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The aim of the study was to assess glucocorticoid sensitivity in survivors of childhood acute lymphoblastic leukemia using in vivo and in vitro tests. Thirty leukemia survivors of both sexes aged ≥18 years participated in the study and at least two years after therapy withdrawal. In vivo tests comprised: a) a very low dose intravenous dexamethasone suppression test for measurement of serum cortisol before, after, and % suppression, compared with 32 age-matched controls; and b) 0.25 mg overnight oral dexamethasone suppression test for assessment of salivary cortisol before, after, and % suppression. In vitro methods comprised: c) glucocorticoid receptor polymorphisms: BcI1-NR3C1 and A3669G; and d) splicing variant of glucocorticoid receptor GR-α mRNA by real-time quantitative polymerase chain reaction, compared with 32 controls. There was a reduction in salivary cortisol, and 73.3% of leukemia survivors showed high sensitivity according to % suppression after oral dexamethasone (p<0.05). Serum cortisol at baseline, after the test, % suppression after intravenous dexamethasone, and the percentage of high sensitivity were reduced in the leukemia group (%F=36.7; p<0.05). The BcI1-NR3C1 and A3669G polymorphisms were present in 11/30 (36.7%) and 5/30 (16.7%) patients, respectively. GR-α mRNA levels were lower in the leukemia group than in the controls (p<0.05). Survivors of acute lymphoblastic leukemia presented with reduced glucocorticoid sensitivity. Glucocorticoid sensitivity allows individualized treatment to avoid adverse effects and may be involved in cardiovascular disease risk among this particular group of cancer survivors.
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Dexametasona , Glucocorticoides , Hidrocortisona , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Glucocorticoides , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Masculino , Feminino , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Hidrocortisona/sangue , Adolescente , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Criança , Adulto , Adulto Jovem , Estudos de Casos e Controles , Saliva/química , Saliva/metabolismo , Sobreviventes de Câncer , Sobreviventes , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Risk scores are used worldwide to predict foodborne disease (FBD) outbreaks in the food service industry. This study aims to develop and validate a new method for the calculation of the FBD risk score for the checklist used to categorize food service outlets. The proposed novel method is based on a risk score for each item using a risk matrix (consequence × probability), overcoming the limitations of the previous scoring process used during the World Cup in Brazil, which was based on a factorial analysis. The classification of consequences was based on critical points identified by experts prior to the World Cup in Brazil. Probability was defined based on the violation percentage of each item evaluated during inspections from 1536 food service outlets. Validation was performed using a secondary database of 3072 food service assessments in two inspection cycles. The risk scores of the new method were compared with those used during the World Cup. Each food service was classified based on their risk score into four categories: A, B, C, and pending. Good concordance (Lin's correlation coefficient = 0.8711 and 0.9205) was observed between the new and previous scores in the two inspection cycles, respectively. Comparison of the classifications showed substantial agreement (Kappa = 0.749, p < 0.001) to the first inspection cycle and near-perfect agreement (Kappa = 0.821; p < 0.001) to the second inspection cycle. This new method allows the inclusion and exclusion of assessment elements depending on local reality. Simpler methods can be used throughout Brazil and serve as a model for other countries' food safety assessments.
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Serviços de Alimentação , Doenças Transmitidas por Alimentos , Brasil , Inocuidade dos Alimentos , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/prevenção & controle , Humanos , Fatores de RiscoRESUMO
We report a novel proposal for reducing the digital divide in rural multigrade schools, incorporating knowledge of robotics with a STEM approach to simultaneously promote curricular learning in mathematics and science in several school grades. We used an exploratory qualitative methodology to implement the proposal with 12 multigrade rural students. We explored the contribution of the approaches to the promotion of curricular learning in mathematics and science and the perceptions of using robotics to learn mathematics and science. As data collection techniques, we conducted focus groups and semi-structured interviews with the participants and analyzed their responses thematically. We concluded that the proposal could contribute to meeting the challenges of multigrade teaching. Our findings suggest that the proposal would simultaneously promote the development of curricular learning in mathematics and science in several school grades, offering an alternative for addressing various topics with different degrees of depth.
