Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of Escherichia coli O157:H7-infected BALB/c mice

<p>Abstract</p> <p>Background</p> <p>Treatment of <it>Escherichia coli </it>O157:H7 infections with antimicrobial agents is controversial due to an association with potentially fatal sequelae. The production of Shiga toxins is believed to be central to the pathogenesis of this organism. Therefore, decreasing the expression of these toxins prior to bacterial eradication may provide a safer course of therapy.</p> <p>Methods</p> <p>The utility of decreasing Shiga toxin gene expression in <it>E. coli </it>O157:H7 with rifampicin prior to bacterial eradication with gentamicin was evaluated <it>in vitro </it>using real-time reverse-transcription polymerase chain reaction. Toxin release from treated bacterial cells was assayed for with reverse passive latex agglutination. The effect of this treatment on the survival of <it>E. coli </it>O157:H7-infected BALB/c mice was also monitored.</p> <p>Results</p> <p>Transcription of Shiga toxin-encoding genes was considerably decreased as an effect of treating <it>E. coli </it>O157:H7 <it>in vitro </it>with the minimum inhibitory concentration (MIC) of rifampicin followed by the minimum bactericidal concentration (MBC) of gentamicin (> 99% decrease) compared to treatment with gentamicin alone (50-75% decrease). The release of Shiga toxins from <it>E. coli </it>O157:H7 incubated with the MIC of rifampicin followed by addition of the MBC of gentamicin was decreased as well. On the other hand, the highest survival rate in BALB/c mice infected with <it>E. coli </it>O157:H7 was observed in those treated with the <it>in vivo </it>MIC equivalent dose of rifampicin followed by the <it>in vivo </it>MBC equivalent dose of gentamicin compared to mice treated with gentamicin or rifampicin alone.</p> <p>Conclusions</p> <p>The use of non-lethal expression-inhibitory doses of antimicrobial agents prior to bactericidal ones in treating <it>E. coli </it>O157:H7 infection is effective and may be potentially useful in human infections with this agent in addition to other Shiga toxin producing <it>E. coli </it>strains.</p

HLA Allele Associations and V-Beta T-Lymphocyte Expansions in Patients With Psoriasis, Harboring Toxin-Producing Staphylococcus aureus

HLA alleles have been associated with psoriasis. Toxin-producing strains of Staphylococcus aureus behave as superantigens, and if present in patients, might play a role in the exacerbation of psoriatic lesions by activating certain V-beta (Vβ) T-lymphocyte subsets. Allele frequencies in 22 patients and 22 controls (alleles determined by DNA/SSP typing) were used to calculate a relative risk of 4.7 (P < .05) for HLA-Cw6. S aureus was isolated from the throat of 11 patients. Enterotoxins A and C were detected by agglutination in the culture filtrate of one isolate. The enterotoxin A and/or C genes were detected by PCR in 9 isolates, and transcripts were detected by RT-PCR in 7 of them. None of the isolates from controls harbored enterotoxin genes. Vβ expansions were detected by RT-PCR in all 22 patients. Low or no Vβ expansions were obtained in controls. The association of HLA-Cw6 with psoriasis in Lebanese concurs with that reported for other ethnic groups. Toxin-producing isolates that colonize patients might play a role in the exacerbation of psoriatic lesions

Diversity and Adaptation of Human Respiratory Syncytial Virus Genotypes Circulating in Two Distinct Communities: Public Hospital and Day Care Center

HRSV is one of the most important pathogens causing acute respiratory tract diseases as bronchiolitis and pneumonia among infants. HRSV was isolated from two distinct communities, a public day care center and a public hospital in Sao Jose do Rio Preto - SP, Brazil. We obtained partial sequences from G gene that were used on phylogenetic and selection pressure analysis. HRSV accounted for 29% of respiratory infections in hospitalized children and 7.7% in day care center children. On phylogenetic analysis of 60 HRSV strains, 48 (80%) clustered within or adjacent to the GA1 genotype; GA5, NA1, NA2, BA-IV and SAB1 were also observed. SJRP GA1 strains presented variations among deduced amino acids composition and lost the potential O-glycosilation site at amino acid position 295, nevertheless this resulted in an insertion of two potential O-glycosilation sites at positions 296 and 297. Furthermore, a potential O-glycosilation site insertion, at position 293, was only observed for hospital strains. Using SLAC and MEME methods, only amino acid 274 was identified to be under positive selection. This is the first report on HRSV circulation and genotypes classification derived from a day care center community in Brazil.FAPESP [2010/50444-4]FAPES

Câncer de mama: caracterização quanto a idade e aos aspectos tumorais (tipo de tumor e extensão) / Breast cancer: characterization as to age to tumor aspects (type of tumor and extension)

Objetivo: Avaliar o perfil das pacientes mulheres com câncer de mama, dos municípios de Goiânia e Aparecida de Goiânia - GO de 2008 a 2012. Metodologia: Estudo retrospectivo, descritivo, que incluiu os casos de câncer de mama ocorridos nas moradoras de Goiânia, identificados pelo Registro de Câncer de Base Populacional de Goiânia, no período de 2008 a 2012. As variáveis estudadas foram: dados sociodemográficos e tipificação (tipo de tumor e extensão) da neoplasia apresentada. Os dados obtidos foram tabulados em planilha na plataforma Excel e analisados através de estatística descritiva. Resultados: Foram registrados 2.303 casos de câncer de mama em mulheres nessas cidades. A média de idade das mulheres com diagnóstico de câncer de mama foi 55 anos, e em relação ao estado civil, um pouco mais de 42% se enquadraram em não solteira e mais de 43% estavam sem dados. Quanto à cor da pele, 37,06% eram brancas e mais de 39% da amostra não tinha completude dessa variável. Quanto aos aspectos tumorais em relação à extensão da doença, identificamos que em mais de 48% dos casos os tumores classificavam-se em localizados, mais de 23% em regionais e apenas 4,23% em metástase. Quanto à lateralidade mais de 35% estavam sem informações, 31,04% eram localizados a direita e 33,40% a esquerda. Quanto ao tipo tumoral a maioria, 85,5% dos casos, apresentou carcinoma ductal invasivo, 4,6% carcinoma ductal in situ, 2,6% carcinoma lobular invasivo e somente 0,30% carcinoma lobular in situ. 106 casos não tinham informação sobre o tipo de tumor. Conclusão: O estudo visa a uma melhor compreensão a respeito do efeito dessa doença nas pacientes: sua evolução, associação com fatores de risco, presença de metástases e mortalidade.

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements