Population-based trend analysis of laparoscopic Nissen and Toupet fundoplications for gastroesophageal reflux disease

The Nissen and Toupet fundoplications are the most commonly used techniques for surgical treatment of gastroesophageal reflux disease. To date, no population-based trend analysis has been reported examining the choice of procedure and short-term outcomes. This study was designed to analyze trends in the use of Nissen versus Toupet fundoplications, and corresponding short-term outcomes during a 10-year period between 1995 and 2004

Genome-wide profiling of p63 DNA-binding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus.

Contains fulltext : 88501.pdf (publisher's version ) (Open Access)Heterozygous mutations in p63 are associated with split hand/foot malformations (SHFM), orofacial clefting, and ectodermal abnormalities. Elucidation of the p63 gene network that includes target genes and regulatory elements may reveal new genes for other malformation disorders. We performed genome-wide DNA-binding profiling by chromatin immunoprecipitation (ChIP), followed by deep sequencing (ChIP-seq) in primary human keratinocytes, and identified potential target genes and regulatory elements controlled by p63. We show that p63 binds to an enhancer element in the SHFM1 locus on chromosome 7q and that this element controls expression of DLX6 and possibly DLX5, both of which are important for limb development. A unique micro-deletion including this enhancer element, but not the DLX5/DLX6 genes, was identified in a patient with SHFM. Our study strongly indicates disruption of a non-coding cis-regulatory element located more than 250 kb from the DLX5/DLX6 genes as a novel disease mechanism in SHFM1. These data provide a proof-of-concept that the catalogue of p63 binding sites identified in this study may be of relevance to the studies of SHFM and other congenital malformations that resemble the p63-associated phenotypes