Staphylococcus aureus binding proteins for prevention of orthopaedic implant-related infections

Orthopaedic implant infections are an increasing problem and management commonly involves implant removal with serious consequences. Biofilm-forming Staphylococci are the most common causative organisms, with Staphylococcus aureus being the most virulent and MRSA increasingly involved. Initial bacterial adhesion is a crucial event in biofilm formation and infection establishment. Directing host antibody against bacterial factors involved in adhesion and biofilm formation may significantly inhibit infection establishment on biomaterials. Two recombinant S. aureus-derived binding proteins (FnBP, IsdA) were investigated as potential vaccine antigens and resultant antibody was assessed to determine whether immune inhibition of bacteria-ligand binding can significantly impact on attachment to plasma-conditioned biomaterial surfaces, in the presence of other bacterial ligands. Adhesion of homologous and heterologous (clinical MRSA) S. aureus to plasma-conditioned steel was significantly reduced (~50% average reduction, p & #60;0.0001) when pre-exposed to anti-rFnBP-A antiserum that was 50-fold more dilute than the actual titre from immunisation. Inhibition was related to ligand presence and not staphylococcal Protein A. Reduced adhesion was not observed with an FnBP-mutant strain, indicating specific inhibitory antibody involvement, and demonstrating the potential of rFnBP-A for prevention of S. aureus implantrelated infection. Adhesion-inhibitory activity was also observed with a purified IgG-fraction of rIsdA antiserum but this activity appeared to be masked by non-IsdA-related interactions when non-IgG-purified antiserum was assessed

Rising influence of synthetic biology in regenerative medicine

Synthetic biology is an emerging area of research that combines the investigative nature of biology with the constructive nature of engineering. Despite the field being in its infancy, it has already aided the development of a myriad of industrially and pharmaceutically useful compounds, devices and therapies and is now being applied within the field of regenerative medicine. By combining synthetic biology with regenerative medicine, the engineering of cells and organisms offers potential avenues for applications in tissue engineering, bioprocessing, biomaterial and scaffold development, stem cell therapies and even gene therapies. This review aims to discuss how synthetic biology has been applied within these distinct areas of regenerative medicine, the challenges it faces and any future possibilities this exciting new field may hold

"The blessed chere of our Lord God works this in us by Grace" : a psychobiography and soteriology of mirroring in Julian of Norwich's Showings

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Measuring abortion stigma in Australia and Aotearoa New Zealand: the development, adaptation, and validation of multiple individual-level instruments

The stigmatisation of abortion is a pervasive influence on the prohibiting, threatening, and undermining of quality abortion care. In Australia and Aotearoa New Zealand (ANZ) abortion stigma impacts abortion care quality, including the experiences of accessing, providing, and supporting abortion. Although there are qualitative reports of how abortion stigma is experienced in ANZ, quantitative details are scant. This thesis aimed to address gaps in quantifying abortion stigma in ANZ. To understand how to best measure abortion stigma in ANZ, we conducted a systematic review of approaches quantifying abortion stigma globally. No instrument measuring abortion stigma in ANZ was found. The Individual Level Abortion Stigma scale (ILAS) and Abortion Providers Stigma Scale – Revised (APSS-R) have the most robust psychometric properties according to rigorous guidelines for evaluating measurement properties. The ILAS and APSS-R measure individual level abortion stigma. Through qualitative inquiry, the ILAS and APSS-R were reviewed for use in ANZ and their appropriateness for measuring stigmatisation of people, groups, and organisations supporting abortion care in ANZ. Four instruments measuring individual-level abortion stigma in ANZ were generated for: A) people who have had an abortion; B) people who provide abortion related care; C) people who publicly support abortion; and, D) groups/organisations supporting and/or providing abortion care. The four ANZ instruments were revised by representatives of the relevant end-user groups. Through an online survey, the instruments have been psychometrically tested for Australia demonstrating validity and reliability. These instruments can improve our understanding of abortion stigma and the evaluation of interventions addressing abortion stigma. Future co-designed research should explore the role of research in stigmatising abortion, revise the instruments for specific subgroups, and explore short form versions of the instruments

Aligning Policing and Public Health Promotion: Insights from the World of Foot Patrol

Foot patrol work is rarely described in relation to public health, even though police routinely encounter health risk behaviors and environments. Through a qualitative study of foot patrol policing in violent ‘hotspots’ of Philadelphia, we explore some prospects and challenges associated with bridging security and public health considerations in law enforcement. Noting existing efforts to help advance police officer knowledge of, and attitudes toward health vulnerabilities, we incorporate perspectives from environmental criminology to help advance this bridging agenda. Extending the notion of capable guardianship to understand foot patrol work, we suggest that the way forward for theory, policy, and practice is not solely to rely on changing officer culture and behavior, but rather to advance a wider agenda for enhancing collective guardianship, and especially ‘place management’ for harm reduction in the city

Visualizing medium and biodistribution in complex cell culture bioreactors using in vivo imaging

There is a dearth of technology and methods to aid process characterization, control and scale-up of complex culture platforms that provide niche micro-environments for some stem cell-based products. We have demonstrated a novel use of 3d in vivo imaging systems to visualize medium flow and cell distribution within a complex culture platform (hollow fiber bioreactor) to aid characterization of potential spatial heterogeneity and identify potential routes of bioreactor failure or sources of variability. This can then aid process characterization and control of such systems with a view to scale-up. Two potential sources of variation were observed with multiple bioreactors repeatedly imaged using two different imaging systems: shortcutting of medium between adjacent inlet and outlet ports with the potential to create medium gradients within the bioreactor, and localization of bioluminescent murine 4T1-luc2 cells upon inoculation with the potential to create variable seeding densities at different points within the cell growth chamber. The ability of the imaging technique to identify these key operational bioreactor characteristics demonstrates an emerging technique in troubleshooting and engineering optimization of bioreactor performance

A scaled-down model for the translation of bacteriophage culture to manufacturing scale

Therapeutic bacteriophages are emerging as a potential alternative to antibiotics and synergistic treatment of antimicrobial-resistant infections. This is reflected by their use in an increasing number of recent clinical trials. Many more therapeutic bacteriophage is being investigated in preclinical research and due to the bespoke nature of these products with respect to their limited infection spectrum, translation to the clinic requires combined understanding of the biology underpinning the bioprocess and how this can be optimized and streamlined for efficient methods of scalable manufacture. Bacteriophage research is currently limited to laboratory scale studies ranging from 1-20 ml, emerging therapies include bacteriophage cocktails to increase the spectrum of infectivity and require multiple large-scale bioreactors (up to 50 L) containing different bacteriophage-bacterial host reactions. Scaling bioprocesses from the milliliter scale to multi-liter large-scale bioreactors is challenging in itself, but performing this for individual phage-host bioprocesses to facilitate reliable and robust manufacture of phage cocktails increases the complexity. This study used a full factorial design of experiments approach to explore key process input variables (temperature, time of infection, multiplicity of infection, agitation) for their influence on key process outputs (bacteriophage yield, infection kinetics) for two bacteriophage-bacterial host bioprocesses (T4 - Escherichia coli; Phage K - Staphylococcus aureus). The research aimed to determine common input variables that positively influence output yield and found that the temperature at the point of infection had the greatest influence on bacteriophage yield for both bioprocesses. The study also aimed to develop a scaled down shake-flask model to enable rapid optimization of bacteriophage batch bioprocessing and translate the bioprocess into a scale-up model with a 3 L working volume in stirred tank bioreactors. The optimization performed in the shake flask model achieved a 550-fold increase in bacteriophage yield and these improvements successfully translated to the large-scale cultures

Antimicrobial resistance mechanisms and potential synthetic treatments

In 1928, penicillin was discovered, changing the field of modern medicine as it provided an opportunity to treat microbial infections. Since then, microorganisms such as bacteria have evolved and now have the ability to resist a wide variety of agents that might otherwise prevent their growth. By 2050, it is estimated that around 10 million lives each year will be lost due to these bacteria. This article provides an insight into how bacteria resist antibiotics and potential new methods of treating these organisms

Bioinspired poly(vinylidene fluoride) membranes with directional release of therapeutic essential oils

Here, the morphology of polypore fungi has inspired the fabrication of poly(vinylidene fluoride) (PVDF) membranes with dual porosity by nonsolvent-induced phase separation (NIPS). The fruiting body of such microorganisms is constituted of two distinct regions, finger- and sponge-like structures, which have been successfully mimicked by controlling the coagulation bath temperature during the NIPS process. The use of water at 10 °C as coagulant resulted in membranes with the highest finger-like/sponge-like ratio (53% of the total membrane thickness), while water at 90 °C allowed the formation of macrovoid-free membranes. The microchannels and the asymmetric porosity were used to enhance the oil sorption capacity of the PVDF membranes and to achieve directional release of therapeutic essential oils. These PVDF membranes with easily tuned asymmetric channel-like porosity and controlled pore size are ideal candidates for drug delivery applications