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    Cell-based therapies and functional outcome in experimental stroke
    (2009) Rissanen, Anna; Schallert, Timothy; Jolkkonen, Jukka
    One of the most promising frontiers in neuroscience is the potential for stem cells to treat brain damage. Cell-based strategies are of particular interest in neurological conditions because mature brains have limited capacity for self-repair. It is often argued that stem cells might be used to replace lost neurons and restore function (Lindvall et al., 2004). Prior to clinical trials, safety and efficacy must be demonstrated in animal models. Indeed, a recent review strongly suggests that preclinical and clinical trial procedures and outcome measures, including behavioral assessments, must be closely aligned and sophisticated (Ginsberg, 2008). Unfortunately, a lack of translational success has been observed in stroke neuroprotection trials conducted thus far, and this experience should serve to caution that histological benefits in animals are not a sufficient reason to move to the clinic carelessly.
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    Transplantation of human embryonic stem cell-derived neural precursor cells and enriched environment after cortical stroke in rats: cell survival and functional recovery
    (2009) Rissanen, Anna; Lappalainen, Riikka S.; Narkilahti, Susanna; Suuronen, Riitta; Corbett, Dale; Sivenius, Juhani; Hovatta, Outi; Jolkkonen, Jukka
    Cortical stem cell transplantation may help replace lost brain cells after stroke and improve the functional outcome. In this study, we transplanted human embryonic stem cell (hESC)-derived neural precursor cells (hNPCs) or vehicle into the cortex of rats after permanent distal middle cerebral artery occlusion (dMCAO) or sham-operation, and followed functional recovery in the cylinder and staircase tests. The hNPCs were examined prior to transplantation, and they expressed neuroectodermal markers but not markers for undifferentiated hESCs or non-neural cells. The rats were housed in either enriched environment or standard cages to examine the effects of additive rehabilitative therapy. In the behavioral tests dMCAO groups showed significant impairments compared with sham group before transplantation. Vehicle groups remained significantly impaired in the cylinder test 1 and 2 months after vehicle injection, whereas hNPC transplanted groups did not differ from the sham group. Rehabilitation or hNPC transplantation had no effect on reaching ability measured in the staircase test, and no differences were found in the cortical infarct volumes. After 2 months we measured cell survival and differentiation in vivo using stereology and confocal microscopy. Housing had no effect on cell survival or differentiation. The majority of the transplanted hNPCs were positive for the neural precursor marker nestin. A portion of transplanted cells expressed neuronal markers 2 months after transplantation, whereas only a few cells co-localized with astroglial or oligodendrocyte markers. In conclusion, hESC-derived neural precursor transplants provided some improvement in sensorimotor function after dMCAO, but did not restore more complicated sensorimotor functions.
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    Challenges and possibilities of intravascular cell therapy in stroke
    (2009) Rissanen, Anna; Jolkkonen, Jukka
    Stroke is the third leading cause of death in Western countries and more importantly a leading cause of adult disability. The recovery process of stroke patients might be enhanced by intensive rehabilitation, which acts through brain plasticity mechanisms. Restorative approaches such as cell-based therapies are clinically appealing as it might be possible to help patients even when treatment is initiated days or weeks after the ischemic insult. An extensive number of experimental transplantation studies have been conducted with cells of different origins (e.g., embryonic stem, fetal neural stem, human umbilical cord blood) with promising results. Noninvasive intravascular administration of cells, which provides a broad distribution of cells to the close proximity of ischemic tissue, has perhaps the most immediate access to clinical applications. However, surprisingly little is known about whole body biodistribution of intravascularly administered cells and mechanisms leading to improved functional recovery. This review examines the recent literature concerning intravascular cell-based therapies in experimental stroke.
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    Long-term assessment of enriched housing and subventricular zone derived cell transplantation after focal ischemia in rats
    (2008) Rissanen, Anna; MacLellan, Crystal L.; Chernenko, Garry A.; Corbett, Dale
    The potential for using stem cells to treat stroke has garnered much interest, but stem cell therapies must be rigorously tested in animal models before transplantation studies progress to clinical trials. An enriched environment enhances transplanted subventricular zone (SVZ) cell migration and functional benefit following stroke in rats. However, the ability of SVZ cells to survive, migrate, differentiate and promote functional recovery at protracted survival times (e.g., 3 months) has not been investigated. The vasoconstrictive peptide endothelin-1 was injected adjacent to the middle cerebral artery to produce focal ischemia. Seven days later, cells derived from the SVZ of adult mice (800,000 cells/rat or vehicle injection) were transplanted into the sensory-motor cortex and striatum, and rats were then housed in enriched or standard conditions. Rats in enriched housing had access to running wheels once per week. Recovery was assessed in the forelimb-use asymmetry task (cylinder) at 1, 2, or 3 months after transplantation immediately prior to euthanasia. Transplanted cell survival and migration were quantified using stereology. Cell phenotype was determined with immunohistochemistry and confocal microscopy. Enriched housing did not enhance survival or migration of transplanted SVZ cells at protracted survival times, and the majority (~ 99%) of cells died within 2 months of transplantation. Cell survival was significantly, and negatively, correlated with microglial activation. Many surviving cells expressed an astrocytic phenotype. Functional recovery was not improved at any time. Therapies involving transplantation of SVZ cells following stroke must be further optimized in order to enhance long-term cell survival and thereby maximize functional benefit.
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    Enriched environment enhances transplanted subventricular zone stem cell migration and functional recovery after stroke
    (2007) Rissanen, Anna; Hewlett, K.; Windle, V.; Chernenko, Garry A.; Ploughman, M.; Jolkkonen, Jukka; Weiss, S.; Corbett, Dale
    Stroke patients suffer from severe impairments and significant effort is under way to develop therapies to improve functional recovery. Stem cells provide a promising form of therapy to replace neuronal circuits lost to injury. Indeed, previous studies have shown that a variety of stem cell types can provide some functional recovery in animal models of stroke. However, it is unlikely that replacement therapy alone will be sufficient to maximize recovery. The aim of the present study was to determine if rodent stem cell transplants combined with rehabilitation resulted in enhanced functional recovery after focal ischemia in rats. Middle cerebral artery occlusion was induced by injection of the vasoconstrictive peptide endothelin-1 adjacent to the middle cerebral artery. Seven days after stroke the rats received adult neural stem cell transplants isolated from mouse subventricular zone or vehicle injection and then subsequently were housed in enriched or standard conditions. The rats in the enriched housing also had access to running wheels once a week. Enriched housing and voluntary running exercise enhanced migration of transplanted stem cells toward the region of injury after stroke and there was a trend toward increased survival of stem cells. Enrichment also increased the number of endogenous progenitor cells in the subventricular zone of transplanted animals. Finally, functional recovery measured in the cylinder test was facilitated only when the stem cell transplants were combined with enrichment and running exercise 7 days after the transplant. These results suggest that the ability of transplanted stem cells in promoting recovery can be augmented by environmental factors such as rehabilitation.
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    Prolonged bihemispheric alterations in unfolded protein response related gene expression after experimental stroke
    (2006) Rissanen, Anna; Sivenius, Juhani; Jolkkonen, Jukka
    After ischemia, endoplasmic reticulum (ER) stress pathways are activated that include unfolded protein response (UPR) and protein synthesis inhibition (PSI). Both of these mechanisms aim to restore ER functioning mainly by inhibition of translation and increased processing of excess proteins in ER. We were interested in the role of these pathways during spontaneous recovery after transient middle cerebral artery occlusion (MCAO) in rats. The spontaneous recovery of rats was assessed with a limb-placing test. The expression of ER-stress-related genes (IRE1, ATF6, GRP78, eif2α, ATF4, PERK) was studied by using in situ hybridization in different brain areas on post-operative days 2, 7, 14 and 28. Elevated signals were detected in striatum contralateral to the lesion on days 2 (PERK and IRE1) and 14 post-ischemia (IRE1). Gene expression was elevated on day 7 in the striatum ipsilateral to the lesion (ATF6 and GRP78) and on day 14 (GRP78) post-ischemia. Furthermore, elevated levels of GRP78 were detected on day 14 after ischemia in the ipsilateral sensorimotor cortex. These results suggest that altered gene expression related to unfolded protein response may be more long lasting than expected following focal cerebral ischemia. In addition, these results show that the response to ER stress differs ipsi- and contralaterally after MCAO in rats. Since these differences are detected in both hemispheres only in areas adjacent to the lesion, UPR may contribute to spontaneous recovery after MCAO in rats.
