Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. In the Mexico City Metropolitan Area (MCMA) megacity, children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health.

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The cancer prevalence in the Malwa region of Punjab (1089/million/year) is much higher than the national average cancer prevalence in India (800/million/year). The participants in the present study were 50 healthy individuals and 49 cancer patients all living in the Malwa region of Punjab, with the healthy people being selected from the same household as the cancer patients. High concentrations of several potentially toxic elements were found in hair samples from people living in Punjab. Compared to standard reference ranges, the metals in excess in both the control and patient groups were aluminium (Al), barium (Ba), manganese (Mn), strontium (Sr) and uranium (U). The most significant findings were high lead (Pb), U and Ba concentrations. The maximum values for Ba, Mn, Pb and U were found in hair from breast cancer patients. The mean concentration of U in hair from the breast cancer patients was 0.63 μg U/g, which is more than double the value found in the control group and over six times higher than the reference range of 0.1 μg U/g. Water, soil, and phosphate fertilizers all seem to play a potential role, causing an increased metal burden in Punjabi people living in the Malwa region. The present study indicates that metals, and especially U, may be a factor in the development of breast cancer among Punjabi women.

The cancer prevalence in the Malwa region of Punjab (1089/million/year) is much higher than the national average cancer prevalence in India (800/million/year). In our previous study on hair metal analysis, we located a high metal burden in Punjabi cancer patients and their live-in relatives, suggesting that an excessive metal exposure is a factor in the pathogenesis of cancer. The present study focused on nail metal analysis, a biological material similar to hair. Previously, we had used BJMMR, 5(4): 480-498, 2015; Article no.BJMMR.2015.053 481 ICP-MS spectroscopy to confirm high exposures to aluminium (Al), barium (Ba), manganese (Mn), lead (Pb), uranium (U and other metals in the hair of Punjabi cancer patients and their healthy relatives (Blaurock-Busch et al. 2014). In this study, we used nail metal analysis to confirm the results of our previous study. We compared the nail metal concentration of healthy Punjabis (N=83) with randomly selected healthy Europeans (N=83) and found highly significant differences between the European and Punjabi groups, including the healthy and the cancer groups.In comparison, our European group showed a low percentage (0 to 13%) of pathological values for aluminium (Al), barium (Ba), cadmium (Cd), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), strontium (Sr), titanium (Ti) and uranium (U), while the healthy Punjabi groups showed between 13% and 99% pathological values for these elements. (Explanation: A test value above the 95% reference range is considered a pathological value.)The greatest metal burden was found in the breast cancer group (N=13), showing 100% pathological values for Al, Fe, Mn and U. This study supports previous research, which demonstrated a significant metal burden in Punjabi people. Water, soil, and phosphate fertilizers may be the cause of this excessive exposure. Original Research Article

This work was carried out in collaboration between all authors. Author EBB designed the study, wrote the protocol, including laboratory analysis and statistics and wrote all drafts of the manuscript. Author YB organized study details and managed literature searches. Author NB was in charge of sample collection and patient management. All authors read and approved the final manuscript.