Les métastases osseuses sont des complications de nombreux cancers tels que le cancer du poumon, du sein et de la prostate. Chez la femme, 70% des patientes présentant un cancer du sein avancé développent des métastases principalement ostéolytiques. Ce type de métastases est associé à une destruction importante de l'os causant chez les patientes des douleurs osseuses et des fractures pathologiques. Les traitements actuellement dispensés tels que les bisphosphonates et le denosumab ne sont pas curatifs mais seulement palliatifs, il est donc indispensable d'identifier de nouveaux facteurs impliqués dans la progression métastatique afin d'améliorer le pronostic et d'imaginer de nouvelles approches thérapeutiques. Dans ce contexte, une analyse transcriptomique comparative a montré que les gènes codant les récepteurs de guidage axonal ROBO1 et ROBO4 étaient surexprimés dans une sous-population de cellules de cancer du sein MDA-MB-231 qui métastasent spécifiquement à l'os (nommée B02). De manière intéressante, une expression élevée de ROBO4 dans les tumeurs primaires de patientes atteintes d'un cancer du sein corrèle avec un mauvais pronostic et un risque accru de rechute à l'os. Chez la souris, une réduction de 50% de la charge tumorale a été observée lorsque les cellules B02 déplétées en ROBO4 ont été inoculées dans la glande mammaire de souris ; et le ciblage des cellules parentales B02 avec un anticorps anti-ROBO4 avant l'injection intra-tibiale diminue l'incidence de la formation de colonies de cellules tumorales. In vitro, la co-culture des cellules B02 avec des cellules ostéoblastiques murines MC3T3-E1 a entraîné une augmentation de la production de SLIT2, le ligand naturel des récepteurs ROBO, par les cellules MC3T3-E1. De plus, le traitement avec un anticorps anti-ROBO4 réduit considérablement l'adhésion des cellules B02 sur les cellules MC3T3-E1. Par ailleurs, la surexpression de ROBO4 dans d'autres modèles cellulaires de cancer du sein a conduit à mettre en évidence la présence d'une glycoforme de ROBO4. L'étude des deux isoformes de ROBO4 (glycosylée et non glycosylée) a révélé le caractère agressif de la forme non glycosylée comparée à la forme glycosylée / Bone metastasis is a complication of many cancers such as lung, breast and prostate. In women, 70% of patients with advanced breast cancer predominantly develop osteolytic metastases. This type of metastasis is associated with significant bone destruction in patients causing bone pain and pathological fractures. The current treatments, such as bisphosphonates and denosumab, are not curative but only palliative, so it is essential to identify new factors involved in the metastatic progression to improve prognosis and to devise new therapeutic approaches. In this context, a comparative transcriptomic analysis demonstrated that axon guidance ROBO1 and ROBO4 receptors were overexpressed in a subpopulation of MDA-MB-231 breast cancer cells that only metastasize to bone (referred to as B02). Interestingly, high ROBO4 expression in primary tumors from patients with breast cancer correlated with poor prognosis and increased risk of relapse to bone. In mice, a 50% reduction in tumor burden was observed when ROBO4-depleted B02 cells were inoculated in the mammary fat pad of mice; and targeting of parental B02 cells with an anti-ROBO4 antibody before intra-tibia inoculation decreased the incidence of tumor cell colony formation. In vitro, the co-culture of B02 cells with murine MC3T3-E1 osteoblastic cells increased SLIT2 production, the primary ligand of ROBO receptors, by MC3T3 cells. Further, the treatment with an anti-ROBO4 antibody dramatically reduced B02 cell adhesion to MC3T3-E1 cells. Moreover, over-expression of ROBO4 in other models of breast cancer led to the discovery of a glycoform of ROBO4. The study of the two ROBO4 isoforms (glycosylated and non-glycosylated) revealed the aggressive nature of the non-glycosylated form compared to the glycosylated form. These results provide strong evidence that the axon guidance receptor ROBO4 is involved in bone metastasis formation and that the use of an antibody directed against the non-glycosylated form of this receptor could lead to the development of innovative therapies to prevent metastasis formation in the bone marrow

