Submitted by Emanuel Varela Cardoso (emanuel.varela@ufcg.edu.br) on 2018-06-08T21:00:15Z No. of bitstreams: 1 THAISA ABRANTES SOUZA GUSMÃO – TESE (PPGEP) 2017.pdf: 3267774 bytes, checksum: 3259599f0f00a0eef121c9d49fc8de4e (MD5) / Made available in DSpace on 2018-06-08T21:00:15Z (GMT). No. of bitstreams: 1 THAISA ABRANTES SOUZA GUSMÃO – TESE (PPGEP) 2017.pdf: 3267774 bytes, checksum: 3259599f0f00a0eef121c9d49fc8de4e (MD5) Previous issue date: 2017-06-08 / Esta pesquisa teve, como objetivo, elaborar pão isento de glúten para doentes celíacos, utilizando a enzima transglutaminase microbiana como adjunto de panificação e prebiótico (inulina) e verificar o efeito na qualidade tecnológica, sensorial e armazenabilidade dos pães. Inicialmente, foi realizada a caracterização físico-química, granulométrica, morfológica e de minerais presentes na farinha de arroz vermelho. A farinha de arroz vermelho (FA), polvilho doce (PD) e suas mesclas (100% FA; 75% FA e 25% PD; 50% FA e 50% PD; 100% PD) foram submetidas à análise de reologia (RVA), espectroscopia de absorção na região do infravermelho com transformada de Fourier (FTIR), difração de raios X e calorimetria exporatória diferencial (DSC). O processo de fabricação dos pães isentos de glúten foi estudado mediante planejamento experimental fatorial completo 22 com 3 experimentos no ponto central, sendo as variáveis independentes [(% enzima transglutaminase microbiana e tempo de fermentação (min)]. As variáveis dependentes do planejamento foram: cor (L*, a* e b*), teor de água, acidez, pH, volume específico e perfil de textura. Utilizou-se, para avaliar as características sensoriais dos pães, um teste de aceitação e de intenção de compra com 60 julgadores não treinados. O armazenamento dos pães de forma pré-assados sob congelamento a -18°C foram estudados durante o período de 90 dias, sendo avaliados periodicamente (01, 05, 15, 30, 60 e 90 dias) em relação à cor, pH, acidez, firmeza e volume específico. A farinha de arroz vermelho apresentou granulometria indicada para a produção de produtos de panificação, não sendo possível descrever uma geometria exata para as partículas. Apresentou alta concentração de fibras (8,80.g.100g-1), proteínas (8,00.g.100g-1), potássio (465,24.mg.100g-1), fósforo (245,50.mg.100g-1) e zinco (24,44 mg 100g-1). A farinha de arroz vermelho e suas mesclas com polvilho doce apresentaram características reológicas adequadas à produção de pães isentos de glúten. A farinha de arroz vermelho apresentou difratogramas de raios X referentes ao padrão de cristalinidade A e o mix com polvilho doce cristalinidade do tipo B. Em relação ao planejamento estatístico, para os atributos teor de água e cor, não foi possível estabelecer modelos significativos. A adição de MTGase e a elevação do seu nível aumentaram o teor de água, o volume específico, a firmeza e a mastigabilidade dos pães. Para abranger o maior número possível de atributos otimizado, foram mantidos os níveis de teor de enzima transglutaminase microbiana entre 0,5 e 1,0% com o tempo de fermentação entre 60-80 (min). Todas as formulações foram bem aceitas sensorialmente, com médias acima de 6,0, exceto para o atributo maciez. A formulação do ponto central (1,0% enzima transglutaminase microbiana e 80 min de tempo de fermentação) foi a que apresentou os maiores índices de aceitação e preferência, com escore 5 (certamente compraria) e escore 4 (possivelmente compraria) para a análise de intenção de compra. Os pães sem glúten com farinha de arroz vermelho, enzima transglutaminase microbiana e prebiótico (inulina) apresentaram características de qualidade aceitáveis durante o armazenamento sob congelamento a -18°C, por 60 dias. Esses resultados mostram que o uso de farinha de arroz vermelho e enzima transglutaminase microbiana em formulações de pão sem glúten, são uma opção para o público celíaco obter produtos com qualidade física e sensorial. / This research aimed to characterize the red rice flour and formulate gluten-free bread for celiacs, applying microbial transglutaminase enzyme as the adjunct of baking and prebiotic (inulin) and verify the effect on the technological, sensorial quality and storability of the breads. First, it determined the physical-chemical, granulometric, morphological characterization and the minerals present in the red rice flour were determined. Red rice flour (FA), sweet manioc starch (PD) and its mixtures (100% FA, 75% FA and 25% PD, 50% FA and 50% PD, 100% PD) were submitted to rheology analysis (RVA), Fourier transform infrared (FTIR) absorption spectroscopy, X-ray diffraction and differential exporatory calorimetry (DSC). In the second stage, processing of gluten-free breads and physical, physical-chemical, sensory and storageability were performed. The breadmaking process was studied by a full factorial design 23 with 3 experiments in the central point, and the independent variables [(% microbial transglutaminase enzyme and fermentation time (min)].The dependent variables in the experimental planning were: Color (L *, a * and b *), water content, acidity, pH, specific volume, firmness, elasticity, chewiness and cohesiveness. We were used to evaluate the sensory characteristics of bread an acceptance test and purchase intent with 60 judges untrained. The storage formulations of gluten-free form loaves under freezing at -18 ° C were studied over a period of 90 days and were periodically evaluated at baseline and at predetermined intervals of 01, 05, 15, 30, 60 and 90 Days in relation to color (L *, a * and b *), pH, acidity, firmness and specific volume. The red rice flour showed granulometry indicated for the production of bakery products, and it is not possible to describe an exact geometry for the particles. Showed high concentration of fibers (8,80.g.100g-1), proteins (8,00.g.100g-1), potassium (465,24.mg.100g-1), phosphorus (245,50.mg .100g-1) and zinc (24.44mg 100g-1). The red rice flour and its mixtures with sweet manioc starch presented rheological characteristics suitable for the production of gluten-free breads. The red rice flour presented x-ray diffractograms related to the crystallinity pattern A and the mix with sweet pozzolan type B crystallinity. Regarding statistical planning, it was not possible to establish significant models for water and color