Detection of antibodies directed at M. hyorhinis p37 in the serum of men with newly diagnosed prostate cancer

<p>Abstract</p> <p>Background</p> <p>Recent epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including cancers of the prostate. Over the past several years, our group has been studying how mycoplasmas could possibly initiate and propagate cancers of the prostate. Specifically, <it>Mycoplasma hyorhinis </it>encoded protein p37 was found to promote invasion of prostate cancer cells and cause changes in growth, morphology and gene expression of these cells to a more aggressive phenotype. Moreover, we found that chronic exposure of benign human prostate cells to <it>M. hyorhinis </it>resulted in significant phenotypic and karyotypic changes that ultimately resulted in the malignant transformation of the benign cells. In this study, we set out to investigate another potential link between mycoplasma and human prostate cancer.</p> <p>Methods</p> <p>We report the incidence of men with prostate cancer and benign prostatic hyperplasia (BPH) being seropositive for <it>M. hyorhinis</it>. Antibodies to <it>M. hyorhinis </it>were surveyed by a novel indirect enzyme-linked immunosorbent assay (ELISA) in serum samples collected from men presenting to an outpatient Urology clinic for BPH (N = 105) or prostate cancer (N = 114) from 2006-2009.</p> <p>Results</p> <p>A seropositive rate of 36% in men with BPH and 52% in men with prostate cancer was reported, thus leading us to speculate a possible connection between <it>M. hyorhinis </it>exposure with prostate cancer.</p> <p>Conclusions</p> <p>These results further support a potential exacerbating role for mycoplasma in the development of prostate cancer.</p

World Antimalarial Resistance Network (WARN) II: In vitro antimalarial drug susceptibility

Intrinsic resistance of Plasmodium falciparum is clearly a major determinant of the clinical failure of antimalarial drugs. However, complex interactions between the host, the parasite and the drug obscure the ability to define parasite drug resistance in vivo. The in vitro antimalarial drug susceptibility assay determines ex-vivo growth of parasite in the presence of serial drug concentrations and, thus, eliminates host effects, such as drug metabolism and immunity. Although the sensitivity of the parasite to various antimalarials provided by such a test provides an important indicator of intrinsic parasite susceptibility, there are fundamental methodological issues that undermine comparison of in vitro susceptibility both between laboratories and within a single laboratory over time. A network of laboratories is proposed that will agree on the basic parameters of the in vitro test and associated measures of quality control. The aim of the network would be to establish baseline values of sensitivity to commonly used antimalarial agents from key regions of the world, and create a global database, linked to clinical, molecular and pharmacology databases, to support active surveillance to monitor temporal trends in parasite susceptibility. Such a network would facilitate the rapid detection of strains with novel antimalarial resistance profiles and investigate suitable alternative treatments with retained efficacy

C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older.

Inflammation is believed to play a role in prostate cancer (PCa) etiology, but it is unclear whether inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) associate with PCa risk in older men. Using Cox regression, we assessed the relationship between baseline concentrations of CRP and IL-6 and the subsequent PCa risk in the Cardiovascular Health Study, a population-based cohort study of mostly European American men of ages >64 years (n = 2,234; mean follow-up = 8.7 years; 215 incident PCa cases). We also tested associations between CRP and IL-6 tagSNPs and PCa risk, focusing on SNPs that are known to associate with circulating CRP and/or IL-6. Neither CRP nor IL-6 blood concentrations was associated with PCa risk. The C allele of IL-6 SNP rs1800795 (-174), a known functional variant, was associated with increased risk in a dominant model (HR = 1.44; 95% CI = 1.03-2.01; p = 0.03), but was not statistically significant after accounting for multiple tests (permutation p = 0.21). Our results suggest that circulating CRP and IL-6 do not influence PCa risk. SNPs at the CRP locus are not associated with PCa risk in this cohort, while the association between rs1800795 and PCa risk warrants further investigation

A simple and rapid approach for screening of SARS-coronavirus genotypes: an evaluation study

BACKGROUND: The Severe Acute Respiratory Syndrome (SARS) was a newly emerged infectious disease which caused a global epidemic in 2002–2003. Sequence analysis of SARS-coronavirus isolates revealed that specific genotypes predominated at different periods of the epidemic. This information can be used as a footprint for tracing the epidemiology of infections and monitor viral evolution. However, direct sequencing analysis of a large number of clinical samples is cumbersome and time consuming. We present here a simple and rapid assay for the screening of SARS-coronavirus genotypes based on the use of fluorogenic oligonucleotide probes for allelic discrimination. METHODS: Thirty SARS patients were recruited. Allelic discrimination assays were developed based on the use of fluorogenic oligonucleotide probes (TaqMan). Genotyping of the SARS-coronavirus isolates obtained from these patients were carried out by the allelic discrimination assays and confirmed by direct sequencing. RESULTS: Genotyping based on the allelic discrimination assays were fully concordant with direct sequencing. All of the 30 SARS-coronavirus genotypes studied were characteristic of genotypes previously documented to be associated with the latter part of the epidemic. Seven of the isolates contained a previously reported major deletion but in patients not epidemiologically related to the previously studied cohort. CONCLUSION: We have developed a simple and accurate method for the characterization and screening of SARS-coronavirus genotypes. It is a promising tool for the study of epidemiological relationships between documented cases during an outbreak

Development of physical and mental health summary scores from the patient-reported outcomes measurement information system (PROMIS) global items

The use of global health items permits an efficient way of gathering general perceptions of health. These items provide useful summary information about health and are predictive of health care utilization and subsequent mortality. Analyses of 10 self-reported global health items obtained from an internet survey as part of the Patient-Reported Outcome Measurement Information System (PROMIS) project. We derived summary scores from the global health items. We estimated the associations of the summary scores with the EQ-5D index score and the PROMIS physical function, pain, fatigue, emotional distress, and social health domain scores. Exploratory and confirmatory factor analyses supported a two-factor model. Global physical health (GPH; 4 items on overall physical health, physical function, pain, and fatigue) and global mental health (GMH; 4 items on quality of life, mental health, satisfaction with social activities, and emotional problems) scales were created. The scales had internal consistency reliability coefficients of 0.81 and 0.86, respectively. GPH correlated more strongly with the EQ-5D than did GMH (r = 0.76 vs. 0.59). GPH correlated most strongly with pain impact (r = −0.75) whereas GMH correlated most strongly with depressive symptoms (r = −0.71). Two dimensions representing physical and mental health underlie the global health items in PROMIS. These global health scales can be used to efficiently summarize physical and mental health in patient-reported outcome studies

Sensitivity to change of the Beach Questionnaire to behaviour, attitudes and knowledge related to sun exposure: quasi-experimental before-after study

Background: Health questionnaires must present accredited measurement properties such as validity, reliability and sensitivity to change, the latter being essential for interventions to be planned and for evaluating their effectiveness. The aim of this study was to evaluate the sensitivity to change of a Beach Questionnaire.Methods: Quasi-experimental before-after study carried out in 2011, for a study population of adolescents attending schools in the Costa del Sol. First, the questionnaire was administered to the adolescents, after which a multicomponent educational intervention was carried out; finally, three months later, the same questionnaire was re-administered to the same adolescents. Changes were assessed in the categories of each item, using the McNemar test, and the changes in the scores, standardised to a range of 0–100, using the Student t test for paired samples, and including the mean of the differences and the 95% confidence interval. The level of statistical significance was set at p < 0.05.Results: 228 adolescents, aged 14–17 years, and 55.3% were girls. Statistically significant changes were observed in sunburn experiences, exposure to the sun at mid-day and attitudes to sun exposure and suncreams. For the seven items related to knowledge about sun exposure, a higher rate of correct answers was observed. The analysis of changes, within the standardised range, revealed a significant improvement in the scores for sun exposure habits (MD 4.33; CI 95% 2.2-6.5), attitudes to sun exposure (MD 2.22; CI 95% 1.2-3.2) and knowledge (MD 9.10; CI 95% 7.1-11.1), but not in those for sun-protection practices (MD 0.23; CI 95% -1.2-1.7).Conclusions: The Beach Questionnaire on behaviour, attitudes and knowledge related to sun exposure is the first such instrument in Spanish language to provide sufficient sensitivity to change. It constitutes a useful tool for epidemiologic research into photoprotection and for skin cancer prevention programmes.The authors would like to acknowledge support from the Research Department of the Costa del Sol Hospital

