L'objectif du travail de thèse, dans le cadre du projet Européen DEMU2NECK, a été de contribuer à développer un modèle volumique déformable et personnalisable du cou, incluant la prise en compte de la capacité d'activation musculaire. Ce modèle vise à contribuer à une meilleure compréhension des liens entre pathologie, posture et activation musculaire pour aider les cliniciens et les fabricants de dispositifs médicaux dans leurs prises de décision. Pour atteindre cet objectif la thèse a été structurée en quatre grandes tâches : après une i) synthèse bibliographique, ii) un modèle générique a été développé et validé. La troisième étape a été iii) le développement d'un modèle de muscle actif et son intégration au modèle générique. L'implémentation de la fonction contractile des muscles lors de simulations musculo-squelettiques isométriques et dynamiques de tâches fonctionnelles simples du cou, a permis de mettre en avant des efforts transverses transmis par les muscles au rachis, allant dans le sens de l'hypothèse d'une contribution à sa stabilisation. La dernière tâche a été iv) la réalisation des premières applications de personnalisation, qui ont porté sur la déformation du modèle générique sur la base de données d'imagerie obtenues sur volontaires. Des comparaisons des réponses des modèles personnalisés et du modèle générique ont mis en avant l'intérêt scientifique de l'approche de personnalisation à travers l'obtention de différences significatives de résultats / The objective of this thesis, as part of the DEMU2NECK European project, was to contribute to develop a 3D, deformable model of the neck, with contractile muscles and including the possibility of patient-specific geometric personalisation. The aim of this model is to contribute to a better understanding of the links that exist between pathologies, cervical spine posture and muscular activation in order to help clinicians and medical devices manufacturers in their decision making process. To achieve this goal, the thesis work was divided into four main tasks: after a i) bibliographic synthesis, ii) a passive generic finite element model was developed and validated. The third step consisted in iii) the development of a finite element muscle model and its integration to the generic passive model. The contractile function of the muscles was implemented during isometric and dynamic simulations of simple functional tasks of the neck. The transverse forces that were transmitted from the muscles to the cervical spine are in good agreement with the hypothesis of a contribution of these forces to the cervical spine stability. The last task covered iv) the personalisation process of the generic model. The responses of subject-specific models based on volunteers were compared with the ones obtained from the generic model. They showed significant differences and, therefore, the scientific relevance of the personalization approach

One hundred women aged 20 to 50 were asked to compare their sexual experience before diagnosis and following treatment for benign and malignant cervical disease. The subjects were divided into five groups: three groups had definite cervical intraepithelial neoplasia (CIN), (Class II or III). Two groups were treated with cryotherapy, and one with hysterectomy. One group had a provisional diagnosis of CIN I, but received no treatment. Subjects in the last group had microinvasive cervical carcinoma and were also treated with hysterectomy. All subjects had ovarian function; all were sexually active at the time of treatment. They were interviewed at least six months post-cryotherapy and 15 months post-hysterectomy. All subjects completed a variant version of the Derogatis Sexual Function Inventory (DSFI).

O câncer cervical é considerado um grande problema de saúde pública e um dos maiores causadores de mortes relacionadas a tumores em mulheres. O principal objetivo desta tese foi aumentar a eficácia antitumoral terapêutica da proteína gDE7 por meio da associação de adjuvantes vacinais em formulações testadas em condições experimentais com a linhagem celular tumoral TC-1. A proteína gDE7 foi produzida a partir de uma linhagem de E. coli e associada a diferentes adjuvantes. A proteína gDE7 coadministrada ao poly(I:C) conferiu proteção antitumoral completa aos camundongos previamente desafiados e induziu ativação de linfócitos T CD8+ E7-específicos polifuncionais, citotóxicos e de fenótipo de memória efetora/efetor. Foi demonstrado que a proteína gDE7 ativa de forma específica a subpopulação de células dendríticas especializada na apresentação cruzada de antígenos para linfócitos T CD8+, tanto em camundongos como em seres humanos. Esses resultados abrem perspectivas para o emprego da proteína gD como plataforma vacinal para o controle de tumores induzidos pelo HPV-16. / Cervical cancer is considered a major public health problem and one of the leading causes of cancer death in women. The main goal of this thesis was the improvement of a therapeutic antitumor vaccine based on gDE7 protein in formulations admixed with adjuvants under experimental conditions with the tumor cell line TC-1. The gDE7 protein was expressed and purified from E. coli, and then tested in combination with different vaccine adjuvants. The gDE7 protein admixed with poly(I:C) conferred complete therapeutic antitumor protection to mice previously challenged with TC-1 cells and induced polyfunctional, cytotoxic E7-specific CD8+ T cells with effector/effector memory phenotype. It was also demonstrated that the gDE7 protein activated a specialized dendritic cell subset involved in specific antigen cross-presentation to CD8+ T cells, both in mice and humans. These results open perspectives for the use of the gD protein use as a vaccine platform for the control of HPV-16-induced tumors.

