Purpose: This study aimed to evaluate the association between peripapillary retinal nerve fiber layer thickness (pRNFLT) and health-related quality of life in Korean adults. Methods: A total of 4,614 adults aged 40 years or older from the 2019 Korea National Health and Nutrition Examination Survey were included in this study. Average pRNFLT was categorized into the thicker eye, thinner eye, and the mean value of both eyes. Complex sample ordinal logistic regression was performed for the five items of the EuroQol 5-Dimension (EQ-5D) and the eight items of the Health-related Quality of Life Instrument with 8 Items (HINT-8), while complex sample linear regression was used for the EQ-5D index. Results: In multivariable analysis adjusted for age and sex, a decrease in thinner eye-pRNFLT was significantly associated with ‘usual activities’ and ‘anxiety/depression’ in the EQ-5D. Furthermore, a decrease in both thinner eye-pRNFLT and mean pRNFLT were significantly associated with a lower EQ-5D index and the ‘vitality’ in the HINT-8. Conclusions Decreased thinner eye-pRNFLT and mean pRNFLT were independently associated with certain declines in health-related quality of life among Korean adults. These findings suggest that structural changes in the optic nerve, which connects the eye and the brain, may be linked to overall quality of life.

Background: and Purpose Whole-exome sequencing (WES) is a valuable tool for identifying causative mutations in adult moyamoya disease (MMD), thereby advancing our understanding of the genetic mechanisms underlying this condition. Here, we conducted the first WESbased association study aimed at identifying genetic modifiers implicated in MMD. Methods: This WES study involved 160 patients with MMD and 189 controls from a multicenter hospital-based biobank, and evaluated combined annotation-dependent depletion (CADD) scores. Mutant-allele frequencies were compared in 369,121 individuals derived from the UK Biobank (UKB) WES. Mutant-allele risk scores (MARSs) were created based on WESidentified mutations. Gene-based association analyses and pooled analyses in East-Asian populations were further performed. Results: Fourteen mutations reached the genome-wide significance criterion (p<5×10-8 ), among which the p.R4810K mutation in the ring finger protein 213 gene (RNF213) showed the strongest significance (odds ratio=117.4, p=8.54×10-24 ). Notably, two mutations—p.G576S (alpha-glucosidase [GAA]) and p.D54N (charged multivesicular body protein 6 [CHMP6])— exhibited high CADD scores of 32 and 25, respectively, whereas the RNF213 p.R4810K mutation demonstrated a moderate deleteriousness score of 10.63. Fourteen mutations exhibited significant differences in allele frequencies between patients and UKB controlled data (p<1×10-8 ).The MARS9 model (incorporating nine missense mutations) showed better predictability for MMD (90.89%). The analysis of gene-based associations revealed four candidate genes: GAA, RNF213, CHMP6, and CARD14 (p=5×10-19 to 4×10-7 ). The subsequent pooled analyses validated four mutations in East Asian populations: p.V1195M, p.D1331G, p.S2334N, and p.R4810K (p<3×10-8 ). Conclusions This pioneering study has corroborated the significance of p.R4810K and identified several causative mutations predisposing patients to MMD, which helps to improve the understanding of its polygenetic nature.

Purpose: We examined the association between age-related macular degeneration (AMD) and arthritis. Methods: Using data from the Korea National Health and Nutrition Examination Survey for 2017 and 2018, we conducted a complex sample analysis of 6,993 individuals with recorded information on AMD, as well as the diagnosis and treatment of osteoarthritis (OA) and rheumatoid arthritis (RA). We compared the diagnosis and treatment of arthritis between the AMD and control groups using logistic regression analysis, with a specific focus on the treatment among patients with arthritis. Results: In the AMD group (n = 1,118) and the control group (n = 5,875), univariate logistic regression analysis showed substantial differences in the diagnosis and treatment of OA and RA. However, after adjusting for age, alcohol consumption, diabetes mellitus, and hypertension in multivariate logistic regression analysis, these differences were no longer substantial. Among patients with OA (n = 246 in the AMD group and n = 821 in the control group), there was a significant association between AMD and OA treatments (odds ratio 1.511, 95% confidence interval 1.051-2.172). Conclusions Patients diagnosed with and treated for OA had a higher likelihood of concurrent AMD than those who did not receive treatment. Therefore, ophthalmic examinations and closer monitoring are recommended for these patients.

