A comparison of particulate hexavalent chromium cytotoxicity and genotoxicity in human and leatherback sea turtle lung cells from a one environmental health perspective.

Evaluating health risks of environmental contaminants can be better achieved by considering toxic impacts across species. Hexavalent chromium [Cr(VI)] is a marine pollutant and global environmental contaminant. While Cr(VI) has been identified as a human lung carcinogen, health effects in marine species are poorly understood. Little is known about how Cr(VI) might impact humans and marine species differently. This study used a One Environmental Health Approach to compare the cytotoxicity and genotoxicity of particulate Cr(VI) in human and leatherback sea turtle (Dermochelys coriacea) lung fibroblasts. Leatherbacks may experience prolonged exposures to environmental contaminants and provide insight to how environmental exposures affect health across species. Since humans and leatherbacks may experience prolonged exposure to Cr(VI), and prolonged Cr(VI) exposure leads to carcinogenesis in humans, in this study we considered both acute and prolonged exposures. We found particulate Cr(VI) induced cytotoxicity in leatherback cells comparable to human cell data supporting current research that shows Cr(VI) impacts health across species. To better understand mechanisms of Cr(VI) toxicity we assessed the genotoxic effects of particulate Cr(VI) in human and leatherback cells. Particulate Cr(VI) induced similar genotoxicity in both cell lines, however, human cells arrested at lower concentrations than leatherback cells. We also measured intracellular Cr ion concentrations and found after prolonged exposure human cells accumulated more Cr than leatherback cells. These data indicate Cr(VI) is a health concern for humans and leatherbacks. The data also suggest humans and leatherbacks respond to chemical exposure differently, possibly leading to the discovery of species-specific protective mechanisms.

A whale of a tale: A One Environmental Health approach to study metal pollution in the Sea of Cortez.

Marine metal pollution is an emerging concern for human, animal, and ecosystem health. We considered metal pollution in the Sea of Cortez, which is a relatively isolated sea rich in biodiversity. Here there are potentially significant anthropogenic inputs of pollution from agriculture and metal mining. We considered the levels of 23 heavy metals and selenium in seven distinct cetacean species found in the area. Our efforts considered two different periods of time: 1999 and 2016/17. We considered the metal levels in relation to (1) all species together across years, (2) differences between suborders Odontoceti and Mysticeti, (3) each species individually across years, and (4) gender differences for each of these comparisons. We further compared metal levels found in sperm whale skin samples collected during these voyages to a previous voyage in 1999, to assess changes in metal levels over a longer timescale. The metals Mg, Fe, Al, and Zn were found at the highest concentrations across all species and all years. For sperm whales, we observed decreased metal levels from 1999 to 2016/2017, except for iron (Fe), nickel (Ni), and chromium (Cr), which either increased or did not change during this time period. These results indicate a recent change in the metal input to the Sea of Cortez, which may indicate a decreased concern for human, animal, and ecosystem health for some metals, but raises concern for the genotoxic metals Cr and Ni. This work was supported by NIEHS grant ES016893 (J.P.W.) and numerous donors to the Wise Laboratory.

Impact of rurality on maternal and infant health indicators and outcomes in Maine.

INTRODUCTION: Rural residents may face health challenges related to geographic barriers to care, physician shortages, poverty, lower educational attainment, and other demographic factors. In maternal and child health, these disparities may be evidenced by the health risks and behaviors of new mothers, the health of infants born to these mothers, and the care received by both mothers and infants. METHODS: To determine the impact of rurality on maternal and child health in Maine, USA, 11 years of data (2000-2010) for the state of Maine from the Pregnancy Risk Assessment Monitoring System (PRAMS) project were analyzed. PRAMS is a national public health surveillance system that uses questionnaires to survey women who had delivered live infants in the previous 2-4 months. Using a geographic information system, each questionnaire response was assigned a rurality tier (urban, suburban, large rural town, or isolated rural community) based on the rural-urban commuting area code of the town of residence of the mother. Results from the four rurality tiers were compared using the survey procedures in Statistical Analysis Software to adjust for the complex sampling strategy of the PRAMS dataset. Means (for continuous variables) and percentages (for categorical variables) were calculated for each rurality tier, along with 95% confidence intervals. Significant differences between rurality tiers were tested for using F-tests or χ2 tests. If significant differences between rurality tiers existed (p<0.05), specific tiers were judged to be different from each other if their 95% confidence intervals did not overlap. RESULTS: A total of 12 600 mothers responded to the PRAMS questionnaire during the study period. Compared to mothers from more urban areas, rural mothers were younger (10.5% of mothers from isolated rural areas were teenagers compared to 6.2% of mothers from urban areas), less well educated, less likely to be married, and more likely to live in lower income households (39.6% of isolated rural mothers had household incomes ≤US$20 000/year vs 28.8% of urban mothers). Rural mothers had higher pre-pregnancy body mass indexes (BMIs; average BMI 26.1 for isolated rural women vs 25.3 for urban women) and were more likely to smoke but less likely to drink alcohol (both before and during pregnancy). Compared to mothers from more urban areas, rural mothers were not sure they were pregnant until a later gestational age but received prenatal care just as early and were just as likely to receive prenatal care as early as they wished. There were no differences among rurality tiers in Caesarean section rates, rates of premature births (<37 weeks gestation), or rates of underweight births (<2500 g). However infants born to rural mothers were less likely to be breastfed (52.9% of isolated rural vs 60.9% of urban infants breast fed for ≥8 weeks). CONCLUSIONS: These results show that, while rural women face significant demographic and behavior challenges, their access to prenatal care, the care they receive while pregnant, and the outcomes of their pregnancies are similar to those of urban women. These results highlight areas where focused pre-pregnancy and prenatal education may improve maternal and child health in rural Maine.

The Maine Savvy Caregiver Project: translating an evidence-based dementia family caregiver program within the RE-AIM Framework.

This article presents findings of a 3-year Savvy Caregiver Program translational study designed with the RE-AIM framework to create a statewide sustainable infrastructure and improve dementia family caregiver outcomes in one rural state. The RE-AIM dimensions--reach, effectiveness, adoption, implementation and maintenance--were evaluated using mixed methods. The program reached 770 caregivers and 87.7% (n = 676) participated in the study with 60.5% (n = 409) residing in rural locations. Participants demonstrated improved confidence, fewer depressive symptoms, and better managed their situation. Trainer resources, partnerships, and adequate planning were essential for program adoption and sustainability. Implications for replication are discussed.

A cardiovascular disease risk factor screening program designed to reach rural residents of Maine, USA.

INTRODUCTION: Cardiovascular disease is the leading cause of death in many countries and a particular burden to rural communities. Hypertension and diabetes are risk factors for cardiovascular disease, but screening for them is suboptimal, particularly in rural settings. Thus screening programs targeting rural dwellers may be important. This article reports the findings of a blood pressure (BP) and blood glucose screening program conducted from a mobile van that visited community events including agricultural fairs across Maine, U.S.A. to bring screening to rural Mainers. The study objectives were to determine: (1) if the screening program was successful at reaching rural Mainers; (2) if rural screenees had a different risk of hypertension or diabetes compared with non-rural screenees; and (3) what characteristics of a community event predict that a screening conducted at that event will reach a high fraction of rural residents. METHODS: The van visited events from 2006-2009 conducting voluntary BP and blood glucose screenings. Results were analyzed by the rurality of the town of residence of the screenees, the rurality of location of the screening event, and the type of screening event (agricultural fair vs other). Systolic BP of 140 mmHg or greater or diastolic BP of 90 mmHg or greater was considered to be hypertension, and systolic BP of 120-139 mmHg or diastolic BP 80-89 mmHg as pre-hypertension. Blood glucose of 140-199 mg/dL was considered to be pre-diabetes and blood glucose of 200 mg/dL or greater as diabetes. Rurality was divided into urban, sub-urban, large rural town, and small rural town/ isolated rural based on Rural Urban Commuting Codes (RUCAs), assigned by zip code. Mean BP and blood glucose values were compared across residence rurality categories by ANOVA, the distribution of screening values into normal/ abnormal categories was compared across residence rurality categories by chi2 test, and the impact of type and rurality of location of screening event on the residence of screenees was assessed with analysis by regression with categorical variables. RESULTS: Over 4 years, 2451 Mainers from 254 towns were screened at 42 events located in 28 towns. Seventy-six percent of screenees lived in rural areas and screenees were more likely to live in rural areas compared with all Maine residents (p < 0.001). Rurality of residence impacted hypertension risk (p = 0.001) but not diabetes risk. Screenees from large rural towns had the highest mean systolic BPs and rural-dwellers had higher hypertension or pre-hypertension risk compared with urban/ sub-urban dwellers. Conducting screenings at agricultural fairs (p = 0.003) and in rural areas (p = 0.001) were independent predictors of attracting more rural screenees. CONCLUSIONS: Holding cardiovascular risk factor screenings in locations that are culturally appropriate and geographically convenient for an at-risk population are common approaches; however, their effectiveness is seldom tested. The results show that both the type of event at which the screening is conducted and the rurality of location of that event help attract rural screenees, and that it is possible for a screening program to reach a population significantly more rural than the population of the state and one that has an elevated hypertension risk.

