Objective: To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer’s dementia and cognitive decline. Methods: In all, 20 participants with Alzheimer’s dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer’s dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion The higher the GR, the lower the prevalence of Alzheimer’s dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer’s dementia and cognitive decline.

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/ KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND 50 ) titers in serum samples. ND 50 titers against the omicron variant (median [interquartile range], 5.3 [< 5.0–12.7]) after full primary vaccination were lower than those against the wild-type (144.8 [44.7–294.0]) and delta (24.3 [14.3–81.1]) variants.Furthermore, 19/30 participants (63.3%) displayed lower ND 50 titers than the detection threshold (< 10.0) against omicron after full primary vaccination. However, the booster vaccine significantly increased ND 50 titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants (P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant.

Stiripentol is an anti-epileptic drug for the treating of refractory status epilepticus. It has been reported that stiripentol can attenuate seizure severity and reduce seizure-induced neuronal damage in animal models of epilepsy. The objective of the present study was to investigate effects of post-treatment with stiripentol on cognitive deficit and neuronal damage in the cornu ammonis 1 (CA1) region of the hippocampus proper following transient ischemia in the forebrain of gerbils. To evaluate ischemia-induced cognitive impairments, passive avoidance test and 8-arm radial maze test were performed. It was found that post-treatment with stiripentol at 20 mg/kg, but not 10 or 15 mg/kg, reduced ischemia-induced memory impairment. Transient ischemia-induced neuronal death in the CA1 region was also significantly attenuated only by 20 mg/kg stiripentol treatment after transient ischemia. In addition, 20 mg/kg stiripentol treatment significantly decreased ischemia-induced astrocyte damage and immunoglobulin G leakage. In brief, stiripentol treatment after transient ischemia ameliorated transient ischemia-induced cognitive impairment in gerbils, showing that pyramidal neurons were protected and astrocyte damage and blood brain barrier leakage were significantly attenuated in the hippocampus. Results of this study suggest stiripentol can be developed as a candidate of therapeutic drug for ischemic stroke.

Background/Aims: To analyze the incidence and risk factors of outcomes after liver transplantation (LT) in the Korean population. Methods: This study analyzed data from the liver cohort of Korean Organ Transplantation Registry (KOTRY) who had LT between May 2014 and December 2017. Study measures included the incidence of post-LT outcomes in recipients of living donor LT (LDLT) and deceased donor LT (DDLT). Cox multivariate proportional hazards model was used to determine the potential risk factors predicting the outcomes. Results: A total of 2,563 adult recipients with LT (LDLT, n=1,956; DDLT, n=607) were included, with mean±standard deviation age of 53.9±8.9 years, and 72.2% were male. The post-LT outcomes observed in each LDLT and DDLT recipients were death (4.0% and 14.7%), graft loss (5.0% and 16.1%), rejection (7.0% and 12.0%), renal failure (2.7% and 13.8%), new onset of diabetes (12.5% and 15.4%), and hepatocellular carcinoma (HCC) recurrence (both 6.7%). In both LDLT and DDLT recipients, the most common post-LT complications were renal dysfunction (33.6% and 51.4%), infection (26.7% and 48.4%), and surgical complication (22.5% and 23.9%). Incidence of these outcomes were generally higher among recipients of DDLT than LDLT. Multivariate analysis indicated recipient age and DDLT as significant risk factors associated with death and graft loss. DDLT and ABO incompatible transplant were prognostic factors for rejection, and HCC beyond Milan criteria at pre-transplant was a strong predictor of HCC recurrence. Conclusions This study is a good indicator of the post-LT prognosis in the Korean population and suggests a significant burden of post-LT complications.

Background: On March 22, 2020, intense social distancing (SD) was implemented in Korea to prevent the spread of coronavirus disease 19 (COVID-19). This study examined the impact of SD on diabetes control in older adults with diabetes. Methods: Adults aged 60 to 90 years with type 2 diabetes mellitus who were physically and mentally independent were recruited. Participants who had complete blood chemistry data from April to July 2019 (pre-SD era) and April to July 2020 (SD era) were enrolled. Data were obtained about physical activity, nutrition, sarcopenia, and psychological and mental health from questionnaires in April to July 2020. Calf circumference was measured. Results: In total, 246 people (100 men, 146 women; mean age, 73.8±5.7 years) participated in this study. The levels of glycated hemoglobin (HbA1c, 7.4%±1.0% vs. 7.1%±0.8%, P<0.001), fasting glucose (142.2±16.7 mg/dL vs. 132.0±27.7 mg/dL, P<0.001), and body weight (62.6±9.4 kg vs. 61.8±10.1 kg, P<0.01) were higher in the SD era than in the pre-SD era. Total physical activity was lower in the SD era (2,584.6±2,624.1 MET-min/week–1 vs. 1,987.3±2,295.0 MET-min/week–1, P<0.001). A larger increase in HbA1c level was associated with increased body weight and decreased physical activity. Conclusion SD had negative effects on diabetes management in older adults with diabetes. Fasting glucose and HbA1c levels and body weight increased during the SD era. Participants with reduced physical activity gained more weight and had higher blood glucose levels. Given that the COVID-19 pandemic is ongoing, health professionals and diabetes educators should monitor changes in lifestyle factors in older adults with diabetes.

