Summary
Background
Low‐osmolar non‐ionic radiocontrast media (RCMs) are commonly used throughout hospitals. However, the incidence of immediate adverse drug reactions (ADRs) to various low‐osmolar ...non‐ionic RCMs is not well studied. We compared the incidence of immediate ADRs among different low‐osmolar non‐ionic RCMs used in computed tomography (CT).
Methods
Severance Hospital has collected data for adverse reactions occurring in‐hospital using an internally developed system. Using this data, we reviewed 1969 immediate ADRs from 286 087 RCM‐contrasted CT examinations of 142 099 patients and compared the immediate ADRs of iobitridol, iohexol, iopamidol, and iopromide. We analysed the incidence of immediate ADRs to different RCMs, as well as the effect of single or multiple CT examinations per day.
Results
Iopromide showed the highest incidence of immediate ADRs (1.03%) and was followed by iopamidol (0.67%), iohexol (0.64%), and iobitridol (0.34%). In cases of anaphylaxis, iopromide also showed the highest incidence (0.041%), followed by iopamidol (0.023%), iohexol (0.018%), and iobitridol (0.012%). Risk of immediate ADR due to multiple CT examinations (1.19%) was significantly higher than the risk due to a single CT examination (0.63%). Risk of anaphylaxis was also higher for multiple CT examinations (0.052%) than for a single CT examination (0.020%).
Conclusions and Clinical Relevance
The incidence of immediate ADRs varied according to the low‐osmolar non‐ionic RCM used. Iopromide‐induced immediate ADRs were more frequent, while iobitridol was associated with fewer immediate ADRs than other RCMs. Multiple CT examinations per day resulted in a higher incidence of immediate ADRs and anaphylaxis than a single CT examination. Clinicians should consider these risk differences of immediate ADRs when prescribing contrasted CT examinations.
Magnetic fields are ubiquitous in the Universe. The energy density of these fields is typically comparable to the energy density of the fluid motions of the plasma in which they are embedded, making ...magnetic fields essential players in the dynamics of the luminous matter. The standard theoretical model for the origin of these strong magnetic fields is through the amplification of tiny seed fields via turbulent dynamo to the level consistent with current observations. However, experimental demonstration of the turbulent dynamo mechanism has remained elusive, since it requires plasma conditions that are extremely hard to re-create in terrestrial laboratories. Here we demonstrate, using laser-produced colliding plasma flows, that turbulence is indeed capable of rapidly amplifying seed fields to near equipartition with the turbulent fluid motions. These results support the notion that turbulent dynamo is a viable mechanism responsible for the observed present-day magnetization.
Initial performance of the COSINE-100 experiment Adhikari, G.; Adhikari, P.; de Souza, E. Barbosa ...
The European physical journal. C, Particles and fields,
02/2018, Volume:
78, Issue:
2
Journal Article
Peer reviewed
Open access
COSINE is a dark matter search experiment based on an array of low background NaI(Tl) crystals located at the Yangyang underground laboratory. The assembly of COSINE-100 was completed in the summer ...of 2016 and the detector is currently collecting physics quality data aimed at reproducing the DAMA/LIBRA experiment that reported an annual modulation signal. Stable operation has been achieved and will continue for at least 2 years. Here, we describe the design of COSINE-100, including the shielding arrangement, the configuration of the NaI(Tl) crystal detection elements, the veto systems, and the associated operational systems, and we show the current performance of the experiment.
Summary
Background
Transient receptor potential vanilloid subfamily, member 1 (TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis (AD). The treatment effect ...of TRPV1 antagonist via topical application in patients with AD remains unknown.
Objectives
To assess the clinical efficacy and safety of PAC‐14028, a TRPV1 antagonist, via topical application in patients with AD.
Methods
In this 8‐week, phase IIb, randomized, double‐blind, multicentre, vehicle‐controlled study, patients with mild‐to‐moderate AD were randomized to receive PAC‐14028 cream 0·1%, 0·3%, 1·0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment (IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis (SCORAD) index and Eczema Area and Severity Index (EASI) 75/90.
Results
A total of 194 patients were enrolled. IGA success rates at week 8 were 14·58% for vehicle cream, 42·55% for PAC‐14028 cream 0·1% (P = 0·0025 vs. vehicle), 38·30% for PAC‐14028 cream 0·3% (P = 0·0087 vs. vehicle) and 57·45% for PAC‐14028 cream 1·0% (P < 0·001 vs. vehicle). In particular, statistically significant differences were found between the vehicle and treatment groups in the IGA success rates with two‐grade improvement. The SCORAD index, EASI 75/90, sleep disturbance score and pruritus visual analogue scale showed a trend towards improvement. No significant safety issues were reported.
Conclusions
PAC‐14028 cream may be an effective and safe treatment modality for the treatment of patients with mild‐to‐moderate AD.
What is already known about this topic?
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases characterized by pruritic erythematous skin lesions and barrier dysfunction.
Transient receptor potential vanilloid subfamily, member 1 (TRPV1) antagonists suppress the release of pruritic and proinflammatory mediators.
The preclinical results demonstrate the feasibility of TRPV1 as a potential therapeutic target for the treatment of AD.
What does this study add?
TRPV1 regulates inflammation and pruritus in patients with AD.
PAC‐14028 cream, a novel TRPV1 antagonist, was superior to vehicle in improving clinical symptoms and signs with a favourable safety profile in adults with mild‐to‐moderate AD.
TRPV1 antagonism may play a role as a promising nonsteroidal topical treatment target for AD with a new mechanism of action.
Linked Editorial: Song and Armstrong. Br J Dermatol 2019; 180:971–972.
