Urinary Metal Levels and Coronary Artery Calcification: Longitudinal Evidence in the Multi-Ethnic Study of Atherosclerosis
Ronald A. Glabonjat, Marta Galvez-Fernandez, Arce Domingo-Relloso, Irene Martinez-Morata, Miranda R. Jones, Anne Nigra, Wendy S. Post, Joel Kaufman, Maria Tellez-Plaza, Linda Valeri, Elizabeth R. Brown, Richard A. Kronmal, R. Graham Barr, Steven Shea, Ana Navas-Acien, and Tiffany R. Sanchez

Abstract

Background
Exposure to metals, a newly recognized risk factor for cardiovascular disease (CVD), could be related to atherosclerosis progression.

Objectives
The authors hypothesized that higher urinary levels of nonessential (cadmium, tungsten, uranium) and essential (cobalt, copper, zinc) metals previously associated with CVD would be associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of CVD in MESA (Multi-Ethnic Study of Atherosclerosis).

Methods
We analyzed data from 6,418 MESA participants with spot urinary metal levels at baseline (2000-2002) and 1 to 4 repeated, continuous measures of CAC over a 10-year period. We used linear mixed-effect models to assess the association of baseline urinary metal levels with baseline CAC and cumulative change in CAC over a 10-year period. Urinary metals (μg/g creatinine) and CAC were log transformed. Models were adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors.

Results
At baseline, the median CAC was 6.3 (Q1-Q3: 0.7-58.2). Comparing the highest to lowest quartile of urinary cadmium, CAC levels were 51% (95% CI: 32%-74%) higher at baseline and 75% (95% CI: 47%-107%) higher over the 10-year period. For urinary tungsten, uranium, and cobalt, the corresponding CAC levels over the 10-year period were 45% (95% CI: 23%-71%), 39% (95% CI: 17%-64%), and 47% (95% CI: 25%-74%) higher, respectively, with no difference for models with and without adjustment for clinical factors. For copper and zinc, the corresponding estimates dropped from 55% to 33% and from 85% to 57%, respectively, after adjustment for clinical factors. The associations of metals with CAC were comparable in magnitude to those for classical CVD risk factors.

Conclusions
Exposure to metals was generally associated with extent of coronary calcification at baseline and follow-up. These findings support that metals are associated with the progression of atherosclerosis, potentially providing a novel strategy for the prevention and treatment of atherosclerosis progression.

JACC (Paywall)

Twenty years of microplastics pollution research—what have we learned?
Richard C. Thompson, Winnie Courtene-Jones, Julien Boucher, Sabine Pahl, Karen Raubenheimer, Albert A. Koelmans

Abstract
Twenty years after the first publication using the term microplastics, we review current understanding, refine definitions and consider future prospects. Microplastics arise from multiple sources including tires, textiles, cosmetics, paint and the fragmentation of larger items. They are widely distributed throughout the natural environment with evidence of harm at multiple levels of biological organization. They are pervasive in food and drink and have been detected throughout the human body, with emerging evidence of negative effects. Environmental contamination could double by 2040 and widescale harm has been predicted. Public concern is increasing and diverse measures to address microplastics pollution are being considered in international negotiations. Clear evidence on the efficacy of potential solutions is now needed to address the issue and to minimize the risks of unintended consequences.

Science [Open access]

Neuroinflammation and Brain Health Risks in Veterans Exposed to Burn Pit Toxins 
Brooks, Athena W.; Sandri, Brian J.; Nixon, Joshua P.; Nurkiewicz, Timothy R.; Barach, Paul; Trembley, Janeen H.; Butterick, Tammy A.

Abstract
Military burn pits, used for waste disposal in combat zones, involve the open-air burning of waste materials, including plastics, metals, chemicals, and medical waste. The pits release a complex mixture of occupational toxic substances, including particulate matter (PM), volatile organic compounds (VOCs), heavy metals, dioxins, and polycyclic aromatic hydrocarbons (PAHs). Air pollution significantly impacts brain health through mechanisms involving neuroinflammation. Pollutants penetrate the respiratory system, enter the bloodstream, and cross the blood–brain barrier (BBB), triggering inflammatory responses in the central nervous system (CNS). Chronic environmental exposures result in sustained inflammation, oxidative stress, and neuronal damage, contributing to neurodegenerative diseases and cognitive impairment.

