领导-成员交换关系在变革型领导与护理差错管理氛围间的中介作用

目的 探讨领导-成员交换关系(LMX)在变革型领导与差错管理氛围间的中介作用,为临床护理管理提供参考。方法 采用 便利抽样方法抽取唐山市4所三级甲等医院的临床护士877人,应用一般资料调查问卷、变革型领导量表、领导-成员交换关系量 表和差错管理氛围量表进行调查。结果 变革型领导总分为94.57±16.68,LMX 总分为56.02±11.67,差错管理氛围总分为 60.94±12.15。变革型领导与差错管理氛围、LMX呈正相关,LMX与差错管理氛围呈正相关(均 P<0.01);变革型领导对差错 管理氛围的间接效应成立,间接效应为0.134;变革型领导作用于差错管理氛围的效应有25.52%是通过 LMX 起作用。结论 变 革型领导能够增强护士长与护士之间的领导-成员交换关系,进而改善差错管理氛围。     

四肽FMRFa对大鼠心室肌Na+/Ca2+交换的抑制

目的　研究四肽FMRFa对大鼠单个心室肌细胞Na⁺/Ca²⁺交换的作用。方法　用膜片钳全细胞记录法测定成年大鼠心室肌细胞Na⁺/Ca²⁺交换电流(I_Na⁺/Ca²⁺)和其他离子通道电流。结果　FMRFa对大鼠心室肌细胞I_Na⁺/Ca²⁺呈浓度依赖性抑制,100μmol·L^-1浓度时抑制内向和外向I_Na⁺/Ca²⁺密度分别达60.1%和56.5%,对内向电流及外向电流的IC₅₀分别为20μmol·L^-1和34μmol·L^-1。FMRFa5μmol·L^-1抑制I_Na⁺/Ca²⁺内向和外向电流密度分别为38.7%和34.9%,但FMRFa5μmol·L^-1及20μmol·L^-1对L型钙电流、钠电流、瞬时外向电流和内向整流钾电流均无显著抑制作用。结论　FMRFa对大鼠心室肌细胞是一个特异性Na⁺/Ca²⁺交换抑制剂。     

开放存取研究对学术交流系统的影响

介绍了传统学术交流模式中各要素存在的问题及局限性,构建了开放存取环境下的学术交流模型,分析了新学术交流系统对各要素的影响,指出了研究开放存取对学术交流系统影响的意义.     

改良脐动静脉双管同步换血治疗重症新生儿高胆红素血症疗效观察

目的观察改良脐动静脉双管进行同步换血治疗重症新生儿高胆红素血症的疗效和安全性。方法将我院收治的64例确诊为新生儿高胆红素血症患儿随机分为两组,对照组32例持续24小时蓝光照射配合静滴白蛋白等综合治疗,治疗组32例在对照组综合治疗的基础上,通过改良后脐动静脉双管进行同步换血治疗后。对两组患儿治疗前后的血清胆红素、血糖、电解质以及血常规进行观察和比较。结果治疗组与对照组对比治疗组血清胆红素较观察组下降明显,治疗前后差异明显,有统计学意义,P0.05。血红蛋白轻微下降,血钾、血氯、血钙、血钠水平没有明显变化,差异不明显,无统计学意义,P0.05。结论改良后脐动静脉双管进行同步换血治疗新生儿高胆红素血症安全、快速降低重症新生儿高胆红素血症患儿的胆红素水平,值得有条件的医院推广。     

Is point of access to needles and syringes related to needle sharing? Comparing data collected from pharmacies and needle and syringe programs in south‐east Sydney

Introduction and Aims. The comprehensive needle and syringe distribution system in New South Wales is partly based on the premise that different points of access to injecting equipment may attract different groups of injecting drug users. This paper examines patterns of equipment acquisition and risk for blood‐borne virus transmission among injecting drug users who use pharmacies and needle and syringe programs (NSP) in south‐east Sydney. Design and Methods. Clients obtaining injecting equipment from four NSP (n = 147) and eight pharmacies (n = 227) in 2006 voluntarily completed a self‐administered questionnaire. Respondents were grouped into three categories based on their needle and syringe acquisition patterns: exclusive use of NSP, exclusive use of pharmacies and use of both. Results. Although it was common for respondents to report using both pharmacies and NSP to obtain needles and syringes (57%), a proportion reported exclusive use of pharmacies (17%) and NSP (14%). Exclusive pharmacy users were more likely to have never received treatment for their drug use and the least likely to have had a recent test for hepatitis C. Compared with respondents who exclusively used NSP, respondents who exclusively used pharmacies were more likely to report receptive sharing of injecting equipment (adjusted odds ratio 5.9, 95% confidence interval 2.02–17.14), as were respondents who reported using both sources (adjusted odds ratio 5.8, 95% confidence interval 2.35–14.40). Discussion and Conclusions. The high prevalence of receptive equipment sharing among pharmacy clients indicates a need to improve access to needles and syringes and ancillary equipment, possibly by including ancillary equipment at no cost in existing pre‐packaged pharmacy products.[Bryant J, Topp L, Hopwood M, Iversen J, Treloar C, Maher L. Is point of access to needles and syringes related to needle sharing? Comparing data collected from pharmacies and needle and syringe programs in south‐east Sydney. Drug Alcohol Rev 2010]     

Tiam1/Rac1 signaling pathway mediates palmitate-induced, ceramide-sensitive generation of superoxides and lipid peroxides and the loss of mitochondrial membrane potential in pancreatic β-cells

The phagocytic NADPH oxidase [NOX] has been implicated in the generation of superoxides in the pancreatic β-cell. Herein, using normal rat islets and clonal INS 832/13 cells, we tested the hypothesis that activation of the small G-protein Rac1, which is a member of the NOX holoenzyme, is necessary for palmitate [PA]-induced generation of superoxides in pancreatic β-cells. Incubation of isolated β-cells with PA potently increased the NOX activity culminating in a significant increase in the generation of superoxides and lipid peroxides in these cells; such effects of PA were attenuated by diphenyleneiodonium [DPI], a known inhibitor of NOX. In addition, PA caused a transient, but significant activation [i.e., GTP-bound form] of Rac1 in these cells. NSC23766, a selective inhibitor of Rac1, but not Cdc42 or Rho activation, inhibited Rac1 activation and the generation of superoxides and lipid peroxides induced by PA. Fumonisin B-1 [FB-1], which inhibits de novo synthesis of ceramide [CER] from PA, also attenuated PA-induced superoxide and lipid peroxide generation and NOX activity implicating intracellularly generated CER in the metabolic effects of PA; such effects were also demonstrable in the presence of the cell-permeable C2-CER. Further, NSC23766 prevented C2-CER-induced Rac1 activation and production of superoxides and lipid peroxides. Lastly, C2-CER, but not its inactive analogue, significantly reduced the mitochondrial membrane potential, which was prevented to a large degree by NSC23766. Together, our findings suggest that Tiam1/Rac1 signaling pathway regulates PA-induced, CER-dependent superoxide generation and mitochondrial dysfunction in pancreatic β-cells.     

Deletion of WASp and N-WASp in B cells cripples the germinal center response and results in production of IgM autoantibodies

Humoral immunodeficiency caused by mutations in the Wiskott-Aldrich syndrome protein (WASp) is associated with failure to respond to common pathogens and high frequency of autoimmunity. Here we addressed the question how deficiency in WASp and the homologous protein N-WASp skews the immune response towards autoreactivity. Mice devoid of WASp or both WASp and N-WASp in B cells formed germinal center to increased load of apoptotic cells as a source of autoantigens. However, the germinal centers showed abolished polarity and B cells retained longer and proliferated less in the germinal centers. While WASp-deficient mice had high titers of autoreactive IgG, B cells devoid of both WASp and N-WASp produced mainly IgM autoantibodies with broad reactivity to autoantigens. Moreover, B cells lacking both WASp and N-WASp induced somatic hypermutation at reduced frequency. Despite this, IgG1-expressing B cells devoid of WASp and N-WASp acquired a specific high affinity mutation, implying an increased BCR signaling threshold for selection in germinal centers. Our data provides evidence for that N-WASp expression alone drives WASp-deficient B cells towards autoimmunity.     

Quantitative chemical exchange saturation transfer (qCEST) MRI – omega plot analysis of RF‐spillover‐corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate

Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST‐weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH‐dependent exchange rate followed a dominantly base‐catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system. Copyright © 2015 John Wiley & Sons, Ltd.     

Quantitative description of radiofrequency (RF) power‐based ratiometric chemical exchange saturation transfer (CEST) pH imaging

Chemical exchange saturation transfer (CEST) MRI holds great promise for the imaging of pH. However, routine CEST measurement varies not only with the pH‐dependent chemical exchange rate, but also with CEST agent concentration, providing pH‐weighted information. Conventional ratiometric CEST imaging normalizes the confounding concentration factor by analyzing the relative CEST effect from different exchangeable groups, requiring CEST agents with multiple chemically distinguishable labile proton sites. Recently, a radiofrequency (RF) power‐based ratiometric CEST MRI approach has been developed for concentration‐independent pH MRI using CEST agents with a single exchangeable group. To facilitate quantification and optimization of the new ratiometric analysis, we quantified the RF power‐based ratiometric CEST ratio (rCESTR) and derived its signal‐to‐noise and contrast‐to‐noise ratios. Using creatine as a representative CEST agent containing a single exchangeable site, our study demonstrated that optimized RF power‐based ratiometric analysis provides good pH sensitivity. We showed that rCESTR follows a base‐catalyzed exchange relationship with pH independent of creatine concentration. The pH accuracy of RF power‐based ratiometric MRI was within 0.15–0.20 pH units. Furthermore, the absolute exchange rate can be obtained from the proposed ratiometric analysis. To summarize, RF power‐based ratiometric CEST analysis provides concentration‐independent pH‐sensitive imaging and complements conventional multiple labile proton group‐based ratiometric CEST analysis. Copyright © 2015 John Wiley & Sons, Ltd.     

Imaging chemical exchange saturation transfer (CEST) effects following tumor‐selective acidification using lonidamine

Increased lactate production through glycolysis in aerobic conditions is a hallmark of cancer. Some anticancer drugs have been designed to exploit elevated glycolysis in cancer cells. For example, lonidamine (LND) inhibits lactate transport, leading to intracellular acidification in cancer cells. Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism that is dependent on intracellular pH. Amine and amide concentration‐independent detection (AACID) and apparent amide proton transfer (APT*) represent two recently developed CEST contrast parameters that are sensitive to pH. The goal of this study was to compare the sensitivity of AACID and APT* for the detection of tumor‐selective acidification after LND injection. Using a 9.4‐T MRI scanner, CEST data were acquired in mice approximately 14 days after the implantation of 10⁵ U87 human glioblastoma multiforme (GBM) cells in the brain, before and after the administration of LND (dose, 50 or 100 mg/kg). Significant dose‐dependent LND‐induced changes in the measured CEST parameters were detected in brain regions spatially correlated with implanted tumors. Importantly, no changes were observed in T₁‐ and T₂‐weighted images acquired before and after LND treatment. The AACID and APT* contrast measured before and after LND injection exhibited similar pH sensitivity. Interestingly, LND‐induced contrast maps showed increased heterogeneity compared with pre‐injection CEST maps. These results demonstrate that CEST contrast changes after the administration of LND could help to localize brain cancer and monitor tumor response to chemotherapy within 1 h of treatment. The LND CEST experiment uses an anticancer drug to induce a metabolic change detectable by endogenous MRI contrast, and therefore represents a unique cancer detection paradigm which differs from other current molecular imaging techniques that require the injection of an imaging contrast agent or tracer. Copyright © 2015 John Wiley & Sons, Ltd.