Summary
Background Adiposity is a known risk factor for psoriasis. Genome‐wide association studies (GWAS) have identified a number of genes associated with risk of psoriasis while the evidence on ...gene–environment interactions in psoriasis is very sparse.
Objectives To investigate the effect modification by adiposity measures on the association between single‐nucleotide polymorphisms (SNPs) from published GWAS and risk of psoriasis.
Methods Our psoriasis GWAS dataset comprised 9194 participants, including 337 individuals with psoriasis and 8857 controls from six GWAS, nested within the Nurses’ Health Study (NHS), NHS II, and Health Professionals’ Follow‐up Study. Clinician‐diagnosed psoriasis was ascertained with high validity. For stratified analyses, body mass index (BMI) was dichotomized at 25, and waist circumference was dichotomized at 30 (women) and 36 inches (men), while waist–hip ratio (WHR) was dichotomized at 0·8 (women) and 1·0 (men).
Results Forty‐one out of 44 previously reported psoriasis‐related SNPs were included in our GWAS datasets. After excluding those with high linkage disequilibrium, 33 remained in the analysis. There were significant interactions between BMI and two SNPs in the IL12B (rs3212227) and IL23R (rs7530511) genes. Further analysis of these two SNPs indicated interactions between rs3212227 and waist circumference or WHR P for interaction (Pint) < 0·05, but not for rs7530511. These observations were confirmed among participants without type 2 diabetes or coronary heart disease. The interactions remained after simultaneously adjusting for BMI as a continuous variable. In addition, we did not observe a significant main effect for rs7530511.
Conclusions The association between a polymorphism in IL12B and psoriasis risk may be modified by measures of overall and central adiposity.
What’s already known about this topic?
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Adiposity has been associated with psoriasis in a prospective study and the chronic, low‐grade inflammatory state associated with adiposity has been postulated as the key underlying mechanism.
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Prior genome‐wide association studies (GWAS) have identified a number of genes associated with risk of psoriasis, with IL12B and IL23R demonstrating the most consistent associations across multiple studies.
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Evidence on the gene–environment interactions in psoriasis has been very sparse.
What does this study add?
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In a post‐GWAS approach, we confirmed the elevated risk of psoriasis associated with the rs3212227 single‐nucleotide polymorphism in IL12B, but only among overweight individuals.
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The association between a polymorphism in IL12B and psoriasis risk may be modified by measures of overall and central adiposity.
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Our study indicated that gene–environment interaction could play an important role in the development of psoriasis.
Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and it is a lethal disease with a recurrence rate of almost 50% within 1 year even after curative resection. The ...purpose of this study was to find out risk factors of early recurrence within the first year of surgery in PDAC.
Methods
From January 2007 to December 2016, 833 patients who underwent pancreatectomy with curative intention for PDAC at a single institute were included in this study, and their medical records were retrospectively reviewed.
Results
The median overall survival (OS) was 22.1 months and the median disease free survival(DFS) was 10.4 months. The 5-year OS rate was 25.9% and DFS rate was 18.6%. After excluding 80 patients who have lost to follow-up, there were 394 patients (54.0%) who have recurred within the first year of surgery. Multivariable logistic regression revealed that the followings were independently associated with early recurrence: neutrophil to lymphocyte ratio > 2.7 (odds ratio OR 1.684, 95% confidence interval CI 1.164 - 2.436), poorly or un-differentiated tumor(OR 2.421, 95% CI 1.678 - 3.492), T stage (T2 OR 2.082, 95% CI 1.384 - 3.134, T3 OR 4.577, 95% CI 2.589 - 8.091), and N stage (N1 OR 1.560, 95% CI 1.075 - 2.265, N2 OR 4.561, 2.831 - 7.348). Adjuvant chemoradiation therapy was a factor that reduces the risk of early recurrence (OR 0.552, 95% CI 0.386 - 0.789).
Conclusions
Identification of risk factors associated with early recurrence in the preoperative and postoperative state may help establish therapeutic strategies to reduce the recurrence rate and improve survival of PDAC patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
The tapetum, the innermost of four sporophytic layers in the anther wall, comes in direct contact with the developing male gametophyte and is thought to play a crucial role in the development and ...maturation of microspores. Here, we report the identification of rice (Oryza sativa) Undeveloped Tapetum1 (Udt1), which is required for the differentiation of secondary parietal cells to mature tapetal cells. T-DNA or retrotransposon Tos17 insertions in the Udt1 gene caused male sterility. The anther walls and meiocytes of the mutants were normal during the early premeiosis stage, but their tapeta failed to differentiate and became vacuolated during the meiotic stage. In addition, meiocytes did not develop to microspores, and middle layer degeneration was inhibited. Consequently, the anther locules contained no pollen. The UDT1:green fluorescent protein fusion protein was localized to the nucleus. This, together with its homology with other basic helix-loop-helix proteins, suggests that UDT1 is a transcription factor. DNA microarray analysis identified 958 downregulated and 267 upregulated genes in the udt1-1 anthers, suggesting that Udt1 plays a major role in maintaining tapetum development, starting in early meiosis.
This paper describes the finite element method using ABAQUS to model the axial compressive behaviour of inclined, tapered and straight–tapered–straight (STS) concrete filled steel tubular stub (CFST) ...columns with square hollow sections. The accuracy of the numerical model was verified by comparing the numerical predictions with experimental study of the 200×200×3.75 RHS filled with C60 concrete with inclined angle of 0–9° and tapered angle of 0–4°. The results show that the compressive behaviours, load vs. strain relationship and failure mode predicted by the numerical simulations were agreeable with experimental results. After the validation, a parametric study was performed with 3 typical steel hollow sections (200×200×3.75 RHS, 300×300×6.3 RHS and 400×400×8.0 RHS) and extended the inclined angle and tapered angle to 0–15° and 0–12° respectively. The parametric study highlights some of the behaviour observed in test and extends the application range. In addition, reduction factor for calculating the axial capacity of this form of CFST columns are proposed.
► Compressive behaviour of inclined, tapered and straight–tapered–straight (STS) concrete-filled steel tubular columns. ► Parametric study on the behaviour of these columns via ABAQUS FE model. ► Develop simple design equations for calculating the compressive capacity of this form of CFST stub columns.
BACKGROUND AND PURPOSE Growing evidence suggests that long‐term abuse of ketamine does harm the heart and increases the risk of sudden death. The present study was performed to explore the ...cardiotoxicity of ketamine and the protective effects of metoprolol.
EXPERIMENTAL APPROACH Rats and rabbits were divided into control, ketamine, metoprolol alone and ketamine plus metoprolol groups. Ketamine (40 mg·kg−1·day−1, i.p.) and metoprolol (20 mg·kg−1·day−1, p.o.) were administered continuously for 12 weeks in rats and 8 weeks in rabbits. Cardiac function, electrophysiological disturbances, cardiac collagen, cardiomyocte apoptosis and the remodelling‐related proteins were evaluated.
KEY RESULTS Rabbits treated with ketamine showed decreased left ventricular ejection fraction, slowed ventricular conduction velocity and increased susceptibility to ventricular arrhythmia. Metoprolol prevented these pathophysiological alterations. In ketamine‐treated rats, cardiac collagen volume fraction and apoptotic cell number were higher than those of control animals; these effects were prevented by co‐administration of metoprolol. Consistently, the expressions of poly (ADP‐ribose) polymerases‐1, apoptosis‐inducing factor and NF‐κB‐light‐chain‐enhancer of activated B cells were all increased after ketamine treatment and sharply reduced after metoprolol administration. Moreover, ketamine enhanced sympathetic sprouting, manifested as increased growth‐associated protein 43 and tyrosine TH expression. These effects of ketamine were prevented by metoprolol.
CONCLUSIONS AND IMPLICATIONS Chronic treatment with ketamine caused significant ventricular myocardial apoptosis, fibrosis and sympathetic sprouting, which altered the electrophysiological properties of the heart and increased its susceptibility to malignant arrhythmia that may lead to sudden cardiac death. Metoprolol prevented the cardiotoxicity of ketamine, indicating a promising new therapeutic strategy.
FeSe(x) (x = 0.80,0.84,0.88,0.92) thin films were prepared on SrTiO(3)(001)(STO), (La,Sr)(Al,Ta)O(3)(001) (LSAT), and LaAlO(3)(001) (LAO) substrates by a pulsed laser deposition method. All of the ...thin films show single-phase and c-axis oriented epitaxial growth, and are superconducting. Among them, the FeSe(0.88) thin films show a T(c,onset) of 11.8 K and a T(c,0) of 3.4 K. The upper critical magnetic field is estimated to be 14.0 T.
► The COFs of NC and CG Cu are comparable without oxidation and delamination. ► As oxidation and delamination occur, the COF of either CG or NC Cu increases to a constant value. ► The enhanced wear ...resistance of the NC Cu is mainly attributed to its higher hardness.
Dry sliding tribological behaviors of nanocrystalline (NC) and coarse grained (CG) Cu were studied by using a ball-on-plate tribometer with a counterface ball of cemented tungsten carbide. The results showed that prior to oxidation and delamination, the steady-state friction coefficients (FCs) of NC and CG Cu are comparable (∼0.35). As oxidation with delamination of wear surface occur, the FC for either CG or NC Cu increases gradually, approaching a steady-state FC (∼0.63). The wear resistance of the NC Cu was enhanced by at least one order of magnitude under the measured loads ranging from 5N to 25N in comparison with the CG counterpart, which is mainly attributed to the higher hardness of the NC layer.
The PHENIX MPC-EX is an W/Si pre-shower detector operating at small angles with respect to the beam in the Relativistic Heavy Ion Collider (RHIC). The Si Mini-Pad sensors are the active element of ...the detector. The expected hadron flux to the Si Mini-Pad sensors will generate significant non-ionizing energy loss in the sensors, which may damage the crystalline structure of the sensor’s bulk material. We investigated the nature of the hadron flux to the Si Mini-Pad sensors through a full simulation and determined its effect on the sensor’s characteristics based on a beam test. The investigation showed key issues in designing a preshower detector using silicon sensors and operating under a large neutron fluence and offered valuable information on the operation of the MPC-EX detector.
Purpose: To evaluate the antitumoral effects of an intra-arterial injection of 3-bromopyruvate (3-BrPA) on liver VX2 tumor in rabbits.
Material and Methods: Twenty rabbits with surgically implanted ...liver VX2 tumors were used. The rabbits were divided into three groups: a control, a saline, and a 3-BrPA group. Four rabbits were not treated at all, and they served as the control group. The saline group (n = 6) received only intra-arterial saline injection. The 3-BrPA group (n = 10) received an intra-arterial injection of 3-bromopyruvate through the hepatic artery. The delivered amounts of 3-bromopyruvate were as follows: 25 ml of 0.5 mM in six rabbits, 25 ml of 1.0 mM in two rabbits, and 25 ml of 2.0 mM in two rabbits. Four days after intra-arterial injection, the rabbits were sacrificed and histopathologic analysis of the explanted livers was performed with comparison of the tumor necrosis ratio (a percentage of the necrotic area versus the entire tumorous area) in each group.
Results: The mean tumor necrosis ratio was 12.5±4.2%, 44.8±24.7%, and 49.4±14.3% in the control, saline, and 3-BrPA groups, respectively. Between the control and the saline group, and between the control and the 3-BrPA group the mean tumor necrosis ratio appeared to be significantly different (P<0.05). However, there was no statistical difference in the mean tumor necrosis ratio between the saline and the 3-BrPA group (P = 0.416).
Conclusion: A single session of intra-arterial injection of 3-BrPA showed no better results in terms of tumor necrosis than that of saline injection in a rabbit VX2 tumor model.
In this work, we aimed to develop chitosan-coated mucoadhesive liposomes containing risedronate to improve intestinal drug absorption. Liposomes containing risedronate were prepared with ...1,2-distearoryl-sn-glycero-3-phosphocholine and distearoryl-sn-glycero-3-phospho-rac-(1-glycerol) using the freeze-drying method, with subsequent coating of the anionic surfaces of the liposomes with chitosan. The in vitro characteristics of the chitosan-coated liposomes were investigated, including their stability, mucoadhesiveness, and Caco-2 cell permeability. This formulation was stable in simulated gastric and intestinal fluids, with the percentage of drug remaining in the liposomes being more than 90% after 24 hours of incubation. Chitosan-coated liposomes also showed strong mucoadhesive properties, implying potential electrostatic interaction with the mucous layer in the gastrointestinal tract. Compared with the untreated drug, chitosan-coated liposomes significantly enhanced the cellular uptake of risedronate, resulting in an approximately 2.1-2.6-fold increase in Caco-2 cells. Further, the chitosan-coated liposomes increased the oral exposure of risedronate by three-fold in rats. Taken together, the results of this study suggest that chitosan-coated liposomes containing risedronate should be effective for improving the bioavailability of risedronate.
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