Plain language summary available online
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Summary
Effects of anti-osteoporosis medications such as anti-resorptive and anabolic agents on healing of osteoporotic spinal fracture were retrospectively investigated. The use of anabolic agent ...significantly enhanced fracture healing, reduced progressive collapse, and presented good pain relief. These findings suggest that proper selection of medication could improve initial management of acute osteoporotic spinal fractures (OSFs).
Introduction
Although anti-osteoporosis medications have beneficial effects on prevention of osteoporotic spinal fractures (OSFs), few studies have compared effects of medications on fracture healing following OSFs. Therefore, the purpose of this study was to elucidate the effects of different anti-osteoporosis medications on radiological and clinical outcomes after acute OSFs.
Methods
A total of 132 patients diagnosed with acute OSFs were enrolled and allocated into three groups group I (
n
= 39, no anti-osteoporosis medication), group II (
n
= 66, bisphosphonate), and group III (
n
= 27, parathyroid hormone (PTH). Radiological parameters including magnetic resonance (MR) classification, occurrence of intravertebral cleft (IVC), and clinical outcomes such as numerical rating scale (NRS) and Oswestry disability index were assessed. Risk analyses for IVC and progressive collapse were done along the related factors and medication type.
Results
IVC sign was observed in 30 patients. The rate of IVC sign was lower in group III (7.4%) than that in group I (20.5%) or group II (30.3%), although the difference was not statistically significant. Moreover, the degree of NRS improvement was better in group III than that in group I or group II (5.7 vs. 3.1 vs. 3.5,
p
< 0.001). On multiple regression analysis, mid-portion type fracture in MR classification was a significant risk factor for progressive OSFs. The use of PTH showed significant lower incidences of occurrence of IVC (odds ratio (OR) = 0.160) and increase in height loss (OR = 0.325).
Conclusions
Different anti-osteoporosis medications presented different clinical and radiological results after acute OSFs. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented better clinical outcomes. Proper selection of medication might improve initial management of acute OSFs.
Tumor necrosis factor receptor-associated factor (TRAF) proteins are key signaling molecules that function in various cellular signaling events including immune response, cell death and survival, ...development, and thrombosis. Their roles in cellular signaling are mediated mostly by direct interactions with various receptors via the TRAF domain. To determine how specific TRAF domains can interact with various receptors with a limited binding interface and how similar binding interfaces of TRAF family members can recognize their specific binding partners, extensive structural studies on TRAF family proteins have been conducted for several decades. In this review, we discuss the current understanding of the structural and molecular diversity of the TRAF domain and TRAF-binding motifs in many receptors according to available structural information.
Abstract
Large laser facilities have recently enabled material characterization at the pressures of Earth and Super-Earth cores. However, the temperature of the compressed materials has been largely ...unknown, or solely relied on models and simulations, due to lack of diagnostics under these challenging conditions. Here, we report on temperature, density, pressure, and local structure of copper determined from extended x-ray absorption fine structure and velocimetry up to 1 Terapascal. These results nearly double the highest pressure at which extended x-ray absorption fine structure has been reported in any material. In this work, the copper temperature is unexpectedly found to be much higher than predicted when adjacent to diamond layer(s), demonstrating the important influence of the sample environment on the thermal state of materials; this effect may introduce additional temperature uncertainties in some previous experiments using diamond and provides new guidance for future experimental design.
Collisionless shocks can be produced as a result of strong magnetic fields in a plasma flow, and therefore are common in many astrophysical systems. The Weibel instability is one candidate mechanism ...for the generation of sufficiently strong fields to create a collisionless shock. Despite their crucial role in astrophysical systems, observation of the magnetic fields produced by Weibel instabilities in experiments has been challenging. Using a proton probe to directly image electromagnetic fields, we present evidence of Weibel-generated magnetic fields that grow in opposing, initially unmagnetized plasma flows from laser-driven laboratory experiments. Three-dimensional particle-in-cell simulations reveal that the instability efficiently extracts energy from the plasma flows, and that the self-generated magnetic energy reaches a few percent of the total energy in the system. This result demonstrates an experimental platform suitable for the investigation of a wide range of astrophysical phenomena, including collisionless shock formation in supernova remnants, large-scale magnetic field amplification, and the radiation signature from gamma-ray bursts.
Aims
Aggressive meningioma remains incurable with neither chemo‐ nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving ...the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression.
Methods
Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression‐free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked‐down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM‐Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)‐pretreated or control IOMM‐Lee cells were implanted subcutaneously in nude mice.
Results
FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of β‐catenin, cyclin D1, p21, interleukin‐8, vascular endothelial growth factor‐A, PLAU, and epithelial‐to‐mesenchymal transition‐related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model.
Conclusions
Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.
Summary
Background
Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated.
Objectives
We compared ...autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non‐severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs).
Methods
Peripheral blood neutrophils from patients with SA (n = 30) and NSA (n = 38) were treated with interleukin (IL)‐8 (100 ng/mL). Autophagy (light chain 3‐II expression) and NET production levels were evaluated by Western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin‐1, and IL‐8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil‐derived neurotoxin (EDN).
Results
Untreated and IL‐8‐treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P < 0.01). IL‐8 increased autophagy and NET levels in PBNs from the SA group, but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P < 0.001). IL‐8‐induced NET production levels negatively were correlated with FEV1/FVC (r = −0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin‐1, and IL‐8 production from AECs. Higher levels of NET‐induced ECP and EDN were released from PBEs in SA compared with NSA groups.
Conclusions and Clinical Relevance
Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA.
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