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Aim Omega-3 fatty acid ethyl ester supplements, available by prescription, are common in the treatment of dyslipidaemia in humans. Recent studies show that 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), a metabolite formed from fish oil supplementation, was able to prevent and reverse high fat diet (HFD)-induced fatty liver in mice. In the present study, we investigated the underlying molecular mechanisms responsible for CMPF's hepatic lipid-lowering effects. Materials and methods CD1 male mice were i.p. injected with CMPF (dosage, 6 mg/kg) for 7 days, followed by 5 weeks of a 60% HFD to induce a fatty liver phenotype. Metabolic parameters, liver morphology, lipid content, protein expression and microarray analysis were assessed. We also utilized primary hepatocytes, an in vitro model, to further investigate the direct effects of CMPF on hepatic lipid utilization and biosynthesis. Results CMPF-treated mice display enhanced hepatic lipid clearance while hepatic lipid storage is prevented, thereby protecting against liver lipid accumulation and development of HFD-induced hepatic insulin resistance. Mechanistically, as CMPF enters the liver, it acts as an allosteric acetyl-coA carboxylase (ACC) inhibitor, which directly induces both fatty acid oxidation and hepatic production of fibroblast growth factor 21 (FGF21). A feed-back loop is initiated by CMPF, which exists between ACC inhibition, fatty acid oxidation and production of FGF21. As a consequence, an adaptive decrease in Insig2/SREBP-1c/FAS protein expression results in priming of the liver to prevent a HFD-induced fatty liver phenotype. Conclusion CMPF is a potential driver of hepatic lipid metabolism, preventing diet-induced hepatic lipid deposition and insulin resistance in the long term.

Objectives: This study was carried out to evaluate the effect of noise exposure and aging on changes in hearing threshold level and the relationship between age and noise. Materials: The author selected 274 male shipyard and assembly line workers as the noise exposed group and 582 males not exposed to noise as the general population group. Data were collected from five years of consecutive annual audiometric tests performed from 2008 to 2012. Results: In the general population and noise exposed groups, there was a reverse phenomenon that hearing threshold level for 2009 was lower than that of 2008, which seemed to be due to the learning effect, but from 2010 hearing threshold level increased. In the noise exposed group, the mean hearing threshold level in the left ear was significantly higher than that for right ear. In the general population group, the older was the age, the higher was the hearing threshold level, especially at 4000 Hz. In the general population and noise exposed groups, frequency, age group and noise exposure independently affected hearing threshold level, and there was no relationship between age and noise exposure. Over all frequencies, the change of hearing threshold level was larger in the noise exposed group than in the general population group. In the noise exposed group below thirty years old, the change at 4000 Hz was remarkable. Conclusions: Age and noise exposure seem to affect hearing threshold level independently and contribute to an additive effect on hearing threshold level.

Data were collected from 5,899 males between 30 and 59 years old by interview, survey, physical examination, blood test, and multidetector computed tomography in the university hospital from January 2010 to December 2011. We confirmed the coronary artery calcium scores of subjects by multidetector computed tomography and identified risk factors of cardiovascular disorders. We investigated the relationship between coronary artery calcification and risk factors of cardiovascular disorders.

Background/Aims Globus is a foreign body sense in the throat without dysphagia, odynophagia, esophageal motility disorders, or gastroesophageal reflux. The etiology is unclear. Previous studies suggested that increased upper esophageal sphincter pressure, gastroesophageal reflux and hypertonicity of esophageal body were possible etiologies. This study was to quantify the upper esophageal sphincter (UES) pressure, contractile front velocity (CFV), proximal contractile integral (PCI), distal contractile integral (DCI) and transition zone (TZ) in patient with globus gastroesophageal reflux disease (GERD) without globus, and normal controls to suggest the correlation of specific high-resolution manometry (HRM) findings and globus. Methods Fifty-seven globus patients, 24 GERD patients and 7 normal controls were studied with HRM since 2009. We reviewed the reports, and selected 5 swallowing plots suitable for analysis in each report, analyzed each individual plot with ManoView. The 5 parameters from each plot in 57 globus patients were compared with that of 24 GERD patients and 7 normal controls. Results There was no significant difference in the UES pressure, CFV, PCI and DCI. TZ (using 30 mmHg isobaric contour) in globus showed significant difference compared with normal controls and GERD patients. The median values of TZ were 4.26 cm (interquartile range [IQR], 2.30-5.85) in globus patients, 5.91 cm (IQR, 3.97-7.62) in GERD patients and 2.26 cm (IQR, 1.22-2.92) in normal controls (P = 0.001). Conclusions HRM analysis suggested that UES pressure, CFV, PCI and DCI were not associated with globus. Instead increased length of TZ may be correlated with globus. Further study comparing HRM results in globus patients within larger population needs to confirm their correlation.

Shift work is closely related with workers' health. In particular, sleep is thought to be affected by shift work. In addition, shift work has been reported to be associated with the type or direction of shift rotation, number of consecutive night shifts, and number of off-duty days. We aimed to analyze the association between the night shift rotation interval and the quality of sleep reported by Korean female shift workers.In total, 2,818 female shift workers from the manufacturing industry who received an employee physical examination at a single university hospital from January to August in 2014 were included. Subjects were classified into three groups (A, B, and C) by their night shift rotation interval. The quality of sleep was measured using the Korean version of the Pittsburgh Sleep Quality Index (PSQI). Descriptive analysis, univariate logistic regression, and multivariate logistic regression were performed.With group A as the reference, the odds ratio (OR) for having a seriously low quality of sleep was 1.456 (95% CI 1.171-1.811) and 2.348 (95% CI 1.852-2.977) for groups B and C, respectively. Thus, group C with the shortest night shift rotation interval was most likely to have a low quality of sleep. After adjustment for age, obesity, smoking status, alcohol consumption, exercise, being allowed to sleep during night shifts, work experience, and shift work experience, groups B and C had ORs of 1.419 (95% CI 1.134-1.777) and 2.238 (95% CI 1.737-2.882), respectively, compared to group A.Our data suggest that a shorter night shift rotation interval does not provide enough recovery time to adjust the circadian rhythm, resulting in a low quality of sleep. Because shift work is influenced by many different factors, future studies should aim to determine the most optimal shift work model and collect accurate, prospective data.

Growth hormone insensitivity syndrome (GHIS), a genetic disease characterized by growth retardation combined with high serum concentration of growth hormone (GH) and low insulin-like growth factor 1 (IGF-1) levels, can be caused by mutations in the GH receptor (GHR) gene. We investigated the molecular defects in the GHR gene in a patient with neurofibromatosis type 1 (NF-1). The patient, a 2-year-old boy with NF-1, was assessed on his short stature by auxological, biochemical and molecular studies. Height of the patient and his family members were measured and compared to normal control. Serum concentrations of GH, IGF-1 and IGF-binding protein 3 (IGFBP3) in the patient were measured during a GH stimulation test. We examined the GHR gene in the patient and his parents. Genomic DNA and mRNA of the GHR gene were extracted from peripheral lymphocytes. All the exons and the flanking regions of the GHR gene were amplified by PCR, and directly sequenced. The patient's height was 75 cm (-2.89 SDS) with gradually reducing growth velocity, while the heights of the other family members were within the normal range. The GH stimulation test revealed that serum GH concentrations in the patient were much higher than those in the control group, and serum IGF-1 and IGFBP3 levels were extremely low. There was no germline mutation in the exons or the flanking regions of the patient's GHR gene. Interestingly, a deletion of 166 bases of exon 7 in the GHR mRNA was found, and it was suggested that the novel mutation resulted in premature termination (M207 fs. X8). This mutation decreases GH binding affinity to the GHR, and, thus, would be responsible for growth retardation.

Sun-Young Han, Ja-Hyun Kim, Ga-Young Gwon and Dong-Hyuk Yeom*Environmental Toxicology Research Center, Korea Institute of Toxicology, DeajeonTo evaluate the effect of endocrine disruption chemicals (EDCs) to aquatic organisms, muddy loach (Misgurnus anguillicaudatus) was exposed to low concentration methomyl for 21 days in order to identify the effect of biomarkers and endocrine. Vitellogenin (VTG) in blood plasma, which used widely as validated biomarker for endocrine disruption, was significantly greater in male fish exposed to 0.4 mg/L and 2 mg/L methomyl, and in female fish exposed to 0.08 mg/L, 0.4 mg/L, and 2 mg/L methomyl for 21 days (p

We present a comprehensive analysis of the change in event-related potential (ERP) due to task difficulty during a visual oddball task. Specifically, we investigated the inter-subject difference in difficulty-related change of ERP patterns using single-trial ERP analysis focusing on P300 and P2 components. ERPs were recorded and analyzed from 14 subjects while performing a visual oddball task with two difficulty levels. After extracting independent components (ICs) from single-trial ERPs, the averaged ERPs were used to identify which ICs originated from major ERP components. The ERP components were estimated from single-trial waveforms by back-projecting relevant ICs onto scalp electrodes after removing all other ICs; thus, the comparison of ERP components could be performed for each subject. The averaged P300 amplitude was smaller and latency was larger for the more difficult task, and this tendency was also observed for single-trial ERP analysis within each subject. P2 amplitude increased for the hard task for both group and individual analyses, suggesting that the P2 may be interpreted as a manifestation of task relevance evaluation or response generation. The P2 amplitude and latency were more notably correlated with response time for the more difficult task.

Background Vitamin D has been known to maintain the body’s balance of calcium and phosphorus as well as skeletal health. There has been increasing emphasis on the importance of vitamin D as recent studies have been reporting the specific functions of vitamin D in the cerebral nervous system and the association between the level of serum vitamin D and depressive symptoms. However, there is currently a paucity of research investigating the association between serum vitamin D and depressive symptoms in Korean subjects. Consequently, this study has aimed to determine the level of serum vitamin D and explore the association between serum vitamin D and depressive symptoms in Korean female workers. Method A medical examination, questionnaire, anthropometric measurements, and a blood test were conducted between February 3 and March 7, 2014 in 1054 subjects among female workers in the manufacturing industry who underwent physical examinations in a university hospital. From this data, we identified the level of serum vitamin D and investigated the association between serum vitamin D deficiency and depressive symptoms. Results The average serum vitamin D level of the 1054 subjects was 9.07 ± 3.25 ng/mL, and the number of subjects in the serum vitamin D deficiency group with less than 10 ng/mL was 721 (68.4 %). The odds ratio of the depressive symptom group with a CES-D score of 16 or above being in the deficiency group with a serum vitamin D level less than 10 ng/mL was found to be 1.55 (95 % CI = 1.15–2.07). Conclusion 68.4 % of female workers in the manufacturing industry were in the deficiency group with serum vitamin D levels less than 10 ng/mL. Additionally, we identified an association between serum vitamin D deficiency and depressive symptoms. In the future, if serum vitamin D deficiency is checked regularly in workers, we expect to achieve better outcomes in managing their depressive symptoms.

Sleep deprivation (SD) is an epidemic phenomenon in modern countries, and its harmful effects are well known. SD acts as an aggravating factor in inflammatory bowel disease. Melatonin is a sleep-related neurohormone, also known to have antioxidant and anti-inflammatory effects in the gastrointestinal tract; however, the effects of melatonin on colitis have been poorly characterized. Thus, in this study, we assessed the measurable effects of SD on experimental colitis and the protective effects of melatonin. For this purpose, male imprinting control region (ICR) mice (n = 24) were used; the mice were divided into 4 experimental groups as follows: the control, colitis, colitis with SD and colitis with SD and melatonin groups. Colitis was induced by the administration of 5% dextran sulfate sodium (DSS) in the drinking water for 6 days. The mice were sleep-deprived for 3 days. Changes in body weight, histological analyses of colon tissues and the expression levels of pro-inflammatory cytokines and genes were evaluated. SD aggravated inflammation and these effects were reversed by melatonin in the mice with colitis. In addition, weight loss in the mice with colitis with SD was significantly reduced by the injection of melatonin. Treatment with melatonin led to high survival rates in the mice, in spite of colitis with SD. The levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-17, interferon-γ and tumor necrosis factor-α, in the serum of mice were significantly increased by SD and reduced by melatonin treatment. The melatonin-treated group showed a histological improvement of inflammation. Upon gene analysis, the expression of the inflammatory genes, protein kinase Cζ (PKCζ) and calmodulin 3 (CALM3), was increased by SD, and the levels decreased following treatment with melatonin. The expression levels of the apoptosis-related inducible nitric oxide synthase (iNOS) and wingless-type MMTV integration site family, member 5A (Wnt5a) genes was decreased by SD, but increased following treatment with melatonin. Treatment with melatonin reduced weight loss and prolonged survival in mice with colitis with SD. Melatonin exerted systemic anti-inflammatory effects. Gene analysis revealed a possible mechanism of action of melatonin in inflammation and sleep disturbance. Thus, melatonin may be clinically applicable for patients with inflammatory bowel disease, particularly those suffering from sleep disturbances.

Inflammatory bowel disease is a chronic inflammatory condition of the gastrointestinal tract. It can be aggravated by stress, like sleep deprivation, and improved by anti-inflammatory agents, like melatonin. We aimed to investigate the effects of sleep deprivation and melatonin on inflammation. We also investigated genes regulated by sleep deprivation and melatonin. In the 2 % DSS induced colitis mice model, sleep deprivation was induced using modified multiple platform water bath. Melatonin was injected after induction of colitis and colitis with sleep deprivation. Also mRNA was isolated from the colon of mice and analyzed via microarray and real-time PCR. Sleep deprivation induced reduction of body weight, and it was difficult for half of the mice to survive. Sleep deprivation aggravated, and melatonin attenuated the severity of colitis. In microarrays and real-time PCR of mice colon tissues, mRNA of adiponectin and aquaporin 8 were downregulated by sleep deprivation and upregulated by melatonin. However, mRNA of E2F transcription factor (E2F2) and histocompatibility class II antigen A, beta 1 (H2-Ab1) were upregulated by sleep deprivation and downregulated by melatonin. Melatonin improves and sleep deprivation aggravates inflammation of colitis in mice. Adiponectin, aquaporin 8, E2F2 and H2-Ab1 may be involved in the inflammatory change aggravated by sleep deprivation and attenuated by melatonin.

We examined local and global differences in neuronal association patterns due to task difficulty. Induced and evoked gamma-band activity (GBA) was investigated using electroencephalograms recorded during visual oddball tasks of two difficulty levels. Significant phase synchronization (PS) in the gamma-band was determined by a double-threshold strategy, devised to detect prominent increases with respect to prestimulus baseline and surrogate data. A considerable increase in the early evoked GBA was observed for both difficulties, and this tended to be delayed for the hard task. Induced GBA was increased at the P300 latency period, but no difficulty-related change was observed. Intense PS among anterior and posterior regions along the midline was observed in a 30-38 Hz band, which was enhanced in the easy task throughout task execution, although the overall pattern of connectivity was similar for both difficulties. This may be the underlying basis of the faster and more accurate response to the easy task. The results showed that the most apparent change in the gamma-band associated with difficulty was observed in the PS pattern, not in the spectral power itself. This may imply that the difficulty-related change in cortical information processing was implemented as a change in the spatiotemporal pattern of interregional connectivity.