In previous studies, we demonstrated that allergenic house dust mite proteases are potent inducers of proinflammatory cytokines from the respiratory epithelium, although the precise mechanisms ...involved were unclear. In this study, we investigated whether this was achieved through activation of protease-activated receptor (PAR)-1 or -2. Pretreatment of A549 respiratory epithelial cells with the clinically important cysteine protease allergen, Der p 1, ablated subsequent PAR-1, but not PAR-2 agonist peptide-induced IL-6 and IL-8 release. HeLa cells transfected with the plasmid coding for PAR-2, in contrast to PAR-1, released significant concentration of IL-6 after exposure to Der p 1. Exposure of HeLa cells transfected with either PAR-1/enhanced yellow fusion protein or PAR-2/enhanced yellow fusion protein to Der p 1 caused receptor internalization in the latter cells only, as judged by confocal microscopy with re-expression of the receptor within 120-min postenzyme exposure. Der p 1-induced cytokine release from both A549 and transfected HeLa cells was accompanied by changes in intracellular Ca(2+) concentrations. Desensitization studies showed that Der p 1 pretreatment of the A549 cells resulted in the abolition of both trypsin- and PAR-2 agonist peptide-induced Ca(2+) release, but not that induced by subsequent exposure to either thrombin or PAR-1 agonist peptide. These data indicate for the first time that the house dust mite allergen Der p 1-induced cytokine release from respiratory epithelial cells is, in part, mediated by activation of PAR-2, but not PAR-1.
The 0-10 Numeric Rating Scale (NRS) is often used in pain management. The aims of our study were to determine the cut-off points for mild, moderate, and severe pain in terms of pain-related ...interference with functioning in patients with chronic musculoskeletal pain, to measure the variability of the optimal cut-off points, and to determine the influence of patients' catastrophizing and their sex on these cut-off points.
2854 patients were included. Pain was assessed by the NRS, functioning by the Pain Disability Index (PDI) and catastrophizing by the Pain Catastrophizing Scale (PCS). Cut-off point schemes were tested using ANOVAs with and without using the PSC scores or sex as co-variates and with the interaction between CP scheme and PCS score and sex, respectively. The variability of the optimal cut-off point schemes was quantified using bootstrapping procedure.
The study showed that NRS scores ≤ 5 correspond to mild, scores of 6-7 to moderate and scores ≥8 to severe pain in terms of pain-related interference with functioning. Bootstrapping analysis identified this optimal NRS cut-off point scheme in 90% of the bootstrapping samples. The interpretation of the NRS is independent of sex, but seems to depend on catastrophizing. In patients with high catastrophizing tendency, the optimal cut-off point scheme equals that for the total study sample, but in patients with a low catastrophizing tendency, NRS scores ≤ 3 correspond to mild, scores of 4-6 to moderate and scores ≥7 to severe pain in terms of interference with functioning. In these optimal cut-off schemes, NRS scores of 4 and 5 correspond to moderate interference with functioning for patients with low catastrophizing tendency and to mild interference for patients with high catastrophizing tendency. Theoretically one would therefore expect that among the patients with NRS scores 4 and 5 there would be a higher average PDI score for those with low catastrophizing than for those with high catastrophizing. However, we found the opposite. The fact that we did not find the same optimal CP scheme in the subgroups with lower and higher catastrophizing tendency may be due to chance variability.
