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Ethnopharmacological Relevance: Uncaria rhynchophylla (UR) is recognized for its therapeutic applications in treating hypertension and inflammation. However, the specific molecular mechanisms how UR and its bioactive constituents modulate inflammatory pathways remain unknown. This study investigates the effects of UR extract and its constituent, hirsuteine (HST), on TRPV1 channel modulation which is related to hypertension and inflammation., Materials and Methods: Electrophysiological recordings and calcium imaging experiments were conducted to assess TRPV1 activation by UR extract and HST in HEK293T cells and sensory neurons., Results: UR extract and HST activated TRPV1 in HEK293T cells, with repeated applications causing channel desensitization. HST application on TRPV1-positive sensory neurons significantly reduced electrical activity compared to capsaicin., Conclusion: This study demonstrated UR extract and HST are a novel TRPV1 agonists inducing channel desensitization and a potent agent for treatment of TRPV1 dependent pain relief., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 KIST. Published by Elsevier B.V. All rights reserved.)

Purpose: This study aimed to compare the pain-related behavioral and physiological responses and puncture-related characteristics between automated and laser lancets and examine the correlation between infants' pain-related responses and facial expressions during heel lancing in a neonatal intensive care unit. Methods: Pain-related responses were assessed using the Neonatal Infant Pain Scale, heart rate, and oxygen saturation through pulse oximetry. Facial expressions were also analyzed using a facial recognition application. Puncture-related characteristics were assessed through puncture marks, number of punctures, and hemostasis. Results: There was a significantly higher puncture mark frequency at 3 min in the automated lancet group than in the laser lancet group. There were no interaction effects of time and group on pain-related behavioral response, heart rate, or oxygen saturation. There were significant positive correlations between the pain-related behavioral response and anger, disgust, fear, and sadness. Conclusion: The laser lancet had relatively good outcomes regarding puncture-related characteristics, although there was no significant difference in pain-related responses. A laser lancet is a novel option for preterm babies at risk of scar-related inflammation and coagulopathies.

Extensive neovascularization is a hallmark of glioblastoma (GBM). In addition to supplying oxygen and nutrients, vascular endothelial cells provide trophic support to GBM cells via paracrine signaling. Here we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity. Mechanistically, Endocan exerts at least part of its functions via direct binding and activation of the PDGFRA receptor. Subsequent downstream signaling enhances chromatin accessibility of the Myc promoter and upregulates Myc expression inducing stable phenotypic changes in GBM cells. Furthermore, Endocan confers radioprotection on GBM cells in vitro and in vivo. Inhibition of Endocan-PDGFRA signaling with ponatinib increases survival in the Esm1 wild-type but not in the Esm1 knock-out mouse GBM model. Our findings identify Endocan and its downstream signaling axis as a potential target to subdue GBM recurrence and highlight the importance of vascular-tumor interactions for GBM development., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Several donor-specific factors influence the functional recovery and long-term outcomes of liver grafts. This study investigated the association between donor fasting glucose (DFG) and recipient outcomes after living donor liver transplantation (LDLT) in 950 cases at a single center. Patients were divided into two groups: low-DFG (< 85 mg/dL, n = 120) and control (≥ 85 mg/dL, n = 830). The five-year graft survival rate was significantly lower in the low-DFG group (71.5%) compared to the control group (80.0%) (P = 0.02). Multivariable Cox regression analysis showed that low DFG was independently associated with graft loss (hazard ratio 1.72, 95% CI 1.15-2.56, P = 0.008). In propensity score-matched groups, the low-DFG group also had lower survival rates (71% vs. 83.1%, P = 0.004). The presence of additional risk factors, such as low graft-to-recipient weight ratio, older donor age, and longer cold ischemic time, further reduced graft survival in the low-DFG group. A DFG level < 85 mg/dL is associated with higher risk of graft failure after LDLT, especially when combined with other risk factors. Low DFG should be considered a prognostic marker in LDLT planning, with potential to improve patient outcomes as further research clarifies the underlying pathophysiological mechanisms., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Hermansky-Pudlak syndrome (HPS), both alone and in conjunction with pulmonary fibrosis (HPS-PF), is a rare, genetically heterogeneous, autosomal recessive disorder that affects multiple organs, including the lungs. In cases of HPS-PF, pulmonary fibrosis is preceded by local inflammation. We present a case of HPS-PF that exhibited histological evidence of extracellular traps (ETs) ensnaring macrophages, leading to cell death in a process known as ETosis. To our knowledge, ETosis has not been previously reported in the HPS-PF population and may represent a mechanism by which pulmonary fibrosis develops in these patients. Further research is needed to explore the potential connection between ETosis and HPS-PF, as this understanding could offer insights into the disease mechanism and pave the way for the development of novel treatment modalities.

Benign prostatic hyperplasia (BPH) is a distressing health problem that can cause serious complications in aging men. Androgens are implicated in the causation of BPH. Portulaca oleracea (PO) is a natural product with diverse pharmacological effects. The objective of this study was to investigate the effect of PO in a rat model of testosterone propionate (TP)-induced BPH and explore the underlying mechanisms. Thirty-five Sprague-Dawley (SD) rats were divided into the following equal groups (n = 7): normal control (NC) group, TP (3 mg/kg) group, finasteride (10 mg/kg) group, 25 and 50 mg/kg PO groups. At the end of the experiment, the body weights (BWs) of the rats were measured before they were euthanized to the establishment obtain serum and prostate weight (PW). TP-induced levels of androgen-related proteins in the prostate were also investigated. In the TP group, prostate size, BW, serum DHT level, prostate epithelial cell thickness and androgen-related protein level were higher than those in the NC group (p < 0.001). PO reversed TP-induced BPH in a dose-dependent manner (p < 0.01) and its effect was similar to that of finasteride. A similar effect of PO on the androgen-related protein level was also observed. We successfully established a TP-induced BPH rat model. This is the first study to demonstrate that inhibition of androgen-related proteins using PO can alleviate BPH., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Objective: To analyze the results of excluding confusable diseases in patients with a presumptive diagnosis of interstitial cystitis (IC)., Methods: We retrospectively reviewed the electronic medical records of consecutive patients with IC between October 2005 and December 2019., Results: Patients with pelvic pain underwent an initial workup. Of these, 646 patients (164 men, 25.4%; 482 women, 74.6%) underwent observational cystoscopy under the suspicion of IC. Fourteen patients had genitourinary tract malignancies (2.2%) (bladder cancer, n = 13; prostate cancer, n = 1). Of the 13 patients with bladder cancer, three were diagnosed during initial observation cystoscopy. The remaining 10 patients were diagnosed during subsequent follow-up cystoscopic surgery. Urinary tuberculosis was identified in seven (1.1%) of 646 patients during the examination. Five (0.8%) of the six patients with suspected urinary tuberculosis at baseline imaging were positive for tuberculosis in the acid-fast bacillus test. One patient developed tuberculous granulomas in the bladder tissue after a cystectomy for intractable pelvic pain., Conclusion: Our results show that continuous efforts to rule out bladder tumors or tuberculosis are still essential in the follow up of patients with suspected IC, even if these diseases are not excluded at the initial examination. Imaging studies are necessary to rule out tuberculosis., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Competing Interests: Disclosures: Sun Jung Kim, Min Young Park, Seung Yoon Yang, Yoon Dae Han, Min Soo Cho, Hyuk Hur, Kang Young Lee, and Byung Soh Min have no financial interests to disclose.

Aim: This study examined the efficacy of AST-001 for the core symptoms of autism spectrum disorder (ASD) in children., Methods: This phase 2 clinical trial consisted of a 12-week placebo-controlled main study, a 12-week extension, and a 12-week follow-up in children aged 2 to 11 years with ASD. The participants were randomized in a 1:1:1 ratio to a high-dose, low-dose, or placebo-to-high-dose control group during the main study. The placebo-to-high-dose control group received placebo during the main study and high-dose AST-001 during the extension. The a priori primary outcome was the mean change in the Adaptive Behavior Composite (ABC) score of the Korean Vineland Adaptive Behavior Scales II (K-VABS-II) from baseline to week 12., Results: Among 151 enrolled participants, 144 completed the main study, 140 completed the extension, and 135 completed the follow-up. The mean K-VABS-II ABC score at the 12th week compared with baseline was significantly increased in the high-dose group (P = 0.042) compared with the placebo-to-high-dose control group. The mean CGI-S scores were significantly decreased at the 12th week in the high-dose (P = 0.046) and low-dose (P = 0.017) groups compared with the placebo-to-high-dose control group. During the extension, the K-VABS-II ABC and CGI-S scores of the placebo-to-high-dose control group changed rapidly after administration of high-dose AST-001 and caught up with those of the high-dose group at the 24th week. AST-001 was well tolerated with no safety concern. The most common adverse drug reaction was diarrhea., Conclusions: Our results provide preliminary evidence for the efficacy of AST-001 for the core symptoms of ASD., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Acute-on-chronic liver failure (ACLF) is a syndrome of patients with chronic liver disease presenting with multiple organ failures. Recently, Sundaram-ACLF-LT Mortality (SALT-M) score has been developed to predict 1-year post-liver transplantation mortality. We validated the SALT-M score in a large-volume, Asian single-centre cohort., Aims: We validated the SALT-M score in a large-volume, Asian single-centre cohort., Methods: We analysed 224 patients of ACLF grade 2-3. Area under the receiver operating characteristic curve (AUROC) and concordance index (c-index) were used to assess and compare the predictability of posttransplant mortality of SALT-M and other scores. Moreover, we compared the survivals of patients with high and low SALT-M, in conjunction with MELD score and ACLF grade., Results: The AUROC for prediction of 1-year post-LT survival was higher in SALT-M (0.691) than in MELD, MELD-Na, MELD 3.0 and delta-MELD. Similarly, the c-index of the SALT-M (0.650) was higher than aforementioned MELD systems. When categorised by the cut-off of SALT-M ≥ 20 and MELD ≥ 30, patients with high SALT-M exhibited lower post-LT survival than those with low SALT-M scores regardless of high or low MELD (40.0% for high SALT-M/high MELD vs. 42.9% for high SALT-M/low MELD vs. 73.8% for low SALT-M/high MELD vs. 63.7% for low SALT-M/low MELD, p < 0.001). In patients with ACLF grade 3, SALT-M effectively stratified the posttransplant mortality (39.4% for high SALT-M vs. 63.1% for low SALT-M, p = 0.018)., Conclusions: SALT-M outperformed previous MELD systems for predicting posttransplant mortality in Asian LT cohort with severe ACLF. Transplantability for patients with severe ACLF could be determined based on SALT-M., (© 2024 John Wiley & Sons Ltd.)

Background: Performing laparoscopic surgery for T4 colon cancer remains controversial because of concerns about whether its oncologic outcomes are comparable to those of open surgery, and postoperative peritoneal metastasis (PM) has been reported to occur more frequently in laparoscopic colectomy for T4 colon cancer. We investigated whether minimally invasive surgery (MIS) demonstrated a higher PM rate than open surgery and analyzed the risk factors for PM in pT4 colon cancer., Methods: This study included 392 patients with pT4 colon cancer who underwent curative surgery at a referral hospital between January 2000 and December 2018. Patients with previous neoadjuvant therapy, synchronous malignancy, metastasis, or those who underwent hyperthermic intraperitoneal chemotherapy were excluded., Results: The MIS group had fewer high-risk clinical features, such as tumors too large for endoscope admission or complications like perforation and fistula. The group also exhibited shorter operative time, intraoperative blood loss, multivisceral resection, hospital stay, fewer postoperative complications, smaller tumor size, lower pT4b ratio, and higher pN+ rates. Multivariate analysis revealed that high-risk clinical features, MIS, pT4b, pN+, tumor size < 5 cm, high histological grade, lymphovascular invasion, and postoperative complications were significant risk factors for PM. During the median 59-month follow-up, the 5-year cumulative incidence of PM was elevated in the MIS group (17.5% vs. 8.2%; P = 0.057). No significant differences were observed in the 5-year overall and disease-free survival rates., Conclusions: Minimally invasive surgery increases the risk of postoperative PM in patients with pT4 colon cancer. Surgeons may require thorough tumor staging and radical resection to prevent PM., Competing Interests: Disclosure: All authors participating in this study have no financial interest to disclose. Ethics Approval: This study was approved by the Institutional Review Board of Severance Hospital, Yonsei College of Medicine (approval no. 4 2022 0555). The committee waived the requirement for informed consent because this was a retrospective review of patient records. Informed Consent: The requirement for written informed consent was waived owing to the observational nature of the study., (© 2024. Society of Surgical Oncology.)

The inhibitory effect of Chrysanthemum indicum L. on adipocyte differentiation can be enhanced by lactic acid bacteria (LAB) fermentation. In this study, we assessed the cellulose resolution, C. indicum L. quantity, and fermentation time and process to verify the LAB selection and fermentation efficiency. In addition, the antioxidant activity, adipocyte signaling and differentiation, and hedgehog (Hh) signaling were investigated, and the changes in compounds before and after fermentation were determined by ultra-high performance liquid chromatography (UHPLC). All strains exhibited satisfactory cellulose resolution. With 20% C. indicum L., fermentation was only effective up to 24 h. The results of the antioxidant assays showed that the 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical scavenging capacities were higher in all fermentations than in unfermented C. indicum L. extract (CI). 3T3-L1 cell differentiation signaling evaluation revealed that CI inhibited adipocyte differentiation by reducing peroxisome proliferator-activated receptor-γ, CCAAT/enhancer binding protein-α, and phosphorylated AMP-activated protein kinase activity in all fermentations. In the Hh signaling analysis, CI fermented with Lactococcus lactis KCTC 3115 significantly increased glioma-associated oncogene 1 (GLI1) activity by inhibiting patched 1 activity and activating smoothened ( P <0.001). UHPLC quantitative analysis revealed elevated levels of luteolin and quercetin. Fermentation with C. indicum L. and L. lactis KCTC 3115 activated GLI1, a transcription factor in the Hh signaling pathway, which enhanced the inhibition of adipocyte differentiation, indicating its potential in anti-obesity treatment. However, the exact compounds affecting GLI1 activity require further elucidation in future studies., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (© 2024 The Korean Society of Food Science and Nutrition.)

Exercise influences clinical Achilles tendon health in humans, but animal models of exercise-related Achilles tendon changes are lacking. Moreover, previous investigations of the effects of treadmill running exercise on rat Achilles tendon demonstrate variable outcomes. Our objective was to assess the functional, structural, cellular, and biomechanical impacts of treadmill running exercise on rat Achilles tendon with sensitive in and ex vivo approaches. Three running levels were assessed over the course of 8 weeks: control (cage activity), moderate-speed (treadmill running at 10 m/min, no incline), and high-speed (treadmill running at 20 m/min, 10° incline). We hypothesized that moderate-speed treadmill running would beneficially impact tendon biomechanics through increased tenocyte cellularity, metabolism, and anabolism whereas high-speed treadmill running would cause a tendinopathic phenotype with compromised tendon biomechanics due to pathologic tenocyte differentiation, metabolism, and catabolism. Contrary to our hypothesis, treadmill running exercise at these speeds had a nominal effect on the rat Achilles tendon. Treadmill running modestly influenced tenocyte metabolism and nuclear aspect ratio as well as viscoelastic tendon properties but did not cause a tendinopathic phenotype. These findings highlight the need for improved models of exercise- and loading-related tendon changes that can be leveraged to develop strategies for tendinopathy prevention and treatment., (© 2024 The Author(s). Journal of Orthopaedic Research published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Background: Living donor liver transplantation (LDLT) offers timely curative treatment for unresectable hepatocellular carcinoma (HCC). This study aims to validate and compare previous prediction models for HCC outcomes in 488 LDLT recipients., Methods: For 488 patients who underwent LDLT for HCC, pretransplant imaging studies assessed by modified RECSIT criteria, tumor markers such as alpha feto-protein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA II), and explant pathology were recruited. C-index of models for the HCC outcomes was compared, followed by further investigation for the predictive performances of the best model., Results: We found MoRAL (11√PIVKA-II + 2√AFP) demonstrated a higher C-index for HCC recurrence than other models that included radiologically viable tumor number and/or size (MoRAL: 0.709, Milan: 0.537, UCSF: 0.575, Up-to-7: 0.572, French AFP: 0.634, Pre-MORAL: 0.637, HALT-HCC: 0.626, Metroticket2.0: 0.629) and also had the highest C-index for HCC-specific deaths (0.706). Five-year HCC recurrence was well stratified upon dividing the patients into three groups by MoRAL cutoffs (11.9% for MoRAL < 100, 29.6% for MoRAL 100-200, and 48.6% for MoRAL > 200, p < 0.001). However, patients with major vessel invasion or portal vein tumor thrombus showed similarly high HCC recurrence regardless of this grouping (p = 0.612)., Conclusion: The MoRAL, based on tumor markers, showed the best predictive performance for HCC recurrence and HCC-specific death among the validated models, except in cases with major vessel invasion or portal vein tumor thrombus., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The crystal phase of pseudocapacitive materials significantly influences charge storage kinetics and capacitance; yet, the underlying mechanisms remain poorly understood. This study focuses on tungsten oxide (WO 3 ), a material exhibiting multiple crystal phases with potential for energy storage. Despite extensive research on WO 3 , the impact of different crystal structures on charge storage properties remains largely unexplored. Here, the successful synthesis and electrochemical characterization of tetragonal WO 3 are reported. This investigation demonstrates that tetragonal WO 3 exhibits superior energy storage capabilities compared to other WO 3 polymorphs. According to in situ Raman spectroscopy and ultraviolet photoelectron spectroscopy combined with in-depth electrochemical analyses, this enhancement is attributed to a unique charge storage mechanism and an expanded potential window facilitated by an engineered electrode work function. This study highlights the critical role of the crystal phase in optimizing the performance of pseudocapacitive materials and provides valuable insights for the development of next-generation energy storage devices., (© 2024 Wiley‐VCH GmbH.)

Background: Huntington disease (HD), a neurodegenerative autosomal dominant disorder, is characterized by involuntary choreatic movements with cognitive and behavioral disturbances. Up to now, no therapeutic strategies are available to completely ameliorate the progression of HD. Schisandra chinensis has various pharmacologic effects such as antioxidant and anti-inflammatory activities. However, the neuroprotective value of seed oil of S. chinensis (SOSC) has not been elucidated yet. The purpose of this study was to determine neuroprotective effects of SOSC by supercritical fluid extraction against 3-nitropropionic acid (3-NPA)-induced HD-like symptoms and neuropathology in an experimental mouse model., Methods: SOSC (75, 150, and 300 mg/kg/day) was orally pre-administration once daily at 1 hour before 3-NPA intoxication., Results: SOSC ameliorated movement dysfunction and lethality following 3-NPA intoxication in connection with reduction of lesion area, neurodegeneration/apoptosis, microglial migration/activation, and mRNA expression of pro-inflammatory cytokines/enzymes in the striatum. SOSC inhibited the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPKs) pathways but stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) in the striatum after 3-NPA intoxication. Schizandrin, a main component of SOSC, reduced protein expression levels of Iba-1 and p-NF-κB in 3-NPA-induced BV2 cells (murine microglia cell line). BV2 cell's conditioned medium inhibited cleaved caspase-3 in 3-NPA-induced SH-SY5Y cells (a neuroblastoma cell line)., Conclusion: SOSC might ameliorate movement dysfunction by inhibiting neuropathology through its anti-inflammatory and antioxidant activities in the striata of 3-NPA-intoxicated mice. These findings suggest that SOSC could serve as a promising therapeutic candidate for HD-like symptoms, providing a foundation for future treatment strategies targeting neuroinflammation and oxidative stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Jo, Lee, Son, Jang, Woo Kwon, Ha, Moon, Kim and Cho.)

Introduction: Although previous studies have shown that severe medial knee osteoarthritis (OA) (Kellgren-Lawrence grade IV) is a risk factor for patient dissatisfaction following medial open-wedge high tibial osteotomy (MOWHTO), it is uncommon to perform arthroplasty as a primary surgical option in patients 55 years of age or younger. Thus, the purpose of our study was to evaluate whether severe medial knee OA is a risk factor for dissatisfaction following MOWHTO depending on patient age based on a cutoff of 55 years., Material and Methods: We retrospectively reviewed the data of 270 consecutive patients who underwent MOWHTO with a minimum of 2 years of follow up. Patients were divided into 2 groups based on satisfaction following surgery, a Satisfied group (new Knee Society Score satisfaction subscore >20) and a Dissatisfied group (≤20). In order to assess risk factors for patient dissatisfaction depending on the age range, a subgroup analysis was conducted based on a cutoff age of 55 years. Preoperative demographics, OA grade, articular cartilage and meniscus status, severity of varus deformity, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and surgical factors were compared., Results: At 2 years after surgery, binomial logistic regression analysis showed that severe medial knee OA was associated with patient dissatisfaction following HTO in the entire cohort (odds ratio [OR] 4.557, 95% confidence interval [CI] 2.300-9.030, p < 0.001). In subgroup analysis depending on age range, severe medial OA was not a risk factor for dissatisfaction in the age ≤55 years group. However, severe medial knee OA in the age >55 years group was a significant risk factor for dissatisfaction after MOWHTO (OR 6.78, 95% CI 2.979-15.431, p < 0.001)., Conclusion: Severe medial OA was not a risk factor for dissatisfaction in patients age 55 years or younger who underwent MOWHTO. Therefore, surgeons can take this result into account when counseling younger patients considering MOWHTO., Level of Evidence: III., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Various acupuncture clinical trials have been conducted on migraine; however, the conclusions remain controversial especially when acupuncture was compared with sham acupuncture. Sham acupuncture is sometimes performed at the same acupuncture points used for verum acupuncture despite the evidence on acupuncture point specificity. Four databases were searched for sham acupuncture or waiting list-controlled acupuncture trials for migraine on December 25, 2023. Sham acupuncture was classified according to the needling points: sham acupuncture therapy at verum points (SATV) or at sham points (SATS). Network meta-analysis was performed based on the frequentist framework for headache pain intensity and response rate. A total of 18 studies involving 1936 participants were analyzed. Headache pain intensity and response rate were significantly improved in verum acupuncture compared with SATS. However, there was no significant difference between SATV and verum acupuncture. When comparing SATS and SATV, there was no significant difference in headache pain intensity and response rate; however, the results were in favor of SATV. The effect of the risk of bias on the certainty of evidence between verum and sham acupunctures was judged to be generally low. SATV should not be misused as a placebo control to evaluate the efficacy of acupuncture., Competing Interests: Compliance with ethics guidelines. Conflicts of interest Boram Lee, Chan-Young Kwon, Hye Won Lee, Arya Nielsen, L Susan Wieland, Tae-Hun Kim, Stephen Birch, Terje Alraek and Myeong Soo Lee declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee., (© 2024. Higher Education Press.)

Background: Several risk prediction models are used in intensive care units (ICUs) to detect delirium risk., Objective: The aim of this study was to compare the sex-specific validity of the Prediction of Delirium in ICU patients (PRE-DELIRIC) and Early Prediction of Delirium in ICU patients (E-PRE-DELIRIC) models for predicting delirium in ICU patients after cardiac surgery., Methods: Retrospective data from electronic medical records of ICU patients who underwent cardiac surgery between January 2019 and December 2022 were examined. Both models were evaluated using sensitivity, specificity, and positive and negative predictive values based on the highest Youden index for female and male patients. Receiver operating characteristic curve analysis was performed., Results: Delirium incidence was 30.7% and 27.5% in female and male patients, respectively. In the PRE-DELIRIC model, the highest Youden index scores for female and male patients were 67.00 and 57.54, respectively, with sensitivities and specificities of 61% and 88%, and 72% and 79%, respectively. In the E-PRE-DELIRIC model, the highest scores for female and male patients were 14.25 and 14.05, with sensitivities and specificities of 78% and 50%, and 70% and 53%, respectively. The area under the curve of the PRE-DELIRIC model for female and male patients was 0.77 and 0.78, respectively, and that of the E-PRE-DELIRIC model was 0.67 and 0.63, respectively., Conclusions: The PRE-DELIRIC model showed higher specificity and was more reliable for male patients, whereas the E-PRE-DELIRIC model demonstrated better sensitivity for female patients due to its inclusion of more female-sensitive factors. A combined approach is recommended for improved reliability and validity in delirium risk assessment in clinical settings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Whether telomere length (TL), an indicator of biological ageing, reflects Alzheimer's disease (AD)-related neuropathological change remains unclear. We investigated the relationships between TL, in vivo AD pathologies, including cerebral beta-amyloid and tau deposition, and cognitive outcomes in older adults., Methods: A total of 458 older adults were included, encompassing both cognitively normal (CN) individuals and those cognitively impaired (CI), with the CI group consisting of individuals with mild cognitive impairment or AD dementia. All participants underwent clinical and neuropsychological assessments, amyloid positron emission tomography (PET) scan and DNA extraction for measuring TL at baseline. A subset of participants (n=140) underwent tau PET scan. At follow-up, the participants underwent neuropsychological assessments annually for up to 4 years., Results: Overall, longer TL was associated with greater brain tau deposition (B=0.139, 95% CI 0.040, 0.238) and a faster decline in global cognition (B = - 0.371, 95% CI - 0.720, -0.023). In the subgroup analysis, the association between longer TL and greater in vivo AD pathologies, as well as faster cognitive decline, was observed particularly in the CI group. Mediation analysis suggested that longer TL was associated with cognitive decline through increased tau deposition in the CI group., Conclusion: Our finding suggests that older adults with relatively longer TL, particularly in the CI group, may have greater in vivo AD pathologies and experience more rapid cognitive decline, potentially mediated by brain tau deposition. Further studies are necessary to elucidate the biological links underlying these associations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Extreme weather phenomena caused by climate change have exacerbated soil erosion and the subsequent dispersion of pollutants. Pseudomonas aeruginosa is known to contribute to the remediation of polluted water and reduce the geochemical mobility of heavy metals in contaminated soil. However, studies on the influence of biopolymers produced by soil microbes and P. aeruginosa on physical soil properties and soil erosion are limited. We aimed to investigate the influence of soil microbes on the mitigation of soil erosion and geochemical dispersion of heavy metals using a naturally occurring microbial substance, P. aeruginosa-based biopolymer (PBB). The PBB comprised carboxyl, hydroxyl, and amine surface functional groups; consequently, the biopolymer effectively sequestered Cd (maximum sorption capacity q m  = 45.7 mg/g), Cu (q m  = 26.7 mg/g), Pb (q m  = 64.9 mg/g), and Zn (q m  = 26.1 mg/g) in the solution. The PBB amendment of the soil improved the physical properties associated with soil erosion, increasing soil aggregation stability and shear strength by 41.6% and 36.8%, respectively. The extraction of heavy metals from soil via synthetic precipitate leaching decreased by 54.2% following the PBB amendment, and a negative correlation was observed between soil aggregate stability and heavy metal extraction, indicating that this microbial substance could immobilize pollutants by adsorbing cationic metal ions and inhibiting water-induced disaggregation. In the soil erosion experiments, soil loss and heavy metal extraction decreased by 70.9% and 43.8%, respectively, following the PBB amendment. These aggregation and sorption effects of the PBB underscore the potential of soil microbes to mitigate soil erosion and immobilize the geochemical dispersion of heavy metals, thereby contributing to the conservation of soil and water quality in areas surrounding contaminated slopes and heavy metal-contaminated areas, such as cut slopes, agricultural fields, mine dumps, and dams., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Myoung-Soo Ko reports financial support was provided by National Research Foundation of Korea. Myoung-Soo Ko reports financial support was provided by Korea Institute of Energy Technology Evaluation and Planning. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Shiitake mushrooms (Lentinula edodes) are a rich source of ergosterol, which can be converted into vitamin D 2 , a valuable nutrient for human health. This study evaluated the enhancement of vitamin D 2 in shiitake-mushroom powders using intense pulsed light (IPL). The initial vitamin D 2 content of the sample was 4.18 μg/g. After IPL treatment at various processing times and lamp voltages, the maximum concentration of vitamin D 2 was reached 100.82 μg/g at 1800 V for 30 min-24 times higher than the control. The IPL effectively converted ergosterol into vitamin D 2 in mushroom powders, with the ultraviolet (UV) range being the most influential. At certain fluences, IPL's effect on vitamin D 2 production surpassed continuous UV treatment. These findings suggest that IPL can significantly enhance vitamin D 2 content in mushroom powders, presenting a promising alternative for fortifying functional foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: We investigated the hypothesis that tau burden in the locus coeruleus (LC) correlates with tau accumulation in cortical regions according to the Braak stages and examined whether the relationships differed according to cortical amyloid beta (Aβ) deposition., Methods: One hundred and seventy well-characterized participants from an ongoing cohort were included. High-resolution T1, tau positron emission tomography (PET), and amyloid PET were obtained., Results: LC tau burden was significantly linked to global tau in neocortical regions, as was tau in both early Braak stage (stage I/II) and later Braak stage areas. This relationship was significant only in Aβ-positive individuals. While LC tau did not directly impact memory, it was indirectly associated with delayed memory through mediation or moderation pathways., Discussion: The findings from living human brains support the idea that LC tau closely relates to subsequent cortical tau accumulation, particularly among individuals with pathological Aβ accumulation, and identify LC tau burden as a promising indicator of cognitive trajectories of AD., Highlights: Tau burden in the LC was significantly associated with cortical tau accumulation. Tau burden in SN or PPN showed no association with cortical tau accumulation. LC tau burden was serially associated with Braak stages. The tau-LC and cortical tau relationship was significant only in the Aβ-positive group. Cortical amyloid's impact on memory worsens with higher tau accumulation in the LC., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Despite consistent recommendations from clinical guidelines, data from randomized trials on a long-term antithrombotic treatment strategy for patients with atrial fibrillation and stable coronary artery disease are still lacking., Methods: We conducted a multicenter, open-label, adjudicator-masked, randomized trial comparing edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with atrial fibrillation and stable coronary artery disease (defined as coronary artery disease previously treated with revascularization or managed medically). The risk of stroke was assessed on the basis of the CHA 2 DS 2 -VASc score (scores range from 0 to 9, with higher scores indicating a greater risk of stroke). The primary outcome was a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major bleeding or clinically relevant nonmajor bleeding at 12 months. Secondary outcomes included a composite of major ischemic events and the safety outcome of major bleeding or clinically relevant nonmajor bleeding., Results: We assigned 524 patients to the edoxaban monotherapy group and 516 patients to the dual antithrombotic therapy group at 18 sites in South Korea. The mean age of the patients was 72.1 years, 22.9% were women, and the mean CHA 2 DS 2 -VASc score was 4.3. At 12 months, a primary-outcome event had occurred in 34 patients (Kaplan-Meier estimate, 6.8%) assigned to edoxaban monotherapy and in 79 patients (16.2%) assigned to dual antithrombotic therapy (hazard ratio, 0.44; 95% confidence interval [CI], 0.30 to 0.65; P<0.001). The cumulative incidence of major ischemic events at 12 months appeared to be similar in the trial groups. Major bleeding or clinically relevant nonmajor bleeding occurred in 23 patients (Kaplan-Meier estimate, 4.7%) in the edoxaban monotherapy group and in 70 patients (14.2%) in the dual antithrombotic therapy group (hazard ratio, 0.34; 95% CI, 0.22 to 0.53)., Conclusions: In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy led to a lower risk of a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding at 12 months than dual antithrombotic therapy. (Funded by the CardioVascular Research Foundation and others; EPIC-CAD ClinicalTrials.gov number, NCT03718559.)., (Copyright © 2024 Massachusetts Medical Society.)

