VictorJuiz/thesis huggingface dataset:
The Effects of Cannabidiol (CBD) and Δ9-Tetrahydrocannabinol (THC), Alone and in Combination, in Animal Models of Epilepsy and the Comorbidities of Epilepsy
Keywords: Cannabidiol
Comorbidities
Depression
Epilepsy
Psychosis
Tetrahydrocannabinol

People with epilepsy often suffer not only from seizures but also from psychiatric comorbidities that accompany the seizures. Recently, cannabidiol (CBD) and combinations of CBD with Δ9-tetrahydrocannabinol (THC) have been proposed for the treatment of epilepsy and the epileptic comorbidities. In the present study, CBD, THC, and combinations of CBD and THC, were evaluated in the mouse maximal electroshock (MES) seizure test, the forced swim test (FST) of antidepressant activity, and the MK-801 model of psychosis. It was found that: 1) CBD and THC were both effective in the MES model, and they were more effective in combination; 2) CBD and THC were ineffective in the FST model, alone or in combination; and 3) CBD and THC were less effective in the MK-801 model but had significant effects in combination. CBD and CBD+THC might be useful in the treatment of epilepsy and possibly psychosis, but not in the treatment of depression.
Elucidating the Role of SPEG in Muscle Development and Function
Keywords: centronuclear myopathy
disease model
excitation-contraction coupling
muscle
SPEG
zebrafish

Centronuclear Myopathy is a congenital neuromuscular disorder mostly caused by mutations on Excitation-Contraction Coupling (ECC) genes. One novel gene mutated in these patients is SPEG (Striated Muscle Preferentially Expressed Protein Kinase). Its absence leads to muscle weakness, increased centralized nuclei in myofibers, and dilated cardiomyopathy, with severe cases including early mortality. Evidence suggests SPEG acts through ECC pathway. However, previous research has focused on cardiac muscle and has been limited by neonatal mortality of the mouse model. Therefore, its function throughout embryonic development and in skeletal muscle remains unknown. The work herein presented demonstrates I successfully generated zebrafish speg KO models which I used to study its role in muscle development and function. These mutants effectively replicate the muscle weakness and decreased survival reported in these patients and KO mice. In absence of therapies, my model also allows future high-throughput experiments in aims to find potential therapies for these patients.
Negative Pressure and its Role in Lung Re-epithelialization
Keywords: Bio-engineered lungs
Cell delivery
Lung regeneration
Lung transplantation
Negative pressure ventilation
Tissue engineering

For end-stage lung disease, lung transplantation remains the only treatment. Transplantation, however, is limited due to the lack of organs. While the generation of new lungs via the recellularization of biological scaffolds is an alternative, proper repopulation of the lung remains a challenge. In an attempt to enhance the re-epithelialization of the decellularized lung airways, the inclusion of negative pressure during cell seeding and bioreactor culture phase was investigated. We designed a negative pressure cell seeding method and a physiological wet negative pressure ventilation device that allowed for control over ventilation parameters such as tidal volume and accommodation of physiological respiratory rates. We also designed a biomimetic lung bioreactor system that accommodates vascular perfusion, physiological ventilation and in vivo spatial orientation. These new technologies and methodologies resulted in significantly higher cell surface coverage and number in the decellularized lung scaffolds than the traditional approaches.
Understanding the Disease Pathogenesis of X-linked Myotubular Myopathy
Keywords: CNM
MTM1
XLMTM

X-linked myotubular myopathy (XLMTM) is a fatal condition caused by mutations in myotubularin 1 (MTM1), which encodes a lipid phosphatase. Despite our increased understanding of XLMTM pathology, how MTM1 functions in skeletal muscle is unknown. To address this, I performed a phenotypic and molecular analysis of Mtm1 knockout mice throughout disease development. These mice exhibit histopathological abnormalities such as central nuclei, muscle hypotrophy, and increased oxidative staining. Alterations in transcriptome (gene expression), epigenome (DNA methylation) and proteome (protein levels of disease markers) are also characteristics of this model. As a secondary aim, I performed AP-MS experiments using a MTM1-6xHis mouse to identify the MTM1 interactome in the context of skeletal muscle. Lastly, as a third aim, I characterized Mtm1 KO C2C12 cell line as a model for XLMTM. This work herein explores the function and interactome of MTM1 in skeletal muscle and expands our current understanding of XLMTM.
Modulation of Spinal Dorsal Horn Long-term Potentiation by Non-ionotropic NMDA Receptor Activity
Keywords: Long Term Potentiation
Non-Ionotropic NMDA Receptor
Spinal Cord Dorsal Horn

Pathological pain is characterized by enhanced synaptic strength within nociceptive pathways of the spinal dorsal horn that arises in the absence of any obvious trigger. Unfortunately, current treatment options often fail to provide adequate and lasting pain relief as they do not address the underlying mechanisms of persistent pain. The enhancement of synaptic transmission between nociceptive afferents and dorsal horn neurons (long-term potentiation; LTP) is associated with sensitization. This project aims to investigate the role of non-ionotropic NMDA receptor (NI-NMDAR) signalling in the plasticity of nociceptive neurons and to induce synaptic depotentiation through a combination of electrophysiological recordings and pharmacological interventions. These data indicate that NI-NMDAR activity could reverse dorsal horn LTP with 7CK, a NMDA receptor glycine site antagonist and was dependent on downstream protein phosphatase-1 activity. Overall, this project will provide essential new insights into the mechanisms by which synaptic depotentiation can be exploited to erase pathological pain.
Implementing Reconfigurable Packet Matchers on Field-programmable Gate Arrays
Keywords: FPGA
Packet Classification

In networking applications, packets of data can be sorted and filtered using a set of rules. Historically, this matching was done using conventional processors. As network speeds grow faster, the need for specialized circuitry to process these packets increases. Field Programmable Gate Arrays (FPGAs) are a technology that allows a user to create custom circuitry that can be changed to suit the application. Using FPGAs, this work looks to evaluate two approaches to performing packet classification at high-speed line rates of 10 Gbits/s and higher, with a 10% per 10 minute turnover in the ruleset. The first approach utilizes next-gen memory to store a million-entry ruleset; the second approach exploits a real-time partial reconfiguration of FPGAs to reprogram the FPGA circuitry with a variety of matching schemas. The two approaches are then compared to other FPGA-based systems, in terms of performance, rule density, and ease of updates.
Epigenetics of Schizophrenia and Suicidality
Keywords: age
DNA
Ideation
Methylation
Suicide

Suicidal behavior is the product of the interaction of many risk factors, such as genetics and environmental factors, and several studies support a strong association between perceived stress and suicidal behaviors. My thesis aimed to understand the DNA methylation age acceleration in individuals with schizophrenia, severe psychosis, and severe current suicide ideation (SI). It also aimed to determine whether DNA methylation could have a mediating effect on the interaction between stress and severe current SI. Bivariate correlation, mediation model 4 on SPSS, Horvath online calculator were used during these analyses. There was no epigenetic age acceleration between schizophrenia and healthy control; likewise, none was found between SI and non-SI groups. Extrinsic epigenetic age acceleration significantly correlated with BPRS disorganization. Furthermore, Horvath Age acceleration showed a significant correlation with the SCL-90 psychotic domain. Furthermore, our data supported the mediating effects of DNA methylation on the interaction between stress and current SI severity.
Vegetarian Diet, Growth, and Nutrition in Early Childhood
Keywords: adiposity
early childhood
height
micronutrients
serum lipids
vegetarian diet

Background: Few studies have evaluated the relationship between vegetarian diet and childhood growth or nutritional status. Methods: A longitudinal cohort study of children aged 6 months to 8 years. Linear mixed effects and generalized estimating equation models were used to determine the association between vegetarian diet and BMI z-score, height-for-age z-score, serum ferritin, 25-hydroxyvitamin D, and serum lipids. Possible effect modification by age and cow’s milk consumption was examined. Results: There was no evidence of an association between vegetarian diet and mean BMI z-score, height-for-age z-score, serum ferritin, 25-hydroxyvitamin D, or serum lipids. Vegetarian diet was associated with higher odds of underweight (OR 1.87, 95%CI: 1.19-2.96; p=0.007). Higher cow’s milk consumption was associated with higher serum lipids among children with vegetarian diet. Conclusion: Children with and without vegetarian diet had similar growth and biochemical measures; however, vegetarian diet was associated with higher odds of underweight.
Impact of Resveratrol, a Uterine Artery Vasodilator, on Placental Oxygen Transport and Fetal Circulatory Physiology: Comparison with Maternal Hyperoxygenation
Keywords: Hemodynamics
Magnetic resonance imaging
Maternal Hyperoxygenation
Oxygenation
Placenta
Resveratrol

Increases in fetal oxygen delivery may be achieved by increasing uterine artery (UtA) blood flow with resveratrol (RSV) or by widening the transplacental partial pressure of oxygen (PO2) gradient with maternal hyperoxygenation (MH). Thus, we investigated the impact of chronic RSV on placental oxygen transport and fetal circulatory physiology in a sheep model of normal human pregnancy. We then compared the impact of RSV with an acute episode of MH. RSV resulted in significantly higher UtA blood flow than MH therapy. Despite this increase, there was no change in fetal oxygenation or hemodynamics compared to controls. MH resulted in increased fetal oxygenation compared to baseline and RSV fetuses. MH therapy also increased fetal pulmonary blood flow and reduced flow through the foramen ovale. Thus, our data suggests that in the setting of normal placental perfusion, MH has a greater impact on fetal oxygen delivery than increases in UtA blood flow.
A GPU-Accelerated Population-Based Boltzmann Machine for Solving Combinatorial Optimization Problems
Keywords: Boltzmann Machine
Combinatorial Optimization
Ising Model
Parallel Tempering
Population Annealing
QUBO

Monte Carlo methods such as Simulated Annealing and Parallel Tempering have been applied to Boltzmann Machines for solving NP-hard combinatorial optimization problems. In practice, their implementations have been limited to small population (only a few CPU cores), not in massively parallel hardware. In this work, we show that Population Annealing algorithm can be applied to Boltzmann Machines and increases their performance in massively parallel hardware. We implement a large-scale GPU-accelerated Population-Based Boltzmann Machine (PBBM) with Population Annealing algorithm for solving all-to-all connected quadratic unconstrained binary optimization problems with up to 20000 binary variables. For 1024-variable problems, PBBM is able to perform parallel energy evaluation and local field calculations on a population size of up to 640 parallel replicas about 500x faster than running replicas serially. Benchmark results on Max-Cut problems show that our implementation outperforms state-of-the-art optimizers and on average is 43x faster and has 2.5x less error.
Delivery of Sodium Channel Subunits via Viral Vectors to Ameliorate Seizures in Dravet Syndrome Mice
Keywords: AAV
brain
Dravet Syndrome
epilepsy
Mice

Dravet Syndrome (DS) is caused primarily by impairment of the voltage-gated sodium channel alpha-1 subunit (Nav1.1) in inhibitory neurons. DS is characterized by febrile seizures, autistic behavior, and sudden unexpected death in epilepsy (SUDEP). Customized adeno-associated virus (AAV) serotype 9 vectors coding for AAV9-Gad1v1-Navβ1 and AAV9-Gad1v2-NaChBac were tested in Scn1a+/- mice, a mouse model of DS, to restore the activity of inhibitory neurons in Scn1a+/- mice. Neonatal injections with AAV9-Gad1v1-Navβ1 resulted in a partial improvement in the mortality of female Scn1a+/- mice and a reduction in the spontaneous seizure frequency in male Scn1a+/- mice, with no effect on the heat-induced seizures. Treatments with AAV9-Gad1v2-NaChBac did not induce inflammation in mouse brain and indicated that Gad1v2 promoter was more selective towards gamma aminobutyric acid (GABA)-ergic inhibitory neurons than the Gad1v1 promoter. The findings of this study demonstrated the capability of AAV as a useful tool in gene therapy for DS.
'The Butcher on the Bus’ is as Familiar to Older Adults as She is to Younger Adults
Keywords: Aging
Context
Faces
Familiarity
Recollection
Repetition

The “butcher on the bus” is an example of familiarity which arises when we find a person familiar (our butcher) but fail to recollect how we know them due to the unfamiliar context (the bus; Mandler, 1980). To address age-related differences in the butcher on the bus, younger and older adults viewed faces in scene contexts. At test, participants viewed studied faces in studied scenes, studied faces in new scenes, and new faces in new scenes. Participants indicated if they recollected the faces and studied scenes, if the faces were familiar but they could not recollect the studied scene, or if the face and scene were new, and then made source judgments to indicate if the test scene matched the studied scene. Recognition discrimination, estimates of recollection and familiarity (Yonelinas Jacoby, 1995), and source judgements revealed no age-related differences, demonstrating that younger and older adults experience this phenomenon similarly.
Impact of Policy Changes on Utilization of Community Medication Review Services in Ontario among People Living with Diabetes
Keywords: Community pharmacy services
Health policy
Interrupted time series analysis
Medication reconciliation

