Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Purpose: Predicting improvements in voiding symptoms following deobstructive surgery for male lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) is challenging when detrusor contractility is impaired. This study aimed to develop an artificial intelligence model that predicts symptom improvement after holmium laser enucleation of the prostate (HoLEP), focusing on changes in maximum flow rate (MFR) and voiding efficiency (VE) 1-month postsurgery. Methods: We reviewed 1,933 patients who underwent HoLEP at Samsung Medical Center from July 2008 to January 2024. The study employed a deep neural network (DNN) for multiclass classification to predict changes in MFR and VE, each divided into 3 categories. For comparison, additional machine learning (ML) models such as extreme gradient boosting, random forest classification, and support vector machine were utilized. To address class imbalance, we applied the least squares method and multitask learning. Results: A total of 1,142 patients with complete data were included in the study, with 992 allocated for model training and 150 for external validation. In predicting MFR, the DNN achieved a microaverage area under the receiver operating characteristic curve (AUC) of 0.884±0.006, sensitivity of 0.783±0.020, and specificity of 0.891±0.010. For VE prediction, the microaverage AUC was 0.817±0.007, with sensitivity and specificity values of 0.660±0.014 and 0.830±0.007, respectively. These results indicate that the DNN's predictive performance was superior to that of other ML models. Conclusions The DNN model provides detailed and accurate predictions for recovery after HoLEP, providing valuable insights for clinicians managing patients with LUTS/BPH.

Purpose: Predicting improvements in voiding symptoms following deobstructive surgery for male lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) is challenging when detrusor contractility is impaired. This study aimed to develop an artificial intelligence model that predicts symptom improvement after holmium laser enucleation of the prostate (HoLEP), focusing on changes in maximum flow rate (MFR) and voiding efficiency (VE) 1-month postsurgery. Methods: We reviewed 1,933 patients who underwent HoLEP at Samsung Medical Center from July 2008 to January 2024. The study employed a deep neural network (DNN) for multiclass classification to predict changes in MFR and VE, each divided into 3 categories. For comparison, additional machine learning (ML) models such as extreme gradient boosting, random forest classification, and support vector machine were utilized. To address class imbalance, we applied the least squares method and multitask learning. Results: A total of 1,142 patients with complete data were included in the study, with 992 allocated for model training and 150 for external validation. In predicting MFR, the DNN achieved a microaverage area under the receiver operating characteristic curve (AUC) of 0.884±0.006, sensitivity of 0.783±0.020, and specificity of 0.891±0.010. For VE prediction, the microaverage AUC was 0.817±0.007, with sensitivity and specificity values of 0.660±0.014 and 0.830±0.007, respectively. These results indicate that the DNN's predictive performance was superior to that of other ML models. Conclusions The DNN model provides detailed and accurate predictions for recovery after HoLEP, providing valuable insights for clinicians managing patients with LUTS/BPH.

Purpose: Predicting improvements in voiding symptoms following deobstructive surgery for male lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) is challenging when detrusor contractility is impaired. This study aimed to develop an artificial intelligence model that predicts symptom improvement after holmium laser enucleation of the prostate (HoLEP), focusing on changes in maximum flow rate (MFR) and voiding efficiency (VE) 1-month postsurgery. Methods: We reviewed 1,933 patients who underwent HoLEP at Samsung Medical Center from July 2008 to January 2024. The study employed a deep neural network (DNN) for multiclass classification to predict changes in MFR and VE, each divided into 3 categories. For comparison, additional machine learning (ML) models such as extreme gradient boosting, random forest classification, and support vector machine were utilized. To address class imbalance, we applied the least squares method and multitask learning. Results: A total of 1,142 patients with complete data were included in the study, with 992 allocated for model training and 150 for external validation. In predicting MFR, the DNN achieved a microaverage area under the receiver operating characteristic curve (AUC) of 0.884±0.006, sensitivity of 0.783±0.020, and specificity of 0.891±0.010. For VE prediction, the microaverage AUC was 0.817±0.007, with sensitivity and specificity values of 0.660±0.014 and 0.830±0.007, respectively. These results indicate that the DNN's predictive performance was superior to that of other ML models. Conclusions The DNN model provides detailed and accurate predictions for recovery after HoLEP, providing valuable insights for clinicians managing patients with LUTS/BPH.

Purpose: The current drain tubes for preventing surgically biliary anastomotic stricture are not naturally and easily removed. If a drain tube using biodegradable material is easily available and the degradation time of the tube is well controlled, surgical anastomotic stricture and fibrosis could be prevented. The aim of this animal study was to evaluate the preventive effect of novel biodegradable stents (BS) on biliary stricture and fibrosis after duct-to-duct (DD) biliary anastomosis. Methods: Ten mini-pigs were allocated to the control group (n = 5) and or the stent group (n = 5). The common bile duct was exposed through surgical laparotomy and then resected transversely. In the stent group, a 4-mm or 6-mm polydioxanone/ magnesium sheath-core BS was inserted according to the width of the bile duct, followed by DD biliary anastomosis. In the control group, DD biliary anastomosis was performed without BS insertion. Results: In the stent group, stents were observed without deformity for up to 4 weeks in all animals. Eight weeks later, histopathologic examination revealed that the common bile duct of the anastomosis site was relatively narrower in circumference in the control group compared to the stent group. The degree of fibrosis in the control group was more marked than in the stent group (3.84 mm vs. 0.68 mm, respectively; P < 0.05). Conclusion Our study showed that novel BS maintained their original shape and radial force for an adequate time and then disappeared without adverse events. The BS could prevent postoperative complications and strictures after DD biliary anastomosis.

Background/Aims: We examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication. Methods: A randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases. Results: In total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences. Conclusions TPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea

Background/Aims: The mucoprotective drug rebamipide is used to treat gastritis and peptic ulcers. We compared the efficacy of Mucosta Ⓡ (rebamipide 100 mg) and its new formulation, AD-203 (rebamipide 150 mg), in treating erosive gastritis. Methods: This double-blind, active control, noninferiority, multicenter, phase 3 clinical trial randomly assigned 475 patients with endoscopically proven erosive gastritis to two groups: AD-203 twice daily or Mucosta Ⓡ thrice daily for 2 weeks. The intention-to-treat (ITT) analysis included 454 patients (AD-203, n=229; Mucosta Ⓡ , n=225), and the per-protocol (PP) analysis included 439 patients (AD-203, n=224; Mucosta Ⓡ , n=215). The posttreatment assessments included the primary (erosion improvement rate) and secondary endpoints (erosion and edema cure rates; improvement rates of redness, hemorrhage, and gastrointestinal symptoms). Drug-related adverse events were evaluated. Results: According to the ITT analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta Ⓡ -treated patients were 39.7% and 43.8%, respectively. According to the PP analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta Ⓡ -treated patients were 39.3% and 43.7%, respectively. The one-sided 97.5% lower limit for the improvement rate difference between the study groups was −4.01% (95% confidence interval [CI], –13.09% to 5.06%) in the ITT analysis and −4.44% (95% CI, –13.65% to 4.78%) in the PP analysis. The groups did not significantly differ in the secondary endpoints in either analysis. Twenty-four AD-203-treated and 20 Mucosta Ⓡ -treated patients reported adverse events but no serious adverse drug reactions; both groups presented similar adverse event rates. Conclusions The new formulation of rebamipide 150 mg (AD-203) twice daily was not inferior to rebamipide 100 mg (Mucosta Ⓡ ) thrice daily. Both formulations showed a similar efficacy in treating erosive gastritis.