Association between statin therapy and mortality in patients on dialysis after atherosclerotic cardiovascular diseases.

Statin therapy is essential for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD). However, the effects of statin therapy in patients receiving chronic dialysis remain uncertain. We aimed to evaluate the effect of statin therapy on long-term mortality in patients on dialysis after a first-time ASCVD. Patients receiving maintenance dialysis aged ≥ 18 years with a first-time ASCVD event between 2013 and 2018 were included in the Korean National Health Insurance Service database. Associations of statin use with long-term mortality were examined using Cox proportional hazards regression models adjusted for demographics and comorbidities. Among 17,242 patients on dialysis, 9611 (55.7%) were prescribed statins after a first-time ASCVD event. Among statin users, 7376 (76.7%) used moderate-intensity statins. During a mean follow-up of 32.6 ± 20.9 months, statin use was associated with a lower risk of all-cause mortality than statin nonuse after adjusting for confounding factors (hazard ratio [HR]: 0.92; 95% confidence interval [CI] 0.88-0.97; p = 0.0009). Despite a lack of evidence, more than half of patients on dialysis were prescribed statins after an ASCVD event. In patients on dialysis after ASCVD, statin therapy significantly reduced the risk of long-term all-cause mortality.

Collinsella urealyticum sp. nov., a urease-positive bacterial strain isolated from swine faeces.

A novel actinobacterial strain, designated AGMB00827T, was isolated from swine faeces. Strain AGMB00827T was obligately anaerobic, Gram-stain-positive, non-motile, non-spore-forming and rod-shaped bacterium. Comparative analyses based on the 16S rRNA gene and whole genome sequence revealed that strain AGMB00827T was affiliated to the genus Collinsella, and was most closely related to Collinsella vaginalis Marseille-P2666T (= KCTC 25056T). Biochemical analysis showed strain AGMB00827T was negative for catalase and oxidase. Interestingly, strain AGMB00827T possessed urease activity, which was determined by traditional methods (API test and Christensen's urea medium), unlike related strains. Furthermore, the major cellular fatty acids (> 10%) of the isolate were C18:1 ω9c, C16:0, C16:0 DMA and C18:2 ω9,12c DMA. Based on the whole genome sequence analysis, the DNA G + C content of strain AGMB00827T was 52.3%, and the genome size and numbers of rRNA and tRNA genes were 1,945,251 bp, 3 and 46, respectively. The average nucleotide identity and digital DNA-DNA hybridization values between strain AGMB00827T and C. vaginalis KCTC 25056 T were 71.0 and 23.2%, respectively. Additionally, the genome analysis revealed that strain AGMB00827T possesses urease gene cluster including ureABC and ureDEFG while the related strains do not have those genes, which is consistent with the urease activity. On the basis of polyphasic taxonomic approach, strain AGMB00827T represents a novel species within the genus Collinsella, for which the name Collinsella urealyticum sp. nov. is proposed. The type strain is AGMB00827T (= KCTC 25287T = GDMCC 1.2724T).

Parabacteroides faecalis sp. nov. Isolated from Swine Faeces.

A Gram-negative, obligate anaerobic, non-motile, non-spore-forming, rod-shaped bacterial strain designated AGMB00274T was isolated from swine faeces. An 16S rRNA gene analysis indicated that strain AGMB00274T belonged to the genus Parabacteroides, with the highest similarity to Parabacteroides johnsonii (P. johnsonii) DSM 18315T (sequence similarity of 94.9%). The genome size of strain AGMB00274T was 4,308,683 bp, with a DNA G+C content of 42.5 mol%. The biochemical analysis of strain AGMB00274T showed that it was positive for gelatin hydrolysis and α-fucosidase, but negative for the acid production from D-glucose, D-mannitol, D-maltose, salicin, glycerol, D-cellobiose, D-mannose, D-melezitose, D-sorbitol, D-trehalose, and negative for α-arabinosidase, glutamic acid decarboxylase, and pyroglutamic acid arylamidase. The dominant cellular fatty acids (> 10%) of the isolate were anteiso-C15: 0 (23.2%), iso-C15: 0 (16.6%), C18: 1 ω9c (16.4%), summed feature 11 (iso-C17: 0 3-OH and/or C18: 2 DMA) (12.5%), and C16: 0 (11.3%). The major respiratory quinones of strain AGMB00274T were MK-9 (55.4%) and MK-10 (44.6%). The major polar lipid was phosphatidylethanolamine. Based on phylogenetic, genetic, physiological, and chemotaxonomic analyses, as a novel species of the genus Parabacteroides, strain AGMB00274T was proposed with the name Parabacteroides faecalis sp. nov. The type strain used was AGMB00274T (= KCTC 25286T = GDMCC 1.2742T).

Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway.

Xanthine oxidase (XO) is an important source of reactive oxygen species. This study investigated whether XO inhibition exerts renoprotective effects by inhibiting vascular endothelial growth factor (VEGF) and NADPH oxidase (NOX) in diabetic kidney disease (DKD). Febuxostat (5 mg/kg) was administered to streptozotocin (STZ)-treated 8-week-old male C57BL/6 mice via intraperitoneal injection for 8 weeks. The cytoprotective effects, its mechanism of XO inhibition, and usage of high-glucose (HG)-treated cultured human glomerular endothelial cells (GECs) were also investigated. Serum cystatin C, urine albumin/creatinine ratio, and mesangial area expansion were significantly improved in febuxostat-treated DKD mice. Febuxostat reduced serum uric acid, kidney XO levels, and xanthine dehydrogenase levels. Febuxostat suppressed the expression of VEGF mRNA, VEGF receptor (VEGFR)1 and VEGFR3, NOX1, NOX2, and NOX4, and mRNA levels of their catalytic subunits. Febuxostat caused downregulation of Akt phosphorylation, followed by the enhancement of dephosphorylation of transcription factor forkhead box O3a (FoxO3a) and the activation of endothelial nitric oxide synthase (eNOS). In an in vitro study, the antioxidant effects of febuxostat were abolished by a blockade of VEGFR1 or VEGFR3 via NOX-FoxO3a-eNOS signaling in HG-treated cultured human GECs. XO inhibition attenuated DKD by ameliorating oxidative stress through the inhibition of the VEGF/VEGFR axis. This was associated with NOX-FoxO3a-eNOS signaling.

Gut Microbiota Eubacterium callanderi Exerts Anti-Colorectal Cancer Activity.

The gut microbiota (GM) is associated with colorectal cancer (CRC) development. However, studies demonstrating the role of GM in CRC are limited to metagenomic analyses. These studies lack direct evidence proving that the candidate strains are involved in CRC, and isolated probiotics for bacteriotherapy. Therefore, to identify novel GM with anti-CRC activity, we previously isolated gut bacteria from the feces of healthy individuals, screened the isolated GM's anti-CRC activity, and discovered that cell-free supernatants of GM isolates demonstrated antiproliferative activity against CRC cells. Here, our study identified one of them as Eubacterium callanderi and chose it for further study because the genus Eubacterium has been suggested to contribute to various aspects of gut health; however, the functions are unknown. First, we confirmed that E. callanderi cell-free supernatant (EcCFS) exerted antiproliferative activity-by inducing apoptosis and cell cycle arrest-that was dose-dependent and specific to cancer cell lines. Next, we discovered that EcCFS active molecules were heat stable and protease insensitive. High-performance liquid chromatography analysis revealed that EcCFS contained high butyrate concentrations possessing anticancer activity. Additionally, gas chromatography-mass spectrometry analysis of the aqueous phase of ethyl acetate-extracted EcCFS and an antiproliferation assay of the aqueous phase and 4-aminobutanoic acid (GABA) suggested that GABA is a possible anti-CRC agent. Finally, in the CT26 allograft mouse model, E. callanderi oral administration and EcCFS peri-tumoral injection inhibited tumor growth in vivo. Therefore, our study reveals that E. callanderi has an anti-CRC effect and suggests that it may be a potential candidate for developing probiotics to control CRC. IMPORTANCE The gut microbiota has been reported to be involved in colorectal cancer, as suggested by metagenomic analysis. However, metagenomic analysis has limitations, such as bias in the analysis and the absence of bacterial resources for follow-up studies. Therefore, we attempted to discover gut microorganisms that are related to colorectal cancer using the culturomics method. In this study, we discovered that Eubacterium callanderi possesses anti-colorectal cancer activity in vitro and in vivo, suggesting that E. callanderi could be used in bacteriotherapy for colorectal cancer treatment.

Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program.

The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI's Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits.

Nocardioides panacis sp. nov., isolated from soil of a ginseng field.

A bacterial strain designated as G188T was isolated from ginseng field soil in the Republic of Korea. Phylogenetic analysis of 16S rRNA gene sequences showed that strain G188T formed a distinct lineage within the genus Nocardioides, family Nocardioidaceae, order Propionibacteriales. Sequence similarity revealed that strain G188T was most closely related to Nocardioides iriomotensis IR27-S3T (97.7 % 16S rRNA similarity). The genome size of strain G188T was 4 901 775 bp, and the genomic DNA G+C content was 72.3 mol%. The average nucleotide identity and DNA-DNA hybridization values with other Nocardioides species were less than 75.6 and 20.1 %, respectively. The main fatty acids of strain G188T were C17 : 0, C17 : 1 ω8c and iso-C16 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylinositol, and the major respiratory quinone was menaquinone 8, supporting that strain G188T was affiliated with the genus Nocardioides. Based on biochemical, chemotaxonomic and phylogenetic analyses, the novel species Nocardioides panacis G188T (KACC 21695T=LMG 31733T) is proposed.

Hanamia caeni gen. nov., sp. nov., a Member of the Family Chitinophagaceae Isolated from Activated Sludge in Korea.

A novel Gram-stain-negative, aerobic, yellowish-pigmented, non-motile, rod-shaped bacterial strain, designated strain BO-59T, was isolated from the activated sludge of a wastewater treatment plant in Hanam City, South Korea. Phylogenetic study based on the 16S rRNA gene sequence positioned BO-59T in a distinct lineage in the family Chitinophagaceae, sharing less than 92.8% sequence similarity with members of the closely related genera Ferruginibacter, Flavitalea, Pseudoflavitalea, Flavisolibacter, Niastella, and Terrimonas. Phylogenomic- and genomic relatedness analyses revealed that strain BO-59T is clearly distinguished from other genera in the family Chitinophagaceae by average nucleotide identity < 66.9%) and the genome-to-genome distance (< 29.5%) values. The strain BO-59T contained MK-7 as the predominant quinone, and iso-C15:0, iso-C17:0 3OH, and iso-C15:1 G as major fatty acids (> 10%). The DNA G + C content was 39.1 mol% based on genome sequence analysis. The polar lipids of strain BO-59T were phosphatidylethanolamine, an unidentified aminophospholipid and three unidentified polar lipids. 16S rRNA gene sequence similarity, physiological, and biochemical characteristics indicated that strain BO-59T represents a novel species of a new genus, for which the name Hanamia caeni gen. nov., sp. nov. is proposed. The type strain is BO-59T (= KACC 19646T = LMG 30865 T).

Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples. We prioritize 32 genes in array-based genome-wide association study (GWAS) loci based on aggregations of rare coding variants; three (EVI5, SH2B3, and PLIN1) had no prior association of rare coding variants with lipid levels. Most of our associated genes showed evidence of association among multiple ancestries. Finally, we observed an enrichment of gene-based associations for low-density lipoprotein cholesterol drug target genes and for genes closest to GWAS index single-nucleotide polymorphisms (SNPs). Our results demonstrate that gene-based associations can be beneficial for drug target development and provide evidence that the gene closest to the array-based GWAS index SNP is often the functional gene for blood lipid levels.

Cell-Free Supernatant of Odoribacter splanchnicus Isolated From Human Feces Exhibits Anti-colorectal Cancer Activity.

The gut microbiota (GM) has been shown to be closely associated with the development of colorectal cancer (CRC). However, the involvement of GM is CRC has mainly been demonstrated by metagenomic profiling studies showing the compositional difference between the GM of healthy individuals and that of CRC patients and not by directly studying isolated gut microbes. Thus, to discover novel gut microbes involved in CRC, we isolated the GM from the feces of healthy individuals and evaluated its anti-CRC activity in vitro and in vivo. After GM isolation, cell-free supernatants (CFSs) were prepared from the isolated gut microorganisms to efficiently screen a large amount of the GM for anti-proliferative ability in vitro. Our results showed that the CFSs of 21 GM isolates had anti-proliferative activity against human colon cancer HCT 116 cells. Of these 21 GM isolates, GM07 was chosen for additional study because it had the highest anti-cancer activity against mouse colon cancer CT 26 cells in vitro and was further evaluated in a CT 26 allograft mouse model in vivo. GM07 was identified as Odoribacter splanchnicus through phylogenetic analysis based on 16S rRNA gene sequencing. Further investigation determined that the CFS of O. splanchnicus (OsCFS) induced anti-proliferative activity via apoptosis, but not cell cycle arrest. Moreover, GC/MS analysis suggested that the putative active molecule in OsCFS is malic acid. Finally, in the CRC mouse model, peri-tumoral injection of OsCFS significantly decreased CRC formation, compared to the control group. Altogether, these findings will provide valuable information for the discovery of potential probiotic candidates that inhibit CRC.

Hypertriglyceridemia Is Associated with More Severe Histological Glomerulosclerosis in IgA Nephropathy.

IgA nephropathy (IgAN) is a globally well-known primary glomerular nephropathy. Hypertriglyceridemia (HTG) is one factor contributing to atherosclerosis and is a common complication of renal failure. HTG is a significant risk factor for decreased renal function in patients with IgAN. We evaluated the association of HTG with the histopathological features of IgAN patients. A total of 480 patients diagnosed with IgAN via kidney biopsy from eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea were included in the final cohort. Pathological features were evaluated by eight expert pathologists with hospital consensus. HTG was defined as a serum triglyceride (TG) level of ≥150 mg/dL. In the study population analysis, the HTG group was older, with more males; higher body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) and spot urine protein ratio; and lower estimated glomerular filtration rate (eGFR). In the lipid profile analysis, eGFR was negatively correlated with TGs/ high-density lipoprotein cholesterol (HDL) and triglyceride-glucose index (TyG). Proteinuria positively correlated with TGs/HDL, non-HDL/HDL, LDL/HDL, TyG, TGs and LDL. The percentages of global sclerosis (GS), segmental sclerosis (SS) and capsular adhesion (CA), and the scores for mesangial matrix expansion (MME) and mesangial cell proliferation (MCP), were more elevated in the HTG group compared to the normal TG group. Multivariable linear regression analysis showed that the percentages of global sclerosis, segmental sclerosis and capsular adhesion, as well as the scores for mesangial matrix expansion and mesangial cell proliferation, were positively associated with TG level. In binary logistic regression, the HTG group showed a higher risk for global sclerosis and segmental sclerosis. In conclusion, HTG is a significant risk factor for glomerulosclerosis in IgAN.

Analyzing Genetic Differences Between Sporadic Primary and Secondary/Tertiary Hyperparathyroidism by Targeted Next-Generation Panel Sequencing.

Secondary hyperparathyroidism (SHPT) is characterized by excessive serum parathyroid hormone levels in response to decreasing kidney function, and tertiary hyperparathyroidism (THPT) is often the result of a long-standing SHPT. To date, several genes have been associated with the pathogenesis of primary hyperparathyroidism (PHPT). However, the molecular genetic mechanisms of uremic hyperparathyroidism (HPT) remain uncharacterized. To elucidate the differences in genetic alterations between PHPT and SHPT/THPT, the targeted next-generation sequencing of genes associated with HPT was performed using DNA extracted from parathyroid tissues. As a result, 26 variants in 19 PHPT or SHPT/THPT appeared as candidate pathogenic mutations, which corresponded to 9 (35%) nonsense, 8 (31%) frameshift, 6 (23%) missense, and 3 (11%) splice site mutations. The MEN1 (23%, 6/26), ASXL3 (15%, 4/26), EZH2 (12%, 3/26), and MTOR (8%, 2/26) genes were frequently mutated. Sixteen of 25 patients with PHPT (64%) had one or more mutations, whereas 3 (21%) of 21 patients with SHPT/THPT had only 1 mutation (p = 0.001). Sixteen of 28 patients (57%) with parathyroid adenoma (PA) had one or more mutations, whereas 3 of 18 patients (17%) with parathyroid hyperplasia (PH) had just one mutation (p = 0.003). Known driver mutations associated with parathyroid tumorigenesis such as CCND1/PRAD1, CDC73/HRPT2, and MEN1 were identified only in PA (44%, 7/16 with mutations). Our results suggest that molecular genetic abnormalities in SHPT/THPT are distinct from those in PHPT. These findings may help in analyzing the molecular pathogenesis underlying uremic HPT development.

