RESUMO
Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, we investigated the associations of the TNF -308G/A and IFNG +874T/A polymorphisms with COVID-19. We analyzed the frequencies of the two polymorphisms in the control groups (CG: TNF -308G/A, n = 497; IFNG +874T/A, n = 397), a group of patients with COVID-19 (CoV, n = 222) and among the subgroups of patients with nonsevere (n = 150) and severe (n = 72) COVID-19. We found no significant difference between the genotypic and allelic frequencies of TNF -308G/A in the groups analyzed; however, both the frequencies of the high expression genotype (TT) (CoV: 13.51% vs. CG: 6.30%; p = 0.003) and the *T allele (CoV: 33.56% vs. CG: 24. 81%; p = 0.001) of the IFNG +874T/A polymorphism were higher in the COVID-19 group than in the control group, with no differences between the subgroups of patients with nonsevere and severe COVID-19. The *T allele of IFNG +874T/A (rs2430561) is associated with susceptibility to symptomatic COVID-19. These SNPs provided valuables clues about the potential mechanism involved in the susceptibility to developing symptomatic COVID-19.
Assuntos
COVID-19 , Predisposição Genética para Doença , Genótipo , Interferon gama , SARS-CoV-2 , Feminino , Humanos , Masculino , Alelos , COVID-19/genética , COVID-19/virologia , Síndrome da Liberação de Citocina/genética , Frequência do Gene , Interferon gama/genética , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/patogenicidade , Fator de Necrose Tumoral alfa/genéticaRESUMO
Carbapenem-resistant Klebsiella pneumoniae (CRKP) exhibit high mortality rates in pediatric patients and usually belong to international high-risk clones. This study aimed to investigate the molecular epidemiology and carbapenem resistance mechanisms of K. pneumoniae isolates recovered from pediatric patients, and correlate them with phenotypical data. Twenty-five CRKP isolates were identified, and antimicrobial susceptibility was assessed using broth microdilution. Carbapenemase production and ß-lactamase genes were detected by phenotypic and genotypic tests. Multilocus sequence typing was performed to differentiate the strains and whole-genome sequencing was assessed to characterize a new sequence type. Admission to the intensive care unit and the use of catheters were significantly positive correlates of CRKP infection, and the mortality rate was 36%. Almost all isolates showed multidrug-resistant phenotype, and most frequent resistant gene was blaKPC. We observed the dissemination of ST307 and clones belonging to CG258, which are considered high risk. In pediatric patients, these clones present with high genomic plasticity, favoring adaptation of the KPC and NDM enzymes to healthcare environments.
Assuntos
Antibacterianos , Carbapenêmicos , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , beta-Lactamases , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/classificação , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/epidemiologia , Brasil , Criança , Antibacterianos/farmacologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Carbapenêmicos/farmacologia , Pré-Escolar , Lactente , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/classificação , Masculino , Feminino , Proteínas de Bactérias/genética , Sequenciamento Completo do Genoma , Adolescente , Genótipo , Epidemiologia Molecular , Farmacorresistência Bacteriana Múltipla/genéticaRESUMO
The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID.
Assuntos
COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , Interferon-alfa , Interleucina-6 , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Transdução de Sinais/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
In brief: Pyruvate metabolism is one of the main metabolic pathways during oocyte maturation. This study demonstrates that pyruvate metabolism also regulates the epigenetic and molecular maturation in bovine oocytes. Abstract: Pyruvate, the final product of glycolysis, undergoes conversion into acetyl-CoA within the mitochondria of oocytes, serving as a primary fuel source for the tricarboxylic acid (TCA) cycle. The citrate generated in the TCA cycle can be transported to the cytoplasm and converted back into acetyl-CoA. This acetyl-CoA can either fuel lipid synthesis or act as a substrate for histone acetylation. This study aimed to investigate how pyruvate metabolism influences lysine 9 histone 3 acetylation (H3K9ac) dynamics and RNA transcription in bovine oocytes during in vitro maturation (IVM). Bovine cumulus-oocyte complexes were cultured in vitro for 24 h, considering three experimental groups: Control (IVM medium only), DCA (IVM supplemented with sodium dichloroacetate, a stimulant of pyruvate oxidation into acetyl-CoA), or IA (IVM supplemented with sodium iodoacetate, a glycolysis inhibitor). The results revealed significant alterations in oocyte metabolism in both treatments, promoting the utilization of lipids as an energy source. These changes during IVM affected the dynamics of H3K9ac, subsequently influencing the oocyte's transcriptional activity. In the DCA and IA groups, a total of 148 and 356 differentially expressed genes were identified, respectively, compared to the control group. These findings suggest that modifications in pyruvate metabolism trigger the activation of metabolic pathways, particularly lipid metabolism, changing acetyl-CoA availability and H3K9ac levels, ultimately impacting the mRNA content of in vitro matured bovine oocytes.
