<em>Aedes aegypti</em>: The Main Enemy of Public Health in Brazil - Challenges and Perspective for Public Health

Mosquitoes (Diptera: Culicidae) are important vectors responsible for transmission of many diseases and parasites. They are causing millions of deaths every year and are considered one of the deadliest animals in the world. The most common arboviruses, such as dengue, chikungunya and Zika, to which the Brazilian population is most exposed and that occur through the bites of the Aedes aegypti mosquito, which is the main aim of this study. These infections caused by these three arboviruses are widely distributed on the national territory and have severe consequence to population in some cases. Without effective vaccine and specific treatment, the maintenance and integration of a continuous entomological and epidemiological surveillance are important, besides the methods to control and to prevent these arboviruses in Brazil. This chapter discusses the role of Fiocruz (Oswaldo Cruz Foundation, the most prominent institution of science and technology in health in Latin America) for the development of new methodologies to diagnose and control mosquito-borne diseases through public health policies for the country

Síntese de aminoálcoois derivados do D-manitol

Aminoalcohols have found important applications in synthetic and medicinal chemistry, being used as chiral building blocks for the synthesis of many biologically active compounds. This class of compounds has been also used as chiral auxiliaries and ligands in asymmetric synthesis. Due to the importance of aminoalcohols in the treatment of several diseases, such as tuberculosis, the aim of this article is the synthesis and preliminary evaluation against tuberculosis of six aminoalcohols in 5 or 6 steps using D-mannitol as starting material, which is a useful carbohydrate employed in many syntheses

The Brazilian consensus for the diagnosis and treatment of hyperthyroidism: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism

INTRODUCTION: Hyperthyroidism is characterized by increased synthesis and release of thyroid hormones by the thyroid gland. Thyrotoxicosis refers to the clinical syndrome resulting from excessive circulating thyroid hormones, secondary to hyperthyroidism or due to other causes. This article describes evidence-based guidelines for the clinical management of thyrotoxicosis. OBJECTIVE: This consensus, developed by Brazilian experts and sponsored by the Department of Thyroid Brazilian Society of Endocrinology and Metabolism, aims to address the management, diagnosis and treatment of patients with thyrotoxicosis, according to the most recent evidence from the literature and appropriate for the clinical reality of Brazil. MATERIALS AND METHODS: After structuring clinical questions, search for evidence was made available in the literature, initially in the database MedLine, PubMed and Embase databases and subsequently in SciELO - Lilacs. The strength of evidence was evaluated by Oxford classification system was established from the study design used, considering the best available evidence for each question. RESULTS: We have defined 13 questions about the initial clinical approach for the diagnosis and treatment that resulted in 53 recommendations, including the etiology, treatment with antithyroid drugs, radioactive iodine and surgery. We also addressed hyperthyroidism in children, teenagers or pregnant patients, and management of hyperthyroidism in patients with Graves' ophthalmopathy and various other causes of thyrotoxicosis. CONCLUSIONS: The clinical diagnosis of hyperthyroidism usually offers no difficulty and should be made with measurements of serum TSH and thyroid hormones. The treatment can be performed with antithyroid drugs, surgery or administration of radioactive iodine according to the etiology of thyrotoxicosis, local availability of methods and preferences of the attending physician and patient.INTRODUÇÃO: O hipertireoidismo é caracterizado pelo aumento da síntese e liberação dos hormônios tireoidianos pela glândula tireoide. A tireotoxicose refere-se à síndrome clínica decorrente do excesso de hormônios tireoidianos circulantes, secundário ao hipertireoidismo ou não. Este artigo descreve diretrizes baseadas em evidências clínicas para o manejo da tireotoxicose. OBJETIVO: O presente consenso, elaborado por especialistas brasileiros e patrocinado pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia, visa abordar o manejo, diagnóstico e tratamento dos pacientes com tireotoxicose, de acordo com as evidências mais recentes da literatura e adequadas para a realidade clínica do país. MATERIAIS E MÉTODOS: Após estruturação das questões clínicas, foi realizada busca das evidências disponíveis na literatura, inicialmente na base de dados do MedLine-PubMed e posteriormente nas bases Embase e SciELO - Lilacs. A força das evidências, avaliada pelo sistema de classificação de Oxford, foi estabelecida a partir do desenho de estudo utilizado, considerando-se a melhor evidência disponível para cada questão. RESULTADOS: Foram definidas 13 questões sobre a abordagem clínica inicial visando ao diagnóstico e ao tratamento que resultaram em 53 recomendações, incluindo investigação etiológica, tratamento com drogas antitireoidianas, iodo radioativo e cirurgia. Foram abordados ainda o hipertireoidismo em crianças, adolescentes ou pacientes grávidas e o manejo do hipertireoidismo em pacientes com oftalmopatia de Graves e com outras causas diversas de tireotoxicose. CONCLUSÕES: O diagnóstico clínico do hipertireoidismo, geralmente, não oferece dificuldade e a confirmação diagnóstica deverá ser feita com as dosagens das concentrações séricas de TSH e hormônios tireoidianos. O tratamento pode ser realizado com drogas antitireoidianas, administração de radioiodoterapia ou cirurgia de acordo com a etiologia da tireotoxicose, as características clínicas, disponibilidade local de métodos e preferências do médico-assistente e paciente.20523

