In cities, social well-being faces obstacles posed by globalization, demographic and climate change, new forms of social organization, and the fragmentation of lifestyles. These changes affect the vulnerability of city societies and impact their health-related urban well-being (UrbWellth). The conceptual model introduced in this paper systematizes the relevant variables while considering previous research, and establishes the target value UrbWellth. The model differs from existing approaches mainly in the analytical distinctions it suggests. These allow us to group the relevant urban influence variables into four sectors and enable a more general and abstract consideration of health-related urban relations. The introduction of vulnerability as a filter and transfer function acts as an effect modifier between UrbWellth and the various urban variables. Full article

Vulvar cancer is the fourth most common gynecological cancer worldwide. However, limited studies have been completed on the molecular characterization of vulvar squamous cell carcinoma resulting in a poor understanding of the disease initiation and progression. Analysis and early detection of the precursor lesion of HPV-independent vulvar squamous cell carcinoma (VSCC), differentiated vulvar intraepithelial neoplasia (dVIN), is of great importance given dVIN lesions have a high level of malignant potential. Here we present an examination of adjacent normal vulvar epithelium, dVIN, and VSCC from six patients by peptide Matrix-assisted laser desorption/ionization Mass Spectrometry Imaging (MALDI-MSI). The results reveal the differential expression of multiple peptides from the protein cytokeratin 5 (CK5) across the three vulvar tissue types. The difference observed in the relative abundance of CK5 by MALDI-MSI between the healthy epithelium, dVIN, and VSCC was further analyzed by immunohistochemistry (IHC) in tissue from eight VSCC patients. A decrease in CK5 immunostaining was observed in the VSCC compared to the healthy epithelium and dVIN. These results provide an insight into the molecular fingerprint of the vulvar intraepithelial neoplasia that appears to be more closely related to the healthy epithelium than the VSCC. Full article

Refractometric sensors based on optical excitation of surface plasmons on the side of an optical fiber is an established sensing architecture that has enabled laboratory demonstrations of cost effective portable devices for biological and chemical applications. Here we report a Surface Plasmon Resonance (SPR) configuration realized in an Exposed Core Microstructured Optical Fiber (ECF) capable of optimizing both sensitivity and resolution. To the best of our knowledge, this is the first demonstration of fabrication of a rough metal coating suitable for spectral interrogation of scattered plasmonic wave using chemical electroless plating technique on a 10 μm diameter exposed core of the ECF. Performance of the sensor in terms of its refractive index sensitivity and full width at half maximum (FWHM) of SPR response is compared to that achieved with an unstructured bare core fiber with 140 μm core diameter. The experimental improvement in FWHM, and therefore the detection limit, is found to be a factor of two (75 nm for ECF in comparison to 150 nm for the large core fiber). Refractive index sensitivity of 1800 nm/RIU was achieved for both fibers in the sensing range of aqueous environment (1.33–1.37) suitable for biosensing applications. Full article

The ovarian cancer biomarker CA125 has been extensively investigated over the last 30 years. The knowledge about the exact molecular nature of this protein, however, remains fragmented. This review provides an overview of the structural research regarding CA125, and presents an orthogonal verification method to confirm the identity of this molecule. The need for independent identification of CA125 is exemplified by several reports where mutually exclusive data concerning the existence of isoforms and the glycan moieties is presented. Mass spectrometry can overcome the pitfalls of a single detection/identification method such as antibody probing. Independent verification of CA125 identity in characterization studies will help establish a refined model of its molecular structure that will promote the development of new approaches for diagnosis, prognosis and therapy of ovarian cancer. Full article

CA125 is the most widely used tumour marker in ovarian cancer with unsatisfactory sensitivity and specificity especially at early stage. It is quantified by antibody-based immunoassays; however different molecular weight isoforms have been described in the literature which have never been validated by mass spectrometry, potentially affecting the diagnostic accuracy and clinical reliability of the test. In this study, CA125 was detected by Western blot and its identity confirmed by mass spectrometry. Two-dimensional (2D) gel electrophoresis in combination with mass spectrometry revealed that positive Western blot signals up to 500 kDa are most likely false-positive interactions of M11-like and OC125-like antibodies. Fibronectin, identified as one of these false-positive interaction partners, increased the reading for CA125 in a first generation ELISA significantly (p = 0.02). The existence of low-molecular weight isoforms of CA125 is therefore questionable and is most likely reflecting cross-reactivity of the antibodies with other proteins. This would explain the conflicting reports on the molecular structure of CA125 and also the inconsistency of CA125 levels by different ELISAs. Our results are also the first steps towards a mass spectrometric assay for CA125 quantification, which would improve sensitivity and reliability. Full article

MALDI imaging mass spectrometry (MALDI-IMS) allows acquisition of mass data for metabolites, lipids, peptides and proteins directly from tissue sections. IMS is typically performed either as a multiple spot profiling experiment to generate tissue specific mass profiles, or a high resolution imaging experiment where relative spatial abundance for potentially hundreds of analytes across virtually any tissue section can be measured. Crucially, imaging can be achieved without prior knowledge of tissue composition and without the use of antibodies. In effect MALDI-IMS allows generation of molecular data which complement and expand upon the information provided by histology including immuno-histochemistry, making its application valuable to both cancer biomarker research and diagnostics. The current state of MALDI-IMS, key biological applications to ovarian cancer research and practical considerations for analysis of peptides and proteins on ovarian tissue are presented in this review. Full article

Most scientific efforts towards early detection of ovarian cancer are commonly focused on the discovery of tumour-associated antigens (TAA). Autologous antibodies against TAA, however, may serve as more sensitive diagnostic markers. They circulate in the blood before TAA and are usually more abundant than the TAAs themselves as a result of amplification through the humoral immune response. Accumulating evidence also suggests that a humoral response already exists during malignant transformation when aberrant gene expression is translated into premalignant cellular changes. This article reviews the current knowledge about autoantibodies against TAA in ovarian cancer and presents current immunoproteomic approaches for their detection. Full article