Summary
Background
Aspirin increases the risk of gastrointestinal bleeding.
Aim
To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.
Methods
Low‐dose (75‐325 mg daily) ...aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti‐inflammatory drugs (NSAIDs), cyclooxygenase‐2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine‐2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers.
Results
A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio HR: 2.75, 95% confidence interval CI: 2.06‐3.65), NSAIDs (HR: 8.61, 95% CI: 3.28‐22.58), steroids (HR: 10.50, 95% CI: 1.98‐55.57), SSRIs (HR: 11.71, 95% CI: 1.40‐97.94), PPIs (HR: 8.47, 95% CI: 2.26‐31.71), and H2RAs (HR: 10.83, 95% CI: 2.98‐39.33) were significantly associated with LGIB.
Conclusions
The risk of LGIB was higher in low‐dose aspirin users than in aspirin nonusers in this nationwide cohort. Low‐dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.
Linked ContentThis article is linked to Taha and Chen et al papers. To view these articles visit https://doi.org/10.1111/apt.14114 and https://doi.org/10.1111/apt.14138.
There are inconsistencies in the literature regarding the prevalence and assessment of chemotherapy-induced peripheral neuropathy (CIPN). This study explored CIPN natural history and its ...characteristics in patients receiving taxane- and platinum-based chemotherapy.
Multi-country multisite prospective longitudinal observational study. Patients were assessed before commencing and three weekly during chemotherapy for up to six cycles, and at 6,9, and 12 months using clinician-based scales (NCI-CTCAE; WHO-CIPN criterion), objective assessments (cotton wool test;10 g monofilament); patient-reported outcome measures (FACT/GOG-Ntx; EORTC-CIPN20), and Nerve Conduction Studies.
In total, 343 patients were recruited in the cohort, providing 2399 observations. There was wide variation in CIPN prevalence rates using different assessments (14.2-53.4%). Prevalence of sensory neuropathy (and associated symptom profile) was also different in each type of chemotherapy, with paclitaxel (up to 63%) and oxaliplatin (up to 71.4%) showing the highest CIPN rates in most assessments and a more complex symptom profile. Peak prevalence was around the 6-month assessment (up to 71.4%). Motor neurotoxicity was common, particularly in the docetaxel subgroup (up to 22.1%; detected by NCI-CTCAE). There were relatively moderately-to-low correlations between scales (r
= 0.15,p < 0.05-r
= 0.48 p < 0.001), suggesting that they measure different neurotoxicity aspects from each other. Cumulative chemotherapy dose was not associated with onset and course of CIPN.
The historical variation reported in CIPN incidence and prevalence is possibly confounded by disagreement between assessment modalities. Clinical practice should consider assessment of motor neuropathy for neurotoxic chemotherapy. Current scales may not be all appropriate to measure CIPN in a valid way, and a combination of scales are needed.
Aims
We investigated the role of transient receptor potential vanilloid receptor type 1 (TRPV1) in simvastatin‐mediated activation of endothelial nitric oxide synthase (eNOS) and angiogenesis.
...Methods
Fluo‐8 NW assay was for Ca2+ detection; Griess's assay was for NO bioavailability; Western blotting and immunoprecipitation were for protein phosphorylation and interaction; tube formation and Matrigel plug assay were for angiogenesis.
Results
In endothelial cells (ECs), treatment with simvastatin time‐dependently increased intracellular level of Ca2+. Pharmacological inhibition or genetic disruption of TRPV1 abrogated simvastatin‐mediated elevation of intracellular Ca2+ in ECs or TRPV1‐transfected HEK293 cells. Loss of TRPV1 function abolished simvastatin‐induced NO production and phosphorylation of eNOS and calmodulin protein kinase II (CaMKII) in ECs and in aortas of mice. Inhibition of TRPV1 activation prevented the simvastatin‐elicited increase in the formation of TRPV1–Akt–CaMKII–AMPK–eNOS complex. In mice, Matrigel plug assay showed that simvastatin‐evoked angiogenesis was abolished by TRPV1 antagonist and genetic ablation of TRPV1. Additionally, our results demonstrated that TRP ankyrin 1 (TRPA1) is the downstream effector in the simvastatin‐activated TRPV1‐Ca2+ signalling and in the consequent NO production and angiogenesis as evidence by that re‐expression of TRPA1 further augmented simvastatin‐elicited Ca2+ influx in TRPV1‐expressed HEK293 cells and ablation of TRPA1 function profoundly inhibited the simvastatin‐induced increase in the phosphorylation of eNOS and CaMKII, formation of TRPV1–Akt–CaMKII–AMPK–eNOS complex, NO bioavailability, tube formation and angiogenesis in ECs or mice.
Conclusion
Simvastatin‐induced Ca2+ influx may through the activation of TRPV1–TRPA1 signalling, which leads to phosphorylation of CaMKII, increases in the formation of TRPV1–CaMKII–AMPK–eNOS complex, eNOS activation, NO production and, ultimately, angiogenesis in ECs.
•There is a major environmental issue about the printed circuit boards throughout the world.•Different physical and chemical recycling techniques have been reviewed.•Nonmetallic fraction of PCBs is ...the unwanted face of this waste stream.•Several applications of the nonmetallic fraction of waste PCBs have been introduced.
E-waste, in particular waste PCBs, represents a rapidly growing disposal problem worldwide. The vast diversity of highly toxic materials for landfill disposal and the potential of heavy metal vapors and brominated dioxin emissions in the case of incineration render these two waste management technologies inappropriate. Also, the shipment of these toxic wastes to certain areas of the world for eco-unfriendly “recycling” has recently generated a major public outcry. Consequently, waste PCB recycling should be adopted by the environmental communities as an ultimate goal.
This article reviews the recent trends and developments in PCB waste recycling techniques, including both physical and chemical recycling. It is concluded that the physical recycling techniques, which efficiently separate the metallic and nonmetallic fractions of waste PCBs, offer the most promising gateways for the environmentally-benign recycling of this waste. Moreover, although the reclaimed metallic fraction has gained more attention due to its high value, the application of the nonmetallic fraction has been neglected in most cases. Hence, several proposed applications of this fraction have been comprehensively examined.
We demonstrate synthetic azimuthal gauge potentials for Bose-Einstein condensates from engineering atom-light couplings. The gauge potential is created by adiabatically loading the condensate into ...the lowest energy Raman-dressed state, achieving a coreless vortex state. The azimuthal gauge potentials act as effective rotations and are tunable by the Raman coupling and detuning. We characterize the spin textures of the dressed states, in agreements with the theory. The lowest energy dressed state is stable with a 4.5-s half-atom-number-fraction lifetime. In addition, we exploit the azimuthal gauge potential to demonstrate the Hess-Fairbank effect, the analogue of Meissner effect in superconductors. The atoms in the absolute ground state has a zero quasiangular momentum and transits into a polar-core vortex when the synthetic magnetic flux is tuned to exceed a critical value. Our demonstration serves as a paradigm to create topological excitations by tailoring atom-light interactions where both types of SO(3) vortices in the |⟨Fover →⟩|=1 manifold, coreless vortices and polar-core vortices, are created in our experiment. The gauge field in the stationary Hamiltonian opens a path to investigating rotation properties of atomic superfluids under thermal equilibrium.
Improving our understanding of the genes regulating grain yield can contribute to the development of more productive wheat varieties. Previously, a highly significant QTL affecting spikelet number ...per spike (SNS), grain number per spike (GNS) and grain yield was detected on chromosome arm 7AL in multiple genome-wide association studies. Using a high-resolution genetic map, we established that the A-genome homeolog of WHEAT ORTHOLOG OF APO1 (WAPO-A1) was a leading candidate gene for this QTL. Using mutants and transgenic plants, we demonstrate in this study that WAPO-A1 is the causal gene underpinning this QTL. Loss-of-function mutants wapo-A1 and wapo-B1 showed reduced SNS in tetraploid wheat, and the effect was exacerbated in wapo1 combining both mutations. By contrast, spikes of transgenic wheat plants carrying extra copies of WAPO-A1 driven by its native promoter had higher SNS, a more compact spike apical region and a smaller terminal spikelet than the wild type. Taken together, these results indicate that WAPO1 affects SNS by regulating the timing of terminal spikelet formation. Both transgenic and wapo1 mutant plants showed a wide range of floral abnormalities, indicating additional roles of WAPO1 on wheat floral development. Previously, we found three widespread haplotypes in the QTL region (H1, H2 and H3), each associated with particular WAPO-A1 alleles. Results from this and our previous study show that the WAPO-A1 allele in the H1 haplotype (115-bp deletion in the promoter) is expressed at significantly lower levels in the developing spikes than the alleles in the H2 and H3 haplotypes, resulting in reduced SNS. Field experiments also showed that the H2 haplotype is associated with the strongest effects in increasing SNS and GNS (H2>H3>H1). The H2 haplotype is already present in most modern common wheat varieties but is rare in durum wheat, where it might be particularly useful to improve grain yield.
Epidermal growth factor receptor (EGFR) mutations typically occur in exons 18-21 and are established driver mutations in non-small cell lung cancer (NSCLC)
. Targeted therapies are approved for ...patients with 'classical' mutations and a small number of other mutations
. However, effective therapies have not been identified for additional EGFR mutations. Furthermore, the frequency and effects of atypical EGFR mutations on drug sensitivity are unknown
. Here we characterize the mutational landscape in 16,715 patients with EGFR-mutant NSCLC, and establish the structure-function relationship of EGFR mutations on drug sensitivity. We found that EGFR mutations can be separated into four distinct subgroups on the basis of sensitivity and structural changes that retrospectively predict patient outcomes following treatment with EGFR inhibitors better than traditional exon-based groups. Together, these data delineate a structure-based approach for defining functional groups of EGFR mutations that can effectively guide treatment and clinical trial choices for patients with EGFR-mutant NSCLC and suggest that a structure-function-based approach may improve the prediction of drug sensitivity to targeted therapies in oncogenes with diverse mutations.
A long-standing issue in topological insulator research has been to find a bulk single crystal material that provides a high-quality platform for characterizing topological surface states without ...interference from bulk electronic states. This material would ideally be a bulk insulator, have a surface state Dirac point energy well isolated from the bulk valence and conduction bands, display quantum oscillations from the surface state electrons and be growable as large, high-quality bulk single crystals. Here we show that this material obstacle is overcome by bulk crystals of lightly Sn-doped Bi1.1Sb0.9Te2S grown by the vertical Bridgman method. We characterize Sn-BSTS via angle-resolved photoemission spectroscopy, scanning tunnelling microscopy, transport studies, X-ray diffraction and Raman scattering. We present this material as a high-quality topological insulator that can be reliably grown as bulk single crystals and thus studied by many researchers interested in topological surface states.
Objective
To identify determinants of shared decision making in patients with multiple myeloma (MM) to facilitate the design of a program to maximize the effects of shared decision making.
Methods
...This prospective longitudinal study recruited 276 adult patients (52% male, mean age 62.86 y, SD 15.45). Each patient completed the eHealth Literacy Scale (eHEALS), Multidimensional Trust in Health Care Systems Scale (MTHCSS), Patient Communication Pattern Scale (PCPS), and 9‐Item Shared Decision‐Making Questionnaire (SDM‐Q‐9) at baseline and the SDM‐Q‐9 again 6 months later. One family member of the patient completed the Family Decision‐Making Self‐Efficacy (FDMSE) at baseline. Structural equation modeling (SEM) was used to investigate the associations between eHealth literacy (eHEALS), trust in the health care system (MTHCSS), self‐efficacy in family decision making (FDMSE), patient communication pattern (PCPS), and shared decision making (SDM‐Q‐9).
Results
SEM showed satisfactory fit (comparative fit index = 0.988) and significant correlations between the following: eHealth literacy and trust in the health care system (β = 0.723, P < 0.001); eHealth literacy and patient communication pattern (β = 0.242, P < 0.001); trust in the health care system and patient communication pattern (β = 0.397, P < 0.001); self‐efficacy in family decision making and patient communication pattern (β = 0.264, P < 0.001); eHealth literacy and shared decision making (β = 0.267, P < 0.001); and patient communication pattern and shared decision making (β = 0.349, P < 0.001).
Conclusions
Patient communication and eHealth literacy were found to be important determinants of shared decision making. These factors should be taken into consideration when developing strategies to enhance the level of shared decision making.
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