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Instituições Acadêmicas , Estudantes , Humanos , Aprendizagem , Grupos Focais , Coleta de DadosRESUMO
PURPOSE: Turner syndrome is defined as total or partial loss of the second sex chromosome in a phenotypically female patient. Due to the possibility of hidden mosaicism of fragments of the Y chromosome and development of gonadoblastoma, we evaluated the presence of such fragments in 2 tissues with different embryonic origins, peripheral blood lymphocytes (mesoderm), and oral mucosal cells (ectoderm) using multiplex polymerase chain reaction. METHODS: DNA samples were collected from 109 patients, and primers for the SRY, TSPY, and AMELX genes were used. RESULTS: We found 14 patients (12.8%) with positive molecular markers for the Y chromosome. The study of tissues of different embryological origin showed the same degree of agreement, sensitivity, and specificity. CONCLUSION: Oral mucosa cells have a simpler method of collection that is less invasive and requires less time for DNA extraction at a lower cost.
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PURPOSE: This cross-sectional study evaluated the relationship between adipokines (leptin, adiponectin, visfatin, and resistin) and adiposity indexes regarding sex and cranial radiotherapy exposure among young acute lymphocytic leukemia survivors. METHODS: A multivariate analysis of covariance (MANCOVA) was used to evaluate the joint effect of sex, cranial radiotherapy, and body mass index (BMI) z-score (model 1) or fat mass index (FMI) (model 2) on adipokines. RESULTS: This study included 55 survivors of childhood acute lymphocytic leukemia between 15 and 23 years of age from both sexes (56.4% female); 43.6% of the sample had undergone cranial radiotherapy (18-24 Gy). The BMI z-score, the FMI, and sex (P<0.050 for all) influenced at least one adipokine, while cranial radiotherapy exposure was marginal in model 2. Parameter estimates from the MANCOVA's final model showed that the BMI z-score (ß=-0.437, P=0.010) and the FMI (ß=-0.209, P=0.004) negatively influenced adiponectin, while the FMI positively affected resistin (ß=0.142, P=0.020). The relationship between leptin, visfatin, and the adiposity ndexes could not be established. In model 1, females presented with increased adiponectin (ß=-1.014, P=0.011) and resistin (ß=-1.067, P=0.002) levels; in model 2, female sex positively affected adiponectin (ß=-1.515, P=0.001) and marginally influenced resistin (ß=-0.707, P=0.054) levels. Cranial radiotherapy negatively determined visfatin levels in both final models (P<0.050). CONCLUSION: Changes in body fat may be associated with adipose tissue dysfunction and should be carefully evaluated in survivors of acute lymphocytic leukemia, considering both sex and cranial radiotherapy exposure, to treat disorders that may possibly aggravate their risk for early cardiovascular disease.
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Scientifically-based, tephritid fly host status determination lies at the heart of strategic regulatory decisions impinging on international fruit trade. Here we conducted intensive field and laboratory studies with peaches as controls, to determine the host status of Physalis peruviana for the Medfly-Ceratitis capitata, as this fruit is experiencing a consumption boom worldwide. A total of 98,132 Uchuvas (local name), collected in Colombia from the plant or the ground over a three-year period (2016-2018) did not yield a single C. capitata larva or pupa, thus reaching a Probit 9 level with 99.9968% efficacy and 96% confidence level. Field-cage studies with enclosed fruit-bearing Uchuva plants, exposing fruit with an intact, damaged or totally removed husk to the attack of C. capitata, also failed to yield infestations. Highly artificial choice experiments, exposing gravid females to unripe and fully ripe fruit, resulted in an absence of infestations, even when overripe Uchuvas were artificially damaged. The husk and surface resins/waxes inhibit fly landings on fruit and oviposition activity. Considering our results and the fact that the foliage, husk and fruit of P. peruviana are repellent/toxic to insects, we conclude that this plant should be treated as a non-natural and non-conditional host of C. capitata.
