Made available in DSpace on 2016-04-27T17:27:11Z (GMT). No. of bitstreams: 1 Gilmar Dias da Conceicao.pdf: 521227 bytes, checksum: d5b9fc242a55387bcbf636d0d4befb59 (MD5) Previous issue date: 2015-08-11 / The objective of this dissertation paper in Masters is the study of the itinerary followed by Nietzsche in elaborating his perspective on the body, starting from the antecedents that determined its devaluation. In this journey, we shall be examining, among other points, the Nietzsche perspective on the human decadency process, with emphasis on what the above mentioned thinker understands by Physiology and the art of convalescence, and showing how it configures the process of human sickness both individually and collectively / O intuito desta dissertação de mestrado é o de estudar o itinerário seguido por Nietzsche na elaboração da sua perspectiva sobre o corpo, a partir dos antecedentes que determinaram sua desvalorização. Nesta trajetória examinaremos, entre outros pontos, a perspectiva de Nietzsche sobre o processo da decadência do homem, salientando o que o referido pensador entende por fisiologia e arte da convalescença, mostrando como se configura o processo da doença no homem individual e no coletivo

Introdução: O trabalho sempre foi, em diversos momentos da história, categoria fundante das relações sociais entre o homem e a natureza e entre os homens e os homens. Entretanto, o trabalho na forma de produção capitalista tem sido alienado e alienador, com efeitos deletérios tanto sobre o corpo físico como para a mente e alma do trabalhador. O servidor público não fica à margem dessa situação, uma vez que o Estado é parte estrutural do capitalismo. Assim, as diversas formas de violência contra o trabalhador, como sobrecarga, subcarga, assédio moral, foram debatidos, ainda que de forma não aprofundada, nesse trabalho. Objetivos: Estabelecer o perfil dos afastamentos de trabalhadores técnicos e administrativos da Universidade de São Paulo (USP) por motivo de doença nos últimos cinco anos (2012 - 2016). Analisar os afastamentos por transtornos mentais nos últimos cinco anos (2012 - 2016). Analisar o contexto de trabalho sob a ótica do trabalhador. Materiais e métodos: Trata-se de pesquisa exploratória quali-quantitativa e sua base de dados se deu por duas vias distintas: uma através de banco de dados dos recursos humanos da Universidade de São Paulo, o sistema Marte e a outra, através de questionários divulgados de forma online nas redes sociais com a participação voluntária de 697 servidores da universidade. A análise dos dados foi realizada por meio de frequências absolutas e percentuais (variáveis qualitativas) e por meio de medidas como média, desvio-padrão, mínimo, mediana e máximo (variáveis quantitativas). Os gráficos apresentados foram feitos com o auxílio do software R, versão 3.4.1 e as análises, através do SAS 9.2. Para todas as comparações adotou-se um nível de significância de 5%. Para análise do discurso dos sujeitos, realizamos a análise textual adotando o método de Reinert via classificação hierárquica descendente, com auxílio do software Iramuteq versão 0.7 alpha 2 e categorização de conceitos chaves. Resultados e discussão: O índice de absenteísmo por doença na Universidade de São Paulo é extremamente alto. As mulheres, negras, nível básico, sem companheiro são as mais propensas a adoecerem. As doenças do tecido osteomuscular e do tecido conjuntivo são as que afastam o maior número de pessoas; entretanto os transtornos mentais e comportamentais, com predominância dos quadros de depressão, ansiedade, stress e alcoolismo, afastam os trabalhadores por mais tempo, ou seja, os dias de afastamento são maiores. As condições de trabalho foram avaliadas como boas, todavia a organização do trabalho e as relações socioprofissionais situam-se em um nível crítico, sendo a dimensão socioprofissional a que necessita de mais intervenções e estudos mais aprofundados. / Introduction: Work has always been, at various moments in history, a foundational category of social relations between man and nature and between men and men. However, labor in the form of capitalist production has been alienated and alienating, with deleterious effects on both the physical body and the mind and soul of the worker. The public servant is not left out of this situation, since the state is a structural part of capitalism. Thus, the various forms of violence against the worker, such as overload, undercarriage, and moral harassment, were debated, albeit in an undefined manner, in this work. Objectives: To establish the profile of technical and administrative workers\' absence from the University of São Paulo (USP) due to illness in the last five years (2012-2016). To analyse the withdrawal of mental disorders in the last five years (2012-2016). Analyse the work context from the perspective of the worker. Materials and methods: This is a qualitative and quantitative exploratory research and its database was taken in two distinct ways: one through a database of human resources at the University of São Paulo, the Mars system and the other through questionnaires published online in social networks with the voluntary participation of 697 university employees. Data were analysed by means of absolute and percentage frequencies (qualitative variables) and by means of measures such as mean, standard deviation, minimum, median and maximum (quantitative variables). The graphs presented were made with the software R, version 3.4.1 and the analyzes, through SAS 9.2. For all comparisons a significance level of 5% was adopted. For the analysis of the subjects\' discourse, we performed the textual analysis adopting the Reinert method through descending hierarchical classification, using the software Iramuteq version 0.7 alpha 2 and categorization of key concepts. Results and discussion: The rate of absenteeism due to illness at the University of São Paulo is extremely high. Women, black, basic level, without partner are the most prone to get sick. The diseases of the musculoskeletal and connective tissue are those that distract the largest number of people; however, mental and behavioral disorders, with a predominance of depression, anxiety, stress and alcoholism, distract the workers longer, that is, the days of withdrawal are greater. Working conditions have been assessed as good, but work organization and socio-occupational relations are at a critical level, with the socio-professional dimension requiring more interventions and more in-depth studies.

