Tae-Hoon Lee

Serum aminotransferase activity and mortality risk in a United States community

Serum aminotransferase [such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] is commonly used as an indicator of liver disease. The aim of the study was to determine the degree to which aminotransferase results are associated with increased mortality at the population level. All adult residents of Olmsted County, Minnesota, who had a health care encounter at Mayo Clinic, Rochester, in 1995 were identified and their AST or ALT results extracted from a laboratory database. These subjects were followed forward from January 1995 to April 2006 and their survival determined. To exclude patients with abnormal results because of a terminal illness, deaths within the first 2 years were excluded. The main outcome measure was survival. Standardized mortality ratios (SMRs) were calculated, based on Minnesota White death rates. During 1995, AST was measured at least once in 18,401 community residents, of whom 2,350 (13%) had results greater than the upper limit of normal (ULN). Of 6,823 subjects who had their ALT measured, 911 (13%) had results higher than ULN. Abnormal AST was associated with a significantly increased SMR (1.32 for 1–2× ULN and 1.78 for >2× ULN). SMR was also higher for abnormal ALT (SMR = 1.21 for 1–2× ULN and 1.51 for >2× ULN). In contrast, normal AST or ALT was associated with a risk of death lower than expected (SMR 0.95 for AST, 0.61 for ALT). Conclusion: Serum levels of AST and ALT obtained in a routine medical care setting are associated with future mortality in community residents. (HEPATOLOGY 2008;47:880–887.)

The Caenorhabditis elegans AMP-activated Protein Kinase AAK-2 Is Phosphorylated by LKB1 and Is Required for Resistance to Oxidative Stress and for Normal Motility and Foraging Behavior

AAK-2 is one of two α isoforms of the AMP-activated protein kinase in Caenorhabditis elegans and is involved in life span maintenance, stress responses, and germ cell cycle arrest upon dauer entry. We found that AAK-2 was phosphorylated at threonine 243 in response to paraquat treatment and that this phosphorylation depends on PAR-4, the C. elegans LKB1 homologue. Both aak-2 mutation and par-4 knockdown increased the sensitivity of C. elegans worms to paraquat, and the double deficiency did not further increase sensitivity, indicating that aak-2 and par-4 act in a linear pathway. Both mutations also slowed body bending during locomotion and failed to reduce head oscillation in response to anterior touch. Consistent with this abnormal motility and behavioral response, expression of the AAK-2::green fluorescent protein fusion protein was observed in the ventral cord, some neurons, body wall muscle, pharynx, vulva, somatic gonad, and excretory cell. Our study suggests that AMPK can influence the behavior of C. elegans worms in addition to its well known function in metabolic control.

Caenorhabditis elegans mitofilin homologs control the morphology of mitochondrial cristae and influence reproduction and physiology

Human mitofilin is a mitochondrial protein that controls cristae formation. Here, we investigated the role of the Caenorhabditis elegans mitofilin homologs, IMMT‐1 and ‐2, in reproduction, physiology, and mitochondrial cristae formation. Mutation of either immt‐1 or immt‐2 produced defects in germline development and egg‐laying. These defects were exacerbated by the double mutation, which greatly reduced motility, increased levels of reactive oxygen species, decreased mitochondrial mass, and imparted resistance to oxidative stress. Cryo‐electron microscopy and electron tomography revealed that each of the single mutations resulted in curved and stacked mitochondrial crista tubules as well as a reduced number of crista junctions. The immt‐2 mutation was also associated with the presence of outer mitochondrial membrane pores, which were larger in the double mutant. IMMT‐1 and IMMT‐2 proteins were localized to the inner mitochondrial membrane, as seen by immunoelectron microscopy, and they behaved as oligomers or large complexes with F1F0 ATP synthase in native polyacrylamide gel electrophoresis. These findings suggest that the two C. elegans mitofilin isoforms have non‐overlapping functions in controlling mitochondrial cristae formation. J. Cell. Physiol. 224: 748–756, 2010.

Evaluation of Elevated Liver Enzymes

Liver enzymes, including aminotransferases and alkaline phosphatase, are some of the most commonly ordered blood tests in a physicians practice. These enzymes have been valuable in screening for liver disease, as well as in diagnosing and monitoring patients with acute and chronic hepatobiliary disorders. Patients with predominantly aminotransferase elevations are thought to have acute or chronic hepatitis from a variety of causes. In patients with predominantly alkaline phosphatase elevations, imaging evaluation is undertaken upfront to exclude large bile duct disorders and infiltrative/mass lesions. A liver biopsy may be reserved for patients for whom these less invasive investigations are unfruitful.

Survival after liver transplantation: Is racial disparity inevitable?

Previous analyses have reported that minority patients undergoing orthotopic liver transplantation (OLT) have poorer survival than Caucasian recipients. The reason for this disparity is unclear. We examined whether racial differences in survival exist at select academic OLT centers. OLT recipients from 4 academic centers were prospectively enrolled in 2 multicenter databases. Data including demographics, liver disease diagnosis, and post‐OLT follow‐up were obtained for 2823 (135 African, 2448 Caucasian, and 240 other race) adult patients undergoing primary OLT between 1985 and 2000. The survival of patients and grafts after OLT was compared across race. The Kaplan‐Meier estimates for 1‐year recipient survival were 90.8% [95% confidence interval (CI): 86.0–95.9] for African Americans, 86.5% (95% CI: 85.1–87.9) for Caucasians, and 84.4% (95% CI: 79.8–89.2) for other races. The 5‐year recipient survival probability was 69.2% (95% CI: 60.1–79.7) for African Americans, 72.2% (95% CI: 70.1–74.4) for Caucasians, and 67.5% (95% CI: 60.5–75.3) for other races. The 10‐year recipient survival probability for African Americans was 54.4% (95% CI: 41.1–72.1), for Caucasians 50.7% (95% CI: 46.4–55.3), and for other races 55.7% (95% CI: 41.5–74.8). There was no difference in patient survival (P = 0.162) or graft survival (P = 0.582) among racial groups. A multivariable proportional hazards model confirmed the absence of an association between race and post‐OLT survival after adjustments for age, gender, total bilirubin, creatinine, prothrombin time, and diagnosis. Conclusion: These data demonstrate that as a proof of principle, minority OLT recipients should not necessarily expect an OLT outcome inferior to that of Caucasians. (HEPATOLOGY 2007.)

Deleted in cancer 1 (DICE1) is an essential protein controlling the topology of the inner mitochondrial membrane in C. elegans.

DICE1 (deleted in cancer 1), first identified in human lung carcinoma cell lines, is a candidate tumor suppressor, but the details of its activity remain largely unknown. We have found that RNA interference of its C. elegans homolog (DIC-1) produced inviable embryos with increased apoptosis, cavities in cells and abnormal morphogenesis. In the dic-1(RNAi) germ line, ced-3-dependent apoptosis increased, and cell cavities appeared at the late-pachytene/oogenic stage, leading to defective oogenesis. Immunofluorescence microscopy of DIC-1 revealed its ubiquitous expression in the form of cytoplasmic foci, and cryoelectron microscopy narrowed down the location of the foci to the inner membrane of mitochondria. After dic-1 RNAi, mitochondria had an irregular morphology and contained numerous internal vesicles. Homozygous embryos from a heterozygous dic-1 mother arrested at the L3 larval stage, in agreement with the essential role of DIC-1 in mitochondria. In summary, C. elegans DIC-1 plays a crucial role in the formation of normal morphology of the mitochondrial cristae/inner membrane. Our results suggest that human DICE1 may have several functions in multiple intracellular locations.

