Nitric oxide releasing plasma polymer coating with bacteriostatic properties and no cytotoxic side effects

Published on 19 March 2015We report a stable plasma polymer coating, using isopentyl nitrite as a volatile precursor, which releases nitric oxide at bacteriostatic concentrations when contacted with water, inhibiting bacterial growth without cytotoxic side effects to human mesenchymal stem/stromal cells.Thomas D. Michl, Bryan R. Coad, Michael Doran, Michael Osiecki, Morteza Hasanzadeh Kafshgari, Nicolas H. Voelcker, Amanda Hüsler, Krasimir Vasilev and Hans J. Griesse

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Mortality of glioblastoma multiforme (GBM) has not improved over the last two decades despite medical breakthroughs in the treatment of other types of cancers. Nanoparticles hold tremendous promise to overcome the pharmacokinetic challenges and off-target adverse effects. However, an inhibitory effect of nanoparticles by themselves on metastasis has not been explored. In this study, we developed transferrin-conjugated porous silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting GBM migration by means of a microfluidic-based migration chip. This platform, designed to mimic the tight extracellular migration tracts in brain parenchyma, allowed high-content time-resolved imaging of cell migration. Tf@pSiNP were colloidally stable, biocompatible, and their uptake into GBM cells was enhanced by receptor-mediated internalisation. The migration of Tf@pSiNP-exposed cells across the confined microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced destabilisation of focal adhesions at the leading front may partially explain the migration inhibition. More corroborating evidence suggests that pSiNP uptake reduced the plasticity of GBM cells in reducing cell volume, an effect that proved crucial in facilitating migration across the tight confined tracts. We believe that the inhibitory effect of Tf@pSiNP on cell migration, together with the drug-delivery capability of pSiNP, could potentially offer a disruptive strategy to treat GBM.</p

Oxygen-permeable microwell device maintains islet mass and integrity during shipping

Islet transplantation is currently the only minimally invasive therapy available for patients with type 1 diabetes that can lead to insulin independence; however, it is limited to only a small number of patients. Although clinical procedures have improved in the isolation and culture of islets, a large number of islets are still lost in the pre-transplant period, limiting the success of this treatment. Moreover, current practice includes islets being prepared at specialized centers, which are sometimes remote to the transplant location. Thus, a critical point of intervention to maintain the quality and quantity of isolated islets is during transportation between isolation centers and the transplanting hospitals, during which 20-40% of functional islets can be lost. The current study investigated the use of an oxygen-permeable PDMS microwell device for long-distance transportation of isolated islets. We demonstrate that the microwell device protected islets from aggregation during transport, maintaining viability and average islet size during shipping.Darling M Rojas-Canales, Michaela Waibel, Aurelien Forget, Daniella Penko, Jodie Nitschke, Fran J Harding, Bahman Delalat, Anton Blencowe, Thomas Loudovaris, Shane T Grey, Helen E Thomas, Thomas W H Kay, Chris J Drogemuller, Nicolas H Voelcker, and Patrick T Coate

Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4 and 9 in breast cancer.</p> <p>Methods</p> <p>The expression levels of TLR3, TLR4 and TLR9 were analyzed on tumors from 74 patients with breast cancer. The analysis was performed by immunohistochemistry.</p> <p>Results</p> <p>Samples of carcinomas with recurrence exhibited a significant increase in the mRNA levels of TLR3, TLR4 and TLR9. Tumors showed high expression of TLRs expression levels by cancer cells, especially TLR4 and 9. Nevertheless, a significant percentage of tumors also showed TLR4 expression by mononuclear inflammatory cells (21.6%) and TLR9 expression by fibroblast-like cells (57.5%). Tumors with high TLR3 expression by tumor cell or with high TLR4 expression by mononuclear inflammatory cells were significantly associated with higher probability of metastasis. However, tumours with high TLR9 expression by fibroblast-like cells were associated with low probability of metastasis.</p> <p>Conclusions</p> <p>The expression levels of TLR3, TLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness in breast cancer. TLRs may represent therapeutic targets in breast cancer.</p

