Content Analysis of Korean Videos Regarding Restless Legs Syndrome on YouTube

Objective@#To evaluate the accuracy and quality of Korean videos associated with restless legs syndrome (RLS) on YouTube. @*Methods@#A YouTube search was performed on April 1, 2020 using the term “restless legs syndrome” in the Korean language. Two reviewers coded the source, content, and demographics of the included videos. Video quality was assessed using the modified DISCERN (mDISCERN) instrument. @*Results@#Among the 80 videos analyzed, 44 (55.0%) were reliable, and 36 (45.0%) were misleading. There was a trend toward a higher number of mean daily views in the misleading videos than in the reliable videos. Most of the misleading videos (72.2%) advocated complementary and alternative medicine as a primary treatment for RLS. Although the reliable videos had higher mDISCERN scores than the misleading videos, the overall quality of the reliable videos was low. @*Conclusion@#Many Korean videos regarding RLS on YouTube involve a risk of exposure to misinformation and are of unsatisfactory quality.

Differential Sensitivity of Wild-Type and BRAF-Mutated Cells to Combined BRAF and Autophagy Inhibition

BRAF inhibitors are insufficient monotherapies for BRAF-mutated cancer; therefore, we investigated which inhibitory pathway would yield the most effective therapeutic approach when targeted in combination with BRAF inhibition. The oncogenic BRAF inhibitor, PLX4720, increased basal autophagic flux in BRAF-mutated cells compared to wild-type (WT) BRAF cells. Interestingly, early autophagy inhibition improved the effectiveness of PLX4720 regardless of BRAF mutation, whereas late autophagy inhibition did not. Although ATG5 knockout led to PLX4720 resistance in both WT and BRAF-mutated cells, the MEK inhibitor trametinib exhibited a synergistic effect on PLX4720 sensitivity in WT BRAF cells but not in BRAF-mutated cells. Conversely, the prolonged inhibition of endoplasmic reticulum (ER) stress reduced basal autophagy in BRAF-mutated cells, thereby increasing PLX4720 sensitivity. Taken together, our results suggest that the combined inhibition of ER stress and BRAF may simultaneously suppress both pro-survival ER stress and autophagy, and may therefore be suitable for treatment of BRAF-mutated tumors whose autophagy is increased by chronic ER stress. Similarly, for WT BRAF tumors, therapies targeting MEK signaling may be a more effective treatment strategy. Together, this study presents a rational combination treatment strategy to improve the efficacy of BRAF inhibitors depending on BRAF mutation status.

Content Analysis of Korean Videos Regarding Restless Legs Syndrome on YouTube

Objective@#To evaluate the accuracy and quality of Korean videos associated with restless legs syndrome (RLS) on YouTube. @*Methods@#A YouTube search was performed on April 1, 2020 using the term “restless legs syndrome” in the Korean language. Two reviewers coded the source, content, and demographics of the included videos. Video quality was assessed using the modified DISCERN (mDISCERN) instrument. @*Results@#Among the 80 videos analyzed, 44 (55.0%) were reliable, and 36 (45.0%) were misleading. There was a trend toward a higher number of mean daily views in the misleading videos than in the reliable videos. Most of the misleading videos (72.2%) advocated complementary and alternative medicine as a primary treatment for RLS. Although the reliable videos had higher mDISCERN scores than the misleading videos, the overall quality of the reliable videos was low. @*Conclusion@#Many Korean videos regarding RLS on YouTube involve a risk of exposure to misinformation and are of unsatisfactory quality.