We present the results of a search for galaxy clusters in the Subaru–XMM Deep Field (SXDF). We reach a depth for a total cluster flux in the 0.5–2 keV band of 2 × 10−15 erg cm−2 s−1 over one of the ...widest XMM–Newton contiguous raster surveys, covering an area of 1.3 deg2. Cluster candidates are identified through a wavelet detection of extended X-ray emission. The red-sequence technique allows us to identify 57 cluster candidates. We report on the progress with the cluster spectroscopic follow-up and derive their properties based on the X-ray luminosity and cluster scaling relations. In addition, three sources are identified as X-ray counterparts of radio lobes, and in three further sources, an X-ray counterpart of the radio lobes provides a significant fraction of the total flux of the source. In the area covered by near-infrared data, our identification success rate achieves 86 per cent. We detect a number of radio galaxies within our groups, and for a luminosity-limited sample of radio galaxies we compute halo occupation statistics using a marked cluster mass function. We compare the cluster detection statistics in the SXDF with that in the literature and provide the modelling using the concordance cosmology combined with current knowledge of the X-ray cluster properties. The joint cluster log(N) − log(S) is overpredicted by the model, and an agreement can be achieved through a reduction of the concordance σ8 value by 5 per cent. Having considered the dn/dz and the X-ray luminosity function of clusters, we conclude that to pin down the origin of disagreement a much wider (50 deg2) survey is needed.
To update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of randomized controlled ...trials to summarize the evidence for the effect of vegetarian dietary patterns on glycemic control and other established cardiometabolic risk factors in individuals with diabetes.
We searched MEDLINE, EMBASE, and Cochrane databases through February 26, 2018 for randomized controlled trials ≥3 weeks assessing the effect of vegetarian dietary patterns in individuals with diabetes. The primary outcome was HbA1c. Secondary outcomes included other markers of glycemic control, blood lipids, body weight/adiposity, and blood pressure. Two independent reviewers extracted data and assessed risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
Nine trials (n = 664 participants) met the eligibility criteria. Vegetarian dietary patterns significantly lowered HbA1c (MD = −0.29% 95% CI: −0.45, −0.12%), fasting glucose (MD = −0.56 mmol/L 95% CI: −0.99, −0.13 mmol/L), LDL-C (MD = −0.12 mmol/L 95% CI: −0.20, −0.04 mmol/L), non-HDL-C (MD = −0.13 mmol/L 95% CI: −0.26, −0.01 mmol/L), body weight (MD = −2.15 kg 95% CI: −2.95, −1.34 kg), BMI (MD = −0.74 kg/m2 95% CI: −1.09, −0.39 kg/m2) and waist circumference (MD = −2.86 cm 95% CI: −3.76, −1.96 cm). There was no significant effect on fasting insulin, HDL-C, triglycerides or blood pressure. The overall certainty of evidence was moderate but was low for fasting insulin, triglycerides and waist circumference.
Vegetarian dietary patterns improve glycemic control, LDL-C, non-HDL-C, and body weight/adiposity in individuals with diabetes, supporting their inclusion for diabetes management. More research is needed to improve our confidence in the estimates.
NCT02600377.
ABSTRACT
Here, we present the results of our multiwavelength campaign aimed at classifying Swift J170800−402551.8 as part of the Swift Deep Galactic Plane Survey (DGPS). We utilized Target of ...Opportunity (ToO) observations with the Neil Gehrels Swift Observatory, Chandra X-ray Observatory, Neutron star Interior Composition Explorer (NICER), X-ray Multi-Mirror Mission (XMM–Newton), Nuclear Spectroscopic Telescope Array (NuSTAR), and the Southern African Large Telescope (SALT), as well as multiwavelength archival observations from Gaia, VST Photometric Hα Survey, and VISTA Variables in the Via Lactea. The source displays a periodicity of 784 s in our XMM–Newton observation. The X-ray spectrum (XMM–Newton and NuSTAR) can be described by thermal bremsstrahlung radiation with a temperature of kT ≈ 30 keV. The phase-folded X-ray light curve displays a double-peaked, energy-dependent pulse profile. We used Chandra to precisely localize the source, allowing us to identify and study the multiwavelength counterpart. Spectroscopy with SALT identified a Balmer H α line, and potential He i lines, from the optical counterpart. The faintness of the counterpart (r ≈ 21 AB mag) favours a low-mass donor star. Based on these criteria, we classify Swift J170800−402551.8 as a candidate intermediate polar cataclysmic variable, where the spin period of the white dwarf is 784 s.
Hamstring muscle injury is highly prevalent in sports involving repeated maximal sprinting. Although neuromuscular fatigue is thought to be a risk factor, the mechanisms underlying the fatigue ...response to repeated maximal sprints are unclear. Here, we show that repeated maximal sprints induce neuromuscular fatigue accompanied with a prolonged strength loss in hamstring muscles. The immediate hamstring strength loss was linked to both central and peripheral fatigue, while prolonged strength loss was associated with indicators of muscle damage. The kinematic changes immediately after sprinting likely protected fatigued hamstrings from excess elongation stress, while larger hamstring muscle physiological cross-sectional area and lower myoblast:fibroblast ratio appeared to protect against fatigue/damage and improve muscle recovery within the first 48 h after sprinting. We have therefore identified novel mechanisms that likely regulate the fatigue/damage response and initial recovery following repeated maximal sprinting in humans.
Hypothetical low-mass particles, such as axions, provide a compelling explanation for the dark matter in the universe. Such particles are expected to emerge abundantly from the hot interior of stars. ...To test this prediction, the CERN Axion Solar Telescope (CAST) uses a 9 T refurbished Large Hadron Collider test magnet directed towards the Sun. In the strong magnetic field, solar axions can be converted to X-ray photons which can be recorded by X-ray detectors. In the 2013-2015 run, thanks to low-background detectors and a new X-ray telescope, the signal-to-noise ratio was increased by about a factor of three. Here, we report the best limit on the axion-photon coupling strength (0.66 × 10-10 GeV-1 at 95% confidence level) set by CAST, which now reaches similar levels to the most restrictive astrophysical bounds.
We show that microstructures built from nonmagnetic conducting sheets exhibit an effective magnetic permeability /spl mu//sub eff/, which can be tuned to values not accessible in naturally occurring ...materials, including large imaginary components of /spl mu//sub eff/. The microstructure is on a scale much less than the wavelength of radiation, is not resolved by incident microwaves, and uses a very low density of metal so that structures can be extremely lightweight. Most of the structures are resonant due to internal capacitance and inductance, and resonant enhancement combined with compression of electrical energy into a very small volume greatly enhances the energy density at critical locations in the structure, easily by factors of a million and possibly by much more. Weakly nonlinear materials placed at these critical locations will show greatly enhanced effects raising the possibility of manufacturing active structures whose properties can be switched at will between many states.
The European Union (EU) has recently published its first list of invasive alien species (IAS) of EU concern to which current legislation must apply. The list comprises species known to pose great ...threats to biodiversity and needs to be maintained and updated. Horizon scanning is seen as critical to identify the most threatening potential IAS that do not yet occur in Europe to be subsequently risk assessed for future listing. Accordingly, we present a systematic consensus horizon scanning procedure to derive a ranked list of potential IAS likely to arrive, establish, spread and have an impact on biodiversity in the region over the next decade. The approach is unique in the continental scale examined, the breadth of taxonomic groups and environments considered, and the methods and data sources used. International experts were brought together to address five broad thematic groups of potential IAS. For each thematic group the experts first independently assembled lists of potential IAS not yet established in the EU but potentially threatening biodiversity if introduced. Experts were asked to score the species within their thematic group for their separate likelihoods of i) arrival, ii) establishment, iii) spread, and iv) magnitude of the potential negative impact on biodiversity within the EU. Experts then convened for a 2‐day workshop applying consensus methods to compile a ranked list of potential IAS. From an initial working list of 329 species, a list of 66 species not yet established in the EU that were considered to be very high (8 species), high (40 species) or medium (18 species) risk species was derived. Here, we present these species highlighting the potential negative impacts and the most likely biogeographic regions to be affected by these potential IAS.
We identified 66 species, that are currently absent from the EU, which pose a very high, high or medium threat to biodiversity and ecosystems. The species span a range of functional groups, with primary producers being numerically dominant. Escape from confinement is the pathway considered to be the most likely route of introduction for many species, particularly among plants and vertebrates.
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