Introdução: A Síndrome dos Ovários Policísticos (SOP) é uma doença que implica em várias alterações como metabólicas, endócrinas e de composição corporal. Atualmente têm se discutido sobre medidas não farmacológicas para seu tratamento, e o exercício tem sido indicado como primeira conduta para melhora de diversos parâmetros. Objetivos: Avaliar os efeitos de dois protocolos de treinamento físico aeróbio sobre parâmetros hormonais, metabólicos, inflamatórios, de composição corporal, índices antropométricos e comprimento do telômero em mulheres com SOP. Material e Métodos: Trata-se de um ensaio clínico controlado com alocação aleatória e randomização estratificada pelo índice de massa corporal em 3 grupos: treinamento aeróbio contínuo (AC) com 28 voluntárias, treinamento aeróbio intermitente (AI) com 29 voluntárias e controle sem treinamento (GC) com 30 voluntárias. As avaliações dos parâmetros hormonais, metabólicos, inflamatórios e comprimento do telômero, foram realizadas por meio da dosagem sanguínea; os índices da composição corporal, avaliados pela circunferência de cintura e quadril e a composição corporal por meio da avaliação da absortometria de raio x de dupla energia. As avalições ocorreram antes e após o período de 16 semanas de intervenção do treinamento físico aeróbio ou de observação no grupo controle. Resultados: No grupo AC houve redução da circunferência de cintura (CC) (p = 0,045), circunferência de quadril (p = 0,032), níveis de colesterol total (p <= 0,01), LDL (p = 0,03) e testosterona (p <= 0,01). No grupo AI houve redução da CC (p = 0,014), relação cintura-quadril (p = 0,012), testosterona (p = 0,019) e índice de androgênio livre (p = 0,037). No grupo GC houve aumento da CC (p = 0,049), gordura corporal total (p = 0,015) e percentual da gordura corporal total (%) (p = 0,034), massa total dos braços (p < 0,01), percentual de gordura do tronco (p = 0,033), % de gordura das pernas (p = 0,021) e massa total ginóide (p = 0,011). Não houve alteração nas demais variáveis. Conclusão: Ambos os protocolos de treinamento reduziram índices antropométricos e hiperandrogenismo. O treinamento intermitente foi mais eficiente no controle do hiperandrogenismo, enquanto ocontínuo além de melhorar o hiperandrogenismo, promoveu redução nos parâmetros lipídicos, sem correlação entre a melhora de ambos parâmetros. Adicionalmente, ambos foram eficazes na prevenção do ganho de gordura corporal e do aumento da CC. Não ocorreram alterações após a intervenção no comprimento do telômero e demais variáveis analisadas. / Introduction: A Polycystic Ovary Syndrome (PCOS) is a disease that implicates in various changes like metabolic, endocrine and body composition. At present, non-pharmacological measures have been discussed for its treatment, and exercise has been indicated as the first conduit for improvement of several parameters.. Objectives: To evaluate the effects of two aerobic physical training protocols on hormonal, metabolic, inflammatory parameters, body composition, anthropometric indices and telomere length in women with PCOS. Material and methods: This was a randomized controlled trial and stratified randomized to body mass index into 3 groups: continuous aerobic training (CA) with 28 volunteers, intermittent aerobic training (IA) with 29 volunteers, and control without training with 30 volunteers. The evaluations of hormonal, metabolic, inflammatory parameters and telomere length were performed by means of a blood sample; body composition indices evaluated by waist and hip circumference and body composition by means of dual energy x-ray absorptiometry. The evaluations occurred before and after the 16-week intervention period of aerobic physical training or observation in the control group. Results: In the AC group, waist circumference (WC) (p = 0.045), hip circumference (HC) (p = 0.032), total cholesterol levels (p <= 0.01), LDL (p = 0.03) and testosterone (p <= 0.01). In the AI group there was a reduction in WC (p = 0.014), waist-hip ratio (p = 0.012), testosterone (p = 0.019) and free androgen index (p = 0.037). In the CG group there was an increase in WC (p = 0.049), total body fat (p = 0.015) and percentage (%) (p = 0.034), total arms mass (p <0.01), % trunk fat (p = 0.033), % of leg fat (p = 0.021) and total gynoid mass (p = 0.011). There was no change in the other variables. Conclusion: Both training protocols reduced anthropometric indices and hyperandrogenism. Intermittent training was more efficient in the control of hyperandrogenism, while the continuous, besides improving hyperandrogenism, promoted a reduction in lipid parameters, without correlation between the improvement of both parameters. Additionally, both wereeffective in preventing body fat gain and increased CC. There were no changes after intervention in telomere length and other variables analyzed.

Os estágios avançados da DPOC são longos e dolorosos processos onde há o aumento dos sintomas, fazendo com que o paciente entre em um ciclo vicioso de deterioração da capacidade física, dispneia, ansiedade e isolamento social. Deste modo, o exercício vem se mostrando um componente importante na DPOC, auxiliando no tratamento medicamentoso para a redução dos sintomas e melhora da qualidade de vida. Neste contexto, não há muitos relatos na literatura sobre o papel da atividade física no padrão de secreção de citocinas e na resposta proliferativa de pacientes com DPOC. Além disso, não há muita concordância sobre o comprimento do telômero e fenótipo celular quando a comparados tabagistas que não desenvolvem a doença e pacientes com DPOC. O objetivo deste trabalho foi comparar alguns parâmetros imunológicos entre pacientes com DPOC e indivíduos tabagistas sem DPOC, e em pacientes com DPOC antes e após o programa de reabilitação oferecido no Hospital das Clínicas da FMUSP. As coletas de sangue foram realizadas em dois momentos para o grupo DPOC (pré e pós-programa de reabilitação pulmonar), e em um único momento para o grupo tabagista. Estas amostras foram processadas para obtenção de células mononucleares do sangue periférico, onde foram analisados os seguintes parâmetros: proliferação celular e apoptose, fenotipagem de linfócitos, comprimento relativo do telômero e dosagem de citocinas. Verificamos que indivíduos tabagistas possuem menores quantidades de proteína C reativa que pacientes com DPOC, e uma tendência a maior número de linfócitos. Além disso, o comprimento relativo do telômero em tabagistas é maior do que em pacientes com DPOC, especialmente em linfócitos TCD8+, e em menor grau em linfócitos TCD4+. Linfócitos TCD8+ de portadores de DPOC apresentaram maiores porcentagens de células terminalmente diferenciadas, sugerindo exaustão celular destes linfócitos, e menores porcentagens de células de memória central e memória efetora. Pacientes com DPOC apresentam maiores quantidades de citocinas comparados aos tabagistas sem DPOC. Já na comparação pré e pós-reabilitação verificamos menores quantidades de leucócitos, menores pontuações nos questionários de sintomas, e maiores distâncias percorridas no teste de caminhada de 6 minutos. Na avaliação da linfoproliferação, para as células estimuladas com mitógeno (fitohemaglutinina) e antígenos (citomegalovirus e Haemophilus influenza) foi possível verificar melhora na resposta linfoproliferativa dos pacientes no período pós-reabilitação, assim como maiores níveis da citocina imunoreguladora IL-10. Deste modo concluímos que pacientes com DPOC possuem um perfil mais pró-inflamatório e de diferenciação terminal que tabagistas sem a doença e que exercício físico é capaz de modular o ambiente inflamatório melhorando alguns parâmetros da resposta imune celular / The advanced stages of COPD are long and painful with increase of symptoms making the patients enter a vicious cycle of deterioration of physical capacity, dyspnea, anxiety and social isolation. Therefore, the exercise shows an important component of COPD pathogenesis, assisting in pharmacological treatment, reducing symptoms and enhancing life quality. In this context, there are no concise reports in literature about the role of physical activity in the pattern of cytokine secretion and proliferative response in COPD patients. Besides this, there is no consensus in the data comparing smokers with COPD and smokers without COPD. Because of this, we compared some immune parameters of smokers with COPD and smokers without COPD, and evaluated the cellular immune response before and after a rehabilitation program offered at the Hospital das Clínicas FMUSP. Blood collection was performed in two moments in the COPD group (before and after the rehabilitation program), and once in smokers without COPD. After that the samples were processed to peripheral blood mononuclear cells isolation, in which were analyzed the cellular proliferation and apoptosis, the lymphocyte phenotypic characteristics, the telomere length and the cytokines levels in serum and culture supernatants. Smokers without COPD have lower levels of C reactive protein, and a trend to greater percentages of lymphocytes than in smoker with COPD. The telomere length of COPD patients was shorter than that of smokers without COPD, especially in TCD8+ lymphocytes, with a non-significant trend in the TCD4+ lymphocytes. The TCD8+ subpopulation of COPD patients comprised greater percentages of terminally differentiated cells, and lower percentages of central memory and effector memory cells, suggesting a bias to more terminally differentiated (and eventually exhausted) cells. Moreover, the levels of pro inflammatory cytokines were greater in COPD patients. Evaluation of the exercise effect, we found greater quantities of leucocytes, lower scores in the symptoms questionnaires and longer distances in the six minute walk test after the rehabilitation program. Besides this, the proliferative response to the mitogen phytohemaglutinin, and the antigens from cytomegalovirus and nontypeable Haemophilus influenza were all improved after the exercise program with greater levels of secretion of the anti-inflammatory cytokine IL-10. In conclusion, COPD patients have a pro inflammatory profile and a bias for more terminally differentiated (and eventually exhausted) cells when compared with smokers without COPD, and that the exercise program is capable of modulating the inflammatory microenvironment enhancing some parameters of the cellular immune response

Introdução: A Síndrome dos Ovários Policísticos (SOP) é uma doença que implica em várias alterações como metabólicas, endócrinas e de composição corporal. Atualmente têm se discutido sobre medidas não farmacológicas para seu tratamento, e o exercício tem sido indicado como primeira conduta para melhora de diversos parâmetros. Objetivos: Avaliar os efeitos de dois protocolos de treinamento físico aeróbio sobre parâmetros hormonais, metabólicos, inflamatórios, de composição corporal, índices antropométricos e comprimento do telômero em mulheres com SOP. Material e Métodos: Trata-se de um ensaio clínico controlado com alocação aleatória e randomização estratificada pelo índice de massa corporal em 3 grupos: treinamento aeróbio contínuo (AC) com 28 voluntárias, treinamento aeróbio intermitente (AI) com 29 voluntárias e controle sem treinamento (GC) com 30 voluntárias. As avaliações dos parâmetros hormonais, metabólicos, inflamatórios e comprimento do telômero, foram realizadas por meio da dosagem sanguínea; os índices da composição corporal, avaliados pela circunferência de cintura e quadril e a composição corporal por meio da avaliação da absortometria de raio x de dupla energia. As avalições ocorreram antes e após o período de 16 semanas de intervenção do treinamento físico aeróbio ou de observação no grupo controle. Resultados: No grupo AC houve redução da circunferência de cintura (CC) (p = 0,045), circunferência de quadril (p = 0,032), níveis de colesterol total (p <= 0,01), LDL (p = 0,03) e testosterona (p <= 0,01). No grupo AI houve redução da CC (p = 0,014), relação cintura-quadril (p = 0,012), testosterona (p = 0,019) e índice de androgênio livre (p = 0,037). No grupo GC houve aumento da CC (p = 0,049), gordura corporal total (p = 0,015) e percentual da gordura corporal total (%) (p = 0,034), massa total dos braços (p < 0,01), percentual de gordura do tronco (p = 0,033), % de gordura das pernas (p = 0,021) e massa total ginóide (p = 0,011). Não houve alteração nas demais variáveis. Conclusão: Ambos os protocolos de treinamento reduziram índices antropométricos e hiperandrogenismo. O treinamento intermitente foi mais eficiente no controle do hiperandrogenismo, enquanto ocontínuo além de melhorar o hiperandrogenismo, promoveu redução nos parâmetros lipídicos, sem correlação entre a melhora de ambos parâmetros. Adicionalmente, ambos foram eficazes na prevenção do ganho de gordura corporal e do aumento da CC. Não ocorreram alterações após a intervenção no comprimento do telômero e demais variáveis analisadas. / Introduction: A Polycystic Ovary Syndrome (PCOS) is a disease that implicates in various changes like metabolic, endocrine and body composition. At present, non-pharmacological measures have been discussed for its treatment, and exercise has been indicated as the first conduit for improvement of several parameters.. Objectives: To evaluate the effects of two aerobic physical training protocols on hormonal, metabolic, inflammatory parameters, body composition, anthropometric indices and telomere length in women with PCOS. Material and methods: This was a randomized controlled trial and stratified randomized to body mass index into 3 groups: continuous aerobic training (CA) with 28 volunteers, intermittent aerobic training (IA) with 29 volunteers, and control without training with 