Effects of ursodeoxycholic acid on synthesis of cholesterol and bile acids in healthy subjects

Background/Aims: Ursodeoxycholic acid ( UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methyl-glutarylcoenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding. Methods: UDCA was given to 8 healthy volunteers ( 5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during ( days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis. Results: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment ( p < 0.05). Conclusions: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy

Note on the Hydrolysis of Nitrobenzene

Wohl describes the oxidation of nitrobenzene to nitrophenols by the action of powdered potassium hydroxide at temperatures between 60° and 90° C. This reaction does not take place under similar conditions with solid sodium hydroxide

Potential of Forages in Crop Diversification and Crop Rotation

Redesign of agricultural systems according to ecological principles has been proposed for the development of sustainable systems. We review a wide variety of ecologically-based crop production practices that focus on forage crops in farming systems and discuss their potential role in enhancing the profitability, environmental sustainability and resilience. Crop-livestock systems that most closely mimic natural systems through appropriate integration of diverse components appear to offer the greatest potential benefits. These systems are more energy efficient and combine high productivity with low ecological footprint. Greater understanding of ecological relationships within crop-livestock systems are required to purposefully and proactively redesign agricultural systems for profitability, sustainability and resilience

Is statistical learning trainable?

Statistical learning (SL) is the ability to implicitly extract regularities in the environment, and likely supports various higher-order behaviors, from language to music and vision. While specific patterns experience are likely to influence SL outcomes, this ability is tacitly conceptualized as a fixed construct, and few studies to date have investigated how experience may shape statistical learning. We report one experiment that directly tested whether SL can be modulated by previous experience. We used a prepost treatment design allowing us to pinpoint what specific aspects of \u201cprevious experience\u201d matter for SL. The results show that performance on an artificial grammar learning task at post-test depends on whether the grammar to be learned at post-test matches the underlying grammar structures learned during treatment. Our study is the first to adopt a pre-post test design to directly modulate the effects of learning on learning itself

Electron kinetics at the plasma interface

The most fundamental response of an ionized gas to a macroscopic object is the formation of the plasma sheath. It is an electron depleted space charge region, adjacent to the object, which screens the object's negative charge arising from the accumulation of electrons from the plasma. The plasma sheath is thus the positively charged part of an electric double layer whose negatively charged part is inside the wall. In the course of the Transregional Collaborative Research Center SFB/TRR24 we investigated, from a microscopic point of view, the elementary charge transfer processes responsible for the electric double layer at a floating plasma-wall interface and made first steps towards a description of the negative part of the layer inside the wall. Below we review our work in a colloquial manner, describe possible extensions, and identify key issues which need to be resolved to make further progress in the understanding of the electron kinetics across plasma-wall interfaces.Comment: 14 pages, 8 figure

Physical Fitness Training in Patients with Subacute Stroke (PHYS-STROKE): multicentre, randomised controlled, endpoint blinded trial

OBJECTIVE: To determine the safety and efficacy of aerobic exercise on activities of daily living in the subacute phase after stroke. DESIGN: Multicentre, randomised controlled, endpoint blinded trial. SETTING: Seven inpatient rehabilitation sites in Germany (2013-17). PARTICIPANTS: 200 adults with subacute stroke (days 5-45 after stroke) with a median National Institutes of Health stroke scale (NIHSS, range 0-42 points, higher values indicating more severe strokes) score of 8 (interquartile range 5-12) were randomly assigned (1:1) to aerobic physical fitness training (n=105) or relaxation sessions (n=95, control group) in addition to standard care. INTERVENTION: Participants received either aerobic, bodyweight supported, treadmill based physical fitness training or relaxation sessions, each for 25 minutes, five times weekly for four weeks, in addition to standard rehabilitation therapy. Investigators and endpoint assessors were masked to treatment assignment. MAIN OUTCOME MEASURES: The primary outcomes were change in maximal walking speed (m/s) in the 10 m walking test and change in Barthel index scores (range 0-100 points, higher scores indicating less disability) three months after stroke compared with baseline. Safety outcomes were recurrent cardiovascular events, including stroke, hospital readmissions, and death within three months after stroke. Efficacy was tested with analysis of covariance for each primary outcome in the full analysis set. Multiple imputation was used to account for missing values. RESULTS: Compared with relaxation, aerobic physical fitness training did not result in a significantly higher mean change in maximal walking speed (adjusted treatment effect 0.1 m/s (95% confidence interval 0.0 to 0.2 m/s), P=0.23) or mean change in Barthel index score (0 (-5 to 5), P=0.99) at three months after stroke. A higher rate of serious adverse events was observed in the aerobic group compared with relaxation group (incidence rate ratio 1.81, 95% confidence interval 0.97 to 3.36). CONCLUSIONS: Among moderately to severely affected adults with subacute stroke, aerobic bodyweight supported, treadmill based physical fitness training was not superior to relaxation sessions for maximal walking speed and Barthel index score but did suggest higher rates of adverse events. These results do not appear to support the use of aerobic bodyweight supported fitness training in people with subacute stroke to improve activities of daily living or maximal walking speed and should be considered in future guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT01953549

Refining multiple sequence alignments with conserved core regions

Accurate multiple sequence alignments of proteins are very important to several areas of computational biology and provide an understanding of phylogenetic history of domain families, their identification and classification. This article presents a new algorithm, REFINER, that refines a multiple sequence alignment by iterative realignment of its individual sequences with the predetermined conserved core (block) model of a protein family. Realignment of each sequence can correct misalignments between a given sequence and the rest of the profile and at the same time preserves the family's overall block model. Large-scale benchmarking studies showed a noticeable improvement of alignment after refinement. This can be inferred from the increased alignment score and enhanced sensitivity for database searching using the sequence profiles derived from refined alignments compared with the original alignments. A standalone version of the program is available by ftp distribution () and will be incorporated into the next release of the Cn3D structure/alignment viewer

High-Sensitivity Cardiac Troponin T and Cognitive Decline in Older Adults: Results of the Berlin Aging Study II

Introduction: There is evidence of an association between markers of cardiac injury and cognition in patients with cardiovascular disease. We hypothesized that levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with cognitive performance and cognitive decline in a population of predominantly healthy older adults. Methods: We included 1,226 predominantly healthy adults >= 60 years from the Berlin Aging Study II. Participants were recruited from the general population of the Berlin metropolitan area from 2009 to 2014. At baseline, participants underwent measurement of hs-cTnT and cognitive testing using the extended Consortium to Establish a Registry for Alzheimer's Disease (CERAD-Plus) battery. In addition, the Digit Symbol Substitution Test (DSST) was performed at baseline and at follow-up (7.3 +/- 1.4 years after the baseline visit). The CERAD test results were summarized into four cognitive domains (processing speed, executive function, visuo-construction, and memory). After summing-up the respective raw scores, we calculated standardized z scores. We performed unadjusted and adjusted linear regression models to assess links between hs-cTnT and cognitive domains. We used linear mixed models to analyze associations between hs-cTnT and cognitive decline according to changes in DSST scores over time. Results: The mean age of study participants at baseline was 68.5 (+/- 3.6) years, 49% were female, and median hs-cTnT levels were 6 ng/L (IQR 4-8 ng/L). We detected no significant association between hs-cTnT and different cognitive domains at baseline after adjustment for age, sex, education, and cardiovascular risk factors. Hs-cTnT was associated with cognitive decline, which remained statistically significant after full adjustment (adjusted beta-coefficient -0.82 (-1.28 to -0.36), p = 0.001). After stratification for sex, the association with hs-cTnT remained statistically significant in men but not in women. Conclusion: Higher hs-cTnT levels in older men are associated with cognitive decline measured with the DSST