Background/Aims: Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD. Methods: Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing. Results: Methylome and transcriptome analyses of liver biopsies revealed significant (p<0.05) hypermethylation and downregulation of C1R, C1S, C3, C6, C4BPA<, and SERPING1, as well as hypomethylation (p<0.0005) and upregulation (p<0.05) of C5AR1, C7, and CD59, in association with the histological severity of MASLD. Furthermore, DNA methylation and the relative expression of nine complement genes in a MASH diet mouse model aligned with human data. Conclusions Our research provides compelling evidence that epigenetic alterations in complement genes correlate with MASLD severity, offering valuable insights into the mechanisms driving MASLD progression, and suggests that inhibiting the function of certain complement proteins may be a promising strategy for managing MASLD.

Objective: : Stereoelectroencephalography (SEEG) is increasingly being recognized as an important invasive modality for presurgical evaluation of epilepsy. This study focuses on the clinical and technical considerations of SEEG investigations when using conventional frame-based stereotaxy, drawing on institutional experience and a comprehensive review of relevant literature. Methods: : This retrospective observational study encompassed the surgical implantation of 201 SEEG electrodes in 16 epilepsy patients using a frame-based stereotactic instrument at a single tertiary-level center. We provide detailed descriptions of the operative procedures and technical nuances for bilateral and multiple SEEG insertions, along with several illustrative cases. Additionally, we present a literature review on the technical aspects of the SEEG procedure, discussing its clinical implications and potential risks. Results: : Frame-based SEEG electrode placements were successfully performed through sagittal arc application, with the majority (81.2%) of cases being bilateral and involving up to 18 electrodes in a single operation. The median skin-to-skin operation time was 162 minutes (interquartile range [IQR], 145–200), with a median of 13 minutes (IQR, 12–15) per electrode placement for time efficiency. There were two occurrences (1.0%) of electrode misplacement and one instance (0.5%) of a postoperative complication, which manifested as a delayed intraparenchymal hemorrhage. Following SEEG investigation, 11 patients proceeded with surgical intervention, resulting in favorable seizure outcomes for nine (81.8%) and complete remission for eight cases (72.7%). Conclusion : Conventional frame-based stereotactic techniques remain a reliable and effective option for bilateral and multiple SEEG electrode placements. While SEEG is a suitable approach for selected patients who are strong candidates for epilepsy surgery, it is important to remain vigilant concerning the potential risks of electrode misplacement and hemorrhagic complications.

Objective: To evaluate the diagnostic performance and image quality of 1.5-mm slice thickness MRI with deep learningbased image reconstruction (1.5-mm MRI + DLR) compared to routine 3-mm slice thickness MRI (routine MRI) and 1.5-mm slice thickness MRI without DLR (1.5-mm MRI without DLR) for evaluating temporal lobe epilepsy (TLE). Materials and Methods: This retrospective study included 117 MR image sets comprising 1.5-mm MRI + DLR, 1.5-mm MRI without DLR, and routine MRI from 117 consecutive patients (mean age, 41 years; 61 female; 34 patients with TLE and 83 without TLE). Two neuroradiologists evaluated the presence of hippocampal or temporal lobe lesions, volume loss, signal abnormalities, loss of internal structure of the hippocampus, and lesion conspicuity in the temporal lobe. Reference standards for TLE were independently constructed by neurologists using clinical and radiological findings. Subjective image quality, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were analyzed. Performance in diagnosing TLE, lesion findings, and image quality were compared among the three protocols. Results: The pooled sensitivity of 1.5-mm MRI + DLR (91.2%) for diagnosing TLE was higher than that of routine MRI (72.1%, P < 0.001). In the subgroup analysis, 1.5-mm MRI + DLR showed higher sensitivity for hippocampal lesions than routine MRI (92.7% vs. 75.0%, P = 0.001), with improved depiction of hippocampal T2 high signal intensity change (P = 0.016) and loss of internal structure (P < 0.001). However, the pooled specificity of 1.5-mm MRI + DLR (76.5%) was lower than that of routine MRI (89.2%, P = 0.004). Compared with 1.5-mm MRI without DLR, 1.5-mm MRI + DLR resulted in significantly improved pooled accuracy (91.2% vs. 73.1%, P = 0.010), image quality, SNR, and CNR (all, P < 0.001). Conclusion The use of 1.5-mm MRI + DLR enhanced the performance of MRI in diagnosing TLE, particularly in hippocampal evaluation, because of improved depiction of hippocampal abnormalities and enhanced image quality.

Background: and Purpose To identify sex differences in daytime sleepiness associated with apnea severity and periodic limb movements during sleep (PLMS) in subjects with obstructive sleep apnea (OSA). Methods: This study used the Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), and Sleep Hygiene Index (SHI) in logistic regression analyses with interaction terms. Severe OSA, excessive daytime sleepiness (EDS), and PLMS were defined as an apnea-hypopnea index of ≥30, an ESS score of ≥11, and a periodic limb movements index of >15, respectively. Results: The 1,624 subjects with OSA (males, 79.1%) comprised 45.3%, 38.2%, and 16.4% with severe OSA, EDS, and PLMS, respectively. Multiple logistic regression without interaction terms showed that sex, severe OSA, and PLMS were not significantly associated with EDS. However, significant interactions were noted between sex and severe OSA and PLMS in EDS in both crude and adjusted models (all p values<0.05). In the adjusted model, severe OSA was associated with EDS in males (p=0.009) but not in females. PLMS were more likely to be associated with EDS in females (p=0.013), whereas PLMS were less likely to be associated with EDS in males (p=0.041). The models were adjusted by the BDI score, SHI, and presence of medical comorbidities. Conclusions There are significant sex differences in subjective daytime sleepiness in subjects with severe OSA and PLMS. Severe OSA and PLMS may influence daytime sleepiness more in males and females, respectively.

Acanthamoeba keratitis (AK) is a rare infectious disease and accurate diagnosis has remained arduous as clinical manifestations of AK were similar to keratitis of viral, bacterial, or fungal origins. In this study, we described the production of a polyclonal peptide antibody against the adenylyl cyclase-associated protein (ACAP) of A. castellanii, and evaluated its differential diagnostic potential. Enzyme-linked immunosorbent assay revealed high titers of A. castellanii-specific IgG and IgA antibodies being present in low dilutions of immunized rabbit serum. Western blot analysis revealed that the ACAP antibody specifically interacted with A. castellanii, while not interacting with human corneal epithelial (HCE) cells and other causes of keratitis such as Fusarium solani, Pseudomonas aeruginosa, and Staphylococcus aureus. Immunocytochemistry (ICC) results confirmed the specific detection of trophozoites and cysts of A. castellanii co-cultured with HCE cells. The ACAP antibody also specifically interacted with the trophozoites and cysts of 5 other Acanthamoeba species. These results indicate that the ACAP antibody of A. castellanii can specifically detect multiple AK-causing members belonging to the genus Acanthamoeba and may be useful for differentially diagnosing Acanthamoeba infections.

OBJECTIVE: This study was conducted to demonstrate the temporal trends in perinatal outcomes of triplet pregnancies over the last two decades. METHODS: The medical records of patients with triplet pregnancies at two Korean tertiary-care hospitals from 1992 to 2012 were retrospectively reviewed in regard to maternal and neonatal outcomes. The study was divided into two periods for analysis: period I (1992–2001) and period II (2003–2012). RESULTS: Over a 21-year period, 65 women with triplet pregnancies and 185 neonates were analyzed. Period II, when compared with period I, was associated with improved maternal outcomes, characterized by a decreased incidence of preeclampsia (31.8% vs. 2.3%, P=0.002) and anemia (68.2% vs. 30.2%, P=0.003) during pregnancy. Regarding neonatal aspects, the composite morbidity of period II was significantly decreased compared with that of period I, as assessed with a generalized estimating equation for logistic regression (26.2% vs. 8.1%, P=0.03). Multivariable analysis revealed that the gestational age at delivery and the period were significantly associated with the composite neonatal morbidity (P<0.001 and 0.007, respectively). CONCLUSION: Improved neonatal morbidity was associated with a higher gestational age at delivery and with the more recent decade.
Anemia ; Female ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Logistic Models ; Medical Records ; Pre-Eclampsia ; Pregnancy ; Pregnancy Outcome ; Pregnancy, Triplet ; Premature Birth ; Retrospective Studies ; Triplets

