JUSTIFICACIÓN: El consumo de tabaco es uno de principales retos de la salud pública de este siglo por ser el primordial problema de salud prevenible que causa una elevada morbi-mortalidad, discapacidad y sufrimiento a la sociedad. En nuestro país el tabaquismo es uno de los 3 factores que provoca más años de vida perdidos ajustados por calidad de vida. La Región de Murcia presenta la tasa de tabaquismo (31,8%) más elevada de nuestro país (27%). Medicina, Enfermería y Magisterio tienen un importante papel ejemplarizante en la población. Ejercer un rol modélico positivo en tabaquismo está mediado por las actitudes, los conocimientos y los comportamientos respecto al consumo de tabaco, estando influidos por las políticas de control existentes en el entorno. Conocer las variables relacionadas con el consumo de tabaco y la exposición al Humo Ambiental de Tabaco (HAT) en los futuros profesionales sociosanitarios puede darnos una idea de las necesidades formativas y asistenciales que éstos presentan para incrementar su posterior apoyo al control del tabaquismo y mejorar su salud. OBJETIVO: Analizar el consumo y la exposición al HAT, así como las actitudes sobre tabaquismo entre estudiantes de ciencias de la salud y la educación en la Universidad de Murcia, con perspectiva de género y equidad. METODOLOGÍA: Estudio observacional mediante cuestionario autocumplimentado y anónimo en 998 estudiantes de Medicina, Enfermería, Magisterio y Trabajo Social de la Universidad de Murcia, realizado en 2010 y 2011. Se elaboró un cuestionario “ad hoc”. Las escalas de percepción de riesgo y rol modélico en tabaquismo fueron validadas en este trabajo. Se analizaron los factores sociales que pueden influir en el consumo de tabaco mediante pruebas parametricas (media, desviación típica, percentiles, porcentaje, IC95%, Ji-cuadrado, ANOVA, Odds Ratio) y no para-métricas (U de Mann-Whitney y Prueba de Kruskal-Wallis). Para validación de las escalas se ha utilizado un Análisis Factorial Exploratorio, corroborando su pertinencia. El alfa de Cronbach se ha usado para medir la fiabilidad. Se ha validado el constructo y la capacidad discriminatoria de las escalas respecto al consumo de tabaco. RESULTADOS: La mayoría de los estudiantes eran mujeres (77,7%), con una edad media de 22,4 años. Uno de cada cuatro fuma actualmente (24,6%; IC95%:21,9%-27,3). La media de cigarrillos/día fue de 10,4 (DT: 7,2). La prevalencia tabáquica es similar entre hombres y mujeres, no observándose diferencias estadísticas, tampoco por nivel socioeconómico, lugar de residencia o situación laboral de progenitores. El consumo es mayor en estudiantes mayores de 25 años (31,7%; IC95%:25%-38,4%), y en la disciplina social (38,3%; IC95%:29,5%-47,1%) y educativa (26,8%; IC95%: 22,4%-31,2%). El consumo fue menor en Medicina (18%; IC95%:14-22) y Enfermería (24,1%; IC95%:16,9%-31,3%). La probabilidad de ser fumador/a es superior en mayores de 25 años (OR:1,7; IC95%:1-2,8; p<0.001), si se convive con personas fumadoras (OR:2,9; IC95%:1,9-4,4), especialmente en las chicas (OR:3,3; IC95%:2,1-5,3), y si fuma el entorno próximo: madre (OR:1,3; IC95%:0,8-2), padre (OR: 1,1; IC95%:0,7-1,7), hermano/a (OR:2; IC95%:1,2-3,4), pareja (OR:4,8; IC95%:2,2-10,5), compañero/a de piso (OR:2,6; IC95%:1,1-6,3), amistades (OR: 6,5; IC95%:1,4-29,9). La escala “Percepción de Riesgo” presenta una aceptable fiabilidad (alfa de Cronbach=0,71; varianza explicada = 46,5%) con 2 dimensiones: “Problemas de salud relacionados con el tabaquismo” y “Creencias sobre la importancia de tabaquismo“. La escala “Rol Modélico” incluye 3 componentes (“Función Informal”, “Función Formal” y “Entorno Favorable”) que explican el 48,6% de la varianza (alfa de Cronbach=0,87). El 61% del alumnado convive con algún fumador/a y el 78,8% está expuesto al HAT (Entre semana: 37,5%; Fines de semana: 76,6%), sin que se observen diferencias entre fumadores y no fumadores, ni por sexo. El alumnado de mayor edad presenta una inferior exposición. Convivir con fumadores aumenta la exposición al HAT (Entre semana: 56%; Fines de semana: 79,7%). La media de exposición al HAT es de 1,07h/24h entre semana y 3,18 h/24h en días festivos. Se ha comprobado una importante reducción tras entrada de la nueva ley, tanto entre semana [47% (OR=0,53; IC95%:0,38-0,74)], como en fines de semana [83% (OR=0,17; IC95%:0,09-0,28)]. CONCLUSIONES: - La prevalencia tabáquica es inferior a la observada en escolares y en población general de la Región de Murcia, aunque a nivel superior que en población con estudios universitarios. - Ni el sexo ni el nivel socioeconómico son un factor decisivo en el consumo de tabaco, siéndolo la edad, la disciplina a estudio y el convivir con fumadores. - El colectivo sanitario fuma en menor proporción. - La exposición al HAT es todavía muy elevada, observándose una significativa mejoría tras la entrada en vigor de la Ley 42/2010. - Es preciso implementar medidas en la Universidad para mejorar la percepción de riesgo y la aceptación del rol modélico de los profesionales sociosanitarios. / Tobacco consumption has become one of the main challenges in public health over the last century. It is one of the biggest avoidable and preventable causes of morbidity and mortality, suffer and disability of the society. In Spain, smoking is one of the main three factors that cause more disability adjusted life years (DALYs). Murcia Region shows the highest smoking rate (31,8%) of our country. Medicine, Nursing and Teaching degrees have an important exemplary role in the society. Performing a positive role model on smoking is mediated by attitudes, knowledge, and behaviors related to tobacco consumption and are influenced by existing control policies. To investigate variables associated with smoking consumption and secondhand smoke exposure among future professionals related to health and social sciences may provide an overall idea of the needed training programs to improve their ultimate support to tobacco control, and try to increase the welfare of the students. OBJETIVE: To analyze tobacco consumption and exposure to secondhand smoke, and the attitudes on smoking among health sciences and education students of the University of Murcia, with a gender and equity perspective. MATERIALS & METHOD: This is a cross-sectional study carried out by a self-reported and anonymous questionnaire in 998 Medicine, Nursing, Teaching and Social Work students at the University of Murcia between 2010 and 2011. A questionnaire was developed ad hoc. The scales to evaluate risk perception and the acceptance level of the role model were validated in the current study. Variables related to social characteristics that might influence smoking consumption were analyzed in the statistical analysis. Parametric (mean, standard deviation, percentiles, Chi-square, ANOVA) and non-parametric (U Mann-Whitney and Kruskal-Wallis) tests were employed to analyze related factors. To assess the structural validation of the scales, exploratory factor analysis, confirming it’s appropriated. Cronbach's alpha was used as an estimate of the reliability. The construct and the discriminatory capability of the scales in relationship to smoking consumption were validated. RESULTS: The majority of the students were women (77,7%), with a mean age of 22,4 years old. One out of four a current smoker (24,6%; 95%CI:21,9%-27,3%). Mean cigarette smoking/day was 10.4 [standard deviation (SD): 7,2]. The prevalence of smoking was similar between men and women, and no significant differences were observed by socioeconomic status, residence or employment status of their parents. Tobacco consumption was higher among students older than 25 years old (31,7%; 95%CI: 25%-38,4%) and in Social Work (38,3%; 95%CI: 29,5%-47,1%) and Teaching (26,8%; 95%CI:22,4%-31,2%) degrees. Tobacco consumption was lower in Medicine (18%; 95%CI:14%-22%) and Nursing degrees (24,1%; 95%CI:16,9%-31,3%). The odds of being a smoker was higher in participants older than 25 years old (OR:1,7; 95%CI:1-2,8; p<0.001), if they were living with smokers (OR:2,9; 95%CI:1,9-4,4), especially in women (OR:3,3; 95%CI:2,1-5,3), or if the mother (OR:1,3; 95%CI:0,8-2), the father (OR:1,1; 95%CI:0,7-1,7), any sibling (OR:2; 95%CI:1,2-3,4), the partner (OR:4,8; 95%CI:2,2-10,5), any flatmate (OR:2,6; 95%CI:1,1-6,3), or friends (OR:6,5; 95%CI:1,4-29,9) were smokers. The Risk perception scale showed an acceptable reliability (Cronbach’s alpha=0,71; explained variance=46,5%) with two dimensions (“Health problems related to smoking” and “Believes on the importance to smoking”). The Role model scale includes 3 components (“Informal Function”, “Formal Function” and “Positive Environment”), explaining 48,6% of the variance (Cronbach’s alpha=0,87). Sixty-one percent of the students lived with any smoker and 78,8% were exposed to secondhand smoke (weekdays: 37,5%; weekends: 76,6%), without any difference between smokers and non-smokers or by gender. Older students showed lower exposure. Living with smokers increases secondhand smoke exposure (weekdays: 56%; weekends: 79,7%). Mean exposure to secondhand smoke was 1,07h/24h during weekdays and 3,18 h/24h weekends. A significant reduction is observed in exposure after the implementation of the new Law during the weekdays 47% (OR=0,53; 95%CI:0,38-0,74) and the weekends 83% (OR=0,17; 95%CI:0,09-0,28). CONCLUSIONS: - The smoking prevalence in our study population is lower compared to high-school students and general population of Murcia Region, although higher compared to university students. Health sciences students present lower occurrence of smoking. - Age, degree and living with smokers are important factors for tobacco consumption; however, gender and the socioeconomic status are not. - Secondhand smoke exposure is still elevated; showing an important improvement after the latest Law on tobacco control became effective. - It is necessary to implement actions at the University in order to improve risk perception and the acceptance of the role model of the health and social professionals.

This thesis looks into the complex relationships which women have had with their bodies throughout the twentieth century. It uses oral history evidence, medical sources, and official government material to examine women’s experiences of and access to physical recreation and sport throughout the life-cycle. It argues that despite the official view that throughout the twentieth century women’s sporting bodies were essentially fragile bodies, unsuited to competitive and manly sports, there were a number of alternative discourses available to women during these years. Women who had strong sporting identities, and confidence in their own physical abilities, were able to test the capabilities of their bodies and maintain their exercise participation throughout adolescence, menstruation, pregnancy and during motherhood, despite the advice of state officials, and many doctors, which advised them against participation. This thesis makes a powerful contribution to what at present is a largely uncharted historical landscape of female participation in and experience of physical recreation in Scotland and the UK in the mid-twentieth century. In a global context, it contributes to our understanding of the relationship between the female body and physical activity throughout the physically and culturally guided female life-cycle, and the particular ways in which women interacted with sport and exercise throughout the twentieth century.

Dynamic loading profiles beneath the human foot during sideslope walking were determined and differences to level walking established. The contact area of the foot was measured, and the arch index derived from the footprint. Thirty healthy adults walked on a tillable walkway which had a polymer sensor pressure platform mounted at the mid-point. The sideways tilt could be adjusted in 2° increments from level to 8°. By walking in both directions on the sideslope, volunteers placed their right foot in either the upslope or downslope position. Loading profiles and contact areas were recorded for upslope and downslope foot placements at each angle of tilt. The characteristics of the electrically resistive polymer sensors were determined prior to the walking trials. The sensor output was non-linear, mean within-sensor variation =3% (maximum 8%), mean hysteresis -9% (maximum 13%), pressure threshold sensitivity =35 kPa, and mean between-sensor variation =8% (maximum 18%) over the surface of the platform. The dynamic behaviour was reliable to 26Hz. The sensor was found to be sensitive to shear. The impact of this characteristic was assessed by comparison with a similar platform incorporating capacitive transducers that were not shear sensitive. The polymer sensor system indicated increased pressures beneath the heel with upslope foot placement, and similar increases beneath the central metatarsals with downslope placement. These features were not apparent in the profiles returned by the second platform. For both platforms, however, the first metatarsal showed increased pressures with downslope placement but decreased pressures with upslope placement. In addition, the initial contact time and duration of loading for the first metatarsal altered significantly. The contact area of the foot changed systematically with sideslope walking, such that the arch index increased with upslope placement and decreased with downslope placement. This study demonstrated that the conventional approach of assessing level walking would fail to identify the increased foot pressures that occur on sideslopes. This may have crucial implications for ulceration risk assessment. The systematic changes in arch index and first metatarsal loading indicate that sideslope walking might be beneficial in revealing aspects of the mechanical behaviour of the human foot if combined with a simultaneous kinematic analysis. Potentially, the method offers a new approach to assessing the functional capacity of the foot for both clinical and research purposes.

The increasing evidence of associations between sedentary behaviour and low levels of physical activity in adults and both immediate and long term health implications is of public health concern. There is a need to further our understanding of adult's health behaviours, to facilitate the development of behaviour change strategies promoting healthy behaviours. This thesis provides four independent but interlinked studies focusing on adult s sedentary behaviour and physical activity in the context of measurement and behaviour change. Chapter 1 provides an introduction to the thesis where the scene is set for the placement of the studies in this thesis in the field of sedentary behaviour, physical activity, and measurement methods. Chapter 2 describes a systematic review of the relationship between sedentary behaviour and physical activity in adults. This systematic review is of primary importance as it was instrumental in shaping and informing the direction of the research described in later chapters. Chapter 3 describes a laboratory study investigating the measurement of energy expenditure during common sitting and standing tasks and also examines the 1.5 MET definition of sedentary behaviour. This study provides evidence that the 1.5 MET threshold for sedentary behaviours seems reasonable however some sitting-based activities may be classified as non-sedentary in people of differing weight status. This study raised some important questions on the validity of objective measurement devices for differentiating between sitting and standing postures. Thus, Chapter 4 of this thesis describes a laboratory study investigating the validity of the ActiGraph inclinometer algorithms for differentiating between sitting and standing postures. Chapter 5 is an intervention investigating sedentary behavior and physical activity compensation outside working hours in a sample of office workers exposed to sit-to-stand desks in the workplace. This thesis found that light physical activity, especially standing, could be one of the most efficient and feasible behaviours to replace sedentary behaviour. Such findings add considerably to the existing literature. Targeting such facets of adults behaviour and specially office workers holds great potential for behaviour change strategies.

Like the rest of the western world, the UK faces a significant increase in the prevalence of diseases associated with lifestyle. Smoking rates have reduced, but increasing obesity has contributed to alarming increases in diabetes. Discovery of the correlation between behaviour and poor health has, since the 1970s, resulted in public health policies emphasising behaviour change, and personal responsibility; an emphasis that survived later research which demonstrated social, genetic and psychological determinants on behaviour and health. The latest version of the NHS constitution exhorts us to ‘recognise that you can make a significant contribution to your own, and your family’s, good health and wellbeing, and take personal responsibility for it.’ This thesis seeks to clarify the meaning and extent of personal responsibility for health, and at its core are four papers published in peer-reviewed journals. The first clarifies the concept concluding that it is best understood in a tripartite conception of a moral agent having obligations and being held responsible if he fails to meet them. The following two papers discuss the nature of the obligations, using utilitarian reasoning and arguments from analogy. First, an exploration of the moral obligations for our own health is undertaken via an analysis of the practice of tombstoning, jumping from height into water. I conclude that the obligations are of process rather than outcome, consisting of an epistemic duty to determine the health related consequences of our acts, and a reflective duty to consider these consequences for us and for those who share our lives. Second, following an examination of the moral status of blood donation, I conclude that despite its presentation as a praiseworthy and supererogatory act, it is more properly regarded as a prima facie obligation, supported by arguments from beneficence and justice. The final paper discusses the final part of the tripartite conception of personal responsibility for health: being held responsible. I discuss the nature of blame and extend the tombstoning analogy as a way of testing my own intuitions in response to an imagined adult son who has undertaken this dangerous activity. I argue that the notion of blame is not generally allowed as part of the patient – professional relationship, and yet without considering blame, the concept of personal responsibility for health is incomplete. I conclude that if the epistemic and reflective duties, individually applied, conclude that an obligation is owed, it is owed to those within personal relationships, and holding people responsible for their health-effecting behaviour is also best undertaken within these relationships. I conclude the thesis by considering the implications for professional practice. Inevitably this leads to consideration of the promotion of personal autonomy in health care. A more relational account of autonomy is suggested. Facilitating the epistemic duty so that individuals are better able to understand the risks of their behaviour requires rethinking of the way that health promoting material and information are presented.

Die E-Zigarette gewinnt in den letzten Jahren immer mehr an Popularität. Die Frage der Toxizität ist jedoch noch nicht abschließend geklärt, und es besteht weltweite Unsicherheit bei der Verwendung der E-Zigarette. Die vorliegende Arbeit untersucht menschliche Nasenschleimhautzellen nach Dampfexposition mit Propylenglykol, einem Hauptbestandteil der Liquide, auf mögliche akute Entzündungsreaktionen, zytotoxische und genotoxische Wirkungen. Die Nasenschleimhautzellen von 10 Probanden wurden im Air-Liquid-Interface kultiviert und anschließend verschiedenen Konzentrationen von Propylenglykol ausgesetzt. Die Analyse erfolgte unter Verwendung eines Trypanblau-Tests, eines Comet-Assays, eines Mikrokern-Tests und eines IL-6- und IL-8-Sandwich-ELISAs. Der Trypanblau-Test zeigte keine Reduktion der Vitalität. Im Sandwich-ELISA konnte kein Anstieg der IL-6- und IL-8-Konzentrationen festgestellt werden. Im Comet-Assay zeigte das Olive Tail Moment in allen untersuchten Konzentrationen eine Schädigung im Vergleich zur Negativkontrolle. Es zeigte sich auch eine dosisabhängige Schädigung. Ein Unterschied zwischen der Reinsubstanz und der Negativkontrolle konnte im Mikrokern-Test festgestellt werden. Es wurden reparierbare Schäden im Comet-Assay gefunden. Im Mikrokern-Test konnten diese nur in der Reinsubstanzkonzentration bestätigt werden. Die E-Zigarette sollte restriktiv verwendet werden, bis Langzeitstudien vorliegen. Darüber hinaus sollten die Hersteller die Inhaltsstoffe der Flüssigkeiten eindeutig angeben. / The e-cigarette has become increasingly popular in recent years. However, the question of toxicity has not yet been clarified and there is global uncertainty in the use of the e-cigarette. The present work investigates propylene glycol, a major component of the liquids, for possible acute inflammatory reactions, cytotoxic and genotoxic effects on human nasal mucosal cells. The nasal mucosal cells from 10 volunteers were cultivated in the air-liquid-interface and then exposed to different concentrations of propylene glycol. The analysis was carried out using a trypan blue test, comet assay, micronucleus test and IL-6 and IL-8 sandwich-ELISA. The trypan blue test showed no reduction in vitality. No increase in IL-6 and IL-8 concentrations could be detected in the sandwich ELISA. In the comet assay, the Olive Tail Moment showed damage compared to the negative control in all examined concentrations. There was also a dose-dependent damage. A difference between the pure substance and the negative control could be found in the micronucleus test. Repairable damage in the comet assay have been found. In the micronucleus test these could only be confirmed in the pure substance concentration. The e-cigarette should be used restrictively until long-term studies are available. In addition, the manufacturers should clearly declare the ingredients of the liquids.

Hintergrund: Circa ein Drittel der Patientinnen und Patienten mit fortgeschrittenen Krebserkrankungen ist von psychischen Komorbiditäten betroffen und circa die Hälfte weist eine psychische Belastung im klinisch signifikanten Bereich auf. Zur psychotherapeutischen Behandlung dieser Patientengruppe stehen unterschiedliche psychotherapeutische Interventionen zur Verfügung. Die CALM-Therapie, eine manualisierte Kurzintervention im Einzelsetting, ist eine dieser Interventionen. Hier bilden vier Module, welche auf den wichtigsten Anliegen und Belastungsfaktoren von Patientinnen und Patienten mit fortgeschrittenen Krebserkrankungen basieren, den inhaltlichen Rahmen. Ziel: Die Treatment Integrity beschreibt das Maß, inwieweit eine psychotherapeutische Intervention wie vorgesehen umgesetzt wurde. Für eine fundierte Interpretation psychotherapeutischer Interventionseffekte sind Kenntnisse über die Treatment Integrity entscheidend. Die vorliegende Arbeit untersuchte Teilaspekte der Treatment Integrity durchgeführter CALM-Therapien im Vergleich zu durchgeführten konventionellen psychoonkologischen Therapien, um einen Beitrag zu einer fundierten Interpretation von Interventionseffekten der CALM-Therapie zu leisten. Methoden: Transkriptionen von zwei CALM-Therapien und zwei Therapien einer konventionellen psychoonkologischen