Genome-Wide Study of Emphysema Progression and Gene-by-Smoking Interaction of Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disease characterized by airflow limitation, an impairment of lung function. Emphysema is a major pathological change of COPD and characterized by the destruction of lung parenchyma. COPD is the third leading cause of death worldwide. The primary environmental risk factor for COPD is cigarette smoking, but individuals vary in their susceptibility to the effects of cigarette smoke and only a minority of smokers will ever develop COPD. This indicates other factors besides smoking are involved in the development and progression of COPD, and these may interact with smoking. This dissertation investigates the genetic determinants of emphysema progression quantified by computed tomography (CT) imaging and studies gene-by-smoking interaction on COPD risk 1) at the genome-wide scale and 2) using a polygenic risk score approach. This dissertation uses data from the COPDGene and ECLIPSE study, a longitudinal cohort of current and former smokers measuring chest CT scan, and the UK Biobank, a large-scale cohort recruiting over 500,000 volunteers throughout the United Kingdom

Transcriptome and translatome profiles of Streptomyces species in different growth phases.

Streptomyces are efficient producers of various bioactive compounds, which are mostly synthesized by their secondary metabolite biosynthetic gene clusters (smBGCs). The smBGCs are tightly controlled by complex regulatory systems at transcriptional and translational levels to effectively utilize precursors that are supplied by primary metabolism. Thus, dynamic changes in gene expression in response to cellular status at both the transcriptional and translational levels should be elucidated to directly reflect protein levels, rapid downstream responses, and cellular energy costs. In this study, RNA-Seq and ribosome profiling were performed for five industrially important Streptomyces species at different growth phases, for the deep sequencing of total mRNA, and only those mRNA fragments that are protected by translating ribosomes, respectively. Herein, 12.0 to 763.8 million raw reads were sufficiently obtained with high quality of more than 80% for the Phred score Q30 and high reproducibility. These data provide a comprehensive understanding of the transcriptional and translational landscape across the Streptomyces species and contribute to facilitating the rational engineering of secondary metabolite production

An Expert Instructor’s Use of Social Congruence, Cognitive Congruence, and Expertise in an Online Case-Based Instructional Design Course

Promoting and sustaining effective discussion—that which contributes to learning—is a skill that eludes many instructors (Darling-Hammond, 2008; Ge, Yamashiro, & Lee, 2000). This study explored the role and strategies of an expert instructor in an online advanced instructional design (ID) course that utilized a case-based learning (CBL) approach. Discussion posts, as well as interview data, were analyzed and coded to explore how the instructor utilized three strategies noted as being critical to students’ learning during problem-centered discussions: social congruence, cognitive congruence, and content expertise (Schmidt & Moust, 1995; Yew & Yong, 2014). Results showed that facilitation choices were made with course goals in mind: modeling the case analysis process and improving students’ ID problem solving. All three strategies were used frequently during discussion facilitation. Strategies tended to be implemented in clusters, with social congruence strategies appearing in every post but four. Implications are discussed for utilizing a combination of these facilitation strategies, in a dynamic manner, within a case-based context

Association between Inflammatory Potential of Diet and Bone-Mineral Density in Korean Postmenopausal Women: Data from Fourth and Fifth Korea National Health and Nutrition Examination Surveys

Post menopause is considered a critical period for bone-mass loss. Impaired bone metabolism during this phase can increase the risk of fractures in old age. Inflammation is a risk factor for bone health, and diet is a potential source of inflammation. However, few studies have examined the association between the dietary inflammatory index (DII®) and bone-mineral density (BMD) in postmenopausal women in Korea. The objective of this study was to determine, by means of a Korean cross-sectional investigation, whether higher DII scores are associated with decreased BMD in postmenopausal women. To that end, the raw data from the fourth and fifth Korea National Health and Nutrition Examination Surveys (KNHANES, 2009–2011) for 2778 postmenopausal women aged over 50 years were analyzed. The subjects’ BMD were measured by dual-energy x-ray absorptiometry, and their DII® scores were calculated from a single 24-h dietary recall. Further, the participants were classified into three groups according to DII® score. Women with more pro-inflammatory diets (i.e., those in the highest tertile of DII®) had significantly lower BMD in the femoral neck as compared with women in the lowest tertile (p for trend \u3c0.05) after adjustment for age, body-mass index (BMI), household income, education status, smoking habits, physical activity, total calcium intake, female-hormone use, age at menopause, and blood vitamin D levels. Multiple logistic regression analyses revealed that the odds ratio (OR) of total femur osteopenia/osteoporosis was higher in women in the highest tertile of DII® than in those in the lowest (OR 1.27, 95% CI 1.00-1.62, p for trend \u3c 0.05). This study established that more pro-inflammatory diets might be associated with lower BMD in postmenopausal Korean women

The Association Between Dietary Inflammatory Index (DII) and Cancer Risk in Korea: A Prospective Cohort Study within the KoGES-HEXA Study

Several epidemiological studies have shown that there are consistently positive associations between dietary inflammatory index (DII (R)) scores and cancer incidence in Western populations. However, few DII-cancer studies have been conducted in East Asian populations. In a large cohort representative of the general Korean population, we investigated whether the DII is associated with overall cancer risk. A total of 163,660 participants (56,781 males and 106,879 females) had evaluable data for analyses. This follow-up study was carried out over the course of 7.9 years. DII scores were calculated based on Semi-Quantitative Food-Frequency Questionnaire (SQ-FFQ) data for 106 food items. Cancers were self-reported based on notification by the participants\u27 medical doctors. Multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). After the follow-up, 1643 incident cases of cancer (520 males and 1123 females) had developed. In a fully adjusted model, women in the highest DII quintile showed a 44% increased risk of getting cancer (HRQ5vsQ1 = 1.44; 95% CI = 1.14-1.82; p-trend = 0.0006), while men showed no apparent association (HRQ5vsQ1 = 0.80; 95% CI = 0.58-1.10). These results indicate that in Korean women, a more pro-inflammatory diet is associated with a higher risk of incident cancer

Positive Association between Dietary Inflammatory Index and the Risk of Osteoporosis: Results from the KoGES_Health Examinee (HEXA) Cohort Study

Previous studies have found that diet’s inflammatory potential is related to various diseases. However, little is known about its relationship with osteoporosis. The aim of this study was to investigate the association between the dietary inflammatory index (DII®) and osteoporosis risk in a large-scale prospective cohort study in Korea. This prospective cohort study included 159,846 participants (men 57,740; women 102,106) from South Korea with a mean follow-up of 7.9 years. The DII was calculated through a validated semi-quantitative FFQ (SQFFQ), and information on osteoporosis was self-reported by the participants. Analyses were performed by using a multivariable Cox proportional hazard model. Higher DII scores were associated with higher osteoporosis risk (HR 1.33; 95% CI 1.12–1.58). In women, a higher DII score indicated a higher risk of osteoporosis (HR 1.33; 95% CI 1.11–1.59). However, a hazards ratio of similar magnitude in men was not significant (HR 1.32; 95% CI 0.64–2.71). Post-menopausal women had higher risks of osteoporosis for higher DII scores (HR 1.33; 95% CI 1.09–1.63), whereas among pre-menopausal women, the relationship was not statistically significant (HR 1.39; 95% CI 0.87–2.21). Also, there was an increase in osteoporosis risk when the DII increased among women participants with irregular physical activity (HR 1.53; 95% CI 1.17–2.01); however, there was no statistically significant increase in osteoporosis risk among women participants with regular physical activity (HR 1.19; 95% CI 0.93–1.52). A more pro-inflammatory diet was significantly associated with higher osteoporosis risk in women. Given the similar magnitude of the hazards ratio, studies with sufficient numbers of men are warranted

Higher Pro-Inflammatory Dietary Score is Associated with Higher Hyperuricemia Risk: Results from the Case-Controlled Korean Genome and Epidemiology Study_Cardiovascular Disease Association Study

In previous studies, the elevated dietary inflammatory index (DII®) scores have been consistently associated with several chronic diseases. However, the relationship with hyperuricemia remains unknown. The aim of this study was to determine if the DII is associated with hyperuricemia risk. The study included 13,701 participants (men 5102; women 8599) in a large-scale cross-sectional study in South Korea. A validated semi-quantitative food frequency questionnaire (SQFFQ) was used to measure dietary intake, and blood samples were obtained to determine hyperuricemia. As the DII score increased, the hyperuricemia risk increased among women (OR 1.35, 95% CI 1.03–1.77, p trend = 0.02). However, no significant results were found for men. Women with lower BMI scores had higher risks of hyperuricemia with higher DII scores (OR 1.62, 95% CI 1.05–2.52, p trend = 0.03). As the DII increased, however, only women who consumed alcohol (“past or current drinkers”) had higher risks of hyperuricemia (OR 1.92, 1.22–3.02, p trend = 0.004). Among the DII components, intake of flavonoids showed a significant association with the hyperuricemia risk in women (OR 0.75, 0.59–0.96, p trend = 0.03). Our results suggest that higher intake of pro-inflammatory diet is significantly associated with higher risk of hyperuricemia among women. These results reinforce the importance of less pro-inflammatory habitual dietary patterns in lowering the risk of hyperuricemia and secondary afflictions such as cardiovascular diseases

Effects of Copy Number Variations on Developmental Aspects of Children With Delayed Development

Objective To determine effects of copy number variations (CNV) on developmental aspects of children suspected of having delayed development. Methods A retrospective chart review was done for 65 children who underwent array-comparative genomic hybridization after visiting physical medicine & rehabilitation department of outpatient clinic with delayed development as chief complaints. Children were evaluated with Denver Developmental Screening Test II (DDST-II), Sequenced Language Scale for Infants (SELSI), or Preschool Receptive-Expressive Language Scale (PRES). A Mann-Whitney U test was conducted to determine statistical differences of developmental quotient (DQ), receptive language quotient (RLQ), and expressive language quotient (ELQ) between children with CNV (CNV(+) group, n=16) and children without CNV (CNV(–) group, n=37). Results Of these subjects, the average age was 35.1 months (mean age, 35.1±24.2 months). Sixteen (30.2%) patients had copy number variations. In the CNV(+) group, 14 children underwent DDST-II. In the CNV(–) group, 29 children underwent DDST-II. Among variables, gross motor scale was significantly (p=0.038) lower in the CNV(+) group compared with the CNV(–) group. In the CNV(+) group, 5 children underwent either SELSI or PRES. In the CNV(–) group, 27 children underwent above language assessment examination. Both RLQ and ELQ were similar between the two groups. Conclusion The gross motor domain in DQ was significantly lower in children with CNV compared to that in children without CNV. This result suggests that additional genetic factors contribute to this variability. Active detection of genomic imbalance could play a vital role when prominent gross motor delay is presented in children with delayed development

Caloric restriction of db/db mice reverts hepatic steatosis and body weight with divergent hepatic metabolism

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver disease and its prevalence is a serious and growing clinical problem. Caloric restriction (CR) is commonly recommended for improvement of obesity-related diseases such as NAFLD. However, the effects of CR on hepatic metabolism remain unknown. We investigated the effects of CR on metabolic dysfunction in the liver of obese diabetic db/db mice. We found that CR of db/db mice reverted insulin resistance, hepatic steatosis, body weight and adiposity to those of db/m mice. H-NMR- and UPLC-QTOF-MS-based metabolite profiling data showed significant metabolic alterations related to lipogenesis, ketogenesis, and inflammation in db/db mice. Moreover, western blot analysis showed that lipogenesis pathway enzymes in the liver of db/db mice were reduced by CR. In addition, CR reversed ketogenesis pathway enzymes and the enhanced autophagy, mitochondrial biogenesis, collagen deposition and endoplasmic reticulum stress in db/db mice. In particular, hepatic inflammation-related proteins including lipocalin-2 in db/db mice were attenuated by CR. Hepatic metabolomic studies yielded multiple pathological mechanisms of NAFLD. Also, these findings showed that CR has a therapeutic effect by attenuating the deleterious effects of obesity and diabetes-induced multiple complications