Rotavirus hospitalization in early childhood: fine motor skills and cognition at six years old-Population-based cohort study.

Rotavirus is linked to severe childhood gastroenteritis and neurological complications, but its impact on neurodevelopment remains uncertain. We examined data from 1,420,941 Korean children born between 2009 and 2011, using the Korean National Health Insurance System. At age 6, we assessed neurodevelopmental outcomes using the validated Korean Developmental Test, covering six major domains. Utilizing propensity score-based Inverse Probability Weighting to ensure covariates including considering covariates including sex, birth weight, changes in body weight from birth to 4-6 months of age, head circumference at 4-6 months of age, residence at birth, economic status, infant feeding types, and birth year. The main analysis that encompassed 5,451 children with rotavirus hospitalization and 310,874 unexposed individuals reveled heightened odds of suspected delays in fine motor skills and cognition among exposed children. Our results suggest an association between rotavirus-related hospitalization in infancy and suspected delays in fine motor function and cognition in 6-year-olds.

Psoas muscle area is associated with prognosis in elderly patients with hip fracture.

INTRODUCTION: Sarcopenia is a key predictor of prognosis in patients with hip fractures. This study utilized computed tomography (CT) scan (1) to determine the association between psoas muscle cross-sectional area (CSA) and mortality, along with other muscles, and (2) to confirm the correlation between muscle CSA and appendicular lean mass (ALM) measured using DXA in elderly patients with hip fracture. MATERIALS AND METHODS: Patients who were aged ≥ 50 years and underwent surgical treatment for hip fracture were eligible for this study. After a series of exclusion criteria, 217 female patients were included. Patient data, including clinical characteristics, such as body mass index (BMI), CSA, and ALM, were retrospectively collected. The Kaplan-Meier survival method and Cox proportional hazards regression analysis were used for the statistical analyses. The correlation between CSA/BMI and ALM was also assessed. RESULTS: Patients in the lowest quartile of psoas muscle CSA/BMI had shorter survival times than those in the other quartiles. When the Cox proportional hazards regression analysis was adjusted for multiple variables, the lowest quartile of the CSA/BMI of the psoas was a risk factor for mortality. The CSA/BMI of the psoas showed the highest correlation coefficient. The CSA/BMI ratio of the other muscles showed a moderately positive correlation with ALM. CONCLUSION: The CSA of the psoas is associated with prognosis in elderly patients with hip fractures and shows a moderately positive correlation with ALM. Hence, the CSA of psoas is useful for predicting survival and muscle mass in elderly patients with hip fractures.

Trends in Incidence and Drug Prescriptions for Croup in Children Under 5 Years of Age: A 2002-2019 Population-Based Study.

BACKGROUND: Tracking national croup trends can provide important insights for childhood health management. This study aimed to analyze the incidence and drug prescription trends in Korean children over a two-decade period. METHODS: This population-based study encompassed 479,783 children aged < 5 years from 2002-2019, utilizing the National Health Insurance Service-National Sample Cohort. We identified participants with a primary croup diagnosis who were admitted to or visited the emergency room. Age-specific and age-adjusted incidence rates/10,000 person-years were calculated. We assessed using orthogonal polynomial contrasts and stratified by various factors (sex, age, residential area, economic status, comorbidities, and healthcare facility types). We observed changes in the use of five medications: inhaled steroids, systemic steroids, inhaled epinephrine, antibiotics, and short-acting bronchodilators. Generalized binomial logistic regression was used to analyze factors influencing prescription strategies. RESULTS: In 2002, the croup-related visits were 16.1/10,000 person-years, increasing to 98.3 in 2019 (P for trend < 0.001). This trend persisted, regardless of age, sex, region, and economic status. Children with comorbid atopic dermatitis or asthma maintained consistent croup rates, while those without comorbidities increased. Treatment trends showed decreasing antibiotic (73-47%) and oxygen use (21.3-3.4%), with increasing nebulized epinephrine (9.3-41.5%) and multiple drug prescriptions (67.8-80.3%). Primary care centers exhibited a greater increase in prescription usage and hospitalization duration than did tertiary healthcare institutions. CONCLUSION: Over the past two decades, croup incidence has risen, accompanied by increased epinephrine use and decreased antibiotic prescriptions. Longer hospitalization and higher medication use were mainly observed in primary care facilities.