The trypanosomatid parasites T. brucei, T. cruzi and Leishmania spp. are responsible for the ‘neglected diseases’ Human African Trypanosomiasis, Chagas disease and Leishmaniasis respectively. In their human infective form in the bloodstream all three trypanosomatid parasites rely heavily on glycolysis for ATP production. Phosphofructokinase (PFK) catalyses the third step of the glycolytic pathway in all organisms using aerobic respiration. It facilitates the phospho transfer from ATP to fructose 6-phosphate (F6P) to make the products fructose 1,6- bisphosphate (F16BP) and ADP. RNAi knockout of T. brucei PFK has shown the enzyme is essential for survival of the bloodstream form parasites. Trypanosomatid PFKs have a unique set of structural and regulatory differences compared to the mammalian host enzyme. These differences, coupled with the availability of trypanosomatid PFK crystal structures present an opportunity for the structure-based design of specific inhibitors against the enzyme. Here we present an enzymatic characterisation of recombinant PFKs from T. brucei, T. cruzi and Leishmania infantum trypanosomatids, their regulation by the allosteric activator AMP, and their inhibition by drug-like inhibitor compounds. Inhibitor compounds (‘CTCB compounds’) were designed against T. brucei PFK with the aim of developing novel treatments against Human African Trypanosomiasis (HAT). We describe the testing, ranking and biophysical characterisation of these compounds as part of a Wellcome Trust Seeding Drug Discovery program. We found that CTCB inhibitor compounds bound to an allosteric pocket unique to trypanosomatid PFKs. We show that the compounds are specific; neither competing with the natural substrates ATP or F6P nor inhibiting the human PFK enzyme. We describe the development and testing of highly potent and specific low molecular weight PFK inhibitors that translate to both killing of cultured T. b. brucei parasites and a cure of stage I HAT in mice models. We describe the tight, 1:1 binding of these compounds with trypanosomatid PFKs, and the thermodynamic characteristics of binding through various biophysical assays. We also show the unprecedented characterisation of the reverse PFK reaction by trypanosomatid and human forms of the enzymes. We found that PFK can also carry out the reverse enzymatic reaction, under physiologically relevant concentrations of ADP and F16BP to produce F6P and ATP. We show that the reverse reaction is also subject to allosteric regulation by AMP, and can be inhibited by the CTCB compounds with a similar potency to the forward reaction. Finally, we describe the mechanism of allosteric activation by AMP and inhibition by the drug-like compounds against trypanosomatid PFKs.

