Continuous Superior Trunk Block versus Single-Shot Superior Trunk Block with Intravenous Dexmedetomidine for Postoperative Analgesia in Arthroscopic Shoulder Surgery: A Prospective Randomized Controlled Trial.

Background/Objectives: Intravenous dexmedetomidine (DEX) can increase the analgesia duration of peripheral nerve block; however, its effect in combination with superior trunk block (STB) remains unclear. We examined whether combining single-shot STB (SSTB) with intravenous DEX would provide noninferior postoperative analgesia comparable to that provided by continuous STB (CSTB). Methods: Ninety-two patients scheduled for elective arthroscopic rotator cuff repair were enrolled in this prospective randomized trial. Patients were randomly assigned to the CSTB or SSTB + DEX group. Postoperatively, each CSTB group patient received 15 mL of 0.5% ropivacaine and a continuous 0.2% ropivacaine infusion. Each SSTB group patient received a 15 mL postoperative bolus injection of 0.5% ropivacaine. DEX was administered at 2 mcg/kg for 30 min post anesthesia, then maintained at 0.5 mcg/kg/h till surgery ended. Pain scores were investigated every 12 h for 48 h post operation, with evaluation of rebound pain incidence and opioid consumption. Results: The SSTB + DEX group had significantly higher median pain scores at 12 h post operation (resting pain, 8.0 vs. 3.0; movement pain, 8.0 vs. 5.0) and a higher incidence of rebound pain (56% vs. 20%) than the CSTB group. However, no significant between-group differences were observed in pain scores postoperatively at 24, 36, or 48 h. The CSTB group required less opioids and fewer rescue analgesics within 12-24 h post operation than the SSTB + DEX group. Conclusions: Compared with CSTB, SSTB + DEX required additional adjuvant or multimodal analgesics to reduce the risk and intensity of postoperative rebound pain in patients who underwent arthroscopic rotator cuff repair.

Minimum 19-Year Clinical Results and Patient Satisfaction After Total Knee Arthroplasty.

BACKGROUND: Long-term (minimum 19-year) outcome data on clinical results and patient satisfaction after posterior-stabilized total knee arthroplasties (TKAs) are missing in the literature. The purpose of the study was to evaluate the clinical and radiographic results as well as patient satisfaction at a mean of 21.2 years after posterior-stabilized TKAs. METHODS: This study included 756 patients (1,350 knees) who had undergone TKAs. There were 96 men and 660 women (mean age, 58 years; range, 40 to 84). The mean follow-up was 21.2 years (range, 19 to 23). At each follow-up visit, the patients were assessed radiographically and clinically. Furthermore, patient satisfaction was determined. RESULTS: The Knee Society total, pain, function, and deformity scores were 42, 18, 33, and 5 points, respectively, at the final follow-up. The mean Western Ontario and McMaster Universities Arthritis Index score was 25 points at the final follow-up. With revision or aseptic loosening as the end point, the 23-year intimated survival for the implant was 96% (95% confidence interval, 91 to 100%). The overall patient satisfaction score at the final follow-up was 83.3 points (range, 81 to 86). Patient satisfaction scores with regard to pain, housework, recreation, and surgery were 84, 81, 82, and 86 points, respectively. CONCLUSIONS: The findings of the present, mean 21-year follow-up clinical study suggest excellent results with regard to the revision rates and survivorship of the posterior-stabilized total knee implants. However, consistent with the literature, we found that about 80% of patients expressed overall satisfaction with their primary TKAs. About 8% of patients were either somewhat or very dissatisfied with the procedure.

Updated Clinical Practice Guidelines for the Diagnosis and Management of Long COVID.

