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Abstract Background To compare the ocular features of highly myopic eyes with posterior staphyloma of wide macular type according to its morphological complexity. Methods In this cross-sectional study, wide macular posterior staphyloma (WMPS) was classified into the primary (Curtin type I) and the compound (Curtin types VI to X) forms based on the configuration within the staphyloma. The grades of myopic maculopathy and the thicknesses of choroid and sclera were compared between the primary and compound forms of WMPS. Results A total of 154 eyes (103 patients) with primary WMPS and 65 eyes (49 patients) with compound WMPS were included. Eyes with compound WMPS had worse visual acuity (P = 0.001) and greater axial length (P

BackgroundIdiopathic transverse myelitis (iTM) is defined as an inflammatory myelopathy of undetermined etiology, even after a comprehensive workup to identify other possible causes. Generally, the characteristics of recurrent iTM are not clearly defined. This study aimed to identify the clinical characteristics and predictive factors of recurrence in patients with iTM.MethodsWe retrospectively recruited patients with transverse myelitis (TM) who visited Chungnam National University Hospital between January 2011 and December 2021. We included patients who were followed up for at least 2 years and excluded those diagnosed with multiple sclerosis or neuromyelitis optica spectrum disorder (NMOSD) during the initial episode or follow-up period. Patients with iTM were categorized into two groups: monophasic idiopathic TM (mTM) and recurrent idiopathic TM (rTM). We compared the clinical characteristics and spinal magnetic resonance imaging findings between the two groups.ResultsIn total, 167 patients were reviewed, of whom 112 were excluded. Finally, we included 55 patients with iTM. In 55 patients, 11 (20.0%) and 44 (80%) were classified into the rTM and mTM groups, respectively. Male predominance was observed in the iTM, rTM, and mTM groups. The percentage of patients with low vitamin D levels was significantly higher in the rTM group (100.0%) compared with the mTM group (70%) (p = 0.049). In addition, longitudinally extensive transverse myelitis (LETM) was observed more frequently in the rTM group, in 8 of 11 (72.7%) patients, compared with 15 of 44 (34.1%) patients in the mTM group, with the difference being statistically significant (p = 0.020). In multivariate regression analysis, female sex, younger age at onset, low serum vitamin D level (20% of the patients with iTM experience recurrence, and LETM is the most significant risk factor for recurrence. In cases of recurrence, there is a favorable response to immunotherapy, and the prognosis is generally good. Although LETM may be the initial symptom of NMOSD, it may be manifestation of iTM, and in cases of idiopathic LETM, it is important to be mindful of the elevated risk of recurrence. Based on these results, idiopathic rTM has good clinical prognosis and response to immunosuppressive treatment.

Abstract This study investigates the impact of glycosylated hemoglobin (HbA1c) on the efficacy of intravitreal dexamethasone (DEX) implants in patients with diabetic macular edema (DME) over a 12-month period. We retrospectively reviewed 90 DME patients treated with DEX implants, categorizing them based on baseline HbA1c levels (≤ 7% and > 7%) and 12-month changes in HbA1c ("improved", "stable", "worsened"). At the 2-month mark, the mean central subfield thickness (CST) reduction in the HbA1c ≤ 7% group was − 147.22 ± 113.79 µm compared to -130.41 ± 124.50 µm in the > 7% group (p = 0.506). Notably, 12-month outcomes between these groups showed no significant difference. The "improved" HbA1c subgroup experienced a more pronounced CST reduction at 2 months (p = 0.042), with outcomes leveling off with other groups by 12 months. Conclusively, DEX implant outcomes in DME were not influenced by either baseline HbA1c levels or their changes over time. This suggests that local alterations in the inflammation milieu may have a potentially stronger impact on DME treatment outcomes, highlighting the importance of considering local factors in DME treatment.

Abstract As retinitis pigmentosa (RP) is chronic and progressive, the chronological sequence of microvascular changes is important for understanding its pathophysiology. We aimed to investigate retinal and choroidal microvascular changes according to the RP stages. The stages of RP were classified into three stages according to the integrity and width of the inner segment ellipsoid zone: early, ≥ 2500 μm; moderate,

BackgroundThis study investigated the impact of COVID-19 pandemic on the incidence and severity of myasthenia gravis (MG) using the National Health Insurance Service (NHIS) database in Korea.MethodsWe analyzed data from patients with MG in the NHIS registry from 2015 to 2021. MG was defined as (1) patients aged ≥18 years with the G70.0 code, and (2) patients who visited tertiary hospitals regarldless of department in Korea (outpatient clinics at least twice or hospitalization at least once), and (3) patients who were prescribed pyridostigmine as MG medications at least once. We designated pre-COVID-19 as 2019 and post-COVID-19 as 2021 and analyzed the MG incidence and prevalence in 2019 and 2021. We compared the clinical data of patients with MG between the two years. MG exacerbation was defined as the administration of intravenous immunoglobulin or plasma exchange. Analysis of COVID-19 cases was conducted using an integrated database from the Korea Disease Control and Prevention Agency and NHIS. Patients with MG were divided into two groups according to COVID-19 status to compare their clinical characteristics.ResultsA total of 6,888 and 7,439 MG cases were identified in 2019 and 2021, respectively. The standardized incidence was 1.56/100,000 in 2019, decreasing to 1.21/100,000 in 2021. Although the frequency of MG exacerbations was higher in 2019, there were no differences in the number and duration of hospitalizations, duration of ICU stays, hostalization expense, and mortality between 2019 and 2021. Patients with MG and COVID-19 had a higher frequency of MG exacerbations than patients without COVID-19, but there were no differences in the number and duration of hospitalizations, hospitalization expense, and mortality.ConclusionThis study was the first nationwide population-based epidemiological study of MG during COVID-19 pandemic in Korea. The incidence of MG decreased during COVID-19 pandemic, and the severity of MG was not affected by COVID-19.

