Search

Jee Yeon Baek,1 Ji-Man Kang,1,2 Ji Young Lee,1 Sung Min Lim,1 Jong Gyun Ahn1,2 1Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Korea; 2Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, KoreaCorrespondence: Jong Gyun Ahn, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea, Tel +82-2-2228-2057, Fax +82-2-393-9118, Email JGAHN@yuhs.acPurpose: Kikuchi–Fujimoto disease (KFD) is a rare, benign, and self-limited disease, characterized by cervical lymphadenopathy and fever. Herein, we analyzed the differences in its clinical manifestations and risk factors for recurrence between children and adults.Patients and Methods: We retrospectively reviewed the medical records of patients diagnosed with KFD at a tertiary referral hospital between 2005 and 2019. Patients were divided into two groups based on their age: children (< 19 years) and adults (≥ 19 years).Results: During the 14-year study period, 127 patients were diagnosed with KFD. Among these, 34 (26.8%) were children and 93 (73.2%) were adults. The fever duration was longer and the frequency of myalgia was higher in adults than in children; however, no other significant symptomatic differences were noted between the two groups. Lymph node evaluation was mainly performed using ultrasound in children (61.8%) and computed tomography in adults (78.5%). Moreover, the frequency of antibiotic use was higher in children than in adults (76.5% vs 54.8%, P = 0.027). In adults, multivariable logistic regression analysis revealed anti-nuclear antibody (ANA) positivity (titer ≥ 1:80) as a risk factor for recurrence (odds ratio: 7.813; 95% confidence interval = 1.818– 33.333; P = 0.006).Conclusion: The clinical features of KFD in children and adults were similar; however, the preferred imaging study and frequency of antibiotic use differed significantly between the two groups. Furthermore, in adults, ANA positivity was associated with KFD recurrence. Thus, patients with KFD who present with ANA positivity at diagnosis will benefit from a regular follow-up for monitoring KFD recurrence.Keywords: histiocytic necrotizing lymphadenitis, recurrence, child, adult

Jae Myeong Kang,1,&ast; Seong-Jin Cho,1,&ast; Seo-Eun Cho,1 Taemo Bang,2 Byung Do Chae,3 Eojin Yi,4 Seung Min Bae,1 Kyoung-Sae Na,1 Jaehun Jung,5 Seung-Gul Kang1 1Department of Psychiatry, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea; 2Artificial Intelligence and Big-Data Convergence Center, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea; 3Unit of Frontier Exploration, Korea Polar Research Institute, Incheon, Republic of Korea; 4Department of Plastic and Reconstructive Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Department of Preventive Medicine, Gachon University College of Medicine, Incheon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Seung-Gul Kang, Department of Psychiatry, Gil Medical Center, Gachon University, College of Medicine, 21, Namdong-daero 774 beon-gil, Namdong-gu, Incheon, 21565, Republic of Korea, Tel +82-32-468-9932, Fax +82-32-468-9962, Email kangsg@gachon.ac.krPurpose: Antarctica is a region with extreme climate, characterized by extreme cold and photoperiod. No research has been conducted on the mental health of Korean Antarctic dispatchers. The aim of this study was to investigate the status of mental illness and changes in mood and sleep among Korean crew members staying for a long-term period in the Antarctic station.Methods: From 2017 to 2020, crew members who were dispatched from South Korea to two Antarctic stations for a one-year period participated in this study. The crew were evaluated for mood and sleep status and mental illness through psychological tests and interviews by board-certified psychiatrists once before departure and twice during their stay in Antarctica. The incidence of mental illness was confirmed and changes in sleep and depression were analyzed.Results: A total of 88 participants were included in the final analysis, and 7 of them (8.0%) were diagnosed with mental disorders such as insomnia in early winter. The total Beck Depression Inventory (BDI) score increased significantly in the early winter period, and the total Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Inventory (PSQI) scores increased in both early and late winter. The difference in changes in mood and sleep symptoms before, during, and after dispatch between the two stations was not significant.Conclusion: This is the first study to investigate the mental illness and mood and sleep status of Korean crews dispatched to Antarctica. In early winter, there were significant increases in mental illness and depressive symptoms, and a worsening of sleep status.Keywords: Antarctic, depression, insomnia, mental illness, sleep, winter-over

Jae Myeong Kang,1,2,* Seo-Eun Cho,2,* Kyoung-Sae Na,2 Seung-Gul Kang1,2 1Sleep Medicine Center, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea; 2Department of Psychiatry, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea*These authors contributed equally to this workCorrespondence: Seung-Gul KangDepartment of Psychiatry, Gil Medical Center, Gachon University, College of Medicine, 21, Namdong-daero 774 Beon-gil, Namdong-gu, Incheon, 21565, Republic of KoreaTel +82 32-458-2818Email kangsg@gachon.ac.krPurpose: Previous spectral analysis studies on obstructive sleep apnea (OSA) involved small samples, and the results were inconsistent. We performed a spectral analysis of sleep EEG based on different severities of OSA using the Sleep Heart Health Study data. This study aimed to determine the difference in EEG spectral power during sleep in the non-OSA group and with different severities of OSA in the general population.Patients and Methods: The participants (n = 5,804) underwent polysomnography, and they were classified into non-OSA, mild OSA, moderate OSA, and severe OSA groups. The fast Fourier transformation was used to compute the EEG power spectrum for total sleep duration within contiguous 30-second epochs of sleep. The EEG spectral powers of the groups were compared using 4,493 participants after adjusting potential confounding factors that could affect sleep EEG.Results: The power spectra differed significantly among the groups for all frequency bands (p corr < 0.001). We found that the quantitative EEG spectral powers in the beta and sigma bands of total sleep differed (p corr < 0.001) among the participants in the non-OSA group and with different severities of OSA, controlling for covariates. The beta power was higher and the sigma power was lower in the OSA groups than in the non-OSA group. The beta power decreased in the order of severe OSA, moderate OSA, mild OSA, and non-OSA.Conclusion: This study suggests that there are differences between the microstructures of PSG-derived sleep EEG of non-OSA participants and those with different severities of OSA.Keywords: sleep EEG, spectral power, polysomnography, OSA, beta power, sigma power

Background: The Everyday Cognition scale (ECog-39) scores are associated with future cognitive decline. We investigated whether the 12-item ECog (ECog-12), which is being collected in Alzheimer's Disease Neuroimaging Initiative (ADNI)4, can predict progression., Methods: Baseline self (PT)- and study partner (SP)-ECog-12 data were extracted from the 39-item version collected in the ADNI. Weibull analysis examined the relationship between baseline ECog-12 and future clinical progression (change in Clinical Dementia Rating Sum of Boxes [CDR-SB] scores and diagnostic conversion)., Results: Higher PT- and SP-ECog-12 scores were associated with faster CDR-SB worsening, with hazard ratios in cognitively unimpaired (CU) 3.34 and 9.61, mild cognitive impairment (MCI) 1.44 and 2.82, and dementia 0.93 and 1.82. They were associated with conversion from CU to MCI 3.01 and 6.24 and MCI to dementia 1.61 and 3.07., Discussion: SP-ECog-12 provided a higher prognostic value for predicting clinical progression, so this can help identify and monitor patients at risk in research and health-care settings., Highlights: The 12-item Everyday Cognition scale (ECog-12) data obtained from both raters increased diagnostic conversion risk from cognitively unimpaired to mild cognitive impairment (MCI) and from MCI to dementia. ECog-12, rated by study partners, was associated with an increased risk of Clinical Dementia Rating Sum of Boxes worsening in all diagnostic groups. Our results provide novel information about the specific scoring outputs and rater types (participant vs. study partner) of ECog-12 that can facilitate screening, prioritization, and longitudinal monitoring of the clinical progression of participants in Alzheimer's Disease Neuroimaging Initiative 4 and other Alzheimer's disease clinical studies, clinical trials, and in health-care settings., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Plasmodium falciparum merozoite surface proteins 1 (PfMSP1) and 2 (PfMSP2) are potential candidates for malaria vaccine development. However, the genetic diversity of these genes in the global P. falciparum population presents a significant challenge in developing an effective vaccine. Hence, understanding the genetic diversity and evolutionary trends in the global P. falciparum population is crucial., Methods: This study analyzed the genetic variations and evolutionary changes of pfmsp1 and pfmsp2 in P. falciparum isolates from the Central Highland and South-Central regions of Vietnam. DNASTAR and MEGA7 programs were utilized for analyses. The polymorphic nature of global pfmsp1 and pfmsp2 was also investigated., Results: A total of 337 sequences of pfmsp1 and 289 sequences of pfmsp2 were obtained. The pfmsp1 and pfmsp2 from Vietnam revealed a higher degree of genetic homogeneity compared to those from other malaria-endemic countries. Remarkably, the allele diversity patterns of Vietnam pfmsp1 and pfmsp2 differed significantly from those of neighboring countries in the Greater Mekong Subregion. Declines in allele diversity and polymorphic patterns of Vietnam pfmsp1 and pfmsp2 were observed., Conclusions: The Vietnam P. falciparum population might be genetically isolated from the parasite populations in other neighboring GMS countries, likely due to geographical barriers and distinct evolutionary pressures. Furthermore, bottleneck effects or selective sweeps may have contributed to the genetic homogeneity of Vietnam pfmsp1 and pfmsp2., (© 2024. The Author(s).)

Background: Although pure hemi-periareolar incisions for mastectomy can prevent visible scarring, nipple-areolar complex (NAC) necrosis is a potential risk. Superficial-arterial inflow of the NAC can be evaluated by indocyanine green angiography (ICG-A)., Objectives: This study evaluated the impact of ICG-A assisted periareolar incision on NAC necrosis during nipple-sparing mastectomy (NSM) and direct-to-implant (DTI) breast reconstruction., Methods: Between December 2018 and November 2021, lateral hemi-periareolar incisions for NSM were routine. After that time, ICG-A-assisted hemi-periareolar incisions were performed between December 2021 and Sept. 2023. The location of the main arterial inflow was evaluated during preoperative ICG-A and the periareolar incision was planned to avoid disruption. NAC necrosis in the ICG-A-assisted and blind-incision groups was compared using univariate and multivariate analyses., Results: A total of 202 breasts were analyzed including 80 breasts from 75 patients in the ICG-A-assisted group and 122 breasts from 115 patients in the blind-incision group. On preoperative ICG-A, superficial-arterial inflow was observed in 67 of 80 (83.75%) breasts. Perfusion of the nipple without superficial-arterial inflow (base-perfusion pattern) was observed in 13 breasts (16.25%). The main arterial inflow was most common in the upper-medial direction at the areolar margins (65.67%). The full-thickness NAC necrosis rate in the ICG-A-assisted incision group was significantly lower than that in the blind-incision group (2.5% vs. 13.1%, p = 0.010). Multivariate analysis demonstrated that ICG-A-assisted incisions significantly reduced the risk of NAC necrosis (odds 0.155, p = 0.030)., Conclusions: ICG-A-assisted pure hemi-periareolar incisions reduced NAC necrosis in DTI breast reconstructions., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Scaling up quantum dots to two-dimensional (2D) arrays is a crucial step for advancing semiconductor quantum computation. However, maintaining excellent tunability of quantum dot parameters, including both nearest-neighbor and next-nearest-neighbor couplings, during 2D scaling is challenging, particularly for silicon quantum dots due to their relatively small size. Here, we present a highly controllable and interconnected 2D quantum dot array in planar silicon, demonstrating independent control over electron fillings and the tunnel couplings of nearest-neighbor dots. More importantly, we also demonstrate the wide tuning of tunnel couplings between next-nearest-neighbor dots, which play a crucial role in 2D quantum dot arrays. This excellent tunability enables us to alter the coupling configuration of the array as needed. These results open up the possibility of utilizing silicon quantum dot arrays as versatile platforms for quantum computing and quantum simulation.

