Biofilm development in time on a silicone voice prosthesis:A case study

Voice prostheses from silicone elastomers become rapidly colonised by a mixed biofilm of bacteria and yeasts. In this study, microorganisms were isolated from biofilms on explanted prostheses after having been in place for various time intervals ranging from 1 to 67 d. The isolates were examined for their identity, adhesion to hexadecane and electrophoretic mobility. Bacteria from early (shorter than 8 d) and late (longer than 8 d) explants could not be classified according to their taxonomy, hydrophobicity or electrophoretic mobility. However, the yeasts clearly revealed a dominance of only hydrophilic Candida albicans isolates from early explants and only hydrophobic C. tropicalis isolates from late explants. These findings may be of significance for the development of strategies to control mixed biofilms on biomaterials.</p

Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors

Objectives—To identify SNPs associated with switching from an ACE-inhibitor to an angiotensin receptor blocker (ARB). Methods—Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and the GoDARTS study in Scotland. Cases were intolerant subjects who switched from an ACE-inhibitor to an ARB, controls were subjects who used ACE-inhibitors continuously for at least 2 years and did not switch. GWAS using an additive model was run in these sets and results were meta-analysed using GWAMA. Results—972 cases out of 5 161 ACE-inhibitor starters were identified. 8 SNPs within 4 genes reached the GWAS significance level (P<5×10-8) in the meta-analysis (RBFOX3, GABRG2, SH2B1 and MBOAT1). The strongest associated SNP was located in an intron of RBFOX3, which contains a RNA binding protein (rs2061538: MAF=0.16, OR=1.52[95%CI: 1.32-1.76], p=6.2x10-9). Conclusions—These results indicate that genetic variation in abovementioned genes may increase the risk of ACE-inhibitors induced adverse reactions

Analysis of BAC-end sequences in rainbow trout: Content characterization and assessment of synteny between trout and other fish genomes

<p>Abstract</p> <p>Background</p> <p>Rainbow trout (<it>Oncorhynchus mykiss</it>) are cultivated worldwide for aquaculture production and are widely used as a model species to gain knowledge of many aspects of fish biology. The common ancestor of the salmonids experienced a whole genome duplication event, making extant salmonids such as the rainbow trout an excellent model for studying the evolution of tetraploidization and re-diploidization in vertebrates. However, the lack of a reference genome sequence hampers research progress for both academic and applied purposes. In order to enrich the genomic tools already available in this species and provide further insight on the complexity of its genome, we sequenced a large number of rainbow trout BAC-end sequences (BES) and characterized their contents.</p> <p>Results</p> <p>A total of 176,485 high quality BES, were generated, representing approximately 4% of the trout genome. BES analyses identified 6,848 simple sequence repeats (SSRs), of which 3,854 had high quality flanking sequences for PCR primers design. The first rainbow trout repeat elements database (INRA RT rep1.0) containing 735 putative repeat elements was developed, and identified almost 59.5% of the BES database in base-pairs as repetitive sequence. Approximately 55% of the BES reads (97,846) had more than 100 base pairs of contiguous non-repetitive sequences. The fractions of the 97,846 non-repetitive trout BES reads that had significant BLASTN hits against the zebrafish, medaka and stickleback genome databases were 15%, 16.2% and 17.9%, respectively, while the fractions of the non-repetitive BES reads that had significant BLASTX hits against the zebrafish, medaka, and stickleback protein databases were 10.7%, 9.5% and 9.5%, respectively. Comparative genomics using paired BAC-ends revealed several regions of conserved synteny across all the fish species analyzed in this study.</p> <p>Conclusions</p> <p>The characterization of BES provided insights on the rainbow trout genome. The discovery of specific repeat elements will facilitate analyses of sequence content (e.g. for SNPs discovery and for transcriptome characterization) and future genome sequence assemblies. The numerous microsatellites will facilitate integration of the linkage and physical maps and serve as valuable resource for fine mapping QTL and positional cloning of genes affecting aquaculture production traits. Furthermore, comparative genomics through BES can be used for identifying positional candidate genes from QTL mapping studies, aid in future assembly of a reference genome sequence and elucidating sequence content and complexity in the rainbow trout genome.</p

Traditional methods v. new technologies – dilemmas for dietary assessment in large-scale nutrition surveys and studies: a report following an international panel discussion at the 9th International Conference on Diet and Activity Methods (ICDAM9), Brisbane, 3 September 2015

The aim of the present paper is to summarise current and future applications of dietary assessment technologies in nutrition surveys in developed countries. It includes the discussion of key points and highlights of subsequent developments from a panel discussion to address strengths and weaknesses of traditional dietary assessment methods (food records, FFQ, 24 h recalls, diet history with interviewer-assisted data collection) v. new technology-based dietary assessment methods (web-based and mobile device applications). The panel discussion ‘Traditional methods v. new technologies: dilemmas for dietary assessment in population surveys’, was held at the 9th International Conference on Diet and Activity Methods (ICDAM9), Brisbane, September 2015. Despite respondent and researcher burden, traditional methods have been most commonly used in nutrition surveys. However, dietary assessment technologies offer potential advantages including faster data processing and better data quality. This is a fast-moving field and there is evidence of increasing demand for the use of new technologies amongst the general public and researchers. There is a need for research and investment to support efforts being made to facilitate the inclusion of new technologies for rapid, accurate and representative data

Bone pain and extremely low bone mineral density due to severe vitamin D deficiency in celiac disease

