Comparison of Real-World Outcomes of Infliximab versus Adalimumab in Biologic-Naïve Korean Patients with Ulcerative Colitis: A Population-Based Study

PURPOSE: Data on the comparative effectiveness of infliximab (IFX) or adalimumab (ADA) in patients with ulcerative colitis (UC) are extremely limited, especially in the Asian population. We compared clinically important outcomes [colectomy, UC-related emergency room (ER) visits, UC-related hospitalizations, and need for corticosteroids] for these two biologics in biologic-naïve Korean patients with UC. MATERIALS AND METHODS: Using National Health Insurance claims, we collected data on patients who were diagnosed with UC and exposed to IFX or ADA between 2010 and 2016. RESULTS: A total of 862 new users of biologics were included, of whom 630 were treated with IFX and 232 were treated with ADA. Over a median follow-up of 1.8 years after starting biologic therapy, there were no significant differences in the risk of colectomy [adjusted hazard ratio (aHR), 1.87; 95% confidence interval (CI), 0.30-11.63], ER visits (aHR, 1.58; 95% CI, 0.79-3.16), hospitalizations (aHR, 0.83; 95% CI, 0.59-1.17), and corticosteroid use (aHR, 1.16; 95% CI, 0.76-1.78) between IFX and ADA users. These results were stable even when only patients who used biologics for ≥6 months were analyzed. Additionally, these results were unchanged in patients treated with biologic monotherapy or combination therapy with immunomodulators. CONCLUSION: In this nationwide population-based study, there was no significant difference in the risk of colectomy, ER visits, hospitalizations, and corticosteroid use between IFX and ADA users. Our findings indicate that IFX and ADA have comparable effectiveness in biologic-naïve Korean patients with UC.ope

Association between Pulse Pressure and Onset of Dementia in an Elderly Korean Population: A Cohort Study

Objective: There is paucity of studies on the association between pulse pressure and the development of dementia, although this association has already been established. This study aimed at investigating the association between pulse pressure and the onset of dementia. Methods: We used the South Korean National Health Insurance Service claims cohort data to select 149,663 patients without dementia aged ≥60 years. We calculated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia using Cox proportional hazard models according to a pulse pressure classification (60 years, particularly those on Medicaid and from rural regions, possibly due to their inability to access hypertension and other medical treatment. The establishment of dementia indicators will help to guide future health policies for the prevention of dementia.ope

Collaborative forest management and sustainability of forest-dependent communities in the Republic of Korea

학위논문 (박사) -- 서울대학교 대학원 : 농업생명과학대학 산림과학부(산림환경학전공), 2021. 2. 윤여창.우리나라 산촌은 생태계 보전과 공익 기능 제공을 위해 사회경제적으로 발전되지 못하였고, 이로 인해 산촌주민의 삶은 매우 빈곤해졌으며 산촌의 지속가능성까지 위협받고 있다. 이 연구는 이러한 산촌 문제의 원인이 산림 이용 규제 정책에서 기인한다고 판단하였다. 그러나 산림 이용 규제 완화는 산림 황폐화를 초래하여 산림자원의 지속가능한 이용을 저해할 수 있다. 정부와 산촌주민이 함께 산림을 관리하는 협력적 산림관리는 산촌의 지속가능성을 향상시키는 대안이 될 수 있다. 이에 협력적 산림관리가 지역사회의 사회경제적 이익과 산림생태계의 지속가능성을 동시에 확보할 수 있는지 규명할 필요가 있다. 이 연구는 산촌주민의 생계가 지속가능할 때 산촌의 지속가능성이 달성될 것으로 간주하였다. 이에 산촌주민이 생계를 지속가능하게 유지하기 위해 전략적으로 협력적 산림관리에 참여하는 의사결정 과정에 초점을 맞추었다. 이 연구의 목적은 산촌주민의 협력적 산림관리제도 참여와 생계 전략 선택 간의 관계를 규명하고, 협력적 산림관리제도 참여가 산촌주민의 생계 지속가능성에 미치는 영향을 규명하는 것이다. 이러한 연구 목적을 달성하기 위해 이 연구는 협력적 산림관리제도 중에서 정부와 산촌주민이 함께 국유림을 관리하는 사례로서 국유림 보호협약 및 국유임산물 양여제도를 분석하였다. 이 연구에서는 선행연구 검토를 통해 2개의 연구 가설을 설정하였다. 첫 번째 가설은 협력적 산림관리제도 참여 여부에 따라 산촌주민의 생계 전략 선택이 달라진다는 것이고, 두 번째 가설은 협력적 산림관리제도에 참여하면 산촌주민의 생계가 지속가능하다는 것이다. 이러한 가설을 검정하기 위해 이 연구는 지속가능한 산촌 생계(SRL) 이론 틀과 사회생태계(SES) 이론 틀을 통합하여 협력적 산림관리제도가 산촌주민의 생계에 미치는 영향을 분석하기 위한 분석 틀을 개발하였다. 이 연구는 서울대학교 남부학술림의 고로쇠나무 수액 채취 계약에 참여하여 협력적으로 산림을 관리하고 있는 전라남도 광양과 구례의 마을을 사례지역으로 선정하였다. 이 연구에서는 교차분석, 다항 로짓 모형, 순서화 로짓 모형, 이항 로짓 모형을 이용하여 가설을 검정하였다. 생계 전략 선택에 따른 가구 단위 생계 성과는 가구 소득수준으로 평가하였으며, 마을 단위 생계 성과는 생계 지속가능성으로 평가하였다. 생계 지속가능성은 평균 가구 소득수준을 경제적 지표, 빈곤 가구 비율을 사회적 지표, 임목축적을 생태적 지표로 선정하여 세 지표를 통합하였다. 분석에 필요한 고로쇠나무 수액 채취 계약 현황과 마을 현황 자료는 2015년을 기준으로 남부학술림 직원과 마을 대표에게 조사하였으며, 가구의 특성과 생계 현황 자료는 2015년, 2016년, 2018년, 2019년에 가구 단위 설문조사를 통해 수집하였다. 최종적으로 17개 마을의 257가구로부터 얻은 응답을 분석에 이용하였다. 분석을 통해 이 연구는 다음과 같은 네 가지 연구 결과를 도출하였다. 첫째, 수액 채취 계약에 참여하는 가구는 다각화 전략을 선택하는 비율이 매우 높지만, 참여하지 않는 가구는 다각화 전략을 선택하지 않는 비율이 높게 나타나 제도 참여 여부에 따라 생계 전략에 차이가 있다. 둘째, 가구 대표의 연령이 낮을수록, 가구원 수가 많을수록, 거주기간이 길수록, 마을 조직 수가 많을수록, 이용 가능한 농지면적이 작을수록, 계약 산림까지 거리가 가까울수록, 계약 산림의 생산성이 낮더라도 저지대일수록 가구가 고로쇠나무 수액 채취 계약에 참여하여 생계를 다각화하는 전략을 선택할 확률이 높은 것으로 나타났다. 셋째, 수액 채취 계약에 참여하여 생계 다각화 전략을 선택하는 가구가 계약에 참여하여 임업 집중화 전략을 선택하거나 기타 소득원 의존 전략을 선택하는 가구보다 소득수준이 높은 것으로 나타났다. 넷째, 수액 채취 계약에 참여하는 가구 비율이 높은 마을일수록 가구가 생계 지속가능성이 높은 집단에 속할 확률이 높아지는 것으로 나타났다. 연구 결과에 따르면, 협력적 산림관리제도는 생계자원을 갖지 못한 저소득층에게 소득 창출 기회를 제공하여 빈곤을 완화하는 데 기여하고 있으며, 협력적 산림관리에 참여하여 산림자원을 많이 이용하더라도 생태적 안정성이 떨어지지 않아 산촌주민의 생계를 지속가능하게 하였다. 이 연구는 산촌의 지속가능성에 기여할 수 있는 정책적 시사점을 도출하였다. 산촌의 지속가능성을 높이기 위해서는 협력적 산림관리 비율이 낮은 지역의 협력적 산림관리를 확대하여 더 많은 빈곤층에게 소득 창출 기회를 제공할 필요가 있다. 또한 산촌주민과의 협력을 강화하기 위해서는 임산물 생산성 증대를 위한 산림관리 등 지역사회 수요를 반영한 국유림 관리 및 경영계획을 수립하는 것이 필요하며, 마을 내에서 원주민과 귀촌민 간의 네트워크를 활성화하고 형평성 있는 이익 분배 시스템을 구축하는 것이 필요하다.As policies to conserve forest ecosystem and provide public benefits have negatively impacted social and economic development in mountainous areas in the Republic of Korea, forest-dependent communities were not able to gain opportunities to improve their livelihoods and became more impoverished while facing threats to their sustainability. In this research, it is proven that the poverty in forest-dependent communities is attributed to the regulation of forest utilization. However, the deregulation of forest utilization can potentially lead to forest degradation and unsustainable use of forest resources. Collaborative forest management (CFM), which provides local people with access to national forest resources in return for managing national forests can be an alternative strategy to improve the sustainability of forest-dependent communities. Thus, there is a need to evaluate CFM outcomes to investigate the impact of CFM on social and economic benefits for forest-dependent communities and ecological sustainability. Given that the sustainability of forest-dependent communities is based on the livelihood sustainability of the community members, this study focused on the decision-making process of households participation in the CFM program to ensure livelihood sustainability. This study aims to identify the relationship between households participation in CFM and their choice of livelihood strategy, as well as the impact of households participation in CFM on livelihood sustainability. For these objectives, the State Forest Protection Agreement and Concession of State Forest Products were analyzed as examples of CFM programs where the government cooperates with local people to manage national forests. The study has two hypotheses: First, household participation in CFM is related to their choice of livelihood strategy (H1). Second, household participation in CFM program makes their livelihood more sustainable (H2). To test the two hypotheses, an analytical framework that integrates theoretical frameworks such as the sustainable rural livelihood (SRL) framework and social-ecological system (SES) framework was developed