Carbon and nitrogen isotopic ratios of urine and faeces as novel nutritional biomarkers of meat and fish intake

Purpose Meat and fish consumption are associated with changes in the risk of chronic diseases. Intake is mainly assessed using self-reporting, as no true quantitative nutritional biomarker is available. The measurement of plasma fatty acids, often used as an alternative, is expensive and time-consuming. As meat and fish differ in their stable isotope ratios, δ13C and δ15N have been proposed as biomarkers. However, they have never been investigated in controlled human dietary intervention studies. Objective In a short-term feeding study, we investigated the suitability of δ13C and δ15N in blood, urine and faeces as biomarkers of meat and fish intake. Methods The dietary intervention study (n = 14) followed a randomised cross-over design with three eight-day dietary periods (meat, fish and half-meat–half-fish). In addition, 4 participants completed a vegetarian control period. At the end of each period, 24-h urine, fasting venous blood and faeces were collected and their δ13C and δ15N analysed. Results There was a significant difference between diets in isotope ratios in faeces and urine samples, but not in blood samples (Kruskal–Wallis test, p < 0.0001). In pairwise comparisons, δ13C and δ15N were significantly higher in urine and faecal samples following a fish diet when compared with all other diets, and significantly lower following a vegetarian diet. There was no significant difference in isotope ratio between meat and half-meat–half-fish diets for blood, urine or faecal samples. Conclusions The results of this study show that urinary and faecal δ13C and δ15N are suitable candidate biomarkers for short-term meat and fish intake

The "lipid accumulation product" performs better than the body mass index for recognizing cardiovascular risk: a population-based comparison

BACKGROUND: Body mass index (BMI, kg/m(2)) may not be the best marker for estimating the risk of obesity-related disease. Consistent with physiologic observations, an alternative index uses waist circumference (WC) and fasting triglycerides (TG) concentration to describe lipid overaccumulation. METHODS: The WC (estimated population minimum 65 cm for men and 58 cm for women) and TG concentration from the third National Health and Nutrition Examination Survey (N = 9,180, statistically weighted to represent 100.05 million US adults) were used to compute a "lipid accumulation product" [LAP = (WC-65) × TG for men and (WC-58) × TG for women] and to describe the population distribution of LAP. LAP and BMI were compared as categorical variables and as log-transformed continuous variables for their ability to identify adverse levels of 11 cardiovascular risk factors. RESULTS: Nearly half of the represented population was discordant for their quartile assignments to LAP and BMI. When 23.54 million with ordinal LAP quartile > BMI quartile were compared with 25.36 million with ordinal BMI quartile > LAP quartile (regression models adjusted for race-ethnicity and sex) the former had more adverse risk levels than the latter (p < 0.002) for seven lipid variables, uric acid concentration, heart rate, systolic and diastolic blood pressure. Further adjustment for age did not materially alter these comparisons except for blood pressures (p > 0.1). As continuous variables, LAP provided a consistently more adverse beta coefficient (slope) than BMI for nine cardiovascular risk variables (p < 0.01), but not for blood pressures (p > 0.2). CONCLUSION: LAP (describing lipid overaccumulation) performed better than BMI (describing weight overaccumulation) for identifying US adults at cardiovascular risk. Compared to BMI, LAP might better predict the incidence of cardiovascular disease, but this hypothesis needs prospective testing

Quasi-Normal Modes of Stars and Black Holes

Perturbations of stars and black holes have been one of the main topics of relativistic astrophysics for the last few decades. They are of particular importance today, because of their relevance to gravitational wave astronomy. In this review we present the theory of quasi-normal modes of compact objects from both the mathematical and astrophysical points of view. The discussion includes perturbations of black holes (Schwarzschild, Reissner-Nordstr\"om, Kerr and Kerr-Newman) and relativistic stars (non-rotating and slowly-rotating). The properties of the various families of quasi-normal modes are described, and numerical techniques for calculating quasi-normal modes reviewed. The successes, as well as the limits, of perturbation theory are presented, and its role in the emerging era of numerical relativity and supercomputers is discussed.Comment: 74 pages, 7 figures, Review article for "Living Reviews in Relativity

Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas

INTRODUCTION: ScFv(FRP5)-ETA is a recombinant antibody toxin with binding specificity for ErbB2 (HER2). It consists of an N-terminal single-chain antibody fragment (scFv), genetically linked to truncated Pseudomonas exotoxin A (ETA). Potent antitumoral activity of scFv(FRP5)-ETA against ErbB2-overexpressing tumor cells was previously demonstrated in vitro and in animal models. Here we report the first systemic application of scFv(FRP5)-ETA in human cancer patients. METHODS: We have performed a phase I dose-finding study, with the objective to assess the maximum tolerated dose and the dose-limiting toxicity of intravenously injected scFv(FRP5)-ETA. Eighteen patients suffering from ErbB2-expressing metastatic breast cancers, prostate cancers, head and neck cancer, non small cell lung cancer, or transitional cell carcinoma were treated. Dose levels of 2, 4, 10, 12.5, and 20 μg/kg scFv(FRP5)-ETA were administered as five daily infusions each for two consecutive weeks. RESULTS: No hematologic, renal, and/or cardiovascular toxicities were noted in any of the patients treated. However, transient elevation of liver enzymes was observed, and considered dose limiting, in one of six patients at the maximum tolerated dose of 12.5 μg/kg, and in two of three patients at 20 μg/kg. Fifteen minutes after injection, peak concentrations of more than 100 ng/ml scFv(FRP5)-ETA were obtained at a dose of 10 μg/kg, indicating that predicted therapeutic levels of the recombinant protein can be applied without inducing toxic side effects. Induction of antibodies against scFv(FRP5)-ETA was observed 8 days after initiation of therapy in 13 patients investigated, but only in five of these patients could neutralizing activity be detected. Two patients showed stable disease and in three patients clinical signs of activity in terms of signs and symptoms were observed (all treated at doses ≥ 10 μg/kg). Disease progression occurred in 11 of the patients. CONCLUSION: Our results demonstrate that systemic therapy with scFv(FRP5)-ETA can be safely administered up to a maximum tolerated dose of 12.5 μg/kg in patients with ErbB2-expressing tumors, justifying further clinical development

Modularization of biochemical networks based on classification of Petri net t-invariants

<p>Abstract</p> <p>Background</p> <p>Structural analysis of biochemical networks is a growing field in bioinformatics and systems biology. The availability of an increasing amount of biological data from molecular biological networks promises a deeper understanding but confronts researchers with the problem of combinatorial explosion. The amount of qualitative network data is growing much faster than the amount of quantitative data, such as enzyme kinetics. In many cases it is even impossible to measure quantitative data because of limitations of experimental methods, or for ethical reasons. Thus, a huge amount of qualitative data, such as interaction data, is available, but it was not sufficiently used for modeling purposes, until now. New approaches have been developed, but the complexity of data often limits the application of many of the methods. Biochemical Petri nets make it possible to explore static and dynamic qualitative system properties. One Petri net approach is model validation based on the computation of the system's invariant properties, focusing on t-invariants. T-invariants correspond to subnetworks, which describe the basic system behavior.</p> <p>With increasing system complexity, the basic behavior can only be expressed by a huge number of t-invariants. According to our validation criteria for biochemical Petri nets, the necessary verification of the biological meaning, by interpreting each subnetwork (t-invariant) manually, is not possible anymore. Thus, an automated, biologically meaningful classification would be helpful in analyzing t-invariants, and supporting the understanding of the basic behavior of the considered biological system.</p> <p>Methods</p> <p>Here, we introduce a new approach to automatically classify t-invariants to cope with network complexity. We apply clustering techniques such as UPGMA, Complete Linkage, Single Linkage, and Neighbor Joining in combination with different distance measures to get biologically meaningful clusters (t-clusters), which can be interpreted as modules. To find the optimal number of t-clusters to consider for interpretation, the cluster validity measure, Silhouette Width, is applied.</p> <p>Results</p> <p>We considered two different case studies as examples: a small signal transduction pathway (pheromone response pathway in <it>Saccharomyces cerevisiae</it>) and a medium-sized gene regulatory network (gene regulation of Duchenne muscular dystrophy). We automatically classified the t-invariants into functionally distinct t-clusters, which could be interpreted biologically as functional modules in the network. We found differences in the suitability of the various distance measures as well as the clustering methods. In terms of a biologically meaningful classification of t-invariants, the best results are obtained using the Tanimoto distance measure. Considering clustering methods, the obtained results suggest that UPGMA and Complete Linkage are suitable for clustering t-invariants with respect to the biological interpretability.</p> <p>Conclusion</p> <p>We propose a new approach for the biological classification of Petri net t-invariants based on cluster analysis. Due to the biologically meaningful data reduction and structuring of network processes, large sets of t-invariants can be evaluated, allowing for model validation of qualitative biochemical Petri nets. This approach can also be applied to elementary mode analysis.</p

Oyster Reefs as Natural Breakwaters Mitigate Shoreline Loss and Facilitate Fisheries

Shorelines at the interface of marine, estuarine and terrestrial biomes are among the most degraded and threatened habitats in the coastal zone because of their sensitivity to sea level rise, storms and increased human utilization. Previous efforts to protect shorelines have largely involved constructing bulkheads and seawalls which can detrimentally affect nearshore habitats. Recently, efforts have shifted towards “living shoreline” approaches that include biogenic breakwater reefs. Our study experimentally tested the efficacy of breakwater reefs constructed of oyster shell for protecting eroding coastal shorelines and their effect on nearshore fish and shellfish communities. Along two different stretches of eroding shoreline, we created replicated pairs of subtidal breakwater reefs and established unaltered reference areas as controls. At both sites we measured shoreline and bathymetric change and quantified oyster recruitment, fish and mobile macro-invertebrate abundances. Breakwater reef treatments mitigated shoreline retreat by more than 40% at one site, but overall vegetation retreat and erosion rates were high across all treatments and at both sites. Oyster settlement and subsequent survival were observed at both sites, with mean adult densities reaching more than eighty oysters m−2 at one site. We found the corridor between intertidal marsh and oyster reef breakwaters supported higher abundances and different communities of fishes than control plots without oyster reef habitat. Among the fishes and mobile invertebrates that appeared to be strongly enhanced were several economically-important species. Blue crabs (Callinectes sapidus) were the most clearly enhanced (+297%) by the presence of breakwater reefs, while red drum (Sciaenops ocellatus) (+108%), spotted seatrout (Cynoscion nebulosus) (+88%) and flounder (Paralichthys sp.) (+79%) also benefited. Although the vertical relief of the breakwater reefs was reduced over the course of our study and this compromised the shoreline protection capacity, the observed habitat value demonstrates ecological justification for future, more robust shoreline protection projects

Is complementary and alternative medicine (CAM) cost-effective? a systematic review

BACKGROUND: Out-of-pocket expenditures of over $34 billion per year in the US are an apparent testament to a widely held belief that complementary and alternative medicine (CAM) therapies have benefits that outweigh their costs. However, regardless of public opinion, there is often little more than anecdotal evidence on the health and economic implications of CAM therapies. The objectives of this study are to present an overview of economic evaluation and to expand upon a previous review to examine the current scope and quality of CAM economic evaluations. METHODS: The data sources used were Medline, AMED, Alt-HealthWatch, and the Complementary and Alternative Medicine Citation Index; January 1999 to October 2004. Papers that reported original data on specific CAM therapies from any form of standard economic analysis were included. Full economic evaluations were subjected to two types of quality review. The first was a 35-item checklist for reporting quality, and the second was a set of four criteria for study quality (randomization, prospective collection of economic data, comparison to usual care, and no blinding). RESULTS: A total of 56 economic evaluations (39 full evaluations) of CAM were found covering a range of therapies applied to a variety of conditions. The reporting quality of the full evaluations was poor for certain items, but was comparable to the quality found by systematic reviews of economic evaluations in conventional medicine. Regarding study quality, 14 (36%) studies were found to meet all four criteria. These exemplary studies indicate CAM therapies that may be considered cost-effective compared to usual care for various conditions: acupuncture for migraine, manual therapy for neck pain, spa therapy for Parkinson's, self-administered stress management for cancer patients undergoing chemotherapy, pre- and post-operative oral nutritional supplementation for lower gastrointestinal tract surgery, biofeedback for patients with "functional" disorders (eg, irritable bowel syndrome), and guided imagery, relaxation therapy, and potassium-rich diet for cardiac patients. CONCLUSION: Whereas the number and quality of economic evaluations of CAM have increased in recent years and more CAM therapies have been shown to be of good value, the majority of CAM therapies still remain to be evaluated

Transmembrane potential induced on the internal organelle by a time-varying magnetic field: a model study

<p>Abstract</p> <p>Background</p> <p>When a cell is exposed to a time-varying magnetic field, this leads to an induced voltage on the cytoplasmic membrane, as well as on the membranes of the internal organelles, such as mitochondria. These potential changes in the organelles could have a significant impact on their functionality. However, a quantitative analysis on the magnetically-induced membrane potential on the internal organelles has not been performed.</p> <p>Methods</p> <p>Using a two-shell model, we provided the first analytical solution for the transmembrane potential in the organelle membrane induced by a time-varying magnetic field. We then analyzed factors that impact on the polarization of the organelle, including the frequency of the magnetic field, the presence of the outer cytoplasmic membrane, and electrical and geometrical parameters of the cytoplasmic membrane and the organelle membrane.</p> <p>Results</p> <p>The amount of polarization in the organelle was less than its counterpart in the cytoplasmic membrane. This was largely due to the presence of the cell membrane, which "shielded" the internal organelle from excessive polarization by the field. Organelle polarization was largely dependent on the frequency of the magnetic field, and its polarization was not significant under the low frequency band used for transcranial magnetic stimulation (TMS). Both the properties of the cytoplasmic and the organelle membranes affect the polarization of the internal organelle in a frequency-dependent manner.</p> <p>Conclusions</p> <p>The work provided a theoretical framework and insights into factors affecting mitochondrial function under time-varying magnetic stimulation, and provided evidence that TMS does not affect normal mitochondrial functionality by altering its membrane potential.</p

Electrophysiological correlates of selective attention: A lifespan comparison

<p>Abstract</p> <p>Background</p> <p>To study how event-related brain potentials (ERPs) and underlying cortical mechanisms of selective attention change from childhood to old age, we investigated lifespan age differences in ERPs during an auditory oddball task in four age groups including 24 younger children (9–10 years), 28 older children (11–12 years), 31 younger adults (18–25), and 28 older adults (63–74 years). In the Unattend condition, participants were asked to simply listen to the tones. In the Attend condition, participants were asked to count the deviant stimuli. Five primary ERP components (N1, P2, N2, P3 and N3) were extracted for deviant stimuli under Attend conditions for lifespan comparison. Furthermore, Mismatch Negativity (MMN) and Late Discriminative Negativity (LDN) were computed as difference waves between deviant and standard tones, whereas Early and Late Processing Negativity (EPN and LPN) were calculated as difference waves between tones processed under Attend and Unattend conditions. These four secondary ERP-derived measures were taken as indicators for change detection (MMN and LDN) and selective attention (EPN and LPN), respectively. To examine lifespan age differences, the derived difference-wave components for attended (MMN and LDN) and deviant (EPN and LPN) stimuli were specifically compared across the four age groups.</p> <p>Results</p> <p>Both primary and secondary ERP components showed age-related differences in peak amplitude, peak latency, and topological distribution. The P2 amplitude was higher in adults compared to children, whereas N2 showed the opposite effect. P3 peak amplitude was higher in older children and younger adults than in older adults. The amplitudes of N3, LDN, and LPN were higher in older children compared with both of the adult groups. In addition, both P3 and N3 peak latencies were significantly longer in older than in younger adults. Interestingly, in the young adult sample P3 peak amplitude correlated positively and P3 peak latency correlated negatively with performance in the Identical Picture test, a marker measure of fluid intelligence.</p> <p>Conclusion</p> <p>The present findings suggest that patterns of event-related brain potentials are highly malleable within individuals and undergo profound reorganization from childhood to adulthood and old age.</p