Purpose: Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer. Materials and Methods: The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell. Results: We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA. Conclusion The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.

Purpose: To assess patient radiation doses during diagnostic and therapeutic neurointerventional procedures from multiple centers and propose dose reference level (RL). Materials and Methods: Consecutive neurointerventional procedures, performed in 22 hospitals from December 2020 to June 2021, were retrospectively studied. We collected data from a sample of 429 diagnostic and 731 therapeutic procedures. Parameters including dose-area product (DAP), cumulative air kerma (CAK), fluoroscopic time (FT), and total number of image frames (NI) were obtained. RL were calculated as the 3rd quartiles of the distribution. Results: Analysis of 1160 procedures from 22 hospitals confirmed the large variability in patient dose for similar procedures. RLs in terms of DAP, CAK, FT, and NI were 101.6 Gy·cm2, 711.3 mGy, 13.3 minutes, and 637 frames for cerebral angiography, 199.9 Gy·cm2, 3,458.7 mGy, 57.3 minutes, and 1,000 frames for aneurysm coiling, 225.1 Gy·cm2, 1,590 mGy, 44.7 minutes, and 800 frames for stroke thrombolysis, 412.3 Gy·cm2, 4,447.8 mGy, 99.3 minutes, and 1,621.3 frames for arteriovenous malformation (AVM) embolization, respectively. For all procedures, the results were comparable to most of those already published. Statistical analysis showed male and presence of procedural complications were significant factors in aneurysmal coiling. Male, number of passages, and procedural combined technique were significant factors in stroke thrombolysis. In AVM embolization, a significantly higher radiation dose was found in the definitive endovascular cure group. Conclusion Various RLs introduced in this study promote the optimization of patient doses in diagnostic and therapeutic interventional neuroradiology procedures. Proposed 3rd quartile DAP (Gy·cm2) values were 101.6 for diagnostic cerebral angiography, 199.9 for aneurysm coiling, 225.1 for stroke thrombolysis, and 412.3 for AVM embolization. Continual evolution of practices and technologies requires regular updates of RLs.

Objective: The aim of study is to investigate the relationship between serum vitamin D, c-reactive protein (CRP) levels, and anxietysymptoms. Methods: Serum vitamin D and CRP levels of 51,003 Korean adult participants were collected retrospectively. Anxiety symptoms wereassessed using the Korean version of Beck Anxiety Inventory. Logistic regression was used to estimate the odds ratio (ORs) of anxietysymptoms by serum vitamin D and CRP levels. The regression was adjusted for covariates, and each model was adjusted mutually for vitaminD and CRP levels. Results: Compared with sufficient vitamin D levels (≥20 ng/mL), insufficient (10–19.99 ng/mL) and deficient (<10 ng/mL) vitamin Dlevels were significantly associated with risk of anxiety symptoms. Also, continuous vitamin D levels were negatively associated with therisk of anxiety symptoms. CRP levels did not affect the relationship between vitamin D levels and risk of anxiety symptoms. Conclusion Insufficient (10–19.99 ng/mL) and deficient (<10 ng/mL) vitamin D levels were significantly associated with risk of anxietysymptoms. After adjusting for CRP levels, the results were not changed, and no evidence of interaction between vitamin D and CRP levelswas found. CRP levels did not account for the association between vitamin D levels and risk of anxiety symptoms.Psychiatry Investig 2020;17(4):312-319

Objective: The aim of this study is to determine the dose-response relationship between physical activity and anxiety symptoms. Methods: We included data of 124,434 participants who had comprehensive health-screening examinations from January 1st, 2012, to December 31st, 2016, in Kangbuk Samsung Hospital, Seoul and Suwon, South Korea. We measured the level of physical activity using the International Physical Activity Questionnaire-short form (IPAQ-SF) and estimated anxiety symptoms using the Beck Anxiety Inventory (BAI). BAI scores of 19 and above were defined as cases. Logistic regression was used to analyze the association between physical activity and BAI-defined anxiety. Furthermore, we assessed whether sex differences might affect the relationship between physical activity and BAI-defined anxiety by stratifying our data. Results: Compared with the sedentary group (0–600 METs-min/week), individuals achieving 600–6,000 METs-min/wk had a significantly lower risk of BAI-defined anxiety with a U-shaped relationship in general adults. After stratifying our data by sex, we found that optimal ranges of physical activity were 600–9,000 METs-min/wk for men, but 1,200–3,000 METs-min/wk for women. Conclusion We identified a U- or J-shaped association between physical activity and anxiety symptoms, suggesting an optimal dose and upper limit of physical activity for decreasing anxiety symptoms. Optimal levels and upper limits of physical activity for reducing anxiety symptoms were higher for men than for women.

BACKGROUND AND OBJECTIVES: Antiarrhythmic effect of renal denervation (RDN) after acute myocardial infarction (AMI) remains unclear. The goal of this study was to evaluate the effect of RDN on ventricular arrhythmia (VA) after AMI in a porcine model. METHODS: Twenty pigs were randomly divided into 2 groups based on RDN (RDN, n=10; Sham, n=10). After implanting a loop recorder, AMI was induced by occlusion of the middle left anterior descending coronary artery. Catheter-based RDN was performed for each renal artery immediately after creating AMI. Sham procedure used the same method, but a radiofrequency current was not delivered. Electrocardiography was monitored for 1 hour to observe VA. One week later, the animals were euthanized and the loop recorder data were analyzed. RESULTS: Ventricular fibrillation event rate and the interval from AMI creation to first VA in acute phase were not different between the 2 groups. However, the incidence of premature ventricular complex (PVC) was lower in the RDN than in the Sham. Additionally, RDN inhibited prolongation of the corrected QT (QTc) interval after AMI. The frequency of non-sustained or sustained ventricular tachycardia, arrhythmic death was lower in the RDN group in the early period. CONCLUSIONS RDN reduced the incidence of PVC, inhibited prolongation of the QTc interval, and reduced VA in the early period following an AMI. These results suggest that RDN might be a therapeutic option in patients with electrical instability after AMI.

