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Durchführbarkeit und Akzeptanz des dreimonatigen TRANSPAC-Bewegungscoachings für jugendliche Patient:innen begleitend zur ambulanten Therapie
No full textHintergrund: Es ist bekannt, dass körperliche Aktivität positive Auswirkungen auf die Gesundheit hat. Insbesondere Jugendliche mit psychischen Problemen profitieren stark von den positiven Effekten körperlicher Aktivität auf ihre geistige Gesundheit und ihren Schlaf. Herkömmliche Therapien wie Psychotherapien und Medikamente haben bislang nicht immer schlüssige und langfristige Auswirkungen. Ausserdem konzentrieren sich die Studien hauptsächlich auf Erwachsene, die an Depressionen leiden. Die TRANSPAC-Studie bietet eine dreimonatige Bewegungscoaching-Intervention mit Jugendlichen zwischen 12 und 18 Jahren an, die unter Schlaf- und psychischen Problemen leiden. Ziel dieser Masterarbeit ist es, die Akzeptanz und Durchführbarkeit des Bewegungscoachings zu untersuchen.
Methoden: Acht Personen, die an der Intervention teilnahmen, wurden mit einem halbstrukturierten Leitfadeninterview befragt. Die Antworten wurden Audio-registriert und mit Hilfe der MaxQDA-Software analysiert und kodiert.
Ergebnisse: Es konnten vier Hauptthemen identifiziert werden (Inhalt und Struktur der Physical activity counselling (PAC)-Sessionen, Erwartungshaltung und Motivation vor der Intervention, Wahrgenommene Effekte von PAC und Spassfaktor, Angetroffene Hindernisse während PAC), sowie 20 Unterthemen. Die Jugendlichen, die an der Intervention teilnahmen, hatten Spass am Coaching und stellten auch positive Auswirkungen auf ihre psychische und physische Gesundheit sowie ihren Schlaf fest. Ihrer Meinung nach sind drei Monate ausreichend. Sie stiessen auch auf Hindernisse, konnten aber dank ihres Coaches ebenfalls Lösungen finden.
Schlussfolgerungen: Im Allgemeinen kann die Intervention als akzeptierbar und durchführbar angesehen werden. Wenn Studien wie diese belegen können, dass Bewegungscoaching eine wirkungsvolle Therapieergänzung von jungen Psychiatriepatient:innen sein kann, könnte dies in der Zukunft neue Türen in der Behandlung von Jugendlichen in der psychologischen Ambulanz öffnen.
Schlüsselwörter: Bewegungscoaching; ambulante psychiatrische Patient:innen; Verzögerte Schlaf-Wach-Phasen-Störung; Hindernisse; Akzeptan
Small molecules for interface engineering: tuning molecular transport characteristics and adhesion mechanisms
Full text linkThe general topic treated within this thesis is the synthesis of molecules for applications on surfaces for functional materials. But before the preparation and integration of molecular components into cutting edge devices, a fundamental understanding of the structure-property relationship of molecules is required. As a result, the structure-property relationship of several molecules associated with functional materials was investigated and can be categorised into two main topics. On one side, there is the interlinking of an organic structure and a bulk metal or metal oxide surface and on the other side, the electric and thermoelectric transport properties of organic structures anchored to gold electrodes. Although, not obvious at the first glance, both topics heavily rely on the way molecules are anchored to surfaces. Additionally, all treated subjects are accompanied by the beauty incorporated in the process of theorising and designing a specific structure, and then bringing it to reality. Therefore, a general introduction involving all of the investigated topics will be presented in the first chapter, followed by three individual chapters that describe the work performed within this PhD thesis. In the second chapter, the exploration of a novel silicon oxide functionalisation strategy utilising benzothiazole based structures will be elucidated. In the third chapter we will be looking at the transport properties of tolane-based structures, where the effect of different contacting modalities, internal conformation and electronic density variation of the backbone onto the transport properties of this very building block will be investigated. Thereafter, we will leave the family of closed-shell organic molecules and dive into the rich and interesting world of open-shell organic molecules (radicals) and their transport properties, which will be the topic of the fourth chapter. All experimental protocols and additional information supporting the research, presented in chapter two to four, are presented in the fifth and last chapter
Isotopic fractionation of molecular oxygen during enzymatic O2-consuming processes in aquatic environments
No full textStable isotope analysis of O2 has emerged as a valuable tool for studying O2 dynamics across various environmental scales, yet there is a lack of fundamental understanding regarding the large variability observed in isotopic fractionation of O2 during biological O2 consumption. Specifically, a wide range of 18O enrichment factors (18ε) from -29 to -1 ‰ has been reported for respiration in aquatic environments, while 18O-kinetic isotope effects (18O-KIEs) ranging from 1.009 to 1.053 (equivalent to 18ε values of -9 ‰ to -50 ‰) have been observed for 26 O2-consuming enzymes. As all biological O2 consumption is performed by O2-consuming enzymes, the variability in isotopic fractionation of O2 at the enzyme level likely contributes to the observed variability in 18ε values. Understanding O2 isotopic fractionation at the enzyme level can provide insights into the underlying sources of 18ε value variability for biological O2 consumption, enhancing the accuracy and reliability of stable isotope analysis of O2 for studying O2-consumption dynamics in aquatic environments. However, stable isotope analysis of O2 is hindered by the lack of reference materials for isotope ratio calibration, often relying on a one-point calibration with ambient air, which can lead to substantial measurement uncertainties. Hence, this thesis aimed to first develop methodologies for improving the measurement precision and accuracy of stable isotope analysis of O2 (Chapter 2), second, investigate the mechanisms driving the variability in isotopic fractionation of O2 at the enzyme level (Chapter 3), and lastly, to provide insights on the effect on O2 isotopic fractionation originally caused by O2 consuming enzymes at the environment level (Chapter 4).
In Chapter 2, a multi-point isotope-ratio calibration approach was developed using spinach leaf thylakoids and source waters with different δ18O and δ17O values to photosynthetically produce O2 with known isotopic compositions. By comparing the δ18O and δ17O values of the source water and produced O2, measurement errors and δ scale correction factors were determined. While no significant bias was observed on the δ18O scale (in a range of δ18O values from -56 to +95 ‰, maximum error 0.8 ‰), a δ17O scale compression was evident (in a range of δ17O values from -30 to +46 ‰, maximum error 3.3 ‰), indicating the need for δ17O scale correction.
In Chapter 3, nineteen 18O-KIEs were determined for several flavin- and copper-dependent oxidases, as well as for one flavin-dependent monooxygenase and one heme-copper dependent oxidase to gain insights into the mechanistic origins of the observed variability in 18O-KIEs. Distinct patterns of isotopic fractionation of O2 were revealed within and between enzyme groups, reflecting differences in active site structures and O2 reduction mechanisms. Both flavin- and copper-dependent enzymes exhibited two distinct ranges of 18O-KIEs associated with two different O2 reduction mechanisms. However, iron- and copper-dependent enzymes displayed a narrower range of lower 18O-KIEs than flavin-dependent enzymes, increasing with the degree of O2 reduction. These findings support generalizations of expected 18O-KIEs for other enzymes and potentially aid in interpreting stable isotopic fractionation across environmental scales.
Finally, Chapter 4 investigated whether microbial ammonia and methane oxidation could contribute to the observed discrepancy in biological O2 consumption 18ε values between laboratory incubations (-18 to -22 ‰) and in situ measurements in aquatic environments (-10 to -18 ‰). By performing experiments with three methanotrophic bacteria and a comammox bacterium we could estimate the in vivo 18ε values of soluble methane monooxygenase (sMMO), particulate methane monooxygenase (pMMO), and ammonia monooxygenase (AMO). The estimated 18ε values for sMMO, pMMO and AMO (-19 ± 1 ‰ to -24 ± 4 ‰) were not significantly different from typical heterotrophic respiration 18ε values. These results indicate that although substantial, O2 consumption by sMMO, pMMO, or AMO cannot explain the observed discrepancy in 18ε values between laboratory incubations and in situ measurements, but provide insights into their potential reaction mechanisms.
