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.

The aim of this study was to verify subacute oral dose toxicity of positively charged 100 nm zinc oxide (ZnO(AE100[+])) nanoparticles (NPs) in Sprague-Dawley rats. ZnO(AE100[+]) NPs were administered to rats of each sex by gavage at 0, 500, 1,000, and 2,000 mg/kg/day for 14 days. During the study period, clinical signs, mortality, body weight, food consumption, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. Increased mortality and clinical signs, decreased body weight, feed consumption, hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet (PT), and lymphocyte (LYM) and increased white blood cells (WBCs), neutrophils (NEUs), alkaline phosphatase (ALP), and histopathological alterations in the spleen, stomach, and pancreas were observed at 2,000 mg/kg/day. Increased clinical signs, decreased body weight, feed consumption, HB, HCT, MCV, MCH, MCHC, and LYM and increased WBCs, NEUs, ALP, and histopathological alterations in the spleen, stomach, and pancreas were seen at 1,000 mg/kg/day. Increased clinical signs, decreased MCV and MCH and increased histopathological alterations in the stomach and pancreas were found at 500 mg/kg/day. These results suggest that the target organs were the spleen, stomach, and pancreas in rats. The no-observed-adverse-effect level was <500 mg/kg for both sexes.
Alkaline Phosphatase ; Animals ; Biochemistry ; Blood Platelets ; Body Weight ; Erythrocyte Indices ; Hematocrit ; Hematology ; Leukocytes ; Lymphocytes ; Mortality ; Nanoparticles* ; Neutrophils ; No-Observed-Adverse-Effect Level ; Organ Size ; Pancreas ; Pathology ; Rats* ; Rats, Sprague-Dawley ; Spleen ; Stomach ; Zinc Oxide* ; Zinc*

BACKGROUND: Elderly patients usually have comorbid and poor general conditions. They are more likely to have complex coronary lesions with cardiac dysfunction. Percutaneous coronary intervention (PCI) in octogenarians remains controversial. In this study, we determined the safety after PCI for octogenarians and their younger counterparts with coronary artery disease. METHODS: We reviewed 1,057 patients (110 octogenarians vs. 947 younger counterparts) who underwent PCI for coronary artery disease at Saint Carollo Hospital. We analyzed the baseline characteristics, angiographic findings, in hospital mortality, and post procedural complications between the two groups. RESULTS: The mean ages of octogenarians and younger counterparts were 83.1+/-4.5 years and 62.6+/-10.3 years, respectively. The octogenarian group had a significantly (p<0.001) higher ratio of female patients compared to their younger counterpart group (57.3% vs. 27.5%). However, the octogenarian group had a significantly (p=0.035) lower ratio of patients with history of diabetes mellitus compare to their younger counterpart group (22.7% vs. 32.6%). Incidence of acute myocardial infarction in octogenarians was significantly (p<0.001) higher than that in the younger counterparts (43.7% vs. 18.0%). There was no significant difference in admission duration, major complication, or in-hospital mortality between two groups. CONCLUSION: Our results revealed that hospital mortality and incidence of major complications in octogenarians who underwent invasive PCI were not higher than those in their younger counterparts, suggesting that PCI could be safely used in patients aged 80 years or older. However, long-term follow-up data are needed.
Aged ; Aged, 80 and over* ; Coronary Artery Disease* ; Coronary Vessels* ; Diabetes Mellitus ; Female ; Follow-Up Studies ; Hospital Mortality ; Humans ; Incidence ; Myocardial Infarction ; Percutaneous Coronary Intervention* ; Saints

A 71-year-old male patient was readmitted to our hospital 1 month after discharge because of relapse of abdominal pain. He had been diagnosed with hepatocellular carcinoma (HCC) 1 year prior and had undergone repeated transcatheter arterial chemoembolization and radiotherapy. During the last hospitalization, he was diagnosed with a liver abscess complicated by previous treatments for HCC and was treated with intravenous antibiotics and abscess aspiration. Follow-up abdominal computed tomography revealed a liver abscess with a duodenal fistula, which was successfully treated with endoscopic Histoacryl injection into the fistula. Liver abscesses with duodenal fistulas rarely occur, but they are intractable and possibly fatal in patients with HCC. In the literature, they have frequently been managed only with abscess treatment without fistula management. We herein report the first case of a patient with a liver abscess complicated by a fistula between the duodenum and the abscess, which was treated with endoscopic Histoacryl injection.
Abscess/*complications ; Aged ; Carcinoma, Hepatocellular/radiotherapy ; Chemoembolization, Therapeutic/*adverse effects ; Cholangiopancreatography, Endoscopic Retrograde ; Duodenal Diseases/*etiology/therapy ; Enbucrilate/*administration & dosage ; Humans ; Intestinal Fistula/*etiology/therapy ; Liver Diseases/*etiology/therapy ; Male ; Radiotherapy/adverse effects

BACKGROUND/AIMS: We investigated the clinical characteristics and follow-up findings of subjects with adrenal incidentalomas in a single, tertiary-care hospital in South Korea. METHODS: The study consisted of a retrospective analysis of 282 adrenal incidentaloma patients who underwent radiographic and endocrinological evaluations at Samsung Medical Center in Seoul, South Korea, between January 2004 and July 2011. RESULTS: Most (86.2%) of the subjects were found to have nonfunctioning tumors. Functioning tumors were seen in 39 patients (13.8%). Among them, 28 (9.9%) had subclinical Cushing syndrome (SCS), six (2.1%) had pheochromocytoma, and five (1.8%) had primary hyperaldosteronism. Malignant adrenal tumors were discovered in three cases: two (0.7%) were primary adrenal cancers, and one (0.4%) was a secondary metastasis from a lung cancer. Significant risk factors for functional tumors were female gender (odds ratio [OR], 3.386; 95% confidence interval [CI], 1.611 to 7.117; p = 0.0013) and a noncontrast attenuation value of > 10 Hounsfield units (OR, 2.806; 95% CI, 1.231 to 6.397; p = 0.0141). During follow-up (mean, 22.5 months) of 72 of the patients, three (4.2%) developed hormonal changes due to functional tumors. One was confirmed as pheochromocytoma by histopathology, and the others were diagnosed with SCS and followed routinely without surgical intervention. No malignant transformation was found in these patients. CONCLUSIONS: Based on these findings, initial hormonal and radiographic evaluations for adrenal incidentalomas appear to be more important than follow-up tests because functional or malignant changes are rare.
*Adrenal Gland Neoplasms/blood/diagnosis/epidemiology/therapy ; Aged ; *Cushing Syndrome/blood/diagnosis/epidemiology/therapy ; Disease Progression ; Female ; Hormones/blood ; Humans ; *Hyperaldosteronism/blood/diagnosis/epidemiology/therapy ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; *Pheochromocytoma/blood/diagnosis/epidemiology/therapy ; Predictive Value of Tests ; Prognosis ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers ; Time Factors ; Tomography, X-Ray Computed ; Tumor Markers, Biological/blood

PURPOSE: To determine predictive factors for stent failure-free survival in patients treated with a retrograde ureteral stent for a malignant ureteral obstruction. MATERIALS AND METHODS: We retrospectively reviewed 71 patients who underwent insertion of a cystoscopic ureteral stent due to a malignant ureteral obstruction between May 2004 and June 2011. Performance status, type of cancer, hydronephrosis grade, location of the obstruction, presence of bladder invasion, C-reactive protein (CRP), serum albumin, and inflammation-based prognostic score (Glasgow prognostic score, GPS) were assessed using a Cox proportional regression hazard model as predicting factors for stent failure. RESULTS: A univariate analysis indicted that hypoalbuminemia (<3.5 g/dL; hazard ratio [HR], 2.43; 95% confidence interval [CI], 1.21 to 4.86; p=0.012), elevated CRP (> or =1 mg/dL; HR, 4.79; 95% CI, 2.0 to 11.1; p=0.001), and presence of a distal ureter obstruction (HR, 3.27; 95% CI, 1.19 to 8.95; p=0.021) were associated with stent failure-free survival. A multivariate analysis revealed that the presence of a mid and lower ureteral obstruction (HR, 3.27; 95% CI, 1.19 to 8.95; p=0.007), GPS > or =1 (HR, 7.22; 95% CI, 2.89 to 18.0; p=0.001), and elevated serum creatinine before ureteral stent placement (>1.2 mg/dL; HR, 2.16; 95% CI, 1.02 to 4.57; p=0.044) were associated with stent failure-free survival. CONCLUSIONS: A mid or lower ureteral obstruction, GPS > or =1, and serum creatinine before ureteral stent insertion >1.2 mg/dL were unfavorable predictors of stent failure-free survival. These factors may help urologists predict survival time.
C-Reactive Protein ; Creatinine ; Humans ; Hydronephrosis ; Hypoalbuminemia ; Multivariate Analysis ; Neoplasm Metastasis ; Proportional Hazards Models ; Retrospective Studies ; Serum Albumin ; Stents ; Ureter ; Ureteral Obstruction ; Urinary Bladder

