DNA damage in workers exposed to mineral oils.

Mineral oils, untreated or mildly treated, have been classified in group 1 as a potential source of cancer by the International Agency for Research on Cancer (IARC). Although numerous studies have implicated metalworking fluids (MWFs) as human carcinogens, toxicology data regarding the mechanism of carcinogenicity are limited. This study is intended to examine the systemic effects of machining workers' exposure to MWFs. The potential toxicity of mineral oils was investigated in 65 lathe workers compared to controls (66 men). The occupational exposure was measured by the National Institute for Occupational Safety and Health (NIOSH) 5026. The DNA damage has been examined by the comet assay method. According to the field assessments, the time-weighted average (TWA) exposure to mineral oil mist was 7.67 ± 3.21 mg/m3. A comet assay of peripheral blood cells showed that tail length (TL) and olive moment (OM) were significantly higher in the exposed group (p < 0.05). A multiple logistic regression analysis revealed that, within subjects with over 10 years of exposure, the odds ratio of worker with high TL, percent of DNA in tail, OM, and tail moment (TM) were 1.68, 1.41, 1.71, and 2.71, respectively. DNA strand break in exposed workers was associated with higher exposure time in years. Mineral oil toxicity could be altered in the presence of by-products and impurities. For a better understanding of genotoxicity, further studies are required.

Oxidative Stress Assessment of Noise Exposure in the Workers Using Hearing Protection in a Pressing Industry.

BACKGROUND AND OBJECTIVE: Exposure to noise by generation of free radicals causes oxidative stress in body. The aim of this study was the evaluation of oxidative stress in workers who have used hearing protection devices during working time. MATERIAL AND METHOD: Pressing workers (n=24) of a home appliance industry were studied using hearing protection devices to reduce noise exposure. Twenty two office staff (without exposure to noise) were considered as a control group. Two groups were matched for age, work experience and smoking. Exposure to noise was measured by dosimeter method at workstations. By obtaining 3 ml blood sample, Malondialdehyde levels, Thiol groups and total antioxidant capacity were evaluated in all subjects. RESULTS: Exposure to sound pressure level in pressing workers by considering the noise reduction factor of the earplug was observed in 77.65 dB with minimum 75.1 dB and Maximum 81.22 dB. Plasma thiol groups (0.076 (0.041-0.119) vs (0.110 (0.076-0.197), mmol/l P =0.0001) and total antioxidant capacity (361.33± 54.65 vs 414.14± 96.82, µmol/ml P = 0.026) in pressing workers significantly decreased than control group. Pearson correlation showed significant results between exposure to noise and oxidative stress parameters. CONCLUSION: Exposure to noise wave cause oxidative stress in different site of body. Oxidative stress is an intermediate way for different disease due to noise exposure. Reducing of noise exposure by earplug in pressing workers is not efficient protection for oxidative stress generation. Therefore, hearing protection devices are not a barrier to the harmful effects of noise in occupational exposure.

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.

Application of a novel exposure limit approach for co-exposure of chemicals: a field study by in-vitro design.

This study has suggested an occupational exposure limit (OEL) based on the co-exposure approach in an iron-foundry industry. Respirable dust was collected in an iron casting industry using the NIOSH 0600 method. The DNA damage was obtained by comet assay. The lower confidence interval of the benchmark dose (BMDL) was employed for exposure limit evaluation. The estimated BMDL of the cell line was extrapolated to human subjects. Based on the Hill model, a BMDL 1.65 µg for chemical mixture has been estimated for the A549 cell line. According to uncertainty factors, permitted daily exposure (PDE) was predicted in humans. However, PDE of 3.9 µg/m3 was specified as the time-weighted average limit for toxic respirable dust in the casting industry. In this study, OEL for active respirable dust in the casting industry has been proposed. The industry-based standard for active respirable dust has been proposed for better management of co-exposure.

Health risk assessment of inhalation exposure to dry fogging of hydrogen peroxide in a dental clinic during the COVID-19 pandemic.