OBJECTIVES.: To investigate the apnea-hypopnea index (AHI) according to the sleep stage in more detail after control of posture. METHODS.: Patients who underwent nocturnal polysomnography between December 2007 and July 2018 were retrospectively evaluated. Inclusion criteria were as follows: age >18 years, sleep efficacy >80%, and patients who underwent polysomnography only in the supine position (100% of the time). Patients were classified into different groups according to the methods: the first, rapid eye movement (REM)-dominant group (AHIREM/AHINREM >2), non-rapid eye movement (NREM)-dominant group (AHINREM/AHIREM >2), and non-dominant group; and the second, light sleep group (AHIN1N2>AHISWS) and slow wave sleep (SWS) group (AHISWS>AHIN1N2). RESULTS.: A total of 234 patients (mean age, 47.4±13.9 years) were included in the study. There were 108 patients (46.2%) in the REM-dominant group, 88 (37.6%) in the non-dominant group, and 38 (16.2%) in the NREM-dominant group. The AHI was significantly higher in the NREM-dominant group than in the REM-dominant group (32.9±22.9 events/hr vs. 18.3±9.5 events/hr, respectively). There were improvements in the AHI from stage 1 to SWS in NREM sleep with the highest level in REM sleep. A higher AHISWS than AHIN1N2 was found in 16 of 234 patients (6.8%); however, there were no significant predictors of these unexpected results except AHI. CONCLUSION.: Our results demonstrated the highest AHI during REM sleep stage in total participants after control of posture. However, there were 16.2% of patients showed NREM-dominant pattern (AHINREM/AHIREM >2) and 6.8% of patients showed higher AHISWS than AHIN1N2. Therefore, each group might have a different pathophysiology of obstructive sleep apnea (OSA), and we need to consider this point when we treat the patients with OSA.
Eye Movements ; Humans ; Polysomnography ; Posture ; Retrospective Studies ; Sleep Apnea, Obstructive ; Sleep Stages ; Sleep, REM ; Supine Position

BACKGROUND AND PURPOSE: To investigate whether appointing a full-time neurointensivist to manage a closed-type neurological intensive care unit (NRICU) improves the quality of critical care and patient outcomes. METHODS: This study included patients admitted to the NRICU at a university hospital in Seoul, Korea. Two time periods were defined according to the presence of a neurointensivist in the preexisting open-type NRICU: the before and after periods. Hospital medical records were queried and compared between these two time periods, as were the biannual satisfaction survey results for the families of patients. RESULTS: Of the 15,210 patients in the neurology department, 2,199 were admitted to the NRICU (n=995 and 1,204 during the before and after periods, respectively; p<0.001). The length of stay was shorter during the after than during the before period in both the NRICU (3 vs. 4 days; p<0.001) and the hospital overall (12.5 vs. 14.0 days; p<0.001). Neurological consultations (2,070 vs. 3,097; p<0.001) and intrahospital transfers from general intensive care units to the NRICU (21 vs. 40; p=0.111) increased from the before to after the period. The mean satisfaction scores of the families of the patients also increased, from 78.3 to 89.7. In a Cox proportional hazards model, appointing a neurointensivist did not result in a statistically significant change in 6-month mortality (hazard ratio, 0.82; 95% confidence interval, 0.652–1.031; p=0.089). CONCLUSIONS: Appointing a full-time neurointensivist to manage a closed-type NRICU had beneficial effects on quality indicators and patient outcomes.
Critical Care Outcomes ; Critical Care ; Humans ; Intensive Care Units ; Korea ; Length of Stay ; Medical Records ; Mortality ; Neurology ; Proportional Hazards Models ; Referral and Consultation ; Seoul

We validated the uniform case definition for differentiating tuberculous meningitis (TBM) from both viral meningitis (VM) and bacterial meningitis (BM) in adults from South Korea, a country with an intermediate TB-burden. ‘Probable’ TBM differentiated ‘definite’ TBM with a sensitivity of 81% and specificity of 98%. ‘Possible TBM’ criteria identified ‘definite’ TBM with a sensitivity of 100% and specificity of 60%. Despite the usefulness of the uniform case definition criteria, there was substantial overlaps among VM, BM, and ‘possible’ TBM, especially in severe cases of VM and indolent cases of BM.

Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis hrough GR acetylation in experimental CS.
Acetyl-CoA Carboxylase ; Acetylation ; Adrenocorticotropic Hormone ; Animals ; Cushing Syndrome* ; Dexamethasone ; Drinking Water ; Hep G2 Cells ; Histone Deacetylase Inhibitors ; Histone Deacetylases* ; Histones* ; Hydrocortisone ; Infusions, Subcutaneous ; Lipogenesis ; Liver ; Rats* ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; Response Elements ; Sterol Regulatory Element Binding Protein 1 ; Valproic Acid