Submitted by PPG Pediatria e Sa?de da Crian?a (pediatria-pg@pucrs.br) on 2018-01-02T12:12:35Z No. of bitstreams: 1 TESE_GENO.final.pdf: 2568933 bytes, checksum: 07252a154299b7fc86a5efe776f3f730 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-01-24T11:02:16Z (GMT) No. of bitstreams: 1 TESE_GENO.final.pdf: 2568933 bytes, checksum: 07252a154299b7fc86a5efe776f3f730 (MD5) / Made available in DSpace on 2018-01-24T11:05:41Z (GMT). No. of bitstreams: 1 TESE_GENO.final.pdf: 2568933 bytes, checksum: 07252a154299b7fc86a5efe776f3f730 (MD5) Previous issue date: 2017-07-03 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Introduction: According to the literature, cesarean delivery represents an obstacle to breastfeeding in the first hours of life and is one of the factors for early weaning. One of the hypotheses to explain these findings is that the production of breast milk may be insufficient in the first hours after a cesarean section. However, the way by which delivery route affects the onset of breastfeeding is not clearly established. Objective: To compare the volume of breast milk at 12 and at 36 hours in puerperal women after normal delivery and cesarean section. Method: Cross-sectional study with quantitative analysis and non probabilistic convenience sampling. All the puerperae (and their newborns) with a singleton pregnancy of 38 to 42 weeks, whose delivery occurred from 8 pm to midnight between September 2016 and January 2017 were eligible for the study. They were divided into two groups, one of post normal delivery and the other of post cesarean section. Breast milk was collected at 12 and 36 hours postpartum with an electric breast pump, and its volume was based on the weight verified in a scale with 0.01 g precision. In addition to the way of delivery and the breast milk volume, variables included time of onset of breastfeeding and maternal as well as newborn characteristics. Results: Seventy-four puerperae were included in the normal delivery group and 26 in the cesarean section group. Both groups were similar for maternal and newborn characteristics. The median volume of milk collected at 12 hours was 0.90 mL (interquartile range 0.28-1.73 mL) in the normal delivery group, and 1.36 mL (interquartile range 0.36-2.91 mL ) in the cesarean section group (p=0.127). The median volume of milk collected at 36 hours was higher in the cesarean section group (4.23 mL, interquartile range 3.05-5.00 mL) than in the normal delivery group (3.22 mL, interquartile range 2.60-4.11 mL) (p=0.025). Regarding the time elapsed between delivery and the first feeding, no differences in milk volume were observed at both 12 and 36 hours in either group. When only cesarean deliverers were evaluated, there was no difference in milk volume between those with labor and no labor at 12 hours (p=0,411) or at 36 hours (p=0681). Conclusion: There was no difference in the volume of milk produced at 12 hours postpartum by puerperae with full term gestation, between the normal and cesarean delivery groups. At 36 hours postpartum, milk volume was higher in the cesarean section group, however the small difference was considered clinically irrelevant. / Introdu??o: Conforme a literatura, o parto ces?reo representa um empecilho para a amamenta??o nas primeiras horas de vida e ? um dos fatores do desmame precoce. Uma das hip?teses para explicar esses fatores ? que a produ??o de leite materno possa ser insuficiente nas primeiras horas ap?s uma cesariana. Entretanto, o modo pelo qual a via de parto afeta o in?cio da amamenta??o n?o est? claramente estabelecido. Objetivo: Comparar o volume do leite produzido as 12 e ?s 36 horas p?s-parto, em pu?rperas de parto normal e parto ces?reo. M?todo: Estudo transversal com an?lise quantitativa e amostragem n?o probabil?stica de conveni?ncia. Foram eleg?veis para o estudo todas as pu?rperas (e seus rec?m-nascidos) com gesta??o ?nica de 38 a 42 semanas, cujo parto ocorreu no hor?rio das 20h ?s 24h entre setembro de 2016 e janeiro de 2017. As pu?rperas foram divididas em dois grupos, um p?s-parto normal e o outro p?s-cesariana. O leite materno foi coletado com um aparelho de ordenha el?trico, as 12 e ?s 36 horas p?s-parto, e o seu volume foi baseado no peso verificado em uma balan?a com precis?o de 0,01 g. Al?m da via de parto e do volume de leite materno, as vari?veis inclu?ram momento de in?cio do aleitamento, caracter?sticas maternas e do neonato. Resultados: Foram inclu?das 74 pu?rperas no grupo parto normal e 26 no grupo parto ces?reo. Ambos os grupos foram semelhantes quanto ?s caracter?sticas maternas e dos rec?m-nascidos. A mediana do volume de leite coletado ?s 12 horas foi de 0,90 mL (intervalo interquartil 0,28-1,73 mL) no grupo parto normal, e de 1,36 mL (intervalo interquartil 0,36-2,91 mL) no grupo cesariana (p=0,127). A mediana do volume de leite coletado ?s 36 horas foi maior no grupo cesariana (4,23 mL, intervalo interquartil 3,05-5,00 mL) do que no grupo parto normal (3,22 mL, intervalo interquartil 2,60-4,11 mL) (p=0,025). Em rela??o ao tempo transcorrido entre o parto e a primeira mamada, n?o foram observadas diferen?as no volume de leite, tanto ?s 12, como ?s 36 horas, em nenhum dos dois grupos. Quando avaliadas somente as pu?rperas de parto ces?reo, n?o houve diferen?a no volume de leite ?s 12 horas (p=0,411) nem ?s 36 horas (p=0,681) entre aquelas com trabalho de parto e sem trabalho de parto. Conclus?o: N?o houve diferen?a no volume de leite produzido ?s 12 horas p?s-parto pelas pu?rperas com gesta??o a termo, entre os grupos parto normal e cesariana. Na coleta das 36 horas p?s-parto, o volume de leite foi maior no grupo cesariana, entretanto a pequena diferen?a foi considerada clinicamente irrelevante.

Submitted by PPG Pediatria e Sa?de da Crian?a (pediatria-pg@pucrs.br) on 2018-01-02T16:51:55Z No. of bitstreams: 1 Disserta??o Mestrado Marilisa.pdf: 905969 bytes, checksum: 348718dad9108301470f73e80e214e5c (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-01-24T12:31:32Z (GMT) No. of bitstreams: 1 Disserta??o Mestrado Marilisa.pdf: 905969 bytes, checksum: 348718dad9108301470f73e80e214e5c (MD5) / Made available in DSpace on 2018-01-24T12:33:57Z (GMT). No. of bitstreams: 1 Disserta??o Mestrado Marilisa.pdf: 905969 bytes, checksum: 348718dad9108301470f73e80e214e5c (MD5) Previous issue date: 2017-03-03 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Cystic fibrosis (CF) has long been described as a fatal genetic disease. Currently, improvement in the care of these patients contributes to longer survival and thereby allows the observation of other symptoms related to mutations of the cystic fibrosis transmembrane chloride regulator (CFTR) gene, responsible for the disease. Although pulmonary disease continues to be the leading cause of morbidity and mortality, CF also requires that attention be given to manifestations of the disease in other organs, such as liver disease. CF-associated liver disease (CFLD) can be considered an independent risk factor for mortality and lung transplantation. The major challenge is to diagnose CFLD, because the changes may remain asymptomatic until advanced stages of the disease. There is currently no single test that is sensitive and specific enough to assess liver function, and early diagnosis of CFLD requires a combination of regular clinical examination, biochemical tests, and imaging studies. There are high expectations for noninvasive tests that are harmless to patients and can be easily repeated and compared in order to detect changes as early as possible. Imaging techniques have improved significantly over the past decade and new technologies are being incorporated into clinical practice. Ultrasonography (US), computed tomography and magnetic resonance imaging (MRI) are the main imaging modalities currently used for examination, but new MRI-based techniques have acquired great importance. Thus, it would be desirable to develop a more accurate method than US, which is the most widely used routine examination, as well as the ultrasound scoring system described by Williams et al in 1995 and used so far. This study aimed to describe possible MRI abnormalities in children with CF and correlate them with US findings, particularly in relation to parameters of parenchyma, border, and liver fibrosis. Methods: Patients with a diagnosis of CF underwent clinical examination, anthropometric measurements, US, and MRI. MRI was performed without sedation or contrast. The liver was evaluated using the scoring system described by Williams et al on US and MRI images. Other MRI features were also analyzed, including degenerative nodules, atrophy of the right hepatic lobe, and posterior notch sign of the hepatic lobe. Results: The US and MRI findings of 20 patients were analyzed. Patient age ranged from 8 to 19 years. Five patients showed US abnormalities with an ultrasound score greater than 3, 4 patients with a score of 7, and 1 patient with a score of 9. When the Williams scoring criteria were applied to MRI, 5 patients were evaluated as having a score of 9. US did not assess liver fibrosis in the same way as MRI. In the US evaluation, 4 patients received a score of 1 for this parameter, while in the MRI evaluation all patients received the maximum score. MRI revealed 4 patients with atrophy of the right hepatic lobe, 3 patients with degenerative nodules, and 2 patients with esophageal varices. Four patients (80%) showed the posterior notch sign of the hepatic lobe. Conclusion: Although there was a good correlation between US and MRI, MRI performed better than US in the assessment of liver fibrosis. The Williams scoring system can also be applied to hepatic MRI. Thus, MRI stands out as a noninvasive method that can provide further information related to CFLD, contributing to the overall assessment of patients with CF. / A fibrose c?stica (FC) foi por muito tempo descrita como uma doen?a gen?tica fatal. Atualmente, a melhora nos cuidados de sa?de destes pacientes possibilitou uma maior sobrevida e assim a observa??o de outras sintomatologias relacionadas ? muta??o do gene CFTR (cystic fibrosis transmembrane chloride regulator), respons?vel pela doen?a. Apesar da doen?a pulmonar continuar sendo a principal causa de morbidade e mortalidade, a FC exige aten??o tamb?m para manifesta??es de doen?a em outros ?rg?os, como o caso da doen?a hep?tica. A doen?a hep?tica associada ? FC (DHFC) pode ser considerada um fator de risco independente para a mortalidade e transplante pulmonar. O grande desafio ? o seu diagn?stico, pois suas altera??es podem permanecer assintom?ticas at? est?gios avan?ados da doen?a. N?o h? dispon?vel um teste que seja sens?vel e espec?fico para avaliar a fun??o hep?tica, o diagn?stico precoce da DHFC requer o conjunto de exame cl?nico regular, exames de bioqu?mica e de imagem. ? grande a expectativa por exames n?o invasivos que sejam in?cuos para o paciente e possam ser facilmente repetidos e comparados para a busca de altera??es o mais precoce poss?vel. As t?cnicas de imagem t?m melhorado significativamente na ?ltima d?cada e as novas tecnologias est?o come?ando a entrar na pr?tica cl?nica. Ultrassonografia (US), tomografia computadorizada e resson?ncia magn?tica (RM) s?o as principais modalidades usadas atualmente, mas novas t?cnicas baseadas em RM est?o em destaque. Desta forma, seria desej?vel desenvolver uma metodologia mais acurada que a US que ? o exame rotineiramente mais difundido, assim como o escore ultrassonogr?fico descrito por Williams et al em 1995, utilizado at? ent?o. Nosso objetivo ? descrever as poss?veis altera??es encontradas na RM em crian?as com FC e correlacionar com os achados da US, principalmente em rela??o aos par?metros de par?nquima, borda e fibrose hep?tica. M?todos: Pacientes com diagn?stico de fibrose c?stica realizaram avalia??o cl?nica, antropom?trica, exames de ultrassonografia e resson?ncia magn?tica. Os exames de resson?ncia magn?tica foram realizados sem seda??o e sem contraste. O f?gado foi avaliado segundo o escore descrito por Williams et al na ultrassonografia e na resson?ncia magn?tica. Foram analisados ainda outros diferentes aspectos na RM entre eles: n?dulos degenerativos, atrofia do lobo hep?tico direito, o sinal do entalhe posterior do lobo hep?tico. Resultados: Os exames de vinte pacientes foram analisadas, os participantes do estudo tinham idade entre 8 e 19 anos. Cinco pacientes apresentaram exame de US alterado com escore ultrassonogr?fico maior que 3, quatro pacientes com escore 7 e um com escore 9. Ao aplicar os crit?rios do escore de Williams na resson?ncia magn?tica, os 5 pacientes foram avaliados com escore 9. A ultrassonografia n?o pode avaliar a fibrose hep?tica da mesma forma que a resson?ncia, na US quatro pacientes receberam pontua??o 1 para o par?metro, j? na RM todos receberam pontua??o m?xima. Na RM, foram identificados quatro pacientes com atrofia do lobo hep?tico direito, tr?s pacientes com n?dulos degenerativos e 2 pacientes com varizes esof?gicas. Quatro pacientes (80%) apresentaram o sinal do entalhe posterior do lobo hep?tico direito. Conclus?o: Existe uma boa correla??o entre US e RM, por?m a RM teve melhor desempenho na avalia??o da fibrose hep?tica. O escore de Williams tamb?m pode ser aplicado para an?lise hep?tica pela RM. Assim a RM se destaca como um m?todo n?o invasivo que nos fornecer ainda outras informa??es relacionadas com a DHFC que contribuem na avali??o global do paciente com FC.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-01-22T16:54:43Z No. of bitstreams: 1 FERNANDA_BRAGA_SEGANFREDO_TES.pdf: 2778630 bytes, checksum: 5fc271d0cea044d5614d83e47e4bcd95 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-01-29T13:42:00Z (GMT) No. of bitstreams: 1 FERNANDA_BRAGA_SEGANFREDO_TES.pdf: 2778630 bytes, checksum: 5fc271d0cea044d5614d83e47e4bcd95 (MD5) / Made available in DSpace on 2018-01-29T13:46:04Z (GMT). No. of bitstreams: 1 FERNANDA_BRAGA_SEGANFREDO_TES.pdf: 2778630 bytes, checksum: 5fc271d0cea044d5614d83e47e4bcd95 (MD5) Previous issue date: 2017-09-06 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Background: Obesity is a worldwide concern of growing proportions, that increases both morbidity and mortality of patients, despite having economic impact. Imbalances in the gut microbiota - the bacteria that inhabit the intestines - are central to the pathogenesis of obesity. Objectives: To assess the association between the gut microbiota and weight loss in overweight/obese adults and its potential manipulation as a target for treating obesity. Methodology: This study is a systematic review review that identified studies using the keywords ?overweight? or ?obesity? and ?microbiota? and related terms. Results: 43 papers were identified. Among these studies, 17 used dietary interventions, 11 used bariatric surgery and 15 used microbiota manipulation. The studies differed in their methodologies as well as their intervention lengths. Restrictive diets decreased the microbiota abundance, correlated with nutrient deficiency rather than weight loss and generally reduced the butyrate producers Firmicutes, Lactobacillus sp. and Bifidobacterium sp. The impact of surgical intervention depended on the given technique and showed a similar effect on butyrate producers, in addition to increasing the presence of the Proteobacteria phylum, which is related to changes in the intestinal absorptive surface, pH and digestion time. Probiotics differed in strain and duration with diverse effects on the microbiota, and they tended to reduce body fat. Prebiotics had a bifidogenic effect and increased butyrate producers, likely due to cross-feeding interactions, contributing to the gut barrier and improving metabolic outcomes. Conclusions: All of the interventions under consideration had impacts on the gut microbiota, although they did not always correlate with weight loss. These results show that restrictive diets and bariatric surgery reduce microbial abundance and promote changes in microbial composition that could have long-term detrimental effects on the colon. In contrast, prebiotics might restore a healthy microbiome and reduce body fat. / Contexto: A obesidade ? uma doen?a de incid?ncia crescente mundialmente, que aumenta a morbidade e mortalidade dos pacientes, al?m de ter impacto na economia. O desequil?brio na microbiota intestinal - microrganismos que habitam o intestino humano - ? apontado como importante na patog?nese dessa doen?a. Objetivos: Avaliar a associa??o entre microbiota intestinal e perda ponderal em pacientes com sobrepeso ou obesidade, e a possibilidade do uso de terapias que tenham como alvo a microbiota intestinal no tratamento dessas condi??es. Metodologia: Este trabalho ? uma revis?o sistem?tica que identificou estudos utilizando os termos ?sobrepeso? ou ?obesidade? e ?microbiota? ou termos relacionados. Resultados: Foram identificados 43 estudos. Dentre esses, 17 utilizaram interven??es nutricionais, 11 realizaram cirurgia bari?trica e 15 usaram manipula??o direta da microbiota intestinal (prebi?ticos, probi?ticos ou simbi?ticos). Os estudos apresentaram metodologias e interven??es (tipo e dura??o) heterog?neas. Interven??es nutricionais restritivas reduziram a abund?ncia microbiana, correlacionada especialmente com defici?ncia de nutrientes, e n?o diretamente com perda de peso; al?m de apresentarem tend?ncia a redu??o dos grupos bacterianos produtores de butirato, como Firmicutes, Lactobacillus sp. e Bifidobacterium sp.. O impacto das interven??es cir?rgicas (cirurgia bari?trica) depende da t?cnica escolhida e apresenta o mesmo efeito nos grupos bacterianos produtores de butirato, adicionalmente aumentando a abund?ncia do filo Proteobacteria, o que est? relacionado com modifica??es na superf?cie absorptiva intestinal, pH e tempo de digest?o. O uso de probi?ticos variou entre os estudos inclu?dos, com diferen?as na dura??o da suplementa??o e cepas utilizadas, resultando em impacto diverso na microbiota, com tend?ncia a redu??o da gordura corporal. O uso de prebi?ticos apresentou efeito bifidog?nico e consequente aumento dos grupos bacterianos produtores de butirato, provavelmente relacionado a alimenta??o cruzada entre as esp?cies, contribuindo para manuten??o da barreira intestinal e melhora dos desfechos metab?licos. Conclus?es: Todas as interven??es consideradas apresentaram impacto na microbiota, entretanto nem sempre correlacionado a perda ponderal. Esses resultados mostram que interven??es nutricionais restritivas e cirurgia bari?trica reduzem a abund?ncia microbiana e promovem mudan?as na microbiota intestinal que podem ser prejudiciais a sa?de do c?lon a longo prazo. Em contraste, o uso de prebi?ticos pode restaurar uma microbiota saud?vel e reduzir gordura corporal.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-01-26T13:27:51Z No. of bitstreams: 1 RAFAELA_SIVIERO_CARON_LIENERT_TES.pdf: 9419976 bytes, checksum: f123a0ee4d12fb6dd455c726f40ece4f (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-01-31T13:24:29Z (GMT) No. of bitstreams: 1 RAFAELA_SIVIERO_CARON_LIENERT_TES.pdf: 9419976 bytes, checksum: f123a0ee4d12fb6dd455c726f40ece4f (MD5) / Made available in DSpace on 2018-01-31T13:29:24Z (GMT). No. of bitstreams: 1 RAFAELA_SIVIERO_CARON_LIENERT_TES.pdf: 9419976 bytes, checksum: f123a0ee4d12fb6dd455c726f40ece4f (MD5) Previous issue date: 2017-11-21 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Background: During 24 hours of peritoneal dialysis (PD), it is estimated that 100 to 300g of the glucose are absorbed, which can generate metabolic changes and nutritional disorders. Objective: To study pathophysiological and clinical aspects related to nutritional status of PD patients. Materials and Methods: Observational study of PD patients evaluating body composition by bioimpedance (Body Composition Monitor; Fresenius Medical Care), examining peritoneal membrane characteristics, measuring biochemical parameters and using inductively coupled plasma mass spectrometer to measure serum concentrations of copper (63Cu), zinc (66Zn), selenium (78Se), chromium (52Cr) and nickel (58Ni). Results for each paper: Article 1: After 1y on PD, 50.6% had dry weight (DW) gain, 41.2% showed lean tissue mass (LTM) loss, and 65.9% presented fat mass (FM) gain and significant differences in DW, body mass index (BMI), adipose tissue mass (ATM), FM and fat tissue index (FTI) were disclosed. Patients with lower dialysate-to-plasma creatinine ratio showed FM gain. We observed a higher percentage of nonfast transporters in DW gain when comparing with no gain. Artigo 2: No differences were disclosed regarding body composition changes between PD modalities (CAPD and APD). Article 3: At baseline 29.9% of the patients were classified as having undernutrition (Lean Tissue Index (LTI) percentile <10th), 55.5% as obese (FTI percentile >90th), 7.9% as having fat tissue undernutrition (FTI percentile <10th) and 23.8% had LTI undernutrition and obesity in combination. The cumulative survival rates were 92%, 83%, 69%, 67% and 60% (12, 24, 36, 48 and 60 months, respectively). Kaplan-Meier survival and Cox regressions analysis showed that only PhA bellow 5? had an impact on mortality during the follow-up, even after adjusting for age, gender and diabetes. Artigo 4: Values below references were disclosed for Zn (5.8 ? 1.1 ?mol/L) in 100%; Cu (15.7 ? 5.0 ?mol/L) in 20.7%; Se (0.59 ? 0.22 ?mol/L) in 75.9%. Values above references were disclosed for Cr (0.29 ? 0.08 ?mol/L) in 86.3% and Ni (0.21 (0.17 ? 