Privacy-preserving cancer type prediction with homomorphic encryption.

Cancer genomics tailors diagnosis and treatment based on an individual's genetic information and is the crux of precision medicine. However, analysis and maintenance of high volume of genetic mutation data to build a machine learning (ML) model to predict the cancer type is a computationally expensive task and is often outsourced to powerful cloud servers, raising critical privacy concerns for patients' data. Homomorphic encryption (HE) enables computation on encrypted data, thus, providing cryptographic guarantees to protect privacy. But restrictive overheads of encrypted computation deter its usage. In this work, we explore the challenges of privacy preserving cancer type prediction using a dataset consisting of more than 2 million genetic mutations from 2713 patients for several cancer types by building a highly accurate ML model and then implementing its privacy preserving version in HE. Our solution for cancer type inference encodes somatic mutations based on their impact on the cancer genomes into the feature space and then uses statistical tests for feature selection. We propose a fast matrix multiplication algorithm for HE-based model. Our final model achieves 0.98 micro-average area under curve improving accuracy from 70.08 to 83.61% , being 550 times faster than the standard matrix multiplication-based privacy-preserving models. Our tool can be found at https://github.com/momalab/octal-candet .

Functional Capacity, Lipid Profile, and Associated Factors in Older Adults Living in Urban and Rural Areas.

This study aimed to analyze the relationship between sociodemographic and lifestyle variables, functional strength, aerobic capacity, and lipid profile of older adults living in urban and rural areas. For this purpose, 208 older adults were evaluated (132 living in rural areas and 73 living in urban areas). Sociodemographic data were collected, and functional strength, aerobic capacity, and lipid profile of older adults living in the southern region of Brazil were evaluated. Only total cholesterol and LDL cholesterol were associated with place of residence (p < 0.05), and living in the countryside was associated with low aerobic capacity (p=0.010). The use of medication (OR = 3.01; p=0.012) and smoking (OR = 0.30; p=0.027) were the only variables that explained aerobic performance, regardless of place of residence. In conclusion, place of residence is not a factor that, alone or in combination with other conditions, affects the functional performance or lipid profile of the older adult population.

Privacy-preserving genotype imputation with fully homomorphic encryption.

Genotype imputation is the inference of unknown genotypes using known population structure observed in large genomic datasets; it can further our understanding of phenotype-genotype relationships and is useful for QTL mapping and GWASs. However, the compute-intensive nature of genotype imputation can overwhelm local servers for computation and storage. Hence, many researchers are moving toward using cloud services, raising privacy concerns. We address these concerns by developing an efficient, privacy-preserving algorithm called p-Impute. Our method uses homomorphic encryption, allowing calculations on ciphertext, thereby avoiding the decryption of private genotypes in the cloud. It is similar to k-nearest neighbor approaches, inferring missing genotypes in a genomic block based on the SNP genotypes of genetically related individuals in the same block. Our results demonstrate accuracy in agreement with the state-of-the-art plaintext solutions. Moreover, p-Impute is scalable to real-world applications as its memory and time requirements increase linearly with the increasing number of samples. p-Impute is freely available for download here: https://doi.org/10.5281/zenodo.5542001.

Supplementation with detox juice added with probiotic improves atherogenic parameters in healthy individuals

Abstract Phytochemicals present in detox juices and probiotics have demonstrated protective effects on cardiovascular risk factors. The consumption of these products alone modulate metabolic mechanisms and biomarkers. However, the effects of the combination of detox juice and probiotics have not yet been evaluated on atherogenic parameters. A randomized controlled study was carried out with 40 healthy volunteers (20 men and 20 women), aged between 18 and 50 years old. The volunteers ingested 200mL of juice for 30 days. Before and after supplementation, the anthropometric and lipid profiles and plasma concentrations of TBARS, Myeloperoxidase, Glutathione, Protein and non-protein Thiols and Vitamin C were analyzed. A reduction in LDL-c (p=0.05), triglycerides (p=0.05) and a significant increase in HDL-c (p=0.002) was observed. There was a significant decrease in the concentrations of TBARS (p=0.01), myeloperoxidases (p=0.02) and a significant increase in the Vitamin C and GSH (p=0.01). There wasn`t improvement in anthropometric parameters and total cholesterol. The findings highlight that supplementation with probiotic detox juice improves the lipid and antioxidant profile, suggesting a possible positive effect in reducing the risk of cardiovascular disease in healthy volunteers. Nevertheless, more robust researches with a prolonged treatment period should be conducted.

Fast and Scalable Private Genotype Imputation Using Machine Learning and Partially Homomorphic Encryption.

The recent advances in genome sequencing technologies provide unprecedented opportunities to understand the relationship between human genetic variation and diseases. However, genotyping whole genomes from a large cohort of individuals is still cost prohibitive. Imputation methods to predict genotypes of missing genetic variants are widely used, especially for genome-wide association studies. Accurate genotype imputation requires complex statistical methods. Due to the data and computing-intensive nature of the problem, imputation is increasingly outsourced, raising serious privacy concerns. In this work, we investigate solutions for fast, scalable, and accurate privacy-preserving genotype imputation using Machine Learning (ML) and a standardized homomorphic encryption scheme, Paillier cryptosystem. ML-based privacy-preserving inference has been largely optimized for computation-heavy non-linear functions in a single-output multi-class classification setting. However, having a large number of multi-class outputs per genome per individual calls for further optimizations and/or approximations specific to this application. Here we explore the effectiveness of linear models for genotype imputation to convert them to privacy-preserving equivalents using standardized homomorphic encryption schemes. Our results show that performance of our privacy-preserving genotype imputation method is equivalent to the state-of-the-art plaintext solutions, achieving up to 99% micro area under curve score, even on real-world large-scale datasets up to 80,000 targets.

