EBV-Associated Gastric Cancer; An In Situ Hybridization Assay on Tissue Microarray: A Multi-Region Study from Four Major Provinces of Iran.

BACKGROUND: Gastric cancer is the fourth leading cause of cancer-related deaths in the world. The identification of gastric cancer subtypes related to recognizable microbial agents may play a pivotal role in the targeted prevention and treatment of this cancer. The current study is conducted to define the frequency of Epstein-Barr virus (EBV) infection in gastric cancers of four major provinces, with different incidence rates of gastric cancers, in Iran. METHODS: Paraffin blocks of 682 cases of various types of gastric cancer from Tehran, South and North areas of Iran were collected. Twelve tissue microarray (TMA) blocks were constructed from these blocks. Localization of EBV in tumors was assessed by in situ hybridization (ISH) for EBV-encoded RNA (EBER). Chi-squared test was used to evaluate the statistical significance between EBV-associated gastric cancer (EBVaGC) and clinicopathologic tumor characteristics. RESULTS: Fourteen out of 682 cases (2.1%) of gastric adenocarcinoma were EBER-positive. EBER was positive in 8 out of 22 (36.4%) of medullary carcinomas and 6 out of 660 (0.9%) of non-medullary type, which was a statistically significant difference (P<0.001). The EBVaGCs were more frequent in younger age (P=0.009) and also showed a trend toward the lower stage of the tumor (P=0.075). CONCLUSION: EBV-associated gastric adenocarcinoma has a low prevalence in Iran. This finding can be due to epidemiologic differences in risk factors and exposures, and the low number of gastric medullary carcinomas in the population. It may also be related to gastric tumor heterogeneity not detected with the TMA technique.

Noise and silver nanoparticles induce hepatotoxicity via CYP450/NF-Kappa B 2 and p53 signaling pathways in a rat model.

Co-exposure to noise and nanomaterials, such as silver nanoparticles (Silver-NPs), is a common occurrence in today's industries. This study aimed to investigate the effects of exposure to noise and the administration of silver-NPs on the liver tissue of rats. Thirty-six adult male albino Wistar rats were randomly divided into six groups: a control group (administered saline intraperitoneally), two groups administered different doses of Silver-NPs (50 mg/kg and 100 mg/kg, 5 days a week for 28 days), two groups exposed to noise in addition to Silver-NPs (at the same doses as mentioned before), and a group exposed only to noise (104 dB, 6 hours a day, 5 days a week for 4 weeks). Blood samples were taken to assess hepatic-functional alterations, such as serum ALP, ALT, and AST levels. Additionally, biochemical parameters (MDA, GPX, and CAT) and the silver concentration in the liver were measured. Histopathological analysis, mRNA expression (P53 and NF-κB), protein expression (CYP450), and liver weight changes in rats were also documented. The study found that the administration of Silver-NPs and exposure to noise resulted in elevated levels of ALP, ALT, AST, and MDA (p < .01). Conversely, GPX and CAT levels decreased in all groups compared with the control group (p < .0001). There was a significant increase (p < .05) in liver weight and silver concentration in the liver tissues of groups administered Silver-NPs (50 mg/kg) plus noise exposure, Silver-NPs (100 mg/kg), and Silver-NPs (100 mg/kg) plus noise exposure, respectively. The expression rate of P53, NF-κB, and cytochromes P450 (CYPs-450) was increased in the experimental groups (p < .05). These findings were further confirmed by histopathological changes. In conclusion, this study demonstrated that exposure to noise and the administration of Silver-NPs exacerbated liver damage by increasing protein and gene expression, causing hepatic necrosis, altering biochemical parameters, and affecting liver weight.

Prediction of size-selective permitted daily exposures for mineral oil mist based on an in vitro study in different scenarios.

The incidence of DNA damage from exposure to specific types of metalworking fluids has been reported. In this research, size-selective permissible limits to prevent genotoxic damage in A549 cell lines exposed to two types of mineral oil were estimated for the first time using a benchmark dose approach and extrapolated to workers. The comet assay was performed based on Olive and Banath protocol to determine DNA damage. Then, the Benchmark Dose, the 95% lower bound confidence limit BMD, and the 95% upper-bound confidence limit BMD were determined using continuous response data. Finally, the four Benchmark Dose levels reported in the A549 cell line were extrapolated to the human population in occupational settings in two phases. This study showed when determining the permissible limits, the type used or unused, the type of injury, the organ affected in the body and the size of the particles should also be considered.

Cell toxicity assessment in co-treatment to metalworking fluids and vibration: an in vitro study of occupational exposure setting.

This study was designed to study dual risk of MWFs and vibration according to exposure simulation of selected industry. Air samples of two types MWFs were evaluated according to NIOSH 5026. Vibration acceleration exposure was assessed based on the ISO 8041:2005 standard. Cell treatment of both MWF air samples and vibration as the same as dual exposure to MWF airborne and vibration was assessed. There is a potency of nitrosamine formation in airborne samples of ethylamine containing MWF, while heterocyclic including bore is found in airborne bore containing MWF. DNA breaks caused by boron-containing MWF were higher than nitrosamine air samples. Oxidative stress production and chronic inflammation were highlighted in the response to cell treatments. The risk of cell toxicity in machining workers was evaluated at a level lower than the occupational exposure limit for MWFs and vibration.

The association between blood, urine, respiratory, neurobehavioral parameters and occupational exposure to organophosphorus pesticides: a cross-sectional study among formulators.

Background: Organophosphate (OP) pesticides are one of the most extensively used chemical compounds all over the world. Objective: The aim of this study is to determine whether occupational exposure of the formulators to the OP pesticides, under normal working conditions, is associated with any hematotoxic, hepatotoxic, nephrotoxic, neurotoxic, and respirotoxic responses among them. Methods: 28 OP formulation plant workers and 17 office workers participated in this cross-sectional study as the exposed and control groups, respectively. Blood and urine samples were collected to measure hematological, biochemical, and urinalysis parameters. American thoracic society questionnaire and spirometry tests were employed to assess the function of their respiratory system. Q16 questionnaire was also used to investigate the prevalence of neurobehavioral symptoms. The data were analyzed by SPSS v.22 software using Kolmogorov-Smirnov, T-test, Mann-Whitney U, Chi-square, Fisher, Pearson, and Spearman tests. Results: No statistically significant difference was found in hematological, biochemical, urinalysis (except in specific gravity), spirometry parameters, as well as respiratory and neurobehavioral symptoms between the exposed and the control groups. For the exposed group, however, the means of spirometry parameters were significantly lower among the smokers. Conclusions: In this study, the expected adverse health effects due to exposure to OP pesticides were not observed among the formulators; however, the risk of developing respiratory dysfunction was found to be more considerable among smoker subjects than the non-smoker ones. Further investigations are required to determine whether formulators' occupational exposures to OP pesticides result in certain adverse health effects.

The effect of simultaneous exposure to cigarette smoke and noise on distortion product otoacoustic emissions in rats.

Cigarette smoking is a possible risk factor for hearing loss. However, the impact of simultaneous exposure to noise and smoke on hearing has remained controversial. This study investigated the combined effect of exposure to cigarette smoking and noise on hearing loss. Three groups of male Wistar rats (275 ± 25 g) were subjected to white noise (102 ± 0.5 dB), cigarette smoking (20 cigarettes), and both cigarette smoking and noise for 8 h and 10 days inside the exposure chamber. The control group was exposed to neither noise nor smoke. Distortion product otoacoustic emissions (DPOAE) were measured before any intervention, and it was repeated 1, 7, and 21 days after the last exposure. One-day postexposure to noise, cigarette smoking, and both cigarette smoking and noise, the mean of DPOAE amplitudes decreased significantly ( p < 0.05) between, respectively, 5.7-30.7, 1.5-7.5, and 5.2-32.6 dB within the frequency range of 4620-9960. Temporal DPOAE change in rats exposed to noise or both cigarette smoking and noise was not significantly different ( p > 0.05). DPOAE amplitudes returned to the baseline values in the group subjected to smoking 21 days postexposure. The most permanent change was observed in rats exposed to both cigarette smoking and noise. Accordingly, simultaneous subacute exposure to noise and cigarette smoking increases the effect of noise on permanent hearing loss. Therefore, smoking workers exposed to noise might be at a greater risk of developing hearing loss, and it is recommended that authorities in charge take note of this evidence.

Diagnostic Accuracy of Serum and Urine S100A8/A9 and Serum Amyloid A in Probable Acute Abdominal Pain at Emergency Department.

STUDY DESIGN: This study was performed to investigate the diagnostic values of some inflammatory biomarkers in abdominal pain. METHODS: Patients over 18 years of age with acute recent abdominal pain who presented to the Emergency Department were evaluated. Serum and urinary samples were taken and evaluated for serum and urine S100A8/A9 and serum amyloid A. All patients were referred to a surgeon and were followed up until the final diagnosis. In the end, the final diagnosis was compared with the levels of biomarkers. RESULTS: Of a total of 181 patients, 71 underwent surgery and 110 patients did not need surgery after they were clinically diagnosed. Mean levels of serum and urine S100A8/A9 had a significant difference between two groups, but serum amyloid A did not show. The diagnostic accuracy of serum S100A8/A9, urine S100A8/A9, and serum amyloid A was 86%, 79%, and 50%, respectively, in anticipation of the need or no need for surgery in acute abdominal pain. CONCLUSIONS: Our study showed that in acute abdominal pain, serum and urine S100A8/A9 can be useful indicators of the need for surgery, but serum amyloid A had a low and nonsignificant diagnostic accuracy.

Protective Effects of N-Acetyl-L-Cysteine on the Density of Spiral Ganglion Cells and Histological Changes Induced by Continuous Noise Exposure in Rats.

BACKGROUND: Noise exposure causes loss of cochlea hair cells, leading to permanent sensorineural hearing loss, and initiates pathological changes to the bipolar primary auditory neurons (ANs). This study focuses on the effects of N-acetyl-l-cysteine (NAC) in protecting the density of spiral ganglion cells and in histological changes induced by continuous noise exposure in rats. METHODS: Twenty-four male Wistar rats were randomly allocated into four experimental groups to receive NAC, saline, noise, or both noise and NAC. Noise exposure continued for ten days. Saline and NAC were injected daily during the noise exposure, and 2 days before and after the noise exposure. Evaluation of cochlear histopathology and the density of spiral ganglion cells was performed 21 days after exposure. RESULTS: In the animals exposed to noise, a reduction in the density of spiral ganglion cells was evident in both the basal and middle turns of the cochlea. This improved on receiving NAC treatment (P = 0.046). In the histopathology evaluation, some histological changes, such as disorganised architecture of the outer hair and supporting cells and a slightly thickened basilar membrane, were found in the basal turns in the noise group. CONCLUSION: NAC offered partial protection against noise exposure by improving the density of spiral ganglion cells and reducing morphological changes.

A New Microwave Shield Preparation for Super High Frequency Range: Occupational Approach to Radiation Protection.

BACKGROUND: Widespread use of X-band frequency (a part of the super high frequency microwave) in the various workplaces would contribute to occupational exposure with potential of adverse health effects.  According to limited study on microwave shielding for the workplace, this study tried to prepare a new microwave shielding for this purpose. METHODS: We used EI-403 epoxy thermosetting resin as a matrix and nickel oxide nanoparticle with the diameter of 15-35 nm as filler. The Epoxy/ Nickel oxide composites with 5, 7, 9 and 11 wt% were made in three different thicknesses (2, 4 and 6 mm). According to transmission / reflection method, shielding effectiveness (SE) in the X-band frequency range (8-12.5 GHz) was measured by scattering parameters directly given by the 2-port Vector Network Analyzer. The fabricated composites characterized by X-ray Diffraction and Field Emission Scanning Electron Microscope. RESULTS: The best average of shielding effectiveness in each thickness of fabricated composites obtained by 11%-2 mm, 7%-4 mm and 7%-6 mm composites with SE values of 46.80%, 66.72% and 64.52%, respectively. In addition, the 11%-6 mm, 5%-6 mm and 11%-4 mm-fabricated composites were able to attenuate extremely the incident microwave energy at 8.01, 8.51 and 8.53 GHz by SE of 84.14%, 83.57 and 81.30%, respectively. CONCLUSIONS: The 7%-4mm composite could be introduced as a suitable alternative microwave shield in radiation protection topics in order to its proper SE and other preferable properties such as low cost and weight, resistance to corrosion etc. It is necessary to develop and investigate the efficacy of the fabricated composites in the fields by future studies.

