Ph.D., Faculty of Science, University of the Witwatersrand, 2011 / Mole rats are a unique family of the rodent order and are known for a subterranean lifestyle, reduced eye size, regressed visual system and unusual patterns of circadian rhythmicity (co-existence of rhythmic and arrhythmic chronotypes within a species has been documented). Such dramatic changes especially that of phenotype, may lead to the prediction of significant differences in organisation of the brain and physiology, therefore these unusual phenotypic features form the core rationale providing the impetus for the present series of studies. Neuroanatomical examination of the mole rat brain for immunohistochemical markers of the cholinergic, catecholaminergic, serotonergic, orexinergic, and histaminergic systems revealed neuronal organisation that was remarkably similar to those previously reported in other rodents and mammals, despite the notable differences in lifestyle and phenotype. These results indicate a strong phylogenetic constraint acting at the systems level of neuronal organisation. The study of sleep and wake in rhythmic and arrhythmic chronotypes of a species of mole rat indicated the arrhythmic chronotype spent more time awake with a longer average duration of a waking episode and less time in sleep with a shorter average duration of a SWS episode. While remaining somewhat similar between mole rat chronotypes, total sleep time in the mole rats was significantly reduced in comparison to other rodents. These results also indicate independence of circadian rhythmicity and sleep homeostasis and possible alteration of specific genes involved in the sleep-wake cycle of the mole rats examined. Stereological assessment of absolute numbers of orexinergic neurons revealed that the arrrhythmic chronotype tends to have more orexinergic neurons per gram of body mass that the rhythmic chronotype, leading to the conclusion that enhanced vigilance and peripheral metabolism of the arrhythmic chronotype may underlie this difference. Immunohistochemical identification of nuclei involved with the sleep-wake cycle, showed no difference in the distribution of these nuclei between circadian chronotypes and no major differences when compared to other rodents. Some interesting and potentially functionally important homogeneities were observed in the distribution of GABAergic interneurons within the pontine region. Furthermore differential orexinergic terminal network densities were observed between chronotypes within the arcuate nucleus and the intergeniculate leaflet. Therefore despite unusual features in lifestyle and phenotype, the organisation of the mole rat brain remains remarkably similar to other rodents; however, distinctions of circadian chronotype consistently produced subtle differences in both the anatomy and physiology of these rodents.

Ph.D., Faculty of Science, University of the Witwatersrand, 2011 / This study investigated the effect of exogenous melatonin administration on transient global cerebral ischemia and adult neurogenesis in adult male Sprague- Dawley rats. It also determined serum melatonin concentrations in all the experimental groups and established any effect of melatonin on estimated total granule cell numbers. Adult male Sprague-Dawley rats were divided into eight groups with each group consisting of 6 rats (n = 6). Post-induction time durations of 72 hours and 7 days was used. Single dose of 5 mg/kg exogenous melatonin was administered at each phases of 30 minutes before and after a 10 minutes transient bilateral occlusion of the common carotid arteries in the different groups, followed by reperfusion. Rats were anesthetized with 20 mg/kg of ketamine and 2.5 mls of blood was collected via cardiac puncture for estimation of serum melatonin concentration using commercially prepared radioimmunoassay ELISA kit. Free floating brain sections cut at 50 μm were immunostained for Ki-67, marker for proliferating cells. The total granule cell number in the dentate gyrus was estimated using the optical fractionator method on plastic embedded brain sections. Mean melatonin concentration (pg/mol) was 268.54 ± 28.73 (72 hours) and 277.83 ± 28.73 (7 days) compared to the sham control; 266.94 ± 37.6 and non surgical 262.96 ± 23.85 respectively. Differences in the concentration were not statistically significant (P<0.05). Histological finding indicated neuropil disruption with potentiation of restoration as the post ischemia days progressed in the melatonin administered groups. The estimated total granule cell number in the dentate gyrus of the hippocampus was not affected by exogenous melatonin administration. However, there was potentiation in proliferations of the neurogenic niche in the dentate gyrus of the hippocampus demonstrating a very strong indications that melatonin enhanced the generations of proliferating cells in adult male Sprague-Dawley rats.

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No description available.

The purpose of this research was to identify the impact of students’ choice of time of day for class activity and their sleep quality on academic performance in multidisciplinary distance education courses at a southeastern U.S. state college. The research addressed the relationship of other individual student characteristics (i.e., age, gender, race/ethnicity, educational background, or course workload) and external factors (i.e., marital status, hours of employment, part-time or full-time status, or caretaker responsibilities represented by the number of children and/or elderly that the student was actively caring for in their home) to the students’ academic performance and to the students’ choice of time of day for class activity and sleep quality. This study analyzed distance education students’ Pittsburgh Sleep Quality Index (PSQI) Global Sleep Quality Scores, their demographic and external factor survey responses, a test grade, and the time of day that the student submitted their test. This study targeted the distance education student population, as they are part of a rapidly growing sector within higher education, and they had previously not served as the primary subjects in research regarding sleep quality and external factor impacts on academic success. Analyses of 208 distance education students resulted in the following research findings: sleep quality was found to be related to academic success, with significant findings of, for example, poorer sleep quality correlating with a lower test grade (r = -0.15; p = .03), likewise the number of hours spent working was related to academic success, with a significant finding of more hours spent working correlating with a lower grade (r = 0.377; p = .008). In this study most other factors were found to have no significant relationship with a students’ grades (age, gender, race/ethnicity, educational background, or course workload, marital status, or caretaker responsibilities). These research findings may enlighten students of the potential impacts of taking distance education classes if they anticipate having to work extensively or if they have, or expect to have, poor sleep quality. Additionally, educational institutions and faculty can learn ways to design better distance education courses and provide improved guidance for students to encourage academic success. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