Objective: This retrospective cohort study aimed to evaluate the effectiveness of posterior long-segment fixation for thoracolumbar osteoporotic vertebral compression fractures (TLOVCFs) and identify prognosis-predicting factors., Methods: Twenty-two patients with TLOVCFs who underwent posterior long-segment fixation between January 2013 and June 2022 were included. Preoperative, postoperative, and final follow-up data were collected, including demographics, bone mineral density, Cobb angle (CA) measurements, and neurological outcomes based on the Frankel classification. The study compared the outcomes of percutaneous versus open screw fixation methods, focusing on radiologic parameters, surgical complications, and neurological improvement., Results: The mean patients' age was 71.9 ± 10.2 years, with a mean follow-up duration of 1383.3 ± 1026.1 days. The CA showed significant improvements, decreasing from a preoperative mean of 27.1° ± 6.8° to a postoperative mean of 17.0° ± 5.9° and maintaining at 20.9° ± 6.7° at the final follow-up. Neurological improvement was noted in 95.4% of patients. Screw loosening was observed in 27.3% of patients, without significant differences between the groups. However, the open surgery group showed less CA progression compared to the percutaneous group., Conclusions: Posterior long-segment fixation effectively improved kyphotic deformity and provided stable outcomes in patients with TLOVCFs. Open screw fixation offered better maintenance of correction with a lower risk of screw loosening compared to percutaneous methods. Therefore, further prospective studies are necessary to establish standardized treatment protocols for TLOVCFs., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The influence of genetic variation on tau protein aggregation, a key factor in Alzheimer's disease (AD), remains not fully understood. We aimed to identify novel genes associated with brain tau deposition using pathway-based candidate gene association analysis in a Korean cohort., Methods: We analyzed data for 146 older adults from the well-established Korean AD continuum cohort (Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease; KBASE). Fifteen candidate genes related to both tau pathways and AD were selected. Association analyses were performed using PLINK: A tool set for whole-genome association and population-based linkage analyses (PLINK) on tau deposition measured by 18 F-AV-1451 positron emission tomography (PET) scans, with additional voxel-wise analysis conducted using Statistical Parametric Mapping 12 (SPM12)., Results: CLU and FYN were significantly associated with tau deposition, with the most significant single-nucleotide polymorphisms (SNPs) being rs149413552 and rs57650567, respectively. These SNPs were linked to increased tau across key brain regions and showed additive effects with apolipoprotein E (APOE) ε4., Discussion: CLU and FYN may play specific roles in tau pathophysiology, offering potential targets for biomarkers and therapies., Highlights: Gene-based analysis identified CLU and FYN as associated with tau deposition on positron emission tomography (PET). CLU rs149413552 and FYN rs57650567 were associated with brain tau deposition. rs149413552 and rs57650567 were associated with structural brain atrophy. CLU rs149413552 was associated with immediate verbal memory. CLU and FYN may play specific roles in tau pathophysiology., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: Robot-assisted surgery is readily applied to every type of colorectal surgeries. However, studies showing the safety and feasibility of robotic surgery (RS) have dealt with rectal cancer more than colon cancer. This study aimed to investigate how technical advantages of RS can translate into actual clinical outcomes that represent postoperative systemic response., Methods: This study retrospectively reviewed consecutive cases in a single tertiary medical center in Korea. Patients with primary colon cancer who underwent curative resection between 2006 and 2012 were included. Propensity score matching was done to adjust baseline patient characteristics (age, sex, body mass index, American Society of Anesthesiologists physical status, tumor profile, pathologic stage, operating surgeon, surgery extent) between open surgery (OS), laparoscopic surgery (LS), and RS groups., Results: After propensity score matching, there were 66 patients in each group for analysis, and there was no significant differences in baseline patient characteristics. Maximal postoperative leukocyte count was lowest in the RS group and highest in the OS group (P=0.021). Similar results were observed for postoperative neutrophil count (P=0.024). Postoperative prognostic nutritional index was highest in the RS group and lowest in the OS group (P<0.001). The time taken to first flatus and soft diet resumption was longest in the OS group and shortest in the RS group (P=0.001 and P<0.001, respectively). Among all groups, other short-term postoperative outcomes such as hospital stay and complications did not show significant difference, and oncological survival results were similar., Conclusion: Better postoperative inflammatory indices in the RS group may correlate with their faster recovery of bowel motility and diet resumption compared to LS and OS groups.

Background: The Orsiro and Genoss DES stents are biodegradable polymer drug-eluting stents (DESs) with ultrathin struts., Objective: To investigate the safety and efficacy of these two ultrathin DESs in real-world practice., Methods: From a single-center prospective registry, we included 751 and 931 patients treated with the Genoss DES and Orsiro stents, respectively. After propensity score matching, we compared 483 patients in each group with respect to a device-oriented composite outcome (DOCO), which comprised cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization up to 2 follow-up years., Results: After propensity score matching, there were no significant between-group differences in clinical and angiographic characteristics. During the median follow-up period of 730 days (interquartile range, 427-730 days), there was no significant between-group difference in the DOCO rate (3.1% in the Genoss DES group vs. 2.9% in the Orsiro group, log-rank p = 0.847)., Conclusions: This study demonstrated comparable safety and efficacy between the Orsiro and Genoss DES stents during a 2-year follow-up period in real-world practice. However, this result should be confirmed in a large randomized controlled trial., Trial Registration: ClinicalTrials.gov Identifier: NCT02038127., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Introduction: Despite the recognized importance of including ethnic diversity in Alzheimer's disease (AD) research, substantial knowledge gaps remain, particularly in Asian populations., Methods: RNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to perform differential gene expression (DGE), gene co-expression network, gene-set enrichment, and machine learning analyses for amyloid beta (Aβ) deposition on positron emission tomography., Results: DGE analysis identified 265 dysregulated genes associated with Aβ deposition and replicated three AD-associated genes in an independent Korean cohort. Network analysis identified two modules related to pathways including a natural killer (NK) cell-mediated immunity. Machine learning analysis showed the classification of Aβ positivity improved with the inclusion of gene expression data., Discussion: Our results in a Korean population suggest Aβ deposition-associated genes are enriched in NK cell-mediated immunity, providing a better understanding of AD molecular mechanisms and yielding potential diagnostic and therapeutic strategies., Highlights: Dysregulated genes were associated with amyloid beta (Aβ) deposition on positron emission tomography in a Korean cohort. Dysregulated genes in Alzheimer's disease were replicated in an independent Korean cohort. Gene network modules were associated with Aβ deposition. Natural killer (NK) cell proportion in blood was associated with Aβ deposition. Dysregulated genes were related to a NK cell-mediated immunity., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Limited evidence exists on the role of depression in the risk of developing stroke and other cardiovascular outcomes in patients who have undergone percutaneous coronary interventions (PCI). We investigated this relationship with data from the Korean National Health Insurance Service database., Methods: Our nationwide retrospective cohort study included 164,198 patients who had undergone PCI between 2010 and 2017. Depression was defined with the ICD-10 codes recorded prior to the PCI. The primary outcome was a new-onset stroke following the PCI. Secondary outcomes included PCI with myocardial infarction (MI), revascularization (PCI or coronary artery bypass grafting), and all-cause mortality. A multivariable Cox proportional hazards regression analysis was used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI), adjusting for potential confounders, including sociodemographic and lifestyle factors, comorbidities, and MI at the index PCI., Results: Over a median follow-up of 5.0 years, acute stroke occurred in 5.7% of patients with pre-existing depression (17.4% of the study population), compared to 3.5% of those without depression. Depression was associated with a 27% increased risk of acute stroke (aHR 1.27, 95% CI 1.20-1.35). Additionally, depression was linked with a 25% elevated risk of all-cause death (aHR 1.25, 95% CI, 1.21-1.29) and an 8% increased risk of revascularization (aHR 1.08, 95% CI 1.04-1.11). The associations with the risk of stroke and all-cause mortality were stronger in patients under 65 years., Conclusions: Our findings suggest that pre-existing depression may increase the risk of stroke and all-cause mortality following PCI, particularly in patients under 65 years. Additionally, depression was significantly associated with an increased need for revascularization. This underscores the potential benefits of managing depression to reduce stroke risk and overall cardiovascular outcomes following PCI., (© 2024 The Association for the Publication of the Journal of Internal Medicine.)