Differential Sensitivity of Wild-Type and BRAF-Mutated Cells to Combined BRAF and Autophagy Inhibition

BRAF inhibitors are insufficient monotherapies for BRAF-mutated cancer; therefore, we investigated which inhibitory pathway would yield the most effective therapeutic approach when targeted in combination with BRAF inhibition. The oncogenic BRAF inhibitor, PLX4720, increased basal autophagic flux in BRAF-mutated cells compared to wild-type (WT) BRAF cells. Interestingly, early autophagy inhibition improved the effectiveness of PLX4720 regardless of BRAF mutation, whereas late autophagy inhibition did not. Although ATG5 knockout led to PLX4720 resistance in both WT and BRAF-mutated cells, the MEK inhibitor trametinib exhibited a synergistic effect on PLX4720 sensitivity in WT BRAF cells but not in BRAF-mutated cells. Conversely, the prolonged inhibition of endoplasmic reticulum (ER) stress reduced basal autophagy in BRAF-mutated cells, thereby increasing PLX4720 sensitivity. Taken together, our results suggest that the combined inhibition of ER stress and BRAF may simultaneously suppress both pro-survival ER stress and autophagy, and may therefore be suitable for treatment of BRAF-mutated tumors whose autophagy is increased by chronic ER stress. Similarly, for WT BRAF tumors, therapies targeting MEK signaling may be a more effective treatment strategy. Together, this study presents a rational combination treatment strategy to improve the efficacy of BRAF inhibitors depending on BRAF mutation status.

ATG5 knockout promotes paclitaxel sensitivity in drug-resistant cells via induction of necrotic cell death

Autophagy regulators are often effective as potential cancer therapeutic agents. Here, we investigated paclitaxel sensitivity in cells with knockout (KO) of ATG5 gene. The ATG5 KO in multidrug resistant v-Ha-ras -transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr) was generated using the CRISPR/Cas9 technology. The qPCR and LC3 immunoblot confirmed knockout of the gene and protein of ATG5, respectively. The ATG5 KO restored the sensitivity of Ras-NIH 3T3/Mdr cells to paclitaxel. Interestingly, ATG5 overexpression restored autophagy function in ATG5 KO cells, but failed to rescue paclitaxel resistance. These results raise the possibility that low level of resistance to paclitaxel in ATG5 KO cells may be related to other roles of ATG5 independent of its function in autophagy. The ATG5 KO significantly induced a G2/M arrest in cell cycle progression. Additionally, ATG5 KO caused necrosis of a high proportion of cells after paclitaxel treatment. These data suggest that the difference in sensitivity to paclitaxel between ATG5 KO and their parental MDR cells may result from the disparity in the proportions of necrotic cells in both populations. Thus, our results demonstrate that the ATG5 KO in paclitaxel resistant cells leads to a marked G2/M arrest and sensitizes cells to paclitaxel-induced necrosis.

ATG5 knockout promotes paclitaxel sensitivity in drug-resistant cells via induction of necrotic cell death

Autophagy regulators are often effective as potential cancer therapeutic agents. Here, we investigated paclitaxel sensitivity in cells with knockout (KO) of ATG5 gene. The ATG5 KO in multidrug resistant v-Ha-ras -transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr) was generated using the CRISPR/Cas9 technology. The qPCR and LC3 immunoblot confirmed knockout of the gene and protein of ATG5, respectively. The ATG5 KO restored the sensitivity of Ras-NIH 3T3/Mdr cells to paclitaxel. Interestingly, ATG5 overexpression restored autophagy function in ATG5 KO cells, but failed to rescue paclitaxel resistance. These results raise the possibility that low level of resistance to paclitaxel in ATG5 KO cells may be related to other roles of ATG5 independent of its function in autophagy. The ATG5 KO significantly induced a G2/M arrest in cell cycle progression. Additionally, ATG5 KO caused necrosis of a high proportion of cells after paclitaxel treatment. These data suggest that the difference in sensitivity to paclitaxel between ATG5 KO and their parental MDR cells may result from the disparity in the proportions of necrotic cells in both populations. Thus, our results demonstrate that the ATG5 KO in paclitaxel resistant cells leads to a marked G2/M arrest and sensitizes cells to paclitaxel-induced necrosis.

Differential Gene Expression Common to Acquired and Intrinsic Resistance to BRAF Inhibitor Revealed by RNA-Seq Analysis

Melanoma cells have been shown to respond to BRAF inhibitors; however, intrinsic and acquired resistance limits their clinical application. In this study, we performed RNA-Seq analysis with BRAF inhibitor-sensitive (A375P) and

The association between smoking or passive smoking and cardiovascular diseases using a Bayesian hierarchical model: based on the 2008-2013 Korea Community Health Survey / 한국역학회지

OBJECTIVES: Smoking and passive smoking have been extensively reported as risk factors of cardiovascular morbidity and mortality. Despite the biological mechanisms underlying the impact of hazardous chemical substances contained in tobacco in cardiovascular diseases (CVD), studies investigating the association between smoking and passive smoking with morbidity are at an inchoate stage in Korea. Therefore, this study aimed to estimate the risks of smoking and passive smoking on cardiovascular morbidity at the national and regional levels.METHODS: This study calculated sex-standardized and age-standardized prevalence of CVD and smoking indices in 253 community health centers (si/gun/gu) in Korea using the 2008-2013 Korea Community Health Survey data. Furthermore, a Bayesian hierarchical model was used to estimate the association of smoking and passive smoking with the prevalence of CVD from the national and regional community health centers.RESULTS: At the national level, smoking was significantly associated with stroke (relative risk [RR], 1.060) and hypertension (RR, 1.016) prevalence, whilst passive smoking at home and work were also significantly associated with prevalence of stroke (RR, 1.037/1.013), angina (RR, 1.016/1.006), and hypertension (RR, 1.010/1.004). Furthermore, the effects of smoking and passive smoking were greater in urban-industrial areas than in rural areas.CONCLUSIONS: The findings of this study would provide grounds for national policies that limit smoking and passive smoking, as well as regionally serve as the basis for region-specific healthcare policies in populations with high CVD vulnerability.

The association between smoking or passive smoking and cardiovascular diseases using a Bayesian hierarchical model: based on the 2008-2013 Korea Community Health Survey / 한국역학회지

OBJECTIVES: Smoking and passive smoking have been extensively reported as risk factors of cardiovascular morbidity and mortality. Despite the biological mechanisms underlying the impact of hazardous chemical substances contained in tobacco in cardiovascular diseases (CVD), studies investigating the association between smoking and passive smoking with morbidity are at an inchoate stage in Korea. Therefore, this study aimed to estimate the risks of smoking and passive smoking on cardiovascular morbidity at the national and regional levels. METHODS: This study calculated sex-standardized and age-standardized prevalence of CVD and smoking indices in 253 community health centers (si/gun/gu) in Korea using the 2008-2013 Korea Community Health Survey data. Furthermore, a Bayesian hierarchical model was used to estimate the association of smoking and passive smoking with the prevalence of CVD from the national and regional community health centers. RESULTS: At the national level, smoking was significantly associated with stroke (relative risk [RR], 1.060) and hypertension (RR, 1.016) prevalence, whilst passive smoking at home and work were also significantly associated with prevalence of stroke (RR, 1.037/1.013), angina (RR, 1.016/1.006), and hypertension (RR, 1.010/1.004). Furthermore, the effects of smoking and passive smoking were greater in urban-industrial areas than in rural areas. CONCLUSIONS: The findings of this study would provide grounds for national policies that limit smoking and passive smoking, as well as regionally serve as the basis for region-specific healthcare policies in populations with high CVD vulnerability.

Evidence-based guidelines for fall prevention in Korea

Falls and fall-related injuries are common in older populations and have negative effects on quality of life and independence. Falling is also associated with increased morbidity, mortality, nursing home admission, and medical costs. Korea has experienced an extreme demographic shift with its population aging at the fastest pace among developed countries, so it is important to assess fall risks and develop interventions for high-risk populations. Guidelines for the prevention of falls were first developed by the Korean Association of Internal Medicine and the Korean Geriatrics Society. These guidelines were developed through an adaptation process as an evidence-based method; four guidelines were retrieved via systematic review and the Appraisal of Guidelines for Research and Evaluation II process, and seven recommendations were developed based on the Grades of Recommendation, Assessment, Development, and Evaluation framework. Because falls are the result of various factors, the guidelines include a multidimensional assessment and multimodal strategy. The guidelines were developed for primary physicians as well as patients and the general population. They provide detailed recommendations and concrete measures to assess risk and prevent falls among older people.

Evidence-Based Guideline for Fall Prevention in Korea

Falls and fall-related injuries are common amongst the elderly population and have deleterious effects on the quality of life or independence in daily living in the elderly. Falling is also associated with substantial morbidity, mortality, nursing home admission, and an increase in medical costs. Given that Korea has shown an extreme demographic shift with its population aging at the fastest pace among developed countries, assessment of fall risks and implementing intervention strategies to the high-risk population are getting more important. The guidelines for the prevention of falls were developed first by The Korean Association of Internal Medicine and The Korean Geriatric Society. These guidelines were developed by an adaptation process and the use of an evidence-based method; 4 guidelines were retrieved by systematic review and by the AGREE (appraisal of guidelines for research and evaluation) II process and 7 statements were made based on the grading of evidence, and these recommendations followed the GRADE (grades of recommendation, assessment, development, and evaluation) framework. Given that falls result from a various combination of many factors, the guidelines contain multidimensional assessment measures and multimodal strategies to prevent falls. These guidelines were developed not only for use by primary physicians but also for patients and the general population. Therefore, these guidelines provide detailed recommendations and concrete measures for the assessment of the risk of a fall and to prevent falls amongst the elderly population.

Levosulpiride-Associated Hemichorea

No abstract available.

Differential Effects of Quercetin and Quercetin Glycosides on Human α7 Nicotinic Acetylcholine Receptor-Mediated Ion Currents

Quercetin is a flavonoid usually found in fruits and vegetables. Aside from its antioxidative effects, quercetin, like other flavonoids, has a various neuropharmacological actions. Quercetin-3-O-rhamnoside (Rham1), quercetin-3-O-rutinoside (Rutin), and quercetin-3-(2(G)-rhamnosylrutinoside (Rham2) are mono-, di-, and tri-glycosylated forms of quercetin, respectively. In a previous study, we showed that quercetin can enhance α7 nicotinic acetylcholine receptor (α7 nAChR)-mediated ion currents. However, the role of the carbohydrates attached to quercetin in the regulation of α7 nAChR channel activity has not been determined. In the present study, we investigated the effects of quercetin glycosides on the acetylcholine induced peak inward current (I(ACh)) in Xenopus oocytes expressing the α7 nAChR. I(ACh) was measured with a two-electrode voltage clamp technique. In oocytes injected with α7 nAChR copy RNA, quercetin enhanced I(ACh), whereas quercetin glycosides inhibited I(ACh). Quercetin glycosides mediated an inhibition of I(ACh), which increased when they were pre-applied and the inhibitory effects were concentration dependent. The order of I(ACh) inhibition by quercetin glycosides was Rutin≥Rham1>Rham2. Quercetin glycosides-mediated I(ACh) enhancement was not affected by ACh concentration and appeared voltage-independent. Furthermore, quercetin-mediated I(ACh) inhibition can be attenuated when quercetin is co-applied with Rham1 and Rutin, indicating that quercetin glycosides could interfere with quercetin-mediated α7 nAChR regulation and that the number of carbohydrates in the quercetin glycoside plays a key role in the interruption of quercetin action. These results show that quercetin and quercetin glycosides regulate the α7 nAChR in a differential manner.

Evidence-based Guideline for Fall Prevention in Korea / 대한내과학회지

Falls and fall-related injuries are common in older population and have deleterious effects to the quality of life or independence of daily living in the elderly. Falling is also associated with substantial morbidity, mortality, nursing home admission and the increase of medical costs. Because Korea has shown extreme demographic shift with its population aging at the fastest pace among developed country, assessment of fall risks and intervention to high risk population are getting more important. The guideline for prevention of falls was developed first by The Korean Association of Internal Medicine and The Korean Geriatric Society. This guideline was developed by adaptation process as evidence-based method; four guidelines were retrieved by systematic review and the Appraisal of Guidelines for Research and Evaluation II process, seven statements were made with the grading of evidence and recommendations followed the Grades of Recommendation, Assessment, Development, and Evaluation framework. Because falls result from various combinations of many factors, the guideline contains multidimensional assessment and multimodal strategy to prevent falls. This guideline was developed for not only primary physician but also patients and general population, therefore it provides detailed recommendations and concrete measures to assess the risk and prevent falls in older people.

Lesional location of intractable hiccups in acute pure lateral medullary infarction

Background & Objective: Hiccups is a disabling condition of lateral medullary infarction (LMI). Unlike other symptoms of LMI, the anatomical lesions of hiccups are not well known. Few studies have evaluated the relationship between the lesional location of LMI and hiccups. We performed this study to correlate hiccups and magnetic resonance imaging (MRI)-based lesional location in pure LMI. Methods: Between January 1997 and February 2013, we identified 24 patients with pure LMI who presented with hiccups in addition to typical lateral medullary syndrome. Sixty six pure LMI patients without hiccups were included as a control group. Clinical and radiologic findings were compared between the two groups. MRI-identified lesions were classified rostrocaudally as rostral, middle and caudal, and horizontally as typical, ventral, large, lateral and dorsal. Results: The pure LMI patients with hiccups had significantly more frequent aspiration pneumonia (P = 0.001) and longer hospital stay (P = 0.03). The patients with hiccups significantly more often had dorsal rather than ventral lesion at horizontal levels (P = 0.012). But, there were no rostro-caudal differences at vertical levels (P = 0.162). Conclusions: We suggest that pure LMI associated with hiccups often locates in the dorsal medulla at horizontal correlation. This MRI-based comparative study has advanced the understanding of the neural substrate for hiccups in LMI, and indicates that hiccups become predictable when specific lesional locations in the lateral medulla are considered.

Lesions in the splenium of the corpus callosum: Clinical and radiological implications

Background: Brain MRI may unexpectedly display abnormalities in splenium of the corpus callosum (SCC). However, the clinical implications of this lesion are unclear and are not always consistent with ischemic infarctions. We performed this study to clarify the clinical and radiological implications in patients with SCC lesions. Methods: We retrospectively reviewed consecutive patients with MRIreported SCC changes between 2009 and 2012. We analyzed clinical and radiological findings, etiologies, cognitive impairment, and clinical outcomes. Results: We found 30 patients (16 females; mean 50.5 years) who had SCC lesions on MRI. Confusion was the most common clinical finding in 50% of cases. Cerebral infarction was the most common etiology (50%). The most consistent SCC changes on MRI were low signal in T1WI, high signal on T2WI and FLAIR, and high signal on DWI. We classified SCC lesions into in situ SCC lesions (SCC only) and multiple (SCC plus) lesions for patients with multiple lesions. The clinical symptoms of SCC only lesions were relatively mild. Cognitive functions were evaluated by Mini Mental State Examination (MMSE) and clinical dementia rating (CDR) scale at the time of discharge and patients with SCC only lesions showed less impaired cognition compared with those with SCC plus lesions. Clinical outcomes were evaluated by the modified Rankin scale at 1 month and patients with SCC only lesions revealed good clinical outcomes compared with those with SCC plus lesions. Conclusions: MRI-reported SCC lesions may have heterogeneous etiologies and present with various symptoms. The clinical course and outcome are relatively good, particularly in small isolated and oval shaped SCC lesions.

Acute Stroke Associated With Combined Protein C and S Deficiency During Pregnancy

Pregnancy related stroke is rare and poorly understood. A 28-year-old pregnant woman at 20 weeks of gestation presented with sudden headache and left homonymous hemianopsia. MRI revealed acute right posterior cerebral artery territory infarction. Laboratory data revealed combined protein C and S deficiencies. Coagulation profiles returned to normal 6 months after the delivery. Although stroke can occur either with protein C or S deficiency, acute cerebral infarction associated with combined protein C and S deficiencies during gestation is very rare.

Cerebral Venous Thrombosis Occurred After Cyclosporine Administration

Cerebral venous thrombosis (CVT) is quite rare and underlying risk factors are diverse. We describe that 60-year-old man developed CVT after use of cyclosporine. He had suffered from leukocytoclastic vasculitis and urticarial vasculitis. Initial MR venogram revealed thrombosis in superior sagittal sinus, right transverse sinus and sigmoid sinus with multiple cortical and deep collateral veins. Anticoagulation was started and maintained for one year, then follow up MR venogram was normal. We suggest that cyclosporine might increase a risk of CVT.

Relationship between Cognitive Impairment and Depression in Dialysis Patients

PURPOSE: Patients with chronic kidney disease frequently show cognitive dysfunction. The association of depression and cognitive function is not well known in maintenance dialysis patients. We evaluated cognitive impairment and depression, as well as their relationship in regards to methods of dialysis, maintenance hemodialysis (MHD) and chronic peritoneal dialysis (CPD). MATERIALS AND METHODS: Fifty-six maintenance dialysis patients were recruited and their clinical and laboratory data were collected. The Korean version of the mini-mental state exam (K-MMSE) was applied to screen the patient's cognitive function, while the Korean version of the Beck Depression Inventory (K-BDI) was used for depression screening. RESULTS: The average age of the participants was 54.2+/-10.2 years; 29 (51.8%) were female. The average dialysis vintage was 4.2+/-3.8 years. The CPD group showed significantly higher K-MMSE score (27.8+/-2.9 vs. 26.1+/-3.1, p=0.010) and lower K-BDI score (12.0+/-8.4 vs. 20.2+/-10.4, p=0.003) compared with the MHD group. The percentage of patients with depression symptoms was higher in the MHD group (51.7% vs. 18.5%). There was a negative correlation between cognitive function and prevalence of depressive symptoms. Depression and education level were shown to be independent predictors for cognitive impairment in multivariate analysis. CONCLUSION: Cognitive impairment was closely correlated with depression. It is important to detect cognitive impairment and depression early in maintenance dialysis patients with simple bedside screening tools.

Inhibitory Effects of Ginsenoside Metabolites, Compound K and Protopanaxatriol, on GABAC Receptor-Mediated Ion Currents

Ginsenosides, one of the active ingredients of Panax ginseng, show various pharmacological and physiological effects, and they are converted into compound K (CK) or protopanaxatriol (M4) by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. The gamma-aminobutyric acid receptorC (GABAC) is primarily expressed in retinal bipolar cells and several regions of the brain. However, little is known of the effects of ginsenoside metabolites on GABAC receptor channel activity. In the present study, we examined the effects of CK and M4 on the activity of human recombinant GABAC receptor (rho1) channels expressed in Xenopus oocytes by using a 2-electrode voltage clamp technique. In oocytes expressing GABAC receptor cRNA, we found that CK or M4 alone had no effect in oocytes. However, co-application of either CK or M4 with GABA inhibited the GABA-induced inward peak current (IGABA). Interestingly, pre-application of M4 inhibited IGABA more potently than CK in a dose-dependent and reversible manner. The half-inhibitory concentration (IC50) values of CK and M4 were 52.1+/-2.3 and 45.7+/-3.9 microM, respectively. Inhibition of IGABA by CK and M4 was voltage-independent and non-competitive. This study implies that ginsenoside metabolites may regulate GABAC receptor channel activity in the brain, including in the eyes.