Associations between earplug use and hearing loss in ROK military personnel.

INTRODUCTION: The easiest way to prevent noise-induced hearing loss (NIHL) is to wear earplugs. The Republic of Korea (ROK) Ministry of National Defense (MND) is supplying earplugs to prevent NIHL, but many patients still suffer from this. We speculated that earplugs would have a high NIHL rate, depending on the rate of use of earplugs, regardless of the rate of supply. Therefore, we conducted this study to investigate the relationship between the use of earplugs and hearing loss by ROK military personnel. METHODS: The study used data from the Military Health Survey conducted in 2014-2015, which included 13 470 questionnaires completed by ROK military personnel. Hearing loss and earplug use were self-reported. Logistic regression analysis was used to assess associations between earplug use and hearing loss. RESULTS: The study sample included 13 470 ROK military personnel (response rate of 71.2%) (Army, 8330 (61.8%); Navy/Marines, 2236 (16.6%); and Air Force, 2904 (21.6%)). Overall, 18.8% of Korean military personnel reported that they always wore earplugs, and 2.8% reported hearing loss. In logistic regression analysis, there were significant differences in the rates of hearing loss associated with wearing earplugs sometimes (OR=1.48, 95% CI 1.07 to 2.05) and never wearing earplugs (OR=1.53, 95% CI 1.12 to 2.10). In subgroup analysis, in Air Force, non-combat branch, forward area and long-term military service personnel increased hearing loss was associated with not wearing earplugs. CONCLUSION: Our study confirmed that within the ROK military, there is an association between hearing loss and lack of earplug use. In the ROK MND, Army, Navy/Marines and Air Force headquarters must provide guidelines for the use of earplugs during field training to protect military personnel's hearings and, if necessary, need to be regulated or institutionalised.

Sirtuin 3 inhibits hepatocellular carcinoma growth through the glycogen synthase kinase-3ß/BCL2-associated X protein-dependent apoptotic pathway.

SIRT3 is a class III histone deacetylase that has been implicated in a variety of cancers. The role of SIRT3 in hepatocellular carcinoma (HCC) remains elusive. In this study, we found that SIRT3 expression was frequently repressed in HCC and its downregulation was closely associated with tumor grade and size. Ectopic expression of SIRT3 inhibited cell growth and induced apoptosis in HCC cells, whereas depletion of SIRT3 in immortalized hepatocyte promoted cell growth and decreased epirubicin-induced apoptosis. Mechanistic studies revealed that SIRT3 deacetylated and activated glycogen synthase kinase-3ß (GSK-3ß), which subsequently induced expression and mitochondrial translocation of the pro-apoptotic protein BCL2-associated X protein (Bax) to promote apoptosis. GSK-3ß inhibitor or gene silencing of BAX reversed SIRT3-induced growth inhibition and apoptosis. Furthermore, SIRT3 overexpression also suppressed tumor growth in vivo. Together, this study reveals a role of SIRT3/GSK-3ß/Bax signaling pathway in the suppression of HCC growth, and also suggests that targeting this pathway may represent a potential therapeutic approach for HCC treatment.

In Vitro and In Vivo Characterizations of Chiglitazar, a Newly Identified PPAR Pan-Agonist.

Solid rationales are still present for the identification of synthetic ligands to simultaneously target multiple PPAR subtypes for the treatment of T2DM. The purpose of this study was to characterize the in vitro and in vivo differential effects of chiglitazar, a non-TZD type of PPAR pan-agonist currently in phase III clinic development in China, from PPARγ-selective agonist like rosiglitazone. Chiglitazar showed transactivating activity in each PPARα, γ, and δ subtype and upregulated the expression of PPARα and/or PPARδ downstream genes involved in the key processes of lipid metabolism and thermogenesis. Comparable blood glucose lowering effect was observed between chiglitazar and rosiglitazone, but chiglitazar did not significantly increase the body weight in KKAy and fat pad weight in db/db mice. Chiglitazar had high distribution in liver, pancreas, and skeleton muscles but was less present in kidney, heart, and adipose in rats. Heart weight increase was not observed in rats treated with chiglitazar for 6 months at a dose as high as 45 mg kg(-1). The in vitro and in vivo differential features of chiglitazar are informative and encouraging for the further development of this synthetic ligand for the potential use in T2DM.

Overlapping nuclei segmentation based on Bayesian networks and stepwise merging strategy.

This paper presents a new approach to the segmentation of fluorescence in situ hybridization images. First, to segment the cell nuclei from the background, a threshold is estimated using a Gaussian mixture model and maximizing the likelihood function of the grey values for the cell images. After the nuclei segmentation, the overlapping and isolated nuclei are classified to facilitate a more accurate nuclei analysis. To do this, the morphological features of the nuclei, such their compactness, smoothness and moments, are extracted from training data to generate three probability distribution functions that are then applied to a Bayesian network as evidence. Following the nuclei classification, the overlapping nuclei are segmented into isolated nuclei using an intensity gradient transform and watershed algorithm. A new stepwise merging strategy is also proposed to merge fragments into a major nucleus. Experimental results using fluorescence in situ hybridization images confirm that the proposed system produced better segmentation results when compared to previous methods, because of the nuclei classification before separating the overlapping nuclei.

