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Masters of Science / There is a need for defined models of human nutritional disorders partly because serious misconceptions about models are common amongst researchers. Historically a large variety of species has been used including primates, pigs, rats, lagomorphs. Advantages various small carnivores and and disadvantages are not well known and availability is a major factor. In 1753 John Hunter used pigs to study bone growth in one of the first scientifically controlled nutrition experiments (Kobler 1960). Rats were most likely the first animals to be bred specifically for scientific purposes and there is evidence that they were used in nutrition experiments during the late eighteenth century (Kobler 1960). Experience with carcinogenesis in animals has shown the great diversity of results which may possibly be obtained from different species (Lave et al. 1988). This is pertinent to nutritional research as there is an established link between diet and cancer. The selection of a suitable substitute to attempt to model possible human response to a variety of procedures is dependent upon criteria among which the following are possibly the more important. Availability; this is of great importance in Southern Africa where the cost of importation of exotic species. must be taken into account. Du Plessis (1981) referred to the fact that our indigenous primates were a valuable resource. A second consideration must be the cost the selected animal in a scientifically acceptable environment. Keeping animals of maintaining and ethically for research purposes in an uncontrolled environment could well lead to erroneous conclusions being made. Thirdly the cost of a research program in which animals are used may be increased if there is insufficient knowledge of the model selected. A paucity of knowledge available about an animal may affect the viability of an experiment. The need for precise information regarding the effects of extended term dietary supplementation of experimental animals has been noted by Fincham et. al. (1987) . Additionally the selected animal should preferably have similar dietary requirements to man, and have a life span which will enable extended term investigations.

Gestational diabetes (GDM) occurs in up to 9% of pregnancies. Perinatal depression affects up to 20% of women during pregnancy, and can extend into the postpartum period. A number of studies have linked depression and diabetes, however, whether this applies to GDM or which might come first is less understood. The purpose of this study was to examine the potential relationship between depression identified in the first trimester of pregnancy and the subsequent development of GDM. Women without pre-existing Type I/II diabetes (n = 1021) were evaluated for depression during the first trimester of pregnancy, and medical records were reviewed to identify a positive history of diabetes. Women identified as depressed during the first trimester were more likely to have GDM compared to those not depressed. After controlling for demographic factors and weight-related variables level of depression in the first trimester still predicted later GDM development. Depression identified in early pregnancy may predict increased risk of subsequent GDM development. Due to the numerous maternal, fetal and neonatal complications associated with GDM, early recognition is essential to promote the best possible outcomes for mother and infant. Recognizing depression as a possible risk factor for GDM development could lead to earlier screening and preventative measures.

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The early environment impacts many aspects of an individual’s developing phenotype. In particular, early environmental conditions are important for shaping the hypothalamic-pituitary-adrenal (HPA) axis, which coordinates an individual’s stress response. These developmental changes are likely mediated by epigenetic modifications, functional changes to the genome that can alter gene expression in response to environmental variation, resulting in significant phenotypic differences (Kundakovic and Champagne 2015; Richards 2006). Determining how early life variation alters epigenetic modifications (such as DNA methylation) of genes throughout the HPA axis, and how these marks change over time, in wild organisms is important for understanding their potential long-term fitness consequences. Here, I examine DNA methylation modifications in the HPA axis in relation to early environmental variation in free-living house sparrows (Passer domesticus). In Chapter 1, I show a relationship between natural variation in the early environment and DNA methylation marks of numerous genes related to HPA axis function, which in turn predict growth trajectories. In Chapter 2, I show that early life stress in particular impacts DNA methylation in genes critical to HPA axis function, but does so differently depending on the life history stage in which stress is encountered. Finally, in Chapter 3, I find that these early life marks have long-term effects past the developmental period, predicting longevity as well as lifetime reproductive output in a sex-specific manner. Overall, my dissertation adds to a growing understanding of the dynamic role of epigenetic modifications in mediating phenotypic responses to the early life environment in wild birds, and demonstrates the potential long-term fitness outcomes of these changes.

Growth performance in vertebrates is regulated by environmental factors including the quality and quantity of food, which influences growth via endocrine pathways such as the growth hormone (GH) / insulin-like growth factor somatotropic axis. In several teleost fishes, circulating concentrations of insulin-like growth factor-1 (Igf1) correlate positively with growth rate, and it has been proposed that plasma Igf1 levels may serve as an indicator of growth variation for fisheries and aquaculture applications. Here, I tested whether plasma Igf1 concentrations might serve as an indicator of somatic growth in olive rockfish (Sebastes serranoides), one species among dozens of rockfishes important to commercial and recreational fisheries in the Northern Pacific Ocean. I reared juvenile olive rockfish under food ration treatments of 1% or 4% wet mass per d for 98 d to experimentally generate variation in growth. Juvenile rockfish in the 4% ration grew 60% more quickly in mass and 22% faster in length than fish in 1% ration. Plasma Igf1 levels were elevated in rockfish under the 4% ration, and individual Igf1 levels correlated positively with growth rate, as well as with individual variation in hepatic igf1 mRNA levels. These data in olive rockfish support the possible use of plasma Igf1 as a positive indicator of growth rate variation in rockfishes. Using my findings from this experiment, I further investigated the use of this biomarker in wild rockfish by examining patterns of Igf1 variation in blue rockfish (Sebastes mystinus) caught within and outside of two Marine Protected Areas (MPAs) along California’s coast: Piedras Blancas MPA and Point Buchon MPA. Individual Igf1 levels correlated positively with increasing size as seen in laboratory reared fish. After correcting plasma Igf1 values for body size, circulating Igf1 was observed to be higher in blue rockfish within the boundaries of the Piedras Blancas MPA compared to fish from an adjacent site with no fishing restrictions. Igf1 levels in blue rockfish caught within the Point Buchon MPA, however, were similar to those outside of that MPA. These results suggest that blue rockfish within the Piedras Blancas MPA may experience enhanced growth relative to conspecifics outside of that MPA’s boundaries, and that such growth increases may be specific to MPA locations. My findings support previous studies that Igf1 is a positive indicator for growth in teleost fish and can be used as a tractable biomarker in wild rockfish which could enhance management efforts of fish stocks within marine protected areas.

Song production in songbirds is controlled by parts of the brain known as the song control regions (SCRs). During spring, gonads increase in size, males sing to attract mates, and SCRs become larger. This neuroplasticity is controlled by the change in day length and increased plasma testosterone (T) levels. Plasma T can be reduced by stress through the production of corticosterone (CORT), through the production of beta-endorphin, or through direct effects on the testes via the nervous system. We determined the T, estradiol, and CORT hormonal profiles of wild House Finches by capturing and sampling blood from the finches every season for two years. To track SCR neuroplasticity in the wild, we also measured the volume of two specific SCRs, the HVC and RA, every season. We then examined the effects of stress on the finch endocrine system in the wild by performing a 30-minute restraint stress protocol once every season and took blood samples before and after the restraint. To determine whether stress and/or CORT affect neuroplasticity in SCRs, we captured male house finches during winter and brought them into captivity. They were allowed to acclimate to captivity for one month on short days (8L:16D) before we transferred them to long days (16L:8D) and restraint stressed half the birds. We measured their gonads, plasma T and CORT levels, volumes of the HVC and RA, and the number of new neurons in the HVC. HVC volumes were smaller in stressed than non-stressed birds, while RA volumes did not differ. There was no difference in number of new neurons or estimated total number of neurons in the HVC between control and restrained birds. Because the HVC is involved in song production, it is possible that stress negatively impacts singing behavior and reproductive success in House Finches. Future work should address how natural stressors may affect neuroplasticity in birds.

