<p>Conclusion of this study: These data suggest that 6 weeks of high-fat feeding induces hypertension but does not produce obesity, dyslipidemia and insulin resistance. However, this model may be useful in studying vascular reactivity in hypertension in the absence of insulin resistance.</p>

Background: Rheumatoid arthritis (RA) is characterised by excessive production of tumour necrosis factor alpha (TNFα). This leads to rheumatoid cachexia, a condition characterised by increased resting energy expenditure (REE) and loss of fat-free mass (FFM) leading to functional disability, decreased strength and balance. The aims of this research work was to: a) to develop a new REE equation in order to continuously monitor abnormal changes in REE in the RA population, b) to investigate if smoking further enhances hypermetabolism and c) to examine if the new anti-TNFα medication reverses this metabolic abnormality. Methods: 68 patients with RA were assessed for demographic and anthropometrical characteristics, REE (indirect calorimetry), body composition (bioelectrical impedance), and disease activity [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score 28 (DAS28) and health assessment questionnaire (HAQ)]. 20 of the total 68 patients, about to start anti-TNFα therapy, underwent the exact same aforementioned procedures but on three separate occasions (Baseline: two weeks prior to anti-TNFα treatment, Time-1 and Time-2: two weeks and three months, respectively, after the drug had been introduced. Results: Study 1: Based on FFM and CRP, a new equation was developed which had a prediction power of R2=0.76. The new equation revealed an almost identical mean with measured REE (1645.2±315.2 and 1645.5±363.1 kcal/day, p>0.05), and a correlation coefficient of r=0.87 (p=0.001). Study 2: Smokers with RA demonstrated significantly higher REE (1513.9±263.3 vs. 1718.1±209.2 kcal/day; p=0.000) and worse HAQ (1.0±0.8 vs. 1.7±0.8; p=0.01) compared to age and FFM matched RA non-smokers. The REE difference was significantly predicted by the interaction smoking/gender (p=0.04). Study 3: Significant increases were observed in REE (p=0.002), physical activity (p=0.001) and protein intake (p=0.001) between the three times of assessment. Moreover, disease activity significantly reduced [ESR (p=0.002), DAS28 (p=0.000), HAQ (p=0.000) and TNFα (p=0.024)] while FFM and total body fat did not change (both at p>0.05). Physical activity and protein intake were found to be significant within-subject factors for the observed REE elevation after 12-weeks on anti-TNFα treatment (p=0.001 and p=0.024, respectively). Conclusions: Findings from the first study revealed that the newly developed REE equation provides an accurate prediction of REE in RA patients. Moreover, the results from the second study showed that cigarette smoking further increases REE in patients with RA and has a negative impact on patients’ self-reported functional status. Finally, our data from the third study suggest that REE remains elevated not because of the maintenance of the RA-related hypermetabolism but due to the concomitant significant increases in physical activity and protein intake.

Rates of obesity (OB) are escalating among Canadian children and youth and the obesogenic environment is likely to cause further increases. An important aspect in providing clinical care to OB children is to have accurate assessment measures, particularly of their body composition and cardiorespiratory fitness. This project entails three interrelated projects aiming to develop novel cardiorespiratory fitness and body composition measurement techniques for an OB pediatric population. The purpose of the first project was to validate a new submaximal fitness protocol specifically geared towards OB children and youth. The second objective of this thesis involved assessing cardiorespiratory efficiency utilizing the Oxygen Uptake efficiency slope. The purpose of the third project was to determine the validity of a half-body scan methodology for measuring body composition in obese children and youth. The goal of developing these novel measurement techniques is improved design and evaluation of interventions aimed at managing pediatric obesity.

Cardiovascular disease (CVD) is one of the major health issues of our time. The prevalence of CVD is increasing, both in industrialized and in developing countries, and causes suffering and a decreased quality of life for millions of people worldwide. CVD can have multiple etiologies, but the main underlying cause is atherosclerosis, which causes blood clot formation and obstructs vital arteries. Multiple risk factors of atherosclerosis have been identified, and body fatness is one of the most important ones.  The main aims of this thesis were to investigate the relation between body fatness and: CVD risk factors (paper I), incident stroke (paper II), and overall mortality (paper III). The results showed that abdominal obesity is strongly associated with both CVD risk factors and stroke incidence (papers I-II). The results also suggested that a substantial part of the association between increased body fat and stroke can be explained by an increase in traditional stroke risk factors associated with increased body fat (paper II). A gynoid fat distribution, with a high share of fat located around the hip, is, on the other hand, associated with lower risk factor levels in both men and women, and with a decreased risk of stroke in women (papers I-II). This illustrates the importance of assessing the overall distribution of body fat rather, than solely focusing on total body fatness. In elderly women, total body fat was found to be associated with increased survival, while abdominal fat moderately increased mortality risk (paper III). Lean mass (fat-free mass) was strongly associated with increased survival among elderly men and women (paper III). Erythrocyte sedimentation rate (ESR) is an indicator of inflammation and, possibly, an indicator of atherosclerotic disease. In paper IV, the relationship between ESR in young adulthood and the later risk of myocardial infarction (MI) was studied. Results showed that higher levels of ESR were associated with a higher MI risk, in a dose-responsive manner, and was independent of other well-established risk factors. In summary, both total and regional fat distribution are associated with CVD risk factors and stroke, but do not seem to correspond to an increase in mortality risk among the elderly. Also, inflammation, detected as an increase in ESR, is associated with long term MI risk in young men.

Diss. (sammanfattning). Uppsala : Sveriges lantbruksuniv. / Härtill 4 uppsatser.

Diss. (sammanfattning) Umeå : Umeå universitet, 2006. / Härtill 4 uppsatser.

Based on Ph. D. Thesis--University of Southampton, 2002. / Includes bibliographical references.

Based on Ph. D. Thesis--University of Southampton, 2002. / Includes bibliographical references.

Made available in DSpace on 2015-05-14T12:14:12Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2241811 bytes, checksum: d494ba9e01bd7d249facca38063cf6ba (MD5) Previous issue date: 2014-04-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Theories of extra dimensions have been extensively studied in recent years with the original intention of solving the hierarchy problem. Among the models of extra dimensions we can mention the braneworld models, more precisely, the Randall-Sundrum model, which considers our universe as a brane embedded in an ambient space with an extra dimension of infinite size. The fundamental aspect of the brane models is that matter and fields are confined in a hypersurface and only gravity has access to all dimensions. Thus, observational tests involving gravity may provide a way of verifying the existence of extra dimensions. With this idea in mind, in this work, we find black hole solutions in a regularized version of a RSII type brane and then we consider two classical tests of general relativity to these solutions. We studied the in uence of transversal movement in the four-dimensional path of the particles. We note that the de ection of light and the time delay, in this scenario, depend on the energy ( frequency ) of the light signal and can, therefore, give rise to the phenomenon of gravitational rainbow. We also discuss a model of thick branes known as the split fermion model. In this model electrons and protons are located on di¤erent hypersurfaces of the brane. We found that, in the presence of a gravitational eld generated by a massive body, these particles will experience di¤erent four-dimensional geometries. This violation of the equivalence principle, from the viewpoint of four-dimensional observers, produces interesting phenomena as, for instance, the gravitational induction of an electric dipole in a hydrogen atom. We veri ed that the Hamiltonian that describes this e¤ect has the same form of the Stark Hamiltonian, i.e., H = ~A ~r, where the tidal acceleration ~A(due to the separation of electron and proton in the extra dimension) substitutes the electric eld and the reduced mass atom replaces the electric charge. / Teorias de dimensões extras têm sido amplamente estudadas nos últimos anos, com o intuito original de resolver o problema da hierarquia. Entre os modelos de dimensões extras podemos citar o modelo de branas Randal-Sundrum, que trata o nosso universo como uma brana imersa em um espaço ambiente com uma dimensão extra de comprimento infinito. O aspecto fundamental do cenário de branas é que a matéria e os campos estão confinados em uma hipersuperfície e, apenas, a gravidade tem acesso a todas as dimensões. Sendo assim, testes observacionais envolvendo a gravitação podem oferecer meios de se verificar a existência das dimensões extras. Com esta ideia em mente, neste trabalho, encontramos soluções de buracos negros em uma versão regularizada de uma brana (ou seja, com espessura) do tipo RSII e aplicamos, então, dois testes clássicos da relatividade geral para estas soluções de buracos negros, estudando a influência do movimento transversal nas trajetórias quadrimensionais das partículas. Constatamos que o desvio da luz e o atraso temporal, neste cenário, passam a depender da energia (frequência) do sinal luminoso, podendo, portanto, dar origem ao fenômeno de arco-íris gravitacional. Discutimos também um modelo de branas com espessura, conhecido como modelo de separação de férmions, formulado com o propósito de explicar a estabilidade do próton sem recorrer a algum tipo de simetria. Neste modelo, elétrons e prótons estão localizados em diferentes hipersuperfícies da brana. Verificamos que na presença de um campo gravitacional gerado por um corpo massivo, estas partículas irão sentir diferentes geometrias quadrimensionais. Esta aparente violação do princípio da equivalência, do ponto de vista de observadores quadrimensionais, produz interessantes fenômenos como, por exemplo, a indução, pela gravidade, de um dipolo elétrico em um átomo de Hidrogênio. Verificamos que a Hamiltoniana que descreve este efeito tem a mesma forma da Hamiltoniana de Stark, ou seja, H = ~A ~r, onde a aceleração de maré ~A (devido à separação de elétron e próton na dimensão extra) está no lugar do campo elétrico e a massa reduzida do átomo substitui a carga elétrica.