Plasmodium vivax Duffy binding protein (PvDBP) is crucial for erythrocyte invasion, interacting with the Duffy Antigen Receptor for Chemokines (DARC) on the erythrocyte surface. The amino-terminal cysteine-rich region II of PvDBP (PvDBPII) is a promising blood stage vaccine candidate, yet the genetic polymorphisms of this protein in global P. vivax isolates complicate the design of effective vaccines against vivax malaria. This study analyzed the genetic polymorphism of PvDBPII in Pakistan P. vivax isolates. A total of 29 single nucleotide polymorphisms (SNPs), including 22 nonsynonymous SNPs, were identified in 118 Pakistan PvDBPII. Most amino acid substitutions occurred in subdomains II and III, with six commonly observed in the global PvDBPII population. The amino acid change patterns in Pakistan PvDBPII generally mirrored those in global PvDBPII, although the frequencies of amino acid changes varied by country. Nucleotide diversity in Pakistan PvDBPII was comparable to that found in global PvDBPII. Evidence of natural selection and recombination in Pakistan PvDBPII aligned with observations in global PvDBPII. Analysis of the haplotype network of global PvDBPII revealed a complexed network of 167 haplotypes, but no geographical clustering was observed. The findings are crucial for understanding the genetic characteristics of Pakistan PvDBPII. A comprehensive analysis of nucleotide diversity and evolutionary trends in the global PvDBPII population offers valuable insights for the development of vivax malaria vaccines based on this antigen., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial or non-financial interests which may be considered as potential conflicts of interest:, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Endoscopic ultrasound-guided fine needle biopsy is an effective method for obtaining tissue samples from various organs; however, challenges such as inadequate specimens persist. This study compared a newly designed Tricore needle with a Franseen needle for endoscopic ultrasound-guided fine needle biopsy of porcine liver. Both needles were tested on four male Yorkshire pigs. Specimens were obtained with an 100% (36/36) success rate with no procedure-related adverse effects. The Tricore needle experienced significantly less resistance during puncture than Franseen needle (3.83 vs. 5.97 N, P < 0.001) and better ultrasound visibility (168.97 vs. 125.04, P = 0.004). The Tricore needle also achieved faster specimen acquisition time (48.94 vs. 59.90 s, P = 0.038), larger total specimen area (6.67 vs. 4.68 mm 2 , P = 0.049), fewer fragments (23.94 vs. 31.94, P = 0.190), lager fragment area (0.28 vs. 0.15 mm 2 , P < 0.001), and more the number of complete portal tracts (15.44 vs. 9.33, P = 0.017) compared to the Franseen needle. The newly designed Tricore needle showed enhanced procedural performance and specimen quantity and quality compared to commercially available Franseen needle. Although further clinical studies are required, the Tricore needle may represent a favorable option for endoscopic ultrasound-guided fine-needle biopsy procedures., (© 2024. The Author(s).)

Background: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME)., Methods: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance., Results: Transcriptome analysis identified IGF2 as one of the top-secreted proteins following oHSV treatment. Moreover, IGF2 expression was significantly upregulated in 10 out of 14 recurrent GBM patients after treatment with oHSV, rQNestin34.5v.2 (71.4%; P = .0020) (ClinicalTrials.gov, NCT03152318). Depletion of IGF2 substantially enhanced oHSV-mediated tumor cell killing in vitro and improved survival of mice bearing BCBM tumors in vivo. To mitigate the oHSV-induced IGF2 in the TME, we constructed a novel oHSV, oHSV-D11mt, secreting a modified IGF2R domain 11 (IGF2RD11mt) that acts as IGF2 decoy receptor. Selective blocking of IGF2 by IGF2RD11mt significantly increased cytotoxicity, reduced oHSV-induced neutrophils/PMN-MDSCs infiltration, and reduced secretion of immune suppressive/proangiogenic cytokines, while increased CD8 + cytotoxic T lymphocytes (CTLs) infiltration, leading to enhanced survival in GBM or BCBM tumor-bearing mice., Conclusions: This is the first study reporting that oHSV-induced secreted IGF2 exerts a critical role in resistance to oHSV therapy, which can be overcome by oHSV-D11mt as a promising therapeutic advance for enhanced viro-immunotherapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Background: Computerized cognitive training (CCT) has been proposed as a potential therapy for cognitive decline. One of the benefits of CCT is a transfer effect, but its mechanism on the memory domain is unclear. This study aimed to investigate the transfer effect of non-memory multidomain CCT on the memory domain and its neural basis in patients with mild cognitive impairment (MCI) through a randomized controlled trial., Methods: Patients with MCI recruited from memory clinics were randomly assigned to either the CCT or the control group. The CCT group received multidomain CCT training excluding memory training, while the control group read educational books with learning-based quizzes twice a week for 8 weeks. Participants underwent memory tests yielding a composite score, other cognitive domain tests, non-cognitive scales, and resting-state functional magnetic resonance imaging (rsfMRI), at baseline and after intervention. Within- and between-group comparisons, group × time interactions, and seed-to-voxel analyses in memory-involving brain networks were performed., Results: The CCT group showed improvement over the control group in memory domain (Group × time, F = 5.87, P = 0.03, η 2  = 0.31), which was related with the increased connectivity in the hippocampal-frontal and fusiform-occipital network. No other cognitive and non-cognitive symptoms differed between groups after adjusting for covariates., Conclusion: Eight weeks of multidomain CCT without memory training improved memory function and restored functional network in the hippocampal and medial temporal region in MCI patients. These results can provide evidence for the transferring ability of CCT on memory functioning with its neural basis., (© 2024 The Author(s). Psychogeriatrics published by John Wiley & Sons Australia, Ltd on behalf of Japanese Psychogeriatric Society.)

Myanmar aims to eliminate malaria by 2030. However, recent increase of malaria incidence is a great challenge to archive that goal. Increasing prevalence of Plasmodium vivax also hinders this endeavor. Monitoring genetic structure of the parasite is necessary to understand genetic nature and evolutionary aspect of P. vivax population in Myanmar. Partial fragment flanking blocks I and II of merozoite surface protein-3 alpha of P. vivax (pvmsp-3α) was amplified from P. vivax isolates collected in Pyin Oo Lwin, Mandalay Region, Myanmar in 2013-2015. Sequence analysis of pvmsp-3α was performed to determine genetic diversity and natural selection of this gene. Spatio-temporal genetic changes of pvmsp-3α in Myanmar P. vivax population were also investigated via comparative analysis of gene sequences obtained in this study and previously reported Myanmar pvmsp-3α sequences. Genetic diversity of Myanmar pvmsp-3α was detected in P. vivax isolates analyzed. Size polymorphisms in block I and amino acid changes and recombination events in block II were main factors contributing to the genetic diversity of pvmsp-3α. Comparative spatio-temporal analysis with previously reported Myanmar pvmsp-3α populations revealed the presence of genetic differences by population with moderate genetic differentiation between populations. Similar pattern of natural selection was also detected in Myanmar pvmsp-3α populations. These suggested that enough size of the P. vivax population sufficient to generate or maintain the genetic diversity remains in the population. Thus, continuous molecular surveillance of genetic structure of Myanmar P. vivax is necessary., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Aims: Endobiliary radiofrequency ablation (RFA) is an emerging endoscopic palliative adjunctive therapy used for the local treatment of unresectable malignant biliary obstruction (MBO). However, irregular ablation ranges caused by insufficient electrode-to-bile duct contact pose a significant obstacle. We investigated the feasibility of a self-expandable stent (SES)-based electrode with a customized RFA generator in the porcine liver and common bile duct (CBD)., Methods: An SES-RFA system with polarity switching was developed to perform endobiliary RFA. The ablation ranges of 20 ablation protocols were evaluated to validate the feasibility of the newly developed RFA system in the porcine liver. Nine of 20 ablation protocols were selected for evaluation in the porcine CBD with cholangiography, endoscopy, and histologic and immunohistochemical analysis., Results: The SES-RFA system with polarity switching was successfully constructed and demonstrated high accuracy and reproducibility. The ablation area was clearly identified between the 2 SESs. The ablation ranges and degree of mucosal damage, including terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling-positive and heat shock protein 70-positive depositions, increased proportionally with ablation protocols in the porcine liver and CBD (all P < .05). Ablation length and depth linearly increased with ablation protocols from 8.74 ± .25 to 31.25 ± .67 mm and 1.61 ± .09 to 11.94 ± .44 mm, respectively., Conclusions: The SES-RFA system with polarity switching between electrodes provided an even circumferential area of ablation and enhanced ablation depth between the electrodes. This novel endobiliary RFA system is a promising modality for local ablation in patients with unresectable MBO., Competing Interests: Disclosure All authors disclosed no financial relationships. Research support for this study was provided by the Korea Medical Device Development Fund, a grant funded by the Korean government (Ministry of Science and ICT; Ministry of Trade, Industry and Energy; Ministry of Health and Welfare, Republic of Korea; and Ministry of Food and Drug Safety; project no. RS-2023-00238092) (Jung-Hoon Park), and the National Research Foundation of Korea with a grant funded by the Korean government (Ministry of Science and ICT, no. 2022R1C1C1003205) (Jung-Hoon Park). The funders had no role in this study., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The extent of perfusion of a deep inferior epigastric artery perforator (DIEP) flap is a primary concern for surgeons. This study aimed to determine whether the flap area or volume can be estimated using perforator and flap characteristics., Methods: Intraoperative flap perfusion was assessed using indocyanine green angiography in patients who underwent DIEP flap breast reconstruction between November 2018 and February 2023. The area perfused by a single dominant perforator was delineated on the surface of the flap and measured using the ImageJ software. Multiple linear regression analysis was conducted to estimate the 'perfusion ratio,' defined as the perfused area divided by the total flap area. Potential predictor variables included flap size (cm 2 ), flap thickness (mm), perforator diameter (mm), perforator rows (medial/lateral), vertical location of perforator (at or above/below the umbilicus), and perforator eccentricity (vertical distance from upper flap margin to perforator, cm)., Results: In total, 101 patients were included in this analysis. The mean 'perfusion ratio' was 67.8% ± 11.5%, predicted by perforator diameter (p = 0.022) and vertical location below umbilicus (p < 0.001) with positive correlations and negatively correlated with flap thickness (p = 0.003) in the multivariable analysis. Both perfusion area and weight were predicted by perforator diameter, vertical location of perforator, flap size, and flap thickness (p < 0.001). The coefficient of determination (adjusted R 2 ) for prediction of perfusion weight was higher than that for the perfusion area (75.5% vs. 69.4%)., Conclusions: Flap volume, rather than area, is determined by a perforator of a given diameter and location., Competing Interests: Conflict of Interest Statement The authors declare that they have no conflict of interest., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Venoactive drugs (VADs) based on Vitis vinifera extract are widely used in Korea. However, studies on the clinical effects and head-to-head comparisons with other groups of VADs are limited. This trial aimed to evaluate whether Vitis vinifera seed extract was noninferior to the micronized purified flavonoid fraction (MPFF) in relieving venous symptoms and improving quality of life in patients with chronic venous disease., Methods: In this double-blind prospective randomized trial, patients from 13 hospitals, who were diagnosed with venous incompetence by duplex ultrasound and classified as clinical class 1, 2, or 3 in the Clinical, Etiological, Anatomical, and Pathophysiological classifications were enrolled. The primary outcome was the change in the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) score at 8 weeks from baseline. Secondary outcomes included changes in the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score at 4 and 8 weeks from baseline. Moreover, the change in leg circumferences was measured at 8 weeks and compared to baseline., Results: In total, 303 patients were enrolled and randomly assigned to receive either Vitis vinifera seed extract (n = 154) or MPFF (n = 149). The CIVIQ-20 scores at 8 weeks were significantly reduced compared to those at baseline in both groups. No significant intergroup difference in the change of CIVIQ-20 at 8 weeks from baseline was observed (-8.31 ± 14.63 vs. -10.35 ± 14.38, P = 0.29, 95% confidence interval -1.65 to 5.72). The lower limit of the 95% confidence interval was within the predefined noninferiority margin of 6.9. Furthermore, the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score scores significantly decreased at 4 and 8 weeks after randomization compared with baseline in both groups. No significant differences were observed in the reduction of each score between groups. The calf circumference measured at 8 weeks was significantly reduced compared to that at baseline in patients receiving Vitis vinifera seed extract., Conclusions: Vitis vinifera seed extract was noninferior to MPFF in relieving venous symptoms and improving the quality of life in patients with chronic venous disease., (Copyright © 2024. Published by Elsevier Inc.)

Acanthamoeba keratitis (AK) is a sight-threatening and difficult-to-treat ocular infection. The significant side effects of current AK treatments highlight the urgent need to develop a safe and effective AK medication. In this study, the amoebicidal activity of Iris setosa Pall. ex Link extract (ISE) against Acanthamoeba was examined and its specific amoebicidal mechanism was explored. ISE induced significant morphological changes in Acanthamoeba trophozoites and exhibited amoebicidal activity against A. castellanii and A. polyphaga . ISE was further fractionated into five subfractions by sequential extraction with n -hexane, chloroform, ethyl acetate, n -butanol, and water, and their amoebicidal activities and underlying amoebicidal mechanisms were investigated. The n -butanol subfraction of ISE (ISE-BuOH) displayed selective amoebicidal activity against the Acanthamoeba species with minimal cytotoxicity in human corneal cells (HCE-2). ISE-BuOH triggered apoptosis-like programmed cell death (PCD) in amoebae, characterized by DNA fragmentation, increased ROS production, and caspase-3 activity elevation. ISE-BuOH also demonstrated a partial cysticidal effect against the amoeba species. ISE-BuOH could be a promising candidate in the development of therapeutic drugs for AK.

Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is a major candidate for the blood-stage malaria vaccine. Genetic polymorphisms of global pfama-1suggest that the genetic diversity of the gene can disturb effective vaccine development targeting this antigen. This study was conducted to explore the genetic diversity and gene structure of pfama-1 among P. falciparum isolates collected in the Khyber Pakhtunkhwa (KP) province of Pakistan. A total of 19 full-length pfama-1 sequences were obtained from KP-Pakistan P. falciparum isolates, and genetic polymorphism and natural selection were investigated. KP-Pakistan pfama-1 exhibited genetic diversity, wherein 58 amino acid changes were identified, most of which were located in ectodomains, and domains I, II, and III. The amino acid changes commonly found in the ectodomain of global pfama-1 were also detected in KP-Pakistan pfama-1. Interestingly, 13 novel amino acid changes not reported in the global population were identified in KP-Pakistan pfama-1. KP-Pakistan pfama-1 shared similar levels of genetic diversity with global pfama-1. Evidence of natural selection and recombination events were also detected in KP-Pakistan pfama-1.

Purpose: Alzheimer's disease (AD) dementia may not be a single disease entity. Early-onset AD (EOAD) and late-onset AD (LOAD) have been united under the same eponym of AD until now, but disentangling the heterogeneity according to the age of sonset has been a major tenet in the field of AD research., Materials and Methods: Ninety-nine patients with AD (EOAD, n=54; LOAD, n=45) and 66 cognitively normal controls completed both [ 18 F]THK5351 and [ 18 F]flutemetamol (FLUTE) positron emission tomography scans along with structural magnetic resonance imaging and detailed neuropsychological tests., Results: EOAD patients had higher THK retention in the precuneus, parietal, and frontal lobe, while LOAD patients had higher THK retention in the medial temporal lobe. Intravoxel correlation analyses revealed that EOAD presented narrower territory of local FLUTE-THK correlation, while LOAD presented broader territory of correlation extending to overall parieto-occipito-temporal regions. EOAD patients had broader brain areas which showed significant negative correlations between cortical thickness and THK retention, whereas in LOAD, only limited brain areas showed significant correlation with THK retention. In EOAD, most of the cognitive test results were correlated with THK retention. However, a few cognitive test results were correlated with THK retention in LOAD., Conclusion: LOAD seemed to show gradual increase in tau and amyloid, and those two pathologies have association to each other. On the other hand, in EOAD, tau and amyloid may develop more abruptly and independently. These findings suggest LOAD and EOAD may have different courses of pathomechanism., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Background: Respiratory syncytial virus (RSV), a highly transmissible virus, is the leading cause of lower respiratory tract infections. We examined molecular changes in the RSV genome before and after the coronavirus disease 2019 (COVID-19) pandemic in Korea, and investigated whether drug-resistant mutations were present., Methods: In this prospective, single-center study, RSV-positive respiratory samples were collected between September 2019 and December 2022. Long-read whole-genome sequencing (WGS) was performed, and the presence of known drug-resistant substitutions for palivizumab, nirsevimab, and suptavumab was investigated., Results: Overall, 288 respiratory samples were collected from 276 children. WGS data were available for 133 samples (71 and 62 samples from the pre- and post-pandemic periods, respectively). All RSV-A strains (n = 56) belonged to the GA2.3.5 (ON1) genotype, whereas all RSV-B strains (n = 77) belonged to the GB5.0.5a (BA) genotype. No significant differences in genotypes were observed between the pre- and post-pandemic periods. In addition, no notable mutations related to nirsevimab or palivizumab resistance were detected in the F gene. However, the L172Q and S173L substitutions, which are known to confer resistance to suptavumab, were present in all RSV-B samples., Conclusion: Despite the unprecedented interruption of RSV seasonality, there were no significant molecular changes in circulating RSV strains in Korea related to nirsevimab or palivizumab resistance before and after the COVID-19 pandemic. However, RSV-specific drug-resistance substitutions for suptavumab were identified., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Concomitant iatrogenic proximal venous stenosis increases venous pressure and can be a risk factor for unfavorable outcomes of lymphaticovenular anastomosis (LVA) in extremities with secondary lymphedema. This study investigated the frequency and relevant factors of venous stenosis in patients diagnosed with secondary lymphedema who underwent LVA., Methods: Patients who underwent preoperative computed tomographic venography (CTV) and LVA for secondary lymphedema of the extremities from October 2018 to March 2022 were included. The incidence of proximal venous stenosis in the affected limb on preoperative CTV and the rate of endovascular intervention were compared between upper and lower extremities. Factors affecting proximal venous stenosis were identified through multivariable analysis using independent variables, including patient age, body mass index, comorbidities, smoking history, radiation therapy, duration of lymphedema, and location of lymphedema., Results: A total of 211 patients were analyzed, including 83 patients with upper extremity and 128 patients with lower extremity lymphedema. The incidence of proximal venous stenosis in the preoperative CTV was 32.5% and 7.8% in upper extremity, and lower extremity lymphedema, respectively (P < .001). The incidence of venous stenosis requiring endovascular intervention was significantly higher in the upper extremity compared with the lower extremity (16.9% vs 6.3%; P = .014). In multivariable analysis, risk factors affecting incidence of venous stenosis requiring endovascular intervention was the patient age (P = .007) and upper extremity (P = .009)., Conclusions: Preoperative evaluation and treatment of venous stenosis in extremities with secondary lymphedema are necessary before LVA surgery, particularly in upper extremity lymphedema., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

To explore the mechanism of Liangfang Wenjing Decoction regulating coiled-coil-helix coiled-coil-helix domain containing 4(CHCHD4) in the treatment of hypoxia on endometriosis(EMs) with cold coagulation and blood stasis. The rat model of cold coagulation and blood stasis syndrome was prepared by the ice-water bath method, and then the EMs model was established by autologous intimal transplantation. The rats were randomly divided into model group, low, medium, and high(4.7, 9.4, and 18.8 g·kg~(-1)) dose groups of Liangfang Wenjing Decoction, Shaofu Zhuyu Decoction group, and sham group, with 10 rats in each group. The rats were given intragastric administration for four weeks. During the modeling, the general condition and vaginal smear of rats were observed, and the blood flow of ears and uterus were detected by laser speckle contrast imaging(LSCI) to judge the syndrome of cold coagulation and blood stasis. After the administration, the general condition of the rats was observed, and the area of ectopic lesions was measured by caliper. The localization and expression of CHCHD4 and hypoxia inducible factors-1α(HIF-1α) were detected by immunohistochemistry, and the mRNA and protein expressions of CHCHD4 and HIF-1α were detected by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot. The primary culture of ectopic endometrial stromal cells(ESCs) from EMs patients was performed, and the CHCHD4 overexpression plasmid was constructed and transfected to establish the ESCs model of CHCHD4 overexpression. The cells were divided into the control group, CHCHD4 overexpression group, CHCHD4 overexpression+control serum group, and CHCHD4 overexpression+Liangfang Wenjing Decoction serum group. The protein expression of CHCHD4 and HIF-1α was detected by Western blot, and the glucose consumption and lactic acid level were detected. The cell proliferation was detected by MTT assay. The experiment found that compared with normal rats, the modeling rats showed symptoms of cold coagulation and blood stasis, such as mental malaise, reduced diet and drinking water, disordered estrous cycle, and blocked blood circulation in ears and uterine microvessels. Compared with the sham group, the ectopic lesions in the model group were uplifted, and the mRNA and protein expressions of CHCHD4 and HIF-1α were significantly increased(P&lt;0.05). Compared with the model group, the symptoms of cold coagulation and blood stasis in each treatment group were improved, and the area of ectopic lesions was significantly reduced(P&lt;0.05 or P&lt;0.01). The mRNA and protein expression levels of CHCHD4 and HIF-1α were significantly decreased(P&lt;0.05 or P&lt;0.01). In the cell model, compared with the control group, the expression of CHCHD4, HIF-1α protein, glucose consumption, lactic acid level, and cell proliferation activity in the CHCHD4 overexpression group were significantly increased(P&lt;0.01). Compared with the CHCHD4 overexpression group, there was no significant change in each index in the control serum group, while the protein expression of CHCHD4 and HIF-1α in the Liangfang Wenjing Decoction serum group was decreased significantly(P&lt;0.05 or P&lt;0.01). The glucose consumption, lactic acid level, and cell proliferation activity decreased significantly(P&lt;0.01). It can be seen from the above that the therapeutic effect of Liangfang Wenjing Decoction on EMs with cold coagulation and blood stasis might be related to reducing the expression of CHCHD4 and then improving the hypoxia of ectopic lesions and ectopic ESCs.

The N-degron pathway determines the half-life of proteins by selectively destabilizing the proteins bearing N-degrons. N-terminal glutamine amidohydrolase 1 (NTAQ1) plays an essential role in the arginine N-degron (Arg/N-degron) pathway as an initializing enzyme via the deamidation of the N-terminal (Nt) glutamine (Gln). However, the Nt-serine-bound conformation of hNTAQ1 according to the previously identified crystal structure suggests the possibility of other factors influencing the recognition of Nt residues by hNTAQ1. Hence, in the current study, we aimed to further elucidate the substrate recognition of hNTAQ1; specifically, we explored 12 different substrate-binding conformations of hNTAQ1 depending on the subsequent residue of Nt-Gln. Results revealed that hNTAQ1 primarily interacts with the protein Nt backbone, instead of the side chain, for substrate recognition. Here, we report that the Nt backbone of proteins appears to be a key component of hNTAQ1 function and is the main determinant of substrate recognition. Moreover, not all second residues from Nt-Gln, but rather distinctive and charged residues, appeared to aid in detecting substrate recognition. These new findings define the substrate-recognition process of hNTAQ1 and emphasize the importance of the subsequent Gln residue in the Nt-Gln degradation system. Our extensive structural and biochemical analyses provide insights into the substrate specificity of the N-degron pathway and shed light on the mechanism underlying hNTAQ1 substrate recognition. An improved understanding of the protein degradation machinery could aid in developing therapies to promote overall health through enhanced protein regulation, such as targeted protein therapies., (© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