Através do presente trabalho investigou-se a expressão do comportamento doentio e a atividade de neutrófilos sanguíneos de camundongos adultos, de meia idade e idosos, após o tratamento com lipopolissacarídeo de bactéria gram negativa (Escherichia coli). O comportamento doentio foi avaliado através da ingestão de alimentos e do peso corpóreo. Nos aparatos comportamentais Campo Aberto e Labirinto em cruz elevado, o comportamento doentio foi avaliado através da atividade geral, da exploração e dos níveis de ansiedade. A atividade de neutrófilos sanguíneos foi estudada através de citometria de fluxo, analisando-se a intensidade e porcentagem de neutrófilos que realizaram fagocitose e da intensidade e porcentagem de neutrófilos que realizaram burst oxidativo, ambos induzidos pelo estímulo in vitro da bactéria Staphylococcus aureus. Os animais foram tratados com solução salina ou LPS (na dose de 200 µg/kg) avaliações foram realizadas 2 horas após o tratamento. No caso da ingestão de alimentos e do peso corpóreo, as avaliações foram realizadas durante 3 dias anteriores ao experimento, e durante 7 dias posteriores ao experimento. Os resultados demonstraram que animais idosos apresentaram diferenças na expressão do comportamento doentio, sendo que houve uma maior motivação em explorar os aparatos comportamentais. Apesar da manutenção da exploração no Campo Aberto e Labirinto em Cruz elevado, a redução da ingestão de alimentos e do peso corpóreo apresentou-se mais acentuada nos camundongos de meia idade e idosos, após tratamento com LPS. A atividade de neutrófilos sanguíneos, avaliadas pela fagocitose e burst oxidativo, apresentou-se aumentada em camundongos idosos após tratamento com LPS. A menor migração de neutrófilos sanguíneos à cavidade peritoneal parece ser responsável por esse aumento de atividade dos neutrófilos de camundongos idosos. Esses resultados sugerem que a expressão do comportamento doentio de camundongos idosos é diferente, com manutenção do comportamento de exploração, e que esses camundongos seriam mais susceptíveis aos efeitos do choque endotóxico, devido à presença de maior quantidade de neutrófilos ativados no sangue. / Through the present work, it has been investigated the expression of sickness behavior and blood neutrophils activity in adult, middle-aged and aged mice, after gram negative (Escherichia coli) lipopolysaccharide treatment. Sickness behavior was evaluated through food ingestion and body weight. On the behavioral apparatus Open Field and Elevated Plus Maze, sickness behavior was evaluated through general activity, exploration and anxiety levels. Blood neutrophils activity was studied through flow cytometric analysis, assessing neutrophil\'s intensity and percentage of phagocytosis and neutrophil\'s intensity and percentage of oxidative burst, both induced by in vitroM stimulus of Staphylococcus aureus bacteria. Animals were treated either with saline solution or LPS (in the 200 µg/kg dose) and analysis were done 2 hours after treatment. In the case of food ingestioin and body weight, analysis were done through 3 days before experiment, and during 7 days after experiment. Results demonstrated that aged animals showed differences in sickness behavior expression, with a greater motivation to explore behavioral apparatus. Despite maintenance of Open Field and Elevated Plus Maze exploration, reduction in food ingestion and body weight were more pronounced in middle-aged and aged mice, after LPS treatment. Blood neutrophils activity, analysed through phagocytosis and oxidative burst, were higher in aged mice after LPS treatment. Lesser blood neutrophils migration to peritoneal cavity seems to be responsible for this enhancement in neutrophil activity. These results suggest that the expression of sickness behavior in aged mice is different, with maintenance of exploratory behavior, and that these mice would be more susceptible to endotoxic effects, due to the presence of higher quantity of activated neutrophils in blood.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-06-26T18:01:00Z No. of bitstreams: 1 MariaJose.pdf: 1185247 bytes, checksum: e3e1229707d87ec37cecf87151e83bc9 (MD5) / Made available in DSpace on 2017-06-26T18:01:00Z (GMT). No. of bitstreams: 1 MariaJose.pdf: 1185247 bytes, checksum: e3e1229707d87ec37cecf87151e83bc9 (MD5) Previous issue date: 2007-12-10 / The educator sickness and its possible repercussions in the pedagogical practice. It is pointed out the articulations among the Brazilian Teaching Organization, the educational reforms, partially deriving from the situation in which the capitalism is, and the incidences related to the organization and management of the school, in order to understand the alterations on the work of the teachers and on the processes of health-sickness in the school context, trying approaches to the notion of subjectiveness to evidence answers signaled as its effects. The objective is to build a sickness profile of the teachers of the County Educational System, from São Luís, in order to identify its possible impacts on the pedagogical practice in the class room, pointing out organizational and environmental characteristics indicated by the teachers as aspects that can favor wearing out situations, enunciating the situation of sickness and its effects on the amount of medical licenses and sick leave and revealing the movements of attention and reaction to the worsening of the teachers health. The theoretical references presents contributions of researchers such as: Antunes (2001, 2004), Oliveira (2000, 2002, 2003), Freitas (2001), Silva (2002), Esteve (1999), Codo (2002), Martinez (2003), Araújo and Paranhos (2003), Araújo et al. (2005), Gasparini, Barreto and Assumption (2005), Bardin (2004), among others. Other contributions were also searched, highlighting on Foucault (2003, 2006, 2007) power-knowledge about the live body, the (re)organization of the medical knowledge and the meaning of the disease; the references were also supported by Minayo-Gomez and Barros (2002) and Barros (2002, 2003) with the incorporation of the discussions on the processes of subjectiveness in the school, that contributes to other perspectives of analysis of the teachers work absences via medical licenses. A qualitative approach of research was adopted, using as procedures and instruments: documental analysis, semi-structured interview, questionnaire filled out without the presence of the researcher and without his comments. For data analysis it was considered the orientations of the Analysis of Content. As subject of the research, it was used the educators of the initial series of Elementary School of a school in the urban zone of São Luís, besides the managers, coordinators and a sample of the morning students. The main results of the study suggest attention to the presence of certain factors described as inadequate to the good working performance and facilitators of the teachers wearing out and to the intense work overload referred to by the teachers, mainly concerning to the amount of students in the class rooms, excess of activities and tasks to accomplish, pedagogical demands, use of the break time and lack of family support. It is possible to state that the data indicates an accusation of the situation of sickness in which the educator is, because among the categories that make for the municipal public service, this is the one that is the most absent of work because of medical licenses.The teachers sickness profile is characterized by high incidence of diseases, especially those related to the osseous-muscular system and the conjunctive tissue, followed by mental and behavior disturbances, diseases of the respiratory and circulatory systems and neoplasias. A high percentage of extended sick leaves were noticed, indicating a continuous absence of an educator, besides the association of diagnoses for the same license, in other words, the teacher not only just gets sick, but also he/she gets sick for several causes. It was observed that in the school, contradicting the indexes, in spite of being sick, the educator, in some cases, remains in the classroom, as if resisting to be away from it. Inferences concerning the repercussions of this sickness in the pedagogical practice allow to associate them to components such as planning, professor/student relationship and evaluation, indicating that it does not isolate itself and it is not immune to the worsening of the teachers health. It can be stated that some observed actions, perhaps insignificant for the teachers, are in fact movements of struggle and reaction against the sickness situations, movements that differ from each other according to the capacity of each one of them to understand and fight against their sickness. Keywords: Teachers work. Sickness. Pedagogical practice. / O adoecimento do/a educador/a e suas possíveis repercussões na prática pedagógica. Destacamos articulações entre a organização do ensino brasileiro, as reformas educacionais em parte decorrentes do estágio em que se encontra o capitalismo na contemporaneidade, e as incidências quanto a organizar e gerir a escola, para uma compreensão das alterações no trabalho docente e nos processos da saúde-doença no contexto escolar, tentando aproximações à noção de subjetivação para evidenciar respostas sinalizadas como efeitos desta. Objetivamos construir um perfil do adoecimento dos/as educadores/as