Mediadores da relação entre o gene FTO e a doença renal do diabetes melito : análise de caminhos

Objetivo: Investigar quais e de que maneira (direta ou indiretamente) variáveis clinicas e metabólicas mediam a associação entre o gene Fat Mass and Obesity – Associated (FTO) e a doença renal crônica (DRC) precoce em pacientes com diabetes tipo 2. Métodos: Estudo transversal conduzido com 236 pacientes com diabetes tipo 2 (53.4% mulheres, com idade média de 60 ± 10 anos). Amostras de DNA foram genotipadas para o polimorfismo rs7204609 (C/T) do gene FTO. Dados clínicos, antropométricos e metabólicos foram coletados. Análise de caminhos foi utilizada para avaliar associações. Os programas SPSS 23.0 e MPlus 5.0 foram utilizados para análises estatísticas. Resultados: A presença do alelo de risco (C) foi mais frequente entre os pacientes com DRC (21.8% vs. 10.8%; P = 0.023). Esse polimorfismo foi positivamente associado com a obesidade central (P < 0.001), que por sua vez foi associada com o mau controle glicêmico (P = 0.004) e hipertensão arterial (P < 0.001). Hipertensão arterial foi associada a alta excreção urinária de albumina (P = 0.004) e, conforme esperado, a alta excreção urinária de albumina foi associada a DRC (P < 0.001). A análise de caminhos demonstrou uma relação indireta entre o gene FTO e a DRC precoce, mediada pela obesidade central, hipertensão arterial e alta excreção urinária de albumina (P = 0.045). Todas as análises foram ajustadas para idade e sexo. Conclusão: A presença do alelo de risco C contribui para a suscetibilidade genética á DRC em pacientes com diabetes tipo 2, especialmente na presença de obesidade central, hipertensão arterial e elevada albuminúria.Objective: To investigate which and how (directly or indirectly) clinical and metabolic variables mediate the association between fat mass and the obesity - associated (FTO) gene and early chronic kidney disease (CKD) in patients with type 2 diabetes. Methods: A cross-sectional study was conducted in a sample of 236 patients with type 2 diabetes (53.4% women, mean age 60 ± 10 years). DNA samples were genotyped for the rs7204609 polymorphism (C/T) in the FTO gene. Clinical, anthropometric, and metabolic data were collected. Path analysis was used to evaluate associations. MPlus software, version 5.0, and SPSS 23.0 software were used to analyze data. Results: Presence of the risk allele (C) was more frequent among patients with CKD (21.8% vs. 10.8%; P = 0.023). This polymorphism was positively associated with central obesity (P < 0.001), which in turn was associated with poor glycemic control (P = 0.004) and hypertension (P < 0.001). Hypertension was associated with high urinary albumin excretion (UAE) (P = 0.004), and, as expected, high UAE was associated with CKD (P < 0.001). Path analysis showed an indirect relationship between the FTO gene and early CKD, mediated by central obesity, hypertension, and high UAE (P = 0.045). All analyses were adjusted for age and sex. Conclusion: The C allele contributes to genetic susceptibility to CKD in patients with type 2 diabetes, especially through the presence of central obesity, hypertension, and high UAE

Reflexões sobre Gadda

O presente ensaio consiste em considerações sobre a vida e a obra do escritor italiano Cario Emilio Gadda. Em relação à primeira procura-se explicar as causas pessoais e existenciais que levaram o escritor ao pessimismo exacerbado, à busca obsessiva da verdade e à especulação filsófica. Ao examinarmos a obra demonstramos como essa primeira motivação intima e pessoal levou-o ao trabalho lingüístico e à elaboração do estilo, tomando-se este um meio para a meta desejada e não um fim em si mesmo, como a crítica inicialmente julgava. Segue-se um breve estudo da linguagem de Gadda, citando as figuras retóricas e os recursos linguisticos mais freqüentes, exemplificando-os com textos do autor, que traduzimos para permitir melhor compreensão. Tentamos, outrossim, mostrar as causas de ordem pessoal que levaram o escritor à pesquisa cognitiva. O ensaio demonstra, através da observação dos traços mais característicos, que todo o trabalho lingüístico operado por Gadda tem a função de representar a quase inexpressável verdade da vida, e que a forma expressiva, portanto, está em função direta da expressão da formaConsiderations regarding the life and writings of Gadda. The essay shows the personal causes that exacerbated his sensitivity and brought him to an obssessive search for truth and philosofic speculation. Observations regarding his language citing his most frequent rethoric figures and the personal and social grounds that led the writer to research in order to get a representation o f the realit

CONSTRUCCIÓN DE SENTIDOS SOBRE LA ESCUELA EN JÓVENES Y ADOLESCENTES: UN ABORDAJE A PARTIR DEL ANÁLISIS DE LA CONFIGURACIÓN ACTUAL DEL MERCADO LABORAL

El presente artículo tiene como fin rastrear aspectos que den cuenta de los elementos que influyen en la construcción de sentidos que los jóvenes le dan a la escuela media en el paso por sus vidas. Siguiendo este objetivo; nos proponemos observar a partir de un análisis comparativo a nivel socio-histórico en el contexto argentino, si hay una reconfiguración de sentidos que se enlace con los cambios experimentados por mercado laboral. En este sentido, comenzamos a indagar a partir de la descripción de una realidad social donde el trabajo ha dejado de ser el eje organizador de la vida de los sujetos en la década de los 90`, y como la escuela se ubicó ante esa realidad en la representación que los jóvenes tienen de ella. Finalmente, arribamos a pensar como pueden ser reconfigurados o no estos sentidos

Gauge-invariant charged, monopole and dyon fields in gauge theories

We propose explicit recipes to construct the euclidean Green functions of gauge-invariant charged, monopole and dyon fields in four-dimensional gauge theories whose phase diagram contains phases with deconfined electric and/or magnetic charges. In theories with only either abelian electric or magnetic charges, our construction is an euclidean version of Dirac's original proposal, the magnetic dual of his proposal, respectively. Rigorous mathematical control is achieved for a class of abelian lattice theories. In theories where electric and magnetic charges coexist, our construction of Green functions of electrically or magnetically charged fields involves taking an average over Mandelstam strings or the dual magnetic flux tubes, in accordance with Dirac's flux quantization condition. We apply our construction to 't Hooft-Polyakov monopoles and Julia-Zee dyons. Connections between our construction and the semiclassical approach are discussed

Ensembles from Ordered and Disordered Proteins Reveal Similar Structural Constraints during Evolution

The conformations accessible to proteins are determined by the inter-residue interactions between amino acid residues. During evolution, structural constraints that are required for protein function providing biologically relevant information can exist. Here, we studied the proportion of sites evolving under structural constraints in two very different types of ensembles, those coming from ordered and disordered proteins. Using a structurally constrained model of protein evolution, we found that both types of ensembles show comparable, near 40%, number of positions evolving under structural constraints. Among these sites, ~ 68% are in disordered regions and ~ 57% of them show long-range inter-residue contacts. Also, we found that disordered ensembles are redundant in reference to their structurally constrained evolutionary information and could be described on average with ~ 11 conformers. Despite the different complexity of the studied ensembles and proteins, the similar constraints reveal a comparable level of selective pressure to maintain their biological functions. These results highlight the importance of the evolutionary information to recover meaningful biological information to further characterize conformational ensembles.Fil: Marchetti, Julia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monzón, Alexander. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Università di Padova; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tosatto, Silvio C.E.. Università di Padova; ItaliaFil: Parisi, Gustavo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Duas variantes do Escore de Risco Nutricional em Pacientes Críticos como preditoras de mortalidade em pacientes admitidos em uma unidade de terapia intensiva de um hospital universitário brasileiro

Objective To evaluate the agreement between the modified version of the Nutritional Risk in the Critically Ill Score (without Interleukin-6) and a variant composed of C-Reactive Protein as well as its capacity to predict mortality. Methods A prospective cohort study was carried out with 315 patients in an Intensive Care Unit of a university hospital from October 2017 to April 2018. The agreement between the instruments was evaluated using the Kappa test. The predictive capacity for estimating mortality was assessed with the Receiver Operating Characteristic curve. Results The critical patients involved in the study had a mean age of 60.8±16.3 years and 53.5% were female. Most patients had C-Reactive Protein levels ?10mg/dL (n=263, 83.5%) and their admission in the Intensive Care Unit was medical (n=219, 69.5%). The prevalence of mortality was observed in 41.0% of the evaluated patients. The proportions at high nutritional risk according to Nutritional Risk in the Critically Ill without Interleukin-6 and with C-Reactive Protein were 57.5% and 55.6%, respectively. The tools showed strong and significant agreement(Kappa=0.935; p=0.020) and satisfactory performances in predicting mortality (area under the curve 0.695 [0.636-0.754] and 0.699 [0.640-0.758]). Conclusion Both versions of the Nutritional Risk in the Critically Ill tool show a satisfactory agreement and performance as predictors of mortality in critically ill patients. Further analysis of this variant and the association between nutrition adequacy and mortality is needed.Objetivo Avaliar a concordância entre a versão modificada do Escore de Risco Nutricional em Pacientes Críticos (sem Interleucina-6) e uma variante composta de Proteína C-Reativa, bem como a capacidade de ambas as versões para predizer mortalidade em pacientes críticos. Métodos Trata-se de um estudo de coorte prospectivo em 315 pacientes admitidos em uma Unidade de Tratamento Intensivo de um hospital universitário brasileiro no período de outubro de 2017 a abril de 2018. A concordância entre os instrumentos foi avaliada pelo teste Kappa. A capacidade preditiva de mortalidade foi avaliada pela curva Receiver Operating Characteristic. Resultados Os pacientes apresentaram idade média de 60,8±16,3 anos, dos quais 53,5% eram mulheres. A maioria dos pacientes apresentou níveis de Proteína C-Reativa ?10mg/dL (n=263; 83,5%). O tipo de admissão na Unidade de Terepia Intensiva foi clínica (n=219; 69,5%), sendo que a prevalência da mortalidade foi observada em41,0% dos pacientes avaliados. O alto risco nutricional, avaliado pelo Nutritional Risk in the Critically Ill sem Interleucina-6 e pela variante com Proteína C-Reativa, foi demonstrado em 57,5% e 55,6% dos pacientes críticos, respectivamente. Os instrumentos demostraram concordância forte e significativa (Kappa=0,935; p=0,020) e desempenho satisfatório para predizer mortalidade (área sob a curva 0,695 [0,636-0,774] e 0,699 [0,640-0,758]). Conclusão Ambas as versões do Escore de Risco Nutricional em Pacientes Críticos apresentam boa concordância e desempenho satisfatório como preditores de mortalidade em pacientes críticos. É ainda necessária uma análise mais aprofundada desta variante, bem como da associação entre adequação nutricional e mortalidade

Relationship between the FTO genotype and early chronic kidney disease in type 2 diabetes : the mediating role of central obesity, hypertension, and high albuminuria

Introduction: Single nucleotide polymorphisms (SNP) in the fat mass and obesity-associated (FTO) gene have been associated with type 2 diabetes (T2D) and its complications. The aim of the present research was to investigate which and how (directly or indirectly) clinical and metabolic variables mediate the association between fat mass and the FTO gene and early chronic kidney disease (CKD) in individuals with T2D. Methods: This cross-sectional study was conducted in a sample of 236 participants with T2D (53.4% women, mean age 60 ± 10 years). DNA samples were genotyped for the rs7204609 polymorphism (C/T) in the FTO gene. Clinical, anthropometric, and metabolic data were collected. Path analysis was used to evaluate the associations. Results: Of the sample, 78 individuals with T2D had CKD (33%). Presence of the risk allele (C) was higher among participants with CKD (21.8 vs. 10.8%; p = 0.023). This polymorphism was positively associated with higher waist circumference, which in turn was associated with higher glycated hemoglobin and higher blood pressure. A higher blood-pressure level was associated with higher urinary albumin excretion (UAE) and as expected, higher UAE was associated with CKD. Path analysis showed an indirect relationship between the FTO gene and early CKD, mediated by waist circumference, blood-pressure levels, and UAE. Conclusions: These findings suggest that the C allele may contribute to genetic susceptibility to CKD in individuals with T2D through the presence of central obesity, hypertension, and high albuminuria