0.26) ?mol/L) in 96.6%. We observed significant positive corretations between Cu and DW (r=0.407, P=0.028), BMI (r=0.460, P=0.012) and FTI (r=0.370, P0.048). Zn was positivily correlated to albumin (r=0.527, P=0.003) and negatively correlated with OH (r=-0.394, P=0.034) and extracellular water (%ECW) (r=-0.466, P=0.014). Se had a positive correlation with serum albumin (r=0.515, P=0.005) and total cholesterol (r=0.443, P=0.021), but a negative correlation with %ECW (r=-0.404, P=0.041) and extracellular water/intracellular water (r=0.398, P0.036). Ni was negatively correlated to dry weight (r=-0.377, P0.044). Cu/Zn ratio was only correlated to BMI (r=0.376, P=0.044). Conclusions: Body composition changes over PD treatment and it does not seems to be related to the exposure of glucose or to the PD modality, however, it seems to be related to patients with slower peritoneal transports at the beginning of the treatment. Detailed analysis of body composition can generate more accurate data of nutritional status. The use of the phase angle as a marker of nutritional status is suggested and further studies are needed to better understand the association of serum microelements and body composition in this population. / Introdu??o: Durante 24 horas de Di?lise Peritoneal (DP), estima-se que cerca de 100 a 300g da glicose s?o absorvidas, o que pode gerar altera??es metab?licas e no estado nutricional. Objetivos: Estudar aspectos fisiopatol?gicos e cl?nicos relacionados ao estado nutricional de pacientes em DP. Materiais e m?todos: Estudo observacional de pacientes em DP com an?lise da composi??o corporal atrav?s da bioimped?ncia espectrosc?pica (Body Composition Monitor, Fresenius Medical Care), avalia??o da caracter?stica de transporte peritoneal, exames bioqu?micos e concentra??o s?rica de cobre (63Cu), zinco (66Zn), sel?nio (78Se), cromo (52Cr) e n?quel (58Ni) atrav?s de espectometria de massa com plasma indutivamente acoplado. Resultados por artigo: Artigo 1: Ap?s 1 ano de DP, 50,6% ganharam peso, 41,2% perderam massa magra, 65,9% aumentaram massa gorda, sendo encontrado aumento significativo para peso, ?ndice de massa corporal (IMC), tecido adiposo e ?ndice de massa gorda. Os pacientes que ganharam peso predominantemente apresentavam baixo transporte peritoneal. Artigo 2: A modifica??o da composi??o corporal encontrada n?o foi diferente entre modalidades de DP, ambulatorial cont?nua (CAPD) e automatizada (APD). Artigo 3: No in?cio da DP, os pacientes foram classificados em: 29,9% desnutridos (massa magra percentil <10), 55,5% obesos (massa gorda percentil >90) e 7,9% como desnutridos por massa gorda (massa gorda percentil <10) e 23,8% desnutri??o e obesidade em combina??o. A sobrevida cumulativa foi de 92%, 83%, 69%, 67% e 60% (12, 24, 36, 48 e 60 meses, respectivamente). O ?ngulo de fase (abaixo de 5?) possui impacto na mortalidade, inclusive ap?s ajuste para idade, sexo e diabetes. Artigo 4: Valores abaixo da refer?ncia foram observados para Zn (5,8 ? 1,1 ?mol/L) em 100%; Cu (15,7 ? 5,0 ?mol/L) em 20,7%; Se (0,59 ? 0,22 ?mol/L) em 75,9%. Valores acima do recomendado foram encontrados para Cr (0,29 ? 0,08 ?mol/L) em 86,3% e Ni (0,21 (0.17 ? 0.26) ?mol/L em 96,6%. Foi observada correla??o positiva entre Cu e peso seco (r=0,407, P=0,028), IMC (r=0,460, P=0,012) e ?ndice de massa gorda (r=0,370, P0,048). Zn apresentou correla??o positiva com albumina (r=0,527, P=0,003) e negativa com hiperhidrata??o (r=-0,394, P=0,034) e percentual de ?gua extracelular (r=-0,466, P=0,014). Se apresentou correla??o positiva com albumina (r=0,515, P=0,005) e colesterol total (r=0,443, P=0,021), mas negativa com percentual de ?gua extracelular (r=-0,404, P=0,041) e ?gua extracelular/?gua intracelular (r=0,398, P0,036). Ni correlacionou-se negativamente com peso seco (r=-0,377, P0,044). Cu/Zn apresentou correla??o com IMC (r=0,376, P=0,044). Conclus?es: A composi??o corporal de pacientes em DP se modifica ao longo do tratamento, o que n?o parece estar relacionado a exposi??o a glicose ou ? modalidade de DP, por?m, as altera??es parecem estar relacionadas ? pacientes que apresentam transportes peritoneais mais lentos no in?cio da terapia. A an?lise da composi??o corporal de forma detalhada pode gerar dados mais precisos de avalia??o nutricional. Sugere-se o uso do ?ngulo de fase como um marcador de estado nutricional e mais estudos s?o necess?rios para o melhor entendimento da associa??o de microelementos s?ricos e composi??o corporal nesta popula??o.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-01-26T17:43:24Z No. of bitstreams: 1 RAFAEL_DOS_SANTOS_MAZZUCA_DIS.pdf: 2501773 bytes, checksum: 8e77692cbd2f35eb9907d89c485c3237 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-02-05T11:21:14Z (GMT) No. of bitstreams: 1 RAFAEL_DOS_SANTOS_MAZZUCA_DIS.pdf: 2501773 bytes, checksum: 8e77692cbd2f35eb9907d89c485c3237 (MD5) / Made available in DSpace on 2018-02-05T11:44:18Z (GMT). No. of bitstreams: 1 RAFAEL_DOS_SANTOS_MAZZUCA_DIS.pdf: 2501773 bytes, checksum: 8e77692cbd2f35eb9907d89c485c3237 (MD5) Previous issue date: 2017-03-10 / Everyyear the number of people with diabetes increases considerably. By the year 2014, more than 414 million cases of the disease have been registered worldwide. A major problem is the increasing number of diabetic patients who develop ulcers in the lower limbs, a complication mainly due to inadequate glycemic control, besides the imbalance in the inflammatory phase during the process of tissue regeneration, which often leads to amputation of the lower limbs.The increase number ofcases andcomplications derived from the diabetesrequire the development of new therapeutic strategies to minimize the development of these ulcers to more severe cases new therapeutic strategies are necessary, aiming to minimize the development of these ulcers thatleads to a poor quality of life due to ulcers, and ultimately, amputations. Cell therapy associated with the use of biomaterials, produced through tissue engineering processes, represents a new alternative for current treatments. The use of bone marrow mononuclear cells has shown to be an important ally for the healing process, since they are a good quality and abundant cells of easy access. The purpose of this study was to evaluate whether the use of a biomaterial as a biological dressing, associated or not with bone marrow mononuclear cells, would improve the regenerative response of ulcer lesions, reducing the time of healing.Streptozotocin was used to induce diabetes in Wistar rats. To simulate an ulcer wound, a punch was created on the animal's back.Themacroscopic analysishave shown that the animals treated with the biomaterial associated with the bone marrow mononuclear cells, had a significantly better regeneration rate in the first 2 days after the formation the wound formation, when compared with the other groupswhere only the biomaterial was applied or did not received any treatment.In addition, histological sections stained with hematoxylin and eosin, allowed to define the degree of regeneration that each animalhave undergone, taking into account the reepithelialization and abundance of inflammatory infiltrate.Our results indicate that the use of the bone marrow mononuclear cellsfraction associated with the biomaterial may be a therapeutic ally in the regeneration of diabetes ulcers. / A cada ano o n?mero de pessoas com diabetes aumenta consideravelmente. At? o ano de 2014, foram registradosmais de 414 milh?es de casos da doen?aem todo o mundo. Um grande problema ? o crescente aumento non?mero de casos de pacientes diab?ticos que desenvolvem ?lceras nos membros inferiores, complica??o decorrente principalmentedo controle glic?micoinadequado, al?m do desequil?briona fase inflamat?ria durante o processo de regenera??o tecidual, que muitas vezes,acabalevando ? amputa??o dos membros inferiores. A partir deste panorama, doaumento de casos da doen?a e tamb?mdoaumento no n?mero de complica??es derivadas da diabetes, s?o necess?rias novas estrat?gias terap?uticas, que visem minimizar o desenvolvimento destas ?lceras at? casos mais graves.A terapia celular associada ao uso de biomateriais, produzidos atrav?s de processos deengenharia tecidual, representam uma nova alternativa para tratamentos atuais. O uso da fra??ode c?lulasmononuclearesda medula ?ssea temse mostrado um importante aliado neste processo, por ser uma fonte de f?cil acesso e com a possibilidade de obten??o de grande quantidade de c?lulas. Este estudoteve como objetivo principal avaliar se o uso de um biomaterial como curativo biol?gico, associado ou n?o ?s c?lulas da fra??o mononuclear da medula ?ssea, seria capaz de melhorara resposta regenerativa de les?es ulcerosas,reduzindoo tempo de cicatriza??o.Por meio do uso da estreptozotocina,foi poss?vel criar um modelo animal de diabetesem ratos Wistar, seguido da realiza??o deuma les?o no dorso do animal para simular uma ferida ulcerosa, frequentemente presente em membros inferiores de diab?ticos.Por meio de an?lises macrosc?picas, com o uso de imagens, foi poss?vel observar que os animais tratados com o biomaterial associado?fra??o de c?lulas mononuclearesda medula ?ssea, tiveram uma taxa de regenera??osignificativamente melhor nos primeiros 2 dias ap?s a forma??o da les?o, quando comparado com os outros gruposaos quais foram aplicados somente o biomaterial ou sem tratamento.Al?m disso, an?lises dos cortes histol?gicos corados comhematoxilinaeeosina, possibilitaramdefiniro grau de regenera??o de cada animal, levando em considera??o a reepiteliza??o da les?o e a abund?ncia de infiltrado inflamat?rio.Os resultados obtidosindicam que o uso da fra??o de c?lulas mononucleares da medula ?ssea associado ao biomaterial pode ser um aliado terap?utico na regenera??o de ?lceras de diabetes.

