8-Methoxypsoralen Induces Apoptosis by Upregulating p53 and Inhibits Metastasis by Downregulating MMP-2 and MMP-9 in Human Gastric Cancer Cells

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOPinduced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

Altered Low Frequency Heart Rate Variability Associated with Agoraphobia in Panic Disorder:A Retrospective Study

Purpose@#This study aimed to compare the clinical features of panic disorder (PD) with comorbid agoraphobia to those of PD alone. We focused on autonomic nervous system (ANS) alterations reflected in heart rate variability (HRV) and executive function deficits reflected in the Stroop test. @*Materials and Methods@#We retrospectively compared psychometric features, Stroop test results, and resting-state HRV across three groups: a subclinical group with anxiety attack history, a PD group without agoraphobia, and a PD group with agoraphobia. The subclinical group included 10 male and 34 female, the PD without agoraphobia group included 17 male and 19 female, and the PD with agoraphobia group included 11 male and 18 female. @*Results@#The PD with agoraphobia group had higher Symptom Checklist–95 scores than the other groups. Both PD groups had longer reaction times in the Stroop test than the subclinical group. There were no significant differences in HRV parameters between the PD groups with and without agoraphobia. Compared with the subclinical group, the PD with agoraphobia group showed significantly lower values of the natural logarithm of low-frequency HRV. @*Conclusion@#Our results do not support that executive function deficits and ANS alterations are more pronounced with comorbid agoraphobia among PD groups. However, PD with agoraphobia patients showed more complex and severe clinical symptoms in their self-reports. Compared with the subclinical group, PD patients with agoraphobia showed specific features in the natural logarithm of low-frequency HRV. Our findings suggest that agoraphobia comorbidity should be considered when evaluating or treating patients with PD.

A Statistical Analysis of Forensic Autopsies Performed in the Jungbu Province of Korea in 2021 / 대한법의학회지

We analyzed 1,079 forensic autopsies conducted in 2021 by the National Forensic Service Daejeon Institute from the Jungbu province in the central part of South Korea, for their manner and cause of death. Among the manner of death (n=1,079), 45.3% (n=489) were categorised as unnatural, 39.5% (n=426) as natural, and 15.2% (n=164) were unknown. Among the unnatural deaths (n=489), 40.7% (n=199) were accidents, 36.8% (n=180) were suicides, 14.1% (n=69) were undetermined, and 8.4% (n=41) were homicides. The major causes of unnatural deaths (n=489) were by trauma, causing 34.4% (n=168), poisoning causing 26.8% (n=131), and asphyxia causing 17.2% (n=84). The major cause of death by trauma (n=168) was falling at 46.4% (n=78), and by asphyxia (n=84) was strangulation at 76.2% (n=64). Among natural deaths (n=426), heart disease was the major cause at 49.8% (n=212) followed by vascular disease at 16.7% (n=71). In future, a time-series statistical analysis on the manner and causes of death in Jungbu province may provide insight and allow for more advanced interpretations about both healthcare and public safety.

Forensic Considerations in Postmortem Cases of Sudden Death during or after Percutaneous Coronary Intervention: Data from The National Forensic Service in Korea, 2015 to 2021 / 대한법의학회지

Sudden death during or after percutaneous coronary intervention (PCI) could be led to potential medicolegal disputes. This study aimed to investigate the clinical and postmortem findings in PCI-related deaths-focusing on the current statusto inform preventive strategies against these fatalities. Forty-three cases were retrieved from the National Forensic Service's postmortem records between 2015 and 2021, and the corresponding postmortem findings and clinical information were analyzed. The analyses revealed a relatively consistent annual incidence of PCI-related deaths. Immediate deaths during or shortly after PCI occurred in 17 cases (39.5%), and delayed PCI-related deaths after discharge from the hospital occurred in 26 cases (60.5%). The causes of PCI-related deaths in the postmortem cases were categorized into four groups: PCI complications (11 cases, 26%), acute myocardial infarction (23 cases, 53%), ischemic heart disease (8 cases, 19%), and others (1 case, 2%). Postmortem examinations played a critical role in determining the cause of death and obtaining medical evidence, including pathological findings of the heart as well as those of coronary artery and stent insertion. Our findings suggest that a detailed examination of the heart, coronary arteries, stent status, and atherosclerosis in PCI-related deaths could help provide more accurate information as medical evidence and prevent/resolve potential medicolegal issues. Further, this could advance our understanding of PCI-related deaths and inform future preventive strategies.

Statistical Analysis of Medicolegal Autopsy of Migrant Workers in Korea / 대한법의학회지

The number of migrant workers is increasing worldwide every year, and their number and role in Korean society is also increasing. However, the poor conditions faced by migrant workers often become a social issue, and it is not uncommon for them to be the subject of forensic autopsies. This study aimed to investigate the current status of medicolegal autopsy on migrant workers in Korea. We collected data of medicolegal autopsies on migrant workers conducted in Korea from 2016 to 2020 by requesting data from the institutions performing medicolegal autopsy. We calculated the autopsy rate and analyzed manner of death and cause of death. The medicolegal autopsy rate for foreign deaths was 16.4%, which was more than five times higher than the autopsy rate for Korean deaths. By manner of death, 43.7% were natural death, 6.4% were homicides, 8.5% were suicides, 23.6% were accidental deaths, 2.7% were undetermined unnatural deaths and 15.0% were unknown. These results showed a high rate of homicide, accidental death, and unknown death compared to Korean. And the proportion of industrial accident deaths and sudden manhood death syndrome were high. Through this study, it was confirmed that medicolegal autopsies are performed at a relatively high frequency when migrant workers die, and the characteristics related to the deaths of migrant workers were identified.

Radiation safety for pain physicians: principles and recommendations

C-arm fluoroscopy is a useful tool for interventional pain management. However, with the increasing use of C-arm fluoroscopy, the risk of accumulated radiation exposure is a significant concern for pain physicians. Therefore, efforts are needed to reduce radiation exposure. There are three types of radiation exposure sources: (1) the primary X-ray beam, (2) scattered radiation, and (3) leakage from the X-ray tube.The major radiation exposure risk for most medical staff members is scattered radiation, the amount of which is affected by many factors. Pain physicians can reduce their radiation exposure by use of several effective methods, which utilize the following main principles: reducing the exposure time, increasing the distance from the radiation source, and radiation shielding. Some methods reduce not only the pain physician’s but also the patient’s radiation exposure. Taking images with collimation and minimal use of magnification are ways to reduce the intensity of the primary X-ray beam and the amount of scattered radiation. It is also important to carefully select the C-arm fluoroscopy mode, such as pulsed mode or low-dose mode, for ensuring the physician’s and patient’s radiation safety. Pain physicians should practice these principles and also be aware of the annual permissible radiation dose as well as checking their radiation exposure. This article aimed to review the literature on radiation safety in relation to C-arm fluoroscopy and provide recommendations to pain physicians during C-arm fluoroscopy-guided interventional pain management.

A Statistical Analysis of Forensic Autopsies Performed in the Jungbu Province of Korea in 2020 / 대한법의학회지

We analyzed the manner and cause of death in 945 forensic autopsies from the Jungbu province (Central part of South Korea) conducted by the National Forensic Service Daejeon institute in 2020. Analysis of the manner of death revealed that 43.6% (412/945 cases) were natural deaths, 41.6% (393/945 cases) were unnatural deaths, and 14.8% (140/945 cases) deaths were unknown. Among the unnatural deaths, the major manner of death (40.7%, 160/393 cases) were by accidents, 29.5% (116/393 cases) were by suicide, 21.6% (85/393 cases) were undetermined, and 8.1% (32/393 cases) were by homicide. Among the unnatural deaths, the major cause of death (42.7%, 168/393 cases) were by trauma, 19.3% (76/393 cases) were by poisoning, and 16.5% (65/393 cases) were by asphyxia. Falling was the major cause of death by trauma (42.9%, 72/168 cases) and strangulation was the major cause of death by asphyxia (72.3%, 47/65 cases). Among natural deaths, heart disease was the major cause (43.7%, 180/412 cases), followed by vascular disease (18.9%, 78/412 cases). This study is the first statistical analysis of the manner and cause of deaths in the Jungbu province. A time-series statistical analysis of the manner and cause of deaths in this province might allow more advanced interpretations about both public safety and healthcare in the future.

Development and Effects a Simulation-based Emergency Airway Management Education Program for Nurses in a Neonatal Intensive Care Unit

PURPOSE: The purpose of this study was to identify the effects of an educational intervention by evaluating neonatal emergency airway management knowledge, critical thinking disposition, problem- solving ability, and confidence in clinical performance after developing and operating a simulation-based neonatal emergency airway management education program for nurses in a neonatal intensive care unit.METHODS: The participants were 30 nurses in a neonatal intensive care unit. Data were collected from June 6 to 15, 2018 and analyzed using IBM SPSS version 22.0.RESULTS: The results of the pretest and posttest for each educational group showed statistically significant improvements in neonatal emergency airway management knowledge, critical thinking, problem- solving ability, and confidence in clinical performance.CONCLUSION: The simulation-based neonatal emergency airway management training program was an effective educational program that enhanced neonatal emergency airway management knowledge, critical thinking disposition, problem-solving ability, and confidence in clinical performance among nurses in a neonatal intensive care unit. Therefore, it is suggested that the program described in this study can contribute to improving nursing quality by enhancing the ability of nurses to cope with emergencies in practice. It can also be used for education for new nurses and contribute to the development of nurses' practices.

Various Forms of Fatal Nicotine Intoxications: Three Cases Report / 대한법의학회지

Recently, fatal nicotine intoxications with electronic cigarette liquid have increased in Korea, but various kinds of cigarettes and smoking cessation aids may also cause fatal poisoning. We report cases of fatal nicotine intoxications involving causes other than the use of liquid nicotine. A 29-year-old woman (case 1) found dead in a hotel room with about 70 patches (21 mg dose) of nicotine on her body. Blood nicotine levels were 7.68 mg/L (heart) and 3.25 mg/L (femoral). A toxic level of zolpidem was also detected. A 28-year-old Uzbekistan man (case 2) was found dead in his uncle's room with his face covered with chewing tobacco. Blood nicotine levels were 7.3 mg/L (heart) and 4.6 mg/L (femoral). Blood alcohol level was 0.139%. A 55-year-old man (case 3) bit his tongue. As he was taken to the hospital, his wife put tobacco powders in his mouth for hemostasis, and he died of cardiac arrest. Blood nicotine levels were 2.01 mg/L (heart) and 0.96 mg/L (femoral). Nicotine-related deaths can be caused by various types of administration including transdermal and transmucosal routes, and relatively small doses may cause death, so meticulous investigation should be taken when such deaths are suspected.

Various Forms of Fatal Nicotine Intoxications: Three Cases Report / 대한법의학회지

Recently, fatal nicotine intoxications with electronic cigarette liquid have increased in Korea, but various kinds of cigarettes and smoking cessation aids may also cause fatal poisoning. We report cases of fatal nicotine intoxications involving causes other than the use of liquid nicotine. A 29-year-old woman (case 1) found dead in a hotel room with about 70 patches (21 mg dose) of nicotine on her body. Blood nicotine levels were 7.68 mg/L (heart) and 3.25 mg/L (femoral). A toxic level of zolpidem was also detected. A 28-year-old Uzbekistan man (case 2) was found dead in his uncle's room with his face covered with chewing tobacco. Blood nicotine levels were 7.3 mg/L (heart) and 4.6 mg/L (femoral). Blood alcohol level was 0.139%. A 55-year-old man (case 3) bit his tongue. As he was taken to the hospital, his wife put tobacco powders in his mouth for hemostasis, and he died of cardiac arrest. Blood nicotine levels were 2.01 mg/L (heart) and 0.96 mg/L (femoral). Nicotine-related deaths can be caused by various types of administration including transdermal and transmucosal routes, and relatively small doses may cause death, so meticulous investigation should be taken when such deaths are suspected.

Bortezomib Treatment for Refractory Antibody-Mediated Rejection Superimposed with BK Virus-Associated Nephropathy during the Progression of Recurrent C3 Glomerulonephritis / 대한이식학회지

A 38-year-old man, who underwent a second kidney transplantation (KT), was admitted because of antibody-mediated rejection (AMR) complicated by BK virus-associated nephropathy (BKVAN). He was placed on hemodialysis at the age of 24 years because of membranoproliferative glomerulonephritis. At the age of 28 years, he underwent a living donor KT from his father; however, 1 year after the transplantation, he developed a recurrence of the primary glomerular disease, resulting in graft failure 2 years after the first KT. Ten years later, he received a deceased-donor kidney with a B-cell-positive-cross-match. He received 600 mg of rituximab before the KT with three cycles of plasmapheresis and immunoglobulin (0.5 g/kg) therapy after KT. During the follow-up, the first and second allograft biopsies at 4 and 10 months after KT revealed AMR with a recurrence of primary glomerular disease that was reclassified as C3 glomerulonephritis (C3GN). He received a steroid pulse, rituximab, plasmapheresis, and immunoglobulin therapies. The third allograft biopsy demonstrated that the BKVAN was complicated with AMR and C3GN. As the azotemia did not improve after repeated conventional therapies for AMR, one cycle of bortezomib (1.3 mg/m²×4 doses) was administered. The allograft function stabilized, and BK viremia became undetectable after 6 months. The present case suggests that bortezomib therapy may be applicable to patients with refractory AMR, even in cases complicated with BKVAN.

Diagnosis and Treatment of Congenital H-type Rectovestibular Fistula / 소아외과

PURPOSE: The congenital H-type rectovestibular fistula, a fistula between the anorectum and genital tract besides a normal anus is a rare variant of anorectal deformities. This disease needs proper treatment but there are no standard of diagnosis and treatment. The purpose of this report is to review a 13-year experience of approach and management for H-type rectovestibular fistula at a single institution. METHODS: From February 2002 to August 2015, we cared for 11 patients who had congenital H-type rectovestibular fistula and reviewed their clinical presentation, accompanied anomalies, diagnostic modalities, operative technique, and postoperative progress. RESULTS: Most patients with H-type rectovestibular fistula presented with symptoms including vestibular defecation and major labial abscess. We could find the fistula tract in most of patients by fistulography using contrast dye. All of the patients had been operated. There were 2 recurrences after surgical treatment who had inflammation and infection associated with the fistula. All other patients recovered without complications. CONCLUSION: We think the operation including fistulectomy and repair of perineal body through a transanal approach can be a feasible option to the congenital H-type rectovestibular fistula. Also, combined inflammation and infection should be treated prior to surgery to reduce postoperative complications.

Usefulness of Extracorporeal Treatment for Combined Intoxication with Controlled-Release Carbamazepine and Topiramate

Controlled-release carbamazepine (CBZ) could be more harmful than the regular form in special situations due to their respective biochemical characteristics. When primary treatment is not effective in acute intoxication, extracorporeal treatment (ECTR) could be an option. We recently applied ECTR to a patient with combined intoxication of topiramate and controlled-release CBZ who deteriorated despite receiving primary treatment. The patient improved after administering ECTR. Early ECTR intervention may be beneficial for the treatment of CBZ intoxication, especially of the controlled-release form.

Secondary publication Sudden Aortic Rupture in Ehlers-Danlos Syndrome Type IV / 대한법의학회지

Ehlers-Danlos syndrome type IV (EDS IV) is a hereditary disorder of the connective tissue, characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations of the gene for type III procollagen (COL3A1), resulting in insufficient collagen production or a defect in the structure of collagen. EDS IV can have fatal complications such as the rupture of great vessels or organs, which can cause hemorrhaging and sudden unexpected death. Here, we report a case of a 43-year-old female who collapsed after a struggle with a neighbor. In this patient, the bifurcation of the bilateral common iliac artery ruptured, with no evidence of trauma, inflammation, or atherosclerosis. Genetic analysis of COL3A1 showed the presence of a c.2771G>A (p.Gly924Arg) mutation, which may be associated with EDS IV. The forensic pathologist should consider the possibility that the spontaneous visceral or arterial rupture was caused by EDS IV. Genetic analysis is not currently a routine procedure during autopsy. However, in this case, we suggest that the patient possibly had an underlying EDS IV condition, and we recommended family members of the deceased to seek genetic analysis and counseling.

