VictorJuiz/thesis huggingface dataset:
Wireless Magnetically-actuated Dexterous Forceps Instruments for Neuroendoscopy
Keywords: Forceps
Magnetic Actuation
Minimally Invasive Surgery
Neuroendoscopy
Surgical Robotics
Surgical Tool

Robot-assisted minimally invasive surgical techniques offer improved instrument precision and dexterity, reduced patient trauma and risk, and lessens the skill gap among surgeons. These approaches are common in general surgery, urology, and gyenaecology. However, they remain largely absent for surgical applications with narrow, confined workspaces such as neuroendoscopy. This limitation stems from a lack of small yet dexterous robotic tools. To address this challenge, this research explores the development of a wireless, dexterous, magnetically-actuated forceps instrument for neuroendoscopic procedures whose goal is to improve intraventricular surgical reach. In this thesis, three magnetic designs were considered and characterized with respect to force and kinematic model accuracy. Furthermore, a custom magnetic system was built to evaluate the instruments’ performance during a pineal region tumour resection on a tumour analogue in a silicone brain phantom. This thesis concludes with a discussion on the performance on the devices and explores potential avenues for improvement.
Effects of Cannabidiol and delta-9-Tetrahydrocannabinol in The Elevated Plus Maze and Forced Swim Tests
Keywords: cannabidiol
cannabis
elevated plus maze
forced swim test
mice
tetrahydrocannabinol

The effects of THC, CBD and a combination of CBD and THC (15:1) were tested in mice models of anxiety (elevated plus maze EPM) and depression (forced swim test FST). Adult, male CD1 mice were injected intraperitoneally (I.P.) with CBD (0-120mg/kg), THC (0-8mg/), CBD + THC (up to 120+8mg/kg), diazepam (0, 2.5mg/kg) or imipramine (0, 30mg/kg). EPM ran for 5mins, FST for 6mins, and open field test for 10mins. CBD was injected 30 or 60mins prior to testing and THC was injected 30mins prior. CBD decreased immobility time in FST. THC increased time spent in the open arms in EPM, and decreased immobility time in FST. The combination of CBD and THC was better than CBD or THC alone in FST at 30mins. CBD did not show anxiolytic effects but showed anti-depressant effects. THC had both anxiolytic and antidepressant effects at some doses. CBD and THC combined might be useful in patients with anxiety and depression.
The Longitudinal Relationships between Biomarkers of Alzheimer’s Disease
Keywords: Alzheimer's disease
Biomarkers

Despite well-described temporal staging, the relationships between Alzheimer’s disease (AD) biomarkers remain unclear. First, using cross-lagged panel models, we examined the reciprocal longitudinal influences between biomarkers of amyloid-beta (Aβ) and phospho-tau (p-tau), hallmark proteins that accumulate in the AD brain, in both asymptomatic/presymptomatic elderly (HC), and in subjects with AD or mild cognitive impairment (AD/MCI) over 48 months. Second, reciprocal relationships between brain Aβ deposition and white matter hyperintensity volumes (WMH), presumed to be of vascular origin, were examined. In HC, cerebrospinal fluid (CSF) Aβ changes led to increased Aβ deposition and increased CSF p-tau concentrations, and CSF p-tau exacerbated Aβ deposition. In contrast, in AD/MCI, CSF p-tau exacerbated Aβ deposition, but p-tau progressed independently of Aβ biomarkers. WMH led to Aβ deposition in HC, while in MCI, it was Aβ deposition that predicted incident WMH. Processes underlying CSF Aβ changes, and cerebrovascular disease, may initiate the amyloid cascade in presymptomatic stages.
High-dose Vtamin D Supplementation, Adiposity, and Serum Lipids in Early Childhood
Keywords: Adiposity
Early Childhood
Serum Lipids
Vitamin D
Waist Circumference
zBMI

Background: Observational research has suggested a relationship between lower vitamin D status and higher adiposity in children. No randomized clinical trials have evaluated this relationship. Methods: This was a secondary analysis of a double-blind randomized clinical trial. Linear regression adjusted for baseline was used to determine the effect of wintertime high-dose (2000 IU/day) vs. standard-dose (400 IU/day) vitamin D supplementation on end of winter adiposity and cardiovascular risk in healthy children aged 1-5 years. Results: 545 children were included in the analysis (n = 275, 50.5% in the 2000 IU/day group). There was no clinically meaningful difference between standard vs. high-dose vitamin D supplementation on BMI z-score or serum lipids. However, children who received high-dose vitamin D had a lower waist circumference z-score than those receiving standard-dose supplementation. Conclusion: High-dose vitamin D supplementation may have a role in minimizing wintertime adiposity gains in preschool children, but further research is needed.
Antiseizure Effects of Cannabinoids in the Amygdala Kindling Model
Keywords: Amygdala
Brain
Cannabinoid
Epilepsy
Kindling
Seizure

Focal Impaired Awareness Seizures (FIAS) are the most common seizures in adults and are typically drug resistant. Amygdala-kindling is a pre-clinical model of FIAS with secondary generalization. The present study was designed to assess the effectiveness and safety of cannabidiol (CBD), ∆9-tetrahydrocannabinol (THC), and a combination of CBD and THC (15:1) in suppressing generalized and focal kindled seizures. CBD alone suppressed both generalized seizures and focal seizures at sub-toxic doses. THC alone also suppressed generalized and focal seizures, but only at doses that produced psychotoxic effects. The addition of a low dose of THC to CBD (15:1) left-shifted the dose- response curve for CBD, producing lower ED50s for both generalized and focal seizures. No toxicity was seen with this combination. CBD and THC both have anti-seizure properties. The addition of small amounts of THC greatly improves the effectiveness of CBD. A combination of CBD and THC may be useful in the clinical management of FIAS.
Adult Neurogenesis in Naked Mole-Rats: Time Course of Cell Maturation and The Effects of Social Novelty
Keywords: naked mole-rat
neurogenesis
social behavior

Naked mole-rats (NMR) are one of the only eusocial mammalian species. Their complex social structure makes them unique for the study of interactions between adult neurogenesis and social behavior. I explored the time course of maturation of newly born cells in neurogenic regions of the adult NMR brain. I found that most new NMR cells mature by 5 months. To test whether cell proliferation is related to processing social cues, I examined the effects of a novel social stimulus in two subordinate subcastes. Soldiers produced more new cells in the subventricular zone than workers. NMRs exposed to a novel social stimulus were more aggressive and investigated their counterpart more than those in a familiar pair. Soldiers in novel pairs, but not workers, spent more time sniffing the genitals of their counterpart. Thus, caste and social context play a role in the rate of proliferation and the behavior of NMRs.
Regulation of Glucagon-like Peptide-1 Secretion by the Exocytotic Protein Munc18-1
Keywords: enteroendocrine
exocytosis
GLP-1
Munc18-1
SNARE
Stxbp1

The incretin glucagon-like peptide-1 (GLP-1) is a rhythmically secreted insulin-secretion enhancing hormone produced in the intestinal L-cell. The increasing incidence of Type 2 Diabetes warrants the advent of new therapies that can increase endogenous GLP-1 secretion, which will manipulate regulatory L-cell secretory pathways such as exocytosis. Three exocytotic proteins have already been identified as regulators of GLP-1 secretion. I hypothesized that the accessory exocytotic protein, Munc18-1, is also an important regulator of GLP-1 secretion in the L-cell - specifically at the peak of its secretion. Munc18-1 expression in many, but not all L-cells was confirmed, and its recruitment to the cell membrane was observed under stimulation. The role of Munc18-1 in GLP-1 secretion was established by loss-of-function experiments in the Munc18-1 knockdown mGLUTag L-cell line, inducible L-cell Munc18-1 knockout mice and primary Munc18-1 knockout L-cells. Together, the results indicate that Munc18-1 is an essential regulator of peak GLP-1 secretion.
Management of Idiopathic Pulmonary Fibrosis: A Survey of Canadian Respirologists
Keywords: Candian
Idiopathic pulmonary fibrosis
Management
Survey

Objective: To characterize the treatment of idiopathic pulmonary fibrosis (IPF) by Canadian respirologists. Methods: We performed a cross-sectional survey of Canadian respirologist who are either Canadian Thoracic Society members or attended the 2018 Canadian Respiratory Conference. Results: Sixty-three respirologists participated (response rate 29%). Substantial variability in the application of guideline recommendations was seen with respect to both acute and chronic management strategies for IPF. Physicians were least confident in their recommendations for antacid use, antifibrotic treatment strategies, and corticosteroid use in IPF exacerbations. Most physicians believe placebo-controlled trials of corticosteroids for IPF exacerbations are needed (92%) and ethical (83%). Physician characteristics are associated with particular practice patterns. Practicing in a transplant centre and involvement in clinical trials were most often associated with specific management strategies. Conclusions: Canadian respirologists report diverse practices regarding IPF treatment. This survey provides insight into the variability of treatment strategies and may guide future trial design.
Interactions between EGF and the IGF-1 Receptor in Mediating hGly2-GLP-2-induced Proliferation in the Murine Small Intestine
Keywords: EGF
Endocrine
GLP-2
Growth Hormones
IGF-1
Intestine

Glucagon-like peptide-2 (GLP-2) is an intestinotrophic hormone that promotes intestinal proliferation through downstream mediators. Two known mediators are insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF), both essential for the proliferative effect of GLP-2. I hypothesized that pre- and/or co-EGF enhances IGF-1-mediated GLP-2-induced proliferation in the murine model. Chronic combination treatment of EGF and GLP-2 increased intestinal growth in C57Bl/6 mice compared to vehicle, GLP-2 and respective EGF treatments. Treatment of pre-EGF+co-EGF+GLP-2 in intestinal epithelial IGF-1 receptor (IGF-1R) knockout mice restored intestinal growth despite the lack of a receptor essential for GLP-2 signaling. Finally, IGF-1 treatment in organoids did not have an additive effect to EGF on proliferation, but managed to replace EGF as an essential growth factor in the media to maintain normal proliferation. Together, these data suggest that exogenous EGF is an essential mediator for GLP-2 that can supersede the missing signaling pathway of IGF-1R.
Bio-printing of Mesenchymal Stem Cells for Skin Reconstruction after Burns
Keywords: Bio-Printing
Burns
Mesenchymal Stem Cells
Skin Regeneration
Tissue Engineering
Wound Healing

Skin regeneration is crucial in burns due to severe damage of the protective barrier. Mesenchy-mal Stem Cells (MSC), with their regenerative properties, are essential for wound repair. We have invented and validated a novel intraoperatively usable hand-held bio-printer, which depos-its MSCs directly on the wounds. We conducted a full-thickness porcine burn study and determined skin regeneration following the deposition of umbilical cord mesenchymal stromal cells with this novel surgical device and examined wound healing at day 28 histologically. Our data demonstrated a significant enhancement in wound healing with similar epidermal re-generation when compared to healthy skin, as well as a significant increase in collagen for-mation, enhanced neovascularization, and less scar and contracture formation compared to con-trols. Here, we showed the safety and efficacy of this novel bio-printer, thus demonstrating its poten-tial as a flexible, surgical device and as an alternative solution for the treatment of burn wounds.
The Effects of Western-diet, Palmitate, and TNFα on Hypothalamic Circadian Rhythms, NPY Expression, Neuroinflammation, and Cellular Insulin Sensitivity
Keywords: circadian rhythms
endocrinology
feeding
hypothalamus
inflammation
insulin resistance

Western diets are typically high in saturated fats and sugar and thus induce weight gain, alter circadian rhythms, increase inflammatory cytokines, and alter whole body glucose homeostasis. However, the links between circadian and hypothalamic energy homeostasis remain undefined. In C57BL/6-J mice, the Western diet significantly decreased peak food consumption, with a concomitant decrease in hypothalamic expression of orexigenic neuropeptides. In vitro, palmitate induced neuropeptide Y (Npy) and Bmal1, and reduced Per2 expression in a BMAL1-dependent manner. TNFα, a palmitate-induced cytokine, activated neuroinflammatory cytokine expression and reduced insulin sensitivity in NPY-expressing neurons. Cellular neuroinflammation occurred through the canonical IKK-β/NF-κB pathway. The induction of insulin resistance by TNFα was maintained after with IKK-β/NF-κB pathway inhibition, indicating that TNFα-mediated neuroinflammation and insulin resistance occurs via distinct mechanisms. With this study, I provide insight into the mechanistic link between fatty acid-induced feeding-related neuropeptide dysregulation, inflammatory activation, circadian rhythms, and insulin resistance.
Intraspecific Variation in Chlorophyll Fluorescence and Pigment Composition in White Spruce (Picea glauca): New Physiological Traits for Identifying Trees Better Adapted to New Climates
Keywords: chlorophyll fluorescence
climate change
intraspecific variation
phenotyping
photosynthesis
white spruce

Analysis of intraspecific variation in photosynthetic productivity and phenology can help us to better understand local adaptation and inform breeding decisions for optimally performing genotypes in extreme and changing environments. We used chlorophyll fluorescence, pigment composition, ground and drone-based spectral reflectance measurements to quantify the variation in photosynthesis of ten 5-year-old white spruce genotypes across a latitudinal gradient in summer, and within one site over a year to determine differences between the ten genotypes in seasonal changes of photosynthesis. The results reveal no genotype-environment interactions or differences between genotypes for pigment composition or fluorescence parameters likely due to a lack of stressful events. However one genotype performed consistently across environments, potentially having stable higher photoprotective capacity than other genotypes. The strong relationship found between vegetation indices measured from the drone and ground based physiological data will enable the high-throughput monitoring of the phenology of photosynthesis in conifer forests.
Using Non-adhesive Microfluidic Wound Dressing to Enhance Wound Healing in Burn Patients
Keywords: Dynamic Cell delivery
Efficient Cell delivery
Microfluidics
Smart Dressing
Stem Cells
Wound dressing

Effective wound closure is crucial for the survival of burn patients but is limited by skin graft thickness and availability. We report a novel non-adhesive wound dressing which participates actively and dynamically in wound repair by allowing cell delivery through built-in channels. We hypothesize that the skin cells will be delivered in clusters and show enhanced proliferation compared to randomly distributed cells. An array of channels is built within the wound dressing with one inlet diverging into several outlets. Fibroblasts and keratinocytes were shown to segregate into clusters upon delivery, illustrating cellular distribution through the microfluidic device. The delivery of fibroblasts through the device in clusters resulted in enhanced proliferation of fibroblasts compared to randomly dispersed cells in 3D and 2D. Animal studies showed successful incorporation and function retainment of delivered cells upon delivery. This design offers a potential therapeutic method to optimize the rate of tissue and wound repair.
Methionine-Mediated Protection of Fetal Programming Induced by Synthetic Glucocorticoid Treatment
Keywords: Antenatal Glucocorticoid
Developmental Programming
Gene Expression
Hippocampus
Methionine Cycle

S-adenosylmethionine (SAM) is a modified amino acid that is produced by the methionine cycle and used during DNA methylation. We investigated the methionine cycle as a mechanism through which prenatal synthetic glucocorticoid (sGC) treatment affects DNA methylation and gene expression in the fetus, and whether maternal supplementation with methionine (SAM precursor) could protect against sGC effects. Results indicate that sGC treatment was associated with increased methionine cycle metabolite levels (male plasma SAM and trend for hippocampal SAM-SAH ratio in females) and increased placental gene expression of methyl-donor transporters (Lat2, Rfc). Maternal methionine supplementation led to upregulation of key methylation-related enzymes (Mat2a, Dnmt3a, Dnmt3b) in the female and male hippocampus, though DNA methylation was unaffected. These findings suggest a potential rebound phenomenon in sGC-treated fetuses, and that maternal methionine supplementation can promote DNA methylation in offspring. Future research will further investigate the effects of sGCs and methionine on region-specific DNA methylation.
Imprinting and recalling amygdala ensembles
Keywords: Amygdala
Behavioural neuroscience
Learning and memory
Memory allocation
Optogenetics
Viral vectors

In the lateral amygdala (LA), memory allocation is a competitive process governed by changes in neuronal excitability. Enhanced levels of excitability can be sustained as a result of previous experience, making those neurons more likely to be allocated to subsequent events. However, the temporal window in which excitability can influence neuronal competition has not been defined, and it is not known whether transient increases in excitability can drive the events required for allocation to occur. Here, we bidirectionally manipulated the activity of a random, sparse subset of LA neurons in mice at various time intervals prior to auditory fear conditioning. Transient optogenetic excitation was sufficient to induce allocation 1-6 hours (but not 12-24 hours) prior to conditioning, evidenced by impaired freezing when photostimulated cells were inhibited during memory retrieval. These findings suggest that in the LA, a limited time window exists in which excitability can bias the outcome of allocation.
Augmenting ORKAMBI® Rescue of F508del-CFTR Primary Respiratory Tissue with L-Arginine-Nitric Oxide Pathway Agonists
Keywords: CFTR Modulators
Cystic Fibrosis
L-Arginine Nitric Oxide Pathway
Mucociliary Clearance
Personalized Medicine
Primary human respiratory epithelial cells

Cystic Fibrosis (CF) is a common autosomal recessive disease in the Caucasian population caused by a mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene, which codes for a major Cl- and HCO3- channel protein. Mutations in CFTR, F508del-CFTR, being the most common mutant, results in airway surface liquid depletion and defects in mucociliary clearance defects, leading to pulmonary dysfunction. ORKAMBI®, the firstan FDA approved therapy to address the basic defects of mutated CFTR in F508del-CFTR patients, only results in modest and variable lung function improvements in lung function. Genome wide association studies may help explain this variability by identifying modifier genes of the CF lung disease phenotypes, such as SLC6A14, a major apical arginine transporter in the airways. L-arginine has beenis regarded as a substrate for activating CFTR channel function through the L-Arginine-Nitric Oxide Pathway and could be used in conjunction with ORKAMBI® to improve lung function. We tested primary human respiratory cell cultures (both bronchial and nasal cells derived from delF508-CFTR patients) with Our an array of assays to determined an individual’s cells’ CFTR function, ciliary beat frequency, and mucociliary clearance velocity using primary F508del patient respiratory cell cultures. Although ORKAMBI® treatment alone improved CFTR function and mucociliary functions, combining ORKAMBI® treatment with NO- pathway agonists further augmented in vitro outcome measurements. This work suggests that stimulation of the arginine-NO pathway in combination with CFTR modulation may result in improved restoration of CFTR function and mucociliary clearance in both in vitro and in vivo models.
Elevational Differentiation Increases Rates of Trait Evolution but not Diversification in Neotropical Passerine Birds
Keywords: Birds
Ecological divergence
Elevation
Neotropics
Speciation
Trait evolution

The importance of ecologically-mediated divergent selection in elevating rates of trait evolution has been poorly studied in the most species-rich biome of the planet, the continental tropics. I performed a macroevolutionary analysis of trait divergence and diversification rates across closely-related pairs of passerine birds, belonging to the Amazon basin and adjacent Andean slopes, to assess whether the difference in elevational range separating species pairs influences the speed of trait evolution and diversification rates. Difference in elevation was used as a proxy for the degree of ecological divergence. I found that the amount of elevational separation is associated with faster differentiation of song frequency, a trait important for premating isolation, and several morphological traits, which may contribute to extrinsic postmating isolation. However, ecological differentiation does not primarily drive bird diversification and, thus, may have limited influence on patterns of species richness along the eastern slope of the tropical Andes.
To believe or not to believe: Stereotypes about agnostics
Keywords: agnostics
atheists
psychology
religion
stereotypes

The present study investigated which stereotypes agnostics share with atheists, and which stereotypes are unique to each group. In Study 1, participants reported stereotypes that they believed society held about agnostics, atheists, Christians, and Muslims. Common stereotypes for agnostics were indecisive and questioning, but for atheists were immoral and intolerant. In Study 2, participants rated how representative 10 key traits from Study 1 were of agnostics, atheists, and four religious groups. Results revealed that agnostics were stereotyped less negatively than atheists. In Study 3, participants had to judge whether a target’s actions, such as being immoral, morally indecisive, or indecisive in general were representative of an agnostic/atheist/Christian/Muslim. Inconsistent with Studies 1 and 2, no significant differences were found for perceptions of agnostics versus atheists. Findings from Studies 1-2 suggest that nonreligious individuals are sometimes viewed as a heterogeneous group, but future research must determine when stereotypes converge and diverge.
Zeta Adsorption Isotherm: From Specific Surface Area Determination to Equilibrium and Kinetics of Water Vapour Adsorption on Silica Nanopowders
Keywords: Adsorption
Equilibrium
Kinetic
Nanopowder
Surface Science
Thermodynamics

We use the zeta adsorption isotherm (ZAI) and propose a method for the long standing problem of determining the specific surface area (SSA) of powders using the N2 adsorption measurements at 77 K, which reduces the error of the conventional BET method, up to an order of magnitude. The consistency of the results obtained is demonstrated using two alpha-alumina samples that have different total surface areas. When the proposed method is applied to convert the amount adsorbed per unit mass to the amount adsorbed per unit area, we show that there is no measurable difference between their adsorption isotherms. In addition, using the ZAI, a new possible criteria for studying the reversibility of water vapour adsorption on silica nanopowders is introduced. Finally, the kinetic experiments of this solid--vapour system are conducted and a proper theoretical model is developed by combining the statistical rate theory (SRT) and the ZAI.