Fatalities Involving Substance Use Among US Oil and Gas Extraction Workers Identified Through an Industry Specific Surveillance System (2014-2019).

OBJECTIVE: Characteristics of oil and gas extraction (OGE) work, including long hours, shiftwork, fatigue, physically demanding work, and job insecurity are risk factors for substance use among workers. Limited information exists examining worker fatalities involving substance use among OGE workers. METHODS: The National Institute for Occupational Safety and Health's Fatalities in Oil and Gas Extraction database was screened for fatalities involving substance use from 2014 through 2019. RESULTS: Twenty-six worker deaths were identified as involving substance use. Methamphetamine or amphetamine was the most common substances (61.5%) identified. Other contributing factors were lack of seatbelt use (85.7%), working in high temperatures (19.2%), and workers' first day with the company (11.5%). CONCLUSIONS: Employer recommendations to mitigate substance use-related risks in OGE workers include training, medical screening, drug testing, and workplace supported recovery programs.

Working Alone and/or in Remote Locations: Opportunities to Prevent the Risk of Fatality From Cardiovascular Events in Oil and Gas Extraction Workers.

OBJECTIVE: The aim of the study is to explore personal and work factors related to fatal cardiac events among oil and gas extraction (OGE) workers. METHODS: The National Institute for Occupational Safety and Health Fatalities in Oil and Gas Extraction database was reviewed to identify fatal cardiac events among OGE workers from 2014 through 2019. A case series design was used to review case files, provide descriptive statistics, and summarize the findings. RESULTS: There were 75 fatalities identified, including 55 (73%) with sufficient information for review. Of the 55 workers, 18 (33%) worked alone. Thirty-six fatal cardiac events (66%) were unwitnessed by a coworker. Toxicology findings suggested some possible exposures to hydrogen sulfide or hydrocarbon gases or vapors. Missing data were common. CONCLUSIONS: This study identified the need for cardiovascular disease prevention and treatment, emergency preparedness, lone worker programs, medical screening, and enhanced exposure control in the OGE industry.

Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes.

BACKGROUND: No targeted immunotherapies reverse type 1 diabetes in humans. However, in a rodent model of type 1 diabetes, Bacillus Calmette-Guerin (BCG) reverses disease by restoring insulin secretion. Specifically, it stimulates innate immunity by inducing the host to produce tumor necrosis factor (TNF), which, in turn, kills disease-causing autoimmune cells and restores pancreatic beta-cell function through regeneration. METHODOLOGY/PRINCIPAL FINDINGS: Translating these findings to humans, we administered BCG, a generic vaccine, in a proof-of-principle, double-blind, placebo-controlled trial of adults with long-term type 1 diabetes (mean: 15.3 years) at one clinical center in North America. Six subjects were randomly assigned to BCG or placebo and compared to self, healthy paired controls (n = 6) or reference subjects with (n = 57) or without (n = 16) type 1 diabetes, depending upon the outcome measure. We monitored weekly blood samples for 20 weeks for insulin-autoreactive T cells, regulatory T cells (Tregs), glutamic acid decarboxylase (GAD) and other autoantibodies, and C-peptide, a marker of insulin secretion. BCG-treated patients and one placebo-treated patient who, after enrollment, unexpectedly developed acute Epstein-Barr virus infection, a known TNF inducer, exclusively showed increases in dead insulin-autoreactive T cells and induction of Tregs. C-peptide levels (pmol/L) significantly rose transiently in two BCG-treated subjects (means: 3.49 pmol/L [95% CI 2.95-3.8], 2.57 [95% CI 1.65-3.49]) and the EBV-infected subject (3.16 [95% CI 2.54-3.69]) vs.1.65 [95% CI 1.55-3.2] in reference diabetic subjects. BCG-treated subjects each had more than 50% of their C-peptide values above the 95(th) percentile of the reference subjects. The EBV-infected subject had 18% of C-peptide values above this level. CONCLUSIONS/SIGNIFICANCE: We conclude that BCG treatment or EBV infection transiently modified the autoimmunity that underlies type 1 diabetes by stimulating the host innate immune response. This suggests that BCG or other stimulators of host innate immunity may have value in the treatment of long-term diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00607230.

Effects of cucurbitacins on cell morphology are associated with sensitization of renal carcinoma cells to TRAIL-induced apoptosis.

Cucurbitacins B and D were among the compounds identified as sensitizers of cancer cells to TRAIL-mediated apoptosis in a high-throughput screen. Therefore a series of cucurbitacins was further investigated for TRAIL sensitization and possible mechanisms of action. A total of six cucurbitacins promoted TRAIL-induced apoptosis (B, I, E, C, D, and K) and one (P) was inactive. Sensitization of renal adenocarcinoma cells to TRAIL was apparent after as little as 1-4 h pretreatment and did not require continued presence of cucurbitacin. Active cucurbitacins induced caspase-8 activation only after subsequent TRAIL addition and caspase activation was required for apoptosis suggesting amplified proximal signaling from TRAIL death receptors. Cucurbitacin-sensitized TRAIL-induced cytotoxicity was inhibited by N-acetyl cysteine. Structure-activity relationship analysis in comparison to published studies suggests that TRAIL-sensitizing and general cytotoxic activities of cucurbitacins may be decoupled. Cucurbitacins are reported to be inhibitors of STAT3 activation. However, their TRAIL-sensitizing activity is STAT3-independent. Treatment of renal carcinoma cells with active cucurbitacins produced rapid and dramatic changes in cell morphology and cytoskeletal organization (also prevented by NAC). Therefore, cucurbitacins may be useful as tools for investigating the molecular mechanism(s) of action of TRAIL sensitizers, particularly with regard to temporal aspects of sensitization and modulation of TRAIL signaling by cell morphology, and could form the basis for future therapeutic development in combination with TRAIL death receptor agonists.