Voigt Bork (footcross4)

As the reliance on metabolic biomarkers within drug discovery and development increases, there is also an increased demand for global metabolomics methods to provide broad metabolome coverage and sensitivity towards differences in metabolite expression and reproducibility. A systematic approach is necessary for the development, and evaluation, of metabolomics methods using either conventional techniques or when establishing new methods that allow for additional gains in sensitivity and a reduction in requirements for amounts of a biological sample, such as those seen with methods based on microseparations. We developed a novel standard mixture and used a systematic approach for the development and optimization of optimal, ion-pair free, liquid chromatography-mass spectrometry (LC-MS) global profiling methods. These methods were scaled-down to microflow-based LC separations and compared with analytical flow ion-pairing reagent containing methods. Average peak volume improvements of 7- and 22-fold were observed in the positive and negative ionization mode microflow methods as compared to the ion-pairing reagent analytical flow methods, respectively. The linear range of the newly developed microflow methods showed up to a 10-fold increase in the lower limit of detection in the negative ionization mode. The developed microflow LC-MS methods were further evaluated using wild-type mouse plasma where up to a 9-fold increase in peak volume was observed. Early oral or enteral nutrition (EEN) has been proven safe, tolerable, and beneficial in elective surgery. In emergency abdominal surgery no consensus exists regarding postoperative nutrition standard regimens. This review aimed to assess the safety and clinical outcomes of EEN compared to standard care after emergency abdominal surgery. The review protocol was performed according to the Cochrane Handbook and reported according to PRISMA. Clinical outcomes included mortality, specific complication rates, length of stay, and serious adverse events. Risk of bias was assessed by Cochrane risk of bias tool and Downs and Black. GRADE assessment of each outcome was performed, and Trial Sequential Analysis was completed to obtain the Required Information Size (RIS) of each outcome. From a total of 4741 records screened, a total of five randomized controlled trials and two non-randomized controlled trials were included covering 1309 patients. The included studies reported no safety issues regarding the use of EEN. A significant reduction in the mortality rate of EEN compared with standard care was seen (OR 0.59 (CI 95% 0.34-1.00), I =0%). Meta-analyses on sepsis and postoperative pulmonary complications showed non-significant tendencies in favor of EEN compared with standard care. GRADE assessment of all outcomes was evaluated 'low' or 'very low'. Trial Sequential Analysis revealed that all outcomes had insufficient RIS to confirm the effects of EEN. EEN after major emergency surgery is correlated with reduced mortality, however, more high-quality data regarding the optimal timing and composition of nutrition are needed before final conclusions regarding the effects of EEN can be made. EEN after major emergency surgery is correlated with reduced mortality, however, more high-quality data regarding the optimal timing and composition of nutrition are needed before final conclusions regarding the effects of EEN can be made. Observational studies have demonstrated the relations of homocysteine (HCY) with bone mineral density (BMD) and bone fracture risk, but yielding contradictory results. The present study was conducted to evaluate whether the genetically predicted plasma HCY levels were causally associated with the change of BMD and the risk of bone fracture. Genetic summary statistics were extracted from genome-wide association study (GWAS) meta-analysis of plasma HCY levels (n=44,147), GWAS meta-analyses of measured forea