Intervention wurden anhand einer qualitativen Inhaltsanalyse nach P. Mayring untersucht. Im Zentrum stand hierbei ein selbst entwickeltes Kategoriensystem zur Analyse des gesamten Textmaterials. Zusätzlich wurden Auffälligkeiten bezüglich Ansprachen von Themenbereichen der CALM-Module unsystematisch beobachtet. Ergebnisse: Die Inhalte der untersuchten CALM-Therapien bezogen sich durchschnittlich zu 99,54% und die der konventionellen psychoonkologischen Therapien durchschnittlich zu 98,71% auf die Themenbereiche der CALM-Module. Die ermittelten Werte für einzelne Therapiesitzungen lagen für CALM-Sitzungen zwischen 98,12% und 100% und für Sitzungen der konventionellen psychoonkologischen Therapie zwischen 96,20% und 100%. Unsystematisch beobachtete Auffälligkeiten zeigten, dass die Themenbereiche der CALM-Module zum Teil sehr spezifisch durch die CALM-Therapeutinnen und -Therapeuten angesprochen und vernetzt wurden. Schlussfolgerung: Unter Berücksichtigung von methodischen Grenzen zeigte sich bezüglich des Anteils von Themenbereichen der CALM-Module innerhalb der beiden untersuchten Therapiegruppen kein maßgeblicher Unterschied. Zusätzlich liefert die vorliegende Arbeit Hinweise für einen spezifischen therapeutischen Umgang mit den Themenbereichen der CALM-Module innerhalb der untersuchten CALM-Therapien. Um ermittelte Interventionseffekte der CALM-Therapie fundiert interpretieren zu können, sollten zukünftige Untersuchungen unterschiedliche Umgangsweisen von Therapeutinnen und Therapeuten der beiden Therapiegruppen mit den Themenbereichen der CALM-Module genauer in den Blick nehmen. / Background: Around one third of patients with cancer is suffering from mental disorders and around one half meets criteria for psychological distress in the clinical range. Various psychotherapeutic interventions are available for the psychotherapeutic treatment of this population of patients. The CALM intervention, a manualized brief individual psychotherapy, is one of these interventions. Four modules, which are based on the most important concerns and sources of distress in advanced cancer populations, form the content framework. Aim: Treatment Integrity describes the extent to which a psychotherapeutic intervention was implemented as intended. Knowledge of Treatment Integrity is essential for a well-founded interpretation of effects of a psychotherapeutic intervention. This study aimed to examine partial aspects of the Treatment Integrity of CALM sessions compared to sessions of a usual psycho-oncological intervention in order to contribute to a well-founded interpretation of specific effects of the CALM intervention. Methods: Transcriptions of two complete CALM therapies and two complete therapies of a usual psycho-oncological intervention were examined using a qualitative content analysis according to P. Mayring. Here, a self-developed system of categories for the analysis of the entire text formed the center. In addition, distinctive features in addressing topics of the CALM modules were observed unsystematically. Results: The content of the examined CALM sessions referred in 99.54%, on average, to the topics of the CALM modulesand , while the content of the usual psycho-oncological sessions referred in 98.71%, on average, to these topics. Determined values for individual sessions ranged between 98.12% and 100% for CALM sessions and between 96.20% and 100% for usual psycho-oncological sessions. Observed distinctive features showed that topics of the CALM modules were sometimes addressed and crosslinked very specifically by the CALM therapists. Conclusion: Taking methodical limits into account, there was no significant difference between the examined CALM session and the sessions of the usual psycho-oncological intervention concerning the percentage of topics of the CALM modules. In addition, the present study provides information for a specific therapeutic handling of topics of the CALM modules within the examined CALM sessions. In order to be able to interpret measured effects of the CALM intervention in a well-founded manner, future examinations should take a closer look at the different ways therapists of both interventions are dealing with the topics of the CALM modules.

Bei der chronischen nicht-bakteriellen Osteomyelitis (CNO) handelt es sich um eine autoinflammatorische Erkrankung der Knochen bislang unbekannnter Ätiologie. Die Patienten leiden unter anderem durch lokale Entzündungen an Knochenschmerzen und hieraus resuliterender funktioneller Einschränkung. Das Ziel dieser Studie war es, die körperliche Aktivität, Fitness und HRQoL von Jugendlichen mit bestätigter CNO-Diagnose im Vergleich zu gesunden Kontrollen zu untersuchen. Dafür wurden 15 Patienten mit CNO und 15 alters- und gesschlechts-gematchte gesunde Jugendliche zwischen 13 und 18 Jahren in die Studie eingeschlossen. Sie füllten hierfür Fragebögen bezüglich ihrer Lebensqualität aus, leisteten auf einem Fahrradergometer einen Ausdauertest zur Messung der aeroben Fitness und trugen für sieben Tage zuhause einen Bewegungssensor (Accelerometer), um die körperliche Aktivität im Alltag zu messen. Zum Untersuchungszeitpunkt waren ein Drittel der Patienten in kompletter Remission, ein weiteres Drittel nur in klinischer und ein Patient nur in radiologischer Remission. Fast die Hälfte (47%) erhielt zu diesem Zeitpunkt keine medikamentöse Therapie mehr. In den objektiven Untersuchungsmethoden (Spiroergometrie und Accelerometrie) konnten keine relevanten Einschränkungen in der körperlichen Fitness und dem durchschnittlichen Aktivitätsniveau festgestellt werden. Dennoch nahmen die CNO-Patienten deutlich weniger am Sportunterricht teil und in den Fragebögen erzielten sie deutlich schlechtere Werte, die auf eine reduzierte Lebensqualität schließen lassen. Vor allem klagten sie deutlich häufiger über Schmerz und gaben deutlich mehr Sorgen an. Obwohl also bei den meisten Jugendlichen ein sehr positiver Krankheitsverlauf festzustellen war, der keinerlei Unterschiede in den objektiven Messmethoden zu den gesunden Jugendlichen mehr zeigte, enthüllten die Fragebögen deutliche Defizite. Zur besseren Messung der HRQoL und der Validierung der Fragebögen für CNO im Vergleich zu objektiven Untersuchungsmethoden werden weitere Studien benötigt. / Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disorder of the skeletal system of yet unknown etiology. Patients present with local bone pain and inflammation and - to our experience - often suffer from functional impairment with significant disabilities of daily life. The objective of this study was to assess physical activity, fitness and health-related quality of life (HRQOL) in adolescents with established diagnosis of CNO versus healthy controls (HC). 15 patients with CNO and 15 age and gender matched HC aged 13-18 years, completed questionnaires, performed an incremental exercise test with gas exchange measures up to voluntary fatigue and wore an accelerometer over 7 days at home to assess physical activity behavior. At the time of assessment, 5 CNO patients were in clinical, one in radiological and 5 in clinical and radiological remission. 7 did not receive any therapy. The results of the exercise test and of the accelerometry did not show any significant difference between CNO and HC. However, reported sports participation was lower in patients with CNO and PedsQL3.0 and 4.0 showed significant lower values in most of the scores indicating reduced HRQOL. Conclusion: Although most CNO patients showed a favorable course of disease without any relevant differences in objective measurements of physical activity and fitness versus HC at the time of assessment, questionnaires revealed perceived limitations. Further studies are needed to measure HRQOL and to validate questionnaires in patients with CNO against objective measures including more participants with a higher level of disease activity.

Zinkoxid-Nanopartikel (ZnO-NP) finden in vielen Produkten des täglichen Verbrauchs Verwendung. Daten über die toxikologischen Eigenschaften von ZnO-NP werden kontrovers diskutiert. Die menschliche Haut ist in Bezug auf die ZnO-NP Exposition das wichtigste Kontakt-Organ. Intakte Haut stellt eine suffiziente Barriere gegenüber NP dar. Bei defekter Haut ist ein Kontakt zu den proliferierenden Stammzellen möglich, sodass diese als wichtiges toxikologische Ziel für NP darstellen. Das Ziel dieser Dissertation war die Bewertung der genotoxischen und zytotoxischen Effekte an humanen mesenchymalen Stammzellen (hMSC) durch niedrig dosierte ZnO-NP nach 24 stündiger Exposition, repetitiven Expositionen und im Langzeitversuch bis zu 6 Wochen. Zytotoxische Wirkungen von ZnO-NP wurden mit 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid-Test (MTT) gemessen. Darüber hinaus wurde die Genotoxizität durch den Comet-Assay bewertet. Zur Langzeitbeobachtung bis zu 6 Wochen wurde die Transmissionselektronenmikroskopie (TEM) verwendet. Zytotoxizität nach 24-stündiger ZnO-NP-Exposition war ab einer Konzentration von 50 µg/ml nachweisbar. Genotoxizität konnten bereits bei Konzentrationen von 1 und 10 µg/ml ZnO-NP beschrieben werden. Wiederholte Exposition verstärkte die Zyto-, aber nicht die