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.

Background: We investigated the changing patterns of insulin secretion and resistance and risk factors contributing to the development of post-transplant diabetes mellitus (PTDM) in kidney recipients under tacrolimus-based immunosuppression regimen during 1 year after transplantation. Methods: This was a multicenter prospective cohort study. Of the 168 subjects enrolled in this study, we analyzed a total 87 kidney transplant recipients without diabetes which was assessed by oral glucose tolerance test before transplantation. We evaluated the incidence of PTDM and followed up the index of insulin secretion (insulinogenic index [IGI]) and resistance (homeostatic model assessment for insulin resistance [HOMA-IR]) at 3, 6, 9 months, and 1 year after transplantation by oral glucose tolerance test and diabetes treatment. We also assessed the risk factors for incident PTDM. Results: PTDM developed in 23 of 87 subjects (26.4%) during 1 year after transplantation. More than half of total PTDM (56.5%) occurred in the first 3 months after transplantation. During 1 year after transplantation, insulin resistance (HOMA-IR) was increased in both PTDM and no PTDM group. In no PTDM group, the increase in insulin secretory function to overcome insulin resistance was also observed. However, PTDM group showed no increase in insulin secretion function (IGI). Old age, status of prediabetes and episode of acute rejection were significantly associated with the development of PTDM. Conclusion In tacrolimus-based immunosuppressive drugs regimen, impaired insulin secretory function for reduced insulin sensitivity contributed to the development of PTDM than insulin resistance during 1 year after transplantation.

PURPOSE: This study evaluated the accuracies of different bite registration techniques for implant-fixed prostheses using three dimensional file analysis. MATERIALS AND METHODS: Implant fixtures were placed on the mandibular right second premolar, and the first and second molar in a polyurethane model. Aluwax (A), Pattern Resin (P), and Blu-Mousse (B) were used as the bite registration materials on the healing abutments (H) or temporary abutments (T). The groups were classified into HA, HP, HB, TA, TP, and TB according to each combination. The group using the bite impression coping was the BC group; impression taking and bite registration were performed simultaneously. After impression and bite taking, the scan bodies were connected to the lab analogs of the casts. These casts were scanned using a model scanner. The distances between two reference points in three-dimensional files were measured in each group. One-way ANOVA and Duncan's test were used at the 5% significance level. RESULTS: The smallest distance discrepancy was observed in the TB group using the temporary abutments. The Blu-Mousse and HP groups showed the largest distance discrepancy. The TB and BC groups showed a lower distance discrepancy than the HP group (P=.001), and there was no significant difference between the groups using the temporary abutments and healing abutments (P>.05). CONCLUSION: Although this study has limitations as an in-vitro investigation, the groups using the temporary abutments to hold the Blu-Mousse record and bite impression coping showed greater accuracy than the group using the healing abutments to hold the pattern resin record.
Bicuspid ; Jaw Relation Record* ; Molar ; Pilot Projects* ; Polyurethanes ; Prostheses and Implants

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*

BACKGROUND/AIMS: ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has been used for preoperative staging of colorectal cancer (CRC). However, the diagnostic accuracy of FDG-PET/CT for detection of lymph node or distant metastasis and its prognostic role have not been well established. We therefore evaluated the diagnostic and prognostic value of FDG-PET/CT in comparison with conventional CT for CRC. METHODS: We investigated 220 patients who underwent preoperative FDG-PET/CT and CT, followed by curative surgery for CRC. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG-PET/CT and CT for detection of lymph node metastasis and distant metastasis were evaluated. In addition, we assessed the findings of FDG-PET/CT and CT according to outcomes, including cancer recurrence and cancer-related death, for evaluation of prognostic value. RESULTS: For detection of lymph node metastasis, FDG-PET/CT had a sensitivity of 44%, a specificity of 84%, and an accuracy of 67%, compared with 59%, 65%, and 62%, respectively, for CT (P=0.029, P=0.000, and P=0.022). For distant metastasis, FDG-PET/CT had a sensitivity of 79%, a specificity of 94%, and an accuracy of 93%, compared with 79%, 87%, and 86%, respectively, for CT (P=1.000, P=0.004, and P=0.037). In addition, positive findings of lymph node metastasis and distant metastasis on FDG-PET/CT were associated significantly with cancer recurrence or cancer-related death (P=0.009, P=0.001, respectively). CONCLUSIONS: Preoperative FDG-PET/CT had a higher specificity and accuracy compared to CT for detection of lymph node metastasis and distant metastasis of CRC. In addition, FDG-PET/CT could be a valuable prognostic tool for CRC.
Colorectal Neoplasms* ; Diagnosis ; Electrons* ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Positron-Emission Tomography ; Prognosis ; Recurrence ; Sensitivity and Specificity

Many epidemiological studies suggest that overweight is associated with an elevated risk of psychiatric disorders and suicidal tendency. However, findings vary across studies, and some have contradictory results. We investigated the relationship of overweight with a range of psychiatric disorders and suicidality in the Korean general population. A multistage cluster sampling design was adopted. A total of 6,022 participants aged 18–74 years completed face-to-face interviews (response rate: 78.7%) including assessment of psychiatric disorders, suicidality, and height and weight. Overweight (defined as body mass index of ≥ 25) was associated with an increase in the lifetime prevalence of depressive disorders (adjusted odds ratio [AOR] 1.38; 95% confidence interval [CI], 1.07–1.77), suicidal ideation (AOR, 1.42; 95% CI, 1.20–1.68), and suicidal plans (AOR, 1.44; 95% CI, 1.02–2.03), controlling for sociodemographic variables. Subgroup analysis found that the association between overweight and depressive disorders exists only in women aged 18–44 years (AOR, 1.75; 95% CI, 1.07–2.89) while the association of overweight with suicidal ideation (AOR, 2.08; 95% CI, 1.53–2.82) and suicide plans (AOR, 2.59; 95% CI, 1.25–5.37) existed only in men aged 18–44 years. Overweight was associated with increased odds of nicotine use disorders in women aged 18–44 years (AOR, 2.35; 95% CI, 1.02–5.43), but the association was in the opposite direction in men aged 45–74 years (AOR, 0.64; 95% CI, 0.43–0.94). In conclusion, overweight is related to various psychiatric disorders and suicidality in Korea. Policy makers and clinicians should pay more attention to the mental health of overweight individuals.
Administrative Personnel ; Body Mass Index ; Cross-Sectional Studies ; Depressive Disorder ; Epidemiologic Studies ; Female ; Humans ; Korea* ; Male ; Mental Disorders ; Mental Health ; Obesity ; Odds Ratio ; Overweight* ; Prevalence* ; Suicidal Ideation ; Suicide ; Tobacco Use Disorder

Transesophageal echocardiography is a useful device to evaluate the posterior structure of heart with an advantage of enabling clearer images, as compared to transthoracic echocardiography. With intraoperative transesophageal echocardiography, we can reconfirm pre-diagnosed lesions, determine the success of the operation, and in particular, diagnose new lesions that are undetected in pre-operative evaluation. In the present case, undiagnosed patent ductus arteriosus was found on intraoperative transesophageal echocardiography during cardiopulmonary bypass. Subsequently, the patent ductus arteriosus was ligated successfully. With transesophageal echocardiography, we can diagnose the structural and functional abnormality of heart unidentified in the pre-operative evaluation. Also, transesophageal echocardiography can play the role of a rescuer to solve the problems that occur during cardiopulmonary bypass.
Cardiopulmonary Bypass* ; Ductus Arteriosus, Patent* ; Echocardiography ; Echocardiography, Transesophageal* ; Heart ; Humans

OBJECTIVE: The lifetime prevalence of alcohol dependence in South Korea remains higher than other countries. The aim of our study is to identify factors associated with remission from alcohol dependence. METHODS: Data from the Korean Epidemiological Catchment Area-Replication (KECA-R) study were used in our study. The Korean version of the Composite International Diagnostic Interview 2.1 (K-CIDI 2.1) was administered. Remission was defined as having no symptom of alcohol dependence for 12 months or longer at the time of the interview. Demographic and clinical variables putatively associated with remission from alcohol dependence were examined by t-test, chi-square-test and logistic regression analysis. RESULTS: The lifetime prevalence rate of alcohol dependence was 7.0%. Among them, 3.2% of the subjects were diagnosed with active alcohol dependence in the previous 12 months, and 3.8% were found to be in remission. Subjects in 35- to 44-year-old group, not living with partner group, and lower level of educational attainment group were more likely to be in the active alcohol dependence state. Of the comorbid mental disorders, dysthymia, anxiety disorder, nicotine use, and nicotine dependence were more common among the actively alcohol-dependent subjects. CONCLUSION: There is considerable level of recovery from alcohol dependence. Attention to factors associated with remission from alcohol dependence may be important in designing more effective treatment and prevention programs in this high-risk population.
Adult ; Alcoholism* ; Anxiety Disorders ; Comorbidity* ; Humans ; Korea ; Logistic Models ; Mental Disorders ; Nicotine ; Prevalence ; Tobacco Use Disorder