Contribution of Osteoblast and Osteoclast Supernatants to Bone Formation: Determination Using a Novel Microfluidic Chip.

We fabricated a microfluidic chip (osteoblast [OB]-osteoclast [OC] chip) that could regulate the mixture amounts of OB and OC supernatants to investigate the effect of different supernatant distributions on osteogenesis or osteoclastogenesis. Computer-aided design was used to produce an OB-OC chip from polydimethylsiloxane. A pressure controller was assembled and different blends of OB and OC supernatants were correctly determined. OB and OC supernatants were placed on the upper panels of the OB-OC chip after differentiation for an in vitro evaluation. We then tested the changes in osteogenesis using MC3T3-E1 cells in the middle chambers. We observed that a 75:25 distribution of OB and OC supernatants was the most potent in osteogenesis. We then primed the osteogenic differentiation of MC3T3-E1 cells using an OB-OC mixed supernatant or an OB supernatant alone (supernatant ratios of 75:25 or 100:0, respectively). These cells were placed on the calvarial defect sites of rats. Microcomputed tomography and histological analyses determined a significantly higher bone formation in the group exposed to the OB-OC supernatant at a ratio of 75:25. In this study, we demonstrate the applicability of an OB-OC chip to evaluate the effect of different supernatant distributions of OB and OC. We observed that the highest bone-forming potential was in MC3T3-E1 cells treated with conditioned media, specifically the OB-OC supernatant at a ratio of 75:25.

The Effect of the COVID-19 Pandemic on Early Adolescent Fractures in the Republic of Korea.

Background and Objectives: Restrictions on daily activities to slow down the propagation of COVID-19 have changed the epidemiological pattern of pediatric fractures in many countries. However, the effect of the pandemic on pediatric fractures has not been fully studied. In this study, we investigated the impact of COVID-19 on early adolescent fractures in Korea. Materials and methods: We conducted a retrospective follow-up on a nationwide cohort of Korean early adolescents born between 2006 and 2009. The prevalence and incidence of pediatric fractures and the frequency of surgical treatment were compared between two different eras. Results: The prevalence and incidence of fractures during the pandemic have both shown a significant decrease: prevalence reduced from 34,626 to 24,789 (p < 0.001), while incidence decreased from 29,804 to 18,898 (p < 0.001). Considering sex, the shift in fracture prevalence was statistically significant (p = 0.020), whereas the incidence was not (p = 0.862). The decline in both fracture prevalence and incidence exhibited significant variation across birth year groups (prevalence, p < 0.001; incidence, p < 0.001), with a more pronounced reduction observed in the older age groups. While the proportion of patients who required surgeries has increased, the mean frequency of surgical treatment per patient remained at a similar level (by prevalence, p = 0.181; by incidence, p = 0.735). The decline in both fracture prevalence and incidence has shown significant variation in relation to fracture sites (prevalence, p < 0.001; incidence, p < 0.001), with a decrease in distal limb fractures and an increase in forearm and axial body fractures. Conclusions: The pediatric fracture pattern in Korea has been notably influenced by the COVID-19 pandemic, warranting further investigation into causal factors. Our findings should help predict epidemiology in the post-pandemic period and thus aid policymaking and patient management.

Association of clinical and social factors with risk of fracture in children with atopic dermatitis.

BACKGROUND: Children with atopic dermatitis (AD) have multiple risk factors for accidental fractures, injuries that can lead to significant morbidity and mortality. However, little is known about the factors that mediate the relationship between AD and fracture in children. OBJECTIVE: Our purpose was to examine the association of AD with fracture and to identify potential mediating factors. METHODS: This retrospective cohort study examined children with and without AD from a longitudinal matched cohort database of 353,040 children registered in the national health insurance service and participated in the national health-screening program of Korea. We defined AD using medical claims and medication prescription records. We investigated accidental fracture events between the index date and the end of follow-up in a propensity score-matched cohort. Pre-specified subgroup analyses considered fractures in four different regions of the body. The mediating effects of 10 possible clinical factors (including the use of antihistamines and systemic corticosteroids) and social factors (including nutritional status and parental safety awareness) were determined. RESULTS: There were 145,704 participating children, 20% with AD and 49% girls. Fractures occurred in 6,652 of the children with AD (23%, mean age: 64.6 ± 29.2 months) and in 24,698 of the control group (21%, mean age 65.0 ± 28.9 months). Children with AD had an 8% greater risk of fracture events overall (adjusted relative risk [aRR]: 1.08, 95% CI: 1.05-1.10). In subgroup analysis, AD was related to increased rates of skull and facial bone fracture (aRR: 1.09, 95% CI: 1.04-1.14), for trunk including vertebrae (aRR: 1.58, 95% CI: 1.22- 2.05), and for distal limbs (aRR: 1.11, 95% CI: 1.07-1.15). However, the relationship with proximal limb fracture was insignificant. Duration of systemic corticosteroid prescription was the largest mediating factor, followed by duration of antihistamine prescription, and infant feeding practices. In particular, the duration of systemic corticosteroid prescription was significantly associated with fracture events (incidence: 20.1% at the 25th percentile and 23.6% at the 75th percentile; difference: 3.4% [95% CI: 2.8-4.0%]). CONCLUSIONS: Children with AD were related to increased fracture events. The key factors with mediating effects were systemic use of corticosteroid and antihistamine. Infant feeding practices had weaker mediating effects.

Finite element analyses of lateral condyle fracture fixation in paediatrics regarding configuration of Kirschner-wire.

BACKGROUND: This study aimed to discover the most stable outcome among different Kirschner-wire (K-wire) configurations for fixation of a lateral condyle fracture (Milch type II) in different loads of stress by using finite element analyses (FEA). METHODS: The right humerus of a 6-year-old boy with a lateral condyle fracture (Milch type II), was modelled with a computer aided engineering. Using FEA, peak von Mises stress and stiffness were evaluated first for a single K-wire fixation by varying the angle (0, 5, 10, 15, 20, 25, 30 degrees). Then, based on the single K-wire result, assessment of peak von Mises stress and stiffness were evaluated via FEA for two- or three-wire fixation under various configurations (two convergent, two parallel, three divergent). RESULTS: Single K-wire fixation by 5 and 25 degrees had the lowest peak von Mises stress. The fracture site showed higher stiffness at 0, 5 and 15 degrees. Considering the collected results and clinical situation, 5 degree K-wire was selected for the FEA of multiple K-wire fixation. For multiple K-wire fixation, three divergent (5-20-35 degrees) K-wires showed better stability, both in peak von Mises stress and stiffness, than any two-K-wire configurations. Among two K-wire fixations, two divergent (5-50 degrees) K-wires provided the lowest von Mises stress in varus and valgus while two divergent (5-65 degrees) K-wires showed better results in flexion, extension, internal and external rotation, and both configurations showed similar results in stiffness. CONCLUSIONS: We successfully created a paediatric lateral condyle fracture (Milch type II) model which was used to conduct FEA on different K-wire configurations to achieve stability of the fracture. Our results show that an initial K-wire inserted at 5 degrees, followed by the insertion of a second divergent wire at either 45 or 60 degrees provides the most stability in two K-wire fixations in this type of fracture repair.

Carpal tunnel release can be a risk factor for trigger finger: National Health Insurance data analysis.

PURPOSE: We aimed to compare trigger finger (TF) development between patients with carpal tunnel syndrome (CTS) treated with carpal tunnel release (CTR) and those treated conservatively, using the National Health Insurance Services data of Korea. We also aimed to investigate risk factors for post-CTR TF development. METHODS: We selected CTS patients with or without CTR (3543 patients in each group) between 2002 and 2015. Sex, age, follow-up duration after CTS diagnosis, and comorbidities associated with TF-development were matched using propensity score. We compared the rates of TF diagnosis and subsequent TF operations between groups. Thereafter, we selected patients with CTS undergoing CTR, for whom minimum follow-up exceeded five years. We compared sex, age, height, weight, and comorbidities associated with TF risk factors between the TF-occurrence and non-TF-occurrence groups. RESULTS: On comparing CTR-treated patients with those treated conservatively for CTS, CTR-treated patients presented with significantly higher rates of TF diagnosis (12.2%) and TF operations (4.7%) than patients without CTR (6.2% and 1.2%, respectively). Among 433 TF-diagnosed patients and 166 TF-operated patients after CTR, most were identified < 5 years after CTR, with 379 diagnosed (87.5%) and 147 operated (88.5%) patients. A total of 240 patients presented with newly developed TF over a five year period. Patients with subsequent TF exhibited a higher female sex rate and shorter height. None of the variables was significant risk factors for TF development in logistic regression analysis. CONCLUSION: We confirmed high incidences of post-CTR TF diagnosis and operations. TF develops most frequently in the first postoperative year.

Therapeutic Potential of Human Fetal Mesenchymal Stem Cells in Musculoskeletal Disorders: A Narrative Review.

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for diverse diseases and injuries. The biological and clinical advantages of human fetal MSCs (hfMSCs) have recently been reported. In terms of promising therapeutic approaches for diverse diseases and injuries, hfMSCs have gained prominence as healing tools for clinical therapies. Therefore, this review assesses not the only biological advantages of hfMSCs for healing human diseases and regeneration, but also the research evidence for the engraftment and immunomodulation of hfMSCs based on their sources and biological components. Of particular clinical relevance, the present review also suggests the potential therapeutic feasibilities of hfMSCs for musculoskeletal disorders, including osteoporosis, osteoarthritis, and osteogenesis imperfecta.

Substance P, A Promising Therapeutic Target in Musculoskeletal Disorders.

A large number of studies have focused on the role of substance P (SP) and the neurokinin-1 receptor (NK1R) in the pathogenesis of a variety of medical conditions. This review provides an overview of the role of the SP-NK1R pathway in the pathogenesis of musculoskeletal disorders and the evidence for its role as a therapeutic target for these disorders, which are major public health problems in most countries. To summarize, the brief involvement of SP may affect tendon healing in an acute injury setting. SP combined with an adequate conjugate can be a regenerative therapeutic option in osteoarthritis. The NK1R antagonist is a promising agent for tendinopathy, rheumatoid arthritis, and osteoarthritis. Research on the SP-NK1R pathway will be helpful for developing novel drugs for osteoporosis.

The Effects of Selenium on Bone Health: From Element to Therapeutics.

Osteoporosis, characterized by low bone mass and a disruption of bone microarchitecture, is traditionally treated using drugs or lifestyle modifications. Recently, several preclinical and clinical studies have investigated the effects of selenium on bone health, although the results are controversial. Selenium, an important trace element, is required for selenoprotein synthesis and acts crucially for proper growth and skeletal development. However, the intake of an optimum amount of selenium is critical, as both selenium deficiency and toxicity are hazardous for health. In this review, we have systematically analyzed the existing literature in this field to determine whether dietary or serum selenium concentrations are associated with bone health. In addition, the mode of administration of selenium as a supplement for treating bone disease is important. We have also highlighted the importance of using green-synthesized selenium nanoparticles as therapeutics for bone disease. Novel nanobiotechnology will be a bridgehead for clinical applications of trace elements and natural products.

Effect of the Duration of NSAID Use on COVID-19.

Background and Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to control pain and fever. However, their effect on COVID-19 infected patients has not been fully studied. In this study, we investigated the effect of the duration of NSAIDs use on COVID-19 infection and clinical outcomes. Materials and Methods: In South Korea, 25,739 eligible patients who received COVID-19 testing between 1 January and 31 July 2020, were included in this retrospective observational cohort analysis. Based on the date of the first COVID-19 test for each patient, NSAID prescription dates were used to separate patients into two groups (short-term group: <2 weeks; long-term group: 8−12 weeks). COVID-19 infectivity and clinical outcomes were analyzed. We used the propensity score-matching (PSM) method. Results: Of the 580 patients who had taken NSAIDs before the date of COVID-19 test, 534 and 46 patients were grouped in the short- and long-term NSAID-use groups, respectively. We did not find a statistically significant increased risk of COVID-19 infection (adjustment for age and sex, p = 0.413; adjustment for age, sex, region of residence, comorbidity, Charlson Comorbidity Index, and current use of medication, p = 0.259) or change in clinical outcomes, including conventional oxygen therapy, admission of intensive care unit, artificial ventilation, or death, between the two groups in which the PSM method was applied. Conclusions: The duration of NSAIDs use did not have a statistically significant effect on COVID-19 infectivity or clinical outcomes. However, further studies looking at clinical presentation and laboratory test results in a large number of people should be performed.

