Neurologic effects of exogenous saccharides: A review of controlled human, animal, and in vitro studies

Objectives: Current research efforts are centered on delineating the novel health benefits of naturally derived saccharides, including growing interest in their abilities to influence neurologic health. We performed a comprehensive review of the literature to consolidate all controlled studies assessing various roles of exogenous saccharide compounds and polysaccharide-rich extracts from plants, fungi, and other natural sources on brain function, with a significant focus on benefits derived from oral intake. Methods: Studies were identified by conducting electronic searches on PubMed and Google Scholar. Reference lists of articles were also reviewed for additional relevant studies. Only articles published in English were included in this review. Results: Six randomized, double-blind, placebo-controlled clinical studies were identified in which consumption of a blend of plant-derived polysaccharides showed positive effects on cognitive function and mood in healthy adults. A separate controlled clinical study observed improvements in well-being with ingestion of a yeast beta-glucan. Numerous animal and in vitro studies have demonstrated the ability of individual saccharide compounds and polysaccharide-rich extracts to modify behavior, enhance synaptic plasticity, and provide neuroprotective effects. Discussion: Although the mechanisms by which exogenous saccharides can influence brain function are not well understood at this time, the literature suggests that certain naturally occurring compounds and polysaccharide-rich extracts show promise, when taken orally, in supporting neurologic health and function. Additional well-controlled clinical studies on larger populations are necessary, however, before specific recommendations can be made

Mother knows best: occurrence and associations of resighted humpback whales suggest maternally derived fidelity to a southern hemisphere coastal feeding ground

Site fidelity is common among migratory cetaceans, including humpback whales (Megaptera novaeangliae). In the Northern Hemisphere it has been found that fidelity to humpback whale feeding grounds is transferred maternally but this has never been shown for the species in the Southern Hemisphere. We examined this in a unique feeding area off west South Africa using resighting data of 68 individually identified humpback whales by means of photographic (tail flukes and dorsal fins) and/or molecular methods (microsatellite genotyping) over an 18 year span. We found short-term association patterns and recurrent visits typical of other feeding grounds. Males and females had different seasonality of attendance. Significant female-dominated presence corresponded to timing of an expected influx of females on their southward migration from the breeding ground: firstly non-nursing (possibly pregnant) females in mid-spring, and mothers and calves in mid-to late summer. The potential benefit of this mid-latitude feeding area for females is illustrated by a record of a cow with known age of at least 23 years that produced calves in three consecutive years, each of which survived to at least six months of age: the first record of successful post-partum ovulation for this species in the Southern Hemisphere. We recorded association of a weaned calf with its mother, and a recurring association between a non-lactating female and male over more than two years. Moreover, three animals first identified as calves returned to the same area in subsequent years, sometimes on the same day as their mothers. This, together with numerous Parent-Offspring relations detected genetically among and between resighted and non-resighted whales is strongly suggestive of maternally derived site fidelity at a small spatial scale by a small sub-population of humpback whales.National Research Foundation (NRF), South Africa [2047517]; PADI Project AWARE (UK) [095]; Earthwatch Institute (project title "Whales of South Africa"

Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia

Background: Primary ciliary dyskinesia (PCD) is a heterogeneous inherited disorder caused by mutations in approximately 50 cilia-related genes. PCD genotype-phenotype relationships have mostly arisen from small case series because existing statistical approaches to investigate relationships have been unsuitable for rare diseases. / Methods: We applied a topological data analysis (TDA) approach to investigate genotype-phenotype relationships in PCD. Data from separate training and validation cohorts included 396 genetically defined individuals carrying pathogenic variants in PCD genes. To develop the TDA models, twelve clinical and diagnostic variables were included. TDA-driven hypotheses were subsequently tested using traditional statistics. / Results: Disease severity at diagnosis measured by FEV1 z-score was (i) significantly worse in individuals with CCDC39 mutations compared to other gene mutations and (ii) better in those with DNAH11 mutations; the latter also reported less neonatal respiratory distress. Patients without neonatal respiratory distress had better preserved FEV1 at diagnosis. Individuals with DNAH5 mutations were phenotypically diverse. Cilia ultrastructure and beat pattern defects correlated closely to specific causative gene groups, confirming these tests can be used to support a genetic diagnosis. / Conclusions: This large scale multi-national study presents PCD as a syndrome with overlapping symptoms and variation in phenotype, according to genotype. TDA modelling confirmed genotype-phenotype relationships reported by smaller studies (e.g. FEV1 worse with CCDC39 mutations), and identified new relationships, including FEV1 preservation with DNAH11 mutations and diversity of severity with DNAH5 mutations

Omura’s whales (Balaenoptera omurai) off northwest Madagascar: ecology, behaviour and conservation needs

The Omura’s whale (Balaenoptera omurai) was described as a new species in 2003 and then soon after as an ancient lineage basal to a Bryde’s/sei whale clade. Currently known only from whaling and stranding specimens primarily from the western Pacific and eastern Indian Oceans, there exist no confirmed field observations or ecological/behavioural data. Here we present, to our knowledge, the first genetically confirmed documentation of living Omura’s whales including descriptions of basic ecology and behaviour from northwestern Madagascar. Species identification was confirmed through molecular phylogenetic analyses of biopsies collected from 18 adult animals. All individuals shared a single haplotype in a 402 bp sequence of mtDNA control region, suggesting low diversity and a potentially small population. Sightings of 44 groups indicated preference for shallow-water shelf habitat with sea surface temperature between 27.4°C and 30.2°C. Frequent observations were made of lunge feeding, possibly on zooplankton. Observations of four mothers with young calves, and recordings of a song-like vocalization probably indicate reproductive behaviour. Social organization consisted of loose aggregations of predominantly unassociated single individuals spatially and temporally clustered. Photographic recapture of a female re-sighted the following year with a young calf suggests site fidelity or a resident population. Our results demonstrate that the species is a tropical whale without segregation of feeding and breeding habitat, and is probably non-migratory; our data extend the range of this poorly studied whale into the western Indian Ocean. Exclusive range restriction to tropical waters is rare among baleen whale species, except for the various forms of Bryde’s whales and Omura’s whales. Thus, the discovery of a tractable population of Omura’s whales in the tropics presents an opportunity for understanding the ecological factors driving potential convergence of life-history patterns with the distantly related Bryde’s whales

A Novel Method to Adjust Efficacy Estimates for Uptake of Other Active Treatments in Long-Term Clinical Trials

BACKGROUND: When rates of uptake of other drugs differ between treatment arms in long-term trials, the true benefit or harm of the treatment may be underestimated. Methods to allow for such contamination have often been limited by failing to preserve the randomization comparisons. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, patients were randomized to fenofibrate or placebo, but during the trial many started additional drugs, particularly statins, more so in the placebo group. The effects of fenofibrate estimated by intention-to-treat were likely to have been attenuated. We aimed to quantify this effect and to develop a method for use in other long-term trials. METHODOLOGY/PRINCIPAL FINDINGS: We applied efficacies of statins and other cardiovascular drugs from meta-analyses of randomized trials to adjust the effect of fenofibrate in a penalized Cox model. We assumed that future cardiovascular disease events were reduced by an average of 24% by statins, and 20% by a first other major cardiovascular drug. We applied these estimates to each patient who took these drugs for the period they were on them. We also adjusted the analysis by the rate of discontinuing fenofibrate. Among 4,900 placebo patients, average statin use was 16% over five years. Among 4,895 assigned fenofibrate, statin use was 8% and nonuse of fenofibrate was 10%. In placebo patients, use of cardiovascular drugs was 1% to 3% higher. Before adjustment, fenofibrate was associated with an 11% reduction in coronary events (coronary heart disease death or myocardial infarction) (P = 0.16) and an 11% reduction in cardiovascular disease events (P = 0.04). After adjustment, the effects of fenofibrate on coronary events and cardiovascular disease events were 16% (P = 0.06) and 15% (P = 0.008), respectively. CONCLUSIONS/SIGNIFICANCE: This novel application of a penalized Cox model for adjustment of a trial estimate of treatment efficacy incorporates evidence-based estimates for other therapies, preserves comparisons between the randomized groups, and is applicable to other long-term trials. In the FIELD study example, the effects of fenofibrate on the risks of coronary heart disease and cardiovascular disease events were underestimated by up to one-third in the original analysis. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN64783481

The Coevolution of Virulence: Tolerance in Perspective

Coevolutionary interactions, such as those between host and parasite, predator and prey, or plant and pollinator, evolve subject to the genes of both interactors. It is clear, for example, that the evolution of pollination strategies can only be understood with knowledge of both the pollinator and the pollinated. Studies of the evolution of virulence, the reduction in host fitness due to infection, have nonetheless tended to focus on parasite evolution. Host-centric approaches have also been proposed—for example, under the rubric of “tolerance”, the ability of hosts to minimize virulence without necessarily minimizing parasite density. Within the tolerance framework, however, there is room for more comprehensive measures of host fitness traits, and for fuller consideration of the consequences of coevolution. For example, the evolution of tolerance can result in changed selection on parasite populations, which should provoke parasite evolution despite the fact that tolerance is not directly antagonistic to parasite fitness. As a result, consideration of the potential for parasite counter-adaptation to host tolerance—whether evolved or medially manipulated—is essential to the emergence of a cohesive theory of biotic partnerships and robust disease control strategies

Effect of Saddle height on skin temperature measured in different days of cycling.

Infrared thermography can be useful to explore the effects of exercise on neuromuscular function. During cycling, it could be used to investigate the effects of saddle height on thermoregulation. The aim of this study was to examine whether different cycling postures, elicited by different knee flexion angles, could influence skin temperature. Furthermore, we also determined whether the reproducibility of thermal measurements in response to cycling differed in the body regions affected or not affected by saddle height. Sixteen cyclists participated in three tests of 45 min of cycling at their individual 50 % peak power output. Each test was performed in a different knee flexion position on the bicycle (20°, 30°, 40° knee flexion when the pedal crank was at 180°). Different knee angles were obtained by changing saddle height. Skin temperatures were determined by infrared thermography before, immediately after and 10 min after the cycling test, in 16 different regions of interest (ROI) in the trunk and lower limbs. Changes in saddle height did not result in changes in skin temperature in the ROI. However, lower knee flexion elicited higher temperature in popliteus after cycling than higher flexion (p = 0.008 and ES = 0.8), and higher knee flexion elicited lower temperature variation in the tibialis anterior than intermediate knee flexion (p = 0.004 and ES = 0.8). Absolute temperatures obtained good and very good intraday reproducibility in the different measurements (ICCs between 0.44 and 0.85), but temperature variations showed lower reproducibility (ICCs between 0.11 and 0.74). Different postures assumed by the cyclist due to different saddle height did not influence temperature measurements. Skin temperature can be measured on different days with good repeatability, but temperature variations can be more sensitive to the effects of an intervention

Computational Models of Classical Conditioning guest editors’ introduction

In the present special issue, the performance of current computational models of classical conditioning was evaluated under three requirements: (1) Models were to be tested against a list of previously agreed-upon phenomena; (2) the parameters were fixed across simulations; and (3) the simulations used to test the models had to be made available. These requirements resulted in three major products: (a) a list of fundamental classical-conditioning results for which there is a consensus about their reliability; (b) the necessary information to evaluate each of the models on the basis of its ordinal successes in accounting for the experimental data; and (c) a repository of computational models ready to generate simulations. We believe that the contents of this issue represent the 2012 state of the art in computational modeling of classical conditioning and provide a way to find promising avenues for future model development

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation