To gain mechanistic insights, we compared effects of low fermentable oligosaccharides, disaccharides and monosaccharides and polyols (FODMAP) and high FODMAP diets on symptoms, the metabolome and the ...microbiome of patients with IBS.
We performed a controlled, single blind study of patients with IBS (Rome III criteria) randomised to a low (n=20) or high (n=20) FODMAP diet for 3 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS). The metabolome was evaluated using the lactulose breath test (LBT) and metabolic profiling in urine using mass spectrometry. Stool microbiota composition was analysed by 16S rRNA gene profiling.
Thirty-seven patients (19 low FODMAP; 18 high FODMAP) completed the 3-week diet. The IBS-SSS was reduced in the low FODMAP diet group (p<0.001) but not the high FODMAP group. LBTs showed a minor decrease in H
production in the low FODMAP compared with the high FODMAP group. Metabolic profiling of urine showed groups of patients with IBS differed significantly after the diet (p<0.01), with three metabolites (histamine, p-hydroxybenzoic acid, azelaic acid) being primarily responsible for discrimination between the two groups. Histamine, a measure of immune activation, was reduced eightfold in the low FODMAP group (p<0.05). Low FODMAP diet increased Actinobacteria richness and diversity, and high FODMAP diet decreased the relative abundance of bacteria involved in gas consumption.
IBS symptoms are linked to FODMAP content and associated with alterations in the metabolome. In subsets of patients, FODMAPs modulate histamine levels and the microbiota, both of which could alter symptoms.
NCT01829932.
Inconsistency in operationally defining sleep efficiency (SE) creates confusion with regard to the conceptualization and use of the construct by researchers and clinicians. The source of the ...inconsistency is the denominator of the widely published operational definition of SE: ratio of total sleep time (TST) to time in bed (TIB) (multiplied by 100 to yield a percentage). When taken literally, TIB includes non-sleep-related activity (e.g., reading, texting, conversing with a partner, watching television) both prior to initiating sleep and after the final awakening. However, the construct of SE refers to TST compared to the amount of time spent attempting to initially fall asleep and sleep discontinuity. Non-sleep related activities in bed do not reflect that construct. Also, time out of bed during nighttime awakenings, a manifestation of sleep discontinuity, should be included in the SE denominator. Using TIB as the denominator can also create a methodological problem when SE is an outcome measure in sleep intervention research. It is proposed that research and practice would benefit by clarifying and adopting a consistent operational definition that more accurately captures the construct of SE. An alternate denominator, duration of the sleep episode (DSE), is suggested, where DSE = sleep onset latency (SOL) + TST + time awake after initial sleep onset but before the final awakening (WASO) + time attempting to sleep after final awakening (TASAFA). The proposed formula for SE would be: SE = TST / DSE (× 100). DSE can be easily calculated using standard sleep diary entries along with one item from the Expanded Consensus Sleep Diary. Implications for insomnia research and practice are discussed.
End stage temporomandibular joint osteoarthritis (TMJ-OA) is characterized by fibrillations, fissures, clefts, and erosion of the mandibular condylar cartilage. The goal of this study was to define ...changes in pericellular and interterritorial delineations of the extracellular matrix (ECM) that occur preceding and concurrent with the development of this end stage degeneration in a murine surgical instability model. Two-photon fluorescence (TPF) and second harmonic generation (SHG) microscopy was used to evaluate TMJ-OA mediated changes in the ECM. We illustrate that TPF/SHG microscopy reconstructs the three-dimensional network of key fibrillar and micro-fibrillar collagens altered during the progression of TMJ-OA. This method not only generates spatially distinct pericellular and interterritorial delineations of the ECM but distinguishes early and end stage TMJ-OA by signal organization, orientation, and composition. Early stage TMJ-OA at 4- and 8-weeks post-injury is characterized by two structurally distinct regions containing dense, large fiber collagens and superficial, small fiber collagens rich in types I, III, and VI collagen oriented along the mesiodistal axis of the condyle. At 8-weeks post-injury, type VI collagen is locally diminished on the central and medial condyle, but the type I/III rich superficial layer is still present. Twelve- and 16-weeks post-injury mandibular cartilage is characteristic of end-stage disease, with hypocellularity and fibrillations, fissures, and clefts in the articular layer that propagate along the mediolateral axis of the MCC. We hypothesize that the localized depletion of interterritorial and pericellular type VI collagen may signify an early marker for the transition from early to end stage TMJ-OA, influence the injury response of the tissue, and underlie patterns of degeneration that follow attritional modes of failure.
The 3-item pain intensity (P), interference with the enjoyment of life (E), and interference with general activity (G), or PEG, has become one of the most widely used measures of pain severity and ...interference. The minimally important differences (MID) and responsiveness of the PEG are essential metrics for solidifying its role in research and clinical care. The current study aims to establish the MID and responsiveness of the PEG by synthesizing data from 1,710 participants across 6 controlled trials. MIDs were estimated using absolute score changes among individuals reporting their pain was "a little better" on a retrospective global change anchor as well as distribution-based estimates using standard deviation thresholds and 1 and 2 standard errors of measurement. Responsiveness was assessed using standardized response means, area under the curve, and treatment effect sizes. MID estimates for the PEG ranged from 0.60 to 1.1 when using 0.35 SD, and 0.78 to 1.22 using 1 standard error of measurement. MID estimates using the global anchor had somewhat more variability but most estimates ranged from 1.0 to 1.75. Responsiveness effect sizes were generally large (>.80) for standardized response means and moderate (>.50) for treatment effect. Similarly, the most area under the curve values demonstrated an acceptable level of scale responsiveness (≥.70). Importantly, MID estimates and responsiveness of the PEG and BPI scales were largely comparable when aggregating data across trials. Our synthesis indicates that 1 point is a reasonable MID estimate on these 0- to 10-point pain scales, with 2 points being an upper bound. PERSPECTIVE: This article synthesizes data from 6 clinical trials to establish the minimally important difference (MID) and responsiveness of the 3-item PEG pain scale. The PEG demonstrated good responsiveness, and 1 to 2 points proved to be reasonable estimates for the lower and upper bounds of the MID.
The PTSD Checklist for DSM‐5 (PCL‐5) is a measure of posttraumatic stress disorder (PTSD) symptom severity that is widely used for clinical and research purposes. Although previous work has examined ...metrics of minimal important difference (MID) of the PCL‐5 in veteran samples, no work has identified PCL‐5 MID metrics among adults in primary care in the United States. In this secondary analysis, data were evaluated from primary care patients (N = 971) who screened positive for PTSD and participated in a large clinical trial in federally qualified health centers in three U.S. states. Participants primarily self‐identified as women (70.2%) and White (70.3%). We calculated test–retest reliability using clinic registry data and multiple distribution‐ and anchor‐based metrics of MID using baseline and follow‐up survey data. Test–retest reliability (Pearson's r, Spearman's ρ, intraclass correlation coefficient) ranged from adequate to excellent (.79–.94), with the shortest time lag demonstrating the highest reliability estimate. The MID for the PCL‐5 was estimated using multiple approaches. Distribution‐based approaches indicated an MID range of 8.5–12.5, and anchor‐based approaches indicated an MID range of 9.8–11.7. Taken together, the MID metrics indicate that PCL‐5 change scores of 9–12 likely reflect real change in PTSD symptoms and indicate at least an MID for patients, whereas PCL‐5 change scores of 5 or less likely are not reliable. These findings can help inform clinicians using the PCL‐5 in similar populations to track patient responses to treatment and help researchers interpret PCL‐5 score changes in clinical trials.
Inbreeding–environment interactions occur when inbreeding leads to differential fitness loss in different environments. Inbred individuals are often more sensitive to environment stress than are ...outbred individuals, presumably because stress increases the expression of deleterious recessive alleles or cellular safeguards against stress are pushed beyond the organism's physiological limits. We examined inbreeding–environment interactions, along two environmental axes (temperature and rearing host) that differ in the amount of developmental stress they impose, in the seed-feeding beetle Collosobruchus maculatus. We found that inbreeding depression (inbreeding load, L) increased with the stressfulness of the environment, with the magnitude of stress explaining as much as 66% of the variation in inbreeding depression. This relationship between L and developmental stress was not explainable by an increase in phenotypic variation in more stressful environments. To examine the generality of this experimental result, we conducted a meta-analysis of the available data from published studies looking at stress and inbreeding depression. The meta-analysis confirmed that the effect of environment on inbreeding depression scale linearly with the magnitude of stress; a population suffers one additional lethal equivalent, on average, for each 30% reduction in fitness induced by the stressful environment. Studies using less-stressful environments may lack statistical power to detect the small changes in inbreeding depression. That the magnitude of inbreeding depression scales with the magnitude of the stress applied has numerous repercussions for evolutionary and conservation genetics and may invigorate research aimed at finding the causal mechanism involved in such a relationship.
Microbial cultures were evaluated for organic acid production and their potential utility for leaching of rare earth elements (REE) from retorted phosphor powder (RPP) and spent fluid catalytic ...cracking (FCC) catalyst. Two bacterial and one fungal strain were isolated from environmental and industrial materials known to contain REE and compared to the industrially important bacterium Gluconobacter oxydans. Gluconic acid was the predominant organic acid product identified in all of the cultures. Maximum REE leaching (49% of the total REE) from the FCC material was observed using cell-free culture supernatants of G. oxydans, with preferential recovery of lanthanum over cerium. The phosphor powder was more difficult to leach; only about 2% of the total REE was leached with G. oxydans. Leaching experiments with the RPP material indicated that the extent of REE solubilization was similar whether whole cell cultures or cell-free supernatants were used. Abiotic control experiments showed that increasing gluconic acid concentrations increased leaching efficiency; for example, total REE leaching from FCC catalyst increased from 24% to 45% when gluconic acid was increased from 10mM to 90mM. However, G. oxydans cell-free culture supernatants containing 10–15mM gluconic acid were more effective than abiotically prepared leaching solutions with higher gluconic acid concentrations, suggesting that other exudate components were important too. Our results indicate that microorganisms producing gluconic and other organic acids can induce effective leaching of REE from waste materials, and that increasing organic acid production will improve recovery.
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•Microorganisms were effective for leaching of REE from end-of-life products.•Gluconic acid was an important biologically produced organic acid for REE leaching.•Increasing gluconic acid concentrations increased leaching efficiency.•Microbial exudate was more effective at leaching than abiotic organic acid solutions.•REE were bioleached effectively from phosphor powders and cracking catalyst.
Genetic diversity is one of the three forms of biodiversity recognized by the World Conservation Union (IUCN) as deserving conservation. The need to conserve genetic diversity within populations is ...based on two arguments: the necessity of genetic diversity for evolution to occur, and the expected relationship between heterozygosity and population fitness. Because loss of genetic diversity is related to inbreeding, and inbreeding reduces reproductive fitness, a correlation is expected between heterozygosity and population fitness. Long-term effective population size, which determines rates of inbreeding, should also be correlated with fitness. However, other theoretical considerations and empirical observations suggest that the correlation between fitness and heterozygosity may be weak or nonexistent. We used all the data sets we could locate (34) to perform a meta-analysis and resolve the issue. Data sets were included in the study, provided that fitness, or a component of fitness, was measured for three or more populations along with heterozygosity, heritability, and/or population size. The mean weighted correlation between measures of genetic diversity, at the population level, and population fitness was 0.4323. The correlation was highly significant and explained 19% of the variation in fitness. Our study strengthens concerns that the loss of heterozygosity has a deleterious effect on population fitness and supports the IUCN designation of genetic diversity as worthy of conservation.
Quantifying impacts of ecological disturbance on ecosystem carbon and water fluxes will improve predictive understanding of biosphere-atmosphere feedbacks. Tree mortality caused by mountain pine bark ...beetles (Dendroctonus ponderosae) is hypothesized to decrease photosynthesis and water flux to the atmosphere while increasing respiration at a rate proportional to mortality. This work uses data from an eddy-covariance flux tower in a bark beetle infested lodgepole pine (Pinus contorta) forest to test ecosystem responses during the outbreak. Analyses were conducted on components of carbon (C) and water fluxes in response to disturbance and environmental factors (solar radiation, soil water content and vapor pressure deficit). Maximum CO2 uptake did not change as tree basal area mortality increased from 30 to 78% over three years of beetle disturbance. Growing season evapotranspiration varied among years while ecosystem water use efficiency (the ratio of net CO2 uptake to water vapor loss) did not change. Between 2009 and 2011, canopy water conductance increased from 98.6 to 151.7 mmol H2O m−2 s−1. Ecosystem light use efficiency of photosynthesis increased, with quantum yield increasing by 16% during the outbreak as light increased below the mature tree canopy and illuminated remaining vegetation more. Overall net ecosystem productivity was correlated with water flux and hence water availability. Average weekly ecosystem respiration, derived from light response curves and standard Ameriflux protocols for CO2 flux partitioning into respiration and gross ecosystem productivity, did not change as mortality increased. Separate effects of increased respiration and photosynthesis efficiency largely canceled one another out, presumably due to increased diffuse light in the canopy and soil organic matter decomposition resulting in no change in net CO2 exchange. These results agree with an emerging consensus in the literature demonstrating CO2 and H2O dynamics following large scale disturbance events are dependent not only on tree mortality but also on the remaining and new vegetation responses because mortality and recovery occur at the same time.
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