Caracterização de um novo isolado de Lysinibacillus sphaericus I5A9 e sua ação larvicida para culicídeos

O controle de populações de vetores é uma ferramenta importante para interromper o ciclo de transmissão de alguns patógenos. Bactérias do gênero Bacillus spp. já são utilizadas no controle de mosquitos devido à sua ação inseticida específica e viabilidade a longo prazo. No entanto, um desafio encontrado em campo é a seleção de mosquitos resistentes, o que faz o estudo de novas bactérias capazes de superar eventos de resistência uma opção importante para aprimorar os programas de controle vetorial. A identificação de novas toxinas bioinseticidas, em um novo isolado de Bacillus spp I5A9, por sequenciamento de nova geração, abriu portas para investigação em uma área de potencial biotecnológico para produção ou primoramento de formulações larvicidas para o controle de populações de mosquitos. O objetivo deste projeto foi investigar as propriedades genômicas, inseticidas e citomorfológicas de um novo isolado de Bacillus spp. (I5A9) coletado e isolado no estado de Pernambuco. A sequência completa do genoma desse isolado bacteriano, coletado a partir de sedimentos de amostras de charco, obtida por sequenciamento de nova geração, foi montada, seguida de predição e anotação de genes. A microscopia eletrônica de transmissão e varredura foi usada em seguida para examinar a ultraestrutura dos sedimentos bacterianos esporulados afim de analisar as características morfológicas desta nova cepa. A atividade tóxica do isolado I5A9 contra larvas de Culex quinquefasciatus (colônia de referência CqSLab) e em colônias resistentes à Bin (REC2, RIAB59), foi avaliada por bioensaios. As características encontradas no genoma de 5.1 Mb evidenciou que este isolado está filogeneticamente relacionado a Lysinibacillus sphaericus. Foram detectados genes que codificam a toxina binária (tipo I), bem como genes que codificam toxinas Cry. As análises das sequências proteicas das toxinas Cry codificadas revelaram diferentes tipos: a primeira e a segunda com 100% de identidade com a conhecida Cry49Aa e a toxina Cry48Aa da cepa L. sphaericus IAB59, que possuem características de uma toxina Cry de três domínios; e a terceira e quarta, ainda desconhecidas, anotadas preliminarmente como toxinas Cry22Aa, que não seguem o padrão. Análises ultraestruturais do cultivo bacteriano revelaram semelhanças com o gênero Bacillus, com visualização de endosporos e presença de diferentes cristais parasporais. O novo isolado I5A9 teve 100% de atividade larvicida para C. quinquefasciatusdas colônias suscetível e resistentes. As características intrínsecas detectadas nesta cepa indicam que seu modo de ação é único em relação aos larvicidas comerciais e que potencialmente também pode ser usada para o controle biológico de espécies de mosquitos. (AU).Controlling vector populations is a pivotal strategy for disrupting the transmission cycle of certain pathogens. Bacillus spp. bacteria are currently utilized for mosquito control owing to their specific insecticidal properties and enduring viability. Nevertheless, a prevalent challenge in the field involves the emergence of resistant mosquito populations. Hence, exploring new bacteria capable of overcoming resistance phenomena becomes crucial for enhancing vector control initiatives. The discovery of novel bioinsecticide toxins within a new Bacillus spp. isolate, designated as I5A9, via next-generation sequencing, has sparked interest in a biotechnologically promising avenue for developing or enhancing larvicidal formulations to curb mosquito populations. The aim of this study was to probe the genomic, insecticidal, and cytomorphological traits of the Bacillus spp. isolate (I5A9) obtained from sediments in the state of Pernambuco. The complete genome sequence of this bacterial strain, isolated from pond sediment samples and obtained through next-generation sequencing, was assembled, followed by gene prediction and annotation. Transmission and scanning electron microscopy were employed to scrutinize the ultrastructure of the sporulated bacterial sediments to analyze the morphological features of this newfound strain. Bioassays were conducted to assess the toxic activity of the I5A9 isolate against larvae of Culex quinquefasciatus (using the reference colony CqSLab) as well as Bin-resistant colonies (REC2, RIAB59). The genomic analysis of the 5.1 Mb genome indicated a phylogenetic relation to Lysinibacillus sphaericus. Genes encoding binary toxin (type I) as well as Cry toxins were identified. Examination of the protein sequences of the encoded Cry toxins revealed distinct types: the first and second exhibited 100% identity with known Cry49Aa and Cry48Aa toxins from the L. sphaericus IAB59 strain, characterized by a three-domain Cry toxin structure; while the third and fourth, yet unidentified, were provisionally denoted as Cry22Aa toxins, deviating from the established pattern. Ultrastructural analysis of the bacterial culture exhibited similarities with the Bacillus genus, showcasing the presence of endospores and various paraspora crystals. The new I5A9 isolate demonstrated 100% larvicidal efficacy against both susceptible and resistant colonies of C. quinquefasciatus. The inherent characteristics identified in this strain suggest a unique mode of action compared to commercial larvicides, indicating its potential for biological mosquito control (AU).2026-06-1