Assuntos
Histonas , Técnicas de Maturação in Vitro de Oócitos , Animais , Bovinos , Feminino , Técnicas de Maturação in Vitro de Oócitos/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos , Acetilcoenzima A/metabolismo , Histonas/metabolismo , Oócitos/metabolismo , Ácido Pirúvico/farmacologia , Ácido Pirúvico/metabolismo , Epigênese Genética , Células do CúmuloRESUMO
This study aims to identify the individual community strategies to avoid violence exposure most used by adolescents from public and private schools in the IX Administrative Region of Rio de Janeiro and investigate the profile of co-occurrence and its prevalence in specific population subgroups. This is a cross-sectional study with 693 individuals. A multidimensional questionnaire collected information regarding strategies to avoid community violence exposure and was self-completed in the classroom. The most used strategies were avoiding walking close to armed people (55.5%), avoiding walking alone (30.5%), and avoiding returning home at dawn (24.7%). Girls adopt more of all (concurrently) the four limiting behaviors to reduce their community violence exposure (53% vs. 32%). Notably, the adoption of such strategies differed by socioeconomic indicators and was higher among adolescents from lower-income households. These findings point to the high frequency of use of such strategies by adolescents, which may hinder and limit the full development of their social and cultural skills.
O objetivo do estudo é conhecer as estratégias individuais mais utilizadas por adolescentes de escolas públicas e privadas da IX Região Administrativa do município do Rio de Janeiro para evitar a exposição à violência comunitária, bem como investigar o perfil de coocorrência e sua prevalência em subgrupos populacionais específicos. Trata-se de um estudo seccional com 693 indivíduos. As informações referentes às estratégias para evitar a exposição à violência comunitária foram coletadas por meio de questionário multidimensional autopreenchido em sala de aula. As estratégias mais utilizadas foram: evitar passar onde há pessoas armadas (55,5%), evitar andar sozinho (30,5%) e evitar voltar para casa de madrugada (24,7%). Observou-se que as meninas adotam mais todos (concomitantemente) os quatro tipos de comportamento limitantes para reduzir sua exposição à violência comunitária (53% vs. 32%). Ressalta-se que a adoção de tais estratégias diferiu segundo os indicadores socioeconômicos, sendo maior entre os adolescentes oriundos de família de estratos de renda mais baixos. Tais achados chamam a atenção para a alta frequência de utilização de tais estratégias por adolescentes, o que pode cercear e limitar o pleno desenvolvimento de suas habilidades sociais e culturais.
Assuntos
Exposição à Violência , Feminino , Humanos , Adolescente , Brasil/epidemiologia , Estudos Transversais , Exposição à Violência/prevenção & controle , Renda , Instituições AcadêmicasRESUMO
OBJECTIVES: We aimed to investigate an outbreak of vancomycin-resistant Enterococcus faecium (VREfm) in paediatric patients from Hospital Pequeno Príncipe. The susceptibility profile was determined, and whole-genome sequencing (WGS) was used to analyse the genetic context of the strains. METHODS: Five VREfm isolates were recovered from sterile sites and surveillance cultures of two paediatric patients with acute lymphoblastic leukaemia. Species identification was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and the minimum inhibitory concentration (MIC) was assessed according to the European Committee for Antimicrobial Susceptibility Testing (EUCAST). WGS was performed to analyse the genetic context of virulence and resistance genes, and in silico multilocus sequence typing was performed to identify the sequence typing of the strains. RESULTS: High-level vancomycin resistance was observed in all isolates (≥256 mg/L). WGS revealed the presence of mobile genetic elements, such as plasmids (rep2, rep11a, repUS15, rep17, and rep18a), insertion sequences, and phages. Multiple resistance genes (aac(6')-aph(2"), dfrG, ermB, and vanA) and virulence genes (acm and efaAfm) were identified. All the isolates were assigned to ST117 (ST1133 - via a novel MLST), an important epidemic lineage associated with nosocomial infections and outbreaks. CONCLUSION: Our results show that the ST117 (ST1133) VREfm isolates are circulating in paediatric patients, which raises a great concern. The development of new drugs as well as the implementation of an antimicrobial stewardship program are necessary for their correct management, limiting the spread of resistance in oncohematological patients.
