQR-carrying plasmid was sequenced using Illumina technology, annotated using RAST and manually curated. Eleven/38 isolates were VIM producers (blaVIM-2 and blaVIM-11) while 1/38 harbored blaIMP-13. One isolate harbored blaVIM-11 and the PMQR qnrS1; however, both markers were located in different plasmids. The qnrS1-harboring plasmid (pP6qnrS1) was 117945bp in size, presented 154 CDS and corresponded to the IncR group. In addition to qnrS1, it harbored several aminoglycoside resistance markers. Although pP6qnrS1 was non-conjugative, it presented an oriT which made it possible for this plasmid to be transferable. This is the first report on P. aeruginosa carrying both blaVIM-11 and qnrS1, plus the first detection of an IncR plasmid in Argentina.

背景与目标： 产生铜绿假单胞菌的金属β-内酰胺酶（MBL）已被很好地鉴定。喹诺酮类药物通常用于治疗对碳青霉烯耐药的铜绿假单胞菌感染。但是，有关该物种PMQR的数据很少。这项研究的目的是报告铜绿假单胞菌同时存在qnrS和blaVIM-11，并表征携带qnrS的质粒。 2012年期间，从布宜诺斯艾利斯的一家医院中回收了38株对碳青霉烯类耐药的铜绿假单胞菌分离株。通过双盘协同试验，使用EDTA和碳青霉烯圆片对MBL的筛选进行了评估。质粒DNA的提取通过使用苯酚-氯仿的方法进行。进行PCR，然后测序以确定每个MBL和PMQR等位基因。进行PCR-BseGI-RFLP以检测aac-（6'）-Ib-cr。在携带PMQR的分离物中对gyrA-QRDR进行了测序。通过PCR表征质粒不相容性组和成瘾系统。使用Illumina技术对携带PMQR的质粒进行测序，使用RAST进行注释，然后手动进行固化。 11/38个隔离株是VIM生产者（blaVIM-2和blaVIM-11），而1/38则带有blaIMP-13。一个隔离株带有blaVIM-11和PMQR qnrS1；但是，两种标记都位于不同的质粒中。携带qnrS1的质粒（pP6qnrS1）大小为117945bp，呈递154个CDS，与IncR组相对应。除qnrS1外，它还包含一些氨基糖苷抗性标记。尽管pP6qnrS1是非结合性的，但它提供了一个oriT，使得该质粒可以转移。这是关于携带blaVIM-11和qnrS1的铜绿假单胞菌的首次报道，也是阿根廷首次检测到IncR质粒的报道。

BACKGROUND & AIMS: :The fadBA operon in the fatty acid beta-oxidation pathway of P. putida KCTC1639 was blocked to induce a metabolic flux of the intermediates to the biosynthesis of medium chain-length PHA (mcl-PHA). Succinate at 150 mg l(-1) stimulated cell growth and also the biosynthesis of medium chain-length-polyhydroxyalkanoate. pH-stat fed-batch cultivation of the fadA knockout mutant P. putida KCTC1639 was carried out for 60 h, in which mcl-PHA reached 8 g l(-1) with a cell dry weight of 10.3 g l(-1).

背景与目标： ：恶臭假单胞菌KCTC1639的脂肪酸β-氧化途径中的fadBA操纵子被阻断，以诱导中间体的代谢通量，以合成中等链长的PHA（mcl-PHA）。 150 mg l（-1）的琥珀酸酯刺激细胞生长，也刺激中等链长的聚羟基链烷酸酯的生物合成。对fadA敲除突变体恶臭假单胞菌KCTC1639进行pH固定补料培养60 h，其中mcl-PHA达到8 g l（-1），细胞干重为10.3 g l（-1）。

BACKGROUND & AIMS: :Segmental duplication is a major structural variation that occurs in chromosomes. Duplication leads to the production of gene copies with increased numbers of related repeat segments, causing the global genome to be in a state of imbalance. In addition, if the added segment contains a centromeric specific DNA, the duplicated chromosome will have structural multiple centromeres. We identified a segmental duplication containing structurally tricentric regions derived from the short arm of chromosome 11 (11L∙ + 11L∙ + 11S∙11S∙11S∙11S, "∙" represents the centromeric DNA repeat loci), and analyzed its implications for cell division and genome-wide expression. In the variant, only the middle centromere of 11S∙11S∙11S∙11S is functionally active. As a result, the structurally tricentric chromosome was stable in mitosis, because it is actually a functional monocentric chromosome. However, the structurally tricentric chromosome, which usually formed a bivalent, was either arranged on the equatorial plane or was lagging, which affected its separation during meiosis. Furthermore, RNA-seq and RT-qPCR analysis showed that the segmental duplication affected genome-wide expression patterns. 34.60% of genes in repeat region showed positive dosage effect. Thus, the genes on chromosome arm 11S-2 didn't exhibit obviously dosage compensation, as illustrated by no peak around a ratio of 1.00. However, the gene dosage effect will reduce after sexual reproduction of a generation.

背景与目标： ：节段重复是发生在染色体上的主要结构变异。复制导致产生具有相关重复片段数量增加的基因拷贝，从而导致全球基因组处于失衡状态。另外，如果添加的片段包含着丝粒特异性DNA，则复制的染色体将具有多个结构着丝粒。我们鉴定出一个片段重复，该片段包含源自11号染色体短臂的结构性三中心区域（11L∙11L∙11S∙11S∙11S∙11S，“∙”代表着丝粒DNA重复基因座），并分析了其对细胞分裂和基因组的影响范围内的表达式。在变体中，只有11S∙11S∙11S∙11S的中间着丝粒起作用。结果，结构上的三中心染色体在有丝分裂中是稳定的，因为它实际上是功能性的单中心染色体。但是，通常形成二价的结构性三中心染色体要么排列在赤道平面上，要么滞后，影响了减数分裂过程中的分离。此外，RNA-seq和RT-qPCR分析表明，节段重复会影响全基因组表达模式。重复区域中34.60％的基因显示出积极的剂量效应。因此，第11S-2号染色体上的基因没有明显的剂量补偿，如1.00左右的峰没有显示。但是，一代有性繁殖后，基因剂量效应将降低。

BACKGROUND & AIMS: :The authors wish to make a correction to Section 2 [...].

背景与目标： ：作者希望对第2节[...]进行更正。