Search

Background: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence., Methods: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication., Results: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low., Conclusion: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To investigate the variation in dental nonmetric traits and to evaluate the utility of this variation for inferring genetic ancestry proportions in a sample of admixed Latin Americans., Materials and Methods: We characterized a sample from Colombia (N = 477) for 34 dental traits and obtained estimates of individual Native American, European, and African ancestry using genome-wide SNP data. We tested for correlation between dental traits, genetic ancestry, age, and sex. We carried out a biodistance analysis between the Colombian sample and reference continental population samples using the mean measure of divergence statistic calculated from dental trait frequencies. We evaluated the inference of genetic ancestry from dental traits using a regression approach (with 10-fold cross-validation) as well as by testing the correlation between estimates of ancestry obtained from genetic and dental data., Results: Latin Americans show intermediate dental trait frequencies when compared to Native Americans, Europeans, and Africans. Significant correlations were observed for several dental traits, genetic ancestry, age, and sex. The biodistance analysis displayed a closer relationship of Colombians to Europeans than to Native Americans and Africans. Mean ancestry estimates obtained from the dental data are similar to the genetic estimates (Native American: 32% vs. 28%, European: 59% vs. 63%, and African: 9% vs. 9%, respectively). However, dental features provided low predictive power for genetic ancestry of individuals in both approaches tested (R 2  < 5% for all genetic ancestries across methods)., Discussion: The frequency of dental traits in Latin Americans reflects their admixed Native American, European and African ancestry and can provide reasonable average estimates of genetic ancestry. However, the accuracy of individual genetic ancestry estimates is relatively low, probably influenced by the continental differentiation of dental traits, their genetic architecture, and the distribution of genetic ancestry in the individuals examined., (© 2018 Wiley Periodicals, Inc.)

Treatment of persons with latent tuberculosis (TB) infection at greatest risk of reactivation is an important component of TB control and elimination strategies. Biomarkers evaluating the effectiveness of treatment of latent TB infection have not yet been identified. This information would enhance control efforts and assist the evaluation of new treatment regimes. We designed a two-group, two-arm, randomised clinical study of tuberculin skin test-positive participants: 26 with documented contact with TB patients and 34 with non-documented contact. Participants in each group were randomly assigned to the immediate- or deferred-isoniazid treatment arms. Assays of in vitro interferon (IFN)-γ secretion in response to recombinant Rv1737 and overlapping synthetic peptide pools from various groups of immunodominant proteins were performed. During isoniazid therapy, a significant increase from baseline in the proportion of IFN-γ responders to the 10-kDa culture filtrate protein, Rv2031, Rv0849, Rv1986, Rv2659c, Rv2693c and the recombinant Rv1737 protein was observed (p⩽0.05). The peptide pool of Rv0849 and Rv1737 recombinant proteins induced the highest percentage of IFN-γ responders after isoniazid therapy. The in vitro IFN-γ responses to these proteins might represent useful markers to evaluate changes associated with treatment of latent TB infection., (Copyright ©ERS 2015.)

Vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG) has variable efficacy in preventing tuberculosis. We hypothesized that some of this variation might be due to differences among BCG strains. To test this, neonates in Orizaba, Mexico, were vaccinated with one of three different BCG strains (BCG-Brazil [BBCG], BCG-Denmark [DBCG], or BCG-Japan [JBCG]). One year after vaccination, peripheral blood mononuclear cells (PBMC) were obtained and recall immune responses to culture filtrate proteins (CFP) of Mycobacterium tuberculosis were evaluated using quantitative real-time PCR. CFP-activated PBMC from BBCG- and DBCG-immunized children expressed high levels of cytokines characteristic of an adaptive immune response (gamma interferon, interleukin-2beta [IL-12beta], and IL-27), while those from children immunized with JBCG did not. In contrast, vaccination with JBCG resulted in significantly greater expression of cytokines characteristic of a proinflammatory immune response (IL-1alpha, IL-1beta, IL-6, and IL-24) in PBMC activated with CFP compared to PBMC from children vaccinated with BBCG or DBCG. Thus, different strains of BCG can activate different immune pathways, which may affect long-term vaccine efficacy.

We analyzed 52 surgically excised ePTFE grafts used as secondary vascular access in chronic hemodialysis patients, structurally and histopathologically. Pseudoaneurysm formation at the site of repeated venipuncture was the main cause of surgical removal later than two years after implantation. Repeated needle punctures, twice per treatment, two or three times a week may result in a perigraft fibrous tissue capsule directly above areas where the graft was punctured. The delicate microporous structure of the graft wall was shown to be disrupted by needle punctures. The needle puncture sites were filled by surrounding connective tissue, and in one case, capillary formation was observed within the puncture sites. Examination by both light and scanning electron microscopy demonstrated identical patterns of pseudointima on the luminal surface. A thin pannus of endothelium-like cells, confined to the vicinity of the anastomoses, was noted in only four cases. On other areas of the luminal surface without endothelium, a red coagulum incorporating blood cells and fibrin was observed. Histological evidence of acute infection was absent in 61% of the cases and only 27% were considered to be clinically infected. Careful needle puncture technique, systematic rotation of puncture sites, and the use of rigorous aseptic technique are essential in preserving the long-term structural integrity of the vascular access, despite the good mechanical properties and reasonable good resistance to infection of ePTFE grafts.

The popularity of expanded polytetrafluoroethylene (PTFE) arteriovenous fistulas for hemodialysis access is increasing. The low infection rate, low thrombogenicity and low body reactivity make it an important blood access for patients on routine hemodialysis. The authors examined 29 PTFE graft fistulas surgically excised from patients on hemodialysis for one or more of the following complications: infection 7, 2 with associated hemorrhage; thrombosis 9; aneurysm 11, 3 with associated thrombosis; stenosis 5, 3 with associated thrombosis; hemorrhage 4 and arterial steal 2. The explanted prostheses were reinforced Gore-tex in 20, Gore-tex thin wall in 1, Impra I in 4, Impra II in 3 and Vitagraft in 1. It was also noted that the implants failed in the short term mainly because of infection, in the medium term mainly because of thrombosis and stenosis, and in the long term usually because of aneurysm.