Long-lasting restoration of memory function and hippocampal synaptic plasticity by focused ultrasound in Alzheimer's disease

Background: Focused ultrasound (FUS) is a medical technology that non-invasively stimulates the brain and has been applied in thermal ablation, blood–brain barrier (BBB) opening, and neuromodulation. In recent years, numerous experiences and indications for the use of FUS in clinical and preclinical studies have rapidly expanded. Focused ultrasound-mediated BBB opening induces cognitive enhancement and neurogenesis; however, the underlying mechanisms have not been elucidated. Methods: Here, we investigate the effects of FUS-mediated BBB opening on hippocampal long-term potentiation (LTP) and cognitive function in a 5xFAD mouse model of Alzheimer's disease (AD). We applied FUS with microbubble to the hippocampus and LTP was measured 6 weeks after BBB opening using FUS. Field recordings were made with a concentric bipolar electrode positioned in the CA1 region using an extracellular glass pipette filled with artificial cerebrospinal fluid. Morris water maze and Y-maze was performed to test cognitive function. Results: Our results demonstrated that FUS-mediated BBB opening has a significant impact on increasing LTP at Schaffer collateral - CA1 synapses and rescues cognitive dysfunction and working memory. These effects persisted for up to 7 weeks post-treatment. Also, FUS-mediated BBB opening in the hippocampus increased PKA phosphorylation. Conclusion: Therefore, it could be a promising treatment for neurodegenerative diseases as it remarkably increases LTP, thereby improving working memory. © 2023 The Author(s)ope

Efficacy and safety of moderate-intensity statin with ezetimibe combination therapy in patients after percutaneous coronary intervention: a post-hoc analysis of the RACING trial

Background: Moderate-intensity statin role with ezetimibe combination therapy following percutaneous coronary intervention (PCI) has not been thoroughly investigated, particularly compared to high-intensity statin monotherapy. We aimed to investigate the effect of ezetimibe combination with moderate-intensity statin in patients with atherosclerotic cardiovascular disease following PCI. Methods: This was a post-hoc analysis of a subset of patients who underwent PCI in the RACING trial. At 26 centres in South Korea, patients with atherosclerotic cardiovascular disease (ASCVD) were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The prespecified endpoints of the RACING trial were used. The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, and nonfatal stroke. Event rates between the two groups were compared using log-rank tests, and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression analysis. Consistent with the RACING trial, the primary and secondary efficacy endpoints were evaluated using an intention-to-treatment approach, and the safety endpoints were assessed in the safety population. The RACING trial was registered at ClinicalTrials.gov (NCT03044665). Findings: Between Feb 14, 2017, and Dec 18, 2018, 3780 participants were enrolled in the RACING trial. Prior history of PCI was found in 2497 patients (67%, median 64 years, 79% male), and was associated with higher rates of the primary endpoint (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.06–1.69; p = 0.014). Among patients with prior PCI, moderate-intensity statin therapy with ezetimibe combination versus high-intensity statin therapy did not increase the risk of the primary endpoint (HR, 0.95; 95% CI, 0.74–1.24; p = 0.781). The proportion of patients with low-density lipoprotein cholesterol (LDL-C) <70 mg/dL at 1, 2, and 3 years was 74%, 76%, and 73%, respectively, in the combination therapy group, and was significantly higher than that in the high-intensity statin monotherapy group (57%, 62%, and 59%, respectively, all p < 0.001). Discontinuation of lipid-lowering drugs occurred less frequently in the combination group (4.2% vs. 7.6%, p = 0.001). Interpretation: The effects of ezetimibe combination therapy observed in the RACING trial were consistently preserved among patients with ASCVD following PCI. Ezetimibe combination could be considered as a suitable therapeutic strategy to achieve strict control of LDL-C and reduce drug intolerance in patients who underwent PCI. Funding: Hanmi Pharmaceutical, Seoul, South Korea © 2026 The Author(s)ope

Patterns and risk factors of cognitive decline among community-dwelling older adults in South Korea

Dementia prevalence is increasing worldwide. Thus, the global impact of cognitive impairment and dementia have become significant public health issues. This study assessed the patterns of and investigated risk factors associated with cognitive decline over time in community-dwelling Korean adults (age ≥65 years). We enrolled 1,369 older adult respondents without cognitive decline in the baseline survey of the Korean Longitudinal Study of Aging (2006-2016) in South Korea. The risk of first-ever mild-to-moderate or severe cognitive decline during the 10-year follow-up (2006-2016) was comparatively evaluated between the cognitive decline group (comprising participants with mild-to-moderate or severe cognitive decline; n = 728) and the normal cognition group (participants without a cognitive decline event; n = 641). The cognitive decline-free survival rates for up to ten years were measured using Kaplan-Meier analysis. The generalized estimation equations model was used to analyze changes in K-MMSE over time from 2006 to 2016. The adjusted Cox proportional hazards model revealed that increased age, female, lower education level, no religious status, and living in a small city were factors that were associated with a higher risk of cognitive decline, as were health-related factors, including lower handgrip strength, a higher number of chronic diseases, and depressive symptoms. Regular exercise, non-drinking status, and active social engagements reduced the risk of cognitive decline. The identified risk factors could facilitate the development of cognitive decline-prevention programs incorporating individualized risk-modification interventions to prevent cognitive decline in older adults.ope

Statin use is associated with better post-operative prognosis among patients with hepatitis B virus-related hepatocellular carcinoma

Background: The high postoperative recurrence rate of hepatocellular carcinoma (HCC) is a significant challenge. Patient metabolic factors are potential disease modifiers and should be examined as risk factors for postoperative prognosis. Here, we assessed the association between long-term statin use and HCC recurrence after surgical resection of hepatitis B virus (HBV)-related HCC.Methods: Patients who initially underwent curative resection for HBV-related HCC between 2005 and 2015 were recruited and followed up until December 2019. Patients were classified into statin user and non-statin user groups based on whether or not they had been prescribed statins for >= 2 years. The primary outcome was HCC recurrence, and the secondary outcome was liver-related mortality. The cumulative incidence by statin use was estimated using the Kaplan-Meier method and compared using the log-rank test. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression.Results: Among 5653 patients with a median 6.1 years of follow-up, HCC recurrence and liver-related mortality occurred in 1603 and 316 patients, respectively. The 5-year cumulative incidence of HCC recurrence in the statin user group (15.9%) was significantly lower than that in the non-user group (21.3%; p = .019). From multivariable Cox regression analysis, statin use was significantly associated with a reduced risk of HCC recurrence (aHR 0.77, 95% CI: 0.61-0.98; p = .035) and liver-related mortality (aHR 0.48, 95% CI: 0.25-0.90; p = .023).Conclusion: Long-term statin use was significantly associated with reduced risk of HCC recurrence and liver-related mortality after curative resection of HBV-related HCC.restrictio

Effect of Preoperative Administration of Intravenous Ferric Carboxymaltose in Patients with Iron Deficiency Anemia after Off-Pump Coronary Artery Bypass Grafting: A Randomized Controlled Trial

Patients scheduled for cardiac surgery often have anemia and iron deficiency. We investigated the effect of the preoperative administration of intravenous ferric carboxymaltose (IVFC) in patients with iron deficiency anemia (IDA) who were due to undergo off-pump coronary artery bypass grafting (OPCAB). Patients who were due to undergo elective OPCAB between February 2019 and March 2022 who had IDA (n = 86) were included in this single center, randomized, parallel-group controlled study. The participants were randomly assigned (1:1) to receive either IVFC or placebo treatment. Postoperative hematologic parameters [hemoglobin (Hb), hematocrit, serum iron concentration, total iron-binding capacity, transferrin saturation, transferrin concentration, and ferritin concentration] and the changes in these parameters during the follow-up period were the primary and secondary outcomes, respectively. The tertiary endpoints were early clinical outcomes, such as the volume of mediastinal drainage and the need for blood transfusions. IVFC treatment significantly reduced the need for red blood cell (RBC) and platelet transfusions. Despite receiving fewer RBC transfusions, patients in the treatment group had higher levels of Hb, hematocrit, and serum iron and ferritin concentrations during weeks 1 and 12 after surgery. No serious adverse events occurred during the study period. Preoperative IVFC treatment in patients with IDA undergoing OPCAB improved the values of the hematologic parameters and iron bioavailability. Therefore, is a useful strategy for stabilizing patients prior to OPCAB.ope

Development and Characterization of Synthetic Norovirus RNA for Use in Molecular Detection Methods