Semaphorin 4B is an ADAM17-cleaved adipokine that inhibits adipocyte differentiation and thermogenesis

Objective: The metalloprotease ADAM17 (also called TACE) plays fundamental roles in homeostasis by shedding key signaling molecules from the cell surface. Although its importance for the immune system and epithelial tissues is well-documented, little is known about the role of ADAM17 in metabolic homeostasis. The purpose of this study was to determine the impact of ADAM17 expression, specifically in adipose tissues, on metabolic homeostasis.Methods: We used histopathology, molecular, proteomic, transcriptomic, in vivo integrative physiological and ex vivo biochemical approaches to determine the impact of adipose tissue-specific deletion of ADAM17 upon adipocyte and whole organism metabolic physiology.Results: ADAM17adipoq-creD/D mice exhibited a hypermetabolic phenotype characterized by elevated energy consumption and increased levels of adipocyte thermogenic gene expression. On a high fat diet, these mice were more thermogenic, while exhibiting elevated expression levels of genes associated with lipid oxidation and lipolysis. This hypermetabolic phenotype protected mutant mice from obesogenic challenge, limiting weight gain, hepatosteatosis and insulin resistance. Activation of beta-adrenoceptors by the neurotransmitter norepinephrine, a key regulator of adipocyte physiology, triggered the shedding of ADAM17 substrates, and regulated ADAM17 expression at the mRNA and protein levels, hence identifying a functional connection between thermogenic licensing and the regulation of ADAM17. Proteomic studies identified Semaphorin 4B (SEMA4B), as a novel ADAM17-shed adipokine, whose expression is regulated by physiological thermogenic cues, that acts to inhibit adipocyte differentiation and dampen thermogenic responses in adipocytes. Transcriptomic data showed that cleaved SEMA4B acts in an autocrine manner in brown adipocytes to repress the expression of genes involved in adipogenesis, thermogenesis, and lipid uptake, storage and catabolism.Conclusions: Our findings identify a novel ADAM17-dependent axis, regulated by beta-adrenoceptors and mediated by the ADAM17-cleaved form of SEMA4B, that modulates energy balance in adipocytes by inhibiting adipocyte differentiation, thermogenesis and lipid catabolism.(c) 2023 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Plasmatic higher levels of homocysteine in Non-alcoholic fatty liver disease (NAFLD)

Background\ud Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between liver steatosis with plasma homocysteine level and MTHFR C677T and A1298C polymorphisms in Brazilian patients with NAFLD.\ud \ud Methods\ud Thirty-five patients diagnosed with NAFLD by liver biopsy and forty-five healthy controls neither age nor sex matched were genotyped for C677T and A1298C MTHFR polymorphisms using PCR-RFLP and PCR-ASA, respectively, and Hcy was determined by HPLC. All patients were negative for markers of Wilson’s, hemochromatosis and autoimmune diseases. Their daily alcohol intake was less than 100 g/week. A set of metabolic and serum lipid markers were also measured at the time of liver biopsies.\ud \ud Results\ud The plasma Hcy level was higher in NAFLD patients compared to the control group (p = 0.0341). No statistical difference for genotypes 677C/T (p = 0.110) and 1298A/C (p = 0.343) in patients with NAFLD and control subjects was observed. The genotypes distribution was in Hardy-Weinberg equilibrium (677C/T p = 0.694 and 1298 A/C p = 0.188). The group of patients and controls showed a statistically significant difference (p < 0.001) for BMI and HOMA_IR, similarly to HDL cholesterol levels (p < 0,006), AST, ALT, γGT, AP and triglycerides levels (p < 0.001). A negative correlation was observed between levels of vitamin B12 and Hcy concentration (p = 0.005).\ud \ud Conclusion\ud Our results indicate that plasma Hcy was higher in NAFLD than controls. The MTHFR C677T and A1298C polymorphisms did not differ significantly between groups, despite the 677TT homozygous frequency was higher in patients (17.14%) than in controls (677TT = 4.44%) (p > 0.05). The suggested genetic susceptibility to the MTHFR C677T and A1298C should be confirmed in large population based studies.The authors acknowledge the Pernambuco University, the Pediatrics Hematology and Oncology Center of Pernambuco University, the Liver Institute of Pernambuco, Federal University of São Paulo and Department of Pediatrics for their help in data collection and clinical analyzes. The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost