A framework for nationwide COVID-19 vaccine safety research in the Republic of Korea: the COVID-19 Vaccine Safety Research Committee

With the introduction of coronavirus disease 2019 (COVID-19) vaccines, the Korea Disease Control and Prevention Agency (KDCA) commissioned the National Academy of Medicine of Korea to gather experts to independently assess post-vaccination adverse events. Accordingly, the COVID-19 Vaccine Safety Research Committee (CoVaSC) was launched in November 2021 to perform safety studies and establish evidence for policy guidance. The CoVaSC established 3 committees for epidemiology, clinical research, and communication. The CoVaSC mainly utilizes pseudonymized data linking KDCA’s COVID-19 vaccination data and the National Health Insurance Service’s claims data. The CoVaSC’s 5-step research process involves defining the target diseases and organizing ad-hoc committees, developing research protocols, performing analyses, assessing causal relationships, and announcing research findings and utilizing them to guide compensation policies. As of 2022, the CoVaSC completed this research process for 15 adverse events. The CoVaSC launched the COVID-19 Vaccine Safety Research Center in September 2022 and has been reorganized into 4 divisions to promote research including international collaborative studies, long-/short-term follow-up studies, and education programs. Through these enhancements, the CoVaSC will continue to swiftly provide scientific evidence for COVID-19 vaccine research and compensation and may serve as a model for preparing for future epidemics of new diseases.

Machine Learning Approach for Active Vaccine Safety Monitoring

Background@#Vaccine safety surveillance is important because it is related to vaccine hesitancy, which affects vaccination rate. To increase confidence in vaccination, the active monitoring of vaccine adverse events is important. For effective active surveillance, we developed and verified a machine learning-based active surveillance system using national claim data. @*Methods@#We used two databases, one from the Korea Disease Control and Prevention Agency, which contains flu vaccination records for the elderly, and another from the National Health Insurance Service, which contains the claim data of vaccinated people. We developed a casecrossover design based machine learning model to predict the health outcome of interest events (anaphylaxis and agranulocytosis) using a random forest. Feature importance values were evaluated to determine candidate associations with each outcome. We investigated the relationship of the features to each event via a literature review, comparison with the Side Effect Resource, and using the Local Interpretable Model-agnostic Explanation method. @*Results@#The trained model predicted each health outcome of interest with a high accuracy (approximately 70%). We found literature supporting our results, and most of the important drug-related features were listed in the Side Effect Resource database as inducing the health outcome of interest. For anaphylaxis, flu vaccination ranked high in our feature importance analysis and had a positive association in Local Interpretable Model-Agnostic Explanation analysis. Although the feature importance of vaccination was lower for agranulocytosis, it also had a positive relationship in the Local Interpretable Model-Agnostic Explanation analysis. @*Conclusion@#We developed a machine learning-based active surveillance system for detecting possible factors that can induce adverse events using health claim and vaccination databases. The results of the study demonstrated a potentially useful application of two linked national health record databases. Our model can contribute to the establishment of a system for conducting active surveillance on vaccination.

Machine Learning Approach for Active Vaccine Safety Monitoring

Background@#Vaccine safety surveillance is important because it is related to vaccine hesitancy, which affects vaccination rate. To increase confidence in vaccination, the active monitoring of vaccine adverse events is important. For effective active surveillance, we developed and verified a machine learning-based active surveillance system using national claim data. @*Methods@#We used two databases, one from the Korea Disease Control and Prevention Agency, which contains flu vaccination records for the elderly, and another from the National Health Insurance Service, which contains the claim data of vaccinated people. We developed a casecrossover design based machine learning model to predict the health outcome of interest events (anaphylaxis and agranulocytosis) using a random forest. Feature importance values were evaluated to determine candidate associations with each outcome. We investigated the relationship of the features to each event via a literature review, comparison with the Side Effect Resource, and using the Local Interpretable Model-agnostic Explanation method. @*Results@#The trained model predicted each health outcome of interest with a high accuracy (approximately 70%). We found literature supporting our results, and most of the important drug-related features were listed in the Side Effect Resource database as inducing the health outcome of interest. For anaphylaxis, flu vaccination ranked high in our feature importance analysis and had a positive association in Local Interpretable Model-Agnostic Explanation analysis. Although the feature importance of vaccination was lower for agranulocytosis, it also had a positive relationship in the Local Interpretable Model-Agnostic Explanation analysis. @*Conclusion@#We developed a machine learning-based active surveillance system for detecting possible factors that can induce adverse events using health claim and vaccination databases. The results of the study demonstrated a potentially useful application of two linked national health record databases. Our model can contribute to the establishment of a system for conducting active surveillance on vaccination.