Effect of working hours and precarious employment on depressive symptoms in South Korean employees: a longitudinal study

Objectives Long working hours and precarious employment are relatively common in South Korea. Since both can impact on mental health, this study examined their independent and combined effects on depressive symptoms of employees. Methods Data were from the Korean Welfare Panel Study (KOWEPS), 2010–2013. A total of 2733 full-time employees without depressive symptoms were analysed. Hierarchical logistic regression models were used to investigate the effect of the number of working hours per week (eg, 35–40u2005hours, 41–52u2005hours, 53–68u2005hours, and >68u2005hours) and employment status (permanent vs precarious employment) on depressive symptoms, measured using the Center for Epidemiological Studies Depression (CES-D) 11 scale. Results Compared with individuals working 35–40u2005hours/week, employees working above 68u2005hours (OR 1.57, 95% CI 1.05 to 2.34) had higher odds of depressive symptoms after full adjustment. Similarly, precarious employees (OR 1.34, 95% CI 1.02 to 1.75) showed worse mental health than permanent employees. In the combined effect model, employees in precarious employment who worked above 68u2005hours/week (OR, 2.03 95% CI 1.08 to 3.83) exhibited the highest odds of depressive symptoms compared with permanent employees working 35 to 40u2005hours/week. Conclusions Long work hours and precarious employment status were associated with higher odds of depressive symptoms. The findings highlight the importance of monitoring and addressing the vulnerable groups of employees to reduce the mental health burden of economically active individuals.

Simple self-tuned notch filter in a bio-potential amplifier

INTERFERENCE FROM power lines is a common problem during the measurement of bio-potential signals. Although the construction of a high CMRR differential amplifier, signal and power isolation, and right leg-driven technique (HUNTER and WEBSTER, 1973) are incorporated into the design of a biopotential amplifier, line frequency potentials may appear as normal mode signals, owing to source imbalance and the nonideal properties of the amplifiers and passive components. In a bio-potential amplifier, analogue notch filters have generally been used to remove any remaining interference. To minimise signal loss from the filtering process, the narrowbandwidth property (high Q) of the notch filter is incorporated. However, the frequency of the power lines always deviates from the centre frequency (50 or 60 Hz). As a result, the performance of this type of notch filters is often degraded. If digital methods (LEVKOV et al., 1984; SCHEER, 1987; CHRISTOY and DOTSINSKY, 1988; YAN, 1993) are employed in realtime, digital signal processors or complex logic circuits are required. In this work, a line frequency rejection filter is designed using a switched capacitor filter (SCF) and a phase locked loop (PLL). It is simple and capable of achieving high Q performance under the line frequency variation.

DIC-1 over-expression enhances respiratory activity in Caenorhabditis elegans by promoting mitochondrial cristae formation.

Deficiency of the Caenorhabditis elegans protein, DIC‐1, located in the inner membrane of mitochondria produces an abnormal mitochondrial morphology. The mechanism by which DIC‐1 controls the topology of the inner membrane was investigated by transiently over‐expressing DIC‐1 in C. elegans. Cryo‐electron microscopy showed that DIC‐1 over‐expression greatly increased the number and fractional area of mitochondrial cristae, suggesting that DIC‐1 actively participates in cristae formation. These morphological changes were accompanied by increases in the oxygen consumption rate and ATP content of C. elegans worms, and decreases in reactive oxygen species (ROS) and sensitivity to paraquat. DIC‐1 knockdown induced the opposite changes in ATP, ROS and paraquat‐sensitivity. The ability of DIC‐1 to increase cristae formation and secondarily, oxidative phosphorylation, suggests a potential use of this factor to control mitochondrial activity.

Effect of Socioeconomic Status on the Linkage Between Suicidal Ideation and Suicide Attempts

Previous suicide attempts are a leading risk factor for completed suicide. To identify specific characteristics of those at high risk for attempts, we investigated associations with socioeconomic status (SES). Data from the 2013 Korean Community Health Survey (KCHS) included adults who reported suicidal ideation (Nxa0=xa0220,245). Attempts in the past 12xa0months were assessed. Associations of demographic, socioeconomic, and suicide-related behavioral factors were analyzed using multiple logistic regression. Among those with suicidal ideation, 862 (3.9%) had attempted suicide. After stratification by age and gender, results showed that low education and unemployed young adult men and women had significantly higher rates of attempts. The lowest income level was associated with significantly higher rates of attempts in only young adult women. Among those with the lowest and highest income, the association between ideation and attempts was attenuated, whereas it was enhanced among other income groups.