Desenvolvimento de sistema estruturado com inteligência artificial para apoio no diagnóstico de patologias oftalmológicas mais relevantes / Development of a structured artificial intelligence system to support the diagnosis of the most relevant ophthalmic diseases

Introdução: A inteligência artificial (IA) está revolucionando a área da saúde. Na oftalmologia, esta tecnologia pode possibilitar diagnósticos mais rápidos e precisos, impedindo a progressão das alterações na visão. Médicos e algoritimosalgoritmos podem ser mais eficientes quando trabalham juntos. Desenvolver um software de IA com alta especificidade e sensibilidade para apoio no diagnóstico de algumas patologias oftalmológicas. Métodos: O software de deep learning foi construído através de redes neurais valendo de duas bases computacionais MobileNet e Inception. Para o treinamento do banco de dados foram utilizadas 2.520 imagens de glaucoma, retinopatia diabética, toxoplasmose ocular, papiledema, descolamento de retina e retina normal. Para a validação foi utilizado 428 imagens patológicas e normais para os cálculos de sensibilidade e de especificidade. Todas as imagens foram cedidas da Sociedade Americana de Especialistas da Retina. Resultados: Os resultados de sensibilidade e especificidade foram no MobileNet de 91% (IC 95%, 89-92%) e 98,5% (IC 95%, 98-99%); no Inception, de 91,4% (IC 95%, 89-93,5%) de 98,4% (IC 95%, 98-98,8%), respectivamente. Não houve diferença significativa entre os dois métodos utilizados. Conclusão: O software apresentou resultados promissores na distinção das condições oftalmológicas pesquisadas. (AU)

Introduction: Artificial intelligence (AI) is revolutionizing health care. In ophthalmology, this technology can enable faster and more accurate diagnoses, preventing the progression of vision Physicians and algorithms are most effective when working together. To develop an AI software with high specificity and sensitivity to support the diagnosis of some ophthalmic diseases. Methods: A deep learning software was built through neural networks using two computational bases, MobileNet and Inception. For training the database, 2520 images of glaucoma, diabetic retinopathy, ocular toxoplasmosis, papilledema, retinal detachment, and normal retina were used. For validation, 428 pathological and normal images were used for calculations of sensitivity and specificity. All images were obtained from the American Society of Retina Specialists. Results: The results of sensitivity and specificity were 91% (95% confidence interval [CI], 89-92%) and 98.5% (95% CI, 98-99%) on MobileNet, and 91.4% (95% CI, 89-93.5%) and 98.4% (95% CI, 98-98.8%) on Inception, respectively. There was no significant difference between the two methods. Conclusion: The software showed promising results in distinguishing the main ophthalmic conditions surveyed. (AU)

Artificial intelligence algorithm for the histopatological diagnosis of skin cancer

Introduction: Cutaneous neoplasms are the most common cancers in the world, and have high morbidity rates. A definitive diagnosis can only be obtained after histopathological evaluation of the lesions. To develop an artificial intelligence program to establish the histopathological diagnosis of cutaneous lesions.Methods: A deep learning program was built using three neural network architectures: MobileNet, Inception and convolutional networks. A database was constructed using 2732 images of melanomas, basal and squamous cell carcinomas, and normal skin. The validation set consisted of 284 images from all 4 categories, allowing for the calculation of sensitivity and specificity. All images were provided by the Path Presenter website.Results: The sensitivity and specificity of the MobileNet model were 92% (95%CI, 83-100%) and 97% (95%CI, 90-100%), respectively; corresponding figures for the Inception model were 98.3% (95%CI, 86-100%) and 98.8% (95%CI, 98.2-100%); lastly, the sensitivity and specificity of the convolutional network model were 91.6% (95%CI, 73.8-100%) and 95.7% (95%CI, 94.4-97.2%). The maximum sensitivity for the differentiation of malignant conditions was 91%, and specificity was 95.4%.Conclusion: The program developed in the present study can efficiently distinguish between the main types of skin cancer with high sensitivity and specificity. (AU)

Desenvolvimento de sistema estruturado com inteligência artificial para apoio no diagnóstico de parasitoses intestinais / Development of a structured artificial intelligence system to support the diagnosis of intestinal parasitoses