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Bakgrund I majoriteten av länderna världen över klassas livmoderhalscancer som den näst vanligaste eller den vanligaste cancerdiagnosen hos kvinnor. Sjukdomen som till största del orsakas av ihållande infektioner med humant papillomvirus (HPV) kan bilda cellförändringar som senare utvecklar cancertumörer i livmoderhalsen. Aggressiva behandlingsformer i olika kombinationer sätts in och ger vanligen en rad olika biverkningar som påverkar kvinnorna på olika sätt. Ett sjukdomslidande är ett lidande som orsakas av sjukdomen i sig samt dess behandlingar. Kvinnor som får livmoderhalscancer har därav en ökad tendens till att uppleva ett lidande.  Syfte Syftet med studien var att belysa kvinnors erfarenheter och upplevelser av att leva med livmoderhalscancer.  Metod En icke-systematisk litteraturöversikt tillämpades och författarna baserade resultatet på 15 vetenskapliga artiklar med kvantitativ samt kvalitativ design. Via databaserna Public Medline (PubMed) samt Cumulative Index to Nursing & Allied Health literature (CINAHL) inhämtades artiklarna med hjälp av olika sökkombinationer. Artiklarna som inkluderades i studien kvalitetsgranskades utifrån bedömningsunderlaget framtaget av Sophiahemmet högskola. Därefter genomfördes en integrerad dataanalys där artiklarna till resultatdelen sorterades in i kategorier och underkategorier, genom detta utformades fyra huvudrubriker med tillhörande underrubriker.  Resultat I litteraturöversiktens resultat beskrivs hur kvinnor upplever livmoderhalscancer. I resultatet framkommer det att beskedet om diagnosen, genomförandet av behandling samt dess biverkningar påverkat majoriteten av kvinnornas fysiska, psykiska och sexuella förmåga. I resultatet framkommer det även att majoriteten av kvinnorna som lever med sjukdomen upplever en förändrad vardag med anledning av detta.  Slutsats Litteraturöversiktens resultat visar sammanfattningsvis att upplevelsen av livmoderhalscancer är varierande hos kvinnor, framför allt på grund av val av behandlingsmetod. Det framgår i resultatet att lidandet hos kvinnor är tydligt inom flertalet områden. Kvinnor upplever fysiska och psykiska hinder i livet både under och efter att ha diagnostiserats med livmoderhalscancer. / Background In the majority of countries around the world, cervical cancer is classified as the second most common or the most common cancer diagnosis in women. The disease, which is largely caused by persistent infections with human papillomavirus (HPV), can form cell changes that later develop cancerous tumors in the cervix. Aggressive forms of treatment in different combinations are used and usually cause a number of different side effects that affect women in different ways. The suffering of illness is a suffering caused by the disease itself and its treatments. Women who get cervical cancer therefore have an increased tendency to experience suffering.  Aim The purpose of this study was to illustrate women's experiences of living with cervical cancer.  Method A non-systematic literature overview was applied and the authors based their results from 15 scientific articles with quantitative and qualitative design. The articles are collected from the databases Public Medline (PubMed) and Cumulative Index to Nursing & Allies Health Literature (CINAHL), using different search combinations. The articles included in the study has been quality audited based on the assessment data produced by Sophiahemmet Högskola. Thereafter, an integrated data analysis was carried out where the articles were sorted into categories, and under categories, through this, four main headings with associated subheadings were designed.  Results In the result of the literature overview, it is described how women experience cervical cancer. The results show that the information about the diagnosis, the implementation of treatment and its side effects affected the majority of the women's physical, mental and sexual abilities. The results also show that the majority of women living with the disease experience a changed everyday life due to this.  Conclusions In summary, the result of the literature overview show that the experience of cervical cancer varies in women, mainly due to the choice of treatment method. The results show a clear suffering of women and in many areas. Women experience physical and mental barriers in life both during and after being diagnosed with cervical cancer.

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Cette étude a été subventionnée par le Fonds de recherche du Québec - Santé (FRQ-S, grant # 21230 – 2) / Les infiltrations foraminales cervicales sont associées à un risque de complications neurologiques majeures. Cette étude compare l’efficacité des infiltrations facettaires, plus sécuritaires, à celle des infiltrations foraminales dans le traitement de la cervico-brachialgie secondaire à une spondylose et/ou à une hernie discale, à 4 semaines post traitement. Cinquante-six sujets ont été randomisés pour recevoir une infiltration foraminale (15 hommes, 13 femmes ; âge moyen 52 ans) ou facettaire (8 hommes, 20 femmes ; âge moyen 44 ans). L’issue principale était l’intensité de la douleur mesurée sur une échelle visuelle analogique (0 – 100). Les issues secondaires étaient le Neck Disability Index et le Medication Quantitative Scale. Suivant les analyses en intention-de-traiter et en intention-du-protocole, pour un score de douleur initial moyen, une réduction significative de l’intensité de la douleur a été observée avec les infiltrations facettaires [45.3% (95%CI: 21.4; 69.2) et 37.0% (95%CI: 9.2; 64.7)] contrairement aux infiltrations foraminales [9.8% (95%CI: +11.5; 31.2) et 17.8% (95%CI: +6.6; 42.2)]. Les infiltrations facettaires ont procuré une amélioration cliniquement (mais non statistiquement) significative du Neck Disability Index [24.3% (95%CI: +2.9; 51.5) et 20.7% (95%CI: +6.2; 47.6),], contrairement aux infiltrations foraminales [9.6% (95%CI: +15.2; 34.4) et 12.8% (95%CI: +11.2; 36.7)]. Les infiltrations facettaires étaient au moins aussi efficaces que les infiltrations foraminales pour un score initial de douleur ≤ 60, alors que l’analyse de non infériorité n’était pas concluante pour un score initial ≥ 80, de même que pour le Neck Disability Index. Les infiltrations n’ont pas été associées à une réduction du score de Medication Quantitative Scale. Les infiltrations facettaires sont efficaces dans le traitement de la névralgie cervico-brachiale et représentent une alternative valable et plus sécuritaire aux infiltrations foraminales. / Transforaminal corticosteroid injections can be performed in the management of cervical radiculopathy but carry the risk of catastrophic complications. This study compares the efficacy of transforaminal and facet corticosteroid injections at 4 weeks post treatment. We randomly assigned 56 subjects to receive CT-guided transforaminal (15 men, 13 women; mean age 52 years; range 28 – 72 years) or facet (8 men, 20 women; mean 44 years; range 26 – 60 years) injections. The primary outcome was pain severity rated on a visual analog scale (0-100). Secondary outcome measures were the Neck Disability Index and the Medication Quantitative Scale. In the intention-to-treat and as-treated analyses, for a mean baseline score, facet injections demonstrated a significant pain score reduction of 45.3% (95%CI: 21.4; 69.2) and 37.0% (95%CI: 9.2; 64.7), while transforaminal injections showed nonsignificant pain score reduction of 9.8% (95%CI: +11.5; 31.2) and 17.8% (95%CI: +6.6; 42.2). While facet injections demonstrated an improvement in Neck Disability Index score of [24.3% (95%CI: +2.9; 51.5); 20.7% (95%CI: +6.2; 47.6),] as opposed to transforaminal injections [9.6% (95%CI: +15.2; 34.4); 12.8% (95%CI: +11.2; 36.7)], the results did not reach statistical significance. Noninferiority of facet to transforaminal injections was demonstrated for baseline pain score ≤ 60, while noninferiority analysis was inconclusive for baseline pain score ≥ 80 and for the Neck Disability Index score. Neither intervention showed a significant medication intake score reduction over time. Facet injections are effective for the treatment of cervical radiculopathy and represent a valid and safer alternative to transforaminal injections.