Undergraduate honors paper--Mount Holyoke College, 2008. Dept of Biological Sciences. / Includes bibliographical references (leaves 64-69).

Undergraduate honors paper--Mount Holyoke College, 2007. Program in Biochemistry. / Includes bibliographical references (leaves 54-58).

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The tsetse transmitted fatal disease of humans, sleeping sickness, is caused by two morphologically identical subspecies of the parasite T. brucei; T. b. rhodesiense and T. b. gambiense. Current distributions of the two forms of disease are not known to overlap in any area, and Uganda is the only country with transmission of both. The distribution of Rhodesian sleeping sickness in Uganda has expanded in recent years, with five districts newly affected since 1998. This movement has narrowed the gap between Rhodesian and Gambian sleeping sickness endemic areas, heightening concerns over a potential future overlap which would greatly complicate the diagnosis and treatment of the two diseases. An improved understanding of the social, environmental and climatic determinants of the distribution of Rhodesian sleeping sickness is required to allow more effective targeting of control measures and to prevent further spread and possible concurrence with Gambian sleeping sickness. The work presented in this thesis investigates the drivers of the distribution and spread of Rhodesian sleeping sickness in districts of central and eastern Uganda which form part of the recent disease focus extension. The spatial distribution of Rhodesian sleeping sickness was examined in Kaberamaido and Dokolo districts where the disease was first reported in 2004, using three different methodologies. A traditional one-step logistic regression analysis of disease prevalence was compared with a two-step hierarchical logistic regression analysis. The two-step method included the analysis of disease occurrence followed by the analysis of disease prevalence in areas with a high predicted probability of occurrence. These two methods were compared in terms of their predictive accuracy. The incorporation of a stochastic spatial effect to model the residual spatial autocorrelation was carried out using a Bayesian geostatistical approach. The geostatistical analysis was compared with the non-spatial models to assess the importance of spatial autocorrelation, to establish which method had the highest predictive accuracy and to establish which factors were the most significant in terms of the disease’s distribution. Links between Rhodesian sleeping sickness and landcover in Soroti district were also assessed using a matched case-control study design. Temporal trends in these relationships were observed using an annually stratified analysis to allow an exploration of the disease’s dispersion following its introduction to a previously unaffected area. This work expands on previous research that demonstrated the source of infection in this area to be the movement of untreated livestock from endemic areas through a local livestock market. With regards to the comparison of regression frameworks, the two-step regression compared favourably with the traditional one-step regression, but the Bayesian geostatistical analysis outperformed both in terms of predictive accuracy. Each of these regression methods highlighted the importance of distance to the closest livestock market on the distribution of Rhodesian sleeping sickness, indicating that the disease may have been introduced to this area via the movement of untreated cattle from endemic areas, despite the introduction of regulations requiring the treatment of livestock prior to sale. In addition, several other environmental and climatic variables were significantly associated with sleeping sickness occurrence and prevalence within the study area. The temporal stratification of the matched case-control analysis highlights the dispersion of sleeping sickness away from the point of introduction (livestock market) into more suitable areas; areas with higher proportions of seasonally flooding grassland, lower proportions of woodland and dense savannah and lower elevations. These findings relate to the habitat preferences of the predominant vector species in the study area; Glossina fuscipes fuscipes, which prefers riverine vegetation. The findings presented highlight the importance of the livestock reservoir as well as the climatic and environmental preferences of the tsetse fly vector for the introduction of Rhodesian sleeping sickness into previously unaffected areas, the subsequent spread of infection following an introduction and the equilibrium spatial distribution of the disease. By enhancing the knowledge base regarding the spatial determinants of the distribution of Rhodesian sleeping sickness within newly affected areas, future control efforts within Uganda may be better targeted to decrease prevalence and to prevent further spread of the disease.

A privação do sono pode comprometer a saúde, uma vez que é durante o ciclo sono/vigília que são produzidos alguns hormônios que desempenham papéis vitais no funcionamento de nosso organismo. Distúrbios do sono em diabéticos do tipo 2, constituem fatores de risco para o agravamento do diabetes, pois podem interferir no controle metabólico através da síndrome da resistência à insulina. A apnéia do sono, insônia, movimentos periódicos das pernas, a higiene do sono e consumo de substâncias psicoativas são citados em estudos, porém pouco explorados. Ferramentas vêm sendo utilizadas na investigação acerca do ciclo sono/vigília, dentre eles o diário de sono, a polissonografia e o Índice de Qualidade do Sono de Pittsburgh (PSQI). Este é composto por sete componentes, onde é avaliada a qualidade subjetiva do sono, latência do sono, duração, eficiência habitual, distúrbios do sono, uso de medicação para dormir e sonolência diurna. O presente estudo foi do tipo observacional-transversal. A qualidade do sono foi investigada em 50 diabéticos pertencentes a um Centro Educativo de Enfermagem para Adultos e Idosos. Para tal, os pacientes diabéticos do tipo 2, após assinatura do termo de consentimento, foram submetidos a uma avaliação cognitiva inicial, através do exame do estado mental, para descartar demência. Foi aplicado um instrumento que avalia a qualidade do sono, denominado Índice de Qualidade do Sono de Pittsburgh (PSQI) e um instrumento para levantar variáveis demográficas e clínicas. A maioria dos participantes era do sexo feminino, casados, com 4 anos de estudo em média, não trabalha e possui renda mensal de 2 salários mínimos. Em relação às variáveis clínicas, 38% apresentam tempo de diagnóstico de diabetes superior a dez anos, 70% são hipertensos, 36% apresentaram valores de Hemoglobina A1c>7%, 72% com nictúria, 85% IMC equivalente à obesidade e 22% usam medicação para dormir. Os componentes do PSQI foram detalhados separadamente e obtido o escore global, sendo que (26) 52% apresentaram escores que indicam qualidade do sono ruim. A relação dos escores obtidos no PSQI com algumas variáveis foi realizada, e identificamos que aqueles com tempo de diagnóstico superior a 10 anos e aqueles com hipertensão, possuíam pior qualidade do sono. A nictúria parece não ter corroborado para uma qualidade do sono ruim. Para aqueles com valores de Hemoglobina A1c >7%, a qualidade do sono foi pior. Entre os que usam medicação para dormir e os que apresentaram IMC normal, a qualidade do sono mostrou-se pior. Os achados desta investigação reforçam a relevância da temática, pois não existem instrumentos específicos para a avaliação do sono do diabético do tipo 2, informações precisas acerca das conseqüências da privação do sono em indivíduos diabéticos do tipo 2, dificultando afirmações acerca da qualidade do sono do diabético. / Lack of sleeping can jeopardize health, because it is during the sleeping/vigil cycle that some hormones, which perform vital roles in the functioning of our organism, are produced. Sleeping malfunctions in type 2 diabetics constitute risk factors to the aggravating of diabetes since they can interfere in the metabolic control through the insulin resistance syndrome. Sleeping apnea, insomnia, occasional leg movements, sleeping hygiene and psychoactive substances consuming are quoted in studies, but scarcely explored. Tools have been used in the sleeping/vigil cycle investigation, and among them there are the sleeping diary, polissonography and Pittsburgh Sleeping Quality Index (PSQI) This one is composed by seven components, where the subjective sleeping quality, sleeping, duration and habitual efficiency latency, sleeping malfunctions, use of sleeping pills and morning sleepiness are evaluated. The present study was observation-transversal type. Sleeping quality was carried in 50 diabetics belonging to an Educational Nursing Center for adults and the elderly. For such investigation the type 2 diabetic patients, after signing the agreement term documents, were submitted to an initial cognitive evaluation, through mental estate exam, so that dementia could be discarded. A tool to evaluate the sleeping quality called Pittsburgh Sleeping Quality Index (PSQI) and another one to bring out demographic and clinic variants were applied. The majority of the participants was feminine, married, an average of 4-year-school, non-working and with an average of 2 minimal wages. Relating to clinic variants, 38% presented diabetes diagnosis time of over 10 years, 70% are hypertensive, 36% presented Hemoglobin A1c >7% values, 72% with nycturia, 85% IMC equivalent to obesity and 22% use sleeping pills. The PSQI components were separately detailed and the global score was obtained showing that (26)52% presented scores which indicate bad sleeping quality. The scores relation obtained in the PSQI along with some variants was carried and it showed that patients with a diagnosis time over 10 years and those with hipertension have the worst sleeping quality. Nycturia doesn´t seem to be a reason for a bad sleeping quality. For those with Hemoglobin A1c values >7% presented a worse sleeping quality. Among the ones who use sleeping medicine and those who presented normal IMC, the sleeping quality was even worse. The findings of this investigation strengthen the thematic relevance because there are no specifics tools for the evaluation of the type 2 diabetics´ sleeping; precise information about the consequences of lack of sleeping in type 2 diabetic individuals, making it difficult to get an affirmation about the sleeping quality of the diabetic.

Trypanosome alternative oxidase (TAO) is the sole terminal oxidase responsible for the aerobic respiration of the parasite T. b. brucei. Specific strains of this parasite cause the neglected tropical disease Human African trypanosomiasis (HAT), and thus TAO is an interesting target for the potential treatment of this disease. Inhibition of TAO with the natural product inhibitors colletochlorin B or ascofuranone has been shown to clear infections of T. b. brucei in mice at high concentrations. However, these natural product inhibitors contain undesirable chemical functionality and have poor physicochemical properties, preventing adequate drug exposure to effectively treat HAT. Robust protocols for the expression and purification of recombinant TAO were developed, which enabled the development of biochemical assays to identify inhibitors of TAO function. Single point inhibition screening of the Medicines Malaria Venture 'kinetoplastid collection' of 400 compounds identified a range of micro-molar inhibitors of TAO. A program of chemical optimisation was carried out around the natural product inhibitor colletochlorin B, with the aim to improve the physicochemical properties and retain inhibitory potency against TAO. The structure activity relationships generated over the course of this exploration identified a dependency on high lipophilicity to retain potent TAO inhibition. The TAO inhibitors synthesised were also assessed for parasite growth inhibition and mammalian cell cytotoxicity to correlate inhibition data with cellular efficacy, in collaboration with Novartis. The physicochemical properties of these novel compounds showed improvement over the natural product colletochlorin B and prompted further assessment of leading compounds in advanced parasite kill kinetic and parasite clearance assays at Novartis. The data generated in these assays for compounds synthesised in this thesis determined that TAO inhibition results in a trypanostatic response, and not a preferred trypanocidal response in T. b. brucei.

Bedsharing between infants and parents interacts with many factors to increase the risk of SIDS, eg maternal smoking, alcohol or drug consumption, overtiredness, excessive bedding and younger infant. However, bedsharing also encourages breastfeeding, settles babies, reduces parental tiredness and increases mother-baby interactions. We studied infants in the natural setting of their own home, in their usual situation (bedsharing or cot-sleeping) to identify risks and benefits, and to understand how bedsharing could be made safer for all infants. Methods: Overnight home video and physiological recordings of 40 bedshare infants (5-27 weeks), were compared with 40 cot infants matched for age and study season. Video data provided a log of infant/parent sleep positions, movements and interactions. The physiological recordings measured respiratory pattern, respiratory airflow, inspired CO2, oxygen saturation (SaO2), heart rate and core, peripheral and environmental temperatures. Results: All infants maintained normal core temperatures overnight although bedshare infants had a higher shin temperature [35.43 vs 34.60°C at 2hrs after sleep onset (difference 0.83, 95% CI: 0.18 to 1.49)]. Bedshare infants had thicker bedding (RR:2.35 (95% CI:1.76 to 3.14) and more face covered time [0.9h/night vs 0.2 (RR:5.62, 95% CI: 3.08 to 10.25)]. Awakenings in the bedshare group were more common, of shorter duration, and caused less change in infant temperatures. Exposure to >3% CO2 occurred in 18 bedshare infants and 1 swaddled, cot-sleep infant. The maximum exposure time was the same for both groups (60mins). These levels of CO2 significantly (p<0.05) elevated breathing rate and maintained normal SaO2. Central apnoeas of 5-10 seconds resulted in drops in SaO2 <90% (BS mean 6.8/night vs cot: 3.1, p<0.001). SaO2 rarely fell below 85% and heart rate did not ever fall below 90bpm. Bedshare infants commonly slept on their side, while cot infants slept supine. Prone sleeping was rare (BS:5 infants, 1.6-3.5h/night vs cot:2, 8.9-10.2) and for bedshare infants involved sleeping on mother�s chest. Bedshare infants woke and fed more frequently (mean wake times/night: 4.6 vs 2.5), but total sleep time was not different. Maternal checks were more frequent in the bedshare group (median:10, IQ range:7-23, max:55) than cot ( 4, 3-6, 16) and bedshare mothers frequently responded to infant initiated movements. During bedsharing baby and mother usually slept facing each other, touching, with infants at mothers� breast level. Father (or sibling) contact was rare. Conclusions: Bedshare infants sleep in a warmer environment and experience more potentially dangerous events such as head-covering and rebreathing. However, all infants in this study maintained normal rectal temperature and SaO2 suggesting they were protected by homeostatic responses. Infant safety is also facilitated by frequent maternal checking and maternal responses to infant movements. The mother-infant proximity during bedsharing allows prompt responses, reduces time infants are upset, and minimises disruption from frequent breast feeding - aspects valued by many. It is not known if infants of smoking mothers or parents with impaired responses eg due to alcohol, respond adequately to the potentially dangerous situations identified. Outcome: The results of this study will be used to formulate recommendations to parents for improving the safety of bedsharing.

This essay examines gender normative and patriarchal elements of the popular fairy            tale Sleeping Beauty in order to expose how patriarchal ideals are upheld. The reason for this is that children may internalize the values taught in these stories, which may lead to them perpetuating patriarchal ideals and gender normative behavior. The popular version of this fairy tale, made by Disney, follows many of the typical patriarchal ideals with a strong male hero, a wicked female witch and a weak and submissive young female, close to nature. This is contrasted by a modern retelling by Cameron Dokey that is, in many ways, gender subversive and challenges the traditional gender roles and attributes. This essay finds that the version made by Disney is a product of its time, and portrays ideals from that period that could affect children of today into internalizing archaic patriarchal ideals. Dokey’s version is better adapted to the current socio-cultural environment and succeeds in aligning the story with modern values and provides a better option to teach children the actual values and gender roles of our society. / Denna uppsats undersöker könsnormativa och patriarkala element i den populära sagan Törnrosa, för att blottlägga hur patriarkala ideal upprätthålls. Anledningen till detta är att barn kan internalisera de värderingar som lärs ut i dessa sagor, vilket kan leda till att de upprätthåller patriarkala ideal och könsnormativa beteenden. Disneys populära version av sagan följer många av de typiska patriarkala idealen, med en stark manlig hjälte, en ond kvinnlig häxa och en svag och undergiven ung kvinna, som är nära kopplad till naturen. Denna version kontrasteras av en modern återberättelse av sagan skriven av Cameron Dokey som på många sätt utmanar traditionella patriarkala könsnormer och sttribut. Disneys version är en produkt av sin tid, och porträtterar ideal från den tiden som kan påverka dagens barn att internalisera ålderdomliga könsideal. Dokeys version är bättre anpassad till den nuvarande socio-kulturella miljön och lyckas med att justera historian till att bättre passa moderna värderingar, och framstår som ett bättre alternativ för att lära barn vårat samhälles könsroller och värderingar.

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