Abstract Background To predict, using deep learning, the first recurrence in patients with neovascular age-related macular degeneration (nAMD) after three monthly loading injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF). Methods Optical coherence tomography (OCT) images were obtained at baseline and after the loading phase. The first recurrence was defined as the initial appearance of a new retinal hemorrhage or intra/subretinal fluid accumulation after the initial resolution of exudative changes after three loading injections. Standard U-Net architecture was used to identify the three retinal fluid compartments, which include pigment epithelial detachment, subretinal fluid, and intraretinal fluid. To predict the first recurrence of nAMD, classification learning was conducted to determine whether the first recurrence occurred within three months after the loading phase. The recurrence classification architecture was built using ResNet50. The model with retinal regions of interest of the entire region and fluid region on OCT at baseline and after the loading phase is presented. Results A total of 1,444 eyes of 1,302 patients were included. The mean duration until the first recurrence after the loading phase was 8.20 ± 15.56 months. The recurrence classification system revealed that the model with the fluid region of OCT after the loading phase provided the highest classification performance, with an area under the receiver operating characteristic curve (AUC) of 0.725 ± 0.012. Heatmap analysis revealed that three pathological fluids, subsided choroidal neovascularization lesions, and hyperreflective foci were important areas for the first recurrence. Conclusions The deep learning algorithm allowed for the prediction of the first recurrence for three months after the loading phase with adequate feasibility. An automated prediction system may assist in establishing patient-specific treatment plans and the provision of individualized medical care for patients with nAMD.

Abstract When medical genetic syndromes are influenced by allelic hierarchies, mutant alleles have distinct effects on clinical phenotypes. Genotype–phenotype correlations for Usher syndrome type 2 (USH2) suggest that the USH2A gene exhibits an allelic hierarchy. Here, we analyzed the phenotypes and genotypes of 16 South Korean patients with USH2A biallelic variants to investigate an allelic hierarchy from audiological and ophthalmological perspectives. Using whole exome and genome sequencing, 18 mutant alleles, including 4 novel alleles, were identified and implicated in USH2A-related disorders. Truncated alleles were linked to earlier onset of subjective hearing loss and more severe thresholds; biallelic truncated alleles had more severe effects. Truncated alleles were also associated with retinal structure degeneration and severe functional deterioration. However, younger patients (aged

Abstract Background We present the detailed multimodal imaging analysis in a case of X-linked retinitis pigmentosa (XLRP) exhibiting a markedly asymmetric presentation with a novel RP2 mutation. Case presentation A 25-year-old woman complained of decreased vision in the right eye as well as night blindness. Her visual acuity was 20/100 (OD) and 20/20 (OS). Fundus examination revealed bone spicule pigmentation with tessellated changes in the fundus within the posterior pole. Optical coherence tomography (OCT) showed generalized disruption of foveal microstructures in the OD. No abnormal findings were identified, but localized ellipsoid zone band losses were observed on OCT in the OS. Fundus autofluorescence revealed multiple patchy hypo-autofluorescent lesions in the OD and a tapetal-like radial reflex against a dark background in the OS. Fluorescein angiography and OCT angiography revealed diffuse mottled hyperfluorescence with reduced retinal vessel density in the OD and no evidence of vascular compromise in the OS. Goldmann perimetry demonstrated a constricted visual field, and electrophysiological assessment revealed an extinguished rod response and a severely impaired cone response in the OD. Molecular genetic tests via next-generation sequencing revealed the pathogenic variant to be a heterozygous frameshift mutation in RP2 (RP2, p.Glu269Glyfs*7), resulting in premature termination of the protein. Conclusions Random X-inactivation may be attributed to interocular differences in the severity of XLRP in female carriers. A novel frameshift mutation in the RP2 gene and a comprehensive phenotypic evaluation in the current study may broaden the spectrum of the disease in XLRP carriers.

Abstract We investigated the associations between retinal vascular geometric measurements and idiopathic epiretinal membrane (ERM). Whether changes in retinal vascular geometry are independent of systemic cardiovascular risk factors was also evaluated. This retrospective, cross sectional study included 98 patients with idiopathic ERM, and 99 healthy age-matched controls. Quantitative retinal vascular parameters were measured from digital retinal fundus photographs using a semi-automated computer-assisted program. Multivariate logistic regression analyses were performed to evaluate associations between retinal vascular geometric parameters and the presence of idiopathic ERM after adjusting for systemic cardiovascular risk factors. There was no significant difference in the baseline characteristics of the two groups, except that the ERM group had a higher proportion of females than the control group. In multivariate regression analyses, female sex (odds ratio [OR] 0.402; 95% CI 0.196–0.802; P = 0.011), wider retinal venular caliber (OR 16.852; 95% CI 5.384–58.997; P

Abstract Background Elevated serum creatine kinase (CK) levels have been reported in patients with Guillain–Barré syndrome (GBS), more frequently in patients with acute motor axonal neuropathy (AMAN) than in those with acute inflammatory demyelinating polyneuropathy (AIDP). However, some patients with AMAN show reversible conduction failure (RCF), characterized by rapid recovery without axonal degeneration. The present study tested the hypothesis that hyperCKemia is associated with axonal degeneration in GBS, regardless of the subtype. Methods We retrospectively enrolled 54 patients with AIDP or AMAN whose serum CK levels were measured within 4 weeks from symptom onset between January 2011 and January 2021. We divided them into hyperCKemia (serum CK ≥ 200 IU/L) and normal CK (serum CK

Abstract Reversible conduction failure (RCF) has been documented in acute motor axonal neuropathy (AMAN) and is considered a sign of nodopathy. Several reports of RCF in acute inflammatory demyelinating polyneuropathy (AIDP) have suggested that it could be a manifestation of nodopathy. We conducted this study to determine the frequency of RCF in AMAN and AIDP and to compare the clinical features between the two groups with or without RCF. RCF was observed in 38.9% and 18.5% patients in the AMAN and AIDP groups in our study, respectively. AIDP patients with anti-ganglioside antibodies represented 29.4% of the cohort. The clinical features of AIDP with RCF were more similar to those of AMAN with RCF than to those of typical AIDP. However, there were no significant differences in the frequency of anti-ganglioside antibody status between the groups. AIDP with RCF may be a manifestation of nodopathy. The current dichotomous electrodiagnostic criteria, classifying demyelinating and axonal neuropathy, are insufficient to define nodopathy. Further studies are required to revise the electrodiagnostic criteria for Guillain–Barré syndrome.

