Pervasive Sign Epistasis between Conjugative Plasmids and Drug-Resistance Chromosomal Mutations

Multidrug-resistant bacteria arise mostly by the accumulation of plasmids and chromosomal mutations. Typically, these resistant determinants are costly to the bacterial cell. Yet, recently, it has been found that, in Escherichia coli bacterial cells, a mutation conferring resistance to an antibiotic can be advantageous to the bacterial cell if another antibiotic-resistance mutation is already present, a phenomenon called sign epistasis. Here we study the interaction between antibiotic-resistance chromosomal mutations and conjugative (i.e., self-transmissible) plasmids and find many cases of sign epistasis (40%)—including one of reciprocal sign epistasis where the strain carrying both resistance determinants is fitter than the two strains carrying only one of the determinants. This implies that the acquisition of an additional resistance plasmid or of a resistance mutation often increases the fitness of a bacterial strain already resistant to antibiotics. We further show that there is an overall antagonistic interaction between mutations and plasmids (52%). These results further complicate expectations of resistance reversal by interdiction of antibiotic use

Incidência e fatores de risco de diarréia e infecções respiratórias agudas em comunidades urbanas de Pernambuco, Brasil Incidence and risks factors for diarrhoea and acute respiratory infections in urban communities of Pernambuco, Brazil

Em estudo de intervenção educativa sobre diarréia e infecções respiratórias agudas (IRA) nos Municípios de Olinda e Recife, realizaram-se duas pesquisas domiciliares em uma amostra de famílias, com pelo menos uma criança abaixo de cinco anos, em abril-maio de 1992 e 1994. Foram estudadas 5.436 crianças. A incidência anual corrigida (IAC) de diarréia foi de 2,7 episódios por criança/ano, com uma incidência de 10,2% nas duas semanas prévias ao inquérito, estável para 1992 e 1994. Os fatores associados de forma constante a um maior risco de diarréia foram a idade da criança abaixo de dois anos, ausência de saneamento básico e de eletrodomésticos no domicílio. IAC de IRA foi de 9,5 episódios por criança/ano. A incidência de IRA foi de 41,0% em 1992 e de 32,6% em 1994, sendo a maioria de vias respiratórias altas (75,9%). Só o fator baixa idade mostrou associação com o maior risco de IRA. Os resultados indicam a importância que ambas patologias ainda têm na saúde das crianças menores de cinco anos, e, no caso da diarréia, a necessidade urgente de ampliar a cobertura dos serviços básicos visando ao impacto na redução da incidência.<br>Magnitude and distribution of Diarrhoea and Acute Respiratory Infections (ARI) in children were studied within a larger research that focused on health education. Two household surveys were conducted in a sample of families with at least one child under five years of Recife and Olinda in April-May 1992 and 1994. The total number of children studied was 5436. The estimated adjusted annual incidence rate (AAIR) of diarrhoea was 2.7 episodes per child. The two-week incidence rate of diarrhoea was 10.2% for both years. Risk factors associated with higher incidence of diarrhoea were age (under two years), lack of sanitation facilities and the absence of electric appliances in the household. The estimated AAIR of ARI was 9.5 episodes per child. The two-week incidence rate of ARI was 41.0% in 1992 and 32.6% in 1994. Majority of ARI affected the high respiratory track (75.9%). The only factor consistently associated with a higher risk of ARI was age (under three years). Study results indicate that both pathologies are still an important health problem for children under five in Pernambuco. In particular, in the case of diarrhoea the need for improving the access to basic services, such as water supply and sewerage system is urgently needed

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non-Small Cell Lung Carcinoma : the ROSING Study

Altres ajuts: Funding for this study was provided bythe iLUNG Program (B2017/BMD-3884) from the Comunidad de Madrid.Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm