The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has provided insights for updating current coronavirus disease 2019 (COVID-19) vaccines. We examined the neutralizing activity of Abs induced by a BA.4/5-containing bivalent mRNA vaccine against Omicron subvariants BN.1 and XBB.1.5. We recruited 40 individuals who had received a monovalent COVID-19 booster dose after a primary series of COVID-19 vaccinations and will be vaccinated with a BA.4/5-containing bivalent vaccine. Sera were collected before vaccination, one month after, and three months after a bivalent booster.Neutralizing Ab (nAb) titers were measured against ancestral SARS-CoV-2 and Omicron subvariants BA.5, BN.1, and XBB.1.5. BA.4/5-containing bivalent vaccination significantly boosted nAb levels against both ancestral SARS-CoV-2 and Omicron subvariants. Participants with a history of SARS-CoV-2 infection had higher nAb titers against all examined strains than the infection-naïve group. NAb titers against BN.1 and XBB.1.5 were lower than those against the ancestral SARS-CoV-2 and BA.5 strains. These results suggest that COVID-19 vaccinations specifically targeting emerging Omicron subvariants, such as XBB.1.5, may be required to ensure better protection against SARS-CoV-2 infection, especially in high-risk groups.

Epilepsy is a brain disorder that affects millions of people worldwide and is usually managed using currently available antiepileptic drugs, which result in adverse effects and are ineffective in approximately 20–25% of patients. Thus, there is growing interest in the development of new antiepileptic drugs with fewer side effects. In a previous study, we showed that a Rehmannia glutinosa (RG) water extract has protective effects against electroshock- and pentylenetetrazol (PTZ)-induced seizures, with fewer side effects. In this study, the objective was to identify the RG components that are responsible for its anticonvulsant effects. Initially, a number of RG components (aucubin, acteoside, catalpol, and mannitol) were screened, and the anticonvulsant effects of different doses of catalpol, mannitol, and their combination on electroshock- and chemically (PTZ or strychnine)-induced seizures in mice, were further assessed. Gamma-aminobutyric acid (GABA) receptor binding assay and electroencephalography (EEG) analysis were conducted to identify the potential underlying drug mechanism. Additionally, treated mice were tested using open-field and rotarod tests. Catalpol, mannitol, and their combination increased threshold against electroshock-induced seizures, and decreased the percentage of seizure responses induced by PTZ, a GABA antagonist. GABA receptor binding assay results revealed that catalpol and mannitol are associated with GABA receptor activity, and EEG analysis provided evidence that catalpol and mannitol have anticonvulsant effects against PTZ-induced seizures. In summary, our results indicate that catalpol and mannitol have anticonvulsant properties, and may mediate the protective effects of RG against seizures.

The small GTP-binding protein Rab25 is associated with tumor formation and progression. However, recent studies have shown discordant effects of Rab25 on cancer cell progression depending on cell lineage. In the present study, we elucidate the underlying mechanisms by which Rab25 induces cellular invasion. We demonstrate that Rab25 increases β1 integrin levels and subsequent activation of EGFR and upregulation of VEGF-A expression, leading to increased Snail expression, epithelial-to-mesenchymal transition and cancer cell invasiveness. Strikingly, we identify that Snail mediates Rab25-induced cancer cell invasiveness through fascin expression and that ectopic expression of Rab25 aggravates metastasis of ovarian cancer cells to the lung. We thus demonstrate a novel role of a β1 integrin/EGFR/VEGF-A/Snail signaling cascade in Rab25-induced cancer cell aggressiveness through induction of fascin expression, thus providing novel biomarkers and potential therapeutic targets for Rab25-expressing cancer cells.
Biomarkers ; Cell Lineage ; Ectopic Gene Expression ; GTP-Binding Proteins ; Lung ; Neoplasm Metastasis ; Ovarian Neoplasms ; Snails ; Up-Regulation ; Vascular Endothelial Growth Factor A