attributes (L *, a * and b *). The addition of MTgase and the elevation of its level increased the water content, the specific volume and firmness of the bread chewiness. To cover as many optimized attributes as possible, it was possible to maintain levels of microbial transglutaminase enzyme content between 0.5 and 1.0% with the fermentation time between 60-80 (min). All formulations were well accepted sensorially, with averages above 6.0, except for the softness attribute. The PC formulation (1.0% MTgase and 80 min TF) presented the best attributes, greater acceptance and preference, presenting the highest scores: 5 (would certainly buy) and score 4 (possibl y buy) for the intention analysis of purchase. Gluten-free breads with red rice flour, microbial transglutaminase enzyme and prebiotic (inulin) had acceptable quality characteristics during storage under freezing at -18 ° C for 60 days. These results show that the use of red rice flour and microbial transglutaminase enzyme in gluten-free bread formulations is an option for the celiac public to obtain products with physical and sensory quality.

Introdução e Objetivos: A maior prevalência de doença celíaca (DC) em indivíduos com diabetes mellitus tipo I (DM1) já é reconhecida. Ambas as doenças tem causa autoimune, em que os genes HLA classe 2 representam o principal fator genético de risco. Porém, existe uma considerável parcela da população que não manifesta tais doenças e são portadores desses genes. Estudo de associação genômica (GWAS) identificaram polimorfismos de susceptibilidade às duas doenças em genes diferentes do sistema HLA, que poderão auxiliar na compreensão da causa e das suas variabilidades clínicas. Os objetivos desse estudo foram avaliar as frequências dos polimorfismos HLA e não HLA em pessoas como DM1 e com DC e relacionar esses dados com a ocorrência de sintomas gastrointestinais, com a idade do diagnóstico da DM1 e com história alimentar. Métodos: Delineamento transversal, com avaliações retrospectivas e prospectivas, em pessoas com DM1 com e sem DC. Foram realizadas entrevista e revisão de prontuário dos pessoas, seguido de coleta de sangue ou saliva. A pesquisa dos genes RGS1, IL2-IL21, BACH2, TLR7/TLR8 e IL18RAP foi realizada por PCR Real-Time. Os alelos DQA1* 0501 e DQB1* 0201 para DQ2.5 e o alelo DQB1*0302 para DQ8 foram identificados a partir da técnica de genotipagem de HLA Tag-single-nuleotide polymorphism (Tag SNP). Resultados: As frequências alélicas e genotípicas entre 273 pessoas com DM1 sem DC e 39 pessoas com DM1 e DC não apresentaram diferença significativa. A presença de sintoma gastrointestinal foi mais frequente nos portadores dos polimorfismos dos genes RGS1 e IL18RAP. O tempo de aleitamento materno, a idade de introdução do glúten e a idade do diagnóstico da DM1 foram semelhantes entre os grupos. A comparação dos cinco polimorfismos com a combinação dos haplótipos para DQ2.5 e DQ8 não apresentou diferença significativa. Nos 312 indivíduos, com DM1 com e sem DC e nos 66 indivíduos portadores de DC sem DM1 foi identificado alelos DQ2.5 e ou DQ8 em 97% dos casos, enquanto que nos indivíduos com DC sem DM1 identificou-se em 76% dos casos. DQ2.5 foi mais frequente entre pessoascom DC e DQ8 foi mais frequentes entre pessoas com DM1. Conclusões: A presença dos polimorfismos dos genes estudados não modificou a chance do indivíduo com DM1 ter ou não DC. Houve associação dos genes RGS1 e IL18RAP com sintomas gastrointestinais. A pesquisa dos alelos DQ2.5 e DQ8, pela técnica Tag-SNP, permitiu determinar um alto valor preditivo negativo no diagnóstico de DC na população com DM1 e com DC, semelhante ao descrito na literatura com a técnica convencional. / Introduction and Objectives: The higher prevalence of celiac disease (CD) in individuals with diabetes mellitus type I (T1D) is already recognized. Both diseases have autoimmune cause, where HLA genes class 2 represent the major genetic risk factor. However, there is a considerable portion of the population that does not manifest such diseases and are carriers of these genes. Genome-wide association studies (GWAS) have identified susceptibility polymorphisms to both diseases in different genes of the HLA system that may assist in understanding the etiology and in its clinical variabilities. The objectives of this study were to evaluate the frequencies of HLA and non-HLA polymorphisms in patients with T1D and CD, related to the occurrence of gastrointestinal symptoms, the age of diagnosis of T1D and food history. Methods: Mixed design with retrospective and prospective evaluations in patients with T1D with and without DC. They were conducted interview and review of medical records of patients, followed by collecting blood or saliva. The search for genes RGS1, IL21-IL2, BACH2, TLR7 / TLR8 and IL18RAP was performed by Real-Time PCR. The alleles DQA1 * 0501 and DQB1 * 0201 for DQ2.5 and DQB1 * 0302 for DQ8 were identified from the Tag-single-nucleotide polymorphism (tag SNP) genotyping HLA technique Results: The allelic and genotypic frequencies between 273 T1D patients without CD and 39 patients with T1D and CD showed no significant difference. The presence of gastrointestinal symptoms were more frequent in patients with polymorphisms of genes RGS1 and IL18RAP. The duration of breastfeeding, the age of introduction of gluten and the age of diagnosis of T1D were similar between the groups. The comparison of the five polymorphisms with the combination of haplotypes for DQ2.5 and DQ8 showed no significant difference. In 312 individuals with DM1 with and without CD and 66 individuals with CD without T1D was identified alleles DQ2.5 and/or DQ8 in 97% of cases, whereas in individuals with CD without T1D was identified in 76% of cases . DQ2.5 was more frequent among patients with CD and DQ8 was more frequent among patients with T1D Conclusions: The presence of polymorphisms of genes studied did not modify the chance of T1D whether or not DC. There was an association of RGS1 and IL18RAP genes with gastrointestinal symptoms. The survey of DQ2.5 and DQ8 alleles by Tag-SNP technique allowed determining a high negative predictive value in the diagnosis of CD in the population of patients with T1D and DC, similar to that described in the literature with the conventional technique.

SAMMANFATTNING Bakgrund: Celiaki är en autoimmun sjukdom med en prevalens på 2/100 i Sverige. Enda behandlingen är att äta en kost fri från gluten. Gluten förekommer i spannmålen vete, råg, korn och att diagnostiseras med celiaki innebär ofta att en förändring av matvanor blir nödvändig. Att leva tillsammans med någon med celiaki har visat sig kunna vara problematiskt då familjelivet kan påverkas negativt och föräldrar till barn med celiaki upplever ofta oro och ängslan för sitt barn. Syfte: Syftet med studien var att undersöka hur mödrar till barn med celiaki upplever och hanterar familjens vardag i relation till barnets specialkost. Metod: Ett målinriktat urval användes och kvalitativa, semi-strukturerade intervjuer genomfördes med nio mödrar till barn med celiaki. Materialet spelades in och transkriberades ordagrant för att sedan analyseras med kvalitativ innehållsanalys. Resultat: Samtliga mödrar upplevde att vardagen hade anpassats efter barnet med celiaki och det fanns olika sätt att hantera den glutenfria kosten. Vissa valde att ha helt glutenfritt hemma för att undvika stress över rädslan att ge barnet fel mat. Andra valde att ha både gluteninnehållande och glutenfria livsmedel hemma p.g.a. ekonomiska skäl samt preferenser från övriga familjemedlemmar. Kunskapsnivån kring celiaki i samhället ansågs låg, vilket upplevdes försvåra vardagen för mödrar till ett barn med celiaki. Majoriteten av mödrarna uttryckte att bästa stödet fanns att tillgå via internet och sociala medier. Slutsats: Enligt mödrar till barn med celiaki innebar sjukdomen en del dilemman och vardagen upplevdes stundvis som orofylld, vilket kan påverka livskvaliteten. Internet och sociala medier sågs som ett bra stöd i vardagen. Ökad kunskap samt större förståelse från omgivningen skulle kunna förbättra familjernas vardag. / ABSTRACT                          Background: Celiac disease (CD) is an autoimmune disorder with a prevalence of 2/100 in Sweden. The only treatment is a diet free from gluten. Gluten occurs in grains of wheat, rye, barley and being diagnosed with CD often means that a change in eating habits is necessary. Living together with someone with CD has been shown to be problematic. Family life may be negatively affected and parents of children with CD experience worry and anxiety for their child. Objective: The aim of the study was to examine how mothers of children with CD experienced and handled everyday life in relation to their child's gluten-free diet (GFD). Method: A targeted selection was used and qualitative, semi-structured interviews were conducted with nine mothers of children with CD. The interviews were recorded and transcribed verbatim and then analyzed with qualitative content analysis. Results: All participants felt that everyday life had been adapted to the child with CD and there were different ways to deal with the GFD. Some chose to have the home as a gluten-free zone to avoid the stress of risking to give the child wrong food. Others chose to have both gluten-containing and gluten-free foods at home because of economic aspects and preferences from other family members. The level of knowledge about CD in the community was considered low, which was perceived to complicate everyday life for mothers of a child with CD. The majority of participants expressed that best support was found through Internet and social media. Conclusion: According to mothers of children with CD, the disease involved some dilemmas and daily life was at times perceived as worrisome, which can affect quality of life. Internet and social media were considered as good support in everyday life. Increased knowledge in society and greater understanding from the environment could improve families everyday life.

