The mammalian carboxylesterase 1 (Ces1/CES1) family comprises several enzymes that hydrolyze many xenobiotic chemicals and endogenous lipids. To investigate the pharmacological and physiological roles of Ces1/CES1, we generated Ces1 cluster knockout (Ces1 ^-/- ) mice, and a hepatic human CES1 transgenic model in the Ces1 ^-/- background (TgCES1). Ces1 ^-/- mice displayed profoundly decreased conversion of the anticancer prodrug irinotecan to SN-38 in plasma and tissues. TgCES1 mice exhibited enhanced metabolism of irinotecan to SN-38 in liver and kidney. Ces1 and hCES1 activity increased irinotecan toxicity, likely by enhancing the formation of pharmacodynamically active SN-38. Ces1 ^-/- mice also showed markedly increased capecitabine plasma exposure, which was moderately decreased in TgCES1 mice. Ces1 ^-/- mice were overweight with increased adipose tissue, white adipose tissue inflammation (in males), a higher lipid load in brown adipose tissue, and impaired blood glucose tolerance (in males). These phenotypes were mostly reversed in TgCES1 mice. TgCES1 mice displayed increased triglyceride secretion from liver to plasma, together with higher triglyceride levels in the male liver. These results indicate that the carboxylesterase 1 family plays essential roles in drug and lipid metabolism and detoxification. Ces1 ^-/- and TgCES1 mice will provide excellent tools for further study of the in vivo functions of Ces1/CES1 enzymes.

Objectives: This study evaluated an unsupervised machine learning method, latent Dirichlet allocation (LDA), as a method for identifying subtypes of depression within symptom data. Methods: Data from 18,314 depressed patients were used to create LDA models. The outcomes included future emergency presentations, crisis events, and behavioral problems. One model was chosen for further analysis based upon its potential as a clinically meaningful construct. The associations between patient groups created with the final LDA model and outcomes were tested. These steps were repeated with a commonly-used latent variable model to provide additional context to the LDA results. Results: Five subtypes were identified using the final LDA model. Prior to the outcome analysis, the subtypes were labeled based upon the symptom distributions they produced: psychotic, severe, mild, agitated, and anergic-apathetic. The patient groups largely aligned with the outcome data. For example, the psychotic and severe subgroups were more likely to have emergency presentations (odds ratio [OR] = 1.29; 95% confidence interval [CI], 1.17–1.43 and OR = 1.16; 95% CI, 1.05–1.29, respectively), whereas these outcomes were less likely in the mild subgroup (OR = 0.86; 95% CI, 0.78–0.94). We found that the LDA subtypes were characterized by clusters of unique symptoms. This contrasted with the latent variable model subtypes, which were largely stratified by severity. Conclusions This study suggests that LDA can surface clinically meaningful, qualitative subtypes. Future work could be incorporated into studies concerning the biological bases of depression, thereby contributing to the development of new psychiatric therapeutics.

OBJECTIVES: The aim of this study was to characterize the community health indicators affecting standardized mortality rate of cerebrovascular diseases(CVD) and to identify the relationship between CVD mortality and community health indicators in Gangwon-do. METHODS: The community health indicators included material deprivation index, medical resource, rates of road pavement and local tax. CVD mortality and the material deprivation index were calculated in the registered death data and the 2000 census which were obtained from the Korean National Statistics Office. The community health indicators were measured using 2001 statistical year book of Ganwon-do. Data were analyzed by using Excel 2003, SAS 9.1. CVD mortality and material deprivation index were visualized by Arcview 9.1. RESULTS: CVD mortality varied by region and sex in Gangwon-do. The highest CVD mortality in male and female were noted at Goseong-gun, the lowest CVD mortality in male was at Yangyang-gun as it of female at Pyeongchang-gun. In Taebaek city where material deprivation index was also the highest; in Pyeongchang-gun was the lowest. Also the higher material deprivation index in some regions was the higher CVD mortality was. CVD mortality was not related with community health indicators. CONCLUSIONS: The results showed the regional difference of mortality of CVD among counties and cities in Gangwon-do. It is recommended that other community health indicators besides material deprivation index, road pavement rate, medical resources and local tax affecting CVD mortality need to be considered to improve the preventive strategies.
Censuses ; Female ; Humans ; Male ; Phenothiazines ; Taxes

