VSL#3(®) supplementation improves fatigue in long COVID: results from the DELong#3 randomized placebo-controlled trial.

This pilot study offers preliminary epidemiologic evidence suggesting links between per- and polyfluoroalkyl substances (PFAS) exposure and domain-specific cognitive performance in actively serving firefighters. It represents an early effort to characterize both recent occupational and cumulative PFAS exposure using integrated environmental measures (post-incident wash water) and biomarkers (blood perfluorooctane sulfonic acid [PFOS]). The study also explores potential effect modification, with findings indicating that cumulative PFOS may influence associations between recent PFAS exposure and processing speed. Processing speed emerged as a domain that may be particularly sensitive, although these observations remain tentative. Overall, the results contribute to a developing understanding of PFAS-related neurotoxicity in high-exposure occupational settings and may help inform the design of future longitudinal studies. Per- and polyfluoroalkyl substances (PFAS) are a globally present class of pollutants used in various industrial applications, including textiles, water- and oil-repellant coatings, and aqueous film-forming foams used by firefighters. Firefighters may be exposed to PFAS through multiple sources, including inhalation of smoke due to the burning of different materials containing PFAS and aerosolized foam, direct or indirect skin contact with contaminated personal protective equipment, and hand-to-mouth transfer during the use of aqueous film-forming foams. Moreover, ingestion and inhalation of indoor dust and air are common PFAS exposure pathways for firefighters. Indoor air and dust inside fire stations contain high concentrations of PFAS originating from contaminated gear, firefighting foams, or other PFAS-containing products that are present inside fire stations. Dust inside fire stations may act as a chemical reservoir of PFAS once compounds seep from contaminated products. Turnout gear may be another major source of PFAS exposure in firefighters. Recent studies have shown that PFAS are present in all three layers of firefighter turnout gear: the outer shell, moisture barrier, and thermal liner. These studies highlight the health risks associated with the materials and finishes used in turnout gear even before it is exposed to its first fire. Epidemiological studies have documented the adverse effects of legacy or long-chain PFAS, such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), on human health, including cancer, immune suppression, thyroid dysfunction, metabolic effects, increased lipid levels, ulcerative colitis, and liver and kidney function in adults. Additionally, evidence from animal and human studies has suggested that PFOS and PFOA can reduce the function of the nervous system and are potentially neurotoxic, correlating with neurobehavioral dysfunction, such as late-onset Alzheimer’s disease (AD) and learning and memory deficits. These studies have suggested two major potential pathways of PFAS neurotoxicity: (1) PFAS can disturb calcium homeostasis and induce calcium increase/overload in neurons. Calcium overload can disrupt the normal function of neurons and provoke neuronal excitement, which could lead to neuronal injury and cell death; and (2) PFOS and PFOA can cross the blood–brain barrier (BBB) and alter neurotransmitter (e.g., dopamine, glutamate, and acetylcholine) concentrations, which can influence the activation of neurons and signal transmission among neurons. Increases or decreases in neurotransmitters could lead to neuron cell death. In particular, PFAS tends to distribute to and accumulate in the hippocampus of the brain, a region implicated in learning and memory, and disturbs hippocampal neurons, leading to cognitive impairment. Several biomonitoring studies have found higher serum PFAS concentrations among firefighters compared to the general population due to their direct contact with PFAS in the workplace. Moreover, firefighters are frequently exposed to considerable occupational stress arising from the high workload, exposure to life-threatening situations, and intense psychological demands inherent in fire and rescue operations. Chronic high stress is found to be associated with cognitive decline in the general population, suggesting that the sustained pressure experienced by firefighters may place them at elevated risk for adverse cognitive and psychological outcomes. However, evidence on the association between PFAS exposure and health outcomes remains limited in this population, with cognitive health outcomes particularly underrepresented in the global literature. As fire departments are one of the first responder professions, it is important to characterize PFAS exposure and measure its impact on firefighter cognitive function.