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1.
Am J Ind Med ; 62(10): 826-837, 2019 10.
Article in English | MEDLINE | ID: mdl-31347715

ABSTRACT

BACKGROUND: The purpose of this study was to estimate the prevalence of hearing loss (HL) among noise-exposed US workers within the Mining, and Oil and Gas Extraction (OGE) sectors. METHODS: Audiograms of 1.9 million workers across all industries (including 9389 in Mining and 1076 in OGE) from 2006 to 2015 were examined. Prevalence and adjusted risk as compared to a reference industry (Couriers and Messengers) were estimated for all industries combined and the Mining and OGE sectors and subsectors. RESULTS: The prevalences of HL in Mining and OGE were 24% and 14%, respectively, compared with 16% for all industries combined. Many Mining and one OGE subsector exceeded these prevalences and most had an adjusted risk (prevalence ratio) significantly greater than the reference industry. Some subsectors, particularly in OGE, could not be examined due to low sample size. The prevalences in Construction Sand and Gravel Mining and Natural Gas Liquid Extraction were 36% and 28%, respectively. Workers within Support Activities for Coal Mining had double the risk of HL than workers in the reference industry. CONCLUSIONS: The many subsectors identified with high prevalences and/or worker risks for HL well above risks in the reference industry need critical attention to conserve worker hearing and maintain worker quality of life. Administrative and engineering controls can reduce worker hazardous noise exposures. Noise and ototoxic chemical exposure information is needed for many subsectors, as is audiometric testing results for OGE workers. Additional research is also needed to further characterize exposures and improve hearing conservation measures.


Subject(s)
Hearing Loss, Noise-Induced/epidemiology , Mining/statistics & numerical data , Occupational Diseases/epidemiology , Oil and Gas Industry/statistics & numerical data , Adult , Audiometry , Female , Hearing Loss, Noise-Induced/etiology , Humans , Male , Middle Aged , Noise, Occupational/adverse effects , Occupational Diseases/etiology , Occupational Exposure/adverse effects , Prevalence , Retrospective Studies , United States/epidemiology
2.
Bioorg Med Chem ; 23(8): 1869-81, 2015 Apr 15.
Article in English | MEDLINE | ID: mdl-25778768

ABSTRACT

Current FDA-approved chemotherapeutic antimetabolites elicit severe side effects that warrant their improvement; therefore, we designed compounds with mechanisms of action focusing on inhibiting DNA replication rather than targeting multiple pathways. We previously discovered that 5-(α-substituted-2-nitrobenzyloxy)methyluridine-5'-triphosphates were exquisite DNA synthesis terminators; therefore, we synthesized a library of 35 thymidine analogs and evaluated their activity using an MTT cell viability assay of MCF7 breast cancer cells chosen for their vulnerability to these nucleoside derivatives. Compound 3a, having an α-tert-butyl-2-nitro-4-(phenyl)alkynylbenzyloxy group, showed an IC50 of 9±1µM. The compound is more selective for cancer cells than for fibroblast cells compared with 5-fluorouracil. Treatment of MCF7 cells with 3a elicits the DNA damage response as indicated by phosphorylation of γ-H2A. A primer extension assay of the 5'-triphosphate of 3a revealed that 3aTP is more likely to inhibit DNA polymerase than to lead to termination events upon incorporation into the DNA replication fork.


Subject(s)
Antimetabolites, Antineoplastic/chemistry , Antimetabolites, Antineoplastic/pharmacology , DNA Replication/drug effects , Nucleic Acid Synthesis Inhibitors/chemistry , Nucleic Acid Synthesis Inhibitors/pharmacology , Thymidine/analogs & derivatives , Thymidine/pharmacology , Breast Neoplasms/drug therapy , Female , Humans , MCF-7 Cells
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