Veterans exposed to burn pit toxins are particularly at risk, reporting higher rates of respiratory issues, neurological conditions, cognitive impairments, and mental health disorders. Studies demonstrate that Veterans exposed to these toxins have higher rates of neuroinflammatory markers, accelerated cognitive decline, and increased risks of neurodegenerative diseases.

This narrative review synthesizes the research linking airborne pollutants such as PM, VOCs, and heavy metals to neuroinflammatory processes and cognitive effects. There is a need for targeted interventions to mitigate the harmful and escalating effects of environmental air pollution exposures on the CNS, improving public health outcomes for vulnerable populations, especially for Veterans exposed to military burn pit toxins.

MDPI International Journal of Molecular Sciences [Open access]

When maize screams, beans listen: How the Three Sisters crop trio repels pests
By Elizabeth Pennisi

For thousands of years small farmers in Mexico and parts of Central America have practiced a form of agriculture, known as milpa, that traces back to the ancient Maya. Tradition holds that mixing crops—typically maize, beans, and squash, the Three Sisters—in a single field improves yields. Scientists now know the beans fix nitrogen into the soil, enriching it for all plants; the maize stalks provide a structure for the beans to climb; and the squash covers the ground, suppressing weeds and keeping the soil moist. But researchers also suspected this “intercropping” has an additional benefit: helping decrease damage by plant pests.

New work, presented this month at the annual meeting of the Ecological Society of America in Los Angeles, suggests harm by pests is indeed reduced in these systems and that plant teamwork is responsible. By showing how the maize signals the beans to lure insects that eat their pests, the work could inspire other studies that might ultimately point to new ways for modern farmers to reduce pesticide use. But other work presented at the meeting suggested replicating the success of the Three Sisters may not be easy. Planting genetically different tomatoes together, a study showed, only protected them against pests when the set of varieties produced the right blend of volatile chemicals. “It is important which [crop variety] you are using,” says Patrick Grof-Tisza, a plant-insect ecologist at Converse University.

Science

Biotransformation of nanoplastics in human plasma and their permeation through a model in vitro blood-brain barrier: An in-depth quantitative analysis
Fazel Abdolahpur Monikh, Šárka Lehtonen, Jukka Kekäläinen, Isabel Karkossa, Seppo Auriola, Kristin Schubert, Alessandra Zanut, Sanni Peltonen, Jonna Niskanen, Mandar Bandekar, Martin von Bergen, Jari T.T. Leskinen, Arto Koistinen, Sara Bogialli, Zhiling Guo, Jussi V.K. Kukkonen, Chunying Chen, Iseult Lynch

Abstract
Challenges in characterizing and quantifying nanoplastics within the human body hinder understanding of their transport, biotransformation, and potential for cellular penetration and barrier crossing. By implementing an innovative analytical workflow, including incorporation of gadolinium (Gd) as a tracer into the polymer matrix of nanoplastics, the fate of nanoplastics relative to an in vitro blood-brain barrier (BBB) model is elucidated in the absence or presence of a biomomolecule corona. The nanoplastics were incubated in human plasma for 5 min, 1 h, 6 h, and 24 h, after which the absorbed proteins and lipids (biocorona) were determined. A total of 268 proteins were identified in the biological coronas on polystyrene (PS) and polyvinyl chloride (PVC) nanoplastics, with the initial compositions being broadly similar on both PS and PVC. Both nanoplastics exhibited a strong affinity for phosphatidylcholines (PC) and lysophosphocholines (LPC) from human plasma. The inherent chemical composition of the nanoplastics plays a pivotal role in the corona’s evolution over time. Human induced pluripotent stem cell (iPSC)-derived endothelial cells (iECs) and astrocytes were exposed for 2 h to 5 µg L−1 of pristine nanoplastics or nanoplastics covered with a biological corona (following incubation in plasma for 6 h). A relatively low concentration of PS and PVC nanoplastics was determined to be present within the cellular layer of the BBB. The number of PVC nanoplastics crossing the BBB was higher than the number of PS nanoplastics. The presence of a biological corona on these particles decreases their uptake and transcytosis. This understanding might further the development of preventive measures or therapeutic strategies to counteract potential nanoplastic-induced neurotoxicity, and provide a foundation for development of in silico models to predict the neurotoxic implications of nanoplastics.

