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Reply to commentary on “Norms for Arguments for or against Asking or Posing Questions”
No full textI thank Yun (Robert) Xie for his careful summary and probing critique of my paper
Characteristics of 9-1-1 Calls Associated with an Increased Risk of Violence Against Paramedics in a Single Canadian Site
No full textViolence is a significant occupational health issue for paramedics, yet underreporting limits efforts to identify and mitigate risk. Leveraging a novel, point-of-event violence reporting system, we aimed to identify characteristics of 9-1-1 calls associated with an increased risk of violence in a single paramedic service in Ontario, Canada. Methods: We retrospectively analyzed all electronic violence and patient care reports filed by paramedics in Peel Region and used logistic regression to identify call-level predictors of any violence and, more specifically, physical or sexual assault. Results: In total, 374 paramedics filed 974 violence reports, 40% of which documented an assault, corresponding to a rate of 4.18 violent encounters per 1000 9-1-1 calls. In adjusted models, the risk of violence was elevated for calls originating from non-residential locations (e.g., streets, hotels, bars), occurring during afternoon or overnight shifts, and involving young or working-age males. Presenting problems related to intoxication, mental health, or altered mental status were strongly associated with increased risk, with particularly high adjusted odds ratios for assault. Conclusions: These findings support the utility of near-miss and violence surveillance systems and highlight the need for multidisciplinary crisis response to high-risk calls, especially those involving mental health or substance use
Feasibility and acceptability of a self-guided internet-delivered dialectical behavior therapy intervention for adults with mental health challenges.
No full textMennonites, the Apocalypse, and the Appeal of the Walking Dead
Full text linkoai:uwindsor.scholaris.ca:20.500.14776/1525
Cell Size regulation by a New Cell Cycle checkpoint: Characterization of clinically relevant Tuberin mutants
No full textTuberous sclerosis (TS) is a multi-system genetic disease caused by the growth of benign tumours primarily in the brain, kidneys, heart, eyes, lungs, and skin. TS has particularly severe consequences on the central nervous system, resulting in seizures, developmental delay and behavioral problems. This disorder affects around 1.5 million individuals worldwide and occurs by a mutation in one of two genes; TSC1 or TSC2. The TSC2 gene encodes for the protein Tuberin, a tumour suppressor protein well known for it's ability to regulated cell growth and the cell cycle. Altered levels of Tuberin and mutations in this protein have been found in several cancers, including medulloblastoma and skin cancer. We have established that Tuberin binds and regulates the G2/M cyclin, Cyclin B1 (CycB1) creating a new G2/M checkpoint. Our results show that the Tuberin/CycB1 interaction regulates cell size and this regulation is nutrient dependent. Several mutations responsible for TS are present in the CycB1 binding domain located in the N-terminal domain of Tuberin. It is our hypothesis that these mutations can affect the Tuberin/CycB1 interaction and result in dysregulation of cell proliferation and cell size. Using site-directed mutagenesis we constructed six TSC2 mutants to study the phenotypes in HEK293 and NIH3T3 cells. We have demonstrated that one mutation, Tuberin-C698Y, has lower affinity for CycB1 binding and presents a nuclear localization instead of the usual cytoplasmic localization of the wild type complex. We are focusing on this mutation to determine the full range of consequences of abrogating this interaction. Importantly, we are inserting the Tuberin-C698Y mutation into the HEK293 cells genome through the CRISPR-Cas9 system to determine the endogenous significance of this specific change. The phenotype of these cells will be studied by immunofluorescence and flow cytometry techniques. Patients with specific TSC2 mutations develop TS and have an increased chance of select cancers. Having a better understanding of how specific changes in this large protein alters fundamental cell biology such as cell proliferation and cell size can ultimately help to effectively treat patients with these specific mutations
SPY1-Mediated Cell Cycle Regulation as a Target to Overcome GSC-induced Therapy Resistance in Glioblastoma
