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.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammatory response, which is inexpensive, easily calculated, and known to show correlation with prognosis of cancer. The aim of this study was to evaluate the relationship between NLR and prognosis of papillary thyroid carcinoma. METHODS: A total of 1,142 patients who underwent total thyroidectomy for papillary thyroid carcinoma between 1995~2005 at Asan Medical Center were enrolled in this study. Patients were categorized according to two groups based on NLR and clinico-pathological variables and disease survival were compared between the two groups. RESULTS: Median age of patients was 45.4 years, and the median follow-up period was 48 months. The cut-off value of NLR for prediction of disease-free survival (DFS) was 2. Comparison of DFS between two groups stratified by NLR (NLR ≤2, NLR>2) showed little statistical difference (P=0.48). After adjusting for risk (N stage), there was no significant difference according to N stage (N0: P=0.86, N1a: P=0.4, N1b: P=0.12). CONCLUSION: NLR did not show correlation with disease free survival of papillary thyroid carcinoma.
Chungcheongnam-do ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Prognosis ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

PURPOSE: The major issue of follicular thyroid carcinoma (FTC) diagnosed after hemithyroidectomy is whether to undergo further treatments. The aim of this study is to examine the clinico-pathological characteristics of FTC and to evaluate the risk factors for distant metastasis. METHODS: From 1993 to 2010, 274 patients underwent initial thyroid surgery and were subsequently diagnosed as FTC. After review of the histological sections by an experienced pathologist, 211 patients were confirmed as FTC and were enrolled in this study. Clinicopathological features were compared based on the presence or absence of distant metastases, and the risk factors for distant metastases and distant metastases-free survival (DMFS) rates were analyzed. RESULTS: The patients included 39 males (18.5%) and 172 females (81.5%), with a mean age of 44.0±14.5 years. The median follow-up period was 99.5 months (range, 13.0~222.0). Distant metastases were detected in 23 patients (10.9%), including 15 synchronous distant metastases and 8 metachronous distant metastases. In multivariate analysis, age ≥45 years, widely invasive FTC, tumor size ≥4.3 cm, and vascular invasion were independent risk factors for distant metastasis. DMFS rates in patients with these risk factors were significantly poorer than those in patients without these risk factors. CONCLUSION: Older age, aggressive histological classification, larger tumor size, and vascular invasion were independent risk factors for distant metastasis. FTC patients with these risk factors may be candidates for further treatments after diagnostic thyroid hemithyroidectomy.
Adenocarcinoma, Follicular* ; Classification ; Female ; Follow-Up Studies ; Humans ; Male ; Multivariate Analysis ; Neoplasm Metastasis* ; Risk Factors* ; Survival Rate ; Thyroid Gland

The Korean Society of Neurogastroenterology and Motility first published guidelines for chronic constipation in 2005 and was updated in 2011. Although the guidelines were updated using evidence-based process, they lacked multidisciplinary participation and did not include a diagnostic approach for chronic constipation. This article includes guidelines for diagnosis and treatment of chronic constipation to realistically fit the situation in Korea and to be applicable to clinical practice. The guideline development was based upon the adaptation method because research evidence was limited in Korea, and an organized multidisciplinary group carried out systematical literature review and series of evidence-based evaluations. Six guidelines were selected using the Appraisal of Guidelines for Research & Evaluation (AGREE) II process. A total 37 recommendations were adopted, including 4 concerning the definition and risk factors of chronic constipation, 8 regarding diagnoses, and 25 regarding treatments. The guidelines are intended to help primary physicians and general health professionals in clinical practice in Korea, to provide the principles of medical treatment to medical students, residents, and other healthcare professionals, and to help patients for choosing medical services based on the information. These guidelines will be updated and revised periodically to reflect new diagnostic and therapeutic methods.
Constipation* ; Delivery of Health Care ; Diagnosis* ; Health Occupations ; Humans ; Korea* ; Methods ; Risk Factors ; Students, Medical

The Korean Society of Neurogastroenterology and Motility first published guidelines for chronic constipation in 2005 and was updated in 2011. Although the guidelines were updated using evidence-based process, they lacked multidisciplinary participation and did not include a diagnostic approach for chronic constipation. This study includes guidelines for diagnosis and treatment of chronic constipation to realistically fit the situation in Korea and to be applicable to clinical practice. The guideline development was based upon the adaptation method because research evidence was limited in Korea, and an organized multidisciplinary group carried out systematical literature review and series of evidence-based evaluations. Six guidelines were selected using the Appraisal of Guidelines for Research & Evaluation II process. A total 37 recommendations were adopted, including 4 concerning the definition and risk factors of chronic constipation, 8 regarding diagnoses, and 25 regarding treatments. The guidelines are intended tohelp primary physicians and general health professionals in clinical practice in Korea, to provide the principles of medical treatment to medical students, residents, and other healthcare professionals, and to help patients for choosing medical services based on the information. These guidelines will be updated and revised periodically to reflect new diagnostic and therapeutic methods.
Constipation* ; Delivery of Health Care ; Diagnosis* ; Health Occupations ; Humans ; Korea* ; Risk Factors ; Students, Medical

PURPOSE: Transurethral resection of bladder tumor (TURBT) can be a challenging procedure for an inexperienced surgeon. We suggest an easy technique for TURBT, which we have named the "grasp and bite" technique. We describe this technique and compare its effectiveness and safety with that of conventional TURBT. MATERIALS AND METHODS: Monopolar TURBT (24-Fr Karl Storz) was performed in 35 patients who had superficial bladder tumors. After defining the tumor margin, the tumor and surrounding mucosa were grasped by use of a loop electrode and resectoscope sheath. With tight grasping, linear moving resection was performed. The patients' demographic, intraoperative, and postoperative data were analyzed between the conventional and grasp and bite TURBT groups. RESULTS: Of 35 patients, 16 patients underwent conventional TURBT (group 1), and the other 19 patients underwent grasp and bite TURBT (group 2). Both groups were similar in age, tumor multiplicity, size, anesthesia method, and location. Grasp and bite TURBT could be performed as safely and effectively as conventional TURBT. There were no significant differences in irrigation duration, urethral catheterization, postoperative hemoglobin drop, or length of hospital stay. No significant side effects such as bladder perforation, severe obturator reflex, or persistent bleeding occurred. There were no significant pathological differences between specimens according to the type of resection technique. CONCLUSIONS: The grasp and bite TURBT technique was feasible for superficial bladder tumors. It may be a good tool for inexperienced surgeons owing to its convenient and easy manner.
Aged ; Cystoscopy ; Electrodes ; Female ; Humans ; Male ; Middle Aged ; Postoperative Complications ; Urinary Bladder/pathology/*surgery ; Urinary Bladder Neoplasms/pathology/*surgery ; Urologic Surgical Procedures/instrumentation/*methods

OBJECTIVE: To assess whether multi-echo Dixon magnetic resonance (MR) imaging with simultaneous T2* estimation and correction yields more accurate fat-signal fraction (FF) measurement of the lumbar paravertebral muscles, in comparison with non-T2*-corrected two-echo Dixon or T2*-corrected three-echo Dixon, using the FF measurements from single-voxel MR spectroscopy as the reference standard. MATERIALS AND METHODS: Sixty patients with low back pain underwent MR imaging with a 1.5T scanner. FF mapping images automatically obtained using T2*-corrected Dixon technique with two (non-T2*-corrected), three, and six echoes, were compared with images from single-voxel MR spectroscopy at the paravertebral muscles on levels L4 through L5. FFs were measured directly by two radiologists, who independently drew the region of interest on the mapping images from the three sequences. RESULTS: A total of 117 spectroscopic measurements were performed either bilaterally (57 of 60 subjects) or unilaterally (3 of 60 subjects). The mean spectroscopic FF was 14.3 +/- 11.7% (range, 1.9-63.7%). Interobserver agreement was excellent between the two radiologists. Lin's concordance correlation between the spectroscopic findings and all the imaging-based FFs were statistically significant (p < 0.001). FFs obtained from the T2*-corrected six-echo Dixon sequences showed a significantly better concordance with the spectroscopic data, with its concordance correlation coefficient being 0.99 and 0.98 (p < 0.001), as compared with two- or three-echo methods. CONCLUSION: T2*-corrected six-echo Dixon sequence would be a better option than two- or three-echo methods for noninvasive quantification of lumbar muscle fat quantification.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Image Processing, Computer-Assisted ; Low Back Pain/*radiography ; Magnetic Resonance Imaging/instrumentation/*methods ; Male ; Middle Aged ; Muscles/radiography ; Spinal Cord