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    Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation
    (2004) Heikkinen, T.; Kalesnykas, G.; Rissanen, Anna; Tapiola, T.; Iivonen, S.; Wang, J.; Chaudhuri, J.; Tanila, H.; Miettinen, R.; Puoliväli, Jukka
    We investigated the effects of ovariectomy (OVX) and 17β-estradiol (0.18 mg per pellet) treatment on spatial learning and memory, hippocampal beta amyloid (Aβ) levels, and amyloid plaque counts in double transgenic mice (A/P) carrying mutated amyloid precursor protein (APPswe) and presenilin-1 (PS1-A246E). After OVX at 3 months of age, the mice received estrogen treatment for the last 3 months of their lifetime before they were killed at 6, 9, or 12 months of age. Estrogen treatment in A/P OVX mice increased the number of correct choices in a position discrimination task in the T-maze, and slightly improved their performance in a win-stay task (1/8 arms baited) in the radial arm maze (RAM). However, estrogen treatment did not reverse the Aβ-dependent cognitive deficits of A/P mice in the water maze (WM) spatial navigation task. Furthermore, ovariectomy or estrogen treatment in OVX and sham-operated A/P mice had no effect on hippocampal amyloid accumulation. These results show that the estrogen treatment in a transgenic mouse model of Alzheimer's disease (AD) improves performance in the same learning and memory tasks as in the normal C57BL/6J mice. However, the estrogen effects in these mice appeared to be unrelated to Aβ-induced cognitive deficits. Our results do not support the idea that estrogen treatment decreases the risk or alleviates the symptoms of Alzheimer's disease by inhibiting the accumulation of Aβ or formation of amyloid plaques.
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    Effects of ovariectomy and estrogen treatment on learning and hippocampal neurotransmitters in mice
    (2002) Heikkinen, Taneli; Puoliväli, Jukka; Liu, Li; Rissanen, Anna; Tanila, Heikki
    This study examined the effects of long-term estrogen treatment (sc 17β-estradiol minipellets) on learning in C57BL/6J female and male mice using a position discrimination task in the T-maze and a win-stay task (1/8 arms baited) in the radial arm maze (RAM). In addition, hippocampal monoamines and ChAT activity were measured at the end of the study and correlated to task performance. Female sham-operated (gonadally intact) and ovariectomized (OVX) mice were treated with estrogen either for 7 or 40 days before the behavioral tests and intact male mice for 7 days before the behavioral tests. In sham-operated mice the 40-day estrogen treatment improved RAM performance and in OVX mice both the 7- and 40-day estrogen treatments improved the performance in both maze tasks. The estrogen treatment also improved RAM performance in males. The hippocampal ChAT, NA, 5-HIAA, and DOPAC levels were decreased in OVX mice. Furthermore, the effects of estrogen treatment on the levels of hippocampal 5-HT and its metabolite 5-HIAA were different in sham-operated than in OVX mice. We could find no correlation between cognitive measures and neurochemical variables. This study gives new information about the effects of estrogen on learning and hippocampal neurotransmitters in mice.
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    In mice tonic estrogen replacement therapy improves non-spatial and spatial memory in a water maze task
    (1999) Rissanen, Anna; Puoliväli, Jukka; van Groen, Thomas; Riekkinen, Paavo Jr.
    Investigated the effects of estrogen replacement therapy on water maze non-spatial and spatial navigation in mice. Three groups of mice were ovariectomized and two of these groups being implanted with s.c. pellets that produce blood levels of estrogen close to those found in estrous (estrogen low, 75–100 pg/ml blood) or proestrous (estrogen high, 300–400 pg/ml). The behavioral assessment was initiated 7 days after pellet implantation. Non-spatial navigation to a clearly visible platform was stimulated by low and high levels of estrogen. However, spatial navigation to a hidden platform was improved by low estrogen levels. We found that estrogen improves two different types of memory processes that depend on striatal (non-spatial navigation) and hippocampal (spatial) memory systems.
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    Interdisciplinary supports for student mental health: Pets Assisting With Student Success - PAWSS at MacEwan University
    (2024) Bialowas, Payden; Oloriz, Abby; Rissanen, Anna
    Student mental health is a critical concern in academic environments, where the pressures of academic life can significantly impact well-being. This study investigates the effectiveness of animal-assisted therapy in alleviating mental health challenges. Collaborating with the Pet Assisting With Student Success (PAWSS) program at MacEwan University, we aimed to understand how interactions with therapy animals could benefit students. Employing a qualitative phenomenological approach, we gathered data on student experiences with the PAWSS program through Qualtrics. Through the survey, we explored the way in which the program influenced students' daily lives and their ease of accessing these therapeutic interactions and considered improvements that could be made to make the program more accessible to students. Participants consistently reported reductions in anxiety and stress after engaging with the PAWSS events or encountering therapy animals in hallways. Our poster includes common themes about students’ experiences with the PAWSS program, which are visually reflective through NVivo. Our findings highlight the profound positive impact of animal-assisted therapy on student stress levels and overall mental health. The human-animal bond fostered through the PAWSS program not only provides immediate relief but also cultivates a supportive campus environment. This research underscores the value of interdisciplinary approaches to mental health support and the transformative potential of integrating animal-assisted therapy into university settings.
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    Effectiveness of virtual discovery learning in medicine
    (2024) Rissanen, Anna; Bistritz, Lana M.; Petrov, Petar A.
    Background/Purpose - After pandemic restrictions were lifted, students were interested in retaining hybrid learning options. In response, the MD program offered a Virtual Discovery Learning (DL) stream during pre-clerkship. This study compares the learning outcomes of virtual vs in-person DL students in the Gastroenterology and Nutrition course. Methods - Using mixed methods, students were separated into Virtual and In-person DL groups. Learning outcome data was collected and anonymized. Overall student performance for MCQ assessments and performance for DL specific questions in those assessments was compared between the two groups using two-tailed T-Test with two sample unequal variance. Qualitatively, we performed focus groups where students provided feedback on their Virtual DL experience, their reasoning for choosing the Virtual DL stream and their impressions of the experience. Results - Statistical analysis of student performance data concluded that there were no statistically significant differences in grade averages between the Virtual and In-person DL groups for the GI final exam (p=0.92), except for one DL specific question on the final (p=0.008). Focus group sessions identified 4 main themes for why students chose virtual learning: Covid-19; Flexibility; Accessibility and Learning Preferences; and Mental Health. Discussion - Students who chose to attend Discovery Learning virtually did not experience any academic advantage or disadvantage in learning compared to students who attended DL in-person, and psychosocial benefits of virtual attendance were identified. This suggests that an optional hybrid model for DL is potentially beneficial to students without impacting learning outcomes.
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    Mental health supports for post-secondary students - focus on animal-assisted wellness and trauma-informed practices
    (2024) Rissanen, Anna
    Mental health-related problems, stress and symptoms of mental illness have been increasing in Canadian postsecondary students. We need more focus on interdisciplinary campus services that help struggling students such as animal-assisted therapy on campus. Also, an important area of interest is understanding the psychosocial determinants of mental health such as the effects of adverse childhood experiences (ACEs), experienced trauma, and added distress from discrimination and racism on post-secondary students. It is important for professors, administrators, and others to understand trauma-informed practices to prevent further harm. In attempts to avoid poor academic performance, and further accumulation of psychosocial problems, we need to address the needs of students. Specifically, trauma informed practices need exploration as research on trauma informed teaching and clinical practice are underutilized in Canadian campuses. Also, it is important to explore interdisciplinary therapy services, such as animal-assisted therapy that has a low barrier of participation. The overall goal for university administrators is to understand the complexity of student mental health that encompasses the diversity of post-secondary students’ mental health challenges, including interdisciplinary and trauma-informed practices. In this presentation I will present the results of a survey about trauma-informed practices utilized in Canadian universities. Also, I will share the results of a preliminary study about the effectiveness of animal-assisted therapy on a Canadian University campus. There is potential that this preliminary research will lead to further studies on how to educate campus members in trauma-informed practices, and further understanding of how we can prevent worsening of traumatized students' distress and improve their quality of life. Also, these are novel research results about additional treatments in student mental health, specifically on animal-assisted wellness and trauma-informed practices in post-secondary education.
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    How much physiology do fourth year nursing students really remember?
    (2024) Purani, Sharlini; Narnaware, Yuwaraj; Neumeier, Melanie; Cuschieri, Sarah; Chahal, Paul
    There is a growing concern that nursing students struggle to retain adequate physiological knowledge throughout their program to meet their entry to practice competencies. However, how much and when this knowledge is lost over a four-year undergraduate Bachelor of Science in Nursing program is yet to be evaluated. According to Narnaware Y. 2021, physiological knowledge retention has yet to be studied as comprehensively as anatomical knowledge retention in healthcare disciplines, including nursing programs. This study aims to assess the extent of physiological knowledge decline among nursing students by their fourth year. It is evaluated by comparing their understanding of physiological knowledge in the first year after their physiology course and the fourth year after completing their Critical Care nursing course. Physiological knowledge loss was assessed in fourth-year nursing students by quizzing them on ten organ systems using the online quizzing platform – Kahoot. About nine to eleven knowledge and comprehension-level multiple-choice questions were delivered. These scores were then compared to first-year quiz scores on the same content to determine overall knowledge loss over three years. The data was analyzed by using SPSS II and compared using 2-sample t-tests. The findings of this research illustrate a general reduction in knowledge loss, with variations in the decline specific to each system. In medical and allied health students, the knowledge loss was significantly lower than previously reported (Pourshanazari et al., 2013). Compared to the third year, knowledge loss in the fourth year, however, is not significantly different (Narnaware et al., 2021).
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    Research recast(ed): Following up with Dr. Cynthia Puddu and Cheyenne Greyeyes
    (2022) Ekelund, Brittany; Cave, Dylan; Puddu, Cynthia; Greyeyes, Cheyenne
    Listen in as we get learn about the updates and progress made on Dr. Cynthia Puddu and Cheyenne Greyeyes' research project with NiGiNan Housing Ventures! Today we are following up with our very first podcast guests, Dr. Cynthia Puddu and Cheyenne Greyeyes, as we learn about how their work with NiGiNan Housing Ventures is coming along, and how things are going at the Omamoo Wango Gamik pilot project. Please follow up with our conversation around Carola Cunningham by watching this webinar on Omamoo Wango Gamik. You can also listen to Carola speak here, at the presentation of her honourary doctorate from MacEwan University.
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    The signal lost in the noise
    (2023) Corlett, John
    Purpose The case studies were examined in the context of a lack of confidence in what constitutes truth and knowledge. Design/methodology/approach A case study design taken examining specific instances where the emergence of populist political tactics in an unfettered media world has undermined public belief in what counts as knowledge and to cast doubt on the validity of the idea of truth. Findings From the examples used, it was seen that not just scholarship, but scholars themselves, found themselves under attack when presenting views that, however rigorously reasoned and supported by research fact, were deemed unacceptable by the extreme political right. Practical implications The knowledge creation purpose of universities is under threat and “business as usual” as a response will not address that threat. Originality/value This calls into question the future of universities and their professoriates in a post-truth world and asks what the academy can do to adapt to continue serve the common good when knowledge gives way to the powerful influence of the evidence-free rhetorical sound bite in the formulation of public policy and public opinion.
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    Research recast(ed): S1E1 - A conversation with Dr. Cynthia Puddu and Cheyenne Greyeyes
    (2021-09) Ekelund, Brittany; Cave, Dylan; Puddu, Cynthia; Greyeyes, Cheyenne
    Today we discuss decolonizing transitions out of care, community-engaged scholarship, and we try to break down some complex concepts like settler colonialism and neoliberalism with Dr. Cynthia Puddu, an assistant professor in the Faculty of Health and Community Studies at MacEwan University. She is joined by Cheyenne Greyeyes, a student and research assistant at MacEwan, who is working alongside Cynthia on a research project, in partnership with Niginan Housing Ventures, documenting the urban Indigenous housing initiative and its approach to preventing houselessness in urban Indigenous youth. The Decolonizing Transitions from Care project is funded by the Government of Canada’s Networks of Centres of Excellence program. The opinions and interpretations in this podcast are those of the researcher and do not necessarily reflect those of the Government of Canada.
