A prospective observational study of the effects of treatment with extended-release tolterodine on health-related quality of life of patients suffering overactive bladder syndrome in Sweden.

OBJECTIVE: Overactive bladder (OAB) is a chronic condition that has a profound impact on health-related quality of life (HRQoL). This study measured changes in bother of OAB symptoms and self-perceived HRQoL over 6 months in patients treated with extended-release (ER) tolterodine in a naturalistic setting. MATERIAL AND METHODS: This was a prospective, single-cohort observational study of patients diagnosed with OAB, naïve to antimuscarinic treatment and prescribed tolterodine ER for the first time. Patients were asked to complete the Overactive Bladder Questionnaire (OAB-q) containing a symptom bother scale (0-100) and an HRQoL scale (0-100), which measures coping, social interaction, concern and sleep, at baseline and after 3 and 6 months. RESULTS: In total, 235 patients (211 women and 24 men), with a mean age of 61 years (30-87), were recruited. The numbers of patients who completed the OAB-q were 220 and 169 at 3 and 6 months, respectively. The mean reductions in the symptom bother score from baseline were 19.6 and 19.3 at 3 and 6 months, respectively. Significant improvement (p < 0.0001) was seen in all HRQoL subscale scores. The proportion of responders who met the minimally important difference (change in the score of 10 or more units between baseline and 6 months) was 64% for the symptom bother score and 34-60% for the total HRQoL and subscale scores. CONCLUSIONS: OAB patients beginning treatment with tolterodine ER reported clinically significant improvement in OAB symptoms and self-perceived HRQoL over the 6 months of this observational study. The rate of discontinuation from treatment was 49%.

Response of rat osteoblast-like cells to microstructured model surfaces in vitro.

The role of surface microtopography in combination with different surface wettability for rat calvaria cell differentiation was examined. Mineralization and alkaline phosphatase (ALP) activity of rat calvaria cells on flat polydimethylsiloxane (PDMS) or PDMS contained pyramids which were either hydrophilic or hydrophobic were compared. ALP expressing cells were more frequent on hydrophilic PDMS contained pyramids. ALP activity, peaked at day 9, was highest for hydrophilic pyramids followed by hydrophobic pyramids and flat hydrophilic PDMS surfaces. A similar pattern was obtained with respect to mineralized nodules. These observations showed that micro-sized surface features promote differentiation of rat calvaria cells. Further, hydrophilic surfaces are more prone to stimulate differentiation in comparison with hydrophobic surfaces. The results suggest that both material surface chemistry and topography affect osteoblast differentiation.

Nanoscale features influence epithelial cell morphology and cytokine production.

Available, easy and fast fabrication methods of nanostructured surfaces, and the knowledge that cells in vivo interacts with nanometer-sized structures/objects, led us to study the impact of nanotopography on cell morphology and cytokine production. Uroepithelial cells were seeded on three different substrate types: two with defined nanometer topographies and a flat control, all three having identical surface chemistry. The nanostructured substrates contained hemispherical pillars or step edges, the latter in the form of parallel grooves and ridges. Qualitative and quantitative analysis of cell morphology and cytokine production were studied. Both quantities were significantly different between cells cultured on hemispherically structured surfaces compared to flat control surfaces. Cells cultured on hemispherically structured surfaces showed a decrease in IL-6 and IL-8 production and were less spread, less round and more stellate (larger dispersion). Only cell morphology differed between cells cultured on grooved surfaces and flat control surfaces. These findings suggest that epithelial cell morphology and cytokine production are dependent on the underlying nanotopography.

Influence of systematically varied nanoscale topography on the morphology of epithelial cells.

With the knowledge that cells can react to lithographically manufactured nanometer-sized surface objects, our interest concerned whether cells would respond to surface structures of systematically increasing size. Our approach to answer this question was to fabricate surfaces with the same surface chemistry and similar surface roughness but increasing size of structural features. To fabricate large areas of patterned surfaces, required for cell culture studies, we used colloidal lithography utilizing colloidal particles as a template for surface nanostructuring. The fabricated surfaces contained hemispherical nanopillars with diameters ranging from 60 to 170 nm. Changes in cell morphology of a pancreatic epithelial cell line (AR4-2J) were studied by evaluating cell area and cell shape. The latter was studied by applying the cell shape classification method using three shape descriptors. The pancreatic cells responded in a systematic way to the surface nanostructures. The cells spread more and became more nonround when cultured on surfaces with increasing size of the topographic features. Index Terms-Biological cells, image analysis, nanotechnology, shape measurement, surfaces.

Cell adhesion on supported lipid bilayers.

The cell and protein repellent properties of supported phospholipid bilayer (SPB) membranes were investigated. The SPBs were prepared by vesicle adsorption on SiO(2) surfaces. The vesicles of phosphatidylcholine fuse and rupture, and form a supported bilayer covering the surface. We carried out cell culture experiments on several surfaces, including SPBs, using two types of epithelial cells to address the cell adhesional properties. The Quartz Crystal Microbalance Dissipation (QCM-D) technique was used to monitor the SPB formation and subsequent protein adsorption. Neither cell type adhered or proliferated on SiO(2) surfaces coated with SPBs, whereas both cell types adhered and proliferated on the three control surfaces of SiO(2), tissue culture glass, and TiO(2). The QCM-D measurements showed that about two orders of magnitude less mass adsorbed on a SPB surface compared to a TiO(2) surface, from serum-containing media (10% fetal bovine serum). The reduced adsorption on the SPB is a likely explanation for the nondetectable epithelial cell adhesion on the SPB surface. Biomembranes are therefore attractive candidate systems to achieve alternating cell-resistant and cell-interacting regions on surfaces, by including specific cell-binding proteins in the latter regions.

Linking the Resource Description Framework to cheminformatics and proteochemometrics.

BACKGROUND: Semantic web technologies are finding their way into the life sciences. Ontologies and semantic markup have already been used for more than a decade in molecular sciences, but have not found widespread use yet. The semantic web technology Resource Description Framework (RDF) and related methods show to be sufficiently versatile to change that situation. RESULTS: The work presented here focuses on linking RDF approaches to existing molecular chemometrics fields, including cheminformatics, QSAR modeling and proteochemometrics. Applications are presented that link RDF technologies to methods from statistics and cheminformatics, including data aggregation, visualization, chemical identification, and property prediction. They demonstrate how this can be done using various existing RDF standards and cheminformatics libraries. For example, we show how IC50 and Ki values are modeled for a number of biological targets using data from the ChEMBL database. CONCLUSIONS: We have shown that existing RDF standards can suitably be integrated into existing molecular chemometrics methods. Platforms that unite these technologies, like Bioclipse, makes this even simpler and more transparent. Being able to create and share workflows that integrate data aggregation and analysis (visual and statistical) is beneficial to interoperability and reproducibility. The current work shows that RDF approaches are sufficiently powerful to support molecular chemometrics workflows.

Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups. METHODS: Short-term (<20 month; n = 53) and long-term survivors (>58 month; n = 47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh frozen tumor specimens. The samples were analyzed using high-resolution single-nucleotide polymorphism array technology to assess gene copy number variations and array-based gene expression profiling. The molecular data were combined with information on clinical parameters. RESULTS: Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n = 50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term than in short-term survivors. In squamous cell carcinoma (n = 28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, messenger RNA expression levels of corresponding genes were increased or decreased, respectively. CONCLUSION: Comprehensive tumor profiling permits the integration of genomic, histologic, and clinical data. We identified gene copy number gains and losses, with corresponding changes in messenger RNA levels that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung.

The effects of continuous and discontinuous groove edges on cell shape and alignment.

Nanofabricated model surfaces and digital image analysis of cell shape were used to address the importance of a continuous sharp edge in the alignment of cells to shallow surface grooves. The grooved model surfaces had either continuous or discontinuous edges of various depths (40-400 nm) but identical surface chemistry and groove/ridge dimensions (15 microm wide). Epithelial cells were cultured on the model surfaces for 10 and 24 h. Fluorescence microscopy combined with image analysis were used to quantify cell area and alignment and to make cell shape classifications of individual cells. The degrees of alignment of cells and the percentages of elongated cell classes increased with groove depth on samples with continuous grooves. Two main differences, with regard to cell response, were observed between the continuous and discontinuous grooved surfaces. First, significantly fewer cells aligned to surface grooves with discontinuous edges than to grooves with continuous edges. Second, there were lower percentages of the elongated cell classes on discontinuous grooves than on continuous ones. We concluded that grooved surfaces with continuous edges are more potent in aligning and inducing elongated cells. The results from the present study suggest that a mechanism of alignment involving orientation along a continuous edge is likely.