30 volunteers. The evaluations of hormonal, metabolic, inflammatory parameters and telomere length were performed by means of a blood sample; body composition indices evaluated by waist and hip circumference and body composition by means of dual energy x-ray absorptiometry. The evaluations occurred before and after the 16-week intervention period of aerobic physical training or observation in the control group. Results: In the AC group, waist circumference (WC) (p = 0.045), hip circumference (HC) (p = 0.032), total cholesterol levels (p <= 0.01), LDL (p = 0.03) and testosterone (p <= 0.01). In the AI group there was a reduction in WC (p = 0.014), waist-hip ratio (p = 0.012), testosterone (p = 0.019) and free androgen index (p = 0.037). In the CG group there was an increase in WC (p = 0.049), total body fat (p = 0.015) and percentage (%) (p = 0.034), total arms mass (p <0.01), % trunk fat (p = 0.033), % of leg fat (p = 0.021) and total gynoid mass (p = 0.011). There was no change in the other variables. Conclusion: Both training protocols reduced anthropometric indices and hyperandrogenism. Intermittent training was more efficient in the control of hyperandrogenism, while the continuous, besides improving hyperandrogenism, promoted a reduction in lipid parameters, without correlation between the improvement of both parameters. Additionally, both wereeffective in preventing body fat gain and increased CC. There were no changes after intervention in telomere length and other variables analyzed.

Os estágios avançados da DPOC são longos e dolorosos processos onde há o aumento dos sintomas, fazendo com que o paciente entre em um ciclo vicioso de deterioração da capacidade física, dispneia, ansiedade e isolamento social. Deste modo, o exercício vem se mostrando um componente importante na DPOC, auxiliando no tratamento medicamentoso para a redução dos sintomas e melhora da qualidade de vida. Neste contexto, não há muitos relatos na literatura sobre o papel da atividade física no padrão de secreção de citocinas e na resposta proliferativa de pacientes com DPOC. Além disso, não há muita concordância sobre o comprimento do telômero e fenótipo celular quando a comparados tabagistas que não desenvolvem a doença e pacientes com DPOC. O objetivo deste trabalho foi comparar alguns parâmetros imunológicos entre pacientes com DPOC e indivíduos tabagistas sem DPOC, e em pacientes com DPOC antes e após o programa de reabilitação oferecido no Hospital das Clínicas da FMUSP. As coletas de sangue foram realizadas em dois momentos para o grupo DPOC (pré e pós-programa de reabilitação pulmonar), e em um único momento para o grupo tabagista. Estas amostras foram processadas para obtenção de células mononucleares do sangue periférico, onde foram analisados os seguintes parâmetros: proliferação celular e apoptose, fenotipagem de linfócitos, comprimento relativo do telômero e dosagem de citocinas. Verificamos que indivíduos tabagistas possuem menores quantidades de proteína C reativa que pacientes com DPOC, e uma tendência a maior número de linfócitos. Além disso, o comprimento relativo do telômero em tabagistas é maior do que em pacientes com DPOC, especialmente em linfócitos TCD8+, e em menor grau em linfócitos TCD4+. Linfócitos TCD8+ de portadores de DPOC apresentaram maiores porcentagens de células terminalmente diferenciadas, sugerindo exaustão celular destes linfócitos, e menores porcentagens de células de memória central e memória efetora. Pacientes com DPOC apresentam maiores quantidades de citocinas comparados aos tabagistas sem DPOC. Já na comparação pré e pós-reabilitação verificamos menores quantidades de leucócitos, menores pontuações nos questionários de sintomas, e maiores distâncias percorridas no teste de caminhada de 6 minutos. Na avaliação da linfoproliferação, para as células estimuladas com mitógeno (fitohemaglutinina) e antígenos (citomegalovirus e Haemophilus influenza) foi possível verificar melhora na resposta linfoproliferativa dos pacientes no período pós-reabilitação, assim como maiores níveis da citocina imunoreguladora IL-10. Deste modo concluímos que pacientes com DPOC possuem um perfil mais pró-inflamatório e de diferenciação terminal que tabagistas sem a doença e que exercício físico é capaz de modular o ambiente inflamatório melhorando alguns parâmetros da resposta imune celular / The advanced stages of COPD are long and painful with increase of symptoms making the patients enter a vicious cycle of deterioration of physical capacity, dyspnea, anxiety and social isolation. Therefore, the exercise shows an important component of COPD pathogenesis, assisting in pharmacological treatment, reducing symptoms and enhancing life quality. In this context, there are no concise reports in literature about the role of physical activity in the pattern of cytokine secretion and proliferative response in COPD patients. Besides this, there is no consensus in the data comparing smokers with COPD and smokers without COPD. Because of this, we compared some immune parameters of smokers with COPD and smokers without COPD, and evaluated the cellular immune response before and after a rehabilitation program offered at the Hospital das Clínicas FMUSP. Blood collection was performed in two moments in the COPD group (before and after the rehabilitation program), and once in smokers without COPD. After that the samples were processed to peripheral blood mononuclear cells isolation, in which were analyzed the cellular proliferation and apoptosis, the lymphocyte phenotypic characteristics, the telomere length and the cytokines levels in serum and culture supernatants. Smokers without COPD have lower levels of C reactive protein, and a trend to greater percentages of lymphocytes than in smoker with COPD. The telomere length of COPD patients was shorter than that of smokers without COPD, especially in TCD8+ lymphocytes, with a non-significant trend in the TCD4+ lymphocytes. The TCD8+ subpopulation of COPD patients comprised greater percentages of terminally differentiated cells, and lower percentages of central memory and effector memory cells, suggesting a bias to more terminally differentiated (and eventually exhausted) cells. Moreover, the levels of pro inflammatory cytokines were greater in COPD patients. Evaluation of the exercise effect, we found greater quantities of leucocytes, lower scores in the symptoms questionnaires and longer distances in the six minute walk test after the rehabilitation program. Besides this, the proliferative response to the mitogen phytohemaglutinin, and the antigens from cytomegalovirus and nontypeable Haemophilus influenza were all improved after the exercise program with greater levels of secretion of the anti-inflammatory cytokine IL-10. In conclusion, COPD patients have a pro inflammatory profile and a bias for more terminally differentiated (and eventually exhausted) cells when compared with smokers without COPD, and that the exercise program is capable of modulating the inflammatory microenvironment enhancing some parameters of the cellular immune response

Orientador: Maria Isabel Nogueira Cano / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-26T06:26:57Z (GMT). No. of bitstreams: 1 DaSilva_MarceloSantos_D.pdf: 9189361 bytes, checksum: 79ecad917f6be7c8b200b549dafc493e (MD5) Previous issue date: 2014 / Resumo: A leishmaniose é um espectro de doenças causadas por parasitos do gênero Leishmania, que afeta milhões de pessoas em todo o mundo. Durante a infecção, os parasitos usam diferentes estratégias para sobreviver as defesas do hospedeiro, incluindo superar a exposição intensa a espécies reativas de oxigênio (ROS), principais responsáveis por causar danos no DNA, sobretudo nos telômeros, induzindo instabilidade genômica, senescência e morte celular. Telômeros são estruturas nos terminais dos cromossomos compostos por sequências de DNA repetitivas e proteínas, cuja função é proteger as extremidades dos cromossomos, evitando fusões terminais e degradação nucleolítica. Neste trabalho nós induzimos estresse oxidativo agudo em formas promastigotas de L. amazonensis através do tratamento com 2 mM de peróxido de hidrogênio (H2O2) por 1h, o qual foi capaz de aumentar os níveis de ROS intracelular, como demonstrado pela reação utilizando CM-H2DCFDA. Além disso, o estresse oxidativo induziu danos no DNA, como mostrado por análise quantitativa de 8-oxodG e núcleos positivos para o ensaio TUNEL. Observamos também, através de parâmetros qualitativos e quantitativos (Southern blot, telomere-PCR e flow-FISH), que o estresse oxidativo, assim como em mamíferos, induziu encurtamento dos telômeros. Analisando a co-localização e interação proteína:DNA por FISH-IIF e ensaios ChIP, foi possível demostrar que o estresse oxidativo causou erosão da extremidade 3¿G overhang, fazendo com que a proteína LaRPA-1 perdesse seu sítio de interação nos telômeros. Além disso, pudemos observar uma maior afinidade de LaRPA-1 para com a fita telomérica rica em C, nesse caso uma região de simples-fita gerada dentro da dupla fita telomérica, provavelmente como consequência do reparo de DNA, sugerindo a participação de LaRPA-1 na resposta a danos oxidativos. Por análise de curvas de crescimento e incorporação de EdU, foi possível observar que o estresse oxidativo induziu diminuição acentuada no número de parasitos em cultura, enquanto os sobreviventes continuaram proliferando e replicando DNA. Observamos também que o estresse oxidativo agudo provocou arrest de ciclo celular na fase G2/M em parte da população em crescimento exponencial. Em conjunto, esses resultados sugerem a presença de um sistema muito eficiente de resposta a danos oxidativos no DNA telomérico, que permite que os parasitos sobrevivam e repliquem DNA mesmo após um estresse agudo / Abstract: Leishmaniasis is a spectrum of diseases caused by parasites of the genus Leishmania that affects million people around the world. During infection, parasites use different strategies to survive host defenses including overcoming exposure to Reactive Oxygen Species (ROS), mainly responsible for causing DNA damage, especially at telomeres which frequently results in genome instability, senescence and cell death. Telomeres are chromosomes end termini structures composed by repetitive DNA coupled with proteins whose function is to protect chromosome ends and avoid end-fusion and nucleolytic degradation. In this work, we induced acute oxidative stress in promastigote forms of Leishmania amazonensis by treating parasites with 2mM hydrogen peroxide (H2O2) for 1 hour, which was able to increase intracellular ROS levels, as demonstrated by CM-H2DCFDA reaction. In addition, oxidative stress induced DNA damage, as confirmed by quantitative analysis of 8-oxodG and TUNEL-positive nuclei. We have also observed using qualitative and quantitative parameters (Southern blot, telomere-PCR and flow-FISH) that oxidative stress, as in mammals, induced telomere shortening. Analysing the protein:DNA co-localization and interaction by FISH-IIF and ChIP assays, it was possible to show that oxidative stress is able to induce erosion of the 3¿G overhang, inducing a displacement of LaRPA-1 from its telomeric interaction site. In addition, we observed an increase in the affinity between LaRPA-1 and the telomeric C-rich strand, in this case, a single-strand region inside the double-strand telomeric DNA generated probably as a consequence of DNA repair, suggesting the participation of LaRPA-1 in oxidative DNA damage response. Analysis of growth curves and EdU incorporation showed that oxidative stress induced a decrease in the number of parasites in culture, while the survivors continued proliferating and replicating DNA. Moreover, as result of acute oxidative stress, part of the parasites in exponential growth shows a G2/M cell cycle arrest. Taken together, these results suggest the presence of a very efficient oxidative damage response in the telomeres that allows parasites to survive and to replicate DNA even after acute stress / Doutorado / Genetica de Microorganismos / Doutor em Genetica e Biologia Molecular

The dose-response relationship between physical activity (PA), disease and mortality has primarily been obtained from self-report questionnaires in Western populations. A major limitation of self-reported PA is the likelihood of measurement error and these recordings cannot account for all 24-h activities, thus negating the influence of sedentary time and daily light intensity activity. Modern-day studies using objective measures of PA are highly controversial in the description of PA, as well as reliable wear time of these objective devices to accurately assess PA behaviour. The aim of the research presented in this thesis was to ascertain the associations between seven-day objectively measured PA (expressed as time spent in four different metabolic equivalent of task (MET) categories), cardiovascular disease risk factors (24-h ambulatory blood pressure and central obesity), chronic stress (General Health Questionnaire total score and serum cortisol) and DNA damage (leukocyte telomere length) in a cohort of African and Caucasian school teachers recruited from the Dr Kenneth Kaunda Education District in the North West Province of South Africa. All parameters were objectively measured (the GHQ was only added for thoroughness on measures of cognitive perceived stress) in the study population. The Africans (n=96) were younger than the Caucasians (n=107) (48.33 versus 51.06 years, p=0.024), but presented with slightly higher waist circumferences, significantly higher 24-h ambulatory systolic blood pressure (SBP, p≤0.000), diastolic blood pressure (DBP, p≤0.000) and mean arterial pressure (MAP, p≤0.000); significantly higher perceived stress scores (GHQ total scores, p=0.001) and significantly shorter telomeres (p≤0.000). The hypertensive participants in the total group (Africans and Caucasians combined) recorded 2.2 hours (12.4%) more daily awake sedentary time than the normotensive participants (p=0.004) and sedentary time was also a slightly better predictor of hypertension than moderate and vigorous activity time (Odds ratio=1.00, p=0.006). Irrespective of race and sex, 24-h SBP and DBP measurements were respectively associated with daily awake sedentary time (ß=0.17, p=0.018 and ß=0.18, p=0.020), light activity time (ß=-0.15, p=0.043 and ß=-0.16, p=0.041), waist circumference (ß=0.45, p≤0.000 and ß=0.33, p≤0.000) and log serum gamma glutamyl transferase (γ-GT, alcohol use) (ß=0.18, p=0.018 and ß=0.24, p=0.004). An older age (ß=-0.28, p≤0.000), higher alcohol consumption (ß=-0.21, p=0.003) and increased central obesity (ß=-0.17, p=0.017) were associated with shorter telomeres. Attenuated cortisol levels (ß=-0.12, p=0.068) showed a tendency towards associations with longer telomeres that may indicate possible cortisol down regulation to protect against DNA damage. Time spent in the different MET-categories showed no direct associations with either cortisol or telomere length. However, a sensitivity analysis indicated that daily light intensity activity time was significantly correlated with lower waist circumference (r=-0.21, p=0.004); a parameter associated with both cortisol (ß=-0.22, p=0.003) and telomere length (ß=-0.17, p=0.017). The thorough recording of PA during the true awake time of 24-h cycles over a period of seven days ensured that the beneficial effect of light intensity activities, as well as the detrimental effect of sedentary time, was highlighted by this study. The average awake time of all ethnic and sex groups were around 17 hours per day, which was more than most previous studies using objective measures of PA. The exclusion of participants who did not comply through wearing the Actiheart for a full seven days (n=143, 40%) did, however, have a negative impact on sample size that may have affected the statistical power for uncovering some significant associations and the high participant burden of the Actiheart device became clear. Therefore, the researchers used the data of the full seven-day recordings to also determine the minimum number of consecutive days the Actiheart device could be worn to accurately estimate energy expenditure and PA. The two-day combination of Wednesday-to-Thursday did not differ from the weekly average TEE, as well as for all MET-categories in all ethnic and sex groups. This two-day combination is practically convenient and would lessen participant burden. Future researchers are urged to test this combination in other populations to standardize Actiheart wear time. It can be concluded from the findings in this study that less daily awake sedentary time, more light intensity activity time, as well as lower alcohol consumption favour improved health as it is beneficial to 24-h ambulatory blood pressure and helps to maintain a healthy waist circumference, which ultimately influence telomere shortening. Furthermore, the two-day combination of Wednesday-to-Thursday seems to be sufficient to accurately estimate weekly energy expenditure and habitual PA with the Actiheart apparatus. / PhD (Human Movement Science), North-West University, Potchefstroom Campus, 2015

The dose-response relationship between physical activity (PA), disease and mortality has primarily been obtained from self-report questionnaires in Western populations. A major limitation of self-reported PA is the likelihood of measurement error and these recordings cannot account for all 24-h activities, thus negating the influence of sedentary time and daily light intensity activity. Modern-day studies using objective measures of PA are highly controversial in the description of PA, as well as reliable wear time of these objective devices to accurately assess PA behaviour. The aim of the research presented in this thesis was to ascertain the associations between seven-day objectively measured PA (expressed as time spent in four different metabolic equivalent of task (MET) categories), cardiovascular disease risk factors (24-h ambulatory blood pressure and central obesity), chronic stress (General Health Questionnaire total score and serum cortisol) and DNA damage (leukocyte telomere length) in a cohort of African and Caucasian school teachers recruited from the Dr Kenneth Kaunda Education District in the North West Province of South Africa. All parameters were objectively measured (the GHQ was only added for thoroughness on measures of cognitive perceived stress) in the study population. The Africans (n=96) were younger than the Caucasians (n=107) (48.33 versus 51.06 years, p=0.024), but presented with slightly higher waist circumferences, significantly higher 24-h ambulatory systolic blood pressure (SBP, p≤0.000), diastolic blood pressure (DBP, p≤0.000) and mean arterial pressure (MAP, p≤0.000); significantly higher perceived stress scores (GHQ total scores, p=0.001) and significantly shorter telomeres (p≤0.000). The hypertensive participants in the total group (Africans and Caucasians combined) recorded 2.2 hours (12.4%) more daily awake sedentary time than the normotensive participants (p=0.004) and sedentary time was also a slightly better predictor of hypertension than moderate and vigorous activity time (Odds ratio=1.00, p=0.006). Irrespective of race and sex, 24-h SBP and DBP measurements were respectively associated with daily awake sedentary time (ß=0.17, p=0.018 and ß=0.18, p=0.020), light activity time (ß=-0.15, p=0.043 and ß=-0.16, p=0.041), waist circumference (ß=0.45, p≤0.000 and ß=0.33, p≤0.000) and log serum gamma glutamyl transferase (γ-GT, alcohol use) (ß=0.18, p=0.018 and ß=0.24, p=0.004). An older age (ß=-0.28, p≤0.000), higher alcohol consumption (ß=-0.21, p=0.003) and increased central obesity (ß=-0.17, p=0.017) were associated with shorter telomeres. Attenuated cortisol levels (ß=-0.12, p=0.068) showed a tendency towards associations with longer telomeres that may indicate possible cortisol down regulation to protect against DNA damage. Time spent in the different MET-categories showed no direct associations with either cortisol or telomere length. However, a sensitivity analysis indicated that daily light intensity activity time was significantly correlated with lower waist circumference (r=-0.21, p=0.004); a parameter associated with both cortisol (ß=-0.22, p=0.003) and telomere length (ß=-0.17, p=0.017). The thorough recording of PA during the true awake time of 24-h cycles over a period of seven days ensured that the beneficial effect of light intensity activities, as well as the detrimental effect of sedentary time, was highlighted by this study. The average awake time of all ethnic and sex groups were around 17 hours per day, which was more than most previous studies using objective measures of PA. The exclusion of participants who did not comply through wearing the Actiheart for a full seven days (n=143, 40%) did, however, have a negative impact on sample size that may have affected the statistical power for uncovering some significant associations and the high participant burden of the Actiheart device became clear. Therefore, the researchers used the data of the full seven-day recordings to also determine the minimum number of consecutive days the Actiheart device could be worn to accurately estimate energy expenditure and PA. The two-day combination of Wednesday-to-Thursday did not differ from the weekly average TEE, as well as for all MET-categories in all ethnic and sex groups. This two-day combination is practically convenient and would lessen participant burden. Future researchers are urged to test this combination in other populations to standardize Actiheart wear time. It can be concluded from the findings in this study that less daily awake sedentary time, more light intensity activity time, as well as lower alcohol consumption favour improved health as it is beneficial to 24-h ambulatory blood pressure and helps to maintain a healthy waist circumference, which ultimately influence telomere shortening. Furthermore, the two-day combination of Wednesday-to-Thursday seems to be sufficient to accurately estimate weekly energy expenditure and habitual PA with the Actiheart apparatus. / PhD (Human Movement Science), North-West University, Potchefstroom Campus, 2015