Two major troponin I (TnI) genes, fetal TnI (ssTnI) and adult TnI (cTnI), are expressed in the mammalian heart under the control of a developmentally regulated program. In this study, the up-stream domain (~1,800 bp) of mouse fetal TnI gene has been cloned and characterized. There is a high homology of this region among mouse, rat and human. Transfection assays indicated that conserved GA-rich sequences, CREB and a CCAAT box within the first 300 bp upstream of the transcription start site were critical for the gene expression. Electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP) assays revealed binding proteins to CREB site in nuclear extracts from myocardial cells. Thyroid hormone (T3) caused a significant inhibitory effect on ssTnI expression in myocardial cells. Cardiac troponin I (cTnI) mutations have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. We modeled one mutation in human cTnI Cv terminus, arginine1 92 histidine (R192H) by cardiac specific expression of the mutated protein (cTnI193His in mouse sequence) in transgenic mice. The main functional alteration detected in cTnI193His mice by ultrasound cardiac imaging examinations was impaired cardiac relaxation manifested by a decreased left ventricular end diastolic dimension (LVEDD) and an increased end diastolic dimension in both atria. Echocardiography revealed a series of changes on the transgenic mice including a reversed E-to-A ratio, increased deceleration time, and prolonged isovolumetric relaxation time. At the age of 12 months, cardiac output in cTnI193His mice was significantly declined, and some transgenic mice showed congestive heart failure. The negative impact of cTnI193His on ventricular contraction and relaxation was further demonstrated in isolated mouse working heart preparations. / Dobutamine stimulation increased heart rate in cTnI193His mice but did not improve CO.The cTnI193His mice had a phenotype similar to that in human RCM patients carrying the cTnI mutation. The results demonstrate a critical role of the COOH-terminal domain of cTnI in the diastolic function of cardiac muscle. This mouse model provides us with a tool to further investigate the pathophysiology and the development of RCM. / by Jianfeng Du. / Thesis (Ph.D.)--Florida Atlantic University, 2008. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.

Transgenic mice were generated to express a restrictive cardiomyopathy (RCM) human cardiac troponin I (cTnI) R192H mutation in the heart. My study's objective was to assess cardiac function during the development of diastolic dysfunction and to gain insight into the pathophysiological impact of the RCM cTnI mutation. Cardiac function was monitored in cTnI193His mice and wild-type littermates for a period of 12 months. It progressed gradually from abnormal relaxation to diastolic dysfunction characterized with micro- echocardiography by a reversed E/A ratio, increased deceleration time, and prolonged isovolumetric relaxation time. The negative impact of cTnI193His on cardiac function was further demonstrated in isolated mouse working heart preparations. Dobutamine stimulation increased heart rate in cTnI193His mice but did not improve CO. The cTnI193His mice had a phenotype similar to that in human RCM patients carrying the cTnI mutation characterized morphologically by enlarged atria and restricted ventricle and functionally by diastolic dysfunction. / by Nariman Gobara. / Thesis (M.S.)--Florida Atlantic University, 2009. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.

This investigation was concerned with measuring aspects of cardiac function in conscious control, diabetic, hypertensive control, and hypertensive diabetic rats. Preliminary studies were conducted to determine catheter suitability and acute responses to atropine and angiotensin II in conscious animals. The catheter-manometer was tested using a square wave impact and was shown to accurately reproduce a left ventricular pressure pulse. Intravenous atropine caused both heart rate and left ventricular +dP/dt to rise. Intravenously administered angiotensin II caused systolic blood pressure to increase dramatically. In this case heart rate fell and +dP/dt was elevated. Hypertension was induced with deoxycorticosterone acetate (DOCA) and saline drinking water. Rats were first made diabetic with streptozotocin (60 mg/kg; i.v.). One week following this, subcutaneous DOCA (25 mg/kg) was administered twice weekly and all animals received saline drinking water. Following 2 and 5 weeks of DOCA treatment rats were catheterized and resting cardiovascular function was measured. DOCA treatment caused increased systolic and diastolic blood pressures to occur in control and diabetic rats at 2 and 5 weeks. Bradycardia was also observed in DOCA-diabetic and DOCA-control rats at 2 and 5 weeks of treatment. Two and 5 week hypertensive diabetic and control rats exhibited elevated -dP/dt and +dP/dt. The rate of contraction was shown to be proportional to the magnitude of systolic blood pressure in all treatment groups. It is concluded that diabetic rats and control rats did not differ in their response to hypertension after 5 weeks of DOCA treatment. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Restrictive cardiomyopathy (RCM) is a cardiac muscle disorder characterized by increased ventricular stiffness and diastolic dysfunction. Patients with RCM often present severe cardiac problems which usually lead to heart failure and sudden death. No effective treatment is available for RCM which makes the finding of novel efficient therapies an urgent necessity. Great progress in molecular biology techniques and advances in transgenic animal development provide great opportunities for the study of RCM and other cardiovascular diseases encountered in clinical patients.... Our laboratory is among the first to generate transgenic mouse models of RCM based on cardiac troponin I (cTnI) missense mutations. In this study, transgenic mice that suffer from RCM have been generated to understand the factors behind the diastolic dysfunction associated with that myocardial disease.... The information obtained from this study allows a better understanding of the role of troponin in RCM and the factors behind the physiopathology of the disease. It will also offer a therapeutic strategy taking into account the physiological characteristic of RCM. / by Pierre-Ives Jean-Charles. / Thesis (Ph.D.)--Florida Atlantic University, 2012. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Restrictive cardiomyopathy (RCM) is represented in part by left ventricular stiffness and diastolic dysfunction. Missense mutations of the cardiac troponin I (cTnI) gene cause idiopathic RCM. These mutations are located in the C-terminus of cTnI and affect cardiac relaxation. Transgenic mouse models presenting the pathology observed in clinical patients with RCM have been generated previously and express the mutant cTnI in their hearts. RCM-linked mutations increase cardiac myofilament Ca2+ sensitivity and promote diastolic dysfunction in the heart. Previous studies using double transgenic mice (cTnI/R193H/ND) showed that ventricular relaxation is enhanced in the cTnI/R193H transgenic mice. In this study, another double transgenic mouse model, (cTnI/R193H/ND/KO), provides an avenue to investigate its rescuing effects on RCMlinked mutations in the cTnI /R193H/KO mouse. Use of molecular biological techniques, transgenic animal developments and murine echocardiography in this study has culminated into a greater understanding of RCM and diastolic dysfunction. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

Abstract not available

A proteína dissulfeto isomerase (PDI) tem ganhado destaque em processos de sinalização celular. O objetivo deste trabalho foi investigar o papel da PDI na sinalização redox induzida por TNF-a em células endoteliais e por Angiotensina II (Ang II) em células musculares lisas vasculares (CMLV). Em cultura de células endoteliais isoladas da veia umbilical humana (HUVECs) os dados demonstraram que a PDI e a ERp46 regulam especificamente a fosforilação da ERK 1/2 induzida por TNF-a, possivelmente via alterações redox sobre a GTPase Ras e participa da angiogenese induzida por TNF-a. Em CMLV de artérias de resistência, os dados sugerem a participação da PDI na contração induzida por Ang II, bem como na disfunção vascular associada à hipertensão arterial, através da regulação da expressão e atividade da Nox1. Desta forma, podemos concluir que a PDI apresenta um papel na regulação da sinalização redox induzida por TNF-a e Ang II em células endoteliais e CMLV, respectivamente. Tais resultados apontam para um novo papel da PDI na fisiopatologia do sistema cardiovascular. / Protein disulfide isomerase (PDI), an oxidoreductase of endoplasmic reticulum, has emerged as a key player in cell signaling. The aim of the present study was to investigate the role of PDI in redox signaling induced by TNF-a in endothelial cells and by Angiotensin II (Ang II) in vascular smooth muscle cells (VSMCs). In human umbilical vein endothelial cells (HUVECs) ERp46 or PDI inhibition reduced specifically TNF-a-induced ERK1/2 phosphorylation, possibly via redox modifications in Ras GTPase and TNF-a-induced angiogenesis. In VSMCs from resistance arteries, our results suggest that PDI positively regulates Nox1 dependent signaling and expression in VSMCs from resistance arteries and could be a new player in the oxidative stress and vascular dysfunction observed in hypertension. Altogether, the results provide evidence for a role for PDI in cardiovascular pathophysiology.