"Long COVID" is a term used to describe a condition when the symptoms and signs associated with coronavirus disease 2019 (COVID-19) persist for more than three months among patients infected with COVID-19; this condition has been reported globally and poses a serious public health issue. Long COVID can manifest in various forms, highlighting the need for appropriate evaluation and management by experts from various fields. However, due to the lack of clear clinical definitions, knowledge of pathophysiology, diagnostic methods, and treatment protocols, it is necessary to develop the best standard clinical guidelines based on the scientific evidence reported to date. We developed this clinical guideline for diagnosing and treating long COVID by analyzing the latest research data collected from the start of the COVID-19 pandemic until June 2023, along with the consensus of expert opinions. This guideline provides recommendations for diagnosis and treatment that can be applied in clinical practice, based on a total of 32 key questions related to patients with long COVID. The evaluation of patients with long COVID should be comprehensive, including medical history, physical examination, blood tests, imaging studies, and functional tests. To reduce the risk of developing long COVID, vaccination and antiviral treatment during the acute phase are recommended. This guideline will be revised when there is a reasonable need for updates based on the availability of new knowledge on the diagnosis and treatment of long COVID.

Potential use of polydimethylsiloxane phantom in acupuncture manipulation practice.

Objectives: Sufficient trials of acupuncture manipulations should be practiced to obtain proficiency. However, there is not an adequate quantitative methodology for selecting a tissue-mimicking phantom that effectively reproduces the mechanical behavior that occurs during acupuncture. The objective of this study was to determine the proper mixing ratio of polydimethylsiloxane (PDMS) to obtain tissue phantom that is the most similar to porcine phantoms. Design: An automatic needle manipulator equipped with a six-degrees-of-freedom force/torque sensor was installed to monitor the interaction force that occurred when the acupuncture needle performed lifting-thrusting and twirling manipulations. Four types of PDMS phantoms, composed of two silicone elastomers with different hardener ratios, were studied alongside four control groups consisting of different porcine sites. A Visual Analog Scale was used to quantify the similarity of the PDMS phantoms to the controls by 11 Korean medical doctors. Results: Using the lifting-thrusting method, PDMS D (mixing ratio of 1:4.5) and control 2 (porcine blade shoulder) revealed no significant difference in the dynamic friction coefficients or maximum and minimum friction force values (P < 0.001). Using the twirling method, PDMS D showed no significant difference from all controls in the viscosity coefficient or maximum and minimum torque values (P ≤ 0.001). By practitioners, PDMS D showed the greatest score. Conclusion: PDMS D delivered a haptic sensation that is most similar to that of biological tissues in the case of acu-needle lifting-thrusting and twirling methods. This finding guides the preparation of tissue phantoms for acu-needle studies and acupuncture training.

The effect of perineural injection therapy on neuropathic pain: a retrospective study.

Background: Among the various pain-related diseases that can be encountered at the clinic, there is a neuropathic pain that is difficult to treat. Numerous methods have been proposed to treat neuropathic pain, such as taking medication, nerve block with lidocaine, or neurolysis with alcohol or phenol. Recently, a method of perineural injection using dextrose instead of lidocaine was proposed. This study was designed to compare the effects of perineural injection therapy (PIT) with buffered 5% dextrose or 0.5% lidocaine on neuropathic pain. Methods: The data were collected from the database of pain clinic from August 1st, 2019 to December 31st, 2022 without any personal information. The inclusion criteria were patients diagnosed with postherpetic neuralgia (PHN), trigeminal neuralgia (TN), complex regional pain syndrome (CRPS), or peripheral neuropathy (PN), and patients who had undergone PIT with buffered 5% dextrose (Dextrose group) or 0.5% lidocaine (Lidocaine group) for pain control. The data of patients, namely sex, age, and pain score (numerical rating scale, NRS) were collected before PIT. The data of NRS, side effects, and satisfaction grade (excellent, good, fair, or poor) were collected one week after each of the four PIT, and two weeks after the last PIT. Results: Overall, 112 subjects were enrolled. The Dextrose group included 89 and Lidocaine group included 23 patients. Because the number of patients in the Lidocaine group was too small to allow statistical analysis, the trend in Lidocaine group was just observed in each disease. There were no significant side effects except for a few bruise cases on the site of injection in all groups. The NRS in most Dextrose groups except CRPS were reduced significantly; however, the Lidocaine group showed a trend of pain reduction only in PHN. The Dextrose group except CRPS showed increased satisfaction two weeks after the final PIT. Conclusion: From the results, it is suggested that PIT with buffered 5% dextrose may have a good effect for neuropathic pain without any side effect except for patients with CRPS. This may offer a window into a new tool that practitioners can employ in their quest to help patients with neuropathic pain.