PURPOSE: The purpose of this study was to identify effects of a strengthening program for the lower back in older women with chronic low back pain. METHODS: The research design was a nonequivalent control group pretest-posttest experiment. The experimental group consisted of 16 older women and the control group, 14, all of whom had experienced low back pain for at least 3 months. The strengthening program for the lower back included lumbar stabilization exercises and education on pain management in daily living. For an 8 week period, exercises were done 3 days a week and on one day education was also given. RESULTS: Pain and disability scores decreased significantly in the experimental group compared to the control group. Flexibility, life satisfaction and lumbar muscle strength scores increased significantly in the experimental group compared to the control group. CONCLUSION: Low back pain and disability can be relieved, and flexibility, muscle strength, and life satisfaction increased through a program to strengthen the lower back. It is suggested that a program to strengthen the lower back would be an effective nursing intervention for older women with low back pain.
Activities of Daily Living ; Aged ; Chronic Disease ; Exercise Therapy ; Female ; Humans ; Low Back Pain/*therapy ; Middle Aged ; Muscle Strength ; Pain Measurement ; Patient Education as Topic ; Patient Satisfaction ; Range of Motion, Articular

PURPOSE: The objective of the study is to describe the experience of health care activities of the menopausal women through phenomenological methodology. METHODS: Seven menopausal women participated in the study. Open in-depth interviews were used to collect data, and data were analyzed by the phenomenological methods suggested by Colaizzi. RESULTS: The data were separated into 4 categories of uncomfortable life due to physical and emotional change, building consistency in daily life through regulating a routine rhythm, recovering normality, recovering stability, and 8 clusters of themes; securing regularity in daily life, securing availability in daily life, regulating through elimination and diminishment, regulating through supplementation, being patient and control self, expressing self, review the context and exchanging views, expending a world through one's faith. CONCLUSION: Participants accepted menopause not as a disease but as a natural course of life and realized that menopausal health problems could be naturally settled in general health care activities in daily life.
Delivery of Health Care ; Female ; Health Behavior* ; Humans ; Menopause

PURPOSE: The purpose of the study was to identify the adaptation process to problem based learning(PBL) among nursing students who have experienced PBL classes for two years. METHOD: Data was collected from 11 nursing students with in-depth interviews and direct observation of their PBL experiences by a researcher who has been a facilitator for PBL class for 3years. Immediately after the interviews all of them were transcribed. It was analyzed by the Ground theory of Corbin and Strauss. RESULTS: A derived core category was 'Acquiring PBL'. 4 stages of the acquiring process were derived and written in time sequence: chaos, confusion, beginning insight, and achievement stage. CONCLUSION: The results will not only expand understanding of the students for the facilitator and school which has adopted PBL but also provide information to develop an orientation program for PBL. Further research on the facilitator's role experiences is recommended.
Students, Nursing/*psychology ; *Problem-Based Learning ; Humans ; Female ; *Education, Nursing ; Adult

PURPOSE: The purpose of the study was to identify the adaptation process to problem based learning(PBL) among nursing students who have experienced PBL classes for two years. METHOD: Data was collected from 11 nursing students with in-depth interviews and direct observation of their PBL experiences by a researcher who has been a facilitator for PBL class for 3years. Immediately after the interviews all of them were transcribed. It was analyzed by the Ground theory of Corbin and Strauss. RESULTS: A derived core category was 'Acquiring PBL'. 4 stages of the acquiring process were derived and written in time sequence: chaos, confusion, beginning insight, and achievement stage. CONCLUSION: The results will not only expand understanding of the students for the facilitator and school which has adopted PBL but also provide information to develop an orientation program for PBL. Further research on the facilitator's role experiences is recommended.
Students, Nursing/*psychology ; *Problem-Based Learning ; Humans ; Female ; *Education, Nursing ; Adult

OBJECTIVETo investigate the importance of the specific structure of L-4F, an apolipoprotein A-1 mimetic, in inhibiting atherosclerosis. The study was designed to compare the effect of L-4F and scramble-4F (SC-4F) in preventing low density lipoprotein (LDL) induced endothelial cell dysfunction. L-4F and SC-4F has the same amino acids but different nucleotide sequence.

METHODSBovine aortic endothelial cells (BAEC) were incubated with single L-4F 10 microg/ml or SC-4F 10 microg/ml, or LDL 6.2 mmol/L in the absence or presence of L-4F 10 microg/ml or SC-4F 10 microg/ml for 24 h and assayed for (1) changes of superoxide anion (O2-*) generation in BAEC by superoxide dismutase (SOD)-inhibitable ferricytochrome C reduction, and (2) the production of nitric oxide (NO) in BAEC by ozone chemiluminescence with VCL3.

RESULTS(1) L-4F and SC-4F themselves had no affect on BAEC O2-* generation. (2) LDL significantly increased O2-* generation in BAEC and LDL-induced O2-* generation was inhibited by pretreatment of LDL with L-4F. However, pretreatment of LDL with SC-4F had no effect on inhibition of LDL-induced O2-* generation. (3) LDL significantly inhibited NO generation in BAEC and pretreatment of LDL with L-4F could inhibit LDL-induced decrease of NO generation, but pretreatment of LDL with SC-4F still inhibited NO generation in BAEC.

CONCLUSIONL-4F can prevent LDL induced endothelial cell dysfunction by maintaining the balance of NO and O2-*, but SC-4F doesn't. It suggests that the specific structure of L-4F may play a crucial role in preventing atherosclerosis and it may provide a new clue for searching a novel approach on prevention and therapeutics of atherosclerosis in the future.

Animals ; Atherosclerosis ; prevention & control ; Cattle ; Cells, Cultured ; Endothelial Cells ; drug effects ; physiology ; Lipoproteins, LDL ; antagonists & inhibitors ; Nitric Oxide ; biosynthesis ; Peptides ; pharmacology ; Superoxides ; metabolism

The purpose of the study was to test the effect of the health promotion program in middle women. The research design was a quasi experimental, nonequivalent control-group pretest-posttest design. The data were collected from February 24 to April 14, 1988. The subjects were midlife women, age 40 to 50 years who reside in Chonju city. The experimental group consisted of 41 subjects and the control group 40 subjects. The instruments used for the study were the Self Efficacy Scale and the Health Promotion Behavior Scale developed by Park(1995). The data was analyzed by SPSS/PC. The study result were as follows: Through the 7 week education program for health promotion, self efficacy and health behavior were effectively changed in middle-aged.
Education ; Female ; Health Behavior ; Health Promotion* ; Humans ; Jeollabuk-do ; Research Design ; Self Efficacy

This study was conducted to develop a theoretical model for the determinants of activities of daily living in Korean rural elderly people. The theoretical model was derived from Lawton's Ecological Model to explain human behavior. The model includes determinant variables for functional status such as age, sex, physical status, cognitive status, physical environment, social environment, and depression. Data for this study was collected from 189 elderly people in a rural district near Chonju City. The data was analyzed with SPSS PC+ 4.1 and LISREL 8. The analysis of the data showed that the first proposed theoretical model did not fit the collected data well. In order to increase the fit of the model to the data, the model was modified by deleting the exogenous variables of sex, physical environment, and social environment. The fit of the modified model to the data was increased and was move suitable. The results of this study show that the determinants of the activities of Korean rural elderly people were age, perceived physical condition, cognitive status, and depressional status. Age has a significant direct and indirect effect on the activities of daily living of rural elderly people. Perceived physical condition has a significant indirect effect through depression on activities of daily living. Cognitive status also has a significant indirect effect through depression of functional status. Depression has a significant direct effect on the functional status. Physical environment and social environment showed reversal relationships to functional status. In conclusion, the results of this study show that personal characteristic factors are more important than environmental characteristic factors for functional status of elderly people. However, the importance of depression to functional status in korean rural elderly people and the reverse relationship between social environment and functional status, reflect Korean specificity. Korean nursing needs to focus more on this Korean specificity in order to develop nursing knowledge and practice appropriate to Korea people.
Activities of Daily Living ; Aged* ; Depression ; Humans ; Jeollabuk-do ; Korea ; Models, Theoretical ; Nursing ; Sensitivity and Specificity ; Social Environment