in this study. The study area is located in Gwangyang-si and Gurye-gun, Jeollanam Province around the Southern Seoul National University (SNU) Forests, where local people are given the rights to utilize forest resources by collecting maple sap. To test the hypotheses, statistical analysis using chi-squared test, multinomial logit model, ordered logit model, and binary logit model was conducted. Livelihood outcomes were evaluated by household income level at the household level and livelihood sustainability at the village level, which was measured by integrating economic (average household income level), social (proportion of poor households to total village households), and ecological (average growing stock) indicators. The author collected the basic information on the status of SNU Forest and village resources by interviewing the Southern SNU Forest management officers and village leaders of local communities with access to the forest resources in the Southern SNU Forest. Interviewers trained by the author surveyed household heads using semi-structured questionnaires in 2015, 2016, 2018, and 2019. Data collected from 257 households across 17 villages were used in the analysis. The results of this study can be summarized into four points. First, CFM participating households are more likely to choose diversification strategies than non-CFM participating households. Second, given that human, social, and physical capital and forest resources provided through CFM programs affected a households choice of livelihood strategies, households whose heads are younger and have been residents of the village for a long period of time and larger households are more likely to choose CFM participating diversification strategies. Also, households of villages with more village organizations, less agricultural lands, located at shorter distances away from the Southern SNU Forests, and with easy access to forest resources in lowlands are more likely to choose CFM participating diversification strategies. Third, households who choose CFM participating diversification strategies have a higher probability of belonging to a higher income level than households who choose CFM participating forestry-based strategies or strategies that rely on other income sources such as subsidies and remittances. Lastly, households of villages that have a higher ratio of CFM participating households to the total number of households are more likely to belong to a group with a high level of livelihood sustainability. This study found that CFM programs contributed to poverty reduction and forest conservation by providing poor households with access to national forest resources and opportunities to generate income from non-timber forest products (NTFPs) while ensuring ecological stability and the sustainable use of forest resources. The findings of this study suggested some policy implications to improve the sustainability of forest-dependent communities. The expansion of national forests covered by CFM programs can be considered to help the poor secure their income sources. To foster cooperation with forest-dependent communities in CFM programs, the study suggests that national forest management plans taking into consideration the demands of forest-dependent communities such as NTFP production be established by the government, and stronger networks among new and old villagers and an equitable benefit-sharing system be established in villages.제 1 장 서 론 1 제 1 절 연구 배경과 필요성 1 제 2 절 연구 목적 5 제 3 절 연구 질문 7 제 4 절 연구의 범위 11 제 5 절 연구의 의의 13 제 2 장 이론적 배경 15 제 1 절 협력적 산림관리 15 1. 협력적 산림관리의 개념과 유형 15 2. 우리나라의 협력적 산림관리 20 3. 선행연구의 검토 39 제 2 절 공유자원 관리 거버넌스 이론 43 1. 공유자원의 특성과 자원관리체제 43 2. 공유자원 관리 거버넌스에 관한 이론 틀 45 3. 선행연구의 검토 50 제 3 절 지속가능한 생계 이론 61 1. 지속가능한 생계 61 2. 지속가능한 산촌 생계에 관한 이론 틀 65 3. 선행연구의 검토 69 제 3 장 연구 방법 76 제 1 절 분석 틀 76 1. 연구 가설 76 2. 분석 틀 개발 85 제 2 절 연구대상지 90 1. 연구대상지의 개황 90 2. 연구대상지의 협력적 산림관리제도 92 제 3 절 분석 방법 100 1. 교차분석 100 2. 다항 로짓 모형 101 3. 순서화 로짓 모형 106 4. 이항 로짓 모형 108 제 4 절 자료 수집 115 1. 남부학술림 현황조사 115 2. 마을 단위 설문조사 115 3. 가구 단위 설문조사 117 제 4 장 결과 및 고찰 118 제 1 절 응답 마을과 가구의 특성 118 1. 응답 마을의 특성 118 2. 응답 가구의 특성 120 제 2 절 협력적 산림관리와 생계 전략 간의 관계 122 1. 협력적 산림관리제도 참여에 따른 생계 전략 122 2. 생계 전략 선택에 영향을 미치는 요인 124 3. 소결 138 제 3 절 협력적 산림관리가 생계에 미치는 영향 139 1. 협력적 산림관리제도 참여가 가구소득에 미치는 영향 139 2. 협력적 산림관리제도 참여가 생계 지속가능성에 미치는 영향 144 3. 소결 156 제 4 절 산촌의 지속가능성을 위한 정책 제언 158 1. 종합적인 결과 158 2. 산촌의 지속가능성 제고를 위한 정책 제언 161 3. 소결 168 제 5 장 결 론 169 제 1 절 연구의 결론 169 제 2 절 연구의 한계 171 참 고 문 헌 173 부 록 190 부록 1. 마을조사표 190 부록 2. 가구조사표 204Docto

Genetic Variations of α-Methylacyl-CoA Racemase Are Associated with Sporadic Prostate Cancer Risk in Ethnically Homogenous Koreans

Background. To assess if the variants of (R)-alpha-methyl-CoA racemase (AMACR) gene would be associated with the risk of sporadic prostate cancer in ethnically homogenous Koreans. Materials and Methods. We enrolled 194 patients with prostate cancer and 169 healthy controls. A total of 17 single nucleotide polymorphisms of the AMACR gene were selected. The distribution of each genotype and haplotype was analyzed and their association with the incidence of prostate cancer was evaluated. Further, we detected AMACR expression in tumor with immunohistochemistry and analyzed its association with genotype regarding prostate cancer risk. Results. AG or GG genotype of rs2278008 (E277K) tended to lower prostate cancer risk. The minor G allele was found to be a significant allele that decreased the risk of prostate cancer (adjusted OR, 0.57; 95% CI, 0.35–0.93, value = 0.025). In patients expression AMACR, AG or GG genotype was also significant genotype in terms of prostate cancer risk (adjusted OR, 0.47; 95% CI, 0.26–0.87, value = 0.017). Further, [GGCGG] haplotype consisted of five coding SNPs of rs2278008, rs34677, rs2287939, rs10941112, and rs3195676 which decreased the risk of prostate cancer ( value = 0.047). Conclusions. Genetic variations of AMACR are associated with the risk of sporadic prostate cancer that underwent radical prostatectomy in Koreans.ope

Development of the Korean Healthy Eating Index for adults, based on the Korea National Health and Nutrition Examination Survey

