Traditional approach of inactivated or live-attenuated vaccine immunization has resulted in impressive success in the reduction and control of infectious disease outbreaks. However, many pathogens remain less amenable to deal with the traditional vaccine strategies, and more appropriate vaccine strategy is in need. Recent discoveries that led to increased understanding of viral molecular biology and genetics has rendered the used of viruses as vaccine platforms and as potential anti-cancer agents. Due to their ability to effectively induce both humoral and cell-mediated immune responses, viral vectors are deemed as an attractive alternative to the traditional platforms to deliver vaccine antigens as well as to specifically target and kill tumor cells. With potential targets ranging from cancers to a vast number of infectious diseases, the benefits resulting from successful application of viral vectors to prevent and treat human diseases can be immense.
Adenoviridae ; Alphavirus ; Communicable Diseases ; Disease Outbreaks ; Genetic Vectors ; Humans ; Immunization ; Molecular Biology ; Poxviridae ; Vaccines

PURPOSE: To understand the meaning of the lived experience with Person under train (PUT) for train or subway operators. METHODS: The study was built on hermeneutic phenomenological themes from individual interviews of present-day train or subway operators in South Korea. Eight participants were selected to participate in the study. All qualitative data were analyzed using the heuristic guides of Van Manen. RESULTS: Four fundamental lifeworld themes and eight sub themes emerged in the findings. The first theme of spatiality had‘the place pressed by the darkness’ and ‘the train drags me there’. The second theme, corporeality had ‘a foreboding fear’, and ‘debris of death that gets stuck in the whole body’. The temporality theme had‘distorted time in chaos’, and ‘memory trapped in time’. Finally the last existential theme of relationality had ‘intrapersonal encounter’ and ‘resentment and guilt’. CONCLUSION: The four existential lifeworld themes provided a framework for in-depth investigation of the operator's “lived experience.” This leads to clear understanding of effects of PUT experience on related individuals. The findings imply that specific active nursing intervention strategies are necessary in order to treat affected train operators, and to prevent further issues in their work and private life.
Hermeneutics ; Heuristics ; Humans ; Korea ; Nursing ; Psychological Trauma ; Qualitative Research ; Railroads

OBJECTIVES: To describe the characteristics of a mumps epidemic in Cheju-do, 1998 and to identify the risk factors associated with mumps infection. METHODS: To estimate attack rate, previously collected data from the Nationally Notifiable Communicable Disease Reporting System and School Health Reporting System, temporarily administered by Division of Education, as well as additional surveillance data were used. In order to identify the clinical characteristics and risk factors associated with mumps, we conducted a questionnaire survey in 17 schools (9 elementary, 4 middle, and 4 high schools) among a population that included healthy students. RESULTS: From March 3 to August 31, 2,195 cases of mumps were identified, and patients under 20 years of age accounted for 2,162 cases (attack rate 13.2, 95% CI 12.6-13.7/1,000). The attack rate for the population under 20 years of age was the highest in Nam county (44.7/1,000), and in the 7-12 years old sub-group(>20.0/1,000). There was no sexual difference. 80.9% and 59.7% of patients presented periauricular and submandibular swelling respectively. Aseptic meningitis was a complication in 2.9% of cases, orchitis in 1.3%, epididymitis in 0.9% and oophoritis in 0.6% respectively. The overall MMR vaccination rate was 59.1% and it decreased in accordance with increasing age. In students aged 10 years old or below, household contact and MMR vaccination status was significantly associated with infection, and only among students with household contact, the risk of one dose MMR(OR=10.22, 95% CI 2.92-35.78) and non-vaccination (OR=11.62, 95% CI 1.96-68.96) was significantly greater when compared with that of two dose vaccination. Among students aged 11 years old or above, household contact history was significantly associated and MMR vaccination status was not associated. CONCLUSIONS: Low vaccination rate and vaccine failure were thought to predispose the population for this large outbreak. To prevent sustained mumps outbreaks, a second MMR vaccination should be encouraged and catch up vaccinations should be given to elderly children who remain susceptible.
Aged ; Child ; Communicable Diseases ; Disease Outbreaks ; Education ; Epididymitis ; Family Characteristics ; Female ; Humans ; Jeju-do* ; Male ; Meningitis, Aseptic ; Mumps* ; Oophoritis ; Orchitis ; Questionnaires ; Risk Factors ; School Health Services ; Vaccination

Disease flare-up after discontinuing epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been considered as a critical issue in lung cancer patients who have experienced radiologic progression after showing initial durable response. This is a case of systemic nocardiosis that occurred after chronic steroid use for radionecrosis from stereotactic radiosurgery. It was initially thought as a disease flare-up after stopping EGFR-TKI.
Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Neoplasms* ; Nocardia Infections* ; Protein-Tyrosine Kinases ; Radiosurgery ; Receptor, Epidermal Growth Factor

The mucosal surfaces are constantly exposed to incoming pathogens which can cause infections that result in severe morbidity and/or mortality. Studies have reported that mucosal immunity is important for providing protection against these pathogens and that mucosal vaccination is effective in preventing local infections. For many years, the sublingual mucosa has been targeted to deliver immunotherapy to treat allergic hypersensitivities. However, the potential of vaccine delivery via sublingual mucosal has received little attention until recently. Recent studies exploring such potential have documented the safety and effectiveness of sublingual immunization, demonstrating the ability of sublingual immunization to induce both systemic and mucosal immune responses against a variety of antigens, including soluble proteins, inter particulate antigens, and live-attenuated viruses. This review will summarize the recent findings that address the promising potential of sublingual immunization in proving protection against various mucosal pathogens.
Hypersensitivity ; Immunity, Mucosal ; Immunization ; Immunotherapy ; Mucous Membrane ; Proteins ; Vaccination ; Vaccines

Influenza virus is one of the major sources of respiratory tract infection. Due to antigenic drift in surface glycoproteins the virus causes annual epidemics with severe morbidity and mortality. Although hemagglutinin (HA) is one of the highly variable surface glycoproteins of the influenza virus, it remains the most attractive target for vaccine development against seasonal influenza infection because antibodies generated against HA provide virus neutralization and subsequent protection against the virus infection. Combination of recombinant adenovirus (rAd) vector-based vaccine and mucosal administration is a promising regimen for safe and effective vaccination against influenza. In this study, we constructed rAd encoding the globular head region of HA from A/Puerto Rico/8/34 virus as vaccine candidate. The rAd vaccine was engineered to express high level of the protein in secreted form. Intranasal or sublingual immunization of mice with the rAd-based vaccine candidates induced significant levels of sustained HA-specific mucosal IgA and IgG. When challenged with lethal dose of homologous virus, the vaccinated mice were completely protected from the infection. The results demonstrate that intranasal or sublingual vaccination with HA-encoding rAd elicits protective immunity against infection with homologous influenza virus. This finding underlines the potential of our recombinant adenovirus-based influenza vaccine candidate for both efficacy and rapid production.
Adenoviridae* ; Administration, Mucosal ; Animals ; Antibodies ; Head* ; Hemagglutinins* ; Immunization* ; Immunoglobulin A ; Immunoglobulin G ; Influenza Vaccines ; Influenza, Human* ; Membrane Glycoproteins ; Mice* ; Mortality ; Orthomyxoviridae* ; Respiratory Tract Infections ; Seasons ; Vaccination ; Viruses

Purpose: Capmatinib, an oral MET kinase inhibitor, has demonstrated its efficacy against non–small cell lung cancer (NSCLC) with MET dysregulation. We investigated its clinical impact in advanced NSCLC with MET exon 14 skipping mutation (METex14) or gene amplification. Materials and Methods: Patients who participated in the screening of a phase II study of capmatinib for advanced NSCLC were enrolled in this study. MET gene copy number (GCN), protein expression, and METex14 were analyzed and the patients’ clinical outcome were retrospectively reviewed. Results: A total of 72 patients were included in this analysis (group A: GCN ≥ 10 or METex14, n=14; group B: others, n=58). Among them, 13 patients were treated with capmatinib (group A, n=8; group B, n=5), and the overall response rate was 50% for group A, and 0% for group B. In all patients, the median overall survival (OS) was 20.2 months (95% confidence interval [CI], 6.9 to not applicable [NA]) for group A, and 11.3 months (95% CI, 8.2 to 20.3) for group B (p=0.457). However, within group A, median OS was 21.5 months (95% CI, 20.8 to NA) for capmatinib-treated, and 7.5 months (95% CI, 3.2 to NA) for capmatinib-untreated patients (p=0.025). Among all capmatinib-untreated patients (n=59), group A showed a trend towards worse OS to group B (median OS, 7.5 months vs. 11.3 months; p=0.123). Conclusion Our data suggest that capmatinib is a new compelling treatment for NSCLC with MET GCN ≥ 10 or METex14 based on the improved survival within these patients.

The number of organs transplanted worldwide is increasing annually. As a result, there is a shortage of available donor organs. This scarcity has led to the progressive broadening of donor organ criteria. The expanded criteria include infections such as bacterial meningitis. A 55-year old male visited our emergency room with cardiac arrest and recovered after cardiopulmonary resuscitation. The cause of the cardiac arrest was bacterial meningitis caused by Streptococcus pneumoniae. While proper antibiotics were applied, the patient met the clinical criteria for brain death. Prophylactic antibiotics were administered to the recipients, and liver and kidney transplantations were done successfully.
Anti-Bacterial Agents ; Brain Death ; Cardiopulmonary Resuscitation ; Donor Selection ; Emergencies ; Heart Arrest ; Humans ; Kidney Transplantation ; Liver ; Male ; Meningitis ; Meningitis, Bacterial ; Organ Transplantation ; Streptococcus ; Streptococcus pneumoniae ; Tissue Donors ; Transplants

The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-kappaB, blocked this lysoPC effect. Indeed, lysoPC induced the NF-kappaB-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-kappaB and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.
Animals ; Benz(a)Anthracenes/pharmacology ; Caffeic Acids/pharmacology ; Cells, Cultured ; Genistein/pharmacology ; Lipoproteins, LDL/metabolism ; Lysophosphatidylcholines/*pharmacology ; Muscle, Smooth, Vascular/cytology/*drug effects/metabolism ; NF-kappa B/antagonists & inhibitors/metabolism ; Oxidative Stress/drug effects ; Phenylethyl Alcohol/analogs & derivatives/pharmacology ; Plasminogen Activator Inhibitor 1/agonists/genetics/*metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Tissue Plasminogen Activator/*metabolism ; Transcription, Genetic/drug effects ; Up-Regulation/drug effects ; Vitamin E/pharmacology

Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor (TNF)-α level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.
Administration, Oral ; Aging ; Animals ; Antibody Formation ; Cholesterol ; Diet ; Diet, High-Fat ; Homicide ; Hyperlipidemias* ; Inflammation ; Lymphocytes ; Mice ; Mice, Obese* ; Physiology ; Reference Values ; Rosuvastatin Calcium ; Rubus* ; Tumor Necrosis Factor-alpha