To evaluate the safety and efficacy of combining EW-7197 with irreversible electroporation (IRE) for improving wound healing, 16 male Sprague-Dawley rats were randomly divided into four groups of four rats each after dorsal excisional wound induction: sham control group; oral administration of EW-7197 for 7 days group; one-time application of IRE group; and one-time application of IRE followed by oral administration of EW-7197 for 7 days group. Measurement of wound closure rate, laser Doppler scanning, histological staining (hematoxylin and eosin and Masson's trichrome), and immunohistochemical analyses (Ki-67 and α-SMA) were performed to evaluate the efficacy. Fifteen of 16 rats survived throughout the study. Statistically significant differences in wound closure rates were observed between the combination therapy group and the other three groups (all P < 0.05). The degrees of inflammation, α-SMA, and Ki-67 were reduced in the EW-7197 and IRE monotherapy groups; however, not statistically significant. The fibrosis score exhibited significant reduction in all three treatment groups, with the most prominent being in the combination therapy group. This study concludes that oral administration of EW-7197 combined with IRE demonstrated effectiveness in improving skin wound in a rat excisional model and may serve as a potential alternative for promoting healing outcomes., (© 2024. The Author(s).)

Background: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients., Methods: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001-2008) and the post-intervention (2009-2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patient-days, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ²., Results: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period ( P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = -16.5; 95% confidence interval [CI], -30.6 to -2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period ( P = 0.881)., Conclusion: The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia., Competing Interests: The authors have no potential conflicts of interest to declare., (© 2024 The Korean Academy of Medical Sciences.)

Purpose: The anatomical distribution, characteristics of lesions, and treatment modalities for peripheral artery disease (PAD) are diverse. Endovascular intervention is popular for symptomatic PAD, for both intermittent claudication (IC) and chronic limb-threatening ischemia (CLTI). We aimed to investigate the endovascular devices used by comparing patients with PAD referred for endovascular revascularization with IC and CLTI., Methods: We identified 736 patients with PAD enrolled in the multicenter PAD registry in South Korea from 2019 to 2022. Of these patients, 636 received endovascular treatment at the time of this study. After excluding missing data, we analyzed 506 patients with IC or CLTI. Patients' characteristics, target lesions, and endovascular device data such as type, length, balloon diameter, and stent, were examined. Procedure outcomes of the aortoiliac, femoropopliteal, and below-the-knee lesions were analyzed., Results: Patients with CLTI were more likely to have diabetes mellitus, below-the-knee interventions, and multilevel PAD than the IC group. Patients with IC had more aortoiliac artery lesions and underwent atherectomies than the CLTI group (63.3% and 61.1% vs. 39.7% and 40.6%, respectively; P < 0.001). In patients with femoropopliteal lesions, those with CLTI were more revascularized with stents than the patients with IC, without significant differences (35.3% vs. 29.1%, P = 0.161). Compared to the IC group, the CLTI patients showed significantly worse rates of primary patency, amputation, and mortality (P = 0.029, P < 0.001, and P < 0.001, respectively)., Conclusion: Among Korean patients with PAD, there is a significant difference in baseline and lesion characteristics, endovascular strategies, and short-term follow-up outcomes among those with IC and CLTI., Competing Interests: Conflicts of interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)

Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) deficiency is one of the most common X-linked hereditary disorders worldwide. G6PD deficiency provides resistance against severe malaria, but paradoxically, G6PD deficiency is also a stumbling block in fighting against malaria. Primaquine (PQ), a drug for the radical cure of Plasmodium vivax, can cause lethal acute hemolytic anemia in malaria patients with inherited G6PD deficiency. In this study, we analyzed the phenotypic and genotypic G6PD deficiency status in 1721 individuals (963 males and 758 females) residing in three malaria-endemic areas within the Gia Lai province, Vietnam. The G6PD activity in individuals ranged from 3.04 to 47.82 U/g Hb, with the adjusted male median (AMM) of 7.89 U/g Hb. Based on the G6PD activity assay results, no phenotypic G6PD deficiency was detected. However, the multiplex polymerase chain reaction to detect G6PD variations in the gene level revealed that 26 individuals (7 males, 19 females) had Viangchan mutations (871 G > A). Sequencing analyses suggested that all the males were hemizygous Viangchan, whereas one was homozygous, and 18 were heterozygous Viangchan in females. These results suggested a relatively low prevalence of G6PD deficiency mutation rate (1.51%) in the minor ethnic populations residing in the Gia Lai province, Vietnam. However, considering these areas are high-risk malaria endemic, concern for proper and safe use of PQ as a radical cure of malaria is needed by combining a G6PD deficiency test before PQ prescription., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The traditional genetic evaluation methods generally consider additive genetic effects only and often ignore non-additive (dominance and epistasis) effects that may have contributed to genetic variation of complex traits of livestock species. The available dense single nucleotide polymorphisms (SNPs) panels offer to investigate the potential benefits of including non-additive genetic effects in the genomic evaluation models. Data from 16 971 genotyped (Illumina Bovine 50 K SNP chip) Korean Hanwoo cattle were used to estimate genetic variance components and prediction accuracy of genomic breeding values (GEBVs) for four carcass and meat quality traits: carcass weight (CWT), eye muscle area (EMA), back fat thickness (BFT) and marbling score (MS). Five different genetic models were evaluated through including additive, dominance and epistatic interactions (additive by additive, A × A; additive by dominance, A × D and dominance by dominance, D × D) successively in the models. The estimates of additive genetic variances and narrow sense heritabilities (h a 2 ) were found similar across the evaluated models and traits except when additive interaction (A × A) was included. The dominance variance estimates relative to phenotypic variance ranged from 1.7-3.4% for CWT and MS traits, whereas, they were close to zero for EMA and BFT traits. The magnitude of A × A epistatic heritability (h aa 2 ) ranged between 14.8 and 27.7% in all traits. However, heritability estimates for A × D and D × D epistatic interactions (h ad 2 and h dd 2 ) were quite low compared to h aa 2 and were contributed only 0.0-9.7% of the total phenotypic variation. In general, broad sense heritability (h G 2 ) estimates were almost twice (ranging between 0.54 and 0.68) the h a 2 for all of the investigated traits. The inclusion of dominance effects did not improve the prediction accuracy of GEBV but improved 2.0-3.0% when epistatic effects were included in the model. More importantly, rank correlation revealed that partitioning of variance components considering dominance and epistatic effects in the model would enable to re-rank of top animals with better prediction of GEBV. The present result suggests that dominance and epistatic effects could be included in the genomic evaluation model for better estimates of variance components and more accurate prediction of GEBV for carcass and meat quality traits in Korean Hanwoo cattle., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess the association of primary and third doses of vaccination with the risk of post-acute sequelae of COVID-19., Methods: This retrospective cohort study utilized a combined database of nationwide health care claims data, COVID-19 patient registry, and vaccination records from South Korea. Individuals diagnosed with COVID-19 in the Omicron variant-dominant period of January-March 2022 were tracked for 30-120 days post-infection. The exposure of interest was the receipt of primary and third doses of the SARS-CoV-2 vaccine. The occurrence of 26 specific conditions in eight domains was compared using Cox regression with inverse probability of treatment weighting., Results: This study included 394 773 unvaccinated individuals and 7 604 081 individuals receiving ≥2 doses of vaccine. Compared with unvaccinated individuals, vaccination with at least two doses was associated with a reduced risk (adjusted hazard ratio; 95% CI) of several conditions, including ischaemic heart disease (0.73; 0.57-0.94), heart failure (0.55; 0.48-0.63), cardiac dysrhythmia (0.72; 0.61-0.85), cardiac arrest (0.41; 0.33-0.51), pulmonary embolism (0.66; 0.52-0.84), venous thromboembolism (0.54; 0.44-0.66), acute renal failure (0.56; 0.46-0.67), new dialysis (0.45; 0.34-0.59), chronic obstructive pulmonary disease (0.74; 0.65-0.84), acute pancreatitis (0.64; 0.51-0.80), and diabetes (0.82; 0.71-0.95). The risks of heart failure, cardiac dysrhythmias, cardiac arrest, pulmonary embolism, and new dialysis were lower in those who were vaccinated with three doses compared with those who were vaccinated with two doses., Discussion: Vaccination was associated with a decreased risk of post-acute sequelae of COVID-19, suggesting its potential role in mitigating the indirect impacts of COVID-19., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Naegleria fowleri invades the brain and causes a fatal primary amoebic meningoencephalitis (PAM). Despite its high mortality rate of approximately 97%, an effective therapeutic drug for PAM has not been developed. Approaches with miltefosine, amphotericin B, and other antimicrobials have been clinically attempted to treat PAM, but their therapeutic efficacy remains unclear. The development of an effective and safe therapeutic drug for PAM is urgently needed. In this study, we investigated the anti-amoebic activity of Pinus densiflora leaf extract (PLE) against N. fowleri. PLE induced significant morphological changes in N. fowleri trophozoites, resulting in the death of the amoeba. The IC50 of PLE on N. fowleri was 62.3±0.95 μg/ml. Alternatively, PLE did not significantly affect the viability of the rat glial cell line C6. Transcriptome analysis revealed differentially expressed genes (DEGs) between PLE-treated and non-treated amoebae. A total of 5,846 DEGs were identified, of which 2,189 were upregulated, and 3,657 were downregulated in the PLE-treated amoebae. The DEGs were categorized into biological process (1,742 genes), cellular component (1,237 genes), and molecular function (846 genes) based on the gene ontology analysis, indicating that PLE may have dramatically altered the biological and cellular functions of the amoeba and contributed to their death. These results suggest that PLE has anti-N. fowleri activity and may be considered as a potential candidate for the development of therapeutic drugs for PAM. It may also be used as a supplement compound to enhance the therapeutic efficacy of drugs currently used to treat PAM.

Irreversible electroporation (IRE) is a non-thermal ablation technique for local tumor treatment known to be influenced by pulse duration and voltage settings, affecting its efficacy. This study aims to investigate the effects of bipolar IRE with different pulse durations in a prostate cancer mouse model. The therapeutic effectiveness was assessed with in vitro cell experiments, in vivo tumor volume changes with magnetic resonance imaging, and gross and histological analysis in a mouse model. The tumor volume continuously decreased over time in all IRE-treated groups. The tumor volume changes, necroptosis (%), necrosis (%), the degree of TUNEL-positive cell expression, and ROS1-positive cell (%) in the long pulse duration-treated groups (300 μs) were significantly increased compared to the short pulse duration-treated groups (100 μs) (all p < 0.001). The bipolar IRE with a relatively long pulse duration at the same voltage significantly increased IRE-induced cell death in a prostate cancer mouse model., (© 2024. The Author(s).)

Eustachian tube balloon dilatation (ETBD) has shown promising results in the treatment of ET dysfunction (ETD); however, recurrent symptoms after ETBD frequently occur in patients with refractory ETD. The excessive pressure of balloon catheter during ETBD may induce the tissue hyperplasia and fibrotic changes around the injured mucosa. Sirolimus (SRL), an antiproliferative agent, inhibits tissue proliferation. An SRL-coated balloon catheter was fabricated using an ultrasonic spray coating technique with a coating solution composed of SRL, purified shellac, and vitamin E. This study aimed to investigate effectiveness of ETBD with a SRL-coated balloon catheter to prevent tissue proliferation in the rat ET after ETBD. In 21 Sprague-Dawley rats, the left ET was randomly divided into the control (drug-free ETBD; n = 9) and the SRL (n = 9) groups. All rats were sacrificed for histological examination immediately after and at 1 and 4 weeks after ETBD. Three rats were used to represent the normal ET. The SRL-coated ETBD significantly suppressed tissue proliferation caused by mechanical injuries compared with the control group. ETBD with SRL-coated balloon catheter was effective and safe to maintain ET luminal patency without tissue proliferation at the site of mechanical injuries for 4 weeks in a rat ET model., (© 2024. The Author(s).)