Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: implications for BOLD-fMRI

Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD response is primarily driven by cerebral blood flow (CBF) changes, but is moderated by M, a scaling parameter reflecting baseline deoxyhemoglobin, and n, the ratio of fractional changes in CBF to cerebral metabolic rate of oxygen consumption (CMRO(2)). We compared M and n between cortical (visual cortex, VC) and subcortical (lentiform nuclei, LN) regions using a quantitative approach based on calibrating the BOLD response with a hypercapnia experiment. Although M was similar in both regions (~5.8%), differences in n (2.21+/-0.03 in VC and 1.58+/-0.03 in LN; Cohen d=1.71) produced substantially weaker (~3.7x) subcortical than cortical BOLD responses relative to CMRO(2) changes. Because of this strong sensitivity to n, BOLD response amplitudes cannot be interpreted as a quantitative reflection of underlying metabolic changes, particularly when comparing cortical and subcortical regions.     

Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse

The basal forebrain (BF) strongly regulates cortical activation, sleep homeostasis, and attention. Many BF neurons involved in these processes are GABAergic, including a subpopulation of projection neurons containing the calcium‐binding protein, parvalbumin (PV). However, technical difficulties in identification have prevented a precise mapping of the distribution of GABAergic and GABA/PV+ neurons in the mouse or a determination of their intrinsic membrane properties. Here we used mice expressing fluorescent proteins in GABAergic (GAD67‐GFP knock‐in mice) or PV+ neurons (PV‐Tomato mice) to study these neurons. Immunohistochemical staining for GABA in GAD67‐GFP mice confirmed that GFP selectively labeled BF GABAergic neurons. GFP+ neurons and fibers were distributed throughout the BF, with the highest density in the magnocellular preoptic area (MCPO). Immunohistochemistry for PV indicated that the majority of PV+ neurons in the BF were large (>20 μm) or medium‐sized (15–20 μm) GFP+ neurons. Most medium and large‐sized BF GFP+ neurons, including those retrogradely labeled from the neocortex, were fast‐firing and spontaneously active in vitro. They exhibited prominent hyperpolarization‐activated inward currents and subthreshold “spikelets,” suggestive of electrical coupling. PV+ neurons recorded in PV‐Tomato mice had similar properties but had significantly narrower action potentials and a higher maximal firing frequency. Another population of smaller GFP+ neurons had properties similar to striatal projection neurons. The fast firing and electrical coupling of BF GABA/PV+ neurons, together with their projections to cortical interneurons and the thalamic reticular nucleus, suggest a strong and synchronous control of the neocortical fast rhythms typical of wakefulness and REM sleep. J. Comp. Neurol., 521:1225–1250, 2013. © 2012 Wiley Periodicals, Inc.     

IL6Rα function in myeloid cells modulates the inflammatory response during irritant contact dermatitis

Irritant contact dermatitis (ICD) is characterized by epidermal hyperplasia, infiltration of leucocytes into lesional skin and inflammatory cytokine release. The cellular infiltrate during ICD comprises primarily cells of the myeloid lineage. Our group has previously shown that the cytokine IL‐6 confers a protective effect to lesional skin during ICD. How IL‐6Rα function in myeloid cells is involved in the inflammatory response during ICD is, however, unknown. In the present study, utilizing a chemical model of ICD, it is shown that mice with a myeloid‐specific knockout of the IL‐6Rα (IL‐6Rα^Δmyeloid) display an exaggerated inflammatory response to benzalkonium chloride (BKC) and Jet propellant‐8 (JP8) fuel, two well‐characterized irritants relative to littermate control. Results from immunohistochemical and flow cytometric analyses revealed that IL‐6Rα^Δmyeloid mouse skin displayed increased epidermal hyperplasia and inflammatory monocyte influx into lesional skin but lower numbers of resident macrophages relative to littermate controls after irritant exposure. Multiplex immunoassay revealed significantly higher levels of pro‐inflammatory cytokines IL‐1α and TNF‐α, but reduced expression of chemokine proteins including CCL2‐5, CCL7, CCL11, CXCL1 and CXCL10 in IL‐6Rα^Δmyeloid mouse skin relative to littermate control following irritant exposure. These results highlight a previously unknown role of IL‐6Rα function in myeloid cells in modulating the inflammatory response and myeloid population dynamics during ICD.     

Fractional Factorial Design Study on the Performance of GAC-Enhanced Electrocoagulation Process Involved in Color Removal from Dye Solutions

The aim of this study was to determine the effects of main factors and interactions on the color removal performance from dye solutions using the electrocoagulation process enhanced by adsorption on Granular Activated Carbon (GAC). In this study, a mathematical approach was conducted using a two-level fractional factorial design (FFD) for a given dye solution. Three textile dyes: Acid Blue 74, Basic Red 1, and Reactive Black 5 were used. Experimental factors used and their respective levels were: current density (2.73 or 27.32 A/m²), initial pH of aqueous dye solution (3 or 9), electrocoagulation time (20 or 180 min), GAC dose (0.1 or 0.5 g/L), support electrolyte (2 or 50 mM), initial dye concentration (0.05 or 0.25 g/L) and current type (Direct Current—DC or Alternative Pulsed Current—APC). GAC-enhanced electrocoagulation performance was analyzed statistically in terms of removal efficiency, electrical energy, and electrode material consumptions, using modeling polynomial equations. The statistical significance of GAC dose level on the performance of GAC enhanced electrocoagulation and the experimental conditions that favor the process operation of electrocoagulation in APC regime were determined. The local optimal experimental conditions were established using a multi-objective desirability function method.     

Design of High Impedance Electromagnetic Surfaces for Mutual Coupling Reduction in Patch Antenna Array

A compact planar meander-bridge high impedance electromagnetic structure (MBHIES) was designed and its bandgap characteristics, mutual coupling reduction abilities were studied and compared in detail. Several parametric analyses were performed to obtain optimized design values and the transmission responses were calculated through the suspended microstrip line and waveguide simulation methods. The achieved bandgap is 2.3 GHz (2.55–4.85 GHz) with −61 dB minimum transmission coefficient level at the center frequency of 3.6 GHz. To see the effectiveness, the proposed design was inserted between a microstrip patch antenna array which operates at 3.8 GHz and whose operating bandwidth falls within the MBHIES bandgap. The surface wave suppression phenomenon was analyzed and simulated results are verified by measuring the fabricated prototypes, both are in good agreement. The configuration reduced the mutual coupling by 20.69 dB in simulation and 19.18 dB in measurement, without affecting the radiation characteristics of the array but increasing the gain slightly.     

基于Copula函数研究莪术-三棱药对治疗“气滞血瘀”证的方剂剂量耦合效应

目的 构建Copula函数，研究莪术Curcuma Rhizoma-三棱Sparganii Rhizoma药对治疗“气滞血瘀”证的方剂剂量耦合效应。方法 从自建方剂数据库中收集治疗“气滞血瘀”证并含莪术-三棱药对的中医方剂，对其中莪术剂量和三棱剂量进行数据处理和检验，从阿基米德Copula函数族、椭圆Copula函数族中选择出最佳的Copula函数建立数学模型，描绘联合分布函数图，测算Kendall秩相关系数和Spearman秩相关系数，监测莪术剂量和三棱剂量数据间的相关性。结果 整理归纳出505首方剂。Gaussian Copula函数模型能较好地反映莪术剂量和三棱剂量之间的相关性，莪术剂量和三棱剂量的Kendall秩相关系数为0.225 6,Spearman秩相关系数为0.333 0，说明莪术剂量和三棱剂量之间具有较强的非线性关系，且呈正相关，当剂量增加时，两者之间的耦合效应会增强。结论 基于Copula函数模型，研究莪术-三棱药对在中医方剂配伍中的剂量相关性，从数据挖掘和数理统计角度为传统经典药对相须为用提供依据，为研究中药药对在中医药方剂配伍中的剂量关系提供新思路。     

The coated antiseptic tip (CAT) syringe

Abstract

Catheter-related blood stream infections (CR-BSI) account for 30% of healthcare acquired infection (HAI). Colonization of connector hubs and contaminated syringes are thought to increase the risk of CR-BSI. The Coated Antiseptic Tip (CAT) syringe was developed to decontaminate connector hubs, thereby reducing the risk of CR-BSI. Needleless valves (n?=?20) and three-way connectors (n?=?20) were contaminated with common critical care pathogens. At hourly intervals, CAT syringes were inserted into the connector hubs and normal saline was injected through the connector. This was repeated with control (non-coated) syringes. The internal surface of the connector hubs were swabbed at t?=?0, t?=?1?h and t?=?4?h, inoculated onto blood agar plates and analysed by a blinded microbiologist. Growth was counted as the number of colony forming units. Baseline swabbing demonstrated 100% bacterial hub colonization in both connectors. The CAT syringe showed a significant reduction in CFU growth at 0 and 1?h compared with control syringes (p?<?0.05). At 4?h, the CAT syringe completely eliminated bacterial growth in both of the connector hubs. The CAT syringe can effectively disinfect both three-way and needleless connectors.     

