Objectives The aim of this thesis was to study the biosynthesis of Maresin 1 (MaR1) in human macrophage and to investigate the potential defect of this pathway in patients with localized aggressive periodontitis as well as the role of MaR1 in regulating phagocyte functions and leukocyte-platelet aggregation using LAP as a disease model. Methods Human recombinant enzyme (12-lipoxygenase and soluble epoxide hydrolyse) and synthetic intermediates were used to investigate the maresin pathway by LC/MS/MS-based lipid mediator (LM) metabololipidomics. Human macrophage 12-LOX sequence was crosschecked with platelet-type 12-LOX. Enzyme expression levels in human myeloid mononuclear lineage were determined with flow cytometry. Peripheral blood was collected from LAP patients and age/gender-matched healthy controls (HC). Neutrophils and monocytes were isolated, and macrophages were obtained from monocytes with GM-CSF incubation. LAP and HC macrophage 12-LOX expression levels were monitored by flow cytometry and endogenous maresin metabolite levels were investigated using LM metabololipidomics. Periodontal pathogens including Porphyromonas gingivalis (P. g) and Aggregatibacter actinomycetemcotimans (A. a) were incubated with neutrophils and macrophages to investigate phagocyte functions. Phagocytosis and intracellular anti-microbial reactive oxygen species (ROS) production were determined using fluorescence plate reader. Bacterial killing by macrophages and in whole blood was evaluated by assessing residual colony forming units following incubation with bacteria. Results We demonstrated that human macrophage 12-LOX is identical with platelet-type 12-LOX and is upregulated from monocyte to different mononuclear lineage. 12-LOX converts DHA to 14S-HpDHA, which is a key intermediate in MaR1 biosynthesis. In addition, soluble epoxide hydrolyze (sEH) is responsible for the further production of novel anti-inflammatory and pro-resolving Maresin 2 (MaR2; 13, 14S, di-HDHA). Since 12-LOX is the key-initiating enzyme, investigation begin with macrophages from LAP patients, which have lower 12-LOX expression (~30% lower) and reduced MaR1 (87.8±50 vs. 239.1±32 pg/ 106 cells) levels compared to macrophages from healthy controls (HC). Functionally, LAP macrophages gave impaired phagocytosis (~40% lower) and killing of periodontal pathogens including Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. In addition, neutrophils from LAP patients also displayed diminished kinetics (~30% slower) and reduced maximal phagocytosis (~20% lower) of these pathogens. Exogenous MaR1 rescued the impairment with LAP phagocytes enhancing phagocytosis (31-65% increase, 1nM), intracellular anti-microbial reactive oxygen species production (26-71% increase, 1nM) and bacterial killing of these periodontal pathogens in vitro. Additionally, MaR1 retained biological action and enhanced bacterial killing in the whole blood ex vivo from HC and LAP patients (22-37% reduction of bacterial titers, 10nM). MaR1 counter-regulated leukocyte-platelet aggregation against two stimulus (platelet activating factor (PAF) and P. gingivalis) and regulated the expression levels of surface adhesion molecules (CD18 and P-selectin). Patients with LAP had elevated leukocyte-platelet aggregation (40% higher compared to HC) in the whole blood that could be reduced by MaR1 in a dose-dependent manner (40-60% reduction of the excess aggregates, 1-100nM). Conclusions These results indicate that 12-LOX is the key enzyme in maresin biosynthetic pathway. LAP macrophages, had lower 12-LOX expression levels and dysregulated maresin biosynthesis. Reduced phagocyte functions were established with both LAP macrophages and neutrophils; exogenous MaR1 rescued this impairment with LAP patients and also enhanced the functions of HC phagocytes. Additionally, MaR1 enhanced bacterial killing and reduced elevated leukocyte-platelet aggregates in LAP whole blood. Together these results suggest that therapeutics targeting maresin pathway may have clinical application treating LAP and oral diseases associated with infection and uncontrolled inflammation.

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Master of Science / Department of Industrial & Manufacturing Systems Engineering / Malgorzata J. Rys / The current state of the dental industry shows an increasing number of dentists and dental hygienists who are reducing hours and retiring early due to the injuries sustained while working. These injuries, or cumulative trauma disorders, can be reduced by applying ergonomics in dental tool design. The goal of ergonomics is to reduce current injuries but also prevent future ones. In addition, population demographics have shown an increasing trend in female dentists. With a shift from the male dominated field, design for different anthropometric measurements needs to be investigated. In order to pinpoint sources of pain, a survey was designed and distributed to dentists in Kansas, Missouri, and Texas. Even with a small sample size (n=24), results confirmed past studies in the dental industry of pain originating in the neck, shoulder, lower back, and wrist/hand region. The reasons stemmed from the repetitive motions and forces applied during dental procedures. Responses also found that ergonomic principles need to be applied to the handle and grip portion of dental scaler design. Dental scaling is the procedure to remove deposits on teeth, such as plaque and calculus, most commonly performed by dental hygienists. First, the history of dental tools, angulation, tool weight, and materials currently utilized were researched before looking into specific design factors for modification. Currently, the handle grip area on all dental tools range in size, but a 10 mm grip has been proven to be optimal. The optimal tool weight has yet to be determined as 15 grams is the lowest weight to be tested. Most tools are made of stainless steel and resins, which are not compressible. An experiment was designed to test a new dental scaler (A) made of a titanium rod with added compressibility in the precision grip area. The aim was to help reduce pressure on the fingers and hand muscles and increase comfort during scaling. The experiment utilized a Hu-Friedy sickle scaler (B) and a Practicon Montana Jack scaler (C) as controls to show two design spectrums, weight and material. The subjects (n=23) were taught the basics of scaling and required to scale using a typodont. The change in grip strength (Δ GS), pinch strength (Δ PS), and steadiness of the subjects hand were tested. An absolute and relative rating technique was utilized pinpointing that the new dental scaler was preferred with the eigenvector (A=0.8615, B=0.1279, C=0.0106). Statistical analysis confirmed this tool preference while also finding the interaction of gender and tool and Δ GS Tool A versus Tool B for males to be significant.

Introduction : L’inconfort causé par les appareils orthodontiques peut significativement affecter la coopération des patients dans leur traitement. La douleur, ainsi que la détérioration de la fonction (mastication, élocution) sont reconnus comme les déterminants majeurs de la coopération des patients traités par appareils amovibles. Invisalign® se positionne comme une alternative esthétique aux multiples inconforts observés lors des traitements fixes avec boîtiers. À ce jour, peu d’études ont cherché à comparer la douleur (quantitativement et qualitativement) perçue entre cette technique et celle avec boîtiers fixes sur une longue période. Objectif : L’objectif de la présente étude est d’évaluer la douleur ressentie par les patients qui suivent un traitement orthodontique avec coquilles correctrices Invisalign® et de la comparer avec celle des patients qui suivent un traitement orthodontique conventionnel avec des boîtiers fixes. Matériels et Méthodes: L’étude compte 70 patients (29 garçons, 41 filles), moyenne d’âge de 16 ans [11 à 30]. Les trois sous-groupes sont Invisalign® (n=31), boîtiers Damon (n=19) et boîtiers Speed (n=20). Les groupes avec boîtiers (Damon et Speed) sont les 2 groupes de l’étude menée au sein de la clinique d’Orthodontie de l’Université de Montréal en 2011 qui comparait la perception de la douleur durant le traitement orthodontique entre boîtiers auto-ligaturants passifs et actifs. L’étude a été organisée en 4 phases correspondant à l’insertion des 4 premiers fils pour les groupes avec boîtiers (Phase 1: 0,016" Supercable, Phase 2: 0,016" CuNiTi, Phase 3: 0,016"x0,022" CuNiTi, Phase 4: 0,019"x0,025" CuNiTi) et à l’insertion des coquilles 1, 4, 7 et 10 pour le groupe Invisalign®. À l’aide d’un questionnaire, l’étude évalue pour chaque phase l’ampleur (grâce à une échelle visuelle analogue EVA), la durée et la localisation de la douleur à 6 différents points (T1: immédiatement après l’insertion, T2: 5h après, T3: 24h après, T4: 3 jours après, T5: une semaine après, T6: 2 semaines après). Résultats: À T1Ph3 le pourcentage de patients rapportant de la douleur était plus élevé avec Damon qu’avec Invisalign® (p=0,032) (Damon=55,6% ; Invisalign®=23,3%) mais il n’y avait pas de différence avec le groupe Speed (p=0,114). Les patients avec Invisalign® rapportaient significativement moins d’irritation des tissus mous (muqueuses, gencives) que les patients avec des boîtiers. Pour les résultats des EVA, les différences étaient statistiquement significatives à 2 temps : T3Ph1 (Médiane Invisalign®=33,31, Médiane Speed=49,47; p=0,025) et T3Ph4 (Médiane Invisalign®=13,15, Médiane Damon=27,28; p=0,014). Pour la majorité des patients la douleur ne nécessitait pas la prise de médicament et il n’y avait pas de différence significative entre les groupes sur ce point. La qualité de vie était légèrement affectée lors de la première phase et moindrement pour le groupe Invisalign® que pour les groupes avec boîtiers. Pour les patients Invisalign®, la douleur atteignait son niveau le plus élevé entre 5 et 24 heures après l’insertion de la première coquille, et diminuait en intensité et en durée à chaque phase. Conclusion: La perception de la douleur lors d’un traitement orthodontique avec Invisalign® est inférieure à celle ressentie lors d’un traitement avec des boîtiers fixes. Cette méthode de traitement est donc une thérapie attirante pour les patients désirant un traitement esthétique et relativement confortable. / Introduction : The discomfort caused by the orthodontic appliances can significantly affect patients cooperation during their treatment. Pain and function deterioration (chewing, speech) are recognized as major determinants of patients cooperation treated with removable appliances. Invisalign® is positioned as an aesthetic alternative to the many discomforts observed during treatment with fixed brackets. To date, few studies have compared the pain (quantitatively and qualitatively) between this technique and fixed appliances over a long period. Objective : The objective of this study is to assess the pain experienced in the first six months with Invisalign® treatment and compare it to the pain felt during conventional orthodontic treatment with fixed self-ligating brackets. Methods : The study was comprised of 70 patients (29 males, 41 females), with an age mean of 15.7 (range 11 to 30). The three subgroups are Invisalign® (n = 31), Damon (n = 19) and Speed (n = 20). The two bracket groups, Damon (passive) and Speed (active), were treated in the Orthodontic Clinic at the University of Montreal in 2011, and were compared (active vs. passive self-ligating brackets) for the perception of pain during orthodontic treatment. The study was conducted in four phases corresponding to the insertion of the first 4 wires for groups with brackets (Phase 1: 0.016 " Supercable, Phase 2: 0.016" CuNiTi, Phase 3: 0.016" x 0.022" CuNiTi, and Phase 4: 0.019" x 0.025" CuNiTi) and the insertion of aligners 1, 4, 7 and 10 for the Invisalign group. Using a questionnaire, the study evaluates the pain magnitude for each phase (using a visual analogue scale VAS), the duration, and location of the pain in 6 different time points (T1: immediately after insertion, T2: 5h later, T3: 24h later, T4: 3 days later, T5: 1 week later, T6: 2 weeks later). Results: At T1Ph3 the percentage of patients reporting pain was higher with Damon than with Invisalign® (p = 0.032) (Damon = 55.6%, Invisalign® = 23.3%), but there was no difference with Speed (p = 0.114). Patients with Invisalign® reported significantly less irritation of the soft tissues (mucous membranes, gums) than patients with brackets. For the VAS results, the differences were statistically significant at 2 stages: T3Ph1 (median Invisalign® = 33.31, Median Speed = 49.47, p = 0.025) and T3Ph4 (median Invisalign® = 13.15, median Damon = 27.28, p = 0.014). For most patients, the pain does not require medication and there was no significant difference between the groups in this respect. Quality of life was slightly affected during the first phase and less for the Invisalign® group than for the bracket groups. For Invisalign® patients, pain reached its highest level between 5 and 24 hours after insertion of the first aligner, and decreased in intensity and duration at each phase. Conclusion: The pain perception during orthodontic treatment with Invisalign® is lower than the pain experienced during treatment with fixed brackets. This method of treatment is therefore an attractive therapy for patients wishing for an aesthetic and reasonably comfortable treatment.

Introduction: L’ostéogenèse imparfaite (OI) est un désordre de collagène héréditaire caractérisé par du tissu conjonctif défectueux avec une incidence de 1 sur 20 000 naissances. Il y a une surreprésentation marquée des malocclusions de Classe III, une occlusion croisée antérieure et postérieure dans la population d’OI. L’objectif principal de cette recherche est d’évaluer si la sévérité des malocclusions présente chez les patients atteints d’OI est proportionnelle à la gravité du syndrome. L’objectif secondaire de cette recherche est d’évaluer si la sévérité de la malocclusion augmente avec l’âge. Matériels et méthodes: Étude rétrospective d’observation effectuée par calcul du Discrepancy Index (DI) de 56 modèles dentaires de patients atteints d’OI. Les résultats du DI ont été comparés à trois variables qui caractérisent la gravité du syndrome: type de OI, type génétique et le Z-score de la grandeur de chaque patient. En outre, l’analyse longitudinale d’un sous-ensemble de 20 modèles a été faite pour déterminer si la sévérité de la malocclusion augmente avec le temps. Résultats: La médiane du DI était de 33,5 [1, 109]. Le DI est plus augmenté chez les patients atteints d’un type de OI plus sévère (p = 0,001) ainsi chez les patients avec un Z-score de grandeur plus bas (p <0,0001). L'analyse longitudinale a démontré une augmentation statistiquement significative de DI au fil du temps. (p=0.05) Conclusion: La malocclusion des patients atteints d’OI semble liée à la gravité de ce syndrome. En outre, la sévérité de la malocclusion semble augmenter avec l'âge. / Introduction: Osteogenesis imperfecta (OI) is an inherited collagen disorder characterized by defective connective tissue with an incidence of 1 in 20,000 births. There is a marked over-representation of Class III malocclusion, negative overjet and lateral openbite in the OI population. Objectives: Primary objective is to evaluate whether the severity of the malocclusions present in OI patients is proportional to the severity of the syndrome. Secondary objective is to evaluate whether the malocclusion severity increases with age. Methods: Retrospective observational study performed by calculating the Discrepancy Index (DI) of 56 dental casts of patients with mild to severe OI. DI scores were compared to three variables that characterize the severity of the syndrome: OI type, genetic type and height z-score of each patient. In addition, longitudinal analysis of a subset of 20 OI casts was done to determine whether the malocclusion increases in severity with time. Results: The median DI score was 33.5 [1, 109]. The DI score increased with increasing severity of OI type (p=0.001) and decreasing height z-score (p<0.0001). In addition, longitudinal analysis of 20 OI patients demonstrated a statistically significant increase in DI over time (p=0.05). Conclusion: The malocclusion characteristic of OI patients seems linked to the severity of the syndrome. In addition, the malocclusion severity seems to increase with age.

INTRODUCTION: Alors qu’il existe aujourd'hui différents genres de traitements orthodontiques esthétiquement acceptables, les patients s'inquiètent maintenant de la durée des traitements. L'appareil AcceleDent® a été introduit sur le marché par OrthoAccel Technologies en 2009. Ce dispositif, placé entre les dents pendant 20 minutes par jour, vibre à une fréquence de 30 Hz et est préconisé pour accélérer le traitement. L’objectif primaire est d’évaluer la précision de la simulation ClinCheck® par rapport aux résultats finaux réels pour les deux groupes. L’objectif secondaire est de déterminer si le résultat final est influencé par une progression plus rapide des gouttières d’alignement. MATÉRIELS & MÉTHODES: Une étude rétrospective qui comprend 38 patients traités avec la technique Invisalign®. Le groupe expérimental, c’est-à-dire celui qui utilise l’AcceleDent®, comprend 13 patients tandis que le groupe contrôle inclut 25 patients. La sévérité de la malocclusion a été quantifiée avec le «Discrepancy Index de l’ABO». Concernant la prédiction des résultats de la simulation ClinCheck® et le résultat du traitement final, l’«Objective Grading System de l’ABO » a été utilisé pour quantifier ces derniers. Toutes les données ont été prises à partir du logiciel OrthoCAD (Cadent, Fairview, NJ). RÉSULTATS ET DISCUSSION: Il n'y a pas de différence statistiquement significative entre la malocclusion des 2 groupes. (p=0,761). Pour les résultats finaux, il existe une différence statistiquement significative. L'alignement est meilleur dans le groupe contrôle (p=0,002). Au sein de chaque groupe, la différence entre les résultats prédits et réels n’est pas statistiquement significative (p=0,056). L’utilisation de l’AcceleDent® semble donner un surplomb horizontal plus proche de celui prédit, cependant ceci n’est pas cliniquement significatif. CONCLUSION: L’utilisation de l’appareil AcceleDent® combiné à une progression plus rapide des coquilles aux sept jours influence négativement l’alignement final chez les patients traités par la technique Invisalign®. / INTRODUCTION: While there are presently many different options for aesthetic orthodontic treatment, patients are now concerned with the length of treatment. The AcceleDent® device was introduced by OrthoAccel Technologies in 2009. This device is placed between the teeth for 20 minutes a day, vibrates at a frequency of 30 Hz and is recommended to accelerate orthodontic treatment. This study’s primary objective is to evaluate the accuracy of the ClinCheck® simulation versus the actual final results. The secondary objective is to determine if the end result is influenced by the increased rate of treatment progression with the aligners. MATERIALS AND METHODS: A retrospective study design was used with 38 patients treated with Invisalign®. The experimental group consisted of 13 patients, while the control group included 25 patients. The severity of malocclusion was quantified with the Discrepancy Index approved by the American Board of Orthodontics. In addition, the ABO’s Objective Grading System was used to compare the prediction of the final result provided by the ClinCheck® simulation and the actual final treatment result. All data were taken from the OrthoCAD software (Cadent, Fairview, NJ). RESULTS AND DISCUSSION: There is no statistically significant difference between the two groups regarding their initial malocclusion (p= 0.761). For the final results, there is a statistically significant difference. The alignment is better in the control group (p = 0.002). Within each group, the difference between the predicted and the actual results are not statistically significant (p = 0.056). The use of AcceleDent® seems to give an overjet similar to that which was predicted; however, this finding is not clinically significant. CONCLUSION: The use of the AcceleDent® combined with changing aligners every seven days negatively influence the final alignment in patients treated with Invisalign®.