Coinfection of Severe Fever With Thrombocytopenia Syndrome Virus and Coxiella burnetii in Developmental Stage of Hard Ticks in Subtropical Region of Korea

Background@#Severe fever with thrombocytopenia syndrome virus (SFTSV) is transmitted through tick bites. Ticks are potential vectors for the bacterium Coxiella burnetii that causes Query fever. Here, we analyzed SFTSV and C. burnetii co-infection rates in ticks in rural areas of Jeju Island, South Korea. @*Methods@#Free ticks were collected from the natural environment of the island between 2016 and 2019, and SFTSV RNA was extracted. Additionally, ribosomal RNA gene sequencing was used to identify Coxiella species. @*Results@#Haemaphysalis longicornis was the most common tick species followed by H. flava. Tick number gradually increased from April, peaked in August, and was lowest in March. Of all the collected ticks, 82.6% (2,851/3,458) were nymphs, 17.9% (639/3,458) adults, and 0.1% (4/3,458) larvae. SFTSV-infected ticks comprised 12.6% of all ticks; their numbers were the lowest in November–December, increased from January, and were mostly identified in the adult stage during June–August. C. burnetii infections were detected in 4.4% of the SFTSVinfected H. longicornis ticks. C. burnetii co-infection was mainly observed in the nymph stage of H. longicornis, with the highest infection rate in January, followed by December and November. @*Conclusion@#Our findings suggest that Jeju Island has a high SFTSV and potential C. burnetii infection in ticks. This study provides important insights regarding SFTS and Q fever risk to humans in South Korea.

Development of the Korea-Polyenvironmental Risk Score for Psychosis

Objective@#Comprehensive understanding of polyenvironmental risk factors for the development of psychosis is important. Based on a review of related evidence, we developed the Korea Polyenvironmental Risk Score (K-PERS) for psychosis. We investigated whether the K-PERS can differentiate patients with schizophrenia spectrum disorders (SSDs) from healthy controls (HCs). @*Methods@#We reviewed existing tools for measuring polyenvironmental risk factors for psychosis, including the Maudsley Environmental Risk Score (ERS), polyenviromic risk score (PERS), and Psychosis Polyrisk Score (PPS). Using odds ratios and relative risks for Western studies and the “population proportion” (PP) of risk factors for Korean data, we developed the K-PERS, and compared the scores thereon between patients with SSDs and HCs. In addition, correlation was performed between the K-PERS and Positive and Negative Syndrome Scale (PANSS). @*Results@#We first constructed the “K-PERS-I,” comprising five factors based on the PPS, and then the “K-PERS-II” comprising six factors based on the ERS. The instruments accurately predicted participants’ status (case vs. control). In addition, the K-PERS-I and -II scores exhibited significant negative correlations with the negative symptom factor score of the PANSS. @*Conclusion@#The K-PERS is the first comprehensive tool developed based on PP data obtained from Korean studies that measures polyenvironmental risk factors for psychosis. Using pilot data, the K-PERS predicted patient status (SSD vs. HC). Further research is warranted to examine the relationship of K-PERS scores with clinical outcomes of psychosis and schizophrenia.

A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial) / 한국유방암학회지

Purpose@#Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. @*Methods@#This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness.Discussion: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy.We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety.

YM155, specific survivin inhibitor, can enhance artesunate-induced cytotoxicity in HCT116 colon cancer cells

Purpose@#A water-soluble variant of the artemisinin called artesunate, approved as an antimalarial agent, can induce cell death on various cancer cell types. We studied the mechanism of cell death of artesunate on HCT116 colorectal cancer cells. @*Methods@#We treated HCT116 colon cancer cells with artesunate, holo-transferrin, deferoxamine mesylate, ferrostatin, necrostatin-1, and YM155. We observed the growth inhibition of artesunate on HCT116 colon cancer cells by morphologic findings. Inhibition of cell growth was assessed by MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) assay and long-term growth inhibition by colony-forming assay. Apoptosis was investigated by flow cytometry and Western blot analysis. @*Results@#Artesunate inhibited the proliferation of HCT116 colon cancer cells effectively. Co-treatment with YM155, a specific survivin inhibitor, enhanced the artesunate-induced cell death. Co-treatment with the iron-chelating agent deferoxamine rescued artesunate induced cell death and increased long-term cell survival and proliferation. @*Conclusion@#In this study, we demonstrated that artesunate-induced cytotoxicity in HCT116 colon cancer cells by suppressing the expression of survivin and partially by ferroptosis. Our findings suggest that the co-treatment artesunate with YM155 can induce more potent cell death on HCT116 colon cancer cells and shows new insight for the treatment of colorectal cancer patients.

