Hematological problems are associated with Coronavirus disease 2019 (COVID-19). Respiratory impairment is the higher point studied, although without experimental studies related to the oxygen transport performed by erythrocytes. Therefore, we decided to investigate if erythrocytes from COVID-19 patients have their functionality changed. The case-control study included hospitalized patients with a positive real-time polymerase chain reaction (RT-PCR) result admitted to University Hospital. Volunteers (negative RT-PCR results) were recruited as a control group. Thus, we assessed different erythrocytes parameters, oxidative stress markers, and biophysical studies using whole blood and isolated hemoglobin. We found a decrease of 51% in oxygen uptake and reduced antioxidant enzyme activity in COVID-19 patients compared to controls. Raman spectrometry showed structural changes in the hemoglobin and lipids of the erythrocytes from COVID-19 patients; thus, these results were consolidated with an increase in Young’s modulus in erythrocytes followed by morphology changes. Besides, isolated hemoglobin from COVID-19 patients has a distinct interaction profile using a ligand model compared to the control. COVID-19 leads to structural, functional, and morphological damage to human erythrocytes. Our data showed structural and molecular changes and induction of oxidative stress in erythrocytes by COVID-19, a new perspective on the contribution of erythrocytes to a respiratory commitment in COVID-19.

ABSTRACT Objective: The risk of malignancy and diagnostic accuracy of fine-needle aspiration biopsy (FNAB) of thyroid nodules (TN) with diameters ≥ 3-4 cm remains controversial. However, some groups have indicated surgical treatment in these patients regardless of the FNAB results. We aimed to evaluate the diagnostic accuracy of the FNAB in systematically resected ≥4 cm TN and if the risk of malignancy is higher in these patients. Subjects and methods: We retrospectively evaluated 138 patients (142 nodules) with TN with diameters ≥4 cm who underwent thyroidectomy. Results: The FNAB results were nondiagnostic/unsatisfactory (ND/UNS) in 2.1% of the cases and benign in 51.4%. They indicated atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in 23.9% of cases, follicular neoplasia/suspicious for a follicular neoplasm (FN/SFN) in 9.2%, suspicion of malignancy (SUS) in 8.5%, and malignant in 4.9%. The histopathological analysis after thyroidectomy revealed a thyroid cancer rate of 100% in the FNABs classified as malignant, 33.3% in SUS cases, 7.7% in FN/SFN, 17.6% in AUS/FLUS, and 4.1% in benign FNABs. None of the ND/UNS FNABs were malignant. The global malignancy diagnosis was 14.8% (n = 21). However, the rate of false negatives for FNAB was low (4.1%). Conclusion: We showed that the risk of malignancy in nodules with diameters ≥4 cm was higher compared to the risk of thyroid cancer in TN in general. However, we found a low rate of false-negative cytological results; therefore, our data do not justify the orientation of routine resection for these larger nodules.

Abstract Simultaneous analysis studies of several agronomic traits in cultivated plants make it possible to identify phenotypic and genotypic differences due to environmental variations, such as altitude. Therefore, the objective was to evaluate, through multivariate analysis of agronomic, physicochemical and physiological characters, passion fruit hybrids cultivated in different environments. The hybrids used were Gigante Amarelo, Rubi do Cerrado and Sol do Cerrado, cultivated in the southern region of Espírito Santo in four municipalities/environments: Marataízes (41 m), Jerônimo Monteiro (104 m), Alegre (711 m), and Ibitirama (1016 m). The agronomic characters of the plants, the physical-chemical characteristics of the fruits and the physical, biochemical and physiological qualities of the seeds were analyzed. The Singh method was used to determine the most important differentiating characters between hybrids growing in different environments. Based on these characters, a dissimilarity matrix was generated and a principal coordinate analysis was performed. It was observed that the pulp yield was influenced by altitude. The three hybrids showed greater performance in terms of agronomic characters at altitude (41 m) than at altitude (104 m). The Sol do Cerrado hybrid showed high performance in the physical-chemical characteristics of the fruits at altitude (104 m).