Knowledge and Visual Differentiation Ability of the Pressure Injury Classification System and Incontinence-Associated Dermatitis among Hospital Nurses: A Descriptive Study.

This study investigated clinical nurses' knowledge and visual differentiation ability of the pressure injury classification system (PICS) and incontinence-associated dermatitis (IAD), additionally analyzing possible influencing factors. A convenience sample of 248 nurses took the PICS and IAD knowledge test (KT) and completed the visual differentiation ability test (VDAT), consisting of 21 photographs with clinical information. The overall mean score for correct answers was 12.65 ± 2.90 points in PICS and IAD KT and 11.43 ± 4.57 points in VDAT. Incorrect responses were most common for statements related to stage II, III, IAD for PICS and IAD KT, and deep tissue pressure injury (DTPI), unstageable, and stage III for VDAT. Significant correlations were found between PICS and IAD KT and VDAT (r = 0.252, p < 0.001). Factors affecting scores for VDAT were the scores of PICS and IAD KT, debridement experience in nursing patients with PI, and the management frequency of PI and IAD. Results indicate that nurses have an overall understanding of PICS and IAD, but low visual differentiation ability regarding stage III, DTPI, and unstageable PI. Continuing education is needed to further improve knowledge and visual differentiation ability for PICS and IAD.

Educational interventions for improving nursing shift handovers: A systematic review.

AIM: This study analyzed the components of educational interventions for handovers among nursing students and nurses. BACKGROUND: A handover is a communication process that occurs when patient care responsibilities and rights are transferred from one nurse to another. This process is important in nursing to ensure the continuity of nursing care and patient safety. DESIGN: A systematic literature review of Korean and international studies was conducted to identify the components of handover educational programs for nursing students and nurses and analyze their effects, thereby providing a basis for the further development of these programs. METHODS: Studies published in English or Korean no later than June 30, 2022, were found via an electronic database search using the MEDLINE, Embase, and CINAHL databases. Three reviewers independently evaluated all the studies. These studies focused on educational interventions for nursing students and nurses regarding covering shift-to-shift nursing handovers. After reviewing 1971 extracted articles, 18 satisfied the inclusion criteria. RESULTS: Nine articles involved nursing students and nine involved nurses. Four articles covered bedside handovers as educational topics. Educational methods included lectures and active practice. Active practice comprised demonstrations, role-play, and feedback. The main content areas of the educational programs were an introduction to handovers; training regarding how to extract important information for handovers; and strategies using informatic and thematic structures, such as mnemonics, and concept mapping. The patient cases for role-play were provided in forms of written scenarios, virtual electronic charts, videos, scenario-based simulated situations, and actual patient cases assigned in clinical practice. The effects of the educational interventions were evaluated regarding knowledge, performance, and self-efficacy. Performance and self-efficacy were significantly higher in a study in which the intervention group was provided additional individual feedback compared to the control group and in a study in which the intervention group received multiple additional practice opportunities. CONCLUSIONS: Handover education for nursing students and nurses should include individual feedback, demonstrations, and opportunities to practice to improve their performance and self-efficacy. Feedback methods should be further developed to increase the effectiveness of educational programs. Sample cases involving patients should be devised to increase these opportunities, and methods for improving educator efficiency should be identified.

Comparison of microalgal hydrochar and pyrochar: production, physicochemical properties, and environmental application.

Microalgal biomass has been considered the third-generation biofuel production feedstock, but microalgae-derived biochar still needs to be thoroughly understood. This study aims to evaluate the production and physicochemical properties of microalgae-derived hydrochar produced by hydrothermal carbonization (HTC) process by comparison with pyrochar produced by dry thermal carbonization (DTC) process for environmental applications. Microalgal biochar was produced with commercially available Chlorella vulgaris microalgae using HTC and DTC processes under various temperature conditions. Pyrochar presented higher pH, ash contents, porosity, and surface area than hydrochar. Hydrochar gave more oxygen-containing functional groups on the surface and higher lead adsorption than pyrochar, making the microalgal hydrochar applicable in soil amendment and various environmental remediations. HTC could be an economically feasible thermochemical process for microalgal biochar production. It can produce hydrochar with high production yield from wet microalgae at low temperatures without a drying process.

Adult dental epithelial stem cell-derived organoids deposit hydroxylapatite biomineral.

Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.

Trends in the treatment of fibromyalgia in South Korea between 2011 and 2018: a retrospective analysis of cross-sectional health insurance data.

OBJECTIVES: Fibromyalgia treatment trends vary globally; however, the trend in South Korea has not been investigated yet. This study aimed to analyse the fibromyalgia treatment trends in South Korea. DESIGN: Retrospective, observational study using serial cross-sectional data. SETTING: The National Patient Samples of the Korean Health Insurance Review & Assessment Service from 2011 to 2018 were used. PARTICIPANTS: A total of 31 059 patients with fibromyalgia were included in this study. The basic characteristics of the patients were stratified by sex, age and comorbidity. A patient was considered to have a condition if it was recorded as a principal diagnosis at least once in a year. PRIMARY AND SECONDARY OUTCOME MEASURES: Trends in the types of medical visits and prescribed treatments were investigated and the values are presented as rates per 100 patients. The types of pharmacological treatment were presented according to the existing clinical guidelines. Additionally, combination prescription trends and associated characteristics were investigated. RESULTS: Of the patients, 66.2% were female. Visits to internal medicine departments showed the most significant increase (2011: 11.34; 2018: 21.99; p<0.001). Non-pharmacological treatment rates declined (physical therapy 2011: 18.11; 2018: 13.69; p<0.001, acupuncture 2011: 52.03; 2018: 30.83; p<0.001). Prescription rates increased for analgesics, relaxants, antiepileptics and antidepressants. Non-steroidal anti-inflammatory drug prescriptions had the highest increase (2011: 27.65; 2018: 40.02; p<0.001). Serotonin-norepinephrine reuptake inhibitor prescriptions showed significant growth (2011: 2.4; 2018: 8.05; p<0.001). Prescription durations were generally longer for women (p<0.001), with higher rate increases in this group. Combinations of ≥3 medication classes increased (2011: 8.2; 2018: 9.64; p=0.041). Women were more likely to receive combination prescriptions (crude OR 1.47 (95% CI 1.29 to 1.68), adjusted 1.18 (95% CI 1.03 to 1.36)). CONCLUSIONS: Our findings provide basic reference data for the development and application of national guidelines for fibromyalgia.

Jagged1 intracellular domain/SMAD3 complex transcriptionally regulates TWIST1 to drive glioma invasion.

Jagged1 (JAG1) is a Notch ligand that correlates with tumor progression. Not limited to its function as a ligand, JAG1 can be cleaved, and its intracellular domain translocates to the nucleus, where it functions as a transcriptional cofactor. Previously, we showed that JAG1 intracellular domain (JICD1) forms a protein complex with DDX17/SMAD3/TGIF2. However, the molecular mechanisms underlying JICD1-mediated tumor aggressiveness remains unclear. Here, we demonstrate that JICD1 enhances the invasive phenotypes of glioblastoma cells by transcriptionally activating epithelial-to-mesenchymal transition (EMT)-related genes, especially TWIST1. The inhibition of TWIST1 reduced JICD1-driven tumor aggressiveness. Although SMAD3 is an important component of transforming growth factor (TGF)-ß signaling, the JICD1/SMAD3 transcriptional complex was shown to govern brain tumor invasion independent of TGF-ß signaling. Moreover, JICD1-TWIST1-MMP2 and MMP9 axes were significantly correlated with clinical outcome of glioblastoma patients. Collectively, we identified the JICD1/SMAD3-TWIST1 axis as a novel inducer of invasive phenotypes in cancer cells.

Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis.

Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment. A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409-0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697-0.794). Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals.

Ultrasound estimates of the epidural depth in the paramedian sagittal oblique and transverse median planes: the correlation between estimated and actual depth to the epidural space in children with scoliosis.

INTRODUCTION: The present study aimed to compare the correlation and agreement of epidural depth estimation using ultrasound in the paramedian sagittal oblique (PSO) versus the transverse median (TM) plane relative to the actual epidural depth observed during midline epidural punctures in children with scoliosis. METHODS: In this prospective observational study, we enrolled 55 children aged 3-14 years with thoracolumbar scoliosis (Cobb angle >10°) requesting postoperative epidural analgesia. Ultrasound imaging was performed to estimate the distance from the skin to the epidural space in the bilateral PSO and TM planes. An anesthesiologist performed midline epidural puncture and measured the actual epidural depth from the skin to the epidural space. The correlation and degree of agreement between the ultrasound-estimated and actual epidural depths were investigated using Pearson's and concordance correlation coefficients. The image quality of the ligamentum flavum and posterior dura mater was compared. RESULTS: In the PSO view, where the larger of the two measurements from both sides was used, both Pearson's and concordance correlation coefficients for comparing the actual epidural and ultrasound-estimated depths were significantly higher than those in the TM view (0.964 vs 0.930, p value=0.002; 0.952 vs 0.892, p value=0.004, respectively). The ligamentum flavum-posterior dura mater unit was more easily distinguished in the PSO view than in the TM view (72.7% vs 38.2%, p value<0.001). CONCLUSIONS: The PSO view can be a reliable guide to facilitate epidural puncture in children with scoliosis with better visualization. TRIAL REGISTRATION NUMBER: NCT04877964.

Geriatric Nutritional Risk Index as a Prognostic Factor for Renal Progression in Patients with Type 2 Diabetes Mellitus.

The aim of this study was to evaluate whether the geriatric nutritional risk index (GNRI) is associated with chronic kidney disease (CKD) progression in patients with type 2 diabetes mellitus (DM). In total, 1100 patients with type 2 DM with a follow-up duration > 1 year were included in this longitudinal study. The risk of CKD progression was assessed according to GNRI quartiles. Patients in the lowest GNRI quartile exhibited a significantly lower estimated glomerular filtration rate (eGFR), compared with those in quartile four. Moreover, these patients had poorer glycemic control and lower hemoglobin levels, body mass index, and albumin levels. Additionally, they exhibited a greater annual decline in eGFR. Multivariate logistic regression analysis showed that old age (>60 years), baseline eGFR, the presence of proteinuria, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and low GNRI were significantly associated with CKD progression. GNRI may serve as a valuable predictive tool for identifying the risk of adverse renal outcomes in patients with type 2 DM. It may potentially serve as a more feasible measure for assessing the nutritional status of these patients, as well as for predicting their clinical outcomes.

Partial in vivo reprogramming enables injury-free intestinal regeneration via autonomous Ptgs1 induction.

Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming that leads to the emergence of injury-responsive cells with fetal-like characteristics. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial cells using OSKM (Oct4, Sox2, Klf4, and c-Myc) in vivo. The OSKM-induced forced dedifferentiation showed similar molecular features of intestinal regeneration, including a transition from homeostatic cell types to injury-responsive-like cell types. These injury-responsive-like cells, sharing gene signatures of revival stem cells and atrophy-induced villus epithelial cells, actively assisted tissue regeneration following damage. In contrast to normal intestinal regeneration involving Ptgs2 induction, the OSKM promotes autonomous production of prostaglandin E2 via epithelial Ptgs1 expression. These results indicate prostaglandin synthesis is a common mechanism for intestinal regeneration but involves a different enzyme when partial reprogramming is applied to the intestinal epithelium.