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The presence and distribution of Scirtothrips dorsalis was reported in Colombia in the Andean, Caribbean, and Orinoquia regions, from 0 to 1,200 meters of altitude (MASL) in the warm climate zone, with less than 2,000 mm rainfall per year and a temperature above 24°C, which corresponds to the tropical dry forest life zone (TDF). Larvae and adults of S. dorsalis were found on 13 plant species belonging to 12 genera in 12 families, of 181 plant species sampled from 129 genera in 47 families sampled. The botanical species with S. dorsalis presence included cotton (Gossypium hirsutum) L., mango (Mangifera indica) L., chili pepper (Capsicum frutescens) L., bell pepper (Capsicum annuum) L., orange (Citrus sinensis) L., jasmine orange (Murraya paniculata) L., rose (Rosa sp.), and the weeds Sesbania exaltata (Mill.), Phyllanthus niruri L., Ludwigia hyssopifolia Vahl, Euphorbia hypericifolia L., Echinochloa colona L., and Amaranthus spinosus (L.). S. dorsalis prefers young leaves and floral structures, but in cotton it was also associated with squares. The low number of host plants is evident, far from the extensive lists obtained by other authors in other latitudes. S. dorsalis invaded Colombia only in recent years, and this is the first study of the presence and distribution of this thrips in the area.
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Distribuição Animal , Cadeia Alimentar , Tisanópteros/fisiologia , Animais , Colômbia , Dieta , Larva/crescimento & desenvolvimento , Larva/fisiologia , Plantas , Dinâmica Populacional , Tisanópteros/crescimento & desenvolvimentoRESUMO
AIM: Resistance to thyroid hormone (RTH), characterized by persistent hyperthyroxinemia with non-suppressed thyrotropin (TSH), is mostly caused by mutations in thyroid hormone receptor beta gene (THRB). Two differential diagnoses should be considered due to similar clinical and laboratory findings: TSH-producing pituitary adenoma (TPA) and Familial Dysalbuminemic Hyperthyroxinemia (FDH). The aim of this study is to describe our single tertiary center experience in the molecular diagnosis of RTH in Brazilian patients, analyzing their clinical and laboratory characteristics and the most common differential diagnosis. SUBJECTS AND METHODS: We enrolled 30 subjects with clinical and laboratory features of RTH. Patient´s evaluations included clinical examination, thyroid hormone profile and imaging tests. Sequencing analysis for THRB hot spot region was conducted on all patients, and those without mutations in beta isoform of the thyroid hormone receptor (TRß) (non-TR-RTH) were investigated for albumin gene (ALB) mutation. RESULTS: Seventeen patients presented mutations in TRß (RTHß); six were non-TR-RTH, three had a diagnosis of FDH with a mutation in ALB, and four were diagnosed with TPA. Two characteristics were different to what is commonly described in the literature: higher serum TSH levels in RTHß patients when compared to the non-TR-RTH group, but this difference did not extend to free T4 (FT4) level; also the percentage of non-TR-RTH was higher than what was reported in other series. CONCLUSION: In the present series, most cases were RTHß with higher levels of TSH. We described three novel mutations in THRB (p.M313V, p.R320G and p.R438P) and the first patients with FDH molecular diagnosis (p.R242H) documented in Brazil.
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Receptores beta dos Hormônios Tireóideos/genética , Síndrome da Resistência aos Hormônios Tireóideos/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Testes de Função Tireóidea , Receptores beta dos Hormônios Tireóideos/metabolismo , Síndrome da Resistência aos Hormônios Tireóideos/genética , Síndrome da Resistência aos Hormônios Tireóideos/metabolismo , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto JovemRESUMO
Congenital hypothyroidism is a clinical emergency due to its potential risk of mental retardation. Constipation might be present in hypothyroid children. However, Hirschsprung disease is rarely associated with congenital hypothyroidism. Herein, a case of congenital hypothyroidism in a one-year-old child mimicking Hirschsprung disease is described. Adequate treatment with levothyroxine sodium tablets controlled intestinal dysmotility that mimicked congenital intestinal aganglionosis due to the critical influence of thyroid hormones on bowel motility.
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Craniopharyngioma is a sellar/suprasellar benign tumor whose aggressiveness may imply in endocrine disturbances (hypothalamic obesity and hormone deficiencies). Fifty-seven patients were evaluated according to clinical characteristics, hypothalamic involvement, type of treatment, anthropometric variables, adiposity indexes (body mass index Z score category at diagnosis and post-treatment, total body fat, visceral adipose tissue, and metabolic syndrome components) and analyzed through multiple regression and logistic models. Patients were stratified according to growth hormone deficiency and recombinant human growth hormone use. Mean ages at diagnosis and at study evaluation were 9.6 and 16.6 years old, respectively. A set of 43/57 (75.4%) patients presented with important hypothalamic involvement, 24/57 (42.1%) received surgical treatment and cranial radiotherapy, and 8/57 (14%) interferon-α exclusively. Fifty-five patients (96.5%) were considered growth hormone deficient, and 26/57 (45.6%) grew despite no recombinant human growth hormone replacement therapy. At diagnosis, 12/57 (21%) patients were obese, and 33/57 (57.9%) at study evaluation, and after 3.2 years (median) post first therapy. There was no influence of height Z score on body mass index Z score. Body mass index Z score at diagnosis positively influenced body mass index Z score, total body fat, waist circumference and the presence of the metabolic syndrome post-treatment. Replacement of recombinant human growth hormone decreased total body fat and visceral adipose tissue. Craniopharyngioma patients worsened body mass index Z score category 3.2 years (median) after first treatment. Body mass index Z score increased due to real weight gain, without height decrease. Replacement of recombinant human growth hormone had beneficial effect on adiposity.
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Adiposidade , Índice de Massa Corporal , Craniofaringioma , Hormônio do Crescimento Humano/metabolismo , Gordura Intra-Abdominal , Adolescente , Criança , Craniofaringioma/metabolismo , Craniofaringioma/patologia , Craniofaringioma/fisiopatologia , Craniofaringioma/terapia , Estudos Transversais , Feminino , Seguimentos , Humanos , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Masculino , Estudos RetrospectivosRESUMO
Colombia is the country with the highest bird diversity in the world. Despite active research in ornithology, compelling morphological information of most bird species is still sparse. However, morphological information is the baseline to understand how species respond to environmental variation and how ecosystems respond to species loss. As part of a national initiative, the Instituto Alexander von Humboldt in collaboration with 12 Colombian institutions and seven biological collections, measured up to 15 morphological traits of 9,892 individuals corresponding to 606 species: 3,492 from individuals captured in field and 6,400 from museum specimens. Species measured are mainly distributed in high Andean forest, páramo, and wetland ecosystems. Seven ornithological collections in Colombia and 18 páramo complexes throughout Colombia were visited from 2013 to 2015. The morphological traits involved measurements from bill (total and exposed culmen, bill width and depth), wing (length, area, wingspan, and the distance between longest primary and longest secondary), tail (length and shape), tarsus (length), hallux (length and claw hallux), and mass. The number of measured specimens per species was variable, ranging from 1 to 321 individuals with a median of four individuals per species. Overall, this database gathered morphological information for >30% of Colombian bird diversity. No copyright, proprietary, or cost restrictions apply; the data should be cited appropriately when used.
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Aves , Ecossistema , Animais , Colômbia , Fenótipo , Áreas AlagadasRESUMO
Androgens are responsible for the development and maintenance of male sex characteristics. Dysfunctions in androgen action due to mutations in the androgen receptor gene (AR) can lead to androgen insensitivity syndrome (AIS) that can be classified as mild (MAIS), partial (PAIS), or complete (CAIS). We have analyzed functional effects of p.Ser760Thr, p.Leu831Phe, p.Ile899Phe, p.Leu769Val, and p.Pro905Arg mutations and the combination p.Gln799Glu + p.Cys807Phe that were identified in patients with PAIS or CAIS. The p.Leu769Val and p.Pro905Arg mutations showed complete disruption of AR action under physiological hormone concentrations; however, they differed in high DHT concentrations especially in the N/C terminal interaction assay. Mutations p.Ser760Thr, p.Leu831Phe, p.Ile899Phe presented transactivation activities higher than 20% of the wild type in physiological hormone concentrations and increased with higher DHT concentrations. However, each one showed a different profile in the N/C interaction assay. When p.Gln799Glu and p.Cys807Phe were analyzed in combination, transactivation activities <10% in physiologic hormone conditions indicated an association with a CAIS phenotype. We conclude that the functional analysis elucidated the role of mutant ARs, giving clues for the molecular mechanisms associated with different clinical AIS manifestations. Differences in hormone-dependent profiles may provide a basis for the response to treatment in each particular case.
