RESUMO
We developed two virtual communities of practice (Endobloc and Pneumobloc) to increase the interaction between general practitioners and nurses in primary care and hospital endocrinologists and pulmonologists. They were designed and developed using an existing web 2.0-based virtual network belonging to the local National Health System, and we quantitatively assessed the usefulness through the participation and use during the first 24 months after the launch in 2010. A total of 26,372 visits (47% Endobloc's visits) and 2351 contributions (Endobloc's contribution 38.9%) to both virtual communities of practice were registered during the first 24 months. The most popular sections were the e-Blog and the e-Consultations section in both virtual communities of practice, but some differences in the pattern of use in other sections were observed. Activity on the virtual communities of practice occurred throughout the day including weekends and holiday periods. We showed that virtual communities of practice are feasible under real-life clinical practice.
Assuntos
Redes Comunitárias/tendências , Gestão do Conhecimento , Mídias Sociais/tendências , Endocrinologia/métodos , Endocrinologia/tendências , Humanos , Internet , Relações Interpessoais , Atenção Primária à Saúde/métodos , Pneumologia/métodos , Pneumologia/tendências , Espanha , Interface Usuário-Computador , Recursos HumanosRESUMO
MicroRNA deregulation could be a crucial event in thyroid carcinogenesis. However, current knowledge is based on studies that have used inherently biased methods. Thus, we aimed to define in an unbiased way a list of deregulated microRNAs in well-differentiated thyroid cancer in order to identify diagnostic and prognostic markers. We performed a microRNA deep-sequencing study using the largest well-differentiated thyroid tumor collection reported to date, comprising 127 molecularly characterized tumors with follicular or papillary patterns of growth and available clinical follow-up data, and 17 normal tissue samples. Furthermore, we integrated microRNA and gene expression data for the same tumors to propose targets for the novel molecules identified. Two main microRNA expression profiles were identified: one common for follicular-pattern tumors, and a second for papillary tumors. Follicular tumors showed a notable overexpression of several members of miR-515 family, and downregulation of the novel microRNA miR-1247. Among papillary tumors, top upregulated microRNAs were miR-146b and the miR-221~222 cluster, while miR-1179 was downregulated. BRAF-positive samples displayed extreme downregulation of miR-7 and -204. The identification of the predicted targets for the novel molecules gave insights into the proliferative potential of the transformed follicular cell. Finally, by integrating clinical follow-up information with microRNA expression, we propose a prediction model for disease relapse based on expression of two miRNAs (miR-192 and let-7a) and several other clinicopathological features. This comprehensive study complements the existing knowledge about deregulated microRNAs in the development of well-differentiated thyroid cancer and identifies novel markers associated with recurrence-free survival.
Assuntos
Adenocarcinoma Folicular/genética , Carcinoma/genética , MicroRNAs/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/mortalidade , Adolescente , Adulto , Idoso , Carcinoma/mortalidade , Carcinoma Papilar , Análise por Conglomerados , Intervalo Livre de Doença , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/mortalidade , Transcriptoma , Adulto JovemRESUMO
Thyroid cancer is a heterogeneous disease with several subtypes characterized by cytological, histological and genetic alterations, but the involvement of epigenetics is not well understood. Here, we investigated the role of aberrant DNA methylation in the development of well-differentiated thyroid tumors. We performed genome-wide DNA methylation profiling in the largest well-differentiated thyroid tumor series reported to date, comprising 83 primary tumors as well as 8 samples of adjacent normal tissue. The epigenetic profiles were closely related to not only tumor histology but also the underlying driver mutation; we found that follicular tumors had higher levels of methylation, which seemed to accumulate in a progressive manner along the tumorigenic process from adenomas to carcinomas. Furthermore, tumors harboring a BRAF or RAS mutation had a larger number of hypo- or hypermethylation events, respectively. The aberrant methylation of several candidate genes potentially related to thyroid carcinogenesis was validated in an independent series of 52 samples. Furthermore, through the integration of methylation and transcriptional expression data, we identified genes whose expression is associated with the methylation status of their promoters. Finally, by integrating clinical follow-up information with methylation levels we propose etoposide-induced 2.4 and Wilms tumor 1 as novel prognostic markers related to recurrence-free survival. This comprehensive study provides insights into the role of DNA methylation in well-differentiated thyroid cancer development and identifies novel markers associated with recurrence-free survival.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Papilar/genética , Impressões Digitais de DNA , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Recidiva Local de Neoplasia/genética , Neoplasias da Glândula Tireoide/genética , Adenoma/genética , Adenoma/mortalidade , Adenoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Epigênese Genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Taxa de Sobrevida , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Proteínas WT1/genética , Adulto Jovem , Proteínas ras/genéticaRESUMO
The aim of this study was to investigate the GH-IGF-I axis in healthy adults and its relationship to obesity. We studied 268 subjects: 134 men and 134 women, and determined anthropometric and body composition variables. Serum total IGF-I was measured by radioimmunoassay, serum free IGF-I concentrations by enzyme linked immunosorbant assay and serum IGFBP3 concentrations by radioimmunoassay. In men, we observed a decrease in total IGF-I, free IGF-I and IGFBP-3 throughout decades. In women, the body mass index and fat mass were higher throughout decades, and we observed a similar decrease to that in men in total IGF-I, free IGF-I and IGFBP3. In men with obesity, as measured by body fat, free IGF-I concentrations were lower than those without obesity; in women with obesity, total IGF-I concentrations and free IGF-I concentrations were lower than in those with obesity. These changes were observed in relationship to obesity when the subjects were adjusted for differences in age. We showed that in controls randomly selected, the GH-IGF-I axis component concentrations that decrease with increasing age are lower in obesity, especially in women, and that this decrease is related to body mass index and body fat.
Assuntos
Envelhecimento , Fator de Crescimento Insulin-Like I/fisiologia , Tecido Adiposo/patologia , Adulto , Fatores Etários , Idoso , Composição Corporal , Índice de Massa Corporal , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade , Radioimunoensaio , Fatores SexuaisRESUMO
OBJECTIVE: Leptin secretion is influenced by many factors and the GH/IGF axis plays an important role in the regulation of body composition, but the physiological interactions between leptin and the IGF-I system remain unknown. In this study we investigated the relationship between leptin, the IGF-I system, and sex, age, anthropometric and body composition variables in a group of healthy adults randomly selected. DESIGN: A cross-sectional study. PATIENTS: The study included 268 subjects, representative of the whole population of the city of L'Hospitalet de Llobregat in sex and age distribution: 134 men aged 41.4 years, range 15-70 years; and 134 women, aged 40.7 years, range 15-70 years. MEASUREMENTS: Body mass index (BMI) was calculated, and body composition was determined by using a bioelectrical impedance analyser. Serum leptin concentrations were determined by using a radioimmunoassay (RIA). Serum total IGF-I concentrations, after acid-ethanol extraction, were also measured by RIA. Serum free IGF-I concentrations were determined by an enzymoimmunometric assay. Serum IGFBP3 concentrations were determined by RIA. Plasma basal TSH concentrations were determined by a specific electrochemiluminescence assay. RESULTS: In men the BMI was similar in all decades and waist/hip ratio increased in the last three decades. Fat-free mass decreased by decade. We observed an increase in leptin in the fourth decade with a decrease in IGF-I, free IGF-I and IGFBP3 throughout the decades. Basal TSH showed an increase in the last two decades. In women, BMI, waist/hip ratio and fat mass increased significantly in the last decades. Leptin concentrations increased in the last decades and total IGF-I, free IGF-I and IGFBP3 decreased by decade without changes in basal TSH concentration. In men, there was a positive correlation between leptin and BMI, waist/hip ratio, total body water, fat-free mass and fat mass, and these anthropometric and body composition variables showed a negative correlation with free IGF-I and IGFBP3, without any correlation with total IGF-I. In women, there was a positive correlation between leptin and BMI, waist/hip ratio, total body water, fat-free mass, and fat mass, which showed a negative correlation with total IGF-I and IGFBP3, without any correlation with free IGF-I. In men, total IGF-I was negatively correlated with waist/hip ratio without any correlation with the other variables and free IGF-I was negatively correlated with BMI and waist/hip ratio, and IGFBP3 did not show any correlation. In women, total IGF-I, free IGF-I and IGFBP3 were negatively correlated with BMI, waist/hip ratio and fat mass. The multiple linear regression analysis produced a model that explained 60.5% of leptin variability in men and 40% in women. Notably, only age, BMI, fat mass and waist/hip ratio brought an independent significant contribution to leptin variability. The final model also explained 28.2% and 60.4% of total IGF-I variability and 17.2% and 27.4% of free IGF-I variability in men and women, respectively. Age and leptin contributed to free IGF-I variability in men, and age and fat mass were significantly and independently associated with total IGF-I in women. CONCLUSIONS: In this well-characterized population of controls randomly selected without chronic disease or drug administration and with biochemically confirmed euthyroidism, we found that both men and women had a significant correlation between leptin levels and the IGF-I system, and anthropometric and body composition variables, but that leptin did not regulate the IGF-I system, and that the IGF-I system did not regulate leptin synthesis and secretion.
Assuntos
Fator de Crescimento Insulin-Like I/análise , Leptina/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Composição Corporal , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Espanha , Estatísticas não Paramétricas , Tireotropina/sangueRESUMO
No disponible
Assuntos
Humanos , Impedância Elétrica , Composição Corporal , Infecções Oportunistas Relacionadas com a AIDS , Valores de Referência , Antiprotozoários , Anfotericina B , Lipossomos , Leishmaniose VisceralRESUMO
Fundamento: El objetivo de este estudio es el análisis de las variables antropométricas y el de los valores de referencia de los parámetros de la composición corporal que tienen interés en la población sana, así como para su comparación en diversas enfermedades, ya que no hay estudios poblacionales que los establezcan. Sujetos y métodos: Se estudiaron 268 sujetos sanos, 134 varones y 134 mujeres, seleccionados a través del censo de L'Hospitalet de Llobregat, y representativos de su población en sexo y edad, con una edad media de 41,4 años los varones y 40,7 años las mujeres, y se valoraron los datos antropométricos, peso, talla, índice de masa corporal, índice cintura/cadera y los parámetros de composición corporal por bioimpedanciometría: agua corporal total, masa no grasa, masa grasa y porcentaje de grasa. Resultados: Veinticuatro varones y 33 mujeres eran obesos; de ellos, dos varones y cuatro mujeres presentaban obesidad mórbida. Los parámetros antropométricos y de composición corporal se distribuyeron por sexos y décadas. El índice de masa corporal fue mayor en las últimas décadas respecto a la primera tanto en varones (p = 0,017) como en mujeres (p = 0,0001), y dicho incremento en mujeres fue a partir de un aumento significativo de la masa grasa (p = 0,0001). El índice cintura/cadera fue de 0,93 (0,08) en varones y de 0,79 (0,07) en mujeres, siendo elevado sobre todo en varones en las últimas décadas. Conclusión: En el análisis de la composición corporal de la población sana de L'Hospitalet de Llobregat, destaca el índice de masa corporal elevado en las últimas décadas, a partir del incremento de masa grasa, y el índice cintura/cadera elevado en varones en las últimas décadas de la vida. (AU)