Improving adherence to medication in stroke survivors (IAMSS): a randomised controlled trial: study protocol

Background: Adherence to therapies is a primary determinant of treatment success, yet the World Health Organisation estimate that only 50% of patients who suffer from chronic diseases adhere to treatment recommendations. In a previous project, we found that 30% of stroke patients reported sub-optimal medication adherence, and this was associated with younger age, greater cognitive impairment, lower perceptions of medication benefits and higher specific concerns about medication. We now wish to pilot a brief intervention aimed at (a) helping patients establish a better medication-taking routine, and (b) eliciting and modifying any erroneous beliefs regarding their medication and their stroke. Methods/Design: Thirty patients will be allocated to a brief intervention (2 sessions) and 30 to treatment as usual. The primary outcome will be adherence measured over 3 months using Medication Event Monitoring System (MEMS) pill containers which electronically record openings. Secondary outcomes will include self reported adherence and blood pressure. Discussion: This study shall also assess uptake/attrition, feasibility, ease of understanding and acceptability of this complex intervention. Trial Registration: Current Controlled Trials ISRCTN3827495

Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer

<p>Abstract</p> <p>Background</p> <p>Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk.</p> <p>Methods</p> <p>A case-control study design was used to test the association between prostate cancer risk and the polymorphisms <it>TNF-A</it>-308 A/G (rs 1800629), <it>RANTES</it>-403 G/A (rs 2107538), <it>IL1-A</it>-889 C/T (rs 1800587) and <it>MCP-1 </it>2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area.</p> <p>Results</p> <p>Diagnosis of prostate cancer was significantly associated with <it>TNF-A </it>GA + AA genotype (OR, 1.61; 95% CI, 1.09–2.64) and <it>RANTES </it>GA + AA genotype (OR, 1.44; 95% CI, 1.09–2.38). A alleles in <it>TNF-A </it>and <it>RANTES </it>influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and <it>IL1-A </it>or <it>MCP-1 </it>polymorphisms.</p> <p>Conclusion</p> <p>Our results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development.</p

Association of genetic polymorphisms in the interleukin-10 promoter with risk of prostate cancer in Chinese

<p>Abstract</p> <p>Background</p> <p>Recent studies identified an increased risk of prostate cancer (PCa) in Caucasian men harboring polymorphisms of genes involved in innate immunity and inflammation. This study was designed to assess whether single nucleotide polymorphisms in the IL-10 promoter play a role in predisposing individuals to PCa in a Chinese population.</p> <p>Methods</p> <p>We genotyped three SNPs of the <it>IL-10 </it>promoter (-1082A/G, -819T/C and -592A/C) using polymerase chain reaction-restriction fragment length polymorphism analysis in 262 subjects with PCa and 270 age-matched healthy controls. Odds ratio and 95% confidence interval were determined by logistic regression for the associations between IL-10 genotypes and haplotypes with the risk of PCa and advanced PCa grade.</p> <p>Results</p> <p>No significant differences in allele frequency or genotype distribution were observed for any of the <it>IL-10 </it>SNPs between PCa patients and control subjects. Significantly higher frequencies of -1082G, -819C and -592C allele and GCC haplotype were observed, however, in early stage patients in comparison to advanced PCa patients (for -1082 G, 13.9% vs 6.1%, OR = 2.48, <it>P </it>= 0.005; for -819 C 40.3% vs 30.8%, OR = 1.51, <it>P </it>= 0.043; for -512C, 40.3% vs 30.8%, OR = 1.51, <it>P </it>= 0.043; and for haplotype GCC 11.1%vs 5.1%, OR = 2.66, P = 0.008, respectively).</p> <p>Conclusions</p> <p>Our results identify that <it>IL-10 </it>promoter polymorphisms might not be a risk factor for PCa in Chinese cohorts, but rather incidence of polymorphisms associates with PCa grade, suggesting that IL-10 expression may impact PCa progression.</p