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Serine incorporator protein 5 (SERINC5) is a key innate immunity factor that operates in the cell to restrict the infectivity of certain viruses. Different viruses have developed strategies to antagonize SERINC5 function but, how SERINC5 is controlled during viral infection is poorly understood. Here, we report that SERINC5 levels are reduced in COVID-19 patients during the infection by SARS-CoV-2 and, since no viral protein capable of repressing the expression of SERINC5 has been identified, we hypothesized that SARS-CoV-2 non-coding small viral RNAs (svRNAs) could be responsible for this repression. Two newly identified svRNAs with predicted binding sites in the 3'-untranslated region (3'-UTR) of the SERINC5 gene were characterized and we found that the expression of both svRNAs during the infection was not dependent on the miRNA pathway proteins Dicer and Argonaute-2. By using svRNAs mimic oligonucleotides, we demonstrated that both viral svRNAs can bind the 3'UTR of SERINC5 mRNA, reducing SERINC5 expression in vitro. Moreover, we found that an anti-svRNA treatment to Vero E6 cells before SARS-CoV-2 infection recovered the levels of SERINC5 and reduced the levels of N and S viral proteins. Finally, we showed that SERINC5 positively controls the levels of Mitochondrial Antiviral Signalling (MAVS) protein in Vero E6. These results highlight the therapeutic potential of targeting svRNAs based on their action on key proteins of the innate immune response during SARS-CoV-2 viral infection.
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OBJECTIVES: To describe clinical characteristics of fracture patients, including a closer look to hip fracture patients, and determine how epidemiological variables may have influenced on a higher vulnerability to SARS-CoV-2 infection, as the basis for the considerations needed to reintroduce elective surgery during the pandemic. DESIGN: Longitudinal prospective cohort study. SETTING: Level I Trauma Center in the East of Spain. PATIENTS/PARTICIPANTS: One hundred forty-four consecutive fracture patients 18 years or older admitted for surgery. INTERVENTION: Patients were tested for SARS-CoV-2 with either molecular and/or serological techniques and screened for presentation of COVID-19. MAIN OUTCOME MEASUREMENTS: Patients were interviewed and charts reviewed for demographic, epidemiological, clinical, and surgical characteristics. RESULTS: We interviewed all patients and tested 137 (95.7%) of them. Three positive patients for SARS-CoV-2 were identified (2.1%). One was asymptomatic and the other 2 required admission due to COVID-19-related symptoms. Mortality for the whole cohort was 13 patients (9%). Significant association was found between infection by SARS-CoV-2 and epidemiological variables including: intimate exposure to respiratory symptomatic patients (P = 0.025) and intimate exposure to SARS-CoV-2-positive patients (P = 0.013). No association was found when crowding above 50 people was tested individually (P = 0.187). When comparing the 2020 and 2019 hip fracture cohorts we found them to be similar, including 30-day mortality. A significant increase in surgical delay from 1.5 to 1.8 days was observed on the 2020 patients (P = 0.034). CONCLUSIONS: Patients may be treated safely at hospitals if strict recommendations are followed. Both cohorts of hip fracture patients had similar 30-day mortality. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Fixação de Fratura/normas , Fraturas do Quadril/complicações , Fraturas do Quadril/epidemiologia , Hospitais/normas , Segurança do Paciente , Pneumonia Viral/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/epidemiologia , Feminino , Seguimentos , Fraturas do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Prevalência , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2 , Espanha/epidemiologia , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto JovemAssuntos
Doenças dos Trabalhadores Agrícolas/microbiologia , Colletotrichum/isolamento & purificação , Úlcera da Córnea/microbiologia , Infecções Oculares Fúngicas/microbiologia , Idoso , Doenças dos Trabalhadores Agrícolas/diagnóstico , Doenças dos Trabalhadores Agrícolas/tratamento farmacológico , Doenças dos Trabalhadores Agrícolas/cirurgia , Antifúngicos/uso terapêutico , Transplante de Córnea , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/cirurgia , Diagnóstico Diferencial , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/cirurgia , Humanos , Ceratite Herpética/diagnóstico , Masculino , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , VoriconazolRESUMO
INTRODUCTION: Pertussis is a highly contagious vaccine-preventable disease. An increasing incidence has been reported in several countries around the world in the last few years. The aim of this study is to analyze the situation of pertussis in the Valencian Community (Spain), with the purpose of verifying the increased incidence of the illness. METHODS: A descriptive analysis of probable and confirmed cases detected during 2011 was conducted. Methods used for Bordetella pertussis detection from clinical samples were: culture isolation, polymerase chain reaction (PCR)-based detection of bacterial DNA, and/or detection of specific IgM antibodies. The disease incidence and other epidemiological variables were estimated. These results were compared to data collected in previous years (2008-2010). The Epidemiological Surveillance Analysis and Microbiological Surveillance Network integrated systems of the regional Department of Health were used as sources of information. RESULTS: In 2011, 249 cases of pertussis were detected (incidence rate of 4.89×10(5) inhabitants). This rate is statistically significantly higher than those reported in 2008 (0.73×10(5) inhabitants), 2009 (0.53×10(5) inhabitants), and 2010 (0.53×10(5) inhabitants). The highest incidence rate was observed in cases younger than one year old (252.97×10(5) inhabitants), with marked differences compared to the rest of age groups. More than two-thirds (69%) of reported cases were confirmed by a laboratory test. Detection of specific serum IgM antibodies was positive in 10% of cases, culture isolation was positive in 17%, and PCR-based detection of bacterial DNA in 35% of cases. CONCLUSIONS: The results of this study show a clear increase of pertussis incidence in the Valencian Community during 2011.
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Coqueluche/epidemiologia , Adolescente , Criança , Pré-Escolar , DNA Bacteriano , Humanos , Incidência , Lactente , Recém-Nascido , Reação em Cadeia da Polimerase , Espanha/epidemiologiaRESUMO
BACKGROUND: Listeria monocytogenes is an uncommon cause of disease, although in certain age groups (infants, elderly, pregnant women and immunocompromised) may be an important cause of meningoencephalitis, and bacteremia. The aim of this study was to detect the incidence of invasive listeriosis cases found in Valencia during a period of 3 years. METHODS: A retrospective study of invasive listeriosis detected in the period 2008-2010 was carried out. The isolation of Listeria from a potentially sterile anatomical location was considered as "case". Data from the Microbiology Surveillance Network of Valencia (RedMIVA) were used as a source of information. RESULTS: 98 cases of invasive listeriosis were detected, of which 58% were men. The largest number of diagnosed cases belonged to the age range 60-80 years (63%). Bacteremic infectious become evident in 57 cases (58%), central nervous system lesions were located in 30 cases (31%) and infectious in sterile liquids occurred in the remaining cases (11%). In 90 strains (92% of cases) could be performed the sensitivity to antibiotics and all were sensitive to ampicillin. Incidence rates were: 0,73 cases/100.000 inhabitants in 2008, 0,70 cases/100.000 inhabitants in 2009 and 0,58 cases/100.000 inhabitants 2010. CONCLUSIONS: The average rate of invasive listeriosis in Valencian Community in the period 2008 to 2010 was 0.67 cases per 100,000 inhabitants. Temporal or geographic clusters of cases were not detected.