Karen Hopcia

Role of Fenton Chemistry in Thiol-Induced Toxicity and Apoptosis

Under certain conditions, many radioprotective thiols can be toxic, causing loss of colony-forming ability in cultured mammalian cells in a biphasic fashion whereby the thiols are not toxic at high or low concentrations of the drug, but cause decreased clonogenicity at intermediate (0.2-1.0 mM) drug levels. This symposium paper summarizes our studies using dithiothreitol (DTT) as a model thiol to demonstrate the role of Fenton chemistry in thiol toxicity. The toxicity of DTT in V79 cells has several characteristics: it is dependent on the medium used during exposure of cells to the drug; the toxicity is decreased or prevented by addition of catalase exogenously, but superoxide dismutase has no effect; the toxicity is increased by addition of copper, either free or derived from ceruloplasmin in serum; and the toxicity can be modified intracellularly by altering glucose availability or pentose cycle activity. Thus the data are consistent with a mechanism whereby DTT oxidation produces H2O2 in a reaction catalyzed by metals, predominantly copper, followed by reaction of H2O2 in a metal-catalyzed Fenton reaction to produce the ultimate toxic species, .OH. Studies comparing 12 thiols have shown that the magnitude of cell killing and pattern of dependence on thiol concentration vary among the different agents, with the toxicity depending on the interplay between the rates of two reactions: thiol oxidation and the reaction between the thiol and the H2O2 produced during the thiol oxidation. The addition of other metals, e.g. Zn2+, and metal chelators, e.g. EDTA, can also alter DTT toxicity by altering the rates of thiol oxidation or the Fenton reaction. Recent studies have shown that in certain cell lines thiols can also cause apoptosis in a biphasic pattern, with little apoptosis at low or high drug concentrations but greatly increased apoptosis levels at intermediate (approximately 3 mM) thiol concentrations. There appears to be a good correlation between those thiols that cause loss of clonogenicity and those that induce apoptosis, suggesting similar mechanisms may be involved in both end points. However, thiol-induced apoptosis is not prevented by addition of exogenous catalase. These observations are discussed in relation to the possible role of Fenton chemistry in induction of apoptosis by thiols.

Radiation-Induced Apoptosis in HL60 Cells: Oxygen Effect, Relationship between Apoptosis and Loss of Clonogenicity, and Dependence of Time to Apoptosis on Radiation Dose

Apoptosis in HL60 human leukemia cells irradiated in vitro was quantified using a DNA fragmentation assay. Dose-response curves for induction of apoptosis in HL60 cells 6 h after irradiation with 280 kVp X rays in air and hypoxia give an oxygen enhancement ratio (OER) of 2.7. This is similar to the OER of 2.8 obtained from survival curves for HL60 cells using a soft agar clonogenic assay. However, HL60 cells are much more sensitive to radiation-induced loss of clonogenicity than to induction of apoptosis at 6 h. For example, 12 Gy in air reduces the surviving fraction to about 0.002 in a clonogenic assay, but 12 Gy does not cause any significant increase in the percentage of apoptosis-like DNA fragmentation 6 h after irradiation compared to unirradiated controls. However, if apoptosis is assayed 2-4 days after irradiation, the HL60 cells show greater sensitivity, with 5 Gy in air causing 45-50% apoptosis at 3 days. When apoptosis is measured 3 days after irradiation, the OER is similar to that obtained for survival and for apoptosis at 6 h. Although the HL60 cells exhibit radiation-induced apoptosis if one waits 2-4 days after low doses of radiation, rather than just 6 h, to conduct the assay, the amount of cells undergoing apoptosis is still not sufficient to account for all the loss of clonogenicity seen when HL60 cells are exposed to ionizing radiation.

The role of the work context in multiple wellness outcomes for hospital patient care workers

Objective:To examine the relationships among low back pain (LBP), inadequate physical activity, and sleep deficiency among patient care workers, and of these outcomes to work context. Methods:A cross-sectional survey of patient care workers (N = 1572, response rate = 79%). Results:A total of 53% reported LBP, 46%, inadequate physical activity, and 59%, sleep deficiency. Inadequate physical activity and sleep deficiency were associated (P = 0.02), but LBP was not significantly related to either. Increased risk of LBP was significantly related to job demands, harassment at work, decreased supervisor support, and job title. Inadequate physical activity was significantly associated with low decision latitude. Sleep deficiency was significantly related to low supervisor support, harassment at work, low ergonomic practices, people-oriented culture, and job title. Conclusions:These findings point to shared pathways in the work environment that jointly influence multiple health and well-being outcomes.

Ergonomic practices within patient care units are associated with musculoskeletal pain and limitations

BACKGROUND With the high prevalence of musculoskeletal disorders (MSDs) for patient care unit workers, prevention efforts through ergonomic practices within units may be related to symptoms associated with typical work-related MSDs. METHODS We completed a cross-sectional survey of patient care workers (n = 1,572) in two large academic hospitals in order to evaluate relationships between self-reported musculoskeletal pain, work interference due to this pain, and limitations during activities of daily living (functional limitations) and with ergonomic practices and other organizational policy and practices metrics within the unit. Bivariate and multiple logistic regression analyses tested the significance of these associations. RESULTS Prevalence of self-reported musculoskeletal symptoms in the past 3 months was 74% with 53% reporting pain in the low back. 32.8% reported that this pain interfered with their work duties and 17.7% reported functional limitations in the prior week. Decreased ergonomic practices were significantly associated with reporting pain in four body areas (low back, neck/shoulder, arms, and lower extremity) in the previous 3 months, interference with work caused by this pain, symptom severity, and limitations in completing activities of daily living in the past week. Except for low back pain and work interference, these associations remained significant when psychosocial covariates such as psychological demands were included in multiple logistic regressions. CONCLUSIONS Ergonomic practices appear to be associated with many of the musculoskeletal symptoms denoting their importance for prevention efforts in acute health care settings.

Psychosocial stress and multi-site musculoskeletal pain: A cross-sectional survey of patient care workers

The aim of this study was to assess the relationship between psychosocial factors at work and multi-site musculoskeletal pain among patient care workers. In a survey of 1,572 workers from two hospitals, occupational psychosocial factors and health outcomes of workers with single and multi-site pain were evaluated using items from the Job Content Questionnaire that was designed to measure psychological demands, decision latitude, and social support. An adapted Nordic Questionnaire provided data on the musculoskeletal pain outcome. Covariates included body mass index, age, gender, and occupation. The analyses revealed statistically significant associations between psychosocial demands and multi-site musculoskeletal pain among patient care associates, nurses, and administrative personnel, both men and women. Supervisor support played a significant role for nurses and women. These results remained statistically significant after adjusting for covariates. These results highlight the associations between workplace psychosocial strain and multi-site musculoskeletal pain, setting the stage for future longitudinal explorations.

Occupational injuries among nurses and aides in a hospital setting

BACKGROUND Patient care workers in acute care hospitals are at high risk of injury. Recent studies have quantified risks and demonstrated a higher risk for aides than for nurses. However, no detailed studies to date have used OSHA injury definitions to allow for better comparability across studies. METHODS We linked records from human resources and occupational health services databases at two large academic hospitals for nurses (n = 5,991) and aides (n = 1,543) in patient care units. Crude rates, rate ratios, and confidence intervals were calculated for injuries involving no days away and those involving at least 1 day away from work. RESULTS Aides have substantially higher injury rates per 100 full-time equivalent workers (FTEs) than nurses for both injuries involving days away from work (11.3 vs. 7.2) and those involving no days away (9.9 vs. 5.7). Back injuries were the most common days away (DA) injuries, while sharps injuries were the most common no days away (NDA) injuries. Pediatric/neonatal units and non-inpatient units had the lowest injury rates. Operating rooms and the float pool had high DA injury rates for both occupations, and stepdown units had high rates for nurses. NDA injuries were highest in the operating room for both nurses and aides. CONCLUSIONS This study supports the importance of a continuing emphasis on preventing back and sharps injuries and reducing risks faced by aides in the hospital setting. Uniform injury definitions and work time measures can help benchmark safety performance and focus prevention efforts.

Work-Family Conflict, Psychological Distress and Sleep Deficiency Among Patient Care Workers

This study examined whether work-family conflict was associated with sleep deficiencies, both cross-sectionally and longitudinally. In this two-phase study, a workplace health survey was completed by a cohort of patient care workers (n = 1,572). Additional data were collected 2 years later from a subsample of the original respondents (n = 102). Self-reported measures included work-family conflict, workplace factors, and sleep outcomes. The participants were 90% women, with a mean age of 41 ± 11.7 years. At baseline, after adjusting for covariates, higher levels of work-family conflict were significantly associated with sleep deficiency. Higher levels of work-family conflict also predicted sleep insufficiency nearly 2 years later. The first study to determine the predictive association between work-family conflict and sleep deficiency suggests that future sleep interventions should include a specific focus on work-family conflict.

Physical Activity and Body Mass Index: The Contribution of Age and Workplace Characteristics

BACKGROUND The workplace is an important domain for adults, and many effective interventions targeting physical activity and weight reduction have been implemented in the workplace. However, the U.S. workforce is aging, and few studies have examined the relationship of BMI, physical activity, and age as they relate to workplace characteristics. PURPOSE This paper reports on the distribution of physical activity and BMI by age in a population of hospital-based healthcare workers and investigates the relationships among workplace characteristics, physical activity, and BMI. METHODS Data from a survey of patient care workers in two large academic hospitals in the Boston area were collected in late 2009 and analyzed in early 2013. RESULTS In multivariate models, workers reporting greater decision latitude (OR=1.02, 95% CI=1.01, 1.03) and job flexibility (OR=1.05, 95% CI=1.01, 1.10) reported greater physical activity. Overweight and obesity increased with age (p<0.01), even after adjusting for workplace characteristics. Sleep deficiency (OR=1.56, 95% CI=1.15, 2.12) and workplace harassment (OR=1.62, 95% CI=1.20, 2.18) were also associated with obesity. CONCLUSIONS These findings underscore the persistent impact of the work environment for workers of all ages. Based on these results, programs or policies aimed at improving the work environment, especially decision latitude, job flexibility, and workplace harassment should be included in the design of worksite-based health promotion interventions targeting physical activity or obesity.

Work stress, sleep deficiency, and predicted 10‐year cardiometabolic risk in a female patient care worker population

OBJECTIVES The aim of this study was to investigate the longitudinal effect of work-related stress, sleep deficiency, and physical activity on 10-year cardiometabolic risk among an all-female worker population. METHODS Data on patient care workers (n=99) was collected 2 years apart. Baseline measures included: job stress, physical activity, night work, and sleep deficiency. Biomarkers and objective measurements were used to estimate 10-year cardiometabolic risk at follow-up. Significant associations (P<0.05) from baseline analyses were used to build a multivariable linear regression model. RESULTS The participants were mostly white nurses with a mean age of 41 years. Adjusted linear regression showed that having sleep maintenance problems, a different occupation than nurse, and/or not exercising at recommended levels at baseline increased the 10-year cardiometabolic risk at follow-up. CONCLUSIONS In female workers prone to work-related stress and sleep deficiency, maintaining sleep and exercise patterns had a strong impact on modifiable 10-year cardiometabolic risk.

Occupational injuries for consecutive and cumulative shifts among hospital registered nurses and patient care associates: A case-control study

Nontraditional work shifts for hospital registered nurses and patient care associates and associated injuries were examined through a case-control study. Inpatient care requires that many staff work nontraditional shifts, including nights and 12-hour shifts, but some characteristics remain unexplored, especially consecutive shifts. A total of 502 cases (injured workers) were matched to single controls based on their hospital, unit type, job type, gender, and age (± 5 years). Conditional logistic regression was used for the analysis, controlling for weekly hours scheduled. For both, consecutive shifts of 2 or more days and some various cumulative shifts over a week and month period, especially night shifts, were associated with increased odds of injury. More investigations on the phenomenon of consecutive shifts are recommended. Additionally, the assessment of shift policy and subsequent injury outcomes is necessary before implementing intervention strategies.