The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

Background: The gut–brain axis (GBA) in Parkinson’s disease (PD) has only been investigated in limited mice models despite dysbiosis of the gut microbiota being considered one of the major treatment targets for neurodegenerative disease. Therefore, this study examined the compositional changes of fecal microbiota in novel transgenic (Tg) mice overexpressing human α-synuclein (hαSyn) proteins under the neuron-specific enolase (NSE) to analyze the potential as GBA model. Results: The expression level of the αSyn proteins was significantly higher in the substantia nigra and striatum of NSEhαSyn Tg mice than the Non-Tg mice, while those of tyrosine hydroxylase (TH) were decreased in the same group. In addition, a decrease of 72.7% in the fall times and a 3.8-fold increase in the fall number was detected in NSE-hαSyn Tg mice. The villus thickness and crypt length on the histological structure of the gastrointestinal (GI) tract decreased in NSE-hαSyn Tg mice. Furthermore, the NSE-hαSyn Tg mice exhibited a significant increase in 11 genera, including Scatolibacter, Clostridium, Feifania, Lachnoclostridium, and Acetatifactor population, and a decrease in only two genera in Ligilactobacillus and Sangeribacter population during enhancement of microbiota richness and diversity. Conclusions The motor coordination and balance dysfunction of NSE-hαSyn Tg mice may be associated with compositional changes in gut microbiota. In addition, these mice have potential as a GBA model.

P-glycoprotein (P-gp) is a transporter that plays an excretory role in epithelial cells. It is encoded by ABCB1, and single nucleotide polymorphisms (SNPs) in this gene can affect systemic drug exposure. Dapagliflozin and sitagliptin, used in type 2 diabetes treatment, are P-gp substrates. Here, we aimed to investigate whether ABCB1 polymorphisms affect dapagliflozin and sitagliptin pharmacokinetics (PK) in healthy Korean subjects.The study population consisted of 100 healthy Korean subjects (94 men and 6 women) who participated in four different clinical trials and received dapagliflozin and sitagliptin doses of 10 and 100 mg, respectively. We determined ABCB1 genotypes for the C3435T, C1236T, and G2677T/A SNPs. The relationship between the genotypes and dapagliflozin PKs was examined.Dapagliflozin and sitagliptin PK parameters were not statistically significantly affected by ABCB1 SNP genotypes. However, homozygous 3435TT subjects showed higher dapagliflozin PK parameters than CT and CC subjects. In subjects with the 3435TT and those with 3435CC and 3435CT genotypes, mean Cmax, AUCinf, and AUC0-1 values of dapagliflozin were 223.06 ng/mL and 194.81 ng /mL (p = 0.2767), 673.58 ng*h/mL and 573.96 ng*h/mL (p = 0.0492), and 128.53 ng*h/mL and 104.61 ng*h/mL (p = 0.2678), respectively.In summary, dapagliflozin and sitagliptin PK parameters were not significantly different between individuals with C1236T and C2677T/A ABCB1 genetic polymorphisms. Dapagliflozin exhibited higher systemic exposure in 3435TT subjects than in CC/CT subjects.

Background and Objectives: Neo-aortic root dilatation (ARD) and annular dilatation (AAD) tend to develop after arterial switch operation (ASO). However, the trend of neo-aortic growth has not been well established. This paper aims to identify this trend, its associated factors, and predictors of neo-aortic dilatation after ASO. Methods: We analyzed the growth trend of the neo-aortic root, annulus, and sinotubular junction (STJ) z-scores using random coefficients model and the risk factors affecting neoaortic dilatation in 163 patients who underwent ASO from 2006 to 2015. Results: Among 163 patients, 41 had a ventricular septal defect, and 11 had Taussig-Bing (TB) anomaly. The median follow-up duration was 6.61 years. The increased in the neo-aortic root z-score was different between the trapdoor and non-trapdoor coronary artery transfer techniques (0.149/year, p<0.001 vs. 0.311/year, p<0.001). Moreover, the neo-aortic annulus and STJ z-score significantly increased over time after ASO (0.067/year, p<0.001; 0.309/ year, p<0.001). Pulmonary artery banding (PAB) was rather a negative affecting factor. The probabilities of freedom from ARD, AAD, and neo-aortic STJ dilatation at 10 years after ASO were 33.4%, 53.9%, and 65.4%. Neo- aortic regurgitation within 1 year was the predictor of ARD, AAD, and neo-aortic STJ dilatation. TB anomaly, PAB, and native pulmonary sinus z-score were other predictors for ARD. Conclusion The growth of neo-aortic root, annulus, and STJ after ASO was greater than somatic growth during childhood. The coronary artery transfer technique affected the growth pattern of the neo-aortic root.

Background and Objectives: Neo-aortic root dilatation (ARD) and annular dilatation (AAD) tend to develop after arterial switch operation (ASO). However, the trend of neo-aortic growth has not been well established. This paper aims to identify this trend, its associated factors, and predictors of neo-aortic dilatation after ASO. Methods: We analyzed the growth trend of the neo-aortic root, annulus, and sinotubular junction (STJ) z-scores using random coefficients model and the risk factors affecting neoaortic dilatation in 163 patients who underwent ASO from 2006 to 2015. Results: Among 163 patients, 41 had a ventricular septal defect, and 11 had Taussig-Bing (TB) anomaly. The median follow-up duration was 6.61 years. The increased in the neo-aortic root z-score was different between the trapdoor and non-trapdoor coronary artery transfer techniques (0.149/year, p<0.001 vs. 0.311/year, p<0.001). Moreover, the neo-aortic annulus and STJ z-score significantly increased over time after ASO (0.067/year, p<0.001; 0.309/ year, p<0.001). Pulmonary artery banding (PAB) was rather a negative affecting factor. The probabilities of freedom from ARD, AAD, and neo-aortic STJ dilatation at 10 years after ASO were 33.4%, 53.9%, and 65.4%. Neo- aortic regurgitation within 1 year was the predictor of ARD, AAD, and neo-aortic STJ dilatation. TB anomaly, PAB, and native pulmonary sinus z-score were other predictors for ARD. Conclusion The growth of neo-aortic root, annulus, and STJ after ASO was greater than somatic growth during childhood. The coronary artery transfer technique affected the growth pattern of the neo-aortic root.

Purpose: Our purpose in the current meta-analysis was to compare the functional outcomes in patients who have received single-radius (SR) or multi-radius (MR) femoral components in randomized controlled trials (RCTs) for primary total knee arthroplasty (TKA). The hypothesis was that there would be no statistically significant difference between two groups in terms of functional outcomes. Materials and methods: We searched the international electronic databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to February 2020 for RCTs that compared functional outcomes of SR and MR femoral component designs after primary TKA. We performed a meta-analysis of nine RCTs using the Knee Society Score for the knee (KSS-knee), KSS-function, Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), degree of knee flexion, extension, and complications, including postoperative infection and revision surgery. Results: The meta-analysis revealed no statistically significant differences in all the analyzed variables, including KSSknee, KSS-function, KOOS, OKS, knee flexion, and knee extension. For postoperative complications, no statistically significant differences were detected for femoral component designs in postoperative infection or incidence of revision surgery between the two groups. Conclusions The current meta-analysis of RCTs did not show any statistically significant differences between SR and MR femoral component designs in terms of postoperative functional outcomes. Evaluated outcomes included functional outcome scores, degree of knee flexion, extension, and complications. However, because of the limited clinical evidence of this study owing to the heterogeneity between the included RCTs, a careful approach should be made in order not to arrive at definite conclusions.

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population.METHODS: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis.RESULTS: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence.CONCLUSION: Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.
Antiviral Agents ; Carcinoma, Hepatocellular ; Cohort Studies ; DNA ; Follow-Up Studies ; Half-Life ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B ; Hepatitis ; Humans ; Immunoglobulins ; Korea ; Liver Transplantation ; Liver ; Organ Transplantation ; Polymerase Chain Reaction ; Recurrence ; Transplants

Purpose: Our purpose in the current meta-analysis was to compare the functional outcomes in patients who have received single-radius (SR) or multi-radius (MR) femoral components in randomized controlled trials (RCTs) for primary total knee arthroplasty (TKA). The hypothesis was that there would be no statistically significant difference between two groups in terms of functional outcomes. Materials and methods: We searched the international electronic databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to February 2020 for RCTs that compared functional outcomes of SR and MR femoral component designs after primary TKA. We performed a meta-analysis of nine RCTs using the Knee Society Score for the knee (KSS-knee), KSS-function, Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), degree of knee flexion, extension, and complications, including postoperative infection and revision surgery. Results: The meta-analysis revealed no statistically significant differences in all the analyzed variables, including KSSknee, KSS-function, KOOS, OKS, knee flexion, and knee extension. For postoperative complications, no statistically significant differences were detected for femoral component designs in postoperative infection or incidence of revision surgery between the two groups. Conclusions The current meta-analysis of RCTs did not show any statistically significant differences between SR and MR femoral component designs in terms of postoperative functional outcomes. Evaluated outcomes included functional outcome scores, degree of knee flexion, extension, and complications. However, because of the limited clinical evidence of this study owing to the heterogeneity between the included RCTs, a careful approach should be made in order not to arrive at definite conclusions.

Background: In February 2020, a coronavirus disease 2019 (COVID-19) outbreak was reported in fitness centers in Cheonan, Korea. Methods: From February 24 to March 13, an epidemiological investigation was conducted on the fitness center outbreak. All those who were screened were tested for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using real-time reverse transcriptase polymerase chain reaction. Contacts were traced and self-isolated for 14 days. We determined the epidemiological characteristics of confirmed cases of SARS-CoV-2 infection, and estimated the time-dependent reproduction number to assess the transmission dynamics of the infection. Results: A total of 116 cases were confirmed, and 1,687 contacts were traced. The source cases were 8 Zumba instructors who led aerobics classes in 10 fitness centers, and had the largest average number of contacts. A total of 57 Zumba class participants, 37 of their family members, and 14 other contacts were confirmed as cases. The attack rate was 7.3%. The contacts at Zumba classes and homes had a higher attack rate than other contacts. The mean serial interval (± standard deviation) were estimated to be 5.2 (± 3.8) days. The time-dependent reproduction number was estimated to be 6.1 at the beginning of the outbreak, but it dropped to less than 1, 2 days after the epidemiological investigation was launched. Conclusion The results suggest that the COVID-19 outbreak was effectively contained with rigorous contact tracing, isolating, and testing in combination with social distancing without a lock-down.

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population. METHODS: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis. RESULTS: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence. CONCLUSION Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.