Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19.

OBJECTIVES: Detailed knowledge on the prevalence of asymptomatic cases of coronavirus disease 2019 (COVID-19) and the clinical characteristics of mild COVID-19 is essential for effective control of the COVID-19 pandemic. We determined the prevalence of asymptomatic cases of COVID-19 and characterized the symptoms of patients with mild COVID-19. METHODS: Study participants were recruited from a community facility designated for the isolation of patients without moderate-to-severe symptoms of COVID-19 in South Korea. The prevalence of asymptomatic patients at admission and the detailed symptoms of mild COVID-19 were evaluated through a questionnaire-based survey. Diagnosis of COVID-19 was confirmed by real-time RT-PCR. RESULTS: Of the 213 individuals with COVID-19, 41 (19.2%) were asymptomatic until admission. Among the remaining patients with mild COVID-19, the most common symptom was cough (40.1%; 69/172), followed by hyposmia (39.5%; 68/172) and sputum (39.5%; 68/172). Of the 68 individuals with hyposmia, 61 (90%) had accompanying symptoms such as hypogeusia, nasal congestion or rhinorrhoea. Fever (>37.5°C) was only observed in 20 (11.6%) individuals. CONCLUSIONS: As much as one-fifth of individuals with COVID-19 remained asymptomatic from exposure to admission. Hyposmia was quite frequent among individuals with mild COVID-19, but fever was not. Social distancing should be strongly implemented to prevent disease transmission from asymptomatic individuals or those with mild and inconspicuous symptoms.

Search for a Dark Matter-Induced Annual Modulation Signal in NaI(Tl) with the COSINE-100 Experiment.

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

First Direct Search for Inelastic Boosted Dark Matter with COSINE-100.

A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.

Effects of resistance training on arterial compliance and plasma endothelin-1 levels in healthy men.

Arterial compliance (AC) is an index of the elasticity of large arteries. Endothelial dysfunction has been reported to result in reduced arterial compliance, which represents increased arterial stiffness. A reduction in AC is elicited by high-intensity resistance training, however the mechanisms are obscure. Because a single bout of resistance exercise causes a transient increase in circulating plasma endothelin-1 in humans, some vasoconstrictors may play a role in the mechanisms. The present study aimed to investigate whether resistance training-induced decrease in AC is associated with changes in circulating vasoconstrictors levels in young men. Young sedentary men were assigned to control (n=5) or training (n=9) groups. The training group performed four-week high-intensity resistance training (weight training exercise; three sessions/week). We measured AC and plasma levels of endothelin-1, angiotensin II, and norepinephrine before and after intervention. Resistance training significantly decreased AC, whereas the changes in plasma levels of neither endothelin-1, nor angiotensin II, nor norepinephrine were significantly different between the control and the training groups. Moreover, we found no significant correlations between changes in circulating plasma levels (endothelin-1, angiotensin II, and norepinephrine) and in the AC. Despite of no alteration of the resting circulating plasma levels (endothelin-1, etc.), we cannot exclude a possibility that the tissue/local concentrations of vasoconstrictors (endothelin-1, etc.) around the vessels might be increased and also involved in a reduction of AC in the training group. Taken together, the present results suggest that circulating vasoconstrictors (endothelin-1, etc.) in plasma are not involved in a reduction in AC by the resistance training.

Background model for the NaI(Tl) crystals in COSINE-100.

The COSINE-100 dark matter search experiment is an array of NaI(Tl) crystal detectors located in the Yangyang Underground Laboratory (Y2L). To understand measured backgrounds in the NaI(Tl) crystals we have performed Monte Carlo simulations using the Geant4 toolkit and developed background models for each crystal that consider contributions from both internal and external sources, including cosmogenic nuclides. The background models are based on comparisons of measurement data with Monte Carlo simulations that are guided by a campaign of material assays and are used to evaluate backgrounds and identify their sources. The average background level for the six crystals (70 kg total mass) that are studied is 3.5 counts/day/keV/kg in the (2-6) keV energy interval. The dominant contributors in this energy region are found to be 210 Pb and 3 H.

Effect of habitual exercise on urinary liver-type fatty acid-binding protein levels in middle-aged and older adults.

The purpose of this study was to examine the effect of habitual exercise on urinary liver-type fatty acid-binding protein (L-FABP), which can reflect the degree of various stresses on renal proximal tubule related to the progression of renal disease, in middle-aged and older adults. Cross-sectional and interventional approaches were used to comprehensively achieve this purpose. In the cross-sectional study, we investigated the relationship between physical activity levels and urinary L-FABP levels in 130 middle-aged and older adults. In the interventional study, subjects (n=31) were divided into two groups: exercise (n=19) and control group (n=12), whereby we examined the effects of 12-week aerobic exercise training on urinary L-FABP levels. The cross-sectional study showed that the urinary L-FABP levels were significantly lower in the higher physical activity group than in the lower physical activity group (P<.05). In the interventional study, 12-week aerobic exercise training significantly decreased urinary L-FABP levels (P<.01). Furthermore, the relative changes in urinary L-FABP levels were significantly correlated with the relative changes in physical activity levels and mean arterial pressure after intervention (r=-.374 and r=.530, respectively). Our results revealed that the urinary L-FABP levels were lower in the higher physical activity individuals, and aerobic exercise training decreased urinary L-FABP levels. These results suggest that habitual exercise appears to be associated with a decrease in the degree of several stresses on renal proximal tubule and to be beneficial for kidney health in middle-aged and older adults.

ASXL1 and DNMT3A mutation in a cytogenetically normal B3 thymoma.

The molecular drivers of thymoma are poorly understood. Outside of the identification of rarely occurring epidermal growth factor receptor and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog mutations via candidate gene sequencing, mutations in common cancer genes have yet to be observed. Only a single thymoma genome sequence has been previously reported, with no mutations in known cancer genes identified. Thus, we attempted to identify somatic driver mutations in a cytogenetically normal thymoma. A stage IVB type B3 thymoma from a 47-year-old male of Asian descent with no history of myasthenia gravis or other autoimmune condition was genomically evaluated. Exome sequencing and low-pass whole-genome sequencing was performed to identify somatic point mutations, copy number changes and structural variants. Mutations in known tumor suppressors DNMT3A (p.G728D) and ASXL1 (p.E657fs), consistent with mutations of known consequence in acute myeloid leukemia, were identified. Contrary to a previous report, this finding suggests the genetic etiology of thymomas may not be fundamentally distinct from other tumor types. Rather, these findings suggest that further sequencing of cytogenetically normal thymoma samples should reveal the specific molecular drivers of thymoma.

Clinical features of subjects with an isolated FEV1 reduction.

BACKGROUND: The clinical significance of an isolated reduction in forced expiratory volume in 1 second (FEV(1); i.e., low FEV(1), but normal forced vital capacity [FVC] and FEV(1)/FVC) has not been established. OBJECTIVE: To examine the clinical features of subjects with an isolated FEV(1) reduction. METHODS: Clinical, spirometry and radiological data were retrospectively collected from 15,192 subjects attending a medical check-up at the Health Promotion Center of the Asan Medical Center, Korea. Predicted spirometry values were calculated from the Korean reference equations, and the lower limit of normal was set at the 5th percentile. Subjects were divided into four groups: isolated FEV(1) reduction, normal (normal FVC, FEV(1) and FEV(1)/FVC), obstructive (low FEV(1)/FVC) and restrictive (low FVC and normal FEV(1)/FVC). The groups were compared in terms of clinical characteristics. RESULTS: Of the 15,192 subjects, 323 (2.1%) had an isolated FEV(1) reduction, 10,591 (69.7%) were normal, 951 obstructive (6.3%) and 3327 (22.0%) restrictive. The isolated FEV(1) reduction group had a higher proportion of subjects with smoking history (63.2% vs. 45.7%), radiology abnormalities (15.5% vs. 4.3%) and history of respiratory disease (8.4% vs. 3.0%) than the normal group (all P < 0.001). CONCLUSION: An isolated FEV(1) reduction suggests abnormal spirometry, and further study is needed to evaluate whether these cases belong to the obstructive or restrictive group.

