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Beneficial effects of omega-3 fatty acid (O3FA) supplementation in a wide range of disease condition have been well studied. However, there is limited information regarding the effects of O3FAs on chronic kidney disease (CKD), especially in diabetic nephropathy (DN) with hypertriglyceridemia. We investigate whether O3FA supplementation could help maintain renal function in patients with diabetes and hypertriglyceridemia. Total 344 type 2 diabetic patients with a history of O3FA supplementation for managing hypertriglyceridemia were included. Reduction in urine albumin to creatinine ratio (ACR) and glomerular filtrate rate (GFR) were examined. Subgroup analyses were stratified according to the daily O3FA doses. Serum total cholesterol, triglyceride, and urine ACR significantly reduced after O3FA supplementation. Overall, 172 (50.0%) patients did not experience renal function loss, and 125 (36.3%) patients had a GFR with a positive slope. The patients treated with O3FAs at 4g/day showed greater maintenance in renal function than those treated with lower dosages (p < 0.001). This dose dependent effect remains significant after adjustment for multiple variables. O3FA supplementation in diabetic patients with hypertriglyceridemia shows benefits of reducing albuminuria and maintaining renal function. The effects are dependent on the dose of daily O3FA supplementation.

The breakage of an epidural catheter is a rare complication during the removal of a thoracic epidural catheter. There are many causes to breakage of an epidural catheter, such as the characteristics of the catheter itself, patient's factors (anatomy, position during insertion and removal of the catheter, and the BMI), and the difficulty of the procedure. Surgical removal is considered if there is a possibility that the retained catheter might cause neurological problems. We experienced a breakage of an epidural catheter during its removal, which led to surgical intervention. To prevent the catheter breakage during its removal, the catheter should be withdrawn without excessive tension. In addition, an understanding of the patient's anatomy is essential.

OBJECTIVES: Single-pill combination therapy (amlodipine/atorvastatin) might be more effective than double-pill therapy (amlodipine+atorvastatin) in patients with diabetes and concomitant hypertension requiring statin therapy. We compared the cost-effectiveness of a single-pill with that of double-pill for control of low density lipoprotein cholesterol (LDL-C) levels, with the ultimate goal of cardiovascular disease prevention, in these patients using a cost-effectiveness analysis model that considered medication adherence. METHODS: Effectiveness was defined as the percentage (%) attainment of target LDL-C levels (

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a prevalent and rapidly increasing disease worldwide; however, no widely accepted screening models to assess the risk of NAFLD are available. Therefore, we aimed to develop and validate a self-assessment score for NAFLD in the general population using two independent cohorts.MethodsThe development cohort comprised 15676 subjects (8313 males and 7363 females) who visited the National Health Insurance Service Ilsan Hospital in Korea in 2008-2010. Anthropometric, clinical, and laboratory data were examined during regular health check-ups and fatty liver diagnosed by abdominal ultrasound. Logistic regression analysis was conducted to determine predictors of prevalent NAFLD and to derive risk scores/models. We validated our models and compared them with other existing methods using an external cohort (N = 66868).ResultsThe simple self-assessment score consists of age, sex, waist circumference, body mass index, history of diabetes and dyslipidemia, alcohol intake, physical activity and menopause status, which are independently associated with NAFLD, and has a value of 0-15. A cut-off point of ≥ 8 defined 58% of males and 36% of females as being at high-risk of NAFLD, and yielded a sensitivity of 80% in men (77% in women), a specificity of 67% (81%), a positive predictive value of 72% (63%), a negative predictive value of 76% (89%) and an AUC of 0.82 (0.88). Comparable results were obtained using the validation dataset. The comprehensive NAFLD score, which includes additional laboratory parameters, has enhanced discrimination ability, with an AUC of 0.86 for males and 0.91 for females. Both simple and comprehensive NAFLD scores were significantly increased in subjects with higher fatty liver grades or severity of liver conditions (e.g., simple steatosis, steatohepatitis).ConclusionsThe new non-laboratory-based self-assessment score may be useful for identifying individuals at high-risk of NAFLD. Further studies are warranted to evaluate the utility and feasibility of the scores in various settings.

BACKGROUND:Glycated albumin (GA) has been increasingly used as a reliable index for short-term glycemic monitoring, and is inversely associated with β-cell function. Because the pathophysiologic nature of type 2 diabetes (T2D) is characterized by progressive decline in insulin secretion, the aim was to determine whether GA levels were affected by diabetes duration in subjects with T2D. METHODS:To minimize the effect of glucose variability on GA, subjects with stably maintained HbA1c levels of 1 year (n = 781) were recruited and categorized as New-T2D and Old-T2D, respectively. Biochemical, glycemic, and C-peptide parameters were measured. RESULTS:GA levels were significantly elevated in HbA1c-matched Old-T2D subjects compared to New-T2D subjects. Duration of diabetes was positively correlated with GA, whereas a negative relationship was found with C-peptide increment (ΔC-peptide). Among insulin secretory indices, dynamic parameters such as ΔC-peptide were inversely related to GA (r = -0.42, p

Transthyretin (TTR) is a known carrier protein for thyroxine (T4) and retinol-binding protein in the blood that is primarily synthesized in the liver and choroid plexus of the brain. Herein, we report that the TTR gene is expressed in skeletal muscle tissue and up-regulated during myotube formation in C2C12 cells. TTR silencing (TTRkd) significantly reduced myogenin expression and myotube formation, whereas myogenin silencing (MYOGkd) did not have any effect on TTR gene expression. Both TTRkd and MYOGkd led to a decrease in calcium channel related genes including Cav1.1, STIM1 and Orai1. A significant decrease in intracellular T4 uptake during myogenesis was observed in TTRkd cells. Taken together, the results of this study suggest that TTR initiates myoblast differentiation via affecting expression of the genes involved during early stage of myogenesis and the genes related to calcium channel.

Metformin is known to alleviate hepatosteatosis by inducing 5’ adenosine monophosphate (AMP)-kinase-independent, sirtuin 1 (SIRT1)-mediated autophagy. Dysfunctional mitophagy in response to glucolipotoxicities might play an important role in hepatosteatosis. Here, we investigated the mechanism by which metformin induces mitophagy through restoration of the suppressed Parkin-mediated mitophagy. To this end, our ob/ob mice were divided into three groups: (1) ad libitum feeding of a standard chow diet; (2) intraperitoneal injections of metformin 300 mg/kg; and (3) 3 g/day caloric restriction (CR). HepG2 cells were treated with palmitate (PA) plus high glucose in the absence or presence of metformin. We detected enhanced mitophagy in ob/ob mice treated with metformin or CR, whereas mitochondrial spheroids were observed in mice fed ad libitum. Metabolically stressed ob/ob mice and PA-treated HepG2 cells showed an increase in expression of endoplasmic reticulum (ER) stress markers and cytosolic p53. Cytosolic p53 inhibited mitophagy by disturbing the mitochondrial translocation of Parkin, as demonstrated by immunoprecipitation. However, metformin decreased ER stress and p53 expression, resulting in induction of Parkin-mediated mitophagy. Furthermore, pifithrin-α, a specific inhibitor of p53, increased mitochondrial incorporation into autophagosomes. Taken together, these results indicate that metformin treatment facilitates Parkin-mediated mitophagy rather than mitochondrial spheroid formation by decreasing the inhibitory interaction with cytosolic p53 and increasing degradation of mitofusins.

The global prevalence of diabetes is rapidly increasing. Studies support the necessity of screening and interventions for prediabetes, which could result in serious complications and diabetes. This study aimed at developing an intelligence-based screeningmodel for prediabetes. Data from the Korean National Health and Nutrition Examination Survey (KNHANES) were used, excluding subjects with diabetes. The KNHANES 2010 data (n = 4685) were used for training and internal validation, while data from KNHANES 2011 (n = 4566) were used for external validation. We developed two models to screen for prediabetes using an artificial neural network (ANN) and support vector machine (SVM) and performed a systematic evaluation of the models using internal and external validation. We compared the performance of our models with that of a screening score model based on logistic regression analysis for prediabetes that had been developed previously. The SVM model showed the areas under the curve of 0.731 in the external datasets, which is higher than those of the ANN model (0.729) and the screening score model (0.712), respectively. The prescreening methods developed in this study performed better than the screening score model that had been developed previously and may be more effective method for prediabetes screening. [ABSTRACT FROM AUTHOR]

AIM: Glucagon is an essential regulator of hepatic glucose production (HGP), which provides an alternative therapeutic target for managing type 2 diabetes with glucagon antagonists. We studied the effect of a novel human monoclonal antibody against glucagon receptor (GCGR), NPB112, on glucose homeostasis in diet-induced obese (DIO) mice. METHODS: The glucose-lowering efficacy and safety of NPB112 were investigated in DIO mice with human GCGR for 11 weeks, and a hyperinsulinemic-euglycemic clamp study was conducted to measure HGP. RESULTS: Single intraperitoneal injection of NPB112 with 5 mg/kg effectively decreased blood glucose levels in DIO mice for 5 days. A significant reduction in blood glucose was observed in DIO mice treated with NPB112 at a dose ≥5 mg/kg for 6 weeks, and its glucose-lowering effect was dose-dependent. Long-term administration of NPB112 also caused a mild 29% elevation in glucagon level, which was returned to the normal range after discontinuation of treatment. The clamp study showed that DIO mice injected with NPB112 at 5 mg/kg were more insulin sensitive than control mice, indicating amelioration of insulin resistance by treatment with NPB112. DIO mice treated with NPB112 showed a significant improvement in the ability of insulin to suppress HGP, showing a 33% suppression (from 8.3 mg/kg/min to 5.6 mg/kg/min) compared to the 2% suppression (from 9.8 mg/kg/min to 9.6 mg/kg/min) in control mice. In addition, no hypoglycemia or adverse effect was observed during the treatment. CONCLUSIONS: A novel human monoclonal GCGR antibody, NPB112, effectively lowered the glucose level in diabetic animal models with mild and reversible hyperglucagonemia. Suppression of excess HGP with NPB112 may be a promising therapeutic modality for the treatment of type 2 diabetes.

Background: Traditionally, tinnitus accompanied by hemifacial spasm has been considered a type of hyperactive neurovascular compression syndrome that is similar to hemifacial spasm alone because of the anatomically close relationship between the facial nerve and cochlear nerve as well as the hyperactive clinical nature. Methods: Participants were 29 subjects who presented with hemifacial spasm and neuroradiological evidence of vascular compression of the cranial (facial/cochlear) nerve. We used magnetoencephalography (MEG) to estimate the activity of the cochlear nerve in patients with and without tinnitus on the ipsilateral side. We compared the difference in the latency and the ratio of the equivalent current dipole (ECD) strength between the ipsilateral and contralateral sides of the spasm and tinnitus. Results: Cochlear nerve activity in patients with tinnitus was increased with a shorter latency (p = 0.016) and stronger ECD strength (p = 0.028) compared with patients without tinnitus. Conclusion: The MEG results from normal-hearing patients who had tinnitus accompanied by hemifacial spasm suggest that the hyperactivity of the auditory central nervous system may be a crucial pathophysiological factor in the generation of tinnitus in these patients. The neurovascular compression that causes sensory input from the pathologic facial nerve activity may contribute to this hyperactivity of the central auditory nervous system. [ABSTRACT FROM AUTHOR]

Glycated albumin (GA) is recognized as a reliable marker for short-term glycemic monitoring in diabetic patients. We investigated the clinical relevance of GA and the ratio of GA to glycated hemoglobin (A1c) in Korean type 2 diabetic patients. In this retrospective study, we compared A1c, GA, and the GA/A1c ratio and analyzed the relationship between glycemic indices and various parameters in 1,038 Korean type 2 diabetic patients. The patients were divided into two groups: a stably maintained A1c group whose A1c levels did not fluctuate by more than 0.5% for at least 6 months and an unstably maintained A1c group whose A1c levels fluctuated by more than 0.5%. Serum GA was strongly correlated with A1c in both groups. Fasting plasma glucose and postprandial glucose were correlated with GA in unstably maintained A1c group, whereas they were correlated with A1c in stably maintained A1c group. The GA/A1c ratio tended to increase as A1c increased. Postprandial glucose and body mass index affected the GA/A1c ratio. Our data show that serum GA may be a more useful glycation index than A1c for monitoring glycemic control in type 2 diabetic patients with fluctuating and poorly controlled glycemic excursions. [ABSTRACT FROM AUTHOR]

Magnetocardiography (MCG) is a device to measure the weak magnetic fields generated from the heart using a superconducting quantum interference device sensor which converts magnetic flux to voltage and is the most sensitive sensor to detect magnetism. In the previous study, authors found that the values of MCG parameters of patients with non-ST-segment myocardial infarction were greater than those of age-matched controls (AMCs). In this study, we selected five different groups of patients considering their severity. We compared 10 MCG parameters recorded from 19 healthy young subjects (26.8 ± 13.4 years), 19 age-matched healthy subjects (55.4 ± 10.7), 23 stable angina patients (56.4 ± 7.6 years) with no stenosis (= 0% on coronary angiogram) and normal echocardiogram, 24 unstable angina patients (61.9 ± 9.8 years) with severe stenosis (ࣙ70%), and 20 Q-wave myocardial infarction (QMI) patients (57.3 ± 11.2 years) with severe stenosis (ࣙ70%). To record the magnetic signals from a heart with minimal noise, a magnetically shielded room was used. The number of abnormal parameters was counted and magnetic field map (MFM) patterns were compared. As a result, young healthy subjects showed the smallest values in all 10 MCG parameters and QMI subjects showed the greatest values. Significant difference was found from dynamics parameters such as current angle, map angle, and distance dynamics between young healthy controls and AMC groups (p < 0.05). No significant difference was found from AMC and stable angina groups even though parameter values of stable angina were slightly greater than those of AMC. Significant difference was found from five parameters between AMC and QMI subjects. These results are supportive to the previous analysis. In addition, the abnormal MCG parameters increased when the ischemic disease was worsened. Abnormal MFM patterns were easily found from QMI patients than stable angina pectoris. It is clear that abnormal MFM and parameters increase when the status of ischemic heart disease patients are getting worse. [ABSTRACT FROM AUTHOR]

Magnetocardiography (MCG) using a superconducting quantum interference device (SQUID) sensor has been known for a noninvasive, noncontact, and safe diagnostic tool to detect ischemic heart disease such as angina and myocardial infarction. The magnetic distribution generated by the electrical activation of the heart reveals the abnormality of the myocardial status. The bust depth of people in 20s and 70s are much different, and the greatest difference is up to 154 mm. The purpose of this study is to identify whether MCG signals and parameter values are changed at the different locations of the SQUID sensor assembly. It would be an important reference for the standard measurement. Four healthy male subjects (33.3 ± 6.3 years) participated in this study. The distance between the chest surface and the bottom of the sensor assembly was 20, 40, 60, and 80 mm. Recording was made using 64-channel MCG system (axial type, first-order gradiometer) developed by Korea Research Institute of Standards and Science (KRISS). MCG were recorded for 30 s in a magnetically shielded room. As the sensor location is getting away from the chest surface; the each mean amplitude of R- and T-wave peak decreases to 70% (at 40-mm distance), 51% and 50% (at 60mm), and 38% and 35% (at 80mm) of the reference amplitude measured at 20-mm distance (y = -0.000002*x3 + 0.0003*x2 - 0.0308*x + 1.4961, R2 = 1.00; where y = averageamplitude remained after reduction), x distance between the chest surface and sensor location). Interindividual difference was less than 5%. The regression equations may be used as a good reference to calculate how much strength will be decreased by the distance. In MCG parameters, most parameters decreased when the distance increased. As an example, the current moment at T-wave peak reduced to 52% (at 40-mm distance), 33% (at 60 mm), and 19% (at 80 mm). Results showed how MCG signal and parameter values decreased rapidly when the sensor assembly was located far from the signal source. The study results may be used as a useful reference to design MCG system and analysis program. [ABSTRACT FROM AUTHOR]

An optical receiver system composing 13 serial data restore/synchronizer modules and a single module combiner converted optical 32-bit serial data into 32-bit synchronous parallel data for a computer to acquire 152-channel magnetoencephalography (MEG) signals. A serial data restore/synchronizer module identified 32-bit channel-voltage bits from 48-bit streaming serial data, and then consecutively reproduced 13 times of 32-bit serial data, acting in a synchronous clock. After selecting a single among 13 reproduced data in each module, a module combiner converted it into 32-bit parallel data, which were carried to 32-port digital input board in a computer. When the receiver system together with optical transmitters were applied to 152-channel superconducting quantum interference device sensors, this MEG system maintained a field noise level of 3 fT/√Hz @ 100 Hz at a sample rate of 1 kSample/s per channel. [ABSTRACT FROM AUTHOR]