ABSTRACT Objective: To identify DNA methylation and gene expression profiles involved in obesity by implementing an integrated bioinformatics approach. Materials and methods: Gene expression (GSE94752, GSE55200, and GSE48964) and DNA methylation (GSE67024 and GSE111632) datasets were obtained from the GEO database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) in subcutaneous adipose tissue of patients with obesity were identified using GEO2R. Methylation-regulated DEGs (MeDEGs) were identified by overlapping DEGs and DMGs. The protein–protein interaction (PPI) network was constructed with the STRING database and analyzed using Cytoscape. Functional modules and hub-bottleneck genes were identified by using MCODE and CytoHubba plugins. Functional enrichment analyses were performed based on Gene Ontology terms and KEGG pathways. To prioritize and identify candidate genes for obesity, MeDEGs were compared with obesity-related genes available at the DisGeNET database. Results: A total of 54 MeDEGs were identified after overlapping the lists of significant 274 DEGs and 11,556 DMGs. Of these, 25 were hypermethylated-low expression genes and 29 were hypomethylated-high expression genes. The PPI network showed three hub-bottleneck genes (PTGS2, TNFAIP3, and FBXL20) and one functional module. The 54 MeDEGs were mainly involved in the regulation of fibroblast growth factor production, the molecular function of arachidonic acid, and ubiquitin-protein transferase activity. Data collected from DisGeNET showed that 11 of the 54 MeDEGs were involved in obesity. Conclusion: This study identifies new MeDEGs involved in obesity and assessed their related pathways and functions. These results data may provide a deeper understanding of methylation-mediated regulatory mechanisms of obesity.

ABSTRACT Objective: The objective of this study was to investigate the association between SNPs in the TIE2 and ANGPT-1 genes and diabetic retinopathy (DR). Subjects and methods: This study comprised 603 patients with type 2 diabetes mellitus (T2DM) and DR (cases) and 388 patients with T2DM for more than 10 years and without DR (controls). The TIE2 rs639225 (A/G) and rs638203 (A/G) SNPs and the ANGPT-1 rs4324901 (G/T) and rs2507800 (T/A) SNPs were genotyped by real-time PCR using TaqMan MGB probes. Results: The G/G genotype of the rs639225/TIE2, the G/G genotype of the rs638203/TIE2 and the T allele of the rs4324901/ANGPT-1 SNPs were associated with protection against DR after adjustment for age, glycated hemoglobin, gender, and presence of hypertension (P = 0.042, P = 0.003, and P = 0.028, respectively). No association was found between the rs2507800/ANGPT-1 SNP and DR. Conclusion: We demonstrated, for the first time, the association of TIE2 rs638203 and rsrs939225 SNPs and ANGPT-1 rs4324901 SNP with protection against DR in a Brazilian population.

ABSTRACT Objective: The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. Materials and methods: The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years’ duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. Results: Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. Conclusion: Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients.

Abstract: Tradescantia pallida (Commelinaceae) has shown promising antibacterial, antioxidant and anticancer activities. This study aimed at extracting hexane from T. pallida (HE-TP) aerial parts to identify and quantify its volatile compounds by GC-MS and GC-FID and at evaluating its antifungal and antiproliferative activities. (E)-4-Methoxycynnamic acid (50.2%), 2,5-di-tert-butyl-1,4-benzoquinone (13.7%) and epijuvabione (10.4%) were the major components identified in HE-TP. HE-TP was incorporated into PDA medium, poured into Petri dishes and transferred to mycelial discs of pathogens. Percentages of inhibition of fungal growth were determined. HE-TP showed remarkable antifungal potential at the dose of 400 µL since it inhibited 100% of Penicillium digitatum and Sclerotinia sclerotiorum growth and 92.6% of Rhizopus stolonifer growth. Besides, HE-TP demonstrated cytotoxic activity against different human tumor cell lines with IC50 values between 231.43 and 428.76 µg/mL. Therefore, results showed that HE-TP has potential against fungi of agronomic interest and tumor cells.

RESUMO Objetivo: Este estudo tem como objetivo identificar como a literatura de estudos de inovação aborda o tema das capacidades para inovação em serviços e propor direções para futuras pesquisas nesse campo. Originalidade/valor: Existe uma lacuna na literatura sobre inovação em serviços em relação ao que é a combinação de capacidades, que garante o sucesso das empresas de serviços, considerando as características que os inovadores de serviços possuem. Design/metodologia/abordagem: Este estudo compreende uma análise bibliométrica de documentos recuperados das bases de dados Scopus e Web of Science. A amostra total examinada é composta por 1.523 estudos publicados entre 1974 e 2020. Os dados foram analisados com o Bibliometrix R-package, que também forneceu diversas formas de visualização. Uma análise de cocitação adicional foi realizada usando o software VosViewer. Resultados: Os resultados indicam que há uma crescente discussão sobre inovação e capacidades em serviços no período em análise, mas ainda é um corpo teórico fragmentado. Existe uma grande variedade de abordagens teóricas que têm sido usadas para descrever capacidades para inovação de serviços. Dessa forma, este estudo contribui para a literatura ao mapear o estado da arte atual no campo da inovação em serviços e ao identificar seus principais temas de pesquisa, o que nos permitiu propor uma agenda de pesquisa para posterior desenvolvimento. Por fim, identificamos que poucos estudos envolvem dados coletados em diferentes regiões geográficas, além de países desenvolvidos.

ABSTRACT Purpose: This study aims to identify how the innovation studies literature addresses the topic of capabilities for service innovation and to propose directions for future research in this field. Originality/value: There is a gap in the literature on service innovation of the combination of capabilities that guarantees the success of service companies considering the characteristics of service innovators. Design/methodology/approach: This study comprises a bibliometric analysis of documents retrieved from Scopus and Web of Science databases. The total sample examined consists of 1523 studies published between 1974 and 2020. The data were analyzed with the Bibliometrix R-package, providing many visualization forms. Additional co-citation analysis was carried out using VosViewer software. Findings: Results indicate a growing discussion about service innovation and capabilities in the period under analysis, but it is still a fragmented theoretical body. There is a great variety of theoretical approaches that have been used to describe capabilities for service innovation. This way, this study contributes to the literature by mapping the current state of the art in the field of service innovation and by identifying its main research themes, which enabled us to propose a research agenda for further development. Finally, we recognize that few studies involve data collected from different geographic regions other than developed countries.

Resumo Tendo em vista a rápida disseminação do novo coronavírus no sistema prisional, o presente trabalho teve como objetivos identificar aglomerados espaciais para ocorrência da COVID-19 na população privada de liberdade (PPL) e analisar a tendência temporal dos casos confirmados no sistema penitenciário do Brasil. Estudo ecológico que considerou como unidades de análise as cinco macrorregiões do Brasil, seus 26 estados e o Distrito Federal. A população foi composta por todos os casos de COVID-19 confirmados, no período de 14 de abril a 31 de agosto de 2020. A fonte de dados utilizada foi o Painel de Monitoramento dos casos de COVID-19 nos sistemas prisionais do Departamento Penitenciário Nacional. Realizou-se análise descritiva, estatística de varredura e análise da tendência temporal. Foram notificados 18.767 casos de COVID-19 na PPL, dos quais 4.724 ocorreram no estado de São Paulo. A estatística de varredura possibilitou a identificação de 14 clusters espaciais de risco para COVID-19 na PPL, sendo o aglomerado de maior risco formado pelo Distrito Federal. Embora o país finalize a série com um comportamento decrescente, observa-se que no período de investigação a tendência apresentou um comportamento maioritariamente crescente. Evidencia-se a necessidade de testagem em massa, monitoramento e registro contínuo dos casos de COVID-19 na PPL do país.