OBJECTIVE: To evaluate magnetic resonance imaging (MRI) observer variability to detect ectopic insertion of the pectoralis minor tendon (EIPMT) and to investigate changes in the rotator interval in patients with EIPMT using MRI. MATERIALS AND METHODS: A total of 507 shoulder MRIs (male:female = 259:248; mean age, 55.4 years) were classified into 1) normal type insertion of the pectoralis minor tendon, 2) complete type EIPMT, and 3) partial type EIPMT independently by two radiologists. Inter-observer agreement was calculated using the kappa coefficient. Thickness of the fibrotic scar tissue in the subcoracoid triangle and humeral side axillary recess was measured. MRIs were reviewed by consensus with regard to the grade of fibrotic scar tissue proliferation in the rotator interval. Comparisons were made between normal and EIPMT and between partial and complete type EIPMT. RESULTS: The incidence of EIPMT was 13.4% (complete type, 7.7%; partial type, 5.7%). Inter-observer agreement was substantial (kappa = 0.775). Fibrotic scar tissue in the subcoracoid triangle was thicker, and the grade of fibrotic scar tissue proliferation in the rotator interval was higher in the EIPMT group than those in the control group. No significant difference was observed in the thickness of humeral side axillary recess. The thicknesses of fibrotic scar tissue in the subcoracoid triangle and humeral side axillary recess as well as the grade of fibrotic scar tissue in the rotator interval were not significantly different between complete and partial type EIPMT. CONCLUSION: MRI enabled detection of EIPMT with substantial observer agreement. Patients with EIPMT show a high tendency for fibrotic scar tissue proliferation in the rotator interval.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Rotator Cuff/pathology/*radiography ; Shoulder/pathology/radiography ; Tendons/pathology/*radiography ; Young Adult

BACKGROUND/AIMS: The D-dimer value is a simple blood test used to evaluate venous thromboembolism (VTE). However, due to its low specificity, another test is needed for a definite diagnosis, such as a radiographic test. We evaluate the factors associated with a false positive D-dimer test and propose a new cut-off value for detecting VTE more effectively in Koreans. METHODS: This was a retrospective, observational study. From January 2009 to December 2009, 2,047 patients (988 men, 63 +/- 15 years) had the D-dimer value checked to evaluate VTE. The main outcome of interest was a positive D-dimer test. Odds ratio and 95% confidence intervals were determined using logistic regression analysis. The new D-dimer cut-off was evaluated using receiver operating characteristics (ROC) curves. RESULTS: The result was positive in 1,093 patients (53%), for a false positive percentage for VTE of 95% and a false negative percentage for VTE of 1%. Significant false positive predictors for a positive D-dimer were increasing age, trauma, postoperative, acute infection, tuberculosis, stroke, malignancy, chronic renal failure, acute coronary syndrome, heart failure, and lung disease. The discriminative value of the D-dimer test was assessed using ROC curve analysis. A D-dimer value of 0.68 mg/L on admission was the best cut-off value for predicting the development of VTE with a sensitivity of 95% and specificity of 57%. CONCLUSIONS: Many factors affect the D-dimer value and we must consider these factors before using the D-dimer value to evaluate VTE. A D-dimer value of 0.68 mg/L appears to be a good cut-off value for evaluating VTE more effectively in Koreans.
Acute Coronary Syndrome ; False Positive Reactions ; Fibrin Fibrinogen Degradation Products ; Heart Failure ; Hematologic Tests ; Humans ; Kidney Failure, Chronic ; Logistic Models ; Lung Diseases ; Male ; Odds Ratio ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Stroke ; Tuberculosis ; Venous Thromboembolism

