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    Biological activities of the essential oil from the leaves of Lantana montevidensis (Spreng) Briq. in mice

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    Ribeiro Filho, Jaime. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. “Documento protegido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001, Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP)—Finance Code BPI and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Financiadora de Estudos e Projetos—Brasil (FINEP).This work aimed to analyze the chemical composition and evaluate the anti-inflammatory and antinociceptive properties of the essential oil obtained from the leaves of Lantana montevidensis (OEFLM) in mice. The chemical composition of the OEFLM was analyzed by GC–MS, and its effects on the central nervous system were determined by the open field and rotarod tests. The antinociceptive and anti-inflammatory screenings were conducted using the formalin test, as well as the acetic acid-induced abdominal contortion assay. The antinociceptive activity was assessed by the tail-flick and hot plate tests. The systemic anti-inflammatory activity was determined using models of paw edema induced by carrageenan, dextran, histamine, or arachidonic acid. The effects of the essential oil on vascular permeability and granuloma formation were also investigated. The chemical composition of the OEFLM revealed the presence of valencene (17.93%), bicyclogermacrene (16.35%), trans-caryophyllene (12.84%) and germacrene D (12.18%). The administration of OEFLM at the dose of 2000 mg/Kg caused no evident toxicity. While OEFLM (25, 50, 100, and 200 mg/kg) did not present significant anxiolytic-loke or sedative effects, it showed promising antinociceptive and anti-inflammatory activities. The results of this study indicate that the OEFLM has analgesic and anti-inflammatory activities in animal models by inhibiting acute and chronic inflammation

    Mefloquine synergism with anti-tuberculosis drugs and correlation to membrane effects: Biologic, spectroscopic and molecular dynamics simulations studies

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    Studies displaying the combination of mefloquine (MFL) with anti-tuberculosis (TB) substances are limited in the literature. In this work, the effect of MFL-association with two first-line anti-TB drugs and six fluoroquinolones was evaluated against Mycobacterium tuberculosis drug resistant strains. MFL showed synergistic interaction with isoniazid, pyrazinamide, and several fluoroquinolones, reaching fractional inhibitory concentration indexes (FICIs) ranging from 0.03 to 0.5. In order to better understand the observed results, two approaches have been explored: (i) spectroscopic responses attributed to the effect of MFL on physicochemical properties related to a liposomal membrane model composed by soybean asolectin; (ii) molecular dynamics (MD) simulation data regarding MFL interaction with a membrane model based on PIM2, a lipid constituent of the mycobacterial cell wall. FTIR and NMR data showed that MFL affects expressively the region between the phosphate and the first methylene groups of soybean asolectin membranes, disordering these regions. MD simulations results detected high MFL density in the glycolipid interface and showed that the drug increases the membrane lateral diffusion, enhancing its permeability. The obtained results suggest that synergistic activities related to MFL are attributed to its effect of lipid disorder and membrane permeability enhancement

    Lançamento: Aedes de A a Z

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    Legendado. Tradução para Libras.Vídeo de lançamento do livro "Aedes de A a Z". Produzido pela Editora Fiocruz: março de 2021. Pauta: Marcella Vieira. Edição: Vanessa Freitas. Revisão: Thaís Pedretti

    Saúde Amanhã: Textos para Discussão 77: Saúde Urbana, cidades e a interseção de sistemas: panorama, agendas, gaps e oportunidades rumo à equidade, sustentabilidade, resiliência e promoção à saúde

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    Publicação cujo objetivo é divulgar resultados de estudos desenvolvidos no âmbito do Projeto Saúde Amanhã, disseminando informações sobre a prospecção estratégica em saúde, em um horizonte móvel de 20 anos. Busca, ainda, estabelecer um espaço para discussões e debates entre os profissionais especializados e instituições do setor. As opiniões emitidas nesta publicação são de exclusiva e de inteira responsabilidade do autor, não exprimindo, necessariamente, o ponto de vista da Fiocruz/MS. O projeto Saúde Amanhã é conduzido pela Fundação Oswaldo Cruz (Fiocruz) no contexto da “Estratégia Fiocruz para a Agenda 2030”/Fiocruz. É permitida a reprodução deste texto e dos dados nele contidos, desde que citada a fonte. Reproduções para fins comerciais são proibidas.Waleska Teixeira Caiaffa, da Universidade Federal de Minas Gerais, foi convidada pela Fiocruz, para autoria e desenvolvimento do conteúdo do trabalho. Amanda Cristina de Souza Andrade, da Universidade Federal de Minas Gerais, foi convidada pela Fiocruz, para autoria e desenvolvimento do conteúdo do trabalho. Aline Dayrell Ferreira Sales, da Universidade Federal de Minas Gerais, foi convidada pela Fiocruz, para autoria e desenvolvimento do conteúdo do trabalho. Débora Moraes Coelho, da Universidade Federal de Minas Gerais, foi convidada pela Fiocruz, para autoria e desenvolvimento do conteúdo do trabalho.Neste capítulo serão abordados aspectos conceituais da saúde urbana, entendendo que o metabolismo complexo das cidades e as interseções dos sistemas urbanos, representados pelos ambientes sociais e físicos (naturais e construídos) conformam redes e conexões de exposições, com relevantes implicações sanitárias, agudização dos problemas sociais, como a violência e os acidentes de trânsito, além da presença de doenças infecciosas emergentes e reemergentes

    Chikungunya virus replicative profile in Vero cells for immunobiological development purposes

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    Os autores externos submeteram sua publicação para apresentação de trabalho no evento “International Symposium on Immunobiologicals”, que foi coordenado e organizado pelo Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), da Fundação Oswaldo Cruz

    Economic evaluations addressing diagnosis and treatment strategies for neglected tropical diseases: an overview

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    Neglected tropical diseases (NTDs) are those affecting vulnerable people and causing additional social and economic burden. The aim of this study was to carry out a general overview of the health economic assessments involving the diagnosis and treatment of six NTDs: cutaneous leishmaniasis (CL), Chagas disease, cysticercosis, filariasis, schistosomiasis and visceral leishmaniasis (VL). The literature search was based on two of the main medical literature databases (Medline and SciELO) and identified 46 studies. Twenty-six studies (57%) addressed therapeutic strategies, while other 20 (43%) assessed diagnostic or both diagnostic and therapeutic approaches. The studies were published between 1994 and 2021, and 57% of them (26/46) were carried out in four countries. Cost-effectiveness analyses were conducted in 59% (27/46) of the studies. Economic studies of NTDs have timidly increased in recent years. Despite the improvement of analytical methods, completeness and accuracy of information, there are few new technologies applied to NTDs and public health systems. In addition, economic studies for NTDs are concentrated in a few countries. Thus, this review points out the need for investment in research, development and training of human resources dedicated to the economic analysis in health, especially on NTDs, as a strategy to reduce inequalities by optimizing the use of health resources

    Novel ruthenium(III) complexes with hydroxybenzophenones: experimental and theoretical characterization and in vitro leishmanicidal activity comparing complexes and ligands

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    FINEP (ref. 134/08)CNPq (448723/2014-0; 308162/2015-3; 428475/2018-3)CAPES (PNPD and MS grant – Finance Code 001)FAPEMIG (APQ-00273-14; APQ-02486-14; PPM-00533-16; APQ-01835-18)In this study, novel ruthenium(III) complexes with hydroxybenzophenones with the general formula cis-[RuCl2(HB)(dppb)] were obtained, where HB = 2-hydroxy-4-(octyloxy)benzophenone (C1), 2-hydroxy4-methoxybenzophenone (C2), 2,20-dihydroxy-4,40-dimethoxybenzophenone (C3), 2,20-dihydroxy-4-methoxybenzophenone (C4), 2,4-dihydroxybenzophenone (C5), and 2,4,40-trihydroxybenzophenone (C6), and dppb = 1,4-bis(diphenylphosphine)butane. These compounds were characterized by elemental analysis, molar conductivity, cyclic voltammetry, infrared and UV-vis spectroscopy, and powder X-ray diffraction. The crystal structures of C2, C3, C4, and C5 were determined by single-crystal X-ray diffraction analysis which confirmed the bidentate coordination of the carbonyl and phenolate oxygens of HB with ruthenium(III). Additionally, the cis geometry and electronic transitions of C1–C6 were investigated using DFT calculations. Finally, the comparative activity against promastigote forms of L. amazonensis was made available for the ligands HB1–HB6 and C1–C6. The ligands significantly inhibited the proliferation of promastigote forms, confirming the results previously published by some of us. Unfortunately, their respective complexes showed no activity. It is important to emphasize that the leishmanicidal activity of 2,20-dihydroxy-4,40-dimethoxybenzophenone (HB3), 2,20-dihydroxy-4-methoxybenzophenone (HB4), and 2,4,40-trihydroxybenzophenone (HB6) ligands is reported here for the first time. Despite the fact that they were less active against promastigote forms when compared to amphotericin B, two of them (HB4 and HB6) were less cytotoxic to J774 macrophages

    Epitranscriptome machinery in Trypanosomatids: New players on the table?

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    Trypanosoma and Leishmania parasites cause devastating tropical diseases resulting in serious global health consequences. These organisms have complex life cycles with mammalian hosts and insect vectors. The parasites must, therefore, survive in different environments, demanding rapid physiological and metabolic changes. These responses depend upon regulation of gene expression, which primarily occurs posttranscriptionally. Altering the composition or conformation of RNA through nucleotide modifications is one posttranscriptional mechanism of regulating RNA fate and function, and modifications including N6-methyladenosine (m6A), N1-methyladenosine (m1A), N5-methylcytidine (m5C), N4-acetylcytidine (ac4C), and pseudouridine (Ψ), dynamically regulate RNA stability and translation in diverse organisms. Little is known about RNA modifications and their machinery in Trypanosomatids, but we hypothesize that they regulate parasite gene expression and are vital for survival. Here, we identified Trypanosomatid homologs for writers of m1A, m5C, ac4C, and Ψ and analyze their evolutionary relationships. We systematically review the evidence for their functions and assess their potential use as therapeutic targets. This work provides new insights into the roles of these proteins in Trypanosomatid parasite biology and treatment of the diseases they cause and illustrates that Trypanosomatids provide an excellent model system to study RNA modifications, their molecular, cellular, and biological consequences, and their regulation and interplay

    Leishmania (V.) braziliensis infection promotes macrophage autophagy by a LC3B-dependent and BECLIN1-independent mechanism

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    Leishmania (Viannia) braziliensis is one of the main etiological agents of tegumentary leishmaniasis in Latin America. The establishment of a successful infection in host cells requires several key events including phago cytosis, phagolysosomal maturation impairment, and parasite replication. Autophagy is accountable for the physiological turnover of cellular organelles, degradation of macromolecular structures, and pathogen elimi nation. In many cases, autophagy control leads to a successful infection, both impairing pathogen elimination or providing nutrients. Here, we have investigated the relationship between autophagy and L. braziliensis infection. We observed that BECLIN1 expression was upregulated early on infection in both in vitro macrophage cultures and biopsies of cutaneous lesions from L. braziliensis infected patients. On the other hand, LC3B expression was downregulated in cutaneous lesions biopsies. A transient pattern of LC3+ cells was observed along L. braziliensis infection, but the number of LC3 puncta did not vary. Additionally, autophagy induction, with rapamycin treatment or through starvation, reduced infection. As expected, rapamycin increased the percentage of LC3+ cells and the number of puncta, but the presence of parasite restricted this effect, indicating LC3-associated autophagy impairment by L. braziliensis. Finally, silencing LC3B but not BECLIN1 promoted infection, confirm ing BECLIN1 independent and LC3B-related control by the parasite. Taken together, these data indicate macrophage autophagic machinery manipulation by L. braziliensis, resulting in successful establishment and survival into the host cell.202

    Caesarean section in pregnancies conceived by assisted reproductive technology: a systematic review and meta-analysis

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    Canadian Institutes of Health Research (CIHR) / Institute of Human Development, child and Youth Health (IHDCYH) / Clinician Investigators Program, Grant number MFM – 146444.Background: Caesarean section rates are higher among pregnancies conceived by assisted reproductive technology (ART) compared to spontaneous conceptions (SC), implying an increase in neonatal and maternal morbidity. We aimed to compare caesarean section rates in ART pregnancies versus SC, overall, by indication (elective versus emergent), and by type of ART treatment (in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), fresh embryo transfer, frozen embryo transfer) in a systematic review and meta-analysis. Methods: We searched Medline, EMBASE and CINAHL databases using the OVID Platform from 1993 to 2019, and the search was completed in January 2020. The eligibility criteria were cohort studies with singleton conceptions after in vitro fertilization and/or intracytoplasmic sperm injection using autologous oocytes versus spontaneous conceptions. The study quality was assessed using the Newcastle Ottawa Scale and GRADE approach. Meta-analyses were performed using odds ratios (OR) with a 95% confidence interval (CI) using random effect models in RevMan 5.3, and I squared (I2 ) test > 75% was considered as high heterogeneity. Results: One thousand seven hundred fifty studies were identified from the search of which 34 met the inclusion criteria. Compared to spontaneous conceptions, IVF/ICSI pregnancies were associated with a 1.90-fold increase of odds of caesarean section (95% CI 1.76, 2.06). When stratified by indication, IVF/ICSI pregnancies were associated with a 1.91- fold increase of odds of elective caesarean section (95% CI 1.37, 2.67) and 1.38-fold increase of odds of emergent caesarean section (95% CI 1.09, 1.75). The heterogeneity of the studies was high and the GRADE assessment moderate to low, which can be explained by the observational design of the included studies. Conclusions: The odds of delivering by caesarean section are greater for ART singleton pregnancies compared to spontaneous conceptions. Preconception and pregnancy care plans should focus on minimizing the risks that may lead to emergency caesarean sections and finding strategies to understand and decrease the rate of elective caesarean sections

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