Obesity during childhood and adolescence is a serious public health concern in Canada and globally. Obesity is a complex disease with genetic, environmental, social, and behavioural determinants. However, our understanding of obesity and its development is limited by a reliance on proxy measurements of adiposity such as body mass index (BMI) and cross-sectional study designs that limit our ability to assess temporality. In this dissertation, I present the first set of body fat percent (BF%) accrual and velocity percentile curves for Canadian children and youth, investigate the relationship between BMI- and BF%-based definitions of obesity, and examine the longitudinal influence of sedentary time, moderate-to-vigorous physical activity (MVPA) and caloric intake on the development of BF%. My analyses are based on the UBC Healthy Bones III Study (HBSIII), a mixed longitudinal study of boys and girls aged 8-12 years at baseline, measured between 1999 and 2012. In HBSIII, adiposity was measured directly as BF% from total body dual energy x-ray absorptiometry (DXA) scans and MVPA and sedentary time were measured objectively using accelerometers. For the first study in my dissertation, I used generalized additive models for location scale and shape (GAMLSS) to develop sex- and ethnic-specific BF% accrual and velocity percentile curves. I present separate curves for Asian and Caucasian boys and girls aged 9-19 years at the 3rd, 10th, 25th, 50th, 75th, 95th, and 97th centiles. In this descriptive study, I found materially different shaped BF% percentile curves for Asian and Caucasian girls but not for boys. Second, I examined the relationship between BMI- and BF%-based definitions of obesity for Asian and Caucasian boys and girls aged 9-19 years. I used multivariable regression models, sensitivity and specificity analysis, receiver operating characteristic (ROC) curves, and Youden’s Index to explore this relationship. I found that BMI identified <50% of those classified with obesity based on BF%, and that classification performance of BMI differed significantly by age and sex subgroups for Asian and Caucasians. In my third analysis, I explored the longitudinal relationship between BF% and sedentary time, MVPA, and caloric intake as boys and girls mature. I fit polynomial multilevel models using MO (years from age at peak height velocity, APHV) as the time variable. Rate of change in BF% across maturity differed between boys and girls and differences in MVPA, sedentary time, and caloric intake between individuals influenced BF% at APHV (MO=0) and rate of change in BF% across maturity. Together, these studies advance our understanding of how body fat accrues as children and youth mature, and highlight the heterogeneity in predictors of adiposity and adiposity measurement accuracy across age, sex, and ethnic groups. / Graduate