Purpose: Vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been the standard of care for advanced and metastatic clear cell renal cell carcinoma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory given the high rates of acquired resistance to TKI therapy despite favorable initial tumor response. Materials and Methods: To define the TKI-resistance mechanism and identify new therapeutic target for TKI-resistant ccRCC, an integrative differential gene expression analysis was performed using acquired resistant cohort and a public dataset. Sunitinib-resistant RCC cell lines were established and used to test their malignant behaviors of TKI resistance through in vitro and in vivo studies. Immunohistochemistry was conducted to compare expression between the tumor and normal kidney and verify expression of pathway-related proteins. Results: Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher proliferative ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 overexpression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the activation of TRAF6 and MAPK/AP-1 pathways. Conclusions These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC.

Purpose: The study aimed to identify which digital biomarkers are collected and which specific devices are used according to vulnerable and susceptible individual characteristics in a living-lab setting. Materials and Methods: A literature search, screening, and appraisal process was implemented using the Web of Science, Pubmed, and Embase databases. The search query included a combination of terms related to “digital biomarkers,” “devices that collect digital biomarkers,” and “vulnerable and susceptible groups.” After the screening and appraisal process, a total of 37 relevant articles were obtained. Results: In elderly people, the main digital biomarkers measured were values related to physical activity. Most of the studies used sensors. The articles targeting children aimed to predict diseases, and most of them used devices that are simple and can induce some interest, such as wearable device-based smart toys. In those who were disabled, digital biomarkers that measured location-based movement for the purpose of diagnosing disabilities were widely used, and most were measured by easy-to-use devices that did not require detailed explanations. In the disadvantaged, digital biomarkers related to health promotion were measured, and various wearable devices, such as smart bands and headbands were used depending on the purpose and target. Conclusion As the digital biomarkers and devices that collect them vary depending on the characteristics of study subjects, researchers should pay attention not only to the purpose of the study but also the characteristics of study subjects when collecting and analyzing digital biomarkers from living labs.

Background: Spinal epidural hematoma is rare condition that can rapidly develop into severe neurologic deficits. The pathophysiology of this development remains unclear. There are several case reports of emergency hematoma evacuations after epidural steroid injection. Case: We report on two patients who developed acute, large amounts of epidural hematoma without neurological deficits after transforaminal epidural steroid injection. After fluoroscopy guided aspiration for epidural hematoma was performed, neurological defects did not progress and the hematoma was shown to be absorbed on magnetic resonance imaging. Conclusions These reports are believed to be the first of treating epidural hematoma occurring after transforaminal epidural steroid injection through non-surgical hematoma aspiration. If large amounts of epidural hematoma are not causing neurological issues, it can be aspirated until it is absorbed.

The purpose of this study was to compare physical and biodegradable properties of 3D printed resorbable membranes that are used for guided tissue regenerations in periodontal tissues. Three types of 3D printed membranes (two types of non β-TCP and one type of β-TCP) were considered. The form and element compositions of 3D printed membranes were analyzed by field-emission scanning electron microscopy (FE-SEM) with energy-dispersive X-ray spectroscopy (EDS). Porosity and pore size were measured using Micro-CT. Also, tensile strength, biodegradability tests were performed. Statistical analyses were carried in tensile strength and cell viability test (p<0.05). The result of SEM images with EDS analyses showed linear layers of lattice structure with presence of C and O in all groups. There was a slight difference in Ca and P among some groups. Tensile strength was significantly different among all groups (p<0.05), and biodegradability showed that the group containing β-TCP resulted in the fastest degradation rate. Therefore, the results of this study concluded that the 3D printed resorbable membrane has variable physical and biodegradable properties for clinical use, where such information would be useful to be considered for the future development of related products and clinical application of the products.

The purpose of this study was to compare physical and biodegradable properties of 3D printed resorbable membranes that are used for guided tissue regenerations in periodontal tissues. Three types of 3D printed membranes (two types of non β-TCP and one type of β-TCP) were considered. The form and element compositions of 3D printed membranes were analyzed by field-emission scanning electron microscopy (FE-SEM) with energy-dispersive X-ray spectroscopy (EDS). Porosity and pore size were measured using Micro-CT. Also, tensile strength, biodegradability tests were performed. Statistical analyses were carried in tensile strength and cell viability test (p<0.05). The result of SEM images with EDS analyses showed linear layers of lattice structure with presence of C and O in all groups. There was a slight difference in Ca and P among some groups. Tensile strength was significantly different among all groups (p<0.05), and biodegradability showed that the group containing β-TCP resulted in the fastest degradation rate. Therefore, the results of this study concluded that the 3D printed resorbable membrane has variable physical and biodegradable properties for clinical use, where such information would be useful to be considered for the future development of related products and clinical application of the products.

Background: Spinal epidural hematoma is rare condition that can rapidly develop into severe neurologic deficits. The pathophysiology of this development remains unclear. There are several case reports of emergency hematoma evacuations after epidural steroid injection. Case: We report on two patients who developed acute, large amounts of epidural hematoma without neurological deficits after transforaminal epidural steroid injection. After fluoroscopy guided aspiration for epidural hematoma was performed, neurological defects did not progress and the hematoma was shown to be absorbed on magnetic resonance imaging. Conclusions These reports are believed to be the first of treating epidural hematoma occurring after transforaminal epidural steroid injection through non-surgical hematoma aspiration. If large amounts of epidural hematoma are not causing neurological issues, it can be aspirated until it is absorbed.

BACKGROUND: Metabolic syndrome (MetS) is a known predictor of diabetes mellitus (DM), but whether longitudinal changes in MetS status modify the risk for DM remains unclear. We investigated whether changes in MetS status over 2 years modify the 10-year risk of incident DM. METHODS: We analyzed data from 7,317 participants aged 40 to 70 years without DM at baseline, who took part in 2001 to 2011 Korean Genome Epidemiology Study. Subjects were categorized into four groups based on repeated longitudinal assessment of MetS status over 2 years: non-MetS, resolved MetS, incident MetS, and persistent MetS. The hazard ratio (HR) of new-onset DM during 10 years was calculated in each group using Cox models. RESULTS: During the 10-year follow-up, 1,099 participants (15.0%) developed DM. Compared to the non-MetS group, the fully adjusted HRs for new-onset DM were 1.28 (95% confidence interval [CI], 0.92 to 1.79) in the resolved MetS group, 1.75 (95% CI, 1.30 to 2.37) in the incident MetS group, and 1.98 (95% CI, 1.50 to 2.61) in the persistent MetS group (P for trend <0.001). The risk of DM in subjects with resolved MetS was significantly attenuated compared to those with persistent MetS over 2 years. In addition, the adjusted HR for 10-year developing DM gradually increased as the number of MetS components increased 2 years later. CONCLUSION: We found that discrete longitudinal changes pattern in MetS status over 2 years associated with 10-year risk of DM. These findings suggest that monitoring change of MetS status and controlling it in individuals may be important for risk prediction of DM.
Diabetes Mellitus ; Epidemiology ; Follow-Up Studies ; Genome ; Life Style ; Proportional Hazards Models

Resveratrol (3,4′,5,-trihydroxystilbene), a phytoalexin present in grapes, exerts a variety of actions to reduce superoxides, prevents diabetes mellitus, and inhibits inflammation. Resveratrol acts as a chemo-preventive agent and induces apoptotic cell death in various cancer cells. However, the role of resveratrol in odontoblastic cell differentiation is unclear. In this study, the effect of resveratrol on regulating odontoblast differentiation was examined in MDPC-23 mouse odontoblastic cells derived from mouse dental papilla cells. Resveratrol significantly accelerated mineralization as compared with the control culture in differentiation of MDPC-23 cells. Resveratrol significantly increased expression of ALP mRNA as compared with the control in differentiation of MDPC-23 cells. Resveratrol significantly accelerated expression of ColImRNA as compared with the control in differentiation of MDPC-23 cells. Resveratrol significantly increased expressions of DSPP and DMP-1 mRNAs as compared with the control in differentiation of MDPC-23 cells. Treatment of resveratrol did not significantly affect cell proliferation in MDPC-23 cells. Results suggest resveratrol facilitates odontoblast differentiation and mineralization in differentiation of MDPC-23 cells, and may have potential properties for development and clinical application of dentin regeneration materials.
Animals ; Cell Death ; Cell Differentiation ; Cell Proliferation ; Dental Papilla ; Dentin ; Diabetes Mellitus ; Inflammation ; Mice ; Miners ; Odontoblasts ; Regeneration ; RNA, Messenger ; Superoxides ; Vitis

