Effect of alcohol consumption on peripheral blood Alu methylation in Korean men.

Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create a substantial public health problem worldwide. To date, no therapeutic can effectively solve these problems. They are complex diseases characterized by both genetic and environmental factors. DNA methylation can act as a downstream effector of environmental signals and account for multi-factorial nature of the disease. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Alu elements host one-quarter of CpG dinucelotides in the genome to function as proxies for global DNA methylation. In this study, we evaluated the Alu methylation in the peripheral blood DNA of healthy volunteers and AUD patients using the pyrosequencing technology. The Alu methylation level is significantly higher in AUD compared to healthy controls (23.4 ± 1.6 versus 22.1 ± 1.0, t = 7.83, p < 0.0001). Moreover, significant correlation was found between Alu methylation and alcohol use disorders identification test score (r = 0.250, p < 0.0001), alcohol problem (r = 0.294, p < 0.0001), and life position (r = -0.205, p = 0.0005). Overall, these novel findings indicate that alcohol-related increase in Alu methylation might play a complex role in the etiology and pathogenesis of AUD. Further studies are required to elucidate the mechanisms underlying this relationship.

Epigenetic inactivation of Homeobox A5 gene in nonsmall cell lung cancer and its relationship with clinicopathological features.

Promoter methylation is an important mechanism in gene silencing and is a key epigenetic event in cancer development. Homeobox A5 (HOXA5) is a master regulator of the morphogenesis and cell differentiation to be implicated as a tumor suppressor gene in breast cancer, but its role in lung cancer is still unknown. In this study, we have investigated the methylation status of the promoter region of the HOXA5 gene in nonsmall cell lung cancers (NSCLCs) using nested and standard methylation-specific PCR (MSP) and correlated the methylation status with clinicopathological features. With standard MSP analysis, HOXA5 methylation were found in 113 (81.3%) of 139 NSCLCs and 72 (51.8%) in their corresponding nonmalignant lung tissues. RT-PCR and immunohistochemical analysis showed that HOXA5 methylation correlates with gene expression. Moreover, in the patients with stage I disease, HOXA5 methylation was more frequent in smokers than in never-smokes (P = 0.01). There was no influence of HOXA5 methylation on survival in all NSCLCs or at stages II-IV. However, in the patients with stage I disease, HOXA5 methylation was associated with a borderline significantly worse survival (P = 0.09). These findings suggest that downregulation of the HOXA5 gene by aberrant promoter methylation occurs in the vast majority of NSCLCs and that it may play a role in the pathogenesis of NSCLC. Additional studies with larger sample sizes are required to evaluate the prognostic value of HOXA5 methylation in patients with stage I NSCLC.

Adoption of a PDA-based home hospice care system for cancer patients.

This study describes a systematic and efficient point-of-care home hospice information system, which can effectively manage patient information and can easily be incorporated into a home hospice service using wired and/or wireless communications and mobile computing technology. To help with the design of a portable home hospice information system, we analyzed the services provided by visiting nurses and the opinions of users, based on the 2005 Guidelines for Cancer Patient Management Program of the Ministry of Health and Welfare of Korea. We performed a service trial with three experienced visiting nurses. A visiting nurse can use a PDA, implementing the hospice information system, to accomplish tasks that range from registering a new patient to performing nursing services based on the patient's condition, as well as accessing guidelines and searching past information for better nursing performance. The system resulted in a saving of 8.5 minutes in recoding time. We expect the findings of this study to help field workers in community nursing care by reducing unnecessary paperwork and by enabling improvements in the quality of point-of-care services.

Hypermethylation of the Ras association domain family 1A (RASSF1A) gene in gallbladder cancer.

The tumor suppressor gene Ras association domain family 1A (RASSF1A) is highly methylated in a wide range of human sporadic tumors. The current study investigated the hypermethylation of RASSF1A, the expression of RASSF1A protein, and the correlation between these and the clinicopathological features of gallbladder (GB) cancer in Korean patients. Formalin-fixed, paraffin-embedded tumors and non-neoplastic GB tissues (22 carcinomas, 8 adenomas, 26 normal epithelia) were collected from patients who had undergone surgical resection. The methylation status of two regions of the RASSF1A CpG island was determined by methylation-specific PCR (MSP), and the expression of RASSF1A protein was examined by immunohistochemistry using tissue microarrays. The K-RAS mutation was analyzed by direct sequencing. Methylation of the RASSF1A promoter (region 1) was detected in 22.7% (5/22) of carcinomas, 12.5% (1/8) of adenomas, and 0% (0/26) of normal gallbladder epithelia (P = 0.025). Methylation of the first exon (region 2) was found in 36.4% (8/22) of carcinomas, 25.0% (2/8) of adenomas, and 8.0% (2/26) of normal gallbladder epithelia (P = 0.038). K-RAS mutations were present in 4.5% (1/22) of carcinomas and 25% (2/8) of adenomas. RASSF1A methylaton was not associated with clinicopathological factors or K-ras mutation. Reduction or loss of RASSF1A expression was observed in most methylated adenocarcinomas. Three RASSF1A-expressing human biliary tract cancer cell lines examined contained unmethylated promoters and exons 1. These results suggest that downregulation of RASSF1A expression by DNA hypermethylation may be involved in GB carcinogenesis.

[Transmission aspect of methicillin-resistant Staphylococcus aureus in the neurosurgical intensive care unit by analysing genotype].

PURPOSE: The aim of this study was to identify the present situation of hospital infection and route of infection by clarifying the transmission aspect of methicillin-resistant Staphylococcus aureus(MRSA) in a Neurosurgical Intensive Care Unit by analysing genotype. METHODS: MRSA was cultured from twenty five patients with a tracheostomy, twenty five health care workers, and environments in the Neurosurgical Intensive Care Unit of one hospital in D city. Data was collected from December 21, 2004 to November 5, 2005. MRSA isolates representing each genotype were analyzed by spaA typing and a multiplex PCR method capable of identifying the structural type of the staphylococcal cassette chromosome mec(SCCmec) carried by the bacteria. RESULTS: As the same genotype and gene sequence were found among health care workers, patients, and environments, it was assumed that there was cross transmission among them. CONCLUSION: This study suggests that first, as the hospital infection by MRSA between health care workers and patients in the Neurosurgical Intensive Care Unit was due to result of cross transmission and the relevance of transmission between them was verified, it is necessary to take preventive measures and conduct education. Secondly, development of nursing interventions and study of infection are needed. Thirdly, consistent investment in prevention against hospital infections and environmental renovation is needed.

[The effects of the ulmus root-bark dressing in tissue regeneration of induced pressure ulcers in rats].

PURPOSE: The purpose of this study was to examine the effects of the ulmus root-bark dressing on tissue regeneration in experimentally-induced pressure ulcers in rats. METHOD: A randomized pretest/post-test control group time-series study design was used. Thirty-three male Sprague-Dawley rats were used in this study. The rats were anesthetized with 100 mg/kg of ketamine. Pressure ulcers were induced at 140 mmHg for three hours using a personally-designed pressing apparatus. For four weeks, the ulmus root-bark dressing was applied every other day in the experimental group (n=18) and a wet gauze dressing in the control group (n=15). For data analysis, the statistical program SPSS WIN 12 was used. The wounds were examined by light microscopy and electron microscopy. RESULT: There were significant statistical differences in the size of the pressure ulcers as time went by (p=0.006). It should be noted that there were no significant statistical differences in the number of capillaries. Using light microscopy the inflammatory infiltration and neovascularization in the dermis in the experimental group emerged densely in the early stages, but recovered rapidly at the latter stages. In addition, the reepithelization of the epidermis occurred earlier than in the control group. By electron microscopy, the cell organelles of the capillary endothelial cells and the basal lamina of capillaries in the experimental group showed a more rapid maturation during the latter stages, compared with the control group. CONCLUSION: According to this study, it can be concluded that the ulmus root-bark dressing is effective regarding the healing of pressure ulcers.

Effects of Progressive Muscle Relaxation Therapy in Colorectal Cancer Patients.

This study aimed to examine the effect of progressive muscle relaxation therapy (PMRT) on cortisol level, the Stress Arousal Checklist (SACL) score, blood pressure, and heart rate in colorectal cancer patients undergoing laparoscopic surgery. Forty-six patients were divided into control and experimental groups. Cortisol levels, blood pressure, and heart rate were measured before surgery and between 8:00 and 11:00 a.m. on the first, third, and fifth days after surgery. SACL score was measured before surgery and on the fifth day after surgery at the same time points. PMRT was performed twice a day for 5 days. Analyses of covariance with advanced covariate levels and t tests showed that PMRT helps colorectal cancer patients achieve a lower stress response and provides an important basis for stress control.

[Effect and Path Analysis of Laughter Therapy on Serotonin, Depression and Quality of Life in Middle-aged Women].

PURPOSE: This study was done to examine how laughter therapy impacts serotonin levels, QOL and depression in middle-aged women and to perform a path analysis for verification of the effects. METHODS: A quasi-experimental study employing a nonequivalent control group and pre-post design was conducted. Participants were 64 middle-aged women (control=14 and experimental=50 in 3 groups according to level of depression). The intervention was conducted five times a week for a period of 2 weeks and the data analysis was conducted using repeated measures ANOVA, ANCOVA and LISREL. RESULTS: Results showed that pre serotonin and QOL in women with severe depression were the lowest. Serotonin in the experimental groups increased after the 10th intervention (p=.006) and the rise was the highest in the group with severe depression (p=.001). Depression in all groups decreased after the 5th intervention (p=.022) and the biggest decline was observed in group with severe depression (p=.007). QOL of the moderate and severe groups increased after the 10th intervention (p=.049), and the increase rate was highest in group with severe depression (p<.006). Path analysis revealed that laughter therapy did not directly affect depression, but its effect was indirectly meditated through serotonin variation (p<.001). CONCLUSION: Results indicate that serotonin activation through laughter therapy can help middle-aged women by lessening depression and providing important grounds for depression control.

Increased methylation of interleukin 6 gene is associated with obesity in Korean women.

Obesity is the fifth leading risk for death globally, and a significant challenge to global health. It is a common, complex, non-malignant disease and develops due to interactions between the genes and the environment. DNA methylation can act as a downstream effector of environmental signals; analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. To assess the effects of excessive weight and obesity on gene-specific methylation levels of promoter regions, we determined the methylation status of four genes involved in inflammation and oxidative stress [interleukin 6 (IL6), tumor necrosis factor α (TNFα), mitochondrial transcription factor A (TFAM), and glucose transport 4 (GLUT4)] in blood cell-derived DNA from healthy women volunteers with a range of body mass indices (BMIs) by methylation-specific PCR. Interestingly, the samples from obese individuals (BMI ≥ 30 kg/m(2)) showed significantly increased hypermethylation for IL6 gene compared to normal weight (BMI < 23 kg/m(2)) and overweight samples (23 kg/m(2) ≤ BMI < 30 kg/m(2)) (P = 0.034 and P = 0.026). However, there was no statistically significant difference in promoter methylation of the other 3 genes between each group. These findings suggest that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment. Further studies are required to elucidate the potential mechanisms underlying this relationship.

[Predictors of hospitalization for alcohol use disorder in Korean men].

PURPOSE: This study was done to identify the patterns and significant predictors influencing hospitalization of Korean men for alcohol use disorder. METHODS: A descriptive study design was utilized. Data were collected using self-report questionnaires from 143 inpatients who met the DSM-5 alcohol use disorder criteria and were receiving treatment and 157 social drinkers living in the community. The questionnaires included Alcohol Use Disorders Identification Test (AUDIT), Alcohol Problems, Alcohol Expectancy Questionnaire (AEQ), Life Position, and The Korean version of the Children of Alcoholics Screening Test (CAST-K). Data were analyzed using descriptive statistics, t-test, χ²-test, F-test, Pearson correlation coefficients, and logistic regression with forward stepwise. RESULTS: AUDIT had significant correlations with alcohol problems, alcohol expectancy, and parents' alcoholism. In logistic regression, factors significantly affecting hospitalization were divorced (OR=4.18, 95% CI: 1.28-13.71), graduation from elementary school (OR=28.50, 95% CI: 8.07-100.69), middle school (OR=6.66, 95% CI: 2.21-20.09), high school (OR=6.31, 95% CI: 2.59-15.36), drinking alone (OR=9.07, 95% CI: 1.78-46.17), family history of alcoholism (OR=2.41, 95% CI: 1.11-5.25), interpersonal relationship problems (OR=1.28, 95% CI:1.17-1.41), and sexual enhancement of alcohol expectancy (OR=0.83, 95% CI: 0.72-0.94), which accounted for 53% of the variance. CONCLUSION: Results suggest that interpersonal relationship programs and customized cognitive programs for social drinkers in the community are needed to decreased alcohol related hospitalization in Korean men.

[Implementation of ontology-based clinical decision support system for management of interactions between antihypertensive drugs and diet].

PURPOSE: The influence of dietary composition on blood pressure is an important subject in healthcare. Interactions between antihypertensive drugs and diet (IBADD) is the most important factor in the management of hypertension. It is therefore essential to support healthcare providers' decision making role in active and continuous interaction control in hypertension management. The aim of this study was to implement an ontology-based clinical decision support system (CDSS) for IBADD management (IBADDM). We considered the concepts of antihypertensive drugs and foods, and focused on the interchangeability between the database and the CDSS when providing tailored information. METHODS: An ontology-based CDSS for IBADDM was implemented in eight phases: (1) determining the domain and scope of ontology, (2) reviewing existing ontology, (3) extracting and defining the concepts, (4) assigning relationships between concepts, (5) creating a conceptual map with CmapTools, (6) selecting upper ontology, (7) formally representing the ontology with Protégé (ver.4.3), (8) implementing an ontology-based CDSS as a JAVA prototype application. RESULTS: We extracted 5,926 concepts, 15 properties, and formally represented them using Protégé. An ontology-based CDSS for IBADDM was implemented and the evaluation score was 4.60 out of 5. CONCLUSION: We endeavored to map functions of a CDSS and implement an ontology-based CDSS for IBADDM.

Effect of body mass index on global DNA methylation in healthy Korean women.

Obesity is known to be strongly associated with cardiovascular disease and cancer, the leading causes of mortality worldwide, and develops owing to interactions between genes and the environment. DNA methylation can act as a downstream effector of environmental signals, and analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Repetitive element DNA methylation has been shown to be associated with prominent obesity-related chronic diseases, but little is known about its relationship with weight status. In this study, we quantified the methylation of Alu elements in the peripheral blood DNA of 244 healthy women with a range of body mass indexes (BMIs) using pyrosequencing technology. Among the study participants, certain clinical laboratory parameters, including hemoglobin, serum glutamic oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total cholesterol, and triglyceride levels were found to be strongly associated with BMI. Moreover, a U-shaped association between BMI and Alu methylation was observed, with the lowest methylation levels occurring at BMIs of between 23 and 30 kg/m(2). However, there was no significant association between Alu methylation and age, smoking status, or alcohol consumption. Overall, we identified a differential influence of BMI on global DNA methylation in healthy Korean women, indicating that BMI-related changes in Alu methylation might play a complex role in the etiology and pathogenesis of obesity. Further studies are required to elucidate the mechanisms underlying this relationship.

An Effect of Optimism, Self-esteem and Depression on Laughter Therapy of Menopausal Women.

PURPOSE: This study examines the difference of optimism, self-esteem and depression to verify an effect of laughter therapy program for menopausal women. METHODS: A quasi-experimental nonequivalent control group pre / post-test design was used. The participants (n=57) were 28 in the experimental group and 29 in the control group. The data were collected in December of 2011. The experimental group participated in laughter therapy for 30 min per session, five times a week for the period of 2 weeks. The questionnaires were used to measure pre / post-test optimism, self-esteem, and depression of menopausal women. RESULTS: The results showed that laughter therapy was effective in increasing optimism (p=.020) and self-esteem (p<.001). And the depression of menopausal women decreased (p=.003). CONCLUSION: The result of the study indicates that laughter therapy for menopausal women may be an effective nursing intervention to improve optimism, self-esteem and depression of menopausal women.

Hypomethylation of the thymosin ß(10) gene is not associated with its overexpression in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide and is usually associated with a late diagnosis and a poor prognosis. Thymosin ß(10) (TMSB10) is a monomeric actin sequestering protein that regulates actin cytoskeleton organization. The aberrant TMSB10 expression has been implicated in the pathogenesis of human cancers. However, its role in carcinogenesis is still controversial. To better understand the role of TMSB10 in lung tumorigenesis and its regulatory mechanism, we examined the methylation status and expression of the TMSB10 gene in non-small cell lung cancers (NSCLCs) using methylation-specific PCR (MSP) and immunohistochemistry (IHC), respectively. MSP analysis showed that the TMSB10 promoter was already unmethylated in most tumor tissues and became demethylated in 20 (14.4%) of the 139 NSCLCs. TMSB10 hypomethylation was not significantly correlated with the clinicopathological features. IHC showed that the TMSB10 protein was strongly expressed in the cytoplasm of malignant cells and its overexpression was detected in 50.0% of the tumor tissues compared to normal tissues. TMSB10 overexpression was frequently observed in sqaumous cell carcinomas compared to adenocarcinomas with border line significance (P = 0.072). However, TMSB10 methylation status was not linked to its overexpression. Collectively, these results suggest that TMSB10 hypomethylation may be a frequent event in NSCLCs, but it may not be a common mechanism underlying TMSB10 overexpression. However, further studies with large numbers of patients are needed to confirm our findings.

Hypermethylation of growth arrest DNA-damage-inducible gene 45 in non-small cell lung cancer and its relationship with clinicopathologic features.

The growth arrest DNA-damage-inducible protein 45 (GADD45) can serve as a key coordinator of the stress response by regulating cell cycle progression, genomic stability, DNA repair, and other stress-related responses. Although deregulation of GADD45 expression has been reported in several types of human tumors, its role in lung cancer is still unknown. DNA hypermethylation of promoter CpG islands is known to be a major mechanism for epigenetic inactivation of tumor suppressor genes. We investigated the methylation status of GADD45 family genes (GADD45A, B, and G) in 139 patients with non-small cell lung cancer (NSCLC) using methylation-specific PCR (MSP) and correlated the results with clinicopathologic features of the patients. Methylation frequencies in tumors were 1.4% for GADD45A, 7.2% for GADD45B, and 31.6% for GADD45G. RT-PCR and MSP analysis showed that promoter methylation of the GADD45G gene resulted in downregulation of its mRNA expression. GADD45G methylation was significantly more frequent in female patients than male patients (P = 0.035). This finding suggests that methylation-associated down-regulation of the GADD45G gene may be involved in lung tumorigenesis.

An improved auto-generation system to obtain reference intervals for laboratory medicine.

OBJECTIVES: Reference values are highly required parameters for all tests in the clinical laboratory, and the supplementary provision of reliable reference intervals is an important task for both clinical laboratories and diagnostic test manufacturers. Despite the progress that has been made in the conceptual aspects of reference intervals, in practice their use is still not completely satisfactory. Most of the laboratories have used various methods to calculate statistic-based reference intervals, and they have mainly focused on extracted data, yet its use is considerably limited. We had to deal with the inconvenience of using a number of programs (SPSS or SAS, MS Excel) in order to calculate the results of reference intervals. METHODS: In order to obtain standardized reference intervals, we developed an integrated program that can calculate, by a nonparametric method, reference intervals with using the Clinical and Laboratory Standards Institute (CLSI) processes as its guideline. We also developed a grouping interface that enables users to customize classification of each group (age, gender, blood group, race, etc) when calculating reference intervals. RESULTS: To verify the developed program, we compared the reference intervals of the current data on 281 persons for 8 total areas, and the reference intervals were was already calculated beforehand with by using this new program. As a result, both results perfectly matched. CONCLUSIONS: This integrated program will be convenience for calculating reasonable values through continual datainspection at an inspection lab for calculating reference intervals. The newly developed program will improve the consistency and reliability of the statistics on reference intervals.

Imaging findings in a case of epidermal inclusion cyst arising within the breast parenchyma.

Epidermal inclusion cysts rarely occur in the breast, but when they do, the consequences can be severe. Here, we report the case of a 23-year-old woman who presented with a palpable mass in the right breast. The mass had persisted for 4 years and had been causing pain for 1 month at the time of the patient's presentation. We examined the mass by means of mammography and sonography. Sonographic examination revealed a well-circumscribed solid, avascular mass suggestive of an epidermal inclusion cyst. Excision was performed at the patient's request. Histopathologic examination of the mass after excision confirmed the diagnosis of epidermal inclusion cyst and its localization within the breast parenchyma. To our knowledge, reports on epidermal inclusion cysts within the breast parenchyma are rare.