International Consensus on drug allergy Demoly, P.; Adkinson, N. F.; Brockow, K. ...
Allergy,
April 2014, Volume:
69, Issue:
4
Journal Article, Conference Proceeding
Peer reviewed
Open access
When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug‐specific antibodies or T cells. DHRs may be allergic or ...nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life‐threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under‐reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more‐expensive or less‐effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class‐induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.
We present a background model for dark matter searches using an array of NaI(Tl) crystals in the COSINE-100 experiment that is located in the Yangyang underground laboratory. The model includes ...background contributions from both internal and external sources, including cosmogenic radionuclides and surface
210
Pb contamination. To build the model in the low energy region, with a threshold of 1 keV, we used a depth profile of
210
Pb contamination in the surface of the NaI(Tl) crystals determined in a comparison between measured and simulated spectra. We also considered the effect of the energy scale errors propagated from the statistical uncertainties and the nonlinear detector response at low energies. The 1.7 years COSINE-100 data taken between October 21, 2016 and July 18, 2018 were used for this analysis. Our Monte Carlo simulation provides a non-Gaussian peak around 50 keV originating from beta decays of bulk
210
Pb in a good agreement with the measured background. This model estimates that the activities of bulk
210
Pb and
3
H are dominating the background rate that amounts to an average level of
2.85
±
0.15
counts/day/keV/kg in the energy region of (1–6) keV, using COSINE-100 data with a total exposure of 97.7 kg
·
years.
We report two microlensing events, KMT-2017-BLG-1038 and KMT-2017-BLG-1146, that are caused by planetary systems. These events were discovered by Korea Microlensing Telescope Network survey ...observations from the 2017 bulge season. The discovered systems consist of a planet and host star with mass ratios of and , respectively. Based on a Bayesian analysis assuming a Galactic model without stellar remnant hosts, we find that the planet KMT-2017-BLG-1038Lb is a super-Jupiter-mass planet ( ) orbiting a mid-M dwarf host ( ) that is located at kpc toward the Galactic bulge. The other planet, KMT-2017-BLG-1146Lb, is a sub-Jupiter-mass planet ( ) orbiting a mid-M dwarf host ( ) at a distance of kpc toward the Galactic bulge. Both are potentially gaseous planets that are beyond their hosts' snow lines. These typical microlensing planets will be routinely discovered by second-generation microlensing surveys, rapidly increasing the number of detections.
On 6 March 2015, Dawn arrived at Ceres to find a dark, desiccated surface punctuated by small, bright areas. Parts of Ceres' surface are heavily cratered, but the largest expected craters are absent. ...Ceres appears gravitationally relaxed at only the longest wavelengths, implying a mechanically strong lithosphere with a weaker deep interior. Ceres' dry exterior displays hydroxylated silicates, including ammoniated clays of endogenous origin. The possibility of abundant volatiles at depth is supported by geomorphologie features such as flat crater floors with pits, lobate flows of materials, and a singular mountain that appears to be an extrusive cryovolcanic dome. On one occasion, Ceres temporarily interacted with the solar wind, producing a bow shock accelerating electrons to energies of tens of kilovolts.
The aim of the present study was to elucidate the fundamental mechanism of bovine oviduct epithelial cell (BOEC) co‐culture on developmental capacity of bovine in vitro oocyte maturation/in vitro ...fertilization (IVM/IVF) embryos. We examined the effects of astaxanthin against nitric oxide‐induced oxidative stress on cell viability by MTT assay, lipid peroxidation (LPO) by using thiobarbituric acid (TBA) reaction for malondialdehyde (MDA) and the expression of antioxidant genes (CuZnSOD, MnSOD and Catalase) or apoptosis genes (Bcl‐2, Caspase‐3 and Bax) by RT‐PCR in BOEC. We also evaluated the developmental rates of bovine IVM/IVF embryos co‐cultured with BOEC pre‐treated with astaxanthin (500 μm) in the presence or absence of sodium nitroprusside (SNP, 1000 μm) for 24 h. Cell viability in BOEC treated with SNP (50-2000 μm) lowered, while astaxanthin addition (50-500 μm) increased it in a dose‐dependent manner. Cell viability in astaxanthin plus SNP (1000 μm) gradually recovered according to the increase in astaxanthin additions (100-500 mm). The LPO in astaxanthin group (50-500 μM) gradually decreased in a dose dependent manner and among SNP or astaxanthin plus SNP group, SNP alone and astaxanthin (50 μM) plus SNP shown a significant increase than other groups (p < 0.05). Expression of apoptosis or antioxidant genes was detected by RT‐PCR. Bcl‐2 and antioxidant genes were detected in astaxanthin or astaxanthin plus SNP group, and Caspase‐3 and Bax genes were only found in SNP group. When bovine IVM/IVF embryos were cultured for 6-7 days under co‐culture system such as BOEC treated with astaxanthin in the presence or absence of SNP, the developmental ability to blastocysts in 500 μm astaxanthin group was the highest of all groups. These results suggest that astaxanthin has a antioxidative effect on cell viability and LPO of BOEC, and development of bovine IVM/IVF embryos due to the induction of antioxidant genes and suppression of apoptosis genes.
Microorganisms such as fungi and bacteria cause many human diseases and therefore rapid and accurate identification of these substances is essential for effective treatment and prevention of further ...infections. In particular, contemporary microbial detection technique is limited by the low detection speed which usually extends over a couple of days. Here we demonstrate that metamaterials operating in the terahertz frequency range shows promising potential for use in fabricating the highly sensitive and selective microbial sensors that are capable of high-speed on-site detection of microorganisms in both ambient and aqueous environments. We were able to detect extremely small amounts of the microorganisms, because their sizes are on the same scale as the micro-gaps of the terahertz metamaterials. The resonant frequency shift of the metamaterials was investigated in terms of the number density and the dielectric constants of the microorganisms, which was successfully interpreted by the change in the effective dielectric constant of a gap area.
Summary
Background
Little is known about factors affecting the quality of life (QoL) of patients with vitiligo, and previous studies have shown conflicting results.
Objectives
To explore the QoL of ...patients with vitiligo and to identify factors affecting QoL.
Methods
A nationwide questionnaire‐based study was conducted with 1123 patients with vitiligo recruited from 21 hospitals in Korea from July 2015 to June 2016. Data were collected using a structured questionnaire for demographic information and the Skindex‐29 instrument. Mild or severely impaired QoL in patients with vitiligo was assessed according to each domain (symptoms, functioning and emotions) of Skindex‐29. Multivariate logistic regression analyses were performed to determine the factors associated with QoL.
Results
Of the enrolled participants, 609 were male and 514 female, with a mean age of 49·8 years (range 20–84). The median duration of disease was 3·0 years (range 0–60). Using multivariate logistic regression modelling, the involvement of visible body parts and a larger affected body surface area were consistently associated with QoL impairment in all three domains of Skindex‐29. Additionally, the QoL of patients aged 20–59 years, who potentially had a more active social life than older patients, was associated with functional impairment. Furthermore, a higher educational background was associated with emotional impairment.
Conclusions
A multitude of factors significantly influence the QoL of patients with vitiligo. A better appreciation of these factors would help the management of these patients.
What's already known about this topic?
Quality of life is highly impaired in patients with vitiligo.
What does this study add?
The involvement of visible body parts and a larger affected body surface area were consistently associated with impaired symptoms, functioning and emotions.
Vitiligo with nonvisible lesions also considerably compromises quality of life; vitiligo should not be regarded as a cosmetic problem.
Patients aged 20–59 years experienced significant functional impairment, and those with a higher educational background had more impairment in their emotions.
Linked Comment: Ezzedine and Eleftheriadou. Br J Dermatol 2018; 178:28–29.
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Lysine-specific demethylase 1 (LSD1), which has been considered as a potential therapeutic target in human cancer, has been known to regulate many biological functions through its non-histone ...substrates. Although LSD1-induced hypoxia-inducible factor alpha (HIF1α) demethylation has recently been proposed, the effect of LSD1 on the relationship between HIF1α post-translational modifications (PTMs) and HIF1α-induced tumor angiogenesis remains to be elucidated. Here, we identify a new methylation site of the HIF1α protein antagonized by LSD1 and the interplay between HIF1α protein methylation and other PTMs in regulating tumor angiogenesis. LSD1 demethylates HIF1α at lysine (K) 391, which protects HIF1α against ubiquitin-mediated protein degradation. LSD1 also directly suppresses PHD2-induced HIF1α hydroxylation, which has a mutually dependent interplay with Set9-mediated HIF1α methylation. Moreover, the HIF1α acetylation that occurs in a HIF1α methylation-dependent manner is inhibited by the LSD1/NuRD complex. HIF1α stabilized by LSD1 cooperates with CBP and MTA1 to enhance vascular endothelial growth factor (VEGF)-induced tumor angiogenesis. Thus, LSD1 is a key regulator of HIF1α/VEGF-mediated tumor angiogenesis by antagonizing the crosstalk between PTMs involving HIF1α protein degradation.
Patients who have residual invasive carcinoma after the receipt of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative breast cancer have poor prognoses. The benefit ...of adjuvant chemotherapy in these patients remains unclear.
We randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival. Secondary end points included overall survival.
The result of the prespecified interim analysis met the primary end point, so this trial was terminated early. The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years; hazard ratio for recurrence, second cancer, or death, 0.70; 95% confidence interval CI, 0.53 to 0.92; P=0.01). Overall survival was longer in the capecitabine group than in the control group (89.2% vs. 83.6% of the patients were alive at 5 years; hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01). Among patients with triple-negative disease, the rate of disease-free survival was 69.8% in the capecitabine group versus 56.1% in the control group (hazard ratio for recurrence, second cancer, or death, 0.58; 95% CI, 0.39 to 0.87), and the overall survival rate was 78.8% versus 70.3% (hazard ratio for death, 0.52; 95% CI, 0.30 to 0.90). The hand-foot syndrome, the most common adverse reaction to capecitabine, occurred in 73.4% of the patients in the capecitabine group.
After standard neoadjuvant chemotherapy containing anthracycline, taxane, or both, the addition of adjuvant capecitabine therapy was safe and effective in prolonging disease-free survival and overall survival among patients with HER2-negative breast cancer who had residual invasive disease on pathological testing. (Funded by the Advanced Clinical Research Organization and the Japan Breast Cancer Research Group; CREATE-X UMIN Clinical Trials Registry number, UMIN000000843 .).
Melatonin, the major secretory product of the pineal gland, scavenges a variety of reactive oxygen and nitrogen species in vivo and in vitro, indicating that melatonin is a potent function as an ...antioxidant. The objective of this study was to investigate the effect of melatonin in the presence or absence of hydrogen peroxide (H₂O₂) on sperm characteristics (motility, viability, survival rate, membrane integrity, lipid peroxidation (LPO) and mitochondria activity) and also to examine the developmental rates to the blastocysts stage of porcine oocytes fertilized in vitro with semen treated with or without melatonin (100 nm) in the presence or absence of H₂O₂ (250 μm). The sperm were treated with melatonin in the presence or absence of H₂O₂ for 3, 6, 9 and 12 h at 37°C and then analysed for the sperm characteristics. The porcine embryos were produced by in vitro maturation and in vitro fertilization (IVM/IVF) using semen treated with or without melatonin (100 nm) in the presence or absence of H₂O₂ (250 μm) for 6 h. The semen characteristics, including motility, viability, survival rate, membrane integrity and mitochondria activity, were higher in the groups that were treated with melatonin in comparison to other groups, irrespective of incubation periods. Malondialdehyde levels in control, melatonin and melatonin + H₂O₂ groups were lower than H₂O₂ only group. A positive correlation was shown among motility, viability, survival rate and membrane integrity, but a negative correlation was observed between LPO and the other evaluation methods. The developmental rates to blastocysts of IVM/IVF porcine oocytes fertilized by semen treated with melatonin were significantly increased compared with any other groups, with the cell number of blastocysts shown to have a similar trend to the developmental rates. These results demonstrate that melatonin can improve the semen characteristics during in vitro storage and support the developmental ability of IVM/IVF embryos in pigs.
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