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This study examined the cognitive development of children born with cleft lip and the impact of mother-child interactions on cognitive outcome. 2 index groups, differing in timing of initial lip repair (early neonatal repair, n=48; late 3-4 month repair, n=55) and one control group (n=100), were initially recruited. Comparisons of mother-child interactions at 2, 6 and 12 months and at 7-8 years, found the late group to differ from the controls on all 5 dimensions at 2 months, but not thereafter.

Assessment of treatment outcome in clinical trials of temporomandibular disorders (TMD) lacks validated patient-based measures of the condition and its improvement. Such measures are questionnaire-based. The questions need to be chosen and framed appropriately. In line with the guidelines of the National Institute for Health and Clinical Excellence in the U. K., this project aimed to start the development of a patient-derived quality of life instrument to measure TMD treatment outcome. Three studies were conducted for this purpose. Study One aimed to establisht he optimal time to assesstr eatmento utcomef or TMD (the Review Period), and the best Reference Period to determine the time-frame of questions. Data consisted of daily diaries of pain intensity from 72 patients who had participated in a clinical trial of conservative TMD treatment. The study involved two stages. The first aimed to identify patientsr espondingto treatment,s o-called" Improvers" andt o excludet he "Non- Improvers" whosed atam ight dilute the results.T his was accomplishedin two ways: firstly by visually assessingin dividual plots of pain versust ime; secondlyb y mathematicallyc alculating the reduction of pain scores during treatment. Criteria for improvement were set and tested for both methods.D efinite improvers were selectedi f they met criteria of both assessmentsIn. the second stage, only improvers' data were examined to analyse the general trend of improvement and establish the review and reference periods. Study One determined 15 weeks as the best review period and four weeks as the best referencep eriod when assessinga commonly used TMD treatment. Study Two was intended to triangulate with Study One and had the same aim. Study Two explored, using a qualitative approach, patients' perception of improvement of TMD symptoms and rates of their recovery. Ten TMD patients showing improvement to conservativet reatmentw ere interviewed. Data were collected using a pre-designedt opic guide and analysed using the Framework approach. The interviewees consistently reported that pain was the symptom with the most impact on their quality of life, and the one to which improvement was linked the most. Other TMD symptoms were also important, but were less linked to patients' suffering and to perceived improvement. Different symptoms followed various rates of recovery. It was not possible to determine a definite time when all symptoms are considered improved. This study confirmed that the approach used in Study One, i. e. assessing TMD recovery based on measurement of pain intensity, was reasonable. It also confirmed that sufficient time (in a frame of some months) is needed before outcome for TMD conservative treatment can be assessed meaningfully. In addition, this study identified important new themes related to patient's journey throughout illness and their perception of received care. Study Three was the core study in this project. It aimed to establish a quality of life measure of TMD treatment outcome using the Oral Health Impact Profile (OHIP) as a starting point, using the reference period identified in studies one and two. A short form of OHIP was derived by identifying OHIP items with the largest impact on TMD patients' quality of life. A case-control design was used and 110 patients (PG) undergoing a variety of conservative treatments and matching controls (CG) were included. Candidate questions (items) for the intendeds hort form (OHIP/TMD-I) were selectedb asedo n three criteria: 1- showings tatistical differencesb etweenP G and CG; 2- showing largests cored ifference (PG:C G) as measuredb y four analysesM: ean, Median, Prevalencea ndI tem-Impact;3 - representinga ll domainso f OHIP's theoretical framework. This was followed by testing aspects of validity and reliability of the short form and comparing them to those of the full OHIP. Twenty items were identified. Their psychometric properties were comparable or better than those of the mother instrument. Future work is neededt o analyset he responsivenestso changew ith treatmento f the short form, to investigatew hetheri temso utwith OHIP aren eededto furnisht he intendedT M) outcome instrument, and to test the psychometric properties of the final instrument in a new sample.

Ce travail de thèse vise à mieux comprendre l'effet de l'environnement buccal sur le comportement d'une bactérie orale probiotique, Streptococcus salivarius K12. La croissance et la maintenance de S. salivarius K12 ont tout d'abord été caractérisées dans une salive artificielle complémentée (CAS) conçue pour l'étude. Dans ce milieu, cette bactérie démontre un taux de croissance élevé et un temps de latence court, mais elle ne produit pas de bactériocines actives. La survie de S. salivarius K12 en phase stationnaire est, en revanche, affectée dans le milieu CAS. Ce phénomène est expliqué par une synthèse moindre des protéines impliquées dans le métabolisme énergétique, dont celui du glycogène. Toutefois, malgré une sensibilité accrue en phase stationnaire, le milieu CAS permet la croissance et la maintenance de S. salivarius K12. Les effets de plusieurs facteurs environnementaux spécifiques de la bouche, sur S. salivarius K12, ont été déterminés en milieu CAS. Ainsi, l'apport de saccharose, conduit à une dégradation de la viabilité. Des enzymes, ajoutées à leur concentration physiologique, affectent également les cellules bactériennes. Le lysozyme accroît la mortalité de S. salivarius par son action sur la paroi bactérienne. La peroxidase améliore sa viabilité en diminuant le potentiel redox du milieu. Le rôle clé du potentiel redox sur S. salivarius K12 est confirmé par l'impact négatif de l'injection d'air enrichi à 5% de CO2, qui accroît le potentiel redox. Enfin, l'amylase a démontré un rôle à la fois positif (augmentation de la biomasse) et négatif (diminution du taux de croissance). En conséquence, les études impliquant des bactéries orales se doivent de prendre en compte ces facteurs environnementaux influant sur les l'état physiologique bactérien. La mise en place de cultures continues respectant les variations de flux salivaire et permettant l'apport périodique de nutriments, tout en combinant l'ensemble des conditions environnementales identifiées précédemment, a permis de simuler la dynamique des conditions buccales. Les résultats démontrent que S. salivarius K12 est bien adapté à ces conditions de culture. Les cellules sont capables de se maintenir à un niveau de cultivabilité constant, malgré la carence nutritionnelle et le lessivage auxquels elles sont soumises. Certains mécanismes moléculaires expliquant cette adaptation ont été caractérisés : activation des voies d'utilisation de sources de carbone alternatives, stockage de l'énergie, augmentation de la compétence génétique naturelle. Finalement, ces travaux ont permis d'identifier certains mécanismes permettant à Streptococcus salivarius K12 de s'adapter à l'environnement buccal, grâce à la mise en place de méthodes d'étude in vitro du comportement des bactéries orales. / This thesis aims to better understand the effect of oral environmental conditions on the behaviorof the probiotic bacteria Streptococcus salivarius K12. Growth and maintenance of S. salivarius K12 have been characterized in a complemented artificial saliva (CAS), designed for this study. In this medium, S. salivarius demonstrated highspecific growth rate and low lag time, but it did not produce active bacteriocins. However, the survival of S. salivarius K12 during stationary phase was affected during fermentation in CAS medium. This was mainly explained by a reduced synthesis of proteins involved in energy and glycogen metabolisms. Thus, despite an increased sensitivity in stationary phase, the "complemented artificial saliva" allowed the growth and maintenance of S. salivarius K12. The effects of several environmental oral factors on S. salivarius K12 were determined in complemented artificial saliva. Adding sucrose decreased cellular viability. Enzymes added to their physiological concentration also affected the bacteria. Lysozyme increased S. salivarius mortality by acting on cellular wall. Peroxidase enhanced viability, by reducing the redox potential. The key role of redox potential on S. salivarius K12 was confirmed by the negative impact of the injection of air containing 5% CO2, which increased redox potential. The amylase demonstrated both positive (biomass increase) and negative roles (reduced growth rate). Consequently, studies involving oral bacteria must integrate these environmental factors that affected the bacterial physiological state. Continuous cultures, taking into account the variations in salivary flow and the periodical supply of nutrients, and combining all environmental conditions previously identified, allowed simulating oral dynamic conditions. From our results, a good adaptation of S. salivarius K12 took place in these culture conditions. Cells were able maintaining a constant level of cultivability despite nutritional starvation and wash out. Some molecular mechanisms explaining this bacterial adaptation have been characterized: activation of alternative carbon sources pathways, energy storage, and increase of natural genetic competence. Finally, this work made it possible identifying some mechanisms used by Streptococcussalivarius K12 to adapt itself to the oral environment, through the establishment of in vitro methods for studying the behavior of oral bacteria.