Loganin Prevents Hepatic Steatosis by Blocking NLRP3 Inflammasome Activation

Activation of the NLRP3 inflammasome is a necessary process to induce fibrosis in nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is a kind of NAFLD that encompasses the spectrum of liver disease. It is characterized by inflammation and ballooning of hepatocytes during steatosis. We tested whether inhibiting the NLRP3 inflammasome could prevent the development and pathology of NASH. We identified loganin as an inhibitor of the NLRP3 inflammasome and investigated whether in vivo administration of loganin prevented NASH symptoms using a methionine-choline deficient (MCD) diet model in mice. We found that loganin inhibited the NLRP3 inflammasome activation triggered by ATP or nigericin, as shown by suppression of the production of interleukin (IL)-1β and caspase-1 (p10) in mouse primary macrophages. The speck formation of apoptosisassociated speck-like protein containing a caspase recruitment domain (ASC) was blocked by loganin, showing that the assembly of the NLRP3 inflammasome complex was impaired by loganin. Administration of loganin reduced the clinical signs of NASH in mice fed the MCD diet, including hepatic inflammation, fat accumulation, and fibrosis. In addition, loganin reduced the expression of NLRP3 inflammasome components in the liver. Our findings indicate that loganin alleviates the inflammatory symptoms associated with NASH, presumably by inhibiting NLRP3 inflammasome activation. In summary, these findings imply that loganin may be a novel nutritional and therapeutic treatment for NASH-related inflammation.

Oral spindle cell/sclerosing rhabdomyosarcoma on mandible with anaplastic lymphoma kinase expression mimicking inflammatory myofibroblastic tumor

Oral spindle cell/sclerosing rhabdomyosarcoma (SCRMS) with anaplastic lymphoma kinase (ALK) expression is extremely rare, and its diagnosis is very challenging in the absence of clinical or pathological indicators. This case presented with gingival swelling and alveolar bone resorption and was suspected clinically to be periodontitis. A biopsy was performed and, due to immunoreactivity with ALK, the patient was misdiagnosed with inflammatory myofibroblastic tumor. However, based on the combined histological and immunohistochemical features, a revised diagnosis of SCRMS with ALK expression was finally concluded. We believe that this report makes a significant contribution to the precise diagnosis of this rare disease for proper treatment.

Dental Radiography for Age Estimation: A Scoping Review

Purpose@#This study was to investigate the types of imaging modalities, analytical methods for age estimation, and the age of the subjects in research on age estimation using dental radiography through a scoping review, and to investigate the overall trends in age estimation studies. @*Materials and Methods@#A scoping review was designed according to the Arksey and O’Malley guidelines and the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Three electronic databases were used as search sources (Medline, Embase, and Cochrane Library). Studies were classified according to the three main components of the research question. “What are the imaging modalities, analytical methods, and target age in dental imaging-based age estimation studies?”Result: The final 198 studies were selected by two reviewers. The most common imaging modality used in studies was panoramic radiography (69.7%), and studies using cone-beam computed tomography have increased over time. Analytical methods for age estimation were 62.6% in studies based on tooth development and 26.3% in studies using pulp/tooth ratio. The subject age was 27.8% for children and 27.3% for adults. Studies conducted in all age groups comprised the smallest category (5.2%). @*Conclusion@#Panoramic radiography has been the most used types of imaging modalities for age estimation, and the most common analytical method was analysis of tooth development. Most studies targeted specific ages, and very few involved all age groups. Dental age estimation studies should be carried out with appropriate consideration of the imaging modality that is analyzed, the methods that are used, and the age that is targeted.

Extract of Curcuma zedoaria R. prevents atherosclerosis in apolipoprotein E-deficient mice

BACKGROUND/OBJECTIVES@#Curcuma zedoaria R. (Zingiberaceae) has been used to treat headache, fever, and hypertension-related symptoms in Asian countries, including Korea, China, and Japan. We investigated whether dietary intake of a C. zedoaria extract (CzE) affected atherosclerosis in vivo.MATERIALS/METHODS: Apolipoprotein E-deficient (ApoEM−/− ) mice (n = 32) were fed a normal diet (ND), a high-cholesterol diet (HCD), an HCD containing CzE (100 mg/kg/day), or an HCD containing simvastatin (10 mg/kg/day) for 12 weeks. The anti-atherosclerotic effects were evaluated by observing changes in fatty streak lesions, immunohistochemical analysis, ex vivo fluorescence imaging, lipid profiles, and western blot analysis. @*RESULTS@#The CzE-fed group showed a 41.6% reduction of atherosclerosis. Furthermore, CzE significantly reduced the levels of serum triglyceride, high-density lipoprotein, the chemokine (C-X3-C-motif ) ligand 1, the adhesion molecules vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin; down-regulation of tumor necrosis factor-α, interleukin-6, high mobility group box-1, and cathepsin levels in the aortic sinuses and aortas of ApoE −/− mice were also observed. @*CONCLUSIONS@#The results suggest that the inclusion of a water extract of C. zedoaria in a HCD is closely correlated with reducing the risk of vascular inflammatory diseases in an ApoE mouse model.

Sagittal split ramus osteotomy, intraoral vertical ramus osteotomy, and lateral corticectomy for asymmetric mandibular prognathism

Objectives@#The purpose of this study was to evaluate the postoperative anteroposterior stability and improvements in facial asymmetry after performing LeFort I osteotomy in the maxilla, sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO) in the mandible, and lateral corticectomy on the IVRO side. @*Materials and Methods@#From July 2009 to October 2018, a retrospective analysis was performed on 11 subjects. Lateral cephalometric radiograph was performed preoperatively (T0), postoperatively (T1), and at 12 months of follow-up (T2), and the B point distance was measured. Posteroanterior cephalometric radiograph was performed preoperatively (S0) and at 12 months of follow-up (S1) and was used to measure five indicators (Ag angle, M-Ag, Co-Ag, Co-Me, and Ag-Me) of facial asymmetry. @*Results@#The B point distances for T0 and T1 were significantly different (P=0.007), whereas those for T1 and T2 were not significantly different (P=0.1). In addition, there was a significant difference between the B point distances of T2 and T0 (P=0.026). Comparison of the facial asymmetry indicators before and after surgery showed a significant difference for all indicators between S0 and S1: the P-values of Ag angle, M-Ag, Co-Ag, Co-Me, and Ag-Me were 0.003, 0.003, 0.008, 0.006, and 0.004, respectively. The Z value was based on negative ranks. @*Conclusion@#There was no significant difference in the B point distances from postoperation to the 12-month follow-up. However, there were significant differences in all five indicators related to facial asymmetry before and after surgery. The values for the five indicators of facial asymmetry all increased postoperatively.

F-box Protein βTrCP1 Is a Substrate of Extracellular Signal-regulated Kinase 2

F-box proteins, consisting of 69 members which are organized into the three subclasses FBXW, FBXL, and FBXO, are the substrate specific recognition subunits of the SKP1-Cullin 1-F-box protein E3 ligase complex. Although βTrCP 1 and 2, members of the FBXW subfamily, are known to regulate some protein stability, molecular mechanisms by which these proteins can recognize proper substrates are unknown. In this study, it was found that βTrCP1 showed strong interaction with members of mitogen-activated protein kinases. Although extracellular signal-regulated kinase (ERK) 3, p38β, and p38δ showed weak interactions, ERK2 specifically interacted with βTrCP1 as assessed by immunoprecipitation. In interaction domain determination experiments, we found that ERK2 interacted with two independent ERK docking sites located in the F-box domain and linker domain, but not the WD40 domain, of βTrCP1. Notably, mutations of βTrCP1 at the ERK docking sites abolished the interaction with ERK2. βTrCP1 underwent phosphorylation by EGF stimulation, while the presence of the mitogen-activated protein kinase kinases inhibitor U0126, genetic silencing by sh-ERK2, and mutation of the ERK docking site of βTrCP1 inhibited phosphorylation. This inhibition of βTrCP1 phosphorylation resulted in a shortened half-life and low protein levels. These results suggest that ERK2-mediated βTrCP1 phosphorylation may induce the destabilization of βTrCP1.

Extract of Curcuma zedoaria R. prevents atherosclerosis in apolipoprotein E-deficient mice

BACKGROUND/OBJECTIVES@#Curcuma zedoaria R. (Zingiberaceae) has been used to treat headache, fever, and hypertension-related symptoms in Asian countries, including Korea, China, and Japan. We investigated whether dietary intake of a C. zedoaria extract (CzE) affected atherosclerosis in vivo.MATERIALS/METHODS: Apolipoprotein E-deficient (ApoEM−/− ) mice (n = 32) were fed a normal diet (ND), a high-cholesterol diet (HCD), an HCD containing CzE (100 mg/kg/day), or an HCD containing simvastatin (10 mg/kg/day) for 12 weeks. The anti-atherosclerotic effects were evaluated by observing changes in fatty streak lesions, immunohistochemical analysis, ex vivo fluorescence imaging, lipid profiles, and western blot analysis. @*RESULTS@#The CzE-fed group showed a 41.6% reduction of atherosclerosis. Furthermore, CzE significantly reduced the levels of serum triglyceride, high-density lipoprotein, the chemokine (C-X3-C-motif ) ligand 1, the adhesion molecules vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin; down-regulation of tumor necrosis factor-α, interleukin-6, high mobility group box-1, and cathepsin levels in the aortic sinuses and aortas of ApoE −/− mice were also observed. @*CONCLUSIONS@#The results suggest that the inclusion of a water extract of C. zedoaria in a HCD is closely correlated with reducing the risk of vascular inflammatory diseases in an ApoE mouse model.

Sagittal split ramus osteotomy, intraoral vertical ramus osteotomy, and lateral corticectomy for asymmetric mandibular prognathism

Objectives@#The purpose of this study was to evaluate the postoperative anteroposterior stability and improvements in facial asymmetry after performing LeFort I osteotomy in the maxilla, sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO) in the mandible, and lateral corticectomy on the IVRO side. @*Materials and Methods@#From July 2009 to October 2018, a retrospective analysis was performed on 11 subjects. Lateral cephalometric radiograph was performed preoperatively (T0), postoperatively (T1), and at 12 months of follow-up (T2), and the B point distance was measured. Posteroanterior cephalometric radiograph was performed preoperatively (S0) and at 12 months of follow-up (S1) and was used to measure five indicators (Ag angle, M-Ag, Co-Ag, Co-Me, and Ag-Me) of facial asymmetry. @*Results@#The B point distances for T0 and T1 were significantly different (P=0.007), whereas those for T1 and T2 were not significantly different (P=0.1). In addition, there was a significant difference between the B point distances of T2 and T0 (P=0.026). Comparison of the facial asymmetry indicators before and after surgery showed a significant difference for all indicators between S0 and S1: the P-values of Ag angle, M-Ag, Co-Ag, Co-Me, and Ag-Me were 0.003, 0.003, 0.008, 0.006, and 0.004, respectively. The Z value was based on negative ranks. @*Conclusion@#There was no significant difference in the B point distances from postoperation to the 12-month follow-up. However, there were significant differences in all five indicators related to facial asymmetry before and after surgery. The values for the five indicators of facial asymmetry all increased postoperatively.

F-box Protein βTrCP1 Is a Substrate of Extracellular Signal-regulated Kinase 2

F-box proteins, consisting of 69 members which are organized into the three subclasses FBXW, FBXL, and FBXO, are the substrate specific recognition subunits of the SKP1-Cullin 1-F-box protein E3 ligase complex. Although βTrCP 1 and 2, members of the FBXW subfamily, are known to regulate some protein stability, molecular mechanisms by which these proteins can recognize proper substrates are unknown. In this study, it was found that βTrCP1 showed strong interaction with members of mitogen-activated protein kinases. Although extracellular signal-regulated kinase (ERK) 3, p38β, and p38δ showed weak interactions, ERK2 specifically interacted with βTrCP1 as assessed by immunoprecipitation. In interaction domain determination experiments, we found that ERK2 interacted with two independent ERK docking sites located in the F-box domain and linker domain, but not the WD40 domain, of βTrCP1. Notably, mutations of βTrCP1 at the ERK docking sites abolished the interaction with ERK2. βTrCP1 underwent phosphorylation by EGF stimulation, while the presence of the mitogen-activated protein kinase kinases inhibitor U0126, genetic silencing by sh-ERK2, and mutation of the ERK docking site of βTrCP1 inhibited phosphorylation. This inhibition of βTrCP1 phosphorylation resulted in a shortened half-life and low protein levels. These results suggest that ERK2-mediated βTrCP1 phosphorylation may induce the destabilization of βTrCP1.

Irreducible Acute Patellar Dislocation with Anatomical Variant:Notched Patella / 대한정형외과학회잡지

Most acute patella dislocations can be reduced closely using a spontaneous or simple maneuver, but it may not be possible if accompanied the by anomalies, such as rotation of the patella, osteophyte ridge protruding from the femur, or anatomical variations. This case report outlines irreducible acute patella dislocation with anatomical variations, a notched patella. If the reduction of an acute patella dislocation fails, an additional radiological examination and reduction under general anesthesia may be necessary with the possibility of an anatomical variant in mind.

Hip Arthrodesis to Treat Severe Hip Osteoarthritis in an Adolescent with Down Syndrome / 대한정형외과학회잡지

Down syndrome is the most common chromosomal disorder and is accompanied by hip osteoarthritis in approximately 28% of patients.This paper reports a case of hip arthrodesis as a treatment for severe hip osteoarthritis in adolescent Down syndrome patients. When performing surgical treatment of patients with Down syndrome, it is necessary to take a comprehensive approach that considers not only the medical point of view, but also the psychological and economic requirements of the patient and their social environment.

Effects of Head Lift Exercise on Oropharyngeal Swallowing Function and Dropout Rate According to Reclining Angle in Patients with Dysphagia after Stroke: A Randomized Trial / 대한연하장애학회지

Objective@#Although the effects of head lift exercise (HLE) in the reclining position have been reported, there is insufficient clinical evidence of the effects. This study compared the effects of HLE in the 0° supine position and 45° reclining position on the swallowing function and the compliance of patients with dysphagia after stroke after both exercises. @*Methods@#This was a randomized, assessor-blinded clinical trial. Thirty-five patients with stroke and dysphagia were assigned randomly to HLE in the 0° supine group (n=18) or HLE in the 45° reclining group (n=17). Patients in both groups performed HLE five days a week for four weeks and received the same conventional dysphagia therapy. The videofluoroscopic dy sphagia scale (VDS) was used to evaluate the swallowing function. The dropout rate and subjective feedback related to compliance with the two exercises were monitored. @*Results@#No significant differences in the baseline characteristics were observed between the two groups. Patients in both groups showed significant improvement in the oral and pharyngeal phases of VDS (P＜0.05). After the intervention, no significant differences were observed between the groups (P＞0.05). Dropout rates of 22% and 6% owing to neck discomfort or fatigue were observed in the HLE in 0° supine group and the HLE in 45° reclining group, respectively. @*Conclusion@#HLE in the 45° reclining position has a similar effect on the swallowing function in patients with dysphagia after stroke to that of HLE in the 0° supine position and is associated with better exercise compliance.

African swine fever: Etiology, epidemiological status in Korea, and perspective on control

African swine fever (ASF), caused by the ASF virus, a member of the Asfarviridae family, is one of the most important diseases in the swine industry due to its clinical and economic impacts. Since the first report of ASF a century ago, ample information has become available, but prevention and treatment measures are still inadequate. Two waves of epizootic outbreaks have occurred worldwide. While the first wave of the epizootic outbreak was controlled in most of the infected areas, the second wave is currently active in the European and Asian continents, causing severe economic losses to the pig industry. There are different patterns of spreading in the outbreaks between those in European and Asian countries. Prevention and control of ASF are very difficult due to the lack of available vaccines and effective therapeutic measures. However, recent outbreaks in South Korea have been successfully controlled on swine farms, although feral pigs are periodically being found to be positive for the ASF virus. Therefore, we would like to share our story regarding the preparation and application of control measures. The success in controlling ASF on farms in South Korea is largely due to the awareness and education of swine farmers and practitioners, the early detection of infected animals, the implementation of strict control policies by the government, and widespread sharing of information among stakeholders. Based on the experience gained from the outbreaks in South Korea, this review describes the current understanding of the ASF virus and its pathogenic mechanisms, epidemiology, and control.

Repurposing Auranofin, an Anti-Rheumatic Gold Compound, to Treat Acne Vulgaris by Targeting the NLRP3 Inflammasome

Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris.Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.

Operative Treatment for Bilateral Chronic Recurrent Dislocation of the Peroneal Tendon: A Case Report / 대한족부족관절학회지

A peroneal dislocation is a rare disease that is often misdiagnosed as a simple sprain and can be treated inadequately in the acute phase.For this reason, it is important to have an appropriate diagnosis in the early stages because it can progress to chronic and recurrent conditions. Surgical treatment is considered mainly when progressing to chronic recurrent dislocation. Recently, patients with an acute peroneal dislocation tend to prefer surgical treatment, so accurate initial diagnosis and management are very important. This paper reports a case of chronic recurrent peroneal tendon dislocation in both ankle joints, which was treated by a superior peroneal retinaculum reconstruction and a groove deepening procedure.

Operative Treatment for Bilateral Chronic Recurrent Dislocation of the Peroneal Tendon: A Case Report / 대한족부족관절학회지

A peroneal dislocation is a rare disease that is often misdiagnosed as a simple sprain and can be treated inadequately in the acute phase.For this reason, it is important to have an appropriate diagnosis in the early stages because it can progress to chronic and recurrent conditions. Surgical treatment is considered mainly when progressing to chronic recurrent dislocation. Recently, patients with an acute peroneal dislocation tend to prefer surgical treatment, so accurate initial diagnosis and management are very important. This paper reports a case of chronic recurrent peroneal tendon dislocation in both ankle joints, which was treated by a superior peroneal retinaculum reconstruction and a groove deepening procedure.

Association between Changes in Anthropometric Indices and in Fasting Insulin Levels among Healthy Korean Adolescents: The JS High School Study

BACKGROUND: This study investigated the association between changes in anthropometric indices and fasting insulin levels among healthy adolescents and whether the association differed by baseline obesity status. METHODS: This analysis was based on data collected for the JS High School study; 884 healthy adolescents aged 15 to 16 years followed up for 24 to 30 months were included. Changes in anthropometric indices and fasting insulin levels were computed as the difference between baseline and follow-up values. Multivariate linear regression models were used to determine the association between changes in anthropometric indices and fasting insulin levels. Based on body mass index (BMI)-for-age and waist circumference (WC)-for-age percentiles, participants were classified as normal weight (<85th percentile), overweight (85th percentile to <95th percentile), or obese (≥95th percentile). RESULTS: Changes in BMI, WC, waist-hip ratio, and waist-height ratio were significantly associated with changes in fasting insulin levels in both sexes (P<0.05). In analyses stratified by baseline obesity status, the association between change in BMI and change in fasting insulin was significantly stronger in overweight (males: standardized β=1.136; females: standardized β=1.262) and obese (males: standardized β=1.817; females: standardized β=2.290) participants than in those with normal weight (males: standardized β=0.957; females: standardized β=0.976) at baseline. Results were similar for changes in WC. CONCLUSION: Changes in anthropometric indices were positively associated with fasting insulin level increases. Moreover, those who were overweight or obese at baseline had a higher absolute increase in fasting insulin levels per one standard deviation unit increase in anthropometric indices than adolescents with normal weight.

Reconsideration of Vigabatrin Effect in Infantile Spasms Treatment / 대한소아신경학회지

PURPOSE@#To investigate the effect of vigabatrin (VGB) as a therapeutic agent for patients with infantile spasms (IS), compare risk factors for treatment response, and review safety of VGB by assessing its side effects.@*METHODS@#Among 35 patients admitted to the Department of Pediatric Neurology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea who received initial monotherapy with VGB under diagnosis of IS, 23 patients who met our inclusion criteria were enrolled and their medical records were retrospectively reviewed.@*RESULTS@#Of these 23 patients, average age at diagnosis was 7.26±4.8 months and average age at spasms was 6.20±3.8 months. Average treatment lag was 1.09±1.8 months. Thirteen patients (56.5%) achieved seizure free status. There was no ophthalmic complication among patients. Remission of hypsarrhythmia at 3 and 6 months after treatment was a good prognostic factor (P=0.026 and P=0.004, respectively).@*CONCLUSION@#VGB is effective enough to become a first-line drug for children with IS. Better prognosis can be expected in patients with clinical remission of hypsarrhythmia on electroencephalography after treatment initiation using VGB compared to those who do not have such remission. Regular eye examination and follow-up check-up are also needed in parallel with the use of VGB.

Influence of National Health Screening Program on All-Cause Mortality in Korea Analysis of the Korean Longitudinal Study of Aging, 2006–2014

BACKGROUND: To investigate the impact of national health screening on all-cause mortality risk, aged over 45.METHODS: Data from Korean Longitudinal Study of Aging 2006–2014 were assessed. A total of 10,254 participants were included at baseline, and survival rate was assessed biennially. Using cox proportional hazards model, the effect of health screening on mortality risk was investigated. Covariates were gender, depression, education, marital status, co-habitants, house income, social engagement, economic satisfaction, private health insurance, residence location, chronic diseases, and health behaviors (smoking, alcohol intake, regular exercise).RESULTS: At baseline 2006, 54.4% of participants didn't undergo health screening. A hazard ratio (HR) for mortality risk of non-participants were 1.36 (95% confidence interval [CI], 1.21–1.53) after adjusting age and gender. Adding marital status and co-habitants to model 1 as covariates, HR was 1.34 (95% CI, 1.18–1.50) (model 2). Adding depression scores and socioeconomic vulnerabilities to model 2, HR was 1.29 s (95% CI, 1.14–1.45) (model 3). Adding chronic diseases to model 3, HR was 1.26 (95% CI, 1.14–1.48) (model 4). Finally, health behaviors have been added to model 4, HR was 1.24 (95% CI, 1.10–1.40) (model 5). In addition, the mortality risk increased as the cumulative number of missing health screenig increased accordingly.CONCLUSION: Health screening was an independent factor to reduce mortality risk. Therefore, active encouragement to participate the health screening should be implemented to reduce all-cause mortality.

Corrigendum to “Attitudes and Dispositions about Doping of the Korean National TeamWho Participated in the Incheon Asian Para Games” / 대한스포츠의학회지

The name of one of the author was incorrectly presented: Geun-Ho Lee should read Kun-Ho Lee.