Purpose: To investigate the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa (RHO-associated RP).Design: We conducted a retrospective, multicenter, observational cohort study.Participants: We reviewed the medical records of 42 patients with RHO-associated RP of 36 families who visited 4 hospitals in Korea.Methods: Patients with molecular confirmation of pathogenic variants of the RHO gene were included. The patients were divided into two subgroups: the generalized and sector RP groups. A central visual field of the better-seeing eye of

Abstract Background We present a case of retinal occlusive vasculitis following brolucizumab administration and the first report of optical coherence tomography angiography (OCTA) findings after treatment. Case presentation A 71-year-old man complained of vision loss in the left eye 6 weeks after brolucizumab injection. His visual acuity was counting fingers, and examination revealed 1 + anterior chamber cells with 2 + vitreous cells. Fundus examination demonstrated vitreous haze, retinal whitening, and vascular sheathing. Fluorescein angiography revealed filling defects in the retinal arteries and veins, and OCTA showed extensive capillary nonperfusion. Under the diagnosis of brolucizumab-associated intraocular inflammation (IOI) and retinal occlusive vasculitis, topical, sub-Tenon, and systemic corticosteroids were administered. After the treatment, visual acuity improved to 20/200, and OCTA revealed gradual improvement in capillary dropout; however, with the limited improvement of reperfusion in the perifoveal areas. Conclusions Prompt evaluation and intensive corticosteroid treatments are required for brolucizumab-associated IOI. OCTA imaging provides detailed information on microvascular changes in the retinal vascular plexuses in brolucizumab-associated retinal occlusive vasculitis.

Abstract This observational cohort study aimed to evaluate the progression pattern of diffuse chorioretinal atrophy (DCA) according to its severity. Highly myopic eyes with DCA were graded according to its extent in the 532-nm (green) and 633-nm (red) wavelengths images of the Optos ultra-widefield scanning laser ophthalmoscope at baseline: grade 1 and 2 were defined when increased reflectance at peripapillary region, not beyond the fovea, were observed in red laser image only and in both laser images, respectively; grade 3 and 4 were defined when increased reflectance beyond the fovea were observed in red laser image only and in both laser images, respectively. A total of 307 eyes (221 patients) were included, and progression of myopic maculopathy during follow-up of ≥ 3 years was evaluated. The mean visual acuity and subfoveal choroidal thickness (CT) differed among DCA grades (P = 0.015 and P

Abstract It has been known that retinal vein occlusion (RVO) is associated with chronic kidney disease, especially end-stage renal disease (ESRD). However, little is known about the effect of kidney transplantation (KT) on RVO incidence in ESRD patients. This study aimed to compare the incidence of RVO in KT recipients (n = 10,498), matched ESRD patients (n = 10,498), and healthy controls (HCs, n = 10,498), using a long-term population-based cohort. The incidence of RVO was 2.74, 5.68, and 1.02 per 1000 patient-years, for the KT group, the ESRD group, and the HCs group, respectively. Adjusted hazard ratios for RVO development compared to the HCs group, were 1.53 and 3.21, in the KT group and the ESRD group, respectively. In the KT group, multivariable regression analysis indicated that an age over 50, a Charlson Comorbidity Index score over 4, and a history of desensitization therapy were associated with an increased risk of RVO. In summary, KT recipients have a lower risk for development of RVO than ESRD patients treated with dialysis. However, the risk is still higher compared to healthy people who have normal kidney functions.

Abstract In this cross-sectional study, we investigated choroidal thickness (CT) and scleral thickness (ST) in highly myopic eyes and their associations with ocular factors. Patients underwent widefield swept-source optical coherence tomography (OCT) to measure the CT and ST at the subfovea and 3000 μm superior, inferior, temporal, and nasal to the fovea and macular curvature. A total of 237 eyes (154 patients) were included. At all five measurement points, thinner CTs and STs were associated with longer axial lengths (r = − 0.548 to − 0.357, all P

This study aimed to identify the clinical significance of iron rim lesions (IRLs) in distinguishing multiple sclerosis (MS) from other central nervous system (CNS) demyelinating diseases, determine the relationship between IRLs and disease severity, and understand the long-term dynamic changes in IRLs in MS. We retrospectively evaluated 76 patients with CNS demyelinating diseases. CNS demyelinating diseases were classified into three groups: MS (n = 30), neuromyelitis optica spectrum disorder (n = 23), and other CNS demyelinating diseases (n = 23). MRI images were obtained using conventional 3T MRI including susceptibility-weighted imaging. Sixteen of 76 patients (21.1%) had IRLs. Of the 16 patients with IRLs, 14 were in the MS group (87.5%), indicating that IRLs were significantly specific for MS. In the MS group, patients with IRLs had a significantly higher number of total WMLs, experienced more frequent recurrence, and were treated more with second-line immunosuppressive agents than were patients without IRLs. In addition to IRLs, T1-blackhole lesions were observed more frequently in the MS group than in the other groups. IRLs are specific for MS and could represent a reliable imaging biomarker to improve the diagnosis of MS. Additionally, the presence of IRLs seems to reflect more severe disease progression in MS.

