Evolutionary Pathways of the Calcitonin (CALC) Genes

Recombinant DNA techniques have made it possible to establish the structure of various genes encoding polypeptide hormones. Comparison of nucleotide sequences of the calcitonin (CALC) genes in man has revealed surprising similarities and variations. These findings and the homologies among the sequences in different species offered an opportunity for speculation about relationships between these genes and about their evolutionary origin. The first gene (CALC-I) directing the synthesis of calcitonin (CT) or CT gene-related peptide (CGRP) comprises six exons and gives rise to two mRNAs by an alternative RNA-processing mechanism. The homology between CGRP and CT reflects their common origin. The human genome contains a second gene (CALC-II) that is structurally related to the CALC-I gene. The CALC-II RNA transcripts do not appear to be differentially processed, as only preproCGRP-II mRNA and not preproCT-II is detected. The first and second CTI CGRP genes probably have evolved from a common ancestor gene early in evolution. Meanwhile, a third genomic locus containing nucleotide sequences highly homologous to exons 2 and 3 of both CALC genes was detected and probably generated by duplication of a part of CALC-II. This locus is not likely to encode a CT- or CGRP-related polypeptide hormone. The CALC genes and this last (pseudo) gene are located on the short arm of chromosome 11. Recently, islet or insulinoma-amyloid polypeptide (IAPP) was isolated as a major constituent of amyloid present in human insulinoma and in pancreatic islet amyloid in noninsulin-dependent diabetes mellitus. lAPP shows 46% amino acid sequence homology with human CGRP-II. In contrast to the CALC-genes, the human IAPP gene is located on chromosome 12. All these findings have provided insight into the mechanisms underlying the increasing diversity of polypeptide hormones

Sofosbuvir plus simeprevir for the treatment of HCV genotype 4 patients with advanced fibrosis or compensated cirrhosis is highly efficacious in real life

Chronic hepatitis C virus (HCV) infection is a major cause of chronic liver disease and liver-related death. Recently, multiple regimens of different direct-acting antiviral agents (DAAs) have been registered. Although treatment with sofosbuvir (SOF) and simeprevir (SMV) is registered for the treatment of genotype 4 patients in some countries, data on efficacy of this combination are lacking. We aimed to assess the efficacy of SOF and SMV with or without RBV during 12 weeks in a real-life cohort of genotype 4 HCV patients. A retrospective multicentre observational study was conducted in 4 hospitals in Amsterdam, the Netherlands, including patients with advanced liver fibrosis or liver cirrhosis treated with SOF plus SMV with or without RBV during 12 weeks for a genotype 4 chronic HCV infection from 1 January 2015 to 1 August 2015. Sustained viral response (SVR) was established at week 12 after end of treatment. A total of 53 patients with genotype 4 HCV infection, treatment naïve and experienced, were included. SVR was achieved in 49 of 53 patients (92%). The four failures all had a virological relapse and did not receive ribavirin. Three were nonresponder to earlier interferon-based treatment, and one was treatment naive. In this real-life cohort of patients with HCV genotype 4 infection and advanced liver fibrosis/cirrhosis, we show that treatment with SOF and SMV is effective. The addition of RBV could be considered in treatment-experienced patients as recommended in guideline

MR Colonography with limited bowel preparation: Patient acceptance compared with that of full-preparation Colonoscopy

Purpose: To prospectively evaluate participants' experience and preference of magnetic resonance (MR) colonography with limited bowel preparation compared with full-preparation colonoscopy in participants at increased risk for colorectal cancer. Materials and Methods: This study had institutional review board approval; all participants gave written informed consent. In this multicenter study, consecutive participants undergoing conventional colonoscopy because of a personal or family history of colorectal cancer or adenomatous polyps underwent MR colonography 2 weeks prior to colonoscopy. They all followed a low-fiber diet and were given lactulose and an oral contrast agent (fecal tagging with gadolinium) 2 days before colonography. Before imaging, spasmolytics were administered intravenously, and a water-gadolinium chelate mixture was administered rectally for distention of the colon. Breath-hold T1- and T2-weighted sequences were performed in the prone and supine positions. Participant experience in terms of, for example, pain and burden was determined by using a five-point scale and was evaluated with a Wilcoxon signed rank test; participant preference was determined by using a seven-point scale and was evaluated with the X 2 statistic after dichotomizing. Results: Two hundred nine participants (77 women, 132 men; mean age, 58 years: range, 23-84 years) were included. One hundred forty-eight participants received sedatives (midazolam) and/or analgesics (fentanyl) during colonoscopy. Participants rated the MR colonography bowel preparation as less burdensome (P <.001) compared with the colonoscopy bowel preparation (10% and 71% of participants rated the respective examinations moderately to extremely burdensome). Participants also experienced less pain at MR colonography (P <.001) and found MR colonography less burdensome (P <.001). Immediately after both examinations, 69% of participants preferred MR colonography, 22% preferred colonoscopy, and 9% were indifferent (P <.001, 69% vs 22%). After 5 weeks, 65% preferred MR colonography and 26% preferred colonoscopy (P <.001). Conclusion: Participants preferred MR colonography without extensive cleansing to colonoscopy immediately after both examinations and 5 weeks later. Experience of the bowel preparation and of the procedure was rated bette