Memórias do Instituto Oswaldo Cruz celebrates 115 years of scientific publishing: what it needs to keep moving on...

Produção científica do Laboratório de Biologia Molecular e Doenças Endêmicas.Produção científica do Laboratório de Genética Molecular de Microrganismos.Produção científica do Laboratório Interdisciplinar de Pesquisas Médicas.The Federal Decree n. 1802, published in December 12th 1907,(1) determined the creation of the "Instituto de Pathologia Experimental de Manguinhos", now the "Instituto Oswaldo Cruz" and one of the current 20 research institutes of "Fundação Oswaldo Cruz - Fiocruz". The same decree also determined the creation of a journal to disseminate the research work of the 'Instituto', stating in its 9th paragraph: "The research work carried out at the 'Instituto de Manguinhos' will be published as Memorias soon after confirming the experiments." The first printed edition of the journal Memórias do Instituto Oswaldo Cruz appeared in April 1909, with the publication of eight articles exclusively from the "Instituto de Manguinhos". Articles were published in dual language, Portuguese and either German or French. That was the beginning of a scientific journal that has demonstrated resilience and adaptation to the huge political, economic and social transformations that Brazil has suffered since the end of the 19th century. It has survived to become a centennial journal that keeps publishing research work in human infectious diseases, their agents and vectors in Latin America. Of course, Memorias do IOC is also a proud member of the exclusive and "highly selective" set of scientific journals in the world that has celebrated more than a century of publishing activity. The centenary milestone notwithstanding, Memórias do IOC pathway has not been a cool journey to success and recognition. Following the turbulent period of two World Wars and the consequences for the biomedical science research, Memórias do IOC existence was severely threatened during the "hard years" of 1960 and 70's decades, when intramural instability, administrative reorganisation and economic crisis under the military dictatorship in Brazil summed up to create a "storm" that caused an interruption of its publishing operation. The journal did not publish any article during the years of 1977-1979. That was an inflexion point in Memórias do IOC pathway, and to give a wide view of the journal till this decadency period, let us remember its early operational years taking as reference the publishing practice of those earlier decades