On the nature of the galactic early-B hypergiants

Despite their importance to a number of astrophysical fields, the lifecycles of very massive stars are still poorly defined. In order to address this shortcoming, we present a detailed quantitative study of the physical properties of four early-B hypergiants (BHGs); Cyg OB2 #12, zeta Sco, HD190603 and BP Cru. These are combined with an analysis of their long-term spectroscopic and photometric behaviour in order to determine their evolutionary status. The long-term datasets revealed that they are remarkably stable over long periods (>40yr), with the possible exception of zeta Sco prior to the 20th century, in contrast to the typical excursions that characterise luminous blue variables (LBVs). Zeta Sco, HD190603 and BP Cru possess physical properties intermediate between B supergiants and LBVs; we therefore suggest that BHGs are the immediate descendants and progenitors (respectively) of such stars (for initial masses in the range ~30-60Msun). In contrast, while the wind properties of Cyg OB2 #12 are consistent with this hypothesis, the combination of extreme luminosity and spectroscopic mass (~110Msun) and comparatively low temperature means it cannot be accommodated in such a scheme. Likewise, despite its co-location with several LBVs above the Humphreys-Davidson (HD) limit, the lack of long term variability and its unevolved chemistry apparently excludes such an identification. Since such massive stars are not expected to evolve to such cool temperatures, the properties of Cyg OB2 #12 are difficult to understand under current evolutionary paradigms. [ABRIDGED]Comment: 36 pages, 19 figures (of which 17 pages are online supplemental material). Accepted for publication in Astronomy and Astrophysic

A psycho-Geoinformatics approach for investigating older adults’ driving behaviours and underlying cognitive mechanisms

Introduction: Safe driving constantly challenges the driver’s ability to respond to the dynamic traffic scene under space and time constraints. It is of particular importance for older drivers to perform sufficient visual and motor actions with effective coordination due to the fact of age-related cognitive decline. However, few studies have been able to integrate drivers’ visual-motor behaviours with environmental information in a spatial-temporal context and link to the cognitive conditions of individual drivers. Little is known about the mechanisms that underpin the deterioration in visual-motor coordination of older drivers. Development: Based on a review of driving-related cognitive decline in older adults and the context of driver-vehicle-environment interactions, this paper established a conceptual framework to identify the parameters of driver’s visual and motor behaviour, and reveal the cognitive process from visual search to vehicle control in driving. The framework led to a psycho-geoinformatics approach to measure older drivers’ driving behaviours and investigate the underlying cognitive mechanisms. The proposed data collection protocol and the analysis and assessments depicted the psycho-geoinformatics approach on obtaining quantified variables and the key means of analysis, as well as outcome measures. Conclusions: Recordings of the driver and their interactions with the vehicle and environment at a detailed scale give a closer assessment of the driver’s behaviours. Using geoinformatics tools in driving behaviours assessment opens a new era of research with many possible analytical options, which do not have to rely on human observations. Instead, it receives clear indicators of the individual drivers’ interactions with the vehicle and the traffic environment. This approach should make it possible to identify lower-performing older drivers and problematic visual and motor behaviours, and the cognitive predictors of risky driving behaviours. A better targeted regulation and tailored intervention programs for older can be developed by further research

Does the diurnal cycle of cortisol explain the relationship between physical performance and cognitive function in older adults?

Background Regular physical activity is a promising strategy to treat and prevent cognitive decline. The mechanisms that mediate these benefits are not fully clear but physical activity is thought to attenuate the harmful effects of chronic psychological stress and hypercortisolism on cognition. However, the circadian pattern of cortisol secretion is complex and it is not known which aspects are most closely associated with increased cognitive function and better physical performance. This is the first study to simultaneously measure cognitive function, the diurnal cycle of salivary cortisol and physical performance in older adults, without cognitive impairment (n = 30) and with amnestic Mild Cognitive Impairment (aMCI) (n = 30). Results Regression analysis showed that better cognitive function was associated with better physical performance. A greater variance in cortisol levels across the day from morning to evening was associated with better cognitive function and physical performance. Conclusions The results support the idea that a more dynamic cortisol secretion pattern is associated with better cognitive function and physical performance even in the presence of cognitive impairment, but our results could not confirm a mediating role in this relationship

Motor skill learning in the middle-aged: limited development of motor chunks and explicit sequence knowledge

The present study examined whether middle-aged participants, like young adults, learn movement patterns by preparing and executing integrated sequence representations (i.e., motor chunks) that eliminate the need for external guidance of individual movements. Twenty-four middle-aged participants (aged 55–62) practiced two fixed key press sequences, one including three and one including six key presses in the discrete sequence production task. Their performance was compared with that of 24 young adults (aged 18–28). In the middle-aged participants motor chunks as well as explicit sequence knowledge appeared to be less developed than in the young adults. This held especially with respect to the unstructured 6-key sequences in which most middle-aged did not develop independence of the key-specific stimuli and learning seems to have been based on associative learning. These results are in line with the notion that sequence learning involves several mechanisms and that aging affects the relative contribution of these mechanisms