After the outbreak of COVID-19, many dental clinics use dry fogging of hydrogen peroxide (H2O2) to disinfect the air and surfaces. Inhalation of highly concentrated solutions of H2O2 may cause severe respiratory problems. This study aimed to estimate the health risk assessments of inhalation exposure to dry fogging of H2O2 in a dental clinic. This cross-sectional, descriptive-analytical study was performed to determine the inhalation exposure and health risk of 9 dental clinic staff with H2O2 in six rooms. Occupational exposure to H2O2 was assessed using the OSHA VI-6 method and a personal pump with the flow rate of 500 mL/min connected to the midget fritted-glass impinger containing 15 mL of TiOSO4 collecting solution. The health effects of H2O2 exposure were assessed using a respiratory symptoms questionnaire. The health risk assessment of inhaled exposure to H2O2 was also performed using the method provided by the Singapore occupational health department. The mean respiratory exposure of clinic staff to H2O2 was ranged from 1.3 to 2.83 ppm for six rooms which was above the limits recommended by international organizations. Dyspnea (44.4%), cough (33.3%), and nasal burning (22.2%) were the most prevalent health problems. The results also showed a medium risk for endodontics and surgery, and lower risk for periodontics, restorative care, orthodontics, and prosthetics. The results of this study indicate that when using an automated hydrogen peroxide-vapor fogger, calculating the spraying time based on room volume and using the rooms after 30 min of fogging is very important and can greatly reduce the risk ranking.

Risk assessment of chemical mixtures by benchmark dose-principle component analysis approach in occupational exposure.

Mixtures of organic solvents are widely used in industrial processes. Risk assessment for chemical co-exposure has always been a challenge in past years. The present study aims to employ principle component analysis (PCA) to produce an entry for benchmark dose approximation in shoemakers based on the color vision effect. A total of 134 subjects consisting of 67 shoemakers and 67 staff workers were employed for Benchmark Dose (BMD) evaluation. Occupational exposure to benzene, toluene, xylene, and n-hexane was evaluated using NIOSH 1501 and OSHA ID-07 methods. The color vision effect was quantified using Lanthony D-15 desaturated test (D-15d). PCA was run for cumulative exposure dose (CED) of the solvents by MATLAB 2018. Finally, the lowest 95% confidence limit of the benchmark dose (BMDL) was determined using US EPA benchmark dose software (BMDS) version 3.2.1. The color confusion index (CCI) level in shoemakers increased from 1 to 1.15 by a median of 1.07. There was a significant difference in the CCI level (p value<0.0001) between exposed and control subjects. The first score of PCA was used as intake dose level (IDL) in solvents co-exposure. Using BMD analysis, the log-logistics model was fitted with a p-value> 0.1 and the lowest BMDL level. BMDL level was evaluated at 1.63, 10.25, 2.21, and 3.35 ppm for benzene, toluene, xylene, and n-hexane, respectively. The results showed a risk of color vision effect with co-exposure to solvents at different levels in the occupational exposure standards. In conclusion BMDL-PCA approach has been suggested for the risk assessment of chemical co-exposure.

Investigating the Ventilation System of an Intensive Care Unit in the COVID-19 Crisis: A Study in a Hospital of Tehran, Iran.

Background: Ventilation system besides other prevention strategies such as surface disinfecting and personal protective equipment (PPE) decrease the risk of coronavirus disease 2019 (COVID-19) infection. This study aimed to examine the ventilation system of an intensive care unit (ICU) in a hospital in Tehran, Iran to evaluate the potency of heating, ventilation, and air conditioning system (HVAC) for COVID-19 spread. Materials and Methods: Contamination of air turnover caves was evaluated in supplier diffuser and extractor grills of negative pressure HVAC by ten samples. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the samples was evaluated by the real time reverse transcription-polymerase chain reaction (PCR). Moreover, air conditioning and sick building syndrome (SBS) was assessed according to MM040EA questioning from health care workers. Results: In the health care workers, respiratory effects were more prevalent compared to other signs. Despite suitable air conditioning, this study highlighted carrier potency of ICU workers for SARS-COV-2. Conclusion: According to our results, although the HVAC of ICU ward had an appropriate air movement, it was not safe enough for health care workers.

Occupational exposure to formaldehyde, lifetime cancer probability, and hazard quotient in pathology lab employees in Iran: a quantitative risk assessment.

