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: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

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 objective of this study was to investigate the effect-site concentration (Ce) of remimazolam at loss of response (LOR) and recovery of response (ROR) in patients underwent general anesthesia using simulation. In addition, the relationships between patient’s factors and simulated Ce at LOR and ROR were examined. Methods: The medical records of 81 patients who underwent elective surgery under general anesthesia using remimazolam with simulation of Ce between August 4, 2021 and October 12, 2021, were retrospectively reviewed. Remimazolam was administered as an induction dose of 6 or 12 mg/kg/h until the patient became unresponsive, followed by 0.3–2 mg/kg/ h to maintain BIS values below 60. Simultaneously, simulations of manual infusion mode were performed using Asan Pump software and the Ce of remimazolam was simulated using the Schüttler model. Whenever infusion rate of remimazolam was manually changed, the simulated Ce was confirmed almost simultaneously. LOR and ROR, defined as unresponsive and eye-opening to verbal commands, respectively, were recorded in the Asan Pump program. Results: The median (1Q, 3Q) simulated Ce at LOR and ROR were 0.7 (0.5, 0.9) and 0.3 (0.2, 0.4) μg/ml, respectively. LOR was achieved in 1.9 min after remimazolam infusion with cumulative doses of 0.3 mg/kg. There was a significant relationship between age and simulated Ce at ROR (Ce at ROR = –0.0043 × age + 0.57, r = 0.30, P = 0.014). Conclusions: For optimal dosage adjustment, simulating Ce while administering remimazolam with a weight-based dose during anesthesia is helpful. Elderly patients may recover from anesthesia at lower Ce of remimazolam.

PURPOSE: This study was to evaluate changes of the mechanical loading pattern after anatomic anterior cruciate ligament (ACL) reconstruction by analyzing uptake patterns using combined single-photon emission computerized tomography and conventional computerized tomography (SPECT/CT). MATERIALS AND METHODS: On SPECT/CT, high signal intensity of the articular surface which shows biological activity and mean increase of mechanical loading was compared with that of the tibiofemoral shaft as a comparative signal. The proportion of positive signals was evaluated in all compartments of the operated knee. Analysis was performed according to combined injury. RESULTS: A relatively high proportion of positive signals was detected in the posterior zone of the lateral tibial plateau (23.5%) and trochlear groove (23.5%) although increased signal intensity was detected in all compartments. There was no statistical difference depending on the presence of combined injury and between single-bundle and double-bundle ACL reconstruction. CONCLUSIONS: Following anatomic ACL reconstruction, higher signal intensity was detected, particularly in the posterior part of the lateral tibial plateau and trochlear groove. Close observation for further signal changes or osteoarthritic changes would be required even if there was no combined injury and anatomic reconstruction was performed.
Anterior Cruciate Ligament Reconstruction ; Anterior Cruciate Ligament ; Knee ; Tomography, Emission-Computed, Single-Photon

BACKGROUND: We assessed the frequency and types of ankle fractures that frequently occur during parachute landings of special operation unit personnel and analyzed the causes. METHODS: Fifty-six members of the special force brigade of the military who had sustained ankle fractures during parachute landings between January 2005 and April 2010 were retrospectively analyzed. The injury sites and fracture sites were identified and the fracture types were categorized by the Lauge-Hansen and Weber classifications. Follow-up surveys were performed with respect to the American Orthopedic Foot and Ankle Society ankle-hindfoot score, patient satisfaction, and return to preinjury activity. RESULTS: The patients were all males with a mean age of 23.6 years. There were 28 right and 28 left ankle fractures. Twenty-two patients had simple fractures and 34 patients had comminuted fractures. The average number of injury and fractures sites per person was 2.07 (116 injuries including a syndesmosis injury and a deltoid injury) and 1.75 (98 fracture sites), respectively. Twenty-three cases (41.07%) were accompanied by posterior malleolar fractures. Fifty-five patients underwent surgery; of these, 30 had plate internal fixations. Weber type A, B, and C fractures were found in 4, 38, and 14 cases, respectively. Based on the Lauge-Hansen classification, supination-external rotation injuries were found in 20 cases, supination-adduction injuries in 22 cases, pronation-external rotation injuries in 11 cases, tibiofibular fractures in 2 cases, and simple medial malleolar fractures in 2 cases. The mean follow-up period was 23.8 months, and the average follow-up American Orthopedic Foot and Ankle Society ankle-hindfoot score was 85.42. Forty-five patients (80.36%) reported excellent or good satisfaction with the outcome. CONCLUSIONS: Posterior malleolar fractures occurred in 41.07% of ankle fractures sustained in parachute landings. Because most of the ankle fractures in parachute injuries were compound fractures, most cases had to undergo surgical repairs.
Adult ; Ankle Fractures/classification/etiology/radiography/*surgery ; Ankle Injuries/etiology/radiography/*therapy ; Ankle Joint/radiography/*surgery ; Aviation ; Bone Plates ; Fracture Fixation, Internal ; Fractures, Comminuted/etiology/radiography/surgery ; Fractures, Open/etiology/radiography/surgery ; Humans ; Male ; Military Personnel ; Retrospective Studies ; Young Adult

PURPOSE: We evaluated the clinical and radiological outcomes of double-bundle anterior cruciate ligament (ACL) reconstruction using an outside-in technique with a follow-up of two- to six-years, especially in terms of the sports activity level and radiological degeneration. MATERIALS AND METHODS: Sixty-seven patients who were available for a minimum two-year follow-up after double-bundle ACL reconstruction using an outside-in technique were retrospectively evaluated. The mean follow-up period was 43.7 months. The knee function and stability were evaluated before the operation, one year after the operation (short-term follow-up), and more than two years after the operation (last follow-up). RESULTS: Regarding the knee function, the Lysholm score, International Knee Documentation Committee (IKDC) evaluation, and hop test showed significant improvement. Regarding the stability, the Lachman test, pivot shift test, KT-2000 arthrometer data, and anterior drawer radiographs using Telos showed significant improvement. Regarding the sports activity level, the patients who returned to pre-injury level activity was 68.7% according to the Tegner activity score and 76.1% according to the Cincinnati sports activity scale score. The incidence of aggravated degeneration or development of greater than IKDC grade A degeneration after surgery was 10.4%. CONCLUSIONS: Double-bundle ACL reconstruction using an outside-in technique showed favorable clinical and radiological outcomes with respect to the knee function and stability, joint degeneraion, and, especially, return to pre-injury sports activity.
Anterior Cruciate Ligament ; Anterior Cruciate Ligament Reconstruction ; Follow-Up Studies ; Humans ; Humulus ; Incidence ; Joints ; Knee ; Retrospective Studies ; Sports

BACKGROUND: We investigated the prevalence of latent tuberculosis infection (LTBI) among the health care workers (HCWs) and analyzed its risk factors in South Korea. METHODS: A standard questionnaire regarding the baseline demographics and risk factors for LTBI was given to each participant and tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (QFT-GIT) assay, and chest radiography were performed. RESULTS: A total of 493 participants, 152 (30.8%) doctors and 341 (69.2%) nurses were enrolled in eight tertiary referral hospitals. The mean age of the subjects was 30.6 years old, and 383 (77.7%) were female. Of the 152 doctors, 63 (41.4%) and 36 (23.7%) were positive by TST and by QTF-GIT, respectively, and among the 341 nurses, 119 (34.9%) and 49 (14.4%) had positive TST and QFT-GIT results, respectively. Overall, the agreement between the two tests was 0.22 by the chance corrected proportional agreement rate (kappa coefficient) in 493 subjects. Experience of working in tuberculosis (TB)-related departments was significantly associated with positive LTBI test results by QFT-GIT assay, not by TST. In multivariate analysis, only age was independently associated with increased risk of a positive TST result, while age and experience of working in TB-related departments (odds ratio, 2.29; 95% confidence interval, 1.01-5.12) were independently associated with increased risk of a positive QFT-GIT result. CONCLUSION: A high prevalence of LTBI was found among South Korean HCWs. Considering the association between the experience of working in TB-related departments and high risk of LTBI, QFT-GIT may be a better diagnostic test for LTBI than TST in HCWs.
Delivery of Health Care ; Demography ; Diagnostic Tests, Routine ; Female ; Health Personnel ; Humans ; Interferon-gamma Release Tests ; Latent Tuberculosis ; Multivariate Analysis ; Prevalence ; Surveys and Questionnaires ; Republic of Korea ; Risk Factors ; Skin Tests ; Tertiary Care Centers ; Thorax ; Tuberculin ; Tuberculin Test ; Tuberculosis