Skeletal Muscle Regeneration by the Exosomes of Adipose Tissue-Derived Mesenchymal Stem Cells.

Profound skeletal muscle loss can lead to severe disability and cosmetic deformities. Mesenchymal stem cell (MSC)-derived exosomes have shown potential as an effective therapeutic tool for tissue regeneration. This study aimed to determine the regenerative capacity of MSC-derived exosomes for skeletal muscle regeneration. Exosomes were isolated from human adipose tissue-derived MSCs (AD-MSCs). The effects of MSC-derived exosomes on satellite cells were investigated using cell viability, relevant genes, and protein analyses. Moreover, NOD-SCID mice were used and randomly assigned to the healthy control (n = 4), muscle defect (n = 6), and muscle defect + exosome (n = 6) groups. Muscle defects were created using a biopsy punch on the quadriceps of the hind limb. Four weeks after the surgery, the quadriceps muscles were harvested, weighed, and histologically analyzed. MSC-derived exosome treatment increased the proliferation and expression of myocyte-related genes, and immunofluorescence analysis for myogenin revealed a similar trend. Histologically, MSC-derived exosome-treated mice showed relatively preserved shapes and sizes of the muscle bundles. Immunohistochemical staining revealed greater expression of myogenin and myoblast determination protein 1 in the MSC-derived exosome-treated group. These results indicate that exosomes extracted from AD-MSCs have the therapeutic potential for skeletal muscle regeneration.

Long-term outcomes of the modified Nirschl technique for lateral Epicondylitis: a retrospective study.

BACKGROUND: Although the Nirschl technique was introduced approximately 40 years ago, only limited information is available about the long-term results, especially concerning extensor power changes after surgery. The purpose of this study was to investigate long-term clinical results of surgical treatment of lateral epicondylitis using the modified Nirschl technique. The main outcome variable was muscle strength for wrist extension because the extensor origin was not reattached after removal of the degenerative extensor tendon. METHODS: Data from 99 patients who underwent surgical lateral epicondylitis treatment between 2007 to 2012 were included in the study. The mean follow-up period was 8.5 years (5 to 10, ± 1.1 years) and the mean age at surgery was 44.8 years (32 to 70, ± 9.8 years). The surgeries were performed using the modified Nirschl method and did not include extensor origin reattachment. Outcome measurements included the Visual Analogue Scale (VAS) score, Disabilities of the Arm, Shoulder and Hand (DASH) score, the MAYO elbow performance score, and Nirschl and Pettrone's grades. Wrist extension and grip strength were analyzed using a digital handgrip dynamometer (microFET2TM system) and JAMA hand dynamometer. RESULTS: Mean time required to return to work was 2.4 months after surgery. At the last follow-up after surgery, the mean VAS score had significantly improved, from 4.9 to 1.1. Mean MAYO elbow performance scores significantly improved, from 64 to 90, and mean DASH scores improved from 50 to 13. The Nirschl and Pettrone's grades were 80% rated as 'excellent' and 16% rated as 'good'. After adjusting for power differences between the dominant and non-dominant arms, the difference between wrist extensor power of the operated elbow and the non-operated opposite elbow at the final follow-up was not statistically significant. No patients complained about wrist extension weakness. CONCLUSION: Although reattachment of the extensor origin was not performed during the modified Nirschl surgical technique, there was no significant weakness in wrist extension power and the long-term follow-up revealed favorable clinical results. LEVEL OF EVIDENCE: Level IV (case series). Retrospective study.

The expression of substance P and calcitonin gene-related peptide is associated with the severity of tendon degeneration in lateral epicondylitis.

BACKGROUND: In this study, we investigated whether substance P (SP) or calcitonin gene-related peptide (CGRP) expression is associated with tendon degeneration in patients with lateral epicondylitis. METHODS: Twenty-nine patients who underwent surgical treatment for lateral epicondylitis were enrolled in the final analyses. Extensor carpi radialis brevis tendon origins were harvested for histological analysis. RESULTS: SP and CGRP immunostaining were negative in healthy tendons but positive in degenerative tendons; moreover, their immunoreactivity increased with degeneration severity. Univariate analysis indicated that variables such as the preoperative visual analog scale (VAS) score or SP or CGRP expression levels were significantly associated with the Movin score. However, multivariate analysis revealed that only higher SP and/or CGRP signals were associated with higher Movin scores. Elevations in SP or CGRP expression were also linked with significantly severe preoperative VAS scores. CONCLUSION: We demonstrated that tendon degeneration severity is associated with increased SP and CGRP expression in the biopsy samples of lateral epicondylitis.

Low serum vitamin B12 levels are associated with degenerative rotator cuff tear.

BACKGROUND: Vitamin B12 (Vit B12) deficiency results in elevated homocysteine levels and interference with collagen cross-linking, which may affect tendon integrity. The purpose of this study was to investigate whether serum Vit B12 levels were correlated with degenerative rotator cuff (RC) tear. METHODS: Eighty-seven consecutive patients with or without degenerative RC tear were enrolled as study participants. Possible risk factors (age, sex, medical history, bone mineral density, and serum chemistries including glucose, magnesium, calcium, phosphorus, zinc, homocysteine, Vitamin D, Vit B12, homocysteine, and folate) were assessed. Significant variables were selected based on the results of univariate analyses, and a logistic regression model (backward elimination) was constructed to predict the presence of degenerative RC tear. RESULTS: In the univariate analysis, the group of patients with degenerative RC tear had a mean concentration of 528.4 pg/mL Vit B12, which was significantly lower than the healthy control group (627.1 pg/mL). Logistic regression analysis using Vit B12 as an independent variable revealed that Vit B12 concentrations were significantly correlated with degenerative RC tear (p = 0.044). However, Vit B12 levels were not associated with tear size. CONCLUSION: Low serum levels of Vit B12 were independently related to degenerative RC tear. Further investigations are warranted to determine if Vit B12 supplementation can decrease the risk of this condition.

Regeneration in Spinal Disease: Therapeutic Role of Hypoxia-Inducible Factor-1 Alpha in Regeneration of Degenerative Intervertebral Disc.

The intervertebral disc (IVD) is a complex joint structure comprising three primary components-namely, nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplate (CEP). The IVD retrieves oxygen from the surrounding vertebral body through CEP by diffusion and likely generates ATP via anaerobic glycolysis. IVD degeneration is characterized by a cascade of cellular, compositional, structural changes. With advanced age, pronounced changes occur in the composition of the disc extracellular matrix (ECM). NP and AF cells in the IVD possess poor regenerative capacity compared with that of other tissues. Hypoxia-inducible factor (HIF) is a master transcription factor that initiates a coordinated cellular cascade in response to a low oxygen tension environment, including the regulation of numerous enzymes in response to hypoxia. HIF-1α is essential for NP development and homeostasis and is involved in various processes of IVD degeneration process, promotes ECM in NP, maintains the metabolic activities of NP, and regulates dystrophic mineralization of NP, as well as angiogenesis, autophagy, and apoptosis during IVD degeneration. HIF-1α may, therefore, represent a diagnostic tool for early IVD degeneration and a therapeutic target for inhibiting IVD degeneration.

Paradoxical Pro-angiogenic Effect of Low-Dose Ellipticine Identified by In Silico Drug Repurposing.

Inadequate vessel maintenance or growth causes ischemia in diseases such as myocardial infarction, stroke, and neurodegenerative disorders. Therefore, developing an effective strategy to salvage ischemic tissues using a novel compound is urgent. Drug repurposing has become a widely used method that can make drug discovery more efficient and less expensive. Additionally, computational virtual screening tools make drug discovery faster and more accurate. This study found a novel drug candidate for pro-angiogenesis by in silico virtual screening. Using Gene Expression Omnibus (GEO) microarray datasets related to angiogenesis studies, differentially expressed genes were identified and characteristic direction signatures extracted from GEO2EnrichR were used as input data on L1000CDS2 to screen pro-angiogenic molecules. After a thorough review of the candidates, a list of compounds structurally similar to TWS-119 was generated using ChemMine Tools and its clustering toolbox. ChemMine Tools and ChemminR structural similarity search tools for small-molecule analysis and clustering were used for second screening. A molecular docking simulation was conducted using AutoDock v.4 to evaluate the physicochemical effect of secondary-screened chemicals. A cell viability or toxicity test was performed to determine the proper dose of the final candidate, ellipticine. As a result, we found ellipticine, which has pro-angiogenic effects, using virtual computational methods. The noncytotoxic concentration of ellipticine was 156.25 nM. The phosphorylation of glycogen synthase kinase-3ß was decreased, whereas the ß-catenin expression was increased in human endothelial cells treated with ellipticine. We concluded that ellipticine at sublethal dosage could be successfully repositioned as a pro-angiogenic substance by in silico virtual screening.

Activation of Hypoxia-Inducible Factor-1α Signaling Pathway Has the Protective Effect of Intervertebral Disc Degeneration.

Intervertebral discs (IVDs) have poor nutrient diffusion, because the nucleus pulposus (NP) lacks direct vascular supply and likely generates adenosine triphosphate by anaerobic glycolysis. Regulation of glycolysis is mediated by hypoxia-inducible factor-1α (HIF-1α), a transcription factor that responds to local oxygen tension. Constitutively active HIF-1α (CA HIF-1α) was created by point mutation and determined the protective role of HIF-1α in IVD degeneration. Under fluoroscopy, rat caudal IVD segments were stabbed by a needle puncture, and pcDNA3- HIF-1α wild-type (WT) or pcDNA3-CA HIF-1α was transfected into NP cell lines. The constitutive activity of CA HIF-1α was analyzed using a luciferase assay after cell lysis. Next, IVD tissue samples were retrieved from five patients with degenerative lumbar spinal stenosis at the time of surgery, and NP cells were cultured. NP cells were transfected with CA HIF-1α, and relevant gene expression was measured. HIF-1α protein levels in the nucleus were significantly higher, and transcriptional activity was 10.3-fold higher in NP cells with CA HIF-1α than in those with HIF-1α WT. Gene transfer of CA HIF-1α into NP cells enhanced the expression of Glut-1, Glut-3, aggrecan, type II collagen, and Sox9. Moreover, CA HIF-1α reduced the apoptosis of NP cells induced by the Fas ligand. The HIF-1α and collagen 2 expression levels were notably increased in the NP cells of the CA HIF-1α transfected segments in histology and immunohistochemistry study. Collectively, these results suggest that activation of HIF-1α signaling pathway may play a protective role against IVD degeneration and could be used as a future therapeutic agent.

Aspirin Is Related to Worse Clinical Outcomes of COVID-19.

Backgroundand Objectives: Aspirin is used globally to reduce pain and inflammation; however, its effect in patients with coronavirus disease (COVID-19) is not fully investigated and remains controversial. We evaluated the association between aspirin and COVID-19 outcomes using nationwide data from the Korean National Health Insurance System. Materials and Methods: This was a retrospective observational cohort study that included 22,660 eligible patients who underwent COVID-19 testing in South Korea between 1 January-31 July 2020. We identified all aspirin users prescribed aspirin within two weeks before or after the index date. The primary outcome was positivity for the COVID-19 test, and secondary outcomes included conventional oxygen therapy, intensive care unit, mechanical ventilation, or death. We applied the propensity score matching method to reduce the possible bias originating from the differences in patients' baseline characteristics. Results: Of those eligible, 662 patients were prescribed aspirin. Among them, 136 patients were on aspirin within two weeks before diagnosis and 526 patients were on aspirin after diagnosis. The COVID-19 test positivity rate was not significantly different according to aspirin use. Aspirin use before COVID-19 was related to an increased death rate and aspirin use after COVID-19 was related to a higher risk of the conventional oxygen therapy. Conclusion: Aspirin use was associated with adverse effects in COVID-19 patients. Further studies for mechanisms are needed.