Activity of pyridyl-pyrazolone derivatives against Trypanosoma cruzi

Produção científica do Laboratório de Biologia Celular.This research received no direct external funding. Originally, the PDL1-based pyrazolone anti-cancer program was supported by a grant from the SATT Nord. The authors thanks CNPq, FAPERJ and Fiocruz. Maria de Nazaré Correia Soeiro and O.M are CNPq and CNE fellows.New affordable drugs are needed for the treatment of infection with the protozoan parasite Trypanosoma cruzi responsible for the Chagas disease (CD). Only two old drugs are currently available, nifurtimox and benznidazole (Bz) but they exhibit unwanted side effects and display a weak activity in the late chronic phase of the disease. In this context, we evaluated the activity of a series of aryl-pyrazolone derivatives against T cruzi, using both bloodstream trypomastigote and intracellular amastigote forms of the parasite. The test compounds originate from a series of anticancer agents targeting the immune checkpoint ligand PD-L1 and bear an analogy with known anti-trypanosomal pyrazolones. A first group of 6 phenyl-pyrazolones was tested, revealing the activity of a single pyridyl-pyrazolone derivative. Then a second group of 8 compounds with a common pyridyl-pyrazolone core was evaluated. The in vitro testing process led to the identification of two non-cytotoxic and highly potent molecules against the intracellular form of T. cruzi, with an activity comparable to Bz. Moreover, one compound revealed an activity largely superior to that of Bz against bloodstream trypomastigotes, while being noncytotoxic (selectivity index >1000). Unfortunately, the compound showed little activity in vivo, most likely due to its very limited plasma stability. However, the study opens novel perspectives for the design of new antitrypanosomal products and the mechanism of action of the compounds is discussed

Entomological assessment of hessian fabric transfluthrin vapour emanators for protecting against outdoor-biting Aedes aegypti in coastal Tanzania

Produção científica do Laboratório de Fisiologia e Controle de Artrópodes Vetores (vigente até jan/2023).This research was primarily funded by the UK Medical Research Council, the Newton Fund and the Wellcome Trust through their join Zika Rapid Response scheme (Award number MC_PC_15086) and the United States Agency for International Development through its Combating Zika and Future Threats: A Grand Challenge for Development scheme (Award number AID-OAA-F16-00095).Nicodem J. Govella is supported by the African Research Leaders Award (Grant Ref: MR/T008873/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO) under the MRC/FCDO Concordat agreement, which is part of the EDCTP2 programme supported by the European Union.Gerry F. Killeen was partially supported by an AXA Research Chair award, jointly funded by the AXA Research Fund and the College of Science, Engineering and Food Sciences at University College Cork.Open access publication was funded and facilitated through the ongoing agreement between PLoS and the IReL consortium of Irish research libraries.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Background: A low technology emanator device for slowly releasing vapour of the volatile pyrethroid transfluthrin was recently developed in Tanzania that provides robust protection against night biting Anopheles and Culex vectors of malaria and filariasis for several months. Here these same emanator devices were assessed in Dar es Salaam city, as a means of protection against outdoor-biting Aedes (Stegomia) aegypti, the most important vector of human arboviruses worldwide, in parallel with similar studies in Haiti and Brazil. Methods: A series of entomological experiments were conducted under field and semi-field conditions, to evaluate whether transfluthrin emanators protect against wild Ae. aegypti, and also compare the transfluthrin responsiveness of Ae. aegypti originating from wild-caught eggs to established pyrethroid-susceptible Ae. aegypti and Anopheles gambiae colonies. Preliminary measurements of transfluthrin vapour concentration in air samples collected near treated emanators were conducted by gas chromatography-mass spectrometry. Results: Two full field experiments with four different emanator designs and three different transfluthrin formulations consistently indicated negligible reduction of human landing rates by wild Ae. aegypti. Under semi-field conditions in large cages, 50 to 60% reductions of landing rates were observed, regardless of which transfluthrin dose, capture method, emanator placement position, or source of mosquitoes (mildly pyrethroid resistant wild caught Ae. aegypti or pyrethroid-susceptible colonies of Ae. aegypti and An. gambiae) was used. Air samples collected immediately downwind from an emanator treated with the highest transfluthrin dose (15g), contained 12 to 19 μg/m3 transfluthrin vapour. Conclusions: It appears unlikely that the moderate levels of pyrethroid resistance observed in wild Ae. aegypti can explain the modest-to-undetectable levels of protection exhibited. While potential inhalation exposure could be of concern for the highest (15g) dose evaluated, 3g of transfluthrin appears sufficient to achieve the modest levels of protection that were demonstrated entomologically. While the generally low levels of protection against Aedes reported here from Tanzania, and from similar entomological studies in Haiti and Brazil, are discouraging, complementary social science studies in Haiti and Brazil suggest end-users perceive valuable levels of protection against mosquitoes. It therefore remains unclear whether transfluthrin emanators have potential for protecting against Aedes vectors of important human arboviruses