Background: Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). Methods: BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. Results: Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. Conclusion These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.

Background: Pompe disease is a rare autosomal recessive disorder caused by the deficiency of a lysosomal enzyme, acid alpha-glucosidase (GAA). Early diagnosis and initiation of treatment with enzyme replacement therapy have remarkable effects on the prognosis of Pompe disease. We performed the expanded screening for late onset Pompe disease (LOPD) at eight centers in Korea. Methods: From September 1, 2015, GAA activity were measured from both dried blood spot (DBS) and mixed leukocyte for 188 available patients. For 12 patients with low GAA activity, we performed Sanger sequencing of GAA gene. Results: Among 188 patients, 115 were males. The mean of age of symptom onset and diagnosis were 34.3 years and 41.6 years. Among 12 patients with decreased GAA activity, two patients were confirmed to have LOPD with genetic test (c.1316T>A [p.M439K] + c.2015G>A [p.R672Q], c.1857C>G [p.S619R] + c.546G>C [leaky splicing]). Other two patients had homozygous G576S and E689K mutation, known as pseudodeficiency allele. Conclusions This study is expanded study of LOPD screening for targeted Korean population. We found two patients with LOPD, and the detection rate of LOPD is 1.06%. With application of modified GAA cutoff value (0.4), which was previously reported, there were no false positive results of GAA activity test using DBS. Therefore, it could be an appropriate screening test for LOPD in especially East-Asian population, in which pseudodeficiency allele is frequent.

Background/Aims: To analyze the incidence and risk factors of outcomes after liver transplantation (LT) in the Korean population. Methods: This study analyzed data from the liver cohort of Korean Organ Transplantation Registry (KOTRY) who had LT between May 2014 and December 2017. Study measures included the incidence of post-LT outcomes in recipients of living donor LT (LDLT) and deceased donor LT (DDLT). Cox multivariate proportional hazards model was used to determine the potential risk factors predicting the outcomes. Results: A total of 2,563 adult recipients with LT (LDLT, n=1,956; DDLT, n=607) were included, with mean±standard deviation age of 53.9±8.9 years, and 72.2% were male. The post-LT outcomes observed in each LDLT and DDLT recipients were death (4.0% and 14.7%), graft loss (5.0% and 16.1%), rejection (7.0% and 12.0%), renal failure (2.7% and 13.8%), new onset of diabetes (12.5% and 15.4%), and hepatocellular carcinoma (HCC) recurrence (both 6.7%). In both LDLT and DDLT recipients, the most common post-LT complications were renal dysfunction (33.6% and 51.4%), infection (26.7% and 48.4%), and surgical complication (22.5% and 23.9%). Incidence of these outcomes were generally higher among recipients of DDLT than LDLT. Multivariate analysis indicated recipient age and DDLT as significant risk factors associated with death and graft loss. DDLT and ABO incompatible transplant were prognostic factors for rejection, and HCC beyond Milan criteria at pre-transplant was a strong predictor of HCC recurrence. Conclusions This study is a good indicator of the post-LT prognosis in the Korean population and suggests a significant burden of post-LT complications.

Background: On March 22, 2020, intense social distancing (SD) was implemented in Korea to prevent the spread of coronavirus disease 19 (COVID-19). This study examined the impact of SD on diabetes control in older adults with diabetes. Methods: Adults aged 60 to 90 years with type 2 diabetes mellitus who were physically and mentally independent were recruited. Participants who had complete blood chemistry data from April to July 2019 (pre-SD era) and April to July 2020 (SD era) were enrolled. Data were obtained about physical activity, nutrition, sarcopenia, and psychological and mental health from questionnaires in April to July 2020. Calf circumference was measured. Results: In total, 246 people (100 men, 146 women; mean age, 73.8±5.7 years) participated in this study. The levels of glycated hemoglobin (HbA1c, 7.4%±1.0% vs. 7.1%±0.8%, P<0.001), fasting glucose (142.2±16.7 mg/dL vs. 132.0±27.7 mg/dL, P<0.001), and body weight (62.6±9.4 kg vs. 61.8±10.1 kg, P<0.01) were higher in the SD era than in the pre-SD era. Total physical activity was lower in the SD era (2,584.6±2,624.1 MET-min/week–1 vs. 1,987.3±2,295.0 MET-min/week–1, P<0.001). A larger increase in HbA1c level was associated with increased body weight and decreased physical activity. Conclusion SD had negative effects on diabetes management in older adults with diabetes. Fasting glucose and HbA1c levels and body weight increased during the SD era. Participants with reduced physical activity gained more weight and had higher blood glucose levels. Given that the COVID-19 pandemic is ongoing, health professionals and diabetes educators should monitor changes in lifestyle factors in older adults with diabetes.

Background: Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). Methods: BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. Results: Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. Conclusion These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.