Background: The clinical implications of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Abs) are increasing. Establishing MOG-Ab assays is essential for effectively treating patients with MOG-Abs. We established an in-house cell-based assay (CBA) to detect MOG-Abs to identify correlations with patients’ clinical characteristics. Methods: We established the CBA using HEK 293 cells transiently overexpressing fulllength human MOG, tested it against 166 samples from a multicenter registry of central nervous system (CNS) inflammatory disorders, and compared the results with those of the Oxford MOG-Ab-based CBA and a commercial MOG-Ab CBA kit. We recruited additional patients with MOG-Abs and compared the clinical characteristics of MOG-Ab-associated disease (MOGAD) with those of neuromyelitis optica spectrum disorder (NMOSD). Results: Of 166 samples tested, 10 tested positive for MOG-Abs, with optic neuritis (ON) being the most common manifestation (4/15, 26.7%). The in-house and Oxford MOG-Ab CBAs agreed for 164/166 (98.8%) samples (κ = 0.883, P < 0.001); two patients (2/166, 1.2%) were only positive in our in-house CBA, and the CBA scores of the two laboratories correlated well (r = 0.663, P < 0.001). The commercial MOG-Ab CBA kit showed one falsenegative and three false-positive results. The clinical presentation at disease onset differed between MOGAD and NMOSD; ON was the most frequent manifestation in MOGAD, and transverse myelitis was most frequent in NMOSD. Conclusions The in-house CBA for MOG-Abs demonstrated reliable results and can potentially be used to evaluate CNS inflammatory disorders. A comprehensive, long-term study with a large patient population would clarify the clinical significance of MOG-Abs.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. Methods: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. Results: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. Conclusion This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Background: We investigated the impacts of tocolytic agents on maternal and neonatal blood glucose levels in women with gestational diabetes mellitus (GDM) who used tocolytics for preterm labor. Methods: This multi-center, retrospective cohort study included women with GDM who were admitted for preterm labor from twelve hospitals in South Korea. We excluded women with multiple pregnancies, anomalies, overt DM diagnosed before pregnancy or 23 weeks of gestation, and women who received multiple tocolytics. The patients were divided according to the types of tocolytics; atosiban, ritodrine, and nifedipine group. We collected baseline maternal characteristics, pregnancy outcomes, maternal glucose levels during hospitalization, and neonatal glucose levels. We compared the frequency of maternal hyperglycemia and neonatal hypoglycemia among three groups. A multivariate logistic regression analysis was performed to evaluate the contributing factors to the occurrence of maternal hyperglycemia and neonatal hypoglycemia. Results: A total of 128 women were included: 44 (34.4%), 51 (39.8%), and 33 (25.8%) women received atosiban, ritodrine, and nifedipine, respectively. Mean fasting blood glucose (FBG) (112.3, 109.6, and 89.5 mg/dL, P < 0.001) and 2-hour postprandial glucose (PPG2) levels (145.4, 148.3, and 116.5 mg/dL, P = 0.004) were significantly higher in atosiban and ritodrine group than those in nifedipine group. Even after adjusting for covariates including antenatal steroid use, gestational age at admission, and pre-pregnancy body mass index, there was an increased risk of high maternal mean FBG (≥ 95 mg/dL) and PPG2 (≥ 120 mg/dL) levels in the atosiban and ritodrine group than in nifedipine group. The atosiban and ritodrine groups are also at increased risk of neonatal hypoglycemia (< 47 mg/dL) compared to the nifedipine group with the odds ratio of 4.58 and 4.67, respectively (P < 0.05). Conclusion There is an increased risk of maternal hyperglycemia and neonatal hypoglycemia in women with GDM using atosiban and ritodrine tocolytics for preterm labor compared to those using nifedipine.

Objective: This study examined whether related experts within the same organ know the standardized viscosity system of fluids and can manufacture solutions consistently. Methods: The subjects of this study were 22 rehabilitation ward nurses, 21 non-rehabilitation ward nurses, and 19 occupational therapists. The additional thickeners, manufacturing time and order, viscosity appropriateness, and solution homogeneity were measured for IDDSI level 4, 3, and 2 solutions manufactured using xanthan gum-based food thickeners. Results: The viscosity appropriateness in the three groups in stages IDDSI levels 4 and 3, but there was a significant difference among the three groups in stage IDDSI level 2. The factors affecting viscosity appropriateness were group and homogeneity of solution. The rehabilitation nurse group produced thicker solutions than the IDDSI standard compared to the other group. The homogeneity of the solution showed significant differences among the three groups in IDDSI levels 4, 3, and 2. The factors affecting homogeneity included the manufacturing order and job group, which often resulted in a clumping phenomenon when water was added first. Compared to the groups of therapists, the clumping phenomenon was significantly higher in the nurse (IDDSI level 3) and non-rehabilitation nurse groups (IDDSI level 4, 3) than the occupational therapists group. Conclusion This study showed that awareness and education about the liquid stage are necessary for medical personnel involved in hydration for patients with dysphagia and that consistent application using a standardized food thickener protocol at an institution is necessary.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Purpose: We used next-generation sequencing (NGS) to investigate the genetic causes of suspected genetic short stature in 37 patients, and we describe their phenotypes and various genetic spectra. Methods: We reviewed the medical records of 50 patients who underwent genetic testing using NGS for suspected genetic short stature from June 2019 to December 2022. Patients with short stature caused by nongenetic factors or common chromosomal abnormalities were excluded. Thirty-seven patients from 35 families were enrolled in this study. We administered one of three genetic tests (2 targeted panel tests or whole exome sequencing) to patients according to their phenotypes. Results: Clinical and molecular diagnoses were confirmed in 15 of the 37 patients, for an overall diagnostic yield of 40.5%. Fifteen pathogenic/likely pathogenic variants were identified in 13 genes (ACAN, ANKRD11, ARID1B, CEP152, COL10A1, COL1A2, EXT1, FGFR3, NIPBL, NRAS, PTPN11, SHOX, SLC16A2). The diagnostic rate was highest in patients who were small for their gestational age (7 of 11, 63.6%). Conclusion Genetic evaluation using NGS can be helpful in patients with suspected genetic short stature who have clinical and genetic heterogeneity. Further studies are needed to develop patient selection algorithms and panels containing growth-related genes.

Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusions Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.