YM155, specific survivin inhibitor, can enhance artesunate-induced cytotoxicity in HCT116 colon cancer cells

Purpose@#A water-soluble variant of the artemisinin called artesunate, approved as an antimalarial agent, can induce cell death on various cancer cell types. We studied the mechanism of cell death of artesunate on HCT116 colorectal cancer cells. @*Methods@#We treated HCT116 colon cancer cells with artesunate, holo-transferrin, deferoxamine mesylate, ferrostatin, necrostatin-1, and YM155. We observed the growth inhibition of artesunate on HCT116 colon cancer cells by morphologic findings. Inhibition of cell growth was assessed by MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) assay and long-term growth inhibition by colony-forming assay. Apoptosis was investigated by flow cytometry and Western blot analysis. @*Results@#Artesunate inhibited the proliferation of HCT116 colon cancer cells effectively. Co-treatment with YM155, a specific survivin inhibitor, enhanced the artesunate-induced cell death. Co-treatment with the iron-chelating agent deferoxamine rescued artesunate induced cell death and increased long-term cell survival and proliferation. @*Conclusion@#In this study, we demonstrated that artesunate-induced cytotoxicity in HCT116 colon cancer cells by suppressing the expression of survivin and partially by ferroptosis. Our findings suggest that the co-treatment artesunate with YM155 can induce more potent cell death on HCT116 colon cancer cells and shows new insight for the treatment of colorectal cancer patients.

Development of an Excel Program for the Updated Eighth American Joint Committee on Cancer Breast Cancer Staging System

PURPOSE: The eighth American Joint Committee on Cancer staging system for breast cancer was recently published to more accurately predict the prognosis by adding biomarkers such as estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. However, this system is very complicated and difficult to use by clinicians. The authors developed a program to aid in setting up the staging system and confirmed its usefulness by applying it to theoretical combinations and actual clinical data. METHODS: The program was developed using the Microsoft Excel Macro. It was used for the anatomic, clinical and pathological prognostic staging of 588 theoretical combinations. The stages were also calculated the stages using 840 patients with breast cancer without carcinoma in situ or distant metastasis who did not undergo preoperative chemotherapy. RESULTS: The anatomic, clinical and pathological prognostic stages were identical in 240 out of 588 theoretical combinations. In the actual patients' data, stages IB and IIIB were more frequent in clinical and pathological prognostic stages than in the anatomic stage. The anatomic stage was similar to the clinical prognostic stage in 58.2% and to the pathological prognostic stage in 61.9% of patients. Oncotype DX changed the pathological prognostic stage in 2.1% of patients. CONCLUSION: We developed a program for the new American Joint Committee on Cancer staging system that will be useful for clinical prognostic prediction and large survival data analysis.

Distress and Quality of Life for Breast Cancer Survivors during Follow-Up Periods in Korea

PURPOSE: Few studies have reported postdiagnosis differences in distress and quality of life (QOL) for breast cancer (BC) survivors. Here we investigated the differences in distress and QOL for BC survivors in Korea, during follow-up. METHODS: Completed questionnaires were collected from 179 BC survivors in 2013. Functional Assessment of Cancer Therapy-Breast was administered to measure the distress and Distress Thermometer and Problem List was administered to measure the QOL. RESULTS: The mean QOL score was 96.69 (standard deviation, ±20.33). Seventy-nine patients (44.1%) with distress-test scores >4 were assigned to the severe distress group. The patient group with higher family income had high QOL score (p=0.008). In addition, QOL scores were significantly higher in patients who lived longer after diagnosis (p=0.016). Patients at high TNM stage had low QOL scores (p=0.006). Furthermore, older patients tended to have high distress scores (p=0.028). Based on duration of the postdiagnosis period, we divided the patients into two groups. Seventy patients had a postdiagnosis period <2 years; 109 patients, postdiagnosis period ≥2 years. Distress score of the under-2-year group (4.26±2.73) was significantly higher (p=0.044) than that of the longer-than-2-year group (3.47±2.42). CONCLUSION: BC survivors showed improvement in physical well-being, emotional well-being, and functional well-being domain of QOL over time. However, social well-being and BC subscale score were only slightly improved over time. It is possible that cancer patients' supporting programs are focused on the recently diagnosed patients or those currently undergoing treatment. Therefore, more support should be made available to long-term BC survivors.

Oncologic manifestations of neurofibromatosis type 1 in Korea / 대한외과학회지

PURPOSE: The aim of this study was to investigate the incidence and spectrum of malignant tumors in Korean neurofibromatosis type 1 (NF1) patients. METHODS: We retrospectively reviewed 125 patients who were diagnosed with NF1 at a single institution from 1995 to 2010. The incidence, location, histologic type, and radiologic findings of malignant tumors as well as development of multiple primary tumors were analyzed. RESULTS: Eighteen malignant tumors occurred in 16 patients (12.8%) among 125 Korean NF1 patients; 9 carcinomas, 8 sarcomas and 1 central nervous system (CNS) tumor. Five tumors were of nervous system origin and 13 were non-nervous system tumors. The locations of the tumors were as follow: 1 CNS, 2 lung, 3 breast, 3 stomach, 3 small bowel, 1 colon, 1 liver, 1 uterus, 1 neck, and 2 in extremities. Three malignant peripheral nerve sheath tumors (MPNSTs) occurred at the neck and extremity, and one in the liver. All three gastrointestinal stromal tumors (GISTs) had multiple tumors in the jejunum, and one MPNST and one pheochromocytoma were accompanied in two GISTs. Multiple primary tumors, benign or malignant were reported in 4 patients (25.0%), synchronously or metachronously. CONCLUSION: Korean NF1 patients had a high risk of developing malignant tumors. The common malignant tumors in Koreans such as breast, lung and stomach cancers developed frequently in addition to the NF1-related tumors such as MPNST or GIST.

The Effect of BF-7 on the Ischemia-induced Learning and Memory Deficits / 대한해부학회지

Abnormal blood supply to brain, such as ischemia induce neuronal damages, possibly leading to dementia. Such damages should be attenuated by neuroprotective materials which make neurons tolerable against limited blood supply or reinforce of blood. For the animal study, transient middle cerebral artery occlusion was operated with SD rat. To check whether BF-7 attenuated the ischemic damage, BF-7 (10 mg/kg) was oral treated for 7 days once a day. To evaluate the learning and memory of the rat, 8-arm maze test was conducted. For clinical study, Rey Complex Figure Test (RCFT) was used with control group (32 person), 200 mg treated group (33 person) and 400 mg treated group (34 person). Treatment of BF-7 greatly reduced the infarct size. Also the neuronal damages in the hippocampus were significantly diminished. Furthermore, The memory impairment by ischemia was recovered. The clinical test showed that BF-7 greatly enhanced the brain function recognizing and memorizing complex two dimensional figures. Our results implicated that BF-7 plays a positive roles on protecting brain and enhancing brain unction clinically.

Analysis of Electrically Evoked Potential in Rabbits with Polyimide Retinal Stimulator

PURPOSE: Electrically evoked potential (EEP) was recorded in rabbits with polyimide-based, multichannel, microelectrode array (MEA) in their eyes, and was compared with the visual evoked potential (VEP) by flash light. METHODS: VEP was recorded under full-field flash light stimulation by 0. 6 J at 2 Hz, while EEP was recorded under electrical current stimulation of the retina by MEA. Latencies and shapes of N1, P100 and N2 in each evoked potential were compared. RESULTS: EEP was recorded in four of six rabbits. N1, P100 and N2 were observed in EEP on the electrical retina stimulation over 2.5 mA, and they resembled those of VEP. However, N1, P100 and N2 of EEP showed shorter latencies than those of VEP, by 15.1 msec (32.9%), 76.8 msec (38.3%) and 99.7 msec (60.1%) respectively. CONCLUSIONS: EEP by electrical retina stimulation with MEA was similar to VEP, indicating that MEA is suitable for the development of the artificial retina prototype. The shorter latencies of EEP should be considered in the parameters of the electrical stimulation of the retina.

Frequencies of Combination Treatment of Atypical Antipsychotics and Selective Serotonin Reuptake Inhibitors in a College Hospital Psychiatric Outpatient Unit / 대한정신약물학회지

OBJECTIVE: The introduction of new psychiatric medications with better efficacy and tolerance seems to increase the frequencies of co-prescriptions of various psychotropic agents. We investigated the frequencies of the combined treatments of atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs) that are supposed to be common in clinical practice. METHODS: Data on 2783 outpatients from March 1, 2002 through June 31, 2002 in Seoul National University Hospital were collected. The number of cases with a co-prescription of atypical antipsychotics with SSRIs were counted and compared by diagnoses. The relations of diagnosis and age to the combined treatment were explored. RESULTS: 499 (17.4%) patients took co-prescriptions of antipsychotics with antidepressants, and 393 (13.7%) patients those of atypical antipschotics with SSRIs. Patients with obsessive compulsive disorder and schizophrenia took the combinations of atypical antipsychotics and SSRIs more frequently than patients with other diagnoses, as 41.6% and 20.8%, respectively. Controlling for diagnostic categories, age was significantly correlated with the presence of those co-prescriptions. CONCLUSION: The findings of the current study reflect evidence-based prescriptions in an educating hospital and provide basic data for further pharmaco-epidemiological studies. The co-prescription of atypical antipsychotic agents with SSRIs seems to occur only in proper indications, under the consideration of the risk of drug-drug interactions and adverse effects.

Frequencies of Combination Treatment of Atypical Antipsychotics and Selective Serotonin Reuptake Inhibitors in a College Hospital Psychiatric Outpatient Unit / 대한정신약물학회지

OBJECTIVE: The introduction of new psychiatric medications with better efficacy and tolerance seems to increase the frequencies of co-prescriptions of various psychotropic agents. We investigated the frequencies of the combined treatments of atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs) that are supposed to be common in clinical practice. METHODS: Data on 2783 outpatients from March 1, 2002 through June 31, 2002 in Seoul National University Hospital were collected. The number of cases with a co-prescription of atypical antipsychotics with SSRIs were counted and compared by diagnoses. The relations of diagnosis and age to the combined treatment were explored. RESULTS: 499 (17.4%) patients took co-prescriptions of antipsychotics with antidepressants, and 393 (13.7%) patients those of atypical antipschotics with SSRIs. Patients with obsessive compulsive disorder and schizophrenia took the combinations of atypical antipsychotics and SSRIs more frequently than patients with other diagnoses, as 41.6% and 20.8%, respectively. Controlling for diagnostic categories, age was significantly correlated with the presence of those co-prescriptions. CONCLUSION: The findings of the current study reflect evidence-based prescriptions in an educating hospital and provide basic data for further pharmaco-epidemiological studies. The co-prescription of atypical antipsychotic agents with SSRIs seems to occur only in proper indications, under the consideration of the risk of drug-drug interactions and adverse effects.

The Role of BF-7 on Enhancement of Memory and Cognitive Funtion / 대한해부학회지

Various factors such as senescence, stress, neurodegenerative diseases including Alzheimer's disease (AD) contribute to the impairments of organs, especially brain. Also, they should be negative factors on normal brain function, like as memory and cognition. In this study, the neuroprotective role of BF-7, extracted from Bombyx mori, was examined agaist scopolamine-induced neurotoxicity in SK-N-SH cells. In order to know if the BF-7 has positive role on the cognition and memory, we examined using SD rat model and human. Scopolamine-induced memory impairments were observed, as measured by the passive avoidance and water maze tests, but treatment with BF-7 significantly improved memory and cognitive function. Moreover, the memory index and memory preservation of clinical experiments using MMSE-K tests were significantly improved memory and cognitive function. This results strongly represent that the BF-7 play effectively positive role in the improvement of brain function including learning and memory. Taken together, our results suggested that the BF-7 should be useful for developing strategies protecting nervous system and improving brain function.

Drug Prescribing Patterns of Outpatients with Schizophrenia in a University Hospital / 신경정신의학

OBJECTIVES: To provide basic data for psychopharmacologic research of schizophrenic patients, we analyzed and characterized prescribing patterns of outpatients with schizophrenia in Seoul National University Hospital (SNUH). METHODS: This study is a descriptive and retrospective report. Subjects were outpatients with schizophrenia in SNUH from March 1, 2002 through June 31, 2002. We obtained data of prescriptions and diagnoses from order communication system (OCS). RESULTS: There were 825 outpatients with schizophrenia (476 males and 349 females). 805 schizophrenia outpatients were taking antipsychotics. The total number of antipsychotic prescription was 862. The percentage of taking atypical antipsychotics was 88.1% among total antipsychotic prescription and 11.9% taking typical antipsychotics. Risperidone was prescribed most frequently (39.0%), and the next was clozapine (29.0%). There were 57 cases of antipsychotic polypharmacy. CONCLUSION: Our results which reflected evidence-based prescriptions in SNUH showed that atypical antipsychotics were replacing typical antipsychotics. But there was a possibility that clinician's selection of medication was influenced by health insurance policy. Clinical guideline for the treatment of schizophrenia seems necessary for effective pharmacotherapy.