Background: Hair transplantation (HT) has been reported to be effective for the treatment of female-pattern hair loss (FPHL). Few studies have investigated HT in FPHL., Objective: To evaluate the clinical features of FPHL treated with HT and analyze the real-world results of HT., Methods: We conducted a retrospective chart review of 195 FPHL patients who underwent hair transplants. The patients' demographics, clinical features, and clinical courses of HT were recorded., Results: The mean (±SD) age of patients was 49.1±11.9 years. Analysis of the severity of hair loss showed that 31.8%, 49.7%, and 18.5% of patients had F1, F2, and F3 types of hair loss (according to the BASP Classification); 88.2% of patients had more than 75% satisfaction with HT. The satisfaction level was significantly higher in the group that had the highest number of hairs implanted. Complications such as pain, facial edema, folliculitis, scar, paresthesia, telogen effluvium were found., Conclusion: This study could provide substantial information of HT in FPHL. Clinicians could deliver more sufficient counsel to FPHL patients about HT., Competing Interests: The authors have nothing to disclose., (© 2024 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Background: Limited research has explored the effect of cardiovascular risk and amyloid interplay on cognitive decline in East Asians., Methods: Vascular burden was quantified using Framingham's General Cardiovascular Risk Score (FRS) in 526 Korean Brain Aging Study (KBASE) participants. Cognitive differences in groups stratified by FRS and amyloid positivity were assessed at baseline and longitudinally., Results: Baseline analyses revealed that amyloid-negative (Aβ-) cognitively normal (CN) individuals with high FRS had lower cognition compared to Aβ- CN individuals with low FRS (p < 0.0001). Longitudinally, amyloid pathology predominantly drove cognitive decline, while FRS alone had negligible effects on cognition in CN and mild cognitive impairment (MCI) groups., Conclusion: Our findings indicate that managing vascular risk may be crucial in preserving cognition in Aβ- individuals early on and before the clinical manifestation of dementia. Within the CN and MCI groups, irrespective of FRS status, amyloid-positive individuals had worse cognitive performance than Aβ- individuals., Highlights: Vascular risk significantly affects cognition in amyloid-negative older Koreans. Amyloid-negative CN older adults with high vascular risk had lower baseline cognition. Amyloid pathology drives cognitive decline in CN and MCI, regardless of vascular risk. The study underscores the impact of vascular health on the AD disease spectrum., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Despite advancements in adoptive regulatory T cell (Treg) therapy, its application in Alzheimer's disease (AD) remains constrained by challenges in ex vivo Treg selection and expansion with antigen specificity. Our previous findings demonstrated the bystander suppressive immunomodulatory mechanism of ex vivo expanded amyloid β-specific mouse Tregs in AD models, prompting inquiry into the efficacy of ex vivo expanded human Tregs in AD., Methods: We developed an effective ex vivo expansion method for manufacturing amyloid β-specific human Tregs (Aβ-hTreg) and evaluated their safety and efficacy in 3xTg mouse models of AD and a phase 1 clinical trial with six AD patients. The phenotype of Aβ-hTreg was analyzed using single-cell transcriptomics. The clinical trial involved intravenous administration of Aβ-hTreg, with three patients receiving a low dose and three receiving a high dose. Exploratory assessments of effectiveness, including cognitive tasks and functional evaluations, were conducted ninety days post-treatment., Results: Behavioral spatial learning and memory impairment, neuroinflammatory and amyloid pathology were dramatically ameliorated by single intrathecal administration of ex vivo expanded Aβ-hTreg to 3xTg AD mice. Single cell transcriptomics analysis revealed alterations in five key genes within a cluster of Tregs under antigen-specific manufacturing conditions. In the clinical trial with six AD patients, dose-limiting toxicity was experienced by none of the participants within five days of receiving GMP-grade Aβ-hTreg (VT301), indicating its good tolerability. Although exploratory assessments of effectiveness did not reach statistically significant values among the groups, these findings offer valuable insights for AD treatment and management, guiding the planning of the next phase of clinical trials., Discussion: This study suggests that hTregs may modulate Alzheimer's disease pathology by suppressing neuroinflammation, while VT301 shows promise as a safe treatment option. However, further research is necessary to confirm its clinical efficacy and optimize treatment strategies., Trial Registration: Title: A Study of Possibility of Using Regulatory T Cells (VT301) for Treatment of Alzheimer's Disease, ClinicalTrials.gov NCT05016427, Study approval date: Ministry of Food and Drug Safety of the Republic of Korea (MFDS) - August 31st, 2020, Institutional Review Board (IRB) of Seoul National University Hospital, Republic of Korea - September 29th, 2020, The date of first patient enrollment: December 7th, 2020. https://clinicaltrials.gov/study/NCT05016427., Competing Interests: Declaration of Competing Interest I hereby declare that I have no financial or personal relationships or circumstances related to this research or work that could be construed as a conflict of interest. Therefore, I have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: We intended to investigate the relationships between visual sensory impairment (VSI) or auditory sensory impairment (ASI) and brain pathological changes associated with cognitive decline in older adults., Methods: We primarily tried to examine whether each sensory impairment is related to Alzheimer's disease (AD) pathology, specifically beta-amyloid (Aβ) deposition, through both cross-sectional and longitudinal approaches in cognitively unimpaired older adults. Self-report questionnaires on vision and hearing status were administered at the baseline. Neuroimaging scans including brain [ 11 C] Pittsburgh Compound B PET and MRI, as well as clinical assessments, were performed at baseline and 2-year follow-up., Results: Cross-sectional analyses showed that the VSI-positive group had significantly higher Aβ deposition than the VSI-negative group, whereas there was no significant association between ASI positivity and Aβ deposition. Longitudinal analyses revealed that VSI positivity at baseline was significantly associated with increased Aβ deposition over 2 years (β = 0.153, p = 0.025), although ASI positivity was not (β = 0.045, p = 0.518). VSI positivity at baseline was also significantly associated with greater atrophic changes in AD-related brain regions over the 2-year follow-up period (β = -0.207, p = 0.005), whereas ASI positivity was not (β = 0.024, p = 0.753). Neither VSI nor ASI positivity was related to cerebrovascular injury, as measured based on the white matter hyperintensity volume., Conclusion: The findings suggest that VSI is probably related to AD-specific pathological changes, which possibly mediate the reported relationship between VSI and cognitive decline. In contrast, ASI appears not associated with AD pathologies but may contribute to cognitive decline via other mechanisms.

Objective: Previous studies have reported that vitamin D deficiency increased the risk of Alzheimer's disease (AD) dementia in older adults. However, little is known about how vitamin D is involved in the pathophysiology of AD. Thus, this study aimed to examine the association and interaction of serum vitamin D levels with in vivo AD pathologies including cerebral beta-amyloid (Aβ) deposition and neurodegeneration in nondemented older adults., Methods: 428 Nondemented older adults were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a prospective cohort that began in 2014. All participants underwent comprehensive clinical assessments, measurement of serum 25-hydroxyvitamin D (25[OH]D), and multimodal brain imaging including Pittsburgh compound B (PiB) positron emission tomography and magnetic resonance imaging. Global PiB deposition was measured for the Aβ biomarker. Intracranial volume-adjusted hippocampal volume (HVa) was used as a neurodegeneration biomarker., Results: Overall, serum 25(OH)D level was not associated with either Aβ deposition or HVa after controlling for age, sex, apolipoprotein E ε4 positivity, and vascular risk factors. However, serum 25(OH)D level had a significant moderating effect on the association between Aβ and neurodegeneration, with lower serum 25(OH)D level significantly exacerbating cerebral Aβ-associated hippocampal volume loss (B = 34.612, p = 0.008)., Conclusion: Our findings indicate that lower serum vitamin D levels may contribute to AD by exacerbating Aβ-associated neurodegeneration in nondemented older adults. Further studies to explore the potential therapeutic effect of vitamin D supplementation on the progression of AD pathology will be necessary.

Objective: Schizophrenia is a severe and chronic mental disorder that significantly impacts cognitive, social, and occupational functions, leading to substantial economic burdens. Long-acting injectable (LAI) antipsychotics have been introduced to improve treatment adherence and outcomes, yet their economic impact remains debated. We aim to analyze the impact of LAIs on the medical costs of Korean schizophrenia patients., Methods: A retrospective analysis of 164 schizophrenia patients treated with LAI antipsychotics, paliperidone palmitate, and aripiprazole monohydrate at Korea University Guro Hospital between January 2017 and July 2022 was performed. Comparisons of inpatient department (IPD) and outpatient department (OPD) healthcare expenditures one year before and after LAI initiation were conducted., Results: LAIs led to an increase in annual OPD costs (1,437.44 ± 1,127.60 to 4,015.42 ± 1,204.59; units: 1,000 KRW) but significantly reduced IPD admission associated costs (3,826.06 ± 5,500.63 to 698.06 ± 3,619.38; units: 1,000 KRW). After LAI administration, there was an overall reduction in total annual healthcare costs (5,263.49 ± 5,333.11 to 4,713.48 ± 3,625.89; units: 1,000 KRW), but it was not statistically significant., Conclusion: Although the use of LAIs did not significantly lower the first-year medical costs of schizophrenia patients, they offer beneficial economic impacts over time by reducing hospitalization-associated costs. Future research should focus on long-term cost analyses and the impacts of newer LAI formulations.

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of psychotherapeutic interventions in the treatment of older adults with depression and whether the effects of different types of psychotherapeutic treatments vary for older adults with depression., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Monoamine oxidase B (MAO-B) has emerged as a therapeutic target for Alzheimer's disease (AD) due to its involvement in the synthesis of γ-aminobutyric acid (GABA) in reactive astrocytes, which inhibits neuronal activity. Suffruticosol B (Suf-B), isolated from Paeonia lactiflora, is one of the resveratrol oligomers. Although resveratrol oligomers have demonstrated neuroprotective effects, it remains unexplored whether Suf-B exerts therapeutic effects on AD by targeting MAO-B. In this study, we investigated whether Suf-B alleviates AD pathology by mitigating reactive astrogliosis and inhibiting the overproduction of astrocytic GABA. After confirming the MAO-B inhibitory effect of Suf-B through MAO-B enzyme assay, we administered Suf-B to APP/PS1 AD model mice. To test the potential therapeutic action of Suf-B in AD, a series of experiments were conducted, including behavioral tests such as the open field test, novel object recognition test, Barnes maze test, passive avoidance test, as well as immunohistochemistry and whole-cell patch-clamp recordings. We found that Suf-B markedly inhibited MAO-B activity without causing cytotoxicity. Immunohistochemistry and electrophysiology experiments demonstrated that Suf-B significantly reduced astrocyte reactivity, as well as an aberrant increase in GABA production and tonic GABA release from astrocytes in AD. Behavior test results indicated that Suf-B treatment restored cognitive function in APP/PS1 mice. In conclusion, Suf-B effectively reduces excessive GABA production in reactive astrocytes by inhibiting MAO-B, normalizing aberrant inhibition in hippocampal neurons in an AD mouse model. These results suggest that Suf-B has potential as a treatment for AD and may be applicable to other brain diseases associated with reactive astrogliosis., (© 2024 John Wiley & Sons Ltd.)