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Síndrome de Resistência a Andrógenos/genética , Receptores Androgênicos/genética , Adolescente , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Mutação/genética , Receptores Androgênicos/metabolismo , Técnicas do Sistema de Duplo-Híbrido , Adulto JovemRESUMO
Contexto: O hormônio do crescimento recombinante humano (rhGH) tem sido considerado como opção terapêutica em diversas situações clínicas. Objetivo: Avaliar evidências de revisões sistemáticas (RS) Cochrane sobre eficácia e segurança do rhGH em diversos contextos. Métodos: Revisão de revisões sistemáticas (RS) Cochrane com descrição qualitativa dos resultados. A busca foi realizada na Biblioteca Cochrane; três pesquisadores avaliaram as revisões quanto aos critérios de inclusão. Resultados: Foram encontradas oito revisões sistemáticas que preencheram os critérios de seleção e concluíram que o uso do rhGH parece ter algum benefício: (a) na doença renal crônica em crianças (aumento da velocidade de crescimento); (b) na fibrose cística (melhora altura, peso e ganho de massa magra); (c) para queimaduras extensas (cicatrização mais rápida da ferida e da área doadora); (d) na síndrome de Turner (aumento da estatura final); (e) na baixa estatura idiopática (aumento da estatura final); (f) na fertilização in vitro (aumento das taxas de gravidez e de nascidos vivos). Não há evidências de benefícios do uso de rhGH na síndrome do intestino curto e na hipofosfatemia ligada ao X. Conclusão: As RSs sugerem que há benefícios no uso de rhGH em pacientes com síndrome de Turner, baixa estatura idiopática, doença renal crônica em crianças, fibrose cística, queimaduras extensas, e durante procedimentos de fertilização in vitro. Porém, para a maioria dos desfechos avaliados nessas situações clínicas, a qualidade das evidências é moderada a muito baixa, confirmando a necessidade de melhores estudos para recomendação dessas intervenções na prática clínica.
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Humanos , Endocrinologia , Medicina Baseada em Evidências , Prática Clínica Baseada em Evidências , Hormônio do Crescimento , RevisãoRESUMO
OBJECTIVE: Acid-labile subunit deficiency (ACLSD), caused by inactivating mutations in both IGFALS gene alleles, is characterized by marked reduction in IGF-I and IGFBP-3 levels associated with mild growth retardation. The aim of this study was to expand the known phenotype and genetic characteristics of ACLSD by reporting data from four index cases and their families. DESIGN: Auxological data, biochemical and genetic studies were performed in four children diagnosed with ACLSD and all available relatives. METHODS: Serum levels of IGF-I, IGFBP-3, acid-labile subunit (ALS), and in vitro ternary complex formation (ivTCF) were determined. After sequencing the IGFALS gene, pathogenicity of novel identified variants was evaluated by in vitro expression in transfected Chinese hamster ovarian (CHO) cells. ALS protein was detected in patients' sera and CHO cells conditioned media and lysates by Western immunoblot (WIB). RESULTS: Four index cases and four relatives were diagnosed with ACLSD. The following variants were found: p.Glu35Glyfs*17, p.Glu35Lysfs*87, p.Leu213Phe, p.Asn276Ser, p.Leu409Phe, p.Ala475Val and p.Ser490Trp. ACLSD patients presented low IGF-I and low or undetectable levels of IGFBP-3 and ALS. Seven out of 8 patients did not form ivTCF. CONCLUSIONS: This study confirms previous findings in ACLSD, such as the low IGF-I and a more severe reduction in IGFBP-3 levels, and a gene dosage effect observed in heterozygous carriers (HC). In addition, father-to-son transmission (father compound heterozygous and mother HC), preservation of male fertility, and marginal ALS expression with potential involvement in preserved responsiveness to rhGH treatment, are all novel aspects, not previously reported in this condition.
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Glicoproteínas/deficiência , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Adolescente , Adulto , Idoso , Animais , Proteínas de Transporte/genética , Criança , Pré-Escolar , Cricetulus , Família , Feminino , Fertilidade , Variação Genética , Glicoproteínas/genética , Transtornos do Crescimento/genética , Heterozigoto , Humanos , Lactente , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/deficiência , Fator de Crescimento Insulin-Like I/deficiência , América Latina , Masculino , Pessoa de Meia-Idade , Mutação , Transfecção , Adulto JovemRESUMO
Bone mass acquisition may be compromised in survivors of childhood acute lymphocytic leukemia due to various factors, including adiposity. Fat accumulation can affect bone through the direct effect of adipokines or indirectly through the state of chronic inflammation. The aim of this study was to evaluate the effect of body composition and adipokines on bone mass in survivors of acute lymphocytic leukemia. This was a cross-sectional study of 56 survivors aged between 15 and 24 years, 44.6 % of whom received cranial radiotherapy (18-24 Gy), assessed according to body fat, lean mass, and bone mineral density (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, and adipokines by a multiple regression analysis. Both lumbar spine L1-L4 (trabecular bone) and total body (cortical bone) bone mineral density were positively correlated with visfatin (p < 0.050). Lean mass index was positively correlated, while waist-to-height ratio was negatively correlated with cortical bone (p < 0.010). Low bone mineral density for chronological age was detected in 5.4 % of patients in total body, and 8.9 % at the lumbar spine. In survivors of acute lymphocytic leukemia, visfatin may play an important role in the complex relationship between body composition and bone. At present, visfatin may represent a model for further study of bone metabolism, and could possibly explain the unknown mechanisms linking bone metabolism and cancer.