Big data differential analysis of microglial cell responses in neurodegenerative diseases / 대한해부학회지

Clinical Neuroanatomy and Neurotransmitter-Mediated Regulation of Penile Erection / 대한배뇨장애요실금학회지

Erectile dysfunction (ED) has an adverse impact on men's quality of life. Penile erection, which is regulated by nerves that are innervated into the erectile tissue, can be affected by functional or anatomical trauma of the perineal region, including specific structures of the penis, causing ED. Penile erection is neurologically controlled by the autonomic nervous system. Therefore, it is of utmost importance to understand the neurogenic structure of the erectile tissue and the types of neurotransmitters involved in the penile erection process. Here, we highlight the basic clinical anatomy and erectile function of the penis. Understanding the clinical connotation of the relationship between penile erectile structure and function may provide fresh insights for identifying the main mechanisms involved in ED and help develop surgical techniques for the treatment of ED.

G protein-coupled receptor, family C, group 5 (GPRC5B) downregulation in spinal cord neurons is involved in neuropathic pain / 대한마취과학회지

BACKGROUND: G protein-coupled receptor, family C, group 5 (GPRC5B), a retinoic acid-inducible orphan G-protein-coupled receptor (GPCR), is a member of the group C metabotropic glutamate receptor family proteins presumably related in non-canonical Wnt signaling. In this study, we investigated altered GPRC5B expression in the dorsal horn of the spinal cord after spinal nerve injury and its involvement in the development of neuropathic pain. METHODS: After induction of anesthesia by intraperitoneal injection of pentobarbital (35 mg /kg), the left L5 spinal nerve at the level of 2 mm distal to the L5 DRG was tightly ligated with silk and cut just distal to the ligature. Seven days after nerve injury, animals were perfused with 4% paraformaldehyde, and the spinal cords were extracted and post-fixed at 4degrees C overnight. To identify the expression of GPRC5B and analyze the involvement of GPRC5B in neuropathic pain, immunofluorescence was performed using several markers for neurons and glial cells in spinal cord tissue. RESULTS: After L5 spinal nerve ligation (SNL), the expression of GPRC5B was decreased in the ipsilateral part, as compared to the contralateral part, of the spinal dorsal horn. SNL induced the downregulation of GPRC5B in NeuN-positive neurons in the spinal dorsal horn. However, CNPase-positive oligodendrocytes, OX42-positive microglia, and GFAP-positive astrocytes were not immunolabeled with GPRC5B antibody in the spinal dorsal horn. CONCLUSIONS: These results imply that L5 SNL-induced GPRC5B downregulation may affect microglial activation in the spinal dorsal horn and be involved in neuropathic pain.

Mechanism Underlying NaF-Induced Apoptosis in Human Oral Squamous Cell Carcinoma

Few studies have evaluated the apoptosis-inducing efficacy of NaF on cancer cells in vitro but there has been no previous investigation of the apoptotic effects of NaF on human oral squamous cell carcinoma cells. In this study, we have investigated the mechanisms underlying the apoptotic response to NaF treatment in the YD9 human squamous cell carcinoma cell line. The viability of YD9 cells and their growth inhibition were assessed by MTT and clonogenic assays, respectively. Hoechst staining, DNA electrophoresis and TUNEL staining were conducted to detect apoptosis. YD9 cells were treated with NaF, and western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, and MMP and proteasome activity assays were performed sequentially. The NaF treatment resulted in a time- and dose-dependent decrease in YD9 cell viability, a dose-dependent inhibition of cell growth, and the induction of apoptotic cell death. The apoptotic response of these cells was manifested by nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, a significant shift of the Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-3, PARP, Lamin A/C and DFF45 (ICAD). Furthermore, NaF treatment resulted in the downregulation of G1 cell cyclerelated proteins, and upregulation of p53 and the Cdk inhibitor p27KIP1. Taken collectively, our present findings demonstrate that NaF strongly inhibits YD9 cell proliferation by modulating the expression of G1 cell cycle-related proteins and inducing apoptosis via mitochondrial and caspase pathways.

