SUMMARY Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) is the main subtype. The cribriform morular variant is a histological phenotype of PTC characterized by its relationship with familial adenomatous polyposis (FAP). Description of the case: We report the genetic assessment of a 20-year-old female patient diagnosed with a cribriform-morular variant of PTC and FAP. We aimed to assess the genetic background of the reported patient, looking for variants that would help us explain the predisposition to tumorigenesis. Genomic DNA was extracted from peripheral blood lymphocytes, and whole exome sequencing was performed. We applied an overrepresentation and gene-set enrichment analysis to look for an accumulation of effects of variants in multiple genes at the genome. We found an overrepresentation of single nucleotide variants (SNVs) in extracellular matrix interactions and cell adhesion genes. Underrepresentation of SNVs in genes related to the regulation of autophagy and cell cycle control was also observed. We hypothesize that the package of alterations of our patient may help to explain why she presented colonic manifestations and thyroid cancer. Our findings suggest that multiple variants with minor impact, when considered together, may be helpful to characterize one particular clinical condition.

OBJECTIVES: Restless legs syndrome (RLS) is a frequent comorbid condition associated with distinct unrelated diseases. While the incidence of RLS has not been definitively confirmed, RLS-like symptoms have been reported in a section of Asian population who also had hyperthyroidism. The prevalence of RLS is generally low in Asian populations. Under these circumstances, we hypothesized that in a population where RLS is common, such as in Brazil, RLS could manifest as a comorbid ailment alongside Graves’ disease, a common hyperthyroid condition. METHODS: In a cross-sectional survey, 108 patients who presented with Graves' disease were analyzed for restless legs or associated symptoms. RESULTS: Twelve patients (11.1%) displayed symptoms of RLS prior to the incidence of Graves’ disease. These patients experienced worsening of the symptoms during their hyperthyroid state. Six patients (5.6%) developed RLS, consequent upon the incidence of Graves’ disease as per the consensus of the panel of the experts. Fifteen patients (13.9%) also presented with RLS-like symptoms without any discernible circadian feature of the syndrome. CONCLUSION: Our findings confirm that Graves’ disease might trigger restless legs-like symptoms, while the condition of hyperthyroidism could also be complicated by definite RLS.

Resumo Introdução: A distribuição, concentração e função dos glicosaminoglicanos nos diversos tecidos da prega vocal ainda não está esclarecida. Objetivo: Avaliar a distribuição e concentração dos glicosaminoglicanos sulfatados nas diferentes camadas da prega vocal humana de acordo com o sexo e a idade. Método: Foram usadas 11 pregas vocais obtidas de cadáveres (sete homens e quatro mulheres) sem lesão de laringe, com menos de 12 horas de óbito e entre 35 e 98 anos. As pregas foram submetidas à extração de glicosaminoglicanos da cobertura e ligamento e leitura pós-eletroforese. Os dados foram comparados segundo camada, idade e sexo. Resultados: A concentração de dermatan sulfato foi significativamente maior em todas as camadas. Não foram observadas diferenças nas concentrações totais de glicosaminoglicanos nas camadas estudadas quanto ao gênero. É significantemente menor em indivíduos abaixo de 60 anos na cobertura. Conclusão: Dermatam sulfato, condroitim sulfato e heparam sulfato foram observados na cobertura e no ligamento de pregas vocais humanas, de ambos os sexos, sendo a concentração de dermatam sulfato foi significativamente maior em todas as camadas. A concentração de glicosaminoglicanos na cobertura é significativamente menor em indivíduos abaixo de 60 anos em comparação com idosos.

Abstract Introduction: The distribution, concentration and function of glycosaminoglycans in the various vocal fold tissues are still unclear. Objective: To evaluate the distribution and concentration of sulfated glycosaminoglycans in different layers of the human vocal fold according to gender and age. Methods: We used 11 vocal folds obtained from cadavers (7 men and 4 women) with no laryngeal lesion, less than 12 h after death, and aged between 35 and 98 years. The folds underwent glycosaminoglycans extraction from the cover and ligament, and post-electrophoresis analysis. Data were compared according to the layer, age and gender. Results: The concentration of dermatan sulfate was significantly higher in all layers. No differences were observed in the total concentrations of glycosaminoglycans in layers studied according to gender. It is significantly lower in the cover of individuals aged below 60 years. Conclusion: Dermatan sulfate, chondroitin sulfate, and heparan sulfate were observed in the human vocal folds cover and ligament of both genders, with the concentration of dermatan sulfate being significantly higher in all layers. Glycosaminoglycans concentration on the cover is significantly lower in individuals below 60 years compared with elderly.

RESUMO CONTEXTO A fibrose periportal é a maior consequência patológica da infecção pelo Schistosoma mansoni. OBJETIVO Avaliar a acurácia de marcadores séricos e construir um índice para avaliar a fibrose. MÉTODOS Pacientes (n=116) com esquistossomose foram avaliados pela ultrassonografia e dosados os níveis de aminotransferases, γ-glutamil transferase, fosfatase alcalina, ácido hialurônico, citocinas e plaquetas. Imagens de ultrasom foram utilizadas para avaliar a fibrose através de classificação de Niamey e identificados 19 pacientes sem fibrose periportal (padrão A e B), 48 com fibrose média a moderada (C e D) e 49 com fibrose avançada (E e F). RESULTADOS Através de análise multivariada, um modelo foi criado, que envolveu a fosfatase alcalina e plaquetas e conseguiu separar pacientes com diferentes padrões de fibrose periportal. Este índice mostrou um melhor desempenho em separar pacientes sem fibrose dos pacientes com fibrose avançada. O índice biológico mostrou uma área sob a curva ROC de 1,000. Usando valores infereiores e acima do ponto de corte, a presença ou ausência de fibrose avançada pode ser prevista em todos os pacientes. CONCLUSÃO O índice construído pode ser usado para separar os pacientes com diferentes padrões de fibrose periportal, especialmente para prever fibrose avançada em pacientes com esquistossomose.

ABSTRACT BACKGROUND Periportal fibrosis is the major pathological consequence of the Schistosoma mansoni infection. OBJECTIVE To evaluate the accuracy of serum markers and to construct an index to assess fibrosis. METHODS Patients (n=116) with schistosomiasis were evaluated by ultrasound scan and measurements of serum levels of aminotransferases, γ-glutamyl transferase, alkaline phosphatase, hyaluronic acid, cytokines and platelets. Ultrasound images were used to evaluate the fibrosis using Niamey's classification and identified 19 patients without periportal fibrosis (patterns A and B), 48 with mild to moderate fibrosis (C and D) and 49 with advanced fibrosis (E and F). RESULTS Using multivariate analysis, a model was created, which involved alkaline phosphatase and platelets and could separate patients with different patterns of fibrosis. This index showed a better performance in separating patients without fibrosis from with advanced periportal fibrosis. The biological index showed an area under the ROC curve of 1.000. Using values below the lowest or above the highest cut-off point, the presence or absence of advanced fibrosis could be predicted in all patients. CONCLUSION The index constructed can be used to separate patients with different patterns of periportal fibrosis, specially to predict advanced fibrosis in schistosomiasis patients.

Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-γ, TNF-α and TGF-β, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, γ-glutamil transferase (γ-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-α (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), γ-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.

Os hormônios exercem importante influência sobre a laringe. A prega vocal contém, entre outras substâncias, o ácido hialurônico, cuja concentração nos tecidos pode variar com a ação dos hormônios. OBJETIVO: O objetivo deste trabalho é analisar comparativamente a concentração do ácido hialurônico nas pregas vocais de ratas durante o ciclo estral e ciclo gravídico-puerperal. FORMA DE ESTUDO: Experimental. MATERIAL E MÉTODO: Foram utilizadas 40 ratas adultas, divididas em dois grupos, no primeiro grupo utilizamos 20 ratas para determinação da concentração do ácido hialurônico no ciclo estral, no segundo grupo, também de 20 animais, foi realizado o mesmo experimento no ciclo gravídico-puerperal. RESULTADOS: No grupo do ciclo estral não observou-se variação da concentração do ácido hialurônico. No grupo do ciclo gravídico-puerperal houve aumento da concentração do ácido hialurônico no subgrupo do puerpério. Na comparação entre os dois grupos do ciclo estral e gravídico-puerperal não houve diferença. Quando comparamos todos os subgrupos há diferença no grupo do puerpério. CONCLUSÕES: Comparando-se todos os subgrupos do ciclo estral e ciclo gravídico-puerperal, só no puerpério houve aumento da concentração do ácido hialurônico.

Hormone plays an important role in the larynx. Among other substances, vocal folds contain hyaluronic acid, which tissue concentration may vary according to hormone action. AIM: the objective of this study is to analyze hyaluronic acid concentration in the vocal folds during estral and gravidic-puerperal cycles. MATERIALS AND METHODS: Experimental study. 40 adult rats were divided into two groups. In the first group we used 20 rats to establish the concentration of hyaluronic acid during the estral cycle and in the second group, 20 animals were submitted to the same procedure but during the gravidic-puerperal cycle. RESULTS: Variations in hyaluronic acid concentration was not observed during the estral cycle. In the gravidic puerperal cycle group, an increase in hyaluronic acid concentration was observed in the puerperal subgroup. Comparing the two groups of estral and gravidic-puerperal cycles, no difference was observed. CONCLUSIONS: In comparing all subgroups of estral and gravidic-puerperal cycles, an increase in hyaluronic acid concentration was noticed only in the puerperal phase.

INTRODUÇÃO: Os marcadores séricos têm sido empregados na avaliação da fibrose hepática em pacientes portadores de hepatite crônica C (HCC). OBJETIVOS: Avaliar a capacidade do índice aspartato aminotransferase (AST)/alanina aminotransferase (ALT), dos níveis séricos de gama-glutamiltransferase (GGT), contagem de plaquetas, do índice AST/plaquetas (APRI) e do ácido hialurônico (AH) em predizer a intensidade da fibrose hepática na HCC e a variação desses marcadores após tratamento com interferon. PACIENTES E MÉTODOS: Em 72 pacientes portadores de hepatite C determinamos no soro o índice AST/ALT, GGT, plaquetas, índice APRI (obtido pelo quociente AST/plaquetas) e o AH, que foram comparados ao estadiamento histológico, segundo os critérios de METAVIR. Receberam tratamento com interferon e ribavirina 65 pacientes. Os indivíduos que concluíram o tratamento (n = 33) realizaram nova dosagem dos marcadores séricos de fibrose para comparar com os níveis pré-tratamento. RESULTADOS: Observamos que a GGT, a contagem de plaquetas, o índice APRI e o AH se correlacionaram com estádio de doença hepática (p < 0,01), exceto o índice AST/ALT. A análise das áreas sob as curvas ROC (AUC) evidenciaram que a melhor associação com estadiamento hepático foi para o índice APRI e a dosagem sérica do AH: AUC (APRI) = 0,85 e AUC (AH) = 0,86. Na avaliação pós-terapia com interferon, apenas a GGT e o índice APRI apresentaram redução de seus níveis (p < 0,05). CONCLUSÃO: O AH e o índice APRI apresentaram maior acurácia no estadiamento da fibrose, podendo ser aplicados como métodos diagnósticos alternativos na HCC.

INTRODUCTION: Serum markers have been used in the assessment of liver fibrosis in patients with chronic hepatitis C (CHC). AIMS: We evaluated the capacity of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, gama-glutamyltransferase (GGT) levels, platelet count, the AST to platelet ratio index (APRI) and serum hyaluronic acid (HA) to predict the intensity of hepatic fibrosis in patients with CHC and the variation of these markers after therapy with interferon. PATIENTS AND METHODS: In 72 patients with hepatitis C, AST/ALT ratio, GGT levels, platelet count, the APRI index (calculated as the ratio of AST to platelets) and serum HA concentration were determined and compared to histological staging according to the scoring system of METAVIR. Sixty-five patients received interferon and ribavirin therapy. The individuals that completed the treatment (n = 33) underwent a new test for serum marker of fibrosis in order to compare it with pre-treatment levels. RESULTS: GGT levels, platelet count, the APRI index and serum HA were correlated with the stage of hepatic fibrosis (p < 0.01), except AST/ALT ratio. The analysis of the areas under the ROC curve (AUC) evidenced that APRI and HA levels were the markers with the best association with hepatic staging: AUC (APRI) = 0.85 and AUC (HA) = 0.86. After therapy with interferon, only GGT and the APRI showed reduction of their levels (p < 0.05). CONCLUSION: HA and the APRI index were the most accurate approaches to liver fibrosis staging and they may be used as alternative diagnostic methods in patients with CHC.

OBJETIVOS: Comparar a concentração total de proteínas no humor aquoso entre pacientes com glaucoma primário de ângulo aberto e sem glaucoma. MÉTODOS: Foram coletadas amostras de humor aquoso de 22 pacientes com glaucoma primário de ângulo aberto (grupo GPAA) no momento da trabeculectomia. Na coleta, 0,1 mL de humor aquoso foi aspirado da câmara anterior através de uma agulha de calibre 26, no início do procedimento cirúrgico. Coleta semelhante foi realizada em 22 pacientes sem glaucoma no início da cirurgia de catarata (grupo controle). A amostra de humor aquoso foi armazenada a -20°C após a coleta. A concentração total de proteínas no humor aquoso foi determinada por meio de um teste colorimétrico. RESULTADOS: A média geométrica da concentração total de proteínas no humor aquoso foi de 32 mg/dL (amplitude: 8-137 mg/dL) no grupo glaucoma primário de ângulo aberto e de 16 mg/dL (amplitude: 2-85 mg/dL) no grupo controle. A razão da concentração total de proteínas no humor aquoso entre estes dois grupos foi de 2,0 (intervalo de confiança de 95%: 1,3 a 3,2; p=0,003). CONCLUSÕES: A concentração total de proteínas no humor aquoso de pacientes com glaucoma primário de ângulo aberto foi aproximadamente duas vezes maior quando comparada aos pacientes sem glaucoma.

PURPOSE: To compare total protein concentration in the aqueous humor of primary open-angle glaucoma and non-glaucomatous patients. METHODS: Aqueous humor samples were obtained from 22 patients just before trabeculectomy for clinically uncontrolled primary open angle glaucoma (POAG group). Aqueous humor (0.1 mL) was aspirated by inserting a 26-gauge needle into the anterior chamber. The same procedure was performed in 22 non-glaucomatous patients just before cataract surgery (control group). Immediately after collection, the aqueous humor was stored at -20°C. Aqueous humor total protein concentration was determined using a colorimetric assay. RESULTS: The geometric mean of total protein concentration of the aqueous humor samples was 32 mg/dL (range: 8-137 mg/dL) in the primary open angle glaucoma group and 16 mg/dL (range: 2-85 mg/dL) in the control group. The ratio of the protein concentration between the two groups was 2.0 (95% confidence interval: 1.3 to 3.2; p=0.003). CONCLUSIONS: The total protein concentration in primary open-angle glaucoma aqueous humor was approximately two times higher than that in non-glaucomatous subjects.