Different therapeutic responses in chronic obstructive pulmonary disease subgroups.

SETTING: Eleven referring hospitals in South Korea. OBJECTIVE: To compare therapeutic responses in chronic obstructive pulmonary disease (COPD) subgroups, classified by diffusing capacity of the lung for carbon monoxide (DL(CO)) and lung volume. DESIGN: A total of 130 stable male COPD patients were classified into four subgroups according to baseline DL(CO) and residual volume/total lung capacity (RV/TLC) ratio. We compared therapeutic responses to short acting ß(2)-agonist (SABA) and 3-month combined inhalation of long-acting ß(2)-agonist (LABA) and corticosteroid among patients with these subgroups. RESULTS: Among the 130 COPD patients, 41 (31.5%) had normal DL(CO) and RV/TLC, 28 (21.5%) low DL(CO) and normal RV/TLC, 31 (23.8%) normal DL(CO) and high RV/TLC, and 30 (23.1%) low DL(CO) and high RV/TLC. The normal DL(CO)/high RV/TLC subgroup showed a significantly larger flow response (changes in forced expiratory volume in 1 s) to salbutamol than the normal DL(CO)/RV/TLC subgroups, and a larger volume response (changes in forced vital capacity) than the two normal RV/TLC subgroups. The normal DL(CO)/high RV/TLC subgroup also showed significantly larger flow and volume response to 3-month combined inhalation of LABA and corticosteroid than the two normal RV/TLC subgroups. CONCLUSION: COPD subgroups classified by DL(CO) and RV/TLC may have different pulmonary function responses to pharmacological treatment.

Distinguishing tuberculosis from Mycobacterium avium complex disease using an interferon-gamma release assay.

SETTING: The QuantiFERON-TB Gold (QFT-G) test can be used to distinguish between tuberculosis (TB) and non-tuberculous mycobacterial disease, but a high background TB infection rate may pose a problem. Although the QuantiFERON-TB (QFT) test, the first-generation QFT-G test, employs a non-specific PPD antigen, avium sensitin is also used as a stimulating antigen. OBJECTIVE: To evaluate the utility of these two interferon gamma release assays (IGRAs), QFT-G and QFT, and the tuberculin skin test (TST), to differentiate TB from Mycobacterium avium complex (MAC) disease in an intermediate TB burden country. METHODS: We compared the diagnostic performance of these three tests in 38 prospectively enrolled patients with TB and 40 with MAC lung disease. RESULTS: The TST yielded positive results in 70.6% of TB and 47.5% of MAC patients; the proportions were respectively 89.5% and 34.3% for QFT-G and 86.8% and 35.3% for QFT. The three tests were of similar accuracy, sensitivity and specificity in diagnosing TB. CONCLUSION: Our findings indicate that the TST and IGRAs could not discriminate between active TB and MAC disease or latent TB infection in a TB-endemic area.

Three phenotypes of obstructive lung disease in the elderly.

SETTING: Eleven referring hospitals in South Korea. OBJECTIVE: To classify the phenotypes in elderly subjects with obstructive lung disease (OLD). METHODS: We analysed 191 subjects aged ≥ 60 years with chronic respiratory symptoms and either obstructive spirometry or bronchial hyperresponsiveness. Factor analysis was performed using commonly measured variables and revealed four significant variables: 1) the ratio of inspiratory capacity to total lung capacity, 2) the total score on the St George's Respiratory Questionnaire, 3) the volume fraction of the lung less than 950 Hounsfield Unit at full inspiration on volumetric computed tomography and 4) post-bronchodilator forced expiratory volume in 1 second (FEV(1)) changes. We performed a cluster analysis on these four variables. RESULTS: The mean age was 68.5 (± 5.2 SD) years and the mean post-bronchodilator FEV(1) was 52.4% (± 16.5) predicted. Three clusters with the following phenotypes were identified: Cluster 1 included subjects with moderate to severe airflow obstruction and bronchodilator reversibility; Cluster 2 subjects had moderate airflow obstruction without bronchodilator reversibility, and Cluster 3 subjects had severe airflow obstruction without bronchodilator reversibility. CONCLUSIONS: We identified three phenotypes in elderly subjects with OLD. Follow-up studies are needed to explore the clinical significance of each phenotype.

Digestibility and dry matter intake of diets containing alfalfa and kenaf.

Two experiments were conducted to determine the dietary value of pellets containing kenaf (Hibiscus cannabinus cv. 'Everglade 41') hay. Averaged across both experiments, kenaf pellets contained 82.6% kenaf hay, 16.6% liquid molasses, and 0.8% mineral oil. The chemical composition of the kenaf pellet was 12.6% crude protein (CP), 41.2% neutral detergent fiber (NDF), and 14.4% acid detergent fiber (ADF). In Exp. 1 (digestion and N balance trial), 18 lambs (body weight [BW] = 36.4 kg) were blocked by BW. Lambs were randomly assigned within a block to Diet 1 (59.5% corn and 40.5% alfalfa pellet), Diet 2 (59.7% corn, 28.4% alfalfa pellets, and 11.9% kenaf pellets), or Diet 3 (59.6% corn, 16.5% alfalfa pellets, and 23.9% kenaf pellets). Diets were formulated so that CP was the first-limiting nutrient. Each diet was limit-fed at 2.4% of BW. Replacing alfalfa pellets with kenaf pellets tended to decrease (P = 0.10) CP and ADF intakes, but increased (P = 0.01) DM digestibility. Diet had no effect (P = 0.33) on N balance. In Exp. 2 (dry matter [DM] intake trial), 32 lambs (BW = 30.4 kg) were blocked by gender and BW. Within a block, lambs were randomly assigned to one of four diets in a 2 x 2 factorial arrangement. Main effects were hay (bermudagrass or fescue) and supplemental protein source (kenaf or alfalfa pellets). Lambs were housed in individual pens with ad libitum access to the assigned hay. Supplemental protein was fed (185 g of DM) once daily. Hay intake was measured weekly for 8 wk. Lambs consumed more (P = 0.002) fescue than bermudagrass hay (743 vs 621 g/ d). Lambs fed fescue hay gained weight more rapidly (P = 0.001) than lambs fed bermudagrass hay (120 vs 72 g/d). Hay intake and ADG were similar (P = 0.90) for lambs fed alfalfa or kenaf pellets. Kenaf hay mixed with molasses and mineral oil can be formed into a pellet. In the diets used in this experiments, kenaf pellets can replace alfalfa pellets in diets fed to lambs without altering forage intake, gain, or N retention.

Prevalence of antibodies to PPD and lipoarabinomannan of Mycobacterium tuberculosis among patients with an indication of fine needle aspiration biopsy.

Recent increase in the incidence of lung cancer often makes it difficult to differentiate between lung cancer and tuberculosis (TB), due to their radiologic similarities. Fine needle aspiration biopsy (FNAB) has been widely employed for the diagnosis of lung cancer and TB, but the diagnostic accuracy of TB is not high enough. As a rapid screening test for tuberculosis, we evaluated serological tests using Mycobacterium tuberculosis PPD and lipoarabinomannan (LAM) antigens. A total of 95 patients with indication of FNAB cytology from initial CT findings were enrolled. 25 patients had TB, 76 thoracic malignancy, and six (7.9%) of the lung cancer patients also had TB, indicating much higher prevalence of TB in thoracic tumor patients. Antibodies to PPD were elevated in 18 (72.0%) of 25 TB patients and in 22 (31.4%) of 70 patients with thoracic malignancy. In contrast, only 3 (4.7%) of 64 healthy controls aged 40 or above were seropositive to PPD antigen. The prevalence of anti-PPD antibodies in thoracic tumor patients was therefore significantly greater than that amongst the healthy controls (p<0.001, chi-square test). However, no significant difference in the prevalence of anti-LAM antibodies was found between study subjects and controls. This study demonstrates that thoracic tumor patients have significantly elevated antibodies to PPD; therefore, high anti-PPD seroreactivity in thoracic tumor patients should be cautiously interpreted. A longitudinal investigation on seropositive thoracic tumor patients is required to determine the role of the serological test for TB in lung cancer patients.

Antimetastatic efficacy of niosomal pentoxifylline and its combination with activated macrophages in murine B16F10 melanoma model.

The aims of the present study were a) to enhance the effectiveness of antimetastatic agent, Pentoxifylline (PTX) by encapsulation in niosomes and b) to investigate the anticancer activity by combination therapy involving activated macrophages and PTX solution/PTX niosomes. Niosomes were prepared by lipid film hydration method. Particle size distribution revealed bimodal distribution with median vesicle size of 462 nm. The entrapment efficacy of PTX niosomes was found to be 9.64%. A cumulative release of 82.43% from niosomal suspension was observed at the end of 21 hours. Intravenous administration of niosomal PTX (6 mg/kg and 10 mg/kg) resulted in significant reduction in lung nodules in an experimental metastatic B16F10 model suggesting accumulation of PTX in a distant target organ-lung. Light microscopic observations of histologic sections showed a decrease in number of tumor islands in the lung. Macrophages activated by intraperitoneal injection of Iscove's Modified Dulbecco's Medium (IMDM) containing 20% fetal calf serum (FCS) followed by in vitro incubation with muramyl dipeptide (MDP) were more effective in controlling tumor spread than those activated by FCS alone. Combination therapy of activated macrophages and PTX solution/niosomal PTX showed no additive or synergistic effect in controlling tumor spread. Carbon clearance studies revealed that PTX inhibits the phagocytic ability of activated macrophages, thereby resulting in the failure of combination therapy.

In vitro contraction of the canine corpus cavernosum penis by direct perfusion with prolactin or growth hormone.

PURPOSE: It is well established that hyperprolactinemia, most typically seen in prolactinoma patients, causes hypogonadism and impotence. There seems to be a good possibility that hyperprolactinemia causes impotence, at least partially via some intrinsic property of prolactin (PRL), rather than through its suppressive effects on the hypothalamic-pituitary-gonadal testosterone dynamics. In the present investigation, we used an in vitro canine model to attempt to clarify whether direct action of PRL on the corpus cavernosum penis may lead to erectile insufficiency. Growth hormone (GH) and placental lactogen (PL), both having close structural and functional homologies to PRL, were also studied. MATERIALS AND METHODS: Isometric tension measurement with cavernous strips was performed in the presence or absence of 10(-5) to 10(-9) M. PRL, GH, or PL in the perfusion medium. The tension change induced by the test substances was normalized relative to that induced by 120 mEq KCl. RESULTS: Both PRL and GH produced dose-related elevations (p < 0.01) of the cavernous tension, whereas PL and thiol-cleaved PRL in comparable doses were without effect (p > 0.05). When the tension rise produced by 120 mEq KCl was taken as 100%, the maximum contractions produced by PRL and GH were 80% and 110%. The minimum effective concentration was 10(-8) to 10(-7) M. for both PRL and GH. Pretreatment with indomethacin (10(-5) M.), but not tetrodotoxin (10(-5) M., partially suppressed (p < 0.05) the effects of PRL. CONCLUSION: These results suggest that PRL and GH directly and specifically produced contraction of the corpus cavernosum penis, resulting in erectile insufficiency, and that the effect of PRL is partially mediated by prostaglandin.

Genes responsible for nisin synthesis, regulation and immunity form a regulon of two operons and are induced by nisin in Lactoccocus lactis N8.

Nisin is a small post-translationally modified lanthionine-containing peptide (lantibiotic) produced by certain Lactococcus lactis strains which has a high antimicrobial activity against several pathogenic Gram-positive bacteria. Northern blots and RT/PCR analysis of the nisin-producing strain N8 revealed that the nisZBTCIPRKFEG gene cluster, responsible for nisin biosynthesis, immunity and regulation, consists of two operons, nisZBTCIPRK and nisFEG. The promoter of the nisFEB operon was mapped. The -35 to -1 region upstream of the transcription start of the nisFEG promoter showed 73% identity with the corresponding region upstream of the nisA and nisZ gene. In contrast to earlier reports, nisin was found to be secreted during the early stages of growth was well as later in the growth cycle. The secreted nisin was adsorbed on the surface of the cells and was released to the medium during mid-exponential growth, when the pH in the medium fell below 5.5. In nisZB antisense and nisT deletion mutant strains constructed in this study the transcription of the nisin operons, nisin production and immunity were lost. Provision of external nisin restored the transcription of both operons in the mutant strains, showing that the operons are coordinately regulated by mature nisin. Nisin induction of the mutant strains also resulted in an increased amount of the NisI protein and an increase in the level of immunity. Induction using higher concentrations of nisin yielded a higher level of immunity. These results showed that the nisin promoters are under positive control in an autoregulatory manner and that antimicrobial peptides can also function as signal molecules.

Cloning and sequence analysis of the gene encoding 3-hexulose-6-phosphate synthase from the methylotrophic bacterium, Methylomonas aminofaciens 77a, and its expression in Escherichia coli.

A DNA fragment of 550 bp was specifically amplified by PCR with primers based on the N-terminal sequence of the purified 3-hexulose-6-phosphate synthase from Methylomonas aminofaciens 77a and on that of a lysyl endopeptidase-derived peptide. Using this PCR product as a probe, a gene coding for 3-hexulose-6-phosphate synthase in M. aminofaciens 77a chromosomal DNA was cloned in Escherichia coli JM109. Sequencing analysis revealed that the gene encoding 3-hexulose-6-phosphate synthase contained a 624-bp open reading frame, encoding a protein composed of 208 amino acid residues with a calculated relative molecular mass of 21,224.

Use of a 64 channel computerized cardiac mapping system in arrhythmia surgery.

A multipoint and computerized intraoperative mapping system has been known to be of value in improving the results of surgery for cardiac arrhythmia. It shows great potential as a new tool in the surgical intervention of the more common and lethal types of supraventricular tachyarrhythmias such as atrial flutter and atrial fibrillation. In addition, it also enhances the ability of the investigators to map and ablate the sometimes fleeting automatic atrial tachycardia. The authors developed a 64 channel computerized cardiac mapping system using a microcomputer (Macintosh IIx) and this has been used for basic research in cardiac electrophysiology as well as in arrhythmia surgery. In this system, bipolar electrograms are obtained from 64 different cardiac sites simultaneously at a sampling rate of 1 Ksample/sec and with a continuous and total data storage of up to 30 seconds. When the reference electrode is selected, delay time from the reference point is displayed on a two dimensional diagram of the heart. This system was used in one patient who underwent a surgical ablation of a ventricular tachycardia in whom we observed a ventricular activation sequence involving a variety of rhythms over several minutes. The system design permits easy expansion to a simultaneous sampling from 256 sites. This 64-channel mapping appeared to have the potential to be of great help in our understanding of cardiac arrhythmia as well as in its diagnosis and surgical treatment.