Emergence of vancomycin-resistant enterococci from vancomycin-susceptible enterococci in hospitalized patients under antimicrobial therapy.

OBJECTIVES: Enterococci are opportunistic pathogens with plastic genomes that evolve, acquire, and transmit antimicrobial-resistant determinants such as vancomycin resistance clusters. While vancomycin-resistant enterococci (VRE) have emerged as successful nosocomial pathogens, the mechanism by which vancomycin-susceptible enterococci (VSE) transform to VRE in hospitalized patients remains understudied. METHODS: Genomes of Enterococcus faecium from two critically ill hospitalized patients subjected to multiple antibiotic therapies, including broad-spectrum antibiotics, were investigated. To identify mechanisms of resistance evolution, genomes of vancomycin-susceptible and -resistant isolates were compared. RESULTS: While VSE isolates were initially identified, VRE strains emerged post-vancomycin therapy. Comparative genomics revealed horizontal transmission of mobile genetic elements containing the Tn1549 transposon, which harbours the vanB-type vancomycin resistance gene cluster. This suggests that broad-spectrum antibiotic stress promoted the transfer of resistance-conferring elements, presumably from another gut inhabitant. CONCLUSION: This is one of the first studies investigating VSE and VRE isolates from the same patient. The mechanism of transmission and the within-patient evolution of vancomycin resistance via mobile genetic elements under antibiotic stress is illustrated. Our findings serve as a foundation for future studies building on this knowledge which can further elucidate the dynamics of antibiotic stress, resistance determinant transmission, and interactions within the gut microbiota.

Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study.

Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional 18 variants previously associated with Se concentrations were extracted from existing genotyping data within EPIC for 1564 case-control pairs. Multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the association between Se status markers, SNP variants and BC risk. Overall, there was no statistically significant association of Se status with BC risk. However, higher GPX3 activity was associated with lower risk of premenopausal BC (4th versus 1st quartile, OR = 0.54, 95 % CI: 0.30-0.98, Ptrend = 0.013). While none of the genetic variant associations (P ≤ 0.05) retained significance after multiple testing correction, rs1004243 in the SELENOM selenoprotein gene and two SNPs in the related antioxidant TXN2 gene (rs4821494 and rs5750261) were associated with respective lower and higher risks of BC at a significance threshold of P ≤ 0.01. Fourteen SNPs in twelve Se pathway genes (P ≤ 0.01) in interaction with Se status were also associated with BC risk. Higher Se status does not appear to be associated with BC risk, although activity of the selenoenzyme GPX3 may be inversely associated with premenopausal BC risk, and SNPs in the Se pathway alone or in combination with suboptimal Se status may influence BC risk.

Coffee consumption and overall and cause-specific mortality: the Norwegian Women and Cancer Study (NOWAC).

Coffee consumption has previously been reported to reduce overall and cause-specific mortality. We aimed to further investigate this association by coffee brewing methods and in a population with heavy coffee consumers. The information on total, filtered, instant, and boiled coffee consumption from self-administered questionnaires was available from 117,228 women in the Norwegian Women and Cancer (NOWAC) Study. We used flexible parametric survival models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause, cardiovascular, and cancer mortality by total coffee consumption and brewing methods, and adjusted for smoking status, number of pack-years, age at smoking initiation, alcohol consumption, body mass index, physical activity, and duration of education. During 3.2 million person-years of follow-up, a total of 16,106 deaths occurred. Compared to light coffee consumers (≤ 1 cup/day), we found a statistically significant inverse association with high-moderate total coffee consumption (more than 4 and up to 6 cups/day, HR 0.89; 95% CI 0.83-0.94) and all-cause mortality. The adverse association between heavy filtered coffee consumption (> 6 cups/day) and all-cause mortality observed in the entire sample (HR 1.09; 95% CI 1.01-1.17) was not found in never smokers (HR 0.85; 95% CI 0.70-1.05). During the follow-up, both high-moderate total and filtered coffee consumption were inversely associated with the risk of cardiovascular mortality (HR 0.79; 95% CI 0.67-0.94; HR 0.80; 95% CI 0.67-0.94, respectively). The association was stronger in the analyses of never smokers (> 6 cups of filtered coffee/day HR 0.20; 95% CI 0.08-0.56). The consumption of more than 6 cups/day of filtered, instant, and coffee overall was found to increase the risk of cancer deaths during the follow-up. However, these associations were not statistically significant in the subgroup analyses of never smokers. The data from the NOWAC study indicate that the consumption of filtered coffee reduces the risk of cardiovascular deaths. The observed adverse association between coffee consumption and cancer mortality is most likely due to residual confounding by smoking.

Coffee Consumption and Whole-Blood Gene Expression in the Norwegian Women and Cancer Post-Genome Cohort.

Norwegians are the second highest consumers of coffee in the world. Lately, several studies have suggested that beneficial health effects are associated with coffee consumption. By analyzing whole-blood derived, microarray based mRNA gene expression data from 958 cancer-free women from the Norwegian Women and Cancer Post-Genome Cohort, we assessed the potential associations between coffee consumption and gene expression profiles and elucidated functional interpretation. Of the 958 women included, 132 were considered low coffee consumers (<1 cup of coffee/day), 422 moderate coffee consumers (1⁻3 cups of coffee/day), and 404 were high coffee consumers (>3 cups of coffee/day). At a false discovery rate <0.05, 139 genes were differentially expressed between high and low consumers of coffee. A subgroup of 298 nonsmoking, low tea consumers was established to isolate the effects of coffee from smoking and potential caffeine containing tea consumption. In this subgroup, 297 genes were found to be differentially expressed between high and low coffee consumers. Results indicate differentially expressed genes between high and low consumers of coffee with functional interpretations pointing towards a possible influence on metabolic pathways and inflammation.

Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99% confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046).

Vitamin D status and PUFA ratios in a national representative cross-section of healthy, middle-aged Norwegian women­the Norwegian Women and Cancer Post-Genome Cohort.

AIMS: Vitamin D and polyunsaturated fatty acids (PUFAs) are derived from partially overlapping sources. Vitamin D is produced in the skin after sun exposure, but is also derived from fatty fish and fish oils. Dietary PUFAs are mainly derived from plant oils that are rich in n-6 PUFAs, but fatty fish provides high amounts of the marine n-3 PUFAs. The Western diet provides an excess of n-6 PUFAs compared to n-3 PUFAs, and the ratios of these may influence human health. Here, we investigated the potential associations of plasma concentrations of vitamin D, marine PUFAs and PUFA ratios. METHODS: Plasma concentrations of vitamin D (25(OH)D), marine PUFAs, and PUFA ratios were measured in 372 women from the Norwegian Women and Cancer (NOWAC) Post-Genome Cohort. Covariability was examined in 310 non-users of cod liver oil, using Spearman's rank correlation and linear regression. RESULTS: In non-users of cod liver oil, the average concentration of vitamin D was 40.3 nmol/L, and marine PUFA concentration was 0.2 mg/g. PUFA ratios were dominated by the n-6 fatty acids. Vitamin D levels were significantly associated with marine fatty acids and weakly associated with PUFA ratios. CONCLUSIONS: Concentrations of vitamin D and marine PUFAs were below recommended levels. The correlation analyses indicated that health-related effects of vitamin D and marine PUFAs respectively may be hard to separate in epidemiological studies. However, measured health effects of PUFA ratios and vitamin D are likely to derive from the influence of the two factors separately. The presented results are the first to show these associations in a nationally representative cohort.

Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Plasma phospholipid fatty acids have been correlated with food intakes in populations with homogeneous dietary patterns. However, few data are available on populations with heterogeneous dietary patterns. OBJECTIVE: The objective was to investigate whether plasma phospholipid fatty acids are suitable biomarkers of dietary intakes across populations involved in a large European multicenter study. DESIGN: A cross-sectional study design nested to the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted to determine plasma fatty acid profiles in >3,000 subjects from 16 centers, who had also completed 24-h dietary recalls and dietary questionnaires. Plasma fatty acids were assessed by capillary gas chromatography. Ecological and individual correlations were calculated between fatty acids and select food groups. RESULTS: The most important determinant of plasma fatty acids was region, which suggests that the variations across regions are largely due to different food intakes. Strong ecological correlations were observed between fish intake and long-chain n-3 polyunsaturated fatty acids (r = 0.78, P < 0.01), olive oil and oleic acid (r = 0.73, P < 0.01), and margarine and elaidic acid (r = 0.76, P < 0.01). Individual correlations varied across the regions, particularly between olive oil and oleic acid and between alcohol and the saturation index, as an indicator of stearoyl CoA desaturase activity. CONCLUSIONS: These findings indicate that specific plasma phospholipid fatty acids are suitable biomarkers of some food intakes in the EPIC Study. Moreover, these findings suggest complex interactions between alcohol intake and fatty acid metabolism, which warrants further attention in epidemiologic studies relating dietary fatty acids to alcohol-related cancers and other chronic diseases.