The association between urinary bisphenol A levels and nonalcoholic fatty liver disease in Korean adults: Korean National Environmental Health Survey (KoNEHS) 2015-2017.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is becoming a global health problem. Bisphenol A (BPA), one of most widely used environmental chemicals, is suspected to be a contributor to the development NAFLD. This study was performed to examine the relationship between human BPA levels and risk of NAFLD. METHODS: The data (n = 3476 adults: 1474 men and 2002 women) used in this study were obtained from the Korean National Environmental Health Survey III (2015-2017). BPA levels were measured in urine samples. NAFLD was defined using hepatic steatosis index after exclusion of other causes of hepatic diseases. RESULTS: There was a significant linear relationship between the elevated urinary BPA concentrations and risk of NAFLD. In a univariate analysis, odds ratio (OR) of the highest quartile of urinary BPA level was 1.47 [95% confidence interval (CI) 1.11-1.94] compared to the lowest quartile. After adjusted with covariates, the ORs for NAFLD in the third and fourth quartiles were 1.31 [95% CI 1.03-1.67] and 1.32 [95% CI 1.03-1.70], respectively. CONCLUSIONS: Urinary BPA levels are positively associated with the risk of NAFLD in adults. Further experimental studies are needed to understand the molecular mechanisms of BPA on NAFLD prevalence.

Psychometric properties of a short self-reported measure of medication adherence among patients with hypertension treated in a busy clinical setting in Korea.

BACKGROUND: We examined the psychometric properties of the Korean version of the 8-item Morisky Medication Adherence Scale (MMAS-8) among adults with hypertension. METHODS: A total of 373 adults with hypertension were given face-to-face interviews in 2 cardiology clinics at 2 large teaching hospitals in Seoul, South Korea. Blood pressure was measured twice, and medical records were reviewed. About one-third of the participants (n = 109) were randomly selected for a 2-week test-retest evaluation of reliability via telephone interview. RESULTS: Internal consistency reliability was moderate (Cronbach α = 0.56), and test-retest reliability was excellent (intraclass correlation = 0.91; P < 0.001), although a ceiling effect was detected. The correlation of MMAS-8 scores with scores for the original 4-item scale indicated that convergent validity was good (r = 0.92; P < 0.01). A low MMAS-8 score was significantly associated with poor blood pressure control (χ(2) = 29.86; P < 0.001; adjusted odds ratio = 5.08; 95% CI, 2.56-10.08). Using a cut-off point of 6, sensitivity and specificity were 64.3% and 72.9%, respectively. Exploratory factor analysis identified 3 dimensions of the scale, with poor fit for the 1-dimensional construct using confirmatory factory analysis. CONCLUSIONS: The MMAS-8 had satisfactory reliability and validity and thus might be suitable for assessment and counseling regarding medication adherence among adults with hypertension in a busy clinical setting in Korea.

Trends and risk factors of the epidemic of charcoal burning suicide in a recent decade among Korean people.

The aims of this study were to analyze annual trends of charcoal burning (CB) suicide, 2000 to 2011, and to examine the risk factors of CB suicide in Korea. Data on suicides (n=138,938) were obtained from the Statistics Korea. The proportion of CB suicides among all suicide deaths reported was 0.7% (84 cases) in 2007, and since 2008 it has rapidly increased to 7.9% (1,251 cases) in 2011. Of significant risk factors of CB suicide, the presence of the media report of Ahn's suicide was the greatest risk factor (adjusted odds ratio, 11.69; 95% CI, 10.30-13.23) of the initial phase of the continuing CB suicides since 2008. Korean Government should urgently consider effective measures against CB suicide, including enforced media regulations on reporting such suicides.

Short-term exposure to di(2-ethylhexyl)phthalate may disrupt hepatic lipid metabolism through modulating the oxidative stress in male adolescent rats.

Di(2-ethylhexyl)phthalate (DEHP) is commonly used to increase the flexibility of plastics. In our previous study, DEHP may increase hepatic lipid accumulation through modulating of acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) expression. Nevertheless, it is hard to understand the association between DEHP and DGAT1 in the liver because only one dosage of DEHP was used. Thus, this study performed to investigate the role of DGAT1 on hepatic lipid metabolism after various dosages of DEHP exposure. Four-week-old male Sprague-Dawley rats (n = 5/group) were administered corn oil (vehicle) or DEHP (0.75, 7.5, 15, or 150 mg/kg/day) once daily for seven days. DEHP 150 mg/kg/day treated group increased body weight gain and relative liver weight compared to the control (P = 0.044 and P = 0.049, respectively). In histological observation, elevation of hepatic lipid accumulation was observed in all DEHP-treated groups, except DEHP 150 mg/kg/day, compared to that in the control (all P < 0.001). Portal inflammatory infiltration and acidophilic bodies were observed in the liver at DEHP 7.5 mg/kg/day and above treated groups. In addition, malondiadehyde levels, a marker of lipid peroxidation, in the liver were increased in DEHP 7.5, 15 and 150 mg/kg/day compared to the control (P = 0.017, P = 0.001, and P = 0.002, respectively). The expression of Dgat1 in the liver was significantly increased in DEHP 7.5, 15 and 150 mg/kg/day compared to the control group (P = 0.019, P = 0.002, and P < 0.001, respectively); however, there were no significant changes in the protein levels. Therefore, excessive oxidative stress caused by DEHP may induce liver damage such as inflammation rather than hepatic lipid accumulation by regulating DGAT1 transcription.

Independent and Synergistic Associations of Aerobic Physical Activity and Resistance Exercise with Nonalcoholic Fatty Liver Disease.

Background/Aims: This study aimed to examine the independent and synergistic association of aerobic physical activity and resistance exercise with nonalcoholic fatty liver disease (NAFLD) using a nationwide representative database. Methods: This was a cross-sectional study using data from the Korea National Health and Nutritional Examination Survey between 2007 and 2010. Multiple logistic regression models were used to examine the independent and synergistic (additive interaction) associations of aerobic physical activity and resistance exercise with NAFLD after adjusting for multiple covariates. Results: The prevalence of NAFLD was 26.2% for men and 17.6% for women. In the fully adjusted multiple logistic regression model to examine the independent association of aerobic physical activity or resistance exercise with NAFLD, the odds ratios for NAFLD were significantly decreased in both men (p=0.03) and women (p<0.01) who had highly active aerobic physical activity. Regarding the frequency of resistance exercise, the odds ratio for NAFLD was decreased in men who did resistance exercise ≥5 days per week (p=0.04), but not in women (p=0.19). However, when investigating the synergistic associations of aerobic physical activity and resistance exercise, the odds ratios for NAFLD significantly decreased when the frequency of both exercises increased together in both men (p for interaction <0.01) and women (p for interaction<0.01). Conclusions: Combining aerobic physical activity and resistance exercise had a synergistic preventive association for NAFLD in Korean men and women.

Expression of calbindin-D28k and its regulation by estrogen in the human endometrium during the menstrual cycle.

Human endometrium resists embryo implantation except during the 'window of receptivity'. A change in endometrial gene expression is required for the development of receptivity. Uterine calbindin-D28k (CaBP-28k) is involved in the regulation of endometrial receptivity by intracellular Ca2+. Currently, this protein is known to be mainly expressed in brain, kidneys, and pancreas, but potential role(s) of CaBP-28k in the human uterus during the menstrual cycle remain to be clarified. Thus, in this study we demonstrated the expression of CaBP-28k in the human endometrium in distinct menstrual phases. During the human menstrual cycle, uterine expression levels of CaBP-28k mRNA and protein increased in the proliferative phase and fluctuated in these tissues, compared with that observed in other phases. We assessed the effects of two sex-steroid hormones, 17beta-estradiol (E2) and progesterone (P4), on the expression of CaBP-28k in Ishikawa cells. A significant increase in the expression of CaBP-28k mRNA was observed at the concentrations of E2 (10(-9 to -7) M). In addition, spatial expression of CaBP-28k protein was detected by immunohistochemistry. CaBP-28k was abundantly localized in the cytoplasm of the luminal and glandular epithelial cells during the proliferative phases (early-, mid-, late-) and early-secretory phase of menstrual cycle. Taken together, these results indicate that CaBP-28k, a uterine calcium binding protein, is abundantly expressed in the human endometrium, suggesting that uterine expression of CaBP-28k may be involved in reproductive function during the human menstrual cycle.

Maintained seroprevalence of toxoplasmosis among the residents of Jeju island, Korea.

Seroepidemiological status of toxoplasmosis among the residents of Jeju island was surveyed and evaluated by ELISA with crude extract of Toxoplasma gondii. The sera of 2,348 residents (male 1,157 and female 1,191) were collected and checked for the IgG antibody titers, which showed 13.2% positive rate (309 sera). The positive rates were increasing gradually according to the age from 4.3% in teenage to 20.6% in seventies. The positive rates were significantly different between the sex by 16.2% for male and 10.2% for female (P<0.05). This positive rate of toxoplasmosis in Jeju island residents is regarded relatively higher than any other regions of Korea. And the high positive rate may be maintained continuously among Jeju island residents without any clear reasons until now but due to some parts peculiar socio-cultural tradition of Jeju island. Therefore, it is necessary to study further the epidemiology of toxoplasmosis of Jeju island.

Urinary Phthalate Levels Associated with the Risk of Nonalcoholic Fatty Liver Disease in Adults: The Korean National Environmental Health Survey (KoNEHS) 2012-2014.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Recent experimental studies suggested that phthalates might induce NAFLD. Therefore, this study aimed to investigate the relationship between phthalates metabolites and NAFLD in the human population. This cross-sectional analysis was performed using data from the Korean National Environmental Health Survey II (2012-2014) among Korean adults (n = 5800). NAFLD was diagnosed using the hepatic steatosis index (HSI) in the absence of other causes of chronic liver diseases. Among the participants (mean age 46 years, 47.5% male), the prevalence of NAFLD was associated with urinary levels of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-benzyl phthalate (MBzP), and mono-n-butyl phthalate (MnBP) compared to the reference group. In the multivariate model, the odds ratios (ORs), 95% confidence interval (CI) for NAFLD were 1.33 (1.00-1.78) and 1.39 (1.00-1.92) in the 3rd and 4th quartile of MEHHP, respectively. Based on the study findings, high levels of urinary phthalates are associated with the prevalence of NAFLD in Korean adults. Further investigation is required to elucidate the causal relationship.

The Impairment of Thyroid Hormones Homeostasis after Short-Term Exposure to Di(2-ethylhexyl)phthalate in Adolescent Male Rats.

Di(2-ethylhexyl)phthalate (DEHP) could induce metabolic disorders through interfering with thyroid homeostasis. Therefore, we evaluated the effects of short term to environmental relevant doses of DEHP on thyroid hormones. Four week old Sprague-Dawley (SD) rats were treated with vehicle (corn oil), and DEHP 0.75, 7.5, and 150 mg/kg/day. The rats were treated with once daily by oral gavage and were sacrificed with after 1 week. They were measured body weight and relative thyroid weight, serum thyroid hormones and histological changes of thyroid. There was no difference in body weight between the control and DEHP exposed rats. Relative thyroid weight in DEHP 150 mg/kg/day treated group was significantly lower than control. Serum thyroxine levels was decreased in rats exposed to 0.75 and 150 mg/kg/day DEHP. No histological changes were observed in the thyroid of rats administered DEHP compared to control. Exposure to DEHP at environmental relevant levels, even short-term exposure, can cause hypothyroidism in adolescent rats even the exposure period is relative short.

Association between Blood Mercury Levels and Non-Alcoholic Fatty Liver Disease in Non-Obese Populations: The Korean National Environmental Health Survey (KoNEHS) 2012-2014.