Abstract Background To date, no genetic analysis of inherited retinal disease (IRD) using whole-exome sequencing (WES) has been conducted in a large-scale Korean cohort. The aim of this study was to characterise the genetic profile of IRD patients in Korea using WES. Methods We performed comprehensive molecular testing in 168 unrelated Korean IRD patients using WES. The potential pathogenicity of candidate variants was assessed using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology variant interpretation guidelines, in silico prediction tools, published literature, and compatibility with known phenotypes or inheritance patterns. Results Causative variants were detected in 86/168 (51.2%) IRD patients, including 58/107 (54.2%) with retinitis pigmentosa, 7/15 (46.7%) with cone and cone-rod dystrophy, 2/3 (66.6%) with Usher syndrome, 1/2 (50.0%) with congenital stationary night blindness, 2/2 (100.0%) with Leber congenital amaurosis, 1/1 (100.0%) with Bietti crystalline dystrophy, 1/1 (100.0%) with Joubert syndrome, 9/10 (90.0%) with Stargardt macular dystrophy, 1/10 (10.0%) with vitelliform macular dystrophy, 1/11 (9.1%) with other forms of macular dystrophy, and 3/4 (75.0%) with choroideraemia. USH2A, ABCA4, and EYS were the most common causative genes associated with IRD. For retinitis pigmentosa, variants of USH2A and EYS were the most common causative gene mutations. Conclusions This study demonstrated the distribution of causative genetic mutations in Korean IRD patients. The data will serve as a reference for future genetic screening and development of treatment modalities for Korean IRD patients.

PurposeThe study aimed to evaluate risk factors for macular atrophy (MA) associated with myopic choroidal neovascularization (mCNV) during long-term follow-up after intravitreal anti-vascular endothelial growth factor (VEGF) treatment in highly myopic eyes.MethodsThe medical records of patients who received intravitreal injection of anti-VEGF agents as mCNV treatment and were followed-up for more than 36 months were retrospectively reviewed. The risk factors for the development of mCNV-MA, which is the fovea-involving patchy atrophy lesion adjacent to mCNV, were investigated using the Cox proportional hazard model.ResultsA total of 82 eyes (74 patients) were included in the study. The mean age at anti-VEGF treatment was 56.3 ± 12.5 years (range, 26-77), and the mean follow-up period was 76.3 ± 33.5 months (range, 36-154). During follow-up, mCNV-MA developed in 27 eyes (32.9%), and its occurrence was estimated to be 24.5% at 3 years and 37.3% at 5 years after the first anti-VEGF treatment. Old age (hazard ratio [HR] = 1.054, 95% confidence interval [CI]: 1.018-1.091; P = 0.003) and greater CNV size at baseline (HR = 2.396, CI: 1.043-5.504; P = 0.040) were significant factors for mCNV-MA development. Eyes with a thinner subfoveal choroid were more likely to show faster enlargement of the mCNV-MA during follow-up.ConclusionsIn mCNV eyes treated with intravitreal anti-VEGF agents, older age and greater mCNV size at baseline were risk factors for the development of MA during long-term follow-up, which was associated with a poor visual prognosis.

Abstract Background To report the successful treatment of ocular toxoplasmosis and present the use of multimodal imaging to describe the changes in ocular toxoplasmic lesions subsequent to treatment. Case presentation A 73-year-old female visited the clinic with decreased visual acuity in the left eye. Fundus examination showed severe vitreous haze with yellow-white infiltrates near the foveal center. Spectral-domain optical coherence tomography (SD-OCT) revealed disorganization of the retinal structure with markedly thickened choroid beneath the active lesion. Highly elevated serum titers of IgG antibodies against Toxoplasma gondii were observed. Topical and systemic steroids with oral Bactrim were administered after a diagnosis of ocular toxoplasmosis was made. After improvement in the severity of vitritis, structural en face swept-source optical coherence tomography (SS-OCT) imaging demonstrated diffuse choroidal dilation with many collateral vascular branches surrounding the active lesion. Eight intravitreal injections of clindamycin (1 mg/0.1 ml) were administered at 1- to 2-week intervals along with systemic antibiotics and steroids. After the treatment, the toxoplasmic lesion resolved to an atrophic chorioretinal scar. Dilated choroidal vessel size was normalized and collateral vascular branches were markedly constricted on structural en face SS-OCT images. Conclusions This is the first detailed report on the morphological changes in the choroidal vasculature surrounding ocular toxoplasmic lesions that were characterized using SS-OCT-A imaging. Multimodal imaging with SS-OCT-A can be valuable in clinical diagnosis as well as in clarifying the mechanism of choroidal structural changes in ocular toxoplasmosis.

Background/Aims: High-mobility group box 1 (HMGB1) elicits inflammatory responses through interactions with the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). We investigated how RAGE and TLR4 expressions are regulated after HMGB1 stimulation in cultured human aortic endothelial cells (HAECs). Methods: RAGE and TLR4 expressions were analyzed by Western blot analysis and immunofluorescence staining. A disintegrin and metalloprotease 17 (ADAM17) activity was measured using a fluorogenic substrate. Results: Upon treatment with HMGB1, both RAGE and TLR4 began to decrease in cell lysate and remained decreased up to 24 h. The decrease in cellular RAGE and TLR4 was accompanied by an increase of N-terminal fragment of RAGE and TLR4 in culture supernatant, indicating ectodomain shedding of the receptors. HMGB1 activated p38 mitogen-activated protein kinase (p38 MAPK) and ADAM17, while HMGB1-induced ADAM17 activation was inhibited by SB203580, a p38 MAPK inhibitor. HMGB1-induced ectodomain shedding of RAGE and TLR4 was prevented by siRNA depletion of ADAM17 as well as TAPI-2, an inhibitor of ADAM family, and SB203580. HMGB1 pretreatment abolished p38 MAPK activation in response to 2nd HMGB1 stimulation. In the cells depleted of ADAM17, HMGB1-induced p38 MAPK activation was prolonged. siRNA depletion of RAGE, but not TLR4, suppressed HMGB1-induced p38 MAPK activation. Conclusion: In response to HMGB1 stimulation, HAECs rapidly undergo ectodomain shedding of RAGE and TLR4, and thereby become insensitive to further HMGB1 stimulation. ADAM17, activated through RAGE-p38 MAPK pathway, is implicated in the ectodomain cleavage of the receptors.

Abstract We establish the existence, nonexistence, and multiplicity of positive solutions to semilinear elliptic systems with integral boundary conditions when positive multiparameters vary on the boundary. We prove the results by using sub- and supersolution argument and fixed point index theory.

