Acute demyelination in children may be a monophasic illness or the sentinel attack of multiple sclerosis (MS) – a chronic inflammatory neurodegenerative demyelinating disease. MS risk is largely determined during childhood and vitamin D may protect against MS. The primary objective of this thesis was to evaluate vitamin D status in children presenting with acute demyelinating syndromes (ADS) as a potential contributor to MS outcome. The LIAISON “25 OH Vitamin D TOTAL” assay was validated to assess the biomarker of vitamin D status – serum 25-hydroxyvitamin D (25(OH)D) concentrations. Consecutive patients (<16 y) were enrolled at presentation with ADS and prospectively evaluated at 23 Canadian centres. MS was defined by a second clinical demyelinating event or by MRI evidence of new lesions over time. Cox proportional hazards regression models assessed risk of MS outcome as a function of serum 25(OH)D tertiles, accounting for factors associated with either MS risk or vitamin D status – age, sex, season, and HLA-DRB1*15 status. Of 211 children with 25(OH)D measured in sera obtained a median of 9 days from onset (interquartile range, 5 – 17 d; maximum 36 days), 20% (n = 41) were diagnosed with MS after 3.7 mos. (3.1 – 7.3 mos.). Risk of MS was lower in children with 25(OH)D levels in the highest tertile (≥ 74 nmol/L) at ADS versus those in the lowest tertile (<50 nmol/L) (HR 0.41; 95% CI 0.18 to 0.97, adjusted model). Children with higher circulating 25(OH)D concentrations at ADS have a lower risk of MS. Further evidence for a role of vitamin D insufficiency during childhood and adolescence contributing to MS risk comes from three MS patients with suboptimally managed pseudo-vitamin D deficiency rickets. Finally, a sun exposure questionnaire was validated in the latter part of this thesis for use in future research into determinants of vitamin D status and their association with risk of MS.

Acute demyelination in children may be a monophasic illness or the sentinel attack of multiple sclerosis (MS) – a chronic inflammatory neurodegenerative demyelinating disease. MS risk is largely determined during childhood and vitamin D may protect against MS. The primary objective of this thesis was to evaluate vitamin D status in children presenting with acute demyelinating syndromes (ADS) as a potential contributor to MS outcome. The LIAISON “25 OH Vitamin D TOTAL” assay was validated to assess the biomarker of vitamin D status – serum 25-hydroxyvitamin D (25(OH)D) concentrations. Consecutive patients (<16 y) were enrolled at presentation with ADS and prospectively evaluated at 23 Canadian centres. MS was defined by a second clinical demyelinating event or by MRI evidence of new lesions over time. Cox proportional hazards regression models assessed risk of MS outcome as a function of serum 25(OH)D tertiles, accounting for factors associated with either MS risk or vitamin D status – age, sex, season, and HLA-DRB1*15 status. Of 211 children with 25(OH)D measured in sera obtained a median of 9 days from onset (interquartile range, 5 – 17 d; maximum 36 days), 20% (n = 41) were diagnosed with MS after 3.7 mos. (3.1 – 7.3 mos.). Risk of MS was lower in children with 25(OH)D levels in the highest tertile (≥ 74 nmol/L) at ADS versus those in the lowest tertile (<50 nmol/L) (HR 0.41; 95% CI 0.18 to 0.97, adjusted model). Children with higher circulating 25(OH)D concentrations at ADS have a lower risk of MS. Further evidence for a role of vitamin D insufficiency during childhood and adolescence contributing to MS risk comes from three MS patients with suboptimally managed pseudo-vitamin D deficiency rickets. Finally, a sun exposure questionnaire was validated in the latter part of this thesis for use in future research into determinants of vitamin D status and their association with risk of MS.

