Determination of the Oxidative Stress Biomarkers of 8-Hydroxydeoxyguanosine and Dityrosine in the Gills, Skin, Dorsal Fin, and Liver Tissue of Atlantic Salmon (Salmo salar) Parr

Oxidative stress is a condition caused by an imbalance in the occurrence of reactive oxygen species in the cells and tissues of organisms. An ultra-performance liquid chromatography–electrospray ionization tandem mass spectrometry (UPLC–ESI–MS/MS) method was developed for the simultaneous determination of two oxidative stress biomarkers, 8-hydroxydeoxyguanosine (8OHDG) and dityrosine (DIY), in the gills, skin, dorsal fin, and liver tissue of Atlantic salmon (Salmo salar) parr. The use of target analyte-specific 13C and 15N internal standards allowed quantification of each target analyte to be performed through the standard solvent calibration curve. The relative recoveries [mean ± (relative standard deviation%)] of 8OHDG and DIY were 101 ± 11 and 104 ± 13% at a fortified concentration of 10 ng/mL (8OHDG) and 500 ng/mL (DIY), respectively, ensuring the accuracy of the extraction and quantification. The chromatographic separation was carried out using a gradient elution program with a total run time of 5 min. The limits of detection (LODs) were 0.11 and 1.37 ng/g wet weight (w.w.) for 8OHDG and DIY, respectively. To demonstrate the applicability of the developed method, it was applied in 907 tissue samples that were collected from Atlantic salmon parr individuals reared in an experimental land-based recirculating aquaculture system (RAS) treated with peracetic acid. Moreover, the possibility of using the dorsal fin as an alternative matrix for the minimally invasive assessment of oxidative stress in Atlantic salmon parr was introduced. To our knowledge, 8OHDG and DIY were used for the first time as biomarkers for biomonitoring the fish health (oxidative stress) of Atlantic salmon parr in RAS.Determination of the Oxidative Stress Biomarkers of 8-Hydroxydeoxyguanosine and Dityrosine in the Gills, Skin, Dorsal Fin, and Liver Tissue of Atlantic Salmon (Salmo salar) ParrpublishedVersio

Aortic valve replacement in octogenarians

<p>Abstract</p> <p>Background and Aims</p> <p>As our population ages and life expectancy increases the number of people aged over 80 and more referred for cardiac surgery is growing. This study sought to identify the outcome of aortic valve replacement (AVR) in octogenarians.</p> <p>Methods</p> <p>68 patients aged 80 years or more underwent AVR at the Freeman Hospital, between April 2001 and April 2004. A retrospective review of the notes and outcomes from the patients' GP and the NHS strategic tracking service was performed. 54% (37) underwent isolated AVR whilst 46% (31) underwent combined AVR and CABG.</p> <p>Results</p> <p>Follow up was 100% complete. The mean age was 83.1 ± s.d. 2.9 years, a mean gradient of 83 ± s.d. 31 mmHg and mean AVA of 0.56 cm². The mean additive EuroSCORE was 8.6 ± s.d. 1.2, the logistic EuroSCORE mean 12.0 ± s.d. 5.9. In hospital 30 day mortality was 13 %. Survival was 80% at 1 year and 78% at 2 years. Median follow up was for 712 days. Stepwise logistic regression identified chronic obstructive airways disease as an independent predictor of mortality (p < 0.05). Survival was not adversely affected by the addition of coronary artery bypass grafts to aortic valve replacement, the presence of peripheral vascular disease, hypertension or diabetes. In this study duration of cross clamp or bypass time were not found to reach significance as independent predictors of mortality.</p> <p>Conclusion</p> <p>Our study demonstrates that the operative mortality for AVR in the over eighties is good, whilst the mid to long term outcome is excellent There is a very low attrition rate with those undergoing the procedure living as long than their age matched population. This study confirms AVR is a safe, acceptable treatment for octogenarians with excellent mid term outcomes.</p

Case-mix and the use of control charts in monitoring mortality rates after coronary artery bypass

BACKGROUND: There is debate about the role of crude mortality rates and case-mix adjusted mortality rates in monitoring the outcomes of treatment. In the context of quality improvement a key purpose of monitoring is to identify special cause variation as this type of variation should be investigated to identify possible causes. This paper investigates agreement between the identification of special cause variation in risk adjusted and observed hospital specific mortality rates after coronary artery bypass grafting in New York hospitals. METHODS: Coronary artery bypass grafting mortality rates between 1994 and 2003 were obtained from the New York State Department of Health's cardiovascular reports for 41 hospitals. Cross-sectional control charts of crude (observed) and risk adjusted mortality rates were produced for each year. Special cause variation was defined as a data point beyond the 99.9% probability limits: hospitals showing special cause variation were identified for each year. Longitudinal control charts of crude (observed) and risk adjusted mortality rates were produced for each hospital with data for all ten years (n = 27). Special cause variation was defined as a data point beyond 99.9% probability limits, two out of three consecutive data points beyond 95% probability limits (two standard deviations from the mean) or a run of five consecutive points on one side of the mean. Years showing special cause variation in mortality were identified for each hospital. Cohen's Kappa was calculated for agreement between special causes identified in crude and risk-adjusted control charts. RESULTS: In cross sectional analysis the Cohen's Kappa was 0.54 (95% confidence interval: 0.28 to 0.78), indicating moderate agreement between the crude and risk-adjusted control charts with sensitivity 0.4 (95% confidence interval 0.17–0.69) and specificity 0.98 (95% confidence interval: 0.95–0.99). In longitudinal analysis, the Cohen's Kappa was 0.61 (95% confidence interval: 0.39 to 0.83) indicating good agreement between the tests with sensitivity 0.63 (95% confidence interval: 0.39–0.82) and specificity 0.98 (95% confidence interval: 0.96 to 0.99). CONCLUSION: There is moderate-good agreement between signals of special cause variation between observed and risk-adjusted mortality. Analysis of observed hospital specific CABG mortality over time and with other hospitals appears to be useful in identifying special causes of variation. Case-mix adjustment may not be essential for longitudinal monitoring of outcomes using control charts

Metabolic shift induced by synthetic co-cultivation promotes high yield of chain elongated acids from syngas

Bio-catalytic processes for sustainable production of chemicals and fuels receive increased attention within the concept of circular economy. Strategies to improve these production processes include genetic engineering of bio-catalysts or process technological optimization. Alternatively, synthetic microbial co-cultures can be used to enhance production of chemicals of interest. It remains often unclear however how microbe to microbe interactions affect the overall production process and how this can be further exploited for application. In the present study we explored the microbial interaction in a synthetic co-culture of Clostridium autoethanogenum and Clostridium kluyveri, producing chain elongated products from carbon monoxide. Monocultures of C. autoethanogenum converted CO to acetate and traces of ethanol, while during co-cultivation with C. kluyveri, it shifted its metabolism significantly towards solventogenesis. In C. autoethanogenum, expression of the genes involved in the central carbon- and energy-metabolism remained unchanged during co-cultivation compared to monoculture condition. Therefore the shift in the metabolic flux of C. autoethanogenum appears to be regulated by thermodynamics, and results from the continuous removal of ethanol by C. kluyveri. This trait could be further exploited, driving the metabolism of C. autoethanogenum to solely ethanol formation during co-cultivation, resulting in a high yield of chain elongated products from CO-derived electrons. This research highlights the important role of thermodynamic interactions in (synthetic) mixed microbial communities and shows that this can be exploited to promote desired conversions.The research leading to these results has received funding from the Netherlands Ministry of Education, Culture and Science and from the Netherlands Science Foundation (NWO) under the Gravitation Grant nr. 024.002.002 and Programme ‘Closed Cycles’ with Project nr. ALWGK.2016.029.info:eu-repo/semantics/publishedVersio

Microwave synthesis, characterization and perspectives of wood pencil-derived carbon

More than 14 billion pencils are manufactured and used globally every year. On average, a pencil is discarded after 60% of its original length has been depleted. In the present work we propose a simple and affordable way of converting this non-neglectable amount of waste into added value carbon product. In particular, we demonstrate the microwave synthesis of carbon from the wood pencil with and without chemical activation. This could be a process stage before the final recycling of the expensive graphite core. In the latter case, irradiation of the wood pencil in a domestic microwave oven heats up the pencil's graphite core, thus inducing carbonization of its wood casing. The carbonized product consists of amorphous carbon nanosheets having relatively low surface area. However, if the wood pencil is soaked in 50% KOH aqueous solution prior to microwave irradiation, a significantly higher surface area of carbon is obtained, consisting of irregular-shaped porous particles. Consequently, the obtained carbon can easily decolorize a methylene blue aqueous solution, can be used to make pocket warmers or gunpowder, and lastly, serves as an excellent adsorbent towards Cr(VI) removal from water, showing a maximum adsorption capacity of 70-75 mg/g within 24 h at 23 degrees C, pH = 3.Web of Science121art. no. 41

Medical treatment of renal cancer: new horizons.