Abstract Background Evidence suggests that alkaline phosphatase attenuates inflammatory response in sepsis by lipopolysaccharide detoxification and adenosine triphosphate dephosphorylation. We sought to determine changes in alkaline phosphatase (AP) activity during septic acute kidney injury (AKI) and clinical parameters associated with AP activity. Methods In this retrospective study, we investigated baseline (when initiating CRRT) and follow-up AP activity on day 3, and associated outcomes in patients who underwent continuous renal replacement therapy (CRRT) due to septic AKI. Results We analyzed the baseline AP activity of 155 patients and day 3 AP activity in 123 patients. Baseline AP activity was not associated with renal or inflammatory biomarkers, or outcomes. It did not significantly differ between the 75 survivors and 80 non-survivors (p = 0.155). AP activity was higher on day 3 than at baseline (105 U/L [interquartile range, 79–156] vs 90 U/L [interquartile range, 59–133]). In particular, liver and bone isoforms increased significantly (p

Purpose: The aim of this study was to investigate the efficacy and safety of a mixed extract of Trigonella foenum-graecum seed and Lespedeza cuneata (TFGL) for the treatment of testosterone deficiency syndrome (TDS). Materials and Methods: Patients were instructed to take a placebo or 200 mg TFGL capsule twice per day for 8 weeks. The primary efficacy variable was the change from baseline in the Aging Males’ Symptoms scale (AMS), as well as levels of serum total and free testosterone. Secondary efficacy measurements included changes from baseline in the number of ‘yes’ answers on the Androgen Deficiency in the Aging Male (ADAM) questionnaire, levels of serum total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride, all domain scores of the International Index of Erectile Function (IIEF), perceived stress scale-10 (PSS-10), as well as changes in body composition. Results: The TFGL group exhibited a significant improvement in the AMS scores at 8 weeks, total testosterone at 8 weeks, and free testosterone at 4 and 8 weeks. At 4 weeks, 25% of the TFGL group changed to negative in terms of ADAM scores and 34.1% of the TFGL group had negative scores at the end of the study. The TFGL group exhibited a significant improvement in total cholesterol, HDL-C, LDL-C, triglyceride, IIEF scores, and PSS-10 scores at 8 weeks. Conclusions: The mixed extract of TFGL resulted in significant improvements in symptoms of TDS, as measured by the AMS, ADAM, PSS-10 and testosterone levels.

Purpose To analyze the effects of clinical and laboratory factors, including insulin-like growth factor (IGF) levels, on the height velocity of normal prepubertal children. Methods Ninety-five healthy prepubertal children (33 boys, 62 girls) were enrolled. The mean chronological age was 6.3±1.4 years, with a height standard deviation score (SDS) of -0.88±0.70. IGF-1, IGF binding protein-3 (IGFBP-3), SDS for anthropometric measurements, and changes in SDS for anthropometric measurements were analyzed for 1 year, and their associations with 1-year height velocity were investigated. Results The group of children with a 1-year height velocity of ≥6 cm were chronologically younger than the group with a 1-year height velocity of

Posterior epidural migration of a lumbar intervertebral disc fragment (PEMLIF) is uncommon because of anatomical barriers. It is difficult to diagnose PEMLIF definitively because of its relatively rare incidence and the ambiguity of radiological findings resembling spinal tumors. This case report describes a 76-year-old man with sudden-onset weakness and pain in both legs. Electromyography revealed bilateral lumbosacral polyradiculopathy with a mass-like lesion in L2-3 dorsal epidural space on lumbosacral magnetic resonance imaging (MRI). The lesion showed peripheral rim enhancement on T1-weighted MRI with gadolinium administration. The patient underwent decompressive L2-3 central laminectomy, to remove the mass-like lesion. The excised lesion was confirmed as an intervertebral disc. The possibility of PEMLIF should be considered when rim enhancement is observed in the epidural space on MRI scans and electrodiagnostic features of polyradiculopathy with sudden symptoms of cauda equina syndrome.

Central nervous system involvement in multiple myeloma (CNS-MM) is a rare condition. Various manifestations of CNS-MM have been reported, including dural, parenchymal, and leptomeningeal involvement. Among them, leptomeningeal involvement is less common and intraventricular involvement is exceptional, with only one case reported in the literature. Herein, we report the first case of CNS-MM manifesting as an intraventricular mass with leptomeningeal involvement combined with perineural spread. We also describe characteristic computed tomography and magnetic resonance imaging findings of intraventricular multiple myeloma.

This report describes a case of a 62-year-old woman with microscopic polyangiitis (MPA) who developed acute spinal subdural hemorrhage. MPA was confirmed by positive autoantibodies to myeloperoxidase and focal segmental necrotizing and pauci-immune crescentic glomerulonephritis on renal biopsy. She did not recover from paraplegia due to acute spinal subdural hemorrhage, despite decompression operation and aggressive immunosuppression. Although spontaneous spinal hemorrhage in MPA patients is very rare, the prognosis for such patients is poor. Considering the possibility of ongoing vasculitis activity in extra-renal organs, clinicians should be very cautious to attenuate the strength of immunosuppressant drugs, even in patients with chronic or irreversible renal pathology.

Background/Aims: Lipopolysaccharide (LPS)-activated monocytes/macrophages develop endotoxin tolerance in part by reducing cell surface toll-like receptor 4 (TLR4) through cluster of differentiation 14 (CD14)-dependent endocytosis. In case of endothelial cells, CD14 is expressed in low copy numbers as compared with monocytes/macrophages. Thus, we explored how endothelial cells regulate TLR4 expression after LPS stimulation. Methods: Cultured human aortic endothelial cells (HAECs) were treated with LPS. TLR4 expression was analyzed by Western blot analysis and immunofluorescence staining. A disintegrin and metalloprotease 17 (ADAM17) activity was measured using a fluorescent substrate. Results: TLR4 in cell lysate began to decrease within 30 min of LPS treatment with a maximal reduction at 2 h, and it was accompanied by an increase of N-terminal fragment of TLR4 in culture supernatant, indicating ectodomain shedding of the receptor. LPS activated p38 mitogen-activated protein kinase (p38 MAPK) and ADAM17, while LPS-induced ADAM17 activation was inhibited by SB203580, a p38 MAPK inhibitor. LPS-induced ectodomain shedding of TLR4 was attenuated by siRNA depletion of ADAM17 as well as TAPI-2 (an inhibitor of ADAM family) and SB203580. LPS pretreatment resulted in a blunted response of p38 MAPK activation to further LPS stimulation. In the cells depleted of ADAM17, LPS-induced p38 MAPK activation was prolonged and LPS-induced intercellular adhesion molecule-1 expression was potentiated. Conclusion: HAECs respond to LPS by rapid shedding of the ectodomain of TLR4 and thereby reduce the responsiveness to subsequent LPS exposure. ADAM17, downstream of p38 MAPK, is implicated in the ectodomain cleavage of TLR4.