Submitted by PPG Gerontologia Biom?dica (geronbio@pucrs.br) on 2018-02-15T17:07:30Z No. of bitstreams: 1 KIK_RAQUEL_MILANI_ EL_TESE.pdf: 2404454 bytes, checksum: a337a96830d5dfc5031b99d093f84bc7 (MD5) / Rejected by Caroline Xavier (caroline.xavier@pucrs.br), reason: Devolvido devido ? falta de capa institucional no arquivo PDF. on 2018-02-16T13:07:06Z (GMT) / Submitted by PPG Gerontologia Biom?dica (geronbio@pucrs.br) on 2018-02-19T11:33:51Z No. of bitstreams: 1 KIK_RAQUEL_MILANI_ EL_TESE.pdf: 2561273 bytes, checksum: 00cae5ff653147fac3f019240bc91347 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-02-23T17:07:08Z (GMT) No. of bitstreams: 1 KIK_RAQUEL_MILANI_ EL_TESE.pdf: 2561273 bytes, checksum: 00cae5ff653147fac3f019240bc91347 (MD5) / Made available in DSpace on 2018-02-23T17:11:48Z (GMT). No. of bitstreams: 1 KIK_RAQUEL_MILANI_ EL_TESE.pdf: 2561273 bytes, checksum: 00cae5ff653147fac3f019240bc91347 (MD5) Previous issue date: 2017-10-30 / The frequency of malnutrition in hospitalized elderly patients is high and, consequently, generates an increase in morbimortality. In order to identify malnutrition in hospitalized elderly patients, it is necessary to make a nutritional assessment. Some limitations related to the application of traditional nutritional assessment tools used in elderly patients can be seen, like anthropometric parameters and even the Mini Nutritional Assessment? (MNA?) when such patients present physical or mental limitations, what can be an even more serious problem when they are unaccompanied. Thus, in the search for nutritional assessment tools, which do not depend on the patient?s colaboration, are easy to find and inexpensive, the measurement of adductor pollicis muscle thickness (APMT) has been studied as an anthropometric parameter. Several studies have used APMT in elderly patients in different surgical and clinical conditions. Despite that, few studies have included only elderly patients and none has analyzed the association between APMT and MNA? and checked the accuracy of APMT in relation to the nutritional risk and malnutrition, considering MNA? as a gold standard. In this context, this thesis presents three original articles with cross-sectional design. In the first article entitled ADDUCTOR POLLICIS MUSCLE THICKNESS IN HOSPITALIZED ELDERLY PATIENTS: RELATION BETWEEN GENDER AND AGE, it was attempted to relate the adductor pollicis muscle thickness of hospitalized elderly patients to gender and age. In this study, 119 hospitalized elderly patients were assessed and no significant difference of the APMT measurement between the dominant and non-dominant hands was observed and it was also observed that such measurement was bigger in the younger individuals (60 and 79 years old) and the male individuals. In the second article entitled ASSOCIATION BETWEEN ADDUCTOR POLLICIS MUSCLE THICKNESS AND NUTRITIONAL PARAMETERS IN HOSPITALIZED ELDERLY PATIENTS, the association between APMT and nutritional parameters in hospitalized elderly patients was analyzed. In this study, 331 hospitalized elderly patients were assessed and the association between APMT and all the nutritional parameters was investigated (MNA?, calf circumference, arm circumference, body mass index and handgrip strength) regardless of gender and age was observed, what reinforces its applicability in the nutritional assessment of elderly patients. In the third article entitled ADDUCTOR POLLICIS MUSCLE THICKNESS ACCURACY IN THE SCREENING OF NUTRITIONAL RISK AND MALNUTRITION IN HOSPITALIZED ELDERLY PATIENTS. This study, that evaluated 291 elderly people, was attempted to determine the cut-off points of APMT and its accuracy as a tool to screen the nutritional risk and malnutrition in hospitalized elderly patients. It was observed that APMT did not reach satisfactory levels of accuracy for nutritional risk and malnutrition for both men and women. Longitudinal studies are suggested in order to advance in the investigation of the role of APMT in the screening of nutritional risk and malnutrition. / A frequ?ncia de desnutri??o em idosos hospitalizados ? alta e tem como consequ?ncia o aumento da morbimortalidade. Para identificar a desnutri??o em idosos hospitalizados ? necess?rio realizar uma avalia??o nutricional. Podem ser verificadas algumas limita??es na aplica??o de instrumentos de avalia??o nutricional tradicionalmente utilizados em idosos, como os par?metros antropom?tricos e at? mesmo a Mini Avalia??o Nutricional? (MNA?), quando h? presen?a de limita??es f?sicas e mentais no idoso, o que ainda se agrava quando o idoso n?o possui acompanhante. Assim, na busca por instrumentos de rastreio nutricional que n?o dependam da colabora??o do paciente, que sejam de r?pida obten??o e de baixo custo, a medida da Espessura do M?sculo Adutor do Polegar (EMAP) tem sido estudada como um par?metro antropom?trico. Diversos estudos t?m utilizado a EMAP com idosos em diferentes condi??es cl?nicas cir?rgicas. Apesar disso, poucos estudos inclu?ram apenas indiv?duos idosos e nenhum analisou a associa??o entre EMAP e MNA? e verificou a acur?cia da EMAP em rela??o ao risco de desnutri??o e desnutri??o, tendo a MNA? como padr?o-ouro. Nesse contexto, esta tese apresenta tr?s artigos originais com delineamento transversal. No primeiro artigo, intitulado ?Espessura do m?sculo adutor do polegar em idosos hospitalizados: rela??o com sexo e idade?, buscou-se relacionar a espessura do m?sculo adutor do polegar de idosos hospitalizados com sexo e idade. Nesse estudo foram avaliados 119 idosos hospitalizados, e n?o foi observada diferen?a significativa da medida da EMAP entre as m?os dominante e n?o dominante. Essa medida apresentou-se maior nos indiv?duos mais jovens (60-79 anos) e nos do sexo masculino. No segundo artigo, intitulado ?Associa??o entre espessura do m?sculo adutor do polegar e par?metros nutricionais em idosos hospitalizados?, foi analisada a associa??o entre EMAP e par?metros nutricionais em idosos hospitalizados. Nesse estudo, foram avaliados 331 idosos hospitalizados, e constatou-se a associa??o da EMAP com todos os par?metros nutricionais investigados (MNA?, circunfer?ncia da panturrilha, circunfer?ncia do bra?o, ?ndice de massa corporal e for?a de preens?o palmar), independentemente do sexo e da idade, o que refor?a sua aplicabilidade na avalia??o nutricional de idosos. No terceiro artigo, intitulado ?Acur?cia da espessura do m?sculo adutor do polegar no rastreio de risco de desnutri??o e de desnutri??o em idosos hospitalizados?, buscou-se determinar os pontos de corte da EMAP e sua acur?cia como instrumento de rastreio do risco de desnutri??o e de desnutri??o em idosos hospitalizados. Neste estudo, que envolveu a avalia??o de 291 indiv?duos idosos, verificou-se que a EMAP n?o atingiu n?veis satisfat?rios de acur?cia para risco nutricional e desnutri??o em ambos os sexos. Sugere-se a realiza??o de estudos longitudinais para avan?ar na investiga??o do papel da EMAP no rastreio do risco de desnutri??o e de desnutri??o em idosos hospitalizados.

Submitted by PPG Gerontologia Biom?dica (geronbio@pucrs.br) on 2018-02-26T12:34:45Z No. of bitstreams: 1 KIK_RAQUEL_MILANI_ EL_TESE.pdf: 2561273 bytes, checksum: 00cae5ff653147fac3f019240bc91347 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-02-26T16:58:45Z (GMT) No. of bitstreams: 1 KIK_RAQUEL_MILANI_ EL_TESE.pdf: 2561273 bytes, checksum: 00cae5ff653147fac3f019240bc91347 (MD5) / Made available in DSpace on 2018-02-26T17:04:52Z (GMT). No. of bitstreams: 1 KIK_RAQUEL_MILANI_ EL_TESE.pdf: 2561273 bytes, checksum: 00cae5ff653147fac3f019240bc91347 (MD5) Previous issue date: 2017-10-30 / The frequency of malnutrition in hospitalized elderly patients is high and, consequently, generates an increase in morbimortality. In order to identify malnutrition in hospitalized elderly patients, it is necessary to make a nutritional assessment. Some limitations related to the application of traditional nutritional assessment tools used in elderly patients can be seen, like anthropometric parameters and even the Mini Nutritional Assessment? (MNA?) when such patients present physical or mental limitations, what can be an even more serious problem when they are unaccompanied. Thus, in the search for nutritional assessment tools, which do not depend on the patient?s colaboration, are easy to find and inexpensive, the measurement of adductor pollicis muscle thickness (APMT) has been studied as an anthropometric parameter. Several studies have used APMT in elderly patients in different surgical and clinical conditions. Despite that, few studies have included only elderly patients and none has analyzed the association between APMT and MNA? and checked the accuracy of APMT in relation to the nutritional risk and malnutrition, considering MNA? as a gold standard. In this context, this thesis presents three original articles with cross-sectional design. In the first article entitled ADDUCTOR POLLICIS MUSCLE THICKNESS IN HOSPITALIZED ELDERLY PATIENTS: RELATION BETWEEN GENDER AND AGE, it was attempted to relate the adductor pollicis muscle thickness of hospitalized elderly patients to gender and age. In this study, 119 hospitalized elderly patients were assessed and no significant difference of the APMT measurement between the dominant and non-dominant hands was observed and it was also observed that such measurement was bigger in the younger individuals (60 and 79 years old) and the male individuals. In the second article entitled ASSOCIATION BETWEEN ADDUCTOR POLLICIS MUSCLE THICKNESS AND NUTRITIONAL PARAMETERS IN HOSPITALIZED ELDERLY PATIENTS, the association between APMT and nutritional parameters in hospitalized elderly patients was analyzed. In this study, 331 hospitalized elderly patients were assessed and the association between APMT and all the nutritional parameters was investigated (MNA?, calf circumference, arm circumference, body mass index and handgrip strength) regardless of gender and age was observed, what reinforces its applicability in the nutritional assessment of elderly patients. In the third article entitled ADDUCTOR POLLICIS MUSCLE THICKNESS ACCURACY IN THE SCREENING OF NUTRITIONAL RISK AND MALNUTRITION IN HOSPITALIZED ELDERLY PATIENTS. This study, that evaluated 291 elderly people, was attempted to determine the cut-off points of APMT and its accuracy as a tool to screen the nutritional risk and malnutrition in hospitalized elderly patients. It was observed that APMT did not reach satisfactory levels of accuracy for nutritional risk and malnutrition for both men and women. Longitudinal studies are suggested in order to advance in the investigation of the role of APMT in the screening of nutritional risk and malnutrition. / A frequ?ncia de desnutri??o em idosos hospitalizados ? alta e tem como consequ?ncia o aumento da morbimortalidade. Para identificar a desnutri??o em idosos hospitalizados ? necess?rio realizar uma avalia??o nutricional. Podem ser verificadas algumas limita??es na aplica??o de instrumentos de avalia??o nutricional tradicionalmente utilizados em idosos, como os par?metros antropom?tricos e at? mesmo a Mini Avalia??o Nutricional? (MNA?), quando h? presen?a de limita??es f?sicas e mentais no idoso, o que ainda se agrava quando o idoso n?o possui acompanhante. Assim, na busca por instrumentos de rastreio nutricional que n?o dependam da colabora??o do paciente, que sejam de r?pida obten??o e de baixo custo, a medida da Espessura do M?sculo Adutor do Polegar (EMAP) tem sido estudada como um par?metro antropom?trico. Diversos estudos t?m utilizado a EMAP com idosos em diferentes condi??es cl?nicas cir?rgicas. Apesar disso, poucos estudos inclu?ram apenas indiv?duos idosos e nenhum analisou a associa??o entre EMAP e MNA? e verificou a acur?cia da EMAP em rela??o ao risco de desnutri??o e desnutri??o, tendo a MNA? como padr?o-ouro. Nesse contexto, esta tese apresenta tr?s artigos originais com delineamento transversal. No primeiro artigo, intitulado ?Espessura do m?sculo adutor do polegar em idosos hospitalizados: rela??o com sexo e idade?, buscou-se relacionar a espessura do m?sculo adutor do polegar de idosos hospitalizados com sexo e idade. Nesse estudo foram avaliados 119 idosos hospitalizados, e n?o foi observada diferen?a significativa da medida da EMAP entre as m?os dominante e n?o dominante. Essa medida apresentou-se maior nos indiv?duos mais jovens (60-79 anos) e nos do sexo masculino. No segundo artigo, intitulado ?Associa??o entre espessura do m?sculo adutor do polegar e par?metros nutricionais em idosos hospitalizados?, foi analisada a associa??o entre EMAP e par?metros nutricionais em idosos hospitalizados. Nesse estudo, foram avaliados 331 idosos hospitalizados, e constatou-se a associa??o da EMAP com todos os par?metros nutricionais investigados (MNA?, circunfer?ncia da panturrilha, circunfer?ncia do bra?o, ?ndice de massa corporal e for?a de preens?o palmar), independentemente do sexo e da idade, o que refor?a sua aplicabilidade na avalia??o nutricional de idosos. No terceiro artigo, intitulado ?Acur?cia da espessura do m?sculo adutor do polegar no rastreio de risco de desnutri??o e de desnutri??o em idosos hospitalizados?, buscou-se determinar os pontos de corte da EMAP e sua acur?cia como instrumento de rastreio do risco de desnutri??o e de desnutri??o em idosos hospitalizados. Neste estudo, que envolveu a avalia??o de 291 indiv?duos idosos, verificou-se que a EMAP n?o atingiu n?veis satisfat?rios de acur?cia para risco nutricional e desnutri??o em ambos os sexos. Sugere-se a realiza??o de estudos longitudinais para avan?ar na investiga??o do papel da EMAP no rastreio do risco de desnutri??o e de desnutri??o em idosos hospitalizados

Submitted by PPG Pediatria e Sa?de da Crian?a (pediatria-pg@pucrs.br) on 2018-03-13T12:49:41Z No. of bitstreams: 1 Vers?o final Mariana tese_corr1203.pdf: 6787616 bytes, checksum: 5ce2258b4a47f2440e87f001a582a45a (MD5) / Approved for entry into archive by Tatiana Lopes (tatiana.lopes@pucrs.br) on 2018-03-20T12:20:15Z (GMT) No. of bitstreams: 1 Vers?o final Mariana tese_corr1203.pdf: 6787616 bytes, checksum: 5ce2258b4a47f2440e87f001a582a45a (MD5) / Made available in DSpace on 2018-03-20T12:24:27Z (GMT). No. of bitstreams: 1 Vers?o final Mariana tese_corr1203.pdf: 6787616 bytes, checksum: 5ce2258b4a47f2440e87f001a582a45a (MD5) Previous issue date: 2018-01-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Objectives: to investigate if exclusive breastfeeding at discharge of very low birth weight preterm infants would be reduced in mothers who expressed breast milk less frequently. To assess clinical factors associated with exclusive breastfeeding failure at discharge of very low birth weight preterm infants. Methods: prospective cohort study, including infants with gestational age ? 30 weeks and / or birth weight ? 1500g. Patients with genetic syndromes, malformations, absolute contraindications to breast milk or those who died were excluded. Patients were divided into two groups, according to times when mothers could express milk at home (Group 1) or not (Group 2). Dependent variable was diet at discharge (exclusive breastmilk, breastmilk and supplement, exclusive supplement) and independent variables were evaluated through Student's t test (parametric quantitative), Mann-Whittney (non- parametric quantitative) and exact test of Fischer (categorical variables) in a univariate model. The variables with p <0.05 were included in a logistic regression model. The project was approved by the institution?s ethics committee. Results: of the 433 patients followed up until hospital discharge, 147 were included in Group 1 and 286 in Group 2. Group 2 received prenatal corticosteroids more frequently, had lower gestational age, higher frequency of enterocolitis and remained hospitalized longer (p <0.001). Group 2 patients received less exclusive breast milk at discharge (p = 0.01). The reduction with increasing patients using formula to complement breast milk (p = 0.04). In a multivariate logistic regression model, only corrected age remained independently associated with exclusive breastfeeding failure at discharge. Conclusion: less opportunities to stimulate milk expression and longer hospital stay are associated with reduction of exclusive breastfeeding at discharge. Each additional week of hospitalization reduces the chance of exclusive breastfeeding by 10%. / Objetivos: investigar se houve redu??o no aleitamento materno exclusivo na alta de prematuros de muito baixo peso associada a redu??o da frequ?ncia de esgota do leite. Descrever fatores cl?nicos associados ? falha do aleitamento materno exclusivo na alta de prematuros de muito baixo peso. M?todos: estudo de coorte prospectivo, incluindo prematuros com idade gestacional ? 30 semanas e/ou peso de nascimento ? 1500g. Foram exclu?dos portadores de s?ndromes gen?ticas, malforma??es, contraindica??es absolutas ao leite materno ou que evolu?ram ao ?bito. Os pacientes foram divididos em dois grupos, de acordo com o per?odo de tempo em que as m?es podiam trazer leite ordenhado em casa (Grupo 1) ou s? podia ser utilizado o leite retirado no hospital (Grupo 2). A vari?vel dependente foi a dieta no momento da alta (leite materno exclusivo, leite materno e complemento, complemento exclusivo) e as independentes foram avaliadas atrav?s deTeste t de Student (quantitativas param?tricas), Mann-Whittney (quantitativas n?o-param?tricas) e teste exato de Fischer (vari?veis categ?ricas) em modelo univariado. As vari?veis com p<0,05 foram inclu?das em modelo de regress?o log?stica. O projeto foi aprovado no comit? de ?tica. Resultados: do total de 433 pacientes acompanhados at? a alta hospitalar, 147 foram inclu?dos no Grupo 1 e 286 no Grupo 2. O Grupo 2 recebeu corticoides com maior frequ?ncia, apresentavam menor idade gestacional, maior frequ?ncia de enterocolite e permaneceram internados por mais tempo, pela idade corrigida na alta (p<0,001). Os pacientes do Grupo 2 receberam menos leite materno exclusivo na alta (p=0,01). A redu??o se deu ?s custas do aumento de aleitamento misto (p=0,04). Quando colocado em modelo de regress?o log?stica, apenas a idade corrigida permaneceu associada de forma independente ? falha de aleitamento materno exclusivo na alta. Conclus?o: a menor frequ?ncia de est?mulo para ordenha e o maior tempo de interna??o hospitalar est?o associados ? redu??o do aleitamento materno exclusivo na alta. Cada semana adicional de interna??o, reduz em 10% a chance de aleitamento materno exclusivo na alta.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-03-16T19:55:06Z No. of bitstreams: 1 THA?S_CRISTINA_MURAD?S_DIS.pdf: 883340 bytes, checksum: 6481cc56bc005f400fcfc1ae75cea11e (MD5) / Approved for entry into archive by Tatiana Lopes (tatiana.lopes@pucrs.br) on 2018-03-28T13:57:53Z (GMT) No. of bitstreams: 1 THA?S_CRISTINA_MURAD?S_DIS.pdf: 883340 bytes, checksum: 6481cc56bc005f400fcfc1ae75cea11e (MD5) / Made available in DSpace on 2018-03-28T14:01:44Z (GMT). No. of bitstreams: 1 THA?S_CRISTINA_MURAD?S_DIS.pdf: 883340 bytes, checksum: 6481cc56bc005f400fcfc1ae75cea11e (MD5) Previous issue date: 2017-12-19 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / New effective compounds for tuberculosis (TB) treatment are currently needed. This study analyzed the anti-TB activity of a series of 16 quinoxaline-derived chalcones. From an initial in vitro screening, six molecules, namely N5, N9, N10, N15, N16, and N23 inhibited the growth of the M. tuberculosis H37Rv laboratory strain. The three compounds (N9, N15 and N23) with the lowest MIC values (3.13, 6.25, 5 ?g/mL, respectively) were further tested against clinical isolates and laboratory strains harboring mutations in katG or inhA genes. From these experimental set, N9 was selected as the lead compound for further investigations. This chalcone displayed a synergistic effect when combined with moxifloxacin, according to assessment in a checkerboard assay. Noteworthy, the anti-TB effects of N9 did not rely on inhibition of mycolic acids or non-hydroxylated fatty acids synthesis, circumventing important mechanisms of resistance in mycobacteria. Considering the safety of the tested chalcones, all the compounds behaved as substrates or inhibitors of at least one cytochrome P450 isoform, as indicated by in silico evaluation. Most compounds lacked tumorigenic, mutagenic, irritant, or reproductive effects, except N3 and N7, as shown by DataWarrior program. The chalcone N9 did not elicit any toxic alteration in doses up to 2000 mg/kg, in female mice. Based on the present results, N9 can be considered a potential candidate for development of a new anti-TB therapeutic choice. / Atualmente, s?o necess?rios novos compostos eficazes para o tratamento da tuberculose (TB). Este estudo analisou a atividade anti-TB de uma s?rie de 16 chalconas derivadas da quinoxalina. A partir de uma triagem inicial in vitro, seis mol?culas, nomeadas N5, N9, N10, N15, N16 e N23 inibiram o crescimento da cepa laboratorial de M. tuberculosis H37Rv. Os tr?s compostos (N9, N15 e N23) com os valores de MIC mais baixos (3.13, 6.25, 5 ?g/mL, respectivamente) foram testados adicionalmente contra isolados cl?nicos e cepas laboratoriais com muta??es nos genes katG ou inhA. A partir deste conjunto experimental, a chalcona quinoxal?nica N9 foi selecionada como composto principal para novas investiga??es. Esta chalcona mostrou um efeito sin?rgico quando combinada com moxifloxacino, de acordo com a avalia??o em ensaio checkerboard. Destaca-se que os efeitos anti-TB de N9 n?o dependeram da inibi??o de ?cidos mic?licos ou da s?ntese de ?cidos graxos n?o hidroxilados, envolvidos em importantes mecanismos de resist?ncia em micobact?rias. Considerando a seguran?a toxicol?gica das chalconas quinoxal?nicas testadas, todos os compostos comportaram-se como substratos ou inibidores de pelo menos uma isoforma do citocromo P450, conforme indicado pela avalia??o in silico. A maioria dos compostos n?o possui efeitos tumorig?nicos, mutag?nicos, irritantes ou reprodutivos, exceto N3 e N7, conforme demonstrado pelo programa DataWarrior. A chalcona quinoxal?nica N9 n?o provocou qualquer altera??o t?xica em doses de at? 2000 mg/kg, em camundongos f?meas. Com base nos resultados atuais, N9 pode ser considerada como potencial candidata para o desenvolvimento de uma nova escolha terap?utica anti-TB.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-03-26T16:55:48Z No. of bitstreams: 1 RODRIGO_BRACCINI_MADEIRA_DA_SILVA_TES.pdf: 6388000 bytes, checksum: c5e864eb62bd553c3a29e7bad1b85fef (MD5) / Rejected by Tatiana Lopes (tatiana.lopes@pucrs.br), reason: Devolvido porque o pdf inserido no TEDE ? de outro aluno. on 2018-03-28T14:20:43Z (GMT) / Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-03-28T14:24:15Z No. of bitstreams: 1 FERNANDA_MAJOLO_TES.pdf: 6002507 bytes, checksum: 764acb66fc06c518428a40b9eb5bdd26 (MD5) / Approved for entry into archive by Tatiana Lopes (tatiana.lopes@pucrs.br) on 2018-03-28T16:23:42Z (GMT) No. of bitstreams: 1 FERNANDA_MAJOLO_TES.pdf: 6002507 bytes, checksum: 764acb66fc06c518428a40b9eb5bdd26 (MD5) / Made available in DSpace on 2018-03-28T16:29:23Z (GMT). No. of bitstreams: 1 FERNANDA_MAJOLO_TES.pdf: 6002507 bytes, checksum: 764acb66fc06c518428a40b9eb5bdd26 (MD5) Previous issue date: 2018-01-11 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Malformations of cortical development (MDC) include a wide spectrum of Central Nervous System (CNS) disorders related to a complex process of cortex formation. Focal Cortical Dysplasia (FCD), a common type of MDC, is reported as the most frequent structural brain lesion found in children with refractory epilepsy to drug treatment undergoing surgery. Surgical treatment, with complete resection of the dysplastic lesion, is able to stop the seizure resistant to antiepileptic drugs, improving the individual's quality of life and reducing morbidity. FCD is characterized by multiple types of alterations both in cortical architecture and in cytologic abnormalities and it?s pathogenesis is still unknown. In 2004, Palmini et al. classified DCF according to white matter and cortical layer architecture. Taylor-type FCD is characterized by cortical laminar disorganization and dysplastic neurons, compromising the organization of the cortex into six-layered traditionally known. Understanding the mechanisms of action of neurological diseases has involved the use of animal models. However, in the case of brain development of epileptic syndromes, many decades of study have failed to provide a conclusive insight of their mechanisms. Modeling neurological diseases is especially attractive for the application of induced pluripotent stem cells (iPSCs), making possible to derive specific neurons for in vitro studies, contributing to the investigation of the disease. The aim of the present study was to investigate the possible differences in neurogenesis and neurodifferentiation of iPSCs from fibroblasts of individuals affected by Taylor-type FCD and normal individuals. iPSCs were generated from skin fibroblasts of two FCD individuals and two healthy individuals, to form the control group. The reprogramming was done through the fibroblasts exposure to viral vectors containing the OCT4, KLF4, SOX2, and c-MYC genes and the clones were characterized by immunohistochemistry. iPSCs were neurodifferentiated and analyzed at the 14th, 22nd and 35th days. We also analyzed the brain tissue, fibroblasts and iPSCs cells from the individuals. Through qRT-PCR, the expression of 14 genes involved in the neurodifferentiation process were quantified. These genes are associated to neural migration and differentiation, synaptic aspects and Notch signaling. Both individuals were diagnosed with Taylor-type FCD, more specifically, type IIb. In general, individuals with dysplasia presented alterations in the relative quantification in the most genes analyzed compared to control individuals in all processes and study groups (fibroblasts, brain tissue, iPSCs 8 and neurodifferentiated cells). The genes involved in the neural migration and differentiation processes, as well as synaptic aspects and Notch signaling presented quite altered expressions in dysplastic individuals, with the beginning of the majority processes early, before the physiologically typical period. From the found results, we can infer that during the embryonic period, in the neurogenesis and neurodifferentiation process, individuals affected by the disease, possibly presents neuroblasts more sensitive to stimulus, presenting differences in the development of the Nervous System. These changes may be directly related to dysplastic brain development. This work extends the understanding of embryonic neurodevelopment, open up opportunities to further investigations of the involvement and influence of each genes analyzed in the pathogenesis of FCD, as well as in each mechanism of action involved in the brain development. / As Malforma??es do Desenvolvimento Cortical (MDC) re?nem uma ampla gama de patologias do Sistema Nervoso Central (SNC) relacionadas a um complexo processo de forma??o do c?rtex. A Displasia Cortical Focal (DCF), tipo comum de MDC, ? relatada como a les?o cerebral estrutural mais frequente encontrada em crian?as com epilepsia refrat?ria ao tratamento medicamentoso submetidas ? cirurgia. O tratamento cir?rgico, com a ressec??o completa da les?o displ?sica, ? capaz de cessar a convuls?o resistente a drogas antiepil?ticas, melhorando a qualidade de vida do indiv?duo e diminuindo a morbidade. A DCF ? caracterizada por m?ltiplos tipos de altera??es tanto na arquitetura cortical quanto em anormalidades citol?gicas e sua patog?nese ainda ? desconhecida. Em 2004, Palmini e colaboradores classificaram as DCF de acordo com observa??es na subst?ncia branca e na arquitetura da camada cortical. A DCF do tipo Taylor ? caracterizada por uma desorganiza??o laminar e neur?nios displ?sicos, comprometendo a organiza??o do c?rtex em seis camadas histol?gicas tradicionalmente conhecidas. A compreens?o dos mecanismos de a??o das doen?as neurol?gicas tem envolvido o uso de modelos animais. Por?m, no caso do desenvolvimento cerebral das s?ndromes epil?pticas muitas d?cadas de estudo n?o conseguiram fornecer uma vis?o conclusiva sobre seus mecanismos. Modelar doen?as neurol?gicas ? especialmente atraente para aplica??o das c?lulas pluripotentes induzidas (iPSCs), possibilitando derivar neur?nios espec?ficos do pr?prio paciente para estudos in vitro, contribuindo para a investiga??o da doen?a. O objetivo do presente estudo foi investigar as poss?veis diferen?as na neurog?nese e neurodiferencia??o de iPSCs a partir de fibroblastos de indiv?duos acometidos pela DCF do tipo Taylor e indiv?duos normais. As iPSCs foram geradas a partir de fibroblastos de pele de dois indiv?duos displ?sicos e dois indiv?duos saud?veis, para compor o grupo controle. A reprograma??o se deu atrav?s da exposi??o dos fibroblastos a vetores virais contendo os genes OCT4, KLF4, SOX2, e c-MYC e os clones gerados foram caracterizados por imunohistoqu?mica. As c?lulas iPSCs foram neurodiferenciadas e analisadas nos per?odos de 14, 22 e 35 dias. Tamb?m foram analisados o tecido cerebral, fibroblastos e c?lulas iPSCs dos indiv?duos. Atrav?s de qRT-PCR, a express?o de 14 genes envolvidos no processo de neurodiferencia??o foram quantificados. Estes genes est?o associados a migra??o e diferencia??o neural, 6 aspectos sin?pticos e sinaliza??o Notch. Ambos os indiv?duos foram diagnosticados com DCF do tipo Taylor, mais especificadamente, do tipo IIb. No geral, os indiv?duos displ?sicos apresentaram altera??es na quantifica??o relativa na maioria dos genes analisados comparados aos indiv?duos controle, em todos os processos e grupos de estudo (fibroblastos, tecido cerebral, iPSCs e c?lulas neurodiferenciadas). Os genes envolvidos nos processos de migra??o e diferencia??o neural, aspectos sin?pticos e sinaliza??o Notch apresentaram express?es bastante alteradas nos indiv?duos displ?sicos, com o in?cio da maioria dos processos precoces, antes do per?odo fisiologicamente t?pico. A partir dos resultados encontrados, podemos inferir que durante o per?odo embrion?rio, no processo de neurog?nese e neurodiferencia??o, indiv?duos acometidos pela doen?a, possivelmente possuem neuroblastos mais sens?veis a est?mulos, apresentando diferen?as no desenvolvimento do Sistema Nervoso. Essas altera??es podem estar diretamente relacionadas com a forma??o do c?rebro displ?sico. Este trabalho amplia a compreens?o do neurodesenvolvimento embrion?rio, abrindo portas para futuras investiga??es de forma mais aprofundada sobre o envolvimento e influ?ncia de cada um dos genes analisados na patog?nese da DCF, bem como em cada mecanismo de a??o envolvido na forma??o do c?rebro.