Studies have shown that air pollution, as well as bark fissure depth and sun exposure of a tree can have an effect on lichen growth as well as abundance of lichen species. The aim of this study was to find out the relative importance of these factors. 211 oaks in south eastern Sweden were surveyed for presence of 17 lichen species, as well as the total number of lichen species. Half of the trees were situated in urban areas and half in the countryside. For each tree the bark fissure depth was measured and the sun exposure of the trunk was estimated. The results showed a significant negative effect on a majority of lichens growing in an urban environment and a significant positive effect on a majority of lichens growing on trees with deep bark fissures. The sun exposure was a less important factor but could not be excluded as a factor affecting lichen occurrence. These results show the negative effect urbanization can have on rare lichen species, as well as be used in the development and maintenance for the nature reserves containing them

Sun-exposed broad leaved deciduous trees have a great species diversity of epiphytic lichens. In Europe, these trees have decreased dramatically in number as wooded pastures have become overgrown with trees and bushes, and broad leaved deciduous stands have been replaced by planted coniferous trees. These are the main reasons for many lichens depending on deciduous trees being red-listed. Epiphytic lichens in overgrown areas could benefit from conservation thinning, but few studies have been performed on how this type of cutting affects the lichens. In a previous study, the presence of red-listed epiphytic lichens in a broad leaved deciduous forest was examined. After the study, thinning of trees and bushes was made. Here we study the effects of this thinning on Lobaria pulmonaria. We tested possible factors that may affect the growth of L. pulmonaria, and if there were any differences in incidence and vitality of the lichen between managed and unmanaged stands. Since Dutch elm disease and ash dieback are well spread in the area, we wanted to see if they also affected the growth of L. pulmonaria. There were no differences in incidence and growth between managed and unmanaged stands. The results were unexpected since other studies show that, for instance, increased sun exposure often has a great effect on the growth of lichens. Many elms and ashes were dead or dying and had a significant negative effect on the change of number of lobes and the lobe surface. The diseases of the trees can thus be assumed to be the greatest cause of why the lichens in the managed stand did not benefit from thinning.

Vitamin D deficiency and insufficiency are now seen as a contemporary health problem in Australia with possible widespread health effects not limited to bone health1. Despite this, the Vitamin D status (measured as serum 25-hydroxyvitamin D (25(OH)D)) of ambulatory adults has been overlooked in this country. Serum 25(OH)D status is especially important among this group as studies have shown a link between Vitamin D and fall risk in older adults2. Limited data also exists on the contributions of sun exposure via ultraviolet radiation and dietary intake to serum 25(OH)D status in this population. The aims of this project were to assess the serum 25(OH)D status of a group of older ambulatory adults in South East Queensland, to assess the association between their serum 25(OH)D status and functional measures as possible indicators of fall risk, obtain data on the sources of Vitamin D in this population and assess whether this intake was related to serum 25(OH)D status and describe sun protection and exposure behaviors in this group and investigate whether a relationship existed between these and serum 25(OH)D status. The collection of this data assists in addressing key gaps identified in the literature with regard to this population group and their Vitamin D status in Australia. A representative convenience sample of participants (N=47) over 55 years of age was recruited for this cross-sectional, exploratory study which was undertaken in December 2007 in south-east Queensland (Brisbane and Sunshine coast). Participants were required to complete a sun exposure questionnaire in addition to a Calcium and Vitamin D food frequency questionnaire. Timed up and go and handgrip dynamometry tests were used to examine functional capacity. Serum 25(OH)D status and blood measures of Calcium, Phosphorus and Albumin were determined through blood tests. The Mean and Median serum 25-Hydroxyvitamin D (25(OH)D) for all participants in this study was 85.8nmol/L (Standard Deviation 29.7nmol/L) and 81.0nmol/L (Range 22-158nmol/L), respectively. Analysis at the bivariate level revealed a statistically significant relationship between serum 25(OH)D status and location, with participants living on the Sunshine Coast having a mean serum 25(OH)D status 21.3nmol/L higher than participants living in Brisbane (p=0.014). While at the descriptive level there was an apparent trend towards higher outdoor exposure and increasing levels of serum 25(OH)D, no statistically significant associations between the sun measures of outdoor exposure, sun protection behaviors and phenotypic characteristics and serum 25(OH)D status were observed. Intake of both Calcium and Vitamin D was low in this sample with sixty-eight (68%) of participants not meeting the Estimated Average Requirements (EAR) for Calcium (Median=771.0mg; Range=218.0-2616.0mg), while eighty-seven (87%) did not meet the Adequate Intake for Vitamin D (Median=4.46ug; Range=0.13-30.0ug). This raises the question of how realistic meeting the new Adequate Intakes for Vitamin D is, when there is such a low level of Vitamin D fortification in this country. However, participants meeting the Adequate Intake (AI) for Vitamin