• Clinical and Experimental Pediatrics
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• v.49 no.7
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• pp.745-750
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• 2006

Purpose : Enteroviruses are the most common cause of aseptic meningitis in patients of all ages. A definite diagnosis of enteroviral meningitis can be established by detection of virus directly in CSF specimens. But this is time-consuming and lacks sensitivity, so polymerase chain reaction(PCR) detecting of viral RNA in patient specimens such as CSF, stool has been demonstrated. But little is known about the influence of sampling time on the results of CSF PCR and stool PCR. We investigated diagnostic utility of PCR of CSF and stool according to sampling time after the onset of symptoms. Methods : PCR results were analyzed according to sampling time for 42 patients diagnosed aseptic meningits in our hospital from $11^{th}$ January to $30^{th}$ August, 2005. Results : The diagnostic yield of the test was higher of CSF specimens obtained ${\leq_-}2$ days after clinical onset(positive PCR results 9/18, 50 percent), compared with CSF collected >2 days after onset(positive PCR results 1/24, 4.2 percent)(P=0.001). Instead, positive PCR results of fecal specimens maintained highly(average 90.5 percent), 10 cases had also positive PCR results even 5-6 days after onset. 10 cases of CSF specimens had positive enterovirus PCR results containing coxsackievirus B5 (n=6), coxsackievirus B3(n=3). 38 cases of stool specimens had positive enterovirus PCR results containing echovirus 18(n=7), echovirus 9(n=3), coxsackievirus B5(n=8), coxsackievirus B3(n=3). 6 cases(coxackie B5) had positive CSF PCR and stool PCR, both. Conclusion : Stool PCR was clinically sensitive for detecting enterovirus during enteroviral meningits and could give a presumptive diagnosis throughout the disease course. A definite diagnosis was obtained by CSF PCR, but its utility was clearly lower for samples obtained >2 days after clinical onset. Therefore, it is recommended that, in addition to performance of CSF PCR, fecal samples obtained from patients with suspected enteroviral meningitis should be tested by PCR, especially when the duration of symptoms is >2 days.

• Journal of Korean Academy of Nursing
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• v.29 no.6
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• pp.1455-1468
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• 1999

The purpose of this study was to investigate the objectives and contents of basic medical sciences at department of nursing in college of nursing, and junior college of nursing, thus ultimately providing the basic data to standardize the curriculum of the basic medical sciences in nursing education. Seventy eight professors who were in charge of teaching basic medical sciences to at 22 colleges of nursing/ department of nursing, and 20 junior colleges of nursing responded to the questionnaires that consisted of the questions regarding objectives and contents, of basic medical sciences. Based on the description of objectives, the description related to nursing, nurse, nursing science was cathegorized as on objective applicable to nursing science, the description related to medicine or clinical medicine as medical model, the description without description related to medicine was cathegorized as knowledge acquisition. The number of schools corresponding to each category were summerized in descending order. The objectives of basic medical sciences were categorized by concepts and number of schools corresponding to the categorized concept. The findings of the study are as follows ; 1. The subjects of basic medical science identified were physiology, anatomy, biochemistry, pathology, microbiology, and pharmacology in most colleges of nursing and junior colleges. Two colleges of nursing/department of nursing (9.1%) and 19 junior colleges of nursing(95%) did not offer biochemistry, 1 college of nursing /department of nursing(5%) did not offer pathology & pharmacology. 2 junior colleges of nursing (10%) did not offer pharmacology, 1 junior college of nursing(5%) did not offer pathology. The other 1 junior college of nursing did not offer microbiology. 2. Objectives of physiology were to acquire knowledge and understanding on human function in both 6 (50%) colleges and 5 junior colleges. Objectives of anatomy were to acquire knowledge on human structure in both 4 (57%) colleges and 2 (50%) junior colleges; knowledge applicable to nursing sciences in both 3 (42.8%) colleges and 2 (50%) junior colleges. Objectives of biochemistry was to obtain knowledge and understanding on biochemistry, and understanding of basic concepts about biochemistry. Objectives of pathology were to obtain knowledge and understanding on pathology in both 4 (57.1%) colleges and 5(62.5%) junior colleges. Objectives of microbiology were to acquire knowledge and understanding on microbiology in both 5(83.8%) colleges and 6(85.7%) junior colleges. Objectives of pharmacology were to acquire knowledge on pharmacology in both 7(100%) colleges and 8(100%) junior colleges. 3. Contents of physiology in 19 (100%) schools were membrane transport, digestion, circulation, nervous system and respiration. In 16(84.2%) were kidney and muscle, that in 13(68.4%) were endocrine physiology. In 11(57.9%) were introduction and that in 9(47.4%) were structure and function of cells. Contents of anatomy in 11(100%) schools were skeletal system, muscle system, digestive system, circulatory system, concepts regarding human structure. In 10(90.9%) schools were endocrine system and nervous system, and in 5(45.5%) schools were blood, urinary system and cell. Contents of biochemistry in 6(100%) schools were history of biochemistry, body regulating factor, bioenergy, health and nutrition, nutrition of cell, energy production system. In 5(83.3%) schools were metabolism of protein and carbohydrate and enzyme, and in 3(50%) schools were metabolism of energy and fat. Contents of microbiology in 13(100%) schools were environment and influenc of bacteria, virus, G(-) rods, purulent cocci, G(+) rods. In 10 (76.9%) were immunity, diphtheria, enterobacteria, and in 9(69.2%) were spirochete, rickettsia and clamydia, and that in 6(46.2%) were sterilization and disinfection. Contents of pathology in 14(100%) schools were cell injury and adaptation, inflammation, respiratory diseases, circulatory diseases. In 10(71.4%) were neurological disorders, in 8(57.1%) were immunity and disease, and in 7 (50%) were tumor and progressive changes. Contents of pharmacology in 15(100%) were cardivascular drugs, introduction to pharmacology, hypnotics, analgesics, local anesthetics, an ticonvulsants. In 12(80%) were drugs activity on sympathetic and parasympathetic nervous system, and in 11(73%) were sulfa drugs, antibiotics, drug abuse and addiction.

• Korean Journal of Microbiology
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• v.44 no.1
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• pp.14-21
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• 2008

Bovine blood, cell, tissue, and organ are used as raw materials for manufacturing biopharmaceuticals, tissue engineered products, and cell therapy. Manufacturing processes for the biologicals using bovine materials have the risk of viral contamination. Therefore viral validation is, essential in ensuring the safety of the products. Bovine herpesvirus type 1 (BHV-1) is the most common bovine pathogen found in bovine blood, cell, tissue, and organ. In order to establish the validation system for the BHV-1 safety of the products, a real-time PCR method was developed for quantitative detection of BHV-1 in raw materials, manufacturing processes, and final products as well as BHV-1 clearance validation. Specific primers for amplification of BHV-1 DNA was selected, and BHV-1 DNA was quantified by use of SYBR Green I. The sensitivity of the assay was calculated to be $2\;TCID_{50}/ml$. The real-time PCR method was validated to be reproducible and very specific to BHV-1. The established real-time PCR assay was successfully applied to the validation of Chinese hamster ovary (CHO) cell artificially infected with BHV-1. BHV-1 DNA could be quantified in CHO cell as well as culture supernatant. Also the real-time PCR assay could detect $10\;TCID_{50}/ml$ of BHV-1 artificially contaminated in bovine collagen. The overall results indicated that this rapid, specific, sensitive, and robust assay can be reliably used for quantitative detection of BHV-1 contamination during the manufacture of biologics.

• Clinical and Experimental Pediatrics
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• v.51 no.11
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• pp.1165-1171
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• 2008

Purpose : This study aimed to identify the true extent of non-responsiveness in full-term infants born from HBsAg-negative or HBsAg-positive mothers and vaccinated against hepatitis B virus (HBV) at 0, 1, and 6 months of age and to evaluate the effect of revaccination among non-responders. Methods : The study included 716 full-term infants born in 2004-2007. Of 716, 662 infants (A group) were born to HBsAg-negative mothers and 54 infants (B group: 50, except HBsAg-positive infants) were born to HBsAg-positive mothers. All infants were administered DNA recombinant vaccines at 0, 1, and 6 months of age. B group infants received hepatitis B immunoglobulin at birth. Anti-HBs titers were tested at 7-12 and 9-15 months in A and B groups, respectively. Three revaccination doses were administered to non-responders whose anti-HBs titers were under 10 mIU/ml; revaccinated infants were retested at 1-3 months after last vaccination. The association between HBeAg seropositivity of mother and the failure of HBV immunoprophylaxis was evaluated. Results : The seroconversion rates after primary hepatitis B vaccination were higher in A group (94.1%) than in B group (78%, P<0.001). The seroconversion rates were high in revaccinated infants (A group non-responders: 96.9%, B group non-responders: 87.5%). The failure of HBV immunoprophylaxis was significantly associated with maternal HBeAg seropositivity (P<0.001). Conclusion : The seroconversion rates after primary hepatitis B vaccination were low in B group infants. Revaccination of non-responders in B group was very effective. Therefore, anti-HBs testing and revaccination of B group is very important. Revaccination of non-responders in A group was also very effective. Thus, testing the immune status of infants born to HBsAg-negative mothers even after primary hepatitis B vaccination should be considered. However, to realize this, further studies on the cost-effectiveness of anti-HBs testing in healthy full-term infants are necessary.

• Journal of Veterinary Clinics
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• v.23 no.2
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• pp.105-110
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• 2006

A three-layer, feed-forward artificial neural network (ANN) with sixteen input neurons, three hidden neurons, and one output neuron was developed to identify the presence of infectious bronchitis (IB) infection as early as possible in laying hen flocks. Retrospective data from flocks that enrolled IB surveillance program between May 2003 and November 2005 were used to build the ANN. Data set of 86 flocks was divided randomly into two sets: 77 cases for training set and 9 cases for testing set. Input factors were 16 epidemiological findings including characteristics of the layer house, management practice, flock size, and the output was either presence or absence of IB. ANN was trained using training set with a back-propagation algorithm and test set was used to determine the network's capability to predict outcomes that it has never seen. Diagnostic performance of the trained network was evaluated by constructing receiver operating characteristic (ROC) curve with the area under the curve (AUC), which were also used to determine the best positivity criterion for the model. Several different ANNs with different structures were created. The best-fitted trained network, IBV_D1, was able to predict IB in 73 cases out of 77 (diagnostic accuracy 94.8%) in the training set. Sensitivity and specificity of the trained neural network was 95.5% (42/44, 95% CI, 84.5-99.4) and 93.9% (31/33, 95% CI, 79.8-99.3), respectively. For testing set, AVC of the ROC curve for the IBV_D1 network was 0.948 (SE=0.086, 95% CI 0.592-0.961) in recognizing IB infection status accurately. At a criterion of 0.7149, the diagnostic accuracy was the highest with a 88.9% with the highest sensitivity of 100%. With this value of sensitivity and specificity together with assumed 44% of IB prevalence, IBV_D1 network showed a PPV of 80% and an NPV of 100%. Based on these findings, the authors conclude that neural network can be successfully applied to the development of a screening model for identifying IB infection in laying hen flocks.

• The Korean Society of Law and Medicine
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• v.21 no.1
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• pp.223-259
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• 2020

With COVID-19 spreading rapidly around the world, research and development issues on treatments and vaccines for the virus are of high interest. Among them, Remdesivir was the first to show noticeable therapeutic effects and began clinical trials, with each country authorizing the use of the drug through emergency approval. However, Gilead Co., Ltd., the developer of Remdesivir, received a lot of criticism from civic groups for submitting the application for the marketing authorization as an orphan drug. This is because when a new drug got a marketing authorization as an orphan drug could be granted an exclusive status for seven year. The long-term exclusive status of an orphan drug comes from the policy purpose of motivating pharmaceutical companies to develop treatment opportunities for patients suffering from rare diseases, which was not appropriate to apply to infectious disease treatments. This paper provides a review of the problems and improvement directions of the domestic system through comparative legal consideration against the United States, Europe and Japan for the statutes which give exclusive status to medicines. The domestic system has a fundamental problem that it does not have explicit provisions in the statute in the manner of granting exclusive status, and that it uses the review system to give it exclusive status indirectly. In addition, in the case of orphan drugs, the "Rare Diseases Management Act" and the "Regulations on Examination of Items Permission and Reporting of Drugs" provide overlapping review periods, and despite the relatively long monopoly period, there seems to be no check clause to recover exclusive status in the event of a change in circumstances. Given that biopharmaceuticals are difficult to obtain patents, the lack of such provisions is a pity of domestic legislation, although granting exclusive rights may be a great motivation to induce drug development. In the United States, given that the first biosimilar also has a one-year monopoly period, it can be interpreted that domestic legislation is quite strictly limited to granting exclusive status to biopharmaceuticals. The need for improvement of the domestic system will be recognized in that it could undermine local pharmaceutical companies' willingness to develop biopharmaceuticals in the future, and in that it is also necessary to harmonize international regulations. Taking advantage of the emergence of COVID-19 as an opportunity, we look again at the problems of the domestic system that grants exclusive rights to medicines and hope that an overall revision of the relevant legislation will be made to establish a unified legal basis.

• Journal of Plant Biotechnology
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• v.43 no.3
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• pp.261-271
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• 2016

Citrus is an economically important fruit crop widely growing worldwide. However, citrus production largely depends on natural hybrid selection and bud sport mutation. Unique botanical features including long juvenility, polyembryony, and QTL that controls major agronomic traits can hinder the development of superior variety by conventional breeding. Diverse factors including drastic changes of citrus production environment due to global warming and changes in market trends require systematic molecular breeding program for early selection of elite candidates with target traits, sustainable production of high quality fruits, cultivar diversification, and cost-effective breeding. Since the construction of the first genetic linkage map using isozymes, citrus scientists have constructed linkage maps using various DNA-based markers and developed molecular markers related to biotic and abiotic stresses, polyembryony, fruit coloration, seedlessness, male sterility, acidless, morphology, fruit quality, seed number, yield, early fruit setting traits, and QTL mapping on genetic maps. Genes closely related to CTV resistance and flesh color have been cloned. SSR markers for identifying zygotic and nucellar individuals will contribute to cost-effective breeding. The two high quality citrus reference genomes recently released are being efficiently used for genomics-based molecular breeding such as construction of reference linkage/physical maps and comparative genome mapping. In the near future, the development of DNA molecular markers tightly linked to various agronomic traits and the cloning of useful and/or variant genes will be accelerated through comparative genome analysis using citrus core collection and genome-wide approaches such as genotyping-by-sequencing and genome wide association study.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.2
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• pp.183-193
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• 2009

Purpose: Rotaviruses, noroviruses, astroviruses, and enteric adenoviruses cause acute gastroenteritis (AGE) in children. Some children with AGE have afebrile convulsions associated with viral gastroenteritis. The purpose of this study was to detect and genotype viruses from children with AGE or benign infantile seizures associated with mild gastroenteritis (BIS-MG). Methods: Between August 2004 and June 2005, 311 children with AGE were included. Four viral agents, including rotavirus, norovirus, astrovirus, and adenovirus, were analyzed from stool specimens of each patient using the latex agglutination method, enzyme immunoassay, and reverse transcriptase polymerase chain reaction. Genotyping of each virus was performed in 217 of the 311 children. Results: Among 217 children (male, 121; female, 96; mean age, 20.6${\pm}$15.4 months), rotavirus was detected in 109 (50.2%), norovirus in 28 (12.9%), adenovirus in 13 (6.0%), and astrovirus in 2 children (0.9%). Genotyping of rotavirus revealed positive results in 97 children; P[8]G3 in 36, P[4]G2 in 21, P[6]G4 in 10, P[4]G4 in 9, P[8]G9 in 6, P[8]G1 in 6, P[4]G3 in 4, P[4]G9 in 3, and P[6]G2 in 2. Genotyping of norovirus showed GII-4 in 27 of 28 children and GII-6 in 1 child. Sixteen children were diagnosed with BIS-MG. Rotavirus was detected in 13 of 16 children with BIS-MG, and norovirus in 2 children. Genotyping of rotavirus detected in children with BIS-MG revealed P[8]G3 in 6 children, P[4]G2 in 2 children, and P[4]G9 in 1 child. Conclusion: Analysis of viruses from stool specimens indicates that both rotavirus and norovirus are the main viruses related to BIS-MG in children.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.2
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• pp.199-206
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• 2009

Purpose: To analyze the clinical spectrum of posttransplantation lymphoproliferative disorder (PTLD) after liver transplantation in children. Methods: From January 1988 to June 2009, we retrospectively reviewed the medical records of 8 PTLD cases among 148 pediatric patients underwent liver transplantation. The age at transplantation, time of presentation after transplantation, clinical manifestations, histologic diagnosis, results of EBV (Epstein-Barr virus) assessments, managements and outcomes of PTLD were investigated. Results: The prevalence of PTLD in liver transplant pediatric recipients was 5.4% (8 of 148). The mean age of patients was 25.4${\pm}$21.3 months (range 10 to 67 months). Seven of 8 patients (87.5%) underwent liver transplantation before 1 year of age. The common clinical presentations were persistent fever (8 of 8, 100%) and bloody diarrhea (6 of 8, 75%). PTLD was diagnosed with gastrointestinal endoscopic biopsies in five patients and surgical biopsies in three. Histologic findings showed early lesion in three patients, polymorphic in two, and monomorphic in three. Burkitt lymphoma and lymphoblastic lymphoma were found in two of 3 monomorphic patients. Seven of 8 patients were found with EBV-positive. Eight patients were treated with dose reduction of immunosuppressants and infusion of ganciclovir. Rituximab was added to four patients. PTLD were successfully managed in all patients except one who died of sepsis during chemotherapy. Conclusion: Major risk factor of PTLD was to undergo liver transplantation before 1 year of age. Continuous monitoring for EBV viral load and gastrointestinal endoscopic biopsy may be useful to early detection of PTLD.

• Pediatric Infection and Vaccine
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• v.24 no.1
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• pp.16-22
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• 2017

Purpose: We suspect there is a difference in the clinical manifestations and treatment response to antiviral drugs for influenza A and B. This study was conducted to investigate this difference. Methods: We collected information on pediatric patients, infected with the influenza virus, admitted to Dongguk University Ilsan Hospital from October 2013 to May 2015. We investigated the clinical manifestations of influenza and differences in treatment response to oseltamivir treatment for the two types of influenza. Results: A total of 138 patients were included. The mean age was $3.5{\pm}4.0$ years. When comparing the diseases associated with influenza A and B, croup (19.2% vs. 1.7%, P=0.001) was more common with influenza A infection. Myositis (0% vs. 6.7%, P=0.021) and gastroenteritis (29.5% vs. 46.7%, P=0.038) were more common with influenza B infection. When comparing the total fever duration from the start of oseltamivir administration, patients treated with oseltamivir within 2 days of fever had the shortest duration. Among the patients treated with oseltamivir, the duration of fever, after the start of oseltamivir treatment, for was shorter for influenza A infection than for influenza B infection ($16.0{\pm}19.1$ hours vs. $28.9{\pm}27.9$ hours, P=0.006). Conclusions: There appear to be differences in the accompanying diseases and antiviral medication responses between the two types of influenza. It is important to administer oseltamivir within 2 days of fever.