A proteína dissulfeto isomerase (PDI) tem ganhado destaque em processos de sinalização celular. O objetivo deste trabalho foi investigar o papel da PDI na sinalização redox induzida por TNF-a em células endoteliais e por Angiotensina II (Ang II) em células musculares lisas vasculares (CMLV). Em cultura de células endoteliais isoladas da veia umbilical humana (HUVECs) os dados demonstraram que a PDI e a ERp46 regulam especificamente a fosforilação da ERK 1/2 induzida por TNF-a, possivelmente via alterações redox sobre a GTPase Ras e participa da angiogenese induzida por TNF-a. Em CMLV de artérias de resistência, os dados sugerem a participação da PDI na contração induzida por Ang II, bem como na disfunção vascular associada à hipertensão arterial, através da regulação da expressão e atividade da Nox1. Desta forma, podemos concluir que a PDI apresenta um papel na regulação da sinalização redox induzida por TNF-a e Ang II em células endoteliais e CMLV, respectivamente. Tais resultados apontam para um novo papel da PDI na fisiopatologia do sistema cardiovascular. / Protein disulfide isomerase (PDI), an oxidoreductase of endoplasmic reticulum, has emerged as a key player in cell signaling. The aim of the present study was to investigate the role of PDI in redox signaling induced by TNF-a in endothelial cells and by Angiotensin II (Ang II) in vascular smooth muscle cells (VSMCs). In human umbilical vein endothelial cells (HUVECs) ERp46 or PDI inhibition reduced specifically TNF-a-induced ERK1/2 phosphorylation, possibly via redox modifications in Ras GTPase and TNF-a-induced angiogenesis. In VSMCs from resistance arteries, our results suggest that PDI positively regulates Nox1 dependent signaling and expression in VSMCs from resistance arteries and could be a new player in the oxidative stress and vascular dysfunction observed in hypertension. Altogether, the results provide evidence for a role for PDI in cardiovascular pathophysiology.

心肺功能是其中一項體能特質，而對於進行較長時間的中至高劇烈程度運動十分重要，也會影響日常活動和健康。但是，還沒有研究香港華裔長者心肺功能水平及其與體能活動參與程度和健康的關條。 / 招募對象是從現有的兩個追蹤研究來的[男女骨折研究(n=998 和884 )和頸動脈粥樣硬化研究( 191 名婦女)， 70 - 79 歲年長男士最大攝氧量的參考範圖為22.3-23.0 毫升/分鐘/公斤(95%信賴區間) , 80 歲以上為19.2-20.2 毫升/分鐘/公斤。80 歲以上女性的參考範園為17.0-18.3 毫升/公斤/分鐘， 70-79 歲為19.3-20.0毫升/公斤/分鐘， 60-69 歲為2 1. 7-23.0 毫升/公斤/分鐘和年齡55-59 歲為22 .1 -23.8毫升/公斤/分鐘。男性的心肺功能與腰圍有相關性。<.0001) ，而女性的相關性還要加上體重(p<.02) ，與年齡有關的最大攝氧量衰退在男性為0.368 毫升/公斤/分鐘/年，而女性為0 .238 毫升/公斤/分鐘/年。 / 70 - 79 歲年長男士6 分鐘步行距離的參考範圍為453.3-466 公尺， 80 歲以上為382.6-403.3 公尺。80 歲以上女性的參考範圍為333.9-357.2公尺和年齡70-79 歲為396.1-406.8 公尺。6 分鐘步行距離與腰圍、身高和學歷有相關性(p:S:.05) ，與年齡有關的6 分鐘步行距離衰退在男性為9.06 公尺/年，而女性為7.35 公尺/年。從長者活動評估量表得出的體能活動參與程度被認為是與最大攝氧量成正相關(男性:r=.241，'女性:r=.214 )和6 分鐘步行距離(男性: r=.257，女性:r=.1 84) 。長者日常步行時間越長最大攝氧量和6 分鐘步行距離較佳(p≤01) ，進行劇烈運動的女性有正常最大攝氧量的機會較高(p=.041) 。男性能符合美國運動醫學學院或香港衛生署指引的明顯比不能達到指引的有較好的心肺功能。能達到指引的男性有1. 68 倍的概率有正常的心肺功能。回溯性研究追查過去的PASE 分數與現在最大攝氧量的相關性，反應出過去的體能活動參與程度對現在的心肺功能影響隨時間減少(男性由目前回到7 年前: r=0.241、0.168、0.120; 女性: r= .214、0.106、0.069 )。 / 患有高血壓男性的最大攝氧量和6 分鐘步行距離較差(p=.014) ，曾患有心肌硬塞或心絞痛男性和糖尿病女性的6 分鐘步行距離較差(p<.04) 。最大攝氧量分別與由社區認知篩選工具評估的男性認知水平（r=.107)和男女長者憂鬱量表分數男性:r=-.112 ，女性: r=-.123) 有相關性。另一方面， 6 分鐘步行距離被發現分別與簡易智能狀態測驗p<.02) 、男性的社區認知篩選工具(p=.046)的認知級別和男女長者憂鬱量表的抑鬱狀態p<.04)有差別。 / 最大攝氧量和6分鐘步行距離的年齡調整相關性連中高程度(男性:R=.459、女性: R=.425) 。除了與最大攝氧量有滿意的相關性，6分鐘步行距離與精神健康有比較密切的相關性。6分鐘步行距離可作為香港華裔長者最大攝氧量的體能代表值。 / Cardiorespiratory fitness (CRF) is one of the main attributes which is important toper form moderate-to-high intensity exercise for prolonged periods which affects daily activities as well as health. However, there are no studies among HK Chinese Elders' CRF and the relationship between this important parameter of physical fitness, PA participation and health outcomes. / By recruiting subjects from two existing cohort studies, the Osteoporetic Fractures in Men & Women Study (n=998 & 884 respectively) and the Carotid Atherosclerosis Study (191 women), the reference ranges of VO₂ peak for men were 22.3-23.0ml/min/kg (95% C.I.) at age 70-79y, and 19.2-20.2 ml/min/kg at age ≥80y. Forwomen, the reference range at age ≥80y was 17.0-18.3 ml/kg/min, 70-79y was19.3-20.0 ml/kg/min, 60-69y was 21.7-23.0 ml/kg/min and for age 55-59y was22.1-23.8 ml/kg/min. Men's VO₂ peak was associated with waist circumference(WC, p<.000l) while women's VO₂ peak additionally associated with weight (p<.02).There was an age-related decline in VO₂ peak at 0.368 ml/kg/minly in men and 0.238ml/kg/minly in women. / The reference ranges of 6MWD for men were 453.3-466.6m (95% C.I.) at age 70-79y, and 382.6-403.3m at age ≥80y. For women, the reference range at age 80≥y was 333.9-357.2m and for age 70-79y was 396.1-406.8 ml/kg/min. 6MWD was associated with WC, height and education (p≤.05). There was an age-related decline in 6MWD at 9.06m/y in men and 7.35m/y in women. / Elders' participation in PA assessed by the Physical Activity Scale for Elderly (PASE), was positively correlated with VO₂ peak (r=.241 in men, r=.214 in women) and 6MWD (r=.257 in men, r=.184 in women). Elderly walked more everyday have better VO₂peak and longer 6MWD (p≤ .0l). Women did more strenuous sport had higher chance of having normal CRF (p=.041). Men who met the guidelines by American College of Sports Medicine (ACSM) & Department of Health (DH), HK had better VO₂ peak than those who failed to meet that guidelines (p<.005). By following the PA guidelines, men had a 1.68-fold probability having normal CRF. A novel approach to retrospectively explore the correlation between the past PASE score and the present VO₂ peak revealed that the effect of past PA participation diminished with time (correlations for men from present, 4y and 7y ago: r=.241, .168, .120; for women r=.214, .106, .069). / Men with hypertension had significantly lower V02 peak and shorter 6MWD (p<.03). Men with history of myocardial infarction and angina also walked shorter in 6MWT while women only with diabetes had shorter 6MWD (p<.04). CRF was found to be correlated with cognitive level in men estimated by CSI-D (p<.0001) and GDS-15 score in both genders (r=-.112 in men, r=-.123 in women). On the other hand, 6MWD was found to be different across cognitive status estimated by MMSE (p<.02) & CSI-D (p=.046 in men only), and depression status estimated by GDS-15 (p<.04) in both genders. / Age-adjusted correlation between VO₂ peak & 6MWD was moderately high (R=.459 in men; R=.425 in women). In addition to the satisfactory correlation with VO₂ peak, stronger associations were found 6MWD, cognitive and mental health. It was suggested 6MWD might be a feasible surrogate for VO₂ peak as a physical fitness measure among HK Chinese elderly. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Yau, Chung Fai Forrest. / "December 2011." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 215-237). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese; appendix in Chinese. / ABSTRACT (IN ENGLISH) --- p.I / ABSTRACT (IN CHINESE) --- p.IV / ACKNOWLEDGEMENT --- p.VI / LIST OF CONTENTS --- p.VII / LIST OF TABLES --- p.XII / SELECTED ABBREVIATIONS --- p.XV / Chapter 1 --- BACKGROUND & OBJECTIVES --- p.1 / Chapter 1.1 --- INTRODUCTION --- p.1 / Chapter 1.2 --- OBJECTIVES OF THE STUDY --- p.3 / Chapter 1.3 --- OUTLINES OF THE THESIS --- p.4 / Chapter 2 --- LITERATURE REVIEW --- p.6 / Chapter 2.1 --- ELDERLY POPULATIONS --- p.6 / Chapter 2.1.1 --- Health --- p.6 / Chapter 2.1.1.1 --- Hypertension, Coronary Heart Disease & Stoke --- p.8 / Chapter 2.1.1.2 --- Diabetes --- p.10 / Chapter 2.1.1.3 --- Chronic Obstructive Pulmonary Disease --- p.11 / Chapter 2.1.1.4 --- Cognitive Function --- p.12 / Chapter 2.1.1.5 --- Depression --- p.13 / Chapter 2.2 --- THE RELATIONSHIP BETWEEN PA & HEALTH --- p.15 / Chapter 2.2.1 --- Participation in PA --- p.22 / Chapter 2.2.1.1 --- PA Recommendation --- p.24 / Chapter 2.2.2 --- Indirect Estimation ofPA Participation --- p.25 / Chapter 2.2.2.1 --- Physical Activity Scale for Elderly. --- p.26 / Chapter 2.3. --- PHYSICAL FITNESS & HEALTH. --- p.28 / Chapter 2.3.1 --- Definition of Physical Fitness. --- p.28 / Chapter 2.3.1.1 --- Cardiorespiratory Fitness --- p.30 / Chapter 2.3.2 --- Direct Assessment of Physical Fitness --- p.33 / Chapter 2.3.2.1 --- Cardiopulmonary Exercise Test --- p.33 / Chapter 2.3.2.1.1 --- Affordable Device for CPET --- p.35 / Chapter 2.3.2.2 --- Six Minutes Walk Test --- p.36 / Chapter 3 --- MATERIALS & METHODS --- p.39 / Chapter 3.1 --- SUBJECTS --- p.39 / Chapter 3.1.1 --- Subjects Source --- p.39 / Chapter 3.1.1.1 --- The Osteoporetic Fractures in Men & Women Study --- p.39 / Chapter 3.1.1.2 --- Carotid Atherosclerosis Study --- p.40 / Chapter 3.1.2 --- Follow up Situation --- p.40 / Chapter 3.1.3 --- Ethical Consideration --- p.41 / Chapter 3.2 --- INSTRUMENTATION --- p.41 / Chapter 3.2.1 --- Questionnaire --- p.41 / Chapter 3.2.1.1 --- Medical History --- p.41 / Chapter 3.2.1.2 --- Smoking Habit --- p.41 / Chapter 3.2.1.3 --- Cognitive & Mental Health --- p.42 / Chapter 3.2.1.3.1 --- Cantonese Mini Mental State Examination & Community Screening Instrument for Dementia --- p.42 / Chapter 3.2.1.3.2 --- Geriatric Depression Scale-15 --- p.42 / Chapter 3.2.1.4 --- Physical Activity Scale for Elderly --- p.43 / Chapter 3.2.1.5 --- Veteran Specific Activity Questionnaire --- p.44 / Chapter 3.2.2 --- Physical Measurements --- p.45 / Chapter 3.2.2.1 --- Height, Weight & Fat Percentage --- p.45 / Chapter 3.2.2.2 --- Waist, Hip Circumferences & WHR --- p.45 / Chapter 3.2.2.3 --- Blood Pressure --- p.45 / Chapter 3.2.2.4 --- Electrocardiograph --- p.46 / Chapter 3.2.3. --- Fitness Tests --- p.46 / Chapter 3.2.3.1 --- Cardiopuhuonary Exercise Test --- p.46 / Chapter 3.2.3.1.1 --- Exclusion Criteria --- p.46 / Chapter 3.2.3.1.2 --- PreTest Consideration --- p.47 / Chapter 3.2.3.1.3 --- Test Sequence & Measures --- p.48 / Chapter 3.2.3.1.4 --- Test Tennination Criteria --- p.49 / Chapter 3.2.3.2 --- Six Minutes Walk Test --- p.50 / Chapter 3.2.3.2.1 --- Six Minute Walk Test Sequence --- p.50 / Chapter 3.3 --- STATISTICS --- p.52 / Chapter 3.3.1 --- Description of Variables --- p.52 / Chapter 3.3.2 --- General Statistical Method --- p.53 / Chapter 3.3.3 --- Comparison between VO₂ peak & 6MWD Relationship with other Variables --- p.54 / Chapter 4 --- RESULTS --- p.56 / Chapter 4.1 --- RESPONSE & PARTICIPATION OF SUBJECTS --- p.56 / Chapter 4.2 --- DEMOGRAPHIC PROPERTIES --- p.63 / Chapter 4.2.1 --- Men --- p.63 / Chapter 4.2.2 --- Women --- p.68 / Chapter 4.2.3 --- Sample Representativeness --- p.71 / Chapter 4.2.4 --- Physical Measurements --- p.75 / Chapter 4.2.4.1 --- Peak Oxygen Uptake --- p.75 / Chapter 4.2.4.2 --- Correlations with Demographic Properties --- p.82 / Chapter 4.2.4.2.1 --- Mean VO₂ peak in Different WC Status --- p.83 / Chapter 4.2.4.2.2 --- Reference Range across Age Groups 98 --- p.84 / Chapter 4.2.4.2.3 --- Mllltivariat Analysis of VO₂ peak --- p.86 / Chapter 4.2.4.3 --- Six Minutes Walk Test --- p.88 / Chapter 4.2.4.3.1 --- UnivariateAnalysis with Demographic Properties --- p.90 / Chapter 4.2.4.3.2 --- Mean 6MWD by WC Status --- p.92 / Chapter 4.2.4.3.3 --- Reference Range by Age Groups --- p.92 / Chapter 4.2.4.3.4 --- Multivariate analysis of 6MWD --- p.94 / Chapter 4.2.5 --- Physical Activity Scale for Elderly --- p.96 / Chapter 4.2.5.1 --- Univariate Analysis with Demographic Properties --- p.97 / Chapter 4.2.5.2 --- Reference Range across Age Groups --- p.98 / Chapter 4.2.5.3 --- Reference Range of PASE --- p.99 / Chapter 4.2.5.4 --- Multivariate Analysis of PASE --- p.100 / Chapter 4.2.6 --- Cognitive & Mental Scores --- p.101 / Chapter 4.2.6.1 --- Community Screening Instrument for Dementia --- p.101 / Chapter 4.2.6.2 --- Mini-Mental State Examination --- p.102 / Chapter 4.2.6.3 --- Geriatric Depression Scale-15 --- p.103 / Chapter 4.3 --- CORRELATIONS OF CRF TESTS --- p.104 / Chapter 4.3.1.1 --- Relationship between 6MWD & VO₂ peak --- p.104 / Chapter 4.3.1.1.1 --- Pearson Correlation between 6MWD & VO₂ peak --- p.104 / Chapter 4.4 --- CRF & LIFESTYLES --- p.106 / Chapter 4.4.1 --- How PA correlates with CRF --- p.107 / Chapter 4.4.1.1 --- Relationship between PASE& VO₂ Peak --- p.107 / Chapter 4.4.1.1.1 --- Pearson Correlation between PASE & V02 peak. --- p.107 / Chapter 4.4.1.1.2 --- Mean VO₂ peak by Quartiles of PASE --- p.109 / Chapter 4.4.1.1.3 --- Mean PASE scores by VO₂ peak status --- p.110 / Chapter 4.4.1.1.4 --- Relationship between PASE leisure activities & VO₂ peak --- p.111 / Chapter 4.4.1.1.5 --- Time spent daily on PASE leisure activities by VO₂ peak status --- p.113 / Chapter 4.4.1.2 --- Relationship between PASE & 6MWD --- p.116 / Chapter 4.4.1.2.1 --- Mean 6MWD by Quartiles of PASE --- p.118 / Chapter 4.4.2 --- Relationship between CRF & Recommended PA Guidelines --- p.119 / Chapter 4.4.2.1 --- ACSM Guidelines --- p.119 / Chapter 4.4.2.2 --- HKDH Guidelines --- p.121 / Chapter 4.4.3 --- Does PASE in the Past Predict Present Maximal Oxygen Uptake --- p.122 / Chapter 4.4.3.1 --- Pearson Correlation between PASE at 3y before & Present VO₂ peak --- p.122 / Chapter 4.4.3.2 --- Pearson Correlation between PASE at 7y before & Present VO₂ peak --- p.124 / Chapter 4.5 --- CRF & HEALTH --- p.126 / Chapter 4.5.1 --- CRF & Physical Health --- p.126 / Chapter 4.5.1.1 --- Relationship between VO₂ peak & Medical History --- p.126 / Chapter 4.5.1.2 --- Relationship between 6MWD and medical history --- p.129 / Chapter 4.5.1.2.1 --- Mean 6MWD of men by chronic diseases --- p.130 / Chapter 4.5.1.2.2 --- Mean 6MWD of women by diabetes --- p.134 / Chapter 4.5.1.3 --- Comparison between VO₂ peak & 6MWD relationship with medical history --- p.135 / Chapter 4.5.2 --- CRF & Cognitive Function --- p.137 / Chapter 4.5.2.1 --- Relationship between MMSE& VO₂ Peak --- p.137 / Chapter 4.5.2.1.1 --- Pearson Correlation betweenMMSE & VO₂ peak --- p.137 / Chapter 4.5.2.1.2 --- Mean VO₂ peak by MMSE Status --- p.139 / Chapter 4.5.2.2 --- Relationship between MMSE & 6MWD --- p.141 / Chapter 4.5.2.2.1. --- Pearson Correlation between MMSE & 6MWD --- p.141 / Chapter 4.5.2.2.2 --- Mean 6MWD by MMSE category --- p.143 / Chapter 4.5.2.3 --- Relationship between CSID & VO₂ peak --- p.144 / Chapter 4.5.2.3.1 --- Pearson Correlation between CSID & VO₂ peak --- p.144 / Chapter 4.5.2.3.2 --- Mean VO₂ peak by CSID Classification --- p.146 / Chapter 4.5.2.4 --- Relationship between CSID & 6MWD --- p.147 / Chapter 4.5.2.4.1 --- Pearson Correlation between CSID & 6MWD --- p.147 / Chapter 4.5.2.4.2 --- Mean 6MWD by CSID Classification --- p.149 / Chapter 4.5.2.5 --- Comparison between VO₂ peak & 6MWD relationship with Cognitive Function --- p.150 / Chapter 4.5.2.5.1 --- Pearson Correlation between MMSE & 6MWD --- p.151 / Chapter 4.5.2.5.2 --- Mean 6MWD by MMSE category --- p.151 / Chapter 4.5.2.5.3 --- Pearson Correlation between CSID & 6MWD --- p.152 / Chapter 4.5.2.5.4 --- Mean 6MWD by CSID Classification --- p.153 / Chapter 4.5.3 --- CRF & Depression --- p.154 / Chapter 4.5.3.1 --- Relationship between GDS & VO₂ peak --- p.154 / Chapter 4.5.3.1.1 --- Speannan Correlation between GDS & VO₂ peak --- p.154 / Chapter 4.5.3.1.2 --- Logistic Regression Analysis --- p.154 / Chapter 4.5.3.2. --- Relationship between GDS & 6MWD --- p.156 / Chapter 4.5.3.2.1. --- Spearman Correlation between GDS & 6MWD --- p.156 / Chapter 4.5.3.2.2. --- Mean 6MWD by depression status. --- p.156 / Chapter 4.5.3.3. --- Comparison between VO₂ peak & 6MWD relationship with GDS --- p.158 / Chapter 4.5.3.3.1. --- Pears on Correlation between GDS & 6MWD --- p.158 / Chapter 4.5.3.3.2. --- Mean 6MWD by depression status --- p.158 / Chapter 5 --- DISCUSSION --- p.160 / Chapter 5.1 --- INTERPRETATION OF RESULTS --- p.160 / Chapter 5.1.1 --- Physical Fitness --- p.160 / Chapter 5.1.1.1 --- Cardiorespiratory Fitness --- p.160 / Chapter 5.1.1.1.1 --- Mode for CPET --- p.160 / Chapter 5.1.1.1.2 --- Criteria for VO₂ peak --- p.161 / Chapter 5.1.1.1.3 --- Reference Range of VO₂ peak among HK elderly --- p.164 / Chapter 5.1.1.1.4 --- Age Related Decline in VO₂ peak --- p.169 / Chapter 5.1.1.1.5 --- Repeatability of Measurements using FitMate[superscript TM] Pro --- p.170 / Chapter 5.1.1.1.6 --- Smoking --- p.170 / Chapter 5.1.1.2 --- Six Minutes Walk Test --- p.171 / Chapter 5.1.1.2.1 --- Reference Range of 6MWD among HK Elderly --- p.172 / Chapter 5.1.2 --- How Estimated PA Level Correlated to CRF --- p.173 / Chapter 5.1.2.1 --- CRF &PA --- p.174 / Chapter 5.1.2.2 --- CRF & Leisure Activities --- p.176 / Chapter 5.1.3 --- Elderly CRF of those who met Recommended PA Guidelines --- p.177 / Chapter 5.1.4 --- Could Past PA Participation Predict Present CRF --- p.180 / Chapter 5.1.5 --- Health --- p.181 / Chapter 5.1.5.1 --- Physical Health --- p.181 / Chapter 5.1.5.2 --- Dementia --- p.185 / Chapter 5.1.5.2.1 --- Community Screening Instrument for Dementia --- p.186 / Chapter 5.1.5.2.2 --- Mini-Mental State Examination --- p.188 / Chapter 5.1.5.2.3 --- Possible Mechanisms of Cognitive Decline & Benefits ofPA --- p.191 / Chapter 5.1.5.3. --- Depression --- p.193 / Chapter 5.1.5.3.1 --- Possible Mechanism of Depression & Benefits of PA --- p.197 / Chapter 5.1.6 --- 6MWD, a Better Physical Fitness Surrogate than VO₂ peak --- p.200 / Chapter 5.2 --- LIMITATIONS AND STRENGTH --- p.205 / Chapter 5.3 --- FUTURE STUDIES --- p.210 / Chapter 6 --- CONCLUSION --- p.211 / Chapter 7 --- REFERENCES --- p.215 / APPENDIX --- p.238

Indiana University-Purdue University Indianapolis (IUPUI) / Gender differences in the basal function of autonomic cardiovascular control are well documented. Consistent baroreflex (BRx) studies suggest that women have higher tonic parasympathetic cardiac activation compared to men. Later in life and concomitant with menopause, a significant reduction in the capacity of the BRx in females increases their risk to develop hypertension, even exceeding that of age-matched males. Loss of sex hormones is but one factor. In female rats, we previously identified a distinct myelinated baroreceptor (BR) neuronal phenotype termed Ah-type, which exhibits functional dynamics and ionic currents that are a mix of those observed in barosensory afferents functionally identified as myelinated A-type or unmyelinated C-type. Interestingly, Ah-type afferents constitute nearly 50% of the total population of myelinated aortic BR in female but less than 2% in male rat. We hypothesized that an afferent basis for sexual dimorphism in BRx function exists. Specifically, we investigated the potential functional impact Ah-type afferents have upon the aortic BRx and what changes, if any, loss of sex hormones through ovariectomy brings upon such functions. We assessed electrophysiological and reflexogenic differences associated with the left aortic depressor nerve (ADN) from adult male, female, and ovariectomized female (OVX) Sprague-Dawley rats. Our results revealed sexually dimorphic conduction velocity (CV) profiles. A distinct, slower myelinated fiber volley was apparent in compound action potential (CAP) recordings from female aortic BR fibers, with an amplitude and CV not observed in males. Subsequent BRx studies demonstrated that females exhibited significantly greater BRx responses compared to males at myelinated-specific intensities. Ovariectomy induced an increased overall temporal dispersion in the CAP of OVX females that may have contributed to their attenuated BRx responses. Interestingly, the most significant changes in depressor dynamics occurred at electrical thresholds and frequencies most closely aligned with Ah-type BR fibers. Collectively, we provide evidence that, in females, two anatomically distinct myelinated afferent pathways contribute to the integrated BRx function, whereas in males only one exists. These functional differences may partly account for the enhanced control of blood pressure in females. Furthermore, Ah-type afferents may provide a neuromodulatory pathway uniquely associated with the hormonal regulation of BRx function.