A 49-year-old man presented with an incidentally detected right renal mass on a health examination. The abdominal computed tomography and magnetic resonance imaging showed a 3-cm right renal mass suspected of being a hypovascular tumor, such as papillary renal cell carcinoma, and an osteoblastic metastatic lesion on the right iliac bone. However, we missed a bone lesion at the time of diagnosis. A laparoscopic radical nephrectomy was performed and the final pathology confirmed unclassified renal cell carcinoma. The follow-up imaging studies showed several neck lymph nodes and multiple bone metastases at the lumbar spine, right iliac bone, and left femur. Thirteen cycles of temsirolimus were administered to the patient, but follow-up positron emission tomography showed newly developed liver and left adrenal metastasis and increased bone metastasis. It is important to note that T1a renal cell carcinoma can present with distant metastasis and thus demands scrupulous examination even though the tumor size may be small.
Carcinoma, Renal Cell ; Femur ; Follow-Up Studies ; Humans ; Liver ; Lymph Nodes ; Magnetic Resonance Imaging ; Middle Aged ; Neck ; Neoplasm Metastasis ; Neoplasms by Histologic Type ; Nephrectomy ; Osteoblasts ; Positron-Emission Tomography ; Sirolimus ; Spine

The emergence and spread of antimicrobial resistance among the pathogenic and commensal Enterobacteriaceae are of great concern worldwide. We characterized the antimicrobial resistance and integrons found in commensal Escherichia coli from healthy humans in the community. Class 1 integrase (intl1) and class 2 integrase (intl2) genes were identified in 22 (13.3%) and 2 (1.2%) of 165 E. coli isolates, respectively. dfrA17-aadA5 and dfrA1-aadA2 were the most common class 1 integrons. The prevalence of each type of class 1 integron among commensal E. coli isolates during 2001~2003 was similar to that of clinical E. coli isolates from hospital-acquired infections during 1994~1999. The resistant rates of commensal E. coli isolates carrying intl1 to ampicillin, streptomycin, gentamicin, sulfamethoxazole, trimethoprim, chloramphenicol, and tetracycline were significantly higher than those of intl1-negative E. coli isolates (p<0.05). Integrons were directly associated with multidrug resistance in commensal E. coli isolates. It is hypothesized that multidrug-resistant Enterobacteriaceae from hospital-acquired infections are a potential reservoir for integrons associated with resistance genes found in commensal E. coli isolates in the community
Ampicillin ; Chloramphenicol ; Drug Resistance, Multiple ; Enterobacteriaceae ; Escherichia coli* ; Escherichia* ; Gentamicins ; Humans* ; Integrases ; Integrons* ; Prevalence ; Streptomycin ; Sulfamethoxazole ; Tetracycline ; Trimethoprim

PURPOSE: To determine treatment policy for early stage endometrial carcinoma, we analyzed the results of postoperative radiotherapy. MATERIALS AND METHODS: From Oct. 1994 to Aug. 2002, 42 patients with FIGO stage I endometrial carcinoma received postoperative radiotherapy. All patients received curative surgery and pelvic lymph node dissection was done in 26 patients. Based on the FIGO staging system, 3 were at stage IA, 21 were at stage IB and 18 were at stage IC. Histologically, there were 14 grade 1, 16 grade 2, and 12 grade 3. Nineteen patients received intracavitary brachytherapy and 23 patients did whole pelvic radiotherapy. The median period of follow-up was 41 months (22 to 100 months). RESULTS: Five-year overall survival, disease-free survival, local control, and regional control rates of all patients were 86.0%, 87.9%, 100%, and 97.5%, respectively. All failures were distant metastases in 5 patients and two patients had simultaneous regional recurrences. There was no intrapelvic failure in patients who received intracavitary radiotherapy. Grade 3 chronic complications were found in 1 patient (4.3%), who received whole pelvic radiotherapy. CONCLUSION: We achieved high rates of loco-regional control and survival by curative surgery and postoperative radiotherapy. However, we need to select the type of radiotherapy based on the risk factors for recurrence to reduce the treatment-related complication.
Brachytherapy ; Disease-Free Survival ; Endometrial Neoplasms* ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Neoplasm Metastasis ; Radiotherapy* ; Recurrence ; Risk Factors