Vitisin B inhibits influenza A virus replication by multi-targeting neuraminidase and virus-induced oxidative stress

The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

Machine Learning Models for Predicting the Occurrence of Respiratory Diseases Using Climatic and Air-Pollution Factors

Objectives@#. Because climatic and air-pollution factors are known to influence the occurrence of respiratory diseases, we used these factors to develop machine learning models for predicting the occurrence of respiratory diseases. @*Methods@#. We obtained the daily number of respiratory disease patients in Seoul. We used climatic and air-pollution factors to predict the daily number of patients treated for respiratory diseases per 10,000 inhabitants. We applied the relief-based feature selection algorithm to evaluate the importance of feature selection. We used the gradient boosting and Gaussian process regression (GPR) methods, respectively, to develop two different prediction models. We also employed the holdout cross-validation method, in which 75% of the data was used to train the model, and the remaining 25% was used to test the trained model. We determined the estimated number of respiratory disease patients by applying the developed prediction models to the test set. To evaluate the performance of each model, we calculated the coefficient of determination (R2) and the root mean square error (RMSE) between the original and estimated numbers of respiratory disease patients. We used the Shapley Additive exPlanations (SHAP) approach to interpret the estimated output of each machine learning model. @*Results@#. Features with negative weights in the relief-based algorithm were excluded. When applying gradient boosting to unseen test data, R2 and RMSE were 0.68 and 13.8, respectively. For GPR, the R2 and RMSE were 0.67 and 13.9, respectively. SHAP analysis showed that reductions in average temperature, daylight duration, average humidity, sulfur dioxide (SO2), total solar insolation amount, and temperature difference increased the number of respiratory disease patients, whereas increases in atmospheric pressure, carbon monoxide (CO), and particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5) increased the number of respiratory disease patients. @*Conclusion@#. We successfully developed models for predicting the occurrence of respiratory diseases using climatic and air-pollution factors. These models could evolve into public warning systems.

The Effect of Frenotomy on the Tongue Length, Motion, and Speech According to Age / 대한이비인후과학회지

Background and Objectives@#Ankyloglossia often results in articulation disorders, which depends on age, articulation ability, and mobility of the tongue. A primary treatment strategy includes surgery and/or speech therapy. This study aimed to evaluate the changes of the tongue length, tongue mobility, and percentage of consonants correct (PCC) after frenotomy.We investigated the optimal surgery timing for ankyloglossia. @*Subjects and Methods@#A total of 136 patients underwent frenotomy for the tongue tie between January 2016 and December 2019. There were 90 males and 46 females, with the mean age of 5.23, which ranged from 2 to 10 years. The length of the tongue was measured for all patients during the operation preoperatively and postoperatively. The mobility of the tongue and PCC were performed preoperatively and 1 month after surgery by two speech therapists. Patients were divided according to age into three groups: 2-3 years, 4-5 years, and over 6 years old. @*Results@#The mean tongue length of all age groups was significantly elongated after surgery(p<0.05). After frenotomy, the mobility of tongue, including horizontal protrusion, protrusion with upward pointing, circumlocution, and lateral movement, was improved. Also, PCCs of all age groups were significantly improved after surgery (p<0.05). @*Conclusion@#Frenotomy can be an effective procedure for children with ankyloglossia in all age groups. After frenotomy, length of the tongue, mobility of the tongue and PCC were significantly improved.

Osteosarcopenia in Patients with Hip Fracture Is Related with High Mortality

BACKGROUND: This study evaluated the prevalence of osteosarcopenia, as well as the relationship between one-year mortality and osteosarcopenia, as defined by criteria of the Asian Working Group on Sarcopenia in patients age 60 or older with hip fracture. METHODS: A total of 324 patients age 60 years or older with hip fracture were enrolled in this retrospective observational study. The main outcome measure was the prevalence of osteosarcopenia, as well as the relationship between osteosarcopenia and 1-year mortality. The diagnosis of sarcopenia was carried out according to the Asian Working Group on Sarcopenia. Whole body densitometry analysis was used for skeletal muscle mass measurement and muscle strength were evaluated by handgrip testing. Mortality was assessed at the end of 1-year. Cox regression analysis was utilized to analyze the risk factor of osteosarcopenia. RESULTS: Of 324 patients with hip fracture, 93 (28.7%) were diagnosed with osteosarcopenia. In total, 9.0% died during the one-year follow-up. A one-year mortality of osteosarcopenia (15.1%) was higher than that of other groups (normal: 7.8%, osteoporosis only: 5.1%, sarcopenia only: 10.3%). Osteosarcopenia had a 1.8 times higher mortality rate than non-osteosarcopenia. CONCLUSION: The present study demonstrates that the prevalence of osteosarcopenia is not rare, and has a higher mortality rate than the non-osteosarcopenia group at the 1-year follow-up period. This is the first study evaluating the relationship between mortality and osteosarcopenia in patients with hip fracture.

High Prevalence of Sarcopenia in Korean Patients after Hip Fracture: a Case-Control Study

Sarcopenia-related falls and fractures are increasing worldwide due to the aging population. The purpose of this study was to 1) evaluate anthropometric characteristics related to hip fracture in Korean patients, 2) investigate sarcopenia prevalence in hip fracture (HF) and non-hip fracture (NF) groups, and 3) investigate the correlation between sarcopenia and osteoporosis. This case-control study examined 359 HF and 1,614 NF normal populations using Korea National Health and Nutrition Examination Survey data. We performed whole-body dual energy X-ray absorptiometry to analyze body composition using the skeletal muscle mass index (SMI: lean mass/height2) and bone mineral density (BMD). In the HF group, using the AWGS definition, the prevalence of sarcopenia in women and men was 44.3% and 68.2%, respectively; in the NF group, it was 7.1% and 16.1%, respectively. Lower appendicular SMI (P < 0.001), leg muscle mass (P < 0.001), and higher prevalence of sarcopenia (P < 0.001) were observed in the HF group after adjustment for age and gender. In multivariate analysis, sarcopenia (OR = 6.52; 95% CI = 4.67-9.09), age (OR = 1.15; 95% CI = 1.13-1.17), and osteoporosis (OR = 1.87; 95% CI = 1.35-2.58) were associated with the occurrence of a hip fracture. This study showed a higher prevalence of sarcopenia in patients with hip fractures compared with a normal population, and higher prevalence of sarcopenia in men.

Dorsal Approach for Distal Radius Fractures

Since the advent of volar locking plate, volar approach for internal fixation has become a major trend in the treatment for unstable distal radius fracture. However, dorsal approach is preferred for certain fracture pattern include AO type C3, dorsal Barton's fractures and concomitant intercarpal ligament injury, because it can afford excellent exposure of the articular surface. Although dorsal approach and plating technique has inherent disadvantages include extensor tendon irritation and rupture, improvements in implant design lead to decrease complication rate. Here, we provide overview of the pros and cons through historic perspective, indications, and surgical technique of the dorsal approach for the distal radius fracture.

Changes in Transepidermal Water Loss and Skin Hydration according to Expression of Aquaporin-3 in Psoriasis

BACKGROUND: Aquaporins (AQPs) are a family of water transporting proteins present in many mammalian epithelial and endothelial cell types. Among the AQPs, AQP3 is known to be a water/glycerol transporter expressed in human skin. OBJECTIVE: The relationship between the expression level of AQP3 and transpidermal water loss (TEWL) in the lesional and peri-lesional skin of psoriasis-affected patients, and skin hydration in the lesional and peri-lesional skin of psoriasis patients, was investigated. METHODS: The expression of AQP3 in psoriasis-affected and healthy control skin was determined using immunohistochemical and immunofluroscence staining. TEWL and skin hydration were measured using a Tewameter(R) TM210 (Courage & Khazaka, Cologne, Germany) and a Corneometer(R) CM 820 (Courage & Khazaka), respectively. RESULTS: AQP3 was mainly expressed in the plasma membrane of stratum corneum and the stratum spinosum in normal epidermis. Unlike the normal epidermis, AQP3 showed decreased expression in the lesional and peri-lesional epidermis of psoriasis. TEWL was increased, and skin hydration was decreased, in the lesional and peri-lesional skin of psoriasis patients, compared with the healthy control sample. CONCLUSION: Although various factors contribute to reduced skin hydration in the lesional and peri-lesional skin of psoriasis, AQP3 appears to be a key factor in the skin dehydration of psoriasis-affected skin.

Three Cases of Allopurinol-induced DRESS Syndrome / 대한피부과학회지

Allopurinol (4-hydroxypyrazolo-[3,4-d]pyrimidine) is an effective and widely used xanthine oxidase inhibitor administered in the treatment of hyperuricemic states such as gout. Allopurinol-induced DRESS (Drug rash with eosinophilia and systemic symptoms) syndrome is characterized by hematologic abnormalities, especially eosinophilia and mononucleosis-like atypical lymphocytosis, skin rash, fever, lymph node enlargement and single or multiple organ involvement, which starts within 8 weeks after the initiation of therapy. We report three cases of allopurinol-induced DRESS syndrome who developed erythematous skin eruption six weeks, nine weeks and seven weeks, respectively, after allopurinol therapy. The clinical, laboratory and histologic findings of these patients were compatible with allopurinol-induced DRESS syndrome.