Background: Although the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has been recommended for accurate estimates of glomerular filtration rate (eGFR), there is little information regarding differences in GFR estimates obtained using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations in East Asian cancer patients. We investigated discrepancies in GFR and toxicities in patients treated with cisplatin-based chemotherapy using three equations equations. Methods: A total of 229 patients were retrospectively recruited. We calculated eGFR using the three equations and separated patients into three categories based on GFR < 10 (group A), 10–50 (group B), and > 50 (group C) mL/min/1.73m². We analyzed chemotherapy toxicities. Results: The mean eGFR calculated using the CG was the lowest of the values derived using the three equations. Estimates using the MDRD and CKD-EPI equations resulted in reclassifying 32 (71.1%) and 33 (73.3%) of 45 patients, originally placed in group B using the CG into group C. However, only 1 (7.7%) of 13 patients placed in group B using the MDRD were reclassified into group C using the CKD-EPI. Twenty-eight of 45 patients classified into group B using the CG equation were treated with reduced doses of cisplatin. However, these patients did not show significant differences in toxicities compared with other patients taking full doses of cisplatin. Conclusion: The CG equations underestimated GFR compared to the MDRD and CKD-EPI equations. Therefore, when GFR is estimated using CG equations, East Asian cancer patients may receive insufficient doses of chemotherapeutic agents, including cisplatin.

Background/Aims: We investigated how diosgenin, a steroidal sapogenin, has anti-tumor necrosis factor-α (TNF-α) effects in human aortic endothelial cells (HAECs). Methods: Tumor necrosis factor receptor 1 (TNFR1) was assessed by Western blot analysis. Intracellular Ca2+ was measured using Fluo-4 AM. Immunofluorescence staining was performed for a disintegrin and metalloprotease 10 (ADAM10). Results: Diosgenin (1 ∼ 100 nM) induced ectodomain shedding of TNFR1 within 30 min and attenuated TNF-α-induced intercellular adhesion molecule-1 (ICAM-1) expression. Upon treatment with diosgenin, extracellular Ca2+ entered into the cells via L-type calcium channels, whereas diosgenin-induced ectodomain shedding of TNFR1 was almost completely inhibited by BAPTA-AM (intracellular Ca2+ chelator), verapamil (L-type calcium channel antagonist) and the absence of extracellular Ca2+. Diosgenin caused translocation of ADAM10 to the cell surface, which was mediated by extracellular Ca2+ influx. Depletion of ADAM10 prevented diosgenin-induced ectodomain shedding of TNFR1 and abolished the inhibitory effect of diosgenin on TNF-α-induced ICAM-1 expression. Diosgenin did not induce extracellular Ca2+ influx and ectodomain shedding of TNFR1 in cells depleted of 1,25D3-membrane associated rapid response steroid-binding receptor (1,25D3-MARRS receptor/ERp57). Conclusion: Diosgenin elicits L-type calcium channel-mediated extracellular Ca2+ influx, and thereby induces ADAM10-mediated ectodomain shedding of TNFR1. This effect of diosgenin was exerted through 1,25D3-MARRS receptor/ERp57.

Background: Volume overload results in higher mortality rates in patients on continuous ambulatory peritoneal dialysis (CAPD). The ratio of bioimpedance (RBI) might be a helpful parameter in adjusting dry body weight in CAPD patients. This study examined whether it is possible to distinguish between non-hypervolemic status and hypervolemic status in CAPD patients by using only RBI. Methods: RBI was calculated as follows: RBI = impedance at 50 kHz/impedance at 500 kHz. Based on the experts’ judgements, a total of 64 CAPD patients were divided into two groups, a non-hypervolemic group and a hypervolemic group. The RBI was measured from right wrist to right ankle (rw-raRBI) by bioimpedance spectroscopy (BCM®, Fresenius Medical Care) before and after the peritosol was emptied. Other RBIs were measured from the right side of the anterior superior iliac spine to the ipsilateral ankle (rasis-raRBI) to control for the electro-physiological effects of peritoneal dialysate. Results: The mean rw-raRBI of non-hypervolemic patients was higher than that of hypervolemic patients in the presence (1.141 ± 0.022 vs. 1.121 ± 0.021, P < 0.001) of a peritosol. Likewise, the mean rasis-raRBI of non-hypervolemic patients was higher than that of hypervolemic patients (presence of peritosol: 1.136 ± 0.026 vs. 1.109 ± 0.022, P < 0.001; absence of peritosol: 1.131 ± 0.022 vs. 1.107 ± 0.022, P < 0.001). Conclusion: The volume status of CAPD patients was able to be simply expressed by RBI. Therefore, this study suggests that when patients cannot be analyzed using BCM, RBI could be an alternative.