当药苷调节兴奋-收缩耦联改善心肌缺血再灌注损伤的机制

目的 探索当药苷通过兴奋-收缩耦联信号通路对缺血再灌注损伤后心脏收缩/舒张功能的影响。方法 24只健康雄性SD大鼠随机分为正常组、模型组、10 μmol·L^-1当药苷给药组与1 μmol·L^-1地高辛给药组，并采用Langendorff系统结合左前降支冠状动脉结扎建立缺血再灌注损伤模型（I/R），2，3，5-氯化三苯基四氮唑（TTC）染色检测各组心脏梗死面积，Powerlab生理记录仪检测血流动力学参数，如左心室舒张压（LVDP）、左心室终末舒张压（LVEDP）、左心室终末收缩压（LVESP）、左心室内压最大上升速率（+dp/dt_max）和左心室内压最大下降速率（-dp/dt_max）；提取分离乳鼠原代心肌细胞（NRCMs），建立缺氧/复氧（H/R）损伤模型，随机分为正常组、模型组、1 μmol·L^-1当药苷给药组和10 μmol·L^-1当药苷给药组，多功能成像细胞分析仪和激光共聚焦显微镜测定各组心肌细胞活力、心率、收缩幅度、收缩时程、达峰时程和舒张时程及钙瞬变峰值。根据前期转录组学测序结果及文献调研，利用实时荧光定量聚合酶链式反应（Real-time PCR）检测L型钙通道相关基因（Cacnb2），细胞色素C氧化酶相关基因（Cox6a2），肌钙蛋白（Tnnc1、Tnni3、Tnnt2）、肌动蛋白（Actc1）、肌球蛋白（Myh6、Myl2、Myl4）等兴奋-收缩耦联通路基因的mRNA表达并对差异基因进行聚类分析。结果 与正常组比较，模型组心肌梗死面积显著增加（P<0.01）、LVDP显著降低（P<0.01）、LVEDP显著上升（P<0.01）、LVESP明显下降（P<0.05）、+dp/dt_max有下降趋势和-dp/dt_max上升趋势及心肌细胞活力降低、心率降低、收缩幅度降低、收缩时程升高、达峰时程升高和舒张时程升高（P<0.01），而当药苷可以逆转上述指标（P<0.05）。此外，心肌细胞经H/R损伤后，Cacnb2、Cox6a2、Tnnc1、Tnni3、Tnnt2、Actc1、Myh6、Myl2、Myl4等兴奋-收缩耦联通路的基因表达下降（P<0.05、P<0.01）。而使用当药苷预处理后，可以增强上述基因的表达（P<0.05）。结论 当药苷通过调节兴奋-收缩耦联信号通路，从而调节原代乳鼠心肌细胞内钙离子水平，增强心肌收缩功能，对抗I/R损伤。     

Effects of Aerosol-Vapor JP-8 Jet Fuel on the Functional Observational Battery,and Learning and Memory in the Rat

To determine whether JP-8 jet fuel affects parameters of the Functional Observational Battery (FOB), visual discrimination, or spatial learning and memory, the authors exposed groups of male Fischer Brown Norway hybrid rats for 28 d to aerosol/vapor-delivered JP-8, or to JP-8 followed by 15 min of aerosolized substance P analogue, or to sham-confined fresh room air. Behavioral testing was accomplished with the U.S. Environmental Protection Agency's Functional Observational Battery. The authors used the Morris swim task to test visual and spatial learning and memory testing. The spatial test included examination of memory for the original target location following 15 d of JP-8 exposure, as well as a 3-d new target location learning paradigm implemented the day that followed the final day of exposure. Only JP-8 exposed animals had significant weight loss by the 2nd week of exposure compared with JP-8 with substance P and control rats; this finding compares with those of prior studies of JP-8 jet fuel. Rats exposed to JP-8 with or without substance P exhibited significantly greater rearing and less grooming behavior over time than did controls during Functional Observational Battery open-field testing. Exposed rats also swam significantly faster than controls during the new target location training and testing, thus supporting the increased activity noted during Functional Observational Battery testing. There were no significant differences between the exposed and control groups' performances during acquisition, retention, or learning of the new platform location in either the visual discrimination or spatial version of the Morris swim task. The data suggest that although visual discrimination and spatial learning and memory were not disrupted by JP-8 exposure, arousal indices and activity measures were distinctly different in these animals.