Brain-specific gene expression by immortalized microglial cell-mediated gene transfer in the mammalian brain

AbstractThe intra-arterial injection of immortalized microglia transfected with the lacZ gene, resulted in the expression of β-galactosidase in the rat brain at 48 h and the activity of β-galactosidase was detected for up to 3 weeks post-injection. More than 30-fold higher activity of β-galactosidase was detected in the brain than in the liver, lung or spleen at 48 h post-injection. This method allows us to easily deliver the gene of interest to the brain without influencing other organs. Our brain-targeting gene delivery system can facilitate gene therapy of several brain disorders, including brain tumor, metabolic disorders, and degenerative disorders, as well as investigation into the roles of particular genes in brain function and development

Unruptured Arteriovenous Malformations of Brain: An overview

Arteriovenous malformations are congenital lesions that occur most commonly in the supratentorial region. These space-occupying vascular lesions consist of multiple arteries and veins, connecting as a fistula without an intervening normal capillary bed. Typically, AVM’s are single lesions, except when associated with hereditary hemorrhagic telangiectasia. The histology includes clusters of normal or dilated arteries and abnormal veins with calcification and occasionally some prior haemorrhage

Polychlorinated biphenyl (118) activates osteoclasts and induces bone resorption in goldfish

To analyze the effect of polychlorinated biphenyl (PCB) 118 on fish bone metabolism, we examined osteoclastic and osteoblastic activities, as well as plasma calcium levels, in the scales of PCB (118)-injected goldfish. In addition, effect of PCB (118) on osteoclasts and osteoblasts was investigated in vitro. Immature goldfish, in which the endogenous effects of sex steroids are negligible, were used. PCB (118) was solubilized in dimethyl sulfoxide at a concentration of 10 ppm. At 1 and 2 days after PCB (118) injection (100 ng/g body weight), both osteoclastic and osteoblastic activities, and plasma calcium levels were measured. In an in vitro study, then, both osteoclastic and osteoblastic activities as well as each marker mRNA expression were examined. At 2 days, scale osteoclastic activity in PCB (118)-injected goldfish increased significantly, while osteoblastic activity did not change significantly. Corresponding to osteoclastic activity, plasma calcium levels increased significantly at 2 days after PCB (118) administration. Osteoclastic activation also occurred in the marker enzyme activities and mRNA expressions in vitro. Thus, we conclude that PCB (118) disrupts bone metabolism in goldfish both in vivo and in vitro experiments. © 2012 The Author(s)

Extremely Low Recombination Velocity on Crystalline Silicon Surfaces Realized by Low-Temperature Impurity Doping in Cat-CVD Technology

To reduce surface recombination velocity (SRV) at the interface between amorphous Si (a-Si) and crystalline silicon (c-Si), we particularly investigated the treatment of c-Si surface prior to a-Si deposition using decomposed radicals of hydrogen (H_2) and phosphine (PH_3). The SRV can be reduced dramatically to 1.6 cm/s only for n-type c-Si, while no such reduction is observed in p-type c-Si. Secondary ion mass spectrometry (SIMS) and the Hall effect measurement actually reveal the existence of phosphorus (P) atoms in c-Si near the surface

Uncertainty quantification in cerebral circulation simulations focusing on the collateral flow: Surrogate model approach with machine learning.

Collateral circulation in the circle of Willis (CoW), closely associated with disease mechanisms and treatment outcomes, can be effectively investigated using one-dimensional-zero-dimensional hemodynamic simulations. As the entire cardiovascular system is considered in the simulation, it captures the systemic effects of local arterial changes, thus reproducing collateral circulation that reflects biological phenomena. The simulation facilitates rapid assessment of clinically relevant hemodynamic quantities under patient-specific conditions by incorporating clinical data. During patient-specific simulations, the impact of clinical data uncertainty on the simulated quantities should be quantified to obtain reliable results. However, as uncertainty quantification (UQ) is time-consuming and computationally expensive, its implementation in time-sensitive clinical applications is considered impractical. Therefore, we constructed a surrogate model based on machine learning using simulation data. The model accurately predicts the flow rate and pressure in the CoW in a few milliseconds. This reduced computation time enables the UQ execution with 100 000 predictions in a few minutes on a single CPU core and in less than a minute on a GPU. We performed UQ to predict the risk of cerebral hyperperfusion (CH), a life-threatening condition that can occur after carotid artery stenosis surgery if collateral circulation fails to function appropriately. We predicted the statistics of the postoperative flow rate increase in the CoW, which is a measure of CH, considering the uncertainties of arterial diameters, stenosis parameters, and flow rates measured using the patients' clinical data. A sensitivity analysis was performed to clarify the impact of each uncertain parameter on the flow rate increase. Results indicated that CH occurred when two conditions were satisfied simultaneously: severe stenosis and when arteries of small diameter serve as the collateral pathway to the cerebral artery on the stenosis side. These findings elucidate the biological aspects of cerebral circulation in terms of the relationship between collateral flow and CH

Large Residual Volume, Not Low Packing Density, Is the Most Influential Risk Factor for Recanalization after Coil Embolization of Cerebral Aneurysms.

BACKGROUND:Tight coil packing with density of at least 20%-25% is known to be important for preventing recanalization after embolization of cerebral aneurysms. However, large aneurysms sometimes recanalize regardless of the packing density, suggesting that the absolute residual volume which is determined by aneurysm volume and packing density may be more important risk factor for recanalization. To validate this hypothesis, we analyzed the factors affecting the outcomes of treated aneurysms at our institute. METHODS AND FINDINGS:We included 355 small and large aneurysms. The following six factors were obtained from every case: aneurysm volume (mL), neck size (mm), packing density (%), residual volume (mL), rupture status at presentation, and stent assistance (with or without stent). The data were then subjected to multivariate logistic regression analysis to identify significant risk factors for recanalization. Recanalization occurred in 61 aneurysms (17.2%). Significant predictors for recanalization were aneurysm volume (odds ratio, 15.3; P < 0.001) and residual volume (odds ratio, 30.9; P < 0.001), but not packing density (odds ratio, 0.98; P = 0.341). These results showed that for each 0.1-mL increase in aneurysm volume and residual volume, the risk of recanalization increased by 1.3 times and 1.4 times, respectively. CONCLUSIONS:The most influential risk factor for recanalization after coil embolization was residual volume, not packing density. The larger the aneurysm volume, the greater the packing density has to be to minimize the residual volume and risk of recanalization. Since tight coil packing has already been aimed, further innovation of coil property or embolization technique may be needed. Otherwise, different treatment modality such as flow diverter or parent artery occlusion may have to be considered

Multivariate logistic regression analysis with five variables (packing density, aneurysm volume, neck, stent, and ruptured aneurysm).

<p>Multivariate logistic regression analysis with five variables (packing density, aneurysm volume, neck, stent, and ruptured aneurysm).</p

Multivariate logistic regression analysis with four variables (residual volume, neck, stent, and ruptured aneurysm).

<p>Multivariate logistic regression analysis with four variables (residual volume, neck, stent, and ruptured aneurysm).</p