Objective: : The association between boule (BOLL) and endothelin receptor type A (EDNRA) loci and intracranial aneurysm (IA) formation has been reported via genome-wide association studies. We sought to identify genome-wide interactions involving BOLL and EDNRA loci for IA in a Korean adult cohort. Methods: : Genome-wide pairwise interaction analyses of BOLL and EDNRA involving 250 patients with IA and 296 controls were performed using the additive effect model after adjusting for confounding factors. Results: : Among 512575 single-nucleotide polymorphisms (SNPs), 23 and 11 common SNPs suggested a genome-wide interaction threshold (p<1.25×10-8) involving rs700651 (BOLL) and rs6841581 (EDNRA). Rather than singe SNP effect of BOLL or EDNRA on IA development, they showed a synergistic effect on IA formation via multifactorial pair-wise interactions. The rs1105980 of PTCH1 gene showed the most significant interaction with rs700651 (natural log-transformed odds ratio [lnOR], 1.53; p=6.41×10-11). The rs74585958 of RYK gene interacted strongly with rs6841581 (lnOR, -19.91; p=1.64×10-9). Although, there was no direct interaction between BOLL and EDNRA variants, two EDNRA-interacting gene variants of TNIK (rs11925024 and rs1231) and FTO (rs9302654), and one BOLL-interacting METTL4 gene variant (rs549315) exhibited marginal interaction with BOLL gene. Conclusion : BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.

Objective: : We performed an expanded multi-ethnic meta-analysis to identify associations between inflammation-related loci with intracranial aneurysm (IA) susceptibility. This meta-analysis possesses increased statistical power as it is based on the most data ever evaluated. Methods: : We searched and reviewed relevant literature through electronic search engines up to August 2022. Overall estimates were calculated under the fixed- or random-effect models using pooled odds ratio (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed according to ethnicity. Results: : Our meta-analysis enrolled 15 studies and involved 3070 patients and 5528 controls including European, Asian, Hispanic, and mixed ethnic populations. Of 17 inflammation-related variants, the rs1800796 locus (interleukin [IL]-6) showed the most significant genome-wide association with IA in East-Asian populations, including 1276 IA patients and 1322 controls (OR, 0.65; 95% CI, 0.56–0.75; p=3.24×10-9) under a fixed-effect model. However, this association was not observed in the European population (OR, 1.09; 95% CI, 0.80–1.47; p=0.5929). Three other variants, rs16944 (IL-1β), rs2195940 (IL-12B), and rs1800629 (tumor necrosis factor-α) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01Conclusion : Our updated meta-analysis with increased statistical power highlights that rs1800796 which maps on the IL-6 gene is associated with IA, and in particular confers a protective effect against occurrence of IA in the East-Asian population.

Objective: : To evaluate the interactions among differentially expressed autophagy and mitophagy markers in subarachnoid hemorrhage (SAH) patients with delayed cerebral ischemia (DCI). Methods: : The expression data of autophagy and mitophagy-related makers in the cerebrospinal fluid (CSF) cells was analyzed by real-time reverse transcription-polymerase chain reaction and Western blotting. The markers included death-associated protein kinase (DAPK)-1, BCL2 interacting protein 3 like (BNIP3L), Bcl-1 antagonist X, phosphatase and tensin homolog-induced kinase (PINK), Unc-51 like autophagy activating kinase 1, nuclear dot protein 52, and p62. In silico functional analyses including gene ontology enrichment and the protein-protein interaction network were performed. Results: : A total of 56 SAH patients were included and 22 (38.6%) of them experienced DCI. The DCI patients had significantly increased mRNA levels of DAPK1, BNIP3L, and PINK1, and increased expression of BECN1 compared to the non-DCI patients. The most enriched biological process was the positive regulation of autophagy, followed by the response to mitochondrial depolarization. The molecular functions ubiquitin-like protein ligase binding and ubiquitin-protein ligase binding were enriched. In the cluster of cellular components, Lewy bodies and the phagophore assembly site were enriched. BECN1 was the most connected gene among the differentially expressed markers related to autophagy and mitophagy in the development of DCI. Conclusion : Our study may provide novel insight into mitochondrial dysfunction in DCI pathogenesis.