BACKGROUND: Vitamin D deficiency and insufficiency are rising healthcare concerns in the United States (US) and worldwide. The latest data collected by the National Health and Nutrition Examination Surveys (NHANES) between 2002-2006 showed that approximately one third of Americans over one-year-old were vitamin D deficient (serum 25-hydroxy vitamin D (25-OHD) < 12 ng/mL) or insufficient (serum 25-OHD < 20 ng/mL) (Looker et al., 2011). Environmental exposures, acute or chronic disease, and genetics can exacerbate vitamin D deficiency. People with malabsorptive disorders such as Inflammatory Bowel Disease (IBD) are at an even greater risk of becoming vitamin D deficient. Pediatric patients with IBD are particularly vulnerable to the short and long-term effects of vitamin D deficiency, given the prominent role played by this agent on skeletal development. More recent data have demonstrated that vitamin D also plays an important role in maintaining and regulating the immune system. For this reason, investigators have been interested in a better understanding of the relationship between vitamin D and inflammation. Vitamin D may prove to be an important adjunct therapy for people suffering from IBD and other autoinflammatory diseases. OBJECTIVES: Many patients and medical providers understand the importance that vitamin D has in a growing child’s skeletal development. However, compliance with daily supplementation remains low. The design of this study allows patients to receive high-dose vitamin D supplementation during scheduled biologic infusions. The goal is to assess the safety and efficacy of high-dose interval vitamin D therapy. The secondary goal of this study will be to determine if optimal vitamin D levels impact the inflammation observed in the gastrointestinal (GI) tract of patients with IBD. METHODS: 60 patients with IBD, between 5-25 years of age, who received regularly scheduled infliximab or vedolizumab infusions, and had serum 25-OHD levels below 30 ng/mL were recruited for the study. These patients were screened for the exclusion criteria, including underlying liver or kidney disease. Enrolled participants were given eight high-dose oral vitamin D3 supplements during scheduled infliximab or vedolizumab infusions for 8-16 months. Serum 25-OHD levels, urine calcium and creatinine levels, and research blood samples were collected at baseline, midpoint, and final visits. Questionnaires were also dispensed to patients to measure quality of life (QoL). This data was collected and analyzed to assess the safety and efficacy of high-dose interval vitamin D supplementation in pediatric patients with IBD. RESULTS: The data from this study showed statistical significance in the change of serum-25OHD level from baseline to midpoint and final visits. The mean increase from baseline to midpoint was 15.71±10.1 ng/mL for the 30 participants who had completed 3 study doses (2,500 mCg or 5,000 mCg) (mean±95% CI). The mean increase from baseline to final visit was 18.1±11.67 ng/mL for the 19 participants who completed all 7 study doses (2,500 mCg or 5,000 mCg) (mean±95% CI). A single factor ANOVA test confirmed statistical significance with p < 0.0001. Urine calcium and creatinine levels did not have a statistically significant change from baseline to final visit for the 12 participants who had completed both samples. Lastly, IMPACT-III QoL scores were not significantly different from baseline. However, there was an overall increase in the mean scores in all 6 subcategories of the survey. As more participants complete the study, the statistical significance and the validity of results will likely be strengthened. CONCLUSION: High-dose interval vitamin D supplementation was a safe and effective way to achieve serum 25-OHD levels to an optimal range (i.e., 40-60 ng/mL) in pediatric patients and young adult patients with IBD. The data suggests that three doses of high-dose vitamin D may be sufficient to bring levels to an optimal and stable plateau. Patient compliance with supplementation was 100% in this study, because of provider-observed ingestion of vitamin D. Patients also noted that this was their preferred method of supplementation. The safety and efficacy results of this study serve as a framework for developing a more standard approach to vitamin D supplementation for our patients with IBD. Future studies may benefit from expanding this method of delivery to patients who have other inflammatory diseases that require both regular oral vitamin D therapy and in person visits for treatments (i.e., intravenous (IV) medication).