da Rede Pública Municipal de Educação de São Luís, para identificar possíveis repercussões deste na prática pedagógica em sala de aula, ressaltando características organizacional-ambientais apontadas pelas docentes como aspectos que podem favorecer situações de desgaste, enunciando o quadro de adoecimento e seus efeitos em termos de licenças médicas e afastamento do trabalho e desvelando movimentos de atenção e reação aos agravos à saúde docente. O referencial teórico apresenta contribuições de pesquisadores como: Antunes (2001, 2004), Oliveira (2000, 2002, 2003), Freitas (2001), Silva (2002), Esteve (1999), Codo (2002), Martinez (2003), Araújo e Paranhos (2003), Araújo et al. (2005), Gasparini, Barreto e Assunção (2005), Bardin (2004), dentre vários. Ainda recorremos a outros aportes, destacando em Foucault (2003, 2006, 2007) o poder-saber sobre o corpo vivo, a (re)organização do saber médico e do significado da doença; também contamos com o apoio de Minayo-Gomez e Barros (2002) e Barros (2002, 2003) pela incorporação das discussões sobre processos de subjetivação na escola, que contribui para outras perspectivas de análise do afastamento do trabalho do/a educador/a, via licenças médicas. Adotamos uma abordagem qualitativa de pesquisa, utilizando como procedimentos e instrumentos: análise documental, entrevista semi-estruturada, questionário autopreenchível e observação participante. Para análise dos dados consideramos as orientações da Análise de Conteúdo. Como sujeitos da pesquisa tivemos as educadoras das séries iniciais do Ensino Fundamental de uma escola da zona urbana de São Luís, além dos/as gestores/as, coordenadores/as e uma amostra dos/as alunos/as, no turno matutino. Os principais resultados do estudo sugerem atenção à existência de determinados fatores descritos como inadequados ao bom desempenho do trabalho e facilitadores do desgaste docente e, à intensa sobrecarga de trabalho referida pelas professoras, principalmente no que concerne à quantidade de alunos/as em sala de aula, excesso de atividades e tarefas a cumprir, exigências pedagógicas, utilização dos horários destinados ao intervalo e falta de apoio familiar. É possível afirmar que os dados apontam para uma denúncia da situação de adoecimento em que se encontra o/a educador/a, pois dentre as categorias que integram o serviço público municipal, esta é a que mais se ausenta do trabalho por motivo de licenças médicas; o perfil do adoecimento docente se caracteriza por elevada incidência de doenças, especialmente aquelas relacionadas ao Sistema osteomuscular e do tecido conjuntivo, seguidas por Transtornos mentais e comportamentais, Doenças do aparelho respiratório, Doenças do aparelho circulatório e Neoplasias. Notamos acentuado percentual de licenças em prorrogação, subtendendo o afastamento contínuo de um/a educador/a, além da associação de diagnósticos para uma mesma licença, ou seja, o/a educador/a não apenas adoece, adoece por várias causas. Observamos que na escola, contrariando os índices, apesar de alguma situação de adoecimento a educadora permanece em sala, como se resistisse a dela ausentar-se. Inferências acerca das repercussões desse adoecimento na prática pedagógica permitem associá-las a componentes como planejamento, relação professor/a-aluno/a e avaliação, denotando que a mesma não se isola nem fica imune aos agravos à saúde docente. Podemos dizer que algumas ações observadas, talvez insignificantes para as professoras, são, na verdade, movimentos de luta e reação contra as situações de adoecimento, movimentos que diferem entre si de acordo com a capacidade de cada uma delas compreender e lutar contra seu adoecer.

Através do presente trabalho investigou-se a expressão do comportamento doentio e a atividade de neutrófilos sanguíneos de camundongos adultos, de meia idade e idosos, após o tratamento com lipopolissacarídeo de bactéria gram negativa (Escherichia coli). O comportamento doentio foi avaliado através da ingestão de alimentos e do peso corpóreo. Nos aparatos comportamentais Campo Aberto e Labirinto em cruz elevado, o comportamento doentio foi avaliado através da atividade geral, da exploração e dos níveis de ansiedade. A atividade de neutrófilos sanguíneos foi estudada através de citometria de fluxo, analisando-se a intensidade e porcentagem de neutrófilos que realizaram fagocitose e da intensidade e porcentagem de neutrófilos que realizaram burst oxidativo, ambos induzidos pelo estímulo in vitro da bactéria Staphylococcus aureus. Os animais foram tratados com solução salina ou LPS (na dose de 200 µg/kg) avaliações foram realizadas 2 horas após o tratamento. No caso da ingestão de alimentos e do peso corpóreo, as avaliações foram realizadas durante 3 dias anteriores ao experimento, e durante 7 dias posteriores ao experimento. Os resultados demonstraram que animais idosos apresentaram diferenças na expressão do comportamento doentio, sendo que houve uma maior motivação em explorar os aparatos comportamentais. Apesar da manutenção da exploração no Campo Aberto e Labirinto em Cruz elevado, a redução da ingestão de alimentos e do peso corpóreo apresentou-se mais acentuada nos camundongos de meia idade e idosos, após tratamento com LPS. A atividade de neutrófilos sanguíneos, avaliadas pela fagocitose e burst oxidativo, apresentou-se aumentada em camundongos idosos após tratamento com LPS. A menor migração de neutrófilos sanguíneos à cavidade peritoneal parece ser responsável por esse aumento de atividade dos neutrófilos de camundongos idosos. Esses resultados sugerem que a expressão do comportamento doentio de camundongos idosos é diferente, com manutenção do comportamento de exploração, e que esses camundongos seriam mais susceptíveis aos efeitos do choque endotóxico, devido à presença de maior quantidade de neutrófilos ativados no sangue. / Through the present work, it has been investigated the expression of sickness behavior and blood neutrophils activity in adult, middle-aged and aged mice, after gram negative (Escherichia coli) lipopolysaccharide treatment. Sickness behavior was evaluated through food ingestion and body weight. On the behavioral apparatus Open Field and Elevated Plus Maze, sickness behavior was evaluated through general activity, exploration and anxiety levels. Blood neutrophils activity was studied through flow cytometric analysis, assessing neutrophil\'s intensity and percentage of phagocytosis and neutrophil\'s intensity and percentage of oxidative burst, both induced by in vitroM stimulus of Staphylococcus aureus bacteria. Animals were treated either with saline solution or LPS (in the 200 µg/kg dose) and analysis were done 2 hours after treatment. In the case of food ingestioin and body weight, analysis were done through 3 days before experiment, and during 7 days after experiment. Results demonstrated that aged animals showed differences in sickness behavior expression, with a greater motivation to explore behavioral apparatus. Despite maintenance of Open Field and Elevated Plus Maze exploration, reduction in food ingestion and body weight were more pronounced in middle-aged and aged mice, after LPS treatment. Blood neutrophils activity, analysed through phagocytosis and oxidative burst, were higher in aged mice after LPS treatment. Lesser blood neutrophils migration to peritoneal cavity seems to be responsible for this enhancement in neutrophil activity. These results suggest that the expression of sickness behavior in aged mice is different, with maintenance of exploratory behavior, and that these mice would be more susceptible to endotoxic effects, due to the presence of higher quantity of activated neutrophils in blood.

Trypanosoma brucei is an extracellular kineotoplastid parasite that causes human African trypanosomiasis (HAT), also known as sleeping sickness. As trypanosomes undergo vector to host transition, heavy transcriptional adaptation such as metabolic shift to glycolysis and upregulated endocytosis occurs. Specifically, glycolysis in the infectious stage becomes the sole source of energy production; thus, the glucose transport mechanism in T. brucei provides one of the most promising therapeutic targets for development of new drugs to treat HAT. Despite an established trypanosome hexose transporter (THT) model for glucose transport across the plasma membrane, there remains gaps in the detailed mechanism of glucose transport especially as it relates to glucose transport across the glycosomal membrane. Using 2-NBDG, a fluorescent glucose analog, we measured glucose uptake rates in the presence of small molecule inhibitors and by using RNA interference (RNAi) to knockdown key proteins to investigate the mechanism of glucose transport in trypanosomes. We have confirmed a direct role of THT in glucose transport of BSF trypanosomes; however, in our investigations, we observed an unexpected ATP-dependence on glucose transport in live trypanosomes, which initiated further study where we focused on the role of endocytosis as an ATP-coupled bulk glucose transport mechanism. Experimental approaches that inhibited endocytosis reduced the observed glucose uptake rate confirming a role for endocytosis-coupled glucose transport in BSF trypanosomes. We provide evidence for an endocytosis-coupled glucose transport mechanism in BSF trypanosomes as an additional and important mechanism that functions in parallel with the established THT model.

Doctor of Philosphy (PhD) / This thesis describes the work carried out during four treks, each over 10-11 days, from 1400m to 5000m in the Nepal Himalaya and further work performed during several two-night sojourns at the Barcroft Laboratory at 3800m on White Mountain in California, USA. Nineteen volunteers were studied during the treks in Nepal and seven volunteers were studied at White Mountain. All subjects were normal, healthy individuals who had not travelled to altitudes higher than 1000m in the previous twelve months. The aims of this research were to examine the effects on sleep, and the ventilatory patterns during sleep, of incremental increases in altitude by employing portable polysomnography to measure and record physiological signals. A further aim of this research was to examine the relationship between the ventilatory responses to hypoxia and hypercapnia, measured at sea level, and the development of periodic breathing during sleep at high altitude. In the final part of this thesis the possibility of preventing and treating Acute Mountain Sickness with non-invasive positive pressure ventilation while sleeping at high altitude was tested. Chapter 1 describes the background information on sleep, and breathing during sleep, at high altitudes. Most of these studies were performed in hypobaric chambers to simulate various high altitudes. One study measured sleep at high altitude after trekking, but there are no studies which systematically measure sleep and breathing throughout the whole trek. Breathing during sleep at high altitude and the physiological elements of the control of breathing (under normal/sea level conditions and under the hypobaric, hypoxic conditions present at high altitude) are described in this Chapter. The occurrence of Acute Mountain Sickness (AMS) in subjects who travel form near sea level to altitudes above 3000m is common but its pathophysiology not well understood. The background research into AMS and its treatment and prevention are also covered in Chapter 1. Chapter 2 describes the equipment and methods used in this research, including the polysomnographic equipment used to record sleep and breathing at sea level and the high altitude locations, the portable blood gas analyser used in Nepal and the equipment and methodology used to measure each individual’s ventilatory response to hypoxia and hypercapnia at sea level before ascent to the high altitude locations. Chapter 3 reports the findings on the changes to sleep at high altitude, with particular focus on changes in the amounts of total sleep, the duration of each sleep stage and its percentage of total sleep, and the number and causes of arousals from sleep that occurred during sleep at increasing altitudes. The lightest stage of sleep, Stage 1 non-rapid eye movement (NREM) sleep, was increased, as expected with increases in altitude, while the deeper stages of sleep (Stages 3 and 4 NREM sleep, also called slow wave sleep), were decreased. The increase in Stage 1 NREM in this research is in agreement with all previous findings. However, slow wave sleep, although decreased, was present in most of our subjects at all altitudes in Nepal; this finding is in contrast to most previous work, which has found a very marked reduction, even absence, of slow wave sleep at high altitude. Surprisingly, unlike experimental animal studies of chronic hypoxia, REM sleep was well maintained at all altitudes. Stage 2 NREM and REM sleep, total sleep time, sleep efficiency and spontaneous arousals were maintained at near sea level values. The total arousal index was increased with increasing altitude and this was due to the increasing severity of periodic breathing as altitude increased. An interesting finding of this research was that fewer than half the periodic breathing apneas and hypopneas resulted in arousal from sleep. There was a minor degree of upper airway obstruction in some subjects at sea level but this was almost resolved by 3500m. Chapter 4 reports the findings on the effects on breathing during sleep of the progressive increase of altitude, in particular the occurrence of periodic breathing. This Chapter also reports the results of changes to arterial blood gases as subjects ascended to higher altitudes. As expected, arterial blood gases were markedly altered at even the lowest altitude in Nepal (1400m) and this change became more pronounced at each new, higher altitude. Most subjects developed periodic breathing at high altitude but there was a wide variability between subjects as well as variability in the degree of periodic breathing that individual subjects developed at different altitudes. Some subjects developed periodic breathing at even the lowest altitude and this increased with increasing altitude; other subjects developed periodic breathing at one or two altitudes, while four subjects did not develop periodic breathing at any altitude. Ventilatory responses to hypoxia and hypercapnia, measured at sea level before departure to high altitude, was not significantly related to the development of periodic breathing when the group was analysed as a whole. However, when the subjects were grouped according to the steepness of their ventilatory response slopes, there was a pattern of higher amounts of periodic breathing in subjects with steeper ventilatory responses. Chapter 5 reports the findings of an experimental study carried out in the University of California, San Diego, Barcroft Laboratory on White Mountain in California. Seven subjects drove from sea level to 3800m in one day and stayed at this altitude for two nights. On one of the nights the subjects slept using a non-invasive positive pressure device via a face mask and this was found to significantly improve the sleeping oxyhemoglobin saturation. The use of the device was also found to eliminate the symptoms of Acute Mountain Sickness, as measured by the Lake Louise scoring system. This finding appears to confirm the hypothesis that lower oxygen saturation, particularly during sleep, is strongly correlated to the development of Acute Mountain Sickness and may represent a new treatment and prevention strategy for this very common high altitude disorder.

No description available.

<p>MobileMe is a recently developed system for monitoring and recording physiological variables. It is wireless, and can therefore be suitable for field research, for example when measuring motion sickness symptoms.</p><p>The aim of this thesis was to conclude whether the MobileMe recording system was valid for research studies. A validation study, consisting of two parts and including 10 subjects, was performed. The first part was a laboratory study, where data from MobileMe and a reference equipment were compared. A field study was also performed, onboard a combat boat, to determine the equipment’s validity in uncontrolled environments. Furthermore, the field study included an investigation of motion sickness symptoms, and provided data for evaluation of motion sickness rating scales.</p><p>Statistical results from the laboratory study, and results from evaluation of data from the field study, showed that MobileMe was valid in both controlled and uncontrolled environments.</p>