Seizure Induction by Artemisia Annua in an Epilepsy Patient Taking Levetiracetam

Artemisia annua is a wormwood. Because it may induce Cytochrome P450 2C19 enzyme, Artemisia annua may have an influence on antiepileptic drugs which are substrates for the enzyme. This influence may negatively affect seizure control of epilepsy patient. We present a patient whose seizures were induced by Artemisia annua, despite he was taking levetiracetam which is not a substrate for the hepatic enzyme. Therefore there would be another mechanism of seizure induction of Artemisia annua besides hepatic metabolism.

Predictors of Relapse in Patients with Organizing Pneumonia / 결핵및호흡기질환

BACKGROUND: Although organizing pneumonia (OP) responds well to corticosteroid therapy, relapse is common during dose reduction or follow-up. Predictors of relapse in OP patients remain to be established. The aim of the present study was to identify factors related to relapse in OP patients. METHODS: This study was retrospectively performed in a tertiary referral center. Of 66 OP patients who were improved with or without treatment, 20 (30%) experienced relapse. The clinical and radiologic parameters in the relapse patient group (n=20) were compared to that in the non-relapse group (n=46). RESULTS: Multivariate analysis demonstrated that percent predicted forced vital capacity (FVC), PaO2/FiO2, and serum protein level were significant predictors of relapse in OP patients (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.97; p=0.018; OR, 1.02; 95% CI, 1.00-1.04; p=0.042; and OR, 0.06; 95% CI, 0.01-0.87; p=0.039, respectively). CONCLUSION: This study shows that FVC, PaO2/FiO2 and serum protein level at presentation can significantly predict relapse in OP patients.

Death due to Gastrointestinal Hemorrhage Associated with Dieulafoy's Lesion / 대한법의학회지

Dieulafoy's lesion is a rare condition that may cause intermittent or massive gastrointestinal bleeding. It is characterized by the exteriorization of an arterial vessel into the lumen of the affected organ, generally the upper digestive tract, through an apparently normal mucosa or a small tear or erosion. We report two patients with Dieulafoy's lesions, one in whom the lesion was misdiagnosed as a submucosal tumor and endoscopic biopsy resulted in fatal bleeding.

A Case of Venlafaxine-Induced Interstitial Lung Disease / 결핵및호흡기질환

A patient treated with venlafaxine for major depression developed an interstitial lung disease (ILD) with the characteristic clinical, radiological and pathological features of chronic hypersensitivity pneumonitis. A high resolution computed tomography scan demonstrated ground glass opacity, mosaic perfusion with air-trapping and traction bronchiectasis in both lungs. The pathological findings were consistent with a nonspecific interstitial pneumonia pattern. Clinical and radiological improvements were noted after the discontinuation of venlafaxine and the administration of a corticosteroid. This report provides further evidence that the anti-depressant venlafaxine can cause ILD.

A Case of Multicentric Castleman's Disease Presenting with Follicular Bronchiolitis / 결핵및호흡기질환

Multicentric Castleman's disease (CD) is a rare atypical lymphoproliferative disorder, which is characterized by various systemic manifestations. Some patients with multicentric CD may have concomitant lung parenchymal lesions, for which lymphoid interstitial pneumonia (LIP) is known to be the most common pathologic finding. Follicular bronchiolitis and LIP are considered to be on the same spectrum of the disease. We describe a case of multicentric CD with pulmonary involvement, which was pathologically proven as follicular bronchiolitis.

Death of a Severe Underweight Infant with Pulmonary Interstitial Glycogenosis / 대한법의학회지

Pulmonary interstitial glycogenosis (PIG) is a very rare interstitial lung disease in infants. It is poorly understood, but its pathological features are distinct; they include uniform alveolar septal thickening, caused by a group of oval to spindle-shaped cells containing abundant glycogen, without apparent inflammation or fibrosis. PIG is usually associated with a good prognosis. However, in the present report, we describe the case of a 5-month-old male infant who died due to PIG; he was severely underweight and not administered proper treatment or care. The pathology of PIG was determined following a medico-legal autopsy.