PURPOSE: This study aimed to evaluate the clinical and radiologic findings suggestive of spontaneous intestinal perforation (SIP) in extremely-low-birth-weight infants (ELBWIs) with persistent gasless abdomen, and to investigate the usefulness of abdominal ultrasonography for the diagnosis of SIP. METHODS: In total, 22 infants with birth weights less than 1,000 g who showed persistent gasless abdomen on simple abdominal radiography were included. Perinatal, neonatal, and perioperative clinical findings were retrospectively reviewed, and the risk factors for intestinal perforation were evaluated. Abdominal sonographic findings suggestive of intestinal perforation were also identified, and postoperative short-term outcomes were evaluated. RESULTS: In total, eight of the 22 infants (36.4%) with gasless abdomen had SIP. The number of infants with patent ductus arteriosus who were treated with intravenous ibuprofen or indomethacin was significantly higher in the SIP group than in the non-SIP group (P<0.05). Greenish or red gastric residue, abdominal distension, or decreased bowel sound were more frequent in infants with SIP (P<0.05), in addition to gray or bluish discoloration of abdomen, suggestive of meconium peritonitis (P<0.05). Pneumoperitoneum on simple abdominal radiography was found in only one of the eight infants (12.5%) with SIP. Intramural echogenicity and echogenic extramural material on abdominal ultrasonography were exclusively observed in infants with SIP. Four infants (50%) with SIP died after surgical intervention. CONCLUSION: Intestinal perforation may occur in ELBWIs with gasless abdomen. As intramural echogenicity and extraluminal echogenic materials on abdominal ultrasonography are indicative of SIP, this technique could be useful for diagnosing SIP.
Abdomen ; Birth Weight ; Diagnosis ; Ductus Arteriosus, Patent ; Humans ; Ibuprofen ; Indomethacin ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Low Birth Weight ; Infant, Newborn ; Intestinal Perforation ; Meconium ; Peritonitis ; Pneumoperitoneum ; Radiography, Abdominal ; Retrospective Studies ; Risk Factors ; Ultrasonography

With the advances in hepatocellular carcinoma (HCC) treatment, the lung metastasis of HCC is becoming increasingly important. In treating the lung metastasis of HCC, a multidisciplinary approach can lead to better results than systemic chemotherapy alone. Here, we report on a patient who presented with pulmonary masses, while the HCC was being controlled in the abdominal cavity. The presence of nontuberculous mycobacteria was identified during the diagnosis of the pulmonary masses. The pulmonary metastases of HCC were treated with a combination of angiotherapy, radiation therapy, and radiofrequency ablation. The patient showed a satisfactory progress with this multidisciplinary localized treatment. We report the clinical progress and review the recent literature regarding the treatment of pulmonary metastasis without intrahepatic HCC herein.
Abdominal Cavity ; Carcinoma, Hepatocellular ; Catheter Ablation ; Diagnosis ; Drug Therapy ; Humans ; Lung ; Neoplasm Metastasis ; Nontuberculous Mycobacteria

BACKGROUND: Soluble epoxide hydrolase (sEH) expressed by endothelial cells catalyzes the metabolism of epoxyeicosatrienoic acids (EETs), which are vasoactive agents. METHODS: We used a unilateral ureteral obstruction mouse model of kidney fibrosis to determine whether inhibition of sEH activity reduces fibrosis, the final common pathway for chronic kidney disease. RESULTS: sEH activity was inhibited by continuous release of the inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA) for 1 or 2 weeks. Treatment with AUDA significantly ameliorated tubulointerstitial fibrosis by reducing fibroblast mobilization and enhancing endothelial cell activity. In an in vitro model of endothelial-to-mesenchymal transition (EndMT) using human vascular endothelial cells (HUVECs), AUDA prevented the morphologic changes associated with EndMT and reduced expression of fibroblast-specific protein 1. Furthermore, HUVECs activated by AUDA prevented the epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells in a co-culture system. CONCLUSION: Our findings suggest that regulation of sEH is a potential target for therapies aimed at delaying the progression of kidney fibrosis by inhibiting EndMT and EMT.
Animals ; Coculture Techniques ; Endothelial Cells* ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Fibroblasts ; Fibrosis* ; Humans ; In Vitro Techniques ; Kidney* ; Metabolism ; Mice ; Renal Insufficiency, Chronic ; Ureteral Obstruction

BACKGROUND: Soluble epoxide hydrolase (sEH) expressed by endothelial cells catalyzes the metabolism of epoxyeicosatrienoic acids (EETs), which are vasoactive agents. METHODS: We used a unilateral ureteral obstruction mouse model of kidney fibrosis to determine whether inhibition of sEH activity reduces fibrosis, the final common pathway for chronic kidney disease. RESULTS: sEH activity was inhibited by continuous release of the inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA) for 1 or 2 weeks. Treatment with AUDA significantly ameliorated tubulointerstitial fibrosis by reducing fibroblast mobilization and enhancing endothelial cell activity. In an in vitro model of endothelial-to-mesenchymal transition (EndMT) using human vascular endothelial cells (HUVECs), AUDA prevented the morphologic changes associated with EndMT and reduced expression of fibroblast-specific protein 1. Furthermore, HUVECs activated by AUDA prevented the epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells in a co-culture system. CONCLUSION: Our findings suggest that regulation of sEH is a potential target for therapies aimed at delaying the progression of kidney fibrosis by inhibiting EndMT and EMT.
Animals ; Coculture Techniques ; Endothelial Cells* ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Fibroblasts ; Fibrosis* ; Humans ; In Vitro Techniques ; Kidney* ; Metabolism ; Mice ; Renal Insufficiency, Chronic ; Ureteral Obstruction