D were observed to have a significantly higher serum 25(OH)D status compared to those not meeting the AI for Vitamin D (p=0.036), showing that meeting the AI for Vitamin D may play a significant role in determining Vitamin D status in this population. By stratifying our data by categories of outdoor exposure time, a trend was observed between increased importance of Vitamin D dietary intake as a possible determinant of serum 25(OH)D status in participants with lower outdoor exposures. While a trend towards higher Timed Up and Go scores in participants with higher 25(OH) D status was seen, this was only significant for females (p=0.014). Handgrip strength showed statistically significant association with serum 25(OH)D status. The high serum 25(OH)D status in our sample almost certainly explains the limited relationship between functional measures and serum 25(OH)D. However, the observation of an association between slower Time Up and Go speeds, and lower serum 25(OH)D levels, even with a small sample size, is significant as slower Timed Up and Go speeds have been associated with increased fall risk in older adults3. Multivariable regression analysis revealed Location as the only significant determinant of serum 25(OH)D status at p=0.014, with trends (p=>0.1) for higher serum 25(OH)D being shown for participants that met the AI for Vitamin D and rated themselves as having a higher health status. The results of this exploratory study show that 93.6% of participants had adequate 25(OH)D status-possibly due to measurement being taken in the summer season and the convenience nature of the sample. However, many participants do not meet their dietary Calcium and Vitamin D requirements, which may indicate inadequate intake of these nutrients in older Australians and a higher risk of osteoporosis. The relationship between serum 25(OH)D and functional measures in this population also requires further study, especially in older adults displaying Vitamin D insufficiency or deficiency.

Submitted by Vasti Diniz (vastijpa@hotmail.com) on 2017-09-08T11:33:23Z No. of bitstreams: 1 arquivototal.pdf: 1921817 bytes, checksum: 7ba035d7ef40f1aafd9f93476aabedd6 (MD5) / Made available in DSpace on 2017-09-08T11:33:23Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1921817 bytes, checksum: 7ba035d7ef40f1aafd9f93476aabedd6 (MD5) Previous issue date: 2016-03-17 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Epigenetics is the study heritable changes of in gene expression without modifications in the primary sequence of DNA. In our study we investigated the influence of sun exposure on global DNA methylation and hydroxymethylation status and at specific sites of the miR-9-1, miR9-3 and MTHFR genes in skin samples of subjects with no history of skin diseases. Skin biopsies were obtained by punch on sun-exposed and sun-protected arm areas from 24 corpses aged 16-89 years old from the Brazilian Service of Death Investigation. Genomic DNA was extracted from skin samples that were ranked according to Fitzpatrick’s criteria as light, moderate and dark brown. Global DNA methylation and hydroxymethylation and DNA methylation at specific sites analyses were performed using an ELISA and MSP, respectively. No significant differences in global DNA methylation and hydroxymethylation levels were found between the skin areas, skin type or age. However, gender-related differences were detected, where women showed higher methylation levels in comparison to those in men. Global DNA methylation levels were higher than hydroxymethylation levels, and the levels of these DNA modifications correlated in skin tissue. For specific sites, it was detected no differences among areas. Additional analyses showed no differences in the methylation status when age, gender and skin type were considered. We conclude that sun exposure does not induce changes in the global DNA methylation and hydroxymethylation status or at specific sites in the miR-9-1, miR-9-3 and MTHFR genes for skin types studied. / A epigenética é o estudo das alterações hereditárias na expressão gênica sem mudanças na sequência primária do DNA. No nosso estudo investigamos a influência da exposição solar sobre o perfil de metilação e hidroximetilação global de DNA e em sítios específicos nos genes miR-9-1, miR-9-3 e MTHFR em amostras de pele humana. Para isso, biópsias foram obtidas por punch circular de área exposta e não exposta ao sol do braço de 24 cadáveres de ambos os sexos, com idade entre 16-89 anos sem histórico de doenças de pele oriundos do Serviço de Verificação de Óbitos da Paraíba (SVO). O DNA foi extraído e a análise de metilação e hidroximetilação global do DNA foi realizada através de Elisa indireto. A análise de metilação nos sítios específicos dos genes miR-9-1, miR-9-3 e MTHFR foi realizada por meio de PCR específica para metilação (MSP) seguida de eletroforese. As análises estatísticas foram realizadas pelo software BioEstat 5.0 ao nível de significância de 5%. Não encontramos diferenças significativas nos níveis de metilação e hidroximetilação global de DNA entre as áreas exposta e não exposta da pele, tipo de pele ou idade. No entanto, foram detectadas diferenças em relação ao gênero, onde as mulheres apresentaram nível de metilação global mais alto em comparação aos homens. O nível de metilação global de DNA foi maior do que o nível de hidroximetilação, sendo estes, correlacionados no tecido da pele. Para sítios específicos, não foi detectada nenhuma diferença entre as áreas. Análises adicionais mostraram não haver diferenças significativas no perfil de metilação quando consideradas a idade, gênero e o tipo de pele. Conclui-se que a exposição ao sol não induz mudanças no perfil de metilação e hidroximetilação global do DNA ou em sítios específicos dos genes miR-9-1, miR-9-3 e MTHFR para os tipos de pele estudado.

Felling of old trees as well as changes in land use and management of wooded pastures has led to the decline of biodiversity associated with old deciduous trees in Europe. This also applies to Sweden’s most species rich tree, the oak tree (Quercus robur), which changes with age and develops, for example, a rougher bark structure, deeper bark fissures and cavities. These give rise to several different microhabitats that favor the presence of lichens, mosses and wood-dependent organisms. To preserve the biodiversity, environmental conditions linked to a high diversity need to be identified and described, of which indicator species are a simplified way of measuring diversity. Epiphytic lichens are well-used indicators of environmental conditions because of their habitat specificity, longevity and sensitivity to air quality and humidity. In this study, the impact of regional (latitude, longitude and dominated landscape) and local (diameter and sun exposure) environmental variables on species richness and occurrence of epiphytic lichens on coarse oak trees (Quercus robur) were analyzed in meadows and pastures in southern Sweden with generalized linear models (GLM). A total number of 2346 oak trees were included in the study, of which about 47 % had presence of at least one of the studied lichen species. All environmental variables demonstrated significant effects on species richness, of which the regional had the greatest effect. Also with the species-specific analyses the same effect of the regional variables was found, while single species showed different requirements for the local factors. The results indicate that global warming may move the Swedish species composition more to the Northeast and that increased homogenization of the landscape may threaten the diversity attached to oaks. The results also demonstrate the importance of preserving a varied landscape with trees of different sizes, ages and different levels of sun exposure to accommodate a greater diversity of epiphytic species, but also other species linked to oak trees.

Contexte : Les cancers cutanés sont les cancers les plus fréquents dans les populations de peau blanche. Si l’exposition aux rayonnements ultraviolets est le facteur de risque le plus connu, peu d’études ont permis une comparaison directe des profils d’exposition solaire associés à ces tumeurs dans une même population, et les déterminants des comportements d’exposition solaire restent peu connus à ce jour. Par ailleurs, bien que les antioxydants, ayant la capacité de neutraliser les radicaux libres, représentent des candidats potentiels pour la chimioprévention des cancers cutanés, l’état actuel des connaissances ne permet pas d’émettre de conclusion claire en ce qui concerne leur rôle vis-à-vis du risque de cancers cutanés.Objectif : L’objectif de cette thèse est de préciser le lien existant entre l’exposition solaire et le risque de cancers cutanés, d’explorer les profils associés à certains comportements d’exposition solaire et d’étudier les associations potentielles entre compléments alimentaires en antioxydants et risque de cancers cutanés dans l’étude française E3N (Étude Épidémiologique auprès de femmes de l’Éducation Nationale).Résultats : Nos résultats suggèrent que les trois types de cancers cutanés sont associés à différents profils d'exposition solaire et que l’utilisation de crème solaire, de lampes UV et de compléments solaires sont associés à plusieurs habitudes favorables et défavorables pour la santé. De plus, nos résultats suggèrent que les consommations de compléments solaires et de compléments en vitamine E sont associées à un risque accru de carcinomes cutanés.Conclusion : Ce travail souligne l’importance de la prévention pour réduire la prévalence des cancers cutanés ainsi que la nécessité de mieux comprendre les profils associés à différents comportements d’exposition solaire et leur impact potentiel sur les associations avec le risque de cancers cutanés. Par ailleurs, nos résultats ne soutiennent pas l’hypothèse d’un effet protecteur de la consommation de compléments alimentaires en antioxydants vis-à-vis du risque de cancers cutanés et appellent à davantage de recherches afin de mieux comprendre leurs