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.

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

Epidemiological data of Bordetella pertussis infection among adolescents and adults are limited in Korea. Patients (> or = 11 yr of age) with a bothersome cough for less than 30 days were enrolled during a 1-yr period at 22 hospitals in Korea. Nasopharyngeal swabs were collected for polymerase chain reaction (PCR) and for bacteriologic culture. In total, 490 patients were finally enrolled, and 34 (6.9%) patients tested positive for B. pertussis; cough duration (14.0 days [7.0-21.0 days]) and age distribution were diverse. The incidence was the highest in secondary referral hospitals, compared to primary care clinics or tertiary referral hospitals (24/226 [10.6%] vs. 3/88 [3.4%] vs. 7/176 [4.0%], P = 0.012), and the peak incidence was observed in February and August (15.8% and 15.9%), with no confirmed cases between March and June. In the multivariate analysis, post-tussive vomiting was significantly associated with pertussis (odds ratio, 2.508; 95% confidence interval, 1.146-5.486) and secondary referral hospital showed a borderline significance. In conclusion, using a PCR-based method, 6.9% of adolescent and adult patients with an acute cough illness had pertussis infection in an outpatient setting. However, hospital levels and seasonal trends must be taken into account to develop a better strategy for controlling pertussis.
Adolescent ; Adult ; Bordetella pertussis/*genetics ; Child ; DNA, Bacterial/*analysis ; Demography ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; *Polymerase Chain Reaction ; Republic of Korea/epidemiology ; Seasons ; Vomiting/etiology ; Whooping Cough/*epidemiology/microbiology/pathology ; Young Adult

BACKGROUND: Limited data on the incidence and clinical characteristics of adult pertussis infections are available in Korea. METHODS: Thirty-one hospitals and the Korean Centers for Disease Control and Prevention collaborated to investigate the incidence and clinical characteristics of pertussis infections among adults with a bothersome cough in non-outbreak, ordinary outpatient settings. Nasopharyngeal aspirates or nasopharyngeal swabs were collected for polymerase chain reaction (PCR) and culture tests. RESULTS: The study enrolled 934 patients between September 2009 and April 2011. Five patients were diagnosed as confirmed cases, satisfying both clinical and laboratory criteria (five positive PCR and one concurrent positive culture). Among 607 patients with cough duration of at least 2 weeks, 504 satisfied the clinical criteria of the US Centers for Disease Control and Prevention (i.e., probable case). The clinical pertussis cases (i.e., both probable and confirmed cases) had a wide age distribution (45.7+/-15.5 years) and cough duration (median, 30 days; interquartile range, 18.0~50.0 days). In addition, sputum, rhinorrhea, and myalgia were less common and dyspnea was more common in the clinical cases, compared to the others (p=0.037, p=0.006, p=0.005, and p=0.030, respectively). CONCLUSION: The positive rate of pertussis infection may be low in non-outbreak, ordinary clinical settings if a PCR-based method is used. However, further prospective, well-designed, multicenter studies are needed.
Adult ; Age Distribution ; Centers for Disease Control and Prevention (U.S.) ; Cough ; Dyspnea ; Humans ; Incidence ; Outpatients ; Polymerase Chain Reaction ; Sputum ; Whooping Cough

Aortic coarctation is usually diagnosed and repaired in childhood and early adulthood. Survival of a patient with an uncorrected coarctation to more than 70 years of age is extremely unusual, and management strategies for these cases remain controversial. We present a case of a 75-year-old woman who was first diagnosed with aortic coarctation and severe aortic valve stenosis 5 years ago and who underwent a successful one-stage repair involving valve replacement and insertion of an extra-anatomical bypass graft from the ascending to the descending aorta.
Aged ; Aorta, Thoracic ; Aortic Coarctation ; Aortic Valve Stenosis ; Female ; Humans ; Thoracic Surgical Procedures ; Transplants

The present study was carried out to examine the toxicity and target organs of oral cholera vaccine (OCV) after repeated oral administration in Sprague-Dawley rats for 6 weeks (3 administrations, once every 2 weeks). OCV is an inactivated oral cholera vaccine that contains Vibrio cholerae and confers protection against cholera caused by V. cholera serogroups O1 (Inaba and Ogawa serotypes) and O139 (strain 4260B). The animals were orally administered either OCV placebo (negative control) or OCV at a dose equivalent to 240 times the anticipated human dose. Throughout the administration period, no significant change was detected in clinical signs, body weight, food or water consumption, urinalysis results, hematological and clinical biochemistry test results, organ weights, necropsy, or histopathological examination results. Minor changes were found in hematological and clinical biochemistry tests; however, these changes were within normal ranges. The above results suggest that oral administration of OCV in rats did not induce any toxicologically meaningful changes, and the target organs could not be determined. This study was conducted in accordance with the guidelines established by Good Laboratory Practice (2009-183, KFDA, December 22, 2009) and the OECD Principles of Good Laboratory Practice (1997).
Administration, Oral ; Animals ; Biochemistry ; Body Weight ; Cholera ; Drinking ; Humans ; Organ Size ; Rats ; Rats, Sprague-Dawley ; Reference Values ; Urinalysis ; Vibrio cholerae

OBJECTIVE: To determine the 9 month period effect of botulinum toxin A (BoNT-A) injection into the salivary gland in children with neurologic disorders and sialorrhea by qualified parent/caregiver-administered questionnaires. METHOD: A total of 17 patients (age 7.6+/-4.24 years) were enrolled in this study. The degree of sialorrhea was assessed at the baseline, 2 weeks, 1, 2, 4, 6 and 9 months after injection. The Drooling Count (DC) was assessed as an objective measurement. The Drooling Frequency and Severity Scale (DFS) and the Teacher Drooling Scale (TDS) were evaluated as a subjective measurement. BoNT-A (0.5 unit/kg) was injected into each submandibular and parotid gland under ultrasonography-guidance. RESULTS: DC, DFS and TDS showed significant improvement at 2 weeks, 1, 2, 4, 6, and 9 months follow-up (p<0.05). Twelve of 17 cases (70.5%) showed more than 50% reduction in DC from the baseline value. CONCLUSION: Ultrasonography-guided BoNT-A injection into the submandibular and parotid gland was a safe and effective method to treat sialorrhea in children with neurologic disorders.
Botulinum Toxins ; Botulinum Toxins, Type A ; Child ; Follow-Up Studies ; Humans ; Nervous System Diseases ; Parotid Gland ; Salivary Glands ; Sialorrhea ; Sorbitol ; Tyramine

PURPOSE: This study compared the results of rotating-platform high-flexion (RP-F) total knee arthroplasty with low contact stress (LCS) for clinical and radiographical assessment after a short-term period. MATERIALS AND METHODS: 68 total knee arthroplasties using a RP-F and LCS system were analyzed retrospectively. Thirty-five of the 68 were osteoarthritic knees and were followed-up for more than 2 years. The clinical evaluation included range of motion (ROM), Knee Society Knee Score and Function Score (KSKS and KSFS), tailor position and kneeling. The radiographic evaluation included femorotibial angle, position of implants, radiolucent line and position of patella. RESULTS: The postoperative ROM, KSKS, and KSFS improved statistically in both implants. Comparing RP-F with LCS there were statistically no differences in ROM (p=0.863), KSKS (p=0.835), KSFS (p=0.535) and tailor position (p=0.489). There were no significant radiographic differences. CONCLUSIONS: Total knee arthroplasty with RP-F and LCS showed similar clinical and radiographic results; it also showed excellent and predictable results at the short-term follow up. However, in RP-F there was 1 case of early osteolysis, 1 case of patella clunk syndrome and 1 case of painful patella crepitus; therefore, further case studies and follow-up are needed.
Arthroplasty ; Follow-Up Studies ; Knee ; Osteoarthritis ; Osteolysis ; Patella ; Prostheses and Implants ; Range of Motion, Articular ; Retrospective Studies ; Ursidae