Lupus erythematosus is a chronic inflammatory autoimmune disease with diverse clinical manifestations ranging from an indolent chronic cutaneous form to a severe potentially life-threatening disease, ...systemic lupus erythematosus. Discoid lupus erythematosus is a subphenotype of chronic cutaneous lupus erythematosus, characterised by scaly disk-shaped plaques which may be localised or widespread, occurring predominantly on sun-exposed skin and which may rarely progress to squamous cell carcinoma. The pathogenesis of discoid LE comprises complex interactions between multiple susceptibility genes involved in immune responses and clearance of apoptotic cells on the one hand, and environmental factors on the other. Herein, we discuss some aspects of the pathogenesis of discoid lupus erythematosus in relation to ultraviolet radiation and malignant transformation.
Lubiprostone activates ClC-2 chloride channels in epithelia. It is approved for treatment of chronic idiopathic constipation in adults and constipation-predominate irritable bowel syndrome in women. ...We tested a hypothesis that lubiprostone can reverse the constipating action of morphine and investigated the mechanism of action. Short-circuit current (Isc) was recorded in Ussing chambers as a marker for chloride secretion during pharmacological interactions between morphine and lubiprostone. Measurements of fecal wet weight were used to obtain information on morphine-lubiprostone interactions in conscious mice. Morphine decreased basal Isc, with an IC(50) of 96.1 nM. The action of dimethylphenylpiperazinium (DMPP), a nicotinic receptor agonist that stimulates neurogenic Isc, was suppressed by morphine. Lubiprostone applied after pretreatment with morphine reversed morphine suppression of both basal Isc and DMPP-evoked chloride secretion. Electrical field stimulation (EFS) of submucosal neurons evoked biphasic increases in Isc. Morphine abolished the first phase and marginally suppressed the second phase. Lubiprostone reversed, in concentration-dependent manner, the action of morphine on the first and second phases of the EFS-evoked responses. Subcutaneous lubiprostone increased fecal wet weight and numbers of pellets expelled. Morphine significantly reduced fecal wet weight and number of pellets. Injection of lubiprostone, 30-min after morphine, reversed morphine-induced suppression of fecal wet weight. We conclude that inhibitory action of morphine on chloride secretion reflects suppression of excitability of cholinergic secretomotor neurons in the enteric nervous system. Lubiprostone, which does not directly affect enteric neurons, bypasses the neurogenic constipating effects of morphine by directly opening chloride channels in the mucosal epithelium.
We present precision measurements of the target and beam-target spin asymmetries from neutral pion electroproduction in deep-inelastic scattering (DIS) using the CEBAF Large Acceptance Spectrometer ...(CLAS) at Jefferson Lab. We scattered 6-GeV, longitudinally polarized electrons off longitudinally polarized protons in a cryogenic 14NH3 target, and extracted double and single target spin asymmetries for ep→e′π0X in multidimensional bins in four-momentum transfer (1.0<Q2<3.2 GeV2), Bjorken-x (0.12<x<0.48), hadron energy fraction (0.4<z<0.7), transverse pion momentum (0<PT<1.0 GeV), and azimuthal angle ϕh between the lepton scattering and hadron production planes. We extracted asymmetries as a function of both x and PT, which provide access to transverse-momentum distributions of longitudinally polarized quarks. The double spin asymmetries depend weakly on PT. The sin2ϕh moments are zero within uncertainties, which is consistent with the expected suppression of the Collins fragmentation function. The observed sinϕh moments suggest that quark gluon correlations are significant at large x.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To assess stroke awareness among patients presenting to the emergency department with an acute ischaemic stroke or transient ischaemic attack (TIA).
A consecutive cohort of patients presenting with a ...cerebrovascular event was prospectively enrolled over a 15-month period and questionnaires were administered. If the patient was unable to respond to the questions or answer the questionnaire, it was administered to the primary caregiver. Comprehension of having a cerebrovascular event, reason for delay in presentation, mode of arrival and knowledge of treatment modalities were determined.
Only 42% of 400 patients thought they were having a stroke or TIA. The median time to presentation was 3.4 h. Delayed presentation was almost equal in men and women. When asked about onset, 19.4% thought that a stroke came on gradually and only 51.9% thought immediate presentation was crucial. 20.8% of patients had heard of thrombolysis.
Community knowledge of ischaemic stroke needs to be enhanced so that individuals present earlier, leading to timely management.
Millisecond pulsars (MSPs) have been firmly established as a class of γ-ray emitters via the detection of pulsations above 0.1 GeV from eight MSPs by the Fermi Large Area Telescope (LAT). Here, using ...13 months of LAT data, significant γ-ray pulsations at the radio period have been detected from the MSP PSR J0034–0534, making it the ninth clear MSP detection by the LAT. The γ-ray light curve shows two peaks separated by 0.274 ± 0.015 in phase which are very nearly aligned with the radio peaks, a phenomenon seen only in the Crab pulsar until now. The ≥0.1 GeV spectrum of this pulsar is well fit by an exponentially cutoff power law with a cutoff energy of 1.8 ± 0.6 ± 0.1 GeV and a photon index of 1.5 ± 0.2 ± 0.1, first errors are statistical and second are systematic. Lastly, the near-alignment of the radio and γ-ray peaks strongly suggests that the radio and γ-ray emission regions are co-located and both are the result of caustic formation.
We report on the search for 0.1-10 GeV emission from magnetars in 17 months of Fermi Large Area Telescope (LAT) observations. No significant evidence for gamma-ray emission from any of the currently ...known magnetars is found. The most stringent upper limits to date on their persistent emission in the Fermi energy range are estimated between ~10--12and10--10 erg s--1 cm--2, depending on the source. We also searched for gamma-ray pulsations and possible outbursts, also with no significant detection. The upper limits derived support the presence of a cutoff at an energy below a few MeV in the persistent emission of magnetars. They also show the likely need for a revision of current models of outer-gap emission from strongly magnetized pulsars, which, in some realizations, predict detectable GeV emission from magnetars at flux levels exceeding the upper limits identified here using the Fermi-LAT observations.
Advances in diagnosing peanut allergy Sicherer, Scott H; Wood, Robert A
The journal of allergy and clinical immunology in practice (Cambridge, MA)
1, Issue:
1
Journal Article
Peer reviewed
Peanut allergy is often severe, potentially fatal, usually persistent, and appears to have increased in prevalence. An accurate diagnosis is essential because there is a significant burden on quality ...of life. The tools available for diagnosis include the medical history, skin prick test (SPT), determination of serum peanut-specific IgE antibodies (PN-IgE), and medically supervised oral food challenges. Numerous studies, almost exclusively in children, have correlated clinical outcomes against SPTs and PN-IgE with informative results. The diagnostic utility of SPT and PN-IgE is maximized by considering the degree of positive result and consideration of the medical history (a priori estimation of risk). Emerging tests that evaluate IgE binding to specific proteins in peanut (component testing) add important additional diagnostic information in specific settings. Studies are increasingly focused on how the results of tests considered in combination (or performed serially) may increase diagnostic accuracy. Here, we review the utility of currently available tests and provide suggestions on how to best use them to accurately predict peanut allergy. Still, the physician-supervised oral food challenge remains the most definitive test available.
In this work we develop a homogenisation methodology to upscale mathematical descriptions of microcirculatory blood flow from the microscale (where individual vessels are resolved) to the macroscopic ...(or tissue) scale. Due to the assumed two-phase nature of blood and specific features of red blood cells (RBCs), mathematical models for blood flow in the microcirculation are highly nonlinear, coupling the flow and RBC concentrations (haematocrit). In contrast to previous works which accomplished blood-flow homogenisation by assuming that the haematocrit level remains constant, here we allow for spatial heterogeneity in the haematocrit concentration and thus begin with a nonlinear microscale model. We simplify the analysis by considering the limit of small haematocrit heterogeneity which prevails when variations in haematocrit concentration between neighbouring vessels are small. Homogenisation results in a system of coupled, nonlinear partial differential equations describing the flow and haematocrit transport at the macroscale, in which a nonlinear Darcy-type model relates the flow and pressure gradient via a haematocrit-dependent permeability tensor. During the analysis we obtain further that haematocrit transport at the macroscale is governed by a purely advective equation. Applying the theory to particular examples of two- and three-dimensional geometries of periodic networks, we calculate the effective permeability tensor associated with blood flow in these vascular networks. We demonstrate how the statistical distribution of vessel lengths and diameters, together with the average haematocrit level, affect the statistical properties of the macroscopic permeability tensor. These data can be used to simulate blood flow and haematocrit transport at the macroscale.
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