Abstract Given the rapid spread of new coronavirus within the prison system, this study’s objective was to identify spatial clusters for the occurrence of COVID-19 in the incarcerated population and analyze temporal trends of confirmed cases in the Brazilian prison system. This ecological study considered the five Brazilian macro-regions to be units of analysis, with its 26 states and the Federal District. The population was composed of all COVID-19 cases confirmed from April 14th to August 31st, 2020. The source used to collect data was the COVID-19 Monitoring Panel from the National Prison Department. Descriptive analysis, scan statistics, and time series were performed. A total of 18,767 COVID-19 cases were reported among the incarcerated population, 4,724 in São Paulo. The scan statistic analysis resulted in 14 spatial risk clusters for COVID-19 among persons deprived of liberty; the highest-risk cluster was in the Federal District. Although the country ends the series with a decreasing behavior, a growing trend was verified in most of the study period. The conclusion is that there is a need to implement mass testing among the incarcerated population while continually monitoring and recording COVID-19 cases.

Resumo Tendo em vista a rápida disseminação do novo coronavírus no sistema prisional, o presente trabalho teve como objetivos identificar aglomerados espaciais para ocorrência da COVID-19 na população privada de liberdade (PPL) e analisar a tendência temporal dos casos confirmados no sistema penitenciário do Brasil. Estudo ecológico que considerou como unidades de análise as cinco macrorregiões do Brasil, seus 26 estados e o Distrito Federal. A população foi composta por todos os casos de COVID-19 confirmados, no período de 14 de abril a 31 de agosto de 2020. A fonte de dados utilizada foi o Painel de Monitoramento dos casos de COVID-19 nos sistemas prisionais do Departamento Penitenciário Nacional. Realizou-se análise descritiva, estatística de varredura e análise da tendência temporal. Foram notificados 18.767 casos de COVID-19 na PPL, dos quais 4.724 ocorreram no estado de São Paulo. A estatística de varredura possibilitou a identificação de 14 clusters espaciais de risco para COVID-19 na PPL, sendo o aglomerado de maior risco formado pelo Distrito Federal. Embora o país finalize a série com um comportamento decrescente, observa-se que no período de investigação a tendência apresentou um comportamento maioritariamente crescente. Evidencia-se a necessidade de testagem em massa, monitoramento e registro contínuo dos casos de COVID-19 na PPL do país.

Abstract Given the rapid spread of new coronavirus within the prison system, this study’s objective was to identify spatial clusters for the occurrence of COVID-19 in the incarcerated population and analyze temporal trends of confirmed cases in the Brazilian prison system. This ecological study considered the five Brazilian macro-regions to be units of analysis, with its 26 states and the Federal District. The population was composed of all COVID-19 cases confirmed from April 14th to August 31st, 2020. The source used to collect data was the COVID-19 Monitoring Panel from the National Prison Department. Descriptive analysis, scan statistics, and time series were performed. A total of 18,767 COVID-19 cases were reported among the incarcerated population, 4,724 in São Paulo. The scan statistic analysis resulted in 14 spatial risk clusters for COVID-19 among persons deprived of liberty; the highest-risk cluster was in the Federal District. Although the country ends the series with a decreasing behavior, a growing trend was verified in most of the study period. The conclusion is that there is a need to implement mass testing among the incarcerated population while continually monitoring and recording COVID-19 cases.

Abstract Autoimmune diseases are characterized by the loss of self-tolerance, leading to immune-mediated tissue destruction and chronic inflammation. Tyrosine kinase 2 (TYK2) protein plays a key role in immunity and apoptosis pathways. Studies have reported associations between single nucleotide polymorphisms (SNPs) in the TYK2 gene and autoimmune diseases; however, results are still inconclusive. Thus, we conducted a systematic review followed by meta-analysis. A literature search was performed to find studies that investigated associations between TYK2 SNPs and autoimmune diseases (multiple sclerosis, systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, psoriasis, rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease). Pooled odds ratios (OR) with 95 % CI were calculated using random (REM) or fixed (FEM) effects models in the Stata 11.0 Software. Thirty-four articles were eligible for inclusion in the meta-analyses, comprising 9 different SNPs: rs280496, rs280500, rs280523, rs280519, rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800. Meta-analysis results showed the minor alleles of rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800 SNPs were associated with protection against autoimmune diseases. Moreover, the A allele of the rs280519 SNP was associated with risk for systemic lupus erythematosus. Our meta-analyses demonstrated that the rs2304256, rs12720270, rs12720356, rs34536443, rs35018800, and rs280519 SNPs in the TYK2 gene are associated with different autoimmune diseases.

ABSTRACT Objectives The presence of thyroglobulin (Tg) in needle washouts of fine needle aspiration biopsy (Tg-FNAB) in neck lymph nodes (LNs) suspected of metastasis has become a cornerstone in the follow-up of patients with papillary thyroid carcinoma (PTC). However, there are limited data regarding the measurement of anti-Tg antibodies in these washouts (TgAb-FNAB), and it is not clear whether these antibodies interfere with the assessment of Tg-FNAB or whether there are other factors that would more consistently justify the finding of low Tg-FNAB in metastatic LNs. Materials and methods We investigated 232 FNAB samples obtained from suspicious neck LNs of 144 PTC patients. These samples were divided according to the patient’s serum TgAb status: sTgAb- (n = 203 samples) and sTgAb+ (n = 29). The TgAb-FNAB levels were measured using two different assays. Tg-FNAB was also measured using two assays when low levels (< 10 ng/mL) were identified in the first assay of the metastatic LNs from the sTgAb+ samples. Results The TgAb-FNAB results were negative in both assays in all samples. Low levels of Tg-FNAB were identified in 11/16 of the metastatic LNs of the sTgAb+ patients and 16/63 of the sTgAb- patients (p < 0.05) using assay 1. The measurement of the Tg-FNAB levels using assay 2 indicated additional metastases in 5 LNs of the sTgAb+ patients. Conclusions Factors other than the presence of TgAb-FNAB may contribute to the higher number of metastatic LNs with undetectable Tg-FNAB in the sTgAb+ group. In addition, the measurement of Tg-FNAB using different assays was useful to enhance the diagnosis of metastatic LNs, particularly when cytological and Tg-FNAB results are discordant.

Leptospirosis is a spirochetal bacterial infection of great public health importance. It has a broad spectrum of clinical manifestations which goes from subclinical infection and self-limited anicteric febrile illness (80-90% of all cases) to icteric leptospiropirosis known as Weil's disease. This is a severe disease characterized by hemorrhage, acute renal failure and jaundice. It is uncommon for leptospirosis to present itself as a primary neurological disease. Additionally, acute pancreatitis is an unusual gastrointestinal manifestation. We report a case of leptospirosis presenting as ascending progressive leg weakness and complicating with acute pancreatitis in an adult patient treated at Hospital Universitário, Universidade Federal de Santa Catarina. The diagnosis was confirmed through ELISA-IgM antibody testing positive for leptospirosis. After antibiotic therapy and support treatment for a few weeks, total resolution of severe manifestations was achieved. Rare and unusual presentations of leptospirosis should be kept in mind in relevant epidemiological scenario.

Os níveis plasmáticos de adiponectina e o gene codante desta proteína, ADIPOQ, parecem explicar parte da interação de doenças como obesidade, resistência à insulina, diabetes melito tipo 2 (DM2) e doença arterial coronariana (DAC). Apresentamos as evidências do papel tanto dos níveis de adiponectina quanto das variantes no ADIPOQ na modulação da DAC, sobretudo na presença de hiperglicemia. Estudos recentes sugerem que níveis de adiponectina total e de alto peso molecular (HMW) são marcadores de bom prognóstico DAC, sobretudo em pacientes de baixo risco cardiovascular, enquanto nos pacientes de alto risco ou com doença já estabelecida podem se associar com pior prognóstico. Apresentamos também as evidências em relação ao possível controle genético dos níveis circulantes de adiponectina, tanto total quanto da isoforma de alto peso molecular, sobretudo em relação ao ADIPOQ. A análise global dos dados sugere que tanto os níveis circulantes de adiponectina quanto polimorfismos no gene ADIPOQ estão implicados na evolução de DAC em pacientes com hiperglicemia e que essas associações podem existir de forma independente.

Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role that adiponectin and ADIPOQ variants might play in the modulation of CAD, especially in the occurrence of hyperglycemia. Recent evidence suggests that total and high molecular weight (HMW) adiponectin levels are apparent markers of better cardiovascular prognosis in patients with low risk of CAD. However, in subjects with established or high risk of CAD, these levels are associated with poorer prognosis. We also provide recent evidences relating to the genetic control of total and HMW adiponectin levels, especially evidence regarding ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia, and that these associations seem to be independent from each other, even if adiponectin levels are partly dependent on ADIPOQ.

As lipodistrofias são um grupo heterogêneo de doenças caracterizadas por perda de tecido adiposo e complicações metabólicas. As formas hereditárias mais importantes de lipodistrofias são: lipodistrofia congênita generalizada e lipodistrofia parcial familiar (LDPF). LDPF resulta de mutações no gene LMNA que codificam as lâminas tipo A. Além da LDPF, mutações no gene LMNA são responsáveis por outras doenças hereditárias, denominadas laminopatias. Descrevemos o caso de uma paciente de 15 anos de idade encaminhada por diabetes melito e hipertrigliceridemia grave. Ao exame físico, apresentava perda generalizada de gordura subcutânea que foi confirmada por DEXA (gordura corporal total 8,6%). Como a paciente apresentava perda de gordura de início na puberdade e resistência insulínica, foi realizada análise molecular do gene LMNA. Identificamos uma substituição em heterozigose no éxon 1 (c.29C>T), resultando na mutação p.T10I. Em sumário, um caso de fenótipo atípico de lipodistrofia generalizada devido à mutação de novo p.T10I no gene LMNA é descrito.

Lipodystrophies are a group of heterogeneous disorders characterized by the loss of adipose tissue and metabolic complications. The main familial forms of lipodystrophy are Congenital Generalized Lipodystrophy and Familial Partial Lipodystrophy (FPLD). FPLD may result from mutations in the LMNA gene. Besides FPLD, mutations in LMNA have been shown to be responsible for other inherited diseases called laminopathies. Here we describe the case of a 15-year-old girl who was referred to our service due to diabetes mellitus and severe hypertriglyceridemia. Physical examination revealed generalized loss of subcutaneous fat, confirmed by DEXA (total body fat 8.6%). As the patient presented with pubertal-onset of generalized lipodystrophy and insulin resistance, molecular analysis of the LMNA gene was performed. We identified a heterozygous substitution in exon 1 (c.29C>T) predicting a p.T10I mutation. In summary, we describe an atypical phenotype of lipodistrophy associated with a de novo appearance of the p.T10I mutation in LMNA gene.

