BACKGROUND & AIMS: :Chemotherapy-induced alopecia is a major problem in clinical oncology. Doxorubicin, a widely used cancer chemotherapy drug, induces disruption of the hair cycle and subsequent alopecia. We show in this report that doxorubicin causes disruption of the hair-follicle-associated blood vessel network resulting in a greatly reduced density of these blood vessels. Dystrophic hair follicles were also observed with abnormal melanogenesis in the mice treated with doxorubicin. Visualization of the effect of doxorubicin on hair-follicle angiogenesis was made possible by the use of transgenic mice in which green fluorescent protein was driven by regulatory elements of the nestin gene (ND-GFP). In these transgenic mice, the hair-follicle stem cells and the follicle structure as well as the blood vessels associated with the hair follicles express ND-GFP. The hair-follicle stem cells did not appear to be affected by doxorubicin, which may explain why hair regrows after chemotherapy. These results suggest that inhibition of hair-follicle-associated angiogenesis by doxorubicin may be an important factor in hair-follicle dystrophy associated with chemotherapy-induced alopecia. The ND-GFP mouse model is thus useful for the study of the role of angiogenesis in the hair-follicle cycle and the effect of drugs on processes associated with chemotherapy-induced alopecia.

背景与目标： 化学疗法引起的脱发是临床肿瘤学中的主要问题。阿霉素是一种广泛使用的癌症化学治疗药物，可引起毛发周期破坏和随后的脱发。我们在这份报告中表明，阿霉素会导致毛囊相关血管网络的破坏，从而导致这些血管的密度大大降低。在用阿霉素治疗的小鼠中还观察到营养不良的毛囊黑色素生成异常。通过使用其中巢蛋白基因（ND-GFP）调控元件驱动绿色荧光蛋白的转基因小鼠，可以看到阿霉素对毛囊血管生成的作用。在这些转基因小鼠中，毛囊干细胞，毛囊结构以及与毛囊相关的血管均表达ND-GFP。毛囊干细胞似乎没有受到阿霉素的影响，这可以解释为什么化疗后头发会长大。这些结果表明，阿霉素抑制与毛囊相关的血管生成可能是与化学疗法引起的脱发有关的毛囊营养不良的重要因素。因此，ND-GFP小鼠模型可用于研究血管生成在毛囊周期中的作用以及药物对与化学疗法引起的脱发相关的过程的作用。

BACKGROUND & AIMS: :We used functional MRI (fMRI) to study the aging influence on functional connectivity of the motor network in the resting state. A network model based on graph theory was used to measure functional connectivity. The total connectivity degree of each region within the motor network was calculated and compared between aged and young groups. We found that the pattern of functional connectivity was changed in aged subjects, including a significant decrease in the functional connectivity degree of the right cingulate motor area and left premotor area compared to young subjects. Our study demonstrates that normal aging modulates the functional connectivity of motor network in the resting state. We postulate that this abnormal functional connectivity of motor network in the baseline state is an important reason contributing to the deteriorated motor ability in aged subjects.

背景与目标： ：我们使用功能性MRI（fMRI）来研究衰老对静止状态下运动网络功能连接的影响。使用基于图论的网络模型来测量功能连通性。计算了电动机网络内每个区域的总连接度，并比较了老年和青年组。我们发现，在老年受试者中，功能连接的模式发生了变化，包括与年轻受试者相比，右侧扣带回运动区和左侧运动前区的功能连接度显着降低。我们的研究表明，正常老化会在静止状态下调节电机网络的功能连通性。我们假设在基线状态下这种运动网络的异常功能连通性是导致老年受试者运动能力下降的重要原因。

BACKGROUND & AIMS: BACKGROUND:Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS, but it is unclear how much motor disability contributed to these abnormal functional interaction patterns. OBJECTIVE:To avoid any influence of impaired task performance, we examined disease-related changes in functional motor connectivity in MS at rest. METHODS:A total of 42 patients with MS and 30 matched controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. RESULTS:Patients with MS showed a spatial expansion of motor resting-state connectivity in deep subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. CONCLUSION:MS is characterised by more widespread motor connectivity in the basal ganglia while cortical motor resting-state connectivity is preserved. The expansion of subcortical motor resting-state connectivity in MS indicates less efficient funnelling of neural processing in the executive motor cortico-basal ganglia-thalamo-cortical loops.

背景与目标： 背景：多发性硬化症（MS）会损害沿皮质-皮质和皮质-皮质下连接的信号传输，影响运动网络内的功能集成。运动任务期间的功能磁共振成像（fMRI）已揭示MS中功能连接的改变，但尚不清楚多少运动障碍导致了这些异常的功能相互作用方式。
目的：为了避免影响任务表现的任何影响，我们研究了静止状态下MS中疾病相关的功能性运动连接改变。
方法：总共42例MS患者和30名相匹配的对照组在3特斯拉接受了20分钟的静息状态fMRI检查。将独立成分分析应用于fMRI数据，以识别运动静止状态连通性中与疾病相关的变化。
结果：患有MS的患者在深层皮层下核中显示出运动静息状态连通性的空间扩展，但在皮质水平上没有。与对照组相比，MS组的壳前部和中部，邻近的苍白球，丘脑前部和后部以及丘脑下区域显示出与运动网络的更强功能连接。
结论：MS的特点是基底神经节的运动连接更加广泛，而皮质运动的静息状态连接得以保留。 MS中皮层下运动静止状态连通性的扩展表明在执行性运动皮层-基底神经节-丘脑-皮层环路中神经处理的漏斗效率较低。

BACKGROUND & AIMS: :This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in people developing post-traumatic stress disorder (PTSD) following recent trauma. Sixty-two participants who had experienced recent acute traumatic events underwent a 7.3 min resting fMRI scan within 2 days post accident. Of these, 22 participants were diagnosed with PTSD within 1 to 6 months. Nineteen age- and sex-matched subjects without PTSD were selected as the trauma-exposed control group. Posterior cingulate cortex connectivity was determined from 17 PTSD patients and 15 control subjects by investigating synchronic low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between PTSD symptom severity and PCC connectivity, the contrast image representing areas correlated with the PCC was correlated with the 17 PTSD subjects' Clinician Administered PTSD Scale (CAPS) scores at diagnosis. Compared with the control group, PTSD patients exhibited decreased functional connectivity in the right lingual and right middle temporal gyri, and left lingual/posterior cingulate cortex. The left inferior temporal gyrus, right middle temporal gyrus, left middle temporal gyrus/insula, left medial frontal lobe/anterior cingulate cortex, and right medial frontal gyrus also showed increased connectivity within two days post accident. A negative correlation was found between PCC connectivity and CAPS scores in the left medial prefrontal cortex (mPFC). These results suggest that patients who develop PTSD exhibit different resting-state patterns of neuronal activity following recent trauma. Abnormal FC of mPFC may be a major risk factor predisposing patients to the development of PTSD.

背景与目标： ：这项研究使用静止状态功能磁共振成像（fMRI）来研究在最近的创伤后发展为创伤后应激障碍（PTSD）的人们的功能连接性是否发生了改变。事故发生后两天内，最近经历过急性创伤事件的62名参与者进行了7.3分钟的静息功能磁共振成像扫描。其中，有22名参与者在1-6个月内被诊断为PTSD。选择十九名没有PTSD的年龄和性别匹配的受试者作为暴露于创伤的对照组。通过使用时间相关性方法研究同步低频fMRI信号波动，从17例PTSD患者和15例对照受试者中确定了扣带后部皮层的连通性。为了评估PTSD症状严重程度与PCC连通性之间的关系，将代表与PCC相关的区域的对比图像与17 PTSD受试者在诊断时由临床医生管理的PTSD量表（CAPS）评分相关联。与对照组相比，PTSD患者的右舌和右颞中回以及左舌/后扣带皮层的功能连接性降低。左下颞回，右中颞回，左中颞回/孤立，左内侧额叶/前扣带回皮层以及右内侧额回在事故发生后两天内也显示出增强的连通性。左内侧前额叶皮层（mPFC）中的PCC连接性和CAPS得分之间呈负相关。这些结果表明，发生创伤后应激障碍的患者在最近的创伤后表现出不同的神经元活动静止状态模式。 mPFC的FC异常可能是使患者易患PTSD的主要危险因素。

BACKGROUND & AIMS: :Musashi1 (Msi1) is a highly conserved RNA-binding protein that is required during the development of the nervous system. Msi1 has been characterized as a stem cell marker, controlling the balance between self-renewal and differentiation, and has also been implicated in tumorigenesis, being highly expressed in multiple tumor types. We analyzed Msi1 expression in a large cohort of medulloblastoma samples and found that Msi1 is highly expressed in tumor tissue compared with normal cerebellum. Notably, high Msi1 expression levels proved to be a sign of poor prognosis. Msi1 expression was determined to be particularly high in molecular subgroups 3 and 4 of medulloblastoma. We determined that Msi1 is required for tumorigenesis because inhibition of Msi1 expression by small-interfering RNAs reduced the growth of Daoy medulloblastoma cells in xenografts. To characterize the participation of Msi1 in medulloblastoma, we conducted different high-throughput analyses. Ribonucleoprotein immunoprecipitation followed by microarray analysis (RIP-chip) was used to identify mRNA species preferentially associated with Msi1 protein in Daoy cells. We also used cluster analysis to identify genes with similar or opposite expression patterns to Msi1 in our medulloblastoma cohort. A network study identified RAC1, CTGF, SDCBP, SRC, PRL, and SHC1 as major nodes of an Msi1-associated network. Our results suggest that Msi1 functions as a regulator of multiple processes in medulloblastoma formation and could become an important therapeutic target.