Mercury is widely distributed in the environment, and a plausible association between mercury exposure and hepatic damage has been reported. Non-alcoholic fatty liver disease (NAFLD), which comprises a spectrum of liver diseases, has recently been recognized in non-obese subjects. However, there have been no studies on the relationship between internal mercury levels and NAFLD in non-obese individuals. Therefore, we investigated the association between blood mercury levels and NAFLD in non-obese subjects. Cross-sectional data (n = 5919) were obtained from the Korean National Environmental Health Survey (2012-2014). NAFLD was defined using the hepatic steatosis index (HSI). Blood mercury levels were log-transformed and divided into quartiles based on a weighted sample distribution. The association between blood mercury levels and NAFLD was analyzed using a multivariate logistic analysis after body mass index stratification. The geometric mean of blood mercury in the overweight group was significantly higher than that of the non-obese group (p < 0.001). The weighted frequencies of patients with NAFLD based on the HSI were 3.0-7.2% for the non-obese subjects and 52.3-63.2% for the overweight subjects. In the multivariate analysis, blood mercury levels were positively associated with NAFLD for both the overweight and non-obese groups (all p for trend < 0.001). Increased blood mercury levels are closely associated with NAFLD. In particular, mercury could be a risk factor for NAFLD in the non-obese population.

A Meta-Analysis of the Efficacy of Hyaluronic Acid Eye Drops for the Treatment of Dry Eye Syndrome.

Hyaluronic acid (HA) is commonly used for treating dry eye syndrome (DES). This meta-analysis was performed to compare the efficacies of HA- and non-HA-based eye drops, including saline and conventional artificial tears (ATs), for the treatment of dry eye disease. Eight databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials, DBpia, KoreaMed, KMBASE, RISS, KISS) were searched for studies comparing the efficacies of HA- and non-HA-based ATs in patients with DES published up to September 2020. Two independent reviewers assessed the quality and extracted the relevant data. The mean differences of Schirmer's (SH) test scores, tear breakup times (TBUT), corneal fluorescein staining scores (Oxford scale, 0-4), and ocular surface disease indexes were calculated. The standard mean difference and 95% confidence interval were calculated using a random effect model. Nineteen studies, including 2078 cases, were included. HA eye drops significantly improved tear production compared with non-HA-based eye drops (standard mean difference (SMD) 0.18; 95% confidence interval (CI) 0.03, 0.33). In a subgroup analysis, the SH test scores and TBUT values after using HA significantly increased compared to those measured after using saline (SMD 0.27; 95% CI 0.05, 0.49 and SMD 0.28; 95% CI 0.03, 0.52, respectively). Based on these results, HA eye drops may be superior to non-HA eye drops including normal saline and ATs. Further research is needed to assess the efficacies stratified by age, treatment duration, the severity of dry eye, and optimal dosages.

Significantly Reduced Alanine Aminotransferase Level Increases All-Cause Mortality Rate in the Elderly after Ischemic Stroke.

(1) Background: A significantly reduced alanine aminotransferase (ALT) level is being recognized as a risk factor of increasing mortality in the elderly in relation to frailty. In the elderly, both frailty and ischemic stroke are not only common, but are also associated with mortality. The aim of this research was to investigate whether a significantly reduced ALT level increases the all-cause mortality rate in the elderly with ischemic stroke. (2) Methods: Between February 2014 and April 2019, a retrospective study of 901 patients with ischemic stroke admitted to a university-affiliated hospital was conducted. Cox proportional hazard regression was used to determine whether a significantly reduced ALT level is an independent risk factor for mortality in elderly patients after an ischemic stroke. (3) Results: This study enrolled 323 older adults (age ≥ 65 years) who were first diagnosed with ischemic stroke. The mean age of the participants was 76.5 ± 6.6 years, the mean survival time was 37.1 ± 20.4 months, and the number of deaths was 96 (29.7%). Our results showed that reduced ALT level (less than 10 U/L) increased the risk of all-cause mortality in the elderly after ischemic stroke (adjusted HR: 3.24, 95% CI: 1.95-5.41; p < 0.001). (4) Conclusions: A significantly reduced ALT level at the time of diagnosis (less than 10 U/L) is an independent risk factor that increases the mortality rate in the elderly after ischemic stroke.

Changes in brain FDG metabolism induced by acupuncture in healthy volunteers.

BACKGROUND: With the aid of newly developed functional brain imaging studies, studies are ongoing to see if acupuncture first acts on specific brain areas to induce effects on the human body. PURPOSE: To examine if stimulation at specific acupuncture points changes brain glucose metabolism patterns, including the limbic system and specific brain areas related to the acupuncture effect in healthy volunteers using fluorodeoxyglucose positron emission tomography combined computed tomography (FDG-PET/CT). MATERIAL AND METHODS: Twenty healthy volunteers (11 men and 9 women; mean age 49.1+/-7.3 years, age range 35-62 years) were included. Two sets of PET/CT scans were obtained from each volunteer, with and without stimulation by acupuncture. Two classic acupoints, LR3 (liver meridian) and ST44 (stomach meridian) were tested at the same time, using disposable sterile stainless steel needles. After initial acupuncture, the needle was kept in place without further stimulation. FDG-PET/CT scan of the brain began 45 min after FDG injection (185-222 MBq). RESULTS: After stimulation of LR3 and ST44 by acupuncture, glucose metabolism in the brain was increased in the left insula (BA 13), bilateral thalami, superior frontal region of the right frontal lobe, and the inferior frontal region of left frontal lobe compared with baseline. On the other hand, glucose metabolism was decreased after acupuncture in the cingulate and parahippocampal (BA 36) regions of the left limbic lobe. CONCLUSION: Changes of glucose metabolism in specific brain areas following stimulation by acupuncture on LR3 and ST44 were documented using FDG-PET/CT.

Effect of income level on adherence to antidepressant treatment in first onset depression outpatients.

Clinical guidelines for depression management recommend continuous antidepressant medication; however, poor adherence to medication is commonly seen in the treatment of depression. Income is an important factor influencing antidepressant medication adherence. The purpose of this study was to investigate the relationship between income level and adherence to antidepressant medication in outpatients with depression. This was a retrospective cohort study using National Health Insurance claim data for services provided between January 1 and December 31, 2012. We examined data from a total of 142,336 individuals aged 18 years or older who were continuously enrolled in treatment after a new episode of major depression and who had initiated antidepressant treatment. The operational definition of adherence to antidepressant treatment was medication being dispensed to the patient at least 80% of the time during 3 and 6 months (ie. MPR ≥80%). To investigate the relationship between income level and adherence to antidepressants, we estimated adjusted odds ratios and 95% confidence intervals using hierarchical logistic regression analysis, adjusting for sociodemographic, clinical, and medical use characteristics. A total of 22.64% and 15.13% of depression patients showed adherence to antidepressants during 3 and 6 months, respectively. A statistically significant association was found between income level and adherence to antidepressants over 3 and 6 months for individuals with employee and self-employed subscribers. In addition, adherence to antidepressants was lower among those with a lower income than those with a higher income. We confirmed that social disparities exist in adherence to antidepressant treatment by income level in this Korean population-based retrospective cohort of depression outpatients.

The Association between Nonalcoholic Fatty Liver Disease and Stroke: Results from the Korean Genome and Epidemiology Study (KoGES).

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is associated with various cardiometabolic diseases. However, the association between NAFLD and stroke is not well known. The purpose of our study is to reveal the relationship between NAFLD and Stroke incidence. (2) Methods: Using data from a Korean prospective cohort study, we excluded participants with heavy alcohol consumption and a history of stroke; hence, 7964 adults aged 40-69 years were included in this study. According to their fatty liver index (FLI), participants were divided into three groups: <30 (n = 4550, non-NAFLD), 30-59.9 (n = 2229, intermediate), and ≥60 (n = 1185, NAFLD). The incidence of stroke according to the degree of FLI was evaluated using the Cox proportional hazard model. (3) Results: During the 12-year follow-up period, 168 strokes occurred. A graded association between NAFLD and stroke incidence was observed, i.e., 1.7% (n = 76), 2.5% (n = 56), and 3.0% (n = 36) for non-NAFLD, intermediate, and NAFLD FLI groups, respectively. After adjusting for confounding variables and compared to the risk of stroke in the non-NAFLD group, the risk of stroke in the NAFLD group was the highest (hazard ratio [HR]: 1.98, 95% confidence interval [CI]: 1.17-3.34), followed by the risk of stroke in the intermediate group (HR: 1.41, 95% CI: 0.94-2.21) (p for trend < 0.001). However, the level of aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyltransferase alone did not show any significant association with stroke. (4) Conclusions: This study demonstrated that the risk of stroke incidence gradually increased with the degree of FLI. Individuals with NAFLD should be properly counseled and monitored for risk for stroke.

Gender Differences in the Relationship between Type 2 Diabetes Mellitus and Employment: Evidence from the Korea Health Panel Study.

Previous studies have analyzed the impact of diabetes mellitus on labor market participation by men and women, but gender difference between type 2 diabetes mellitus (T2DM) and employment has not been the focus. This study aims to explore gender differences between T2DM and employment status. Data from the Korea Health Panel Study, 2013-2015 were analyzed by distinguishingT2DM and non-diabetes (N = 11,216). The empirical model was established and the generalized two-stage least squares (2SLS) was estimated, controlling for endogeneity. A family history of diabetes, as an instrumental variable, was related to an individual's genetic predisposition to develop diabetes. The estimated results for the 2SLS showed the interaction effects between T2DM and employment. T2DM had a statistically significant and negative effect on employment for women only. The comparison with non-diabetes showed that women with T2DM had a lower probability of employment by 51.9% (p < 0.05). Exposing gender bias in employment suggests that healthcare policies and disease management programs for diabetic patients should adopt gender-specific remedies.

Dopaminergic antagonists inhibit bile chemotaxis of adult Clonorchis sinensis and its egg production.

Human clonorchiasis, caused by Clonorchis sinensis, is endemic in East Asian countries. C. sinensis metacercariae excyst in the duodenum of mammalian hosts, migrate to the intrahepatic bile duct, and mature into adults in the milieu of bile. We have previously shown that newly excysted juvenile C. sinensis move chemotactically toward bile and bile acids. Here, the chemotactic behavior of adult C. sinensis (CsAd) toward bile and bile acids was investigated. CsAds moved toward 0.05-5% bile and were most attracted to 0.5% bile but moved away from 10% bile. Upon exposure to 1-10% bile, CsAds eventually stopped moving and then died quickly. Among bile acids, CsAds showed strong chemotaxis toward cholic acid (CA) and deoxycholic acid. On the contrary, CsAds repelled from lithocholic acid (LCA). Moreover, at higher than 10 mM LCA, CsAds became sluggish and eventually died. Dopamine D1 receptor antagonists (LE-300 and SKF-83566), D2/3 receptor antagonists (raclopride and its derivative CS-49612), and a dopamine re-uptake inhibitor inhibited CA-induced chemotaxis of CsAds almost completely. Clinically used antipsychotic drugs, namely chlorpromazine, haloperidol, and clozapine, are dopaminergic antagonists and are secreted into bile. They completely inhibited chemotaxis of CsAds toward CA. At the maximum doses used to treat patients, the three tested medicines only expelled 2-12% of CsAds from the experimentally infected rabbits, but reduced egg production by 64-79%. Thus, antipsychotic medicines with dopaminergic antagonism could be considered as new anthelmintic candidates for human C. sinensis infections.

Association between Peptic Ulcer Disease and Osteoporosis: The Population-Based Longitudinal Cohort Study in Korea.

OBJECTIVES: The association between peptic ulcer disease (PUD) and osteoporosis remains unclear. We investigated the association between PUD and osteoporosis by classifying individuals based on gender in a prospective study on 10,030 adults in Korea at a 12-year follow-up examination. DESIGN AND SETTING: The baseline survey of the Ansung-Ansan cohort studies was conducted from May 2001 to February 2003, and 10,030 participants (5018 from the Ansung study and 5012 from the Ansan study) completed the examination. PRIMARY OUTCOME MEASURES: The risk of developing osteoporosis was higher in both men and women in the PUD group than in the control group. RESULTS: At the 12-year follow-up, osteoporosis had developed in 11.1% (21/189) and 29.9% (56/187) of men and women in the PUD group, respectively. Meanwhile, in the control group, 4.8% (70/1464) and 16.5% (271/1639) of men and women, respectively, were presented with osteoporosis. The incidence rates per 1000 person-years were 20.5% and 68.5% in men and women in the PUD group and 11.2% and 42.3% of men and women in the control group, respectively. The risk of developing osteoporosis was higher in both men and women in the PUD group than in the control group (men: hazard ratio [HR] = 1.72, 95% confidence interval [CI] = 1.02-2.92; women: HR = 1.62, 95% CI = 1.20-2.18). CONCLUSION: The risk of developing osteoporosis was significantly higher in both men and women in the PUD group than in the control group.