Although antibiotic-induced dysbiosis has been demonstrated to exacerbate intestinal inflammation, it has been suggested that antibiotic prophylaxis may be beneficial in certain clinical conditions such as acute pancreatitis (AP). However, whether broad-spectrum antibiotics, such as meropenem, influence the dissemination of multidrug-resistant (MDR) bacteria during severe AP has not been addressed. In the currently study, a mouse model of obstructive severe AP was employed to investigate the effects of pretreatment with meropenem on bacteria spreading and disease outcome. As expected, animals subjected to biliopancreatic duct obstruction developed severe AP. Surprisingly, pretreatment with meropenem accelerated the mortality of AP mice (survival median of 2 days) when compared to saline-pretreated AP mice (survival median of 7 days). Early mortality was associated with the translocation of MDR strains, mainly Enterococcus gallinarum into the blood stream. Induction of AP in mice with guts that were enriched with E. gallinarum recapitulated the increased mortality rate observed in the meropenem-pretreated AP mice. Furthermore, naïve mice challenged with a mouse or a clinical strain of E. gallinarum succumbed to infection through a mechanism involving toll-like receptor-2. These results confirm that broad-spectrum antibiotics may lead to indirect detrimental effects during inflammatory disease and reveal an intestinal pathobiont that is associated with the meropenem pretreatment during obstructive AP in mice.
Neutrophil overstimulation plays a crucial role in tissue damage during severe infections. Neuraminidase (NEU)-mediated cleavage of surface sialic acid has been demonstrated to regulate leukocyte responses. Here, we report that antiviral NEU inhibitors constrain host NEU activity, surface sialic acid release, ROS production, and NETs released by microbial-activated human neutrophils. In vivo, treatment with Oseltamivir results in infection control and host survival in peritonitis and pneumonia models of sepsis. Single-cell RNA sequencing re-analysis of publicly data sets of respiratory tract samples from critical COVID-19 patients revealed an overexpression of NEU1 in infiltrated neutrophils. Moreover, Oseltamivir or Zanamivir treatment of whole blood cells from severe COVID-19 patients reduces host NEU-mediated shedding of cell surface sialic acid and neutrophil overactivation. These findings suggest that neuraminidase inhibitors can serve as host-directed interventions to dampen neutrophil dysfunction in severe infections.
Background: Brazil has the second largest COVID-19 number of cases, worldly. Even so, underdiagnosis in the country is massive. Nowcasting techniques have helped to overcome the underdiagnosis. Recent advances in machine learning techniques offer opportunities to refine the nowcasting. This study aimed to analyze the underdiagnosis of COVID-19, through nowcasting with machine learning, in a South of Brazil capital. Methods: The study has an observational ecological design. It used data from 3916 notified cases of COVID-19, from April 14th to June 02nd, 2020, in Florianopolis, Santa Catarina, Brazil. We used machine-learning algorithm to classify cases which had no diagnosis yet, producing the nowcast. To analyze the underdiagnosis, we compared the difference between the data without nowcasting and the median of the nowcasted projections for the entire period and for the six days from the date of onset of symptoms to diagnosis at the moment of data extraction. Results: The number of new cases throughout the entire period, without nowcasting, was 389. With nowcasting, it was 694 (UI95 496-897,025). At the six days period, the number without nowcasting was 19 and 104 (95% UI 60-142) with. The underdiagnosis was 37.29% in the entire period and 81.73% at the six days period. Conclusions: The underdiagnosis was more critical in six days from the date of onset of symptoms to diagnosis before the data collection than in the entire period. The use of nowcasting with machine learning techniques can help to estimate the number of new cases of the disease.
RESUMO -A pesquisa foi realizada entre novembro de 2008 e março de 2009 a fim de levantar o perfil profissional de trabalhadores, proprietários e gestores de estabelecimentos de alimentação fora do lar em municípios da Região Litorânea Central do Estado de Santa Catarina. Metodologia: A pesquisa foi realizada em sete municípios: Florianópolis, São José, Governador Celso Ramos, Biguaçu, Palhoça, Paulo Lopes e Garopaba. Foram respondidos 1.516 questionários: 1.110 por funcionários (73,22%) e 406 por gestores ou proprietários (26,78%). Resultados: Os resultados apontaram para a ampla demanda de trabalhadores que não possuíam certificação técnica para as atividades que estavam desempenhando. Em relação aos gestores e proprietários, percebeu-se, principalmente, a necessidade de investirem em formação profissional para as rotinas administravas que exerciam. Considerações Finais: Avaliaram-se como imprescindíveis programas de capacitação profissional para trabalhadores, gestores e proprietários envolvidos com o setor de alimentação fora do lar na área investigada. Por outro lado, é pertinente a concepção de indicadores que permitam levantar dados relacionados à qualidade dos serviços de alimentação oferecidos aos turistas e à população residente.
Objetivo: Este artigo propõe criar um instrumento para analisar a adequação de protocolos de classificação de risco para COVID-19 às orientações da Organização Mundial de Saúde (OMS) e analisa o protocolo utilizado por Santa Catarina. Método: A pesquisa descritiva foi composta de três partes: 1) extração de informações concernentes à análise de risco e à COVID-19 dos documentos da OMS; 2) elaboração de instrumento para análise da adequação de protocolos de classificação de risco para COVID-19 às orientações da OMS; 3) aplicação do instrumento ao protocolo utilizado no estado de Santa Catarina. Resultados: Cinco documentos da OMS foram revistos. O instrumento construído contemplou cinco dimensões: avaliação do risco em si, avaliação da exposição, avaliação do contexto, caracterização do risco e confiabilidade. Informações parciais com relação à avaliação do risco em si e à confiabilidade foram encontradas no protocolo do governo catarinense. Não foram encontradas informações com relação às demais dimensões. Discussão: O desencontro entre a matriz utilizada pelo estado de Santa Catarina e as orientações para análise de risco da OMS são grandes. Assim, sem uma análise adequada desses fatores toda a estratégia de implementação de ações pode ser comprometida, expondo a população do estado a risco.
Objective: To analyze the underdiagnosis of COVID-19 through nowcasting with machine learning in a Southern Brazilian capital city. Methods: Observational ecological design and data from 3916 notified cases of COVID-19 from April 14th to June 2nd, 2020 in Florianópolis, Brazil. A machine-learning algorithm was used to classify cases that had no diagnosis, producing the nowcast. To analyze the underdiagnosis, the difference between data without nowcasting and the median of the nowcasted projections for the entire period and for the six days from the date of onset of symptoms were compared. Results: The number of new cases throughout the entire period without nowcasting was 389. With nowcasting, it was 694 (95%CI 496–897). During the six-day period, the number without nowcasting was 19 and 104 (95%CI 60–142) with nowcasting. The underdiagnosis was 37.29% in the entire period and 81.73% in the six-day period. The underdiagnosis was more critical in the six days from the date of onset of symptoms to diagnosis before the data collection than in the entire period. Conclusion: The use of nowcasting with machine learning techniques can help to estimate the number of new disease cases.
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