Effect of Long-Term Zinc Pollution on Soil Microbial Community Resistance to Repeated Contamination

The aim of the study was to compare the effects of stress (contamination trials) on the microorganisms in zinc-polluted soil (5,018 mg Zn kg−1 soil dry weight) and unpolluted soil (141 mg Zn kg−1 soil dw), measured as soil respiration rate. In the laboratory, soils were subjected to copper contamination (0, 500, 1,500 and 4,500 mg kg−1 soil dw), and then a bactericide (oxytetracycline) combined with a fungicide (captan) along with glucose (10 mg g−1 soil dw each) were added. There was a highly significant effect of soil type, copper treatment and oxytetracycline/captan treatment. The initial respiration rate of chronically zinc-polluted soil was higher than that of unpolluted soil, but in the copper treatment it showed a greater decline. Microorganisms in copper-treated soil were more susceptible to oxytetracycline/captan contamination. After the successive soil contamination trials the decline of soil respiration was greater in zinc-polluted soil than in unpolluted soil

The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-κB transcriptional activity in models of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease that produces synovial proliferation and joint erosions. The pathologic lesions of RA are driven through the production of inflammatory mediators in the synovium mediated, in part, by the transcription factor NF-κB. We have identified a non-steroidal estrogen receptor ligand, WAY-169916, that selectively inhibits NF-κB transcriptional activity but is devoid of conventional estrogenic activity. The activity of WAY-169916 was monitored in two models of arthritis, the HLA-B27 transgenic rat and the Lewis rat adjuvant-induced model, after daily oral administration. In both models, a near complete reversal in hindpaw scores was observed as well as marked improvements in the histological scores. In the Lewis rat adjuvant model, WAY-169916 markedly suppresses the adjuvant induction of three serum acute phase proteins: haptoglobin, α1-acid glycoprotein (α1-AGP), and C-reactive protein (CRP). Gene expression experiments also demonstrate a global suppression of adjuvant-induced gene expression in the spleen, liver, and popliteal lymph nodes. Finally, WAY-169916 was effective in suppressing tumor necrosis factor-α-mediated inflammatory gene expression in fibroblast-like synoviocytes isolated from patients with RA. Together, these data suggest the utility of WAY-169916, and other compounds in its class, in treating RA through global suppression of inflammation via selective blockade of NF-κB transcriptional activity

Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes

BACKGROUND:DNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation. METHODS:Methylation levels were assessed using Illumina 450k arrays on 9,894 individuals of European ancestry from 12 cohort studies. Linear-mixed-models were used to study the association of additive MTHFR 677C>T and genetic-risk score (GRS) based on 18 homocysteine-associated SNPs, with genome-wide methylation. RESULTS:Meta-analysis revealed that the MTHFR 677C>T variant was associated with 35 CpG sites in cis, and the GRS showed association with 113 CpG sites near the homocysteine-associated variants. Genome-wide analysis revealed that the MTHFR 677C>T variant was associated with 1 trans-CpG (nearest gene ZNF184), while the GRS model showed association with 5 significant trans-CpGs annotated to nearest genes PTF1A, MRPL55, CTDSP2, CRYM and FKBP5. CONCLUSIONS:Our results do not show widespread changes in DNA-methylation across the genome, and therefore do not support the hypothesis that mildly elevated homocysteine is associated with widespread methylation changes in leukocytes

Cost, quality, and value in coronary artery bypass grafting

Objective: Pay-for-performance measures, part of the Affordable Care Act, aim to reduce health care costs by linking value with Medicare payments, but until now the concept of value has not been applied to specific procedures. We sought to define value in coronary artery bypass grafting (CABG) and provide a framework to identify high-value centers. Methods: In a multiinstitutional statewide database, clinical patient-level data from 42,839 patients undergoing CABG were matched with cost data. Hierarchical models adjusting for relevant preoperative patient characteristics and comorbidities were used to estimate center-specific risk-adjusted costs and risk-adjusted postoperative length of stay. Variation in value across centers was assessed by the correlation between risk-adjusted measures of quality (mortality, morbidity/mortality) and resource use (costs and length of stay). Results: There were no significant correlations between risk-adjusted costs and risk-adjusted mortality (r = 0.20, P = .45) or morbidity/mortality (r = 0.15, P = .57) across centers. Risk-adjusted costs and length of stay were not significantly associated (r = 0.23, P = .37) because of cost accounting differences across centers. This may explain the lack of correlation between risk-adjusted quality and risk-adjusted cost measures. When risk-adjusted length of stay and morbidity/mortality were used for the framework, there was a strong positive correlation (r = 0.67, P = .003), indicating that higher risk-adjusted quality is associated with shorter risk-adjusted length of stay. Conclusions: Risk-adjusted length of stay and risk-adjusted combined morbidity/mortality are important outcome measures for assessing value in cardiac surgery. The proposed framework can be used to define value in CABG and identify high-value centers, thereby providing information for quality improvement and pay-for-performance initiatives

Prediction of Costs and Length of Stay in Coronary Artery Bypass Grafting

Background. Although more than 200,000 bypass operations are performed in the United States annually, few data exist on the predictors of costs and resource use for this procedure. Questions related to clinical outcomes, costs, and resource use in coronary artery bypass grafting (CABG) were addressed. Methods. In a multiinstitutional statewide database, patient level data from 42,839 patients undergoing isolated CABG were combined with cost data. After adjustment for cost-to-charge ratios and inflation, the association of length of stay and costs with the Society of Thoracic Surgeons-Predicted Risk of Mortality (STS-PROM) was analyzed. Patients were randomly divided into development (60%) and validation (40%) cohorts. Regression models were developed to analyze the impact of patient characteristics, comorbidities, and adverse events on postoperative length of stay and total costs. Results. Postoperative length of stay and total direct costs for CABG averaged 6.9 days and $38,847. Length of stay and costs increased from 5.4 days and$33,275 in the lowest-risk decile (mean STS-PROM of 0.6%) to 13.8 days and $69,122 in the highest-risk decile (mean STS-PROM 19%). Compared with adverse events, patient characteristics had little impact on length of stay and costs. on validation, the models that combined preoperative and postoperative variables explained variance better (R-2 = 0.51 for length of stay; R-2 = 0.47 for costs) and were better calibrated than the preoperative models (R-2 = 0.10 for length of stay; R-2 = 0.14 for costs). Conclusions. The STS-PROM and preoperative regression models are useful for preoperative prediction of costs and length of stay for groups of patients, case-mix adjustment in hospital benchmarking, and pay for performance measures. The combined preoperative and postoperative models identify incremental costs and length of stay associated with adverse events and are more suitable for prioritizing quality improvement efforts. (C) 2014 by The Society of Thoracic Surgeon