The quantification of athlete pre-competitive sleep behaviour is of interest owing to the possibility that sleep loss may have a negative effect on health and performance. The purpose of this study was to monitor and quantify the sleep/wake patterns of South African cyclists prior to competitive races. A total of 336 cyclists, male and female and of differing competition levels, cycling in either the 2015 Tsogo Sun Amashova or the 2016 Telkom 94.7 Cycle Challenge completed an altered version of the Competitive Sports and Sleep Questionnaire. The questionnaire asked cyclists to report on precompetitive sleep over the past year. A subset of 92 cyclists also recorded a Core Consensus Sleep Diary for the three nights leading up to the races. The questionnaire showed that 67% of the cyclists reported worsened sleep at least once prior to competition within the past 12 months. The sleep diary found that the cyclists’ average sleep duration the night before the races was 6h19min (±1h38min), which was significantly less than two and three nights prior to the races. Sleep quality was also shown to deteriorate significantly the night before the races. The contributing factors leading to worsened pre-competitive sleep were the time the cyclists had to wake-up as well as perceived increases in sleep latency and awakenings after sleep onset. Anxiety was found to be the major cause of sleep disturbances. While females were found to be significantly more likely to report having experienced poorer sleep before competition in the past year, the sleep diary showed no difference in sleep the night before the races between the sexes. Females were significantly more likely to report instances of unpleasant dreams and waking up during the night. Again, the sleep diary data did not corroborate these findings. Females were also found to report significantly more accounts of nervousness or thoughts about competition as being the cause of sleep problems. There was no difference in sleep loss the night before competition when comparing competition-level groups. The only significant difference was that recreational cyclists were more likely to report sleeping in foreign environments as a cause of sleep disturbances. Despite a large percentage of cyclists experiencing pre-competitive sleep loss, over half (55%) perceived sleep loss to have no impact on their performance. Analysis of pre-sleep behaviour also revealed that the cyclists engaged in several practices that may have a negative effect on subsequent sleep. The vast majority of the cyclists (61%) indicated having no specific strategy to help them sleep the night before competition. Fifteen percent of cyclists reporting using media devices to help them fall asleep, a practice that has been shown to disrupt sleep. In conclusion, most cyclists, regardless of sex and level of competition experience precompetitive sleep loss attributed largely to anxiety but with the perception that this loss in sleep does not negatively impact their performance.

The current study aimed to examine the naturalistic relationship between physical activity and sleep by exploring frequency, type, and timing of exercise and their association with a variety of sleep variables (e.g., sleep onset latency, wake after sleep onset, sleep efficiency). Young adults (n = 1003) completed a variety of self-report questionnaires, including a week-long sleep diary and a survey of typical frequency, type, and timing of exercise completed in the past week. Increased frequency of physical activity was related to increased sleep efficiency (total sleep time/time in bed), decreased time in bed, and decreased time spent awake in bed in the morning. Greater amounts of exercise energy expenditure (i.e., metabolic equivalents) per week was related to increased sleep efficiency, and decreased time in bed and time spent awake in bed in the morning. After controlling for other factors, this relationship remained true only for time spent awake in bed in the morning. Early morning exercisers reported shorter total sleep time and time in bed than those who typically exercised at other times. No exercise differences were found between those who met the research diagnostic criteria for insomnia and those who did not. This study provides valuable information to help guide future experimental and intervention studies.

Circadian systems drive daily oscillations in physiology in organisms from bacteria to humans. These oscillations are coordinated by specific changes in environmental cues, the most important of which is light. In animals, circadian regulation of brain function creates rhythmic patterns in behaviors like sleep. Circadian dysregulation is a common feature of many human diseases and environmental causes of circadian disruption increase susceptibility to many diseases including cancer. Importantly, circadian disruption is also commonly seen in hospitalized patients, which could have negative effects on health outcomes. Understanding the basic biology of circadian-regulatory systems and their physiological functions is essential for identifying the impact of circadian rhythms on human health. This dissertation describes a body of work using the fruit fly Drosophila melanogaster to better understand circadian regulation and its impact on behavior and physiology.

Primary dysmenorrhoea, or painful menstruation in the absence of pelvic pathology, is a common, and often debilitating, gynaecological condition that affects between 45 to 95% of menstruating women. Despite the high prevalence, dysmenorrhoea is often poorly treated, and even disregarded, by health professionals, pain researchers, and the women themselves, who may accept it as a normal part of the menstrual cycle. The overall purpose of this thesis is two-fold: first, to contribute knowledge about the impact and consequences of recurrent severe menstrual pain on pain sensitivity, mood, quality of life and sleep in women with primary dysmenorrhoea, and secondly, to investigate day-time and night-time treatment of recurrent primary dysmenorrhoeic pain. For this thesis, I completed five separate studies on three different groups of young, otherwise healthy women with a history of severe primary dysmenorrhoea, and age-matched controls without dysmenorrhoea. The first two studies, presented in Chapter 2, addressed the question of whether women with primary dysmenorrhoea are hypersensitive to experimental pain. I used clinically-relevant experimentally-induced muscle pain stimuli (intramuscular injection of hypertonic saline and ischaemia) in referred and non-referred sites of menstrual pain, at different phases of the menstrual cycle. Women with dysmenorrhoea, compared to women without dysmenorrhoea, had increased sensitivity to deep-muscle pain both within the area of referred menstrual pain and at a remote pain-free site. Further, the increased muscle pain sensitivity was evident even in phases of the menstrual cycle when women did not have menstrual pain, illustrating that the changes in pain perception extend outside of the painful menstruation phase. These findings suggest that women with dysmenorrhoea show long-lasting changes in pain processing possibly because of the recurrent dysmenorrhoeic pain. A secondary aim of the study presented in Chapter 2a, was to determine the impact of menstrual cycle phase on experimentally-induced muscle pain sensitivity in women with and without primary dysmenorrhoea. My results suggest that menstrual cycle phase has no effect on pain sensitivity in either group of women. As part of my studies, I investigated the impact of dysmenorrhoeic pain on quality of life and mood. I found that women with dysmenorrhoea had a significantly reduced quality of life (Chapter 3) and poorer mood (Chapter 2a and Chapter 5), during menstruation compared to their pain-free follicular phase, and compared to the menstruation phase of the pain-free control women. These data highlight the negative impact that primary dysmenorrhoea has on young women, for up to a few days every month. Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed as the first-line therapy for menstrual pain. Yet, severe dysmenorrhoeic pain is often poorly managed, especially at night, when the pain likely disrupts sleep. I conducted two studies investigating the effectiveness of diclofenac potassium, a readily-available NSAID with a low side-effect profile, compared to placebo, in alleviating severe primary dysmenorrhoeic pain across the day (Chapter 4), and during the night (Chapter 5). I also investigated the effectiveness of diclofenac potassium in improving subjective and objective sleep quality (Chapter 5). I found that the daily recommended dose (150 mg) of diclofenac potassium, administered at three timepoints across the first 24 hours of menstruation, significantly reduced perceived menstrual pain, compared to placebo. I confirmed that dysmenorrhoeic pain reduces polysomnographic and subjective measures of sleep quality compared with the pain-free follicular phase. I also showed, for the first time, that diclofenac potassium is effective, compared to placebo, in alleviating nocturnal pain, along with restoring subjective sleep quality and polysomnographic measures of objective sleep quality in women with severe primary dysmenorrhoea. My studies have addressed several gaps in the knowledge about primary dysmenorrhoea. I have shown that women with primary dysmenorrhoea are hypersensitive to deep muscle pain, supporting the hypothesis of other researchers that the recurrent menstrual pain experienced by these women is associated with central sensitisation, and may predispose women with primary dysmenorrhoea to other chronic painful conditions. Therefore, limiting the monthly noxious input into the central nervous systems of these women, by means of effective treatment of dysmenorrhoea, may improve their long-term health. The research presented in this thesis further highlights the efficacy of diclofenac potassium in relieving not only day-time and night-time dysmenorrhoeic pain, but also in restoring objective and subjective pain-induced sleep disturbances in women with dysmenorrhoea. Further, my research has shown that dysmenorrhoeic pain has an immediate negative impact on quality of life and mood during menstruation. The results of this thesis show the multi-factorial impact of dysmenorrhoea and should stimulate further research about the long-term benefits of effective treatment of menstrual pain.

Out of 60 million Americans suffering from sleep disorder, an estimated 18 million have sleep apnea. According to the U.S. Department of Health & Human Services, sleep apnea is a chronic condition that disrupts a patient’s sleep. While the annual cost of treating sleep apnea patients in the United States is approximately $3.18 billion (including screening costs) it is estimated that untreated sleep apnea may cause $3.4 billion in additional medical costs. A polysomnography (PSG) is an all-night sleep study which monitors various physical functions during sleep including electrical activity of the heart, brain wave patterns, eye movement, muscle tone, body movements, and breathing. It is currently, the most accurate and sophisticated test for the diagnosis of sleep-disordered breathing (SDB), but also, the most expensive. The cost of an overnight sleep study is estimated between $900 and $3,000. In addition, the PSG is not mobile and has to be administered outside a patient’s home. The Long QT Syndrome (LQTS) is a rhythm disorder that causes erratic (unpredictable) heartbeats. The LQTS has been linked to patients with the most severe form of sleep apnea. If LQTS is left untreated, sudden cardiac death may occur. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection