https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24679 Wed 17 Nov 2021 16:32:22 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:12764 Sat 24 Mar 2018 08:18:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:12777 Sat 24 Mar 2018 08:18:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20807 V1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of Na_V1.5. Methods: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. Results: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P <.05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted Na_V1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-Na_V1.5 had the greatest effect in reducing Na_V1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS. Conclusions: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt Na_V1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.]]> Sat 24 Mar 2018 08:05:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19964 Sat 24 Mar 2018 07:58:33 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17801 50 years to assess awareness regarding BE, willingness to participate in screening, and preferences regarding method of screening. Methods evaluated were sedated endoscopy (sEGD), unsedated transnasal endoscopy (uTNE) and video capsule (VCE). Results: A total of 136 from 413 (33 %) adults responded [47 % males, mean (SD) age 63 (10.2) years], and 26 % of responders knew of BE at baseline. After reading the information on BE, 72 % were interested in screening. A history of undergoing screening tests and GI symptoms were predictive of interest. Unsedated techniques were preferred by 64 % (VCE: 56 % and uTNE: 8 %) versus sEGD (36 %). Conclusions: The majority of adults were willing to undergo screening for BE/EAC, with a preference for unsedated techniques.]]> Sat 24 Mar 2018 07:57:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19976 Sat 24 Mar 2018 07:54:30 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28387 Sat 24 Mar 2018 07:36:00 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27168 Sat 24 Mar 2018 07:31:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27248 Sat 24 Mar 2018 07:29:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22752 Sat 24 Mar 2018 07:14:15 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21659 Mon 11 Mar 2019 12:16:36 AEDT ]]>