Renal cell carcinoma (RCC) makes up 2-3% of adult cancers. The introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors in the mid-2000s radically changed the management of RCC. These targeted treatments superseded immunotherapy with interleukin-2 and interferon. The pendulum now appears to be shifting back towards immunotherapy, with the evidence of prolonged overall survival of patients with metastatic RCC on treatment with the anti-programmed cell death 1 ligand monoclonal antibody, nivolumab. Clinical prognostic criteria aid prediction of relapse risk for resected localised disease. Unfortunately, for patients at high risk of relapse, no adjuvant treatment has yet shown benefit, although further trials are yet to report. Clinical prognostic models also have a role in the management of advanced disease; now there is a pressing need for predictive biomarkers to direct therapy. Treatment selection for metastatic disease is currently based on histology, prognostic group and patient preference based on side effect profile. In this article, we review the current medical and surgical management of localised, oligometastatic and advanced RCC, including side effect management and the evidence base for management of poor-risk and non-clear cell disease. We discuss recent results from clinical trials and how these are likely to shape future practice and a renaissance of immunotherapy for renal cell cancer

Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine

Background: The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management. Methods: A metabolomics approach based on GC-MS was used to investigate the performance of volatile organic compounds (VOCs) in general and, more specifically, volatile carbonyl compounds (VCCs) present in urine as potential markers for PCa detection. Results: Results showed that PCa patients (n = 40) can be differentiated from cancer-free subjects (n = 42) based on their urinary volatile profile in both VOCs and VCCs models, unveiling significant differences in the levels of several metabolites. The models constructed were further validated using an external validation set (n = 18 PCa and n = 18 controls) to evaluate sensitivity, specificity and accuracy of the urinary volatile profile to discriminate PCa from controls. The VOCs model disclosed 78% sensitivity, 94% specificity and 86% accuracy, whereas the VCCs model achieved the same sensitivity, a specificity of 100% and an accuracy of 89%. Our findings unveil a panel of 6 volatile compounds significantly altered in PCa patients' urine samples that was able to identify PCa, with a sensitivity of 89%, specificity of 83%, and accuracy of 86%. Conclusions: It is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa.info:eu-repo/semantics/publishedVersio

Plasmin Inhibitors Prevent Leukocyte Accumulation and Remodeling Events in the Postischemic Microvasculature

Clinical trials revealed beneficial effects of the broad-spectrum serine protease inhibitor aprotinin on the prevention of ischemia-reperfusion (I/R) injury. The underlying mechanisms remained largely unclear. Using in vivo microscopy on the cremaster muscle of male C57BL/6 mice, aprotinin as well as inhibitors of the serine protease plasmin including tranexamic acid and ε-aminocaproic acid were found to significantly diminish I/R-elicited intravascular firm adherence and (subsequent) transmigration of neutrophils. Remodeling of collagen IV within the postischemic perivenular basement membrane was almost completely abrogated in animals treated with plasmin inhibitors or aprotinin. In separate experiments, incubation with plasmin did not directly activate neutrophils. Extravascular, but not intravascular administration of plasmin caused a dose-dependent increase in numbers of firmly adherent and transmigrated neutrophils. Blockade of mast cell activation as well as inhibition of leukotriene synthesis or antagonism of the platelet-activating-factor receptor significantly reduced plasmin-dependent neutrophil responses. In conclusion, our data suggest that extravasated plasmin(ogen) mediates neutrophil recruitment in vivo via activation of perivascular mast cells and secondary generation of lipid mediators. Aprotinin as well as the plasmin inhibitors tranexamic acid and ε-aminocaproic acid interfere with this inflammatory cascade and effectively prevent postischemic neutrophil responses as well as remodeling events within the vessel wall