Since 2007, the Ontario government has funded pharmacy medication review services (MedsCheck Annual [MCA]) for residents taking 3+ chronic medications. In 2010, MedsCheck was broadened to include patients with diabetes (MCD). In 2016, a policy change added several components to Medscheck services, including diabetes-specific training for pharmacists and diabetes-specific education/goal-setting with patients. The objective of this thesis was to examine the impact of the 2010 and 2016 policy changes on the monthly rate of MedsCheck service delivery among adults living with diabetes. Using interrupted time-series analysis, our study demonstrated that the 2010 policy change slightly increased delivery of MedsCheck services, whereas the 2016 policy change resulted in a dramatic decline in the use of MedsCheck services; with evidence of possible displacement from MCD to MCA. Future research is needed to better understand the impact of the policy changes on access and effectiveness of MedsCheck services, and barriers/facilitators of MedsCheck implementation.
Maternal BMI, Breastfeeding and Perinatal Factors that Influence Early Childhood Growth Trajectories
Keywords: Breastfeeding
Childhood obesity
Maternal and infant health
Maternal BMI
R programming
Scoping review

Obesity among children is a global concern. Fetal programming and early life nutrition have been implicated in both childhood and adult obesity. Perinatal interventions aimed at reducing the risk of child obesity may be important for prevention. It was hypothesized that anthropometric and genetic analysis can identify a priority population that would benefit from an exclusive breastfeeding intervention. To test this hypothesis, a scoping review was conducted, and ALSPAC cohort data was analyzed. The scoping review results show early life risk factors were multi-factorial, they were also socially patterned and accumulative. These data suggest children with overweight and obese mothers, who were low income and from an ethnic minority group were at higher risk for obesity and could be targeted for preventive intervention. The results from the ALSPAC study show maternal BMI and the genetic risk score are the strongest independent predictors of obesity at 17 years of age.
Characterization of Matrin-3 Mutations Associated with Amyotrophic Lateral Sclerosis
Keywords: ALS
disease model
drosophila
MATR3
mouse
neurodegeneration

Amyotrophic lateral sclerosis (ALS) is a fatal disease that is characterized by progressive motor neuron degeneration. Matrin-3 (MATR3) is an RNA-binding protein that is involved in alternative splicing regulation. S85C and F115C are dominantly inherited MATR3 mutations that are linked to familial ALS. I investigated the role of MATR3 mutations in ALS pathogenesis using two models: 1) transgenic flies expressing human wild-type or mutant MATR3 in the motor neurons and 2) MATR3 S85C knock-in mice. I found that mutant MATR3 expression in the motor neurons is more toxic to flies than wildtype MATR3. In addition, MATR3 S85C knock-in mice show features reminiscent of ALS including severe motor impairments associated with degeneration of the Purkinje cells and α-motor neurons. Interestingly, a striking loss of MATR3 expression was observed in the affected neuronal populations. These fly and mouse models will be useful for future studies on the mechanism underlying MATR3-related ALS pathogenesis.
Body Mass Index Trajectories, Concurrent Body Mass Index, and Cardiometabolic Risk in Young Children
Keywords: cardiometabolic risk
cohort
Growth
obesity

Background: Little is known about the relationship between rapid BMI gain trajectories and increased cardiometabolic risk (CMR) in early childhood. Objectives: To identify age and sex standardized body mass index (zBMI) trajectories in children 0-60 months. To examine the association zBMI trajectories and CMR. To determine the role of concurrent zBMI in this association. Methods: Latent Class Mixed Models were used to identify zBMI trajectories. Linear regression was performed to determine the association between zBMI trajectories and CMR. Mediation analyses were performed to determine the role of concurrent zBMI. Results: Children in the rapidly BMI gain trajectory had higher total CMR score and waist circumference score compared to the stable low group. Concurrent zBMI mediated the associations. Conclusions: Monitoring zBMI trajectories and weight status in early childhood may be helpful for clinicians to identify children at increased risk of cardiometabolic disease.
Investigating the Impact of Running-specific Prostheses Use for Children and Youth with Lower Limb Absence
Keywords: biomechanics
lower limb absence
paediatrics
running-specific prostheses
sport participation

For children and youth with lower limb absence, the functionality of their prostheses plays an important role in sport participation. The limited functionality of daily-use prostheses (DUPs) necessitates the use of specialized devices such as running-specific prostheses (RSPs); however, much remains unknown regarding their use in paediatric populations. The thesis objective is to investigate the impact of RSP use for children and youth. First, a systematic literature review about running biomechanics using RSPs was conducted which explored the compensatory strategies used by amputees. Second, a study protocol for the evaluation of paediatric RSP running biomechanics is proposed and the intrasession reliability of the start-stop task was assessed in typically developing children. Third, a qualitative analysis through semi-structured interviews was conducted to understand children’s experiences using RSPs. In conclusion, RSPs have positively contributed to children’s participation in sports; however, design improvements can still be made to better suit children’s needs.
An Affect-aware Socially Assistive Robot for Exercise Facilitation
Keywords: Affective Computing
Assistive and Social Robotics
Human-Robot Interaction

Older adults generally engage in less physical activities than other age groups, which can increase the risk of developing diseases associated with aging. It is increasingly difficult for caregivers to support older adults due to the global decline in the old-age support ratio. Socially assistive robots have shown success in supporting older adults and extending the capability of healthcare workers. This thesis aims to develop: 1) an affect elicitation and detection methodology using a social robot to directly elicit user affect that occurred during human-robot interactions (HRIs) to train affect detection models; 2) an autonomous socially assistive robot to facilitate upper body exercises. Exploratory experiments with both younger and older adults were conducted to validate the robot’s ability to elicit user affect and facilitate exercises. The results showed that the robot successfully elicited and detected user affect as well as facilitated exercising, and that the participants also reported high acceptance of the robot.
The Role of Inflammatory Cytokines in the Palmitate-mediated Dysregulation of NPY in Hypothalamic Neurons
Keywords: Cytokine
Hypothalamus
Neuron
Obesity
Oleate
Palmitate

A contributing factor to the development of obesity is the consumption of saturated fats. Saturated fatty acids such as palmitate dysregulate energy homeostasis by inducing neuroinflammation and orexigenic Npy mRNA in the hypothalamus. Inflammatory analysis identified cytokines that may mediate the induction of Npy mRNA by palmitate: NAMPT/visfatin, MIF, IL-17F and IL-6. With the exception of NAMPT/visfatin, treatment of the NPY/AgRP-expressing mHypoE-46 cell line with the aforementioned cytokines nor conditioned media from palmitate-treated cells were able to directly induce Npy mRNA suggesting a minimal role for cytokines. The monounsaturated fatty acid oleate successfully blunted palmitate-mediate increases in Npy and inflammation in mHypoE-46 cells through mechanisms involving PKA but not SIRT1. This study demonstrates that inflammation and Npy are distinct processes that are induced in a specific population of NPY/AgRP neurons and suggest that differential mechanisms mediate the dysregulatory effects of palmitate in a population-specific manner.
First Generation Molybdenum-Nitride-graphite Supercapacitor Electrodes Produced from Solution Precursor Plasma Spray
Keywords: Cyclic Voltammetry
Molybdenum-nitride-graphite Electrodes
Solution Precursor Plasma Spray
Supercapacitor Electrodes

First-generation molybdenum-nitride-graphite electrodes were fabricated and studied as a low-cost alternative to ruthenium oxide electrodes. They were fabricated using solution precursor plasma spray, and thereafter, heat treated using an ammonia temperature programmed reaction. Initially, a proof of concept study was conducted, successfully demonstrating that graphite could be added to the molybdenum nitride electrodes. The proof of concept revealed that graphite could withstand the high temperatures of the plasma plume and the subsequent heat treatment without decomposing into one of its gaseous products. Subsequently, an optimization study was carried out to identify the spray conditions that would produce the highest capacitance electrodes. By using a solution containing 91 g/L of graphite at a standoff distance of 80 mm and a gas composition of 50% argon and 50% nitrogen, an electrode with a capacitance of 180 mF/cm2 was fabricated – outperforming previously developed molybdenum nitride electrodes at the CACT by 188%.