Background/Objectives: This study investigates the impact of supercritical antisolvent (SAS) process parameters on the particle formation of telmisartan, a poorly water-soluble drug. Methods: A fractional factorial design was employed to examine the influence of the SAS process parameters, including solvent ratio, drug solution concentration, temperature, pressure, injection rate of drug solution, and CO₂ flow rate, on particle formation. Solid-state characterizations of the SAS process particles using XRD and FT-IR confirmed their amorphous nature. The effect of particle size on the kinetic solubility, dissolution, and oral bioavailability of telmisartan was also assessed. Results: Using a mixture of dichloromethane and methanol, telmisartan amorphous nano-microparticles with sizes between 200 and 2000 nm were produced. The key parameters, particularly drug solution concentration and temperature, significantly affected the particle size. Interestingly, the ratio of the solvent mixture also had a significant effect on the particle morphology. Further experiments were performed to determine the conditions for preparing telmisartan amorphous nano-microparticles with various sizes by controlling the solvent mixture ratio and the concentration of the drug solution. It was revealed that a reduction in the amorphous particle size enhanced both the kinetic solubility and dissolution rates, leading to a significantly increased in vivo oral bioavailability in rats compared to unprocessed telmisartan. Conclusions: These findings suggest that SAS processing, utilizing adjustments of process parameters, offers an effective strategy for enhancing the bioavailability of poorly soluble drugs by generating amorphous spherical nano-microparticles with optimized particle size.

Objectives: This study aims to evaluate (1) the effect and safety of acupuncture in patients with knee osteoarthritis (KOA) and explore (2) whether the effect of acupuncture differed according to acupuncture type, acupuncture dose and follow-up time., Design: Systematic review and pairwise and exploratory network meta-analysis., Setting: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals and Wanfang from inception to 13 November 2023., Participants: Randomised controlled trials comparing acupuncture with sham acupuncture, non-steroidal anti-inflammatory drugs (NSAIDs), usual care or waiting list groups, intra-articular (IA) injection and blank groups in patients with KOA., Interventions: Eligible interventions included manual acupuncture (MA) and electroacupuncture (EA)., Main Outcomes Measures: The primary outcome was pain intensity at the end of treatment., Results: 80 trials (9933 participants) were included. Very low certainty evidence suggested that acupuncture may reduce pain intensity compared with sham acupuncture (standardised mean difference, SMD -0.74, 95% CI -1.08 to -0.39, corresponded to a difference in Visual Analogue Scale of -18.50 mm, -27.00 to -9.75), NSAIDs (SMD -0.86 -1.26 to -0.46, corresponded to -21.50 mm, -31.50 to -11.50), usual care or waiting list groups (SMD -1.01, -1.47 to -0.54, corresponded to -25.25 mm, -36.75 to -13.50) and blank groups (SMD -1.65, -1.99 to -1.32, corresponded to -41.25 mm, -49.75 to -33.00), but not IA injection. Similar results were also found in other outcomes. For most of the subgroup analyses, acupuncture type, acupuncture dose and follow-up time did not show a significant relative effect. Only when compared with NSAIDs, a higher dose of acupuncture may provide greater pain relief (interaction p<0.001). The network meta-analysis revealed that electroacupuncture (SMD -0.75, 95% CI -1.34 to -0.17) had a greater effect on pain relief in patients with KOA compared with manual acupuncture., Conclusions: The findings suggest that acupuncture may provide clinically important effects in reducing pain and improving physical function in patients with KOA, but the certainty of evidence was very low. Electroacupuncture and higher dose of acupuncture probably are two potential contributing factors., Prospero Registration Number: CRD42021232177., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: In degenerative lumbar spondylolisthesis, interbody fusion surgery (IFS) has long been recommended as the gold standard of surgical management. However, IFS is less recommended for high-risk patients such as the elderly because it involves extensive surgery, with a long operation time and high volumes of blood loss, which lead to marked perioperative morbidity. We report an alternative primary and salvage treatment technique for high-risk lumbar spondylolisthesis through posterior lumbar element reinforcement using interspinous fixation (ISF) and decompression alone without interbody fusion., Methods: Plain radiographs, computed tomography scans, and magnetic resonance imaging, taken at different intervals, were used to measure local disc height (DH), vertebral body slippage (BS), and segmental motion angle (SMA). A visual analogue scale (VAS) and the Oswestry disability index (ODI) were applied pre-operation and at the last follow-up., Results: The local SMA decreased significantly by 3.46±3.07°, from 10.61±3.42° preoperatively to 7.15±3.70 at the last follow-up (p<0.001). The DH decreased from 8.61±2.88 mm preoperatively to 8.41±2.48 mm at the last follow-up (p=0.074). The BS decreased from 3.49±4.29 mm preoperatively to 3.41±4.91 mm at the last follow-up (p=0.092). None of the patients reported worsening pain or an increased ODI after surgery, and there were no surgery-related complications., Conclusion: Posterior lumbar element reinforcement by decompression alone with SPIRE™ fixation is an alternative primary and salvage treatment option for select patients with spondylolisthesis.

Background/aims: Combi-elastography is a B-mode ultrasound-based method in which two elastography modalities are utilized simultaneously to assess metabolic dysfunction-associated steatotic liver disease (MASLD). However, the performance of combi-elastography for diagnosing metabolic dysfunction-associated steatohepatitis (MASH) and determining fibrosis severity is unclear. This study compared the diagnostic performances of combi-elastography and vibration-controlled transient elastography (VCTE) for identifying hepatic steatosis, fibrosis, and high-risk MASH., Methods: Participants who underwent combi-elastography, VCTE, and liver biopsy were selected from a prospective cohort of patients with clinically suspected MASLD. Combi-elastography-related parameters were acquired, and their performances were evaluated using area under the receiver-operating characteristic curve (AUROC) analysis., Results: A total of 212 participants were included. The diagnostic performance for hepatic steatosis of the attenuation coefficient adjusted by covariates from combi-elastography was comparable to that of the controlled attenuation parameter measured by VCTE (AUROC, 0.85 vs 0.85; p=0.925). The performance of the combi-elastography-derived fibrosis index adjusted by covariates for diagnosing significant fibrosis was comparable to that of liver stiffness measured by VCTE (AUROC, 0.77 vs 0.80; p=0.573). The activity index from combi-elastography adjusted by covariates was equivalent to the FibroScan-aspartate aminotransferase score in diagnosing high-risk MASH among participants with MASLD (AUROC, 0.72 vs 0.74; p=0.792)., Conclusions: The performance of combi-elastography is similar to that of VCTE when evaluating histology of MASLD.

Receptor kinase (RK) families process information from small molecules, short peptides, or glycan ligands to regulate core cellular pathways in plants. To date, whether individual plant RKs are capable of processing signals from distinct types of ligands remains largely unexplored. Addressing this requires the discovery of structurally unrelated ligands that engage the same receptor. Here, we focus on FLAGELLIN-SENSING 2 (FLS2), an RK that senses a peptide of bacterial flagellin to activate antibacterial immunity in Arabidopsis. We interrogate >20,000 potential interactions between small molecules and the sensory domain of FLS2 using a large-scale reverse chemical screen. We discover two small molecules that interact with FLS2 in atypical ways. The surrogate ligands weakly activate the receptor to drive a functional antibacterial response channeled via unusual gene expression programs. Thus, chemical probes acting as biased ligands can be exploited to discover unexpected levels of output flexibility in RKs signal transduction., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background/Objectives : Intestinal Behçet's disease (iBD) often requires surgical intervention, with a significant proportion of patients needing reoperation. This study aimed to investigate the risk factors associated with reoperation in patients with iBD who underwent initial bowel resection and to evaluate the perioperative and long-term outcomes in these patients. Methods : This was a retrospective case-control study analyzing patients who underwent their initial bowel resection due to iBD between 2005-2021 at a tertiary referral hospital. Reoperation was considered a surgery due to postoperative complications (within 30 days of the initial surgery) or disease progression. Results: A total of 81 patients were included. The median follow-up duration was 107.1 months, during which 26 patients (32%) underwent reoperation. Multivariable analysis showed that the presence of hematological disorders (hazards ratio [HR], 9.13; 95% confidence interval [CI], 3.79-22.02, p < 0.001), higher c-reactive protein (CRP) levels before the initial surgery (HR, 1.01; 95% CI, 1.01-1.02, p < 0.001), and a shorter specimen resection length (HR, 0.96; 95% CI, 0.93-0.99, p = 0.011) were risk factors for reoperation. Patients who underwent reoperation had higher rates of postoperative complications (69.2% vs. 43.6%, p = 0.031), required longer antibiotic use (12 vs. 7 days, p = 0.012), and had extended hospital stays (18 vs. 9 days, p = 0.011). They also had worse 5-year survival rates than those who did not undergo reoperation (83.5% vs. 98.4%, p = 0.012). Conclusions : Concurrent hematological disorders, high preoperative CRP levels, and short specimen resection were associated with an increased risk of reoperation in patients with iBD who underwent their initial bowel resections. They also had worse perioperative and long-term outcomes.

