Functional assessment of Nramp-like metal transporters and manganese in Caenorhabditis elegans.

Nramp1 (natural resistance-associated macrophage protein-1) is a functionally conserved iron-manganese transporter in macrophages. Manganese (Mn), a superoxide scavenger, is required in trace amounts and functions as a cofactor for most antioxidants. Three Nramp homologs, smf-1, smf-2, and smf-3, have been identified thus far in the nematode Caenorhabditis elegans. A GFP promoter assay revealed largely intestinal expression of the smf genes from early embryonic through adult stages. In addition, smf deletion mutants showed increased sensitivity to excess Mn and mild sensitivity to EDTA. Interestingly, these smf deletion mutants demonstrated hypersensitivity to the pathogen Staphylococcus aureus, an effect that was rescued by Mn feeding or knockdown of the Golgi calcium/manganese ATPase, pmr-1, indicating that Mn uptake is essential for the innate immune system. This reversal of pathogen sensitivity by Mn feeding suggests a protective and therapeutic role of Mn in pathogen evasion systems. We propose that the C. elegans intestinal lumen may mimic the mammalian macrophage phagosome and thus could be a simple model for studying Mn-mediated innate immunity.

S100 Calcium-Binding Protein A9, a Potential Novel Diagnostic Biomarker for Idiopathic Pulmonary Fibrosis

Background@#Neutrophilic inflammation is a characteristic feature of idiopathic pulmonary fibrosis (IPF). S100 calcium-binding protein A9 (S100A9) is a neutrophil-derived protein involved in the development of neutrophil-related chronic inflammatory disorders. However, the role of S100A9 in IPF remains unclear. @*Methods@#We used enzyme-linked immunosorbent assays to measure S100A9 levels in bronchoalveolar lavage fluid (BALF) and serum obtained from healthy controls (HCs) and patients with IPF, non-specific interstitial pneumonia, hypersensitivity pneumonitis, and sarcoidosis. @*Results@#Compared with HCs, BALF S100A9 levels were significantly higher in IPF patients (P 0.533 ng/ mL had lower survival rates, compared with patients who had levels ≤ 0.553 ng/mL (n = 49; hazard ratio [HR], 3.62; P = 0.021). Combination analysis revealed that IPF patients with S100A9 levels in BALF> 0.553 ng/mL or neutrophil percentages > 49.1% (n = 43) had significantly lower survival rates than patients with S100A9 levels in BALF ≤ 0.553 ng/mL and neutrophil percentages ≤ 49.1% (n = 41) (HR, 3.91; P = 0.014). Additionally, patients with serum S100A9 levels > 0.077 ng/mL (n = 29) had significantly lower survival rates than patients with levels ≤ 0.077 ng/mL (n = 53, HR, 2.52; P = 0.013). S100A9 was expressed on neutrophils and macrophages in BALF from IPF patients as well as α-smooth muscle actin positive cells in the lung tissues. @*Conclusion@#S100A9 is involved in the development and progression of IPF. Moreover, S100A9 levels in BALF and serum may be surrogate markers for IPF diagnosis and survival prediction, particularly when analyzed in combination with neutrophil percentages.

Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study / 한국역학회지

OBJECTIVES@#Bilirubin is an endogenous antioxidant that protects cells against oxidative stress. Increased plasma levels of bilirubin have been associated with a reduced risk of ischemic heart disease (IHD) in previous studies. Nonetheless, whether those associations reflect a true protective effect of bilirubin on IHD, rather than confounding or reverse causation, remains unknown. Therefore, we applied two-sample Mendelian randomization to evaluate the causal association between bilirubin levels and IHD risk in a Korean population.@*METHODS@#A total of 5 genetic variants—TRPM8 (rs10490012), USP40 (rs12993249), ATG16L1 (rs2119503), SLCO1B1 (rs4149014), and SLCO1B3 (rs73233620)—were selected as genetic instruments for serum bilirubin levels using a community-based cohort, the Korean Genome and Epidemiology Study, comprising 33,598 subjects. We then evaluated their impact on IHD using the Korean Cancer Prevention Study-II cohort.@*RESULTS@#Among the 5 instrumental variables that showed significant associations with serum bilirubin levels, rs12993249 (USP40) showed the most significant association (p<2.36×10

Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study / 한국역학회지

OBJECTIVES: Bilirubin is an endogenous antioxidant that protects cells against oxidative stress. Increased plasma levels of bilirubin have been associated with a reduced risk of ischemic heart disease (IHD) in previous studies. Nonetheless, whether those associations reflect a true protective effect of bilirubin on IHD, rather than confounding or reverse causation, remains unknown. Therefore, we applied two-sample Mendelian randomization to evaluate the causal association between bilirubin levels and IHD risk in a Korean population. METHODS: A total of 5 genetic variants—TRPM8 (rs10490012), USP40 (rs12993249), ATG16L1 (rs2119503), SLCO1B1 (rs4149014), and SLCO1B3 (rs73233620)—were selected as genetic instruments for serum bilirubin levels using a community-based cohort, the Korean Genome and Epidemiology Study, comprising 33,598 subjects. We then evaluated their impact on IHD using the Korean Cancer Prevention Study-II cohort. RESULTS: Among the 5 instrumental variables that showed significant associations with serum bilirubin levels, rs12993249 (USP40) showed the most significant association (p<2.36×10−105). However, we found no significant association between serum bilirubin levels and IHD. Sensitivity analyses demonstrated a consistent association, suggesting that our observations were robust. CONCLUSIONS: Using two-sample Mendelian randomization, we found no association between serum bilirubin levels and IHD. Further studies that confirm the observed interactions among other ethnicities are warranted.

Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study / 한국역학회지

OBJECTIVES: Bilirubin is an endogenous antioxidant that protects cells against oxidative stress. Increased plasma levels of bilirubin have been associated with a reduced risk of ischemic heart disease (IHD) in previous studies. Nonetheless, whether those associations reflect a true protective effect of bilirubin on IHD, rather than confounding or reverse causation, remains unknown. Therefore, we applied two-sample Mendelian randomization to evaluate the causal association between bilirubin levels and IHD risk in a Korean population.METHODS: A total of 5 genetic variants—TRPM8 (rs10490012), USP40 (rs12993249), ATG16L1 (rs2119503), SLCO1B1 (rs4149014), and SLCO1B3 (rs73233620)—were selected as genetic instruments for serum bilirubin levels using a community-based cohort, the Korean Genome and Epidemiology Study, comprising 33,598 subjects. We then evaluated their impact on IHD using the Korean Cancer Prevention Study-II cohort.RESULTS: Among the 5 instrumental variables that showed significant associations with serum bilirubin levels, rs12993249 (USP40) showed the most significant association (p<2.36×10−105). However, we found no significant association between serum bilirubin levels and IHD. Sensitivity analyses demonstrated a consistent association, suggesting that our observations were robust.CONCLUSIONS: Using two-sample Mendelian randomization, we found no association between serum bilirubin levels and IHD. Further studies that confirm the observed interactions among other ethnicities are warranted.

The J-curve between Diastolic Blood Pressure and Risk of All-cause and Cardiovascular Death

BACKGROUND AND OBJECTIVES@#The J-curve phenomenon between diastolic blood pressure (DBP) and mortality has been reported repeatedly in treated patients. However, the baseline risk of low DBP has not been fully explored. This study was to examine the relationship between DBP and risk of mortality from all-cause, atherosclerotic vascular diseases (ASCVD), and ischemic heart disease (IHD) using a prospective cohort of general population.@*METHODS@#We analyzed 1,234,435 participants of the Korean Cancer Prevention Study cohort (789,255 men, 30–95 years of age) who had a medical evaluation from 1992 to 1995 using Cox proportional hazards models.@*RESULTS@#A total of 22.5 million person-years were followed up (mean age 46.6 years, deaths 193,903 cases). The hazard ratios of mortality from all-cause and ASCVD, among those with DBP < 60 mmHg compared to 70–79 mmHg were 1.23 (95% confidence interval [CI], 1.16–1.30) and 1.37 (95% CI, 1.20–1.57), respectively, after adjustment for multivariable including systolic blood pressure. Increased risks of all-cause death in the lowest DBP category group were maintained in men or women, 30–59 or ≥60 years of age, smoker or non-smoker and diabetes mellitus (DM) or non-DM subgroups. The risk in DBP 60–69 mmHg groups increased in several subgroups. However, the risk for ASCVD death in 30–59 years and DM group, and risk for IHD death in most subgroups except for elderly (≥60 years) decreased.@*CONCLUSION@#A J-curve relationship between low DBP and all-cause death was found consistently. The baseline risk in the general population may be considered for risk assessment, particularly in case of interventions that lower DBP below 60 mmHg.

The J-curve between Diastolic Blood Pressure and Risk of All-cause and Cardiovascular Death

BACKGROUND AND OBJECTIVES: The J-curve phenomenon between diastolic blood pressure (DBP) and mortality has been reported repeatedly in treated patients. However, the baseline risk of low DBP has not been fully explored. This study was to examine the relationship between DBP and risk of mortality from all-cause, atherosclerotic vascular diseases (ASCVD), and ischemic heart disease (IHD) using a prospective cohort of general population. METHODS: We analyzed 1,234,435 participants of the Korean Cancer Prevention Study cohort (789,255 men, 30–95 years of age) who had a medical evaluation from 1992 to 1995 using Cox proportional hazards models. RESULTS: A total of 22.5 million person-years were followed up (mean age 46.6 years, deaths 193,903 cases). The hazard ratios of mortality from all-cause and ASCVD, among those with DBP < 60 mmHg compared to 70–79 mmHg were 1.23 (95% confidence interval [CI], 1.16–1.30) and 1.37 (95% CI, 1.20–1.57), respectively, after adjustment for multivariable including systolic blood pressure. Increased risks of all-cause death in the lowest DBP category group were maintained in men or women, 30–59 or ≥60 years of age, smoker or non-smoker and diabetes mellitus (DM) or non-DM subgroups. The risk in DBP 60–69 mmHg groups increased in several subgroups. However, the risk for ASCVD death in 30–59 years and DM group, and risk for IHD death in most subgroups except for elderly (≥60 years) decreased. CONCLUSION: A J-curve relationship between low DBP and all-cause death was found consistently. The baseline risk in the general population may be considered for risk assessment, particularly in case of interventions that lower DBP below 60 mmHg.

Screening for Normal Cognition, Mild Cognitive Impairment, and Dementia with the Korean Dementia Screening Questionnaire

OBJECTIVE: The Korean Dementia Screening Questionnaire (KDSQ) is an informant-based instrument used to screen for cognitive dysfunction. However, its ability to only dichotomously discriminate between dementia and normal cognition has been previously investigated. This study investigated the ability of the KDSQ to classify not only dichotomous but also multiple stages of cognitive dysfunction. METHODS: We examined 582 participants. Receiver operating characteristic (ROC) curves were used to determine dichotomous classification parameters. Multi-category ROC surfaces were evaluated to classify the three stages of cognitive dysfunction. RESULTS: Dichotomous classification using the ROC curve analyses showed that the area under the curve was 0.92 for dementia for subjects without dementia and 0.96 for dementia in controls. Simultaneous multi-category classification analyses showed that the volume under the ROC surface (VUS) was 0.57 and that the derived optimal cut-off points were 2 and 8 for controls, MCI, and dementia. The estimated Youden index for the KDSQ was 0.48, and the derived optimal cut-off points were 5 and 10. The overall classification accuracy of the VUS and Youden index was 61.2% and 58.6%, respectively. CONCLUSION: The KDSQ is useful for classifying dichotomous and multi-category stages of cognitive dysfunction.