In summary, this work demonstrates that a comprehensive understanding of isotopic fractionation of O2 at the enzyme level, coupled with improved calibration methodologies, can significantly enhance our fundamental and mechanistic understanding of the variability in O2 isotopic fractionation during biological O2 consumption. This, in turn, can improve the reliability and accuracy of stable isotope analysis as a tool for studying important O2-consuming processes, providing deeper insights into O2 consumption dynamics across different environmental contexts and contributing to more accurate modeling of biological O2 consumption and ecosystem health assessments
Structural analysis, rational design, and optimization of novel microtubule targeting agents
No full textMicrotubule targeting agents represent a significant class of drugs, with currently more than 20 approved formulations utilized in anti-inflammatory, anti-infective, and predominantly anti-cancer therapies. These agents interact with α,β-tubulin heterodimers within microtubules, impacting their dynamic behavior which is crucial in cellular processes like signaling, transport, or cell division. Despite the extensive range of molecules studied and trialed, central challenges in their therapeutic application remain, such as high toxicity, particularly neuropathies, low efficacy at tolerable doses as well as drug resistance. Efforts to address these issues include the characterization of new binding sites and molecules which demonstrate exceptional activity in resistant cell lines. This thesis contributes to this ongoing research, focusing on the structural characterization of maytansine-site ligands and the design of ligands for the Todalam site
Synthesis towards spherical molecules
Full text linkHighly symmetric molecules have fascinated scientists in organic chemistry since this research field was established in the middle of the 19th century. Not only because of unknown physical behavior upon perturbation of the electronic shell of such highly ordered compounds, but also overcoming the synthetic challenges by finding appropriate strategies for these extraordinary molecular architectures provides this work a unique character.
This work is divided in two parts A and B, whereby part A focuses on the aimed synthesis of spherical shaped molecules, called spherophanes. The closest known molecule which was synthesized is buckminsterfullerene C60, reported in the 1980s. Part B describes the approach towards a square pyramidal shaped cage molecule, which combines the hemisphere of a calix[4]arene unit with a flat porphyrin.
Part A: The novelty of synthesizing and isolating this sort of spherical molecules with rigid Ar-bridge-Ar units and hence unpredictable physical behavior was addressed in a variety of
Enhancer control of transcriptional activity via modulation of burst frequency
Full text linkIn mammalian cells, transcriptional regulation strongly relies on cis-regulatory elements such as enhancers that can be located at large genomic distances from their target genes. Their action can be broadly defined as the ability to increase the amount of transcription generated at a cognate promoter. The Giorgetti laboratory and others have recently shown that this effect strongly depends on the genomic distance between the enhancer and promoter: enhancer action increases as the enhancer-promoter genomic distance decreases. However, how this is achieved at the level of single cells remains poorly understood. Within a single cell, transcription is a highly dynamic and stochastic process that occurs in bursts of promoter activity separated by periods of transcriptional inactivity. Whether different genomic distances from an enhancer translate in different promoter burst kinetics, and how this relates to the underlying mechanisms of enhancer-promoter communication remains unclear.
To answer these questions, we performed live-cell imaging of nascent transcription in mouse embryonic stem cell (mESC) lines harboring a bottom-up engineered genomic locus allowing to change enhancer-promoter distance without further regulatory confounding effects. By imaging transcription dynamics in multiple cell lines where an ectopic Sox2 promoter is located at different distances from the Sox2 control region (SCR) enhancer, we found that genomic distance from the enhancer controls the frequency, but not the duration, amplitude or size of bursts from the promoter. As a result, genomic distance from the enhancer also impacts the amount of cell-to-cell and temporal variability in transcriptional output from the promoter: a distal enhancer results in larger amounts of transcriptional noise than a proximal enhancer. Using mathematical modeling, we further show that the promoter operates as a multi-state system where the enhancer selectively increases the transition rate from a ’basal’ lowly transcribing regime to more transient, transcriptionally active regime, in a way that depends on its distance from the promoter. Our results provide quantitative insight into how an enhancer acts on a promoter in single cells, and into how the large-scale architecture of a locus determine transcription levels as well as temporal and cell-to-cell variability
Cardiorespiratory fitness, obesity-related cardiovascular risk factors and cognitive abilities during childhood development: the EXAMIN YOUTH follow-up study
Full text linkBackground
Cardiovascular diseases (CVD) are one of the leading causes of death in adults worldwide. But
cardiovascular (CV) risk factors such as hypertension and obesity originate in early life.
Elevated blood pressure (BP) and body mass index (BMI) during childhood and adolescence
are associated with subclinical vascular changes. Both CV risk factors track from childhood
into adulthood and are independent predictors of CVD in later years. Narrower retinal arteriolar
(CRAE) and wider venular diameters (CRVE), along with increased pulse wave velocity
(PWV), have been linked to an increased risk of CV risk and mortality in adults.
Objectives
The objectives of this PhD project were: 1) to analyze the association between CV risk factors
with vascular health, 2) to investigate the association between initial vascular health with
development of BP, and 3) to examine the association between cardiorespiratory fitness (CRF)
with CV risk factors, vascular health, and cognitive abilities at follow-up.
Methods
This PhD project is based on the EXAMIN Youth Study. This prospective school-based cohort
study encompassed an initial assessment of 1171 pre-pubertal children aged six to eight years.
Children were screened for anthropometry, BP, CRF, vascular health, and cognition. Four years
later, at ages ten to twelve, 749 of the same children were reexamined utilizing the same
standardized methods. Blood pressure was measured using a validated BP device for children
and adolescents, CRF was assessed using the 20m shuttle run test, and vascular health was
evaluated through static retinal vessel analysis and an oscillometric device for determining
PWV. Skin autofluorescence was used to determine advanced glycation end products (sAGEs)
levels and cognitive abilities were assessed using the Flanker Task.
Results
Our results show that children with initial increased BP had developed narrower CRAE and
higher PWV four years later. Vice versa, we also found that children with initial narrower
CRAE and higher PWV had developed significantly higher BP after four years. Higher CRF at
baseline was associated with favorable developments in BP, BMI, and vascular health.Furthermore, children with higher initial CRF displayed significantly lower levels of sAGEs
and better performance in the Flanker task at follow-up.
Conclusion
Retinal arteriolar diameter and PWV independently predict progression of childhood BP, while
initial BP is linked with development of micro- and macrovascular impairments, describing a
bivariate temporal relationship between vascular health and BP. Both diagnostic tool as a
standalone or in conjunction have the potential to improve CV risk stratification. We identified
CRF as a key modulator for the risk trajectories of BMI, BP and microvascular health in
children. Furthermore, higher CRF may help mitigate the formation of sAGEs and improve
cognitive abilities. Childhood present a window of opportunity for initiation of primary
prevention strategies, targeting at enhancing PA and CRF to contribute holistically to both CV
health and cognitive advancement
Ethics at work: understanding individual and social conditions for ethical behavior at work
Full text linkThe objective was to understand the individual and social conditions for ethical behavior at work. This led to a study of moral reasoning shown by subjects in others’ research. The general method was to analyze others’ interviews and narratives to examine the amount of moral reasoning when deciding dilemmas. This analysis resulted in the simple designation of 4 groups: ‘Criminals,’ ‘Rationalizers,’ ‘Agonizers,’ and ‘Altruists.’ It was observed that both ‘Altruists’ and ‘Criminals’ showed low-to-no moral reasoning; it seemed noteworthy that groups with opposite effects on society (beneficial, harmful) both used intuition and low moral reasoning. The conclusion consisted of simply raising questions; nothing was proven. The questions included whether less worry and disequilibrium were better for ethical decision making. Also discussed were “structured wholes” (consistent thinking across moral dilemmas) and whether work misconduct was caused by the system or human nature. There were no answers, but rather a discussion of these questions
Chronic pain among Somali pastoralists: towards understanding and informing culturally sensitive pain management among adult pastoralists in Eastern Ethiopia
Full text linkBackground and context
Chronic pain is one of the most debilitating health concerns and can be considered a disease in its own right. To live with chronic pain means that daily life is challenging with the condition also affecting the social network and the community as a whole. Chronic pain is clearly associated with poor mental health, inability to work, reduced quality of life and increased risk of mortality. Despite chronic pain being one of the leading causes of disability worldwide, it lacks the necessary prioritization in health care agendas. This applies to both high-income and low-/middle-income countries. Pain remains particularly neglected in the global South and among marginalized communities. This is a dire situation in consideration of demographic ageing and more specifically of recent projections that emphasize the growing number of non-communicable diseases, such as cancer and associated pain in the upcoming decades.
Pastoralists are known for their resilience to withstand hardships in everyday life. However, their remoteness, seasonal mobility and exposure to physically challenging work and a harsh environment wracked by conflict, displacement and devastating droughts have made them especially vulnerable to poorer health, including chronic pain. Yet, policy makers have long neglected the Somali pastoralist population in Ethiopia and their limited access to basic health care services.
The requirements and approaches for the treatment of pain are shaped not only by biological dimensions but also by psychosocial, cultural, spiritual and environmental factors. Gaining in-depth insights into how pain is perceived and dealt with among pastoralists can provide valuable information for designing multidimensional and interdisciplinary treatment approaches that better consider pastoralists’ strengths, needs and their unique context. In doing so, pain management can be improved for this marginalized population.
Aims
The main objective of this dissertation is to shed light on the perceptions, notions and burden of chronic pain among adult pastoralists in the Somali Regional State (SRS) of Ethiopia.
The specific aim of the initial qualitative study phase with Somali pastoralists and health professionals was to gain first insights into how pain is perceived and dealt with. The results from the qualitative study phase helped inform the development of a structured questionnaire. This questionnaire was used in a household survey with the primary aim of assessing the overall burden of chronic pain in adult pastoralists in the SRS.
The dissertation is embedded within the Jigjiga University One Health Initiative (JOHI) in the SRS. The initiative strives to improve the health and wellbeing of pastoralists, using transdisciplinary research approaches.
Methods
The dissertation followed a mixed-methods sequential exploratory study design based on Creswell and Plano Clark. Two qualitative studies were the basis for the final quantitative study.
In a first step, the qualitative interview study took place with 17 health professionals (mainly nurses) working in different biomedical care settings – with the intent to explore how they perceive pastoralists in the context of pain management. The initial selection of participants was purposive (secondary and tertiary care) and later entailed an element of theoretical sampling (primary care).
In a second step, a qualitative study was conducted with 20 adult Somali pastoralists suffering from chronic pain. Participants were purposively selected within primary, secondary and tertiary care facilities aiming at maximum variability. At a later stage, participants were also interviewed at their homes. The results of the two qualitative studies were the basis for the development of a pastoralist-specific questionnaire. The questionnaire focused on the burden chronic pain (prevalence, location, severity, frequency and impact) as well as on coping practices and treatment pathways.
In a third step, a quantitative household survey was conducted among adult pastoralists (aged 18 or older, N=299) in six randomly selected villages. In each village, 50 households were randomly selected using GPS-based household location and recruitment. The pastoralist-specific questionnaire was applied in this survey.
Results
Both qualitative studies revealed that chronic pain among pastoralists is perceived as a multicausal and relational experience. To distinguish pain from other symptoms or illnesses, pastoralists had no single word to describe their pain in the local language. Pastoralists described distinct illness beliefs with spirituality and religiosity having a mediating role and experienced communality providing support. However, stigmatization and aspects of stoicism hindered open pain reporting. In addition, the attitudes of health professionals contained demeaning elements. The results of the household survey served to further elaborate on the issues raised in the qualitative studies. The survey findings revealed a chronic pain prevalence among adult Somali pastoralists of nearly 30% with women and the elderly being particularly vulnerable. The body sites most commonly affected by chronic pain were the knees, followed by the lower back. The engagement in physical work, such as loading livestock, as well as household and agricultural work activities, may contribute to the pastoralists’ elevated risk of chronic pain. Moreover, most female participants had experienced the harmful practice of female genital cutting (FGC). The majority of participants with chronic pain visited biomedical health facilities to seek treatment. Nearly half of the pain-affected persons visited a traditional healer. Nevertheless, most participants reported interference of chronic pain with their daily life.
Conclusion
The findings of this dissertation shed light on the high burden of chronic pain that is negatively impacting pastoralists themselves as well as their livelihoods, their animals and surrounding communities. These secondary effects of chronic pain reflect the relevance of integrated “One Health” solutions in this unique setting. Moreover, the consideration of diverse perspectives on this marginalized population allows for a comprehensive picture of this debilitating health concern. The data highlight important aspects that are essential for designing culturally sensitive pastoralist-specific pain management. This also means recognizing the importance of pastoralists' self-care practices and lay health knowledge, and not imposing Western medical approaches without reflection.
The findings are consistent with recent global health agendas advocating for equitable and affordable access to comprehensive health services that leave no one behind, especially not the most vulnerable populations