Com a introdução da ultra-sonografia cervical (USC) no seguimento dos pacientes com carcinoma papilífero de tiróide (CPT), tornou-se freqüente o encontro de pequenos linfonodos (LNs) cervicais. Porém, apesar de a USC apresentar alta sensibilidade, o estudo citológico obtido por punção aspirativa (PAAF) e, nos últimos anos, a dosagem da tiroglobulina (Tg) no lavado da agulha da PAAF (Tg-PAAF) vêm assumindo papel importante no diagnóstico de LNs cervicais. O objetivo deste estudo é verificar a acurácia da combinação da USC, citologia e Tg-PAAF em LNs suspeitos. Estudamos 32 pacientes que apresentavam 44 LNs à USC, classificados como "inflamatórios" (19) ou "suspeitos" (25). Dos 25 LNs suspeitos, 15 apresentavam Tg-PAAF elevada (13 com citologia compatível com metástases e 2 com citologia não-diagnóstica). Esses 15 LNs (11 pacientes) foram confirmados como metástase de CP pelo exame histopatológico. Os 19 LNs "inflamatórios" e os 10/25 LNs "suspeitos" apresentaram citologia negativa e Tg-PAAF indetectável. Concluímos que a USC apresenta alta sensibilidade na detecção de linfonodos cervicais, porém citologia e dosagem de Tg-PAAF são fundamentais para o diagnóstico. A associação USC, citologia e Tg-PAAF pode ser considerada a abordagem mais sensível e específica na detecção de LNs metastáticos em pacientes com CPT.

The widespread use of neck ultrasonography (US) during the follow-up of patients with papillary thyroid carcinoma (PTC) has led to the discovery of small cervical lymph nodes (LN). Although US has a high sensitivity for diagnosing LN, fine needle aspiration biopsy (FNA) and measurement of thyroglobulin in fine needle aspirates (FNA-Tg) have proven to be invaluable tools. The aim of this study is to determine the sensitivity of the combined use of neck US, FNA biopsy and FNA-Tg for diagnosis of cervical lymph nodes. We have studied 32 patients with 44 LN detected by US, 19 classified as inflammatory and 25 as suspicious. 15 of those 25 suspicious LN had high FNA-Tg (13 of the 15 had positive cytology and 2 indeterminate). All of these 15 LN (11 patients) were proven to be PTC metastasis by histopathology. All 19 inflammatory LN and those 10/25 suspicious LN, had cytology negative for malignancy and undetectable FNA-Tg. We conclude that fine needle aspiration biopsy and FNA-Tg combined with neck US are essential for detecting positive cervical lymph nodes due to its high sensitivity and specificity and it should be considered the standard for investigating locally recurrent disease in patients with PTC.

A síndrome de Wolfram (SW) é uma condição neurodegenerativa progressiva de herança autossômica recessiva caracterizada pela presença de diabetes mellitus e atrofia óptica. Freqüentemente também estão presentes o diabetes insipidus e disacusia neurossensorial, explicando o acrônimo DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, deafness) pelo qual a síndrome é também conhecida. Além desses, outros comemorativos tais como bexiga neurogênica, ataxia, nistagmo e predisposição a doenças psiquiátricas podem também estar presentes. Em 1994 identificou-se no cromossomo 4p16.1 um dos genes responsáveis pela SW, que foi denominado WFS1 ou wolframina. Esse gene codifica uma proteína de 890 aminoácidos de localização no retículo endoplasmático. A função da proteína wolframina ainda não está completamente definida, porém sua localização no retículo endoplasmático sugere um papel na regulação da homeostase do cálcio, transporte de membrana ou processamento protéico. O entendimento de como alterações na função da wolframina resultam em diabetes e neurodegeneração é essencial para o desenvolvimento de terapias para prevenir ou atenuar as conseqüências da SW.

Wolfram syndrome (WS) is an autosomal recessive progressive neurodegenerative disorder characterized by diabetes mellitus and optic atrophy. Diabetes insipidus and sensorineural deafness are also noted frequently, explaining the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) by which the syndrome is also referred. Additional manifestations such as atonic bladder, ataxia, nystagmus and predisposition for psychiatric illness may be present. The Wolfram syndrome gene, WFS1, was mapped to chromosome 4p16.1 by positional cloning. It encodes an 890-amino-acid polypeptide named wolframin. Although the wolframin function is still not completely known, its localization to the endoplasmic reticulum suggests it can play a role in calcium homeostasis, membrane trafficking and protein processing. Knowing the cellular function of wolframin is necessary for understanding the pathophysiology of Wolfram syndrome. This knowledge may lead to development of therapies to prevent or reduce the outcomes of WS.