BACKGROUND/AIMS: Helicobacter pylori is a distinctive pathogen that lives in the gastric mucosa and is a well known risk factor of gastric adenocarcinoma. Iron deficiency aggravates the development of H. pylori-induced premalignant and malignant lesions in a cagA-dependent manner, enhancing H. pylori virulence. The aim of this study was to identify the relationship between iron deficiency and H. pylori eradication rates. MATERIALS AND METHODS: Participants who received 7 days of first-line triple therapy with serum iron level measured in parallel were retrospectively investigated between 2005 and 2014. H. pylori eradication was confirmed by the rapid urease test or 13C-urea breath test at least 4 weeks after completion of triple therapy. Iron deficiency was defined as either a serum iron level less than 50 µg/dL or a serum ferritin level less than 12 ng/mL. RESULTS: A total of 194 patients received 7 days of first-line triple therapy along with parallel serum iron level measurements over the 10-year period. The mean average age was 53.3 years (range, 21~86 years), and 135 patients (69.6%) were male. The overall H. pylori eradication rate was 83.5%. Proportions of eradication success with ferritin level less than 12 ng/mL and iron less than 50 µg/dL were 90.5% and 88.6%, respectively. However, there was no statistical difference in eradication rates according to iron deficiency. CONCLUSIONS: Iron deficiency might not be related with H. pylori eradication rates in this study. Further large-scale studies are needed to confirm this result.
Adenocarcinoma ; Breath Tests ; Disease Eradication ; Ferritins ; Gastric Mucosa ; Helicobacter pylori* ; Helicobacter* ; Humans ; Iron* ; Male ; Retrospective Studies ; Risk Factors ; Urease ; Virulence

OBJECTIVES: Asia sand dust (ASD) is known to cause various human diseases including respiratory infection. The aim of this study was to examine the effect of ASD on inflammatory response in human middle ear epithelial cells (HMEECs) in vitro and in vivo. METHODS: Cell viability was assessed using the cell counting kit-8 assay. The mRNA levels of various genes including COX-2, TNF-a, MUC 5AC, MUC 5B, TP53, BAX, BCL-2, NOX4, and SOD1 were analyzed using semiquantitative realtime polymerase chain reaction. COX-2 protein levels were determined by western blot analysis. Sprague Dawley rats were used for in vivo investigations of inflammatory reactions in the middle ear epithelium as a result of ASD injection. RESULTS: We observed dose-dependent decrease in HMEEC viability. ASD exposure significantly increased COX-2, TNF-a, MUC5AC, and MUC5B mRNA expression. Also, ASD affected the mRNA levels of apoptosis- and oxidative stress-related genes. Western blot analysis revealed a dose-dependent increase in COX-2 production. Animal studies also demonstrated an ASD-induced inflammatory response in the middle ear epithelium. CONCLUSION: Environmental ASD exposure can result in the development of otitis media.
Animals ; Asia ; Asian Continental Ancestry Group* ; Blotting, Western ; Cell Count ; Cell Survival ; Cyclooxygenase 2 ; Dust* ; Ear, Middle* ; Epithelial Cells ; Epithelium ; Gene Expression* ; Humans ; In Vitro Techniques ; Mucins* ; Otitis Media ; Polymerase Chain Reaction ; Rats, Sprague-Dawley ; RNA, Messenger