Thesis. 1976. M.S.--Massachusetts Institute of Technology. Dept. of Nutrition and Food Science. / Microfiche copy available in Archives and Science. / Vita. / Bibliography: leaves 69-78. / M.S.

No description available.

The clinical management of Factor XI (FXI) deficiency is problematic due to the marked phenotypic heterogeneity between individuals with this disorder and the lack of a reliable test to predict bleeding risk. FXI-deficient individuals are currently at risk of being over- or under treated, with associated risks of transfusion-related complications or haemorrhage respectively. The improvement of care of FXI-deficient patients requires the development of measures that can predict bleeding phenotype and enable the identification of individuals who need treatment at times of haemostatic challenge. In addition, for those requiring treatment, there is a need for development of tests which can determine the optimal type and dose of FXI replacement on an individually tailored basis, as well as assays which can accurately monitor the effect of treatment and guide clinicians in the requirement for further perioperative treatment. This thesis addresses these objectives by studying global haemostasis assays and bleeding scores as tools to predict bleeding tendency and by studying the utility of global haemostasis assays as potential tests by which FXI replacement treatment can be determined and monitored. For prediction of bleeding tendency, this research demonstrated that the thrombin generation assay (TGA) was able to differentiate bleeding tendency provided the sample conditions used in the assay were optimised to assess FXI involved coagulation pathways thought to be of relevance in vivo: using platelet rich plasma with inhibition of in vitro contact activation and a low tissue factor trigger. Thromboelastometry measured using the same sample type was similarly able to distinguish bleeding phenotype. However, when the potential clinical utility of the assays was compared using receiver operating characteristic curve analysis, thromboelastometry was inferior to TGA as an identifier of bleeding tendency. When the thromboelastometry sample type used was whole blood, or where assays were performed in the presence of tissue plasminogen activator the assays did not differentiate bleeding phenotype. For purposes of treatment planning, the potential of the TGA to determine the optimal dose of FXI replacement was assessed by in vitro spiking experiments using two commercially available FXI concentrates and samples from individuals with major FXI deficiency. Each concentrate improved thrombin generation, but dose response curves were found to differ, suggesting different properties for the two products. The clinical utility of the approach was then demonstrated with comparable TGA results obtained in ex vivo samples from patients treated with FXI concentrate and baseline samples spiked in vitro with equivalent amounts of the same FXI concentrate. The utility of global haemostasis assays to monitor the effect of FXI replacement in FXI-deficient individuals undergoing surgery was also tested. Improvement in assay parameters after treatment with solvent-detergent fresh frozen plasma or FXI concentrate was demonstrated suggesting assay value in FXI replacement monitoring. Finally the use of recently developed bleeding assessment tools and bleeding scores as descriptive, diagnostic or predictive measures was tested along with correlation with FXI:C levels and TGA parameters. This analysis confirmed that bleeding scores have a limited value in the clinical assessment of FXI deficiency.

Qiao, Mu. / "June 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 190-209). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

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Made available in DSpace on 2014-06-11T19:31:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-05-21Bitstream added on 2014-06-13T19:01:22Z : No. of bitstreams: 1 martins_rcb_dr_arafcf.pdf: 1033721 bytes, checksum: c453fe7fa51bca1f3a487b85434b382d (MD5) / Unimep / O estado nutricional da população infantil é um indicador relevante de saúde e qualidade de vida da população. Entretanto, faltam estudos longitudinais que dêem conta de avaliar a evolução do estado nutricional num mesmo grupo populacional, que confiram maior confiabilidade aos resultados. Assim, o objetivo desta pesquisa é, a partir de quatro estudos transversais e um longitudinal, avaliar a evolução do estado nutricional de escolares de 1a a 4a séries da rede pública do ensino fundamental da área urbana do município de Piracicaba/SP, de 2003 a 2006. Nesse período foram realizadas 16068 avaliações, sempre no segundo semestre de cada ano, em 9683 escolares de 12 unidades de ensino situadas nas 5 regiões administrativas da cidade de Piracicaba. Esses grupos de escolares avaliados anualmente foram chamados de levantamentos transversais. Ao grupo de escolares (n=347) acompanhado da 1a a 4a série, durante o mesmo período dos estudos transversais chamou-se grupo longitudinal. Foram aferidos o peso e a estatura e levantados dados de identificação pessoal (nome completo, sexo, data de nascimento, série e turma na escola). Os dados foram processados pelo programa Epi-info adotando-se a população de referência do NCHS/CDC - National Center Health Statistics/ Centers for Disease control and prevention - 2000 e expressos em escore-Z (Z) e percentil (P) dos indicadores de estatura para idade (E/I), peso para idade (P/I) e índice de massa corporal/idade (IMC/I). Para a classificação do estado nutricional foram adotados três critérios de pontos de corte segundo a curva da população de referência: NCHS/CDC, WHO – World Health Organization - e o adotado pelo Ministério da Saúde do Brasil. Para análise transversal, os escolares foram agrupados por idade, ano de avaliação e região. Já no estudo longitudinal foram agrupados por idade, que coincide com o ano... / The nutritional status of the pediatric population is a relevant indicator of the health and quality of life of the population. However, more longitudinal studies are needed to assess the nutritional status of a particular population group over time to improve the reliability of the results. Therefore, the objective of this study is to use four crosssectional studies and one longitudinal study to assess the nutritional status over time of first- to fourth-graders attending public elementary schools in the city of Piracicaba, SP, from 2003 to 2006. A total of 16068 assessments of 9683 schoolchildren of 12 schools located in the five administrative regions of Piracicaba were made during this period, always in the second semester of each year. These groups of schoolchildren assessed on a yearly basis were called cross-sectional groups. Another group of schoolchildren (n=347) was followed from first to fourth grades during the same period the cross-sectional studies were done. They were called longitudinal group. The following data were collected: name, gender, birth date, grade, class, weight and height. The data were processed by the software Epi-info using the NCHS/CDC - National Center for Health Statistics / Centers for Disease Control and Prevention - 2000 population as reference and expressed as z-scores (Z) and percentiles (P) of the indicators height-for-age (H/A), weight-for-age (W/A), and body mass index-forage (BMI/A). The nutritional status was classified according to the cutoff points given by the NCHS/CDC, World Health Organization (WHO) and that used by the Brazilian Ministry of Health. The schoolchildren were grouped by age, year of assessment and region for the cross-sectional assessment and grouped by age (which coincides with the year of assessment) for the longitudinal assessment. Changes in the nutritional status of these schoolchildren were characterized by reducing... (Complete abstract click electronic access below)

Resumo: Não disponível / Abstract: Upper aero digestive tract (UADT) cancer is an important cause of morbidity and mortality worldwide. Chronic alcohol intake and dietary deficiency zinc, tobacco smoking, and gastroesophageal reflux disease are the major risk factors to the UADT cancer. In the present study, we utilized a diet that mimic inadequate zinc intake (Zn-) diet and supplemented it with unconjugated bile deoxycholic acid (DCA), a component associated with gastroesophageal reflux disease and high fat diets. The aim of this study was to assess the additional influence of exposure to cigarette smoke and ethanol intake on the epithelial alterations of the esophagus and tongue induced by Zn-+DCA diet. Male C57BL/6 mice animals were allocated into six groups: Groups 1 to 3 were fed modified diet (Zn-+ 0.2% DCA) and groups 4 to 6 were fed control diet. After 5-weeks, groups 2 and 5 intake ethanol 10% ad libitum and groups 3 and 6 were exposed to cigarette smoke for 15 weeks. All animals were euthanized at the end of week 20 and tongue and esophagus were collected for histological analysis and immunohistochemical analysis of cell proliferation using Ki- 67 marker and cyclooxygenase 2 expression (COX-2). The Zn-+DCA diet treatment trend to increased cell proliferation indexes and the incidence of hyperkeratosis in the tongue and esophagus but not in COX-2 expression. No additional effect of 15-week treatment with ethanol or cigarette smoke was observed. These findings indicate that dietary zinc deficiency supplemented with deoxycolic acid appears to be an important factor of epithelial aggression and that deleterious effect of ethanol and cigarette smoke could be detected in a long-term exposure. / Orientador: Luis Fernando Barbisan / Coorientador: Maria Aparecida Marchesan Rodrigues / Banca: Noeme Souza Rocha / Banca: Luis Antonio Justulin Junior / Mestre

