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The mechanisms of amyloid-mediated islet inflammation and beta-cell death
No full textType 2 diabetes (T2D) is a multifactorial metabolic disorder characterized by progressive loss of beta-cell function and mass. Islet amyloid, formed by the aggregation of human islet amyloid polypeptide (hIAPP; amylin) is a hallmark of T2D, which contributes to islet inflammation and beta-cell dysfunction/death. Our lab has previously shown that islet amyloid formation is associated with elevated production of pro-inflammatory cytokines, in particular interleukin (IL)-1beta, which in turn upregulates the expression of Fas cell death receptor and promotes apoptosis in beta cells. Immune cells, mainly macrophages, are the major source of these inflammatory mediators in T2D, suggesting their potential involvement in amyloid-associated islet inflammation. Islet macrophages are broadly categorized into pro-inflammatory (M1) macrophages and anti-inflammatory (M2) macrophages. The plasticity of macrophages allows them to switch their phenotypes in response to different environmental factors. Here, we propose that amyloid formation changes the balance between macrophage subpopulations, by shifting their phenotype towards pro-inflammatory M1 macrophages, which then results in elevated islet IL-1beta production and beta-cell apoptosis.
We have used cultured human islets as an ex vivo experimental model of islet amyloid formation. Isolated islets from cadaveric donors were handpicked (purity >95%) and cultured at basal glucose (5.5 mM; little to no amyloid formation) and elevated glucose (11.1 mM; amyloid formation) for up to 7 days. Quantitative immunolabeling was performed on paraffin-embedded islet sections for insulin (beta cells) and each CD68 (pan-macrophage marker), iNOS (M1 marker), CD163 (M2 marker), glucagon (alpha cells), thioflavin S (amyloid), or TUNEL (apoptosis).
Our findings demonstrate that human islets form amyloid during 7-day culture at elevated glucose (11.1 mM) but not at basal glucose (5.5 mM). Islet macrophages maintained a stable population at both basal and elevated glucose conditions during the culture period. Importantly, amyloid formation was associated with elevated iNOS-positive (M1) macrophages and reduced CD163-positive (M2) macrophages, indicating an amyloid-associated shift in the macrophage phenotypes. This shift in macrophage phenotypes correlated with increased beta-cell apoptosis and reduced islet beta-to-alpha cell ratio, suggesting a potential mechanistic link between amyloid formation, change in macrophage phenotypes and beta-cell death.
In summary, our findings suggest that amyloid formation promotes islet inflammation in cultured human islets by shifting the macrophage phenotype towards pro-inflammatory (M1) macrophages, leading to an increase in beta-cell apoptosis. Therefore, modulating the balance between islet M/M2 macrophages may provide a potential therapeutic strategy to reduce amyloid-associated beta-cell death, thereby improving beta-cell survival in patients with T2D.February 202
ᓯᕗᒧᐊᕐᕕᒃ Sivumuarvik, a place where one moves forward: a framework for design empathy in Nunavut
No full textCountry food is central to Inuit identity, communities, and the local economy in Nunavut (QIA, 2019). Spaces that facilitate the acquisition, processing, sharing, education, and storage of this food are essential for strengthening Inuit identity, building resilient communities, supporting food security, and adapting architecture from a southern model to one suited to northern and Inuit contexts. The previously nomadic Inuit way of life deeply connected food and place, with housing built from elements of the land (snow) or harvested animals (caribou skins). However, this intrinsic connection between place and identity is often lacking in the current built environment. This practicum explores Inuit cultural values that shape and reinforce identity, as expressed through their material culture. It considers placemaking and a sense of place as key methods for revitalizing the built environment’s relationship with people and the land. Ultimately, proposing a design approach rooted in Inuit societal values, employing a hybrid methodology that integrates Aajiiqatigiingniq, an Inuit research framework and empathy design into the architectural and design processes. The result is a new typology for community food-related infrastructure in Nunavut, in the design proposal of ᓯᕗᒧᐊᕐᕕᒃ Sivumuarvik, A Place Where One Moves Forward.February 202
Impacts of interdisciplinary project-based learning on high school students' future-readiness: a mixed methods study
No full textProject-based learning (PBL) is an emerging pedagogy which shows promise in improving student outcomes but has not been widely studied. An explanatory sequential mixed methods study was conducted in rural Manitoba which examined participant-reported future readiness across several purposes of education to better understand reported differences in future readiness between an education based on traditional pedagogy and one based on PBL. The participants’ current life situation was considered as a moderating variable to determine if it impacted what facets of each pedagogy participants believed was most helpful. Participants from the group which received primarily traditional pedagogy were first surveyed in January of the year after they graduated, and then select participants of this group were interviewed roughly four months later. A year later a group of students who received primarily PBL went through the same process of surveys and interviews. 18 participants were surveyed from each group, and from those who were surveyed 8 were interviewed from each group. Survey results indicated that students who attended university or were taking a gap year had nearly identical future readiness scores, while students going to college or directly into the workforce with no further plans for education saw an increase in future readiness from the PBL pedagogy. The interviews indicated that while gap-year and university attending students shared concerns about readiness for high stakes testing, the collaborative and more independent nature of PBL was found to increase future readiness across all groups.February 202
Infant feeding and child cognition and behaviour: quantifying pathways to understand the link in the CHILD cohort study
No full textIntroduction: Research has shown that breastfeeding is related to improved child cognitive and behavioural outcomes (CBOs), however, few studies have examined pathways to explain these associations. The objectives of this dissertation are to examine 1) the relationship between breastfeeding and child CBOs and 2) four pathways to help explain this link: breast milk components, the gut microbiome, maternal depression, and the parent-child relationship.
Methods: This dissertation uses data from the CHILD cohort study (n=2,342 parent-infant dyads). Infant feeding practices, maternal depression and parent-child relationship were repeatedly measured from birth to two years using standardized questionnaires. Breast milk samples, collected at 3-4 months, were analyzed for fatty acids and human milk oligosaccharides (HMOs); stool samples, collected a 3 and 12 months, were analyzed for microbiome diversity and composition. The Bayley Scales of Infant and Toddler Development and the Child Behaviour Checklist were used to measure child CBOs at 2 and 5 years. Linear regression, adjusting for confounders, was used to assess the relationships between infant feeding, breast milk components and child CBOs. Interaction terms were used to investigate moderation by child sex, family socioeconomic risk or maternal secretor status. Mediation analysis was used to assess the role of the gut microbiome, maternal depression and the parent-child relationship.
Results: Longer breastfeeding duration and more exclusive breastfeeding were related to better child CBOs with the strongest associations observed for behaviour at five years, and stronger associations for those with more socioeconomic risk factors. Higher concentrations of the HMOs 3’-sialyllactose and lacto-N-hexaose were related to better language and cognitive scores, respectively. The gut microbiome did not mediate the relationship between infant feeding and CBOs; however, maternal depression and the parent-child relationship were mediators of this association.
Conclusion: Breast milk components as well as maternal mental health and the parent-child relationship all contribute to the relationship between infant feeding and CBOs, with the parent-child relationship having the strongest effect size in mediation models. This research can provide evidence for policies and programs to support breastfeeding, maternal mental health and a positive parent-child relationship and inform the development of supplements for babies who cannot be breastfed.International Society for Research in Human Milk and Lactation Trainee Expansion Award
University of Manitoba Graduate Student FellowshipFebruary 202
Fourteen to life: giving constitutional effect to the age-based presumption of diminished moral blameworthiness by respecting Parliament’s two-pronged test for adult sentence applications pursuant to section 72 of the Youth Criminal Justice Act
No full textSince the inception of the Youth Criminal Justice Act (YCJA) 20 years ago, the Supreme Court of Canada (SCC) has considered the adult sentence applications framework on only one occasion in R v DB, 2008 SCC 25. Additionally, Parliament enacted a major legislative overhaul of the provisions related to adult sentence applications in 2012. Without further input from the SCC, trial and appellate courts across Canada have filled the gaps in interpreting section 72 of the YCJA. On November 23, 2023, the SCC has announced they will hear the appeals of R v IM, 2023 ONCA 378 and R v SB, 2023 ONCA 369 and revisit the issue the presumption of diminished moral blameworthiness. The adult sentence application provisions are arguably the most important provision within the Act, given the serious jeopardy that goes along with an adult sentence.
Courts across Canada have struggled to give constitutional effect to the age-based presumption of diminished moral blameworthiness. In this thesis, I present a critical examination of the current approaches to adult sentence applications and outline the best practices for youth court judges, Crown attorneys and defence lawyers. In support of this end, I have conducted a survey of 20 years of trial level adult sentence decisions from across Canada tracking the age, race, gender, support structures, and cognitive and mental health challenges, among other factors. I have framed this inquiry with the Critical Legal Studies tradition. However, given that adult sentence applications touch on a broad range of complex issues, portions of this thesis engage other legal and interdisciplinary theories including Critical Discourse Analysis, Law and Emotion Theory, Critical Race Theory and Disability Legal Theory.
Ultimately, this thesis highlights the importance of respecting the letter and spirit of the law set forth by Parliament and by the Supreme Court of Canada in DB, in anticipation of the SCC’s upcoming consideration of these very important principlesFebruary 202
Kawasaki disease in Kenya and review of the African literature
No full textBackground
Kawasaki disease has been described across the globe, although publications from Africa are limited. To our knowledge, there are no publications on Kawasaki disease from Kenya, which triggered this report.
Methods
A retrospective cross-sectional study was undertaken to identify in-patients with a discharge diagnosis of Kawasaki disease, over 2 different 5-year periods, at two pediatric hospitals in Nairobi, Kenya. We reviewed the medical records of all patients and report their clinical findings, diagnostic workup and treatment. In addition, we undertook a detailed review of the literature.
Results
Twenty-three patients with Kawasaki disease were identified, of those 12 (52.2%) had incomplete disease. The mean age was 2.3 years (SD+/-2.2) (range 0.3–10.3) with a male to female ratio of 1:1. The mean duration of fever at diagnosis was 8.3 days (SD+/-4.7) (range 2–20). Oral changes were the most common clinical feature and conjunctivitis the least common. Thrombocytosis at diagnosis was seen in 52% (12/23). Twenty-one patients (91.3%) were treated with intravenous immunoglobulin and all except 1 received aspirin. Baseline echocardiograms were performed in 95.7% (22/23) and found to be abnormal in 3 (13.6%). Follow-up data was limited. Our literature review identified 79 publications with documented cases of Kawasaki disease in children from 22 countries across the African continent with a total of 1115 patients including those from this report. Only 153 reported cases, or 13.7%, are from sub-Saharan Africa.
Conclusions
This is the first publication on Kawasaki disease from Kenya and one of the largest reports from sub-Saharan Africa. It is the first to have a complete review of the number of published cases from the African continent. Challenges in the diagnosis and management of Kawasaki disease in many African countries include disease awareness, infectious confounders, access and cost of intravenous immunoglobulin, access to pediatric echocardiography and follow-up. Increasing awareness and health care resources are important for improving outcomes of Kawasaki disease in Africa
From the White Horse Plain to the shores of Lake Manitoba: migration stories of my maternal Metis family the Brelands, Naults/Neaults, Thiberts, and Zaces/Zastres.
No full textThe socioeconomic and cultural beginnings of the Metis are found within family, extending outward through kinship networks or kinscapes created and maintained to connect families and communities to each other across distances (Lakomaki 2014 in St-Onge and Macdougall 2021, 90). Mobility and migration were both familiar and necessary elements of Metis life. Scholar Chris Anderson (2014) described his own historic self-understanding of being Metis “as a form of memory and nostalgia rooted in the people, places, and events tied to a core of Metis peoplehood, despite its widespread marginalization in contemporary white society” (270).