Formaldehyde is a colorless and highly irritating substance that is used as a preservative and chemical fixative in tissue processing in pathological laboratories. Formaldehyde is mutagenic and is classified by the IARC as the definitive carcinogen (A1 group). This cross-sectional descriptive-analytical study was performed to determine the respiratory exposure of 60 employees of pathology labs with formaldehyde and to estimate carcinogenic and non-carcinogenic risk in Iran in 2018-2019. Occupational exposure to formaldehyde was assessed in summer season using the NIOSH 3500 method and a personal sampler with flow of 1 l/min connected to two Glass Midget Impingers containing 20 ml of 1% sodium bisulfate solution. The respiratory symptoms questionnaire provided by the American Thoracic Society was used to assess the health effects of formaldehyde exposure. The carcinogenic and non-carcinogenic risk assessment of inhaled exposure to formaldehyde was also performed using the USA Environmental Protection Agency (OEHHA) method. The mean respiratory exposure of employees to formaldehyde was 0.64 mg/m3 (range: 0.1474 to 1.3757). Occupational exposure in 28.3% (n = 17) of employees was above the OSHA recommended range. Wheezing (24%), burning eyes (25%), and cough (21.7%) were the most prevalent health problems. The mean ± SD of the carcinogenic risk among the employees was 3.45 × 10-4 ± 2.27 × 10-4. The highest mean of carcinogenic risk was found in lab workers (4.44 × 10-4). Given the high level of carcinogenic and non-carcinogenic risk of respiratory exposure to formaldehyde in pathological employees, especially lab worker, the use of management controls, engineering controls, and respiratory protection equipment to reduce exposure levels of all workers to less than the allowed exposure limits seems necessary.

Synergistic bactericidal activity of a naturally isolated phage and ampicillin against urinary tract infecting Escherichia coli O157.

OBJECTIVES: Bacteriophages are infectious replicating entities that are under consideration as antimicrobial bioagents to control bacterial infections. As an alternative or supplement to antibiotics, bacteriophages can be used to circumvent the resistance to existing antibiotics. The aim of this study was to assess the synergistic effect of a naturally isolated phage and ampicillin against Escherichia coli O157. MATERIALS AND METHODS: In the present study, a natural phage against E. coli O157 was isolated, the morphology and molecular characteristics of the phage were identified, and the combination of bacteriophage and antibiotic to combat clinically isolated drug-resistant E. coli O157 was evaluated. RESULTS: The results showed the synergistic action between a naturally isolated phage and ampicillin in solid (disk diffusion test) and liquid culture media. Addition of the isolated phage, gT0E.co-MGY2, to the microbial lawn of bacteria in modified antibiotic disk diffusion test, altered susceptibility pattern of E. coli O157 from resistant to sensitive based on the inhibition zones. Combinations of bacteriophage and ampicillin significantly enhanced the killing of bacterial strains when compared to treatment with ampicillin or phage alone in liquid culture. Moreover, it lasted few hours for ampicillin to reverse the growth of E. coli O157, while the bacteriophage and combination treatment stopped the proliferation of bacteria from the beginning, and this can compensate the delayed onset of antibiotic action. CONCLUSION: The synergistic action of bacteriophages and antibiotics is an alternative that cannot only be effective against bacterial infections but also contribute to the reduction of antibiotic resistance.

Novel Approaches for Efficient Delivery of Tyrosine Kinase Inhibitors.

Epidermal growth factor receptors (EGFRs) have potential to be considered as therapeutic target for cancer treatment especially in cancer patients with overexpression of EGFR. Cetuximab as a first monoclonal antibody and Imatinib as the first small molecule tyrosine kinase inhibitor (SMTKI) were approved by FDA in 1998 and 2001. About 28 SMTKIs have been approved until 2015 and a large number of compound with kinase inhibitory activity are at the different phases of clinical trials. Although Kinase inhibitors target specific intracellular pathways, their tissue or cellular distribution are not specific. So treatment with these drugs causes serious dose dependent side effects. Targeted delivery of kinase inhibitors via dendrimers, polymeric nanoparticles, magnetic nanoparticles and lipid based delivery systems such as liposomes, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) can lead to reduction of side effects and improving therapeutic efficacy of the drugs in the target organs. Furthermore formulation of these drugs is challenged by their physicochemical properties such as solubility and dissolution rate. The main approaches in order to increase dissolution rate, are particle size reduction, self-emulsification, cyclodextrin complexation, crystal modification and amorphous solid dispersion. Synergistic therapeutic effect, decreased side effects and drug resistant, reduced cost and increased patient compliance are the advantages associated with using combination therapy especially in the treatment of cancer. Combination of TKIs with chemotherapeutic agents or biopharmaceuticals such as monoclonal antibodies and oligonucleotides and also combination of two TKIs within one formulation is possible by new targeting delivery systems. This article reviews the recent advances in the design and development of delivery systems for TKIs.

Protein engineering of microbial cholesterol oxidases: a molecular approach toward development of new enzymes with new properties.

Cholesterol oxidase, a flavoenzyme, catalyzes two reactions in one active site: oxidation and isomerization. This enzyme has been isolated from a variety of microorganisms, mostly from actinomycetes. This enzyme has been widely used in clinical laboratories for cholesterol assays and was subsequently determined to have other potential applications. Engineering of cholesterol oxidase have enabled the identification of critical residues, and the information derived could lead to the rational development of improved types of the enzyme with increased stability and better functional properties. This review is the first that exclusively summarizes the reported results on the engineering of bacterial cholesterol oxidases aimed at improving their thermal and chemical stability, catalytic activity, and substrate specificity.

Modified phages: novel antimicrobial agents to combat infectious diseases.

Researchers increasingly believe that microbial, molecular and synthetic biology techniques along with genetic engineering will facilitate the treatment of persistent infectious diseases. However, such therapy has been plagued by the emergence of antibiotic-resistant bacteria, resulting in significant obstacles to treatment. Phage therapy is one promising alternative to antibiotics, especially now that recent modifications to ubiquitous phages have made them more controllable. Additionally, convincing in vitro and in vivo studies of genetically modified lytic phages and engineered non-lytic phages have confirmed the advantages of novel, specific bactericidal agents over antibiotics in some cases. There is still a need for a better understanding of phage therapy, however, before it can be adopted widely.

High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy.

Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major efforts are underway to understand underlying mechanisms. Resistance can be either intrinsic or acquired. We derived a series of subcloned MCF7 cell lines that were either highly sensitive or naturally resistant to tamoxifen and studied the factors that lead to drug resistance. Gene-expression studies revealed a signature of 67 genes that differentially respond to tamoxifen in sensitive vs. resistant subclones, which also predicts disease-free survival in tamoxifen-treated patients. High-throughput cell-based screens, in which >500 human kinases were independently ectopically expressed, identified 31 kinases that conferred drug resistance on sensitive cells. One of these, HSPB8, was also in the expression signature and, by itself, predicted poor clinical outcome in one cohort of patients. Further studies revealed that HSPB8 protected MCF7 cells from tamoxifen and blocked autophagy. Moreover, silencing HSBP8 induced autophagy and caused cell death. Tamoxifen itself induced autophagy in sensitive cells but not in resistant ones, and tamoxifen-resistant cells were sensitive to the induction of autophagy by other drugs. These results may point to an important role for autophagy in the sensitivity to tamoxifen.

Genetically engineered phage harbouring the lethal catabolite gene activator protein gene with an inducer-independent promoter for biocontrol of Escherichia coli.

Complications of chemotherapy, such as appearance of multidrug resistance, have persuaded researchers to consider phage therapy as a new method to combat bacterial infections. In vitro experiments were performed to assess the therapeutic value of genetically modified phages for controlling gastrointestinal Escherichia coli O157:H7 cells in Luria-Bertani (LB) media and contaminated cow milk. We constructed a modified nonreplicating M13-derived phage expressing a lethal catabolite gene activator protein (CAP) that is a Glu181Gln mutant of CAP. The modified phagemid was propagated in the lethal CAP-resistant strain XA3DII. Time-kill assay experiments showed a considerable reduction in the number of surviving bacteria in both LB media and contaminated cow milk. Our further study using other test strains demonstrated that the host range of lethal phage is limited to E. coli strains that produce pili. This study provides a possible strategy for the exploitation of genetically engineered nonlytic phages as bactericidal agents by minimizing the risk of release of progeny phages and endotoxins into the environment. The phage was engineered to remain lethal to its bacterial target, but incapable of replicating therein. Furthermore, the addition of an inducer to express the lethal protein is not required.