VictorJuiz/thesis huggingface dataset:
Dietary curcumin intervention targets both white adipose tissue inflammation and brown adipose tissue thermogenesis
Keywords: Adipose tissue inflammation
Energy expenditure
Insulin resistance
Macrophage
Thermogenesis
UCP1

Increased adipose tissue inflammation and reduced energy expenditure are among the key causative factors of obesity and its related metabolic disorders. Therapeutic tools targeting these two pathological events are desired. Previous studies have mainly attributed the body-weight lowering effect of curcumin and other dietary polyphenols to their anti-inflammatory properties in adipose tissues and elsewhere. We found that in high-fat diet (HFD)-fed mice, dietary curcumin intervention reduced not only epididymal adipose tissue macrophage infiltration but also the ratio of M1-like versus M2-like macrophages. In vitro curcumin treatment also reduced pro-inflammatory cytokine expression in macrophages and adipocytes. Furthermore, curcumin intervention in HFD-fed mice increased energy expenditure and body temperature in response to cold challenge, associated with increased brown adipocyte uncoupling protein 1 expression. We conclude that curcumin-intervention plays a dual modulatory role in preventing metabolic disorders by attenuating white adipose tissue inflammation and increasing brown adipocyte activity.
Exploring the role of Credit Assignment of Error in Motor Learning
Keywords: Balance Beam
Credit Assignment
Error
Motor Learning

Errors are critical to motor learning. The source of error can be environmental forces or poor motor control. The central nervous system (CNS) likely distinguishes between sources of error. If the CNS attributes error to motor control (i.e., internal credit assignment) adaptations will transfer across situations; errors attributed to the environment (i.e. external credit assignment) may lead to context-specific learning. I tested this hypothesis by manipulating the perceived source of error as participants learned balance-beam walking. The Aware (AW) and Unaware (UN) groups experienced subthreshold platform perturbations during practice; Control group (CN) practiced without perturbations. AW was informed that the platform would move (external credit assignment); UN was told the platform would not move (internal credit assignment). UN improved performance faster than CN during acquisition, and showed greater learning than CN on a narrow beam transfer. Credit assignment may affect learning and could influence how motor skills should be taught.
A Cost-Effectiveness Analysis of Preimplantation Genetic Screening with In Vitro Fertilization In Ontario
Keywords: aneuploidy
cost-effectiveness
economic evaluation
infertility
in vitro fertilization
preimplantation genetic screening

Background: Preimplantation genetic screening (PGS) is an increasingly common addition to IVF cycles in an effort to improve upon current embryo selection techniques by limiting the transferrable cohort of embryos to those that are euploid. Objective: To examine the cost-effectiveness of preimplantation genetic screening (PGS) with IVF compared to IVF alone in terms of additional live births. Methods: A decision analytic model was created using TreeAge Pro to compare IVF with PGS to IVF alone for women of different age groups with one to ten blastocysts from the societal perspective. Sequential single embryo transfers of blastocysts from a single oocyte retrieval were modelled until all blastocysts were exhausted, treatment was discontinued or a live birth was achieved. Results: PGS became both incrementally less costly and more effective as the number of blastocysts and the age of the woman increased. IVF alone was the superior strategy â more effective and less costly - for all women under age 35. This was also true when three or fewer blastocysts were available, regardless of age. Sensitivity analysis showed that the model was most sensitive to the implantation rates and early pregnancy loss rates of both IVF with PGS and IVF alone. Conclusions: Using currently available data, PGS appears to be more costly and less effective than IVF alone in the majority of scenarios. However, PGS may be less costly and more effective for older women with a large number of blastocysts. Future research should focus on improving available population-based PGS outcome data.
Tryptophan and Serotonin Metabolism During Pregnancy Related to Season and Seasonality Status of Women
Keywords: Brain Development
Placenta
Pregnancy
Serotonin
Tryptophan

We investigated seasonal differences in plasma tryptophan, large neutral amino acids (LNAAs), and kynurenine between 15 and 18 weeks of pregnancy in 20 â highly seasonalâ women and 35 non-seasonal controls. Placentae from a subset of the 55 women (15 non-seasonal and 7 highly seasonal) giving birth in the fall-winter period were also collected to measure rate-limiting enzymes of the indoleamine pathway. Results indicated a significant seasonality group by season interaction for plasma tryptophan and LNAAs, and a significant main effect of season for plasma kynurenine. In highly seasonal women only, tryptophan levels were significantly lower in fall compared with winter or spring, and significantly higher in winter compared with summer. No pairwise group differences in LNAAs were observed. Levels of kynurenine were significantly lower in the summer compared with winter. Fall-winter term placental MAOA protein was significantly higher in highly seasonal women compared with non-seasonal women. Other mRNA and protein levels of key indoleaminergic enzymes were not significantly different between seasonality groups. These findings suggest that both season and seasonality status of pregnant women influence plasma tryptophan, LNAAs, and kynurenine levels and placental MAOA protein expression during pregnancy.
Associations between Plasma 25-Hydroxyvitamin D, Hormonal Contraceptives, and Premenstrual Symptoms
Keywords: Ethnicity
Hormonal Contraceptives
Vitamin D
Women's Health

Premenstrual symptoms are experienced by the majority of women and may cause significant personal and professional impairment; however, little is known about their pathophysiology and risk factors. The purpose of this thesis was to determine the prevalence of common premenstrual symptoms in a multiethnic Canadian population and to explore the associations of plasma 25-hydroxyvitamin D and hormonal contraceptive use with these symptoms. Symptom prevalence was found to vary widely between common symptoms, ranging from 11% to 75%. Prevalence of individual symptoms did not differ between ethnic groups, with the exception of cramps. Hormonal contraceptive use was associated with a reduction in the risk of experiencing several symptoms at moderate/severe severity. Plasma 25-hydroxyvitamin D was also inversely associated with the prevalence and severity of several premenstrual symptoms. These findings suggest HC use may be an effective targeted treatment and vitamin D status may be a risk factor for individual premenstrual symptoms.
Evaluating the Effects of General Anesthesia on Sleep in Children Undergoing Elective Surgery
Keywords: Actigraphy
General anesthesia
Pediatric
Sleep disturbances
Surgery

Background: There is increasing interest towards factors that may contribute to impaired sleep following surgery, but there remains a gap in knowledge regarding the impact of general anesthesia on sleep. The objective of this study was to identify potential effects of a general anesthetic on sleep and related behavioural consequences. Methods: Children, aged 18 months to 8 years, wore an actigraph to estimate sleep-wake patterns for 7 consecutive nights prior to and after surgery. Data regarding baseline behaviour patterns were collected using behavioural assessments. One and three months after surgery, the actigraph was worn again for 7 nights with completion of behavioural assessments. Sleep and behavioural patterns were compared with a control group of healthy children. Results: No significant differences were found in preoperative and postoperative sleep and behavioural patterns. Overall, general anesthesia did not cause sleep disturbance or negative behaviour changes. These findings are reassuring to physicians and parents.
Pharmacy Service Users' Support for and Willingness to Use Community Pharmacist Prescribing Services in Ontario
Keywords: Canada
community pharmacy
Independent prescribing
Non-medical prescribing
Pharmacist prescribing
Pharmacy service users

Objective(s): In 2012, pharmacists in Ontario were authorized to independently prescribe, including renew, and adapt prescriptions. This study described Ontario pharmacy service usersâ views, support for and willingness to use pharmacist prescribing services in the community. Methods: Semi-structured interviews with adults who had filled or refilled prescription(s) at a community pharmacy within the past three months were conducted. Interview transcripts were coded and analyzed using thematic analysis. Results: Participants expressed that community pharmacist prescribing services had potential benefits, including being personally convenient. They also had some concerns, such as pharmacists potentially lacking access to clinical information (e.g. laboratory results and health records) that might be required to safely prescribe. Support for and willingness to use pharmacist prescribing services appeared to be contingent on perceptions of personal convenience, complexity of prescribing service, and cultural authority of pharmacists. Conclusion: Acceptance of pharmacist prescribing appears to be influenced by perceptions of benefits and risks. These findings could inform strategies to enhance public uptake of pharmacist prescribing services.
The Potential Catalytic Effects of Fructose and its Epimers on Postprandial Carbohydrate Metabolism in Subjects without Diabetes and a Systematic Review and Meta-analysis in all Subjects
Keywords: Catalytic effects
D-Allulose
D-Fructose
D-Psicose
glucose incremental area under the curve (iAUC)
Postprandial carbohydrate metabolism