Correlation Between Neighborhood Built Environment and Leisure Walking Time Around a Riverside Park.

OBJECTIVES: This study aimed to investigate whether the distance to a riverside park and the neighborhood built environment are related to individuals' leisure walking time by examining the case of the Geumho riverside park in Daegu, South Korea. BACKGROUND: Walking, being an inexpensive means of transportation with numerous health benefits, is influenced by the conditions of neighborhood built environments. METHODS: A survey was conducted from October 12 to November 8, 2022, including 184 adults aged 18 years or older. The dependent variable was the total weekly minutes of leisure walking, and the independent variables included the neighborhood built environment measured objectively using geographic information systems as well as demographic/individual characteristics and health attitude data. Analysis of variance was conducted to determine whether leisure walking time differed depending on the distance to the riverside park, and regression analysis was conducted to examine the association between leisure walking time and the neighborhood built environment. RESULTS: Individuals living within a quarter-mile of the park walked an average of 155 min per week for leisure, which was significantly more than those living further than 1 mile (mean = 85.14 min/week). Moreover, greater access to the park, higher crosswalk density, and a lower road density were associated with more leisure walking time for residents. CONCLUSIONS: The findings of this study indicate that good access to riverside parks and pedestrian-centered neighborhood environments may be related to leisure walking among residents. These findings hold significance for urban planning and the formulation of public health policies.

The Effectiveness and Safety of Cupping Therapy on CV8 Shenque for Urticaria; a Protocol for Systematic Review and Meta-Analysis.

Purpose: Urticaria is a common mast-cell-driven disease that poses a great burden on patients and society. Suggested therapeutic methods include avoidance of triggers and the use of medications, such as H1-antihistamines; however, limitations remain regarding efficacy, dealing with comorbidities, and adverse events. Cupping therapy (CT) at CV8 Shenque has been used in traditional Chinese medicine for the treatment of various dermatological diseases, including urticaria. The efficacy of the treatment has been revealed by previous clinical trials and case reports. This study was performed to provide a protocol for a systematic review and meta-analysis to analyze the effectiveness and safety of CT at CV8 Shenque for urticaria patients. Patients and Methods: Searches of electronic databases using manual searches and contact with the corresponding authors will be performed using predefined criteria for all randomized controlled trials on CT at CV8 Shenque for urticaria patients. Every part of the process will be conducted by two independent researchers, with conflicts being solved by a third author. The primary outcomes will be symptom scores, quality of life, and effective rate. Secondary outcomes will be adverse events and diagnostic test results. RevMan 5.4 software will be used to perform the meta-analysis. The Cochrane Collaboration "Risk of bias" tool will be used for risk of bias judgments. Results: Our study will evaluate the effectiveness and safety of CT at CV8 Shenque as a treatment option for urticaria. Conclusion: This systematic review is the first to investigate the effect of CT at CV8 Shenque for urticaria patients. Our study will provide objective evidence of an alternative approach to urticaria for clinicians and patients. Study Registration: PROSPERO (Registration number: CRD42023434913).

Assessment of Equine Influenza Virus Status in the Republic of Korea from 2020 to 2022.

Equine influenza virus (EIV) causes acute respiratory disease in horses and belongs to the influenza A virus family Orthomyxoviridae, genus Orthomyxovirus. This virus may have severe financial implications for the horse industry owing to its highly contagious nature and rapid transmission. In the Republic of Korea, vaccination against EIV has been practiced with the active involvement of the Korea Racing Authority since 1974. In this study, we monitored the viral RNA for EIV using PCR, as well as the antibody levels against 'A/equine/South Africa/4/03 (H3N8, clade 1)', from 2020 to 2022. EIV was not detected using RT-PCR. The seropositivity rates detected using a hemagglutination inhibition assay were 90.3% in 2020, 96.7% in 2021, and 91.8% in 2022. The geometric mean of antibody titer (GMT) was 83.4 in 2020, 135.7 in 2021, and 95.6 in 2022. Yearlings and two-year-olds in training exhibited lower positive rates (59.1% in 2020, 38.9% in 2021, and 44.1% in 2022) than the average. These younger horses may require more attention for vaccination and vaccine responses against EIV. Continuous surveillance of EIV should be performed to monitor the prevalence and spread of this disease.

Therapeutic Effects of Combination of Nebivolol and Donepezil: Targeting Multifactorial Mechanisms in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor neurons in the spinal cord. Although the disease's pathophysiological mechanism remains poorly understood, multifactorial mechanisms affecting motor neuron loss converge to worsen the disease. Although two FDA-approved drugs, riluzole and edaravone, targeting excitotoxicity and oxidative stress, respectively, are available, their efficacies are limited to extending survival by only a few months. Here, we developed combinatorial drugs targeting multifactorial mechanisms underlying key components in ALS disease progression. Using data analysis based on the genetic information of patients with ALS-derived cells and pharmacogenomic data of the drugs, a combination of nebivolol and donepezil (nebivolol-donepezil) was identified for ALS therapy. Here, nebivolol-donepezil markedly reduced the levels of cytokines in the microglial cell line, inhibited nuclear factor-κB (NF-κB) nucleus translocation in the HeLa cell and substantially protected against excitotoxicity-induced neuronal loss by regulating the PI3K-Akt pathway. Nebivolol-donepezil significantly promoted the differentiation of neural progenitor cells (NPC) into motor neurons. Furthermore, we verified the low dose efficacy of nebivolol-donepezil on multiple indices corresponding to the quality of life of patients with ALS in vivo using SOD1G93A mice. Nebivolol-donepezil delayed motor function deterioration and halted motor neuronal loss in the spinal cord. Drug administration effectively suppressed muscle atrophy by mitigating the proportion of smaller myofibers and substantially reducing phospho-neurofilament heavy chain (pNF-H) levels in the serum, a promising ALS biomarker. High-dose nebivolol-donepezil significantly prolonged survival and delayed disease onset compared with vehicle-treated mice. These results indicate that the combination of nebivolol-donepezil efficiently prevents ALS disease progression, benefiting the patients' quality of life and life expectancy.

Annexin A2 Stabilizes Oncogenic JAG1 Intracellular Domain by Inhibiting Proteasomal Degradation in Glioblastoma Cells.

Glioblastoma (GBM) is the most lethal brain cancer, causing inevitable deaths of patients owing to frequent relapses of cancer stem cells (CSCs). The significance of the NOTCH signaling pathway in CSCs has been well recognized; however, there is no NOTCH-selective treatment applicable to patients with GBM. We recently reported that Jagged1 (JAG1), a NOTCH ligand, drives a NOTCH receptor-independent signaling pathway via JAG1 intracellular domain (JICD1) as a crucial signal that renders CSC properties. Therefore, mechanisms regulating the JICD1 signaling pathway should be elucidated to further develop a selective therapeutic regimen. Here, we identified annexin A2 (ANXA2) as an essential modulator to stabilize intrinsically disordered JICD1. The binding of ANXA2 to JICD1 prevents the proteasomal degradation of JICD1 by heat shock protein-70/90 and carboxy-terminus of Hsc70 interacting protein E3 ligase. Furthermore, JICD1-driven propagation and tumor aggressiveness were inhibited by ANXA2 knockdown. Taken together, our findings show that ANXA2 maintains the function of the NOTCH receptor-independent JICD1 signaling pathway by stabilizing JICD1, and the targeted suppression of JICD1-driven CSC properties can be achieved by blocking its interaction with ANXA2.