Case report A 29-year-old wheelchair-bound woman was presented to us by the gastroenterologist with suspected osteomalacia. She had lived in the Netherlands all her life and was born of Moroccan parents. Her medical history revealed iron deficiency, growth retardation, and celiac disease, for which she was put on a gluten-free diet. She had progressive bone pain since 2 years, difficulty with walking, and about 15 kg weight loss. She had a short stature, scoliosis, and pronounced kyphosis of the spine and poor condition of her teeth. Laboratory results showed hypocalcemia, an immeasurable serum25-hydroxyvitamin D level, and elevated parathyroid hormone and alkaline phosphatase levels. Spinal radiographs showed unsharp, low contrast vertebrae. Bone mineral density measurement at the lumbar spine and hip showed a T-score of -6.0 and -6.5, respectively. A bone scintigraphy showed multiple hotspots in ribs, sternum, mandible, and long bones. A duodenal biopsy revealed villous atrophy (Marsh 3C) and positive antibodies against endomysium, transglutaminase, and gliadin, compatible with active celiac disease. A bone biopsy showed severe osteomalacia but normal bone volume. She was treated with calcium intravenously and later orally. Furthermore, she was treated with high oral doses of vitamin D and a gluten-free diet. After a few weeks of treatment, her bone pain decreased, and her muscle strength improved. Discussion In this article, the pathophysiology and occurrence of osteomalacia as a complication of celiac disease are discussed. Low bone mineral density can point to osteomalacia as well as osteoporosis. © International Osteoporosis Foundation and National Osteoporosis Foundation 2011

Why Don't CD8+ T Cells Reduce the Lifespan of SIV-Infected Cells In Vivo?

In January 2010 two groups independently published the observation that the depletion of CD8+ cells in SIV-infected macaques had no detectable impact on the lifespan of productively infected cells. This unexpected observation led the authors to suggest that CD8+ T cells control SIV viraemia via non-lytic mechanisms. However, a number of alternative plausible explanations, compatible with a lytic model of CD8+ T cell control, were proposed. This left the field with no consensus on how to interpret these experiments and no clear indication whether CD8+ T cells operated primarily via a lytic or a non-lytic mechanism. The aim of this work was to investigate why CD8+ T cells do not appear to reduce the lifespan of SIV-infected cells in vivo

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Omega-3 fatty acids and vitamin D in immobilisation: Part A - Modulation of appendicular mass content, composition and structure

Objectives: Muscle size decreases in response to short-term limb immobilisation. This study set out to determine whether two potential protein-sparing modulators (eicosapentaenoic acid and vitamin D) would attenuate immobilisation-induced changes in muscle characteristics. Design: The study used a randomised, double-blind, placebo-controlled design. Setting: The study took part in a laboratory setting. Participants: Twenty-four male and female healthy participants, aged 23.0±5.8 years. Intervention: The non-dominant arm was immobilised in a sling for a period of nine waking hours a day over two continuous weeks. Participants were randomly assigned to one of three groups: placebo (n=8, Lecithin, 2400 mg daily), omega-3 (ω-3) fatty acids (n=8, eicosapentaenoic acid (EPA); 1770 mg, and docosahexaenoic acid (DHA); 390 mg, daily) or vitamin D (n=8, 1,000 IU daily). Measurements: Muscle and sub-cutaneous adipose thickness (B-mode ultrasonography), body composition (DXA) and arm girth (anthropometry) were measured before immobilisation, immediately on removal of the sling and two weeks after re-mobilisation. Results: Muscle thickness (-5.4±4.3%), upper and lower arm girth (-1.3±0.4 and -0.8±0.8%, respectively), lean mass (-3.6±3.7%) and bone mineral content (BMC) (-2.3±1.5%) decreased significantly with limb immobilisation in the placebo group (P0.05) towards attenuating the decreases in muscle thickness, upper/lower arm girths and BMC observed in the placebo group. The ω-3 supplementation group demonstrated a non-significant attenuation of the decrease in DXA quantified lean mass observed in the placebo group. Sub-cutaneous adipose thickness increased in the placebo group (P<0.05). ω-3 and vitamin D both blunted this response, with ω-3 having a greater effect (P<0.05). All parameters had returned to baseline values at the re-mobilisation phase of the study. Conclusion: Overall, at the current doses, ω-3 and vitamin D supplementation only attenuated one of the changes associated with non-injurious limb immobilisation. These findings would necessitate further research into either a) supplementation linked to injury-induced immobilisation, or b) larger doses of these supplements to confirm/refute the physiological reserve potential of the two supplements

Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for “Holes” in the T Cell Repertoire

Background: Cytotoxic T cell (CTL) cross-reactivity is believed to play a pivotal role in generating immune responses but the extent and mechanisms of CTL cross-reactivity remain largely unknown. Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious sequence identity. The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands. Principal Findings: First, we analyzed peptide scans of the HIV epitope SLFNTVATL (SFL9) and found that TCR specificity is position dependent and that biochemically similar amino acid substitutions do not drastically affect recognition. Inspired by this, we developed a general model of TCR peptide recognition using amino acid similarity matrices and found that such a model was able to predict the cross-reactivity of a diverse set of CTL epitopes. With this model, we were able to demonstrate that seemingly distinct T cell epitopes, i.e., ones with low sequence identity, are in fact more biochemically similar than expected. Additionally, an analysis of HIV immunogenicity data with our model showed that CTLs have the tendency to respond mostly to peptides that do not resemble self-antigens. Conclusions: T cell cross-reactivity can thus, to an extent greater than earlier appreciated, be explained by amino acid similarity. The results presented in this paper will help resolving some of the long-lasting discussions in the field of T cel