Generation and characterization of sodium-dicarboxylate cotransporter-deficient mice.

The sodium-dependent dicarboxylate cotransporter (NaDC1) has a proposed function of reabsorbing various Krebs cycle intermediates in the kidney and the small intestine. Since Krebs cycle intermediates have been suggested to be important for renal cell survival and recovery after hypoxia and reoxygenation, the transporter may play a role in the recovery of the kidney. Additionally, mutations in the transporter homolog in Drosophila led to fly longevity which was thought to be similar to that induced by caloric restriction (CR). To clarify the role of the sodium dicarboxylate cotransporter in vivo we generated cotransporter-deficient mice. These knockout mice excreted significantly higher amounts of various Krebs cycle intermediates in their urine; thus confirming the proposed function to reabsorb these metabolic intermediates in the kidney. No other phenotypic change was identified in these mice, however. Transporter deficiency did not affect renal function under normal physiological conditions, nor did it have an effect on renal damage and recovery from ischemic injury. Additionally, the absence of the transporter did not lead to metabolic or physiological changes associated with CR. Our results suggest that although the sodium dicarboxylate cotransporter is involved in regulating levels of various Krebs cycle intermediates in the kidney, impaired uptake of these intermediates does not significantly affect renal function under normal or ischemic stress.

Methanogen population in a marine biofilm corrosive to mild steel.

This study was conducted to analyze the methanogen population in a corrosive marine biofilm based on 16S rDNA analysis, using a PCR-cloning-sequencing approach. There were 80 methanogen clones developed from the PCR-amplified DNA extracted from the biofilm on the mild steel surface. All clones were categorized into one of five operational taxonomy units (OTUs). Two OTUs (comprising 57 clones) were affiliated with the acetotrophic Methanosaeta genus; the remaining three OTUs (23 clones) were affiliated with the hydrogenotrophic genera of Methanogenium, Methanoplanus and Methanocalculus. The hydrogenotrophic methanogens could directly cause metal corrosion through cathodic depolarization, whereas the acetotrophic methanogens grew syntrophically with corrosion-causing sulfate-reducing bacteria, as observed by fluorescent in situ hybridization, and thus contribute indirectly to metal corrosion.

Diabetic nephropathy is associated with the 5'-end dinucleotide repeat polymorphism of the aldose reductase gene in Chinese subjects with Type 2 diabetes.

AIMS: We investigated whether the promoter dinucleotide repeat polymorphism of the aldose reductase gene (5'-ALR2), implicated in the development of nephropathy in Type 1 diabetes, was associated with diabetic nephropathy in Type 2 diabetes. METHODS: In 265 Southern Chinese with Type 2 diabetes the 5' -ALR2 polymorphism was identified in genomic DNA using polymerase chain reaction and automated fluorescent scanning. They were classified as normoalbuminuric (n = 128), microalbuminuric (n = 85) or albuminuric (n = 52) according to the mean albumin excretion rate of two 12-h overnight collections. RESULTS: The 5' -ALR2 allele and genotype distributions differed significantly among the three groups of patients (P < 0.003 and P < 0.01, respectively). Normoalbuminuric patients had the lowest Z - 2 allele frequency: 17.6% vs. 28.2% and 23.1% for microalbuminuric and albuminuric patients, respectively, and the highest Z + 2 allele frequency: 36.7% vs. 21.2% and 23.1% in microalbuminuric and albuminuric patients, respectively. They also had the lowest Z - 2/X genotype frequency (X = any allele other than Z + 2): 18.8% vs. 36.5% in microalbuminuric (P < 0.01) and 38.5% in albuminuric patients (P < 0.02), respectively, but the highest Z + 2/Y genotype frequency (Y = any allele other than Z - 2): 50.7% vs. 27.0% and 34.6% in microalbuminuric (P < 0.001) and albuminuric patients, respectively. In a multiple logistic regression model, the Z - 2/X genotype (odds ratio 3.10; P < 0.025) was an independent risk factor of diabetic nephropathy, microalbuminuria or albuminuria, together with age, mean arterial pressure and body mass index. CONCLUSIONS: The 5' -ALR2 dinucleotide repeat polymorphism is associated with the development of diabetic nephropathy in Southern Chinese with Type 2 diabetes.

Overexpression of aldose reductase in liver cancers may contribute to drug resistance.

