Variants in genes related to inflammation and endothelial function can increase the risk for carotid atherosclerosis in southwestern China

AimTo investigate the potential association between polymorphisms in genes involved in endothelial function, inflammation and carotid atherosclerosis.MethodsThis was a three-center, population-based sectional survey conducted in Sichuan province of southwestern China. We randomly selected 8 different communities in Sichuan, and the residents in each community volunteered to participate in the survey by face-to-face questionnaire. A total of 2,377 residents with high stroke risk population in the 8 communities were included. Carotid atherosclerosis was evaluated by carotid ultrasound, and the 19 single nucleotide polymorphisms (SNPs) in 10 endothelial function as well as inflammation relevant genes were measured in the high stroke risk population. Carotid atherosclerosis was defined by the presence of carotid plaque or any carotid stenosis ≥15% or mean intima-media thickness (IMT) > 0.9 mm. Generalized multifactor dimensionality reduction (GMDR) approach was used to analyze gene–gene interactions among the 19 SNPs.ResultsAmong the 2,377 subjects with high stroke risk, 1,028 subjects had carotid atherosclerosis (43.2%), of which 852 (35.8%) cases had carotid plaque, 295 (12.4%) cases had ≥15% carotid stenosis, whereas 445 (18.7%) had mean IMT > 0.9 mm. Multivariate logistic regression revealed that IL1A rs1609682 TT and HABP2 rs7923349 TT served as independent risk factors for carotid atherosclerosis (OR, 1.45, 95% CI: 1.034–2.032, p = 0.031, and OR, 1.829, 95% CI: 1.228–2.723, p = 0.003). GMDR analysis indicated that there was a significant gene–gene interaction found among IL1A rs1609682, ITGA2 rs1991013, and HABP2 rs7923349. After adjusting the covariates, the high-risk interactive genotypes in the 3 variants were significantly associated with a significantly higher risk for carotid atherosclerosis (OR, 2.08, 95% CI: 1.257–5.98, p < 0.001).ConclusionThe prevalence of carotid atherosclerosis was observed to be extremely high in the high-risk stroke population in southwestern China. There were associations observed between the specific variants in inflammation and endothelial function relevant genes and carotid atherosclerosis. The high-risk interactive genotypes among IL1A rs1609682, ITGA2 rs1991013, and HABP2 rs7923349 significantly increased the risk of carotid atherosclerosis. These results are expected to provide novel strategies for the prevention of carotid atherosclerosis. The gene–gene interactive analysis used in this study may be very helpful to elucidate complex genetic risk factors for carotid atherosclerosis

A Method for Evaluating the Maximum Capacity of Grid-Connected Wind Farms Considering Multiple Stability Constraints

Boosting the capacity of grid-connected wind farms will greatly contribute to increasing the share of sustainable energy in the global generation mix. It is imperative to study the way to quantitatively assess the maximum capacity of grid-connected wind farms in combination with power system stability characteristics. In this work, a method to evaluate the maximum capacity of grid-connected wind farms considering the joint constraints of frequency and voltage stability is proposed based on the global intrinsic property of frequency stability and the local characteristic of voltage stability. Firstly, the maximum capacity of grid-connected wind farms in the power grid with high wind power penetration is assessed globally based on the frequency stability constraints, and then locally considering the voltage stability constraints of each local power grid. Further on, a quantitative method to evaluate the capacity of grid-connected wind farms is proposed based on the correlation between the local static voltage stability margin and the local capacity of grid-connected wind farms, as well as the global constraint of the maximum capacity of grid-connected wind farms. Finally, the effectiveness of the proposed method is verified by the simulation results of an actual regional power grid

Interactions among -2, and variants are associated with aspirin responsiveness and adverse events in patients with ischemic stroke

Background: The effect of gene variants and their interactions on response to aspirin and clinical adverse outcomes after an acute ischemic stroke (IS) is not fully understood. The aim of this study was to investigate the association of aspirin-relevant gene variants and their interactions with clinical adverse outcomes in IS patients taking aspirin. Methods: A total of 14 variants from six genes encoding COX enzymes ( COX-1, COX-2 ), platelet membrane receptors ( TXAS1, P2Y1, P2Y12 ) and glycoprotein receptor (GPIIIa) were examined in 850 acute IS patients. Gene–gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) analysis. All patients were followed up for 1 year after admission. Primary outcome was a composite of recurrent ischemic stroke (RIS), myocardial infarction (MI) and death. Results: The primary outcome occurred in 112 (13.5%) patients (81 RIS, 16 MI and 15 deaths). There were no significant differences in the frequencies of the genotypes of the 14 variants between the patients with and without primary outcome using single-locus analytical approach. However, there was significant gene–gene interaction among rs20417, rs1371097 and rs2317676. The high-risk interactive genotypes of rs20417, rs1371097 and rs2317676 were independently associated with primary adverse outcome of RIS, MI, and death after acute IS. Conclusion: The three-loci interactions are associated with sensitivity of IS patients to aspirin and aspirin-induced adverse clinical events. The combinatorial analysis used in this study may be helpful to elucidate complex genetic risk of aspirin resistance (AR). Clinical trial registration: The study described here is registered at http://www.chictr.org/ (unique identifier: ChiCTR-OCH-14004724)

The TXA2R rs1131882, P2Y1 rs1371097 and GPIIIa rs2317676 three-loci interactions may increase the risk of carotid stenosis in patients with ischemic stroke

Abstract Background The genetic risk factors for carotid stenosis are not fully understood. The aim of this study is to investigate the relationship between variants in platelet activation-relevant genes and carotid stenosis in patients with ischemic stroke (IS). Methods Eleven variants of platelet activation-relevant genes, aggregates of platelet-leukocyte, and platelet aggregation were examined in 236 IS patients with carotid stenosis and 378 patients without carotid stenosis. High-resolution B-mode ultrasound was used to assess carotid stenosis. Generalized multifactor dimensionality reduction (GMDR) methods were applied in analyzing gene-gene interactions to determine whether there was any interactive role of assessed variants in affecting risk of carotid stenosis. Results Platelet aggregation and aggregates of platelet-leukocyte showed higher value in patients with carotid stenosis, compared with patients without carotid stenosis. Excluding potential disturbance variables, these 11 variants were not associated with carotid stenosis. However, according to the GMDR analysis, gene-gene interactions among TXA2R rs1131882, P2Y1 rs1371097 and GPIIIa rs2317676 had a synergistic influence on carotid stenosis. The high-risk interactions between the three variants showed a relationship with higher platelet activation, and have independent associations with risk of carotid stenosis (OR = 2.72, 95% CI: 1.28–7.82, P = 0.001). Conclusion The interactions among rs1131882, rs1371097 and rs2317676 perhaps increase the risk of symptomatic carotid stenosis, and maybe a potential marker for carotid stenosis. In this study, the combinatorial analysis made good use in elucidating complex risk factors in the heredity of carotid stenosis

Ischemic stroke risk in a southeastern Chinese population: Insights from 5-lipoxygenase activating protein and phosphodiesterase 4D single-nucleotide polymorphisms

Through a genome-wide linkage scan, an Icelandic genetic research group identified two new genes associated with ischemic stroke: the 5-lipoxygenase activating protein (ALOX5AP) gene and the phosphodiesterase 4D (PDE4D) gene. Because they regulate arterial inflammation and are closely related to atherosclerosis and plaque instability, these two mutated genes have become a research hotspot. The purpose of this study was to investigate the association between the risk of ischemic stroke and single-nucleotide polymorphisms (SNPs) in the ALOX5AP and PDE4D genes in a southeastern Chinese population. Methods: A total of 459 patients with stroke and 462 control individuals were recruited in the study. Four ALOX5AP SNPs (SG13S32, SG13S42, SG13S89, and SG13S114), and three PDE4D SNPs (SNP83, SNP87, and SNP45) were studied. SNP genotypes were determined by polymerase chain reaction amplification followed by allele-specific primer extension, with detection by matrix-assisted laser desorption/ionization time-of-flight. Data were coded and entered in SPSS Windows (version 16.0). Odds ratios and 95% confidence intervals were calculated using multivariate logistic regression analysis. Generalized multifactor dimensionality reduction (GMDR) analysis was applied to detect gene–gene interactions. Results: No statistically significant differences were found in the SNP genotype frequencies between cases and controls for the seven SNPs studied. GMDR analysis revealed no evidence of interactions between these seven polymorphic sites and an increased stroke risk. In addition, no association between different stroke types and the control group was detected. Results showed that only the ALOX5AP gene, and specifically the rs9551963 and rs4769060 genotypes, exhibited significantly different distributions between the stroke and control groups in female participants. Conclusion: No association was found between SNPs of ALOX5AP or PDE4D and the risk of overall ischemic stroke in a southeastern Chinese population. Interactions between these two genes were not risk factors for cerebral infarction. In atherothrombotic and small-artery disease subtypes, none of the seven SNPs was associated with any stroke risk; however, the ALOX5AP gene might be related to ischemic stroke incidence in females

Hydration and compressive strength of supersulfated cement with low-activity high alumina ferronickel slag

This research aims to explore the feasibility of using low-activity high alumina ferronickel slag (FS), carbide slag and hemihydrate phosphogypsum (HG) as main ingredients to fabricate supersulfated cement (SSC). The effect of HG dosage and FS fineness on hydration and compressive strength of SSC-FS was systematically investigated. Experimental results indicated that high mechanical strength can be achieved at ambient temperature by adjusting HG dosage and FS fineness. Increase in HG dosage postpones the initial formation of hydrates to some extent, but the amount of the final hydration products is promoted to generate higher mechanical strength. FS with smaller particle size has higher reaction activity that significantly accelerates the hydration process of SSC, leading to higher compressive strength and smaller volume expansion of SSC, and more ettringite crystals with smallish morphology formed in the pastes. If the particle size of FS is too small, however, ettringite crystals tend to precipitate at the surface of FS particles, which is unfavorable for the development of microstructure and will restrict the generation of C-S-H, thus resulting in a decrease in compressive strength and an increase in volume expansion.Web of Science136art. no. 10489

Factors associated with favourable outcome in large hemispheric infarctions

Abstract Background Large hemispheric infarction (LHI) is a devastating condition with high mortality and poor functional outcome in most conservatively treated patients. The purpose of this study was to explore factors associated with favorable outcome in patients with LHI. Methods We prospectively enrolled consecutive patients with LHI. Favorable outcome was defined as a modified Rankin Scale (mRS) score of 0 to 3 at 90 days. Multivariate logistic regression analysis was employed to identify the independent factors associated with favorable outcome. Results Two hundred fifty-six cases with LHI were identified: 41 (16.0%) died during hospitalization, 94 (36.7%) died at 3 month, and 113 (44.1%) survived with favorable outcome at day 90. Compared with patients with unfavorable outcome, the favorable cases were younger (55.8 ± 14.7 vs. 66.2 ± 14.1), had less history of hypertension (38.9% vs. 59.3%), lower baseline NIHSS score (median NIHSS score 11 vs. 17), lower blood pressure on admission (systolic 134.7 ± 24.9 vs. 145.1 ± 26.1 mmHg; diastolic 80.2 ± 14.9 vs. 86.9 ± 16.2 mmHg; respectively), lower level of baseline serum glucose (7.2 ± 3.3 vs. 8.2 ± 3.3 mmol/L), a lower frequency of stroke-related complications (55.8% vs. 91.4%), more use of antiplatelets (93.8% vs. 57.1%) and statins (46.9% vs. 25.7%) in the acute phase of stroke, but less use of osmotic agents (69.9% vs. 89.3%), mechanical ventilation (1.8% vs. 20.0%) or decompressive hemicraniectomy (1.8% vs. 15.7%). Multivariable analysis identified the following factors associated with favorable outcome: age (odds ratio, OR 0.95, 95% confidence interval [CI] 0.92–0.98, p < 0.001), baseline NIHSS score (OR 0.90, 95% CI 0.84–0.96, p = 0.002), statins used in acute phase (OR 2.49, 95% CI 1.10–5.65, p = 0.029), brain edema (OR 0.05, 95% CI 0.01–0.21, p < 0.001) and pneumonia (OR 0.42, 95% CI 0.19–0.93, p = 0.032). Conclusion More than one third of patients with LHI have relatively favorable clinical outcomes at 90 days. Younger age, lower baseline NIHSS score, absence of brain edema and pneumonia, and statins used in the acute phase were associated with favorable outcome of patients with LHI at 90 days