Mechanism Underlying NaF-Induced Apoptosis in Human Oral Squamous Cell Carcinoma

Few studies have evaluated the apoptosis-inducing efficacy of NaF on cancer cells in vitro but there has been no previous investigation of the apoptotic effects of NaF on human oral squamous cell carcinoma cells. In this study, we have investigated the mechanisms underlying the apoptotic response to NaF treatment in the YD9 human squamous cell carcinoma cell line. The viability of YD9 cells and their growth inhibition were assessed by MTT and clonogenic assays, respectively. Hoechst staining, DNA electrophoresis and TUNEL staining were conducted to detect apoptosis. YD9 cells were treated with NaF, and western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, and MMP and proteasome activity assays were performed sequentially. The NaF treatment resulted in a time- and dose-dependent decrease in YD9 cell viability, a dose-dependent inhibition of cell growth, and the induction of apoptotic cell death. The apoptotic response of these cells was manifested by nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, a significant shift of the Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-3, PARP, Lamin A/C and DFF45 (ICAD). Furthermore, NaF treatment resulted in the downregulation of G1 cell cyclerelated proteins, and upregulation of p53 and the Cdk inhibitor p27KIP1. Taken collectively, our present findings demonstrate that NaF strongly inhibits YD9 cell proliferation by modulating the expression of G1 cell cycle-related proteins and inducing apoptosis via mitochondrial and caspase pathways.

Nutrition Knowledge and Eating Behaviors of Elementary School Children in Seoul / 대한지역사회영양학회지

This study was aimed to examine nutrition knowledge, dietary attitudes, and eating habits of elementary school students and to examine if their characteristics differ by gender. Subjects were 5th and 6th graders of an elementary school (n = 317) in Seoul, and the survey was done during July 2007. Mean height, weight, BMI of subjects was 148.1 cm. 41.7 kg, 19.0, and 14.3% of subjects were categorized as the overweight/obese group. Anthropometric data were not significantly different by gender. Mean score of nutrition knowledge was 14.9 out of 20 showing moderate knowledge levels, and girls scored higher on nutrition knowledge than boys (p < 0.05). Subjects showed knowledge deficit in areas such as nutrients, food groups and specific weight control information. The percentages of correct answers regarding meals for brain function were significantly higher in girls than in boys (p < 0.05). They got nutrition information mainly from mass media and family/relatives. The mean score of dietary attitudes was 41.2 (possible score: 10-50) indicating somewhat positive attitudes, and the score of eating behaviors was 34.8 (possible score: 15-45). Subjects showed problems in eating habits such as having unbalanced diets and snack foods. 82.6% of subjects had unbalanced meals, and these percentages were higher in girls (87.2%) than in boys (78.1%, p < 0.05). Vegetables and fish/shellfish were the most disliked foods. Specific eating behaviors, such as eating slowly, eating grains and having processed foods less frequently, were better in girls than in boys (p < 0.05). Results also showed that majority of subjects need to improve specific behaviors including having diverse foods, eating meals slowly, having meals at regular times, having adequate foods in each food groups, and eating sweets or salty foods less frequently. Only 52.7% of subjects perceived their body images as normal, and 56.4% had experience of weight control. Reasons for weight control were different by gender (p< 0.05). Based on these findings, nutrition education for school children should focus on modifying eating habits or eating behaviors, by suggesting practically applicable methods and providing nutrition information that is interesting and suitable to school-aged children.

Apoptotic Effect of Co-Treatment with a Natural Product, Chios Gum Mastic, and a Proteasome Inhibitor, Lactacystin, on Human Osteosarcoma Cells / 대한해부학회지

Chios gum mastic (CGM) is a resinous exudate obtained from the stem and the main leaves of Pistacia lenticulus tree native to Mediterranean areas. Recently, it was reported that CGM induced apoptosis in a few cancer cells in vitro. Since recent studies indicated the synergistic interactions between the apoptotic stimulus and a proteasome inhibitor, the ubiquintin-proteasome pathway has become an attractive target in cancer therapy. And to date, there has been no report of the synergistic apoptotic effect between CGM and a proteasome inhibitor to become an attractive target in cancer therapy. Therefore, this study was undertaken to investigate the synergistic apoptotic effect of co-treatment with a natural product, CGM, and a proteasome inhibitor, lactacystin, on human osteosarcoma (HOS) cells. To investigate whether the co-treatment of CGM and lactacystin compared with each single treatment efficiently induced apoptosis on HOS cells, MTT assay, DNA electrophoresis, Hoechst staining, DNA hypoploidy assay, Westen blot analysis, immunofluorescent staining, proteasome activity and mitochondrial membrane potential (MMP) change were performed. In this study, HOS cells co-treated with CGM and lactacystin showed several lines of apoptotic manifestation such as nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF and DFF40 (CAD) onto nuclei, and activation of caspase-7, caspase-3, PARP and DFF45 (ICAD) whereas each single treated HOS cells hardly showed. We presented data indicating that the co-treatment of CGM and lactacystin induced potentially apoptosis whereas each single treatment did slightly. Moreover, the co-treatment of CGM and lactacystin potentiated the inhibition of proteasome activity. Therefore, our data provide the possibility that combination therapy of CGM and lactacystin could be considered as a novel therapeutic strategy for human osteosarcoma.

Apoptotic Effect of Co-Treatment with a Natural Product, Chios Gum Mastic, and a Synthetic Chenodeoxycholic Acid Derivative, HS-1200, on Human Osteosarcoma Cells / 체질인류학회지

Chios gum mastic (CGM) is a resinous exudate obtained from the stem and the main leaves of Pistacia lenticulus tree native to Mediterranean areas. Recently it reported that CGM induced apoptosis in a few cancer cells in vitro. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with a natural product, CGM and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. To investigate whether the co-treatment of CGM and HS-1200 compared with each single treatment efficiently reduced the viability of HOS cells, MTT assay was conducted. Induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and DNA hypoploidy, Westen blot analysis and immunofluorescent staining were performed to study the alterations of the expression level and translocation of apoptosis-related proteins in co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) change were also assayed. In this study, HOS cells co-treated with CGM and HS-1200 showed several lines of apoptotic manifestation whereas each single treated HOS cells did not. Although the single treatment of 40 microgram/mL CGM or 25 micrometer HS-1200 for 24 h did not induce apoptosis, the cotreatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of CGM and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

Effect of vital tooth bleaching agent on dentin bonding / 대한치과보존학회지

To evaluate the effect of vital tooth bleaching agent and alcohol pretreatment on dentin bonding, flat dentin windows were produced on the buccal side of the crowns of fifty-five extracted, human premolars. A bleaching gel, Opalescence(R) with 10% of carbamide peroxide (Ultradent Product, USA) was daily applied on the teeth of three experimental groups for six hours for 10 consecutive days, while teeth of a control group were not bleached. After 6 hours of bleaching gel application, the specimens were washed and stored in saline until the next day application. After application of One-step(R) dentin bonding agent (Bisco, USA), Z-250(R) resin (3M-ESPE, USA) was bonded to dentin with a mount jig. Shear bond strength was measured with an Instron machine (Type 4202, Instron Corp., USA) after 24 hours. The results were analyzed using one-way ANOVA and Duncan's multiple range test at p 0.05) and between delayed bonding group and un-bleached control group (p > 0.05). In the condition of the present study, it seems that alcohol pretreatment after bleaching procedure can reduce the adverse effect of vital bleaching agent on dentin bonding.