Manipulating the Properties of Hydrogels to Promote Ependymal Cell Behaviour for Spinal Cord Repair

Spinal cord injury (SCI) occurs when the spinal cord is physically crushed, impinged, severed, or otherwise damaged; resulting in irreversible disruption to the neuronal pathways responsible for motor and sensory function. The main obstacles to spinal cord repair include neuronal damage, loss of oligodendrocytes (leading to axonal demyelination), and scar formation with glial and fibrotic components. Despite the prevalence of SCI and its costly impact on society, treatment remains limited. Ependymal cells (ECs) lining the central canal show promise as a pool of endogenous stem cells within the spinal cord. These cells are found to proliferate, differentiate, and migrate in response to injury, however at present, little is known about this neurogenic niche and how the local microenvironment influences cellular behaviour. This project aims to investigate whether endogenous EC behaviour can be altered by manipulating the properties of the surrounding matrix. Nestin is a type VI intermediate filament protein and a marker of neural stem and progenitor cells in the central nervous system. Characterisation of transgenic mice expressing green fluorescent protein (GFP) under the control of nestin was carried out within this thesis; identifying these cells as ECs and pericytes in the spinal cord. (Nestin) GFP-positive ECs colocalised with a number of stem cell markers including: CD24, Sox2, and foxJ1. ECs were also shown to express chemokine receptor type 4 (CXCR4), the main receptor to stromal cell-derived factor-1 (SDF-1); both of which are involved in the directed migration of neural cells through chemotaxis. The results of spinal cord slice cultures and intraspinal injections presented in this thesis suggest that EC behaviour can be manipulated using hydrogels and SDF-1α; towards repair of SCI

A systematic review of interventions to increase the use of standardized outcome measures by rehabilitation professionals

Objective: To determine the types and effectiveness of interventions to increase the knowledge about, attitudes towards, and use of standardized outcome measures in rehabilitation professionals.  Data Sources: An electronic search using Medline, EMBASE, PsycINFO, CINAHL, Ergonomics Abstracts, Sports Discus. The search is current to February 2016.  Study Selection: All study designs testing interventions were included as were all provider and patient types. Two reviewers independently conducted a title and abstract review, followed by a full-text review.  Data extraction: Two reviewers independently extracted a priori variables and used consensus for disagreements. Quality assessment was conducted using the Assessment of Quantitative Studies published by the Effective Public Health Practice Group.  Data Synthesis: We identified 11 studies involving at least 1200 providers. Nine of the studies showed improvements in outcome measure use rates but only three of these studies used an experimental or quasi-experimental design. Eight of the studies used an educational approach in the intervention and three used audit and feedback. Poor intervention description and quality of studies limited recommendations.  Conclusions: Increased attention to testing interventions focused on known barriers, matched to behavior change techniques, and with stronger designs is warranted

Knowledge Translation Activities in Occupational Therapy Organizations: The Canadian Landscape

Despite acknowledging the importance of knowledge translation (KT), the occupational therapy profession has demonstrated only emerging KT activity. Organizations are seen as playing an important role in supporting KT. To date, there have been no known attempts to explore KT activities conducted by occupational therapy organizations in Canada. The purpose of this study was to identify and describe KT activities occurring in Canadian occupational therapy organizations. An environmental scan was used to identify KT activities. The websites of occupational therapy national and provincial associations and/or regulatory bodies and the educational programs were searched. A Knowledge Mobilization Matrix (KMM) website was applied to each organizational website. The total KMM scores were highest for universities and lowest for regulatory organizations. The type and nature of the KT activities varied according to the type of organization. Canadian occupational therapy leadership organizations play an important role in supporting KT

Bifidobacterium breve UCC2003 Exopolysaccharide Modulates the Early Life Microbiota by Acting as a Potential Dietary Substrate

Background: Bifidobacterium represents an important early life microbiota member. Specific bifidobacterial components, exopolysaccharides (EPS), positively modulate host responses, with purified EPS also suggested to impact microbe–microbe interactions by acting as a nutrient substrate. Thus, we determined the longitudinal effects of bifidobacterial EPS on microbial communities and metabolite profiles using an infant model colon system. Methods: Differential gene expression and growth characteristics were determined for each strain; Bifidobacterium breve UCC2003 and corresponding isogenic EPS-deletion mutant (B. breve UCC2003del). Model colon vessels were inoculated with B. breve and microbiome dynamics monitored using 16S rRNA sequencing and metabolomics (NMR). Results: Transcriptomics of EPS mutant vs. B. breve UCC2003 highlighted discrete differential gene expression (e.g., eps biosynthetic cluster), though overall growth dynamics between strains were unaffected. The EPS-positive vessel had significant shifts in microbiome and metabolite profiles until study end (405 h); with increases of Tyzzerella and Faecalibacterium, and short-chain fatty acids, with further correlations between taxa and metabolites which were not observed within the EPS-negative vessel. Conclusions: These data indicate that B. breve UCC2003 EPS is potentially metabolized by infant microbiota members, leading to differential microbial metabolism and altered metabolite by-products. Overall, these findings may allow development of EPS-specific strategies to promote infant health

16S sequencing and functional analysis of the fecal microbiome during treatment of newly diagnosed pediatric inflammatory bowel disease

JJA is funded by a National Institute of Health Research Academic Clinical Fellowship and has received an Action Medical Research training fellowship. TC is funded by a Crohn’s in Childhood research association fellowship. CMC received a PhD studentship from SULSA Spirit industrial studentship. The NGS analysis was made possible by the award of a grant from the Source Bioscience 110th year anniversary promotion to CMC. The Rowett Institute receives funding from the Scottish Government (RESAS).Peer reviewedPublisher PD

The effect of self-sorting and co-assembly on the mechanical properties of low molecular weight hydrogels

Self-sorting in low molecular weight hydrogels can be achieved using a pH triggered approach. We show here that this method can be used to prepare gels with different types of mechanical properties. Cooperative, disruptive or orthogonal assembled systems can be produced. Gels with interesting behaviour can be also prepared, for example self-sorted gels where delayed switch-on of gelation occurs. By careful choice of gelator, co-assembled structures can also be generated, which leads to synergistic strengthening of the mechanical properties

Comparative genomics profiling of clinical isolates of Aeromonas salmonicida using DNA microarrays

BACKGROUND: Aeromonas salmonicida has been isolated from numerous fish species and shows wide variation in virulence and pathogenicity. As part of a larger research program to identify virulence genes and candidates for vaccine development, a DNA microarray was constructed using a subset of 2024 genes from the draft genome sequence of A. salmonicida subsp. salmonicida strain A449. The microarray included genes encoding known virulence-associated factors in A. salmonicida and homologs of virulence genes of other pathogens. We used microarray-based comparative genomic hybridizations (M-CGH) to compare selected A. salmonicida sub-species and other Aeromonas species from different hosts and geographic locations. RESULTS: Results showed variable carriage of virulence-associated genes and generally increased variation in gene content across sub-species and species boundaries. The greatest variation was observed among genes associated with plasmids and transposons. There was little correlation between geographic region and degree of variation for all isolates tested. CONCLUSION: We have used the M-CGH technique to identify subsets of conserved genes from amongst this set of A. salmonicida virulence genes for further investigation as potential vaccine candidates. Unlike other bacterial characterization methods that use a small number of gene or DNA-based functions, M-CGH examines thousands of genes and/or whole genomes and thus is a more comprehensive analytical tool for veterinary or even human health research

A dedicated flavin-dependent monooxygenase catalyzes the hydroxylation of demethoxyubiquinone into ubiquinone (coenzyme Q) in \u3ci\u3eArabidopsis\u3c/i\u3e

Ubiquinone (Coenzyme Q) is a vital respiratory cofactor and liposoluble antioxidant. In plants, it is not known how the C-6 hydroxylation of demethoxyubiquinone, the penultimate step in ubiquinone biosynthesis, is catalyzed. The combination of cross-species gene network modeling along with mining of embryo-defective mutant databases of Arabidopsis thaliana identified the embryo lethal locus EMB2421 (At1g24340) as a top candidate for the missing plant demethoxyubiquinone hydroxylase. In marked contrast with prototypical eukaryotic demethoxyubiquinone hydroxylases, the catalytic mechanism of which depends on a carboxylatebridged di-iron domain, At1g24340 is homologous to FADdependent oxidoreductases that instead use NAD(P)H as an electron donor. Complementation assays in Saccharomyces cerevisiae and Escherichia coli demonstrated that At1g24340 encodes a functional demethoxyubiquinone hydroxylase and that the enzyme displays strict specificity for the C-6 position of the benzoquinone ring. Laser-scanning confocal microscopy also showed that GFP-tagged At1g24340 is targeted to mitochondria. Silencing of At1g24340 resulted in 40 to 74% decrease in ubiquinone content and de novo ubiquinone biosynthesis. Consistent with the role of At1g24340 as a benzenoid ring modification enzyme, this metabolic blockage could not be bypassed by supplementation with 4-hydroxybenzoate, the immediate precursor of ubiquinone’s ring. Unlike in yeast, in Arabidopsis overexpression of demethoxyubiquinone hydroxylase did not boost ubiquinone content. Phylogenetic reconstructions indicated that plant demethoxyubiquinone hydroxylase is most closely related to prokaryotic monooxygenases that act on halogenated aromatics and likely descends from an event of ho

Oiling the Brain: A Review of Randomized Controlled Trials of Omega-3 Fatty Acids in Psychopathology across the Lifespan

Around one in four people suffer from mental illness at some stage in their lifetime. There is increasing awareness of the importance of nutrition, particularly omega-3 polyunsaturated fatty acids (n-3 PUFA), for optimal brain development and function. Hence in recent decades, researchers have explored effects of n-3 PUFA on mental health problems over the lifespan, from developmental disorders in childhood, to depression, aggression, and schizophrenia in adulthood, and cognitive decline, dementia and Alzheimer’s disease in late adulthood. This review provides an updated overview of the published and the registered clinical trials that investigate effects of n-3 PUFA supplementation on mental health and behavior, highlighting methodological differences and issues

Changing behaviour 'more or less'-do theories of behaviour inform strategies for implementation and de-implementation? A critical interpretive synthesis

BACKGROUND: Implementing evidence-based care requires healthcare practitioners to do less of some things (de-implementation) and more of others (implementation). Variations in effectiveness of behaviour change interventions may result from failure to consider a distinction between approaches by which behaviour increases and decreases in frequency. The distinction is not well represented in methods for designing interventions. This review aimed to identify whether there is a theoretical rationale to support this distinction. METHODS: Using Critical Interpretative Synthesis, this conceptual review included papers from a broad range of fields (biology, psychology, education, business) likely to report approaches for increasing or decreasing behaviour. Articles were identified from databases using search terms related to theory and behaviour change. Articles reporting changes in frequency of behaviour and explicit use of theory were included. Data extracted were direction of behaviour change, how theory was operationalised, and theory-based recommendations for behaviour change. Analyses of extracted data were conducted iteratively and involved inductive coding and critical exploration of ideas and purposive sampling of additional papers to explore theoretical concepts in greater detail. RESULTS: Critical analysis of 66 papers and their theoretical sources identified three key findings: (1) 9 of the 15 behavioural theories identified do not distinguish between implementation and de-implementation (5 theories were applied to only implementation or de-implementation, not both); (2) a common strategy for decreasing frequency was substituting one behaviour with another. No theoretical basis for this strategy was articulated, nor were methods proposed for selecting appropriate substitute behaviours; (3) Operant Learning Theory makes an explicit distinction between techniques for increasing and decreasing frequency. DISCUSSION: Behavioural theories provide little insight into the distinction between implementation and de-implementation. Operant Learning Theory identified different strategies for implementation and de-implementation, but these strategies may not be acceptable in health systems. Additionally, if behaviour substitution is an approach for de-implementation, further investigation may inform methods or rationale for selecting the substitute behaviour