Central Line-Associated Bloodstream Infection Prevention by Central Venous Catheter Management Staff in the Surgical Intensive Care Unit

PURPOSE: Patients in the intensive care unit (ICU) are more susceptible to nosocomial infections, including central line-associated bloodstream infection (CLABSI), surgical site infection, urinary tract infection or ventilator-associated pneumonia. This study is a comparative analysis of how central venous catheter (CVC) management staff affects CLABSI. METHODS: We performed a two-phase review of all patients transferred to the surgical ICU (SICU) from January 2013 to June 2014. CVC management staff was introduced in October 2013. Electronic medical records provided the data for a comparative analysis of incidence rates and risks of CLABSI, as well as the subjects' general characteristics. RESULTS: This study included 248 patients before the introduction of a CVC management staff member and 196 patients after the introduction. General patient characteristics before and after the CVC management staff was in place did not differ significantly. The CLABSI rate decreased by 4.61 cases/1,000 device days after the introduction (6.26 vs. 1.65; odds ratio, 4.47; 95% confidence interval, 1.39~14.37; p=0.009). However, the mortality rate and length of ICU stay did not change after CVC management staff was in place (12.9% vs. 10.7%, p=0.480; 16.00±24.89 vs. 15.87±18.80, p=0.954; respectively). CONCLUSION: In this study, the introduction of CVC management staff effectively reduced CLABSI rates in current ICU system.

Departmant of Neurology Sırnak State Hospital, Şırnak, Turkey

@#Isolated middle cerebral artery (MCA) dissection with atherosclerosis is a rare entity, and its clinical progression is not well known. We recently came across a case of isolated MCA dissection with atherosclerosis. A 62-year-old man presented to the emergency department with right-sided weakness and mild aphasia. Diffusion-weighted imaging (DWI) showed a multifocal infarction in the left MCA region, and perfusion Magnetic resonance imaging (MRI) detected a moderate time delay in the left MCA region. High-resolution MRI and transfemoral cerebral angiography revealed that the atherosclerotic plaque was accompanied by the dissecting intimal flap. Despite 40 days of antiplatelet therapy, the ischemic stroke recurred and the dissection did not heal. After stenting, the MCA and intracranial circulation revealed a widened lumen and improved flow across the dissection, and no embolic sequelae in the distal intracranial circulation. This case suggest that in MCA dissection with atherosclerosis, early stage intracranial stenting may be a better therapeutic strategy than medical treatment, to prevent recurrent cerebral infarction

Ictal Eletroencephalographic Findings of Nonconvulsive Status Epilepticus Associated With Glufosinate Ammonium Poisoning

No abstract available.

A Prospective Korean Multicenter Study for Infectious Complications in Patients Undergoing Prostate Surgery: Risk Factors and Efficacy of Antibiotic Prophylaxis

This multicenter study was undertaken to determine the efficacy of antibiotic prophylaxis and identify the risk factors for infectious complications after prostate surgery in Korean patients. A total of 424 patients who underwent surgery of the prostate were reviewed. All patients underwent urinalysis and urine culture preoperatively and postoperatively. Efficacy of antibiotic prophylaxis and risk factors for infectious complications were investigated. Infectious complications were observed in 34.9% of all patients. Factors independently associated with infectious complications were diabetes mellitus (adjusted OR, 1.99; 95% CI, 1.09-3.65, P=0.025) and operation time (adjusted OR, 1.08; 95% CI, 1.03-1.13, P=0.004). Clinicians should be aware of the high risk of infectious complications in patients with diabetes and those who undergo a prolonged operation time. Neither the type nor duration of prophylactic antibiotics resulted in differences in infectious complications.

Incontinence Pad Usage in Medical Welfare Facilities in Korea / 대한배뇨장애요실금학회지

PURPOSE: The prevalence of urinary incontinence and the usage of incontinence pads by elderly residents in Korean medical welfare facilities were investigated. METHODS: From a total of 1,832 facilities, 33 medical welfare facilities in the capital area were randomly selected; all nursing homes were excluded. All data were collected by questionnaires to investigate the residents' age and sex, the presence or absence of urinary incontinence, incontinence pad usage per month, and management methods for urinary incontinence. Surveys were also conducted from January 2010 to August 2010. RESULTS: A total number of residents in medical welfare facilities were 2,783, and all of them were selected for this study. Approximately, 65.3% of residents (1,816 individuals) had incontinence. The mean usage was 75 incontinence pads per month. Only 15.6% of residents received proper management for urinary incontinence, while the remaining 84.4% of residents did not have any experience in evaluating or managing their urinary symptoms. CONCLUSIONS: The prevalence of urinary incontinence in medical welfare facilities in Korea was about 65.3%. However, the management of urinary incontinence was insufficient. Urologists should make further efforts for the proper management of urinary incontinence in elders in these facilities.

