Characterization of the Growth Hormone Secretagogue Receptor in Dilated Cardiomyopathy

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease of skeletal and myocardial degeneration. Eventually, dilated cardiomyopathy develops from ischemia, inflammation and fibrosis. Due to the high mortality rate, there is an emerging need to diagnose DMD cardiomyopathy at early stages. Currently, DMD cardiomyopathy is diagnosed by imaging investigations and detection of circulating biomarkers. However, current imaging strategies detect functional and morphological changes but fall short in detecting molecular changes that underlie this disease. Circulating biomarkers provide information on the molecular level, but they are not cardiac-specific. Therefore, there is an emerging need for a biomarker that is endogenous to cardiac tissues. The growth hormone secretagogue receptor (GHSR) and its ligand, ghrelin are produced by both cardiomyocytes and vascular endothelial cells and could be an indicator of DMD cardiomyopathy. The work described in this thesis sought to characterize GHSR as a cardiac-localized biomarker in DMD cardiomyopathy. Histopathology and confocal imaging using a novel fluorescent ghrelin analog, Cy5-ghrelin(1-19), were used to investigate changes in cardiac tissue architecture and GHSR and inflammatory markers in the mdx:utrn-/- mouse model of DMD. My studies show that GHSR is elevated in mdx:utrn-/- myocardial tissues and correlate strongly with the macrophage marker F4-80 and the pro-inflammatory cytokine IL-6. Interestingly, I also show that both ghrelin and des-acyl ghrelin bind to sites in large cardiac vessels of mdx:utrn-/- which might be an indicator of vascular inflammation. Finally, my project shows the first report of GHSR in cardiac macrophages. In summary, my work suggests that, in dilated cardiomyopathy, elevations in GHSR correlate with the inflammatory phenotype as mediated by both the myocardium and macrophages

Advanced Driving Assistance Prediction Systems

Future automobiles are going to experience a fundamental evolution by installing semiotic predictor driver assistance equipment. To meet these equipment, Continuous driving-behavioral data have to be observed and processed to construct powerful predictive driving assistants. In this thesis, we focus on raw driving-behavioral data and present a prediction method which is able to prognosticate the next driving-behavioral state. This method has been constructed based on the unsupervised double articulation analyzer method (DAA) which is able to segment meaningless continuous driving-behavioral data into a meaningful sequence of driving situations. Thereafter, our novel model by mining the sequences of driving situations can define and process the most influential data parameters. After that, our model by utilizing these parameters can interpret the dynamic driving data and predict the next state of the determined vehicle. Proficiency of this model has been evaluated using over three terabytes driving behavioral data which include 16 drivers’ data, totally for more than 17 hours and over 456 Km

Corrosion of implant materials in the human body

This paper extensively examines the complex problem of implant corrosion occurring within the human body. The corrosion of implants gives rise to substantial challenges, encompassing compromised implant durability, patient safety concerns, and potential adverse impacts on the long-term functionality of the medical device. The study\u27s primary objectives include offering a concise overview of the various corrosion mechanisms that impact a range of implant materials and outlining health complications linked to the byproducts of implant corrosion. Furthermore, it delves into a cost analysis specific to hip or knee revision arthroplasty, which has become a prevalent scenario in implant failure cases on a global scale and particularly within the context of Canada in recent years

Thermosensitive chitosan-based hydrogels for extrusion-based bioprinting and injectable scaffold for articular tissue engineering