Resumo Estudos de análise simultânea de diversos caracteres agronômicos em plantas cultivadas permitem identificar diferenças fenotípicas e genotípicas devido a variações ambientais, como a altitude. Diante disso, objetivou-se avaliar através da análise multivariada de caracteres agronômicos, fisico-químicos e fisiológicos, híbridos de maracujazeiros cultivados em diferentes ambientes. Os híbridos utilizados foram Gigante Amarelo, Rubi do Cerrado e Sol do Cerrado, cultivados na região sul do Espírito Santo em quatro municípios/ambientes: Marataízes (41 m), Jerônimo Monteiro (104 m), Alegre (711 m), e Ibitirama (1016 m). Foram analisados os caracteres agronômicos das plantas, as características físico-químicas dos frutos e as qualidades físicas, bioquímicas e fisiológicas das sementes. O método Singh foi usado para determinar os caracteres diferenciadores mais importantes entre híbridos crescendo em diferentes ambientes. Com base nesses caracteres, uma matriz de dissimilaridade foi gerada e uma análise de coordenadas principais foi realizada. Observou-se que o rendimento de polpa foi influenciado pela altitude. Os três híbridos apresentaram maior desempenho em termos de caracteres agronômicos na altitude (41 m) do que na altitude (104 m). O híbrido Sol do Cerrado apresentou alto desempenho nas características físico-químicas dos frutos na altitude (104 m).

Abstract The greatest challenge in onion breeding programs is achieving gains from plant selection in an efficient manner. Selection indices are already in use for many species but are rare in onion. The aim of this study was to characterize the gain from selection in onion germplasm through nonparametric indices. To bring about this dynamic, four experiments were conducted with different sets of genotypes. Several agronomic characteristics were evaluated. Estimates of gains and selection of genotypes were obtained from the selection index based on rank sum, from the genotype-ideotype distance index, and from the multiplicative index. To test the efficiency of the indices used, the coefficient of coincidence was calculated. The total gains from selection were greater through use of the multiplicative index, with values of 31.84% for the advanced lines and 37.4% for the segregating genotypes. It was possible to select superior onion lines in each experiment. The coefficients of coincidence, all with values greater than 0.5, confirmed that the indices provided a margin of safety in the selection of superior genotypes.

Resumen El mayor desafío en los programas de mejoramiento de cebollas es obtener beneficios de la selección de manera satisfactoria. Los índices de selección ya se utilizan en diversas especies, pero son raros en cebolla. El objetivo de este estudio fue caracterizar la ganancia de la selección en germoplasma de cebolla a través de índices no paramétricos. Para lograr esta dinámica, se llevaron a cabo cuatro experimentos con diferentes conjuntos de genotipos. Se evaluaron varias características agronómicas. Las estimaciones de ganancias y selección de genotipos se obtuvieron a partir del índice de selección basado en la suma de rangos, del índice de distancia genotipo-ideotipo y del índice multiplicativo. Para probar la eficiencia de los índices utilizados, se calculó el coeficiente de coincidencia. Las ganancias totales de la selección fueron mayores mediante el uso del índice multiplicativo, siendo los valores de 31,84% para las líneas avanzadas y 37,4% para los genotipos segregantes. Fue posible seleccionar líneas de cebolla superiores en cada experimento. Los coeficientes de coincidencia, todos con valores superiores a 0,5, confirmaron que los índices proporcionaron un margen de seguridad en la selección de genotipos superiores.

Abstract The present study investigated by palynological and chemical analysis (Flame Atomic Absortion Spectrometry) about the botanical origin and the heavy metals content (arsenic, cadmium, chromium, lead and mercury) of monthly honey samples of Apis mellifera L. over two years. The pollen types Apiaceae, Mimosa caesalpiniifolia, M. tenuiflora and Myrcia indicated the main floristic sources used by bees. M. tenuiflora was the most frequent of the pollen types, and because it predominates in different months in each year, which may indicate more than one species of the genus being foraged by the beehive. The climatic influence (rainfall and temperature) on the pollen diversity was investigated and was not statistically supported. The chemical analysis showed that the heavy metal content of the samples were below their respective limits of quantification, and, therefore, the samples can be considered safe for human consumption.

