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Objective: To study the presence of SARS-CoV-2 on surfaces (high, medium and low contacts) and airs in non-sanitary spaces with high public influx to evaluate the risk of environmental contagion. Method: Surfaces and airs were analysed by RT-qPCR to detect the presence of SARS-CoV-2. Results: A total of 394 surfaces and air samples were obtained from spaces with high public influx such as offices, shopping centres and nursing homes. The virus was not detected in any of the samples analysed. Conclusion: Although we cannot emphatically conclude that there is no risk of environmental infection by SARS-CoV-2 in non-sanitary spaces, we can affirm that the risk is almost non- existent.
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OBJECTIVE: To study the presence of SARS-CoV-2 on surfaces (high, medium and low contact) and airs in non-sanitary spaces with high public influx to evaluate the risk of environmental contagion. METHODS: Surfaces and airs were analysed by RT-qPCR to detect the presence of SARS-CoV-2. RESULTS: 394 surfaces and air samples were obtained from spaces with high public influx such as offices, shopping centres and nursing homes. The virus was not detected in any of the samples analysed. CONCLUSION: Although we cannot emphatically conclude that there is no risk of environmental 27 infection by SARS-CoV-2 in non-sanitary spaces, we can affirm that the risk is almost non- existent.
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COVID-19 , SARS-CoV-2 , Humanos , RiscoRESUMO
BACKGROUND & AIMS: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB. METHODS: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies. RESULTS: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth. CONCLUSIONS: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB. LAY SUMMARY: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer.
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Colina Quinase , Hepatoblastoma , Neoplasias Hepáticas , beta Catenina/genética , Biomarcadores Tumorais/análise , Proteínas de Ligação ao Cálcio/genética , Colina Quinase/antagonistas & inibidores , Colina Quinase/metabolismo , Metilação de DNA , Descoberta de Drogas/métodos , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Hepatoblastoma/genética , Hepatoblastoma/metabolismo , Hepatoblastoma/mortalidade , Hepatoblastoma/patologia , Ensaios de Triagem em Larga Escala , Humanos , Lactente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Prognóstico , Medição de Risco/métodosRESUMO
BACKGROUND: Legionella pneumophila (L. pneumophila) was isolated from three cooling towers involved in three community outbreaks of Legionnaires disease. Each cooling tower had two different chromosomal DNA subtypes. However, only one matched identically to the clinical strains. To try to understand why only one of the environmental strains caused clinical cases we investigated the intrinsic virulence of these strains. METHODS: We selected six strains of L. pneumophila sg.1: two strains (A1 and B1) from cooling tower 1, two strains (A2 and B2) from tower 2 and two strains (A3 and B3) from tower 3. One of the two subtypes (A) exhibited the same chromosomal DNA subtype as the strains isolated from the patients in each outbreak and the other exhibited a different subtype. The replication within macrophages, the presence of lipopolysaccharide epitope recognized by MAb 3/1 and the growth kinetics in BCYE broth were investigated. Isolates were typed by pulsed field electrophoresis. RESULTS: The A strains did not have a higher virulence level, but were able to grow and survive better than strains B in BCYE broth. CONCLUSIONS: These results suggest that the strains better adapted to the environment will manage to displace the others and will be able to spread and infect humans. The adaptation to the environmental conditions could play an important role in the pathogenesis of the strains.
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Legionella pneumophila/isolamento & purificação , Microbiologia da Água , Ar Condicionado , Legionella pneumophila/classificação , Legionella pneumophila/crescimento & desenvolvimento , Legionella pneumophila/patogenicidadeRESUMO
Genotypic variability and clonal persistence are important concepts in molecular epidemiology as they facilitate the search for the source of sporadic cases or outbreaks of legionellosis. We studied the genotypic variability and persistence of Legionella pulsed-field gel electrophoresis (PFGE) patterns over time (period > 6 months) in 34 positive cooling towers from two different areas. In area A, radius of 70 km, 52 indistinguishable PFGE patterns were differentiated among the 27 cooling towers. In 13 cooling towers we observed >or= 2 PFGE patterns. Each cooling tower had its own indistinguishable Legionella PFGE pattern which was not shared with any other cooling tower. In area B, radius of 1 km, 10 indistinguishable PFGE patterns were obtained from the seven cooling towers. In four, we observed >or= 2 PFGE patterns. Three of these 10 indistinguishable PFGE patterns were shared by more than one cooling tower. In 27 of 34 cooling towers the same PFGE pattern was recovered after 6 months to up to 5 years of follow-up. The large genotypic diversity of Legionella observed in the cooling towers aids in the investigation of community outbreaks of Legionnaires' disease. However, shared patterns in small areas may confound the epidemiological investigation. The persistence of some PFGE patterns in cooling towers makes the recovery of the Legionella isolate causing the outbreak possible over time.
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Ar Condicionado/instrumentação , Eletroforese em Gel de Campo Pulsado/métodos , Variação Genética , Legionella pneumophila/classificação , Legionella pneumophila/crescimento & desenvolvimento , Microbiologia da Água , Contagem de Colônia Microbiana , DNA Bacteriano/análise , Genótipo , Legionella pneumophila/genética , Legionella pneumophila/isolamento & purificação , Espanha , Abastecimento de ÁguaRESUMO
The molecular epidemiology of clinical and environmental Legionella species isolates was studied in seven hospitals from 1989 to 2006. The number of environmental pulsed field gel electrophoresis (PFGE) patterns ranged from one to nine according to the hospital. Genomic PFGE pattern persistence was observed in 71% of the hospitals, even after 17 years in some hospitals, and the relationship between environmental and clinical isolates was established. The isolates associated with hospital-acquired Legionnaires' disease corresponded to the persistent environmental PFGE patterns of Legionella pneumophila in potable water supplies.
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Infecção Hospitalar/epidemiologia , Legionella pneumophila/isolamento & purificação , Doença dos Legionários/epidemiologia , Microbiologia da Água , Análise por Conglomerados , Impressões Digitais de DNA , DNA Bacteriano/genética , Eletroforese em Gel de Campo Pulsado , Genótipo , Hospitais , Humanos , Legionella pneumophila/classificação , Epidemiologia Molecular , Abastecimento de ÁguaRESUMO
The concentrations of Legionella pneumophila in cooling towers may vary considerably over short periods of time, producing significant fluctuations throughout the year. Despite genetic variability, in small geographical areas the same indistinguishable pulsed-field gel electrophoresis patterns may be shared among different cooling towers and persist over time.
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Eletroforese em Gel de Campo Pulsado/métodos , Variação Genética , Legionella pneumophila/genética , Microbiologia da Água , Contagem de Colônia Microbiana , DNA Bacteriano/análise , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Legionella pneumophila/crescimento & desenvolvimento , Abastecimento de ÁguaRESUMO
BACKGROUND AND OBJECTIVE: Superheat-and-flush is one of the methods of disinfection used against Legionella in hospital water distribution systems. An outbreak of nosocomial legionellosis (NL) was detected in the hospital Germans Trias i Pujol in January 1996. The aim of this study was to evaluate the impact of this disinfection technique at an environmental and clinical level. MATERIAL AND METHOD: Water samples were collected daily from central and tap water points 3 days prior to 15 days after superheating and flushing. Clinical surveillance of NL was performed 30 consecutive days following disinfection. RESULTS: After superheat-and-flush, the inoculum of Legionella pneumophila decreased in the central points but increased after day 11, achieving maximum values at 15 days. On the other hand, L. pneumophila was not detected in tap water points after 4 days but recolonization was observed after day 7, achieving 66% at day 9. No clinical cases of NL were detected during the study period. CONCLUSIONS: Superheat-and-flush is an effective albeit transitory method of rapid disinfection in outbreaks of NL.