30921 research outputs found
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Beyond expectations: investigating nilotinib’s potential in attenuating neurodegeneration in alzheimer’s disease
Get PDFAbstract Neurodegenerative diseases, such as Alzheimer’s disease (AD), pose a formidable global challenge. While therapeutic options are available, their limitations are significant, necessitating the development of innovative treatment approaches. Here, we highlight the importance of repurposing drugs and discuss the future of drug treatments for AD. We review the potential of tyrosine kinase inhibitors (TKI) for mitigating AD pathology and symptoms, as well as neurodegenerative processes more broadly. We focus on nilotinib, a selective BCR-ABL tyrosine kinase inhibitor, which has unique mechanisms of action involving the modulation of cell responses and removal of toxic proteins associated with AD pathogenesis. Encouraging studies have demonstrated its efficacy, calling for further investigation through clinical trials to assess its potential in various neurodegenerative conditions. However, despite these promising preclinical findings, no clinical studies have yet conclusively demonstrated its efficacy in treating AD. Considering the future directions in AD research, personalized medicine approaches hold promise by incorporating patient-specific factors, including sex and gender differences, to tailor nilotinib treatment for improved efficacy and safety profiles
Unlocking hidden potential of rice bran: Enzymatic treatment for enhancing techno-functional properties
Get PDFRice bran (RB) is a by-product with limited application due to technological constraints. Enhancing its technological functionality as potential food ingredient will improve the sustainability of rice production. The aim was to study the impact of enzymatic and thermal treatments on defatted rice bran using six distinct commercial enzymes (carbohydrases and proteases) and dry heating by evaluating its technological, nutritional and functional properties. Enzymatic treatment increased up to 208% the soluble dietary fiber content (8.19 g/100 g) of defatted RB. Moreover, the solvent retention capacity, including water, oil, sodium carbonate, and sucrose, exhibited a noteworthy increase across all treatments (p < 0.05). Bran color changed after treatments, increasing its luminosity (L*) and decreasing the value of a* in all cases, but b* decreased when treated with protein-acting enzymes while increased with carbohydrate-acting enzymes. Proteases played a pivotal role in reducing particle size and forming gels requiring minimal force for application. Microscopic analysis revealed that carbohydrases treated samples exhibited prominent cell wall breakage, while protease-treated ones showed a gel-like surface with less distinct protein bodies and layered walls. These comprehensive study sheds new transformations brought about by these enzymatic interventions, offering valuable insights into the optimization of rice bran functionality
Cost-effectiveness of nirsevimab and maternal RSVpreF for preventing respiratory syncytial virus disease in infants across Canada
Get PDFAbstract Background Nirsevimab, a long-acting monoclonal antibody, and RSVpreF, a maternal vaccine, are newly approved respiratory syncytial virus (RSV) prophylactics for infants in Canada. Both have the potential to expand prevention efforts, but there is limited evidence regarding their cost-effectiveness and how it varies across the country, despite disparate hospitalisation rates and resource use among different populations. Methods We developed a decision tree model to follow twelve monthly birth cohorts through their first year of life, incorporating risk differentiation based on Canadian region, prematurity, and comorbidities. The model tracked medically attended infections, including hospitalisations, intensive care unit admissions, and outpatient visits, comparing costs (in 2024 Canadian dollars) and effectiveness (in quality-adjusted life years (QALYs)) of nine different immunisation strategies compared to no intervention. The analysis was conducted from both healthcare and societal perspectives. We conducted threshold price analyses, varying the price-per-dose of each product to determine the threshold prices at which expanded coverage becomes cost-effective. Results At base case prices, the optimal strategy varies by region, but in all cases, the optimal strategy is both cost-saving and more effective than no intervention. In southern Canada, it is optimal to immunise only palivizumab-eligible infants (those born very prematurely or with high-risk comorbidities) with nirsevimab, resulting in cost savings of 28.68 and QALY gains of 0.00007 per infant). In Nunavik and Nunavut, immunising all infants under 6 months and all infants under twelve months with nirsevimab are the best strategies, respectively (cost savings of 1067.03 and QALY gains of 0.000884 per infant in Nunavut). Universal, country-wide immunisation with nirsevimab would require a price-per-dose of under $112 to become the most cost-effective prevention strategy. Conclusions The optimal strategy for preventing respiratory syncytial virus disease in Canadian infants depends on product price and regional risk level and resource use. Canadian policy should account for these factors
Expanding the application of germinated wheat by examining the impact of varying alpha-amylase levels from grain to bread
Get PDFControlled germination is recognized for its potential to enhance both the nutritional profile and functional properties of grains, but there is limited information about the level of wheat germination that promotes functional changes without losing breadmaking potential. This research aims to analyze the physicochemical changes in wheat during germination for 36 h, focusing on evaluating kernel changes, the flour breadmaking functionality, and bread characteristics. Pasting properties progressively decreased as the germination progressed, and apparent viscosity was barely detected after 36 h germination. Initial decline in gluten index was observed at 24 and 36 h germination, but gluten kept its aggregation capabilities. Optimal germination periods of 6–18 h significantly improved flour functionality, evidenced by increased Gluten Performance Index, gluten index, and enhanced dough mixing properties. Further, mini-breads, developed after optimizing breadmaking conditions, displayed increased 2D areas in 24 and 36 h and lower crumb hardness in 24 and 36 h of germinated bread compared to those obtained with sound wheat flour. Significant correlations were found among alpha amylase activity, Falling number, total and damaged starch content, RVA parameters, gelatinization enthalpy, and breadcrumb texture parameters. Developing mini bread using different levels of germinated flour demonstrates its viability for breadmaking offering a promising innovation within the whole-grain food industry
Wheat gluten: A functional protein still challenging to replace in gluten-free cereal-based foods
Get PDFBackground and Objectives
Wheat gluten in cereal-based products has unique functionality derived from its viscoelastic properties. Nevertheless, many food applications require its replacement to obtain gluten-free foods but keeping similar quality characteristics. This review analyzes the distinctive characteristics of wheat gluten, and the technological strategies implemented to mimic its behavior within the gluten-free systems.
Findings
The viscoelastic behavior of wheat gluten is due to the interplay of glutenins and gliadins after being hydrated and subjected to mechanical stress. Disulfide bonds and noncovalent interactions are key in holding its structure and explaining its solubility and hydrophobicity. Gluten-free flours and starches have represented the first adopted strategies for gluten replacement, but results have not been completely satisfactory. To tackle this issue, non-wheat protein addition, physical treatments, hydrocolloids, enzymes, and emulsifiers have allowed recreation of a pseudo gluten network of the cereal-based foods.
Conclusions
Despite technological sensorial achievements, a gap still exists when gluten-free products are compared with their wheat-based counterparts. A better comprehension about the combined actions of different processing aids and technologies could offer future answers.
Significance and Novelty
The review points out the main characteristics of the wheat gluten uniqueness, shedding light on its replacement strategies to guide future research
Student and faculty perspectives of gender inclusive and affirming practices in undergraduate nursing education
Get PDFBackground: Transgender and gender diverse people have unique healthcare needs, which can be addressed through the provision of gender affirming care. Nurses, the largest healthcare workforce, can help meet this need. Further, nursing schools produce thousands of nurses annually, and thus are critical sites to address gender affirming care meaningfully. Yet how gender affirming care is being taught in undergraduate nursing education is unclear. Three levels of curriculum (formal, informal, and hidden) influence students’ learning about equitable care for transgender and gender diverse patients, as well as nursing students and educators. Currently, there is no nursing research on the state of transgender and gender diverse education across the three levels of curriculum (called gender inclusive and affirming practices).
Purpose: This thesis aimed to explore gender inclusive and affirming practices across undergraduate nursing education in Canada. Three objectives guided the paper-based thesis: 1) to map evidence of gender inclusive and affirming practices in undergraduate nursing education literature; 2) to explore gender inclusive and affirming practices within schools of nursing in Canada; and 3) to (re)vision gender inclusive and affirming practices for nursing education.
Methods: To commence this work, a scoping review, which included scholarly articles (n=47) and a search of schools of nursing websites (n=22), was conducted to map the literature on gender inclusive and affirming practices in undergraduate nursing education. As informed by the scoping review and drawing queer theory and Hafferty’s three levels of curriculum, an interpretive description study explored the perspectives of undergraduate nursing students and educators in Canada. Data collection included initial and follow-up semi-structured focus groups with students (n=18) and interviews with educators (n=7).
Findings: Results from this thesis indicate that nursing education is cisnormative across all levels of curriculum. Cisnormativity – the normalization of cisgender/non-transgender people and othering of transgender and gender diverse people – is perpetuated in nursing education when gender affirming care is set to the fringes (formal); when language remains highly gendered, or pronouns are not used (informal); or when there is no transvisibility or limited access to gender inclusive washrooms (hidden). Some consequences of cisnormativity include nursing students not feeling prepared to care for transgender and gender diverse people, nurse educators not being prepared to teach this content, and transgender and gender diverse students being othered.
Conclusions: Multi-level action to disrupt cisnormativity is needed within and beyond nursing education. Schools of nursing can support faculty development in gender inclusive and affirming practices and create safer, more representative and inclusive environments. Nursing governing bodies can create explicit requirements for gender inclusive and affirming practices in accreditation and licensing processes.The 2SLGBTQ+ Health Hub Fellowship; The Canadian Nurses Federation, Tylenol® Fund to Advance Diversity in Nursing and Health Equity Research; The Dean of Rady Faculty of Health Sciences Graduate Student Achievement Prize; The College of Nursing Endowment Fund Graduate Student Research Grant; The Graduate Student Open Access Publishing Fund; The Margaret Elder Hart Award; and Graduate Nursing Students Association Scholarship Major Stream; and, The Irene Nordwich Foundation.May 202
Effect of dry-fractionated pea protein on the physicochemical properties and the nutritional features of gluten-free focaccia flat bread
Get PDFThe aim of this work was to formulate a gluten-free focaccia flat bread based on rice and corn flour fortified with dry-fractionated pea protein concentrate (55 g/100 g protein content). A simplex-centroid mixture design with ten formulations helped to study how the flour ratios influenced the physical and sensory properties of dough and breads. The special cubic model significantly described all the responses determined in the dough and flour mixes, and most of those determined in the focaccia. The pea protein concentrate influenced the pasting properties of the flour mixes resulting in a decrease of viscosity. The midpoint of the experimental domain (focaccia containing 5 g/100 g of pea protein concentrate and 20 g/100 g of rice flour and corn flour each) was optimal, being not affected by the discolorations typical of pea (a* = 11.97, b* = 31.86, corresponding to an orange hue), having crumb hardness and chewiness of 9.11 N and 4.83 N, respectively, and moderate legume odor and flavor (5.6 and 5.3 c.u. in a 0–9 scale, respectively). The selected formulation could be labelled as “source of protein” (energy value provided by proteins >12%), “source of fiber” (fiber >3 g/100 g), and “low-fat” (fat <3 g/100 g)
Community and malleable identity in the furry fandom
Get PDFThis thesis examines the social and personal aspects of identity creation in the furry fandom – a fandom centred around anthropomorphic characters. Based on data collected from 25 online interviews of furry community members, I learned that furries challenge and create social norms outside of the mainstream to find belonging within the furry fandom. The various furry spaces populated by members (e.g., furry-specific websites or conventions) encourage the safe exploration and assertion of identities that may be maligned in other spaces. The data is analyzed in two broad categories: external elements addressed in the sections on norms and belonging; and internal dynamics examined in the sections on fursona (anthropomorphic avatar) embodiment and identity. This thesis concludes that furries construct malleable identities through the creation and use of fursonas, and based on one interviewee’s assertion, fully explores the concept of identity as a form of collaborative fiction.May 202
(Un)Supporting English for specific academic purposes in graduate school: experiences of EAL graduate students in Education and Engineering at a Canadian university
Get PDFThis qualitative case study explores international graduate students’ experiences (IGSs) learning and using English for Academic Purposes (EAP) to support their graduate work in Education and Engineering at the University of Manitoba. These experiences are discussed in relation to IGSs’ interactions with the available resources offered by the institution. This study is framed by language socialization theory and sociocultural theory. The students played an active role in their learning through interactions with various semiotic resources and socialization with members of the target academic communities while developing their worldviews, statuses, and identities (Duff, 2010, 2019; Ochs & Schieffelin, 2017). The data collection engaged both student participants and instructor participants from Education and Engineering in semi-structured interviews. I also incorporated analysis of documents and my reflective self-narrative to gain insights into students’ experiences in learning EAP and how they navigated the system using individual strategies to socialize, legitimize their statuses for adaptation, and thrive in the university. IGSs perceived EAP as influential to their studies, career development, and intercultural communication while viewing it as an ongoing learning process despite their strong language proficiency and educational backgrounds. The findings confirmed the significance of familiarizing the IGSs with Canadian postsecondary education’s academic discourses and sociocultural contexts. Education student participants faced obstacles engaging in academic activities and discussions and completing graduate work due to unfamiliarity with the locally focused topics and curriculum in classrooms. Although Engineering counterparts found strengths in the common academic language foundation in engineering disciplines, they had difficulties in concise and precise technical writing, thesis writing, and writing for publication. The findings suggested the need for support services specifically tailored for disciplinary purposes at different stages of graduate programs because the available supports were too generic and basic. Recommendations for practices are offered to institutional policymakers, responsive faculties, instructors, and IGSs. Research results contribute to the literature on language socialization of postsecondary students in the context of English-speaking institutions by comparing and contrasting the experiences of students from the disciplines of Education and Engineering.May 202
Beyond cyp51: A novel reduced spore dormancy pathway confers azole resistance in Fusarium graminearum
Get PDFFusarium graminearum is a major pathogen of wheat and barley, causing annual global agricultural losses exceeding one billion dollars. Historically azole fungicides (demethylation inhibitors) have effectively managed F. graminearum infections in Canada, but recent data suggests increasing resistance in populations. Azoles inhibit ergosterol biosynthesis by binding to the active site of Cyp51. Resistance to azoles is often driven by mutations in the cyp51 gene that alter the enzyme binding site, lowering azole binding affinity. In this study, F. graminearum strain DAOMC 233423 was exposed to increasing concentrations of tebuconazole, prothioconazole, a combination of both fungicides, or a solvent carrier control (four replicates each) until strain extinction in the fungicide treatments. All evolved strains exceeded the initial MIC (minimum inhibitory concentration) by 2×-5.1× but only one strain, TBF1, maintained its reduced sensitivity to azoles after long term storage in the freezer. All evolved strains retained a normal growth rate, and were able to successfully infect a fusarium head blight-susceptible wheat cultivar. Strain TBF1, evolved to tebuconazole, retained stable tebuconazole resistance, which was accompanied by impaired spore production. Whole genome sequencing analyses identified a single base insertion in the smt3 gene in TBF1, resulting in a premature stop codon. The smt3 gene deletion strains phenocopied the TBF1 strain, with decreased tebuconazole sensitivity and altered macroconidia germination behaviour. Surprisingly, no mutations were identified in any cyp51 genes.February 202