Identification of a founder effect involving n.197C>T variant in RMRP gene associated to cartilage‑hair hypoplasia syndrome in brazilian patients

Produção científica do Laboratório de Hanseníase.This study was partially supported by funds from Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq—INAGEMP (465549/2014-4).Coordenação de Aperfeiçoamento de Pessoal de Nível Superior- CAPES—INAGEMP (88887.136366/2017–00) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul—FAPERGS—INAGEMP (17/2551-0000521-0).Maria Eduarda Gomes was supported by fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 and Fundação para o Desenvolvimento Científico e Tecnológico em Saúde—FIOTEC (VPPCB-002-FIO-22).Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder frequently linked to n.72A>G (previously known as n.70A>G and n.71A>G), the most common RMRP variant worldwide. More than 130 pathogenic variants in this gene have already been described associated with CHH, and founder alterations were reported in the Finnish and Japanese populations. Our previous study in Brazilian CHH patients showed a high prevalence of n.197C>T variant (former n.195C>T and n.196C>T) when compared to other populations. The aim of this study was to investigate a possible founder effect of the n.197C>T variant in the RMRP gene in a series of CHH Brazilian patients. We have selected four TAG SNPs within chromosome 9 and genotyped the probands and their parents (23 patients previously described and nine novel). A common haplotype to the n.197C>T variant carriers was identified. Patients were also characterized for 46 autosomal Ancestry Informative Markers (AIMs). European ancestry was the most prevalent (58%), followed by African (24%) and Native American (18%). Our results strengthen the hypothesis of a founder effect for the n.197C>T variant in Brazil and indicate that this variant in the RMRP gene originated from a single event on chromosome 9 with a possible European origin

Description of Corynebacterium hiratae sp. nov. isolated from a human tissue bone a novel member of Corynebacterium Genus

Produção científica do Laboratório Interdisciplinar de Pesquisas Médicas.This work was supported by Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) # E-17/205.900/2022 and # E-26/202.088/2020.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) # 309948/2018-5.Secretaria de Ciencia y Técnica de la Universidad de Buenos Aires (UBACyT) # 20020170100109 BA.Background: Corynebacterium spp. are widely disseminated in the environment, and they are part of the skin and mucosal microbiota of animals and humans. Reports of human infections by Corynebacterium spp. have increased considerably in recent years and the appearance of multidrug resistant isolates around the world has drawn attention. Objectives: To describe a new species of Corynebacterium from human tissue bone is described after being misidentified using available methods. Methods: For taxonomic analyses, phylogenetic analysis of 16S rRNA and rpoB genes, in silico DNA-DNA hybridization, average nucleotide and amino acid identity, multilocus sequence analysis, and phylogenetic analysis based on the complete genome were used. Findings: Genomic taxonomic analyzes revealed values of in silico DNA-DNA hybridization, average nucleotide and amino acids identity below the values necessary for species characterization between the analyzed isolates and the closest phylogenetic relative Corynebacterium aurimucosum DSM 44532ᵀ. Main conclusions: Genomic taxonomic analyzes indicate that the isolates analyzed comprise a new species of the Corynebacterium genus, which we propose to name Corynebacterium hiratae sp. nov. with isolate 332ᵀ (=CBAS 826ᵀ=CCBH 35,014ᵀ) as the type strain

Investigação molecular de protozoários da classe Kinetoplastea e família Sarcocystidae em mamíferos silvestres no estado do Amazonas

Animais silvestres são importantes reservatórios de patógenos em diversos ecossistemas e participam do ciclo de transmissão de variadas doenças que também acometem as populações humanas. Diante do aumento da temperatura global, mudanças climáticas e os processos de antropização do ambiente, observamos maior proximidade e contato entre animais de vida livre, animais domésticos e humanos, sendo este um fator importante para a ocorrência de doenças zoonóticas. A Toxoplasmose, Leishmaniose, Doença de Chagas são zoonoses de grande importância para saúde pública, que ocorrem na região Amazônica e contam com a participação de mamíferos silvestres no seu ciclo de transmissão. Neste estudo, foi realizada uma investigação molecular, por meio de Nested-PCR, de protozoários da classe Kinetoplastea e família Sarcocystidae em mamíferos silvestres recebidos no Centro de Triagem de Animais Silvestres (CETAS) da Superintendência do IBAMA no Amazonas. Um total de 95 mamíferos foram amostrados, 47 da ordem Primates, 34 da ordem Pilosa, 2 da ordem Cingulata, 7 da ordem Rodentia, 2 da ordem Carnivora e 2 da ordem Didelphimorphia. A partir dos resultados de identificação molecular, foi observada a presença de protozoários Kinetoplastea e Sarcocystidae em 29 mamíferos silvestres de 11 espécies distintas, pertencentes a Superordem Xenarthras e Ordem Primates. Dentre as espécies de parasitas encontrados estão Endotrypanum sp. em exemplares de Choloepus didactylus, Sarcocystis sp. em Saimiri sp., C. didactylus, Dasypus novemcinctus e Tamandua tetradactyla, Toxoplasma gondii em Lagothrix cana, Saguinus bicolor e Saimiri sciureus, Trypanosoma rangeli em exemplares de Sapajus apella e Trypanosoma minasense-like em Bradypus tridactylus, Cebus albifrons, L. cana, Pithecia sp., S. bicolor, Saguinus midas e S. apella. Foram encontrados também, sequências similares aos de protozoários de vida livre Parabodo caudatus e Bodo sp. em amostras de C. didactylus e Dimastigella sp. em amostras de Saimiri sp. e S. bicolor. Embora Trypanosoma cruzi e Leishmania spp. tenham sido os principais alvos no protocolo de detecção, nenhuma evidência foi encontrada nos animais amostrados. Este estudo mostrou que os Xenarthras e Primatas, podem albergar diversas espécies de protozoários/parasitas, gerando reflexão quanto a dinâmica de transmissão e o risco à população humana, tornando evidente a importância do monitoramento ativo destes parasitas em mamíferos silvestres.Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM)Wild animals are important pathogens reservoirs in various ecosystems; they participate in transmission cycle of many diseases that also affect human populations. In the face of rising global temperatures, climate change and environmental anthropization processes, we are seeing greater proximity and contact between free-living animals, domestic animals and humans, which is an important factor in the occurrence of zoonotic diseases. Toxoplasmosis, Leishmaniasis and Chagas Disease are zoonoses of great importance to public health, which occur in the Amazon region and involve wild mammals in their transmission cycle. This study carried out a molecular investigation, using Nested-PCR, of protozoa of the Kinetoplastea class and the Sarcocystidae family in wild mammals received at the Centro de Triagem de Animais Silvestres (CETAS) of the IBAMA Superintendence in Amazonas. A total of 95 mammals were sampled, 47 of Primates order, 34 of Pilosa order, 2 of Cingulata order, 7 of Rodentia order, 2 of Carnivora order and 2 of Didelphimorphia order. The results of the molecular identification, pointed out the presence of Kinetoplastea and Sarcocystidae in 29 wild mammals of 11 different species, of Superorder Xenarthras and Order Primates. Among the parasite species found were Endotrypanum sp. in specimens of Choloepus didactylus, Sarcystis sp. in Saimiri sp., C. didactylus, Dasypus novemcinctus and Tamandua tetradactyla, Toxoplasma gondii in Lagothrix cana, Saguinus bicolor and Saimiri sciureus, Trypanosoma rangeli in Sapajus apella and Trypanosoma minasense-like in Bradypus tridactylus, Cebus albifrons, L. cana, Pithecia sp., S. bicolor, Saguinus midas and S. apella. Sequences similar to free-living protozoa Parabodo caudatus and Bodo sp. were also discovered in samples of C. didactylus and Dimastigella sp. in samples of Saimiri sp. and S. bicolor. Although Trypanosoma cruzi and Leishmania spp. were the main targets in detection protocol, no evidence was found in animals sampled. This study has showed that Xenarthras and Primates can harbor many species of protozoa/parasites, generating reflection on the dynamics of transmission and the risk to human population, making the importance of active monitoring of these parasites in wild mammals evident