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Adiposidade , Densidade Óssea , Citocinas/sangue , Vértebras Lombares/metabolismo , Nicotinamida Fosforribosiltransferase/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sobreviventes , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Valor Preditivo dos TestesRESUMO
Studies about selenium status in patients with Turner syndrome (TS) are non-existent in the literature. The aim of this study was to evaluate selenium status in patients with TS, while considering the different ages of the studied population and the relation with body composition. In total, 33 patients with TS were evaluated and grouped according to their developmental stages (children, adolescents, and adults). Selenium concentrations in their plasma, erythrocytes, urine, and nails were determined by using hydride generation atomic absorption spectrometry and erythrocyte glutathione peroxidase activity were measured by using Randox commercial kits. Additionally, height, weight, body fat percentage, waist circumference, and waist-height ratio were measured to characterize the patients. No differences in the selenium concentrations in the plasma, erythrocyte, urine, and nails or in the glutathione peroxidase activity were observed among the age groups (p > 0.05). The evaluated selenium levels were less than the established normal ones. The patients with larger waist circumference, body fat percentage, body mass index, and waist-height ratio showed lower glutathione peroxidase enzyme activity (p = 0.023). The present study shows that most patients with TS are deficient in selenium and that those with a greater accumulation of body fat have a lower GPx activity.
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Selênio/sangue , Selênio/urina , Síndrome de Turner/sangue , Síndrome de Turner/urina , Adolescente , Adulto , Criança , Humanos , Unhas/química , Adulto JovemRESUMO
PURPOSE: Testotoxicosis is an autosomal dominant form of gonadotropin-independent precocious puberty caused by heterozygous constitutively activating mutations of the luteinizing hormone/choriogonadotropin receptor (LHCGR) gene. The aim of this study was to describe two Brazilian siblings with testotoxicosis, to confirm the molecular diagnosis, and to perform an in silico analysis of a novel mutation in the hot spot of the LHCGR gene. MATERIALS AND METHODS: Molecular analysis of the mutation on the LHCGR gene was performed by direct Sanger sequencing, followed by an in silico analysis using HOPE bioinformatics tool to predict a functional defect of the mutant. RESULTS: Both patients presented with gonadotropin-independent precocious puberty before the age of four years. Genetic analysis revealed a novel non-maternally inherited p.Asp578Val mutation of the LHCGR gene. An in silico analysis showed that the p.Asp578Val mutation disturbed amino acid physicochemical features regarding its size, charge, and hydrophobicity value. CONCLUSIONS: Clinical and hormonal profile of the siblings here evaluated was not different while compared to those patients previously described. An in silico mutation analysis reinforced the causative role of recurrent activating mutations in the intracellular loop and transmembrane helices of the LHCGR. The segregation of this mutation with the offsprings' phenotype indicated that it is causative.
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Puberdade Precoce/genética , Receptores do LH/genética , Adolescente , Brasil , Criança , Humanos , Masculino , Mutação , IrmãosRESUMO
Clinical and laboratory diagnosis and treatment of central precocious puberty (CPP) remain challenging due to lack of standardization. The aim of this revision was to address the diagnostic and therapeutic features of CPP in Brazil based on relevant international literature and availability of the existing therapies in the country. The diagnosis of CPP is based mainly on clinical and biochemical parameters, and a period of follow-up is desirable to define the "progressive" form of sexual precocity. This occurs due to the broad spectrum of pubertal development, including isolated premature thelarche, constitutional growth and puberty acceleration, progressive and nonprogressive CPP, and early puberty. Measurement of basal and stimulated LH levels remains challenging, considering that the levels are not always in the pubertal range at baseline, short-acting GnRH is not readily available in Brazil, and the cutoff values differ according to the laboratory assay. When CPP is suspected but basal LH values are at prepubertal range, a stimulation test with short-acting or long-acting monthly GnRH is a diagnostic option. In Brazil, the treatment of choice for progressive CPP and early puberty is a long-acting GnRH analog (GnRHa) administered once a month or every 3 months. In Brazil, formulations of GnRHa (leuprorelin and triptorelin) are available and commonly administered, including 1-month depot leuprorelin 3.75 mg and 7.5 mg, 1-month depot triptorelin 3.75 mg, and 3-month depot leuprorelin 11.25 mg. Monthly or 3-month depot GnRHa are effective and safe to treat CPP. Arch Endocrinol Metab. 2016;60(2):163-72.
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Hormônio Liberador de Gonadotropina/uso terapêutico , Terapia de Reposição Hormonal/métodos , Puberdade Precoce/diagnóstico , Puberdade Precoce/tratamento farmacológico , Fatores Etários , Antropometria , Brasil , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Hormônio Luteinizante/sangue , Masculino , Fatores SexuaisRESUMO
In 2014, Brazil hosted one of the most popular sport competitions in the world, the FIFA World Cup. Concerned about the intense migration of tourists, the Brazilian government decided to deploy a food safety strategy based on inspection scores and a grading system applied to food services. The present study aimed to evaluate the results of the food safety strategy deployed during the 2014 FIFA World Cup in Brazil. To assess food safety, an evaluation instrument was applied twice in 1927 food service establishments from 26 cities before the start of the competition. This instrument generated a food safety score for each establishment that ranged from 0.0 (no flaws observed) to 2565.95, with four possible grades: A (0.0-13.2); B (13.3-502.6); C (502.7-1152.2); and pending (more than 1152.3). Each food service received a stamp with the grade of the second evaluation. After the end of the World Cup, a study was conducted with different groups of the public to evaluate the acceptance of the strategy. To this end, 221 consumers, 998 food service owners or managers, 150 health surveillance auditors, and 27 health surveillance coordinators were enrolled. These participants completed a survey with positive and negative responses about the inspection score system through a 5-point Likert scale. A reduction in violation scores from 393.1 to 224.4 (p < 0.001) was observed between the first and second evaluation cycles. Of the food services evaluated, 38.7% received the A stamp, 41.4% the B stamp, and 13.9% the C stamp. All positive responses on "system reliability" presented a mean of 4.0 or more, indicating that the public believed this strategy is reliable for communicating risks and promoting food safety. The strategy showed positive results regarding food safety and public acceptance. The deployed strategy promoted improvements in the food safety of food services. The implementation of a permanent policy may be well accepted by the public and may greatly contribute to a reduction in foodborne diseases (FBDs).
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ABSTRACT Clinical and laboratory diagnosis and treatment of central precocious puberty (CPP) remain challenging due to lack of standardization. The aim of this revision was to address the diagnostic and therapeutic features of CPP in Brazil based on relevant international literature and availability of the existing therapies in the country. The diagnosis of CPP is based mainly on clinical and biochemical parameters, and a period of follow-up is desirable to define the “progressive” form of sexual precocity. This occurs due to the broad spectrum of pubertal development, including isolated premature thelarche, constitutional growth and puberty acceleration, progressive and nonprogressive CPP, and early puberty. Measurement of basal and stimulated LH levels remains challenging, considering that the levels are not always in the pubertal range at baseline, short-acting GnRH is not readily available in Brazil, and the cutoff values differ according to the laboratory assay. When CPP is suspected but basal LH values are at prepubertal range, a stimulation test with short-acting or long-acting monthly GnRH is a diagnostic option. In Brazil, the treatment of choice for progressive CPP and early puberty is a long-acting GnRH analog (GnRHa) administered once a month or every 3 months. In Brazil, formulations of GnRHa (leuprorelin and triptorelin) are available and commonly administered, including 1-month depot leuprorelin 3.75 mg and 7.5 mg, 1-month depot triptorelin 3.75 mg, and 3-month depot leuprorelin 11.25 mg. Monthly or 3-month depot GnRHa are effective and safe to treat CPP. Arch Endocrinol Metab. 2016;60(2):163-72.