The diploma thesis is dedicated to the way of using and way of functioning of the coordinated rehabilitation and the multi-disciplinary team in the organization Focus in Pelhřimov which works with the people with mental disorders. The thesis is divided in the theoretical and practical part. The theoretical part describes the history and function of the coordinated rehabilitation, mental health care history, psychiatric reform and multi-disciplinary cooperation functioning. There is used the strategy of quality analysis in the research part. It was done by the questionnaire and the technique of half-structured interview. The results coming out of the interview were focused on the functioning of multi-disciplinary team in the institution and the cooperating subjects in the first part. The second part was dedicated to the basic parts of the coordinated rehabilitation provided in the organization in view of the fact that there were other participating professionals and non-formal participants during the care of the person with mental disorder. The aim of the research was to map the sectors of the coordinated rehabilitation used by the individuals with mental disorders in the organization Focus in Pelhřimov. The research team was created with the help of the method of the snow ball and basic criteria was employment of an "communication partner" in the particular organization. Their ability to evaluate their job and take part in the lead interview depended on their experience in Focus. In connection with the thesis aim there was also set the main research question: What parts of the coordinated rehabilitation are used in the organization Focus in Pelhřimov? Partial questions were devolved from that which were connected to the particular parts of the coordinated rehabilitation and the function of the multi-disciplinary team. The first contact and the next cooperation is developed by the seriousness, necessity and wishes of the client. The work with the client with mental disorder is based on the philosophy of recuperation, not recovery. In the relationship and the concentration, the work is done in all sectors of the coordinated rehabilitation. The client has the closest relationship to the key worker who provides the care in the multi-disciplinary team and other professionals in the organization. There is the conclusion from the results that there was an agreement that the coordinated rehabilitation is used in this institution and no other from the basic sectors can be omitted. The results of the diploma thesis can be used as feedback for the organization Focus in the practice where it can be useful for mapping of the sectors of coordinated rehabilitation and making clear the needs of the individuals with mental disorder. Taking into consideration the recommendation to use the feedback of the respondents about information sharing, to prefer common space of the whole team and bigger promotion.

O tema central desta tese é a esperança escatológica. Através de uma pesquisa histórico-bíblica, o autor desta tese busca identificar o significado que os conceitos tiqwah e elpis tinham para os seus receptores judaico-cristãos originários. Jürgen Moltmann, ao propor uma hermenêutica política da esperança, busca retomar este tema a partir dos contextos nos quais ele se originou. Toda a concepção de esperança cristã desenvolvida por Moltmann tem seus desdobramentos na dimensão pública da missão do cristão no mundo. Portanto, a esperança escatológica produz uma etologia que lhe é própria. Nela, a esperança é instrumentalizada pela fé que assume o mundo como locus de ação transformadora, tornando, através da prática do amor, a redenção cosmo-antropológica uma possibilidade alcançável na efetivação dos princípios éticos da justiça e da verdade. Neste sentido, na etologia da esperança, o outro se torna referência da missio spei, e é para ele, como parte de uma realidade maior (kósmos), que o sentido redentivo da história escatológica está direcionado teleologicamente. É para o futuro que a esperança escatológica projeta seu olhar e deseja ver sua utopia se realizar plenamente. Já o binômio saúde e doença, como novo paradigma hermenêutico de teologicidade do neoprotestantismo brasileiro, concebe a esperança num contorno soteriológico diferente, no qual o presente vivido, aqui-agora, é compreendido como o locus em que se materializa a dimensão histórica da salvação do crente. A cura integral do anthrôpos é o sinal contundente de que a soteria bíblica tem, na dimensão histórica imediata, seu significado psicossomático cabalmente confirmado. É para este éon que o olhar da fé neoprotestante busca sua auto-realização integral. Neste sentido, a espiritualidade neoprotestante desenvolve uma etologia desescatologizada, que afirma a transcendência deste mundo e perde de seu horizonte hermenêutico a dimensão futúrica da esperança escatológica tal como se preconizou no protocristianismo. No entanto, existe a possibilidade de estabelecer um diálogo construtivo entre estas duas epistemologias da fé: a moltmanniana e a neoprotestante brasileira. Achar este ponto em comum é a tarefa que se propõe satisfazer o autor desta tese. / The central subject of this thesis is the escathological hope. Through a Historic-Biblical research, the author of this thesis searchs to identify the meaning that the concepts tiqwah and elpis had for their Jewish-Christians receivers originary. Jürgen Moltmann, when propose a politic of hope hermeneutic searchs to retake this subject leaving from the contexts in which it has originated. All the Christian hope conception developed by Moltmann has its unfoldings in the public dimension of the Christians mission in the world. Therefore, the escathological hope produces an ethology that it is proper to itself. In it, the hope is instrumentalized by the faith that assumes the world as locus of transformer action, becoming, through the practical of love, the cosmo-anthropologycal redemption a reachable possibility in the efetivation of the ethical principles of justice and truth. In this direction, in the ethology of hope, the other becomes reference of the missio spei, and its for it, as a part of a bigger reality (kósmos), that the redentive meaning of escathological history is directed teleologically. It is to the future that the eschatological hope projects its look and desires to see its uthopy carry through fully. Already the binomial health-disease as new hermeneutic paradigm of teologicity of Brazilian neoprotestantism, conceives the hope in a different soteriologic contour, in which the lived present, here-now, is understood as the locus where the historical dimension of the believer`s salvation materializes. The integral cure of the anthrôpos is the forceful sign that the Biblical soteria has, in the immediate historical dimension, its psychosomatic meaning completely confirmed. Its for this éon that the neoprotestant look of faith search its integral auto-accomplishment. In this direction, the neoprotestant spirituality develops a desescathologized ethology that affirms the transcendence of this world and loses of its hermeneutic horizon the futuric dimension of the eschatological hope such as if it praised in the protochristianism. However, the possibility to establish a constructive dialogue enters these two faith epistemologies: the moltmannian and the Brazilian neoprotestant exists. Finding this point in common its the task that the author of this thesis proposes to satisfy.

- Compulsory vaccination This diploma thesis deals with the legal regulation of compulsory vaccination in the Czech Republic. The subject of the thesis is a conflict between compulsory vaccination and fundamental rights and freedoms as a result of the protection of public health. An option to refuse the compulsory vaccination, regulation of following sanctions and the absence of compensatory scheme for vaccine injury issue are also analysed. The first chapter introduces the compulsory vaccination issue. It presents terms related to the compulsory vaccination and current vaccination categories. The second chapter describes the legal regulation of compulsory vaccination with its legal basis in international law. It is concerned with the function of international treaties in the Czech legal system. Moreover, it presents a criticism of compulsory vaccination with respect to its claimed unconstitutionality. This chapter also introduces a public debate concerning compulsory vaccination along with pro and con arguments. The third chapter is, on the one hand concerned with the rejection of compulsory vaccination, and its following sanctions on the other hand. The case law of the Constitutional Court has been analysed with respect to both secular and religious conscientious objections. Moreover, the chapter...

Background: Only few studies deal with the workload of physical therapists and the health consequences, although this occupational group is quite important for the health care system in many industrialized countries (e.g. ca. 136 000 people are currently employed as physical therapists in Germany). Therefore, the current state of knowledge of work-related diseases and disorders of physical therapists is insufficient. The aim of the 'Physical Therapist Cohort' (PTC) study is to analyze the association between work-related exposures and diseases among physical therapists in Germany. This article describes the protocol of the baseline assessment of the PTC study. Methods/Design: A cross-sectional study will be conducted as baseline assessment and will include a representative random sample of approximately 300 physical therapists employed in Germany (exposure group), and a population-based comparison group (n = 300). The comparison group will comprise a sample of working aged (18–65 years) inhabitants of a German city. Variables of interest will be assessed using a questionnaire manual including questions regarding musculoskeletal, dermal, and infectious diseases and disorders as well as psychosocial exposures, diseases and disorders. In addition to subjective measures, a clinical examination will be used to objectify the questionnaire-based results (n = 50). Discussion: The study, which includes extensive data collection, provides a unique opportunity to study the prospective association of work-related exposures and associated complaints of physical therapists. Baseline results will give first clues with regard to whether and how prevalent main exposures of physiotherapeutic work and typical work areas of physical therapists are associated with the development of work-related diseases. Thereby, this baseline assessment provides the basis for further investigations to examine causal relationships in accordance with a longitudinal design.

More than 16 years post-apartheid, South Africa is still regarded as the most unequal society in the world. The government is facing various obstacles and challenges in improving the standard of living and quality of life for all its citizens, for example in facilitating the access to clean drinking water and sanitation, building houses and providing basic education. In addition, the country is facing the world’s largest HIV/AIDS epidemic with a national prevalence rate of 18.1 %, equalling approximately 5.7 million people who are currently infected. (Pressly, 2009; UNAIDS, 2008c) Against this background, the aim of this thesis was to study the Madwaleni community, situated in a deeply rural area of the former apartheid homeland Transkei. Applying the Community Oriented Primary Care approach, a strategy of ‘community assessment and diagnosis’ was used to obtain a holistic community profile and to determine the perceptions of its community members regarding their health and social problems and needs, intending to make recommendations to health care providers working at Madwaleni Hospital regarding future health education and disease prevention programmes. (Brown and Fee, 2002) This research used a cross-sectional design. In a preliminary survey, qualitative data was collected in short interviews with health care providers working at Madwaleni Hospital (N=46). The information served as a basis to develop and design parts of the Madwaleni community survey questionnaire. The questionnaire consisted of 36 questions, complying with the aim and objectives of this thesis. It was used for the structured interviews with the main study population, all of whom were members of the Madwaleni community (N=200), whereas half of the main study population were men and half were women, then again, half were unaware of their HIV status and half were HIV+ and had joined the Madwaleni HIV/AIDS programme. Key findings 1) Madwaleni community profile and characteristics Thoughtful sexual behaviour: Particularly interesting in light of the HIV/AIDS epidemic, more than 90 % of the sexually active community members were monogamous at the time of the survey. While only 36.4 % of the men and women unaware of their HIV status used condoms, 76.5 % of the HIV+ community members claimed to do so, indicating that the Madwaleni HIV wellness programme and especially its counselling and health education components are adequate and valuable in serving their purpose. High rates of illiteracy and insufficient education: Only 56.5 % of the interviewed community members were ‘functionally literate’ at the time of the survey. Of those, only 8 % had received a matriculation and not one of the community members had received any higher degree. In addition, 19.5 % of the sampled men and women were not able to read at all. High rates of unemployment, poverty and dependency on welfare grants: Only 20 % of the Madwaleni community members were employed at the time of the survey. Taking the daily income per capita as a reference, one third of the community members suffered from ‘moderate poverty’, defined as an income of 1 to 2 US $ per day, while the other two thirds suffered from ‘extreme poverty’, defined as an income of less than 1 US $ per day, although more than 90 % of the corresponding households received at least one type of welfare grant already. Large household sizes and predominance of traditional dwellings: In the Madwaleni community, an average of eight people lived together per household at the time of the survey, whereas 95 % of the community members lived in traditional dwellings, constructed from freely occurring natural resources. In need of safe drinking water, sanitary systems and access to electricity: More than 80 % of the Madwaleni community members obtained their drinking water from rivers or stagnant dams, while only 6.5 % used rain water and 9.5 % had access to piped water. In addition, almost 70 % of the community members had no access to any sanitary systems, using nearby bushes instead. Furthermore, more than 90 % had no access to electricity. The majority used paraffin for cooking, candles for lighting and wood for heating their homes. Small-scale cultivation to provide an extra source of food: In the Madwaleni area, 90 % of the families owned a small garden patch attached to their houses, used for small-scale cultivation. In addition, almost 90 % owned livestock, mainly poultry, cattle and goats. Crops and animals were used to provide an extra source of food; however, not one of the households could solely live on subsistence farming. Difficulties in accessing health care facilities: On average, each of the community members needed three-quarters of an hour to access their closest clinic and almost one and a half hours to reach Madwaleni Hospital, with 40 % and 60 % respectively depending on public taxi transport to get there. No substantial improvement of the living circumstances since apartheid: Comparing the Madwaleni community characteristics with corresponding data from apartheid-times, no substantial improvement of the living circumstances and conditions could be noticed, proving that governmental and non-governmental actions, programmes and services have not yet reached all remote communities. Similar community characteristics in the neighbouring communities: Comparing these characteristics with corresponding features of communities in the immediate or surrounding areas, namely Cwebe, Ntubeni, Mboya, Shixini and Zithulele, various similarities could be detected, indicating that the