Physician Training Related to Environmental Hazards near Ash Superfund Sites.

Physicians do not receive formal environmental health training in medical schools. The objectives of this study were to provide health care providers with basic environmental medicine training to better advise, treat or refer patients in the community and to observe any differences in the environmental medicine learning gains pre/post- test assessment. To rectify the problem of the lack of physicians' training related to environmental hazards, we conducted an environmental health workshop which targeted physicians living near Health Zone 1, Superfund ash sites. Fifty health care providers from both St. Vincent Family Medicine and Department of Health, Duval County Health Department (DOH-Duval) participated in a pre-test survey before the training and a post-test survey following the training. We used a non-parametric Wilcoxon Signed-Rank test to compare pre- and post- knowledge of training participants. At the 10% level of significance, the number of incorrect answers significantly declined in the post-training survey compared to the pre-training survey for all participants from both facilities combined (p=0.083). Site-specific analysis show, while a significant difference was found for participants from the St. Vincent's site (p=0.084), the difference for participants from the DOH-Duval site was not significant (p = 0.102), although the number of incorrect answers declined. The training resulted in learning gains for the 50 participants and the evaluations were very positive with 100% of physicians recommending this training to other health care providers. Additionally, training participants gave a high mark for the environmental medicine pocket guide. In 2019, the ash sites are 90% remediated and cleanup is expected to be completed in 2022. There is still a need for additional training for physicians due to other active sites (i.e., Kerr-McGee) in the community. This study highlights the importance of providing environmental hazards training to physicians and the approach by which it could be delivered effectively.

The Protective Effects of Flavonoids in Cataract Formation through the Activation of Nrf2 and the Inhibition of MMP-9.

Cataracts account for over half of global blindness. Cataracts formations occur mainly due to aging and to the direct insults of oxidative stress and inflammation to the eye lens. The nuclear factor-erythroid-2-related factor 2 (Nrf2), a transcriptional factor for cell cytoprotection, is known as the master regulator of redox homeostasis. Nrf2 regulates nearly 600 genes involved in cellular protection against contributing factors of oxidative stress, including aging, disease, and inflammation. Nrf2 was reported to disrupt the oxidative stress that activates Nuclear factor-κB (NFκB) and proinflammatory cytokines. One of these cytokines is matrix metalloproteinase 9 (MMP-9), which participates in the decomposition of lens epithelial cells (LECs) extracellular matrix and has been correlated with cataract development. Thus, during inflammatory processes, MMP production may be attenuated by the Nrf2 pathway or by the Nrf2 inhibition of NFκB pathway activation. Moreover, plant-based polyphenols have garnered attention due to their presumed safety and efficacy, nutritional, and antioxidant effects. Polyphenol compounds can activate Nrf2 and inhibit MMP-9. Therefore, this review focuses on discussing Nrf2's role in oxidative stress and cataract formation, epigenetic effect in Nrf2 activity, and the association between Nrf2 and MMP-9 in cataract development. Moreover, we describe the protective role of flavonoids in cataract formation, targeting Nrf2 activation and MMP-9 synthesis inhibition as potential molecular targets in preventing cataracts.

Myocardial infarction classification and its implications on measures of cardiovascular outcomes, quality, and racial/ethnic disparities.

Heart disease continues to be the leading cause of death in the United States, with approximately 805 000 cumulative deaths from myocardial infarctions (MI) from 2005 to 2014. Gender and racial/ethnic disparities in MI diagnoses are becoming more evident in quality review audits. Although recent changes in diagnostic codes provided an improved framework, clinically distinguishing types of MI remains a challenge. MI misdiagnoses and health disparities contribute to adverse outcomes in cardiac medicine. We conducted a literature review of relevant biomedical sources related to the classification of MI and disparities in cardiovascular care and outcomes. From the studies analyzed, African Americans and women have higher rates of mortality from MI, are more probably to be younger and present with other comorbidities and are less probably to receive novel therapies with respect to type of MI. As high-sensitivity troponin assays are adopted in the United States, implementation should account for how race and sex differences have been demonstrated in the reference range and diagnostic threshold of the newer assays. More research is needed to assess how the complexity of health disparities contributes to adverse cardiovascular outcomes. Creating dedicated medical quality teams (physicians, nurses, clinical documentation improvement specialists, and medical coders) and incorporating a plan-do-check-adjust quality improvement model are strategies that could potentially help better define and diagnose MI, reduce financial burdens due to MI misdiagnoses, reduce cardiovascular-related health disparities, and ultimately improve and save lives.

Involvement of NFƙB and MAPK signaling pathways in the preventive effects of Ganoderma lucidum on the inflammation of BV-2 microglial cells induced by LPS.

Ganoderma lucidum extract (GLE) is a potent ancient Asian remedy for the treatment of various diseases. This study investigated GLE preventive effects on LPS-stimulated inflammation of BV-2 microglial cells. The results show that pre-treatment with GLE decreased expression of pro-inflammatory cytokines: G-CSF, IL1-α, MCP-5, MIP3α, and, with a higher effect in MIP3α. In RT-PCR assays, pre-treatment with GLE decreased mRNA expression of CHUK, NFκB1/p150, and IKBKE (NFƙB signaling), which may be associated with the neuropathology of Alzheimer's disease. The data show GLE inhibiting ability on pro-inflammatory mediators' release and suggest a potential role of GLE in neurodegenerative disease prevention.

Effect of apigenin on whole transcriptome profile of TNFα-activated MDA-MB-468 triple negative breast cancer cells.

The lack of hormone receptors in triple negative breast cancer (TNBC) is associated with the inefficacy of anti-estrogen chemotherapies, leaving fewer options for patient treatment and higher mortality rates. Additionally, as with numerous types of inflammatory breast cancer, infiltration of tumor associated macrophages and other leukocyte sub-populations within the tumor inevitably lead to aggressive, chemo-resistant, metastatic and invasive types of cancer which escape immune surveillance. These processes are orchestrated by the release of potent cytokines, including TNFα, IL-6 and CCL2 from the stroma, tumor and immune cells within the tumor microenvironment. The present study evaluated apigenin modulating effects on the pro-inflammatory activating action of TNFα in TNBC MDA-MB-468 cells, derived from an African American woman. Initially, cell viability was determined to establish an optimal sub-lethal dose of TNFα and apigenin in MDA-MB-468 cells. Subsequently, various treatments effects were evaluated using whole transcriptomic analysis of mRNA and long intergenic non-coding RNA with Affymetrix HuGene-2.1-st human microarrays. Gene level differential expression analysis was conducted on 48,226 genes where TNFα caused significant upregulation of 53 transcripts and downregulation of 11 transcripts. The largest upward differential shift was for CCL2 [+61.86 fold change (FC); false discovery rate (FDR), P<0.0001]; which was down regulated by apigenin (to +10.71 FC vs. Control; FDR P-value <0.001), equivalent to an 83% reduction. Several TNFα deferentially upregulated transcripts were reduced by apigenin, including CXCL10, C3, PGLYRP4, IL22RA2, KMO, IL7R, ROS1, CFB, IKBKe, SLITRK6 (a checkpoint target) and MMP13. Confirmation of CCL2 experimentally induced transcript alterations was corroborated at the protein level by ELISA assays. The high level of CCL2 transcript in the cell line was comparable to that in our previous studies in MDA-MB-231 cells. The differential effects of TNFα were corroborated by ELISA, where the data revealed a >10-fold higher releasing rate of CCL2 in MDA-MB-468 cells compared with in MDA-MB-231 cells, both of which were attenuated by apigenin. The data obtained in the present study demonstrated a high level of CCL2 in MDA-MB-468 cells and a possible therapeutic role for apigenin in downregulating TNFα-mediated processes in these TNBC cells.

Community-Based Participatory Research at Jacksonville Florida Superfund Ash Site: Toxicology Training to Improve the Knowledge of the Lay Community.

Until the late 1960's, Jacksonville, Florida incinerated its solid waste with the resultant ash deposited in landfills or used to fill flood-prone areas. These filled areas were later developed into parks, school sites and residential areas. Lead in soil at these sites was the major toxicant of concern and driver of clean-up actions. During the period of assessment of lead-levels in soil, there were no established lines of communication between the City and residents of affected neighborhoods resulting in mistrust in the community. To address communication issues, a community-based, culturally sensitive Community Environmental Toxicology Curriculum (CETC) and a short video were developed for community stakeholders to inform them of risks, health effects, remediation processes and preventive measures. Pre-and post-tests were developed to measure knowledge gained from the toxicology training. Learning gains averaged 47% and 24% for the community leaders and residents respectively. Most participants strongly agreed that the community toxicology curriculum was a useful tool for promoting awareness of environmental risks in their community and addressing the gap in trust between residents and agencies involved in site remediation.

Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1.

Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused a -3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer.

Fish consumption patterns and mercury exposure levels among women of childbearing age in Duval County, Florida.

Consumption of fish containing methylmercury can pose serious health concerns including neurotoxic effects in adults and toxicity to the fetuses of mothers exposed during pregnancy. In the study described in this article, the authors examined fish consumption patterns and measured hair mercury levels of women of childbearing age in a coastal county in Florida. Women from the community participated in a risk factor assessment survey (N = 703). Hair samples (n = 698) were collected and analyzed for mercury. The authors identified 74.8% below detection limit; 25.2% had detectable limits of mercury, while 7% exceeded 1 pg/g. Hair mercury levels increased with fish consumption and age. Race, income, and education levels were also associated with increased hair mercury levels. Women of Asian/Pacific Islander origin had the highest levels. Although reported fish consumption exceeded the recommendations for women of childbearing age, the study population had lower mercury levels than other comparative studies in Florida and at national levels.

Mercury exposure education provided by women's health clinics in Duval County, Florida.

Duval County (Jacksonville, FL, USA) has a long history of environmental health hazards, especially prevalent within its urban core, referred to as Health Zone 1. In 2009, the Duval County Health Department conducted a survey of awareness of and actual exposure to methylmercury among women in the county. The survey found that women with more education or higher incomes had a higher awareness of potential mercury exposures. Furthermore, women in the urban core were less aware and had higher exposure than those in more affluent areas. This study assesses the mercury-exposure awareness and education by healthcare providers serving women of child-bearing age. We surveyed 28 women's health clinic offices. Sixty-one percent (17/28) indicated that they provide mercury exposure education to female patients, either written or verbal. Of these, only half (8/17) provide written education materials. Ninety-three percent of the providers indicated that a benefit to providing education on mercury exposure, is having "healthier developing fetuses and young children in the community". Two barriers identified by providers to offering information on mercury exposure and risk were (a) a lack of interest among patients, and (b) a lack of clear, understandable educational materials. The long-term goal of our * -8project is to develop and distribute culturally effective, low literacy materials for distribution by health clinics, to document the increased awareness of mercury exposure risks, and to lessen the adverse health outcomes that may result from mercury exposure among vulnerable population groups in Duval County.

Organophosphorus and pyrethroid insecticide urinary metabolite concentrations in young children living in a southeastern United States city.

Pesticide metabolites are routinely measured in the urine of children in the United States. Although the sources of these metabolites are believed to include residues in food from agricultural applications and residues from applications in everyday environments (e.g., homes), few studies have been able to demonstrate an association between indoor residential pesticide applications and pesticide metabolite concentrations. To better quantify the effects of potential risk factors related to demographics, household characteristics, occupation, and pesticide use practices on urinary biomarker levels, we performed a study in a city (Jacksonville, Florida) previously determined to have elevated rates of pesticide use. We enrolled a convenience sample of 203 children ranging in age from 4 to 6 years; their caregivers completed a questionnaire and the children provided a urine sample, which was analyzed for a series of organophosphorus and pyrethroid insecticide metabolites. The questionnaire responses substantiated much higher pesticide use for the study participants as compared to other studies. Urinary metabolite concentrations were approximately an order of magnitude higher than concentrations reported for young children in other studies. Few statistically significant differences (at the p<0.05 level) were observed, however, several trends are worth noting. In general, mean urinary pesticide metabolite concentrations were higher for males, Caucasians, and those children living in homes with an indoor pesticide application occurring within the past four weeks. Comparing the urinary pesticide metabolite concentrations in this study to those reported in the NHANES and GerES studies showed that the children living in Jacksonville had substantially higher pyrethroid pesticide exposures than the general populations of the United States and Germany. Further research is needed in communities where routine pesticide use has been documented to obtain information on the most important routes and pathways of exposure and to develop the most effective strategies for reducing pesticide exposures for children.

Multimedia measurements and activity patterns in an observational pilot study of nine young children.

A pilot observational exposure study was performed to evaluate methods for collecting multimedia measurements (air, dust, food, urine) and activity patterns to assess potential exposures of young children to pesticides in their homes. Nine children (mean age=5 years) and their caregivers participated in this study, performed in the Duval County, Florida, in collaboration with the Centers for Disease Control and Prevention and the Duval County Health Department. For all nine children, the total time reported for sleeping and napping ranged from 9.5 to 14 h per day, indoor quiet time from 0 to 5.5 h per day, indoor active time from 0.75 to 5.5 h per day, outdoor quiet time from 0 to 1.5 h per day, and outdoor active time from 0.5 to 6.5 h per day. Each home had one to three pesticide products present, with aerosols being most common. Pesticide inventories, however, were not useful for predicting pesticide levels in the home. Synthetic pyrethroids were the most frequently identified active ingredients in the products present in each home. Fifteen pesticide active ingredients were measured in the application area wipes (not detected (ND) to 580 ng/cm(2)), 13 in the play area wipes (ND-117 ng/cm(2)), and 14 in the indoor air samples (ND-378 ng/m(3)) and the socks (ND-1000 ng/cm(2)). Cis-permethrin, trans-permethrin, and cypermethrin were measured in all nine homes. Chlorpyrifos was measured in all nine homes even though it was not reported used by the participants. All urine samples contained measurable concentrations of 3-phenoxybenzoic acid (3-PBA). The median 3-PBA urinary concentration for the nine children was 2.2 mug/l. A wide variety of pesticide active ingredients were measured in these nine homes at median concentrations that were often higher than reported previously in similar studies. These data highlight the need for additional observational studies in regions where pesticides are used in order to understand the factors that affect young children's exposures and the education/mitigation strategies that can be used to reduce children's exposures.