Highlights
• A biological corona immediately forms on the surfaces of nanoplastics upon contact with biofluids.
• The composition of the biological corona was similar on both PS and PVC.
• The chemical composition of the nanoplastics determines the corona’s evolution over time.
• The number of PVC nanoplastics crossing the BBB was higher than the number of PS.
• Biological corona decreases the uptake and transcytosis of nanoplastics in BBB.

Link (Nano Today)

Hearing Loss and Urinary trans,trans-Muconic Acid (t,t-MA) in 6- to 19-Year-Old Participants of NHANES 2017–March 2020
Rae T. Benedict, Franco Scinicariello, Henry G. Abadin, Gregory M. Zarus, Roberta Attanasio

Abstract
Hearing loss (HL) is associated with poorer language development and school performance. Ototoxic substances such as metals and solvents, including benzene, are a risk factor associated with HL. This study examines potential associations between the benzene metabolite trans,trans-muconic acid (t,t-MA) and HL in youth of the National Health and Nutrition Examination Survey (NHANES). Logistic regression calculated adjusted odds ratio (aOR) associations between HL and urinary t,t-MA quartiles, natural-log transformed, and doubled urinary t,t-MA. Hearing threshold pure-tone average (PTA) at speech frequencies (SF) 0.5, 1, 2, and 4 kHz and high frequencies (HF) 3, 4, and 6 kHz were analyzed for slight HL (PTA > 15 dB) and mild HL (PTA > 20 dB). Urinary t,t-MA was statistically significantly associated with both slight SF and HF HL. For each doubling of t,t-MA there were increased odds of having slight SFHL (aOR = 1.42; 95% CI: 1.05, 1.92), slight HFHL (aOR = 1.31; 95% CI: 1.03, 1.66), mild SFHL (aOR = 1.60; 95% CI: 1.10, 2.32), and mild HFHL (aOR = 1.45; 95% CI: 1.03, 2.04). To our knowledge, this is the first population-based report of an association between SFHL, HFHL, and the benzene metabolite t,t-MA in youth 6 to 19 years old.

Link (MDPI Toxics)

Which Environmental Pollutants Are Toxic to Our Ears?—Evidence of the Ototoxicity of Common Substances
Gregory M. Zarus, Patricia Ruiz, Rae Benedict, Stephan Brenner, Krystin Carlson, Layna Jeong, Thais C. Morata

Abstract
Ototoxicity refers to the adverse effects of substances on auditory or vestibular functions. This study examines the evidence of ototoxicity’s association with exposure to common environmental pollutants, as documented in toxicological profiles by the Agency for Toxic Substances and Disease Registry. Our aim was to evaluate whether the evidence supports modifying the charting of ototoxic effects in the summary tables of these toxicological profiles and providing a guide for scientists to access these data. Health outcomes of interest included hearing loss, vestibular effects, cochlear lesions, tonal alterations, cellular damage, and ototoxicity-related outcomes (neurological, nephrotoxic, hepatic, and developmental effects). We obtained ototoxicity information for 62 substances. Hearing-related effects were reported, along with neurological effects. Overall, 26 profiles reported strong evidence of ototoxicity, including 13 substances previously designated as ototoxic by other health and safety agencies. Commonly studied outcomes included hearing loss, damage to ear anatomy, and auditory dysfunction. Vestibular dysfunction and tinnitus are rarely studied. Our findings highlight the lack of conclusive evidence of ototoxic properties for many substances, especially for pesticides and herbicides. This review supports charting the evidence of ototoxicity separately in toxicological profiles’ summary tables. Improving the communication of ototoxicity-related health effects might impact their recognition and prompt further research. A stronger evidence base could support improved prevention efforts in terms of serious health outcomes.

Link (MDPI Toxics)

Assessing the health burden from air pollution
Torben Sigsgaard, Barbara Hoffmann

Abstract
Human health is affected by air pollution, causing cardiometabolic, respiratory, and neurological disease and increased mortality. Pollutants include gases [for example, nitrogen dioxide (NO2), NOx, and ozone] and particulate matter, which is commonly characterized by its aerodynamic diameter of less than 2.5 μm (PM2.5) or less than 10 μm (PM10). Air pollutants are mainly emitted by energy production, industry, traffic, heating, and agriculture. Exposure to air pollution affects most organ systems, causing a wide array of physiological changes, organ dysfunction, and manifest clinical disease (1, 2). Therefore, a burden of disease assessment that adequately reflects all related exposure-outcome relationships and their impacts on disease and mortality in the target population is important to guide population-based prevention.

Link (Science) [Paywall]