Objective: We elucidated the effect of monochorionicity on neonatal and long-term neurologic outcomes on an individual basis in triplets. Methods: We retrospectively reviewed the perinatal outcomes and development and growth at 18 to 24 months corrected age (CA) of triplets born alive between 24 and 32 weeks of gestational age (GA) between 2009 and 2021 from the Seoul National University Hospital database. Neurod­evelopmental impairment (NDI) was defined as any delay among the Bayley-III domains (motor and language), cerebral palsy, hearing impairment, or visual loss and was performed at a CA of 18 to 24 months. Results: We included 40 sets of triplets (120 infants), comprising 26, 10, and 4 sets of trichorionic (TC), dichorionic (DC), and monochorionic (MC) triplets, respectively. Ten infants, unaffected by monochorionicity out of 30 DC infants, were included in the non-MC group. Eighty-eight infants were included in the non-MC group, and 32 infants were affected by monochorionicity. In vitro fertilization-embryo transfer was more frequent in the non-MC group (P<0.05), and twin-to-twin transfusion syndrome affected only the MC group (P<0.01). At 24 months of CA, a combined delay of language and cognition in Bayley-III was evident in the MC group (P<0.05). Although NDI did not significantly differ between the 2 groups (P=0.059), the composite outcome of NDI+ postnatal death was significantly different (P<0.05). NDI+ postnatal death correlated with GA, Z-score of birth weight, brain injury, and monochorionicity in the univariate analysis (P<0.05). Multivariate analysis revealed a significant correlation between monochorionicity and NDI+ postnatal death. (P<0.05). Conclusion Monochorionicity is associated with adverse long-term neurodevelopmental out comes.

Objective: We elucidated the effect of monochorionicity on neonatal and long-term neurologic outcomes on an individual basis in triplets. Methods: We retrospectively reviewed the perinatal outcomes and development and growth at 18 to 24 months corrected age (CA) of triplets born alive between 24 and 32 weeks of gestational age (GA) between 2009 and 2021 from the Seoul National University Hospital database. Neurod­evelopmental impairment (NDI) was defined as any delay among the Bayley-III domains (motor and language), cerebral palsy, hearing impairment, or visual loss and was performed at a CA of 18 to 24 months. Results: We included 40 sets of triplets (120 infants), comprising 26, 10, and 4 sets of trichorionic (TC), dichorionic (DC), and monochorionic (MC) triplets, respectively. Ten infants, unaffected by monochorionicity out of 30 DC infants, were included in the non-MC group. Eighty-eight infants were included in the non-MC group, and 32 infants were affected by monochorionicity. In vitro fertilization-embryo transfer was more frequent in the non-MC group (P<0.05), and twin-to-twin transfusion syndrome affected only the MC group (P<0.01). At 24 months of CA, a combined delay of language and cognition in Bayley-III was evident in the MC group (P<0.05). Although NDI did not significantly differ between the 2 groups (P=0.059), the composite outcome of NDI+ postnatal death was significantly different (P<0.05). NDI+ postnatal death correlated with GA, Z-score of birth weight, brain injury, and monochorionicity in the univariate analysis (P<0.05). Multivariate analysis revealed a significant correlation between monochorionicity and NDI+ postnatal death. (P<0.05). Conclusion Monochorionicity is associated with adverse long-term neurodevelopmental out comes.

Objective: We elucidated the effect of monochorionicity on neonatal and long-term neurologic outcomes on an individual basis in triplets. Methods: We retrospectively reviewed the perinatal outcomes and development and growth at 18 to 24 months corrected age (CA) of triplets born alive between 24 and 32 weeks of gestational age (GA) between 2009 and 2021 from the Seoul National University Hospital database. Neurod­evelopmental impairment (NDI) was defined as any delay among the Bayley-III domains (motor and language), cerebral palsy, hearing impairment, or visual loss and was performed at a CA of 18 to 24 months. Results: We included 40 sets of triplets (120 infants), comprising 26, 10, and 4 sets of trichorionic (TC), dichorionic (DC), and monochorionic (MC) triplets, respectively. Ten infants, unaffected by monochorionicity out of 30 DC infants, were included in the non-MC group. Eighty-eight infants were included in the non-MC group, and 32 infants were affected by monochorionicity. In vitro fertilization-embryo transfer was more frequent in the non-MC group (P<0.05), and twin-to-twin transfusion syndrome affected only the MC group (P<0.01). At 24 months of CA, a combined delay of language and cognition in Bayley-III was evident in the MC group (P<0.05). Although NDI did not significantly differ between the 2 groups (P=0.059), the composite outcome of NDI+ postnatal death was significantly different (P<0.05). NDI+ postnatal death correlated with GA, Z-score of birth weight, brain injury, and monochorionicity in the univariate analysis (P<0.05). Multivariate analysis revealed a significant correlation between monochorionicity and NDI+ postnatal death. (P<0.05). Conclusion Monochorionicity is associated with adverse long-term neurodevelopmental out comes.

Objective: We elucidated the effect of monochorionicity on neonatal and long-term neurologic outcomes on an individual basis in triplets. Methods: We retrospectively reviewed the perinatal outcomes and development and growth at 18 to 24 months corrected age (CA) of triplets born alive between 24 and 32 weeks of gestational age (GA) between 2009 and 2021 from the Seoul National University Hospital database. Neurod­evelopmental impairment (NDI) was defined as any delay among the Bayley-III domains (motor and language), cerebral palsy, hearing impairment, or visual loss and was performed at a CA of 18 to 24 months. Results: We included 40 sets of triplets (120 infants), comprising 26, 10, and 4 sets of trichorionic (TC), dichorionic (DC), and monochorionic (MC) triplets, respectively. Ten infants, unaffected by monochorionicity out of 30 DC infants, were included in the non-MC group. Eighty-eight infants were included in the non-MC group, and 32 infants were affected by monochorionicity. In vitro fertilization-embryo transfer was more frequent in the non-MC group (P<0.05), and twin-to-twin transfusion syndrome affected only the MC group (P<0.01). At 24 months of CA, a combined delay of language and cognition in Bayley-III was evident in the MC group (P<0.05). Although NDI did not significantly differ between the 2 groups (P=0.059), the composite outcome of NDI+ postnatal death was significantly different (P<0.05). NDI+ postnatal death correlated with GA, Z-score of birth weight, brain injury, and monochorionicity in the univariate analysis (P<0.05). Multivariate analysis revealed a significant correlation between monochorionicity and NDI+ postnatal death. (P<0.05). Conclusion Monochorionicity is associated with adverse long-term neurodevelopmental out comes.

Objective: We elucidated the effect of monochorionicity on neonatal and long-term neurologic outcomes on an individual basis in triplets. Methods: We retrospectively reviewed the perinatal outcomes and development and growth at 18 to 24 months corrected age (CA) of triplets born alive between 24 and 32 weeks of gestational age (GA) between 2009 and 2021 from the Seoul National University Hospital database. Neurod­evelopmental impairment (NDI) was defined as any delay among the Bayley-III domains (motor and language), cerebral palsy, hearing impairment, or visual loss and was performed at a CA of 18 to 24 months. Results: We included 40 sets of triplets (120 infants), comprising 26, 10, and 4 sets of trichorionic (TC), dichorionic (DC), and monochorionic (MC) triplets, respectively. Ten infants, unaffected by monochorionicity out of 30 DC infants, were included in the non-MC group. Eighty-eight infants were included in the non-MC group, and 32 infants were affected by monochorionicity. In vitro fertilization-embryo transfer was more frequent in the non-MC group (P<0.05), and twin-to-twin transfusion syndrome affected only the MC group (P<0.01). At 24 months of CA, a combined delay of language and cognition in Bayley-III was evident in the MC group (P<0.05). Although NDI did not significantly differ between the 2 groups (P=0.059), the composite outcome of NDI+ postnatal death was significantly different (P<0.05). NDI+ postnatal death correlated with GA, Z-score of birth weight, brain injury, and monochorionicity in the univariate analysis (P<0.05). Multivariate analysis revealed a significant correlation between monochorionicity and NDI+ postnatal death. (P<0.05). Conclusion Monochorionicity is associated with adverse long-term neurodevelopmental out comes.

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.

Objective: To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer’s dementia and cognitive decline. Methods: In all, 20 participants with Alzheimer’s dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer’s dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion The higher the GR, the lower the prevalence of Alzheimer’s dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer’s dementia and cognitive decline.

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.

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 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.