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    Third-year nursing student’s physiological knowledge retention
    (2023) Narnaware, Yuwaraj; Foster-Boucher, Caroline; Neumeier, Melanie; Chahal, Paul
    Anatomy and physiology are considered foundational courses in medical, nursing and allied-health care programs. However, there is a growing concern that students struggle to retain this essential knowledge over time. Numerous studies have demonstrated the difficulty of medical, nursing and allied healthcare students to retain and apply anatomical knowledge as they progress through their programs of study (Doomernik et al., 2017). However, physiological knowledge retention has not been studied as extensively as anatomical knowledge retention in health care disciplines, with very few studies focusing on nursing students (Aari et al., 2004). Of those studies, most are conducted after graduation (Aari et al., 2004) or are focused on a single or a limited number of organ systems (Pourshanazari et al., 2013). The present study aims to determine the level of physiological knowledge retained by nursing students in the third year between completing their physiology course in first-year nursing and third-year Nursing Care of Families with Young Children course. To answer this question, nursing students were quizzed on ten organ systems using the online quizzing system Kahoot. Each Kahoot quiz included nine to eleven knowledge and comprehension-level multiple-choice questions. These scores were compared to first-year quiz scores on the same content to determine overall knowledge retention over two years. Data were statistically analyzed using SPSS II, and means were compared using 2-sample t-tests. The scores are described for each organ system by reporting the mean and standard deviation (±SD). Statistical significance was set at P < 0.05 for all tests. The mean score of questions from all organ systems in year one was 62.89 ± 10.49 (±SD). Comparing that score to matched test items evaluated in the Nursing Care of Families with Young Children course, there is a decrease in the overall mean score from 62.89 ± 10.49 (±SD) to 50.95 ± 13.02 (±SD). This equates to an 88.06% retention rate, or 11.94% knowledge loss within two years. Organ-specific knowledge retention was highest for inflammation (100%), respiratory physiology (99.10%), and vascular physiology (95.01%), followed by blood (89.16%), digestive physiology (86.28%), endocrinology (83.76%), defences (82.50%) and renal physiology (82.19%). Retention was comparatively lower for fluid and electrolyte balance (79.36%) and reproductive physiology (77.54%). These results demonstrate a high level of knowledge retention overall, with variations in retention being system specific. The level of knowledge retention in this study was significantly higher than previous rates reported in medical and allied-health students (Pourshanazari et al., 2013) and higher than anatomical knowledge retention levels in the same population (Narnaware and Neumeier, 2021). However, knowledge retention in the third year is not significantly different from the second year (Narnaware et al., 2021).
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    Physiological knowledge retention in second-year bachelor of science and psychiatric nursing students
    (2023) Narnaware, Yuwaraj; Pawliuk, Brandi; Neumeier, Melanie; Cuschieri, Sarah; Chahal, Paul
    Numerous studies have demonstrated the difficulty of retaining and applying anatomical and physiological knowledge experienced by students in medical and allied health disciplines, although few studies focus on nursing students (Narnaware and Neumeier, 2020, 2021a). MacEwan University students in the Bachelor of Science in Nursing (BScN) and the Bachelor in Psychiatric Nursing (BPN) programs take the same first-year physiology course. With the understanding that discipline choice potentially impacts knowledge retention, this study aimed to determine the overall difference in physiological knowledge retention between second-year BScN and BPN students and if there is a difference based on the organ system.
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    Content retention of cell and membrane transport for physical education students
    (2023) Martin, Noah; Chahal, Paul; Narnaware, Yuwaraj
    Human physiology is considered a foundational course in the Physical Education program. The objective of the present study was to evaluate content retention of cell and plasma membrane transport for first-year Physical Education University Transfer physiology students over eight weeks. Results show that the knowledge retention was observed to be week-specific, highest in weeks one and three and lower for other weeks. Therefore, content reinforcement can be used as an interventional strategy to improve long-term knowledge retention in Physical Education University Transfer students.
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    Content reinforcement of cell and membrane transport between kinesiology and arts & science students
    (2023) Ma, Robin; Chahal, Paul; Narnaware, Yuwaraj
    The present study evaluates content reinforcement of cell membrane transport over eight weeks for Physical Education and Arts and Science physiology students. The highest retention for physical education students was in weeks 1 and 3, whereas for the Arts and Science students, it was the highest in weeks 2 and 3. Knowledge was comparatively higher for Physical Education students than for the Arts and Science students. Therefore, relatively more robust interventional strategies need to be implemented for Arts and Science students to improve knowledge retention.