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: The 24-hour mean blood pressure (mBP) is the best predictor of organ damage; however, it is not easily applicable in clinical practice. The APrODiTe study suggested that systolic blood pressure (SBP) values at 7:00 AM and 9:30 PM were associated with the 24-hour mSBP in patients with chronic kidney disease (CKD). We investigated the association of the SBP values at these time-points with the renal outcomes in patients with diabetic CKD during 1-year follow-up. METHODS: Ninety-six patients with diabetic CKD were included at 1-year follow-up. The renal outcomes were an increase in the random urine protein/creatinine ratio or estimated glomerular filtration rate (eGFR) deterioration, which means a decrease in eGFR ≥5 mL/min/1.73 m² compared to the baseline values. RESULTS: The baseline SBP values at 7:00 AM, and 9:30 PM, and the 24-hour mSBP were 135.6±24.9 mmHg, 141.7±25.6 mmHg, and 136.4±20.7 mmHg, respectively. The SBP values measured at the same time-points after 1 year were similar to those at baseline. The SBP at 7:00 AM was significantly associated with eGFR deterioration in the univariate and multivariate analyses (odds ratio [OR]: 1.032; 95% confidence interval [CI]: 1.006–1.059; p=0.016). The SBP at 7:00AM and 24-hour mSBP did not show a concordant association with sustained proteinuria in the linear and logistic analyses. In the subgroup analysis, the association between the SBP at 7:00 AM and eGFR deterioration persisted in patients with CKD stage 3–5 (OR: 1.041; 95% CI: 1.010–1.073; p=0.010). CONCLUSION The SBP at 7:00 AM, in addition to the 24-hour mSBP, is also associated with eGFR deterioration in patients with diabetic CKD, particularly in those with CKD stage 3–5.

OBJECTIVES: Stress management is related to public healthcare and quality of life; an accurate stress classification method is necessary for the design of stress monitoring systems. Therefore, the goal of this study was to design a novel stress classification model using a deep learning method. METHODS: In this paper, we present a stress classification model using the dataset from the sixth Korea National Health and Nutrition Examination Survey conducted from 2013 to 2015 (KNHANES VI) to analyze stress-related health data. Statistical analysis was performed to identify the nine features of stress detection, and we evaluated the performance of the proposed stress classification by comparison with several stress detection models. The proposed model was also evaluated using Deep Belief Networks (DBN). RESULTS: We designed profiles depending on the number of hidden layers, nodes, and hyper-parameters according to the loss function results. The experimental results showed that the proposed model achieved an accuracy and a specificity of 66.23% and 75.32%, respectively. The proposed DBN model performed better than other classification models, such as support vector machine, naive Bayesian classifier, and random forest. CONCLUSIONS: The proposed model in this study was demonstrated to be effective in classifying stress detection, and in particular, it is expected to be applicable for stress prediction in stress monitoring systems.
Classification* ; Dataset ; Delivery of Health Care ; Forests ; Korea ; Learning ; Machine Learning ; Methods ; Nutrition Surveys ; Quality of Life ; Sensitivity and Specificity ; Support Vector Machine

PURPOSE: Human papillomavirus (HPV) infection is a well-known cause of cervical cancer, which, along with its precursors, can be diagnosed and treated with cervical conization (CC). This study aimed to assess HPV- and procedure-related knowledge among women who had undergone CC. MATERIALS AND METHODS: Between February and May 2014, consecutive women who had undergone CC at five different educational hospitals were recruited. All patients had undergone a loop electrosurgical excision procedure as the method of CC. A survey was conducted with a self-developed, 29-item questionnaire, measuring knowledge related to HPV and CC. We analyzed the responses of 160 patients who completed the questionnaire. RESULTS: Mean total knowledge scores (±standard deviation) for HPV and CC were 5.2±3.0 of a possible 13.0 and 8.3±4.2 of a possible 16.0, respectively. While 73% of the patients knew that HPV is the main cause of cervical cancer, only 44% knew that HPV is sexually transmitted. The purpose of CC was correctly identified by 71% of the patients. However, 35% failed to indicate the anatomical area resected at the time of CC in the schematic diagram. Women who were younger (p<0.001), had higher education level (p<0.001), and higher family income (p=0.008) had higher knowledge scores. In contrast, neither interval from CC to survey nor disease severity were associated with total knowledge score. CONCLUSION: The level of knowledge related to HPV and CC was unexpectedly low in women who had undergone CC. Intuitive educational resources may improve this knowledge, and further cohort studies are warranted.
Adult ; Cervix Uteri/*pathology/*virology ; *Conization ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Middle Aged ; Papillomaviridae/*physiology ; Republic of Korea ; Sexual Behavior ; *Surveys and Questionnaires ; Uterine Cervical Neoplasms/virology ; Young Adult

PURPOSE: Return of spontaneous circulation (ROSC) is closely related to a favorable treatment outcome in out-of-hospital cardiac arrest and is also a reliable treatment target in clinical trials. The aim of this study is the identification of major factors affecting field ROSC by analyzing the updated data encompassing the pre-hospital treatment processes. METHODS: This is a retrospective review of cardiopulmonary resuscitation (CPR) cases performed by 119 rescuers before hospital arrival from January 2012 to December 2014 in one province. Cases with traumatic cardiac arrest, unnecessary CPR, arrest occurred during transport, under age 14 years, and incomplete medical records were excluded. RESULTS: Of 1,832 patients enrolled in the study, ROSC was achieved in 99 cases (5.4%). Among them, 50 (50.5%) had ROSC at the event field and others achieved ROSC during the transport process, respectively. Total cases were divided into two groups based on ROSC before arrival at the hospital. Age, underlying cardiovascular illnesses, the event place, presence of a witness, bystander CPR, application of an automated external defibrillator (AED), the initial shockable rhythm, defibrillation, advanced airway, hydration, the arrival time of rescuer CPR, application time of AED, and defibrillation showed significant statistical differences. In multivariate analysis, age, defibrilOf 1,832 patients enrolled in the study, ROSC was achieved in 99 cases (5.4%). Among them, 50 (50.5%) had ROSC at the event field and others achieved ROSC during the transport process, respectively. Total cases were divided into two groups based on ROSC before arrival at the hospital. Age, underlying cardiovascular illnesses, the event place, presence of a witness, bystander CPR, application of an automated external defibrillator (AED), the initial shockable rhythm, defibrillation, advanced airway, hydration, the arrival time of rescuer CPR, application time of AED, and defibrillation showed significant statistical differences. In multivariate analysis, age, defibrillation, hydration, bystander CPR, and the call-to-rescuer CPR interval appeared to be correlated with field ROSC. CONCLUSION: To improve the survival rate through field ROSC, a public campaign to improve bystander CPR, prompt recognition of cardiac arrest, and rapid application of pre-hospital treatment and political support of the public institution are mandatory.
Cardiopulmonary Resuscitation ; Defibrillators ; Emergency Medical Services ; Heart Arrest ; Humans ; Medical Records ; Multivariate Analysis ; Out-of-Hospital Cardiac Arrest* ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Case reports of indium-related lung disease in workers have raised public concern to the human toxicity of indium (In) and its compounds. However, studies evaluating the exposure or health of workers in In smelting plants are rare. Therefore, in this study, we focused on four In smelting plants, with the main objective of characterizing In in smelter plants in China and discussing the potential exposure biomarkers of In exposure. We recruited 494 subjectsat four In smelting plants in China. Personal air samples, first morning urine and spot blood samples were collected. In concentrations in samples were analyzed using inductively coupled plasma mass spectrometry. In concentrations in air samples did not exceed the permissible concentration-time weighed average, but the smelter workers had a higher internal exposure to In. Positive correlations were observed between the air In and urine In concentrations, and between the air In and blood In concentrations. This study provides basic data for the following In exposure and health risk assessment.
Adult ; Air Pollutants, Occupational ; blood ; urine ; Biomarkers ; blood ; urine ; China ; Environmental Monitoring ; Female ; Humans ; Indium ; blood ; urine ; Male ; Mass Spectrometry ; Metallurgy ; Middle Aged ; Occupational Exposure ; Young Adult