Background/Aims: We investigated how 1,25-dihydroxyvitamin D3 (1,25D3) inhibits the effects of lipopolysaccharide (LPS) in human aortic endothelial cells. Methods: Cellular signaling was explored by determination of protein abundance with Western blot, measurement of cytosolic Ca2+ concentration and immunofluorescence staining for a disintegrin and metalloprotease 10 (ADAM10). Results: LPS stimulated the expression of intercellular adhesion molecule 1 (ICAM-1) through toll-like receptor 4 (TLR4) and subsequent activation of p38 mitogen-activated protein kinase (p38 MAPK). Pretreatment with 1,25D3 attenuated LPS-induced p38 MAPK activation and ICAM-1 expression by causing ectodomain shedding of TLR4. This effect of 1,25D3 depended on its ability to induce a rapid extracellular Ca2+ influx through L-type calcium channels because the ectodomain shedding was prevented by the absence of extracellular Ca2+ or the presence of verapamil. TLR4 ectodomain shedding was also induced by Bay K8644 (L-type calcium channel agonist). Both 1,25D3 and Bay K8644 caused extracellular Ca2+ influx-dependent ADAM10 translocation to the cell surface. Depletion of ADAM10 by siRNA transfection prevented 1,25D3- and Bay K8644-induced ectodomain shedding of TLR4, and abolished the inhibitory effect of 1,25D3 on LPS-induced ICAM-1 expression. Conclusion: 1,25D3 causes ectodomain shedding of TLR4 and thereby decreases the responsiveness of cells to LPS. ADAM10, activated by extracellular Ca2+ influx, was implicated in the ectodomain cleavage of TLR4.

In July 2023, cases of highly pathogenic avian influenza (HPAI) were reported at 2 shelters for stray cats in Seoul, South Korea. The cause of infection was suspected to be improperly sterilized raw food made from domestic duck meat, which was manufactured in South Korea. All viruses isolated from cats at the shelters and from the raw food belonged to HPAI A(H5N1) clade 2.3.4.4b. The gene constellation of all viruses was most similar to that of viruses isolated in Korea in November 2022. Of note, the viruses isolated from infected cats harbored mutations E627K or D701N in polymerase basic 2, which are indicative of adaptation to mammals. Postmortem examination revealed systemic pathologic lesions and the presence of widespread virus in different tissues. Thus, consumption of raw duck meat contaminated with HPAI virus likely caused systemic symptoms and death in cats, indicating the introduction of mammal-adapted mutations of the virus.

In this work, we investigate the existence and multiplicity results for positive solutions to a singular $(p_1,p_2)$-Laplacian system with coupled integral boundary conditions and a parameter $(\mu,\lambda) \in \mathbb{R}_+^3 $. Using sub-super solutions method and fixed point index theorems, it is shown that there exists a continuous surface $\mathcal{C}$ which separates $\mathbb{R}_+^2 \times (0,\infty)$ into two regions $\mathcal{O}_1$ and $\mathcal{O}_2$ such that the problem under consideration has two positive solutions for $( \mu,\lambda) \in \mathcal{O}_1,$ at least one positive solution for $( \mu,\lambda) \in \mathcal{C}$, and no positive solutions for $( \mu,\lambda) \in \mathcal{O}_2.$

In this article, we consider nonlocal p-Laplacian boundary-value problems with integral boundary conditions and a non-negative real-valued boundary condition as a parameter. The main purpose is to study the existence, nonexistence and multiplicity of positive solutions as the boundary parameter varies. Moreover, we prove a sub-super solution theorem, using fixed point index theorems.

This article shows the existence of at least one solution to nonlinear differential systems with coupled nonlocal boundary conditions on an infinite interval. Our main tool is the Alternative of Leray-Schauder.

Oxidative stress has been implicated as critical pathogenic factors contributing to the etiology of diabetic retinopathy and other retinal diseases. This study investigated antioxidative effect of ascorbic acid and astaxanthin on ARPE-19 cells within an oxidative stress model induced by common biological sources of reactive oxygen species (ROS). Hydrogen peroxide (H2O2) at concentrations of 0.1–0.8 mM and 20–100 mJ/cm2 of ultraviolet B (UVB) were treated to ARPE-19 cells. Cell viability and intracellular ROS level changes were measured. With the sublethal and lethal dose of each inducers, 0–750 μM of ascorbic acid and 0–40 μM of astaxanthin were treated to examine antioxidative effect on the model. Ascorbic acid at concentrations of 500 and 750 μM increased the cell viability not only in the UVB model but also in the H2O2 model, but 20 and 40 μM of astaxanthin only did so in the UVB model. The combination of ascorbic acid and astaxanthin showed better antioxidative effect compared to each drug alone, suggesting a synergistic effect.

Idiopathic hypereosinophilia (IHE)/idiopathic hypereosinophilic syndrome (IHES) has been defined by a persistent elevation of the blood eosinophil count exceeding 1.5×103/μL, without evidence of reactive or clonal causes. While T-cell clonality assessment has been recommended for unexplained hypereosinophilia, this approach is not often applied to routine practice in the clinic. We hypothesized that the clonality would exist in a subset of IHE/IHES patients. We aimed to investigate the candidate mutations and T-cell clonality in IHE/IHES and to explore the role of mutations in eosinophil proliferation. We performed targeted capture sequencing for 88 genes using next-generation sequencing, T-cell receptor (TCR) gene rearrangement assays, and pathway network analysis in relation to eosinophil proliferation. By targeted sequencing, 140 variants in 59 genes were identified. Sixteen out of 30 patients (53.3%) harbored at least one candidate mutation. The most frequently affected genes were NOTCH1 (26.7%), SCRIB and STAG2 (16.7%), and SH2B3 (13.3%). Network analysis revealed that our 21 candidate genes (BIRC3, BRD4, CSF3R, DNMT3A, EGR2, EZH2, FAT4, FLT3, GATA2, IKZF, JAK2, MAPK1, MPL, NF1, NOTCH1, PTEN, RB1, RUNX1, TET2, TP53 and WT1) are functionally linked to the eosinophilopoietic pathway. Among the 21 candidate genes, five genes (MAPK1, RUNX1, GATA2, NOTCH1 and TP53) with the highest number of linkages were considered major genes. A TCR assay revealed that four patients (13.3%) had a clonal TCR rearrangement. NOTCH1 was the most frequently mutated gene and was shown to be a common node for eosinophilopoiesis in our network analysis, while the possibility of hidden T cell malignancy was indwelling in the presence of NOTCH1 mutation, though not revealed by aberrant T cell study. Collectively, these results provide new evidence that mutations affecting eosinophilopoiesis underlie a subset of IHE/IHES, and the candidate genes are inferred to act their potential roles in the eosinophilopoietic pathway.

A 53-year-old woman presented with complaints of blurred vision in the left eye. She had been treated for recurrent non-functioning pituitary adenoma (NFPA). A vitreous biopsy followed by histopathologic examination showed the presence of Candida albicans. Meanwhile, Cushing׳s disease was diagnosed and gamma knife surgery was performed. Vitrectomy and antifungal treatment improved ocular infection and inflammation. Herein, we describe the first case of C. albicans endophthalmitis in a patient with NFPA evolving into Cushing׳s disease.

In this article we study the existence, nonexistence, and multiplicity of positive solutions for a singular multi-point boundary value problem with positive parameter. We use the fixed point index theory on a cone and a well-known theorem for the existence of a global continuum of solutions to establish our results.

This report describes the case of a hypertensive 51-year-old male with a 3-year history of peritoneal dialysis. We followed the patient through his diagnosis of severe obstructive sleep apnea (OSA) and treatment with continuous positive airway pressure (CPAP). Therapeutic use of CPAP led to the improvement of not only sleep-related problems, but also cognitive function and quality of life. To our knowledge, this is the first paper describing the benefits of longterm CPAP treatment in an OSA patient undergoing dialysis. This case report emphasizes the need for the proactive diagnosis and treatment of OSA in end-stage renal disease patients to improve patient-centered healthcare.

In this article, using a fixed point index theorem on a cone, we prove the existence and multiplicity results of positive solutions to a one-dimensional p-Laplacian problem defined on infinite intervals. We also establish the nonexistence results of nontrivial solutions to the problem.

To report an asymmetry analysis of macular inner retinal layers using swept-source optical coherence tomography (OCT) and to evaluate the utility for glaucoma diagnosis.Observational, cross-sectional study.Seventy normal healthy subjects and 62 glaucoma patients.Three-dimensional scans were acquired from 70 normal subjects and 62 open angle glaucoma patients by swept-source OCT. The thickness of the retinal nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex, and total retina were calculated within a 6.2×6.2 mm macular area divided into a 31×31 grid of 200×200 μm superpixels. For each of the corresponding superpixels, the thickness differences between the subject eyes and contra-lateral eyes and between the upper and lower macula halves of the subject eyes were determined. The negative differences were displayed on a gray-scale asymmetry map. Black superpixels were defined as thickness decreases over the cut-off values.The negative inter-ocular and inter-hemisphere differences in GCIPL thickness (mean ± standard deviation) were -2.78 ± 0.97 μm and -3.43 ± 0.71 μm in the normal group and -4.26 ± 2.23 μm and -4.88 ± 1.46 μm in the glaucoma group. The overall extent of the four layers' thickness decrease was larger in the glaucoma group than in the normal group (all Ps

Relapsing polychondritis (RP) is a rare, chronic, and potentially fatal multisystemic inflammatory disorder targeting cartilaginous structures. This disorder is frequently associated with rheumatoid arthritis, systemic vasculitis, connective tissue diseases, and hematologic disorders, but renal involvement is unusual. In the literature, associated renal pathology includes mesangial expansion, IgA nephropathy, tubulointerstitial nephritis, and segmental necrotizing crescentic glomerulonephritis. We report a case of a 49-year-old male found to have RP and nephrotic syndrome, with confirmed membranous nephropathy on kidney biopsy. He responded well to corticosteroids and cyclosporine. This is the first case of renal associated RP confirmed by renal biopsy in Korea. Membranous nephropathy associated with RP has never before been reported.

We analyze the positive solutions to the singular boundary value problem \begin{equation*}\begin{cases} -(|u'|^{p-2}u)'=\lambda \frac{g(u)}{u^\beta}; (0,1),\\ u(0)=0=u(1), \end{cases}\end{equation*} where $p>1,\beta\in(0,1),\lambda>0$ and $g:[0,\infty) \rightarrow\mathbb{R}$ is a $C^1$ function. In particular, we discuss examples when $g(0)>0$ and when $g(0)

We study a two point boundary-value problem describing the steady states of a Logistic growth population model with diffusion and constant yield harvesting. In particular, we focus on a model when a certain nonlinear boundary condition is satisfied.

We discuss the existence of positive solutions to $-Delta u=lambda f(u)$ in $Omega$, with $u=0$ on the boundary, where $lambda$ is a positive parameter, $Omega$ is a bounded domain with smooth boundary $Delta $ is the Laplacian operator, and $f:(0,infty)o R$ is a continuous function. We first discuss the cases when $f(0)>0$ (positone), $f(0)=0$ and $f(0)

Reverse genetics (RG) systems are extensively utilized to investigate the characteristics of influenza viruses and develop vaccines, predominantly relying on human RNA polymerase I (pol I). However, the efficiency of RG systems for avian-origin influenza viruses may be compromised due to potential species-specific interactions of RNA pol I. In this study, we reported the polymerase activities of the duck RNA pol I promoter in avian cells and the generation of recombinant avian-derived influenza viruses using a novel vector system containing the duck RNA pol I promoter region to enhance the rescue efficiency of the RG system in avian cells. Initially, we explored a putative duck promoter region and identified the optimal size to improve the existing system. Subsequently, we established an RG system incorporating the duck RNA pol I promoter and compared its rescue efficiency with the human pol I system by generating recombinant influenza viruses in several cell lines. Notably, the 250-bp duck RNA pol I promoter demonstrated effective functionality in avian cells, exhibiting higher polymerase activity in a minigenome assay. The newly constructed RG system was significantly improved, enabling the rescue of influenza viruses in 293T, DF-1, and CCL141 cells. Furthermore, HPAI viruses were successfully rescued in DF-1 cells, a result that had not been achieved in previous experiments. In conclusion, our novel RG system harboring duck RNA pol I offers an additional tool for researching influenza viruses and may facilitate the development of vaccines for poultry.