Quality of analgesic treatment in patients with advanced prostate cancer: do we do a better job now? The Swiss Group for Clinical Cancer Research (SAKK) experience

Goals of work: The aim of this study was to evaluate pain intensity and the application of the WHO guidelines for cancer pain treatment in patients with prostate cancer treated at Swiss cancer centers. Materials and methods: We analyzed a series of five multicenter phase II clinical trials which examined the palliative effect of different chemotherapies in patients with advanced hormone-refractory prostate carcinoma. Of 170 patients, 1,018 visits were evaluable for our purpose, including ratings of pain intensity by patients and prescribed analgesics. Main results: No or mild pain was indicated by patients in 36 to 55% of the visits, more than mild pain in 30 to 46%. In 21% of the visits, the WHO pain treatment criteria (treatment according to one of the three steps; oral, rectal or transdermal application of the main dose; administration on a regular schedule) were fulfilled, and the Cleeland index was positive according to all recommendations. In 6% of the visits, neither the WHO criteria were fulfilled nor was the Cleeland index positive. This indicates insufficient pain treatment not following the WHO guidelines and that the prescribed analgesics were not sufficiently potent for the rated pain intensity. Conclusions: In this selective Swiss sample, the standard of analgesic treatment is high. However, there is still scope for improvement. This cannot solely be solved by improving the knowledge of the physicians. Programs to change the patients' attitude towards cancer pain, training to improve the physicians' communication skills, and institutional changes may be promising strategie

Trimethylamine-N-Oxide Postprandial Response in Plasma and Urine Is Lower After Fermented Compared to Non-Fermented Dairy Consumption in Healthy Adults.

Trimethylamine-N-oxide (TMAO) can be produced by the gut microbiota from dietary substrates and is associated with cardiovascular disease. While dairy products contain TMAO precursors, the effect of fermented dairy on TMAO metabolism remains unclear. We used plasma and urine samples collected for two randomised cross-over studies to evaluate the effects of fermented dairy consumption on TMAO metabolism. In Study 1, thirteen healthy young men tested a yogurt and an acidified milk during postprandial tests and a two-week daily intervention. In Study 2, ten healthy adults tested milk and cheese during postprandial tests. TMAO and five related metabolites were measured in plasma and urine by LC-MS/MS and NMR. Faecal microbiota composition was assessed in Study 1 (16S rRNA metagenomics sequencing). Fermented milk products were associated with lower postprandial TMAO responses than non-fermented milks in urine (Study 1, p = 0.01; Study 2, p = 0.02) and in plasma, comparing yogurt and acidified milk (Study 1, p = 0.04). Daily consumption of dairy products did not differentially affect fasting TMAO metabolites. Significant correlations were observed between microbiota taxa and circulating or urinary TMAO concentrations. Fermentation of dairy products appear, at least transiently, to affect associations between dairy products and circulating TMAO levels

GC-MS Based Metabolomics and NMR Spectroscopy Investigation of Food Intake Biomarkers for Milk and Cheese in Serum of Healthy Humans.

The identification and validation of food intake biomarkers (FIBs) in human biofluids is a key objective for the evaluation of dietary intake. We report here the analysis of the GC-MS and 1H-NMR metabolomes of serum samples from a randomized cross-over study in 11 healthy volunteers having consumed isocaloric amounts of milk, cheese, and a soy drink as non-dairy alternative. Serum was collected at baseline, postprandially up to 6 h, and 24 h after consumption. A multivariate analysis of the untargeted serum metabolomes, combined with a targeted analysis of candidate FIBs previously reported in urine samples from the same study, identified galactitol, galactonate, and galactono-1,5-lactone (milk), 3-phenyllactic acid (cheese), and pinitol (soy drink) as candidate FIBs for these products. Serum metabolites not previously identified in the urine samples, e.g., 3-hydroxyisobutyrate after cheese intake, were detected. Finally, an analysis of the postprandial behavior of candidate FIBs, in particular the dairy fatty acids pentadecanoic acid and heptadecanoic acid, revealed specific kinetic patterns of relevance to their detection in future validation studies. Taken together, promising candidate FIBs for dairy intake appear to be lactose and metabolites thereof, for lactose-containing products, and microbial metabolites derived from amino acids, for fermented dairy products such as cheese

Assessment of lactase activity in humans by measurement of galactitol and galactonate in serum and urine after milk intake.

Lactase is an enzyme that hydrolyzes lactose into glucose and galactose in the small intestine, where they are absorbed. Hypolactasia is a common condition, primarily caused by genetic programming, that leads to lactose maldigestion and, in certain cases, lactose intolerance. Galactitol and galactonate are 2 products of hepatic galactose metabolism that are candidate markers for the intake of lactose-containing foods. The primary objective of the study was to explore the changes in serum and urine metabolomes during postprandial dairy product tests through the association between lactase persistence genotype and the postprandial dynamics of lactose-derived metabolites. We characterized the 6-h postprandial serum kinetics and urinary excretion of lactose, galactose, galactitol, and galactonate in 14 healthy men who had consumed a single dose of acidified milk (800 g) which contained 38.8 g lactose. Genotyping of LCT-13910 C/T (rs4988235) was performed to assess primary lactase persistence. There were 2 distinct postprandial responses, classified as high and low metabolite responses, observed for galactose, and its metabolites galactitol and galactonate, in serum and urine. In all but 1 subject, there was a concordance between the high metabolite responses and genetic lactase persistence and between the low metabolite responses and genetic lactase nonpersistence (accuracy 0.92), galactitol and galactonate being more discriminative than galactose. Postprandial galactitol and galactonate after lactose overload appear to be good proxies for genetically determined lactase activity. The development of a noninvasive lactose digestion test based on the measurement of these metabolites in urine could be clinically useful. This trial was registered at clinicaltrials.gov as NCT02230345

Biomarker of food intake for assessing the consumption of dairy and egg products

Foods of animal origin constitute one of the predominant food groups consumed in Western diets. They play an essential role in human nutrition as they represent an excellent source of high quality proteins, vitamins, minerals and fats. Foods of animal origin are highly diverse (e.g. meat, fish, dairy products and eggs) and their associations with a range of nutritional and health outcomes are therefore heterogeneous. Such associations are also often weak or debated due to the difficulty in establishing correct assessments of dietary intake. Therefore, in order to better characterize associations between the consumption of specific foods of animal origin and health outcomes, it is important to identify reliable biomarkers of food intake (BFIs). BFIs provide a more accurate measure of intake and are independent of the memory and sincerity of the subjects as well as of their knowledge about the consumed foods. To date, only a very limited number of compounds have been proposed as biomarkers of the intake of foods of animal origin and further studies are necessary to validate them and to discover new candidate BFIs. We have, therefore, conducted a systematic search of the scientific literature to evaluate the current status of potential BFIs for each category of foods of animal origin commonly consumed in Europe. This review reports on candidate biomarkers for dairy products and eggs intake, while biomarkers for fish and meat intake will be published separately. Remarkably, validated BFIs for dairy products and eggs are not available. A series of challenges hinders their identification and validation, in particular the heterogeneous composition of each food within a product category and the lack of specificity of the markers identified so far. Untargeted metabolomic strategies may allow the identification of novel food biomarkers, that, when taken separately or in combination, could be used to assess the intake of dairy products and eggs

Critical Exponents of the Classical 3D Heisenberg Model: A Single-Cluster Monte Carlo Study

We have simulated the three-dimensional Heisenberg model on simple cubic lattices, using the single-cluster Monte Carlo update algorithm. The expected pronounced reduction of critical slowing down at the phase transition is verified. This allows simulations on significantly larger lattices than in previous studies and consequently a better control over systematic errors. In one set of simulations we employ the usual finite-size scaling methods to compute the critical exponents $\nu,\alpha,\beta,\gamma, \eta$ from a few measurements in the vicinity of the critical point, making extensive use of histogram reweighting and optimization techniques. In another set of simulations we report measurements of improved estimators for the spatial correlation length and the susceptibility in the high-temperature phase, obtained on lattices with up to $100^3$ spins. This enables us to compute independent estimates of $\nu$ and $\gamma$ from power-law fits of their critical divergencies.Comment: 33 pages, 12 figures (not included, available on request). Preprint FUB-HEP 19/92, HLRZ 77/92, September 199

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Cell cycle-dependent phosphorylation of pRb-like protein in root meristem cells of Vicia faba

The retinoblastoma tumor suppressor protein (pRb) regulates cell cycle progression by controlling the G1-to-S phase transition. As evidenced in mammals, pRb has three functionally distinct binding domains and interacts with a number of proteins including the E2F family of transcription factors, proteins with a conserved LxCxE motif (D-type cyclin), and c-Abl tyrosine kinase. CDK-mediated phosphorylation of pRb inhibits its ability to bind target proteins, thus enabling further progression of the cell cycle. As yet, the roles of pRb and pRb-binding factors have not been well characterized in plants. By using antibody which specifically recognizes phosphorylated serines (S807/811) in the c-Abl tyrosine kinase binding C-domain of human pRb, we provide evidence for the cell cycle-dependent changes in pRb-like proteins in root meristems cells of Vicia faba. An increased phosphorylation of this protein has been found correlated with the G1-to-S phase transition