Background: Reference materials are essential for the quality assurance of molecular detection methods. We developed and characterized synthetic norovirus GI and GII RNA reference materials. Methods: Norovirus GI and GII RNA sequences including the ORF1-ORF2 junction region were designed based on 1,495 reported norovirus sequences and synthesized via plasmid preparation and in vitro transcription. The synthetic norovirus GI and GII RNAs were evaluated using six commercial norovirus detection kits used in Korea and subjected to homogeneity and stability analyses. A multicenter study involving five laboratories and using four commercial real-time PCR norovirus detection assays was conducted for synthetic norovirus RNA characterization and uncertainty measurements. Results: The synthetic norovirus GI and GII RNAs were positively detected using the six commercial norovirus detection kits and were homogeneous and stable for one year when stored at -20°C or -70°C. All data from the five laboratories were within a range of 1.0 log copies/μL difference for each RNA, and the overall mean concentrations for norovirus GI and GII RNAs were 7.90 log copies/μL and 6.96 log copies/μL, respectively. Conclusions: The synthetic norovirus GI and GII RNAs are adequate for quality control based on commercial molecular detection reagents for noroviruses with high sequence variability. The synthetic RNAs can be used as reference materials in norovirus molecular detection methods.ope

Digital cognitive behavioral therapy for insomnia on depression and anxiety: a systematic review and meta-analysis

Despite research into the development of digital cognitive behavioral therapy for insomnia (dCBT-I), research into the outcomes of dCBT-I on insomnia and the associated clinical conditions of depression and anxiety have been limited. The PubMed, PsycINFO (Ovid), Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) on adult patients with insomnia also having reported measures of depressive or anxiety symptoms. In total, 2504 articles were identified after duplicate removal, and 22 RCTs were included in the final meta-analysis. At the post-treatment assessment, the dCBT-I group had a small to moderate effect in alleviating depressive (standardized mean difference (SMD) = -0.42; 95% CI: -0.56, -0.28; p < 0.001; k = 21) and anxiety symptoms (SMD = -0.29; 95% CI: -0.40, -0.19; p < 0.001; k = 18), but had a large effect on sleep outcome measures (SMD = -0.76; 95% CI: -0.95, -0.57; p < 0.001; k = 22). When considering treatment adherence, the treatment effects of those in the high adherent groups identified a more robust outcome, showing greater effect sizes than those in the low adherent groups for depression, anxiety, and sleep outcomes. Furthermore, additional subgroup analysis on studies that have used the fully automated dCBT-I treatment without the support of human therapists reported significant treatment effects for depression, anxiety, and sleep outcomes. The results demonstrated that digital intervention for insomnia yielded significant effects on alleviating depressive and anxiety symptoms as well as insomnia symptoms. Specifically, the study demonstrated significant effects on the above symptoms when considering treatment adherence and implementing fully automated dCBT-I.ope

The Expression of Programmed Death-Ligand 1 on Immune Cells Is Related to a Better Prognosis in Biliary Tract Cancer

Background/Aims: Programmed death-ligand 1 (PD-L1) expression in tumor cells is associated with a poor biliary tract cancer (BTC) prognosis; tumor-infiltrating immune cells in the tumor microenvironment are associated with a better prognosis. The effect of PD-L1 expression on immune cells on survival is unclear. We investigated the relationship between PD-L1 expression in immune cells and BTC prognosis. Methods: PD-L1 expression was evaluated using an anti-PD-L1 22C3 mouse monoclonal primary antibody, and its relationships with clinical characteristics and prognosis were analyzed using the Cox proportional hazard model to investigate the prognostic performance of PD-L1 in BTC. Results: Among 144 analyzed cases, patients with positive PD-L1 expression in tumor cells and negative PD-L1 expression in immune cells showed poorer overall survival rates than those exhibiting other expressions (tumor cells: hazard ratio [HR]=1.023, p<0.001; immune cells: HR=0.983, p=0.021). PD-L1 expression in tumor cells was an independent predictor of poor overall survival (HR=1.024, p<0.001). In contrast, PD-L1 expression in immune cells was a predictive marker of good prognosis (HR=0.983, p=0.018). Conclusions: PD-L1 expression in immune cells may be used as an independent factor to evaluate the prognosis of patients with BTC. (Gut Liver, Published online December 13, 2022)ope

Practical role of preoperative echocardiography in low-risk non-cardiac surgery

Background: Due to increased needs to reduce non-fatal as well as fatal cardiac events, preoperative echocardiography remains part of routine clinical practice in many hospitals. Data on the role of preoperative echocardiography in low-risk non-cardiac surgery (NCS) other than ambulatory surgeries do not exist. We aimed to investigate the role of preoperative echocardiography in predicting postoperative adverse cardiovascular events (CVEs) in asymptomatic patients undergoing low-risk NCS. Methods: The study population was derived from a retrospective cohort of 1,264 patients who underwent elective low-risk surgery at three tertiary hospitals from June 1, 2021, to June 30, 2021. Breast, distal bone, thyroid, and transurethral surgeries were included. Preoperative examination data including electrocardiography, chest radiography, and echocardiography were collected. The primary outcome was a composite of postoperative adverse CVEs including all-cause death, myocardial infarction, cerebrovascular events, newly diagnosed or acutely decompensated heart failure (HF), lethal arrhythmia such as sustained ventricular tachycardia/fibrillation, and new-onset atrial fibrillation within 30 days after the index surgery. Results: Preoperative echocardiography was performed in 503 patients (39.8%), most frequently in patients with breast surgery (73.5%), followed by transurethral (37.7%), distal bone (21.6%), and thyroid surgeries (11.9%). Abnormal findings were observed in 5.0% of patients with preoperative echocardiography. Postoperative adverse CVEs occurred in 10 (0.79%) patients. Although a history of previous HF was an independent predictor of postoperative CVE occurrence (adjusted odds ratio, aOR: 17.98; 95% confidence interval, CI: 1.21–266.71, P = 0.036), preoperative echocardiography did not significantly predict CVE in multivariate analysis (P = 0.097). However, in patients who underwent preoperative echocardiography, the presence of abnormal echocardiographic findings was independently associated with development of CVE after NCS (aOR: 23.93; 95% CI: 1.2.28–250.76, P = 0.008). In particular, the presence of wall motion abnormality was a strong predictor of postoperative adverse CVE. Conclusion: In real-world clinical practice, preoperative echocardiography was performed in substantial number of patients with potential cardiac risk even in low-risk NCS, and abnormal findings were independently associated with postoperative CVE. Future studies should identify patients undergoing low-risk NCS for whom preoperative echocardiography would be helpful to predict adverse CVE.ope

Feasibility of the virtual reality-based assessments in patients with panic disorder

Introduction: Recurrences and diagnostic instability of panic disorder (PD) are common and have a negative effect on its long-term course. Developing a novel assessment tool for anxiety that can be used in a multimodal approach may improve these problems in panic disorder patients. This study assessed the feasibility of virtual reality-based assessment in panic disorder (VRA-PD). Methods: Twenty-five patients with PD (ANX group) and 28 healthy adults (CON group) participated in the study. VRA-PD consisted of four modules based on the key components of cognitive behavior therapy for an anxiety disorder: “Baseline evaluation module” (M0), “Daily environment exposure module” (M1), “Relaxation module” (M2), and “Interoceptive exposure module” (M3). Multiple evaluations, including self-rating anxiety scores (AS) and physiological responses [heart rate variability (HRV) index], were performed in three steps at M1, M2, and M3, and once at M0. Comparisons between patients with PD and healthy controls, factor analysis of variables in VRA-PD, changes in responses within modules, and correlation analysis between variables in VRA-PD and anxiety symptoms assessed by psychological scales were performed. Results : All participants completed the VRA-PD without discontinuation. The ANX group reported significantly higher AS for all steps and a smaller HRV index in M1 (steps 1 and 2) and M2 (step 1). Repeated-measures analysis of covariance (ANCOVA) revealed significant interaction effects for AS in M1 (F = 4.09, p = 0.02) and M2 (F = 4.20, p = 0.02), and HRV index in M2 (F = 16.22, p < 0.001) and M3 (F = 21.22, p = 0.02). The HRV index only indicated a good model fit for the three-factor model, reflecting the construct of the VRA-PD. Both AS and HRV indexes were significantly correlated with anxiety and depression symptoms. Discussion : The current study provides preliminary evidence that the VRA-PD could be a valid anxiety behavior assessment tool.ope