living circumstances and conditions might be generalisable to a certain degree, at least to deeply rural communities in the former Transkei area. More disadvantaged than the general South African population: The Madwaleni community differed significantly from the general South African population in 75 % of the compared characteristics. For example, amongst the community members the illiteracy rate (21.7 % vs. 13.6 %, p = 0.002) and unemployment rate (80.5 % vs. 25.5 %, p < 0.001) were significantly higher. In addition, the ‘poverty headcount ratio of 2 US $ per day’ showed that significantly more people were suffering from poverty in the Madwaleni area (92.2 % vs. 34 %, p < 0.001). The Madwaleni community members were less likely to have access to clean drinking water, along with significantly higher proportions of them using river water as their main source of drinking water (75.5 % vs. 5.1 %, p < 0.001). Also, they were less likely to have access to any sanitation or toilet facilities (31.3 % vs. 91.8 %, p < 0.001) or to electricity (8.5 % vs. 80.2 %, p < 0.001). 2) Weightiest health and social problems as experienced by the Madwaleni community In the Madwaleni area, the three health problems with the highest impact on the community were TB, HIV/AIDS and hypertension. On the basis of the applied 3-to-0-point rating matrix, they were rated by more than 95 % of the community members as being relevant problems, with mean values of 2.33, 2.30 and 2.14 respectively. Interestingly, women rated HIV/AIDS higher than men. Musculoskeletal problems and headache were additional health problems with relevant impact on the Madwaleni community, rated by more than 90 %, with mean values above 1.80. While pain and discomfort experienced by PLWHA have been recognised and researched before, there are no corresponding studies on rural communities and further research is necessary to identify the contributing factors. Additional relevant health problems: Interestingly, six health problems were rated higher by HIV untested than by HIV+ community members, namely bilharzia/ schistosomiasis, epilepsy, Herpes Zoster, HIV/AIDS, lung infections and stroke. Since the HIV+ men and women were educated about and screened for all of those diseases within the Madwaleni HIV/AIDS programme, this might explain the deviating rating patterns between the different sub-samples. Moreover, these results demonstrate that health education and disease prevention programmes are able to reduce the perceived burden of health problems and might therefore serve as a substantial argument in their favour. Interestingly, for the Madwaleni community, social matters had a higher impact on their lives than health problems, whereas the three social problems with the highest impact on the community were alcohol abuse, dependency on social grants and smoking. They were rated by more than 98 % of the community members as being relevant problems, with mean values of 2.75, 2.73 and 2.72 respectively. In accordance with these findings, employment & lack of work opportunities, education & illiteracy, food supply and poverty were additional social problems with relevant impact in the Madwaleni area, rated by more than 90 %, with mean values above 2.00. 3) Recommendations for future health education and disease prevention programmes At the time of the survey, the three most relevant health education and disease prevention topics for the Madwaleni community were HIV/AIDS, TB and healthy nutrition. They were rated by more than 95 % of the community members as being relevant health education problems, with mean values of 2.65, 2.51 and 2.36 respectively. In addition, STIs, alcohol & drug-related problems, water & sanitation and body & muscle pain were rated as the subsequent issues of relevance, with mean values above 2.00, supporting the identified community characteristics as well as the listing of the weightiest health and social problems. In addition, valuable new insight could be gained. For instance, HIV untested men rated the topic HIV/AIDS lower than all other community members, which is particularly interesting since men only constitute a minority of 20 % of the people testing for HIV in the Madwaleni area. Besides, topics not previously considered, such as injury prevention and basic first aid, were in-fact relevant for more than 85 % of the community members and require further attention. Furthermore, deviating rating patterns between men and women and the corresponding need for gender-specific educational workshops became evident, for example, for men about prostate & testicular cancer check-up or erectile dysfunction and for women about breast & cervical cancer check-up & papsmears or nutrition & growth. In addition, HIV+ community members rated depression & stress and psychiatric diseases higher than HIV untested men and women, with further studies required to identify the underlying reasons for these deviating rating patterns. Taking all findings from this Madwaleni community survey into consideration, health care providers working at the hospital and its peripheral clinics should first and foremost concentrate their efforts on maintaining the existing programmes, particularly, the Madwaleni HIV/ARV programme and the workshops on hypertension and diabetes mellitus. In addition, if qualified and motivated personnel can be recruited and the necessary funding can be raised, future health education and disease prevention programmes should focus on TB, alcohol & substance abuse-related problems as well as water & sanitation.

Problématique : Durant la période fœtale, le métabolisme global du fœtus fonctionne en hypoxie, ce qui limite la phosphorylation oxydative dans la mitochondrie, et par conséquent la production d’adénosine triphosphate (ATP). Ces conditions sont nécessaires pour le développement intra-utérin. Lors de la naissance, l’augmentation des concentrations d’oxygène et un stress oxydatif permettent une transition métabolique. Une charge oxydative supplémentaire en période néonatale pourrait perturber cette transition métabolique et causer des complications. La nutrition parentérale (NP) administrée aux nouveau-nés prématurés apporte un triple fardeau oxydatif : une exposition à des peroxydes oxydants autogénérés par l’interaction des composants de la NP, une carence en vitamine C (instable en solution), et une déficience en glutathion, vu la charge oxydative élevée. Cette charge oxydative excessive affecte l’homéostasie redox au foie et aux poumons, ainsi que le métabolisme énergétique hépatique, et ce, par des effets immédiats et à long-terme. La méthylation de l’ADN est un possible mécanisme qui explique les effets à long terme. Le but de ce travail était de caractériser l’impact à court- et long-terme de la NP néonatale sur l’homéostasie redox, la méthylation de l’ADN, et le métabolisme des glucides et lipides, en isolant chacun des facteurs nutritionnels. Méthodes : Des cochons d’Inde ont été divisés dans les groupes suivants 1) NP : nutrition intraveineuse complète ; 2) NP+ glutathion disulfure (GSSG) (6 ou 12µM- substrat pour la synthèse intra-cellulaire de glutathion); 3) Diète complète : nutrition orale complète 4) Diète déficiente en Vitamine C; 5) Diète déficiente en Cystéine; 6) Diète double déficiente; ou. À 1 semaine de vie, la moitié des animaux était sacrifié et l’autre moitié a commencé à manger une diète complète jusqu’à l’âge adulte. Résultats et discussion : Les animaux ayant reçu une NP néonatale ont un métabolisme énergétique permettant la synthèse de nicotinamide adénine dinucléotide phosphate (NADPH) par l’augmentation de l’activité de la glucokinase (captation de glucose), et diminution de celles de la phosphofructokinase-1 (PFK-1) (glycolyse) et acétyl-CoA-carboxylase-1 (ACC)(lipogenèse). À l’âge adulte, les animaux ont une diminution des niveaux de GSSG, indiquant un débalancement de l’homéostasie redox vers le côté réducteur programmé par la NP néonatale. L’activité augmentée de l’ACC suggère une tendance à accumuler les lipides au foie à la suite d’une diète riche en glucides. L’ajout de glutathion à la NP ne prévient pas ces perturbations, car les déficiences en glutathion et vitamine C jouent un rôle sur la modulation des niveaux protéiques de l’ACC. Les diètes néonatales déficientes en vitamine C et cystéine augmentent l’activité de la PFK-1. Cette augmentation se maintient jusqu’à l’âge adulte chez les mâles, mais pas chez les femelles. Les niveaux protéiques de la glucokinase et ACC sont diminués à 1 semaine, et ceux de l’ACC sont élevés à 3 mois dans les groupes ayant reçu une des diètes déficientes. Ces effets sont similaires à ceux trouvés dans les animaux nourris avec la NP, suggérant que la déficience de la NP en ces nutriments et non les peroxydes cause ces effets. Dans tous les groupes, un stress oxydatif a été démontré à 1 semaine de vie, soit par l’augmentation des niveaux de GSSG, ou la diminution du GSH. Cet effet est vrai pour le foie et le poumon. Une réponse de Nrf2 est observée aussi au foie, ce qui caractérise un niveau bas de stress oxydatif. La baisse de GSH pulmonaire chez les animaux déficients est secondaire à l’inhibition oxydative de la voie de transméthylation au foie. Une diminution des niveaux d’ARNm de glutathion réductase et glutarédoxine sont observées, ce qui favorise encore le stress oxydatif pulmonaire. À long terme, les effets sont les opposés, soit débalancement de l’homéostasie redox vers le côté réducteur au foie et poumon. La méthylation de l’ADN était diminuée au foie des animaux nouveau-nés recevant les diètes déficientes, mais aucun changement n’a été observé aux poumons. Cette diminution est en accord avec les hauts niveaux d’ARNm des gènes de la protéine régulatrice de la glucokinase, et AMPK. À long-terme, l’effet inverse est observé pour la méthylation de l’ADN Conclusion : La NP modifie le flot d’énergie au foie à 1 semaine visant favoriser le métabolisme redox en détriment du métabolisme énergétique. Cet effet semble créer une déficience énergétique fonctionnelle, qui se développe en une lipogenèse accrue en âge adulte. Cela peut représenter un exemple de la plasticité développementale. Bien qu’un stress oxydatif en âge néonatal ne soit pas létal, il affecte le métabolisme énergétique et redox à long-terme, probablement par la méthylation de l’ADN. Les résultats de ce travail démontrent que ces animaux adultes ont une capacité accrue d’entreposer de l’énergie, soit par une lipogenèse plus élevée, soit par une accumulation d’énergie redox (glutathion). Aucune maladie métabolique n’était observée chez les animaux, mais il est attendu à ce que ces animaux développent ces maladies plus facilement suite à l’exposition à des insultes (habitudes de vie malsaines, tabagisme, etc.). / Problematic: During the fetal period, the general metabolism works under hypoxia, limiting oxidative phosphorylation in mitochondria and adenine triphosphate (ATP) synthesis. These conditions are necessary for intrauterine development. After birth, the increasing oxygen concentrations and the associated oxidative stress induce a metabolic transition. An excessive oxidative load during the neonatal period could perturb this transition. Parenteral nutrition (PN) administered to premature newborns comes with a triple oxidative burden: contaminating peroxides generated in solution, vitamin C deficiency (unstable in solution), and glutathione deficiency (caused by the high oxidative load). This oxidative load affects redox homoeostasis in the liver and lungs, as well as energy metabolism in the liver. These effects are not only immediate, but they are also delayed. DNA methylation is a candidate mechanism explaining the long-term effects. The objective of this work was to characterize the short- and long-term impacts of neonatal PN over redox homoeostasis, DNA methylation and carbohydrate and lipid metabolism by isolating each of these factors. Methods: Six groups of three-day-old guinea pigs received for 4 days either: 1) Total PN; 2) PN+glutathione disulfide (GSSG) (6 or 12µM-anti-peroxide);3) Vitamin C deficient; 4) Cysteine deficient; 5) Double deficient; or 6) Complete diets. At 1 week of life, half of the animals were sacrificed, and the other half started eating nutritionally complete diets until adulthood. Results and discussion: NP animals had energy metabolism shifted favouring nicotinamide adenine dinucleotide phosphate (NADPH) synthesis, as evidenced by the increase in glucokinase activity (glucose trapping in hepatocytes) and decrease in phosphfuctokinase-1 (PFK-1) (glycolysis) and acetyl-CoA-carboxyalase-1 (ACC) (lipogenesis) activities. Adding GSSG to parenteral nutrition prevents these changes. During adulthood, ACC activity is increased, suggesting a tendency to accumulate lipids after a diet rich in carbohydrates. Adding GSSG to PN does not prevent these changes as they seem to be caused by the nutritional deficiencies in vitamin C and cysteine. Neonatal diets deficient in vitamin C and cysteine increase PFK-1 activity. This increase is maintained until adulthood in males but not in females. Protein levels of glucokinase and ACC are decreased at 1 week of life and ACC levels are increased at adulthood in deficient groups. These effects are like the ones observed in PN animals. In all groups, oxidative stress is demonstrated in 1-week-old animals, either by an increase in GSSG levels, or a decrease in GSH. This is true for the liver and lungs. An Nrf2 response is also observed in the liver, suggesting a low level of oxidative stress. The decrease in lung GSH is secondary to the oxidative inhibition of the transmethylation pathway in the liver. Decreased levels of glutathione reductase and glutaredoxin mRNA levels are observed in lungs, favouring pulmonary oxidative stress. At adulthood, an imbalance in redox homeostasis towards a reducing state is observed in lungs and liver. DNA methylation was decreased in the liver of deficient animals at 1-week, but no changes were observed in lungs. This decrease is in accordance with the decrease in mRNA levels of glucokinase regulatory protein and AMPK. At adulthood, the opposite effect was observed for DNA methylation. Conclusion: Parenteral nutrition alters the energy flow in the liver of 1-week-old animals, favouring redox metabolism over energy metabolism. This effect seems to create a phenotype of functional energy deficiency which translates into an increased lipogenesis at adult age. This may be an example of developmental plasticity. Although neonatal oxidative stress is not lethal, it affects energy and redox metabolism at adulthood, probably through DNA methylation. The presented results demonstrate these animals have an increased capacity of storing energy, either through increased lipogenesis, or by an increase in redox energy accumulation (glutathione). No metabolic disease was observed. Although it would be expected that these animals would develop these diseases more easily after exposure to insults, such as unhealthy lifestyle habits, smoking, and others.

Lite-Agro studies applications of TinyML in pear (Pyrus communis) tree disease identification and explores hardware implementations with an ESP32 microcontroller. The study works with the DiaMOS Pear Dataset to learn through image analysis whether the leaf is healthy or not, and classifies it according to curl, healthy, spot or slug categories. The system is designed as a low cost and light-duty computing detection edge solution that compares models such as InceptionV3, XceptionV3, EfficientNetB0, and MobileNetV2. This work also researches integration with federated learning frameworks and provides an introduction to federated averaging algorithms.

Die Entwicklung eines Embryos und Fetus beeinflusst die Anfälligkeit für kardiovaskuläre Erkrankungen im weiteren Verlauf des Lebens entscheidend. Zugrundeliegende Mechanismen sind jedoch weitestgehend unbekannt. Unter Zuhilfenahme eines neuen Mausmodells für intrauterine kardiale Wachstumsretardierung zielt die vorliegende Dissertation auf die Identifikation adaptiver Wachstumsmechanismen ab, welche die Anpassung der Organgröße und die Aufrechterhaltung einer normalen Herzfunktion ermöglichen. Vielzählige Gene des Aminosäure (AS)-Metabolismus und der Proteinhomeostase zeigten eine vermehrte Expression in neugeborenen Mausherzen nach gestörter Embryonalentwicklung. Es wurde angenommen, dass sowohl die AS-Verfügbarkeit als auch die Aktivität der mechanistic target of rapamycin (mTOR) Signalkaskade entscheidend für eine normale Herzentwicklung und postnatales kompensatorisches Wachstum sind. Der mTOR Komplex 1 (mTORC1) wurde in prä- und perinatalen Mäusen mittels Rapamycin-Behandlung trächtiger Weibchen inhibiert. Die Auswirkungen einer prä- und postnatalen AS-Restriktion wurden anhand einer Niedrigproteindiät untersucht. Rapamycin-behandelte Neugeborene zeichneten sich durch vermindertes Gesamtwachstum sowie Entwicklungsverzögerung aus. Dabei war die kardiale Entwicklung besonders betroffen. Kardiale Proliferationsraten waren nicht verändert, die verminderte Herzgröße wurde jedoch auf eine verringerte Kardiomyozytengröße sowie eine erhöhte Apoptoserate zurückgeführt. Die intrauterine AS-Restriktion wurde überraschend gut von den Mausherzen toleriert. Zusammenfassend konnte gezeigt werden, dass die mTOR Signalkaskade essentiell für eine normale Herzentwicklung sowie kompensatorisches kardiales Wachstum ist. Darüber hinaus stellt die pränatale Rapamycin-Behandlung möglicherweise ein neues Modell der intrauterinen Wachstumsretardierung dar, welches Untersuchungen von Programmierungs-Mechanismen vor allem während der fötalen und perinatalen Herzentwicklung ermöglicht. / Intrauterine development influences the susceptibility to cardiovascular disease in adulthood, although the underlying molecular mechanisms are vastly unknown. Utilizing a new mouse model of impaired heart development, this thesis aims at identifying pre- and postnatal adaptive growth mechanisms to restore organ size and allow normal cardiac function. Unbiased functional annotation of genes differentially expressed in neonatal hearts after impaired intrauterine development revealed numerous gene clusters involved in amino acid (AA) metabolism and protein homeostasis. It was hypothesized that both AA availability and mechanistic target of rapamycin (mTOR) pathway activation are crucial for normal heart development and compensatory cardiac growth. mTOR complex 1 (mTORC1) was inhibited in fetal and neonatal mice by rapamycin treatment of pregnant dams. The effects of pre- and postnatal AA restriction were studied by feeding dams a low protein diet (LPD) throughout pregnancy and keeping the offspring on LPD postnatally. Rapamycin treated neonates were characterized by overall growth restriction and developmental delay, where cardiac development was especially affected (reduction of heart size, weight and heart weight to body weight ratio, severe thinning and noncompaction of the ventricular myocardium as well as immature myocardial morphology). While proliferation rates were unaffected, the reduced neonatal heart size was attributed to decreased cardiomyocyte size and increased apoptosis. Strikingly, the murine heart appeared to be surprisingly resistant to intrauterine AA restriction. In conclusion, the data revealed mTOR being essential for normal as well as compensatory cardiac development and growth. Moreover, prenatal rapamycin treatment might represent a new model of intrauterine growth restriction, which potentially allows the investigation of developmental programming mechanisms within the heart particularly in the fetal and neonatal phase of development.