No full textGlioblastoma (GBM) is an extremely lethal type of brain tumour that evades all intricate attempts of modern therapies. Extensive genetic analyses of GBM have indicated a variety of deregulated molecular pathways involved in DNA repair, apoptosis, cell migrationadhesion, and cell cycle regulation. Brain tumour-initiating cells (BTICs) aid in the initiation, progression, and therapy resistance of the heterogenous mass of glioblastoma and are responsible for post-therapy tumour recurrence. BTICs share properties with normal neural stem cells (NSCs), including the ability to self-renew and give rise to differentiated progeny. Previously, our lab established that the levels of an atypical cell cycle protein, SPY1 (RINGO; gene SPDYA) are elevated in malignant human glioma and its upregulation correlates with poor prognosis of patients with GBM. SPY1 is responsible for the symmetric division of BTICs in subsets of high-grade glioma leading to aberrant expansion of those aggressive populations of cells. Spy1 activates Cyclin-Dependent Kinases (CDK) and has been demonstrated to override protective cell cycle checkpoints. We hypothesize that selected targeting of SPY1-CDKs is effective in eliminating BTIC populations and could contribute to more improved therapeutic intervention for subsets of GBM patients in the future. My research project will validate the potential of SPY1-CDK2 targeting for better control over the growth and progression of GBM. The objectives of my study will allow for the evaluation of GBM biology in the face of SPY1 depletion and functional assessment utilizing GBM patient-derived neurosphere cultures and in vivo zebrafish-derived Xenograft (PDX) screening platform
Learning and development in Higher Education through Extension Action
Full text linkIn a pandemic context, insecurity in the face of challenges and adverse situations is experienced. It is important to revisit the training of professionals, to better prepare them to deal with new technological tools, in an educational and market ecosystem, innovating the concepts of learning in the digital age. This component favours students in the construction of knowledge, and not only in the accumulation of information. In this context, remote learning proves to be an effective and inclusive solution. While there are reluctant attitudes and difficulties with remote learning, there is an opportunity for students and teachers to explore and innovate in teaching-learning. This proposal brings the experience of stimulating the development of skills, through extension action, in higher education
Investigation of the Enhancement of Neuroprotective Efficacy of Water Soluble Ashwagandha Extract Alone and in Combination with Ubisol- Q10 for Parkinson's Disease
No full textParkinson's disease (PD) is the second most common chronic and progressive neurodegenerative disease and the most common movement disorder. PD is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), leading to symptoms such as tremors, bradykinesia, postural instability, and rigidity. Biochemical pathologies of PD include oxidative stress, autophagy and mitochondrial dysfunction, and neuroinflammation. Current treatments for PD provide only symptomatic relief and fail to halt progression of neurodegeneration. Prolonged treatment can result in adverse motor/behavioural side effects. Previous studies have shown that supplementary antioxidants such as coenzyme Q10 have neuroprotective abilities and can target mechanisms of oxidative stress and mitochondrial and autophagic dysfunction, however, it has limited bioavailability since it is lipophilic.A water-soluble formulation of CoQ10 (Ubisol-Q10) was created to increase bioavailability. Ubisol-Q10 was shown to protect cultured neurons from paraquat (PQ) (an environmental toxin known to cause PD) toxicity and DA neurons in PQ induced rodent models of PD. Ethanolic ashwagandha has also been shown to provide neuroprotective, anti-inflammatory, and even neuro-regenerative properties in PQ induced rodent models of PD. Similar to CoQ10, ashwagandha extract phytochemicals are lipophilic, resulting in poor bioavailability. The same technology used in Ubisol-Q10 was used to enhance solubility of ashwagandha extract. Previously, we investigated the efficacy of combined Ubisol-Q10 and ethanolic ashwagandha treatments and we have begun to test the enhanced efficacy of the combination of both water-soluble formulations. Both physiological and behavioral components of PD progression in response to treatment in rats will be studied in this project. We anticipate that this combinatorial treatment will halt the progression by reducing oxidative stress, stabilizing mitochondrial function and activating autophagy mechanisms