The orbicularis oculi (OOc) is a sphincteric muscle of the eyelids, whereas contraction of the orbicularis oris (OOr), another sphincteric muscle, causes narrowing of the lips. Facial muscle fibers normally blend with adjacent muscles. However, muscle fibers connecting the various facial muscles that have different actions and that are located at distant sites, such as the OOc and the OOr have been rarely reported. Herein, we report a rare case of connecting fibers between the inferior margin of the OOc and the OOr. These connecting fibers were blended with the OOr between the inserting fibers of the levator labii superioris and levator anguli oris. Contraction of such variant muscles might affect typical facial expressions.

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC50of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC50 of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.

Background: Remimazolam is a new ultra short-acting benzodiazepine originally developed as an improved version of midazolam. Recent studies have demonstrated non-inferiority of remimazolam to propofol in general anesthesia. However, to date, few studies have investigated the induction bolus dose of remimazolam required to achieve general anesthesia. We aimed to determine the 95% effective dose (ED95) of remimazolam bolus required to achieve loss of consciousness (LOC) and the appropriate doses for different age groups. Methods: Patients aged 20–79 years with the American Society of Anesthesiologists physical status of I or II were enrolled in this study. A total of 120 patients were included representing young, middle-aged, and elderly groups. Loss of eyelash reflex and verbal response after the administration of remimazolam was considered successful LOC. The ED95 of remimazolam was determined using a biased coin up-and-down design with sequential allocation and the isotonic regression method. Results: The ED95 of remimazolam for induction of general anesthesia was 0.367 mg/kg (95% CI [0.277, 0.392]) in the young group, 0.369 mg/kg (95% CI [0.266, 0.394]) in the middle-aged group, and 0.249 mg/kg (95% CI [0.199, 0.288]) in the elderly group. During the study period, none of the patients required rescue medications for hypotension or bradycardia. Conclusions This study investigated the ED95 of remimazolam bolus for anesthesia induction. The precise dosing of the ED95 can help maintain hemodynamic stability during the induction of anesthesia.

Lung cancer is the leading cause of cancer death worldwide as well as in China. For many years, conventional oncologic treatments such as surgery, chemotherapy, and radiotherapy (RT) have dominated the field of non-small cell lung cancer (NSCLC). The recent introduction of immunotherapy in clinical practice, led to a paradigm shift in lung cancer as in many other solid tumors. Recent pre-clinical and clinical data have shown RT may also modify antitumor immune responses through induction of immunogenic cell death and reprogramming of the tumor microenvironment. This has led many to reexamine RT as a partner therapy to immuno-oncology treatments and investigate their potential synergy in an exponentially growing number of clinical trials. Clinical trials combining radiotherapy and immunotherapy are attracting major attention, experts were invited to discuss frontier and controversial academic topics: (1) Recent developments of clinical synergy between radiation and immune checkpoint inhibitors (ICIs) in the treatment of NSCLC; (2) Will immunotherapy and radiotherapy increase the toxicity risk for cancer patients; (3) How to cope the mixed responses/disassociated responses phenomenon in checkpoint inhibition therapy to NSCLC with local ablative therapy; (4) Combining radiotherapy and immunotherapy in the treatment of NSCLC brain metastases.

Background: Metabolic syndrome is a nationwide health problem, which is associated with the development of cardiovascular diseases, diabetes, and chronic renal failure. The prevalence of metabolic syndrome in Korea significantly increased from 1998 to 2007. After that, the prevalence was stable in female but still increasing in male. The objective of this study was to evaluate how the prevalence and risk factors for metabolic syndrome changed in Korean adults through the last decade. Methods: Data from the Korea National Health and Nutrition Examination Survey 2008 to 2017 was used. National Cholesterol Education Program Adult Treatment Panel III were used to define metabolic syndrome. We compared how each metabolic syndrome component and the risk factors changed through the years. Results: A total of 51,177 (30,092 female and 21,085 male) people were included in this study. The prevalence of metabolic syndrome in male increased from 24.5% in 2008 to 28.1% in 2017, whereas that in female was stable at 20.5% in 2008 from 18.7% in 2017. Waist circumference measurements and fasting glucose levels increased through the decade in male, whereas only fasting glucose levels increased in female. Conclusion Since the last decade, the prevalence of metabolic syndrome in Korean adults has increased in male but remained stable in female. Lifestyle intervention in male, namely ceasing smoking and drinking could prevent increasing metabolic syndrome prevalence in Korean adults.

Background: Several studies have shown that elevated serum uric acid levels are associated with cardiovascular disease. High sensitivity C-reactive protein (hs-CRP) has been shown to be a measure of the severity and prognosis of cardiovascular disease. The aim of this study was to investigate the association of hs-CRP with hyperuricemia. Methods: From March 2016 to November 2017, a total of 26,987 patients who received a health check-up at a Soonchunhyang University Cheonan Hospital, Korea, were enrolled. Foreigners, patients who had hs-CRP score greater than 10 or white blood cell score greater than 10,000, those who did not respond sincerely, those who had previously been diagnosed with gout and cerebrovascular disease, and females were excluded. Data were collected from 2,808 patients. Results: The subjects were divided into four sections by 25th percentile, 50th percentile, 75th percentile, and 100th percentile based on the distribution of hs-CRP. Serum hs-CRP levels were 1.85 (1.34–2.56), 2.59 (1.90–3.54), and 3.64 (2.70–4.93) respectively in the second, third, and fourth quartiles based on the first quartile. The odds ratios were 1.46 (1.05–2.03), 1.76 (1.27–2.45), and 2.27 (1.64–3.14) after adjusting the disturbance variables of age, body mass index, smoking status, and regular exercise. Conclusion In this study, we evaluated the relationship between serum hs-CRP and hyperuricemia, which are the risk factors for cardiovascular disease, and found statistically significant correlations. These results were still significant after adjusting for age, smoking, exercise, and body mass index.

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.
Apoptosis ; Autophagy* ; Caspase 3 ; Chloroquine ; Endothelial Cells* ; Fibroblast Growth Factor 2 ; Helminths ; Intercellular Signaling Peptides and Proteins ; Mebendazole* ; Microtubules ; Phosphorylation ; Phosphotransferases ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A

BACKGROUND: Diabetic patients are known to have unusually high mean intraocular pressure (IOP); attributable to autonomic dysfunction and genetic factors. A recent study reported that diabetic complications occur in not only diabetes but also prediabetes. We performed this study to analyze the relationship between glycated hemoglobin A1c (HbA1c) levels and IOP in non-diabetics using electronic medical records at the health screening center of Soon Chun Hyang University Seoul Hospital.METHODS: We considered 16,643 individuals who visited the health screening center of Soon Chun Hyang University Seoul Hospital between November 2015 and September 2017. In total, 3,029 subjects were included in the study. Exclusion criteria included a history of hypertension, diabetes, stroke, cardiovascular disease, hepatitis (A-C), cancer, other disease, fasting blood glucose of 126 mg/dL or higher, HbA1c of 6.5% or higher, and individuals whose binocular IOP could not be measured. We categorized subjects into two groups; those with HbA1c less than or equal to 5.6%, and those with HbA1c greater than 5.6% and less than 6.5%. The mean IOP of each group was compared by gender.RESULTS: After adjusting for factors affecting IOP, analysis of variance was performed to analyze the relationship between HbA1c and IOP. There was no statistically significant difference between the HbA1c groups in males. However, there was a significant difference in IOP between females in the the higher and lower HbA1c groups.CONCLUSION: There was a statistically significant relationship between mean IOP and HbA1c in females without diabetes. Further research is needed with prospective and extensive data collection.
Blood Glucose ; Data Collection ; Diabetes Complications ; Diabetes Mellitus ; Electronic Health Records ; Fasting ; Female ; Health Promotion ; Hemoglobin A, Glycosylated ; Hepatitis ; Humans ; Hypertension ; Intraocular Pressure ; Male ; Mass Screening ; Myocardial Infarction ; Prediabetic State ; Prospective Studies ; Seoul ; Telescopes

BACKGROUND/OBJECTIVES: Recent studies showed vitamin D deficiency is linked to chronic diseases in addition to skeletal metabolism which could threaten the elderly. We analyzed health conditions and socio-demographic factors associated with vitamin D deficiency in community dwelling people aged 65 years and older. SUBJECTS/METHOD: Data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2010 to 2012 were obtained. A total of 2,687 subjects aged 65 years and older were participated. The cutoff value of the Vitamin D deficiency was considered as serum 25-hydroxyvitamin D [25(OH)D] ≤ 20 ng/mL (50 nmol/L). RESULTS: The overall prevalence rate of vitamin D deficiency in the elderly was 62.1%. The factors such as female, obesity, metabolic syndrome, current smoker, and skipping breakfast were positively associated with vitamin D deficiency, but high intensity of physical activity and more than 9 hours of sleep duration were negatively associated with vitamin D deficiency (all P < 0.05). CONCLUSIONS: It is important that health professions know that the factors proved in this study are connected to vitamin D deficiency thus provide information and intervention strategies of vitamin D deficiency to old aged people.
Aged* ; Aging ; Breakfast ; Chronic Disease ; Female ; Health Occupations ; Humans ; Independent Living* ; Korea* ; Metabolism ; Motor Activity ; Nutrition Surveys ; Obesity ; Prevalence ; Risk Factors ; Vitamin D Deficiency* ; Vitamin D* ; Vitamins*

BACKGROUND: The recent revision of South Korea's Mental Health Law emphasizes the role of the Mental Health Review Board. For this study, we examined the current status of continuing hospitalization judgement in Mental Health Review Board at the national level and aimed to determine the directions of improvement. METHODS: Using a qualitative case study as the research method, we interviewed 30 Mental Health Review Board members and analyzed the results. RESULTS: Each municipality had very different continuing hospitalization judgement methods. In our systematic review, which consisted of document inspection, we identified reliability problems due to limitations in Mental Health Review Board's operating systems, discharge orders, etc. Additionally, continuing hospitalization judgement needs to improve the objectivity, fairness, and effectiveness of their screening examinations. CONCLUSION: Based on the results of this study, we suggest policy proposals to improve these systems, such as standardizing examination processes, strengthening on-site inspections, increasing the independence and neutrality of judgment in Mental Health Review Board, building community mental health infrastructures, and establishing integrated management systems.
Hospitalization ; Judgment ; Jurisprudence ; Mass Screening ; Mental Health ; Methods ; Qualitative Research