Assuntos
Enterococcus faecium , Leucemia-Linfoma Linfoblástico de Células Precursoras , Enterococos Resistentes à Vancomicina , Humanos , Criança , Vancomicina/farmacologia , Tipagem de Sequências Multilocus , Brasil/epidemiologia , Genótipo , Enterococos Resistentes à Vancomicina/genética , Surtos de DoençasRESUMO
The oviduct provides a suitable microenvironment from the gametes' final maturation until initial embryo development. Dynamic functional changes are observed in the oviduct cells, mainly controlled by steroid hormones and well-orchestrated during the estrous cycle. However, based on the roles played by the oviduct, additional layers of complexity might be present in its regulatory process. There is a cellular process that includes metabolic adaptation that can guide molecular modifications. This process is known as metaboloepigenetics. Therefore, we aimed to better understand how this crosstalk occurs in oviductal epithelial cells (OEC). Due to limited in situ access to the oviduct, we used the primary in vitro cell culture as a culture model and glucose as a metabolic disturbed factor. For that, cells derived from the oviductal epithelial layer were collected from cows at either follicular or luteal stages (n = 4 animals per group). They were cultured on a monolayer culture system under normoglycemic (2.7 mM glucose) or hyperglycemic conditions (27 mM glucose). On day five of culture, attached cells were submitted to analysis of mitochondrial metabolism (mitochondrial membrane potential - MMP) and epigenetics markers (5- methylcytosine - 5 mC and histone 3 lysine 9 acetylation - H3K9ac). Moreover, the culture media were submitted to the metabolites analysis profile by Raman spectrometry. Data were analyzed considering the effect of glucose level (normoglycemic vs. hyperglycemic), stages when OEC were harvested (follicular vs. luteal), and their interaction (glucose level * cycle stage) by two-way ANOVA. As a result, the high glucose level decreased the H3K9ac and MMP levels but did not affect the 5 mC. Regardless of the metabolic profile of the culture media, the glucose level was the only factor that changed the Raman shifts abundance. Although this present study evaluated oviductal epithelial cells after being submitted to an in vitro monolayer culture system, which is known to lead to cell dedifferentiation, yet, these results provide evidence of a relationship between epigenetic reprogramming and energy metabolism under these cell culture conditions. In conclusion, the levels of metabolites in culture media may be crucial for cellular function and differentiation, meaning that it should be considered in studies culturing oviductal cells.
Assuntos
Tubas Uterinas , Oviductos , Feminino , Animais , Bovinos , Oviductos/metabolismo , Células Epiteliais/metabolismo , Epigênese Genética , Meios de Cultura , Glucose/farmacologia , Glucose/metabolismoRESUMO
Resumo O objetivo do estudo é conhecer as estratégias individuais mais utilizadas por adolescentes de escolas públicas e privadas da IX Região Administrativa do município do Rio de Janeiro para evitar a exposição à violência comunitária, bem como investigar o perfil de coocorrência e sua prevalência em subgrupos populacionais específicos. Trata-se de um estudo seccional com 693 indivíduos. As informações referentes às estratégias para evitar a exposição à violência comunitária foram coletadas por meio de questionário multidimensional autopreenchido em sala de aula. As estratégias mais utilizadas foram: evitar passar onde há pessoas armadas (55,5%), evitar andar sozinho (30,5%) e evitar voltar para casa de madrugada (24,7%). Observou-se que as meninas adotam mais todos (concomitantemente) os quatro tipos de comportamento limitantes para reduzir sua exposição à violência comunitária (53% vs. 32%). Ressalta-se que a adoção de tais estratégias diferiu segundo os indicadores socioeconômicos, sendo maior entre os adolescentes oriundos de família de estratos de renda mais baixos. Tais achados chamam a atenção para a alta frequência de utilização de tais estratégias por adolescentes, o que pode cercear e limitar o pleno desenvolvimento de suas habilidades sociais e culturais.
Abstract This study aims to identify the individual community strategies to avoid violence exposure most used by adolescents from public and private schools in the IX Administrative Region of Rio de Janeiro and investigate the profile of co-occurrence and its prevalence in specific population subgroups. This is a cross-sectional study with 693 individuals. A multidimensional questionnaire collected information regarding strategies to avoid community violence exposure and was self-completed in the classroom. The most used strategies were avoiding walking close to armed people (55.5%), avoiding walking alone (30.5%), and avoiding returning home at dawn (24.7%). Girls adopt more of all (concurrently) the four limiting behaviors to reduce their community violence exposure (53% vs. 32%). Notably, the adoption of such strategies differed by socioeconomic indicators and was higher among adolescents from lower-income households. These findings point to the high frequency of use of such strategies by adolescents, which may hinder and limit the full development of their social and cultural skills.
RESUMO
Resumo A pandemia de Covid-19 produziu uma série de agravos sociais, como crescimento exponencial da pobreza e da fome, aumento nas taxas de desemprego, interrupção de atividades de trabalhadores informais, piora das condições de moradia da população de baixa renda e transtornos psíquicos. No Brasil, essa realidade foi enfrentada de forma insuficiente no que se refere às ações minimizadoras do governo, incluindo programas de transferência de renda. Ainda assim, apenas no primeiro ano de pandemia, a concessão dos chamados benefícios eventuais passou de 3 para 7,8 milhões de pessoas. Apesar da existência de muitos estudos estatísticos sobre a piora das condições socioeconômicas da população, ainda são raros os estudos que investigam o problema na perspectiva das pessoas socioeconomicamente mais atingidas. A pesquisa ouviu 27 chefes de família de baixa renda, atendidos em um CRAS do DF, sobre os efeitos da pandemia em suas vidas. Os resultados permitiram compreender, em profundidade, os sofrimentos e dificuldades vividas em aspectos como: trabalho e renda; alimentação; educação de crianças; sofrimentos psíquicos; obtenção e uso de benefícios eventuais e apontam para novas estratégias, programas e políticas capazes de mitigar os efeitos da pandemia que perdurarão ainda por longo tempo.
Abstract The Covid-19 pandemic produced a series of social problems, such as the exponential growth of poverty and hunger, an increase in unemployment rates, interruption of activities of informal workers, worsening of the housing conditions of the low-income population and psychological disorders. In Brazil, this reality has been insufficiently addressed in terms of minimizing government actions, including income transfer programs. Even so, only in the first year of the pandemic, the granting of so-called occasional benefits went from 3 to 7.8 million people. Despite the existence of many statistical studies on the worsening of the socioeconomic conditions of the population, studies that investigate the problem from the perspective of the most socioeconomically affected people are still rare. The research heard 27 low-income family heads, assisted at a CRAS in the DF, Brazil, about the effects of the pandemic on their daily lives. The results made it possible to understand, in depth, the sufferings and difficulties experienced in aspects such as: work and income; food; children's education; psychic sufferings; obtaining and using eventual benefits and point to new strategies, programs and policies capable of mitigating the effects of the pandemic that will last for a long time.Resumo: A pandemia de Covid-19 produziu uma série de agravos sociais, como crescimento exponencial da pobreza e da fome, aumento nas taxas de desemprego, interrupção de atividades de trabalhadores informais, piora das condições de moradia da população de baixa renda e transtornos psíquicos. No Brasil, essa realidade foi enfrentada de forma insuficiente no que se refere às ações minimizadoras do governo, incluindo programas de transferência de renda. Ainda assim, apenas no primeiro ano de pandemia, a concessão dos chamados benefícios eventuais passou de 3 para 7,8 milhões de pessoas. Apesar da existência de muitos estudos estatísticos sobre a piora das condições socioeconômicas da população, ainda são raros os estudos que investigam o problema na perspectiva das pessoas socioeconomicamente mais atingidas. A pesquisa ouviu 27 chefes de família de baixa renda, atendidos em um CRAS do DF, sobre os efeitos da pandemia em suas vidas. Os resultados permitiram compreender, em profundidade, os sofrimentos e dificuldades vividas em aspectos como: trabalho e renda; alimentação; educação de crianças; sofrimentos psíquicos; obtenção e uso de benefícios eventuais e apontam para novas estratégias, programas e políticas capazes de mitigar os efeitos da pandemia que perdurarão ainda por longo tempo.
RESUMO
The epigenetic reprogramming that occurs during the earliest stages of embryonic development has been described as crucial for the initial events of cell specification and differentiation. Recently, the metabolic status of the embryo has gained attention as one of the main factors coordinating epigenetic events. In this work, we investigate the link between pyruvate metabolism and epigenetic regulation by culturing bovine embryos from day 5 in the presence of dichloroacetate (DCA), a pyruvate analog that increases the pyruvate to acetyl-CoA conversion, and iodoacetate (IA), which inhibits the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), leading to glycolysis inhibition. After 8 h of incubation, both DCA and IA-derived embryos presented higher mitochondrial membrane potential. Nevertheless, in both cases, lower levels of acetyl-CoA, ATP-citrate lyase and mitochondrial membrane potential were found in blastocysts, suggesting an adaptative metabolic response, especially in the DCA group. The metabolic alteration found in blastocysts led to changes in the global pattern of H3K9 and H3K27 acetylation and H3K27 trimethylation. Transcriptome analysis revealed that such alterations resulted in molecular differences mainly associated to metabolic processes, establishment of epigenetic marks, control of gene expression and cell cycle. The latter was further confirmed by the alteration of total cell number and cell differentiation in both groups when compared to the control. These results corroborate previous evidence of the relationship between the energy metabolism and the epigenetic reprogramming in preimplantation bovine embryos, reinforcing that the culture system is decisive for precise epigenetic reprogramming, with consequences for the molecular control and differentiation of cells.