Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Thesis (Ph.D.). / Title from title page of PDF (viewed 2008/01/30). Written for the Division of Experimental Medicine. Includes bibliographical references.

Thèse (M. Sc.)--Université Laval, 2004. / Bibliogr.: f. [67]-74. Publié aussi en version électronique.

Thèse (Ph. D.)--Université Laval, 2004. / Bibliogr.: f. [180]-216. Publié aussi en version électronique.

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Auteursnaam op omslag: Francy Crijns. Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Orientador: Eloiza Helena Tajara da Silva / Banca: Dorotéia Rossi Silva Souza / Banca: Fábio César Gozzo / Banca: Victor Evangelista de Faria Ferraz / Banca: Elaine Sbroggio de Oliveira Rodini / Resumo: A Neurofibromatose Tipo 1 (NF1) é uma doença autossômica dominante causada por mutações no gene NF1, responsável pela síntese da proteína neurofibromina. Muitos estudos publicados sobre NF1 têm focado as alterações desse gene e de seu produto em indivíduos afetados, mas as análises de expressão protéica são escassas. No presente estudo, nós investigamos diferenças quantitativas e qualitativas da expressão de proteínas entre amostras de neurofibroma e pele adjacente histologicamente normal, utilizando abordagem proteômica. As proteínas de neurofibroma e pele normal foram separadas por eletroforese bidimensional (2-DE) e identificadas por peptide mass fingerprinting, utilizando espectrometria de massas por dessorção e ionização a laser auxiliada por matriz com base no tempo de vôo (MALDI-TOF). Cinco proteínas foram identificadas: a caspase 14 e a proteína de choque térmico 27/HSP 27, que exibiram expressão reduzida em neurofibromas; a imunoglobulina, a flavina redutase e a proteína de ligação a fosfatidiletanolamina/PEBP, com expressão elevada em neurofibromas. Do nosso conhecimento, este é o primeiro relato de análise comparativa de neurofibromas e pele normal de pacientes com neurofibromatose tipo 1. Das proteínas identificadas, a HSP27 e a PEBP estão conectadas com as vias de sinalização celular p21ras ou cAMP, também relacionadas com a atuação da neurofibromina. A caspase 14 não exibe um elo conhecido com essas cascatas e tal fato pode abrir novos caminhos para o estudo da neurofibromatose. Estudos adicionais ainda são necessários para elucidar o papel dessas proteínas no desenvolvimento da neurofibromatose. Nosso estudo é um passo inicial na descoberta de mecanismos moleculares desta doença e mostra o valor da utilização da análise proteômica na identificação de novos parceiros da neurofibromina relacionados com o desenvolvimento da NF1. / Abstract: Neurofibromatosis Type 1 (NF1) is a common autosomal dominant disorder caused by mutations in the NF1 gene. Many of the studies published on NF1 have focused attention on the gene level, but protein expression analyses are scarce. In the present study, we investigated quantitative and qualitative differences in neurofibroma and histologically normal surrounding skin protein expression of NF1 patients, using a proteomic approach. Proteins from neurofibroma and normal skin were separated by two-dimensional electrophoresis (2-DE) and identified by peptide mass fingerprinting, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). Five proteins were identified: caspase 14 and heat shock protein 27 kDa protein/HSP 27 (downregulated in neurofibroma), immunoglobulin, flavin reductase and phosphatidylethanolamine binding protein/PEBP (upregulated in neurofibroma). To our knowledge, this is the first report of a comparative analysis of neurofibromas and normal skin from neurofibromatosis type 1 patients. Of the proteins identified, HSP27 and PEBP have a connection with p21ras or cAMP signaling. Caspase 14 has no known link with these pathways and may open a new avenue for studying neurofibromatosis. Further studies are still needed to elucidate the actual roles of the differentially expressed proteins. Our work is an initial step toward uncovering the molecular mechanism of this disease and shows the value of using proteomic analysis to identify novel partners of neurofibromin related to the development of NF1. / Doutor

Class of 2017 Abstract / Objectives: The purpose of the study was to identify the types of motivation that promote sustained physical activity among adolescents between the ages of 11-17 who are diagnosed with type 1 diabetes (T1D) to prevent diabetes related complications. Methods: Questionnaires were distributed and collected among the Juvenile Diabetes Research Foundation’s (JDRF) listserv, Facebook page, and events in Phoenix and Tucson, Arizona on motivations for managing diabetes and exercise and confidence in diabetes management and performing physical activity. Demographic data was collected on age, gender, and race/ethnicity. Physical activity, levels of activity intensity, weight, height, health- related risk behaviors, chronic health conditions, and use of preventative services were also included in this study. Results: 11 adolescents completed questionnaires, categorized by participants who exercise less than 60 minutes daily (Group below recommended exercise level, GBRE) and participants who exercise more or equal to 60 minutes daily (Group meeting recommended exercise level, GMRE). GBRE’s average mean age was 15.75 and GMRE’s average mean age was 13.92. GMRE was associated with higher intensity physical activity (42.85% versus 0%). GBRE had a relative autonomy index (RAI) of 1.67 on the Treatment Self-regulation Questionnaire (TSRQ) compared to GMRE with a RAI of 3.81 (Mann-Whitney U 19, p-value 0.412). GBRE scored 73.75 on the Diabetes Self-efficacy Scale (DSES) and GMRE scored 78.71 (Mann-Whitney U 7, p-value 0.23). Conclusions: Adolescents who exercised ≥ 60 minutes daily were observed to be self-motivated in managing their diabetes, especially maintaining exercise recommendations to decrease diabetes related complications.

Type 1 diabetes is an autoimmune disease that involves destruction of pancreatic cells that produce insulin. The disease typically presents in children and adolescents. The burden of disease management, fear of complications, and disruption of normal childhood that the disease causes place youth with type 1 diabetes at increased risk for developing depression compared to peers without the disease. The presence and severity of depression correlates with disease outcomes. Use of continuous subcutaneous insulin infusion pumps has been shown to improve youth’s quality of life compared to use of multiple daily insulin injections. Although quality of life measures are associated with the risk of developing depression, no studies have compared depression symptomatology in youth using insulin pumps to those using multiple daily insulin injections. The proposed project will assess relative depression symptomatology in youth ages 10-17 using insulin pumps and multiple daily insulin injections. The results of this proposed project could help inform clinicians’ decisions about whether to initiate type 1 diabetes therapy in youth with either insulin pumps or insulin injections. Given the financial burden of depression, it could also potentially encourage insurance companies to increase coverage of insulin pumps.