Chronic exposure to zinc chromate induces centrosome amplification and spindle assembly checkpoint bypass in human lung fibroblasts.

Hexavalent chromium (Cr(VI)) compounds are known human lung carcinogens. Solubility plays an important role in its carcinogenicity with the particulate or insoluble form being the most potent. Of the particulate Cr(VI) compounds, zinc chromate appears to be the most potent carcinogen; however, very few studies have investigated its carcinogenic mechanism. In this study, we investigated the ability of chronic exposure to zinc chromate to induce numerical chromosome instability. We found no increase in aneuploidy after a 24 h exposure to zinc chromate, but with more chronic exposures, zinc chromate induced concentration- and time-dependent increases in aneuploidy in the form of hypodiploidy, hyperdiploidy, and tetraploidy. Zinc chromate also induced centrosome amplification in a concentration- and time-dependent manner in both interphase and mitotic cells after chronic exposure, producing cells with centriolar defects. Furthermore, chronic exposure to zinc chromate induced concentration- and time-dependent increases in spindle assembly checkpoint bypass with increases in centromere spreading, premature centromere division, and premature anaphase. Last, we found that chronic exposure to zinc chromate induced a G2 arrest. All together, these data indicate that zinc chromate can induce chromosome instability after prolonged exposures.

Particulate depleted uranium is cytotoxic and clastogenic to human lung epithelial cells.

Depleted uranium (DU) is commonly used in military applications and consequently exposure to soldiers and non-combatants is potentially frequent and widespread. DU is suspected to be a carcinogen, potentially affecting the bronchial cells of the lung. Few studies have considered DU in human bronchial cells. Accordingly, we determined the cytotoxicity and clastogenicity of particulate DU in human bronchial epithelial cells (BEP2D cells). DU-induced concentration-dependent cytotoxicity in human bronchial epithelial cells, and was not clastogenic after 24h but induced chromosomal aberrations after 48h. These data indicate that if DU is a human bronchial carcinogen, it is likely acting through a mechanism that involves DNA breaks after longer exposures.

Building on Self-efficacy for Experienced Family Caregivers: The Savvy Advanced Program.

BACKGROUND AND OBJECTIVES: The Savvy Advanced psychoeducation program was designed for previously trained caregivers of persons living with dementia to refine their problem-solving and planning skills and enhance their sense of self-efficacy as dementia progressed for the care recipient. Implementation, feasibility, participant satisfaction, and perceived program benefits were also evaluated. RESEARCH DESIGN AND METHODS: A total of 100 dementia family caregivers participated in the 12-month evaluation of Savvy Advanced. A pragmatic quasi-experimental no control design was used to examine changes in caregiver self-efficacy, competence, personal gain, skill mastery, and symptoms of depression from baseline to 5 and 12 months postintervention. Implementation feasibility, and participant satisfaction and perceived program benefits, were also evaluated. RESULTS: Having previously participated in a psychoeducation intervention, caregivers were quickly engaged and interactive. Caregivers demonstrated significant improvement in competence, personal gain, self-efficacy, and symptoms of depression at 5 months postprogram. Gains were sustained for competence and personal gain at 12 months. Caregivers were highly satisfied with the program and supporting materials. Challenges to implementation included caregiver recruitment and trainer sustainability. DISCUSSION AND IMPLICATIONS: Caregivers can benefit from episodic interventions as their situation changes and new challenges arise. Savvy Advanced is one means to address these needs. Evaluation in a randomized trial is required to establish efficacy; examination of alternative modes of delivery for caregivers unable to attend in person is warranted.

Metal tissue levels in Steller sea lion (Eumetopias jubatus) pups.

The endangered Western population of the Steller sea lion declined for three decades for uncertain reasons. We present baseline data of metal concentrations in pups as a first step towards investigating the potential threat of developmental exposures to contaminants. Seven metals were investigated: arsenic, cadmium, silver, aluminum, mercury, lead and vanadium. Vanadium was detected in only a single blubber sample. Mercury appears to be the most toxicologically significant metal with concentrations in the liver well above the current action level for mercury in fish. The concentrations of aluminum, arsenic, silver, cadmium and lead were present in one-fourth to two-thirds of all samples and were at either comparable or below concentrations previously reported. Neither gender nor region had a significant effect on metal burdens. Future work should consider metal concentrations in juveniles and adults and toxicological studies need to be performed to begin to assess the toxicity of these metals.

The cytotoxicity and genotoxicity of particulate and soluble hexavalent chromium in leatherback sea turtle lung cells.

Hexavalent chromium [Cr(VI)] is a marine pollution of concern as recent studies show it has a global distribution, with some regions showing high Cr concentrations in marine animal tissue, and it is extensively used. Leatherback sea turtles (Dermochelys coriacea) are an endangered marine species that may experience prolonged exposures to environmental contaminants including Cr(VI). Human activities have led to global Cr(VI) contamination of the marine environment. While Cr(VI) has been identified as a known human carcinogen, the health effects in marine species are poorly understood. In this study, we assessed the cytotoxic and genotoxic effects of particulate and soluble Cr(VI) in leatherback sea turtle lung cells. Both particulate and soluble Cr(VI) induced a concentration-dependent increase in cytotoxicity. Next, using a chromosome aberration assay, we assessed the genotoxic effects of Cr(VI) in leatherback sea turtle lung cells. Particulate and soluble Cr(VI) induced a concentration-dependent increase in clastogenicity in leatherback sea turtle lung cells. These data indicate that Cr(VI) may be a health concern for leatherback sea turtles and other long-lived marine species. Additionally, these data provide foundational support to use leatherback sea turtles as a valuable model species for monitoring the health effects of Cr(VI) in the environment and possibly as an indicator species to assess environmental human exposures and effects.

Ku80 deficiency does not affect particulate chromate-induced chromosome damage and cytotoxicity in Chinese hamster ovary cells.

Particulate hexavalent chromium ((Cr(VI)) compounds are human lung carcinogens. These compounds induce DNA damage, chromosome aberrations, and concentration-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between Cr(VI)-induced DNA damage and chromosome aberrations is poorly understood. Accordingly, this study focused on examining the role of Ku80, a gene involved in nonhomologous end-joining repair, in particulate chromate-induced cytotoxicity and chromosome damage in CHO cells. Three different cell lines were used: CHO-K1 (parental), xrs-6 (Ku80 deficient), and 2E (xrs-6 complemented with Ku80 gene). Levels of cell death were higher in xrs-6 cells when compared to wild type, suggesting that Ku80 was important for protecting cells from lead chromate. However, Ku80 played no role in protecting cells from particulate Cr(VI)-induced chromosome instability (CIN) as gene complementation with Ku80 (2E cells) studies and uptake experiments showed similar frequency and amounts of chromosome damage between the cell lines and that any observed difference based on administered concentration was actually due to differences in Cr(VI) uptake. The spectrum of chromosome damage was also unaffected by Ku80 deficiency. These data indicate that Ku80 protects cells from cytotoxicity but is not involved in protecting cells from particulate chromate-induced CIN.

The Impact of Maternal Obesity and Excessive Gestational Weight Gain on Maternal and Infant Outcomes in Maine: Analysis of Pregnancy Risk Assessment Monitoring System Results from 2000 to 2010.

The objective of this study is to understand the relationships between prepregnancy obesity and excessive gestational weight gain (GWG) and adverse maternal and fetal outcomes. Pregnancy risk assessment monitoring system (PRAMS) data from Maine for 2000-2010 were used to determine associations between demographic, socioeconomic, and health behavioral variables and maternal and infant outcomes. Multivariate logistic regression analysis was performed on the independent variables of age, race, smoking, previous live births, marital status, education, BMI, income, rurality, alcohol use, and GWG. Dependent variables included maternal hypertension, premature birth, birth weight, infant admission to the intensive care unit (ICU), and length of hospital stay of the infant. Excessive prepregnancy BMI and excessive GWG independently predicted maternal hypertension. A high prepregnancy BMI increased the risk of the infant being born prematurely, having a longer hospital stay, and having an excessive birth weight. Excessive GWG predicted a longer infant hospital stay and excessive birth weight. A low pregnancy BMI and a lower than recommended GWG were also associated with poor outcomes: prematurity, low birth weight, and an increased risk of the infant admitted to ICU. These findings support the importance of preconception care that promotes achievement of a healthy weight to enhance optimal reproductive outcomes.

11-year trends in pregnancy-related health indicators in Maine, 2000-2010.

The objective of this study is to understand health and demographic trends among mothers and infants in Maine relative to the goals of Healthy People 2020. Pregnancy risk assessment monitoring system (PRAMS) data from Maine for 2000-2010 were used to determine yearly values of pregnancy-related variables. Means (for continuous variables) and percentages (for categorical variables) were calculated using the survey procedures in SAS. Linear trend analysis was applied with study year as the independent variable. The slope and significance of the trend were then calculated. Over the study period, new mothers in Maine became better educated but the fraction of households with incomes <$20,000/year remained stagnant. Maternal prepregnancy BMI increased. Average pregnancy weight gain decreased but the number of women whose pregnancy weight gain was within the recommended range was unchanged. The rates of smoking and alcohol consumption (before and during pregnancy) increased. The Caesarean section rate rose and the fraction of infants born premature (<37 wks gestation) or underweight (<2500 gms) remained unchanged. The fraction of infants who were breast-fed increased. These results suggest that, despite some positive trends, Maine faces significant challenges in meeting Healthy People 2020 goals.

The genotoxicity of particulate and soluble chromate in sperm whale (physeter macrocephalus) skin fibroblasts.

Hexavalent chromium is a marine pollutant of concern, both for the health of ocean ecosystems and for public health. Hexavalent chromium is known to induce genotoxicity in human and other terrestrial mammals. It is also known to be present in both water and air in the marine environment. However, currently there are limited data concerning both chromium levels and its toxicological effects in marine mammals. This study investigated the cytotoxic and genotoxic effects of soluble and particulate hexavalent chromium in sperm whale skin fibroblasts. Both forms of hexavalent chromium induced concentration-dependent increases in cytotoxicity and genotoxicity indicating that these compounds can be a health risk if the whales are exposed to them. These data support a hypothesis that chromium is a concern in the marine environment in general and for the health of sperm whales in particular.

The cytotoxicity and genotoxicity of hexavalent chromium in Steller sea lion lung fibroblasts compared to human lung fibroblasts.

In this study we directly compared soluble and particulate chromate cytotoxicity and genotoxicity in human (Homo sapiens) and sea lion (Eumetopias jubatus) lung fibroblasts. Our results show that hexavalent chromium induces increased cell death and chromosome damage in both human and sea lion cells with increasing intracellular chromium ion levels. The data further indicate that both sodium chromate and lead chromate are less cytotoxic and genotoxic to sea lion cells than human cells, based on an administered dose. Differences in chromium ion uptake explained some but not all of the reduced amounts of sodium chromate-induced cell death. By contrast, uptake differences could explain the differences in sodium chromate-induced chromosome damage and particulate chromate-induced toxicity. Altogether they indicate that while hexavalent chromium induces similar toxic effects in sea lion and human cells, there are different mechanisms underlying the toxic outcomes.

Silver nanospheres are cytotoxic and genotoxic to fish cells.

Nanoparticles are being widely investigated for a range of applications due to their unique physical properties. For example, silver nanoparticles are used in commercial products for their antibacterial and antifungal properties. Some of these products are likely to result in silver nanoparticles reaching the aquatic environment. As such, nanoparticles pose a health concern for humans and aquatic species. We used a medaka (Oryzias latipes) cell line to investigate the cytotoxicity and genotoxicity of 30nm diameter silver nanospheres. Treatments of 0.05, 0.3, 0.5, 3 and 5microg/cm(2) induced 80, 45.7, 24.3, 1 and 0.1% survival, respectively, in a colony forming assay. Silver nanoparticles also induced chromosomal aberrations and aneuploidy. Treatments of 0, 0.05, 0.1 and 0.3microg/cm(2) induced damage in 8, 10.8, 16 and 15.8% of metaphases and 10.8, 15.6, 24 and 24 total aberrations in 100 metaphases, respectively. These data show that silver nanoparticles are cytotoxic and genotoxic to fish cells.

Particulate and soluble hexavalent chromium are cytotoxic and genotoxic to Steller sea lion lung cells.

Hexavalent chromium is an environmental contaminant. Within the environment, marine waters are a common site for hexavalent chromium deposition. We have recently reported significantly high levels of chromium in skin tissue from North Atlantic right whales. These findings demonstrate that marine species are being exposed to chromium. It is possible that such exposures may be playing a role in population declines evident among certain marine mammals, such as the Steller sea lion. We developed a Steller sea lion lung cell line from Steller sea lion lung tissue. Hexavalent chromium was cytotoxic to these primary lung fibroblasts as 1, 2.5, 5, 10 and 25microM sodium chromate induced 104, 99, 92, 58 and 11% relative survival, respectively. It was also genotoxic as 0, 1, 2.5, 5 and 10microM sodium chromate damaged chromosomes in 6, 11, 21, 36, and 39% of metaphases and damaged 6, 12, 27, 49 and 57 total aberrations in 100 metaphases, respectively. We also considered the toxicity of particulate hexavalent chromium, as it is the more potent carcinogen in humans. We found that 0.1, 0.5, 1, 5 and 10microg/cm(2) particulate chromate induced 95, 88, 91, 70, and 52% relative cell survival, respectively. These concentrations were genotoxic and damaged chromosomes in 9, 13, 18, and 23% of metaphases and induced 9, 15, 20 and 30 total aberrations per 100 metaphases, respectively. These data indicate that if sufficiently exposed, chromium may adversely affect the struggling Steller sea lion population. It would be prudent to investigate the effects chromium has in other Steller sea lion organs in order to derive a better understanding of how chromium in the marine environment may be affecting the declining Steller sea lion population.

Particulate depleted uranium is cytotoxic and clastogenic to human lung cells.

Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and non-combatants is potentially frequent and widespread. DU is considered a suspected human carcinogen, affecting the bronchial cells of the lung. However, few investigations have studied DU in human bronchial cells. Accordingly, we determined the cytotoxicity and clastogenicity of both particulate (water-insoluble) and soluble DU in human bronchial fibroblasts (WTHBF-6 cells). We used uranium trioxide (UO3) and uranyl acetate (UA) as prototypical particulate and soluble DU salts, respectively. After a 24 h exposure, both UO3 and UA induced concentration-dependent cytotoxicity in WTHBF-6 cells. Specifically, 0.1, 0.5, 1, and 5 microg/cm2 UO3 induced 99, 57, 32, and 1% relative survival, respectively. Similarly, 100, 200, 400, and 800 microM UA induced 98, 92, 70, and 56% relative survival, respectively. When treated with chronic exposure, up to 72 h, of either UO3 or UA, there was an increased degree of cytotoxicity. We assessed the clastogenicity of these compounds and found that at concentrations of 0, 0.5, 1, and 5 microg/cm2 UO3, 5, 6, 10, and 15% of metaphase cells exhibit some form of chromosome damage. UA did not induce chromosome damage above background levels. There were slight increases in chromosome damage induced when we extended the UO3 treatment time to 48 or 72 h, but no meaningful increase in chromosome damage was observed with chronic exposure to UA.