Background: Damaged cartilage can be treated using the creation of microfractures (MFxs) or the porcine-derived collagen-augmented chondrogenesis technique (C-ACT)., Purpose: To provide the midterm results of a multicenter randomized controlled trial comparing MFx and C-ACT for knee cartilage defects., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: The study cohort comprised 36 patients with medial femoral condyle cartilage defects who were followed up for 6 years with clinical and magnetic resonance imaging data (n = 14 treated with MFx alone, n = 22 treated with C-ACT). Clinical outcomes were assessed preoperatively and at 1, 2, and 6 years postoperatively using a visual analog scale (VAS) for pain, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the International Knee Documentation Committee (IKDC) subjective score. Magnetic resonance imaging scans were performed preoperatively and at 1 and 6 years postoperatively, and the repaired cartilage tissue was evaluated using the magnetic resonance observation of cartilage repair tissue (MOCART) score. The repaired tissue/reference cartilage ratio was quantified using T2 mapping. Adverse events during follow-up were also evaluated., Results: In both groups, the VAS pain score improved and was maintained for 1, 2, and 6 years postoperatively compared with preoperatively ( P < .05 for all). Although there were no significant differences between groups in the VAS pain, KOOS, or IKDC scores at any time point, the change in the IKDC-Activities of Daily Living subscore from preoperatively to 6 years postoperatively was better in the C-ACT group than the MFx group ( P = .0423). At 6 years postoperatively, the MOCART assessment showed superior results regarding the surface of the repair tissue in the C-ACT group compared with the MFx group ( P = .0288). There were no differences between the groups in the total MOCART score or other subscores., Conclusion: The study results suggest that C-ACT has similar effects to MFx in improving pain, joint function, and imaging findings and may be superior to MFx in improving daily life function and improving the quality of the surface of the cartilage tissue., Registration: ClinicalTrials.gov identifier: NCT02539030., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: research support and materials for this study were received from Sewon Cellontech. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Background: Increasing evidence has emerged for traditional, complementary and integrative medicine (TCIM) to treat COVID-19 which requires systematic summaries of the net benefits of interventions against standard care and one another. The study aims to conduct a systematic review and network meta-analysis (NMA) regarding TCIM therapies for treating mild/moderate acute COVID-19, potentially informing the WHO guideline development and clinical decision-making., Methods and Analysis: We will search Embase, MEDLINE, Virtual Health Library on Traditional Complementary and Integrative Medicine, Cochrane Central Register of Controlled Trials, WHO's International Clinical Trials Registry Platform with additional searches of Chinese and Korean literature sources for randomised controlled trials comparing TCIM with placebo, standard care, no treatment or with an alternate type of TCIM to treat COVID-19. We will limit the search dates from 2020 to 28 March 2024. Reviewers will, in duplicate, screen eligible articles, extract data and evaluate the risk of bias. We will conduct frequentist network meta-analyses for network comparisons and each outcome. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach and classify interventions from most to least effective or harmful., Ethics and Dissemination: This NMA is based on the existing trials and data which is not subject to ethical approval. We will publish the NMA in a peer-reviewed journal. This may provide methodological reference and clinical evidence for TCIM on future epidemic-prone diseases., Prospero Registration Number: CRD42024517321., Competing Interests: Competing interests: We would like to disclose that Dr. Guyatt Gordon and Dr. Thabane Lehana are listed as members of the Editorial Board of BMJ Open, as noted on their website (https://bmjopen.bmj.com/pages/editorial-board). This association has been declared in accordance with the journal’s submission policies. All other authors have no potential conflicts of interest to declare related to this submission., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Metabolic syndrome is a significant risk factor for poor graft outcomes in kidney transplant (KT) patients. However, the effects of variability in metabolic parameters on graft outcomes in KT patients have not been completely elucidated. A total of 852 KT patients were included from the Korean Organ Transplantation Registry. The study exposure was variability in body mass index (BMI) or other metabolic parameters measured at 6 months, 1 year, and 2 years after KT. Patients were classified into tertiles according to the degree of variability. The primary outcome was a composite of adverse kidney outcomes, such as death-censored graft loss or ≥ 30% decline in estimated glomerular filtration rate. The adverse kidney outcomes occurred in 73 (8.6%) participants. The high-BMI variability group had a higher risk for adverse kidney outcomes compared to the low-variability group. High variabilities in triglyceride, fasting blood glucose, and systolic blood pressure were also associated with adverse kidney outcomes. Furthermore, high variability in metabolic syndrome-related composite indices, such as the triglyceride and glucose index and metabolic variability scores, showed a higher risk for adverse kidney outcomes. In conclusion, high variability in metabolic parameters could be associated with an increased risk of adverse kidney outcome in KT patients., (© 2024. The Author(s).)

Background: The first commercial systems for pulsed field ablation (PFA) were recently approved by the Food and Drug Administration, but their safety profile in nationwide practice remains underexplored., Objectives: This study aimed to describe reported adverse events with PFA systems after their market release and to compare the relative proportion of complications associated with PFA vs radiofrequency (RF) ablation catheters., Methods: We conducted a search of the Manufacturer and User Facility Device Experience database for adverse event reports involving Food and Drug Administration-approved PFA and RF catheters from January 1, 2024, to July 31, 2024., Results: A total of 1237 reports detailing clinical complications (n=156 for PFA and n=315 for RF) or catheter malfunctions (n=336 for PFA and n=430 for RF) were analyzed. The most common adverse events reported for PFA were pericardial effusion, vasovagal response, and hemolysis, compared with pericardial effusion, ischemic stroke, and esophageal damage for RF ablation. The proportion of reported adverse events that were deaths was lower with PFA than with RF (2.6% vs 8.9%; P=.010). Hemolysis (9.0% vs 0%), coronary events (5.8% vs 0.6%), and vasovagal responses (14.1% vs 0%) were reported more frequently after PFA (P<.001 for all). In contrast, esophageal damage (0% vs 4.1%; P<.001) and pulmonary vein stenosis (0% vs 1.9%; P=.184) were not reported with PFA, but only with RF. Regarding catheter malfunctions, mechanical problems were reported in higher proportion after PFA than after RF (87.2% vs 17.2%; P<.001)., Conclusion: The reported complications associated with PFA and RF ablation differ significantly. Close attention to PFA-specific complications is essential for ensuring the safe use of PFA and for mitigating risk., Competing Interests: Disclosures Dr Piccini is supported by grant R01AG074185 from the National Institutes of Aging. He also receives grants for clinical research from Abbott, the American Heart Association, Boston Scientific, iRhythm, and Philips and serves as a consultant for ABVF, Abbott, Boston Scientific, Kardium, Medtronic, Milestone Pharmaceuticals, Sanofi, Philips, and UpToDate. Dr Loring has received grant support from Boston Scientific and the Department of Veterans Affairs and serves as a consultant for Huxley Medical and Boston Scientific. Dr Pokorney reports research support from Milestone Pharmaceuticals, Boston Scientific, and Medtronic and speaker/consultant/advisory board support from Boston Scientific, Medtronic, Philips, Zoll, Bristol Myers Squibb, Pfizer, Johnson & Johnson, and Milestone Pharmaceuticals. Dr Friedman has received research grants from the Abbott, American Heart Association, Biosense Webster, Boston Scientific, Medtronic, Merit Medical, National Cardiovascular Data Registry, Phillips, and National Institutes of Health, and consulting fees from Abbott, Alleviant, Boston Scientific, NI Medical, Medtronic, Microport, and Sanofi. Drs Cho, Lee, and Black-Maier had no relevant disclosures., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)