INTRODUCTION: Celiac disease is a chronic immune disorder for which the only treatment is strict life-long adherence to a gluten-free diet (GFD). Collaborative management through regular follow-up with a care team that includes physicians and dietitians may improve long-term outcomes. However, many individuals with celiac disease are lost to follow-up. OBJECTIVE: This primary objective of this study was to identify factors associated with pediatric celiac disease patients being lost to follow-up. Secondary aims included identifying adherence to recommended care practices by both patients and providers. METHODS: A chart review of 250 randomly selected children with biopsy-confirmed celiac disease diagnosed between 2010 and 2014 at Boston Children’s Hospital (BCH) was conducted. Follow-up records were reviewed from diagnosis to 2017. Eligible children were diagnosed prior to age 18 and did not attend BCH solely for a second opinion. Demographics, medical history, visit information, and lab results were collected using an online database. RESULTS: Of the 241 eligible subjects (64% female, 1-17 years, median 9.7 years) the median time until lost to follow-up was 2.8 years from diagnosis (IQR, 1.0-4.7 years) with 22 subjects (9%) not attending any follow-up visits with their pediatric gastroenterologist (GI) after diagnosis and an additional 37 subjects (14%) lost within the first year. A majority of subjects (83%) attended a GFD education visit with a registered dietitian, although this was not associated with follow-up adherence (P>0.5). Excluding those who had aged out of the clinical practice, children who were adherent to follow-up had a younger mean age of diagnosis (95% CI 0.5-3.1, P<0.01). Children who were insured under Medicaid/CHIP (N=20) were more likely to be lost within one year compared to those with private health insurance (P<0.01). Celiac serologies taken at time of last clinical visit were abnormal in 25% of the subjects with available results (N=141) and the median time since diagnosis in this positive serology subgroup was 20 months (IQR, 12-29 months). DISCUSSION: The present study illustrates that children with celiac disease are not being followed-up adequately and that identifiable disparities exist in the pediatric celiac disease population. Within three years of diagnosis, 50% of the cohort was lost to follow-up with the majority of subjects lost within the first year of diagnosis. Children diagnosed at a younger age were more adherent to follow-up compared to those diagnosed during adolescence. Factors associated with decreased adherence included reliance on public medical insurance and older age at diagnosis. Improvement in long-term management of celiac disease may be achieved by increased outreach and education.

Introdução: A doença celíaca (DC) é definida como enteropatia imune-mediada causada por uma permanente sensibilidade ao glúten em indivíduos geneticamente predispostos. O glúten está presente em cereais como trigo, centeio e cevada e deve ser excluído da alimentação pelo resto da vida. A avaliação da Qualidade de Vida (QV), neste contexto, assume crucial importância por ser uma forma de avaliar as conseqüências em longo prazo da doença e de seu tratamento na perspectiva da própria criança, além de ser um importante indicador de saúde global destes indivíduos. Objetivo: Avaliar a Qualidade de Vida de crianças com DC e comparar com controles pareados sem a doença. Sujeitos e Métodos: Estudo caso-controle onde foram incluídas 72 crianças: 24 celíacas (8 meninos) de 6 a 12 anos, em uso de dieta sem gluten por pelo menos 1 ano. Os celíacos foram recrutados através da Associação dos Celíacos do Brasil no Rio grande do Sul, nos ambulatórios de gastropediatria do Hospital de Clinicas de Porto Alegre e Hospital da Criança Santo Antonio. O grupo controle foi composto por 48 escolares pareados por sexo, idade atual, escolaridade da criança e materna. A Qualidade de Vida foi avaliada através da escala AUQUEI - Autoquestionnaire Enfant Imagé. Uma escala adaptada ao contexto pediátrico através de suporte de imagens, que engloba os domínios pertinentes a QV infantil, sob um enfoque subjetivo. Resultados: As crianças celíacas apresentaram melhores escores de QV que seus pares sem a doença. Os celíacos apresentaram escores mais elevados em 23 das 26 questões e em todos os domínios avaliados. A diferença entre os grupos incidiu na faixa etária de 6 até os 9 anos. Meninas celíacas apresentaram menores escores que os meninos. O perfil de respostas foi semelhante em ambos os grupos – maior escore nas atividades de lazer e recreação e menor escore quanto à autonomia e separação. Não houve diferença significativa entre tempo de aleitamento materno e idade de introdução do glúten na dieta. A família fazer a dieta junto com a criança celíaca não afetou os índices de QV. Conclusão: A DC esteve associada a uma melhor QV nas crianças avaliadas. Meninos celíacos e mais jovens apresentaram os maiores escores. Estes achados sugerem que a QV variou conforme as fases do desenvolvimento e quanto à experiência com a doença, o que nos leva a considerar que doenças crônicas que não cursem com incapacidade física podem não comprometer a QV de seus portadores ou até mesmo estar associadas à melhor QV em crianças. / Introduction: Celiac disease (CD) is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. The gluten is present in cereals as wheat, rye and barley and it should be excluded from patient’s diet for the rest of their life. The assessment of Quality of Life (QoL), assumes in this context a crucial importance for evaluating the consequences of the illness and its treatment in the child’s point of view beyond a significant indicator of these individuals global health. Objective: Evaluate the QoL of celiac children and compare it to healthy paired control group. Patients and Methods: Case-control study that included 72 children: 24 celiac children (8 boys) between 6 and 12 years of age and 48 paired control group, in diet gluten-free . Celiac children were recruited from Brazilian Celiac Association in the State of Rio Grande do Sul, from the outpatients of the Gastroenterology Service at the Hospital de Clínicas de Porto Alegre, both located in southern Brazil. The control group was composed of school-children paired by gender, age, child’s school level and mother’s school level. Quality of Life assessment was performed using AUQUEI (Autoquestionnaire Enfant Imagé) questionnaire. It has been adapted to the pediatric context through imaging support, enabling comparisons to healthy children, besides placing the child QoL-relevant domains under a subjective focus. Results: Celiac children presented better QoL scores than their healthy pairs. Celiac children had higher scores in 23 out of total 26 questions and in all assessed domains. The profile of answers was similar in both groups – lower scores in Autonomy and higher scores in Leisure. The difference between the groups occurred in the 6-9 age group. Celiac girls showed lower scores than celiac boys. The profile of answers was similar in both the groups – highest scores in the activities of leisure and recreation and lowest scores in autonomy and separation. It did not have significant difference between time of breast feeding and age of introduction of gluten in the diet. The family to make the diet together with the celiac child did not affect QoL scores. Conclusion: Celiac Disease was associated with better QoL in assessed children. Younger celiac boys showed the highest scores. These findings suggest that the QoL varies according to the stages of cognitive development and experience with illness. It makes us suppose that chronic diseases in childhood that do not imply physical disability may not affect the QoL of the patients, or may even be associated with better quality of life scores in children.

