Computational and experimental study of proximal flow in ventricular catheters. Technical note

The treatment of hydrocephalus with shunt insertion is fraught with high failure rates. Evidence indicates that the proximal holes in a catheter are the primary sites of blockage. The authors have studied ventricular catheter designs by using computational fluid dynamics (CFD), two-dimensional water table experiments, and a three-dimensional (3D) automated testing apparatus together with an actual catheter. With the CFD model, the authors calculated that 58% of the total fluid mass flows into the catheter's most proximal holes and that greater than 80% flows into the two most proximal sets of holes within an eight-hole catheter. In fact, most of the holes in the catheters were ineffective. These findings were experimentally verified using two completely different methodologies: a water table model of a shunt catheter and a 3D automated testing apparatus with an actual catheter to visualize flow patterns with the aid of ink. Because the majority of flow enters the catheter's most proximal holes, blockages typically occur at this position, and unlike blockages at distal holes, occlusion of proximal holes results in complete catheter failure. Given this finding, new designs that incorporated varying hole pattern distributions and size dimensions of the ventricular catheter were conceived and tested using two models. These changes in the geometrical features significantly changed the entering mass flow rate distribution. In conclusion, new designs in proximal ventricular catheters with variable hole diameters along the catheter tip allowed fluid to enter the catheter more uniformly along its length, thereby reducing the probability of its becoming occluded.     

Downregulation of uPA inhibits migration and PI3k/Akt signaling in glioblastoma cells

The ability of glioma cells to migrate great distances from a primary tumor mass is the primary cause of tumor recurrence. The urokinase-type plasminogen activator (uPA) is a serine protease that can initiate proteolytic cascades, which result in remodeling of extracellular matrix and basement membrane, allowing cells to move across and through these barriers. The binding between uPA and its receptor uPAR also mediates several signaling events that seem to contribute to the evolution of a migratory phenotype. In this study, we determined how the downregulation of uPA affects the signaling pathways leading to cell migration. Stably transfecting human glioblastoma cells with antisense uPA decreased the amount of cell-bound uPA and disrupted actin cytoskeleton formation and cell migration. The phosphatidylinositol 3-kinase (PI3k) and Akt signaling pathway has been suggested to mediate migration in various cancer cells. The antisense-uPA clones also had less phosphorylated PI3k and Akt than control cells, a finding associated with decreased cell migration, G2/M-phase arrest, and decreased clonogenic survival. Decreased activation of PI3k and the antiapoptotic factor Akt was not sufficient to induce apoptosis in the antisense-uPA clones, but staurosporine sensitized them to apoptosis to a greater extent than control cells. These results indicate that PI3k/Akt pathway is involved in the signaling cascade required to induce cell migration and that uPA has a direct role in regulating migration.     

Anatomical relationships between Sylvian fissure and the sphenoid ridge

During pterional craniotomy, the sphenoid ridge is resected to facilitate the dissection of the arachnoid in the Sylvian fissure. It is a common intra-operative perception that a deep sphenoid ridge often accompanies a shallow fissure. We explored this unique relationship between the sphenoid ridge and the Sylvian fissure. We studied 46 fresh adult cadavers and measured the depth of both the sphenoid ridges and the Sylvian fissure. The deepest portion of the sphenoid ridge was determined and its depth measured by using a narrow ruler with a sliding gauge. The depth of the Sylvian fissure was measured from the middle cerebral artery bifurcation perpendicularly to the surface of the temporal pole where the arachnoid was cut. An inverse relationship exists between the Sylvian fissure and the sphenoid ridge. The depth of the sphenoid ridge averages 7.28 mm +/- 0.3 mm while the depth of the Sylvian fissure averages 9.0 mm +/- 0.4 mm. Approximately 25% of studied population have deep ridges, i.e. greater than 10 mm, and approximately 25% have shallow ridges, i.e. less than 4 mm. The extent to which the sphenoid ridge projects into the Sylvian fissure determines the depth of the Sylvian fissure thus explaining their inverse relationship. Importantly, encountering a shallow sphenoid ridge during surgery most likely will result in the dissection of a deep Sylvian fissure while a deep ridge predicts a shallow fissure.     

Activation of caspase-9 with irradiation inhibits invasion and angiogenesis in SNB19 human glioma cells

Glioblastoma multiforme, the most common brain tumor, typically exhibits markedly increased angiogenesis, which is crucial for tumor growth and invasion. Antiangiogenic strategies based on disruption of the tumor microvasculature have proven effective for the treatment of experimental brain tumors. Here, we have overexpressed human caspase-9 by stable transfection in the SNB19 glioblastoma cell line, which normally expresses low levels of caspase-9. Our studies revealed that overexpression of caspase-9 coupled with radiation has a synergistic effect on the inhibition of glioma invasion as demonstrated by Matrigel assay (> 65%). Furthermore, sense caspase stable clones cocultured with fetal rat brain aggregates along with radiation showed complete inhibition as compared to the parental and vector controls. During in vitro angiogenesis, SNB19 cells cocultured with human microvascular endothelial cells (HMEC) showed vascular network formation after 48-72 h. In contrast, these capillary-like structures were inhibited when HMEC cells were cocultured with sense caspase stable SNB19 cells. This effect was further enhanced by radiation (5 Gy). Signaling mechanisms revealed that apoptosis is induced by cleavage of caspase-9 by radiation, loss of mitochondrial membrane potential and activation of caspase-3. These results demonstrate that activation of caspase-9 disrupts glioma cell invasion and angiogenesis in vitro. Hence, overexpression of proapoptotic molecules such as caspase-9 may be an important determinant of the therapeutic effect of radiation in cancer therapy.     

Methods of early detection： would clinical breastexamination and breast ultrasonography be a good alternative to mammography？

Breast cancer is one of the leading causes of cancer deaths among women[1].In the past 40 years,breast cancer incidence has doubled or even tripled in developed countries such as South Korea and Japan; whereas it is about 20% to 30% in China and India in the past decade[2-4]. An increasing incidence rate of 3%     

Healthcare Workers’ (HCWs) attitudes towards mandatory influenza vaccination: A systematic review and meta-analysis

Influenza is a disease responsible for thousands of deaths every year. Although healthcare workers (HCWs) represent a way of contagion for patients, vaccination coverage among them is low. Mandatory vaccination has been proposed, but controversies remain. This systematic review and meta-analysis aimed to assess the acceptance of mandatory vaccination by HCWs, and to investigate associated characteristics. MEDLINE, Scopus, Embase, PsycInfo, CINAHL and Web of Science were used to search for studies assessing the topic. PRISMA statements were followed. Of the 13,457 univocal records found, 52 studies were included in the systematic review and 40 in the meta-analysis. The pooled proportion of HCWs accepting the policy was of 61% (95% CI: 53%- 68%) but with great heterogeneity between continents (from 54% in Europe to 69% in Asia) and in different professionals (from 40% in nurses to 80% in students). Vaccinated HCWs agreed more frequently with mandatory vaccination than non-vaccinated ones. More studies that consider mandatory vaccination acceptance as the main outcome are needed, but the results of this study confirm that in some settings the majority of HCWs favour mandatory vaccination. This, combined with effects that a flu epidemic could have if overlapped to pandemics with similar symptoms, requires renewed considerations on mandatory vaccination.