La bio-impression est une forme avancée de fabrication additive qui permet de créer des structures 3D vivantes (contenant des cellules) et de créer des modèles 3D de tissus ou, à plus long terme, des tissus implantables pour remplacer les tissus ou organes malades ou endommagés. La bio-impression connaît une croissance rapide mais doit faire face à plusieurs défis. L'un d'entre eux consiste à trouver des matériaux extrudables contenant des cellules (appelée bioencres) qui combinent toutes les propriétés requises. Les hydrogels de chitosan thermosensibles qui forment des solutions à température ambiante mais gélifient rapidement à la température du corps sont d’intéressants candidats comme bioencre mais à ce jour il n'y a pas encore eu de résultats convaincants démontrant leur potentiel. De plus, les méthodes rhéologiques permettant de prédire leur imprimabilité font toujours défaut. L'objectif général de ce doctorat était d'étudier et optimiser les hydrogels thermosensibles à base de chitosan fabriqué avec un mélange de deux bases faibles, (bêta-glycérophosphate et hydrogénocarbonate de sodium) pour la bio-impression par extrusion, notamment pour l'ingénierie des tissus articulaires. Nous avons tout d’abord développé une approche rhéologique pour évaluer leur potentiel en tant que bioencres. Les cinétiques de gélification à température ambiante et du corps ont été caractérisées. Puis les essais de viscosité et de récupération ont été adaptés pour prendre en compte l’absence de stabilité des gels. La fidélité de forme et les propriétés mécaniques des structures imprimées ont également été caractérisées en fonction du taux de cisaillement appliqué et les résultats corrélés avec les données rhéologiques. Nous avons démontré qu'il était possible d'imprimer une structure avec une fidélité et une maniabilité adéquate; cependant, une concentration élevée de chitosan (3%p/v) est nécessaire, ce qui entraîne un taux de mortalité élevé des cellules, tandis que réduire la concentration à 2%p/v entraîne une très mauvaise fidélité de la forme. Nous avons surmonté ces limites en utilisant une approche basée sur la bio-impression FRESH (Freeform reversible embedding of suspended hydrogel). Un bain de support chaud a été conçu afin de soutenir les structures bioprintées et d'améliorer la thermoréticulation du chitosan pendant l'impression. Cette approche augmente drastiquement la fidélité et les propriétés mécaniques des structures imprimées avec une concentration de chitosane (2% p/v) adaptée à l'encapsulation de cellules. ii Enfin, nous avons étudié l'impact du chargement de particules de bioverre osteoconducteurs dans ces hydrogels thermosensibles, en vue de leur utilisation pour la fabrication de tissus osseux minéralisés. Les propriétés mécaniques et la cytocompatibilité in vitro étant affectées de manière négative par l'ajout de bioglass, notre stratégie a consisté à concentrer le bioverre sous forme de microbilles, puis incorporer ces microbilles dans l'hydrogel à base de chitosan chargé de cellules. Cette nouvelle stratégie a permis d'améliorer considérablement les propriétés mécaniques et la viabilité des cellules. Cet hydrogel bioactif hybride n’est pas utilisable comme bioencre, mais il est injectable et pourrait être utilisé comme matrice injectable pour la régénération de défauts osseux. Cependant, il reste encore beaucoup d’optimisation à faire pour la bio-impression de tissus de gradient complexes.Bioprinting is an advanced method that enables to engineer living 3D structures mimicking the tissue complexity found in-vivo. It allows to create 3D tissues to study drugs/biological mechanisms, also, in longer-term, implantable tissue to replace diseased/damaged body tissues/organs. Bioprinting is growing rapidly but faces several challenges. One of them is to find ideal bioinks which combine all the required properties. Hydrogels are generally used since cells require an aqueous environment. But it is very challenging to stack hydrogels into a 3D structure because hydrogels are weak by nature and cannot support the structure without collapsing. Among the potential candidates are thermosensitive chitosan hydrogels which form solutions at room temperature but rapidly gel at body temperature. However, their potential in bioprinting has not been yet studied. Moreover, comprehensive rheological methods to predict their printability are still missing. The general objective of this Ph.D. was to study and optimize the thermosensitive chitosan-based hydrogels for extrusion-based bioprinting and injectable scaffold for articular tissue engineering. The first objective was to develop a rheological approach to study printability of these time- and temperature-dependent hydrogels and assess their potential as bioinks. Chitosan-based physical hydrogels prepared by combining chitosan acidic solution with weak bases like beta-glycerophosphate and sodium-hydrogen-carbonate were studied. Gelation kinetics, shear-thinning viscosity as a function of shear rate corresponding to that applied during printing, and recovery tests were performed. The resolution and mechanical properties were characterized as a function of applied shear rate and results were correlated with rheological data. This work allowed us to determine the best chitosan hydrogel formulation for 3Dprinting and compare it with conventionally used bioink, alginate/gelatin. This methodology can also be useful for other temperature- and time-dependent materials. We demonstrated that printing structures with adequate fidelity and handability using chitosan-based hydrogels was feasible; however, a high concentration (3%w/v) was required, leading to high mortality rate of encapsulated cells. Decreasing chitosan concentration resulted in poor shape fidelity. The second objective was therefore to develop a method using Freeform reversible embedding of suspended hydrogel (FRESH) bioprinting to overcome these limitations. A warm support bath was designed to support chitosan-based bioprinted structures and enhance chitosan thermo-crosslinking during printing. This approach iv drastically increases the fidelity and mechanical properties of structures printed with low concentration chitosan (2%w/v) suitable for cell encapsulation. Lastly, we studied the impact of loading bioglass particles into such thermosensitive hydrogels for potential bone-mineralized tissue repair, which could promote bone ingrowth through osteoconductivity. The mechanical properties and in-vitro cytocompatibility are affected adversely by bioglass addition. A new strategy was implemented to encapsulate bioglass within chitosan-based microbeads, then incorporate these microbeads in the cell-laden chitosan-based hydrogel. This strategy improved mechanical properties and cell viability. This hybrid hydrogel could be used to form an injectable cell-loaded scaffold. The bioactive microbeads were freezable, increasing their potential for clinical applications. We demonstrated the potential of the thermosensitive chitosan-based hydrogels for bioprinting, especially with the FRESH approach. This opens interesting avenues toward tissue engineering. However, much works still remain to be done before bioprinting complex gradient tissues

Development and Application of the Pelvic Tracker

Backpacks are commonly used by students of all ages and there has been a growing concern in many countries in relation to the backpack loads carried by school children and its association with the rise in complaints of neck, shoulder and back pain. Of further concern is the work of Hestbaek et al. (2006) which has shown a correlation between experiencing back pain as an adolescent and experiencing low back pain as an adult. In recent years, a number of studies have investigated physiological and movement kinematic responses to load carriage, such as oxygen consumption, heart rate, gait pattern and trunk posture (Hong et al., 2000; Pascoe et al., 1997). However, most of the studies that focused on children carrying loads looked only at gait patterns and trunk and neck postures. None of the previous studies investigated the compensatory pelvic motions of school children due to increased loads. Also, it was reported that one of the major limitations of measuring pelvic kinematics whilst carrying a backpack was occlusion of retro-reflective markers, and consequently this limits the type of activity and subject to be measured using an optical motion tracking system. Despite the presence of a variety of models, there are still debates on their reliability and repeatability, and consequently there is no clearly defined standard or consensus. In this thesis, a novel methodology was developed to measure pelvic kinematics. Its repeatability and reliability was validated experimentally by comparing it to the most relevant previous method. The result of this experiment showed that the new method improved the repeatability, reliability and reproducibility of kinematics data of the pelvis and overcomes a number of theoretical and experimental limitations, such as marker occlusion. The validated method was used to develop a protocol to measure the pelvic kinematics in adolescents whilst carrying loaded backpacks of 17% and 25% of their body weight during different activities of daily living on the basis of a survey which was conducted to explore the average daily weight that children carry to school in the UK. The result of this experiment revealed that as the load increased to 25% of the body weight, the instability in postural control increased and significant changes in pelvic tilt and rotation were noted in almost all activities. It was revealed in this study that female and male subjects used different mechanism to compensate for the effect of a heavy backpack. It was evident that carriage of loaded backpack will result in alteration of the movement of the pelvis and may in future promote postural deviation and increase lower back pain.Open Acces

Evaluation of Hydrogeochemical Characteristics of San Joaquin, Tulare, and Mojave Aquifers, Southern California

Before making attempts to enhance and manage the quality of water, a thorough understanding of these processes is necessary since the chemical quality of groundwater is impacted by a number of linked processes. This would be more important in arid and semiarid regions like the southern part of California where more rely on groundwater for agriculture and drinking water uses than the other states. As a result, fundamental knowledge of the governing processes of groundwater chemistry is required for effective water resource management. Thus, this study is primarily concerned with three aspects in Mojave, Tulare, and San Joaquin aquifers: The first step is chemical properties of groundwater with respect to hydrogeochemical aspects and salinity. Without different managerial approaches, irrigation with poor-quality water can have a variety of adverse effects, such as increased soil salinity/sodicity, poor penetration, soil hardening, and/or plant-specific ion toxicity. Together, these variables inhibit crop growth and, eventually, a crop\u27s economic output. Numerous indices have been proposed and are often employed in groundwater for this purpose, including Na%, SAR (sodium adsorption ratio), RSC (residual sodium carbonate), MH (magnesium hazard), PI (permeability index), and PS (potential salinity). In the second section, we go into more detail about the levels of heavy metals in groundwater and how pollution indices like HPI (heavy metal pollution index), HEI (heavy metal evaluation index), and CI (contamination index) can be used to evaluate the health risks of consuming groundwater that is overly contaminated with these heavy metals. The concentration of nitrate in the aquifers is the third factor. The multi-isotope systematics (δ15N- and δ18O-NO3) method is highlighted in this study, along with typical δ15N- and δ18O-NO3 ranges of known NO3 sources, as well as many other parameters, including the effects of pH, EC, reduction-oxidation, and other elements/ions on nitrate concentration and δ15N- and δ18O-NO3 determination. In addition, this paper covers how to map water quality indicators in the Mojave, Tulare, and San Joaquin aquifers using a GIS (geographical information system) based on water quality information system and spatial analysis with IDW (inverse distance weighted) interpolation