Socioeconomic Costs of Overactive Bladder and Stress Urinary Incontinence in Korea / 대한배뇨장애요실금학회지

PURPOSE: We quantified and described the economic burden of overactive bladder and stress urinary incontinence in Korea. We calculated direct costs by identifying public and private data sources that contain population-based data on resource utilization by patients with stress urinary incontinence and overactive bladder. METHODS: For estimating indirect costs (productivity loss), the human capital approach was applied. Data were collected from several institutes, including the Health Insurance Review Agency. RESULTS: The estimated total economic cost in treating overactive bladder was 117 billion Korean Won (KRW, the currency of South Koea) in 2006 and 145 billion KRW in 2007. The estimated total cost in treating stress urinary incontinence was 122 billion KRW in 2006 and 59 billion KRW in 2007. CONCLUSIONS: By quantifying the total economic costs of overactive bladder and stress urinary incontinence, this study provides an important perspective in Korea. Because the average age of the Korean population is rapidly increasing, this study provides important information on the direct and indirect costs of overactive bladder and stress urinary incontinence for an aging society.

The Associations between Alcohol Intake and HDL Cholesterol Subclasses in Korean Population

OBJECTIVE: Alcohol intake has been found to be associated with high-density lipoprotein (HDL) cholesterol. However, the association of alcohol intake with HDL cholesterol subclasses is unclear. Therefore, this study was conducted to determine the association between alcohol intake and HDL cholesterol subclasses among Koreans. METHODS: This study included in 1,101 healthy Koreans (men: 765, women: 336) who underwent health check-up at two hospitals in the Korean Cancer Prevention Study 2 (KCPS2). The amounts of alcohol intake were classified into 4 groups: non-, light, moderate, and heavy drinkers (0, or =50.0 g/day, respectively). The proportions of HDL cholesterol subclasses were measured after subclasses were identified by 4-30% gradient gel electrophoresis. Multiple regression models were used to estimate regression coefficients after multivariate adjustments. RESULTS: The concentration of HDL, HDL2 and HDL3 significantly increased with increasing amount of alcohol intake. After adjusted for age, body mass index (BMI), waist and smoking status, alcohol consumers of <12.5 g/day, 12.5-49.9 g/day and more than 50.0g/day showed significant positive associations with HDL, HDL2 and HDL3 concentration when compared to non-alcohol drinkers in men. In particular, The strongest positive associations were obtained with HDL2b and HDL3c. CONCLUSION: HDL2 and HDL3 were significantly associated with increasing amount of alcohol intake in Koreans. In particular, HDL2b among HDL2 and HDL3c among HDL3 showed the strongest positive association with increasing amount of alcohol intake.

Prediction of Colorectal Cancer Risk Using a Genetic Risk Score: The Korean Cancer Prevention Study-II (KCPS-II)

Colorectal cancer (CRC) is among the leading causes of cancer deaths and can be caused by environmental factors as well as genetic factors. Therefore, we developed a prediction model of CRC using genetic risk scores (GRS) and evaluated the effects of conventional risk factors, including family history of CRC, in combination with GRS on the risk of CRC in Koreans. This study included 187 cases (men, 133; women, 54) and 976 controls (men, 554; women, 422). GRS were calculated with most significantly associated single-nucleotide polymorphism with CRC through a genomewide association study. The area under the curve (AUC) increased by 0.5% to 5.2% when either counted or weighted GRS was added to a prediction model consisting of age alone (AUC 0.687 for men, 0.598 for women) or age and family history of CRC (AUC 0.692 for men, 0.603 for women) for both men and women. Furthermore, the risk of CRC significantly increased for individuals with a family history of CRC in the highest quartile of GRS when compared to subjects without a family history of CRC in the lowest quartile of GRS (counted GRS odds ratio [OR], 47.9; 95% confidence interval [CI], 4.9 to 471.8 for men; OR, 22.3; 95% CI, 1.4 to 344.2 for women) (weighted GRS OR, 35.9; 95% CI, 5.9 to 218.2 for men; OR, 18.1, 95% CI, 3.7 to 88.1 for women). Our findings suggest that in Koreans, especially in Korean men, GRS improve the prediction of CRC when considered in conjunction with age and family history of CRC.

Adiponectin is Associated with Impaired Fasting Glucose in the Non-Diabetic Population / 한국역학회지

OBJECTIVES: Adiponectin is strongly associated with diabetes in the Western population. However, whether adiponectin is independently associated with impaired fasting glucose (IFG) in the non-obese population is unknown. METHODS: The serum adiponectin, insulin resistance (IR), and waist circumference (WC) of 27,549 healthy Koreans were measured. Individuals were then classified into tertile groups by gender. IFG was defined as a fasting serum glucose of 100-125 mg/dL without diabetes. IR was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). The association of adiponectin and IFG was determined using logistic regression analysis. RESULTS: WC and adiponectin were associated with IFG in both men and women. However, the association of WC with IFG was attenuated in both men and women after adjustment for the HOMA-IR. Adiponectin was still associated with IFG after adjustment for and stratification by HOMA-IR in men and women. Strong combined associations of IR and adiponectin with IFG were observed in men and women. Multivariate adjusted odds ratios (ORs) (95% confidence interval [CI]) among those in the highest tertile of IR and the lowest tertile of adiponectin were 9.8 (7.96 to 12.07) for men and 24.1 (13.86 to 41.94) for women. CONCLUSION: These results suggest that adiponectin is strongly associated with IFG, and point to adiponectin as an additional diagnostic biomarker of IFG in the non-diabetic population.

Experimental Animal Models of Neurogenic Bladder Dysfunction / 대한배뇨장애요실금학회지

Neurogenic bladder is related to various types of neurogenic disease and injury, including cerebrovascular accident, brain tumor, spinal cord injury, and Parkinson's disease. The results of urodynamic study show different types of detrusor and sphincter function. According to these urodynamic results, the physician decides on a treatment plan, such as anticholinergics or alpha-blockers. In the development of a new medication, it is necessary to test the medication's efficacy and toxicity by using a laboratory animal. The proper laboratory animal should have several characteristics. These are biological similarity to humans, a short generation period, and an environment that is easy to control. We describe the development of laboratory animals for the study of neurogenic bladder by decerebration, stroke, and spinal cord injury.

Association between Alcohol Intake and Abdominal Obesity among the Korean Population / 한국역학회지

OBJECTIVES: Although abdominal obesity has been reported to be highly related with alcohol intake, the results are still inconclusive. Therefore, this study was conducted to explore the association between alcohol and abdominal obesity among the Korean population. METHODS: This study included 8,603 participants (men: 5,195, women: 3,408) aged 30 to 87 who visited the health promotion centers in Seoul for routine health examinations from April, 2006 to June, 2007. Abdominal obesity was defined as WC > or =90 cm for men and > or =85 cm for women in accordance with the Korean Society for the Study of Obesity. For ever drinkers, total alcohol consumption in grams was classified into four groups (group 1, non-drinkers; group 2, 1-10 g of alcohol per day; group 3, 11-20 g of alcohol per day; and group 4, over 20 g of alcohol per day). RESULTS: The mean age of the study population was 45.4 yr old (men) and 45.3 yr (women). The average waist circumference was 85.3 cm in men and 75.3 cm in women. A high alcohol intake was associated with high waist circumference in both genders. In multivariate analysis, the group of men and women drinkers consuming >20 g in a day had a large waist circumference compared with men and women non-drinkers. CONCLUSION: This study showed that a high alcohol intake was related to high waist circumference. Such association remained independently even after adjustment for smoking, which is strongly related to abdominal obesity.

Multiple Epidermoid Cysts Arising from the Extratesticular Scrotal, Spermatic Cord and Perineal Area

An extratesticular scrotal epidermoid cyst is a relatively very rare condition, and an epidermoid cyst arising from the spermatic cord area is extremely rare. We report a case of multiple epidermoid cysts arising from the extratesticular scrotum, spermatic cord, and lower extremities. To our best knowledge, concomitant occurrence of these lesions has not been reported previously in the literature.