Made available in DSpace on 2015-07-22T20:49:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-22 / Introdução: o diagnóstico da doença celíaca é um processo complexo devido à multiplicidade dos sintomas, sinais, grupos de risco, formas de apresentação e intersecção dos sintomas com outras doenças. Para a confirmação da suspeita diagnóstica, é imprescindível a realização da biopsia do intestino delgado, o padrão-ouro. Objetivo: desenvolver um sistema de apoio à decisão, em ambiente web, integrado a um classificador automático para reconhecimento dos casos de doença celíaca. Métodos: um sistema web foi construído para suportar um protocolo eletrônico esquematizado para atendimento e registro dos dados clínicos dos pacientes. Uma avaliação preliminar de usabilidade foi realizada. Uma base de dados de retrospectiva com 178 casos clínicos para treinamento foi construída. Foram testados 270 classificadores automáticos disponíveis no software Weka 3.6.1, utilizando cinco técnicas de inteligência artificial, a saber, árvores de decisão, classificador bayesiano, k-vizinhos próximos, máquinas de vetor de suporte e redes neurais artificiais. As métricas analisadas foram área sob a curva ROC, sensibilidade, especificidade e taxa de acerto, utilizadas nessa sequência como critério para seleção do algoritmo a ser implantado no sistema web. O algoritmo com maior AUC foi selecionado e acoplado ao sistema web, gerando o software intitulado SADCEL. Uma base de dados de teste foi construída, com 38 casos clínicos, para a avaliação do SADCEL em relação à utilidade diagnóstica. A hipótese diagnóstica apontada pelo SADCEL foi comparada às indicadas pelos especialistas durante a realização da consulta por meio de estatística kappa. Resultados: o sistema web foi avaliado pelos usuários com nível excelente de usabilidade, com SUS-score de 83,5 ± 10,0. Na fase de treinamento, as melhores métricas foram apresentadas pelo algoritmo AODE F-1, do tipo classificador bayesiano, com taxa de acerto 80,0%, sensibilidade 0,78, especificidade 0,80 e AUC 0,84. Comparado ao padrão ouro, o SADCEL alcançou uma precisão de 84,2% com um nível de concordância diagnóstica de k = 0,68 (p <0,0001), o que indicou um bom nível de concordância. A mesma taxa de acerto foi obtida na comparação entre as indicações do diagnóstico dos especialistas e o padrão-ouro, com k = 0,64 (p-value <0,0001). Entre a indicação do especialista e do SADC, obteve-se k = 0,46 (p-value = 0,0008), o que indica concordância moderada. Conclusão: o nível de precisão alcançado pelo algoritmo de classificação automática integrado ao sistema web evidencia a utilidade potencial da SADCEL no auxílio ao diagnóstico de doença celíaca / Introduction: the diagnosing of celiac disease involves some complexity due to its multiple symptoms, signs, risk groups, presentation and the wide possibility of differential diagnosis. In order to confirm the diagnosis of celiac disease, it is required to perform the biopsy or the small intestine, the gold standard. Objective: to develop a decision making support system, in web environment, including an automated classifier to recognize cases of celiac disease, to be previously selected among experimental models drawing upon techniques of artificial intelligence. Methods: a web system was implemented to support an electronic protocol designed to help with celiac disease investigation and collect clinical data. A preliminary assessment of this system usability was performed through the analysis of a questionnaire based on the System Usability Scale (SUS) completed by 10 direct users of the web system implemented. A retrospective database with 178 cases was build for training the automated classifier. A total of 270 automated classifiers available in the software Weka 3.6.1 were tested using 5 artificial intelligence techniques – decision tree, K-nearest-neighbor, Bayesian classifier, support vector machine and artificial neural networks. The parameters area under the receiver operating characteristic curve (AUC), sensitivity, specificity and correctness rate were used, in the order above, as criteria to select the classification algorithm to be implemented in the web system. The algorithm with the largest AUC was included in the web system whose software was named SADCEL. A database with 38 clinical cases was built to assess the diagnostic power this software. The diagnostic hypothesis obtained from SADCEL was compared with those reached by the specialists participating in the study using Kappa Statistic. Results: the preliminary usability score attained by the web system was 83.5 ± 10.0 (excellent). The Bayesian classifying algorithm AODE F1 had the best performance scoring 80.0% for correctness, 0.78 for sensitivity, 0.84 for specificity and 0.84 for AUC. Compared with the study gold standard, SADCEL achieved an accuracy of 84.2% with a level of agreement with the diagnostic gold standard rated as k = 0.68 (p-value < 0.0001), indicative of good level of agreement. The level of agreement between the specialist diagnostic hypothesis and the diagnostic gold standard was rated as k = 0.64 (p-value < 0.0001). The agreement between the specialist and SADCEL diagnostic hypotheses was rated as k = 0.46 (p-value) indicative of moderate level of agreement. Conclusion: the level of accuracy attained by the classifying algorithm incorporated in this study´s web system evidences the potential usefulness of SADCEL in helping with diagnosing celiac disease in clinical set. This study is, thus, expected to be a contribution towards the establishing of a computational means of diagnosing the celiac disease. / TEDE