Background/objectives: The objective of this study was to describe the development process of the Korean Healthy Eating Index (KHEI) based on the Korea National Health and Nutrition Examination Survey (KNHANES). Subjects/methods: The components of KHEI were selected based on Dietary Guidelines for Koreans, domestic and overseas dietary quality indices, and results of the analysis of association with chronic diseases. The standards for scoring of KHEI were selected based on the 2015 Dietary Reference Intakes for Koreans (KDRI). The KHEI scores of Korean adults were calculated using a 1-day 24-h recall data in the 2013-2015 KNHANES. Results: The KHEI included eight adequacy components evaluating the proper intake of recommended foods such as fruit, vegetable, and milk and three moderation components evaluating the consumption of food that limit intake such as sodium and saturated fatty acid. In addition, three balance components assessing the balance of energy intake were included. The KHEI score was defined to range from the minimum of 0 point to the maximum of 100 points. Among Korean adults, the total KHEI score was 63.2 out of 100. Gender and age differences were found in the average of total KHEI scores. Women showed higher score than men (61.7 in men and 64.7 in women, respectively). By age group, 20s and 30s showed the lowest scores with 57.4 and 61.1 respectively, and the scores increased with age by peaking at 67.8 in ages 60-69 and slowed down again in ages 70 or over. Conclusions: The KHEI can be useful for establishing and assessing national nutritional policies and in epidemiological studies to assess the relationship between overall dietary quality and chronic diseases. KHEI will need to be continuously updated to reflect changes in dietary guidelines and the KDRI..ope

National Epidemiologic Survey of Thyroid cancer (NEST) in Korea

The Korea Central Cancer Registry conducted the National Epidemiologic Survey of Thyroid cancer (NEST) to investigate changes in the epidemiological and clinical characteristics of thyroid cancer patients between 1999 and 2008. The NEST was designed to collect representative samples of patients with thyroid cancer diagnosed in the years 1999, 2005, and 2008 using a proportionally stratified and systematic random sampling method. Among 42,891 participants diagnosed with thyroid cancer, 5,796 participants were included in the final study population. This survey collected information on diagnostic methods and date, route of diagnosis, prior medical history and history of thyroid-related disease, tumor, lymph node, metastasis and collaborative stage, and treatment. The NEST dataset was also linked to the cause-of-death database from Statistics Korea. The mean age of the study participants was 46.9 years. The ratio of men to women was 1:5.5. In the analysis of the histologic type of cancer, the proportion of papillary thyroid carcinoma showed an increasing trend (p<0.01). In contrast, the proportion of distant metastasis and the mean tumor size of thyroid cancers showed decreasing trends over time (p<0.01, respectively).ope

Association between employment status change and depression in Korean adults

OBJECTIVES: This study investigated the association between employment status and depression. METHODS: Data from the Korea Welfare Panel Study (KOWEPS) collected from 2008 to 2011 were used. A total of 7368 subjects were included in this study after exclusion of subjects with missing data and those who were self-employed or could not work. Depression was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Employment status, age, sex, region, education, marital status, income, head of household, self-rated health, smoking status, drinking habits, and the current year's and the previous year's CES-D scores were included in the model as independent variables. A generalised linear mixed-effects model for longitudinal binary data was used. RESULTS: Compared with those who were permanently employed, individuals who moved from permanent to precarious employment (OR 1.45, 95% CI 1.23 to 1.70) or to unemployment (OR 1.78, 95% CI 1.30 to 2.43) and from precarious employment to unemployment (OR 1.65, 95% CI 1.32 to 2.06) showed a significantly increased the odds of having depression. Continuing precarious employment (OR 1.54, 95% CI 1.30 to 1.83) or unemployment (OR 1.45, 95% CI 1.23 to 1.70) also significantly increased the odds of having depression. These results were particularly identified in men and head of household women. The effects were not significant among non-head of household women. CONCLUSIONS: Precarious employment and unemployment were clearly associated with having depression. In addition, in view of our findings, policy makers should consider sex and head of household status when developing welfare policies. The inequity between precarious jobs and permanent jobs should be tackled.ope

A randomized controlled trial of physical activity, dietary habit, and distress management with the Leadership and Coaching for Health (LEACH) program for disease-free cancer survivors

Background: We aimed to evaluate the potential benefits of the Leadership and Coaching for Health (LEACH) program on physical activity (PA), dietary habits, and distress management in cancer survivors. Methods: We randomly assigned 248 cancer survivors with an allocation ratio of two-to-one to the LEACH program (LP) group, coached by long-term survivors, or the usual care (UC) group. At baseline, 3, 6, and 12 months, we used PA scores, the intake of vegetables and fruits (VF), and the Post Traumatic Growth Inventory (PTGI) as primary outcomes and, for secondary outcomes, the Ten Rules for Highly Effective Health Behavior adhered to and quality of life (QOL), the Hospital Anxiety and Depression Scale (HADS), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Results: For primary outcomes, the two groups did not significantly differ in PA scores or VF intake but differed marginally in PTGI. For secondary outcomes, the LP group showed a significantly greater improvement in the HADS anxiety score, the social functioning score, and the appetite loss and financial difficulties scores of the EORTC QLQ-C30 scales from baseline to 3 months. From baseline to 12 months, the LP group showed a significantly greater decrease in the EORTC QLQ-C30 fatigue score and a significantly greater increase in the number of the Ten Rules for Highly Effective Health Behavior. Conclusion: Our findings indicate that the LEACH program, coached by long-term survivors, can provide effective management of the QOL of cancer survivors but not of their PA or dietary habits. Trial registration: Clinical trial information can be found for the following: NCT01527409 (the date when the trial was registered: February 2012).ope

대사공학적으로 설계된 코리네박테리움 글루타미쿰에서 유당이용 증대와 염색체에서의 유전자 발현을 통한 2'-푸코실락토오스의 안정적 생산

학위논문 (석사)-- 서울대학교 대학원 : 농업생명과학대학 농생명공학부, 2018. 8. 서진호.The ingredient that differentiates human milk with mammalian milk is oligosaccharides. 50 ~ 80% of human milk oligosaccharides (HMOs) are fucosylated. 2'-Fucoyllactose (2'-FL) is the most abundant in fucosyl oligosaccharides. 2'-FL has prebiotic effects on promoting the growth of beneficial bacteria in the intestines, inhibits the growth of pathogenic bacteria, and improves immunity and brain development. Therefore, 2'-FL is getting attention as a key material for infant formula, functional foods, medicines and cosmetics. Corynebacterium glutamicum, which was used in this study, is a Gram-positive bacterium approved as GRAS (Generally Recognized As Safe) and has already been widely used for amino acid production industrially. Previous studies have produced 2'-FL using metabolically engineered C. glutamicum. 2'-FL is synthesized by α-1,2 fucosylation of lactose and GDP-L-fucose. The GDP-L-fucose biosynthetic pathway was introduced into C. glutamicum and lactose was transported into the cells by introducing the lacYA operon. α-1,2 Fucosylation was achieved by expressing codon optimized α-1,2 fucosyltransferase (COfucT2) derived from Helicobacter pylori. Batch fermentation and fed-batch fermentation were carried out, resulting in production of 2'-FL of 0.6 g/L in batch fermentation and 11.5 g/L in fed-batch fermentation. In this study, C. glutamicum was further engineered to enhance the production of 2-FL. The following three strategies were employed. First, some genes were removed so that only necessary genes can be expressed for 2-FL production in order to minimize a metabolic burden on the cell. Among the genes used previously, phosphomannomutase (manB) and GTP-mannose-1-phosphate guanylyltransferase (manC) already exist on the chromosome of C. glutamicum. The two genes were removed from the expression vector and as a result, 0.62 g/L of 2-FL was produced in batch fermentation. Second, in the lacYA operon, only lacY was expressed to improve the utilization of lactose, and 0.93 g/L of 2-FL was produced in batch fermentation. Third, the lactose permease gene (lacY) was expressed with the RBS (Ribosome Binding Site) and tac promoter, resulting in more lactose transport into the cell. As a result, 2'-FL was able to be produced at 1.94 g/L in batch fermentation and this is 3.3 times higher compared with the control strain which is developed in previous studies. Furthermore, the constructed strain was grown in fed-batch fermentation to improve the performance of 2-FL production. 25.5 g/L of 2-FL is produced in fed-batch fermentation, a 2.2 fold enhancement relative to the control strain. Next, the use of antibiotics should be avoided for industrial fermentations. Since 2'-FL is used for foods and medicines, antibiotics-free production of 2-FL could improve consumers' perception and can save the cost of separation and purification of antibiotics. Therefore, to construct a fermentation system that stably produces 2-FL without using antibiotics, the genes necessary for producing 2'-FL were inserted into the chromosome of C. glutamicum. For the chromosomal integration, a double crossover method using the pK19mobsacB vector was used and the IS (Insertion Sequence) element was selected as a site for insertion. It was possible to introduce the genes on the chromosome of C. glutamicum by inserting COfucT2 into the site where ISCg2b is deleted. Then, ISCg2f and ISCg1a were further disrupted to provide a site for the insertion of the 2'-FL biosynthesis related genes, such as gmd and wcaG. As a result, 0.84 g/L of 2'-FL was produced in the batch fermentation without using kanamycin. When the genes (COfucT2, gmd, wcaG) are expressed simultaneously on plasmids and chromosomes, 3.01 g/L of 2-FL could be produced in flask fermentation without using antibiotics. A fermentation system for producing high concentration of 2'-FL without using antibiotics was constructed. This study is expected to provide a technical basis for industrial production of 2'-FL by engineered C. glutamicum.I. INTRODUCTION 1 1. Human milk 1 2. Human milk oligosaccharides (HMOs) 4 3. 2-Fucosyllactose (2-FL) 7 3.1. Structure and functions of 2-FL 7 3.2. 2-FL production method 10 3.3. Biosynthesis of GDP-L-fucose 12 3.4. α-1, 2-fucosyltransferase 15 4. Corynebacterium glutamicum 17 4.1. What is C. glutamicum 17 4.2. 2-FL production in C. glutamicum 19 5. Research objectives 23 II. MATERIALS AND METHODS 24 1. Reagents and Enzymes 24 2. Strains and Plasmids 24 2.1. Strains 24 2.2. Plasmids 25 3. DNA Manipulation and Transformation 38 3.1. Preparation of DNA 38 3.2. Polymerase Chain Reaction (PCR) 38 3.3. Digestion and ligation of DNA 38 3.4. Transformation of E. coli 39 3.5. Electroporation of C. glutamicum 39 4. Genetic manipulation methods 41 4.1. Construction of gene deletion vectors 41 4.2. Construction of gene insertion vectors 43 4.3. Screening of genetically manipulated strain 43 5. Media and Culture conditions 45 5.1. Media 45 5.2. Culture conditions 45 6. Analysis 47 6.1. Dry cell weight 47 6.2. Analysis of fermentation metabolites 47 III. RESULTS AND DISCUSSIONS 48 1. Development of strain with high 2-FL productivity 48 1.1. Finding unnecessarily overexpressed genes 48 1.2. Enhancement of lactose utilization 51 1.2.1. Construction of strain expressing lacY 51 1.2.2. Replacement of lacY promoter into strong promoter with Ribosome-binding site (RBS) 53 2. Development of 2-FL producing gene-inserted strains 59 2.1. Determination of chromosomally integration site 63 2.2. Construction of ISCg2b deleted strain 64 2.3. Construction of COfucT2 inserted strain 69 2.4. Construction of ISCg2f deleted strain 73 2.5. Construction of ISCg1a deleted strain 79 2.6. Construction of gmd-wcaG inserted strain 84 3. Development of strains for trehalose reduction 92 3.1. Construction of treY knock-out strain 96 3.2. Construction of otsA knock-out strain 96 IV. CONCLUSIONS 101 V. REFERENCES 103 국 문 초 록 112Maste

Gaps in health behaviours and use of preventive services between patients with diabetes and the general population: a population-based cross-sectional study

Objectives: Although both the prevalence and treatment rate of diabetes have increased, the degree of adherence to healthy behaviours by patients with diabetes has not yet been comprehensively evaluated. This study examines the differences in health management and mental health status according to diabetes status and awareness of that diagnosis. Methods: This was a cross-sectional study of 14 655 people using data from the Korean National Health and Nutrition Examination Study 2010-2012, which used sampling weights. Multiple logistic regression analyses were used to compare health-risk behaviours, preventive healthcare utilisation and mental health status according to diabetes diagnosis and awareness of the disease. Results: Compared with people without diabetes, people with diabetes had comparably worse smoking status (adjusted OR (aOR) 1.09, 95% CI 0.92 to 1.30), insufficient physical activity (aOR 1.09, 95% CI 0.95 to 1.24) and were less likely to receive cancer screenings and regular health check-ups (aOR 0.75, 95% CI 0.66 to 0.85). Furthermore, compared with people unaware of their diabetes, people aware of their diabetes had lower odds of physical inactivity (aOR 0.66, 95% CI 0.45 to 0.99) and greater odds of receiving colon cancer screening (aOR 1.55, 95% CI 1.17 to 2.05) and influenza vaccination (aOR 1.56, 95% CI 1.15 to 2.11). Conclusions: People with diabetes were no better in terms of health behaviours and preventive healthcare utilisation than those who were without diabetes. Further efforts and political attention to ensure the delivery of quality care for people with diabetes are needed.ope