Events around conception such as maternal undernutrition and twinning may have effects on offspring physiology and disease risk in adulthood. Periconceptional undernutrition alters offspring physiology and adult pathology without affecting birth size, while twinning affects birth size and physiology but with inconsistent effects on adult pathology. We investigated the effects of these two periconceptional events and their interaction on maternal cardiovascular adaptation to pregnancy and fetal growth, physiology and endocrinology in late gestation in sheep. Pre and/or postconception undernutrition resulted in increased uterine blood flow in late gestation, but no change in maternal blood volume. Preconception undernutrition alone resulted in a relatively large placenta with a small, slow-growing fetus in late gestation. In contrast, postconception undernutrition alone resulted in a fetus with rapid late-gestation growth that was maintained through a maternal fast. Fetuses of ewes undernourished throughout both periods were similar in growth rate and size to controls. Maternal fasting also demonstrated that plasma levels of C-type natriuretic peptide are acutely and independently regulated by nutrient supply in mother and fetus. Fetuses of ewes undernourished both pre- and postconception had increased glucose disposal following a glucose challenge. Hypothalamic-pituitary-adrenal axis tests in these fetuses showed decreased pituitary adrenocorticotropin hormone response to direct stimulation but increased adrenal response to decreased cortisol negative feedback. Twin fetuses grew more slowly in late gestation than singletons. Twins also had a smaller insulin response to arginine and a greater insulin response to glucose, but periconceptional undernutrition abolished this difference. Twins had suppressed baseline hypothalamic-pituitary-adrenal axis function and decreased adrenal sensitivity compared to singletons, but increased fetal pituitary adrenocorticotropin hormone response to direct stimulation and decreased cortisol negative feedback. These studies suggest that firstly, fetal size is a poor reflection of fetal growth trajectory, physiology and endocrinology. Secondly, pre- and postconception undernutrition affect late-gestation fetal growth in different ways, while undernutrition in both periods alters fetal endocrine status in late gestation. Thirdly, the biology of twin fetal development is fundamentally different from that of singletons, which may explain the inconsistency of the relationship between birth weight and adult disease risk in twins. / Auckland Medical Research Foundation, Health Research Council of New Zealand

Events around conception such as maternal undernutrition and twinning may have effects on offspring physiology and disease risk in adulthood. Periconceptional undernutrition alters offspring physiology and adult pathology without affecting birth size, while twinning affects birth size and physiology but with inconsistent effects on adult pathology. We investigated the effects of these two periconceptional events and their interaction on maternal cardiovascular adaptation to pregnancy and fetal growth, physiology and endocrinology in late gestation in sheep. Pre and/or postconception undernutrition resulted in increased uterine blood flow in late gestation, but no change in maternal blood volume. Preconception undernutrition alone resulted in a relatively large placenta with a small, slow-growing fetus in late gestation. In contrast, postconception undernutrition alone resulted in a fetus with rapid late-gestation growth that was maintained through a maternal fast. Fetuses of ewes undernourished throughout both periods were similar in growth rate and size to controls. Maternal fasting also demonstrated that plasma levels of C-type natriuretic peptide are acutely and independently regulated by nutrient supply in mother and fetus. Fetuses of ewes undernourished both pre- and postconception had increased glucose disposal following a glucose challenge. Hypothalamic-pituitary-adrenal axis tests in these fetuses showed decreased pituitary adrenocorticotropin hormone response to direct stimulation but increased adrenal response to decreased cortisol negative feedback. Twin fetuses grew more slowly in late gestation than singletons. Twins also had a smaller insulin response to arginine and a greater insulin response to glucose, but periconceptional undernutrition abolished this difference. Twins had suppressed baseline hypothalamic-pituitary-adrenal axis function and decreased adrenal sensitivity compared to singletons, but increased fetal pituitary adrenocorticotropin hormone response to direct stimulation and decreased cortisol negative feedback. These studies suggest that firstly, fetal size is a poor reflection of fetal growth trajectory, physiology and endocrinology. Secondly, pre- and postconception undernutrition affect late-gestation fetal growth in different ways, while undernutrition in both periods alters fetal endocrine status in late gestation. Thirdly, the biology of twin fetal development is fundamentally different from that of singletons, which may explain the inconsistency of the relationship between birth weight and adult disease risk in twins. / Auckland Medical Research Foundation, Health Research Council of New Zealand