The Serum Uric Acid Level Is Related to the More Severe Renal Histopathology of Female IgA Nephropathy Patients.

Hyperuricemia is a significant risk factor for cardiovascular morbidity and chronic kidney disease progression. IgA nephropathy (IgAN) is a well-known primary glomerular nephropathy. Hyperuricemia is associated with a poor prognosis in IgAN patients. We evaluated the association of hyperuricemia with the histopathological severity of IgAN in male and female patients; 658 patients diagnosed with IgAN via kidney biopsy were initially included. Baseline patient data were collected by eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea. Pathological features were independently evaluated by eight expert pathologists working in the hospitals, and the consensus was reached. Of the initial 658 patients, 517 were finally included (253 males and 264 females). Hyperuricemia was defined as a serum uric acid (UA) level >7.0 mg/dL for males and >5.6 mg/dL for females; 108 (42.7%) males and 95 (35.9%) females exhibited hyperuricemia. Compared to the patients with normal UA levels, the global glomerulosclerosis, segmental sclerosis, mesangial matrix expansion (MME), endocapillary proliferation (ECP), interstitial fibrosis (IF), and tubular atrophy (TA) scores were higher in hyperuricemic males and females. In multivariable linear regression, the serum UA level correlated significantly with the MME, ECP, IF, and TA scores of female IgAN patients only.

An advanced RFID-based system to localize gastric and colon cancers during laparoscopic surgery.

BACKGROUND: We aimed to improve the tumor localization system using radiofrequency identification (RFID) technology used during laparoscopic surgery for gastric and colorectal cancer. To this end, we developed a detection algorithm and designed improvement for the RFID clip. METHODS: To evaluate the proposed system, a swine-based animal study was conducted, followed by experiments on porcine stomachs and colons using the EASIE-R simulator. The success rates of endoscopic clipping, detection time, and detection accuracy, which is the distance between the detection point and RFID tag, were measured. RESULTS: Results of the in vivo swine animal study showed success in all three clippings and detections of the RFID clips. Results of the 60 RFID endoclip attempts using the EASIE-R simulator showed a total clipping success rate of 85.0% (n = 51/60; stomach, 83.3%, n = 25/30; colon, 86.7%, n = 26/30). The median detection times were 29.2 s for the stomach and 25.5 s for the colon. The median detection accuracy was 4.0 mm for the stomach and 4.5 mm for the colon. CONCLUSIONS: We confirmed that the proposed RFID-based system showed improvements over the system of a previous study. This RFID-based system is effective at localizing gastric and colorectal tumors.

Nocardioides convexus sp. nov. and Nocardioides anomalus sp. nov., isolated from soil and mineral water.

Two bacterial strains designated as W3-2-3T and HKS04T were isolated from mineral water and a soil sample, respectively, in the Republic of Korea. The 16S rRNA genes of the two strains shared a sequence similarity of 93.5 %. Phylogenetic analysis based on 16S rRNA gene sequences showed that strains W3-2-3T and HKS04T formed a distinct lineage within the genus Nocardioides of the family Nocardioidaceae (order Propionibacteriales). The closely related species of strain W3-2-3T were Nocardioides albidus (98.9 %), Nocardioides caeni (98.8 %), Nocardioides kongjuensis (98.6 %), Nocardioides aromaticivorans (98.5 %), Nocardioides nitrophenolicus (98.4 %), Nocardioides flava (98.2 %) and Nocardioides ginsengisoli (98.1 %). The closest species of strain HKS04T was Nocardioides halotolerans (98.7 %). The genome sizes of strains W3-2-3T and HKS04T were 4741198 and 5 120341 bp, respectively. The genomic DNA G+C contents of strains W3-2-3T and HKS04T were 73.3 and 72.1 mol%, respectively. The main fatty acids of strain W3-2-3T were C17:1 ω6c and iso-C16:0 and those of strain HKS04T were iso-C16:0 and iso-C16:0 H. The main polar lipids of both strains were diphosphatidylglycerol and phosphatidylglycerol and the predominant respiratory quinone was MK-8(H4), supporting the affiliation of these strains with the genus Nocardioides. Based on the results of biochemical, chemotaxonomic and phylogenetic analyses, two novel species, Nocardioides convexus W3-2-3T (KACC 21211T=LMG 31251T) and Nocardioides anomalus HKS04T (KACC 18879T=LMG 31249T), are proposed.

The Impact of Obesity on the Severity of Clinicopathologic Parameters in Patients with IgA Nephropathy.

Several studies reported the effect of obesity on the progression of IgA nephropathy (IgAN). However, the impact of obesity on the clinicopathologic presentation of IgAN remains uncertain. This is a retrospective cross-sectional study from eight university hospitals in South Korea. Patients were categorized into three groups using the Asia-Pacific obesity classification based on body mass index (BMI). Clinical and histopathologic data at the time of renal biopsy were analyzed. Among 537 patients with IgAN, the obese group was more hypertensive and had lower estimated glomerular filtration rate and more proteinuria than other groups. The histologic scores for mesangial matrix expansion (MME), interstitial fibrosis, tubular atrophy, and mesangial C3 deposition differed significantly between the three groups. Among these histopathologic parameters, BMI was independently positively associated with MME score on multivariable linear regression analysis (p = 0.028). Using multivariable logistic regression analysis, the obese group was independently associated with higher MME scores compared to the normal weight/overweight group (p = 0.020). However, BMI was not independently associated with estimated glomerular filtration rate or proteinuria on multivariable analysis. Obesity was independently associated with severe MME in patients with IgAN. Obesity may play an important pathogenetic role in mesangial lesions seen in IgAN.

Effects of transcranial direct current stimulation using miniaturized devices vs sertraline for depression in Korea: A 6 week, multicenter, randomized, double blind, active-controlled study.

We compared the efficacy and safety of transcranial direct current stimulation (tDCS) vs. Sertraline in the treatment of Major Depressive Disorder (MDD) in South Korean participants. This was a multi-center, double blind, active controlled study with non-inferiority testing. Patients were randomly assigned to receive tDCS (n = 45) or Sertraline (n = 47). tDCS was administered in 30-min, 2 mA prefrontal stimulation sessions for 10 consecutive weekdays, followed by 2 treatments at 4 and 6 weeks. Sertraline was administered at a dose of 50 mg per day for 6 weeks. The primary outcome measure was a change in the Montgomery-Asberg Depression Rating Scale (MADRS) score at six weeks. Mean MADRS scores decreased by 14.58 ± 8.51 points in the tDCS group and 12.32 ± 8.56 points in the Sertraline group. There was no significant main effect of group (p = 0.5877) or time by group interaction across weeks 0, 3, and 6 (p = 0.1539). Noninferiority of tDCS compared with Sertraline was not demonstrated. The mean difference between the Sertraline and tDCS group was -2.258 (95% confidence interval [CI], -5.795 to 1.27811), and the lower boundary of the CI was lower than the prespecified noninferiority margin of -3.56. There were no significant group differences in the rate of adverse events. In the present study, the noninferiority of tDCS to Sertraline for the treatment of depression was not found in this Korean population.

Allelic Heterogeneity at the CRP Locus Identified by Whole-Genome Sequencing in Multi-ancestry Cohorts.

