A large CRISPR-induced bystander mutation causes immune dysregulation.

A persistent concern with CRISPR-Cas9 gene editing has been the potential to generate mutations at off-target genomic sites. While CRISPR-engineering mice to delete a ~360 bp intronic enhancer, here we discovered a founder line that had marked immune dysregulation caused by a 24 kb tandem duplication of the sequence adjacent to the on-target deletion. Our results suggest unintended repair of on-target genomic cuts can cause pathogenic bystander mutations that escape detection by routine targeted genotyping assays

Escherichia coli O157:H7 Productor de toxina Shiga aisladas de muestras de agua relacionadas a Establecimientos pecuarios de engorde a corral

Recientemente han ocurrido brotes debido vegetales contaminados por Escherichia coli productor de toxina Shiga (stec). Estos productos frescos se contaminan a través del contacto directo de heces bovinas (abono), o indirectamente a través de irrigación con agua contaminada. Este estudio tuvo como objetivo establecer la prevalencia de stec O157:H7 en muestras de agua relacionadas a establecimientos pecuarios de engorde a corral (epec) de la provincia de Entre Ríos, Argentina, y su eventual relación con cepas vinculadas a enfermedad transmitida por alimentos. Usando como indicadores microbiológicos, coliformes, Escherichia coli, y anaerobios sufito-reductores, se estudió la eficiencia en el saneamiento de los efluentes de un epec que contaba con un sistema de lagunas sanitarias. Entre abril/2009 y julio/2011 se estudiaron 320 muestras de agua vinculadas a efluentes de 11 epec. Las cepas fueron caracterizadas feno-genotípicamente y subtipificadas por macrorrestricción y electroforesis de campo pulsado. Algunos de los perfiles identificados están incluidos en la base de datos nacional, correspondiendo a cepas obtenidas de casos de Síndrome Urémico Hemolítico, diarrea, muestras alimenticias y de origen animal. Los epec deben implementar estrategias de control con objeto de limitar el ingreso de stec en el medioambiente acuático. En el sistema de lagunas sanitarias estudiado se constató una franca disminución de los indicares utilizados pero insuficiente para eliminar su aporte al ambiente. La optimización de su funcionamiento es función de su mantenimiento, en especial la frecuente remoción de barros de las primeras piletas

A large CRISPR-induced bystander mutation causes immune dysregulation.

A persistent concern with CRISPR-Cas9 gene editing has been the potential to generate mutations at off-target genomic sites. While CRISPR-engineering mice to delete a ~360 bp intronic enhancer, here we discovered a founder line that had marked immune dysregulation caused by a 24 kb tandem duplication of the sequence adjacent to the on-target deletion. Our results suggest unintended repair of on-target genomic cuts can cause pathogenic "bystander" mutations that escape detection by routine targeted genotyping assays

Evaluation of the colorectal cancer screening Programme in the Basque Country (Spain) and its effectiveness based on the Miscan-colon model

The population-based Basque Colorectal Cancer (CRC) Screening Programme started in 2009 with a biennial immunochemical quantitative test (FIT) biennial and colonoscopy under sedation in positive cases. The population target of 586,700 residents was from 50 to 69 years old and the total coverage was reached at the beginning of 2014. The aim of our study was to determine possible scenarios in terms of incidence, mortality and reduction of Life-years-Lost (L-y-L) in the medium and long term of CRC. Methods: Invitations were sent out by the Programme from 2009 to 2014, with combined organizational strategies. Simulation was done by MISCAN-colon (Microsimulation Screening Analysis) over 30 years comparing the results of screening vs no-screening, taking the population-based Cancer Registry into account. Lifetime population and real data from the Programme were used from 2008 to 2012. The model was run differentially for men and women. Results: 924,416 invitations were sent out from 2009 to 2014. The average participation rate was 68.4%, CRC detection rate was 3.4% and the Advanced Adenoma detection rate was 24.0‰, with differences observed in sex and age. Future scenarios showed a higher decrease of incidence (17.2% vs 14.7%), mortality (28.1% vs 22.4%) and L-y-L (22.6% vs 18.4%) in men than women in 2030. Conclusions: The Basque Country CRC Programme results are aligned to its strategy and comparable to other programmes. MISCAN model was found to be a useful tool to predict the benefits of the programme in the future. The effectiveness of the Programme has not been formally established as case control studies are required to determine long term benefits from the screening strategy