Evaluating the miR-302b and miR-145 expression in formalin-fixed paraffin-embedded samples of esophageal squamous cell carcinoma.

BACKGROUND: MicroRNAs are involved in key cellular processes regulating, and their misregulation is linked to cancer. The miR-302-367 cluster is exclusively expressed in embryonic stem and carcinoma cells. This cluster also promotes cell reprogramming and stemness process. In contrast, miR-145 is mostly regarded as a tumor suppressor, where it regulates cellular functions such as cell division, differentiation, and apoptosis. By suppressing the main pluripotency factors (OCT4, SOX2, MYC and KLF4), miR-145 silences the self-renewal program in ESCs. Therefore, the main aim of this study is to find a potential link between the expression level of hsa-miR-302b and hsa-miR-145 with tumor vs. non-tumor as well as high-grade vs. low-grade states of the esophageal tissue samples. METHODS: A total number of 40 formalin-fixed, paraffin-embedded (FFPE) samples of esophageal squamous-cell carcinoma (ESCC) were obtained, and the tumor and marginal non-tumor areas delineated and punched off by an expert pathologist. Total RNA was extracted with Trizol, and cDNA synthesized using the miRCURY LNA™ Universal RT microRNA PCR Kit. Real-time reverse transcription polymerase chain reaction (RT-PCR) assays were performed using specific LNA-primers and SYBR Green master mix. RESULTS: The expression level of miR-302b failed to show any significant difference, neither between tumor and their non-tumor counterparts, nor among tumors with different grades of malignancies (p > 0.05). In contrast, miR-145 was significantly down regulated in all grades of tumor samples (p < 0.001). However, its expression level could not discriminate between different grades of malignancy (p > 0.05). CONCLUSION: Our data revealed a significant down-regulation of miR-145 in ESCC tissue samples. Based on our ROC curve analysis data (AUC = 0.74, p < 0.001) miR-145 could be regarded as a potential tumor marker for diagnosis of esophageal cancer.

Adverse effects of formaldehyde vapor on mouse sperm parameters and testicular tissue.

BACKGROUND: Formaldehyde (FA), one of the simplest organic molecules, is a flammable, pungent, irritating and colorless gas. This study aimed to investigate the effects of various concentrations of FA vapor on sperm parameters and testicular tissue. MATERIALS AND METHODS: In this experimental study, we randomly assigned 36 adult male mice to one control and two experimental groups (n=12 for each group). The control group (C) did not receive FA. Group F1 (low concentration) was exposed to 10 ppm FA vapor and the F2 (high concentration) group was exposed to 20 ppm FA vapor. FA was administered for ten days, eight hours per day for both groups. At the end of the exposure period, half of the animals in each group were sacrificed 24 hours after exposure to detect any short-term effects; the rest of the mice were sacrificed 35 days later to assess for long-term effects. Sperm parameters were analyzed by Computer-assisted Sperm Analyzer (CASA) and histological changes determined. In addition, we studied changes in testosterone hormone. Data were analyzed by one-way ANOVA followed by the Scheffe test using SPSS software. RESULTS: Long-term effects of FA in the experimental groups included significant reductions in sperm cell numbers and sperm viability. A drastic reduction in progressive motility and increased abnormal sperm percentage (p<0.001) compared with the control group was also noted. Histological study of testes specimens in the experimental group revealed displacement of germinal cells, along with degeneration of Leydig cells and seminiferous tubules. CONCLUSION: Exposure to FA vapor can destroy testicular structure and decrease percentages of concentration, viability, normal morphology, and progressive motility, in addition to increasing the percentage of immotile sperm.

The investigation of degradation and mineralization of high concentrations of formaldehyde in an electro-Fenton process combined with the biodegradation.

This study was done to evaluate the degradation and mineralization of formaldehyde (≈ 8000 mg/L) in an electro-Fenton process (EFP) in combination with biodegradation. In the first step, the influence of several important parameters including solution pH, current density, H(2)O(2) concentration, and reaction time were tested on the efficiency of the EFP in degradation and mineralization of formaldehyde in a concentrated solution. The optimum pH and current density was found to be around 10 and 8.5 mA/cm(2), respectively. The formaldehyde degradation in the EFP increased with an increased H(2)O(2) concentration. Under optimum pH and current density, the complete degradation and 51% mineralization of formaldehyde was attained in the EFP using a H(2)O(2) concentration of 10mM/min at a short reaction time of 6 min. The biodegradation of the effluent of EFP under optimum conditions (complete formaldehyde removal) was also tested. The results demonstrated that the concentration of the EFP effluent could be efficiently reduced in the bioreactor to below 50mg/L after a biodegradation time of 16d. Accordingly, results showed that EFP was a very efficient process for degradation and mineralization of a high concentration of formaldehyde so that its effluent could be efficiently post-treated with a biological process.

Occupational exposure to perchloroethylene in dry-cleaning shops in Tehran, Iran.

Perchloroethylene, the most widely used solvent in dry cleaning, is toxic to the liver, kidneys and central nervous system and may be a human carcinogen. An exposure assessment was carried out in 69 dry-cleaning shops using perchloroethylene in Tehran city, Iran. The 8-h time weighted average (TWA) breathing zone air samples and end-exhaled air samples were obtained from 179 workers who worked as the job titles included machine operator (n=71), presser (n=63) and counter area (clerk) (n=45). The mean perchloroethylene concentrations in breathing zone air were 11.5 ppm, 9.6 ppm and 7.2 ppm respectively. The mean perchloroethylene concentrations in end-exhaled air of the same participants in Saturday morning (prior to shift of workweek) were 1.7 ppm, 1.5 ppm and 1.1 ppm, but in Thursday evening (end of shift at end of workweek) were 2.4 ppm, 2.0 ppm and 1.5 ppm respectively. This study found that, the mean perchloroethylene concentrations in breathing zone air and end-exhaled air in the dry-cleaning workers were lower than the TLV (25 ppm) and BEI (5 ppm) recommended by ACGIH. Regression analysis showed that the concentration of perchloroethylene in breathing zone air (TWA) was highly and significantly correlated with the concentration of perchloroethylene in end-exhaled air in Saturday morning with a regression equation Y=0.147X + 0.031 (r=0.99, p<0.001) and also in Thursday evening with a regression equation Y=0.201X + 0.072 (r=0.98, p<0.001) where X is the concentration of perchloroethylene in breathing zone air and Y is that the concentration of perchloroethylene in end-exhaled air. The results also showed the potential utility of measuring the concentration of perchloroethylene in end-exhaled air as a method for assessing relative exposure in dry cleaning shops which use it.

Assessment of outer hair cell function and blood antioxidant status of rabbits exposed to noise and metal welding fumes.

OBJECTIVES: To investigate the interaction between welding fumes and noise in causation of hearing impairment. METHODS: Groups of rabbits (n=6) were exposed to noise, welding fumes or combination of both prior to Distortion Product Otoacoustic-Emissions (DPOAEs) analysis. The function of outer hair cells (OHCs) was examined by DPOAE assessment over a broad range of frequencies. Variations in DPOAE amplitude were compared between control (n=6) and exposed (n=18) groups. RESULTS: The DPOAEs levels measured at different frequencies (1379-6299 Hz) were found to decrease significantly (P<0.05) in rabbits exposed to 110 dB sound pressure level (SPL) broadband noise (8h/day, 12 days). In rabbits, exposed to carbon-steel welding fumes alone (157 mg/m(3)), the threshold shift was limited to the high frequencies (2759-6299 Hz), whereas, mixed exposure to noise and fumes resulted in reduction of DPOAEs at all the frequencies. Changes in DPOAEs were associated with increased susceptibility of erythrocytes to oxidation (P<0.05). Exposure to noise or fumes alone or simultaneously, suppressed total antioxidant ability of plasma as measured by ferric reducing ability of plasma (FRAP). Noise alone or in combination with fumes resulted in depletion of blood glutathione (GSH). Despite suppression of FRAP in the exposed groups, GSH was found to remain unchanged due to welding fumes suggesting that antioxidants other than GSH are affected by toxicants present in metal welding fumes. CONCLUSION: Exposure to very high levels of welding fumes can increase noise-related effects on OHC function by extending hearing threshold shift to wide band frequencies.