3D-Structural Characterization of MicroRNA Expressed in Leprosy / Caracterização Estrutural em 3D de MicroRNAs Expressos na Hanseníase

Introduction: Hansen's disease, or leprosy is caused by Mycobacterium leprae (M. leprae), is a major public health problem in developing countries, and affecting the skin and peripheral nerves. However, M. leprae can also affect bone tissue, mucous membranes, liver, eyes, and testicles, producing a variety of clinical phenotypes. MicroRNAs (miRNAs) have been expressed in the various clinical forms of leprosy and could potentially be used for its diagnosis. Objective: in silico design of the molecular structure of miRNAs expressed in leprosy. Methodology: we performed a nucleotide sequence search of 17 miRNAs expressed in leprosy, designing in silico the molecular structure of the following miRNAs: miRNA-26a, miRNA-27a, miRNA-27b, miRNA-29c, miRNA-34c, miRNA-92a-1, miRNA- 99a-2, miRNA-101-1, miRNA-101-2, miRNA-125b-1, miRNA-196b, miRNA-425-5p, miRNA-452, miRNA-455, miRNA-502, miRNA-539, and miRNA-660. We extracted the nucleotides were from the GenBank of National Center for Biotechnology Information genetic sequence database. We aligned the extracted sequences with the RNA Folding Form, and the three-dimensional molecular structure design was performed with the RNAComposer. Results: we demonstrate the nucleotide sequences, and molecular structure projection of miRNAs expressed in leprosy, and produces a tutorial on the molecular model of the 17 miRNAs expressed in leprosy through in silico projection processing of their molecular structures. Conclusion: we demonstrate in silico design of selected molecular structures of 17 miRNAs expressed in leprosy through computational biology.

Introdução: a doença de Hansen, ou hanseníase é causada pelo Mycobacterium leprae (M. leprae), é um grande problema de saúde pública nos países em desenvolvimento e afeta, a pele e os nervos periféricos. Entretanto, o M. leprae também pode comprometer o tecido ósseo, membranas mucosas, fígado, olhos e testículos, produzindo uma variedade de fenótipos clínicos. MicroRNAs (miRNAs) têm sido expressos nas várias formas clínicas da hanseníase e podem ser potencialmente utilizados para seu diagnóstico. Objetivo: objetivou-se com esse experimento modelar computacionalmente a estrutura molecular dos miRNAs expressos na hanseníase. Metodologia: realizou-se como metodologia uma pesquisa das sequências nucleotídicas de 17 miRNAs expressos na hanseníase, desenhando em modelo computacional a estrutura molecular dos seguintes miRNAs: miRNA-26a, miRNA-27a, miRNA-27b, miRNA- 29c, miRNA-34c, miRNA-92a-1, miRNA-99a-2, miRNA-101-1, miRNA-101-2, miRNA-125b-1, miRNA-196b, miRNA-425-5p, miRNA-452, miRNA-455, miRNA-502, miRNA-539, e miRNA-660. Extraiu-se os nucleotídeos do banco de dados do GenBank of National Center for Biotechnology Information . Alinhou-se as sequências extraídas com o RNA Folding Form, e o projeto da estrutura molecular tridimensional foi realizado com o RNAComposer. Resultados: demonstrou-se como resultados as sequências dos nucleotídeos e a projeção da estrutura molecular dos miRNAs expressos na hanseníase, e produzimos um tutorial sobre o modelo molecular dos 17 miRNAs expressos em hanseníase através do processamento de suas estruturas moleculares em projeção computacional. Conclusão: foi demonstrado computacionalmente o projeto de estruturas moleculares selecionadas de 17 miRNAs expressos em hanseníase através da biologia computacional.

Relevance of a skilled vascular surgeon and optimized facility practices in the long-term patency of arteriovenous fistulas: a prospective study / Relevância de um cirurgião vascular qualificado e práticas hospitalares otimizadas na patência a longo prazo das fístulas arteriovenosas: um estudo prospectivo

Abstract Introduction: Arteriovenous fistulas (AVF) are the best hemodialysis vascular accesses, but their failure rate remains high. Few studies have addressed the role of the vascular surgeon's skills and the facility's practices. We aimed to study these factors, with the hypothesis that the surgeon's skills and facility practices would have an important role in primary failure and patency rates at 12 months, respectively. Methods: This was a single-center, prospective cohort study carried out from March 2005 to March 2017. Only incident patients were included. A single surgeon made all AVFs, either in the forearm (lower) or the elbow (upper). Vascular access definitions were in accordance with the North American Vascular Access Consortium. Results: We studied 113 AVFs (65% lower) from 106 patients (39% diabetics, 58% started with catheter). Time to first connection was 21.5 days (IR: 14 - 31). Only 14 AVFs (12.4%) underwent primary failure and 18 failed during the first year. Functional primary patency rate was 80.9% (SE 4.1) whereas primary unassisted patency rate, which included PF, was 70.6% (4.4). Logistic regression showed that diabetes (OR = 3.3, 95%CI 1.38 - 7.88, p = .007) and forearm location (OR = 3.03, 95CI% 1.05 - 8.76, p = 0.04) were predictors of AVF failure. Patency of lower and upper AVFs was similar in non-diabetics, while patency in diabetics with lower AVFs was under 50%. (p = 0.003). Conclusions: Results suggest that a long-lasting, suitable AVF is feasible in almost all patients. The surgeon's skills and facility practices can have an important role in the long term outcome of AVF.

Resumo Introdução: Fístulas arteriovenosas (FAV) são os melhores acessos vasculares para hemodiálise, mas sua taxa de falhas permanece alta. Poucos estudos abordaram o papel das habilidades do cirurgião vascular e das práticas hospitalares. Nosso objetivo foi avaliar esses fatores, com a hipótese de que as habilidades do cirurgião e as práticas hospitalares teriam um papel importante nas taxas de falhas primárias e perviedade em 12 meses, respectivamente. Métodos: Este foi um estudo de coorte prospectivo de um único centro, realizado de março de 2005 a março de 2017. Apenas os pacientes incidentes foram incluídos. Um único cirurgião fez todas as FAVs, seja no antebraço (inferior) ou no cotovelo (superior). As definições de acesso vascular estavam de acordo com o Consórcio Norte-Americano de Acesso Vascular. Resultados: Estudamos 113 FAVs (65% inferiores) de 106 pacientes (39% diabéticos, 58% começaram com cateter). O tempo até a primeira conexão foi de 21,5 dias (RI: 14 - 31). Apenas 14 FAV (12,4%) tiveram falha primária e 18 falharam durante o primeiro ano. A taxa de patência funcional primária foi de 80,9% (SE 4,1), enquanto a taxa de permeabilidade primária não assistida, que incluiu FP, foi de 70,6% (4,4). A regressão logística mostrou que o diabetes (OR = 3,3, 95% IC 1,38 - 7,88, p = 0,007) e localização no antebraço (OR = 3,03, 95% IC 1,05 - 8,76, p = 0,04) foram preditores de falha da FAV. A patência das FAVs inferior e superior foi semelhante em não-diabéticos, enquanto a perviedade em diabéticos com FAV inferior foi menor que 50%. (p = 0,003). Conclusões: Nossos resultados sugerem que uma FAV duradoura e adequada é viável em quase todos os pacientes. As habilidades do cirurgião e das práticas hospitalares podem ter um papel importante no resultado a longo prazo da FAV.

Relevance of a skilled vascular surgeon and optimized facility practices in the long-term patency of arteriovenous fistulas: a prospective study.

INTRODUCTION: Arteriovenous fistulas (AVF) are the best hemodialysis vascular accesses, but their failure rate remains high. Few studies have addressed the role of the vascular surgeon's skills and the facility's practices. We aimed to study these factors, with the hypothesis that the surgeon's skills and facility practices would have an important role in primary failure and patency rates at 12 months, respectively. METHODS: This was a single-center, prospective cohort study carried out from March 2005 to March 2017. Only incident patients were included. A single surgeon made all AVFs, either in the forearm (lower) or the elbow (upper). Vascular access definitions were in accordance with the North American Vascular Access Consortium. RESULTS: We studied 113 AVFs (65% lower) from 106 patients (39% diabetics, 58% started with catheter). Time to first connection was 21.5 days (IR: 14 - 31). Only 14 AVFs (12.4%) underwent primary failure and 18 failed during the first year. Functional primary patency rate was 80.9% (SE 4.1) whereas primary unassisted patency rate, which included PF, was 70.6% (4.4). Logistic regression showed that diabetes (OR = 3.3, 95%CI 1.38 - 7.88, p = .007) and forearm location (OR = 3.03, 95CI% 1.05 - 8.76, p = 0.04) were predictors of AVF failure. Patency of lower and upper AVFs was similar in non-diabetics, while patency in diabetics with lower AVFs was under 50%. (p = 0.003). CONCLUSIONS: Results suggest that a long-lasting, suitable AVF is feasible in almost all patients. The surgeon's skills and facility practices can have an important role in the long term outcome of AVF.