We previously reported that Hydnocarpi Semen (HS) has a wound healing effect on diabetic foot ulcer lesion in mice. In this study, ethylacetate (EtOAc) fraction from HS extract were evaluated for their wound healing activity by using in vitro acute inflammation model. GC and GC/MS analysis shows that the main constituents in EtOAc fraction are chaulmoogric acid, hydnocarpic acid, and gorlic acid. EtOAc fraction activated macrophages to increase the production of TNF-alpha. The fraction also increased the production of TGF-beta and VEGF, which induced fibroblast activation and angiogenesis. These results suggest that the mechanism that the fraction helps to enhance healing of skin wound is possibly associated with the production of TNF-alpha, as well as secretion of VEGF, TGF-beta and HS may have a new bioactive material for the treatment of skin wound.
Animals ; Cytokines ; Diabetic Foot ; Fatty Acids ; Fibroblasts ; Inflammation ; Macrophages ; Mice ; Semen ; Skin ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha ; Ulcer ; Vascular Endothelial Growth Factor A ; Wound Healing

BACKGROUND: It is important to assess the level of consciousness in patients with brain injuries to determine modes of treatment and prognosis. We evaluated the Bispectral Index (BIS) to determine if it could be used as an objective tool for evaluation of the level of consciousness in brain-injured patients. We also compared the BIS values to clinical sedation scales such as the Glasgow Coma Scale (GCS), Richmond Agitation-Sedation Scale (RASS), and the Reaction Level Scale (RLS). METHODS: Thirty eight patients with brain injuries that were admitted to the neurosurgery intensive care unit (NSICU) were enrolled in this study. An investigator evaluated the clinical sedation scales (GCS, RASS, RLS), while a blind observer noted the BIS in the same patient. The BIS score was obtained three times at an interval of 5 hours. The BISs were measured for 1 minute at 5 min prior to the nursing assessment, during the nursing assessment, and at 5 min after the nursing assessment. The BISs used in the data analysis were the maximal, minimal, and mean values obtained during 1 min, which were defined as BISmax, BISmin, and BISmean. A Spearman's rank correlation coefficient was used to determine if the clinical sedation scales were correlated with the BIS scores. RESULTS: In 38 patients, the BISmax, BISmin, and BISmean were found to be significantly correlated with the GCS, RASS, and RLS. The BISmean had the highest correlation with GCS (r = 0.445, P < 0.01), while the BIS min had the lowest correlation with RLS (r = -0.278, P < 0.01). CONCLUSIONS: The results of BIS monitoring were found to be significantly correlated with sedation scales in patients with brain injuries. These findings suggest that BIS can be used as an objective and continuous method for assessment of the level of consciousness in patients with brain injury.
Brain ; Brain Injuries ; Consciousness ; Consciousness Monitors ; Glasgow Coma Scale ; Humans ; Intensive Care Units ; Neurosurgery ; Nursing Assessment ; Prognosis ; Research Personnel ; Statistics as Topic ; Weights and Measures

Non-typhoidal Salmonella (NTS) is an important commensal microorganism. The purpose of this study was to determine the epidemiological relation between NTS isolates from livestock and NTS isolates from human by analyzing antimicrobial susceptibilities and performing molecular typing. We determined the serotypes of 36 human clinical isolates and 64 livestock isolates, performed antimicrobial susceptibility testing against 8 antibiotics, and determined the molecular types of isolated NTS spp. by pulsed field gel electrophoresis (PFGE). In human isolates, S. enteritidis was the most common serotype (17 isolates; 47.2%) and S. typhimurium the second most (8 isolates; 22.2%). In livestock isolates, S. typhimurium was the most common serotype (15 isolates; 23.44%), and S. enteritidis was the second most (14 isolates; 21.88%). Ampicillin and tetracycline resistance were 50% (32/64 isolates) each among broiler-chicken NTS isolates. No human or livestock NTS isolates showed resistance to ciprofloxacin, TMP-SMX, or ceftriaxone. However, 19.4% (7/36) and 46.8% (30/64) of the human and livestock NTS isolates were resistant to nalidixic acid (MIC > or =16 mg/mL), respectively. The presence of the three identical PFGE molecular types from human and broiler-chicken NTS isolates suggests the possibility of transmission from livestock to humans.
Adult ; Animals ; Chickens ; Cluster Analysis ; Drug Resistance, Bacterial ; Female ; Humans ; Korea ; Male ; Nalidixic Acid/pharmacology ; Salmonella Infections/epidemiology/metabolism/*microbiology ; Salmonella Infections, Animal/epidemiology/metabolism/*microbiology ; Salmonella enteritidis/metabolism ; Salmonella typhimurium/*metabolism ; Serotyping

PURPOSE: Many studies have demonstrated that sporadic MSI-H colorectal cancers share several clinicopathological features with hereditary nonpolyposis colorectal cancers. However, microsatellite instability (MSI) in HNPCC and sporadic colorectal cancer occur through two different mechanisms. The aim of this study was to define the clinicopathological significance of MSI in sporadic colorectal cancers. METHODS: Using paraffin-embedded specimens from 291 consecutive sporadic colorectal cancer patients, a total of 5 microsatellite markers (D2S123, D5S346, D17S250, BAT25 and BAT26) were used to evaluate the MSI status. Age, gender, tumor size, site, grade, stage, vascular invasion and CEA level were evaluated. RESULTS: The incidence of MSI-H was 7.9% (23/291) in sporadic colorectal cancer. These were more likely to be right-sided (56.5% vs 17.5%, P<0.05) and poorly differentiated (31.8% vs 5.5%, P<0.05), compared with microsatellite stable cancers. However, there was no significant difference according to gender, tumor size, grade, stage, and vascular invasion. MSI-H cancers had a tendency for an earlier age and lower CEA level but this did not reach statistical significance. CONCLUSION: These results suggest that sporadic MSI-H colorectal cancers are more likely to be right-sided, and poorly differentiated. Although sporadic MSI-H colorectal cancers show MSI as with HNPCC, the carcinogenesis and clinicopathological features are different from those of HNPCC. Additional more study will be needed to further define the role of MSI in the survival and adjuvant chemotherapy of sporadic colorectal cancer.
Carcinogenesis ; Chemotherapy, Adjuvant ; Colorectal Neoplasms* ; Humans ; Incidence ; Microsatellite Instability* ; Microsatellite Repeats*

PURPOSE: The cause of aseptic meningitis remains mostly unknown because viral culture and identification is difficult. Thus, we report a study on 123 children with aseptic meningitis in Gyeongju in 2002 to identify the causing virus and the relationship with the clinical manifestation. METHODS: We prospectively investigated the patients, admitted to Dongguk University Hospital, into two groups between April and October 2002. Group 1 included 123 patients diagnosed as aseptic meningitis. Group 2, the adimssion control, included 120 patients, who suffered from none-enteroviral diseases. Specimens of CSF and stool were collected to perform reverse transcription polymerase chain reaction(RT-PCR), and enteroviral culuture was done in RT-PCR positive patients as well. RESULTS: The male to female sex ratio was 2.2:1 and the mean age was 6.2+/-3.7 years. The clinical manifestations were fever, headache and vomiting. The RT-PCR for enterovirus, performed in 58 cases of CSF in group 1, showed 5.2% positive results and negative result in viral culture. The RT-PCR for enterovirus used in stool specimens showed 89.3% and 41.1% of positive results in group 1 and group 2, respectively. Viral culture of stool specimens showed five cases of echovirus 13 and four cases of echovirus 6 in group 1, whereas three cases of echovirus 6 and one case of coxsackie B4 were detected in group 2. CONCLUSION: The etiologic viruses of the aseptic meningitis outbreak in Gyeongju in 2002 is presumed to be echovirus 13 and echovirus 6. Since echovirus 13 firstly appeared with various age distributions, the outbreak may have emerged due to a lack of acquisition of immunity to this virus.
Age Distribution ; Child ; Echovirus 6, Human ; Enterovirus ; Enterovirus B, Human ; Female ; Fever ; Gyeongsangbuk-do ; Headache ; Humans ; Male ; Meningitis, Aseptic* ; Prospective Studies ; Reverse Transcription ; Sex Ratio ; Vomiting