RESUMO A obtenção de vegetais biofortificados, com destaque para a alface, é uma ferramenta para melhorar o estado nutricional da população. Os índices de seleção podem maximizar a seleção simultânea de boas características agronômicas e altos níveis de carotenoides. O objetivo deste estudo foi estimar os parâmetros genéticos e a eficiência de diferentes índices para a seleção de genótipos de alface biofortificados combinados com características agronômicas adequadas. As análises estatísticas foram realizadas com 91 genótipos pertencentes ao banco de germoplasma de alface biofortificada da Universidade Federal de Uberlândia. As variáveis analisadas foram: índice de clorofila das folhas, diâmetro da planta, diâmetro do caule e número de folhas por planta. Os valores encontrados para herdabilidade no sentido restrito (h²) variaram de 89,63% (diâmetro do caule) a 96,05% (clorofila), apresentando alta magnitude. O índice de Smith-Hazel, a soma de “ranks” de Mulamba & Mock, a seleção direta e indireta e o índice base de Williams foram usados para prever os ganhos de seleção. No total, 17 indivíduos foram selecionados usando as metodologias de seleção. Os índices de Smith-Hazel, Williams e Mulamba & Mock são eficientes em mostrar bons ganhos diretos para as características avaliadas. Treze genótipos foram selecionados por todos os índices apresentando características agronômicas favoráveis, sendo promissores para o avanço de geração no programa de melhoramento para obter linhagens de alface biofortificadas.

ABSTRACT Obtaining biofortified vegetables with an emphasis on lettuce is a tool to improve the nutritional status of the population. Selection indices can maximize the simultaneous selection of good agronomic traits and high carotenoid levels. The objective of this study was to estimate the genetic parameters and efficiency of different indices in selecting genotypes of biofortified lettuce with high concentrations of carotenoids and favorable agronomic traits. Statistical analyses were performed on 91 genotypes belonging to the vegetable germplasm bank of the Federal University of Uberlândia, Brazil. The variables analyzed were the chlorophyll index of the leaves, plant diameter, stem diameter, and number of leaves per plant. The values found for narrow sense heritability (h²) ranged from 89.63% (stem diameter) to 96.05% (chlorophyll), showing a high magnitude. The Smith-Hazel index, sum of ranks by the Mulamba & Mock index, direct and indirect selection, and Williams base index were used to predict the selection gains. A total of 17 individuals were selected using the selection methodologies. The Smith-Hazel, Williams, and Mulamba & Mock indices were efficient in showing good direct gains for the evaluated traits. Thirteen genotypes were selected for all indices presenting suitable agronomic traits, which show promise for advancing generations within the breeding program to obtain biofortified lettuce strains.

RESUMO O Plano Global de Eliminação da Filariose Linfática, lançado pela Organização Mundial da Saúde em 2000, propõe o uso de testes de detecção de antígeno circulante filarial como ferramenta diagnóstica para avaliação e monitoramento das ações de controle da parasitose. Entretanto, esses testes, apesar de apresentarem alta sensibilidade, não conseguem detectar com eficiência a infecção em seu estágio inicial, quando ainda não existe a presença de helmintos adultos. Considerando essa limitação, a pesquisa de anticorpos antifilariais tem sido apontada como uma alternativa, uma vez que os anticorpos produzidos contra as larvas infectantes do parasito são detectados antes da presença de antígeno circulante filarial. O objetivo deste estudo foi definir o ponto de corte e avaliar a acurácia do kit Filaria Detect™ IgG4 produzido com o antígeno recombinante Wb123 para diagnóstico da filariose linfática no Brasil. Para isso, foi realizado um estudo de avaliação de teste diagnóstico, no qual foram utilizadas 256 amostras de soro: 79 (30,9%) obtidas de indivíduos microfilarêmicos e 177 (60,1%), de indivíduos amicrofilarêmicos e que testaram negativo para os testes imunológicos Bm14 CELISA e Og4C3 ELISA. A definição do ponto de corte ideal, bem como da acurácia do kit Filaria Detect™ IgG4, foi obtida através da construção de curvas ROC, sendo a densidade óptica de 0,239 aquela na qual o teste obteve melhor desempenho, com sensibilidade de 81,0% e especificidade de 96,6%. Os resultados obtidos demonstraram que o kit Filaria Detect™ IgG4 é uma ferramenta promissora para investigação e monitoramento de áreas submetidas ao tratamento em massa para filariose linfática.

ABSTRACT The Global Programme to Eliminate Lymphatic Filariasis, launched by the World Health Organization in the year 2000, proposes the use of circulating filarial antigen tests as a diagnostic tool to assess and monitor initiatives to control filarial infection. However, despite a high sensitivity, these tests are not efficient to detect infection at early stages, before worms have reached the adult stage. Considering this limitation, anti-filarial antibody testing has been suggested as an alternative, given that the antibodies produced against the larvae are detectable before the presence of circulating filarial antigen. The objective of the present study was to determine the diagnostic cut-off and the accuracy of the Filaria Detect™ IgG4 kit employing recombinant Wb123 antigen for diagnosis of lymphatic filariasis in Brazil. For that, we performed a diagnostic evaluation study in which 256 serum samples were analyzed: 79 (30.9%) obtained from microfilaremic individuals and 177 (60.1%) from amicrofilaremic individuals who tested negative with the Bm14 CELISA and Og4C3 ELISA immunologic tests. The ideal cutoff as well as the Filaria Detect™ IgG4 kit accuracy were determined based on ROC curve analyses, with an optical density of 0.239 identified as the cutoff with the best performance, with 81.0% sensitivity and 96.6% specificity. The results show that the Filaria Detect™ IgG4 kit is a promising tool for investigation and monitoring of areas undergoing mass drug administration for lymphatic filariasis.

RESUMEN En el programa mundial de eliminación de la filariasis linfática, puesto en marcha por la Organización Mundial de la Salud en el año 2000, se propone el uso de pruebas de detección del antígeno filárico circulante como instrumento de diagnóstico para la evaluación y el seguimiento de las medidas de control de la parasitosis. Sin embargo, esas pruebas, a pesar de tener un alto grado de sensibilidad, no permiten detectar con eficiencia la infección en su fase inicial, cuando todavía no existen helmintos adultos. En vista de esa limitación, se ha señalado como una opción el estudio de anticuerpos antifiláricos, puesto que los anticuerpos producidos contra las larvas infectantes del parásito se detectan antes de la existencia de antígeno filárico circulante. El objetivo de este estudio fue definir el punto de corte y evaluar la exactitud del estuche Detect™ para pruebas de anticuerpos antifiláricos IgG4, fabricado con el antígeno recombinante Wb123, para el diagnóstico de la filariasis linfática en Brasil. Para ello, se realizó un estudio de evaluación de la prueba diagnóstica, en el cual se utilizaron 256 muestras de suero, a saber, 79 (30,9%) obtenidas de personas microfilarémicas y 177 (60,1%) de personas amicrofilarémicas, que arrojaron resultados seronegativos en las pruebas inmunológicas CELISA Bm14 y ELISA Og4C3. La definición del punto de corte ideal y de la exactitud del estuche Detect™ se obtuvo con la construcción de curvas de la característica operativa del receptor (ROC); una densidad óptica de 0,239 marcó el mejor nivel de desempeño de la prueba, con una sensibilidad de 81,0% y una especificidad de 96,6%. Los resultados obtenidos demostraron que el estuche Detect™ es un instrumento prometedor para la investigación y el seguimiento de las regiones donde se realiza un tratamiento masivo de la filariasis linfática.

Resumo Objetivo: Avaliar em uma amostra de pacientes com distúrbios da diferenciação do sexo (DDS), dados relacionados à idade, ao encaminhamento e sua correlação com as queixas iniciais, ao sexo ao encaminhamento e ao sexo final e diagnóstico etiológico. Métodos: Revisão retrospectiva da idade por ocasião da primeira consulta e motivo dela, sexo social inicial e após definição do diagnóstico, cariótipo e diagnóstico etiológico de todos os casos atendidos em um ambulatório especializado em DDS entre 1989 e 2016. Foram excluídos casos que não compreendiam DDS e diagnósticos de DDS que não cursam comumente com ambiguidade genital, não necessitam de acompanhamento especializado. Resultados: Dos 1.793 casos atendidos, 1.139 foram diagnosticados com algum DDS. Excluíram-se 430 (272 síndrome de Turner, 66 síndrome de Klinefelter e 92 disgenesia gonadal pura), totalizando 709. Desses, 82,9% foram encaminhados por ambiguidade genital, somente um quarto ainda no primeiro mês de vida e 6,6% por atraso puberal, a maioria com 10 anos ou mais; 68,6% tiveram diagnóstico de DDS XY; 22,4% DDS XX e 9% de anomalias dos cromossomos sexuais. Conclusões: Este estudo apresenta a maior casuística na literatura de pacientes com DDS atendidos em um único serviço. O momento de encaminhamento da maioria dos pacientes com ambiguidade genital foi aquém do ideal e casos mais leves de ambiguidade e muitos com manifestações puberais foram encaminhados ainda mais tardiamente. Os resultados reforçam a importância do ensino continuado a profissionais que terão o primeiro contato com esses pacientes, principalmente pediatras e neonatologistas.

Abstract Objective: To evaluate, in a sample of patients with disorders of sex development (DSD), data related to the age at referral and their correlation with the initial complaints, gender at referral, defined gender after diagnosis and etiological diagnosis. Methods: Retrospective review of the age at the first consultation and the reason for it, initial social gender and gender after the diagnosis, karyotype and etiological diagnosis of all cases treated at a DSD outpatient clinic between 1989 and 2016. Cases that did not involve DSD and DSD diagnoses that do not usually involve ambiguous genitalia, thus not requiring specialized monitoring, were excluded. Results: Of the 1793 treated cases, 1139 were diagnosed with some type of DSD. This study excluded 430 cases (272 with Turner's syndrome, 66 with Klinefelter syndrome, and 92 with pure gonadal dysgenesis), thus a total 709 individuals were included. Of these, 82.9% were referred due to ambiguous genitalia; only one-quarter were still in the first month of life, and 6.6% were referred due to pubertal delay, with most of them aged 10 years or older. Of these patients, 68.6% had a diagnosis of XY DSD, 22.4% of XX DSD, and 9% of sex chromosome abnormalities. Conclusions: This study presents the largest series in the literature of patients with DSD treated in a single center. The time of referral of the majority of patients with ambiguous genitalia fell short of the ideal, and milder cases of ambiguous genitalia and many with pubertal manifestations were referred even later. The results reinforce the importance of continuing education for professionals who will have the first contact with these patients, mainly pediatricians and neonatologists.

RESUMO Objetivou-se com este estudo caracterizar genótipos de tomateiro do tipo salada com hábito de crescimento determinado, selecionar genótipos resistentes ao ácaro rajado, de maior produtividade e qualidade de frutos. O experimento foi conduzido na Estação Experimental de Hortaliças (18º 42’ 43,19” S e 47º 29’ 55,8” O, 873 m de altitude) da Universidade Federal de Uberlândia (UFU), campus Monte Carmelo, de janeiro a junho de 2018. O delineamento experimental foi em blocos casualizados, contendo 16 tratamentos [12 populações da geração F3RC2 e quatro testemunhas: duas cultivares comerciais (Santa Clara e Rio Grande), o genitor recorrente (UFU-057) e a espécie silvestre Solanum pennellii (LA-716)] com três repetições. Os acessos UFU-057F3RC210#3.6.1 e UFU-057F3RC213#2.1.2 possuem alto potencial para o melhoramento genético visando resistência ao ácaro rajado. Os genótipos UFU-13#4.4.1; UFU-7#4.7.1; UFU-7#4.3.2, UFU-13#2.5.2 e UFU-13#2.1.3 apresentaram teor de acilaçúcares superior ao S. pennellii, a maior produtividade e número de frutos por planta. Sugere-se a combinação entre os genótipos anteriormente descritos com UFU-8#2.4.1 para obtenção de híbridos com alto teor de acilaçúcares, resistência ao ácaro rajado, alta produtividade e incremento na massa de fruto.

ABSTRACT The objective of this study was to characterize genotypes of the salad-type tomato with a determinate growth habit and select genotypes resistant to the two-spotted spider mite for higher productivity and fruit quality. The experiment was conducted at the Horticultural Experimental Station (18°42’43.19” S and 47°29’55.8” W, 873 m altitude) of the Universidade Federal de Uberlândia (UFU), Monte Carmelo campus, from January to June 2018. The experimental design was in randomized blocks containing 16 treatments [12 populations of the F3RC2 generation and four controls: two commercial cultivars (Santa Clara and Rio Grande), the recurrent parent (UFU-057) and the wild species Solanum pennellii (LA-716)] with three repetitions. The accessions UFU-057F3RC210#3.6.1 and UFU-057F3RC213#2.1.2 have high potential for genetic improvement regarding resistance to the two-spotted spider mite. The genotypes UFU-13#4.4.1, UFU-7#4.7.1, UFU-7#4.3.2, UFU-13#2.5.2 and UFU-13#2.1.3 present higher acylsugar concentrations than S. pennellii, in addition to higher productivity and number of fruits per plant. It is suggested to explore combinations between those genotypes previously described with UFU-8#2.4.1 to obtain hybrids with high acylsugar concentrations, two-spotted spider mite resistance, high productivity and increased fruit mass.

ABSTRACT: Bees generally use different botanical sources of resins for the production of propolis. The elucidation of botanical sources of propolis and identification of the effects of seasonality on the chemical profile of propolis are recognized as two important aspects in the development of a high quality product. Thus, our objective was to elucidate the botanical source and identify the effect of the seasons on the chemical profile of propolis produced in southern Brazil. The chemical profile of the samples was analysed by spectrophotometric and chromatographic techniques and the results were coupled to multivariate analysis. Field observation of the foraging behaviour of Apis mellifera L. revealed its preference for the Baccharis dracunculifolia DC. species. p-Coumaric acid, 3, 4-dicaffeoylquinic acid, 3, 5-dicaffeoylquinic acid, drupanin, and artepillin C which were identified in both plant and propolis samples. Moreover, higher artepillin C amounts have been detected in samples collected in the summer and autumn, while the main compounds of p-coumaric acid and quercetin were available in spring and winter sampled propolis, respectively. Baccharis dracunculifolia has been identified as a plant species preferred by A. mellifera in foraging resin for the production of propolis in southern Brazil. The contents of balsam, total phenolic compounds, and flavonoids varied significantly over the seasons, with values above the minimum required by the legislation, thus assuring a quality pattern for this biomass.

Self-nanoemulsion drug delivery systems (SNEDDS) represent a potential carrier to improve solubility and bioavailability of health care products. In this sense, copaiba oil (CO) loaded on cosurfactant-free SNEDDS formulations (CO-SNEDDS) were obtained by using phase diagram performed on different concentrations of constituents (oil, surfactant and water). The CO-SNEDDS are composed of 1% (m/m) of oil phase, 20% (m/m) of Tween 80, and 79% (m/m) of double-distilled water. Specifically, varying the oil phase to 1% of CO affords the so-called SNECO system, and 1% of CO blended on a 1:1 ratio with coconut oil or sunflower oil affords, respectively, the SNECO-COO and SNECO-SO derivative systems. CO sample was authenticated by gas chromatography equipped with a flame ionization detector and the CO-SNEDDS samples were characterized by droplet particle size, zeta potential, polarized light microscopy, pH, conductivity, refractive index, rheological and surface tension analyses. According to the antioxidant tests reducing power and hydroxyl inhibiting formation, the findings displayed 47.89 and 72.92% for SNECO, 46.48 and 84.11% for SNECO-COO, and 52.46 and 74.48% for SNECO-SO, respectively. From now on CO-SNEDDS based systems become available as promising targets for novel medicinal investigations and also could be undertaken for the oral administration of poorly water soluble drugs.

Abstract: We have identified specimens of the leafhopper Gypona cerea DeLong & Freytag (Cicadellidae: Iassinae: Gyponini) collected from a crop of dwarf cashew (Anacardium occidentale Linnaeus 1753) located in Canto do Buriti, Piauí, Northeastern Brazil. The damage caused to the crop included inflorescences covered with sticky exudates, presence of sooty mold, and yellowing and drying of new shoots and inflorescences. Such documentation serves as a warning about possible outbreaks of infestation in the region and the likelihood of its expansion to other cashew producing areas.

ABSTRACT Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. Subjects and methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. Results: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. Conclusions: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.

ABSTRACT A molecular simulation algorithm was implemented to calculate chemical potentials of hard-core molecular systems at high densities. The method is based on the Widom particle insertion method and the step-function character of free energy variations. The algorithm was evaluated for hard-sphere mixtures at infinite dilution approximation by varying the solute/solvent diameter ratio, for systems with reduced densities from 0.1 to 0.8. The proposed methodology was verified by comparing simulations of trimers diluted in spheres and of single-component dimer systems with results from the literature. Then, the method was applied to mixtures of hard-spheres and dimers at several conditions regarding composition, reduced density, and bond-length/diameter ratio. The results were used to validate equations of state from the literature. The proposed approach was able to obtain accurate chemical potentials for different hard-core molecular mixtures. Lower uncertainties were obtained when comparing with traditional methods, especially at high densities.