Iron Labeling and Pre-Clinical MRI Visualization of Therapeutic Human Neural Stem Cells in a Murine Glioma Model

Treatment strategies for the highly invasive brain tumor, glioblastoma multiforme, require that cells which have invaded into the surrounding brain be specifically targeted. The inherent tumor-tropism of neural stem cells (NSCs) to primary and invasive tumor foci can be exploited to deliver therapeutics to invasive brain tumor cells in humans. Use of the strategy of converting prodrug to drug via therapeutic transgenes delivered by immortalized therapeutic NSC lines have shown efficacy in animal models. Thus therapeutic NSCs are being proposed for use in human brain tumor clinical trials. In the context of NSC-based therapies, MRI can be used both to non-invasively follow dynamic spatio-temporal patterns of the NSC tumor targeting allowing for the optimization of treatment strategies and to assess efficacy of the therapy. Iron-labeling of cells allows their presence to be visualized and tracked by MRI. Thus we aimed to iron-label therapeutic NSCs without affecting their cellular physiology using a method likely to gain United States Federal Drug Administration (FDA) approval.For human use, the characteristics of therapeutic Neural Stem Cells must be clearly defined with any pertubation to the cell including iron labeling requiring reanalysis of cellular physiology. Here, we studied the effect of iron-loading of the therapeutic NSCs, with ferumoxide-protamine sulfate complex (FE-Pro) on viability, proliferation, migratory properties and transgene expression, when compared to non-labeled cells. FE-Pro labeled NSCs were imaged by MRI at tumor sites, after intracranial administration into the hemisphere contralateral to the tumor, in an orthotopic human glioma xenograft mouse model.FE-Pro labeled NSCs retain their proliferative status, tumor tropism, and maintain stem cell character, while allowing in vivo cellular MRI tracking at 7 Tesla, to monitor their real-time migration and distribution at brain tumor sites. Of significance, this work directly supports the use of FE-Pro-labeled NSCs for real-time tracking in the clinical trial under development: "A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically modified Neural Stem Cells Expressing Escherichia coli Cytosine Deaminase for Treatment of Recurrent High-Grade Gliomas"

MAT foundation design reference for Metro Manila

To design mat foundation, there are certain values which are required for calculations and analyses, one of which would be the vertical modulus of subgrade reaction. It can be obtained through various deterministic testings such as the Plate Load Test. On the other hand, the study calculated this factor through the use of Standard Penetration Test (SPT) results by using four methods that were obtained from the review of related literature, namely, by definition of the said parameter (Das, 2008), by standard equation (Vesic, 1961), by empirical models (Moayed & Naeini, 2006 Ou, 2006), and by the equation formulated by Bowles (Bowles, 1995). Comparative study and validation were also performed to confirm the most recommendable method to be used to compute for the soil spring constant, given the limitations of the SPT results, by correlation of this parameter to the California Bearing Ratio (CBR) test results. Through this, the study considered and used the equation formulated by Bowles to calculate for the vertical modulus of subgrade reaction. Then, a Geographic Information Systems (GIS) software was utilized to generate maps of these values by the method of ordinary kriging. These maps presented the locations with the predominantly high and low values of the soil spring constant. They were also used to create a digitized reference of the values of the vertical modulus of subgrade reaction for the design of mat foundations for preliminary design through the use of Visual Basic Applications 2010

Mat foundation design reference for Metro Manila, Philippines

© Int. J. of GEOMATE. To design mat foundations, there are certain values which are required for calculations and analyses, one of which would be the vertical modulus of subgrade reaction. It can be obtained through various deterministic tests such as the Plate Load Test. On the other hand, the study calculated this factor through the use of Standard Penetration Test (SPT) results by using four different methods. Comparative study and validation were also performed to confirm the most recommendable method to be used to compute for the soil spring constant, given the limitations of the SPT results, by correlation of this parameter to the California Bearing Ratio (CBR) test results. Through this, the study considered and used the equation formulated by Bowles to calculate the vertical modulus of subgrade reaction. Then, a Geographic Information Systems (GIS) software was utilized to generate maps of these values by the method of ordinary kriging. These maps presented the locations with the predominantly high and low values of the soil spring constant. They were also used to create a digitized reference of the values of the vertical modulus of subgrade reaction for the design of mat foundations for preliminary design through the use of Visual Basic Applications 2010

A Study on the relationship between intangible assets and stock price volatility of listed firms in the Philippine Stock Exchange: Year 2004 - 2013