背景与目标： ：Musashi1（Msi1）是神经系统发育过程中所需的高度保守的RNA结合蛋白。 Msi1已被表征为干细胞标志物，控制着自我更新和分化之间的平衡，并且还与肿瘤发生有关，在多种肿瘤类型中高表达。我们分析了一大批髓母细胞瘤样本中的Msi1表达，发现与正常小脑相比，Msi1在肿瘤组织中高表达。值得注意的是，高Msi1表达水平证明是不良预后的迹象。已确定在髓母细胞瘤的分子亚组3和4中Msi1表达特别高。我们确定Msi1是肿瘤发生所必需的，因为通过小干扰RNA抑制Msi1表达可减少异种移植物中Daoy髓母细胞瘤细胞的生长。为了表征Msi1在髓母细胞瘤中的参与，我们进行了不同的高通量分析。核糖蛋白免疫沉淀后再进行微阵列分析（RIP芯片）用于鉴定优先与Daoy细胞中Msi1蛋白相关的mRNA种类。我们还使用聚类分析来鉴定与我们的髓母细胞瘤队列中的Msi1表达模式相似或相反的基因。网络研究确定RAC1，CTGF，SDCBP，SRC，PRL和SHC1是与Msi1相关的网络的主要节点。我们的结果表明，Msi1在髓母细胞瘤形成过程中起多个过程的调节作用，并可能成为重要的治疗靶点。

BACKGROUND & AIMS: The distal His in peroxidases forms a hydrogen bond with the adjacent Asn, which is highly conserved among many plant and fungal peroxidases. Our previous work [Nagano, S., Tanaka, M., Ishimori, K., Watanabe, Y., & Morishima, I. (1996) Biochemistry 35, 14251-14258] has revealed that the replacement of Asn70 in horseradish peroxidase C (HRP) by Val (N70V) and Asp (N70D) discourages the oxidation activity for guaiacol, and the elementary reaction rate constants for the mutants was decreased by 10-15-fold. In order to delineate the structure-function relationship of the His-Asn couple in peroxidase activity, heme environmental structures of the HRP mutant, N70D, were investigated by CD, 1H NMR, and IR spectroscopies as well as Fe2+/Fe3+ redox potential measurements. While N70D mutant exhibited quite similar CD spectra and redox potential to those of native enzyme, the paramagnetic NMR spectrum clearly showed that the hydrogen bond between the distal His and Asp70 is not formed in the mutant. The disappearance of the splitting in the 1H NMR signal of heme peripheral 8-methyl group observed in 50% H2O/50% D2O solution of N70D-CN suggests that the hydrogen bond between the distal His and heme-bound cyanide is also disrupted by the mutation, which was supported by the low C-N vibration frequency and large dissociation constant of the heme-bound cyanide in the mutant. Together with the results from various spectroscopies and redox potentials, we can conclude that the improper positioning of the distal His induced the cleavages of the hydrogen bonds around the distal His, resulting in the substantial decrease of the catalytic activity without large structural alterations of the enzyme. The His-Asn hydrogen bond in the distal site of peroxidases, therefore, is essential for the catalytic activity by controlling the precise location of the distal His.

背景与目标： 过氧化物酶的远端His与相邻的Asn形成氢键，在许多植物和真菌的过氧化物酶中高度保守。我们以前的工作[Nagano，S.，Tanaka，M.，Ishimori，K.，Watanabe，Y.＆Morishima，I.（1996）Biochemistry 35，14251-14258]揭示了辣根过氧化物酶C中Asn70的替代。 Val（N70V）和Asp（N70D）（HRP）抑制了愈创木酚的氧化活性，并且突变体的基本反应速率常数降低了10-15倍。为了描述过氧化物酶活性中His-Asn对的结构-功能关系，通过CD，1H NMR和IR光谱以及Fe2 / Fe3氧化还原电位测量研究了HRP突变体N70D的血红素环境结构。尽管N70D突变体显示出与天然酶非常相似的CD光谱和氧化还原电位，但顺磁NMR光谱清楚地表明，在该突变体中未形成远端His和Asp70之间的氢键。在N70D-CN的50％H2O / 50％D2O溶液中观察到的血红素外围8-甲基的1H NMR信号分裂的消失表明，His末端和与血红素结合的氰化物之间的氢键也被N70破坏。较低的CN振动频率和突变体中血红素结合氰化物的较大解离常数为突变提供了支持。结合各种光谱学和氧化还原电势的结果，我们可以得出结论，His末端的不正确定位导致了His末端周围氢键的裂解，导致催化活性显着下降，而酶的结构没有很大变化。 。因此，过氧化物酶远端的His-Asn氢键通过控制远端His的精确位置，对于催化活性至关重要。

