Thesis (Ph. D.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves 150-157).

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 118-126).

Thesis (M.A.)--University of Wisconsin--Madison, 1970. / eContent provider-neutral record in process. Description based on print version record.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1974. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis--University of Wisconsin--Madison, 1972. / Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

No description available.

Background: Exercise associated muscle cramping (EAMC) is a common medical condition encountered by endurance athletes, yet information regarding EAMC in cyclists in lacking. Aim of the study: To determine the epidemiology, clinical characteristics, and independent risk factors associated with EAMC in cyclists participating in a mass participation cycling event. Design: Cross-sectional study Setting: 2016 Cape Town Cycle Tour (CTCT), South Africa Participants: 22560 consenting cycle race entrants Methods: Epidemiological data (lifetime prevalence and annual incidence) and clinical characteristics (main muscle groups affected, timing of onset, severity [mild - severe] and frequency of serious forms of EAMC [sEAMC]) in cyclists with a history of EAMC (hEAMC) are reported on. A multiple regression analysis was applied in order to determine if the following factors were associated risk factors for EAMC in cyclists with a hEAMC: chronic disease composite score, cycling training / racing history (years of recreational cycling, years of participation in distance cycling events > 2 hours, average number of training sessions per week, average weekly cycling distance in the last 12 months, and average training speed), history of chronic disease (history of cardiovascular disease [CVD], risk factors for CVD, symptoms of CVD, metabolic/hormonal disease, respiratory disease, gastrointestinal disease, nervous system/psychiatric disease, kidney/bladder disease, haematological/immune system disease, and cancer) and allergies, and history of cycling injuries. Results: A total of 35914 cyclists entered the race, 27349 completed the online pre-race medical screening questionnaire, and 22560 gave informed consent for the use of their data in this study (62.82% of all race entrants). The lifetime prevalence of EAMC was 30.6%, with an annual incidence of 18.7%. The quadriceps muscle group was the most commonly affected muscle group (47.7%), the most common time period for the onset of EAMC was during the fourth quarter of the race (63.0%), and mild (less than 5 minutes) EAMC occurred more frequently (67.0%) than other forms of EAMC. Serious EAMC was reported by 5.6% of the study population, and included whole body EAMC (3.2%) and EAMC associated with dark urine (2.2%). Novel independent risk factors associated with an increased risk of hEAMC in cyclists were: a higher chronic disease composite score (PR=1.34 per 2 unit increase; p<0.0001), a history of any allergies (PR=1.17; p<0.0001), a history of an acute onset injury (PR=1.31; p<0.0001), a history of a gradual onset injury (PR=1.29; p<0.0001), and increased number of years participating in cycling events of > 2 hours (PR=1.34 per 2 unit increase, p<0.0001). Increased number of years as a recreational cyclist (PR=0.96 per 5 unit increase, p=0.0012) and increased average weekly training/racing frequency in the last 12 months (PR=0.95 per 2 unit increase, p=0.0015) were associated with a decreased risk of EAMC. From the univariate analysis, we identified a significantly higher prevalence of lifetime hEAMC in male cyclists (PR=2.16; p<0.0001), and a higher prevalence of hEAMC in the ≥51-year age category (37.6%). Conclusion: One in three cyclists report a lifetime hEAMC. In cyclists with a hEAMC, the quadriceps muscle group is the most commonly affected muscle group, EAMC commonly occurs in the last quarter of the race, most EAMC cases are reported as mild, and sEAMC is not common. The results from this study could influence the future prevention and management programmes of EAMC in recreational cyclists, and assist medical personnel in the planning and implementation of medical care at mass participation cycling events. A higher chronic disease composite score, a history of allergies, a history of injury (acute onset or gradual onset) and training / racing variables are novel independent risk factors associated with a hEAMC in cyclists taking part in a mass participation cycling event. Risk factors for EAMC need to be taken into consideration when implementing prevention and management programmes of EAMC in cyclists. Clinicians should also consider that in some cases, EAMC may be associated with underlying chronic diseases or allergies, and/or the medications used to treat such conditions. In addition, injury history and training variables need to be considered in the prevention and management of EAMC in cyclists. Keywords: muscle cramping, exercise associated muscle cramping, EAMC, cyclists, clinical characteristics, epidemiology, risk factors, chronic disease / Dissertation (MPhysiotherapy)--University of Pretoria, 2020. / Physiotherapy / MPhysiotherapy / Restricted

The transthyretin-associated amyloidoses are a group of protein-folding disorders caused by deposition of the liver-secreted plasma protein transthyretin (TTR) in various tissues of the body. The sporadic form of the disease is caused by deposition of wild-type TTR whereas the inherited form is caused by deposition of mutated TTR; there are over 100 known amyloidogenic mutations of the TTR gene. The transcriptional regulation of the mouse transthyretin gene has been well studied. Organ-specific modulation of TTR mRNA is achieved by coordinated binding of hepatocyte-specific and ubiquitously expressed transcription factors to regulatory regions in the proximal promoter and upstream enhancer region. The hypothesis of this dissertation is that non-coding genetic sequence variations in the promoter of the transthyretin gene situated upstream of the regulatory regions, alter its transcriptional regulation, contributing to the onset and expression of transthyretin-associated amyloidosis. Previously, we identified a significant association of a non-coding polymorphism of the TTR promoter, rs3764479, with age of onset and survival in patients with ATTRwt amyloid disease. In this dissertation, electrophoretic mobility shift assays (EMSA) were used to investigate transcription factor binding of HepG2 nuclear proteins to short DNA probes with and without rs3764479. These mobility shift studies revealed that HepG2 nuclear extract proteins showed higher affinity to the wild-type TTR sequence than to one containing the rs3764479 SNP. Competition EMSAs suggested SNP-related changes in the binding of transcription factors hepatocyte nuclear factor-1 (HNF1) and hepatocyte nuclear factor-3b may alter TTR gene transcription. To investigate transthyretin gene regulation in V122I ATTR amyloid, the most prevalent TTR gene variant in the United States, the proximal promoter region from patients with V122I ATTR amyloidosis was sequenced and analyzed. In total, 8 SNPs were identified; one (rs955705399) was significantly associated with disease between the two V122I genotype-positive cohorts studied with and without cardiomyopathy. It is postulated that the presence of SNPs could influence gene expression and ultimately disease pathogenesis. In summary, these studies suggest that presence of disease-associated non-coding genetic variations modify transthyretin gene expression by disrupting transcription factor binding and may, in part, explain the clinical heterogeneity seen in patients with transthyretin-associated amyloidoses.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24503号 / 医博第4945号 / 新制||医||1064(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 羽賀 博典, 教授 椛島 健治, 教授 後藤 慎平 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

付記する学位プログラム名: グローバル生存学大学院連携プログラム / 京都大学 / 新制・課程博士 / 博士(医学) / 甲第24510号 / 医博第4952号 / 新制||医||1064(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中山 健夫, 教授 小杉 眞司, 教授 村井 俊哉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM