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.

Purpose: Binocular diplopia is a primary complication that may arise after scleral buckling surgery in patients with rhegmatogenous retinal detachment. This study examined the incidence of and risk factors for binocular diplopia after scleral buckling surgery; it also evaluated the rate of strabismus surgery success in patients with diplopia. Methods: Medical records of 417 patients who underwent scleral buckling surgery for rhegmatogenous retinal detachment at a single institution from January 2017 to June 2022 were retrospectively reviewed. Patients who experienced binocular diplopia for > 6 months were included in the diplopia group. Results: After surgery, 22 patients (5.3%) developed binocular diplopia. There were no significant correlations of diplopia onset with buckle position (i.e., the affected muscle), cryophotocoagulation, subretinal fluid drainage, and the use of gas or oil injections. Prism therapy restored binocular single vision in three patients. Ten patients chose to undergo strabismus surgery, and one patient underwent encircling band removal. All strabismus surgery patients displayed adhesion between the buckle and extraocular muscle. After surgery, 60% of these patients regained binocular single vision. Conclusions Clear risk factors leading to ocular movement disorders and diplopia after scleral buckling remain undefined. If diplopia persists despite prism-based conservative treatment, strabismus surgery may offer relief.

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.

Purpose: To evaluate the test-retest reliability of a contour-based stereoacuity test using a head-mounted display (HMD) and compare it with other stereotests. Methods: Thirty-two healthy adults aged 23-47 years were recruited from a tertiary hospital between August 2017 and July 2018. Two separate contour-based circles (crossed disparity: 135-1,350 arcsecs) were generated on a high-resolution phone display (Galaxy S7; Samsung, Seoul, Korea) using an HMD (Galaxy Gear VR). Two images were independently projected to each eye as graded circles with a random dot background. The results of the new HMD stereotest were compared to those of the standard Randot and TNO stereotests. The test-retest reliability was assessed using the Bland-Altman plot and Cohen’s kappa statistics. Results: Among the 32 study participants, 17 (53%) were males and the mean age was 30.1 ± 4.8 years (range: 23-47). The mean stereoacuity was 160.3 ± 53.5 arcsecs in the first HMD stereotest (HMD1), 28.4 ± 12.5 arcsecs in the Randot stereotest, 96.1 ± 83.5 arcsecs in the TNO stereotest, and 143.3 ± 47.7 arcsecs in the second HMD stereotest (HMD2). The Bland-Altman plot showed a mean difference of 0.042 (-0.189 to +0.272, 95% limits of agreement) between HMD1 and HMD2. The reliability analysis showed an intraclass correlation coefficient of 0.499 (p = 0.022) and agreement of 81.25% in Cohen’s kappa statistics (Cohen’s kappa index = 0.119, p = 0.017). Conclusions The HMD stereotest without monocular cues showed fair test-retest reliability and reproducibility. Further studies using a high resolution display are needed to confirm the validity of the HMD stereotest.

Purpose: The purpose of this study was to conduct a systematic review to investigate the socio-economic benefits of the poison control center (PCC) and to assess whether telephone counseling at the poison control center affects the frequency of emergency room visits, hospitalization, and length of stay of patients with acute poisoning. Methods: The authors conducted a medical literature search of the PubMed, EMBASE, and Cochrane Library databases. Two reviewers evaluated the abstracts for eligibility, extracted the data, and assessed the study quality using a standardized tool. Key results such as the cost-benefit ratio, hospital stay days, unnecessary emergency room visits or hospitalizations, and reduced hospital charges were extracted from the studies. When meta-analysis was possible, it was performed using RevMan software (RevMan version 5.4). Results: Among 299 non-duplicated studies, 19 were relevant to the study questions. The cost-benefit ratios of PCC showed a wide range from 0.76 to 36 (average 6.8) according to the level of the medical expense of each country and whether the study included intentional poisoning. PCC reduced unnecessary visits to healthcare facilities. PCC consultation shortened the length of hospital stay by 1.82 (95% CI, 1.07-2.57) days. Conclusion The systematic review and meta-analysis support the hypothesis that the PCC operation is cost-beneficial. However, when implementing the PCC concept in Korea in the future, it is necessary to prepare an institutional framework to ensure a costeffective model.

Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.

Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.

Objective: Aneurysmal subarachnoid hemorrhage (SAH) is a common emergency condition, resulting in high morbidity and mortality. The delta neutrophil index (DNI), which reflects the fraction of circulating immature granulocytes, is significantly associated with systemic inflammation after infection or sterile injury. Aneurysmal SAH also leads to systemic inflammation after a brain injury. This study aimed to evaluate the relationship between the DNI and poor neurologic outcomes in patients with aneurysmal SAH. Methods: We retrospectively identified patients (>18 years old) with aneurysmal SAH consecutively admitted to the emergency department (ED) between January 1, 2011, and November 30, 2018. The diagnosis of aneurysmal SAH was confirmed using clinical and radiological findings. DNI was determined at 0, 24, 48, and 72 hours after ED admission. The primary result was a poor neurologic outcome using the modified Rankin scale. Results: A total of 352 patients with aneurysmal SAH were included in this study. A multivariable logistic regression model revealed that a high value of DNI at 24 hours after ED admission was a strong independent predictor of poor neurologic outcome upon discharge (odds ratio [OR], 1.471; 95% confidence interval [CI], 1.081-2.001; P=0.014). Among patients with aneurysmal SAH, DNI >1.0% at 24 hours was significantly associated with poor neurologic outcomes upon discharge (OR, 5.037; 95% CI, 3.153-8.044; P<0.001). Conclusion DNI can be determined easily and rapidly after ED admission without any additional cost or time burden. A high DNI value at 24 hours after ED admission is significantly associated with a poor neurologic outcome upon discharge among patients with aneurysmal SAH.