We previously found that about 29% of human liver cancers overexpressed aldose reductase (AR) and about 54% of them overexpressed an AR-like gene called ARL-1 that has similar enzymatic activities to AR. Since these aldo-keto reductases can reduce a broad spectrum of substrates including cytotoxic aldehydes, we were interested to find out if these enzymes can contribute to the resistance of liver cancer chemotherapy by inactivating some of the anticancer drugs. HepG2 cells, a stable line of liver cells, were induced to overexpress AR by hypertonicity. Cells that were cultured in hypertonic medium became more resistant to daunorubicin, suggesting that overexpression of AR made the cells more resistant to this drug. This is confirmed by the fact that addition of AR inhibitor sensitizes the cells to this drug again. This information may be important for designing new drugs to treat this deadly disease.

Aldose reductase-deficient mice develop nephrogenic diabetes insipidus.

Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various diseases associated with diabetes mellitus, such as cataract, retinopathy, neuropathy, and nephropathy. However, its physiological functions are not well understood. We developed mice deficient in this enzyme and found that they had no apparent developmental or reproductive abnormality except that they drank and urinated significantly more than their wild-type littermates. These ALR2-deficient mice exhibited a partially defective urine-concentrating ability, having a phenotype resembling that of nephrogenic diabetes insipidus.

Purification, identification, and characterization of an osmotic response element binding protein.

Kidney cells, especially the epithelial cells lining the collecting tubules in the inner medulla, are constantly exposed to concentrated urine. They are protected from the osmotic effect of high levels of sodium ion and urea by accumulating compatible osmolytes such as sorbitol, betaine, and myo-inositol. These osmolytes are involved in maintaining cell volume and electrolyte contents because they do not perturb the protein structure and function over a wide range of concentrations. Sorbitol is produced via the reduction of glucose by aldose reductase (AR), while betaine and myo-inositol are transported into the cells through specific transporters. Under hyperosmotic stress, transcriptions of genes encoding these proteins are highly induced. The induction of transcription was found to be mediated through the osmotic response elements (OREs) located in the 5' flanking sequences of these genes. We had earlier identified the OREs in human AR gene. In this study we purified and identified the osmotic response element binding protein (OREBP). OREBP is a transcription factor of approximately 200 kDa in size, characterized by a Rel-like DNA binding domain and a glutamine-rich transactivation domain. Dominant negative OREBP significantly diminished hyperosmotic AR gene induction. Immunohistochemical analysis showed that this transcription factor is rapidly translocated into the nucleus upon hyperosmotic stress.

Identification and characterization of multiple osmotic response sequences in the human aldose reductase gene.

Aldose reductase (AR) has been implicated in osmoregulation in the kidney because it reduces glucose to sorbitol, which can serve as an osmolite. Under hyperosmotic stress, transcription of this gene is induced to increase the enzyme level. This mode of osmotic regulation of AR gene expression has been observed in a number of nonrenal cells as well, suggesting that this is a common response to hyperosmotic stress. We have identified a 132-base pair sequence approximately 1 kilobase pairs upstream of the transcription start site of the AR gene that enhances the transcription activity of the AR promoter as well as that of the SV40 promoter when the cells are under hyperosmotic stress. Within this 132-base pair sequence, there are three sequences that resemble TonE, the tonicity response element of the canine betaine transporter gene, and the osmotic response element of the rabbit AR gene, suggesting that the mechanism of osmotic regulation of gene expression in these animals is similar. However, our data indicate that cooperative interaction among the three TonE-like sequences in the human AR may be necessary for their enhancer function.

An (A-C)n dinucleotide repeat polymorphic marker at the 5' end of the aldose reductase gene is associated with early-onset diabetic retinopathy in NIDDM patients.

To study the relationship between the aldose reductase gene and diabetic complications, an (A-C)n dinucleotide repeat sequence 2.1 kb upstream of the transcription start site of this gene was identified and studied. There are seven alleles at this locus with a polymorphism information content of 0.73 and a heterozygosity of 0.77 among the Chinese population in Hong Kong. One of the alleles (Z-2) was found to be associated with early onset of retinopathy in patients with non-insulin-dependent diabetes (P = 0.007), suggesting that aldose reductase or a gene in the close vicinity may be involved in the pathogenesis of this diabetic complication.

Treatment of Taenia saginata infection with mixture of areca nuts and pumpkin seeds.

In January and February 1974, 32 adults (20 males and 12 females) and a 13-year-old girl with taeniasis saginata were treated with the mixture of boiled areca nuts and pumpkin seeds at Mastoban, Jen-ai District, Nantou County, Taiwan. A total of 48 worms including 42 scolices were recovered from 29 cases. Side-effects were observed in 4 cases including 3 with complaints of dizziness, tinnitus, nausea and vomiting, and one with coma and abdominal pain. Mixtures of 75-150 g areca nuts and 50-100 g pumpkin seeds were judged effective and safe.