Abstract Background Amaranthus palmeri is an economically important plant species worldwide. The rapid growth and competitive potential of crops make A. palmeri a major problem. Studies on the dissemination potential of this weed in Brazil and worldwide are necessary to identify the regions with high climatic potential. Similarly, we analyzed the behavior of the species in the face of predicted climate change. Studies of this type can be performed using ecological niche modeling. Objective This work aimed to determine areas with climatic suitability for A. palmeri in the present and future climates in Brazil and globally. Methods We projected the potential distribution of A. palmeri based on the environmental requirements and stress parameters that limit this species in Brazil. Results For the current climate, our model identified regions with favorable climatic suitability for A. palmeri on most continents. The results showed that the suitability of A. palmeri in the Brazilian territory will decrease owing to predicted climate change. The future model highlighted decreases in the suitable northern, northeastern, and midwestern areas. An annual study of the occurrence of A. palmeri using the weekly growth index predicted by the model showed great potential for the species throughout the year, with a decrease in the driest months (July to August), indicating the preference of the species for moist soils. Tropical and subtropical zones are currently experiencing a reduction in suitable areas because of climate change in northeastern Brazil and western Australia. Temperate zone sites have potential areas of expansion for A. palmeri (northern USA, Russia, and China) under climate change. Conclusions Based on the results of this study, management strategies should be planned to contain the global spread of A. palmeri.

ABSTRACT Objective To determine the frequency of drug therapy problems among older adults in Primary Health Care, and to analyze the factors associated with their identification in the initial patient assessment, carried out by pharmacists offering medication therapy management services. Methods A cross-sectional study conducted with data from 758 older adults followed up in medication therapy management services in Primary Health Care in the cities of Belo Horizonte, Betim, and Lagoa Santa (MG, Brazil). Univariate and multivariate analyses were performed to evaluate the factors associated with identification of four or more drug therapy problems in the initial clinical assessment. Results A total of 1,683 drug therapy problems were identified, 73.6% of older patients had at least one problem. The most frequent problems were nonadherence (23.0%) and the need for additional drug therapy (18.0%). Polypharmacy, chronic obstructive pulmonary disease, hypertension, diabetes mellitus, heart failure, and aged 75 years or older remained positively and statistically associated with identification of four or more drug therapy problems (p<0.05). Conclusion There is a high frequency of problems related to medication use among older users of Primary Health Care, and the medication therapy management services should be prioritized to the older patients, who present with polypharmacy, chronic obstructive pulmonary disease, hypertension, diabetes mellitus, heart failure, and age ≥ 75 years, since they are more likely to have more drug therapy problems.

Abstract Snake envenomation is a public health problem, and while serum therapy prevents death, the local effects of venoms can lead to amputations or morbidities. Thus, alternative treatments deserve attention. In this study, we tested eight derivatives of 1,2,3-triazole against some toxic activities of Bothrops jararaca venom. The derivatives were synthesized, and their structures analyzed by infrared and nuclear magnetic resonance. After that, the ability of compounds to inhibit hemolysis, coagulation, proteolysis, hemorrhaging, edema, and lethal activities of B. jararaca venom was investigated. The derivatives were incubated with B. jararaca venom (incubation protocol), administered before (prevention protocol) or after (treatment protocol) injecting venom into the mice. Then, hemorrhaging assay occurred. As a result, most of the derivatives inhibited the activities, even if they were incubated, injected before or after B. jararaca venom. However, the derivatives TRI 07 and TRI 18 seemed to be the most efficient in impairing hemorrhaging. The derivatives showed a low drug score of toxicity based on an in silico technique. Therefore, the derivatives fulfilled physicochemical and biological requirements to become drugs, and they may be a brand new initiative for designing antivenom molecules to complement antivenom therapy to efficiently block tissue necrosis or any other local effects.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infection that may break the healthcare system of several countries. Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. Finally, we also discuss patent protection issues, cost effectiveness and scalability of synthetic routes for some of the most studied repurposing candidates since these are key aspects to meet global demand for COVID-19 treatment.

Abstract Introduction: adequate iodine intake during pregnancy is essential for the synthesis of thyroid hormones, which are important for the physiological functions of the mother and appropriate maturation of the central nervous system of the fetus. Objective: the objective of the present study was to determine the levels of urinary iodine excretion and thyroid function, antioxidants and oxidative stress markers in pregnant women. Methods: the study was conducted on 191 pregnant women and 62 non-pregnant women who were evaluated regarding nutritional status. Analyses of urinary iodine, of oxidative stress markers and thyroid function were performed, revealing iodine insufficiency in 81 pregnant women. Results: there was no change in the thyroid stimulating hormone concentration in 89% of the pregnant women. Antithyroperoxidase antibody values were higher in the control group compared to the pregnant women's group (64.5% and 12.6%, respectively) and antithyroglobulin antibody values were also higher in the control group (11.6%). Assessment of oxidative stress revealed higher levels of advanced oxidation protein products, of total antioxidant capacity and of superoxide dismutase antioxidants in pregnant women. Classification of ioduria with respect to oxidative stress markers revealed lower α-tocopherol levels for the pregnant women with iodine insufficiency. Conclusion: on this basis, the results suggest that iodine insufficiency did not induce changes in thyroid stimulating hormone levels or antibodies and those pregnant women with adequate urinary iodine excretion had a better profile of the α-tocopherol antioxidant, indicating that iodine may play a significant role in antioxidant capacity during gestation.

Resumen Introducción: la ingesta adecuada de yodo durante el embarazo es esencial para la síntesis de las hormonas tiroideas, que son importantes para las funciones fisiológicas de la madre y la maduración apropiada del sistema nervioso central del feto. Objetivo: el objetivo del presente estudio fue determinar los niveles de excreción de yodo urinario y función tiroidea, antioxidantes y marcadores de estrés oxidativo en mujeres embarazadas. Métodos: el estudio se realizó en 191 mujeres embarazadas y 62 mujeres no embarazadas que fueron evaluadas con respecto al estado nutricional. Se realizaron análisis de yodo urinario, marcadores de estrés oxidativo y función tiroidea, que revelaron insuficiencia de yodo en 81 embarazadas. Resultados: no hubo cambios en la concentración de hormona estimulante tiroidea en el 89% de las mujeres embarazadas. Los valores de anticuerpos antitiroperoxidasa fueron mayores en el grupo control en comparación con el grupo de mujeres embarazadas (64,5% y 12,6%, respectivamente) y los de anticuerpos antitiroglobulina fueron también mayores en el grupo control (11,6%). La evaluación del estrés oxidativo reveló niveles más altos de productos avanzados de proteína de oxidación, de capacidad antioxidante total y de antioxidantes de superóxido dismutasa en mujeres embarazadas. La clasificación de la yoduria con respecto a marcadores de estrés oxidativo reveló menores niveles de α-tocopherol para las mujeres embarazadas con insuficiencia de yodo. Conclusión: sobre esta base, los resultados sugieren que la insuficiencia de yodo no indujo cambios en los niveles de hormona estimulante de la tiroides o anticuerpos y las mujeres embarazadas con excreción urinaria adecuada de yodo tuvieron un mejor perfil del antioxidante α-tocopherol, lo que indica que el yodo puede desempeñar un papel significativo en la capacidad antioxidante durante la gestación.

Abstract Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic tumor of the jaws, histologically characterized by the presence of agglomerates of cells with eosinophilic cytoplasm. The patient, a 62-year-old Caucasian woman, presented an intraosseous lesion in the mandibular symphysis. A clinical examination revealed a discrete volumetric increase with a hard consistency, palpable to extraoral and intraoral examinations. Imaging studies revealed an extensive radiolucent area, without defined limits, extending from the region of the right second premolar to the left canine. Incisional biopsy analysis indicated a diagnosis of CCOC. The treatment proposed was segmental resection of the mandible with a safety margin. After six months without recurrence, definitive mandibular reconstruction was performed using an iliac crest graft, followed by rehabilitation with implant-supported denture after five months. After three years of post-resection follow-up, the patient has shown no evidence of recurrence or metastasis. She continues to be under follow-up. To conclude, CCOC must be considered a malignant tumor with aggressive behavior. Previous studies have shown that resection with free margins is a treatment with a lower rate of recurrence. Nevertheless, long-term follow-up is necessary for such patients.

BACKGROUND Malaria persists as a major public health problem. Atovaquone is a drug that inhibits the respiratory chain of Plasmodium falciparum, but with serious limitations like known resistance, low bioavailability and high plasma protein binding. OBJECTIVES The aim of this work was to perform molecular modelling studies of 2-hydroxy-1,4-naphthoquinones analogues of atovaquone on the Qo site of P. falciparum cytochrome bc1 complex (Pfbc1) to suggest structural modifications that could improve their antimalarial activity. METHODS We have built the homology model of the cytochrome b (CYB) and Rieske iron-sulfur protein (ISP) subunits from Pfbc1 and performed the molecular docking of 41 2-hydroxy-1,4-naphthoquinones with known in vitro antimalarial activity and predicted to act on this target. FINDINGS Results suggest that large hydrophobic R2 substituents may be important for filling the deep hydrophobic Qo site pocket. Moreover, our analysis indicates that the H-donor 2-hydroxyl group may not be crucial for efficient binding and inhibition of Pfbc1 by these atovaquone analogues. The C1 carbonyl group (H-acceptor) is more frequently involved in the important hydrogen bonding interaction with His152 of the Rieske ISP subunit. MAIN CONCLUSIONS Additional interactions involving residues such as Ile258 and residues required for efficient catalysis (e.g., Glu261) could be explored in drug design to avoid development of drug resistance by the parasite.

Objetivo : O consumo de quantidade adequada de iodo durante a gestação é de fundamental importância para o desenvolvimento neurológico do feto. O objetivo deste estudo foi avaliar o estado nutricional iódico em gestantes do estado de São Paulo, Brasil.Material e métodos : Analisamos a concentração urinária de iodo (UIC) em 191 gestantes e em 58 mulheres não gestantes de mesma faixa etária. Foram utilizados os critérios da OMS para definir suficiência iódica (mediana de UIC: 150-249 µg/L entre as gestantes e 100-199 µg/L para as não gestantes).Resultados : A mediana de UIC das gestantes estudadas esteve abaixo da recomendada (mediana = 137,7 μg/L; 95% IC = 132,9 – 155,9) enquanto a das mulheres não grávidas se mostrou na faixa adequada (mediana = 190 μg/L; 95% IC = 159,3 – 200,1). Entre as gestantes, 57% apresentaram UIC < 150 μg/L.Conclusões : Apesar de uma maior amostragem ser necessária para a confirmação desses achados, os resultados levantam preocupação quanto à suficiência iódica nas mulheres grávidas no Brasil, principalmente diante das novas determinações governamentais brasileiras quanto à redução das concentrações de iodo no sal de cozinha para 15-45 mg/kg. Arq Bras Endocrinol Metab. 2014;58(3):282-7

Objective : The intake of adequate amounts of iodine during pregnancy is essential for the neurological development of the fetus. The aim of this study was to assess iodine nutrition status in pregnant women from the state of São Paulo, Brazil.Material and methods : We analyzed urinary iodine concentration (UIC) in 191 pregnant and 58 non-pregnant women matched by age. We used the World Health Organization criteria to define sufficient iodine supply (median UIC: 150-249 µg/L among pregnant women, and 100-199 µg/L for non-pregnant women).Results : Median UIC of the pregnant women studied was lower than the recommended value (median = 137.7 µg/L, 95% CI = 132.9 – 155.9), while non-pregnant women had UIC levels within the appropriate range (median = 190 μg/L; 95% IC = 159.3-200.1). UIC was below 150 µg/L in 57% of the pregnant women.Conclusions : Although a larger sample is needed to consolidate these findings, these results raise concerns about the adequacy of the iodine supply of pregnant women in Brazil, especially considering the new determinations of the Brazilian government, which have recently reduced the concentrations of iodine in table salt to 15-45 mg/kg of salt. Arq Bras Endocrinol Metab. 2014;58(3):282-7

OBJETIVO: Criar intervalos de referência longitudinais para os valores de índices de pulsatilidade (IP) dos fluxos nas artérias umbilicais (AU), cerebral média (ACM) e uterinas (AUt) e IP venoso do fluxo no ducto venoso (DV) com uma amostra da população brasileira. MÉTODOS: Estudo observacional longitudinal realizado de fevereiro de 2010 a maio de 2012. Gestantes de baixo risco foram submetidas a exames ultrassonográficos quinzenais da 18ª a 40ª semana para obtenção dos IP das AU, AUt, ACM e IP venoso do DV. Modelos lineares mistos foram usados para elaboração de intervalos de referência longitudinais (percentis 5, 50 e 95) dos IP dos vasos mencionados. Os IP das porções placentária e abdominal do cordão umbilical foram comparados por meio do teste t de amostras independentes. Valores de p bilaterais menores do que 0,05 foram considerados significativos. RESULTADOS: Cento e sessenta e quatro gestantes foram submetidas a 1.242 exames ultrassonográficos. Houve redução significativa nos valores de todos esses parâmetros com o avançar da IG. Entre a 18ª e a 40ª semana de gravidez, as medianas de IP da AU (porções abdominal e placentária do cordão), da ACM, do DV e do IP médio das AUt variaram de 1,19 a 0,74; 1,33 a 0,78; 1,56 a 1,39; 0,58 a 0,41; e 0,98 a 0,66, respectivamente. As equações obtidas para predição das medianas foram: IP-AU=1,5602786 - (0,020623 x IG); Logaritmo do IP-ACM=0,8149111 - (0,004168 x IG) - [0,002543 x (IG - 28,7756)²]; Logaritmo do IP-DV=-0,26691- (0,015414 x IG); IP-AUt=1,2362403 - (0,014392 x IG). Houve diferença significativa entre os IP-AU obtidos nas extremidades placentária e abdominal fetal (p<0,001). CONCLUSÃO: Foram estabelecidos intervalos de referência longitudinais dos parâmetros doplervelocimétricos gestacionais mais importantes em uma amostra da população brasileira. Estes podem ser mais adequados para o acompanhamento das modificações hemodinâmicas materno-fetais em gestações normais ou não, o que ainda requer validação futura.

PURPOSE: To create longitudinal reference intervals for pulsatility index (PI) of the umbilical (UA), middle cerebral (MCA), uterine (UtA) arteries and ductus venosus (DV) in a Brazilian cohort. METHODS: A longitudinal observational study performed from February 2010 to May 2012. Low risk pregnancies were scanned fortnightly from 18 to 40 weeks for the measurements of PI of the UA, MCA, DV and UtA. Linear mixed models were used for the elaboration of longitudinal reference intervals (5th, 50th and 95th percentiles) of these measurements. PI obtained for the placental and abdominal portions of the umbilical artery were compared by the t-test for independent samples. Two-sided p values of less than 0.05 were considered statistically significant. RESULTS: A total of 164 patients underwent 1,242 scans. There was significant decrease in PI values of all vessels studied with gestational age (GA). From the 18th to the 40th week of pregnancy, the median PI values of UA (abdominal and placental ends of the cord), MCA, DV and the mean PI of the UtA ranged from 1.19 to 0.74, 1.33 to 0.78, 1.56 to 1.39, 0.58 to 0.41, and 0.98 to 0.66, respectively. The following equations were obtained for the prediction of the medians: PI-UA=1.5602786 - (0.020623 x GA); Logarithm of the PI-MCA=0.8149111 - (0.004168 x GA) - [0.02543 x (GA - 28.7756)²]; Logarithm of the PI-DV=-0.26691- (0.015414 x GA); PI-UtA = 1.2362403 - (0.014392 x GA). There was a significant difference between the PI-UA obtained at the abdominal and placental ends of the umbilical cord (p<0.001). CONCLUSIONS: Longitudinal reference intervals for the main gestational Doppler parameters were obtained in a Brazilian cohort. These intervals could be more adequate for the follow-up of maternal-fetal hemodynamic modifications in normal and abnormal pregnancies, a fact that still requires further validation.

INTRODUÇÃO: No Brasil a depressão é um problema de saúde pública, tendo 10 milhões de pessoas com esse diagnóstico. A queda de idosos é outro comprometedor da saúde, que muitas vezes apresenta uma combinação com a depressão. OBJETIVOS: Verificar a associação entre estados depressivos e número de quedas. MATERIAIS E MÉTODOS: Estudo seccional em que foi aplicado o GDS-15 e um questionário específico. Os dados foram trabalhados no programa R pelo teste Qui-Quadrado, ao nível de significância de 95%. Foram incluídas idosas que participam do Projeto Prev-Quedas e o critério de exclusão foi apresentar deficiência auditiva não corrigida ou apresentar estágios avançados de distúrbios cognitivos e/ou doenças mentais que impedissem o entendimento das perguntas. DISCUSSÃO E RESULTADOS: Foram entrevistadas 78 idosas, com idade média de 72 anos. O percentual de pessoas com possível quadro de depressão foi de 21,8%. Não foi encontrada associação entre depressão e as variáveis idade, estado civil, morar com alguém (p > 0,05). Foi encontrada associação entre quedas e depressão (p < 0,01). CONCLUSÃO: A tendência a estados depressivos encontrada na amostra foi considerada alta, acima da média nacional observada em 1999. A associação encontrada entre o quadro de depressão e um maior número de quedas sofridas pelos participantes pode indicar a necessidade de maior atenção das políticas públicas ao problema. A ausência de medidas preventivas estaria ligada ao pior padrão de qualidade de vida relacionada à saúde.

INTRODUCTION: In Brazil depression is a public health problem. About 10 million people received this diagnosis in this country. The elderly falls are another serious health problem which is frequently related to depression. OBJECTIVE: To verify association between depressive states and number of falls. MATERIALS AND METHODS: Sectional study which used the GDS-15 and a questionnaire related to falls. For the descriptive analysis, test of normality and forces of association (Chi-Squared) it was used the R program, version 2.8.1, with the confidence level of 95%. DISCUSSION AND RESULTS: 78 old women were interviewed (mean age of 72 years). The percentage of depression was 21.8%. Falls were significantly associated with depression (p < 0,01). CONCLUSIONS: The percentage of depression observed in the study was relatively high if we compare with data in Brazil in 1999. The association between depression and a greater number of falls can indicate the need of attention of public policy. The lack of prevention can be related to a worse quality of life.

Foram sintetizados, em um único pote reacional, alguns derivados da α- e β-lapachonas a partir de reação de hetero Diels-Alder, em etanol aquoso, entre estirenos substituídos (como dienófilos) e o-quinonas metídeos (o-QMs) metilênicas e arílicas geradas por condensação de Knoevenagel da 2-hidróxi-1,4-naftoquinona com formaldeído e aldeídos aromáticos.

Methylene and aryl o-quinone methides (o-QMs) generated by Knoevenagel condensation of 2-hydroxy-1,4-naphthoquinone with formaldehyde and arylaldehydes, undergo facile hetero Diels-Alder reaction with some substituted styrenes (as dienophiles) in aqueous ethanol media providing derivatives of α- and β-lapachone.

Thiazoles comprise an important class of heterocyclic compounds present in many potent biologically active molecules. This heterocyclic ring also shows various applications in organic synthesis to obtain new compounds. This paper presents different methodologies for the preparation of thiazole ring systems, as well as their synthetic applications.