Poly(HexaMethylene Biguanide) hydrochloride (PHMB) CAS No. [32289-58-0] is a particularly effective member of the biguanides antiseptic chemical group, and has been in use since the early fifties in numerous applications. It has been proposed that PHMB be classified as a category 3 carcinogen although PHMB is not genotoxic. It has been hypothesized that PHMB may have epigenetic properties effects, including non-genotoxic modifications of DNA bases, DNA methylation and mitogenic cytokine production. These properties have been assessed in vitro using 3 cell types: Caco-2 cells (from a human colon adenocarcinoma) with a non-functional p53 gene. (∆p53: mut p53), N2-A (Neuro-2A cells, mouse neural cells), the brain being a possible target organ in rodents and HepG2 cells (human hepatocellular carcinoma) with functional p53 gene. From the concentration 1 µg/mL up to 20 µg/mL of PHMB, no effect was observed, either growth stimulation or inhibition. Viability testing using neutral red led to an IC 50 of 20–25 µg/mL after treatment with PHMB for 3 h, whereas the MTT test led to IC50 values of 80 µg/mL, 160 µg/mL and 160 µg/mL respectively for HepG2 cells, Neuro-2A cells and Caco-2 cells. PHMB does not induce significant oxidative stress (production of MDA or lipoperoxidation, nor does it induce hydroxylation of DNA (8-OH-dG) and/or its hypermethylation (m5dC), the latter being strongly implicated in DNA replication and regulation and cell division. PHMB does not induce significant production of mitogenic cytokines such as TNF-α (tumor necrosis factor), interleukins (IL-1 alpha), and the transcription factor nuclear factor kappa B (NF-κB) which can cause either apoptosis or stimulate the growth of transformed cells or tumors. Instead, from concentrations of 20 to 100 µg/mL, PHMB kills cells of all types in less than 3 h. The expression of genes involved in the mechanisms of cell death induced by PHMB, including p53, the pro apoptotic gene bax and others, the anti-apoptotic bcl-2 and caspase-3 has been evaluated by RT-PCR. Finally, the status of GAP-junctions (GJIC) in the presence of PHMB has been determined and appeared to not be significantly affected. Taken together the data show that in vitro PHMB does not exhibit clear and remarkable epigenetic properties except a slight increase of some cytokines and transcription factor at higher concentrations at which cell lysis occurs rapidly. Full article

Induced pluripotent stem cells (IPS) are an artificially derived type of pluripotent stem cell, showing many of the same characteristics as natural pluripotent stem cells. IPS are a hopeful therapeutic model; however there is a critical need to determine their response to environmental toxins. Effects of arsenic on cells have been studied extensively; however, its effect on IPS is yet to be elucidated. Arsenic trioxide (ATO) has been shown to inhibit cell proliferation, induce apoptosis and genotoxicity in many cells. Based on ATOs action in other cells, we hypothesize that it will induce alterations in morphology, inhibit cell viability and induce a genotoxic effect on IPS. Cells were treated for 24 hours with ATO (0–9 µg/mL). Cell morphology, viability and DNA damage were documented. Results indicated sufficient changes in morphology of cell colonies mainly in cell ability to maintain grouping and ability to remain adherent. Cell viability decreased in a dose dependent manner. There were significant increases in tail length and moment as well as destruction of intact DNA as concentration increased. Exposure to ATO resulted in a reproducible dose dependent sequence of events marked by changes in morphology, decrease of cell viability, and induction of genotoxicity in IPS. Full article

Mortality represents an important outcome measure following coronary artery bypass grafting. Shorter survival times may reflect poor surgical quality and an increased number of costly postoperative complications. Quality control efforts aimed at increasing survival times may be misleading if not properly adjusted for case-mix severity. This paper demonstrates how to construct and cross-validate efficiency-outcome plots for a specified time (e.g., 6-month and 1-year survival) after coronary artery bypass grafting, accounting for baseline cardiovascular risk factors. The application of this approach to regional centers allows for the localization of risk stratification rather than applying overly broad and non-specific models to their patient populations. Full article

A synthetic tripodal-based thiourea receptor (PNTTU) was used to explore the receptor/ligand binding affinity using CTB cells. The human extravillous CTB cells (Sw.71) used in this study were derived from first trimester chorionic villus tissue. The cell proliferation, migration and angiogenic factors were evaluated in PNTTU-treated CTB cells. The PNTTU inhibited the CTBs proliferation and migration. The soluble fms-like tyrosine kinase-1 (sFlt-1) secretion was increased while vascular endothelial growth factor (VEGF) was decreased in the culture media of CTB cells treated with ≥1 nM PNTTU. The angiotensin II receptor type 2 (AT₂) expression was significantly upregulated in ≥1 nM PNTTU-treated CTB cells in compared to basal; however, the angiotensin II receptor, type 1 (AT₁) and vascular endothelial growth factor receptor 1 (VEGFR-1) expression was downregulated. The anti-proliferative and anti-angiogenic effect of this compound on CTB cells are similar to the effect of CTSs. The receptor/ligand affinity of PNTTU on CTBs provides us the clue to design a potent inhibitor to prevent the CTS-induced impairment of CTB cells. Full article

The cardiovascular and stroke mortality rates in Arkansas are among the highest in the USA. The annual trends of stroke and cardiovascular mortality are barely correlated to smoking cessation; while the prevalence of risk factors such as obesity; cholesterol and hypertension increased over the 1979–2007 period. The study determined the effect of chronic exposure to PM_2.5 on non-accidental; cardiovascular; stroke and lung cancer mortality in Arkansas over the 2000–2010 period using the World Health Organization’s log-linear health impact model. County chronic exposures to PM_2.5 were computed by averaging spatially-resolved gridded concentrations using PM_2.5 observations. A spatial uniformity was observed for PM_2.5 mass levels indicating that chronic exposures were comparable throughout the state. The reduction of PM_2.5 mass levels by 3.0 μg/m³ between 2000 and 2010 explained a significant fraction of the declining mortality. The effect was more pronounced in southern and eastern rural Arkansas as compared to the rest of the state. This study provides evidence that the implementation of air pollution regulations has measurable effects on mortality even in regions with high prevalence of major risk factors such as obesity and smoking. These outcomes are noteworthy as efforts to modify the major risk factors require longer realization times. Full article

Recently the existence and prevalence of health and health care disparities has increased with accompanying research showing that minorities (African Americans, Hispanics/Latinos, Native Americans, and Pacific Islanders) are disproportionately affected resulting in poorer health outcomes compared to non-minority populations (whites). This is due to multiple factors including and most importantly the social determinants of health which includes lower levels of education, overall lower socioeconomic status, inadequate and unsafe housing, and living in close proximity to environmental hazards; all contributing to poor health. Given the ever widening gap in health and health care disparities, the growing number of individuals living at or below the poverty level, the low number of college graduates and the growing shortage of health care professionals (especially minority) the goals of this paper are to: (1) Define diversity and inclusion as interdependent entities. (2) Review the health care system as it relates to barriers/problems within the system resulting in the unequal distribution of quality health care. (3) Examine institutional and global benefits of increasing diversity in research. (4) Provide recommendations on institutional culture change and developing a diverse culturally competent healthcare workforce. Full article

In 2012 the U.S. Centers for Disease Control (CDC) set the blood Pb reference value at ≥5 µg/dL. Clinical analysis of children’s blood Pb levels is the common way to diagnose environmental Pb contamination, and intervention ensues with education and household dust cleanup. Recent review indicates that education and household dust cleanup are not effective at reducing children’s Pb exposure. Here we review mapping environmental Pb and children’s blood Pb response as an alternative approach for proactive Pb dust intervention. New Orleans was divided into a high (≥100 mg/kg) and low (<100 mg/kg) soil Pb communities. The children’s blood Pb prevalence ≥5 µg/dL for the high and low Pb domains were 58.5% and 24.8% respectively pre-Katrina vs. 29.6% and 7.5% post-Katrina. Elevated soil Pb (mg/kg) and consequently Pb loading (µg/square area) permeates the high Pb domain and outdoor locations lack Pb dust safe play areas. The U.S. EPA 400 mg/kg soil Pb standard poses an outside Pb dust loading burden >37 times larger than allowed on interior residential floor environments. Environmental Pb dust is decreasing because of the transfer of large quantities of low Pb soil into selected communities. City-scale soil Pb mapping is an alternative diagnostic tool that provides information for planning proactive medicine to prevent clinical Pb exposure in the first place. Full article

Increasing urbanization across the globe, combined with an increased use of chemicals in various regions, contributes to several environmental events that influence environmental health. Measures that identify environmental factors and events should be introduced to facilitate epidemiological investigations by health services. The Brazilian Ministry of Health published a new list of notifiable diseases on 25 January 2011 and introduced environmental events as a new category of notifiable occurrences. The Center for Epidemiologic Surveillance in State of Sao Paulo, Brazil, created an online notification system that highlights “environmental events”, such as exposure to chemical contaminants, drinking water with contaminants outside of the recommended range, contaminated air, and natural or anthropogenic disasters. This paper analyzed 300 notifications received between May 2011 and May 2012. It reports the number of notifications with event classifications and analyzes the events relating to accidents with chemical substances. This paper describes the characteristics of the accidents that involved chemical substances, methods used, types of substances, exposed population, and measures adopted. The online notification of environmental events increases the analysis of the main events associated with diseases related to environmental chemicals; thus, it facilitates the adoption of public policies to prevent environmental health problems. Full article