BACKGROUND/AIMS: Little is known about the efficacy of low-dose transdermal fentanyl (TDF) patches in opioid-naive patients with moderate-to-severe cancer pain. METHODS: This study had an open-label, prospective design, and was conducted between April 2007 and February 2009 in seven tertiary cancer hospitals; 98 patients were enrolled. TDF was started using a low-dose formulation (12.5 microg/hr), and the dose was adjusted according to the clinical situation of individual patients. Pain intensity, the TDF doses used, and adverse events (AEs) were monitored over 4 weeks. Data were analyzed using the intent-to-treat and per-protocol principles. RESULTS: Of the 98 patients enrolled, 64 (65%) completed the study. The median pain intensity decreased from 6.0 to 3.0 (p < 0.001) at the follow-up visit. The efficacy of low-dose TDF on pain relief was consistent across groups separated according to gender (p < 0.001), age (p < 0.001), metastasis (p < 0.001), previous treatment (p < 0.001), and baseline pain intensity (p < 0.001). The decrease in pain intensity was significantly greater in the severe group compared with the moderate group (mean +/- SD, 5.10 +/- 2.48 vs. 2.48 +/- 1.56; p < 0.001). TDF dose (27.8 microg/hr vs. 24.8 microg/hr, p = 0.423) and the mean treatment time (7.5 days vs. 7.9 days, p = 0.740) required for pain control were not different between the two pain-intensity groups. Patients had AEs of only mild or moderate intensity; among these, nausea (38%) was the most common, followed by vomiting (22%) and somnolence (22%). CONCLUSIONS: Low-dose TDF was an effective treatment for patients with cancer pain of moderate-to-severe intensity. Further randomized trials assessing the efficacy of TDF for severe pain and/or optimal starting doses are warranted.
Administration, Cutaneous ; Adult ; Aged ; Aged, 80 and over ; Analgesics, Opioid/*administration & dosage/adverse effects ; Female ; Fentanyl/*administration & dosage/adverse effects ; Humans ; Intention to Treat Analysis ; Male ; Middle Aged ; Neoplasms/*complications ; Pain/diagnosis/*drug therapy/etiology ; Pain Measurement ; Prospective Studies ; Republic of Korea ; Severity of Illness Index ; Tertiary Care Centers ; Time Factors ; Transdermal Patch ; Treatment Outcome

A 66-year-old female who had undergone surgery for a herniated disc at the L5-S1 level at another hospital 3 months earlier was admitted with persistent back and leg pain. She was diagnosed with spondylodiscitis at the L5-S1 level by magnetic resonance imaging. A biopsy was performed, and Candida parapsilosis and Enterococcus faecium were isolated from the excised material. We report herein a case of successful treatment of polymicrobial spondylodiscitis in accordance with accurate microbiological diagnosis. Based on this case, we hope to encourage physicians to perform biopsies more aggressively or repeatedly to improve the diagnostic yield.
Aged ; Biopsy ; Candida ; Coinfection ; Diagnosis ; Discitis* ; Enterococcus faecium ; Female ; Hope ; Humans ; Intervertebral Disc Displacement ; Leg ; Magnetic Resonance Imaging

Hemangioma of the liver is usually asymptomatic and incidentally discovered. However, giant hemangioma of the liver may be symptomatic, which is an indication for treatment. A 31-year-old female was admitted with a fever and 1-month history of a nonproductive cough. Her blood test results revealed thrombocytopenia, anemia, and mild coagulopathy. A giant hemangioma of the liver was the cause of her symptoms and signs, and was too large for surgical treatment. Therefore, we performed two sessions of transcatheter hepatic arterial embolization (TAE). The patient has been doing well without fever for 1 year following the second TAE procedure. Surgical resection and enucleation are the traditional treatments of choice for symptomatic giant hemangioma of the liver. However, the signs and symptoms of giant hemangioma of the liver improved by TAE in the present case. We herein report a case of complicated giant hemangioma of the liver that was partially treated by TAE and conservative management.
Adult ; Anemia ; Cough* ; Female ; Fever* ; Hemangioma* ; Hematologic Tests ; Humans ; Liver* ; Thrombocytopenia