The study was conducted to explore the relationship between the intangible assets and stock price volatility of companies listed in the Philippine Stock Exchange. The study checks if the intensity of intangible assets found in companies annual reports affects the volatility of their stock price. In some cases, it was expected that intangible assets intensity would result to a positive effect on stock price volatility. The study used data from the 58 sampled publicly-listed companies with data 2004 to 2013. These firms were selected from four different industry groups: service, financial, industrial, and property. The data was analyzed using the SAS software to determine if intangible assets have a significant effect on stock price volatility. An OLS regression was run and results from the entire data showed insignificant relationship between intangible assets and stock price volatility. Results from the study suggest that apart from the variables used, there may be other factors that affect the relationship of intangible assets with stock price volatility. Given that the Philippine market is relatively young and still developing as compared to markets of developed countries, the concept and utilization of intangible assets might not be perceived as significant and impactful. Future studies should then focus on how firms account for their intangible assets to understand the effect of book value to the volatility of their stock prices. In addition, future studies should consider the perspective of investors and stakeholders on what role intangibles asset can play in order to maintain their firms value and position in the Philippine market

Correlation of compliance to infection control measures in the incidence of occupational-related exposure among nurses assigned in intensive care units of De La Salle University Medical Center

The study aimed to correlate the compliance of nurses in the different ICUs to their incidences of occupational-related exposure in De La Salle University Medical Center (DLSUMC). It also determined the relationship between incidence and compliance separately towards the different ICUs. The data was collected through a questionnaire and analyzed through a Pearson chi-square test and frequency. Out of the 44 responses, results showed that ICU nurses in DLSUMC were highly compliant to different infection control measures. However, the relationship between the compliance of nurses in infection control measures towards the incidence of occupational-related exposure was found to be non-significant. The significant value for each occupational-related exposure are as follows: incurrence of needle stick or sharp-related injury (sig. 0.139\u3e0.05), incurrence of splashing or mucosal injury (sig. 0.969\u3e0.05) and exposure to communicable diseases without proper protection (sig. 0.139\u3e0.05). Meanwhile, the relationship between the departments of the Intensive Care Units (ICUs) and incidence of occupational-related exposure among nurses was found to be significant since significant value was (sig. 0.00

MRI Visualization of FE-Pro-labeled NSCs targeting human glioma in an orthotopic mouse model.

<p>(A) Consecutive T2-weighted MR images of mouse brain in 30% sucrose and 4% PFA. FE-Pro-labeled NSCs are shown as hypointense (dark) signals (white dotted boxes) in the left hemisphere and in the contralateral right hemisphere, where human U251 glioma cells were implanted. (B) Higher magnification, Prussian blue stained sections from the areas outlined by the boxes in (A) (top, left hemisphere; bottom, right hemisphere, tumor area outlined by black dotted line). (C) Consecutive T2-weighted MRI images of mouse brain in Fomblin that received PBS sham injection on left hemisphere and human glioma U251 on the right hemisphere. No low-intensity signals were detected in this control. (D) Higher magnification, Prussian blue stained sections from the areas outlined by the boxes in (C) (top, left hemisphere; bottom, right hemisphere, tumor area outlined by black dotted line). MRI conditions: 7.0 Tesla, Rapid Acquisition Relaxation Enhancement sequence, 78 µm/pixel, 300 µm/slice, T_R/T_E = 1500/23.1 ms. Scale bars = 100 µm (B and D).</p

Cellular viability of FE-Pro-labeled NSCs.

<p>(A) Cellular biomass normalized to non-labeled NSC cell growth at day 1 as measured by absorbance of protein-bound sulforhodamine B (SRB) at 570 nm. Data are mean±SE of triplicate samples and were analyzed using paired t-test between non-labeled vs. each FE-Pro dosage. P<0.05 was considered statistically significant. (B) Representative FACS plots showing the viable and apoptotic cell populations at 24 hours post-label and before sub-culturing. (C–D) Bar graphs showing the percentage of healthy cells at days 1, 4 and 8 for non-labeled NSCs (C), and FE-Pro-labeled NSCs (D) after sub-culturing passage at each time point. (E): Confocal images of healthy FE-Pro labeled and non-labeled NSCs (left panel) and apoptosis-induced FE-Pro labeled and non-labeled NSCs (right panel) at Day 6 post-labeling. Staining: PI (red), YO-Pro-1 (green). A FE-Pro dosage of 50∶3 µg/ml was used for each labeled sample unless otherwise indicated. Abbreviations: FE-Pro, Ferumoxide-Protamine Sulfate complex; PI, propidium iodide; Magnification: 20×.</p

Retention of FE-Pro label in HB1.F3.CD NSCs.

<p>Data is displayed as means +/− SD of Prussian blue positive iron-loaded NSCs (% of total cell number). The data were obtained from 5 random fields of each independently labeled triplicate sample at 24, 48 and 96 h post-labeling.</p