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: 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: This study aimed to identify prognostic factors based on treatment outcomes for congenital diaphragmatic hernia (CDH) at a single-center and to identify factors that may improve these outcomes. Methods: Thirty-five neonates diagnosed with CDH between January 2011 and December 2021 were retrospectively analyzed. Pre- and postnatal factors were correlated and analyzed with postnatal clinical outcomes to determine the prognostic factors. Highest oxygenation index (OI) within 24 hours of birth was also calculated. Treatment strategy and outcome analysis of published literatures were also performed. Results: Overall survival rate of this cohort was 60%. Four patients were unable to undergo anesthesia and/or surgery. Three patients who commenced extracorporeal membrane oxygenation (ECMO) post-surgery were non-survivors. Compared to the survivor group, the non-survivor group had a significantly higher occurrence of pneumothorax on the first day, need for high-frequency ventilator and inhaled nitric oxide use, and high OI within the first 24 hours. The non-survivor group showed an early trend towards the surgery timing and a greater number of patch closures. Area under the receiver operating characteristic curve was 0.878 with a sensitivity of 76.2% and specificity of 92.9% at an OI cutoff value of 7.75. Conclusion OI within 24 hours is a valuable predictor of survival. It is expected that the application of ECMO based on OI monitoring may help improve the opportunity for surgical repair, as well as the prognosis of CDH patients.

Background: Depression and anxiety are prevalent and can cause suffering in patients with Parkinson’s disease (PD). The Korean version of the Hospital Anxiety and Depression Scale (K-HADS) has been widely used to assess depression and anxiety symptoms in Korean patient with PD. The present study aimed to assess the reliability and validity of the K-HADS using Rasch measurement analysis. Methods: A total of 106 PD patients (54 males, 52 females) who met the diagnostic criteria of the United Kingdom Brain Bank were recruited. Unidimensionality, the Rasch model fit, response category functioning, patient-item distribution, and the separation reliability of the K-HADS depression (K-HADS-D) and anxiety (K-HADS-A) subscales were statistically evaluated. Results: The mean K-HADS-D and K-HADS-A scores were 8.08±4.69 (mean±standard deviation) and 5.44±4.18, respectively. Cronbach’s α coefficients of the K-HADS-D and K-HADS-A were 0.82 and 0.83. The Rasch analysis revealed that the K-HADS-D and K-HADS-A showed unidimensionality and no disordered functioning was observed in the 4-point polytomous scale. However, both K-HADS-D and K-HADS-A exhibited suboptimal separation reliability, while the K-HADS-A showed inadequate scale targeting with floor effect. Conclusions The present study comprises the first validation of the K-HADS using the Rasch measurement model, suggesting that the K-HADS-D and K-HADS-A are clinimetrically acceptable and reliable scales for use in Korean patients with PD. However, the moderate person separation indices implicate the relatively low discriminatory ability of the K-HADS in our study patients.

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.
Antineoplastic Agents ; Asian Continental Ancestry Group ; Drug Therapy ; Education ; Endometrial Neoplasms ; Female ; Gyeonggi-do ; Humans ; Immunotherapy ; Korea ; Ovarian Neoplasms ; Radiotherapy ; Uterine Cervical Neoplasms

Alterations in sulfur amino acid metabolism are associated with an increased risk of a number of common late-life diseases, which raises the possibility that metabolism of sulfur amino acids may change with age. The present study was conducted to understand the age-related changes in hepatic metabolism of sulfur amino acids in 2-, 6-, 18- and 30-month-old male C57BL/6 mice. For this purpose, metabolite profiling of sulfur amino acids from methionine to taurine or glutathione (GSH) was performed. The levels of sulfur amino acids and their metabolites were not significantly different among 2-, 6- and 18-month-old mice, except for plasma GSH and hepatic homocysteine. Plasma total GSH and hepatic total homocysteine levels were significantly higher in 2-month-old mice than those in the other age groups. In contrast, 30-month-old mice exhibited increased hepatic methionine and cysteine, compared with all other groups, but decreased hepatic S-adenosylmethionine (SAM), S-adenosylhomocysteine and homocysteine, relative to 2-month-old mice. No differences in hepatic reduced GSH, GSH disulfide, or taurine were observed. The hepatic changes in homocysteine and cysteine may be attributed to upregulation of cystathionine β-synthase and down-regulation of γ-glutamylcysteine ligase in the aged mice. The elevation of hepatic cysteine levels may be involved in the maintenance of hepatic GSH levels. The opposite changes of methionine and SAM suggest that the regulatory role of SAM in hepatic sulfur amino acid metabolism may be impaired in 30-month-old mice.
Aging ; Amino Acids, Sulfur ; Animals ; Child, Preschool ; Cystathionine ; Cysteine ; Down-Regulation ; Glutathione ; Homocysteine ; Humans ; Infant ; Male* ; Metabolism* ; Metabolomics ; Methionine ; Mice* ; Plasma ; S-Adenosylhomocysteine ; S-Adenosylmethionine ; Sulfur* ; Taurine ; Up-Regulation

OBJECTIVE: We examined whether amantadine can prevent the development of dyskinesia. METHODS: Patients with drug-naïve Parkinson's disease (PD), younger than 70 years of age and in the early stage of PD (Hoehn and Yahr scale < 3), were recruited from April 2011 to December 2014. The exclusion criteria included the previous use of antiparkinsonian medication, the presence of dyskinesia, significant psychological disorders, and previous history of a hypersensitivity reaction. Patients were consecutively assigned to one of 3 treatment groups in an open label fashion: Group A-1, amantadine first and then levodopa when needed; Group A-2, amantadine first, dopamine agonist when needed, and then levodopa; and Group B, dopamine agonist first and then levodopa when needed. The primary endpoint was the development of dyskinesia, which was analyzed by the Kaplan-Meier survival rate. RESULTS: A total of 80 patients were enrolled: Group A-1 (n = 27), Group A-2 (n = 27), and Group B (n = 26). Twenty-four patients were excluded from the analysis due to the following: withdrawal of amantadine or dopamine agonist (n = 9), alternative diagnosis (n = 2), withdrawal of consent (n = 1), and breach in the protocol (n = 12). After exclusion, 5 of the 56 (8.93%) patients developed dyskinesia. Patients in Group A-1 and A-2 tended to develop dyskinesia less often than those in Group B (cumulative survival rates of 0.933, 0.929, and 0.700 for A-1, A-2, and B, respectively; p = 0.453). CONCLUSION: Amantadine as an initial treatment may decrease the incidence of dyskinesia in patients with drug-naïve PD.
Amantadine ; Diagnosis ; Dopamine Agonists ; Dyskinesias ; Humans ; Hypersensitivity ; Incidence ; Levodopa ; Parkinson Disease ; Survival Rate

OBJECTIVE: Musculoskeletal problems are more common in patients with Parkinson's disease (PD) than in normal elderly, but the impact of musculoskeletal problems on health-related quality of life (HRQoL) in patients with PD is unknown. METHODS: Four hundred consecutive patients with PD were enrolled for the evaluation of musculoskeletal problems and HRQoL. HRQoL was assessed by the 36-Item Short Form Health Survey, which comprised physical health and mental health. RESULTS: Of the total patients, 265 patients had musculoskeletal problems, and 135 patients did not have musculoskeletal problems. Patients with musculoskeletal problems reported lower levels of HRQoL in terms of physical health than did patients without musculoskeletal problems (p < 0.05). In women, all components of physical health were lower in patients with musculoskeletal problems than in patients without musculoskeletal problems (p < 0.05). Meanwhile, in men, only the bodily pain score of physical health was lower in patients with musculoskeletal problems than in patients without musculoskeletal problems. Mental health and physical health were negatively correlated with depression, Unified Parkinson's Disease Rating Scale I & II scores, and pain severity from musculoskeletal problems, in that order (p < 0.01 for all). CONCLUSION: These results suggest that musculoskeletal problems in patients with PD affect HRQoL significantly, mainly in terms of physical health rather than mental health and especially in women rather than men. Musculoskeletal problems should not be overlooked in the care of patients with PD.
Aged ; Depression ; Female ; Health Surveys ; Humans ; Male ; Mental Health ; Parkinson Disease ; Quality of Life

BACKGROUND: Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly all cause types of chronic kidney disease. Although classic peroxisome proliferator-activated receptor γ (PPARγ) agonists have a protective effect on diabetic nephropathy, much less is known about their direct effects in renal fibrosis. This study aimed to investigate possible beneficial effects of lobeglitazone, a novel PPARγ agonist, on renal fibrosis in mice. METHODS: We examined the effects of lobeglitazone on renal tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) induced renal fibrosis mice. We further defined the role of lobeglitazone on transforming growth factor (TGF)-signaling pathways in renal tubulointerstitial fibrosis through in vivo and in vitro study. RESULTS: Through hematoxylin/eosin and sirius red staining, we observed that lobeglitazone effectively attenuates UUO-induced renal atrophy and fibrosis. Immunohistochemical analysis in conjunction with quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that lobeglitazone treatment inhibited UUO-induced upregulation of renal Smad-3 phosphorylation, α-smooth muscle actin, plasminogen activator inhibitor 1, and type 1 collagen. In vitro experiments with rat mesangial cells and NRK-49F renal fibroblast cells suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are mediated by inhibition of the TGF-β/Smad signaling pathway. CONCLUSION: The present study demonstrates that lobeglitazone has a protective effect on UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of non-diabetic origin renal disease.
Actins ; Animals ; Atrophy ; Blotting, Western ; Collagen Type I ; Diabetic Nephropathies ; Fibroblasts ; Fibrosis* ; In Vitro Techniques ; Mesangial Cells ; Mice* ; Peroxisomes* ; Phosphorylation ; Plasminogen Activator Inhibitor 1 ; Polymerase Chain Reaction ; Rats ; Renal Insufficiency, Chronic ; Reverse Transcription ; Transforming Growth Factor beta ; Transforming Growth Factors ; Up-Regulation ; Ureter* ; Ureteral Obstruction*

Essential thrombocythemia (ET) is characterized by most cases in which platelet counts exceed 1 million/µL. ET is usually no symptoms during non-pregnancy, but arterial and venous thrombosis and hemorrhage may develop in pregnancy. Pregnancy in these patients is associated with many complications in both pregnant women and fetuses such as recurrent abortion, intrauterine fetal growth restriction, preterm delivery, preeclampsia, and stillbirth. In these patients, aspirin, low-molecular-weight heparin (LMWH), and interferon alpha (INF-α) are recommended during pregnancy. We report a case of four consecutive abortions despite being treated with INF-α, low dose aspirin, and LMWH in patient with ET.
Abortion, Habitual* ; Aspirin ; Female ; Fetal Development ; Fetus ; Hemorrhage ; Heparin, Low-Molecular-Weight ; Humans ; Interferon-alpha ; Platelet Count ; Pre-Eclampsia ; Pregnancy ; Pregnant Women ; Stillbirth ; Thrombocythemia, Essential* ; Venous Thrombosis