Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

Background: Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity. Methods/Design: Sixty patients with stable angina will be recruited and randomised 1: 1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases. Discussion: This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training

Mining and analysis of audiology data to find significant factors associated with tinnitus masker

Objectives: The objective of this research is to find the factors associated with tinnitus masker from the literature, and by using the large amount of audiology data available from a large NHS (National Health Services, UK) hearing aid clinic. The factors evaluated were hearing impairment, age, gender, hearing aid type, mould and clinical comments. Design: The research includes literature survey for factors associated with tinnitus masker, and performs the analysis of audiology data using statistical and data mining techniques. Setting: This research uses a large audiology data but it also faced the problem of limited data for tinnitus. Participants: It uses 1,316 records for tinnitus and other diagnoses, and 10,437 records of clinical comments from a hearing aid clinic. Primary and secondary outcome measures: The research is looking for variables associated with tinnitus masker, and in future, these variables can be combined into a single model to develop a decision support system to predict about tinnitus masker for a patient. Results: The results demonstrated that tinnitus maskers are more likely to be fit to individuals with milder forms of hearing loss, and the factors age, gender, type of hearing aid and mould were all found significantly associated with tinnitus masker. In particular, those patients having Age<=55 years were more likely to wear a tinnitus masker, as well as those with milder forms of hearing loss. ITE (in the ear) hearing aids were also found associated with tinnitus masker. A feedback on the results of association of mould with tinnitus masker from a professional audiologist of a large NHS (National Health Services, UK) was also taken to better understand them. The results were obtained with different accuracy for different techniques. For example, the chi-squared test results were obtained with 95% accuracy, for Support and Confidence only those results were retained which had more than 1% Support and 80% Confidence. Conclusions: The variables audiograms, age, gender, hearing aid type and mould were found associated with the choice of tinnitus masker in the literature and by using statistical and data mining techniques. The further work in this research would lead to the development of a decision support system for tinnitus masker with an explanation that how that decision was obtained

Orphan receptor GPR110, an oncogene overexpressed in lung and prostate cancer

<p>Abstract</p> <p>Background</p> <p>GPR110 is an orphan G protein-coupled receptor--a receptor without a known ligand, a known signaling pathway, or a known function. Despite the lack of information, one can assume that orphan receptors have important biological roles. In a retroviral insertion mutagenesis screen in the mouse, we identified GPR110 as an oncogene. This prompted us to study the potential isoforms that can be gleaned from known GPR110 transcripts, and the expression of these isoforms in normal and transformed human tissues.</p> <p>Methods</p> <p>Various epitope-tagged isoforms of GPR110 were expressed in cell lines and assayed by western blotting to determine cleavage, surface localization, and secretion patterns. GPR110 transcript and protein levels were measured in lung and prostate cancer cell lines and clinical samples, respectively, by quantitative PCR and immunohistochemistry.</p> <p>Results</p> <p>We found four potential splice variants of GPR110. Of these variants, we confirmed three as being expressed as proteins on the cell surface. Isoform 1 is the canonical form, with a molecular mass of about 100 kD. Isoforms 2 and 3 are truncated products of isoform 1, and are 25 and 23 kD, respectively. These truncated isoforms lack the seven-span transmembrane domain characteristic of GPR proteins and thus are not likely to be membrane anchored; indeed, isoform 2 can be secreted. Compared with the median gene expression of ~200 selected genes, GPR110 expression was low in most tissues. However, it had higher than average gene expression in normal kidney tissue and in prostate tissues originating from older donors. Although identified as an oncogene in murine T lymphomas, GPR110 is greatly overexpressed in human lung and prostate cancers. As detected by immunohistochemistry, GPR110 was overexpressed in 20 of 27 (74%) lung adenocarcinoma tissue cores and in 17 of 29 (59%) prostate adenocarcinoma tissue cores. Additionally, staining with a GPR110 antibody enabled us to differentiate between benign prostate hyperplasia and potential incipient malignancy.</p> <p>Conclusion</p> <p>Our work suggests a role for GPR110 in tumor physiology and supports it as a potential therapeutic candidate and disease marker for both lung and prostate cancer.</p

A donor-specific epigenetic classifier for acute graft-versus-host disease severity in hematopoietic stem cell

Background Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological conditions. Acute graft-versus-host disease (aGVHD) is a prevalent immune-mediated complication following HSCT. Current diagnostic biomarkers that correlate with aGVHD severity, progression, and therapy response in graft recipients are insufficient. Here, we investigated whether epigenetic marks measured in peripheral blood of healthy graft donors stratify aGVHD severity in human leukocyte antigen (HLA)-matched sibling recipients prior to T cell-depleted HSCT. Methods We measured DNA methylation levels genome-wide at single-nucleotide resolution in peripheral blood of 85 HSCT donors, matched to recipients with various transplant outcomes, with Illumina Infinium HumanMethylation450 BeadChips. Results Using genome-wide DNA methylation profiling, we showed that epigenetic signatures underlying aGVHD severity in recipients correspond to immune pathways relevant to aGVHD etiology. We discovered 31 DNA methylation marks in donors that associated with aGVHD severity status in recipients, and demonstrated strong predictive performance of these markers in internal cross-validation experiments (AUC = 0.98, 95 % CI = 0.96–0.99). We replicated the top-ranked CpG classifier using an alternative, clinical DNA methylation assay (P = 0.039). In an independent cohort of 32 HSCT donors, we demonstrated the utility of the epigenetic classifier in the context of a T cell-replete conditioning regimen (P = 0.050). Conclusions Our findings suggest that epigenetic typing of HSCT donors in a clinical setting may be used in conjunction with HLA genotyping to inform both donor selection and transplantation strategy, with the ultimate aim of improving patient outcome

A Large Scale Double Beta and Dark Matter Experiment: GENIUS

The recent results from the HEIDELBERG-MOSCOW experiment have demonstrated the large potential of double beta decay to search for new physics beyond the Standard Model. To increase by a major step the present sensitivity for double beta decay and dark matter search much bigger source strengths and much lower backgrounds are needed than used in experiments under operation at present or under construction. We present here a study of a project proposed recently, which would operate one ton of 'naked' enriched GErmanium-detectors in liquid NItrogen as shielding in an Underground Setup (GENIUS). It improves the sensitivity to neutrino masses to 0.01 eV. A ten ton version would probe neutrino masses even down to 10^-3 eV. The first version would allow to test the atmospheric neutrino problem, the second at least part of the solar neutrino problem. Both versions would allow in addition significant contributions to testing several classes of GUT models. These are especially tests of R-parity breaking supersymmetry models, leptoquark masses and mechanism and right-handed W-boson masses comparable to LHC. The second issue of the experiment is the search for dark matter in the universe. The entire MSSM parameter space for prediction of neutralinos as dark matter particles could be covered already in a first step of the full experiment - with the same purity requirements but using only 100 kg of 76Ge or even of natural Ge - making the experiment competitive to LHC in the search for supersymmetry. The layout of the proposed experiment is discussed and the shielding and purity requirements are studied using GEANT Monte Carlo simulations. As a demonstration of the feasibility of the experiment first results of operating a 'naked' Ge detector in liquid nitrogen are presented.Comment: 22 pages, 12 figures, see also http://pluto.mpi-hd.mpg.de/~betalit/genius.htm

Psychometric Properties of the Chinese Version of the Perceived Stress Scale in Policewomen

BACKGROUND: The 10-item Perceived Stress Scale (PSS-10) is one of most widely used instruments to measure a global level of perceived stress in a range of clinical and research settings. This study was conducted to examine the psychometric properties of the Simplified Chinese version of the PSS-10 in policewomen. METHODOLOGY: A total of 240 policewomen were recruited in this study. The Simplified Chinese versions of the PSS-10, the Beck Depression Inventory Revised (BDI-II), and the Beck Anxiety Inventory (BAI) were administered to all participants, and 36 of the participants were re-tested two weeks after the initial testing. PRINCIPAL FINDINGS: The overall Cronbach's alpha was 0.86, and the test-retest reliability coefficient was 0.68. Exploratory Factor Analysis (EFA) yielded 2 factors with eigenvalues of 4.76 and 1.48, accounting for 62.41% of variance. Factor 1 consisted of 6 items representing "negative feelings"; whereas Factor 2 consisted of 4 items representing "positive feelings". The item loadings ranged from 0.72 to 0.83. The Confirmatory factor analysis (CFA) indicated a very good fit of this two-factor model to this sample. The PSS-10 significantly correlated with both BDI-II and BAI, indicating an acceptable concurrent validity. CONCLUSIONS: The Simplified Chinese version of the PSS-10 demonstrated adequate psychometric properties for evaluating stress levels. The results support its use among the Chinese population

Highly efficient PCR assay to discriminate allelic DNA methylation status using whole genome amplification

<p>Abstract</p> <p>Background</p> <p>We previously developed a simple method termed <it>Hpa</it>II-<it>McrBC </it>PCR (HM-PCR) to discriminate allelic methylation status of the genomic sites of interest, and successfully applied it to a comprehensive analysis of CpG islands (CGIs) on human chromosome 21q. However, HM-PCR requires 200 ng of genomic DNA to examine one target site, thereby precluding its application to such samples that are limited in quantity.</p> <p>Findings</p> <p>We developed <it>Hpa</it>II-<it>McrBC </it>whole-genome-amplification PCR (HM-WGA-PCR) that uses whole-genome-amplified DNA as the template. HM-WGA-PCR uses only 1/100th the genomic template material required for HM-PCR. Indeed, we successfully analyzed 147 CGIs by HM-WGA-PCR using only ~300 ng of DNA, whereas previous HM-PCR study had required ~30 μg. Furthermore, we confirmed that allelic methylation status revealed by HM-WGA-PCR is identical to that by HM-PCR in every case of the 147 CGIs tested, proving high consistency between the two methods.</p> <p>Conclusions</p> <p>HM-WGA-PCR would serve as a reliable alternative to HM-PCR in the analysis of allelic methylation status when the quantity of DNA available is limited.</p