Introdução e Objetivos: A maior prevalência de doença celíaca (DC) em indivíduos com diabetes mellitus tipo I (DM1) já é reconhecida. Ambas as doenças tem causa autoimune, em que os genes HLA classe 2 representam o principal fator genético de risco. Porém, existe uma considerável parcela da população que não manifesta tais doenças e são portadores desses genes. Estudo de associação genômica (GWAS) identificaram polimorfismos de susceptibilidade às duas doenças em genes diferentes do sistema HLA, que poderão auxiliar na compreensão da causa e das suas variabilidades clínicas. Os objetivos desse estudo foram avaliar as frequências dos polimorfismos HLA e não HLA em pessoas como DM1 e com DC e relacionar esses dados com a ocorrência de sintomas gastrointestinais, com a idade do diagnóstico da DM1 e com história alimentar. Métodos: Delineamento transversal, com avaliações retrospectivas e prospectivas, em pessoas com DM1 com e sem DC. Foram realizadas entrevista e revisão de prontuário dos pessoas, seguido de coleta de sangue ou saliva. A pesquisa dos genes RGS1, IL2-IL21, BACH2, TLR7/TLR8 e IL18RAP foi realizada por PCR Real-Time. Os alelos DQA1* 0501 e DQB1* 0201 para DQ2.5 e o alelo DQB1*0302 para DQ8 foram identificados a partir da técnica de genotipagem de HLA Tag-single-nuleotide polymorphism (Tag SNP). Resultados: As frequências alélicas e genotípicas entre 273 pessoas com DM1 sem DC e 39 pessoas com DM1 e DC não apresentaram diferença significativa. A presença de sintoma gastrointestinal foi mais frequente nos portadores dos polimorfismos dos genes RGS1 e IL18RAP. O tempo de aleitamento materno, a idade de introdução do glúten e a idade do diagnóstico da DM1 foram semelhantes entre os grupos. A comparação dos cinco polimorfismos com a combinação dos haplótipos para DQ2.5 e DQ8 não apresentou diferença significativa. Nos 312 indivíduos, com DM1 com e sem DC e nos 66 indivíduos portadores de DC sem DM1 foi identificado alelos DQ2.5 e ou DQ8 em 97% dos casos, enquanto que nos indivíduos com DC sem DM1 identificou-se em 76% dos casos. DQ2.5 foi mais frequente entre pessoascom DC e DQ8 foi mais frequentes entre pessoas com DM1. Conclusões: A presença dos polimorfismos dos genes estudados não modificou a chance do indivíduo com DM1 ter ou não DC. Houve associação dos genes RGS1 e IL18RAP com sintomas gastrointestinais. A pesquisa dos alelos DQ2.5 e DQ8, pela técnica Tag-SNP, permitiu determinar um alto valor preditivo negativo no diagnóstico de DC na população com DM1 e com DC, semelhante ao descrito na literatura com a técnica convencional. / Introduction and Objectives: The higher prevalence of celiac disease (CD) in individuals with diabetes mellitus type I (T1D) is already recognized. Both diseases have autoimmune cause, where HLA genes class 2 represent the major genetic risk factor. However, there is a considerable portion of the population that does not manifest such diseases and are carriers of these genes. Genome-wide association studies (GWAS) have identified susceptibility polymorphisms to both diseases in different genes of the HLA system that may assist in understanding the etiology and in its clinical variabilities. The objectives of this study were to evaluate the frequencies of HLA and non-HLA polymorphisms in patients with T1D and CD, related to the occurrence of gastrointestinal symptoms, the age of diagnosis of T1D and food history. Methods: Mixed design with retrospective and prospective evaluations in patients with T1D with and without DC. They were conducted interview and review of medical records of patients, followed by collecting blood or saliva. The search for genes RGS1, IL21-IL2, BACH2, TLR7 / TLR8 and IL18RAP was performed by Real-Time PCR. The alleles DQA1 * 0501 and DQB1 * 0201 for DQ2.5 and DQB1 * 0302 for DQ8 were identified from the Tag-single-nucleotide polymorphism (tag SNP) genotyping HLA technique Results: The allelic and genotypic frequencies between 273 T1D patients without CD and 39 patients with T1D and CD showed no significant difference. The presence of gastrointestinal symptoms were more frequent in patients with polymorphisms of genes RGS1 and IL18RAP. The duration of breastfeeding, the age of introduction of gluten and the age of diagnosis of T1D were similar between the groups. The comparison of the five polymorphisms with the combination of haplotypes for DQ2.5 and DQ8 showed no significant difference. In 312 individuals with DM1 with and without CD and 66 individuals with CD without T1D was identified alleles DQ2.5 and/or DQ8 in 97% of cases, whereas in individuals with CD without T1D was identified in 76% of cases . DQ2.5 was more frequent among patients with CD and DQ8 was more frequent among patients with T1D Conclusions: The presence of polymorphisms of genes studied did not modify the chance of T1D whether or not DC. There was an association of RGS1 and IL18RAP genes with gastrointestinal symptoms. The survey of DQ2.5 and DQ8 alleles by Tag-SNP technique allowed determining a high negative predictive value in the diagnosis of CD in the population of patients with T1D and DC, similar to that described in the literature with the conventional technique.