Utilizing genealogical reconstructions and ancestor biographies, this thesis recounts the migration stories of the Breland, Nault/Neault, Thibert, and Zace/Zastre families from which I am a direct descendent. It examines and describes the precolonial beginnings of these Metis families, their early presence on the lands of the northern plains and northwest, their migration to the Red River Settlement, and their subsequent dispersal to the western shores of Lake Manitoba where they established the communities of Ste. Rose du Lac and Cayer.
The work is framed by two Indigenous studies frameworks, Wahkootowin (Macdougall 2010; Wildcat 2018; Campbell 2007) and Insurgent Research (Adam Gaudry 2011). Key concepts that provide context for each family’s story include relationality (Moreton-Robinson 2017; Wildcat & Voth 2023), peoplehood (Andersen 2014; Hancock 2021), nationhood (Andersen 2014), and community (Stevenson 2020; Hogue 2015, Andersen 2014).October 202
Assessing and Documenting Gender Identity in Emergency Departments: A Narrative Literature Review
No full textBackground: Many equity-deserving populations utilize the emergency department (ED) as they lack access to primary health care. Transgender and gender diverse (TGD) people are one of those populations. Despite improving rights for TGD people in Canada, transphobia, trans-hate, and cis-normativity are rising in the country. The literature shows that TGD people avoid the ED due to previous experiences of oppression within the health care system. The current state of science supports the need for health care providers (HCPs) to receive more education on the experiences of TGD patients.
Methods: A narrative literature review was utilized to synthesize best practices for accurately assessing and documenting the gender identity (GI) of patients who present to the ED.
Findings: The literature recommends that HCPs include GI in their documentation and electronic patient records; however, this frequently does not occur. Without acknowledging, affirming, and documenting patients' GI, ED HCPs perpetuate existing discrimination and miss key information by not accurately accounting for their TGD patients' identities. This poster will present the literature review’s implications (importance of documenting GI, how questions about GI are asked by HCPs, patient and HCP comfort with GI questions, and the preferred method of asking GI questions) and recommendations (a two-step questionnaire that asks about sex assigned at birth and gender identity).
Conclusion: HCPs must work to improve equity for their patients, especially for TGD patients. To work towards addressing health inequities, the medical community must first accurately acknowledge and affirm diverse identities. The first step is a two-step questionnaire
Nutritional composition of dried fishes from Bangladesh and functional properties of their protein isolates
No full textDried fishes (DFs) are considered to be rich in protein, fat, ash and easy to store as well as transport at room temperature. However, they have been neglected for a long time with respect to their nutritional quality, consumption safety and their potential as an innovative food ingredient. To alleviate the serious public health challenge posed by malnutrition and find new possibilities for the food industry, it is particularly important to study the nutritional profile of dried fish and explore their functional characteristics to pave the way for subsequent industrial applications. Therefore, this study explored the nutrient composition of seven different DFs (Bombay duck: BD, Harpadon nehereus; ribbon fish: RF, Trichiurus iepturus; white sardine: WS, Escualosa thoracata; freshwater barb: FB, Puntius spp.; Ganges River sprat: GR, Corica soborna; fermented barb: FM, Puntius spp.; fermented anchovies: FA, Setipnna spp.) collected from four cities (Cox’s Bazar: C; Dhaka: D; Mymensingh: M; Sylhet: S) in Bangladesh. In addition, further investigation was conducted on determining the functional properties of dried fish protein isolates (DFPIs) from Dhaka at neutral pH (7.0), thereby to broaden the value-addition of DFs and explore potential applications of the isolated proteins as ingredients in the food industry. We found that two small indigenous DFs, WS and GR, showed good potential as a protein source because both of them contained more than 75% protein, in which the essential amino acids (EAA) content accounted for 50% of the total amino acids, and the scores of various individual EAAs exceeded 100. In addition, there were significantly (p<0.05) lower contents of sodium and higher potassium in WS and GR, making them good sources of these minerals. An excellent fatty acid profile was detected in WS based on the high levels of EPA (6-7%), DHA (~19%) and other n-3 fatty acids (total n-3 fatty acid: 32-35%), making it a great source of health-promoting essential fatty acids. All the DFs analyzed in this study are good sources of vitamin B12. However, the presence of high levels of heavy metals in several of the DFs, except for WS, is not desirable due to potential adverse effects on human health. In addition, a relatively high cholesterol content (0.17-0.25 µg/g) in GR also limits its promotion potential among consumers as a source of healthy nutrients. In terms of DFPIs’ functional proprieties, it was found that the high concentration of NaCl contained in DFs increased the ionic strength of the extraction environment and caused the isoelectric point (IP) to move towards to acidic direction (pH 4.5). Under neutral pH conditions, BD-D exhibited higher solubility (85.03±1.06%), relatively stable heat coagulability (6.23 ± 0.41 %), excellent water/oil holding capacity (water holding: 7.00 ± 0.47 g/g; oil holding: 20.13 ± 0.14 ml/g), as well as strong gelling ability (least gel concentration: 3%) and emulsifying properties (oil droplets size of 2-3.5 μm; emulsion stability: 70-100 %). Far-UV CD results reflect that β-sheet (20-35%) and random coil (35-46%) are the predominant secondary structures of DFPIs, indicating highly denatured structures. The almost zero ellipticity in the near-UV spectrum also implies that except the GR, most of the tertiary structures in DFPIs are also unfolded. The polypeptide profile lacked the characteristic band of myofibrillar protein at 200 kDa. Instead, the broad bands at 37-25 and 15-10 kDa indicate that the myofibrillar and sarcoplasmic protein of DFPIs have been degraded into shorter peptides with low molecular weights.October 202
Consistent cord blood DNA methylation signatures of gestational age between South Asian and white European cohorts
No full textBackground
Epigenetic modifications, particularly DNA methylation (DNAm) in cord blood, are an important biological marker of how external exposures during gestation can influence the in-utero environment and subsequent offspring development. Despite the recognized importance of DNAm during gestation, comparative studies to determine the consistency of these epigenetic signals across different ethnic groups are largely absent. To address this gap, we first performed epigenome-wide association studies (EWAS) of gestational age (GA) using newborn cord blood DNAm comparatively in a white European (n = 342) and a South Asian (n = 490) birth cohort living in Canada. Then, we capitalized on established cord blood epigenetic GA clocks to examine the associations between maternal exposures, offspring characteristics and epigenetic GA, as well as GA acceleration, defined as the residual difference between epigenetic and chronological GA at birth.
Results
Individual EWASs confirmed 1,211 and 1,543 differentially methylated CpGs previously reported to be associated with GA, in white European and South Asian cohorts, respectively, with a similar distribution of effects. We confirmed that Bohlin’s cord blood GA clock was robustly correlated with GA in white Europeans (r = 0.71; p = 6.0 × 10–54) and South Asians (r = 0.66; p = 6.9 × 10–64). In both cohorts, Bohlin’s clock was positively associated with newborn weight and length and negatively associated with parity, newborn female sex, and gestational diabetes. Exclusive to South Asians, the GA clock was positively associated with the newborn ponderal index, while pre-pregnancy weight and gestational weight gain were strongly predictive of increased epigenetic GA in white Europeans. Important predictors of GA acceleration included gestational diabetes mellitus, newborn sex, and parity in both cohorts.
Conclusions
These results demonstrate the consistent DNAm signatures of GA and the utility of Bohlin’s GA clock across the two populations. Although the overall pattern of DNAm is similar, its connections with the mother's environment and the baby's anthropometrics can differ between the two groups. Further research is needed to understand these unique relationships