Label-free identification of antibiotic resistant isolates of living Escherichia coli: Pilot study.

We introduce a label-free spectroscopic method to classify subtypes of quinolone-nonsusceptible Escherichia coli (E. coli) isolates obtained from human blood cultures. Raman spectroscopy with a 30-nm gold-deposited, surface-enhanced Raman scattering (SERS) substrate was used to evaluate three multilocus sequencing typing (MLST)-predefined groups including E. coli ATCC25922, E. coli ST131:O75, and E. coli ST1193:O25b. Although there was a coffee-ring effect, the ring zone was selected at the ideal position to screen E. coli isolates. Strong Raman peaks were present at 1001-1004 cm-1 (CC aromatic ring breathing stretching vibrational mode of phenylalanine), 1447-1448 cm-1 (CH2 scissoring deformation vibrational mode), and 1667 cm-1 (amide I α-helix). Although the three MLST-predefined E. coli isolates had similar Raman spectral patterns, a support vector machine (SVM) learning algorithm-assisted principal component analysis (PCA) analysis had superior performance in detecting the presence of quinolone-nonsusceptible E. coli isolates as well as classifying similar microbes, such as quinolone-nonsusceptible E. coli ST131:O75 and E. coli ST1193:O25b isolates. Therefore, this label-free and nondestructive technique is likely to be useful for clinically diagnosing quinolone-nonsusceptible E. coli isolates with the MLST method.

Genome-wide association study of serum lipids confirms previously reported associations as well as new associations of common SNPs within PCSK7 gene with triglyceride.

Previous reports including genome-wide association studies (GWASs) have described associations of serum lipids with genomic variations. In the present study, we examined the association of ∼2.5 million single-nucleotide polymorphisms (SNPs) from 3041 Japanese healthy volunteers obtained from the Japan Pharmacogenomics Data Science Consortium (JPDSC) database with serum lipids. We confirmed the previously reported associations of 14 SNPs in 5 regions for low-density lipoprotein (LDL) cholesterol, 23 SNPs in 12 regions for high-density lipoprotein (HDL) cholesterol, 16 SNPs in 6 regions for triglyceride and 5 SNPs in 1 region for phospholipid. Furthermore, we identified 16 possible novel candidate genes associated with LDL cholesterol, HDL cholesterol or triglycerides, where SNPs had P-values of <1 × 10(-5). Further replication analyses of these genes with Korean data revealed significant associations of SNPs located within the PCSK7 gene and triglyceride (Pmeta=7.98 × 10(-9) and 1.91 × 10(-8) for rs508487 and rs236911, respectively). These associations remained significant even by the conditional analysis adjusting for three neighboring variations associated with triglyceride. Our present data suggest that PCSK7 as well as PCSK9 may be associated with lipids, especially triglyceride, and may serve as a candidate for a new drug target to treat lipid abnormality syndromes.

Multidetector computed tomography may be an adequate screening test to reduce periprocedural stroke in atrial fibrillation ablation: a multicenter propensity-matched analysis.

BACKGROUND: Whether routine transesophageal echocardiography (TEE) in addition to multidetector computed tomography (MDCT) has incremental value in preventing periprocedural stroke before atrial fibrillation (AF) ablation is unclear. OBJECTIVE: The purpose of this study was to evaluate whether screening with MDCT is sufficient for preventing periprocedural stroke. METHODS: From 4 tertiary centers, we enrolled 1147 patients (902 males, age 57 ± 11 years) with optimal anticoagulation and preserved left ventricular ejection function who had undergone MDCT and routine TEE (group 1, n = 678) or selective TEE (group 2, n = 469) as screening tests before AF ablation. Based on a propensity score analysis, 2 groups with 412 matched pairs were created. RESULTS: Patient baseline characteristics were comparable between the matched groups. In group 1 (n = 412), thrombi were detected in 4 patients (1.0%) on TEE, and ablation was not performed. These patients also showed thrombi (n = 3) or blood stasis (n = 1) on MDCT. For thrombi detection, MDCT had sensitivity and negative predictive value of 100%. In group 2 (n = 412), thrombi were detected in 7 patients (1.7%) on MDCT. Of these patients , 2 (0.5%) also showed thrombi on TEE. Periprocedural stroke incidence did not differ between the groups (0.2% each, P = 1.0). CONCLUSION: The incidence of periprocedural stroke was low and did not differ significantly between the group assigned to routine TEE vs selective TEE screening in AF patients undergoing anticoagulation therapy if the patients had conditions associated with low thrombus risk. Thus, preprocedural TEE may not be necessary before AF ablation in patients who have undergone preprocedural cardiac MDCT that shows no evidence of left atrial appendage thrombus.

