Abstract Aedes aegypti (Diptera: Culicidae) is the main vector of some neglected diseases, including dengue. It is very important to develop formulations that increase effectiveness of vector control with low toxicity. Quercetin is a plant-derived flavonoid that modulates the development of some insects. The low water solubility of quercetin impairs the development of water-dispersible commercial products. To circumvent this problem, the preparation of nanoformulations is considered promising. Thus, this study aimed to evaluate the effect of bulk and quercetin nanosuspension against A. aegypti larvae and also to investigate their ecotoxicity. Quercetin nanosuspension was produced by a solvent displacement method followed by solvent evaporation and was maintained in two different temperatures (4 and 25 ºC). Its size distribution and zeta potential were monitored along 30 days. The influence of quercetin nanosuspension and bulk-quercetin was investigated at various concentrations against A. aegypti and the green algae Chlorella vulgaris. The quercetin nanosuspension presented higher stability at 4 ºC and negative zeta potential values. Quercetin nanosuspension and bulk-quercetin adversely affected the larvae development, especially at the highest concentrations. Larvae mortality was between 44% and 100% (48 h) for quercetin nanosuspension at 100 and 500 ppm, respectively. The bulk-quercetin induced around 50% mortality regardless the concentration used at this same time-period. Absence of emerging mosquitoes from water was observed on the survival larvae of all the treated groups. Quercetin nanosuspension was less toxic than bulk-quercetin against C. vulgaris, especially at higher concentrations. These data indicate that quercetin nanosuspension may represent a potential larvicide for A. aegypti control, once they induced larvae death and inhibited the survival ones to emerge from water. In addition, it did not demonstrated ecotoxicity against a non-target organism, highlighting its better properties, when compared to the bulk-quercetin.

RESUMO Introdução: A betatalassemia é causada pela síntese deficiente da cadeia ß da hemoglobina, o que leva à ocorrência das anemias crônica, microcítica e hipocrômica. Mais de 200 mutações já foram associadas a esse tipo de talassemia, mesmo que diferentes populações apresentem frequências variadas para cada uma delas. Objetivos: Os objetivos deste estudo foram determinar as frequências das mutações CD39, IVS1-1, IVS1-6 e IVS1-110 em indivíduos betatalassêmicos da cidade de Franca, São Paulo, e avaliar a influência dos genótipos sobre alterações hematológicas. Métodos: Amostras de sangue venoso foram coletadas de 25 voluntários previamente diagnosticados com betatalassemia. Foram realizados hemogramas completos, e a identificação das mutações foi feita utilizando a técnica de reação em cadeia da polimerase (PCR). Resultados: A mutação CD39 foi encontrada em 44% dos indivíduos, seguida por IVS1-6 (36%) e IVS1-110 (16%). Um paciente (4%) não apresentou nenhuma das mutações. A mutação IVS1-6 correlacionou-se inversamente ao red cell distribution width (RDW) (rs = -0,44; p = 0,034), enquanto a presença da mutação CD39 mostrou-se correlacionada a menores valores de volume corpuscular médio (VCM) (rs = -0,44; p = 0,034). Modelos de regressão linear multivariados mostraram que os portadores da mutação CD39 possuem menores valores de hemoglobina (ß = -0,61; p = 0,044) e hematócrito (ß = -2,1; p = 0,018). Conclusão: Os resultados mostraram alta frequência da mutação CD39 na cidade de Franca, e as correlações observadas entre a presença da mutação CD39 e as alterações hematológicas sugerem influência do genótipo sobre o fenótipo da betatalassemia, o que poderia contribuir para as variações clínicas dessa hemoglobinopatia.

ABSTRACT Introduction: Beta-thalassemia is caused by a deficient synthesis of the ß-chain of hemoglobin, which leads to a chronic, microcytic and hypochromic anemia. More than 200 mutations have already been associated with this type of thalassemia, and their frequencies may vary according to the population. Objectives: The objectives of this study were to determine the frequencies of CD39, IVS1-1, IVS1-6 and IVS1-110 mutations in people with beta-thalassemia from the city of Franca, São Paulo, and to evaluate the influence of the genotypes on hematological alterations. Methods: Venous blood samples were collected from 25 volunteers previously diagnosed with beta-thalassemia. Complete blood counts (CBC) were performed, and the identification of the mutations was carried out using the polymerase chain reaction (PCR). Results: The CD39 mutation was found in 11 (44%) individuals, followed by IVS1-6 (9; 36%) and IVS1-110 (4; 16%). One patient (4%) did not present any of these mutations. IVS1-6 mutation was inversely correlated to red cell distribution width (RDW) (rs = -0.44; p = 0.034), and CD39 was correlated to lower mean corpuscular volume (MCV) (rs = -0.44; p = 0.034). Multivariable linear regression models showed that the CD39 mutation carriers have lower levels for hemoglobin (ß = -0.61; p = 0.044) and hematocrit (ß = -2.1; p = 0.018). Conclusion: The results showed a high frequency of the CD39 mutation in the city of Franca, and the correlations observed between the presence of CD39 mutation and the hematological alterations suggest a genotype influence on the phenotype of beta-thalassemia, which would contribute to the clinical variations of this hemoglobinopathy.

Objetivo: Estabelecer as recomendações portuguesas relativas à indicação de realização da DXA e de iniciação de tratamento para a prevenção de fraturas de fragilidade. Métodos: Foi reunido um painel multidisciplinar, representando o leque das especialidades médicas e associações de doentes dedicadas à osteoporose, bem como especialistas nacionais neste domínio e em economia da saúde, com o objetivo de desenvolver recomendações com base na evidência científica e no consenso dos especialistas. As decisões foram suportadas por dados epidemiológicos, sócio-económicos e de qualidade de vida obtidos recentemente sobre as fraturas osteoporóticas. Resultados: Foram desenvolvidas 10 recomendações que abordam as questões de quem deve ser objeto de investigação com a DXA e quem deve ser tratado com terapêutica para prevenção de fraturas. Os limiares para a avaliação e intervenção baseiam-se na análise de custo-eficácia das intervenções em diferentes limiares da probabilidade a dez anos de fratura osteoporótica, calculados com base na versão portuguesa da FRAX® (FRAX®Port) tendo em consideração os dados epidemiológicos e económicos portugueses. Enumeram-se as limitações da FRAX® e, sempre que possível, propõem-se orientações para uma adaptação. Conclusões: Os limiares de custo-eficácia para realização de DXA e a instituição de terapêutica para a prevenção das fraturas de fragilidade são agora facultados à população portuguesa. Estes limiares são práticos, baseiam-se em dados epidemiológicos e económicos nacionais e em evidência científica e são corroborados por um painel multidisciplinar de especialistas e de instituições científicas. A implementação destas recomendações oferece perspetivas muito promissoras no que diz respeito a uma utilização mais eficaz dos recursos de saúde na prevenção das fraturas osteoporóticas em Portugal.

Objective: To establish Portuguese recommendations regarding the indications for ordering bone densitometry measurement to (DXA) and for starting treatment to prevent osteoporotic fractures. Methods: A multidisciplinary panel, representing a wide range of medical specialties and patient associations related to osteoporosis, as well as national experts in this field and in health economics, met to develop recommendations based on available evidence and expert consensus. Recently obtained data on the epidemiologic, economic and quality-of-life aspects of osteoporotic fractures in Portugal were used to support decisions. Results: Ten recommendations were developed covering the issues of indications for ordering DXA measurements and whom to treat with anti-fracture medications. Thresholds for assessment and intervention are based on the cost-effectiveness analysis of interventions at different thresholds of a ten-year probability of osteoporotic fractures, calculated with the Portuguese version of FRAX® (FRAX®Port), and taking into account Portuguese epidemiologic and economic data. Limitations of FRAX® are highlighted and guidance for appropriate adjustment is provided, when possible. Conclusions: Cost-effectiveness thresholds for DXA examination and drug intervention aiming at fragility fracture prevention are provided for the Portuguese population. These are practical, based on national epidemiological and economic data, evidence-based, and supported by a multidisciplinary panel of experts and scientific societies. Implementation of these recommendations has the possibility to assure the most effective use of health resources in the prevention of osteoporotic fractures in Portugal.

We briefly review the surgical approaches to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 (medullary thyroid carcinoma/multiple endocrine neoplasia type 2). The recommended surgical approaches are usually based on the age of the affected carrier/patient, tumor staging and the specific rearranged during transfection codon mutation. We have focused mainly on young children with no apparent disease who are carrying a germline rearranged during transfection mutation. Successful management of medullary thyroid carcinoma in these cases depends on early diagnosis and treatment. Total thyroidectomy should be performed before 6 months of age in infants carrying the rearranged during transfection 918 codon mutation, by the age of 3 years in rearranged during transfection 634 mutation carriers, at 5 years of age in carriers with level 3 risk rearranged during transfection mutations, and by the age of 10 years in level 4 risk rearranged during transfection mutations. Patients with thyroid tumor >5 mm detected by ultrasound, and basal calcitonin levels >40 pg/ml, frequently have cervical and upper mediastinal lymph node metastasis. In the latter patients, total thyroidectomy should be complemented by extensive lymph node dissection. Also, we briefly review our data from a large familial medullary thyroid carcinoma genealogy harboring a germline rearranged during transfection Cys620Arg mutation. All 14 screened carriers of the rearranged during transfection Cys620Arg mutation who underwent total thyroidectomy before the age of 12 years presented persistently undetectable serum levels of calcitonin (<2 pg/ml) during the follow-up period of 2-6 years. Although it is recommended that preventive total thyroidectomy in rearranged during transfection codon 620 mutation carriers is performed before the age of 5 years, in this particular family the surgical intervention performed before the age of 12 years led to an apparent biochemical cure.

Turgida turgida tem sido amplamente relatada parasitando espécies de Didelphis na América do Norte e América do Sul com base em microscopia óptica. No entanto, as características que diferenciam T. turgida de outras espécies de Physalopteridae, devem ser observadas utilizando microscopia eletrônica de varredura (MEV). Uma fêmea, de gambá-de-orelha-branca, Didelphis albiventris, chegou morta no Centro de Reabilitação de Animais Silvestres (CRAS) no município de Campo Grande, Estado de Mato Grosso do Sul, Brasil. Durante a necropsia, os nematóides adultos foram coletados do estômago e do intestino, identificados macroscopicamente e submetidos à MEV para a determinação específica. Este é o primeiro relato de T. turgida confirmado por MEV na região Neotropical, e o primeiro relato em uma área urbana no estado de Mato Grosso do Sul.

Turgida turgida have been largely reported parasitizing Didelphis species in North and South America based on light microscopy observation. However, the features that differentiate T. turgida from other physalopterid species should be observed using scanning electron microscopy (SEM). A female white-bellied opossum, Didelphis albiventris, arrived dead at the Centro de Reabilitação de Animais Silvestres (CRAS) in the municipality of Campo Grande, state of Mato Grosso do Sul, Brazil. During the necropsy, adult nematodes were collected from stomach and intestine. The nematodes were determined to be adult specimens and submitted to SEM for the species determination. This is the first report of T. turgida confirmed by SEM in the Neotropical region and the first report in an urban area in the state of Mato Grosso do Sul, Brazil.

O objetivo deste trabalho foi avaliar o desempenho produtivo e os aspectos fisiológicos e econômicos de quatro clones asiáticos Prang Besar de seringueira [Hevea brasiliensis (Willd. ex A. Juss.) Muell. Arg.], sob diferentes sistemas de sangria. O experimento foi instalado na Fazenda Santa Gilda, Município de Guararapes, SP, em delineamento de blocos ao acaso, com parcelas subdivididas no tempo. Os tratamentos principais foram os clones PB 260, PB 235, PB 330 e PB 217, submetidos a nove sistemas de sangria: ½S d/3.ET 2,5% 8/y; ½S d/3.ET 5% 8/y; ½S d/4.ET 2,5% 8/y; ½S d/4.ET 5% 8/y; ½S d/5.ET 2,5% 8/y; ½S d/5.ET 5% 8/y; ½S d/7.ET 2,5% 8/y; ½S d/7.ET 5% 8/y e ½S d/2 (testemunha). As variáveis avaliadas foram: perímetro do caule, produção de borracha seca, secamento do painel; foi avaliada, também, a viabilidade econômica. Os resultados mostram a superioridade econômica dos sistemas ½S d/5.ET 2,5% 8/y e ½S d/7.ET 5% 8/y, para o clone PB 260; ½S d/7.ET 2,5% 8/y para o clone PB 235; e ½S d/3.ET 2,5% 8/y e ½S d/3.ET 5% 8/y, para os clones PB 330 e PB 217, comparados com a testemunha. A menor incidência de secamento do painel foi observada no sistema ½S d/7.ET 5% 8/y, exceto para o clone PB 235.

The objective of this work was to evaluate the yield performance, and economic and physiologic aspects of four Asian clones Prang Besar of rubber tree [Hevea brasiliensis (Willd. ex A. Juss.) Muell. Arg.], in different tapping systems. The trial was placed at Santa Gilda farm, City of Guararapes, São Paulo State, Brazil, in a randomized block design with split-plot in time. The main treatments were PB 260, PB 235, PB 330 and PB 217 clones submitted to nine systems of tapping: ½S d/3.ET 2.5% 8/y; ½S d/3.ET 5% 8/y; ½S d/4.ET 2.5% 8/y; ½S d/4.ET 5% 8/y; ½S d/5.ET 2.5% 8/y; ½S d/5.ET 5% 8/y; ½S d/7.ET 2.5% 8/y; ½S d/7.ET 5% 8/y and ½S d/2 (check). The variables evaluated were: girth increment, dry rubber production, brown bast; it was also evaluated the economic viability. Results indicated the economical superiority of the ½S d/5.ET 2.5% 8/y and ½S d/7.ET 5% 8/y systems in PB 260 clone; ½S d/7.ET 2.5% 8/y system in PB 235 clone; and ½S d/3.ET 2.5% 8/y and ½S d/3.ET 5% 8/y in PB 330 and PB 217 clones, compared with the check. The smallest incidence of panel desiccation was observed in ½S d/7.ET 5% 8/y system, except for PB 235 clone.

CCarcinoma de pequenas células dos seios paranasais são tumores extremamente raros e agressivos. Apesar de os pulmões serem o sítio mais prevalente destes tumores, este trabalho enfoca o acometimento de um sitio extrapulmonar, os seios paranasais. Nós relatamos o caso de uma paciente com carcinoma de pequenas células primário do seio maxilar. Incluímos neste estudo uma discussão acerca de todos os casos relatados em literatura, abrangendo suas metástases, tratamento e expectativa de vida.

Primary small cell neuroendocrine carcinomas (SCC) of the sinusal tract are extremely uncommon and aggressive tumors. Although the lungs are the most prevalent site of these tumors, this report focuses on the involvement of an extrapulmonary site, the paranasal sinuses. We report the case of a female patient with a primary small cell carcinoma of maxillary sinus. A literature discussion with all reported cases of SCC and its metastasis, treatment and survival expectations are included.

A new parasite species of Leishmania is described, L. (Leishmania) forattinii sp. n., which was isolated from a pooled triturate of liver and spleen of a opossum (Didelphis marsupialis aurita) and from skin samples from a rodent (Proechmys iheringi denigratus), captured in primary forest on the Atlantic Cost of Brazil. Our results on the basis of biological and molecular criteria indicate that this taxonomically distinct parasite ias a new species of the L. mexicana complex, but closely related to L. (L.) aristidesi Laison & shaw, 1979, as revelated by phenetic and phylogenetic numerical analyses of the enzyme data. L. forattinii was clearly distinguishable from other Leishmania species of the genus usisng enzyme electrophoresis, monoclonal antibodies, molecular karyotypes, analysis of restriction enzyme digestion patterns of kinetoplast DNA (kDNA), as well as the use of kDNA hybridization procedures.