Whole-genome sequencing (WGS) can improve assessment of low-frequency and rare variants, particularly in non-European populations that have been underrepresented in existing genomic studies. The genetic determinants of C-reactive protein (CRP), a biomarker of chronic inflammation, have been extensively studied, with existing genome-wide association studies (GWASs) conducted in >200,000 individuals of European ancestry. In order to discover novel loci associated with CRP levels, we examined a multi-ancestry population (n = 23,279) with WGS (∼38× coverage) from the Trans-Omics for Precision Medicine (TOPMed) program. We found evidence for eight distinct associations at the CRP locus, including two variants that have not been identified previously (rs11265259 and rs181704186), both of which are non-coding and more common in individuals of African ancestry (∼10% and ∼1% minor allele frequency, respectively, and rare or monomorphic in 1000 Genomes populations of East Asian, South Asian, and European ancestry). We show that the minor (G) allele of rs181704186 is associated with lower CRP levels and decreased transcriptional activity and protein binding in vitro, providing a plausible molecular mechanism for this African ancestry-specific signal. The individuals homozygous for rs181704186-G have a mean CRP level of 0.23 mg/L, in contrast to individuals heterozygous for rs181704186 with mean CRP of 2.97 mg/L and major allele homozygotes with mean CRP of 4.11 mg/L. This study demonstrates the utility of WGS in multi-ethnic populations to drive discovery of complex trait associations of large effect and to identify functional alleles in noncoding regulatory regions.

Effect of drug compliance on health care costs in newly-diagnosed dementia: Analysis of nationwide population-based data.

BACKGROUND: The cost-effectiveness of both cholinesterase inhibitors and memantine by delaying nursing home placement has been supported by numerous studies. The importance of sustained pharmacological treatment in dementia has been relatively less recognized by public health policies compared to early diagnosis. We investigated the effect of the drug (donepezil, rivastigmine, galantamine, and memantine) compliance on the health care costs in newly-diagnosed dementia. METHODS: National Health Insurance Service (NHIS) database which covers the entire population of South Korea was used for analysis. Health care expenditure of patients newly-diagnosed with dementia in between 2012 and 2014 was investigated for 3-5 years. For drug compliance, we used Medication Possession Ratio (MPR) that indicates the percentage of time a patient has access to medication. Multivariate linear regression analysis including generalized estimated equation and gamma distribution was used for statistical analysis. RESULTS: We identified 252,594 patients who were both prescribed with cognitive enhancers and newly diagnosed with dementia. When initial MPR increased 20%, total health care costs decreased 8.4% (RR = 0.916, 95%; CI 0.914 to 0.916). Same relationship was shown with medical costs related to dementia, admission to a general hospital, and emergency room visits. When MPR increased 20% compared to the previous year, the total health care costs, admission to a general hospital, emergency room visits, and admission to a nursing hospital decreased. CONCLUSIONS: This population-based retrospective cohort study provides evidence that patients newly-diagnosed with dementia who showed higher initial drug compliance or maintained antidementia drugs (Cholinesterase inhibitors and memantine) would benefit in total health-care costs.

Associated risk factors for psychological distress in patients with gastric epithelial neoplasm undergoing endoscopic submucosal dissection.

This study aimed to evaluate the psychological distress and associated risk factors for distress among patients with gastric epithelial neoplasm undergoing endoscopic submucosal dissection (ESD).A total of 91 patients treated with ESD for gastric epithelial neoplasm between May 2015 and June 2016 were prospectively enrolled. Sociodemographic factors, psychological distress, anxiety, depression, stress, and associated risk factors for psychological distress were evaluated the day before ESD.Twenty-six (28.6%) patients were identified as patients with psychological distress. The psychological distress group had a higher female ratio and more depression and anxiety symptoms than the non-distress group. Distress was also related to stress level. A multivariate analysis showed that unmarried status (odds ratio [OR], 4.94; 95% confidence interval [CI], 1.13-21.56, P = .034), anxiety (OR, 1.24; 95% CI, 1.12-1.39, P <.001), and stress (OR, 1.06; 95% CI, 1.01-1.12, P = .011) were associated with psychological distress.An unmarried status and a high level of anxiety and stress were associated with more psychological distress in patients undergoing gastric ESD. It could be helpful to screen and proactively monitor patients with such conditions before performing gastric ESD.