Summary
Background
The risk factors for gastrointestinal bleeding (GIB) in clopidogrel users have not been identified.
Aim
To clarify whether clopidogrel use is a risk factor for upper GIB (UGIB) and ...lower GIB (LGIB) and identify the risk factors in clopidogrel users.
Methods
Using the National Health Insurance Research Database of Taiwan, 3238 clopidogrel users and 12 952 age‐, sex‐, and enrolment time‐matched controls in a 1:4 ratio were extracted for comparison from a cohort dataset of 1 000 000 randomly sampled subjects. Cox proportional hazard regression models were used to identify the independent risk factors for UGIB and LGIB in all enrollees and clopidogrel users after adjustments for age, gender, comorbidity i.e., coronary artery disease, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease (CKD), cirrhosis, uncomplicated peptic ulcer disease, and peptic ulcer bleeding (PUB), and medications e.g., nonsteroidal anti‐inflammatory drugs (NSAIDs), cyclooxygenase‐2 inhibitors, aspirin, steroids, selective serotonin reuptake inhibitors (SSRIs), warfarin and alendronate.
Results
Cox proportional hazard regression analysis showed that use of clopidogrel increased the risk of UGIB hazard ratio (HR): 3.66; 95% confidence interval (CI): 2.96–4.51 and LGIB HR: 3.52, 95% CI: 2.74–4.52. Age, CKD, PUB history, use of aspirin and NSAIDs were independent risk factors for UGIB in the clopidogrel users. Age, CKD, PUB history, use of aspirin and SSRIs were independent risk factors for LGIB.
Conclusions
In clopidogrel users, age, CKD, PUB history, use of aspirin and NSAIDs are independent risk factors for UGIB; age, CKD, PUB history, use of aspirin and SSRIs are independent risk factors for LGIB.
Background
Thymic stromal lymphopoietin (TSLP), IL‐25, and IL‐33 system contribute to the initiation and development of Th2 responses. This study aimed to explore the involvement of TSLP, IL‐25, ...IL‐33, and their receptors in type 2 T‐helper (Th) responses in chronic rhinosinusitis with nasal polyps (CRSwNPs) and their cross‐regulation in human nasal epithelial cells (HNECs).
Methods
Immunohistochemistry, quantitative RT‐PCR, ELISA, Bio‐Plex assay, and flow cytometry were used to detect the expression of TSLP/common γ‐like TSLP receptor (TSLPR)/IL‐7 receptor α (IL‐7Rα), IL‐25/IL‐17B receptor (IL‐17RB), and IL‐33/membrane‐bound ST2 (ST2L)/soluble ST2 (sST2) in sinonasal mucosa and HNECs. HNECs cultured at an air–liquid interface were used to explore the expression in regulation of these cytokine systems.
Results
Compared with controls and noneosinophilic CRSwNP, the expression of TSLP/TSLPR/IL‐7Rα and ST2L/sST2 was significantly increased in eosinophilic CRSwNP, predominantly in epithelial cells. In contrast, the expression of IL‐33 and IL‐25/IL‐17RB was enhanced in epithelial cells in both eosinophilic and noneosinophilic CRSwNP compared to controls. The expression of TSLP, TSLPR, and ST2L was positively correlated with symptom and computer tomography scan scores in eosinophilic CRSwNP and with Th2 cytokine expression in sinonasal mucosa. The expression of ST2L was correlated with TSLP and its receptor expression. TSLP could induce ST2L expression that promoted IL‐33‐induced TSLP expression in HNECs. In addition, TSLP/TSLPR/IL‐7Rα and ST2L could be induced by Th2 cytokines, while IL‐25/IL‐17RB and IL‐33 could be upregulated by Th1/Th17 cytokines, in HNECs.
Conclusions
The positive feedback loop between TSLP, IL‐33 and their receptors, and Th2 cytokines may facilitate Th2‐skewed inflammation in eosinophilic CRSwNP.
Objectives
The aim of this study was to investigate the predictive factors for relapse of IgG4‐related disease (IgG4‐RD) and observe the long‐term clinical outcomes in patients with IgG4‐RD.
Methods
...We included in the present analysis 122 patients who were newly diagnosed with IgG4‐RD, treated with glucocorticoid (GC) monotherapy or GC and immunosuppressant combination therapy, and followed for at least 3 years. Clinical relapse, response and side effects were recorded.
Results
The cumulative relapse rates of patients in this study were 10.66%, 22.95% and 27.87% at 12, 24 and 36 months, respectively. Complete drug withdrawal was an independent risk factor for disease relapse. Higher serum IgG4 concentrations, involvement of more organs, higher IgG4 RI scores and elevation of eosinophils at baseline were closely associated with disease relapse. Re‐elevation of serum IgG4 concentrations and low GC maintenance dosage during the follow‐up period were significantly associated with clinical relapse. The GC dosage should be more than 6.25 mg day−1 as monotherapy during the maintenance stage; moreover, combining with immunosuppressants can reduce the GC dosage. Adding GC or immunosuppressants for patients with re‐elevation of serum IgG4 levels could prevent later disease relapse. No serious complications were noted during long‐term follow‐up.
Conclusions
The combination of GC with immunosuppressants was more effective than GC monotherapy during the steroid tapering and maintenance stages. Higher serum IgG4 levels, involvement of more organs, higher IgG4 RI scores, history of allergy, eosinophil elevation at baseline, re‐elevation of serum IgG4 levels and lower GC maintenance dosage at follow‐up might be predictive of relapse.
Leveraging the recent research interest in emerging economies, this Perspective paper argues that an institution-based view of international business (IB) strategy has emerged. It is positioned as ...one leg that helps sustain the "strategy tripod" (the other two legs consisting of the industry- and resource-based views). We then review four diverse areas of substantive research: (1) antidumping as entry barriers; (2) competing in and out of India; (3) growing the firm in China; and (4) governing the corporation in emerging economies. Overall, we argue that an institution-based view of IB strategy, in combination with industry- and resource-based views, will not only help sustain a strategy tripod, but also shed significant light on the most fundamental questions confronting IB, such as "What drives firm strategy and performance in IB?"
Three-dimensional (3D) topological Dirac semimetals (TDSs) are a recently proposed state of quantum matter that have attracted increasing attention in physics and materials science. A 3D TDS is not ...only a bulk analogue of graphene; it also exhibits non-trivial topology in its electronic structure that shares similarities with topological insulators. Moreover, a TDS can potentially be driven into other exotic phases (such as Weyl semimetals, axion insulators and topological superconductors), making it a unique parent compound for the study of these states and the phase transitions between them. Here, by performing angle-resolved photoemission spectroscopy, we directly observe a pair of 3D Dirac fermions in Cd3As2, proving that it is a model 3D TDS. Compared with other 3D TDSs, for example, β-cristobalite BiO2 (ref. 3) and Na3Bi (refs 4, 5), Cd3As2 is stable and has much higher Fermi velocities. Furthermore, by in situ doping we have been able to tune its Fermi energy, making it a flexible platform for exploring exotic physical phenomena.
Three-dimensional (3D) topologicalWeyl semimetals (TWSs) represent a state of quantum matter with unusual electronic structures that resemble both a '3D graphene' and a topological insulator. Their ...electronic structure displays pairs of Weyl points (through which the electronic bands disperse linearly along all three momentum directions) connected by topological surface states, forming a unique arc-like Fermi surface (FS). Each Weyl point is chiral and contains half the degrees of freedom of a Dirac point, and can be viewed as a magnetic monopole in momentum space. By performing angle-resolved photoemission spectroscopy on the non-centrosymmetric compound TaAs, here we report its complete band structure, including the unique Fermi-arc FS and linear bulk band dispersion across the Weyl points, in agreement with the theoretical calculations1, 2. This discovery not only confirms TaAs as a 3DTWS, but also provides an ideal platform for realizing exotic physical phenomena (for example, negative magnetoresistance, chiral magnetic effects and the quantum anomalous Hall effect) which may also lead to novel future applications.
This experiment was conducted to assess the comparative effects of dietary antibiotics and oregano essential oil (OEO) addition on growth performance, antioxidant status and intestinal health of ...broilers. A total of 384 one-day-old broilers were randomly allocated to 4 treatments with 6 replicates of 16 broilers each. The 4 treatments were: an antibiotic-free control diet (control), control + 20 mg/kg colistin sulfate and 20 mg/kg virginiamycin (antibiotics), control + 200 mg/kg natural oregano essential oil (NOEO), and control + 200 mg/kg synthetic oregano essential oil (SOEO). The experiment lasted for 42 d. Results showed that birds fed with OEO had greater (P < 0.05) average daily gain (ADG) and lower (P < 0.05) feed conversion ratio (FCR) than those fed with control diet during d 1 to 21. Besides, birds fed with NOEO had the greatest (P < 0.05) ADG in the four groups during d 22 to 42. The serum oxidative stress parameters showed that OEO improved (P < 0.05) the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glutathione reductase (GR) of birds on day 21 and the activity of total antioxidant capacity (T-AOC) of birds on d 42. Relative to control, NOEO increased (P < 0.05) the activity of T-AOC in jejunum and decreased (P < 0.05) the level of malondialdehyde (MDA) in serum and jejunum. Moreover, OEO supplementation increased (P < 0.05) the concentrations of sIgA in duodenum and jejunum, Lactobacillus and total anaerobes in cecum, as well as activities of trypsin, chymotrypsin, lipase and amylase in duodenum, but restrained (P < 0.05) the amount of Escherichia coli. The NOEO supplementation increased (P < 0.05) total anaerobes of broilers on d 42 and the villus height to crypt depth ratio (VH/CD) of ileum. These results suggest that OEO improved antioxidant status and intestinal health of broilers which contributed to the growth performance improvement of broilers. Dietary OEO supplementation can be a promising alternative to antibiotic growth promoters for improving poultry production.
► A TiAl3 coating has been developed on Ti–6Al–4V by hot-dip aluminizing. ► The coating provides a high degree of protection for Ti–6Al–4V at 700°C. ► A layered structure of ...Al2O3/TiAl3/TiAl2/TiAl/alloy forms at 700°C. ► A layered structure of Al2O3/(TiAl3+TiAl2)/TiAl/Ti3Al/alloy forms at 800°C.
Hot-dip aluminizing and interdiffusion treatment were used to develop a TiAl3-rich coating on Ti–6Al–4V alloy. Interrupted oxidation at temperatures from 600 to 900°C and isothermal oxidation at 700 and 800°C of the coating were conducted. The coating markedly decreases the oxidation rate in comparison with the alloy at temperatures below 800°C during the interrupted oxidation. The oxidation kinetics follows parabolic relations at 700 and 800°C during the isothermal oxidation. A layered structure of Al2O3/TiAl3/TiAl2/TiAl/alloy from the outside to the inside forms after oxidation at 700°C without changing the main body of the coating.
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