Genotoxizität. Eine intrazelluläre NP-Akkumulation mit Penetration der Zellorganelle wurde bei einer Exposition bis zu 6 Wochen beobachtet. Die Ergebnisse deuten auf zytotoxische und genotoxisches Effekte von ZnO-NP hin. Bereits geringe Dosen von ZnO-NP können bei wiederholter Exposition toxische Wirkungen hervorrufen sowie eine langfristige Zellakkumulation. Diese Daten sollten bei der Verwendung von ZnO-NP an geschädigter Haut berücksichtigt werden. / Zinc oxide nanoparticles (ZnO-NP) are widely used in many products of daily consumption. Data on the toxicological properties of the ZnO-NP used are discussed controversially. Human skin is the most important organ in terms of ZnO-NP exposure. Intact skin has been shown to provide an adequate barrier against NPs, while defective skin allows NP contact with proliferating cells. Among proliferating cells, stem cells are the main toxicological target for NPs. Therefore, the aim of this dissertation was to evaluate the genotoxic and cytotoxic effects of human mesenchymal stem cells (hMSC) by low-dose ZnO-NP after 24 hours of exposure, repetitive exposures and in long-term experiments up to 6 weeks. Cytotoxic effects of ZnO-NP were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT). In addition, genotoxicity was assessed by the comet assay. Transmission electron microscopy (TEM) was used for long-term observation after 6 exposure periods. The results of the study show that ZnO-NP has a cytotoxic effect starting at high concentrations of 50 µg/mL and could demonstrate genotoxic effects in hMSC exposed to 1 and 10 µg/ml ZnO-NP. Repeated exposure enhanced cytotoxicity but not genotoxicity. Intracellular NP accumulation with penetration of the cell organelles was observed at exposure up to 6 weeks. The results indicate the cytotoxic and genotoxic potential of ZnO-NP. Even small doses of ZnO-NP can cause toxic effects with repeated exposure and long-term cell accumulation. These data should be considered when using ZnO-NP on damaged skin.

The circadian cycle, although seasonally adjusted, consists of two phases: a nocturnal period of darkness and a diurnal period of light. Many parameters of human physiology display either a nocturnal or diurnal peak as seen in athletic performance, immune, endocrine, physiology and cognitive function, respectively. The studies included in this thesis focused on the diurnal (morning or AM versus evening or PM) effect of high-intensity self-paced exercise on physiological and immunological measures and the influence of individual preference for activity or chronotype on these responses. Self-paced time-trials were completed in an environmental chamber (6°C) in the AM and PM and displayed a similar effect on physiological and biological parameters. Performance times were non-statistically quicker (P > 0.05) at PM. Physiological parameters heart rate, rate of perceived exertion, lung function and self-paced treadmill speed were not found to be statistically different at AM or PM trial (p > 0.05). Core body temperature (CBT), was significantly higher (p0.05). CD8+ T-lymphocyte cell-surface markers for naïve/senescence and differentiation (CD27CD45RA and CD27CD28) reported no diurnal difference between AM and PM exercise in experienced and experienced/recreational distance runners respectively (P > 0.05). However, a higher percentage of highly differentiated phenotypes were found in the recreationally active population. Neutrophils displayed a pronounced elevation in response to PM exercise with the mechanism driving this response unclear at this time. Cortisol concentration displayed less inflammatory responses in the morning compared to the evening with higher values pre, post and one-hour post AM trials. Chronotype showed no effect on physiology or biology at rest or in response to exercise. Chapter 4 presents data from a study that investigated diurnal physiology and immune response to high-intensity exercise in highly-trained men. Recreational and experienced endurance male runners at differing diurnal time-points were investigated in Chapter 5, while individual chronotype differences and circadian phase responses were explored in Chapter 6.In summary, it is concluded from this work that there was a lack of evidence showing a diurnal effect on running performance and subsequent immune response. Elevated circulating immune counts prior to exercise, irrespective of diurnal phase, appear to govern exercise-induced responses. The effect of high intensity exercise is subject to three distinct variables: the fitness status and experience of the individual completing the exercise, the time of day at which the exercise is undertaken, and the phase response of exercise at that point of the circadian cycle. No diurnal phase mediated a divergent effect on variables examined was observed at 09.00hrs and 17.00hrs. These time-points should be considered not sufficiently dissimilar to elucidate diurnal variation in trained and healthy males.