Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: A decline in masticatory function may indicate brain dysfunction related to dementia, but the relationship between masticatory function and dementia risk remains unclear. This study aimed to investigate whether masticatory function is associated with the risk of cognitive decline and dementia. Methods: Data were obtained from the nationwide prospective cohort study of randomly sampled community-dwelling Koreans aged ≥ 60 years. The 5,064 non-demented participants, whose number of chewing cycles per bite was assessed by clinical interview, were followed for 8 years with biennial assessments of cognitive performance and clinical diagnoses of all-cause dementia and Alzheimer’s disease (AD). Structural brain magnetic resonance imaging was collected from a subset of cohort participants and their spouses for imaging analyses. Results: Males who chewed ≥ 30 cycles/bite had faster decline in global cognition and memory function and were at higher risk for incident all-cause dementia (hazard ratio [HR], 2.91; 95% confidence interval [CI], 1.18–7.18) and AD (HR, 3.22; 95% CI, 1.14–9.11) compared to males with less than 10 cycles/bite. Additionally, increased chewing cycles in males were associated with reduced brain volume, particularly in regions involved in compensatory cognitive control of mastication. There was no significant association between chewing cycles and the risk of dementia or brain volume in females. Conclusion Older men who frequently chew their meals could be considered a notable population at risk for dementia who should be carefully assessed for their cognitive trajectories.

Background and Objectives: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. Methods: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. Results: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). Conclusions There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Objective: The purpose of this study was to investigate the efficacy of medication management as a method of early intervention in dementia. Methods: This study used data of survey and Mini-Mental State Examination for Dementia Screening score of 46 dementia patients given medication management. Participants were separated into three groups based on the duration of medication management. Then we compared the change in cognitive ability and the frequency of community service usage. Results: The decline of Mini-Mental State Examination score that each group reported was -0.93±2.69, -1.38±1.71, and -1.00± 3.52 and there was no significant difference. In terms of the community service, after being given the medication management, the usage of community service increased. Conclusion Continuous medication management might relieved the decrease of cognitive ability and encourage dementia patients to participate in community service.

Background: Aging is one of major causes triggering neurophysiological changes in many brain substructures, including the hippocampus, which has a major role in learning and memory. Thioredoxin (Trx) is a class of small redox proteins. Among the Trx family, Trx2 plays an important role in the regulation of mitochondrial membrane potential and is controlled by TrxR2. Hitherto, age-dependent alterations in Trx2 and TrxR2 in aged hippocampi have been poorly investigated. Therefore, the aim of this study was to examine changes in Trx2 and TrxR2 in mouse and rat hippocampi by age and to compare their differences between mice and rats. Results: Trx2 and TrxR2 levels using Western blots in mice were the highest at young age and gradually reduced with time, showing that no significant differences in the levels were found between the two subfields. In rats, however, their expression levels were the lowest at young age and gradually increased with time. Nevertheless, there were no differences in cellular distribution and morphology in their hippocampi when it was observed by cresyl violet staining. In addition, both Trx2 and TrxR2 immunoreactivities in the CA1-3 fields were mainly shown in pyramidal cells (principal cells), showing that their immunoreactivities were altered like changes in their protein levels. Conclusions Our current findings suggest that Trx2 and TrxR2 expressions in the brain may be different according to brain regions, age and species. Therefore, further studies are needed to examine the reasons of the differences of Trx2 and TrxR2 expressions in the hippocampus between mice and rats.

Background and Objectives: Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. Methods: Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment.Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. Results: mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively.Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01). Conclusions Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.

Background: Aging is one of major causes triggering neurophysiological changes in many brain substructures, including the hippocampus, which has a major role in learning and memory. Thioredoxin (Trx) is a class of small redox proteins. Among the Trx family, Trx2 plays an important role in the regulation of mitochondrial membrane potential and is controlled by TrxR2. Hitherto, age-dependent alterations in Trx2 and TrxR2 in aged hippocampi have been poorly investigated. Therefore, the aim of this study was to examine changes in Trx2 and TrxR2 in mouse and rat hippocampi by age and to compare their differences between mice and rats. Results: Trx2 and TrxR2 levels using Western blots in mice were the highest at young age and gradually reduced with time, showing that no significant differences in the levels were found between the two subfields. In rats, however, their expression levels were the lowest at young age and gradually increased with time. Nevertheless, there were no differences in cellular distribution and morphology in their hippocampi when it was observed by cresyl violet staining. In addition, both Trx2 and TrxR2 immunoreactivities in the CA1-3 fields were mainly shown in pyramidal cells (principal cells), showing that their immunoreactivities were altered like changes in their protein levels. Conclusions Our current findings suggest that Trx2 and TrxR2 expressions in the brain may be different according to brain regions, age and species. Therefore, further studies are needed to examine the reasons of the differences of Trx2 and TrxR2 expressions in the hippocampus between mice and rats.

Background and Objectives: Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. Methods: Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment.Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. Results: mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively.Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01). Conclusions Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.

Objective: The aim of this study was to develop a Korean version of the Thinking About Life Experiences (TALE-K) scale and to analyze the characteristics of autobiographical memory function (AMF) in community-dwelling older adults. Methods: To develop TALE-K, a translation and back-translation procedure followed by an understanding test was performed. Then, a survey was conducted to examine the associations of AMF with psychosocial variables using TALE-K, Index of Well-Being (IWB), Meaning in Life Scale for older adults, Revised UCLA Loneliness Scale, Medical Outcomes Study Social Support Survey, and Brief Resilience Scale. Results: Data from 75 community-dwelling older adults were used for the final analysis. The average scores of all three sub-scales of TALE-K were below 3 points (less frequent than occasionally). The correlation results showed that TALE-K total score was significantly associated with IWB and the Meaning in life scale for older adults. The multiple linear regression results present-ed that higher AMF was significantly associated with higher IWB, along with having siblings, higher meaning in life and resilience,and lower loneliness. Conclusion Including a validation study of TALE-K, studies for understanding the characteristics of AMF in older adults using TALE-K are needed.