The dissertation thesis points to a wide range of possibilities of therapeutic use with fairy-tale material and at the same time offers a concrete example of working with adolescents with educational problems. We worked with ten respondents, 5 boys and 5 girls who were clients of the Center for Educational Care. Based on the assumption that the fairy tale metaphor represents a non-threatening stimulus, the respondents were asked to formulate their own lives into a fairy tale. All participants were willing to work with a fairy-tale metaphor even on subjectively unpleasant topics, and in none of the stories did we encounter any significant resistance. The analysis of stories through Propp's morphology of the fairy tale brought a characteristic story of a child with an educational problem and at the same time proved to be a meaningful therapeutic tool. The analysis of the data through a narratively oriented approach inspired by McAdams and his identity as a life story yielded a demonstration of the identity of an adolescent with educational problems. An important outcome of the work is the evaluation of the internally experienced responsibility of this specific group of adolescents. Keywords: adolescents, risk behavior, fairy tale, life story, therapeutic tool

The study reports on the development of a photo therapy tool for educational psychologists within the South African context. A literature study explores the nature, advantages, characteristics and the application of photo therapy with clients in a therapeutic setting. The developmental intervention research design guided the practical development of an electronic photo therapy tool that can be applied by educational psychologists in a therapy setting with clients. The empirical research is qualitative in nature, as the effectiveness of the newly developed photo therapy tool is evaluated by emerging adults and educational psychologists as an intervention strategy. In order to accomplish this purpose, emerging adults, as well as educational psychologists shared their perceptions of the newly developed photo therapy tool. Thus the usefulness of the photo therapy tool was investigated as an intervention approach. Qualitative data generation techniques, focus group interviews and photographs were utilised. The research results show that the newly developed electronic photo therapy tool has the potential, as a modern therapeutic tool, to be used by educational psychologists as an intervention strategy. The developmental intervention research design is a continuous process, and as the life world is forever changing, improvements to the photo therapy tool can always be added according to new suggestions and ideas. The findings allow theorisation about the significance of the photo therapy tool. The study further determines that there is definite potential in the electronically created photo therapy tool, as both the young adults and the educational psychologists perceived the photo therapy tool as a possible and valuable tool in the therapeutic intervention process. / Psychology of Education / D. Ed. (Educational Psychology)

A leptospirose humana é uma doença infecciosa aguda de amplo espectro clínico e que cursa com alterações metabólicas e dislipidêmicas envolvendo colesterol total e frações, triglicerídeos e ácidos graxos não esterificados (AGNEs). Dentre os mecanismos celulares envolvidos na sua fisiopatologia encontram-se a inibição da enzima Na, K ATPase pela endotoxina GLP e a lipotoxicidade, ambos agravados pela redução dos níveis circulantes da albumina, molécula que exerce um papel fundamental na adsorção de moléculas lipídicas. Neste estudo observacional, determinamos as concentrações séricas de bilirrubina, creatinina e albumina e, pela técnica de cromatografia líquida de alta performance, a concentração sérica dos AGNEs de cadeia longa (C16: C18) de 27 pacientes com síndrome de Weil durante o período de internação hospitalar, dos quais cinco vieram a falecer. Verificamos correlações significantes (p<0,05) ao longo da internação hospitalar, nas concentrações séricas de marcadores bioquímicos de gravidade da doença (bilirrubina, creatinina e albumina), AGNEs, ácido oléico e ácido linoléico, e relação molar ácido oléico/ albumina, com r (Pearson) de -0,7981, -0,7699, 0,9014, -0,8795 -0,9816, -0,9694, -0,9821, respectivamente. A relação molar ácido oléico/ albumina e ácido oléico+ linoléico/albumina foi significantemente mais elevada nos pacientes que faleceram (p<0,001), retornando aos valores semelhantes aos do grupo controle nos pacientes que evoluíram para a cura. Na análise por Curva Roc, a relação molar ácido oléico/albumina se mostrou um bom teste preditivo, com valor de corte 0,705 associado com maior especificidade e sensibilidade prognóstica. Nossos resultados sugerem que a utilização parenteral da albumina humana em pacientes com leptospirose pode ser uma potente ferramenta terapêutica nos casos mais graves ao interferir positivamente no resgate do equilíbrio bioquímico das relações molares ácido oléico/ albumina e ácido oléico+linoléico/albumina.

A leptospirose humana é uma doença infecciosa aguda de amplo espectro clínico e que cursa com alterações metabólicas e dislipidêmicas envolvendo colesterol total e frações, triglicerídeos e ácidos graxos não esterificados (AGNEs). Dentre os mecanismos celulares envolvidos na sua fisiopatologia encontram-se a inibição da enzima Na, K ATPase pela endotoxina GLP e a lipotoxicidade, ambos agravados pela redução dos níveis circulantes da albumina, molécula que exerce um papel fundamental na adsorção de moléculas lipídicas. Neste estudo observacional, determinamos as concentrações séricas de bilirrubina, creatinina e albumina e, pela técnica de cromatografia líquida de alta performance, a concentração sérica dos AGNEs de cadeia longa (C16: C18) de 27 pacientes com síndrome de Weil durante o período de internação hospitalar, dos quais cinco vieram a falecer. Verificamos correlações significantes (p<0,05) ao longo da internação hospitalar, nas concentrações séricas de marcadores bioquímicos de gravidade da doença (bilirrubina, creatinina e albumina), AGNEs, ácido oléico e ácido linoléico, e relação molar ácido oléico/ albumina, com r (Pearson) de -0,7981, -0,7699, 0,9014, -0,8795 -0,9816, -0,9694, -0,9821, respectivamente. A relação molar ácido oléico/ albumina e ácido oléico+ linoléico/albumina foi significantemente mais elevada nos pacientes que faleceram (p<0,001), retornando aos valores semelhantes aos do grupo controle nos pacientes que evoluíram para a cura. Na análise por Curva Roc, a relação molar ácido oléico/albumina se mostrou um bom teste preditivo, com valor de corte 0,705 associado com maior especificidade e sensibilidade prognóstica. Nossos resultados sugerem que a utilização parenteral da albumina humana em pacientes com leptospirose pode ser uma potente ferramenta terapêutica nos casos mais graves ao interferir positivamente no resgate do equilíbrio bioquímico das relações molares ácido oléico/ albumina e ácido oléico+linoléico/albumina.

Text in Afrikaans / Rituals are part of our everyday life and are usually performed unconsciously. In this dissertation rituals are used consciously, within a therapeutic context, with the purpose to facilitate healing and growth. The aim of the research is to focus the readers' attention on the therapeutic potential of rituals and its value as an intervention strategy. The study concentrates on the grieving process. The researcher therefore specifically wants to show how rituals are used during grief counselling. The following research problem was investigated in the study: "What is the attitude, opinion and knowledge of professional caregivers concerning the use of rituals as a therapeutic tool during grief counselling?" Out of the research data the following hypothesis was formulated: - To grief over a loss is essential. Because of the basic properties and remedial functions of rituals, rituals can be a valuable therapeutic tool in the facilitation of this process. - There is an inherent connection between professional caregivers' attitudes, opinions and knowledge of therapeutic rituals and the regular and effective use of them during grief counselling. - The use of rituals during grief counselling is only one component in the comprehensive pastoral care of the bereaved. / Practical theology / M.Th.

Denne D-uppsats i Musikterapi ved Kungliga Musikhögskolan i Stockholm undersøger på et fænonomenologisk grundlag, hvordan fem kvinder i et gruppeterapiforløb oplevede at arbejde med stemmen som terapeutisk redskab. Det overordnede formål med projektet var at udvikle en metode til at arbejde med stemmen som terapeutisk redskab.   I et eksperimentelt projekt over ti sessioner af hver to timers varighed, blev der arbejdet med forskellige aspekter af det at arbejde med stemmen, herunder afslapning/mindfulness før alle praktiske øvelser, vejrtræknings- og stemmetekniske øvelser og forskellige stemmeimprovisations øvelser. Maleri og tegning blev taget ind som en ekstra dimension i forhold til at arbejde med de psykologiske processer. Sessionerne blev filmet som dokumentation og siden blev sessionerne transkriberet, beskrevet og analyseret. Alle samtaler i gruppeterapien udgik fra Irving D.Yaloms eksistentielle psykologiske vinkel. Via en fænomenologisk forskningsmetode og med triangulering af spørgeskemaer er øvelserne og deres effekter på deltagernes oplevelse af blandt andet selvværd, det at tage sin plads og præstation, blevet undersøgt. Resultaterne indikerer 1) at afslapning/mindfulness kan have en positiv indvirkning på deltagernes personlige processer, 2) at stemmetekniske øvelser kan åbne op for flere forskellige personlige processer, herunder processer relateret til sociale regler, selvværd, præstation og det at blive mere bevidst om ens egen krop og dens funktioner i forhold til stemmen og vejrtrækningen. Resultaterne indikerer også, at vejrtrækningsøvelser og afslapning påvirker hinanden gensidigt og at vejrtrækningsøvelser kan bruges som individuelt værktøj i relation til angstdæmpning. Improvisationsøvelser findes at kunne åbne for meget forskellige personlige processer alt efter stemmetekniske forudsætninger. Følelser af frihed i forhold til stemmeidealer, manglende teknik, indlejrede sociale konventioner, forhold til autoriteter og regler, samt følelsen af at lege og eksperimentere, er nogen af de temaer som deltagerne oplevede der kom fokus på. Deltagerne oplevede at de var i stand til at overføre disse oplevelser til deres private livsforhold og at de her kunne skabe en forandring. I forhold til Male/tegne øvelsen viser resultaterne at deltagerne oplevede at kunne uddybe deres udfordringer og processer yderligere, og at de oplevede øvelsen overraskende nem, kravløs og legende.   Et uforudset resultat var, at det at arbejde med en medfølende intention i forhold til en selv, viste sig at være den allerstørste faktor for at forløbet udgjorde en terapeutisk forskel for de deltagende. Generelt oplevede deltagerne selve gruppeterapien som en støttende og kærlig proces og derfor inspirende i forhold til den enkeltes udfordring og proces. / This Magister Thesis in Music Therapy at the Royal Academy of Music in Stockholm examines on a phenomenological basis how five women in a group therapy process experienced working with voice exercises as a therapeutic tool. The overall objective of the project was to develop a method to work with the voice as a therapeutic tool. In an experimental course over ten sessions of two hours duration, the women worked with various aspects of voicework, including relaxation /mindfulness before all practical exercises, breathing and technical voice exercises and various voiceimprovisation exercises. Painting and drawing were taken in as an extra dimension to the work of the psychological processes. The sessions were video recorded as documentation and afterwards the sessions were transcribed, described and analyzed. All conversations in the group therapy were based on Irving D.Yaloms existential psychology. Through a phenomenological research method and triangulation of questionnaires, -the exercises and their influence on participants' experience, among others of self-esteem, of being able to take one´s needed space - and of performance, were examinded. The results indicates 1) that relaxation /mindfulness can have a positive impact on participants' personal processes, 2) that technical voice exercises can open up several different personal processes, including processes related to social rules, self-esteem, achievement and to become more aware of ones own body and its functions in relation to the voice and breathing. The results also indicate that breathing exercises and relaxation have a mutual influence on one another and that breathing exercises can be used as a tool for the individual, concerning anxiety reduction. Improvisation exercises can help opening up to different personal processes, depending on the level of technical experience of the voice the participant possesses. Feelings of freedom in relation to voice ideals, lack of voice technique, embedded social conventions, relationship to authorities and rules, as well as the feeling of playing and experimenting, were some of the themes the participants experienced to have a focus on. The participants found that they were able to transfer these experiences to their private life conditions and here to create a change. In relation to the painting / drawing exercise, it was found that the participants experienced to immerse their challenges and processes further and that they experienced this exercise surprisingly easy, non-demanding and playful. As an unexpected result it was found, that working with a compassionate intention towards oneself in the process made the largest therapeutic difference for the participants. In general, participants experienced the group therapy as supportive and with a loving atmosphere which inspired the individual´s challenges and processes.

Text in Afrikaans / Rituals are part of our everyday life and are usually performed unconsciously. In this dissertation rituals are used consciously, within a therapeutic context, with the purpose to facilitate healing and growth. The aim of the research is to focus the readers' attention on the therapeutic potential of rituals and its value as an intervention strategy. The study concentrates on the grieving process. The researcher therefore specifically wants to show how rituals are used during grief counselling. The following research problem was investigated in the study: "What is the attitude, opinion and knowledge of professional caregivers concerning the use of rituals as a therapeutic tool during grief counselling?" Out of the research data the following hypothesis was formulated: - To grief over a loss is essential. Because of the basic properties and remedial functions of rituals, rituals can be a valuable therapeutic tool in the facilitation of this process. - There is an inherent connection between professional caregivers' attitudes, opinions and knowledge of therapeutic rituals and the regular and effective use of them during grief counselling. - The use of rituals during grief counselling is only one component in the comprehensive pastoral care of the bereaved. / Practical theology / M.Th.