Introdução: Sistemas de inteligência artificial são tecnologias promissoras de assistência em saúde e diagnóstico laboratorial, que podem ser implementados como métodos de suporte para o diagnóstico de parasitoses intestinais. Este estudo objetivou desenvolver um software de IA que auxilia no diagnóstico laboratorial de parasitoses intestinais, com alta sensibilidade e especificidade. Métodos: O software foi desenvolvido utilizando duas redes neurais, Inception e MobileNet. Primeiro imagens de ovos dos parasitas Ascaris lumbricoides, Trichiuris trichiura, Taenia sp, Hymenolepis nana, Schistosoma mansoni e larvas de Strongyloides stercoralis, foram utilizados para treinar o banco de dados. Posteriormente 2.740 imagens cedidas pelo Laboratório de Parasitologia da Universidade do Oeste de Santa Catarina foram testadas no software. Resultados: O software apresentou sensibilidade de 82,3% (95% intervalo de confiança (IC), 71,9%-89,1%) e especificidade de 95,1% (95% IC, 94,3%-97,8%) para MobileNet e sensibilidade de 72,1% (95% IC, 52,6%-115%) e especificidade de 92,1% (95% IC, 91,7%-97,7%) para Inception. Conclusão: O software apresentou resultados promissores na análise de parasitas intestinais, reforçando que, no futuro, a presença de sistemas de suporte de diagnóstico das parasitoses pode vir a se tornar mais rápido e eficiente. (AU)

Introduction: Artificial intelligence systems are promising technologies for health care and laboratory diagnosis, which can be implemented as support methods for the diagnosis of intestinal parasitoses. This study aimed to develop an artificial intelligence software that assists the laboratory diagnosis of intestinal parasitoses with high sensitivity and specificity. Methods: The software was developed using two neural networks, Inception and MobileNet. First, images of eggs from the parasites Ascaris lumbricoides, Trichuris trichiura, Taenia sp., Hymenolepis nana, Schistosoma mansoni and Strongyloides stercoralis larvae were used to train the database. Then, 2,740 images provided by the Parasitology Laboratory of the Universidade do Oeste de Santa Catarina were tested in the software. Results: The software had a sensitivity of 82.3% (95% confidence interval [CI], 71.9% ­ 89.1%) and a specificity of 95.1% (95% CI, 94.3% ­ 97,8%) for MobileNet and a sensitivity of 72.1% (95% CI, 52.6% ­ 115%) and a specificity of 92.1% (95% CI, 91.7% ­ 97.7%) for Inception. Conclusion: The software showed promising results in the analysis of intestinal parasites, reinforcing that, in the future, the presence of diagnostic support systems for parasitoses may become faster and more efficient. (AU)

Method of histopathological diagnosis of mammary nodules through deep learning algorithm / Método de diagnóstico histopatológico de nódulos mamários por meio do algoritmo de aprendizagem profunda

ABSTRACT Introduction: Artificial intelligence systems are promising health care technologies, mainly in medical subareas such as pathology, and can be used as support methods for the histological diagnosis of mammary nodules. Objective: This study describes the method and results of the development of artificial intelligence software for the histopathological analysis of mammary nodules. Methods: The software was developed by using two neural networks - Inception and MobileNet. The database used for learning the conditions analyzed (histologically normal breast, fibroadenoma, fibrocystic changes, in situ ductal carcinoma, invasive carcinoma of no special type and invasive lobular carcinoma) was obtained after authorization of the Path Presenter site with 5,298 images. The 2,740 images used for the validation of the system were obtained from the Pathology Institute of Passo Fundo. Results: The present software had sensitivity of 80.5% [95% confidence interval (CI), 71.9%-89.1%] and specificity of 96.1% (95% CI, 94.3%-97.8%) for MobileNet and sensitivity of 73.8% (95% CI, 52.6%-115%) and specificity of 94.7% (CI 95%, 91.7%-97.7%) for Inception. For the differentiation of malignant conditions, it obtained a maximum sensitivity of 78.7% and specificity of 95.8%; for differentiation of benign conditions, the maximum sensitivity was 82.6% and the specificity was 97.4%. Conclusion: The present software presented promising results in the histopathological analysis of mammary nodules. It reinforced the idea that in the future the presence of diagnostic support systems in breast pathologies may play a crucial role in health care.

RESUMEN Introducción: Los sistemas de inteligencia artificial son tecnologiasprometedoras en asistencia en salud, principalmente en áreas médicas como la patologia; pueden ser usados para el diagnóstico histopatológico de nódulos mamarios. Objetivo: Este estudio presenta el método y los resultados de la construcción de un software de inteligencia artificial para análisis histopatológico de nódulos mamarios. Métodos: El software fue desarrollado usando dos redes neurales. Se obtuvo la base de datos para el aprendizaje de las condicionas analizadas (mama histológicamente normal, fibroadenoma, cambios fibroquisticos de la mama, carcinoma ductal in situ, carcinoma invasivo de tipo no especial y carcinoma lobular invasivo) después de la aprobación de la página Path Presenter, con 5.298 imágenes. Las imágenes utilizadas para validación del sistema se obtuvieron del Instituto de Patologia de Passo Fundo, totalizando 2.740 imágenes. Resultados: El softwarepresentósensibilidaddel80,5% [intervalo de confianza (IC) 95%, 71,9%-89,1%] y especificidad de 96,1% (95% IC, 94,3%-97,8%) para MobileNet y sensibilidad de 73,8% (95% IC, 52,6%-115%) y especificidad de 94,7% (95% IC, 91,7%-97,7%) para Inception. Para diferenciación de condiciones malignas, obtuvo-se sensibilidad máxima de 78,7% y especificidad de 95,8%; para diferenciación de condiciones benignas, la sensibilidad máxima fue de 82,6% y la especificidad, de 97,4%. Conclusión: El software presentó resultados prometedores en el análisis histopatológico de nódulos mamarios, reforzando la idea de que, en el futuro, la presencia de sistemas de soporte diagnóstico de enfermedades mamarias puede desempenar un papel crucial en la rutina del sistema de salud.

RESUMO Introdução: Sistemas de inteligência artificial são tecnologias promissoras de assistência em saúde, principalmente em subáreas médicas, como a patologia; podem ser utilizados como métodos de suporte para o diagnóstico) histopatológico de nódulos mamários. Objetivo: Este estudo apresenta a metodologia e os resultados da construção de um software de inteligência artificial para análise histopatológica de nódulos mamários. Métodos: O softwarefoi desenvolvido utilizando duas redes neuraispara a sua construção: Inception e MobileNet. O banco de dados utilizado para a aprendizagem das condições analisadas (mama histologicamente normal, fibroadenoma, alteração fibrocística, carcinoma ductal in situ, carcinoma invasivo do tipo não especial e carcinoma lobular invasivo) foi obtido após autorização do site Path Presenter, com 5.298 imagens. As imagens utilizadas para a validação do sistema foram obtidas do Instituto de Patologia de Passo Fundo, totalizando 2.740 imagens. Resultados: O software apresentou sensibilidade de 80,5% [intervalo de confiança (IC) 95%, 71,9%-89,1%] e especificidade de 96,1 % (95% IC, 94,3%-97,8%)para o MobileNet e sensibilidade de 73,8% (95% IC, 52,6%-115%) e especificidade de 94,7% (95% IC, 91,7%-97,7%) para o Inception. Para a diferenciação de condições malignas, obteve-se sensibilidade máxima de 78,7% e especificidade de 95,8%; para diferenciação de condições benignas, a sensibilidade máxima foi de 82,6% e a especificidade, de 97,4%. Conclusão: O software apresentou resultados promissores na análise histopatológica de nódulos mamários, reforçando que, no futuro, a presença de sistemas de suporte de diagnóstico das patologias mamárias pode se fazer presente na rotina do sistema saúde.

Evolution of potential biomarkers of acute muscle injury after physical exercise

Skeletal muscle injury is a frequent event and diagnosis using the classical blood markers sometimes produces unsatisfactory results. Therefore, objective of the study was to detect new biomarkers in plasma, saliva and urine in response to acute muscle damage induced by physical exercise. A cross-sectional study was conducted with 27 American football players. Before the physical exercises (T0), 60 minutes (T1) and 24 hours (T2) after physical exercise, was determined the clinical, biochemical and molecular parameters, including ADA, TBARS, leukocytes, lymphocytes and comet assay. The serum ADA was significantly higher in T1 and T2, in the urine there was a significant increase in T1, in the saliva there was no significant differences. There was an increase in serum TBARS in T2, saliva and urine in T1. The leukocytes increased in T1 and decreased in T2. Through the comet assay was observed significant DNA damage in T1 and T2. Serum and urinary ADA activity, serum, urinary and salivary TBARS are robust and promising biomarkers of acute muscle injury and that the comet assay allows a quick and effective evaluation of DNA lesions induced by physical exercise and could be used to monitor athletes avoiding injuries that are more serious.

Oxidative, inflammatory and cardiometabolic biomarkers of clinical relevance in patients with metabolic syndrome / Biomarcadores oxidativos, inflamatórios e cardiometabólicos de relevância clínica em pacientes com síndrome metabólica

ABSTRACT Introduction: Obesity is characterized by excessive deposition of fat in adipose tissue and is associated with the development of pathological damage in several metabolic processes that are associated with oxidative stress and inflammation. Objective: To evaluate the levels of adiponectin, inflammatory markers and oxidative markers, with the objective of determining a biomarkers profile in adults that influences the metabolic risk of developing the metabolic syndrome (MetS). Methods: The groups studied included 84 adults (48 Without MetS and 36 With MetS). General and biochemical parameters were determined. Adiponectin levels, inflammatory markers [C-reactive protein (CRP)], interleukin 6 (IL-6), adenosine deaminase (ADA), dipeptidyl peptidase-IV (DPP-IV) and oxidative markers [thiobarbituric acid reactive substances (TBARS), sulfhydryl groups (SH), total ferric antioxidant power (FRAP) and vitamin C] were also measured. Results: The MetS group presented a significant increase in insulin, triglycerides, cholesterol, low-density lipoprotein cholesterol (LDL-C), glutamic-pyruvic transaminase (GPT) and uric acid, as well as gamma-glutamyl transferase (GGT), glutamic-oxaloacetic transaminase (GOT), and vitamin C. Conclusion: The combination of IL-6, ultra-sensitive C-reactive protein (us-CRP), ADA, DPP-IV and the increase of TBARS, with the reduction of vitamin C, SH groups and adiponectin, promote inflammation and compromise insulin sensitivity, thus presenting an active role in the pathogenesis of MetS. These findings are significant because they may assist in monitoring clinical changes, in the prevention of future cardiometabolic events in individuals with MetS, and in the identification of inflammatory and oxidative markers that assist in the monitoring and prevention of MetS.

RESUMO Introdução: A obesidade caracteriza-se pela deposição excessiva de gordura no tecido adiposo e está associada ao desenvolvimento de danos patológicos em vários processos metabólicos que estão relacionados com o estresse oxidativo e a inflamação. Objetivo: Avaliar os níveis de adiponectina, marcadores inflamatórios e marcadores oxidativos, com o objetivo de determinar um perfil de biomarcadores em adultos que influencie o risco metabólico de desenvolver síndrome metabólica (SMet). Métodos: Os grupos estudados incluíram 84 adultos (48 sem SMet e 36 com SMet). Parâmetros gerais e bioquímicos foram determinados. Níveis de adiponectina, marcadores inflamatórios [proteína C reativa ultrassensível (PCR-us), interleucina 6 (IL-6), adenosina deaminase (ADA), dipeptidil peptidase-IV (DPP-IV)] e marcadores oxidativos [thiobarbituric acid reactive species (TBARS), sulfhydryl (SH) grupos, total antioxidante capacity ferric (FRAP) e vitamina C] também foram medidos. Resultados: O grupo com SMet apresentou aumento significativo de insulina, triglicerídeos, colesterol, colesterol da llipoproteína de baixa densidade (LDL-C), transaminase glutâmica pirúvica (TGP) e ácido úrico, bem como gamaglutamiltransferase (GGT), transaminase glutâmica oxalacética (TGO), hemoglobina glicada (HbA1C), homeostasis model assessment of insulin resistance (HOMA-IR), glicose, SH e TBARS, e redução significativa de sensibilidade insulínica (SI), lipoproteína de alta densidade (HDL-C) e vitamina C. Conclusão: A combinação de IL-6, PCR-us, ADA, DPP-IV e o aumento de TBARS, com a redução de vitamina C, grupos SH e adiponectina promovem inflamação e comprometem a sensibilidade à insulina, apresentando assim um papel ativo na patogênese da SMet. Esses achados são significativos porque podem auxiliar no monitoramento de alterações clínicas, na prevenção de futuros eventos cardiometabólicos em indivíduos com SMet e na identificação de marcadores inflamatórios e oxidativos que auxiliam no monitoramento e na prevenção da SMet.

Influence of obesity on the serum concentration of retinol-binding protein 4 (RBP4) in young adults / Influência da obesidade sobre a concentração sérica da proteína ligadora do retinol 4 (RBP4) em adultos jovens

ABSTRACT Introduction: Obesity is a chronic low-grade inflammation, in which macrophages play an important role in the maintenance of inflammation by producing pre-inflammatory and inflammatory substances such as retinol-binding protein 4 (RBP4), which acts as a trigger for adipose tissue inflammation and associated with obesity co-morbidities. Objective: This study evaluated the serum concentration of RBP4 and biomarkers of insulin resistance (IR) in young adult patients with normal weight, overweight and obese. Methods: A cross sectional study was conducted involving 149 subjects: 54 healthy individuals (32 women and 22 men), 27 overweight (17 women and 10 men) and 68 obese (41 women and 27 men). The anthropometric measures and the concentrations of RBP4, insulin, HbA1c and glucose were determined, in addition to the calculations for homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (IS). Results: overweight and obese patients showed significantly higher levels of glucose, HbA1c, insulin, and HOMA-IR (p < 0.0001), and decreased IS (p > 0.0001) when compared with the normal weight group. There was an increase in RBP4 proportional to the increase in body mass index (BMI); the obese group showed significantly higher levels (p < 0.05). Conclusion: This study suggests that RBP4 may play a key role in the development of inflammation and IR in young obese individuals, as it may promote significant disturbances in insulin metabolism and may contribute to the development of obesity-related co-morbidities. This parameter can represent a hope in the identification of new inflammatory and IR markers to assist in the diagnosis and follow-up of overweight and obese patients.

RESUMO Introdução: Na obesidade, ocorre inflamação crônica de baixo grau, na qual os macrófagos desempenham um papel importante na manutenção desta inflamação por produzirem sustâncias pré-inflamatórias e inflamatórias, como a proteína transportadora de retinol (RBP4), que funciona como gatilho para a inflamação do tecido adiposo, aliando-se a comorbidades da obesidade. Objetivo: Este estudo avaliou a concentração sérica de RBP4 e biomarcadores de resistência insulínica (RI) em pacientes adultos jovens, com peso normal, sobrepeso e obesos. Métodos: Foi conduzido um estudo transversal que envolveu 149 indivíduos: 54 saudáveis (32 mulheres e 22 homens), 27 com sobrepeso (17 mulheres e 10 homens) e 68 obesos (41 mulheres e 27 homens). As medidas antropométricas e as concentrações de RBP4, insulina, HbA1c e glicose foram determinadas, além dos cálculos do modelo de avaliação da homeostase da resistência à insulina (HOMA-IR) e da sensibilidade insulínica (SI). Resultados: Pacientes obesos e com sobrepeso mostraram níveis significativos maiores de glicose, HbA1c, insulina e HOMA-IR (p > 0,0001) e diminuição da SI (p > 0,0001), quando comparados com o grupo de peso normal. Observou-se um aumento de RBP4 proporcional ao aumento do índice de massa corporal (IMC); o grupo obeso apresentou níveis significativamente superiores (p < 0,05). Conclusão: Este estudo sugere que a RBP4 pode ter papel-chave no desenvolvimento da inflamação e da RI em obesos jovens, uma vez que pode promover perturbações significativas no metabolismo da insulina, além de contribuir para o desenvolvimento de comorbidades relacionadas com obesidade. Este parâmetro pode representar uma esperança na identificação de novos marcadores inflamatórios e de RI que auxiliem o diagnóstico e o acompanhamento de pacientes com sobrepeso e obesos.

Evaluation of salivary oxidative parameters in overweight and obese young adults

ABSTRACT Background Obesity is characterized by a deposition of abnormal or excessive fat in adipose tissue, and is linked with a risk of damage to several metabolic and pathological processes associated with oxidative stress. To date, salivary oxidative biomarkers have been minimally explored in obese individuals. Thus, the aim of this study was to assess the concentrations of salivary oxidative biomarkers (ferric-reducing antioxidant power, uric acid, sulfhydryl groups) and lipid peroxidation in obese and overweight young subjects. Materials and methods Levels of lipid peroxidation, ferric-reducing antioxidant power, uric acid, and SH groups were determined in the saliva and serum of 149 young adults, including 54 normal weight, 27 overweight, and 68 obese individuals. Anthropometric measurements were also evaluated. Results Salivary levels of ferric-reducing antioxidant power, sulfhydryl groups, and lipid peroxidation, as well as serum levels of ferric-reducing antioxidant power, uric acid, and lipid peroxidation were higher in obese patients when compared with individuals with normal weight. There were correlations between salivary and serum ferric-reducing antioxidant power and salivary and serum uric acid in the obese and normal-weight groups. Conclusions Our results indicate that the increase in salivary levels of ferric-reducing antioxidant power, sulfhydryl groups, and lipid peroxidation, and serum levels of ferric-reducing antioxidant power, uric acid, and lipid peroxidation could be related to the regulation of various processes in the adipose tissue. These findings may hold promise in identifying new oxidative markers to assist in diagnosing and monitoring overweight and obese patients.

Evaluation of salivary oxidative parameters in overweight and obese young adults.

BACKGROUND: Obesity is characterized by a deposition of abnormal or excessive fat in adipose tissue, and is linked with a risk of damage to several metabolic and pathological processes associated with oxidative stress. To date, salivary oxidative biomarkers have been minimally explored in obese individuals. Thus, the aim of this study was to assess the concentrations of salivary oxidative biomarkers (ferric-reducing antioxidant power, uric acid, sulfhydryl groups) and lipid peroxidation in obese and overweight young subjects. MATERIALS AND METHODS: Levels of lipid peroxidation, ferric-reducing antioxidant power, uric acid, and SH groups were determined in the saliva and serum of 149 young adults, including 54 normal weight, 27 overweight, and 68 obese individuals. Anthropometric measurements were also evaluated. RESULTS: Salivary levels of ferric-reducing antioxidant power, sulfhydryl groups, and lipid peroxidation, as well as serum levels of ferric-reducing antioxidant power, uric acid, and lipid peroxidation were higher in obese patients when compared with individuals with normal weight. There were correlations between salivary and serum ferric-reducing antioxidant power and salivary and serum uric acid in the obese and normal-weight groups. CONCLUSIONS: Our results indicate that the increase in salivary levels of ferric-reducing antioxidant power, sulfhydryl groups, and lipid peroxidation, and serum levels of ferric-reducing antioxidant power, uric acid, and lipid peroxidation could be related to the regulation of various processes in the adipose tissue. These findings may hold promise in identifying new oxidative markers to assist in diagnosing and monitoring overweight and obese patients.

Association between the glutathione S-transferase P1 (GSTP1) Ile105Val gene polymorphism in obese and overweight patients over 60 years / Associação entre o polimorfismo Ile105Val do gene da glutationa S-transferase P1 (GSTP1) em pacientes obesos e com sobrepeso acima de 60 anos

ABSTRACT INTRODUCTION: Obesity is related to the possibility of a number of metabolic damage associated with oxidative stress. The enzymes of the glutathione S-transferase (GST) family have the function of promoting detoxification; however, polymorphisms in the glutathione S-transferase P1 (GSTP1) gene generate less efficient alleles as well as a decrease in their amount and activity. OBJECTIVE: This study aimed to analyze the frequency of the alleles (A and G) and the genotypes of the GSTP1 Ile105Val gene polymorphism, and its association with obesity in the elderly. MATERIALS AND METHODS: This was a cross-sectional study involving 232 subjects aged between 60-98 years, of both sexes, originating from southern Brazil. The volunteers were categorized according to the body mass index (BMI) in three groups: normal weight (n = 52), overweight (n = 133), and obese (n = 47). Anthropometry was evaluated and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genetic analysis, from peripheral blood samples. RESULTS: The allelic frequency in the elderly obese group was 37.2% for A and 62.8% for G allele, and the genotypic frequency observed was AA 8.5%, AG 57.4% and GG 34.1%. Both the G allele as the GG and AG genotypes were significantly higher in the obese group compared to the other groups (p < 0.001). CONCLUSION: A higher prevalence of the G allele was observed in elderly obese group, responsible for encoding an abnormal enzyme and consequent reduction of antioxidant defenses, which contribute to inflammation process and obesity in the elderly.

RESUMO INTRODUÇÃO: A obesidade está relacionada com a possibilidade de numerosos danos metabólicos associados ao estresse oxidativo. As enzimas da família glutationa S-transferase (GST) têm como função promover a detoxificação, entretanto, polimorfismos no gene da glutationa S-transferase P1 (GSTP1) geram alelos menos eficientes, bem como diminuição da sua quantidade e atividade. OBJETIVO: Este estudo teve como objetivo analisar a frequência dos alelos (A e G) e dos genótipos do polimorfismo Ile105Val do gene GSTP1, além de sua associação à obesidade em idosos. MATERIAIS E MÉTODOS: Tratou-se de um estudo transversal, o qual envolveu 232 indivíduos com idades entre 60 e 98 anos, de ambos os sexos, oriundos da região Sul do Brasil. Os voluntários foram caracterizados de acordo com o índice de massa corporal (IMC) em três grupos: peso normal (n = 52), sobrepreso (n = 133) e obesos (n = 47). A antropometria foi avaliada, e a técnica de reação em cadeia da polimerase-polimorfismo no comprimento de fragmentos de restrição (PCR-RFLP) foi usada para análise genética a partir de amostras de sangue periférico. RESULTADOS: A frequência alélica no grupo de idosos obesos foi de 37,2% para o alelo A e 62,8% para o G, e a frequência genotípica observada, de AA 8,5%, AG 57,4% e GG 34,1%. Tanto o alelo G quanto os genótipos GG e AG foram significativamente maiores no grupo obeso quando comparados com os dos demais grupos (p < 0,001). CONCLUSÃO: Observou-se maior prevalência do alelo G no grupo de idosos obesos, responsável pela codificação de uma enzima anormal e consequente diminuição das defesas antioxidantes, que contribuem para o processo inflamatório e a obesidade em idosos.

Adipocytokines, inflammatory and oxidative stress markers of clinical relevance altered in young overweight/obese subjects.

OBJECTIVE: The aim of the study was to assess the influence of overweight and obesity in youth on adipocytokines levels, inflammatory and oxidative markers. DESIGN AND METHODS: Cross-sectional study of 149 young adults (54 normal weight, 27 overweight, 68 obese).Clinical and biochemical parameters, including lipid profile, fasting glucose, insulin and HOMA were determined. The levels of adipocytokines(adiponectin, retinol-binding protein 4 (RBP4), and resistin), markers of inflammation (high-sensitivity C-reactive protein (hs-CRP) adenosine deaminase (ADA), dipeptidyl peptidase-IV (DPP-IV) activities, serum IL-6 levels and oxidative stress (malondialdehyde and ferric reducing antioxidant power - FRAP) were measured. RESULTS: Obese subjects presented significantly lower levels of Sulfhydryl groups (SH groups), adiponectin, HDL-C and the highest levels of RBP4, hs-CRP, resistin, IL-6, ADA, DPP-IV activities, and oxidative markers than compared to those who were of normal weight. There was a positive correlation between hs-CRP, IL-6, DDP-IV activity, anthropometric measurements and biochemical parameters. CONCLUSIONS: This analysis shows that resistin, RBP4, IL-6, ADA and DPP-IV activities and the reduction of adiponectin can promote inflammation, impairment of insulin sensitivity, and may contribute development of the pathways involved in obesity. These findings may hold promise in identifying new inflammatory markers, benchmarks that assist in the diagnosis and monitoring of patients with overweight and obese.

Correlação entre a concentração sérica de interleucina-6 (IL-6) e biomarcadores de resistência insulínica em adultos jovens obesos / Correlation between serum interleukin-6 (IL-6) and insulin resistance biomarkers in obese young adults

Introdução: O tecido adiposo é um importante órgão endócrino secretor de adipocinas como a interleucina-6 (IL-6), que estimula a produção de proteínas de fase aguda no fígado, conduzindo a um estado inflamatório subclínico associado ao surgimento de comorbidades presentes na obesidade, como a resistência à insulina (RI). O objetivo deste estudo foi avaliar a concentração de IL-6 em jovens obesos, com sobrepeso e de peso normal, correlacionando as concentrações dessa citocina com biomarcadores de RI. Métodos: Foi conduzido um estudo transversal que envolveu 149 indivíduos: 54 saudáveis (32 mulheres e 22 homens), 27 com sobrepeso (17 mulheres e 10 homens) e 68 obesos (41 mulheres e 27 homens). As medidas antropométricas e as concentrações de IL-6, insulina, hemoglobina glicada e glicose foram determinadas, assim como os cálculos do Modelo de Avaliação da Homeostase (HOMA) e da sensibilidade insulínica (SI). Resultados: Pacientes obesos mostraram níveis de IL-6, glicose, insulina e HOMA significativamente superiores e redução da SI quando comparados com pacientes de peso normal. Correlações positivas foram observadas entre IL-6, glicose, insulina e HOMA. Conclusão: Este estudo sugere que a IL-6 pode ter um papel-chave no desenvolvimento da RI em obesos e que o aumento de sua produção pode contribuir para a inflamação do tecido adiposo e interferir significativamente na atividade da insulina. Embora mais estudos clínicos sejam necessários para elucidar os reais mecanismos de interferência da IL-6 sobre a SI, sugere-se que essa citocina poderá ser, no futuro, uma determinação importante para avaliar e monitorar a RI em obesos jovens (AU)

Introduction: Adipose tissue is a major endocrine organ responsible for secretion of adipokines, such as interleukin-6 (IL-6), which stimulates the production of acute phase proteins in the liver, leading to a proinflammatory condition associated with the development of comorbidities in obesity, such as insulin resistance (IR). The aim of this study was to evaluate the IL-6 concentration in obese, overweight, and normal-weight young adults, correlating the concentrations of this cytokine with IR biomarkers. Methods: A cross-sectional study was conducted involving 149 subjects: 54 healthy subjects (32 women and 22 men), 27 overweight subjects (17 women and 10 men) and 68 obese subjects (41 women and 27 men). The anthropometric measures and IL-6, insulin, glucose, and glycated hemoglobin concentrations were determined, as well as HOMA and insulin sensitivity levels. Results: Obese patients showed significantly higher IL-6 levels of glucose, insulin, and HOMA and lower SI compared with normal-weight patients. Positive correlations were observed between IL-6, glucose, insulin, and HOMA. Conclusions: The present study suggests that IL-6 may have a key role in the development of IR in obese patients, and increasing its production can contribute to inflammation in adipose tissue and significantly interfere with insulin activity. Although further clinical studies are needed to elucidate the actual IL-6 interference mechanisms on SI, we believe that this cytokine may be an important factor to evaluate and monitor IR in obese young adults in the future (AU)

Influence of hemodialysis on the plasma concentration of adenosine deaminase in patients with chronic kidney disease / Influência da hemodiálise na concentração plasmática da adenosina deaminase em pacientes com doença renal crônica

ABSTRACT Introduction: Over the past years there has been a significant increase in hospitalizations and treatments due to kidney complications that eventually resulted in the increased number of patients on dialysis. The adenosine deaminase (ADA) enzyme mediates the formation of some defense cells of the organism and is therefore a marker of inflammation. Objective: The objective of this study was to evaluate biomarkers of renal function and serum ADA of hemodialysis patients. Materials and methods: Blood samples were collected from 80 patients – 40 women and 40 men – between 19 and 60 years old, before and after the completion of hemodialysis. Results: There was a significant difference in levels of creatinine, urea and ADA in pre- and post-hemodialysis periods (p < 0.0001). There was a significant increase in post-dialysis ADA regardless of sex; however there was a significantly greater increase in men. Conclusion: The results showed a reduction in urea and creatinine parameters, evidencing the main purpose of hemodialysis. This study suggests that the determination of ADA activity could be used to monitor inflammation in hemodialysis patients, however wider and more specific studies are needed to show the effectiveness of serum ADA activity as an inflammatory marker in patients with chronic kidney disease. .

RESUMO Introdução: No decorrer dos últimos anos, houve aumento significativo nas internações e nos tratamentos decorrentes de complicações renais que resultaram, consequentemente, no aumento de pacientes sujeitos a diálise. A adenosina deaminase (ADA) atua como enzima mediadora na formação de algumas células de defesa do organismo, sendo, portanto, marcadora de processos inflamatórios. Objetivos: O objetivo deste trabalho foi avaliar biomarcadores da função renal e da ADA sérica de pacientes em hemodiálise Materiais e métodos: Amostras de sangue foram coletadas de 80 pacientes – 40 mulheres e 40 homens – entre 19 e 60 anos, antes e após a realização da hemodiálise. Resultados: Houve diferença significativa nas dosagens de creatinina, ureia e ADA no pré e pós-hemodiálise (p < 0,0001). Observou-se aumento significativo da ADA no pós-hemodiálise independentemente do sexo, no entanto houve aumento considerável nos homens. Conclusão: Os resultados mostraram redução nos parâmetros de ureia e creatinina, evidenciando o propósito principal da hemodiálise. Por meio deste estudo, sugere-se que a determinação da atividade da ADA pode ser utilizada para monitorar o processo inflamatório de pacientes em hemodiálise, contudo estudos mais amplos e específicos são necessários para mostrar a eficiência da dosagem de ADA sérica como marcador inflamatório para pacientes com doença renal crônica. .

Adenosine deaminase, dipeptidyl peptidase-IV activities and lipid peroxidation are increased in the saliva of obese young adult.

BACKGROUND: Obesity is the hallmark of the metabolic syndrome representing a major global health problem. It is considered a state of chronic inflammation with minimal exploration of salivary biomarkers. Thus, the intent of the present study was to assess the activities of salivary dipeptidyl peptidase IV (DPP-IV), adenosine deaminase (ADA) and lipid peroxidation in obese young and overweight young subjects. METHODS: ADA, DPP-IV activities and lipid peroxidation were investigated in saliva, as well as insulin, glucose, HbA1c, HOMA and anthropometric measurements in 149 young adults, including 54 with normal weight, 27 overweight and 68 obese subjects. RESULTS: Salivary ADA and DPP-IV activities as well as lipid peroxidation were higher in patients with obesity compared to the normal weight group. Correlations between ADA/DPP-IV activities, lipid peroxidation/ADA activity, ADA activity/hip circumference and BMI/weight were observed. CONCLUSIONS: Our results indicate that the increase in the salivary ADA and DPP-IV activities as well as in the lipid peroxidation could be related of the regulation to various aspects of adipose tissue function and inflammatory obesity. It is suggested that these salivary biomarkers may be used as biochemical test in clinical abnormalities present in obesity, in the absence of oral inflammatory diseases.