BACKGROUND AND OBJECTIVES: Antiarrhythmic effect of renal denervation (RDN) after acute myocardial infarction (AMI) remains unclear. The goal of this study was to evaluate the effect of RDN on ventricular arrhythmia (VA) after AMI in a porcine model.METHODS: Twenty pigs were randomly divided into 2 groups based on RDN (RDN, n=10; Sham, n=10). After implanting a loop recorder, AMI was induced by occlusion of the middle left anterior descending coronary artery. Catheter-based RDN was performed for each renal artery immediately after creating AMI. Sham procedure used the same method, but a radiofrequency current was not delivered. Electrocardiography was monitored for 1 hour to observe VA. One week later, the animals were euthanized and the loop recorder data were analyzed.RESULTS: Ventricular fibrillation event rate and the interval from AMI creation to first VA in acute phase were not different between the 2 groups. However, the incidence of premature ventricular complex (PVC) was lower in the RDN than in the Sham. Additionally, RDN inhibited prolongation of the corrected QT (QTc) interval after AMI. The frequency of non-sustained or sustained ventricular tachycardia, arrhythmic death was lower in the RDN group in the early period.CONCLUSIONS: RDN reduced the incidence of PVC, inhibited prolongation of the QTc interval, and reduced VA in the early period following an AMI. These results suggest that RDN might be a therapeutic option in patients with electrical instability after AMI.
Animals ; Arrhythmias, Cardiac ; Autonomic Denervation ; Coronary Vessels ; Denervation ; Electrocardiography ; Humans ; Incidence ; Methods ; Myocardial Infarction ; Renal Artery ; Swine ; Tachycardia, Ventricular ; Ventricular Fibrillation ; Ventricular Premature Complexes

ymptoms of Parkinson’s disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Cyclin-Dependent Kinase 5 ; Cyclin-Dependent Kinases ; Dopaminergic Neurons ; Homeostasis ; Mitochondria ; Mitochondrial Dynamics ; Neurodegenerative Diseases ; Parkinson Disease ; Phosphorylation ; Phosphotransferases ; Primates ; Substantia Nigra

OBJECTIVE: In this study, the relationship between occupational stress and suicidal ideation was investigated, focusing on gender differences among Korean employees. METHODS: Cross-sectional data for 53,969 workers were collected at Kangbuk Samsung Hospital health screening centers. Risk of suicidal ideation was assessed using a self-reported questionnaire examining suicidal ideation during the past year. Occupational stress was measured using 24 items of the Korean Occupational Stress Scale-Short Form (KOSS-SF). Logistic regression analysis was employed to estimate the odds ratios and 95% confidence intervals of the relationships between suicidal ideation and components of occupational stress. RESULTS: In multivariable-adjusted models, all job stress contributed to increased risk of suicidal ideation in males. Most subscales, except insufficient job control and organizational system, were risk factors of suicidal ideation in females. Further adjustments for depression markedly attenuated this relationship. However, the effects of insufficient job control and lack of reward on suicidal ideation remained significant in males, and interpersonal conflict remained significant in females. CONCLUSION: The results suggest that occupational stress plays a significant role in increasing risk of suicidal ideation through elevation of depressive symptoms. Gender differences in components of occupational stress associated with suicidal ideation were also observed.
Depression ; Female ; Humans ; Logistic Models ; Male ; Mass Screening ; Odds Ratio ; Reward ; Risk Factors ; Suicidal Ideation ; Suicide

OBJECTIVE: The aim of the present study was to provide clinical consensus and evidence regarding initial treatment strategies for the pharmacological treatment of social anxiety disorder (SAD) in Korea. METHODS: We prepared a questionnaire to derive a consensus from clinicians regarding their preference for the pharmacological treatment of SAD in Korea. Data regarding medication regimens and psychotropic drugs used during initial treatment, the doses used, and the pharmacological treatment duration were obtained. Responses were obtained from 66 SAD experts, and their opinions were classified into three categories (first-line, second-line, third-line) using a chi-square analysis. RESULTS: Clinicians agreed upon first-line regimens for SAD involving monotherapy with selective serotonin reuptake inhibitors (SSRIs) or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine, or combined therapy using antidepressants with betablockers or benzodiazepines on a standing or as-needed basis. First-line psychotropic drug choices for initial treatment included the following: escitalopram, paroxetine, sertraline, venlafaxine, and propranolol. The medication dosage used by domestic clinicians was found to be comparable with foreign guidelines. Domestic clinicians tended to make treatment decisions in a shorter amount of time and preferred a similar duration of maintenance treatment for SAD when compared with foreign clinicians. CONCLUSION: This study may provide significant information for developing SAD pharmacotherapy guidelines in Korea, especially in the early stage of treatment.
Antidepressive Agents ; Anxiety Disorders ; Anxiety ; Benzodiazepines ; Citalopram ; Consensus ; Drug Therapy ; Korea ; Paroxetine ; Propranolol ; Psychotropic Drugs ; Serotonin Uptake Inhibitors ; Sertraline ; Venlafaxine Hydrochloride