Recapitulation of previous genome-wide association studies with two distinct pathophysiological entities of gastric cancer in the Korean population.

Gastric cancer (GC) is the most common malignancy. The incidence rates remain remarkably high in East Asians. Although genome-wide association studies in the Han Chinese and Japanese populations have so far yielded susceptibility loci for GC, these findings need to be validated in an independent ethnic group. To identify the potential heterogeneity by histological classified subtypes (intestinal and diffuse), we examined the previously reported associations in the Korean population. PRKAA1 at 5p13.1 was found to be more strongly associated with intestinal type (odds ratio, OR=1.39, 95% CI (confidence interval) =1.22-1.58, P=3.77 × 10(-7)) than diffuse type. In addition, PSCA at 8q23.3 was significantly replicated in diffuse type (OR=1.49, 95% CI=1.32-1.67, P=2.43 × 10(-11)) but far less significant in intestinal type. In conclusion, these findings could bring additional insights into the etiologic heterogeneity in gastric carcinogenesis mechanisms.

A genome-wide association study of a coronary artery disease risk variant.

Although over 30 common genetic susceptibility loci have been identified to be independently associated with coronary artery disease (CAD) risk through genome-wide association studies (GWAS), genetic risk variants reported to date explain only a small fraction of heritability. To identify novel susceptibility variants for CAD and confirm those previously identified in European population, GWAS and a replication study were performed in the Koreans and Japanese. In the discovery stage, we genotyped 2123 cases and 3591 controls with 521 786 SNPs using the Affymetrix SNP Array 6.0 chips in Korean. In the replication, direct genotyping was performed using 3052 cases and 4976 controls from the KItaNagoya Genome study of Japan with 14 selected SNPs. To maximize the coverage of the genome, imputation was performed based on 1000 Genome JPT+CHB and 5.1 million SNPs were retained. CAD association was replicated for three GWAS-identified loci (1p13.3/SORT1 (rs599839), 9p21.3/CDKN2A/2B (rs4977574), and 11q22.3/ PDGFD (rs974819)) in Koreans. From GWAS and a replication, SNP rs3782889 showed a strong association (combined P=3.95 × 10(-14)), although the association of SNP rs3782889 doesn't remain statistically significant after adjusting for SNP rs11066015 (proxy SNP with BRAP (r(2)=1)). But new possible CAD-associated variant was observed for rs9508025 (FLT1), even though its statistical significance did marginally reach at the genome-wide a significance level (combined P=6.07 × 10(-7)). This study shows that three CAD susceptibility loci, which were previously identified in European can be directly replicated in Koreans and also provides additional evidences implicating suggestive loci as risk variants for CAD in East Asian.

Relationship between expression of vascular endothelial growth factor and intratumoral hemorrhage in human pituitary adenomas.

AIMS AND BACKGROUND: Although pituitary adenoma is a primary brain tumor that occasionally accompanies intratumoral hemorrhage, there are little reports about the molecular mechanism of intratumoral bleeding in pituitary adenoma. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and vascular permeability of various brain tumors. The authors studied the relationship between intratumoral hemorrhage and the expression of VEGF in human pituitary adenomas. METHODS: VEGF expression was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) in 71 pituitary adenomas. Clinical factors to investigate were age, gender, hormonal functioning, and radiological findings of pituitary adenomas. Radiological findings which were investigated by magnetic resonance (MR) images were intratumoral hemorrhage, cystic change, tumor size, and cavernous sinus invasion. The relationship between these factors and VEGF expression was statistically analyzed. RESULTS: VEGF was expressed in 25 cases (35.2%). Functioning tumors, hemorrhage, cystic change, and cavernous sinus invasion were 32 (45.1%), 18 (25.4%), 12 (16.9%), and 21 (29.6%) respectively. The expression of VEGF showed a significant relationship with the intratumoral hemorrhage of the adenomas (P <0.001). However, age, gender, tumor size, hormonal functioning, cyst formation, and cavernous sinus invasion had no relationship with VEGF expression (P >0.05). CONCLUSIONS: This study suggests that VEGF expression may be responsible for intratumoral hemorrhage of pituitary adenomas. Therefore, VEGF can be a novel target to prevent a catastrophic apoplexy in pituitary adenomas and to establish roles in angiogenesis-based therapeutics of pituitary adenomas.

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.