Enhancing medical radiation science education through a design science research methodology

Recently, there has been a call for research-informed and research-developed practice in health sciences education. This prompts the consideration of alternative suitable research approaches that could be used to enhance health sciences education practice, including medical radiation sciences education (MRSE) practice. In this discussion paper, the authors uphold design science research (DSR) methodology as a suitable research approach to enhance MRSE practice and research. An overview of the DSR methodology and an example of a project that used DSR methodology are presented to demonstrate the application of this methodology in MRSE practice and research. The paper concludes that the use of DSR methodology could be instrumental in addressing practice related challenges while developing a theoretical contribution to the discipline.     

Use of a motorized bicycle exercise trainer to normalize frequency-dependent habituation of the H-reflex in spinal cord injury

BACKGROUND/OBJECTIVES: Spasticity in patients with spinal cord injury (SCI) is difficult to manage. Exercise and stretching is advocated as a management tool, but these activities are difficult to perform for most patients as a result of multiple barriers. This report shows the effect of passive range-of-motion exercise in a walking-like pattern on frequency-dependent habituation of the H-reflex in the lower extremities of an individual with spastic tetraplegia due to SCI. METHODS: The participant, a man with a chronic ASIA B C7 SCI due to a gunshot wound, used a motorized bicycle exercise trainer (MBET) developed at the Jackson T. Stephens Spine & Neurosciences Institute at the University of Arkansas for Medical Sciences that could be operated from the individual's wheelchair. He used the MBET for 1 hour, 5 days a week, for 13 weeks. H-reflex habituation was tested at the beginning of the study and then periodically over the course of 17 weeks, including 4 weeks after exercise had ceased. RESULTS: Significant habituation of the H-reflex was evident beginning at the 10th week of training. The habituation in the H-reflex reached a normal level at 5- and 10-Hz frequencies at 12 weeks. Subjective assessment of spasticity indicated that it was significantly reduced. The H-reflex amplitude was maintained at normal levels during the remaining week of the course of exercise and for 2 additional weeks after exercise ceased. The H-reflex habituation, however, returned to near baseline when reassessed at week 17, 4 weeks after the exercise program had concluded. Subjective assessment indicated that spasticity also had returned to pretraining levels. CONCLUSIONS: Habituation of the H-reflex, and perhaps spasticity, can be managed by a routine passive range-of-motion exercise program using a MBET, but the exercise program may need to be continuous. The benefit of reduced medication for spasticity and possibly improved quality of life could be a motivating factor for an individual with SCI and spasticity to continue the program. Because of the low complexity of the program, ease of use, and small size, this system could be inexpensive and could be used by an individual in the home. Ongoing studies will determine the minimum amount of MBET training required for maintaining long-term H-reflex habituation.     

Carboxy-terminal residues of major histocompatibility complex class II-associated peptides control the presentation of the bacterial superantigen toxic shock syndrome toxin-1 to T cells

Previous studies have shown that the presentation of some bacterial superantigens by major histocompatibility complex (MHC) class II molecules is strongly influenced by class II-associated peptides. For example, presentation of the toxic shock syndrome toxin-1 (TSST-1) superantigen by antigen-processing-defective T2-I-A^b cells (which expresses I-A^b that is either empty or associated with invariant chain-derived peptides) can be strongly enhanced by some, but not other, I-A^b-binding peptides. Here we investigate the contribution of I-A^b-associated peptides in the presentation of TSST-1 to T cells. The data show that overlapping peptides expressing the same core I-A^b-restricted epitope, but with various N and C termini, can differ profoundly in their ability to promote TSST-1 presentation to T cells. Analysis of altered and truncated peptides indicates that residues at the C-terminal end of the peptide have a dramatic effect on TSST-1 presentation. This effect does not involve a cognate interaction between the peptide and the TSST-1 molecule, but appears to depend on the length of the C-terminal region. These data are consistent with crystallographic studies suggesting that TSST-1 may interact with the C-terminal residues of MHC class II-associated peptides. We also examined the capacity of naturally processed peptides to promote TSST-1 binding using a superantigen blocking assay. The data demonstrated that a naturally processed epitope is dominated by peptides that do not promote strong TSST-1 binding to I-A^b. Taken together, these data suggest that TSST-1 binding to MHC class II molecules is controlled by the C-terminal residues of the associated peptide, and that many naturally processed peptide/class II complexes do not present TSST-1 to T cells. Thus, the peptide dependence of TSST-1 binding to class II molecules may significantly reduce the capacity of TSST-1 to stimulate T cells.     

A perivascular niche for brain tumor stem cells

Cancers are believed to arise from cancer stem cells (CSCs), but it is not known if these cells remain dependent upon the niche microenvironments that regulate normal stem cells. We show that endothelial cells interact closely with self-renewing brain tumor cells and secrete factors that maintain these cells in a stem cell-like state. Increasing the number of endothelial cells or blood vessels in orthotopic brain tumor xenografts expanded the fraction of self-renewing cells and accelerated the initiation and growth of tumors. Conversely, depletion of blood vessels from xenografts ablated self-renewing cells from tumors and arrested tumor growth. We propose that brain CSCs are maintained within vascular niches that are important targets for therapeutic approaches.     

Mutational analysis of PDGFR-RAS/MAPK pathway activation in childhood medulloblastoma

Aberrant signalling via platelet derived growth factor receptors (PDGFRs) and the RAS/MAPK pathway has been implicated in the development of medulloblastoma, the most common malignant brain tumour in childhood. To determine whether genetic mechanisms play a role in the activation of PDGFR-RAS/MAPK signalling in medulloblastoma, we performed a direct sequence analysis of the established mutational "hotspots" of known targets of activating mutations within the pathway (PDGFRA, NRAS, KRAS, HRAS and BRAF) and PDFRFB, in a cohort of 28 primary tumours. A synonymous sequence variation in PDGFRA (CCG to CCA; PRO 567 PRO) was detected in two cases (approximately 7%), but not in 150 normal chromosomes assessed, suggesting that the PDGFRA locus may be associated with medulloblastoma development in certain cases. No evidence for oncogenic mutations affecting NRAS, KRAS, HRAS, BRAF or PDFRFB was found in any case. These data demonstrate that activating mutations in established mutational hotspots within the PDGFR-RAS/MAPK pathway are rare events in medulloblastoma development, and suggest that alternative mechanisms are responsible for RAS/MAPK pathway activation in this disease.