effets à long terme sur la santé. / Background: Skin cancers are the most common cancers in white-skinned populations. While exposure to solar radiation is the best known risk factor, few studies have allowed a direct comparison of exposure profiles associated with these tumours within a single population, and little is known about the determinants of sun exposure behaviors. Moreover, although antioxidants, which have the ability of scavenging free radicals, are potential candidates for the chemoprevention of skin cancers, the current state of the literature does not allow to make clear conclusions with regards to their role on skin cancer risk.Objectives: The objective of this thesis is to examine the associations between UV exposures and skin cancer risk, to describe the profiles associated with several sun exposure behaviors, and to explore the potential associations between antioxidant dietary supplements and the risk of skin cancer in the French E3N (Étude Épidémiologique auprès de femmes de l’Éducation Nationale) study.Results: Our results suggest that the three types of skin cancers are associated with different sun exposure profiles and that sunscreen use, sunbed use, and solar supplement use are associated with both healthy and risky behaviors. In addition, our findings suggest that the use of solar supplements and vitamin E supplements is associated with an increased risk of non-melanoma skin cancers.Conclusions: This work emphasizes the importance of prevention to reduce the prevalence of skin cancers as well as the need to better understand the profiles associated with sun exposure behaviors and their potential impact on the associations with the risk of skin cancer. Furthermore, our results do not support the hypothesis of a protective effect of the consumption of antioxidant dietary supplements on the risk of skin cancer and call for more research in order to better understand their long-term effects on health.

As the prevalence of vitamin D deficiency continues to grow, mounting evidence supporting its link with chronic disease strengthens suggesting vitamin D’s candidacy in the prevention and treatment of multiple disease states and their complications. Dietary guidelines, however, do not take sun exposure into account. The present study sought to explore the impact of sun exposure on vitamin D status (serum 25(OH)D), and identify other significant determinants of serum levels which may have the greatest effects on overall health. Participants (n = 34) were pre-menopausal women aged 18 to 50 years (mean age 39 ± 6 years), who had their blood drawn at a local pathology lab and a follow-up appointment at a health assessment lab for the collection of other measurements. Mean serum 25(OH)D level was 64 ± 18 nmol/L, and mean dietary vitamin D intake was approximately 327 ± 229 IU/day. Although 82% of participants were below the RDA guidelines (600 IU/day for females ages 9-50 years) for dietary vitamin D intake, only 32% had serum 25(OH)D levels < 50 nmol/L (the recommended level of sufficiency for bone health) reflecting deficiency. While serum 25(OH)D levels were significantly correlated to dietary vitamin D intake (r = 0.42, p = 0.0139), it is reasonable to assume that participants obtained adequate vitamin D from sun exposure. Fasting serum insulin levels were significantly, positively correlated with BMI (r = 0.83, p < 0.0001), and sun exposure index (Body Surface Area x Minutes of Direct Sunlight) was significantly, positively correlated with serum 25(OH)D levels (fall weekend SEI: r = 0.47, p = 0.0059; spring weekend SEI: r = 0.43, p = 0.0135; average weekend SEI: r = 0.43, p = 0.013; and average overall SEI: r = 0.39, p = 0.0247). Reported sun exposure appeared to be least during winter weekdays and the most during summer weekends. Regression analysis was used to determine the strongest predictors of serum 25(OH)D levels, which were found to be sun exposure, dietary vitamin D intake, skin reflectance, age, BMI, and ethnicity (R2 = 0.58 , p = 0.0031), demonstrating that simple questionnaires, such as those employed in this study, can help to predict serum 25(OH)D status and thus be considered in the future treatment of vitamin D deficiency.