• Tuberculosis and Respiratory Diseases
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• v.85 no.3
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• pp.264-272
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• 2022

Background: The current conventional drug susceptibility test (DST) for Mycobacterium tuberculosis (Mtb) takes several weeks of incubation to obtain results. As a rapid method, molecular DST requires only a few days to get the results but does not fully cover the phenotypic resistance. A new rapid method based on the ability of viable Mtb bacilli to hydrolyze fluorescein diacetate to free fluorescein with detection of fluorescent mycobacteria by flow cytometric analysis, was recently developed. Methods: To evaluate this cytometric method, we tested 39 clinical isolates which were susceptible or resistant to isoniazid (INH) or rifampin (RIF), or ethambutol (EMB) by phenotypic or molecular DST methods and compared the results. Results: The susceptibility was determined by measuring the viability rate of Mtb and all the isolates which were tested with INH, RIF, and EMB showed susceptibility results concordant with those by the phenotypic solid and liquid media methods. The isolates having no mutations in the molecular DST but resistance in the conventional phenotypic DST were also resistant in this cytometric method. These results suggest that the flow cytometric DST method is faster than conventional agar phenotypic DST and may complement the results of molecular DST. Conclusion: In conclusion, the cytometric method could provide quick and more accurate information that would help clinicians to choose more effective drugs.

• Tuberculosis and Respiratory Diseases
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• v.85 no.3
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• pp.256-263
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• 2022

Background: Mycobacterium tuberculosis (Mtb) is resistant to the β-lactam antibiotics due to a non-classical transpeptidase in the cell wall with β-lactamase activity. A recent study showed that meropenem combined with clavulanate, a β-lactamase inhibitor, was effective in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). However, in Korea, clavulanate can only be used as drugs containing amoxicillin. In this study, we investigated the susceptibility and genetic mutations of drug-resistant Mtb isolates to amoxicillin-clavulanate and meropenem-clavulanate to improve the diagnosis and treatment of drug-resistant TB patients. Methods: The minimum inhibitory concentration (MIC) of amoxicillin-clavulanate and meropenem-clavulanate was examined by resazurin microtiter assay. We used 82 MDR and 40 XDR strains isolated in Korea and two reference laboratory strains. Mutations of drug targets blaC, blaI, ldtA, ldtB, dacB2, and crfA were analyzed by polymerase chain reaction and DNA sequencing. Results: The MIC₉₀ values of amoxicillin/clavulanate and meropenem/clavulanate in drug-resistant Mtb isolates were 64/2.5 and 16/2.5 mg/L, respectively. Gene mutations related to amoxicillin/clavulanate and meropenem/clavulanate resistance could not be identified, but T448G mutation was found in the blaC gene related to β-lactam antibiotics' high susceptibility. Conclusion: Our results provide clinical consideration of β-lactams in treating drug-resistant TB and potential molecular markers of amoxicillin-clavulanate and meropenem-clavulanate susceptibility.

• Tuberculosis and Respiratory Diseases
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• v.86 no.1
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• pp.47-56
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• 2023

Background: There is a global increase in isolation of nontuberculous mycobacteria (NTM). The aim of the study was to analyze longitudinal trends of NTM identification and pattern of antimicrobial susceptibility testing. Methods: NTM recovery rates, distribution of NTM species identification, and antimicrobial susceptibility pattern of NTM at Pusan National University Yangsan Hospital between January 2016 and December 2020 were retrospectively analyzed. Results: A total of 52,456 specimens from 21,264 patients were submitted for mycobacterial culture, of which 2,521 from 1,410 patients were NTM positive over five years (January 2016 to December 2020). NTM isolation showed an increasing trend from 2016 to 2020 (p<0.001, test for trend) mainly caused by Mycobacterium avium complex. The vast majority of M. avium complex were susceptible to key agents clarithromycin and amikacin. For Mycobacterium kansasii, resistance to rifampin and clarithromycin is rare. Amikacin was the most effective drug against Mycobacterium abscessus subspecies abscessus and Mycobacterium subspecies massiliense. Most of M. subspecies massiliense were susceptible to clarithromycin, while the majority of M. abscessus subspecies abscessus were resistant to clarithromycin (p<0.001). Conclusion: There was an increasing trend of NTM isolation in our hospital. Resistance to key drugs was uncommon for most NTM species except for M. abscessus subspecies abscessus against clarithromycin.

• IMMUNE NETWORK
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• v.22 no.6
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• pp.48.1-48.13
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• 2022

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection. Cynomolgus macaques infected with Delta variants showed infectious viruses and viral RNA in the upper (nasal and throat) and lower respiratory (lung) tracts during the acute phase of infection. After 3 days of infection, lesions consistent with diffuse alveolar damage were observed in the lungs. For cellular immune responses, all macaques displayed transient lymphopenia and neutrophilia in the early stages of infection. SARS-CoV-2 Delta variant spike protein-specific IgM, IgG, and IgA levels were significantly increased in the plasma of these animals 14 days after infection. This new NHP Delta variant infection model can be used for comparative analysis of the difference in severity between SARS-CoV-2 variants of concern and may be useful in the efficacy evaluation of vaccines and universal therapeutic drugs for mutations.

• Pediatric Infection and Vaccine
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• v.30 no.3
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• pp.180-187
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• 2023

In Korea, >90% of children and adolescents aged <19 years have been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since 2020. Among confirmed cases of pediatric coronavirus disease 2019 (COVID-19), 40-60% of patients developed neurologic symptoms such as seizures, headache, and encephalitis. Herein, we report the case of a 3-year-old female patient with SARS-CoV-2 infection who presented with seizures and altered consciousness and was diagnosed with COVID-19 encephalitis. The patient recovered after treatment with intravenous immunoglobulin, high-dose steroids, anti-seizure drugs, and an anti-viral agent. She was discharged after regaining the ability to speak words and walk alone on hospital day 39. Complete recovery was observed at the 1-year follow-up. The findings in this case suggest that early detection and active intervention is associated with better outcomes in patients with COVID-19 encephalitis.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.871-881
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• 1996

Objective: In the early short-term therapy of pulmonary tuberculosis, PZA is used for the first two months on 6EHRZ therapy but PZA is not effective in the case of long-tenn use PZA for retreatment in the sensitive relapse or acquired drug resistance for PZA. But in the endemic area as Korea, if we can't use PZA in the retreatment of pulmonary tuberculosis, we can't expect the success for retreatment of pulmonary tuberculosis, therefore we need new drugs substituting for PZA. In these days, 4 - fluoroquinolone derivatives were investigated and only ofloxacin and ciprofloxacin of derivatives were known to be effective but the effectiveness was also not certain because the result was experimental or combined with other bacteriocidal drugs and datas on effectiveness of pulmonary tuberculosis were so little. Therefore these drugs should be use with other two or three strong-acting drugs in the last period of retreatment of pulmonary tuberculosis. The ofloxacin or ciprofloxacin is used in some area in Korea but randomly and needed more study. We did this study for proving the effectiveness of these drugs and establishment of retreatment regimen for pulmonary tuberculosis. Methods: Retrospective cohort study of 83 drug-resistant pulmonary tuberculosis patients at National Masan Tuberculosis Hospital from Jan. 1994 to dec. 1995 was made. All the patients taken medicine for 2nd ami-tuberculosis regimens for the first lime. We separated the patients by two groups.(Group I : OFX+ PTA + CS+PAS + Injection, Group II: PZA + PTA+ CS + PAS + Injection). We compared the difference between two groups and tested the confidence limit about results after treatment by $\chi$2-test and T-test. Results : 1. The age distribution was most frequent in fourth decade(29.2% in Group I, 37.1% in Group II) and the mean age was 43.9 year in Group I, and 39.0 year in Group II, but had no significant difference between two groups. The sex distribution was more frequent in the males(68.8% in Group I, 85.7% in Group II), but had no significant difference. 2. Family history was 29.2% in Group I, 28.6% in Group II, but had no significant difference. 3. In the respect of extent of disease, far-advanced stare was 60.4% in Group I, 74.3% in Group II, but had no significant difference. 4. The side effects for drugs showed in 58.3% in Group I and 65.7% in Group II, and the gastrointestinal trouble showed 25.0% in Group and arthralgia 34.3% in Group II predominantly respectively and had the significant difference(p<0.05). 5. The negative conversion rate on sputum AFB smear was 87.5% in Group I and 80.0% in Group II, but had no significant difference. But the negative conversion rate on sputum AFB culture was 83.3% in Group I and 57.1 % in Group II and had the significant difference(p<0.05). 6. The success rate of treatment was 87.5 % in Group I and 83.3 % in Group II but had no significant difference. Conclusion : In the retreatment of pulmonary tuberculosis, ofloxacin is useful drug for the patients who are not available to use PZA and can be use effectively substituting for PZA.

• Journal of Preventive Medicine and Public Health
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• v.9 no.1
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• pp.109-116
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• 1976

Reorganization of myun health care service is one of the main issues in health care delivery in rural Korea. The fundamenta, concept of the role and function of the myun health subcenter is that it is the basic unit of rural health care service and is to provide comprehensive health care service through the integration of curative and preventive services. The aim of this study is to analyze the patterns of curative activities in the myun health subcenter in terms of the most prevalent types of diseases, necessary diagnostic methods and required equipment, types of treatment, necessary drugs and materials, and finally the cost of curative services. The population on which this study was done was the 1596 patients who visited the two myun health subcenters (Sunwon Myun and Naega Myun) in Kang Wha County, the area of the Yonsei University Community Health Teaching Project, during period from May 1, 1975 to June 10, 1976. For the patient's record in the clinic, problem oriented medical records were used. Decisions regarding the disease classification, the diagnostic methods used and selection of the most appropriate and adequate medical treatment were made by a group of three experienced physicians after reviewing the medical records which had been written by public physicians who were treating patients in the study area. The records were reviewed by resident staff members of the Department of Preventive Medicine, of Yonsei University College of Medicine. A brief summary of results of the study is as follow: 1. 29.9% of the patients who visited the clinics were ages between 0-4. No sex difference was observed among patients less than 20 years of age. However, among patients over 20 years old, females predominated. Thus it is evident that the majority of patients were either children or mothers and grandmothers. 2. The distance from the individual villages to the myun health subcenter was one of important factors in determining the ratio of clinic visits. However, other factors such as the activities of the health workers also affected the rates substantially. 3. The most common 25 diseases comprised 90.2% of all the diseases recorded. Acute respiratory infection (25.5%), Skin (12.7%) , diarrheal diseases (6.8%), neuralgia and back pain (4.9%) and. all other injuries (3.9%) were the five most common diseases. 4. Of all the diseases diagnosed and treated, 9.2% required simple laboratory tests for diagnosis, 6.5% required X-ray examination, and altogether 13.6% required either laboratory test or X-ray examination. 5. Treatment and management of 42.0% of the cases could be accomplished with simple, inexpensive drugs, 12.8% required the use of more expensive drugs (mostly antibiotics) and injections were required in 19.7% of the cases. Minor surgery and referral were necessary in 5% of the cases. 6. The cost for diagnosis and treatment was estimated with a standard which was set by general concensus. The average cost of diagnosis was 144 per case and the cost of treatment was 726 per case, The Total average cost per visit was 870.

• Journal of Life Science
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• v.32 no.5
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• pp.375-390
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• 2022

Influenza viruses are zoonotic respiratory pathogens, and influenza infections have caused a substantial burden on public health systems and the livestock industry. Although currently approved seasonal influenza vaccines have shown potent protection efficacy against antigenically well-matched strains, there are considerable unmet needs for the efficient control of viral infections. Enormous efforts have been made to develop broadly protective universal influenza vaccines to tackle the huge levels of genetic diversity and variability of influenza viruses. In addition, antiviral drugs have been considered important interventions for the treatment of viral infections. The viral neuraminidase inhibitor oseltamivir is the most widely used antiviral medication to treat influenza A and influenza B viruses. However, unsatisfactory clinical outcomes resulting from side effects and the emergence of resistant variants have led to greater attention being paid to plants as a natural resource for anti-influenza drugs. In particular, the recent COVID-19 pandemic has underpinned the need for safe and effective antiviral drugs with a broad spectrum of antiviral activity to prevent the rapid spread of viruses among humans. This review outlines the results of the antiviral activities of various natural products isolated from plants against influenza viruses. Special focus is paid to the virucidal effects and the immune-enhancing effects of antiviral natural products, since the products have broad applications as inactivating agents for the preparation of inactivated vaccines and vaccine adjuvants.

• Information Systems Review
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• v.24 no.1
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• pp.21-37
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• 2022

Drug repositioning, one of the methods of developing new drugs, is a useful way to discover new indications by allowing drugs that have already been approved for use in people to be used for other purposes. Recently, with the development of machine learning technology, the case of analyzing vast amounts of biological information and using it to develop new drugs is increasing. The use of machine learning technology to drug repositioning will help quickly find effective treatments. Currently, the world is having a difficult time due to a new disease caused by coronavirus (COVID-19), a severe acute respiratory syndrome. Drug repositioning that repurposes drugsthat have already been clinically approved could be an alternative to therapeutics to treat COVID-19 patients. This study intends to examine research trends in the field of drug repositioning using machine learning techniques. In Pub Med, a total of 4,821 papers were collected with the keyword 'Drug Repositioning'using the web scraping technique. After data preprocessing, frequency analysis, LDA-based topic modeling, random forest classification analysis, and prediction performance evaluation were performed on 4,419 papers. Associated words were analyzed based on the Word2vec model, and after reducing the PCA dimension, K-Means clustered to generate labels, and then the structured organization of the literature was visualized using the t-SNE algorithm. Hierarchical clustering was applied to the LDA results and visualized as a heat map. This study identified the research topics related to drug repositioning, and presented a method to derive and visualize meaningful topics from a large amount of literature using a machine learning algorithm. It is expected that it will help to be used as basic data for establishing research or development strategies in the field of drug repositioning in the future.

• Asian-Australasian Journal of Animal Sciences
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• v.5 no.3
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• pp.411-418
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• 1992

Recently, onset of bacterial disease, especially infiltration of chronic respiratory diseases have been increasing at high rate. The main cause of these diseases are originated from inappropriate sanitary management and slow progress in introducing system and herd free system, which are the base of productivity improvement in bigger pig management, Methods for the prevention and removal of these diseases, are divided into four categories. The first category includes prevention and removal of infectious diseases by organizing strict animal quarantine, enforcing vaccination, and legal regulation and disposal at the time of outbreak. The second category includes improvement of production systems. This purpose can be achieved by discontinuing the open herd system, which brings on the invasion of foreign pathogens and replacing the system by the closed type of farm. To Continue eradication process step-wisely by performing the all-in all-out system at every pig pen or herd level is also effective for this purpose. The third category includes introduction of herd free system can be achieved by repopulating conventional pigs with SPF pigs. If these means are unrealizable from economic or technical viewpoint, medicated early weaning system is perfomed. This system consists of disinfection of pigsty at pre-postpartum stage, application of drugs to pregnant sows and newborn piglets in accordance with the medication program, and early weaning and rearing of newborn piglets in isolation. The fourth category is sanital leading by veterinarians, aimed to eliminating incentives for diseases through diagnoses. Their main activities include periodical monitoring and improvement leading on each responsible subject.