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: This study investigated the anti-obesity effects of a combination of Syzygium aromaticum L. and Sorbus commixta Hedl. (SS) in vitro and in vivo. Methods: The extracts of Syzygium aromaticum extract (SA) and Sorbus commixta extract (SC) were prepared individually using distilled water. They were mixed in a 1:2 ratio for use in the experiment. To assess the anti-obesity potential of SS in vitro, we examined cell proliferation, cellular triglyceride (TG), and total cholesterol (TC) levels, as well as lipogenesis and β-oxidation in 3T3-L1 cells. To confirm its anti-obesity potential in vivo, C57BL/6J mice were fed a 60% high-fat diet (HFD) to induce obesity. SA alone, SC alone, and their combination compound, SS (at a dosage of 200 mg/kg) were orally administered for 6 weeks. Thereafter, to conduct a comparative evaluation, serum analysis, western blotting of liver tissues, and histopathological analysis were performed. Results: Both SS200 and SS400 significantly inhibited the cellular TG and TC contents in the 3T3-L1 cells. Furthermore, treatment of the cells with SS (at a dose 200 and 400 μg/mL) also led to a noticeable regulation of key lipogenic and β-oxidation factors. Treatment of obese mice with SS resulted in a greater reduction in serum leptin and TG levels compared to treatment with the individual compounds (SA and SC). Furthermore, activation of AMPactivated protein kinase α by SS treatment resulted in the suppression of sterol regulatory element-binding proteins (SREBP)-1, leading to the inhibition of acetyl-CoA carboxylase (ACC) expression. Conclusion Our results suggest that SS may have the potential to prevent obesity through a reduction in the TG and TC levels and regulation of lipogenesis and β-oxidation.

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

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.

OBJECTIVE: To report successful cases of extubation from invasive mechanical ventilation at our institution using pulmonary rehabilitation consisting of noninvasive ventilation (NIV) in neuromuscular patients with experience of reintubation. METHODS: Patients who experienced extubation failure via the conventional weaning strategy but afterwards had extubation success via NIV were studied retrospectively. Continuous end-tidal CO₂ (ETCO₂) and pulse oxyhemoglobin saturation (SpO₂) monitoring were performed. Extubation success was defined as a state not requiring invasive mechanical ventilation via endotracheal tube or tracheotomy during a period of at least 5 days. RESULTS: A total of 18 patients with ventilatory failure who initially experienced extubation failure were finally placed under part-time NIV after extubation. No patient had any serious or long-term adverse effect from NIV, and all patients left the hospital alive. CONCLUSION: NIV may promote successful weaning in neuromuscular patients with experience of reintubation.
Humans ; Neuromuscular Diseases* ; Noninvasive Ventilation* ; Oxyhemoglobins ; Rehabilitation ; Respiration, Artificial ; Retrospective Studies ; Tracheotomy ; Weaning*

OBJECTIVE: To compare the respiratory muscle strength between patients with stable and acutely exacerbated (AE) chronic obstructive pulmonary disease (COPD) at various stages. METHODS: A retrospective medical record review was conducted on patients with COPD from March 2014 to May 2016. Patients were subdivided into COPD stages 1–4 according to the Global Initiative for Chronic Obstructive Lung Disease guidelines: mild, moderate, severe, and very severe. A rehabilitation physician reviewed their medical records and initial assessment, including spirometry, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), COPD Assessment Test, and modified Medical Research Council scale. We then compared the initial parameters in patients with a stable condition and those at AE status. RESULTS: The AE group (n=94) had significantly lower MIP (AE, 55.93±20.57; stable, 67.88±24.96; p=0.006) and MIP% (AE, 82.82±27.92; stable, 96.64±30.46; p=0.015) than the stable patient group (n=36). MIP, but not MEP, was proportional to disease severity in patients with AE and stable COPD. CONCLUSION: The strength of the inspiratory muscles may better reflect severity of disease when compared to that of expiratory muscles.
Dyspnea ; Humans ; Medical Records ; Muscle Strength ; Muscles ; Pulmonary Disease, Chronic Obstructive* ; Rehabilitation ; Respiratory Muscles* ; Retrospective Studies ; Spirometry

No abstract available.
Humans ; Noninvasive Ventilation* ; Weaning*

PURPOSE: To assess the ability of a mechanical in-exsufflator (MI-E), either alone or in combination with manual thrust, to augment cough in patients with neuromuscular disease (NMD) and respiratory muscle dysfunction. MATERIALS AND METHODS: For this randomized crossover single-center controlled trial, patients with noninvasive ventilator-dependent NMD were recruited. The primary outcome was peak cough flow (PCF), which was measured in each patient after a cough that was unassisted, manually assisted following a maximum insufflation capacity (MIC) maneuver, assisted by MI-E, or assisted by manual thrust plus MI-E. The cough augmentation techniques were provided in random order. PCF was measured using a new device, the Cough Aid. RESULTS: All 40 enrolled participants (37 males, three females; average age, 20.9±7.2 years) completed the study. The mean (standard deviation) PCFs in the unassisted, manually assisted following an MIC maneuver, MI-E-assisted, and manual thrust plus MI-E-assisted conditions were 95.7 (40.5), 155.9 (53.1), 177.2 (33.9), and 202.4 (46.6) L/min, respectively. All three interventions significantly improved PCF. However, manual assistance following an MIC maneuver was significantly less effective than MI-E alone. Manual thrust plus MI-E was significantly more effective than both of these interventions. CONCLUSION: In patients with NMD and respiratory muscle dysfunction, MI-E alone was more effective than manual assistance following an MIC maneuver. However, MI-E used in conjunction with manual thrust improved PCF even further.
Cough* ; Female ; Humans ; Insufflation ; Male ; Neuromuscular Diseases ; Respiratory Muscles*

PURPOSE: To assess the ability of a mechanical in-exsufflator (MI-E), either alone or in combination with manual thrust, to augment cough in patients with neuromuscular disease (NMD) and respiratory muscle dysfunction. MATERIALS AND METHODS: For this randomized crossover single-center controlled trial, patients with noninvasive ventilator-dependent NMD were recruited. The primary outcome was peak cough flow (PCF), which was measured in each patient after a cough that was unassisted, manually assisted following a maximum insufflation capacity (MIC) maneuver, assisted by MI-E, or assisted by manual thrust plus MI-E. The cough augmentation techniques were provided in random order. PCF was measured using a new device, the Cough Aid. RESULTS: All 40 enrolled participants (37 males, three females; average age, 20.9±7.2 years) completed the study. The mean (standard deviation) PCFs in the unassisted, manually assisted following an MIC maneuver, MI-E-assisted, and manual thrust plus MI-E-assisted conditions were 95.7 (40.5), 155.9 (53.1), 177.2 (33.9), and 202.4 (46.6) L/min, respectively. All three interventions significantly improved PCF. However, manual assistance following an MIC maneuver was significantly less effective than MI-E alone. Manual thrust plus MI-E was significantly more effective than both of these interventions. CONCLUSION: In patients with NMD and respiratory muscle dysfunction, MI-E alone was more effective than manual assistance following an MIC maneuver. However, MI-E used in conjunction with manual thrust improved PCF even further.
Cough* ; Female ; Humans ; Insufflation ; Male ; Neuromuscular Diseases ; Respiratory Muscles*