O objetivo desta dissertação foi o de analisar a Proposta de Formação Continuada do Professor em parceria com a equipe interdisciplinar, desenvolvida pela Secretaria de Educação de São Bernardo do Campo no período de 1996-2003. Identificar com professores da rede municipal de ensino desse Município que atuam na Educação Especial e que vivenciaram esse processo: como repercutiu em suas práticas e se modificou a visão que possuíam sobre a deficiência; se conferiu-lhes instrumentos que os auxiliassem a enfrentar as situações do dia-a-dia, no atendimento à diversidade e na compreensão das situações dela decorrentes; se contribuiu para refletir sobre o seu papel profissional na mediação de um projeto pedagógico mais flexível e transformador; se levou a mudanças no âmbito do ser professor, do saber e do fazer pedagógico. Este trabalho está fundamentado nos estudos da psicologia histórico-cultural de Vygotsky e seus seguidores, nas concepções que embasam a formação do professor e nas contribuições dos pressupostos sobre a Interdisciplinaridade. A metodologia adotada foi o da modalidade qualitativa, imprescindível à análise das percepções e significados atribuídos pelos participantes a esse modelo formativo, expressos em entrevistas e com uso de questionários. A análise dos dados das entrevistas foi realizada em três etapas: 1) categorização das respostas das entrevistadas; 2) categorização definida sob o prisma das teorias que fundamentaram a investigação; 3) reflexões sobre as categorizações, estabelecendo uma convergência dos dados analisados na perspectiva dos dois grupos de categorias. Evidenciaram-se: a importância do processo formativo, valorizando o papel do professor e propiciando crescimento profissional; a contribuição da atividade partilhada e dos vários campos teóricos para apropriação de conhecimentos sobre a criança e suas condições de aprendizagem, fortalecendo o professor para a tomada de decisões mais refletidas e autônomas; as dificuldades relativas à formação dos profissionais da equipe que coordenavam o processo; a pouca clareza na definição dos papéis dos diferentes profissionais; o pouco envolvimento de alguns e excesso de demanda de outros; as dificuldades estruturais e de organização das unidades, deflagrando ausência de sintonia entre Secretaria de Educação e Escola. A análise mostrou que a proposta auxiliou os educadores entrevistados a reconhecerem a importância de um projeto pedagógico elaborado em bases teóricas que ampliem a condição de o professor intervir na aprendizagem de seus alunos com mais clareza e decisão. Por outro lado, assinalou a importância de realizar modelos de formação que ofereçam ao professor um referencial de trabalho mais voltado à análise, reflexão e reconstrução da prática. / This dissertation has as an objective the analysis of the Continuous Development Project, in partnership with an interdisciplinary group, developed by the São Bernardo Educational Department between the years of 1996-2003; to identify along with teachers who work with special education in that city and which have had such experience: how it reflected on their teaching and if it modified their point-of-view on the impairments; if it gave them tools to help with everyday occurrences such as the observation of the diversities and the comprehension of situations occurring due to them; if it helped them to ponder about their roles in the conciliation of more flexible and changing academic tasks; if it led to a transformation on their abilities of being teachers, having knowledge and academic skills. It has been based on Vygotsky (and disciples) historical-cultural psychology studies, regarding the concepts that support the development of the teacher and their contributions to interdisciplinary group formation. The implemented methodology considered quality, essential to the examination of the perceptions and meanings the participants assigned to this development standard, through interviews and surveys. The interviews analysis was carried on in three steps: 1st was the classification of the answers; the classification 2, defined under the hood of the theories that sustained the study; pondering on the classifications leading to a convergence of verified data on the points-of-view of both classified groups. The significance of the developing process valuing the role of the teacher and providing with professional growth became evident; the contribution of the shared activities and academic fields for the gathering of knowledge of kids and for the learning processes, stimulating the teacher on more pondered and independent decision making; the difficulties related to the development of the professionals on the group that coordinated the project; the lack of understanding on the definition of roles of the distinct professionals; the lack of commitment of some professionals and the excessive demand of others; the structural and organizational obstacles of the facilities showing the deficient synchronization between the School Board and the School itself. The analysis has shown that the project helped the surveyed educators to recognize the value of an academic project supported on conceptual basis, which broadens the role of the educators on a clearer and more independent teaching method. On the other hand, it has revealed the importance of the creation of a development standard which can provide the teacher with analytic, pondered, and skill remodeled work orientation.

Este trabalho emergiu de minha inquietação sobre o significado atribuído pelos pais ao cuidar de um filho com deficiência mental. Em nossa sociedade pessoas com deficiência freqüentemente são rotuladas como inferiores, anormais e sofrem diversas formas de preconceitos, muitos deles baseados em razões equivocadas sobre suas reais capacidades. A compreensão do significado atribuído pelos pais ao cuidar do filho com deficiência mental, se faz relevante diante da importância das relações estabelecidas entre pais e filhos para a saúde mental da criança e desenvolvimento de suas potencialidades. Para desvelar o significado dessa experiência existencial tomei como base o referencial teórico metodológico da fenomenologia, que se propõe ao retorno às coisas mesmas, a tirar o véu, desocultar facetas que se encontram obscuras para uma consciência no que se refere à compreensão de um fenômeno. Segundo essa proposta teórico filosófica, o fenômeno que para mim se mostrava oculto era o de “cuidar do filho com deficiência mental’, e a forma de alcançar alguns graus de sua compreensão foi recorrer às pessoas que vivenciam este cuidar, ou seja, os pais.A partir dessas idéias me propus a conhecer a experiência de pais de pessoas com deficiência mental, buscando compreender sua vivência de cuidado.Assim, foram entrevistados 11 casais de pai e mãe e duas mães, que tinham filhos que apresentavam algum tipo de deficiência mental, não sendo nenhum deles recém nascidos ou bebês, para que o encontro se desse com pais que já tivessem uma experiência de cuidado com os filhos, evitando os primeiros momentos de vida com o filho com deficiência, que podem ser de grande conflito para eles. As entrevistas tinham como pergunta norteadora: “como vem sendo cuidar de seu filho”?. Os relatos foram analisados segundo a busca do invariante, das convergências nas descrições das experiências dos pais. Pude compreender que, para os pais encontrados, apesar deles já terem vivenciado alguns anos de cuidado do filho, a deficiência ainda se mostra como algo que tira a humanidade do filho, colocando-os em contato com a dificuldade de conceber a possibilidade de ser-com-deficiência. Entretanto, frente às dificuldades sociais com as quais se deparam, se remetem ao conhecimento experiencial adquirido através da convivência e do reconhecimento das potencialidades do filho para buscar e encontrar meios de favorecer o desenvolvimento do filho como ser humano pleno. O apego ao filho com deficiência é vivido como possibilidade de mudança de postura frente ao outro e reconhecimento da diversidade existencial humana. Pude apreender dos relatos que os pais têm se mostrado participantes no cuidado, embora com atitudes ainda permeadas por concepções onde caberia à mulher a maior parte das responsabilidades para com o filho, mas revelando percepções e vivências significativas no ser-com-o-filho. Entendo que as facetas desveladas neste trabalho poderão contribuir para a compreensão do indivíduo com deficiência como pessoa plena, expressão de uma das diversas possibilidades existenciais humanas. Unitermos: Deficiência mental, pais, fenomenologia.(FAPESP- 01/01698-4). / This work emerged from my disquiet about the meaning given by parents upon caring for a mental handicapped son. In our society, handicapped people are often labeled as inferior, abnormal and suffer several forms of prejudice, many of them based on misunderstanding reasons about their real capacities. The comprehension of the meaning attributed by parents upon caring for a mental handicapped son, as far as I am concerned, makes relevant the importance of relations established among parents and children concerned to child’s mental health as well as the development of their potentialities. In order to find out the meaning of this existential experience I used the reference of the phenomenological theory methodology, that is to return to the simple things, to take off the veil, uncover aspects that are still covered to a conscience concerned to the comprehension of a phenomenon. According to this theoretical and philosophic methodology, the phenomenon that remained obscure to me was “caring for a handicapped mental son”, and the way to reach some degrees of its comprehension was to feel back on people who live this kind of care, I mean, the parents. From these ideas, I proposed myself to know the experience of mental handicapped people’s parents, viewing to understand their real life care experience. Thus, eleven couples and two mothers that had children who presented a kind of mental handicap were interviewed, however none of their offspring were neither newborn babies nor babies, focusing parents that had already had any experience on this matter, avoiding the first moment of life with a son presenting this deficiency, what might be a great trauma to them. The interview had as guide question “ how has it been to care of your son?” The reports were analyzed according to the search on to the invariant, from the convergence descriptions from the parents’ experiences. I could understand that, with the parents interviewed, despite having lived some years of caring, the deficiency remains as something that gets out the son‘s humanity, putting them in contact with the difficulty in conceiving the possibility about being-with-deficiency. However, we have also to consider the social difficulties they face; they launch themselves to called acquired experimental knowledge through the acquaintance and recognition of their children’s potentialities to search and meet the son’s development as a complete human beings. The attachment to a handicapped son is lived as a posture changing possibility in front of one another and recognition of the humane existential diversity. Though the reports the fathers have given I could learn they have been active on their care, though with attitudes still consolidated to misconceptions in which the women assume most responsibilities concerned to the son, but revealing perceptions and meaningful experiences on being-with-the son. Based en that I gathered I would like to say I do understand that the facet found out in the work will contribute to the comprehension of the handicapped individual as a complete person, expression of one of the several humane existential possibilities. Key words: Mental handicap, parents, phenomenology. (FAPESP - 01/01698-4)

Non-alcoholic fatty liver disease (NAFLD) now affects around one in four adults in the human population and parallels the global increase in obesity. Within the spectrum of NAFLD, simple steatosis is associated with insulin resistance and type 2 diabetes while progression to steatohepatitis (NASH) is associated with an increased risk of liver cirrhosis and all-cause mortality. The molecular pathology of NAFLD is incompletely understood, however observational studies in human cohorts suggest the regulation of DNA methylation may play a role. 5-hydroxymethylcytosine (5hmC) is a cytosine modification generated from 5- methylcytosine (5mC) by the Ten eleven translocase isoenzymes (Tets) as part of a demethylation process. The aim of this project was to examine the role of Tet enzyme activity on the pathogenesis and progression of NAFLD. Detailed characterisation of two established murine dietary interventions allowed the selection of a NAFLD mouse model which broadly recapitulated the metabolic, histological and transcriptional features of human disease. Using DNA immunoprecipitation coupled with whole genome next generation sequencing and RNA micro expression arrays I examined the effect of high fat diet feeding (HFD) on hepatic DNA 5hmC levels within annotated gene regions. Whilst the global 5hmC profile was not altered by HFD, there was profound genic enrichment of 5hmC in upregulated mediators of cholesterol synthesis and transport (Lss, Sc4mol, Fdps, Hsd17b7, Cyp17a1, Mvd, Cyp1a2, Dhcr7 and Apoa4) with no enrichment in genes with other pathological functions (drug detoxification, inflammation, cell cycle regulation). Induced peaks of 5hmC enrichment were subsequently abolished following rescue of the NAFLD phenotype by conversion to control diet. Cross species validation was performed in vitro utilising embryonic stem cell derived hepatocytes challenged with a cocktail of high energy substrates. My in vivo findings were broadly replicated with specific 5hmC enrichment in genes synthesising lipotoxic molecules (PLIN2, CIDEC, APOA4, ACADVL, HMGCS2, APOA5, CYP2J2, IGFBP1, PPAP2C, ACSL1, APOC3, ANGPTL4, NRG1) with no enrichment in upregulated genes of alternative function. To determine whether or not the 5hmC enrichment seen is of functional relevance, I studied Tet1-/- C57BL/6J mice. Tet1-/- mice are grossly normal in appearance, however loss of Tet1 conferred a striking resistance to diet induced obesity with reduced body fat mass, improved insulin-sensitivity and near complete absence of NAFLD compared to wild type littermates. Furthermore, the HFD fed Tet1-/- liver transcriptome showed a ‘protective’ profile, with suppression of genes for lipid synthesis, inflammation and fibrosis. Thus, in multiple cross-species models of NAFLD, over nutrition induces genic hydroxymethylation specifically within activated genes driving the synthesis and transport of lipid molecules. Such changes are reversible with resolution of the NAFLD phenotype strengthening functional association. Tet1 deficiency conveys an obesity and NAFLD resistant phenotype. I therefore introduce Tet1 mediated hydroxymethylation as a novel mechanism for NAFLD pathogenesis.