Bakgrund: Diabetes mellitus typ 2 är den mest ökande och livshotande metaboliska sjukdomen i världen. I Sverige var 468 402 patienter diagnostiserade med sjukdomen år 2022. Patienten har ett stort ansvar för att utföra egenvård och genomföra nödvändiga livsstilsförändringar för att förebygga sjukdomsrelaterade komplikationer. Exempel är att förändra kost- och motionsvanor. Syftet: Att beskriva sjuksköterskors erfarenheter av egenvård hos patienter med diabetes mellitus typ 2. Metod: Litteraturöversikten som genomfördes hade en kvalitativ ansats. I studien inkluderades 12 kvalitativa vetenskapliga studier. Analysen av studierna genomfördes i enlighet med de fem steg som Friberg (2022a) rekommenderar. Resultat: Vid analys av studierna som ingick i materialet identifierades tre teman och sex subteman. Tema Utmaningar i att stödja till egenvård med subtema Hinder för egenvård och Kulturella värderingar och religiösa övertygelsers påverkan. Tema Betydelsen av kommunikation med subtema Att övertyga betydelsen av egenvård och Att skapa relation med patienterna. Tema Kunskapens betydelse med subtema Kunskapsbrist hos patienterna och Patientens behov av utbildning. Slutsats: I ett mångkulturellt samhälle är det viktigt att öka kulturella kompetenser bland sjuksköterskor för att kunna stödja personer med diabetes typ 2 till genomförandet av egenvård. Kommunikationen mellan sjuksköterskor och patienter bör anpassas efter de behov och förutsättningar individen har, där en god relation är central. Dessutom behövs strategier utvecklas för att öka patienternas kunskap om sjukdomen. / Background: Diabetes mellitus type 2 is the most increasing and life-threatening metabolic disease in the world. In Sweden, 468,402 patients were diagnosed with the disease in 2022.The patient has a great responsibility for performing self-care and implementing the necessary lifestyle changes to prevent disease-related complications. Examples are changing diet and exercise habits. Purpose: To describe nurses' experiences of self-care in patients with diabetes mellitus type 2. Method: The literature review conducted had a qualitative approach. The study included 12 qualitative scientific studies. The analysis of the studies was done according to the five steps Friberg (2022a) recommends. Results: When analyzing the studies included three themes and six subthemes were identified. The theme, Challenges in supporting self-care with subtheme, Obstacles to self-care and Influence of cultural values and religious beliefs. The theme, Importance of communication, with subtheme Convincing the importance of self-care and Creating a relationship with the patients. The theme, Importance of knowledge with subtheme Lack of knowledge in patientsand Patient's need for education. Conclusion: In a multicultural society, it is important to increase cultural competence among nurses to support people with type 2 diabetes to implement self-care. Communication between nurses and patients should be adapted to the needs and conditions of the individual, where a good relationship is central. In addition, strategies need to be developed to increase patients' knowledge of the disease.

The adrenal glands are two major endocrine organs responsible for multiple physiological processes, including the stress response, modulating the immune system and metabolism. The adrenal is composed of an outer cortex and an inner medulla with distinct developmental origin and function. While tissue-specific stem/progenitor populations of the adrenal cortex have been widely identified and characterised, the presence of a functional stem/progenitor population in the medulla is unclear. Establishing cell hierarchy of the adrenal medulla essential to understand normal homeostasis, disease pathogenesis and establishing regenerative medicine strategies, therefore the identification of a stem/progenitor population would provide an important starting point for further basic and translational studies. Cell composition of the adrenal medulla includes three main cell types: chromaffin cells, which secrete catecholamines, neurons, which stimulate catecholamine production, and a third cell type with an unspecified “support” function called sustentacular cells. Using transcriptomics and genetic approaches in mouse, I established that a population of sustentacular cells express the stem/progenitor marker SOX2. These cells are present throughout life and have a developmental origin congruent with the rest of the gland. Through genetic lineage-tracing using the Sox2CreERT2 strain, I demonstrate that SOX2+ cells are an expanding population, capable of giving rise to the catecholamine-producing chromaffin cells, consistent with a stem cell role in vivo. I further demonstrate the self-renewal potential of SOX2+ cells through in vitro isolation and expansion, using a Sox2eGFP mouse line. Analysis of SOX2+ cells in physiological organ challenge suggests potential involvement of these cells in the response to perturbation of normal homeostasis. Through analysis of FFPE sections of human adrenals, I confirm the presence of SOX2+ cells in the normal adult organ, as well as in pheochromocytomas. Taken together, these data support the identification of a previously undescribed stem cell population in the mammalian adrenal medulla and confirm its functional relevance.