BACKGROUND & AIMS: :High-grade serous ovarian carcinoma (HGSOC) is the most prevalent and malignant ovarian tumor.To identify co-expression modules and hub genes correlated with platinum-based chemotherapy resistant and sensitive HGSOC, we performed weighted gene co-expression network analysis (WGCNA) on microarray data of HGSOC with 12 resistant samples and 16 sensitive samples of GSE51373 dataset.A total of 5122 genes were included in WGCNA, and 16 modules were identified. Module-trait analysis identified that the module salmon (cor = 0.50), magenta (cor = 0.49), and black (cor = 0.45) were discovered associated with chemotherapy resistant, and the significance for these platinum-resistant modules were validated in the GSE63885 dataset. Given that the black module was validated to be the most related one, hub genes of this module, alcohol dehydrogenase 1B, cadherin 11, and vestigial like family member 3were revealed to be expressional related with platinum resistance, and could serve as prognostic markers for ovarian cancer.Our analysis might provide insight for molecular mechanisms of platinum-based chemotherapy resistance and treatment response in ovarian cancer.

背景与目标： 高级别浆液性卵巢癌（HGSOC）是最普遍，最恶性的卵巢肿瘤。为鉴定与铂类化疗耐药和敏感性HGSOC相关的共表达模块和中枢基因，我们进行了加权基因共表达网络分析（WGCNA） ）在HGSOC的微阵列数据上，包含GSE51373数据集的12个抗性样品和16个敏感样品.WGCNA中总共包含5122个基因，并鉴定了16个模块。组件特征分析确定发现组件鲑鱼（cor = 0.50），品红色（cor = 0.49）和黑色（cor = 0.45）与耐化学药品性相关，并且在GSE63885中验证了这些耐铂金组件的重要性。数据集。假设黑色模块已被证实是最相关的模块，则该模块的中枢基因，乙醇脱氢酶1B，钙黏着蛋白11和类似家族成员3的残留基因被发现与铂耐药相关，并且可以作为卵巢癌的预后标志物我们的分析可能会为卵巢癌基于铂的化学疗法耐药性和治疗反应的分子机制提供深刻见解。

BACKGROUND & AIMS: :This paper examines the association between social networks and contraceptive use. Using data from a survey of women belonging to voluntary associations in Yaoundé, Cameroon, we find that the behavior and characteristics of the members of a respondent's personal networks are associated with her contraceptive use, over and above a set of her own individual characteristics that are usually found to be important. Respondents who report that their network partners approve of contraception, use it, and encourage the respondent to use are more likely to use contraception themselves; the association with encouragement is particularly strong. Moreover, there is a strong association between the specific methods of contraception used by a respondent and those used by her network partners, suggesting that members of personal networks exchange and evaluate specific methods. Because most of the respondent's network partners were interviewed, we are able to compare the respondent's perceptions of contraceptive use by her network partners with the network partner's actual use. We find that it is perceptions of use that matter, even if those perception are incorrect.

背景与目标： ：本文探讨了社交网络与避孕药具使用之间的关联。使用来自喀麦隆雅温得的自愿协会妇女调查的数据，我们发现，受访者个人网络成员的行为和特征与其使用避孕药具相关，而不仅仅是她自己的一系列个人特征。通常被认为很重要。报告其网络合作伙伴批准，使用避孕药具并鼓励受访者使用避孕药具的受访者更可能自己使用避孕药具；与鼓励的联系特别牢固。此外，受访者使用的特定避孕方法与她的网络伙伴使用的避孕方法之间有很强的联系，这表明个人网络的成员可以交换和评估特定的方法。因为大多数受访者的网络伙伴都接受了采访，所以我们能够将受访者对其网络伙伴使用避孕药具的看法与网络伙伴的实际使用情况进行比较。我们发现，重要的是使用感知，即使这些感知是不正确的。

BACKGROUND & AIMS: :Associations between previous joint replacement and B-cell lymphoid malignancies have been reported, but despite numerous reports, associations with the disease subtypes have received little attention. Using a UK-based register of haematological malignancies and a matched general population-based cohort, joint replacements from linked hospital inpatient records were examined. Cases diagnosed 2009-2015 who were aged 50 years or more were included; 8,013 mature B-cell neoplasms comprising myeloma (n = 1,763), diffuse large B-cell lymphoma (DLBCL, n = 1,676), chronic lymphocytic leukaemia (CLL, n = 1,594), marginal zone lymphoma (MZL, n = 957), follicular lymphoma (FL, n = 725) and classical Hodgkin lymphoma (CHL, n = 255), together with monoclonal gammopathy of uncertain significance (MGUS, n = 2,138) and monoclonal B-cell lymphocytosis (MBL, n = 632). Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated relative to 10 age- and sex-matched controls using conditional logistic regression. Having had a joint replacement before diagnosis was associated with myeloma (OR = 1.3, 95% CI 1.1-1.5, p = 0.008) and MGUS (OR = 1.3, 95% CI 1.1-1.5, p < 0.001). Excluding replacements in the year before diagnosis, the MGUS risk remained, elevated where two or more joints were replaced (OR = 1.5, 95% CI 1.2-2.0, p = 0.001), with hip (OR = 1.2, 95% CI 1.0-1.5, p = 0.06) or knee replacements (OR = 1.5, 95% CI 1.2-1.8, p < 0.001). Associations with CHL and two or more replacements (OR = 2.7, 95% CI 1.3-5.6, p = 0.005) or hip replacements (OR = 1.9, 95% CI 1.0-3.4, p = 0.04); and between DLBCL and knee replacements (OR = 1.3, 95% CI 1.0-1.6, p = 0.04) were also observed. Our study reports for the first time a relationship between joint replacements and MGUS; while absolute risks of disease are low and not of major public health concern, these findings warrant further investigation.

背景与目标： ：以前的关节置换术与B细胞淋巴样恶性肿瘤之间的关联已有报道，但尽管有许多报道，但与疾病亚型的关联却很少受到关注。使用基于英国的血液系统恶性肿瘤登记表和相匹配的基于人群的队列研究，对相关医院住院记录中的关节置换进行了检查。纳入诊断为2009-2015年且年龄≥50岁的病例； 8,013个成熟的B细胞肿瘤，包括骨髓瘤（n = 1,763），弥漫性大B细胞淋巴瘤（DLBCL，n = 1,676），慢性淋巴细胞性白血病（CLL，n = 1,594），边缘区淋巴瘤（MZL，n = 957），滤泡性淋巴瘤（FL，n = 725）和经典霍奇金淋巴瘤（CHL，n = 255），以及意义不明的单克隆丙种球蛋白病（MGUS，n = 2,138）和单克隆B细胞淋巴瘤（MBL，n = 632）。使用条件逻辑回归，相对于10个年龄和性别匹配的对照，计算了赔率（OR）和95％置信区间（95％CI）。在诊断之前进行过关节置换术的患者与骨髓瘤（OR == 1.3，95％CI 1.1-1.5，p = 0.008）和MGUS（OR == 1.3，95％CI 1.1-1.5，p <0.001）相关。不包括诊断前一年的置换，MGUS风险仍然存在，在两个或多个关节置换时（OR = 1.5，95％CI 1.2-2.0，p = 0.001），髋关节（OR = 1.2，95％CI 1.0- 1.5，p = 0.06）或膝关节置换术（OR = 1.5，95％CI 1.2-1.8，p <0.001）。与CHL和两个或多个置换术（OR = 2.7，95％CI 1.3-5.6，p = 0.005）或髋关节置换术（OR = 1.9，95％CI 1.0-3.4，p = 0.04）的关联;以及在DLBCL和膝关节置换之间（OR = 1.3，95％CI 1.0-1.6，p = 0.04）也被观察到。我们的研究首次报告了关节置换与MGUS之间的关系。尽管疾病的绝对风险很低，而且不涉及主要的公共卫生问题，但这些发现值得进一步调查。

BACKGROUND & AIMS: OBJECTIVE:By binding to its high-affinity receptor FcεR1, IgE activates mast cells, macrophages, and other inflammatory and vascular cells. Recent studies support an essential role of IgE in cardiometabolic diseases. Plasma IgE level is an independent predictor of human coronary heart disease. Yet, a direct role of IgE and its mechanisms in cardiometabolic diseases remain incompletely understood. Approach and Results: Using atherosclerosis prone Apoe-/- mice and IgE-deficient Ige-/- mice, we demonstrated that IgE deficiency reduced atherosclerosis lesion burden, lesion lipid deposition, smooth muscle cell and endothelial cell contents, chemokine MCP (monocyte chemoattractant protein)-1 expression and macrophage accumulation. IgE deficiency also reduced bodyweight gain and increased glucose and insulin sensitivities with significantly reduced plasma cholesterol, triglyceride, insulin, and inflammatory cytokines and chemokines, including IL (interleukin)-6, IFN (interferon)-γ, and MCP-1. From atherosclerotic lesions and peritoneal macrophages from Apoe-/-Ige-/- mice that consumed an atherogenic diet, we detected reduced expression of M1 macrophage markers (CD68, MCP-1, TNF [tumor necrosis factor]-α, IL-6, and iNOS [inducible nitric oxide synthase]) but increased expression of M2 macrophage markers (Arg [arginase]-1 and IL-10) and macrophage-sterol-responsive-network molecules (complement C3, lipoprotein lipase, LDLR [low-density lipoprotein receptor]-related protein 1, and TFR [transferrin]) that suppress macrophage foam cell formation. These IgE activities can be reproduced in bone marrow-derived macrophages from wild-type mice, but muted in cells from FcεR1-deficient mice, or blocked by anti-IgE antibody or complement C3 deficiency. CONCLUSIONS:IgE deficiency protects mice from diet-induced atherosclerosis, obesity, glucose tolerance, and insulin resistance by regulating macrophage polarization, macrophage-sterol-responsive-network gene expression, and foam cell formation.

背景与目标： 目的：通过与高亲和力受体FcεR1结合，IgE可以激活肥大细胞，巨噬细胞以及其他炎症和血管细胞。最近的研究支持IgE在心脏代谢疾病中的重要作用。血浆IgE水平是人类冠心病的独立预测因子。然而，IgE及其在心血管代谢疾病中的作用的直接作用仍不完全清楚。方法和结果：使用易发生动脉粥样硬化的Apoe-/-小鼠和IgE缺乏的Ige-/-小鼠，我们证明了IgE缺乏会减少动脉粥样硬化的病变负担，病变脂质沉积，平滑肌细胞和内皮细胞含量，趋化因子MCP（单核细胞趋化蛋白） ）-1表达和巨噬细胞积累。 IgE缺乏症还会减少体重增加，并增加葡萄糖和胰岛素敏感性，同时血浆胆固醇，甘油三酸酯，胰岛素和炎性细胞因子和趋化因子（包括IL（白介素）-6，IFN（干扰素）-γ和MCP-1）显着降低。从食用动脉粥样化饮食的Apoe-/-Ige-/-小鼠的动脉粥样硬化病变和腹膜巨噬细胞中，我们检测到M1巨噬细胞标志物（CD68，MCP-1，TNF [肿瘤坏死因子]-α，IL-6，和iNOS [诱导型一氧化氮合酶]），但M2巨噬细胞标志物（Arg [精氨酸酶] -1和IL-10）和巨噬细胞-甾醇反应网络分子（补体C3，脂蛋白脂酶，LDLR [低密度脂蛋白]的表达增加）受体]相关蛋白1和TFR [转铁蛋白]）抑制巨噬细胞泡沫细胞的形成。这些IgE活性可以在野生型小鼠的骨髓巨噬细胞中复制，但在FcεR1缺陷型小鼠的细胞中却被静音，或者被抗IgE抗体或补体C3缺陷所阻断。
结论：IgE缺乏症通过调节巨噬细胞极化，巨噬细胞-甾醇反应网络基因表达和泡沫细胞形成，保护小鼠免受饮食诱导的动脉粥样硬化，肥胖，葡萄糖耐量和胰岛素抵抗。

BACKGROUND & AIMS: :Depression is more common among drug users (15-63 %) than the general population (5-16 %). Lack of social support network members may be associated with low mental health service (MHS) use rates observed among drug users. We investigated the relationship between social network members' roles and MHS use among frequent drug users using Social Ties Associated with Risk of Transition into Injection Drug Use data (NYC 2006-2009). Surveys assessed depression, MHS use, demographics, drug use and treatment, and social network members' roles. Participants reporting lifetime depressive episode with start/end dates and information on social/risk network members were included (n = 152). Adjusting for emotional support and HIV status, having one or more informational support network members remained associated with MHS use at last depressive episode (adjusted odds ratio (AOR) 3.37, 95 % confidence interval (CI) 1.38-8.19), as did history of drug treatment (AOR 2.75, 95 % CI 1.02-7.41) and no legal income (AOR 0.23, 95 % CI 0.08-0.64). These data suggest that informational support is associated with MHS utilization among depressed drug users.

背景与目标： ：吸毒者（15-63％）中的抑郁症比普通人群（5-16％）更常见。缺乏社会支持网络成员可能与在吸毒者中观察到的精神卫生服务（MHS）使用率低有关。我们调查了社交网络成员的角色与频繁吸毒者中MHS使用之间的关系，使用的是与转换为注射毒品使用风险相关的社交纽带（NYC 2006-2009）。调查评估了抑郁症，MHS的使用，人口统计学，药物的使用和治疗以及社交网络成员的作用。包括报告终生抑郁发作的患者（包括开始/结束日期）以及有关社会/风险网络成员的信息（n = 152）。调整情绪支持和HIV状况后，在上一次抑郁发作中，拥有一个或多个信息支持网络成员仍与MHS使用相关（调整后的优势比（AOR）3.37，95％置信区间（CI）1.38-8.19），药物治疗（AOR 2.75，95％CI 1.02-7.41），没有合法收入（AOR 0.23，95％CI 0.08-0.64）。这些数据表明，信息支持与抑郁药物使用者中MHS的利用有关。

BACKGROUND & AIMS: BACKGROUND:Most single ventricle patients undergo Fontan procedure in a staged manner. However, optimal timing of Fontan completion after an intermediate staging surgery is controversial. Therefore, we investigated the long-term impact of age at Fontan completion on the exercise performance in adolescents. METHODS:We analyzed National Institutes of Health/National Heart, Lung and Blood Institute Pediatric Heart Network Fontan Cross-Sectional Study dataset consisting of children and adolescents 6 to 18 years of age recruited in 2003 to 2004. Multivariate linear regression techniques were used to evaluate association of age at Fontan procedure with percent predicted VO2 maximum, percent predicted maximum O2 pulse, and heart rate reserve in patients who achieved ventilatory anaerobic threshold (VAT). RESULTS:Of the 405 patients who had undergone only one Fontan operation and ramp cycle ergometry, 72% had prior intermediate surgery. Mean age at Fontan completion and exercise testing was 3.4±2 and 12.4±3.2 years. Three hundred twelve patients reached VAT suggesting adequate cardiopulmonary effort. In patients who reached VAT, each year increase in age at Fontan completion was associated with a decline of 1.5 (95% CI -2.5 to -0.5) points in percent-predicted VO2 maximum and a decline of 4.1 (95% CI -6.0 to -2.1) beat/min in heart rate reserve after adjusting for all pertinent variables. CONCLUSIONS:Fontan completion at a younger age is associated with better exercise performance in adolescents.

背景与目标： 背景：大多数单心室患者分阶段接受Fontan手术。然而，中级分期手术后丰坦完成的最佳时机存在争议。因此，我们调查了丰坦完成年龄对青少年运动表现的长期影响。
方法：我们分析了美国国立卫生研究院/国家心脏，肺和血液研究所儿科心脏网络Fontan跨部门研究数据集，该数据集由2003年至2004年招募的6至18岁的儿童和青少年组成。使用多元线性回归技术进行评估达到通气性无氧阈值（VAT）的患者中Fontan手术的年龄与预计最大VO2百分比，最大预期O2脉冲百分比和心率储备的相关性。
结果：在仅接受过一次丰坦手术和斜波测功的405例患者中，有72％曾接受过中级手术。丰坦完成和运动测试的平均年龄为3.4±2岁和12.4±3.2岁。 312名患者达到了增值税，表明有足够的心肺功能。在达到增值税的患者中，丰坦完成时年龄的每年增加与百分比最大预测VO2值下降1.5（95％CI -2.5至-0.5）点相关，而下降4.1（95％CI -6.0至95％CI -6.0）。 -2.1）调整所有相关变量后，心跳储备的心跳/分钟。
结论：年轻时的丰坦完成与青少年更好的运动表现有关。

BACKGROUND & AIMS: :The Indian Ocean has long been a hub of interacting human populations. Following land- and sea-based routes, trade drove cultural contacts between far-distant ethnic groups in Asia, India, the Middle East and Africa, creating one of the world's first proto-globalized environments. However, the extent to which population mixing was mediated by trade is poorly understood. Reconstructing admixture times from genomic data in 3,006 individuals from 187 regional populations reveals a close association between bouts of human migration and trade volumes during the last 2,000 years across the Indian Ocean trading system. Temporal oscillations in trading activity match phases of contraction and expansion in migration, with high water marks following the expansion of the Silk Roads in the 5th century AD, the rise of maritime routes in the 11th century and a drastic restructuring of the trade network following the arrival of Europeans in the 16th century. The economic fluxes of the Indian Ocean trade network therefore directly shaped exchanges of genes, in addition to goods and concepts.

背景与目标： ：印度洋长期以来一直是人口互动的中心。沿着陆路和海路，贸易推动了亚洲，印度，中东和非洲的远距离民族之间的文化交流，创造了世界上第一个原始全球化的环境。但是，人们对由贸易介导的人口混合程度的了解很少。根据来自187个区域人口的3,006个人的基因组数据重构混合时间，揭示了过去2,000年来印度洋贸易体系中的人类迁徙与贸易量之间的紧密联系。贸易活动的时间波动与移民扩张和收缩的阶段相适应，公元5世纪丝绸之路的扩张，11世纪海上航线的兴起以及贸易网络的大规模重组之后，高水位标志着高水位标志。 16世纪欧洲人的到来。因此，除了商品和概念之外，印度洋贸易网络的经济波动直接影响了基因的交换。

BACKGROUND & AIMS: :The area of mobile technologies applied to health (mHealth) is a growing worldwide trend that has generated enormous expectations for the mitigation of problems related to medical services delivery and public health stemming from a lack of resources and the limited number of specialists. The numerous opportunities offered by mobile technologies, together with their ease of use, have attracted the interest both of governments and universities. This is the case of the Ibero-American Mobile Technologies and Health Network (CYTED-RITMOS, Spanish acronym). As a result of the network's first year of activity, in October 2015 the RITMOS International Workshop was held in Barcelona to present the priority areas in Latin America where research, development, and innovation (R&D+i) projects on mobile health could be carried out and possible solutions found. The objective of this article is to present the potentialities and applicability of mHealth in the Region of the Americas.

背景与目标： ：应用于健康的移动技术（mHealth）领域正在发展，在全球范围内，由于缺乏资源和专家人数有限，人们对减轻与医疗服务提供和公共卫生有关的问题抱有极大的期望。移动技术所带来的众多机遇及其易用性吸引了政府和大学的兴趣。伊比利亚美洲移动技术和卫生网络（CYTED-RITMOS，西班牙首字母缩写）就是这种情况。作为网络第一年的活动的结果，2015年10月，RITMOS国际研讨会在巴塞罗那举行，介绍了拉丁美洲的优先领域，可以在该领域开展有关移动医疗的研究，开发和创新（R＆D i）项目，以及找到可能的解决方案。本文的目的是介绍移动医疗在美洲地区的潜力和适用性。

BACKGROUND & AIMS: :Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) mediates the docking and entry of dendritic cells to lymphatic vessels through selective adhesion to its ligand hyaluronan in the leukocyte surface glycocalyx. To bind hyaluronan efficiently, LYVE-1 must undergo surface clustering, a process that is induced efficiently by the large cross-linked assemblages of glycosaminoglycan present within leukocyte pericellular matrices but is induced poorly by the shorter polymer alone. These properties suggested that LYVE-1 may have limited mobility in the endothelial plasma membrane, but no biophysical investigation of these parameters has been carried out to date. Here, using super-resolution fluorescence microscopy and spectroscopy combined with biochemical analyses of the receptor in primary lymphatic endothelial cells, we provide the first evidence that LYVE-1 dynamics are indeed restricted by the submembranous actin network. We show that actin disruption not only increases LYVE-1 lateral diffusion but also enhances hyaluronan-binding activity. However, unlike the related leukocyte HA receptor CD44, which uses ERM and ankyrin motifs within its cytoplasmic tail to bind actin, LYVE-1 displays little if any direct interaction with actin, as determined by co-immunoprecipitation. Instead, as shown by super-resolution stimulated emission depletion microscopy in combination with fluorescence correlation spectroscopy, LYVE-1 diffusion is restricted by transient entrapment within submembranous actin corrals. These results point to an actin-mediated constraint on LYVE-1 clustering in lymphatic endothelium that tunes the receptor for selective engagement with hyaluronan assemblages in the glycocalyx that are large enough to cross-bridge the corral-bound LYVE-1 molecules and thereby facilitate leukocyte adhesion and transmigration.

背景与目标： ：淋巴管内皮透明质酸受体1（LYVE-1）通过选择性粘附在白细胞表面糖萼中的配体透明质酸介导树突细胞对接和进入淋巴管。为了有效结合透明质酸，LYVE-1必须经历表面聚集，这一过程是由白细胞周细胞基质内存在的大量糖胺聚糖交联组合有效诱导的，但仅由较短的聚合物就很难诱导。这些性质表明，LYVE-1在内皮细胞质膜中的活动性可能有限，但是迄今为止，尚未对这些参数进行生物物理研究。在这里，使用超高分辨率荧光显微镜和光谱结合原发性淋巴内皮细胞受体的生化分析，我们提供了LYVE-1动力学确实受到膜下肌动蛋白网络限制的第一个证据。我们表明肌动蛋白破坏不仅增加了LYVE-1横向扩散，而且还增强了透明质酸结合活性。但是，与相关的白细胞HA受体CD44不同，它在细胞质尾巴中使用ERM和锚蛋白基序结合肌动蛋白，而LYVE-1与肌动蛋白的直接相互作用很少，如通过共免疫沉淀法测定的。取而代之的是，如超分辨率激发发射耗尽显微镜结合荧光相关光谱法所示，LYVE-1的扩散受到膜下肌动蛋白皮质内瞬时捕获的限制。这些结果表明肌动蛋白介导的对淋巴管内皮细胞LYVE-1簇的约束，使受体与糖萼中的透明质酸组合物选择性结合，所述透明质酸组合物足够大，可以跨桥结合皮质的LYVE-1分子，从而促进白细胞的形成。粘附和转运。