Hearing effects from intermittent and continuous noise exposure in a study of Korean factory workers and firefighters

<p>Abstract</p> <p>Background</p> <p>South Korea and surrounding countries in East Asia are believed to have the highest proportion in the world of high frequency hearing loss due to occupational noise exposure, yet there has been limited information published in international journals, and limited information for control of noise in local workplaces beyond strategies from western countries. We exploit medical surveillance information from two worker groups to enhance local knowledge about noise-induced hearing loss and explore the possible importance of shift work to risk.</p> <p>Methods</p> <p>Four-years of hearing data were evaluated for 81 male farm machine factory workers and 371 male firefighters who had successfully completed a health examination and questionnaires for the duration of the study period. The averages of hearing thresholds at 2, 3, and 4 kHz were used as the primary end-point for comparison. Repeat measure analysis adjusted for age, exposure duration and smoking status was used to measure the difference in hearing threshold between the two groups.</p> <p>Results</p> <p>Noise levels were measured in the factory at a mean of 82 dBA, with a range of 66-97. No concurrent measurements were taken for the firefighters, but historic comparison values showed a wider range but a similar mean of 76-79 dBA. Although losses during follow-up were negligible, the factory workers had significantly (<it>P </it>< 0.0001) more hearing loss at the baseline of the study than the firefighters in both ears at 2, 3, and 4 kHz, adjusted for age, duration of employment and smoking status. Among those with 10 years of employment, mean losses at these frequencies among the factory workers fell into the impairment range (> 25 dB loss). Firefighters also showed increased losses associated with longer exposure duration, but these were significantly less marked. Losses at lower frequencies (< or = 1 kHz) were negligible in both groups.</p> <p>Conclusions</p> <p>Korean work environments with continuous noise exposure in the measured range should consider implementation of a hearing conservation program. Further evaluation of hearing loss in workers exposed to irregular or intermittent high noise levels, such as firefighters, is also warranted.</p

Constraining parameter space in type-II two-Higgs doublet model in light of a 126 GeV Higgs boson

We explore the implications of a 126 GeV Higgs boson indicated by the recent LHC results for two-Higgs doublet model (2HDM). Identifying the 126 GeV Higgs boson as either the lighter or heavier of CP even neutral Higgs bosons in 2HDM, we examine how the masses of Higgs fields and mixing parameters can be constrained by the theoretical conditions and experimental constraints. The theoretical conditions taken into account are the vacuum stability, perturbativity and unitarity required to be satisfied up to a cut-off scale. We also show how bounds on the masses of Higgs bosons and mixing parameters depend on the cut-off scale. In addition, we investigate whether the allowed regions of parameter space can accommodate particularly the enhanced di-photon signals, ZZ* and WW* decay modes of the Higgs boson, and examine the prediction of the signal strength of Z{\gamma} decay mode for the allowed regions of the parameter space.Comment: To be published in JHEP, 20 pages, 11 figures, Figures and results are updated for the recent LHC result

Increased carotid IMT in overweight and obese women affected by Hashimoto's thyroiditis: an adiposity and autoimmune linkage?

<p>Abstract</p> <p>Background</p> <p>Hashimoto's thyroiditis is the most important cause of hypothyroidism. It is a systemic disease that can even affect the cardiovascular system, by accelerating the atherosclerotic process. Aim of this study was to examine whether autoimmune thyroiditis has an effect on the intima-media thickness of the common carotid artery (IMT-CCT), independently of the thyroid function and well-known cardiovascular risk factors. Hashimoto's thyroiditis is a systemic disease. The aim is to examine whether autoimmune thyroiditis and adiposity can effect carotid IMT independently of thyroid hormones and cardiovascular risk factors.</p> <p>Methods</p> <p>A total of 104 obese women (BMI ≥ 25.0 kg/m^-2), with FT3 and FT4 serum levels in the normal range and TSH levels < 4.5 μU/ml, were investigated. None of these patients was taking any kind of drug influencing thyroid function. Measurements were made of the IMT-CCT, BMI, waist circumference, blood pressure levels, as well as fasting TSH, FT3, FT4, anti-thyroid antibodies, insulin, fasting glycemia, triglycerides, total and HDL-cholesterol serum concentrations.</p> <p>Results</p> <p>Of the 104 women, 30 (28.8%) were affected by autoimmune thyroiditis. Significantly higher values of IMT-CCT (p < 0.05), TSH (p < 0.05), and triglycerides (p < 0.05) were obtained, and significantly lower values of FT4 (p < 0.05), in patients with Hashimoto's thyroiditis as compared to those with a normal thyroid function. When examining the whole group together, at multiple regression analysis Hashimoto's thyroiditis maintained a positive association with the IMT (p < 0.001), independently of age, hypertension, BMI, and the fasting serum levels of TSH, FT3, FT4, insulin, fasting glycemia, triglycerides, total and HDL-cholesterol levels.</p> <p>Conclusions</p> <p>The present study shows that Hashimoto's thyroiditis is associated to an increased IMT only in overweight and obese, independently of the thyroid function, BMI and cardiovascular risk factors. These results suggest that Hashimoto's thyroiditis is a marker of evolution of the atherosclerosis if combined to adiposity.</p

Gene Expression Pattern in Transmitochondrial Cytoplasmic Hybrid Cells Harboring Type 2 Diabetes-Associated Mitochondrial DNA Haplogroups

Decreased mitochondrial function plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM). Recently, it was reported that mitochondrial DNA (mtDNA) haplogroups confer genetic susceptibility to T2DM in Koreans and Japanese. Particularly, mtDNA haplogroup N9a is associated with a decreased risk of T2DM, whereas haplogroups D5 and F are associated with an increased risk. To examine functional consequences of these haplogroups without being confounded by the heterogeneous nuclear genomic backgrounds of different subjects, we constructed transmitochondrial cytoplasmic hybrid (cybrid) cells harboring each of the three haplogroups (N9a, D5, and F) in a background of a shared nuclear genome. We compared the functional consequences of the three haplogroups using cell-based assays and gene expression microarrays. Cell-based assays did not detect differences in mitochondrial functions among the haplogroups in terms of ATP generation, reactive oxygen species production, mitochondrial membrane potential, and cellular dehydrogenase activity. However, differential expression and clustering analyses of microarray data revealed that the three haplogroups exhibit a distinctive nuclear gene expression pattern that correlates with their susceptibility to T2DM. Pathway analysis of microarray data identified several differentially regulated metabolic pathways. Notably, compared to the T2DM-resistant haplogroup N9a, the T2DM-susceptible haplogroup F showed down-regulation of oxidative phosphorylation and up-regulation of glycolysis. These results suggest that variations in mtDNA can affect the expression of nuclear genes regulating mitochondrial functions or cellular energetics. Given that impaired mitochondrial function caused by T2DM-associated mtDNA haplogroups is compensated by the nuclear genome, we speculate that defective nuclear compensation, under certain circumstances, might lead to the development of T2DM

Peccei-Quinn NMSSM in the light of 125 GeV Higgs

We study the phenomenology of the Peccei-Quinn invariant extension of the next-to-minimal supersymmetric standard model (NMSSM) in view of the recent discovery of a 125 GeV Higgs boson. The minimal model having no quadratic and cubic terms of the NMSSM singlet field predicts a light singlino-like lightest supersymmetric particle (LSP). The model is strongly constrained by the Higgs invisible decay and the dark matter characteristic of the LSP, while some constraints can be relaxed by assuming that the saxion, the CP-even companion of the axion in the Peccei-Quinn sector, causes a late-time entropy production diluting the thermal LSP density. The collider signal of the model contains multi-jet and $h/W/Z$ plus missing energy, which can be discovered in the early stage of the 14 TeV LHC running.Comment: 40 pages, 10 figures, 6 tables. v3: references added, several statements added and corrected, comments on the small tadpole soft term added in sec. 2.

High-dose clevudine impairs mitochondrial function and glucose-stimulated insulin secretion in INS-1E cells

<p>Abstract</p> <p>Background</p> <p>Clevudine is a nucleoside analog reverse transcriptase inhibitor that exhibits potent antiviral activity against hepatitis B virus (HBV) without serious side effects. However, mitochondrial myopathy has been observed in patients with chronic HBV infection taking clevudine. Moreover, the development of diabetes was recently reported in patients receiving long-term treatment with clevudine. In this study, we investigated the effects of clevudine on mitochondrial function and insulin release in a rat clonal β-cell line, INS-1E.</p> <p>Methods</p> <p>The mitochondrial DNA (mtDNA) copy number and the mRNA levels were measured by using quantitative PCR. MTT analysis, ATP/lactate measurements, and insulin assay were performed.</p> <p>Results</p> <p>Both INS-1E cells and HepG2 cells, which originated from human hepatoma, showed dose-dependent decreases in mtDNA copy number and cytochrome c oxidase-1 (Cox-1) mRNA level following culture with clevudine (10 μM-1 mM) for 4 weeks. INS-1E cells treated with clevudine had reduced total mitochondrial activities, lower cytosolic ATP contents, enhanced lactate production, and more lipid accumulation. Insulin release in response to glucose application was markedly decreased in clevudine-treated INS-1E cells, which might be a consequence of mitochondrial dysfunction.</p> <p>Conclusions</p> <p>Our data suggest that high-dose treatment with clevudine induces mitochondrial defects associated with mtDNA depletion and impairs glucose-stimulated insulin secretion in insulin-releasing cells. These findings partly explain the development of diabetes in patients receiving clevudine who might have a high susceptibility to mitochondrial toxicity.</p

Prediction of Liver-Related Events Using Fibroscan in Chronic Hepatitis B Patients Showing Advanced Liver Fibrosis

Liver stiffness measurement (LSM) using transient elastography (FibroScan®) can assess liver fibrosis noninvasively. This study investigated whether LSM can predict the development of liver-related events (LREs) in chronic hepatitis B (CHB) patients showing histologically advanced liver fibrosis.Between March 2006 and April 2010, 128 CHB patients with who underwent LSM and liver biopsy (LB) before starting nucleot(s)ide analogues and showed histologically advanced fibrosis (≥F3) with a high viral loads [HBV DNA ≥2,000 IU/mL] were enrolled. All patients were followed regularly to detect LRE development, including hepatic decompensation (variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome) and hepatocellular carcinoma (HCC).The mean age of the patient (72 men, 56 women) was 52.2 years. During the median follow-up period [median 27.8 (12.6-61.6) months], LREs developed in 19 (14.8%) patients (five with hepatic decompensation, 13 with HCC, one with both). Together with age, multivariate analysis identified LSM as an independent predictor of LRE development [P<0.044; hazard ratio (HR), 1.038; 95% confidence interval (CI), 1.002-1.081]. When the study population was stratified into two groups using the optimal cutoff value (19 kPa), which maximized the sum of sensitivity (61.1%) and specificity (86.2%) from a time-dependent receiver operating characteristic curve, patients with LSM>19 kPa were at significantly greater risk than those with LSM≤19 kPa for LRE development (HR, 7.176; 95% CI, 2.257-22.812; P = 0.001).LSM can be a useful predictor of LRE development in CHB patients showing histologically advanced liver fibrosis

Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection

Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS) sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species

Chronic Exposure to the Herbicide, Atrazine, Causes Mitochondrial Dysfunction and Insulin Resistance

There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ), is heavily used and obesity-prevalence maps of people with a BMI over 30. Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function. Sprague-Dawley rats (n = 48) were treated for 5 months with low concentrations (30 or 300 µg kg−1 day−1) of ATZ provided in drinking water. One group of animals was fed a regular diet for the entire period, and another group of animals was fed a high-fat diet (40% fat) for 2 months after 3 months of regular diet. Various parameters of insulin resistance were measured. Morphology and functional activities of mitochondria were evaluated in tissues of ATZ-exposed animals and in isolated mitochondria. Chronic administration of ATZ decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level. A high-fat diet further exacerbated insulin resistance and obesity. Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt. These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent