Genetic variants of PTGS2, TXA2R and TXAS1 are associated with carotid plaque vulnerability, platelet activation and TXA2 levels in ischemic stroke patients

<div><p>Eicosanoids may play a role in ischemic stroke. However, the associations of variants in cyclooxygenase (COX) pathway genes and interaction among these variants with carotid plaque vulnerability are not fully understood. In present study, twelve variants in COX pathway genes were examined using matrix-assisted laser desorption ionization time-of-flight mass spectrometry method in 396 patients with ischemic stroke and 291 controls. Platelet aggregation, platelet-leukocyte aggregates, and urine 11-dehydrothromboxane B2 (11-dTxB2) were also measured. According to the results of carotid high-resolution B-mode ultrasound, the patients were stratified into the following groups [i.e., non-carotid plaque and carotid plaque. The carotid plaque was further classified into subgroups of echolucent plaque (ELP) and echogenic plaque (EGP)]. Additionally, gene-gene interactions were analyzed to assess whether there was any interactive role for assessed variants in affecting carotid plaque vulnerability, platelet activation and 11-dTxB2 levels. There were no significant differences in the frequencies of genotypes of the twelve variants between patients and controls. Among 396 patients, 294 cases (74.2%) had carotid plaques (106 had ELP, 188 had EGP). Frequency of <i>PTGS2</i> rs20417CC, <i>TXAS1</i> rs2267679TT, <i>TXAS1</i> rs41708TT, <i>PTGIS</i> rs5602CC, and <i>TXA2R</i> rs1131882TT genotype was significantly higher in patients with plaque compared with patients without plaque, or in patients with ELP compared with patients with EGP. 11-dTxB₂ levels, platelet aggregation and platelet-leukocyte aggregates were significantly higher in patients with ELP compared with patients without plaque or with EGP. Multivariate logistic regression analysis revealed that <i>PTGS2</i> rs20417CC, <i>TXA2R</i> rs1131882TT, and high-risk interaction among variants in <i>PTGS2</i> rs20417, <i>TXA2R</i> rs1131882 and <i>TXAS1</i> rs41708 were independently associated with the risk of ELP after adjusting for confounding variables. The variants in COX pathway genes and the high-risk interactions among variants in <i>PTGS2</i> rs20417, <i>TXA2R</i> rs1131882 and <i>TXAS1</i> rs41708 were associated with high 11-dTxB2 and platelet activation, and independently associated with the risk of carotid plaque vulnerability. These variants might be potential markers for plaque instability.</p></div

Additional file 1 of Systematic review and meta-analysis of single-stage vs two-stage revision for periprosthetic joint infection: a call for a prospective randomized trial

Additional file 1

Associations between genotype combinations and echolucent plaque.

<p>Associations between genotype combinations and echolucent plaque.</p

Comparison of 11-dTxB₂, platelet aggregation and platelet-leukocyte aggregates among genotypes.

<p>Comparison of 11-dTxB₂, platelet aggregation and platelet-leukocyte aggregates among genotypes.</p

Comparison of the best models, prediction accuracies, cross-validation consistencies, and <i>P</i> values for echolucent plaque identified by GMDR.

<p>Comparison of the best models, prediction accuracies, cross-validation consistencies, and <i>P</i> values for echolucent plaque identified by GMDR.</p

Multivariate analysis of the major risk factors for echolucent plaques.

<p>Multivariate analysis of the major risk factors for echolucent plaques.</p

Data_Sheet_1_Exploring brain network oscillations during seizures in drug-naïve patients with juvenile absence epilepsy.docx

ObjectiveWe aimed to investigate the brain network activity during seizures in patients with untreated juvenile absence epilepsy.MethodsThirty-six juvenile absence epilepsy (JAE) patients with a current high frequency of seizures (more than five seizures during a 2 h EEG examination) were included. Each participant underwent a 2 h video EEG examination. Five 10 s EEG epochs for inter-ictal, pre-ictal, and post-ictal, and five 5 s EEG epochs for ictal states were extracted. Five 10 s resting-state EEG epochs for each participant from a sex- and age-matched healthy control (HC) were enrolled. The topological parameters of the brain networks were calculated using a graph theory analysis.ResultsCompared with the resting state of the HC group, the global efficiency, local efficiency, and clustering coefficients of the JAE group decreased in the inter-ictal state. In addition, the ictal state showed significantly increased global and local efficiency and clustering coefficients (p ConclusionThe present study supported the idea that the changes in the EEG brain networks in JAE patients are characterized by decreased global and local efficiency and clustering coefficient in the alpha band. Moreover, the onset of seizures is accompanied by excessively enhanced network efficiency. JAE patients with different ictal discharge patterns may have different functional network oscillations.</p

The predicated TFBS of differentially methylated CpG sites within the b<i>Boule</i> promoter.

<p>Arrows indicate differentially methylated CpG sites. The TFBS is underlined.</p

The methylation profile of the long CpG island in the b<i>Boule</i> 5' flanking region.

<p>(A) Schematic diagram of the long CGI within the b<i>Boule</i> promoter. (B) Schematic depiction of the CpG sites for methylation analysis. Nucleotide numbering is relative to +1 at the initiating ATG codon. The short vertical bars represent the CpG dinucleotides. (C) Methylation status of the b<i>Boule</i> promoter in the testes of cattle and cattle-yak hybrids. Each line represents an individual bacterial clone that was sequenced. Open circles indicate unmethylated CpG sites. Black circles indicate methylated CpG sites.</p

mRNA expression of b<i>Boule</i> in BMECs treated with 5-Aza-dC.

<p>mRNA expression was detected in treated cells but not in untreated cells by qRT-PCR. All experiments were performed three times. The bar above the histogram indicates the SEM. Different uppercase letters denote significant differences between different groups with a significance level of P < 0.01. Different lowercase letters denote significant differences between different groups with a significance level of P < 0.05.</p