Racial inequalities in the development of multimorbidity of chronic conditions: results from a Brazilian prospective cohort

Produção científica do Laboratório de Educação em Ambiente e Saúde.Antecedentes e objetivos: A ocorrência de multimorbidade e seus impactos têm afetado de forma diferenciada os subgrupos populacionais. As evidências sobre sua incidência provêm principalmente de regiões de alta renda, com exploração limitada das disparidades raciais. Este estudo investigou a associação entre grupos raciais e o desenvolvimento de multimorbidade e de condições crônicas no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Métodos: Foram analisados dados de participantes autodeclarados brancos, pardos (raças mistas) e pretos na linha de base do ELSA-Brasil (2008-2010) que estavam em risco para a multimorbidade. O desenvolvimento de condições crônicas foi avaliado a partir das visitas presenciais e autorrelato de diagnóstico por telefone até a terceira visita de seguimento (2017-2019). A multimorbidade foi definida quando na visita de seguimento o participante possuía duas ou mais morbidades. Foram estimadas incidências acumuladas, taxas de incidência e razões das taxas de incidência (RTI) ajustadas a partir de modelos de Poisson. Resultados: Em um acompanhamento de 8,3 anos, em comparação aos participantes brancos: os pardos tiveram uma incidência 27% maior de hipertensão e obesidade; e os pretos tiveram uma incidência 62% e 45% maior, respectivamente. Os pretos também tiveram 58% mais diabetes. A incidência de câncer foi maior entre os brancos. A multimorbidade afetou 41% dos participantes, com uma taxa bruta de incidência de 57,5 casos por 1.000 pessoasano (variando de 56,3 para brancos a 63,9 para pretos). Estimativas ajustadas mostraram incidência 20% maior de multimorbidade em pretos comparados aos brancos (RTI: 1,20; IC 95%: 1,05-1,38). Conclusões: Foram observadas disparidades raciais significativas no risco de condições crônicas e multimorbidade. Muitas associações revelaram um aumento gradiente no risco de doenças de acordo com tons de pele mais escuros. Abordar causas fundamentais como o racismo e a discriminação racial, juntamente com a consideração dos determinantes sociais da saúde, é vital para o cuidado abrangente da multimorbidade. Políticas intersetoriais e equitativas são essenciais para a garantia do direito à saúde aos grupos historicamente marginalizados.This work was supported by Brazil’s Ministry of Health and Ministry of Science, Technology and Innovation (to ELSA-Brasil).The Studies and Projects Funder—FINEP (to ELSA-Brasil).The National Scientific and Technological Development Council—CNPq (to ELSA-Brasil and Productivity Scholarship to Rosane Härter Griep).The Carlos Chagas Rio de Janeiro State Research Support Foundation—FAPERJ (PhD grant Nota 10 E-26/200,636/2021 to Fernanda Esthefane Garrides Oliveira; Young Scientist of Our State program E-26/201,277/2021 to Leonardo Soares Bastos Scientist of Our State program to Rosane Härter Griep and Maria de Jesus Mendes da Fonseca).The funders played no role in the study’s conceptualisation, design, data collection, analysis, decision to publish or preparation of the manuscript.Background: The occurrence of multimorbidity and its impacts have differentially affected population subgroups. Evidence on its incidence has mainly come from high-income regions, with limited exploration of racial disparities. This study investigated the association between racial groups and the development of multimorbidity and chronic conditions in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: Data from self-reported white, brown (pardos or mixed-race), and black participants at baseline of ELSABrasil (2008–2010) who were at risk for multimorbidity were analysed. The development of chronic conditions was assessed through in-person visits and self-reported diagnosis via telephone until the third follow-up visit (2017–2019). Multimorbidity was defined when, at the follow-up visit, the participant had two or more morbidities. Cumulative incidences, incidence rates, and adjusted incidence rate ratios (IRRs) were estimated using Poisson models. Results: Over an 8.3-year follow-up, compared to white participants: browns had a 27% greater incidence of hypertension and obesity; and blacks had a 62% and 45% greater incidence, respectively. Blacks also had 58% more diabetes. The cancer incidence was greater among whites. Multimorbidity affected 41% of the participants, with a crude incidence rate of 57.5 cases per 1000 person-years (ranging from 56.3 for whites to 63.9 for blacks). Adjusted estimates showed a 20% higher incidence of multimorbidity in black participants compared to white participants (IRR: 1.20; 95% CI: 1.05–1.38). Conclusions: Significant racial disparities in the risk of chronic conditions and multimorbidity were observed. Many associations revealed a gradient increase in illness risk according to darker skin tones. Addressing fundamental causes such as racism and racial discrimination, alongside considering social determinants of health, is vital for comprehensive multimorbidity care. Intersectoral, equitable policies are essential for ensuring health rights for historically marginalized groups

In vitro antifungal activity of MMV Pathogen Box® compounds alone or in combination with antifungal drugs against mucormycosis agents

Mucormycosis is a severe fungal infection that demands immediate and decisive intervention upon suspicion. The causative agents of mucormycosis exhibit inherent resistance to echinocandins and voriconazole, and their in vitro susceptibility to terbinafine is highly variable and species-specific. Considering these factors and the limitations of currently available antifungal therapies, the identification of novel antifungals with potent activity against mucormycosis is of paramount importance. This study aims to identify compounds from the MMV Pathogen Box® presenting antifungal activity against selected mucormycosis agents and to evaluate their potential synergistic effects when combined with antifungal drugs. A screening of the Pathogen Box® compounds was conducted, isolated or in combination with sub-inhibitory concentrations of amphotericin B, isavuconazole or posaconazole, against a Rhizopus oryzae strain. Hits from the screenings were further evaluated against eight Mucoralean strains for minimal inhibitory and fungicidal concentration determinations and to confirm synergistic interactions using the checkerboard method. Ultrastructural studies were performed using scanning electron microscopy. MMV675968 exhibited fungicidal activity against a R. oryzae strain. All but one Rhizopus spp. strains presented MIC ≤ 1 μg/mL, with a geometric mean of 0.78 μg/mL observed across all isolates for this compound, which did not change significantly the cellular structure of this fungus. The combination screening with antifungal drugs revealed six additional compounds potentially active against the R. oryzae strain, two of them demonstrated proven synergism through the checkerboard assay. This first study with the MMV Pathogen Box® and Zigomycetes highlights promising new treatment options for mucormycosis in the future

Violência contra as mulheres que vivem em contextos rurais

Este Sumário Executivo contém os resultados da Tese de Doutorado intitulada: “Entre dados e histórias de vida: (rompendo) o silenciamento da violência contra mulheres que vivem em contextos rurais” apresentada no Programa de Pós-graduação em Saúde Pública, da Escola Nacional de Saúde Pública Sergio Arouca, na Fundação Oswaldo Cruz. Autora: Luciane Stochero Orientadora: Liana Wernersbach PintoFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) – Bolsa Faperj Nota 10