The objective was to determine the ‘catalytic’ (doses <10g/meal) effects of fructose and allulose (psicose) on postprandial carbohydrate metabolism in healthy participants (FACE Trial) and to conduct a systematic review and meta-analysis (SRMA) on the acute effects of fructose and its epimers on postprandial glycemic and insulinemic responses. The FACE trial was conducted in 25 healthy participants and did not find any significant effects of fructose or allulose on any glycemic or insulinemic endpoints. The SRMA (n=233) found that allulose, but not fructose or tagatose, significantly reduced glucose and insulin iAUC. Overall, results suggest that allulose can serve as a low-calorie alternative to fructose in the diet and leads to modest improvements in glucose and insulin responses in those with and without diabetes, however, research is needed to elucidate the lack of findings in the FACE trial and the limits of our SRMA.
Investigation of Gene Splicing Variants Contributing Risk to Psychiatric Disorders
Keywords: Bipolar Disorder
Gene Splicing
GWAS
Psychiatric Genetics
Schizophrenia

The majority of the variants found through genome-wide association studies (GWAS) to be associated with psychiatric disorders are not found to cause a protein coding change, therefore it is predicted that these variants are causing gene expression changes, including changes to alternative splicing. Datasets of variants associated with alternative splicing changes in the general population have also been curated with the aim of aiding the search for functional GWAS variants. This study uses these datasets to identify variants associated with alternatively spliced isoforms in schizophrenia and bipolar disorder. Alternatively spliced isoforms in four genes (APOPT1, AS3MT, NEK4 and RPGRIP1L) were identified that converge on the mitochondria and cilia, implicating these cellular structures in psychiatric disease and providing avenues of genes and pathways for further study. A method to study alternative splicing changes in psychiatric disorders is presented that would also be a useful tool for studying other complex genetic disorders.
A Physiological Study to Determine the Enteral Threonine Requirements in Infants 1 to 6 Months of Age: Preliminary Results
Keywords: amino acid
indicator
Infant
oxidation
requirement
threonine

Threonine is an indispensable amino acid that is greatly used by the gut and both deficient and excessive intakes of threonine are known to negatively impact the mucosal environment. Current infant threonine requirements are based on estimates of breast milk composition, however these estimates have not been validated using newer methods. The main objective of this thesis was therefore to determine the enteral threonine requirement in 1 to 6 month olds using the indicator amino acid oxidation method. Multiple methodological and ethical aspects were considered and provide the groundwork for the current and future enteral amino acid studies in infants. Thus far, preliminary results are encouraging and appear to demonstrate that study methods are working as anticipated. As enrolment ensues beyond the completion of this thesis, a threonine requirement for this 1 to 6 month old population will be defined.
Pregnancy Outcomes After Exposures to TNF-Alpha Inhibitors in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis with the Application of GRADE Assessment
Keywords: GRADE
Inflammatory Bowel Disease
Meta-Analysis
Pregnancy
Systematic Review
TNF-alpha Inhibitors

This systematic review examined on whether there are more adverse pregnancy outcomes among inflammatory bowel disease (IBD) patients taking TNF-alpha inhibitors (TNFi) in pregnancy compared to non-exposed IBD controls and healthy population. This review searched PubMed, Embase, and WoS and other sources to look for relevant studies. Two reviewers independently extracted information on 6 adverse pregnancy outcomes (SA/SB, PTB/PMB, LBW, SGA, CA) comparing TNFi-exposed group and non-exposed controls. 32 case reports, 25 case series, and 9 cohort studies were included in this review. There was no increased risk in any of the adverse pregnancy outcomes comparing TNFi-exposed group to IBD controls. There was increased risk of preterm birth (RR [95% CIs] = 2.66 [1.36, 5.19] and low birth weight (RR [95% CIs] = 2.36 [1.27, 4.36] comparing TNFi-exposed group to healthy control, which was consistent with in IBD pregnancy. Overall, there was no increased risk in adverse pregnancy outcomes after taking TNFi in IBD pregnancy.
Uptake and Sequestration of Aggregated α-Synuclein
Keywords: Aggregation
Autophagy
Neurodegeneration
Parkinson's Disease
Prion-like Propagation
Îą-Synuclein

This study aims to investigate the mechanisms underlying the seeding properties of α-synuclein (α-syn). Presently, researchers hypothesize oligomeric species of α-syn are responsible for the cytotoxicity induced by α-syn. While α-syn oligomers are strongly implicated in the induction of aggregation, their abilities relative to α-syn fibrils have not been thoroughly characterized. To address this question, recombinant WT and oligomer-prone α-syn were used to treat immortalized human embryonic kidney cells (HEK 293T) stably expressing the A53T α-syn mutant conjugated to YFP, resulting in the formation of punctate structures. This redistribution of α-syn did not coincide with increases in detergent insoluble α-syn suggesting these punctate structures do not represent true aggregates. Furthermore, the exogenous α-syn treatment did not result in disruptions to autophagy. These findings suggest our model reflects the initial stages of the aggregation process. This information is important to understanding the molecular basis for the initiation and progression of synucleinopathies.
Investigating the Role of Inositol Polyphosphate 4-Phosphatase Type II (INPP4B) in Cellular Transformation
Keywords: Cancer
Cellular Transformation
INPP4B

Inositol Polyphosphate 4-Phosphatase Type II (INPP4B) was established to play a tumour suppressive role in breast, ovarian, prostate, thyroid and other cancers. This was attributed to the ability of INPP4B to dampen oncogenic Akt signaling. Recent studies reveal that INPP4B also has oncogenic properties in Acute Myeloid Leukemia (AML), colon, skin and breast cancers. Here, the role of INPP4B in cancer initiation is address through a Mouse Embryonic Fibroblast (MEF) model of cellular transformation. The loss of Inpp4b was not required or sufficient to induce neoplastic transformation with Ras or E1A. Inpp4b loss, however, did cooperate with SV40 T-Large to increase transformation associated with increases in pAkt and pS6 expression. These phenotypes were decreased with the overexpression of INPP4B. Inpp4b overexpression did not induce cellular transformation with either E1A or Ras alone. These findings support a tumor suppressive role for INPP4B in the context of SV40 T-Large MEF transformation that is mediated through pAkt signaling.
Calcineurin Inhibitor-induced Endothelial Cell Injury - A Role for Complement
Keywords: Calcineurin inhibitor
Calcineurin inhibitor toxicity
Complement
Endothelial cell
Transplantation

Calcineurin inhibitor (CNI) use significantly reduced acute rejection rates and revolutionized early allograft and patient outcomes post-transplantation. However, known nephro- and vascular toxicity preclude its use and contribute to chronic allograft injury, negatively impacting longer term outcomes. Evolving evidence suggest a role for complement dysregulation in the pathogenesis of CNI-induced endothelial injury. In an in vitro model using Blood Outgrowth Endothelial Cells (BOEC) isolated from healthy donors and a donor with a pathogenic MCP/CD46 variant, we showed that cyclosporine resulted in a dose and time dependent increase in complement deposition, enhanced by anti-CD59 sensitization. We showed for the first time that MCP/CD46 deficient BOECs were genetically predisposed to be more susceptible to cyclosporine-induced complement deposition (multiple-hit hypothesis). We found complement factor H surface dysregulation to play a key role in cyclosporine-induced complement activation on BOEC surfaces, with glycocalyx abolishment possibly being the key mechanism leading to alternative pathway dysregulation.
Evaluating the Real-World Effectiveness of Bupropion Versus Varenicline for Smoking Cessation: Exploring the Role of Nicotine Metabolism and Medication Adherence
Keywords: adherence
bupropion
nicotine metabolism
pharmacotherapy
smoking cessation
varenicline

Bupropion and varenicline are effective, first-line prescription-only pharmacotherapies for smoking cessation; however, their real-world use is limited by affordability and accessibility. Using a novel internet-based randomized design, we evaluated the real-world effectiveness of mailed bupropion and varenicline, as well as the roles of nicotine metabolism (NMR) and medication adherence, in a sample of interested smokers using web-based recruitment and follow up. Quit rates at end of treatment (EOT) were significantly higher for varenicline (30.2%) compared to bupropion (19.6%). Quit rates at 6 months (14.0%) and 12 months (12.1%) were not significantly different between bupropion and varenicline. Increased medication compliance significantly improved cessation outcomes at EOT. NMR was associated with nicotine dependence. Varenicline benefited Slow Metabolizers of nicotine whilst bupropion benefited Normal Metabolizers. Even though real-world quit rates were comparable to clinical trials, improving medication compliance and implementing personalized pharmacological and behavioral interventions are promising approaches to increase efficacy of smoking cessation pharmacotherapies.
Neural Correlates of Delusions in Patients with Alzheimer's Disease
Keywords: Alzheimer's disease
Delusion
MRI
Neuropathology
Psychosis
Resting-state

The neural correlates of delusions in Alzheimer's disease (AD) remain unclear. This thesis examined the neuropathological, structural volumetric, and resting-state functional connectivity (rs-fc) correlates associated with delusions in AD. We hypothesized that delusional AD patients will have greater disease severity characterized by higher AD pathology load and increased atrophy, as well as altered rs-fc compared to non-delusional patients. We found that delusions were associated with Lewy body pathology, vascular pathology, and vascular risk factors, but were not correlated with increased AD pathology. Patients who developed delusions showed increased atrophy of regions within the default mode network (DMN) following the onset of delusions, while the cohort that did not develop delusions did not exhibit significant atrophy in the DMN over a similar time frame. We found that decreased connectivity within the DMN, in particular disintegration of the inferior parietal lobule with the overall network, may be associated with delusions in AD.
Exploring Pain Self-Management Behaviours in Breast Cancer Survivors: A Mixed-Methods Study
Keywords: Breast Cancer
Pain
Self-Management

Objective: To describe pain self-management behaviours (PSMB), and barriers and facilitators to PSMB in breast cancer (BC) survivors following primary cancer treatment. Methods: This study used a sequential explanatory mixed-methods design. BC survivors (n=53) who were 6 months (ď ą2 months) post-treatment for BC completed measures assessing pain catastrophizing, fear of cancer recurrence (FCR), and pain self-efficacy. Participants also completed the Barriers Questionnaire II (BQ-II) to assess barriers to pain management, and the Pain Self-Care Behaviours Questionnaire (PSCBQ) to assess engagement in PSMB. Interviews were conducted with a subset of participants (n=10) to further describe PSMB and barriers and facilitators to PSMB. Results: The most common PSMB participants reported via the PSCBQ were walking, distraction strategies, other exercise, and relaxation. Barriers and facilitators to PSMB included those identified by the BQ-II, as well as novel barriers and facilitators such as pain acceptance, information, and social support. Conclusion: BC survivors engage in a variety of PSMB and encounter many barriers and facilitators to PSMB not identified by existing quantitative measures. Future research should acknowledge the importance of barriers and facilitators such as pain acceptance, information (on what to expect and on PSMB in general), and social support.
Assessment of Anti-α-Galactosidase A IgG Antibody Development in Fabry Disease Patients by ELISA and Purification of a Recombinant Human α-Galactosidase A from a Stable Overexpressing Human Cell Line
Keywords: alpha-galactosidase A
antibodies
ELISA
Fabry disease
lysosomal storage disorder
protein purification

Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency in α-galactosidase A (α-gal A). Enzyme replacement therapy (ERT) consists of regular infusions of recombinant α-gal A. Fabry disease patients commonly develop IgG antibodies against this enzyme and there is a concern that they may reduce the efficacy and safety of ERT. We developed an ELISA to measure anti-α-gal A IgG antibodies and found that 61% of patients on ERT were seropositive. We also designed a fast, single-chromatography purification protocol for α-gal A from the supernatant of a human embryonic kidney 293T cell line engineered to stably overexpress a 6xhis-tagged human α-gal A. We obtained 0.342 mg/L with the expected molecular weight but lower enzymatic activity than expected. This α-gal A is bound by antibodies from seropositive patients and not by those from healthy individuals, which suggests that it may serve as antigen in our ELISA to measure anti-α-gal A antibodies.