Coeliac disease (CD) is a chronic gastrointestinal condition, the only treatment for which is a gluten-free diet (GFD). Following a GFD is restrictive, burdensome, and can impact health-related quality of life (HRQOL). People with CD can experience long delays to diagnosis and evidence suggests large variations in follow-up care, but the relationship between health care experiences and HRQOL is unknown. The main aim of this research was to develop a patient-reported outcome measure and patient experience questionnaire, and use these to investigate the relationship between adults' experiences of health care services and HRQOL in CD. The questionnaires, named the Coeliac Disease Assessment Questionnaire (CDAQ) and the Coeliac Disease Patient Experience Questionnaire (CD-PEQ), were developed following qualitative interviews with adults with CD, and refined with input from experts, and cognitive interviews. The CDAQ was also subject to a translatability assessment to assess its linguistic and cultural translatability, and a cross-sectional survey to assist with item reduction and scale generation. Members of Coeliac UK (n=267) completed the CDAQ and CD-PEQ, together with the SF-36v2 and demographic questions as part of a postal survey. Psychological health, vitality, general health, and dietary burden were found to have the greatest impact on HRQOL, with physical health and social isolation the least affected. HRQOL was found to have a strong correlation with patients' experiences of health care services. Aspects most strongly related were: the provision of information; communication with HCPs; difficulty obtaining prescriptions; and GPs' knowledge. This research has identified aspects of health care services that are strongly related to HRQOL in CD. Health care providers are recommended to focus service improvement efforts on these areas. A reliable and valid disease-specific patient-reported outcome measure and patient experience questionnaire have been developed as part of this study. The CDAQ is suitable for use in research studies, including clinical trials, to assess HRQOL in CD.

Introdução: A doença celíaca (DC) é definida como enteropatia imune-mediada causada por uma permanente sensibilidade ao glúten em indivíduos geneticamente predispostos. O glúten está presente em cereais como trigo, centeio e cevada e deve ser excluído da alimentação pelo resto da vida. A avaliação da Qualidade de Vida (QV), neste contexto, assume crucial importância por ser uma forma de avaliar as conseqüências em longo prazo da doença e de seu tratamento na perspectiva da própria criança, além de ser um importante indicador de saúde global destes indivíduos. Objetivo: Avaliar a Qualidade de Vida de crianças com DC e comparar com controles pareados sem a doença. Sujeitos e Métodos: Estudo caso-controle onde foram incluídas 72 crianças: 24 celíacas (8 meninos) de 6 a 12 anos, em uso de dieta sem gluten por pelo menos 1 ano. Os celíacos foram recrutados através da Associação dos Celíacos do Brasil no Rio grande do Sul, nos ambulatórios de gastropediatria do Hospital de Clinicas de Porto Alegre e Hospital da Criança Santo Antonio. O grupo controle foi composto por 48 escolares pareados por sexo, idade atual, escolaridade da criança e materna. A Qualidade de Vida foi avaliada através da escala AUQUEI - Autoquestionnaire Enfant Imagé. Uma escala adaptada ao contexto pediátrico através de suporte de imagens, que engloba os domínios pertinentes a QV infantil, sob um enfoque subjetivo. Resultados: As crianças celíacas apresentaram melhores escores de QV que seus pares sem a doença. Os celíacos apresentaram escores mais elevados em 23 das 26 questões e em todos os domínios avaliados. A diferença entre os grupos incidiu na faixa etária de 6 até os 9 anos. Meninas celíacas apresentaram menores escores que os meninos. O perfil de respostas foi semelhante em ambos os grupos – maior escore nas atividades de lazer e recreação e menor escore quanto à autonomia e separação. Não houve diferença significativa entre tempo de aleitamento materno e idade de introdução do glúten na dieta. A família fazer a dieta junto com a criança celíaca não afetou os índices de QV. Conclusão: A DC esteve associada a uma melhor QV nas crianças avaliadas. Meninos celíacos e mais jovens apresentaram os maiores escores. Estes achados sugerem que a QV variou conforme as fases do desenvolvimento e quanto à experiência com a doença, o que nos leva a considerar que doenças crônicas que não cursem com incapacidade física podem não comprometer a QV de seus portadores ou até mesmo estar associadas à melhor QV em crianças. / Introduction: Celiac disease (CD) is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. The gluten is present in cereals as wheat, rye and barley and it should be excluded from patient’s diet for the rest of their life. The assessment of Quality of Life (QoL), assumes in this context a crucial importance for evaluating the consequences of the illness and its treatment in the child’s point of view beyond a significant indicator of these individuals global health. Objective: Evaluate the QoL of celiac children and compare it to healthy paired control group. Patients and Methods: Case-control study that included 72 children: 24 celiac children (8 boys) between 6 and 12 years of age and 48 paired control group, in diet gluten-free . Celiac children were recruited from Brazilian Celiac Association in the State of Rio Grande do Sul, from the outpatients of the Gastroenterology Service at the Hospital de Clínicas de Porto Alegre, both located in southern Brazil. The control group was composed of school-children paired by gender, age, child’s school level and mother’s school level. Quality of Life assessment was performed using AUQUEI (Autoquestionnaire Enfant Imagé) questionnaire. It has been adapted to the pediatric context through imaging support, enabling comparisons to healthy children, besides placing the child QoL-relevant domains under a subjective focus. Results: Celiac children presented better QoL scores than their healthy pairs. Celiac children had higher scores in 23 out of total 26 questions and in all assessed domains. The profile of answers was similar in both groups – lower scores in Autonomy and higher scores in Leisure. The difference between the groups occurred in the 6-9 age group. Celiac girls showed lower scores than celiac boys. The profile of answers was similar in both the groups – highest scores in the activities of leisure and recreation and lowest scores in autonomy and separation. It did not have significant difference between time of breast feeding and age of introduction of gluten in the diet. The family to make the diet together with the celiac child did not affect QoL scores. Conclusion: Celiac Disease was associated with better QoL in assessed children. Younger celiac boys showed the highest scores. These findings suggest that the QoL varies according to the stages of cognitive development and experience with illness. It makes us suppose that chronic diseases in childhood that do not imply physical disability may not affect the QoL of the patients, or may even be associated with better quality of life scores in children.

Introdução: A doença celíaca (DC) é definida como enteropatia imune-mediada causada por uma permanente sensibilidade ao glúten em indivíduos geneticamente predispostos. O glúten está presente em cereais como trigo, centeio e cevada e deve ser excluído da alimentação pelo resto da vida. A avaliação da Qualidade de Vida (QV), neste contexto, assume crucial importância por ser uma forma de avaliar as conseqüências em longo prazo da doença e de seu tratamento na perspectiva da própria criança, além de ser um importante indicador de saúde global destes indivíduos. Objetivo: Avaliar a Qualidade de Vida de crianças com DC e comparar com controles pareados sem a doença. Sujeitos e Métodos: Estudo caso-controle onde foram incluídas 72 crianças: 24 celíacas (8 meninos) de 6 a 12 anos, em uso de dieta sem gluten por pelo menos 1 ano. Os celíacos foram recrutados através da Associação dos Celíacos do Brasil no Rio grande do Sul, nos ambulatórios de gastropediatria do Hospital de Clinicas de Porto Alegre e Hospital da Criança Santo Antonio. O grupo controle foi composto por 48 escolares pareados por sexo, idade atual, escolaridade da criança e materna. A Qualidade de Vida foi avaliada através da escala AUQUEI - Autoquestionnaire Enfant Imagé. Uma escala adaptada ao contexto pediátrico através de suporte de imagens, que engloba os domínios pertinentes a QV infantil, sob um enfoque subjetivo. Resultados: As crianças celíacas apresentaram melhores escores de QV que seus pares sem a doença. Os celíacos apresentaram escores mais elevados em 23 das 26 questões e em todos os domínios avaliados. A diferença entre os grupos incidiu na faixa etária de 6 até os 9 anos. Meninas celíacas apresentaram menores escores que os meninos. O perfil de respostas foi semelhante em ambos os grupos – maior escore nas atividades de lazer e recreação e menor escore quanto à autonomia e separação. Não houve diferença significativa entre tempo de aleitamento materno e idade de introdução do glúten na dieta. A família fazer a dieta junto com a criança celíaca não afetou os índices de QV. Conclusão: A DC esteve associada a uma melhor QV nas crianças avaliadas. Meninos celíacos e mais jovens apresentaram os maiores escores. Estes achados sugerem que a QV variou conforme as fases do desenvolvimento e quanto à experiência com a doença, o que nos leva a considerar que doenças crônicas que não cursem com incapacidade física podem não comprometer a QV de seus portadores ou até mesmo estar associadas à melhor QV em crianças. / Introduction: Celiac disease (CD) is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. The gluten is present in cereals as wheat, rye and barley and it should be excluded from patient’s diet for the rest of their life. The assessment of Quality of Life (QoL), assumes in this context a crucial importance for evaluating the consequences of the illness and its treatment in the child’s point of view beyond a significant indicator of these individuals global health. Objective: Evaluate the QoL of celiac children and compare it to healthy paired control group. Patients and Methods: Case-control study that included 72 children: 24 celiac children (8 boys) between 6 and 12 years of age and 48 paired control group, in diet gluten-free . Celiac children were recruited from Brazilian Celiac Association in the State of Rio Grande do Sul, from the outpatients of the Gastroenterology Service at the Hospital de Clínicas de Porto Alegre, both located in southern Brazil. The control group was composed of school-children paired by gender, age, child’s school level and mother’s school level. Quality of Life assessment was performed using AUQUEI (Autoquestionnaire Enfant Imagé) questionnaire. It has been adapted to the pediatric context through imaging support, enabling comparisons to healthy children, besides placing the child QoL-relevant domains under a subjective focus. Results: Celiac children presented better QoL scores than their healthy pairs. Celiac children had higher scores in 23 out of total 26 questions and in all assessed domains. The profile of answers was similar in both groups – lower scores in Autonomy and higher scores in Leisure. The difference between the groups occurred in the 6-9 age group. Celiac girls showed lower scores than celiac boys. The profile of answers was similar in both the groups – highest scores in the activities of leisure and recreation and lowest scores in autonomy and separation. It did not have significant difference between time of breast feeding and age of introduction of gluten in the diet. The family to make the diet together with the celiac child did not affect QoL scores. Conclusion: Celiac Disease was associated with better QoL in assessed children. Younger celiac boys showed the highest scores. These findings suggest that the QoL varies according to the stages of cognitive development and experience with illness. It makes us suppose that chronic diseases in childhood that do not imply physical disability may not affect the QoL of the patients, or may even be associated with better quality of life scores in children.