Body Burden Research Articles

Total body burden of neurotoxicant Hg in Chinese mitten crab (Eriocheir sinensis) - Considerations of distribution and human risk assessment

The Chinese mitten crab (Eriocheir sinensis) is considered one of the 100 most invasive alien species in the world. Despite this, its role in ecosystems, among others, in the trophodynamics of pollutants including mercury, is still not fully understood. Becoming an increasingly important and widespread element of the trophic chain in new areas arouses interest from humans as consumers. Hence it is important to determine the level of contaminants (including Hg) in alien species. In the present study, great attention was paid separately to the soft tissues and hard tissues of the exoskeleton, which may play an important role in the detoxification of the crab's body from toxic Hg. The study was conducted on crabs collected in 2011–2021 in the Vistula Lagoon. Concentrations of total mercury and its forms were carried out using a Direct Mercury Analyzer, DMA-80 (Milestone, Italy). The present study showed that mercury accumulation of the crab's body largely occurred through the gills, followed by the oral route. The distribution of Hg in the crab's organs was related to the trophic origin of the mercury, while halide-bound mercury and semilabile forms from the respiration (filtration) process were redistributed into the crab's exoskeleton. Male crabs, compared to females, had a higher Hg burden on internal organs such as their hepatopancreas and gonads. Hg concentration in hard tissues was closely related to the type of mineralization of the carapace. The elimination of Hg from the muscles and from the hepatopancreas into the carapace was one of the important detoxification processes of the crab's body. Thus, moulting crabs effectively remove Hg protecting its body from the neurotoxin. As a result, a smaller Hg load is biomagnified, making the crab's muscle tissue fit for human consumption. The observed decrease in Hg concentrations from 2011 to 2021, as well as the spatial variability of Hg in the crab's muscles, testify that the crab can serve as a biomonitor for ecosystem changes.

Elevated levels of serum per- and poly-fluoroalkyl substances (PFAS) in contact lens users of U.S. young adults

Despite evidence indicating the presence of per- and poly-fluoroalkyl substances (PFAS) in contact lenses (CL), it remains unclear whether CL use increases PFAS exposure in the general population. We aimed to determine whether CL users have higher serum concentrations of PFAS than non-users, using data of 1660 adults aged 20–39 years participating in the National Health and Nutrition Examination Survey 1999–2000 and 2003–2008. We classified the individuals into CL users and non-users using the record of vision correction types during a vision test. Serum concentrations of six individual PFAS were measured, and the overall PFAS burden was calculated by item response theory scoring. Survey-weighted linear models were used to compare serum PFAS levels between CL users and non-users after adjusting for covariates. Distributions of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) concentrations were compared with reference values (e.g., human biomonitoring [HBM]-II values) indicating potential for adverse health effects. Survey-weighted linear models revealed that covariate-adjusted serum PFOA concentration was higher in CL users (geometric mean [GM]: 3.68 ng/mL; 95% CI: 3.00, 4.50) than in non-users (GM: 3.27 ng/mL; 95% CI: 2.81, 3.80; p = 0.02). Similarly, CL users had a significantly higher serum PFHxS concentration (GM: 1.58 ng/mL; 95% CI: 1.13, 2.20) than non-users (GM: 1.30 ng/mL; 95% CI: 1.10, 1.66; p = 0.03). CL users also had a significantly higher overall burden of PFAS than non-users. The differences in PFAS concentrations between CL users and non-users were more pronounced in females than in males. Moreover, a larger proportion of lens users (4.5%), compared to non-users (3.9%), had PFOA concentrations above the HBM-II, where adverse health effects are expected from PFOA exposure. This study suggests that CL use in general U.S. young adults may contribute significantly to PFAS body burden, which can potentially lead to public health problem.

Environmental concentrations of metals (Cu and Zn) differently affect the life history traits of a model freshwater ostracod

Zinc (Zn) and copper (Cu) are common contaminants of inland water bodies under severe anthropogenic pressure. The main aim of this study was to test the influence of environmental aqueous concentrations of Zn and Cu on the fitness-related life history traits of the cosmopolitan freshwater ostracod Heterocypris incongruens. Overall, eight subchronic laboratory experiments were conducted to test the effects of exposure to two Cu (260 and 460 µg Cu L−1) and Zn (230 and 410 µg Zn L−1) concentrations compared to the control conditions using asexual individuals originating from a wild population and from a commercial toxicity test (Ostracodtoxkit f). The response of ostracods to exposure to Zn and Cu differed considerably. The Cu treatments significantly reduced the total hatching success and hatching dynamics of resting eggs, increased the mortality of juveniles and reduced the survival of adults, dramatically decreasing the fitness of ostracods. On the other hand, the Zn treatments were less harmful and did not affect adult survival or the timing of juvenile hatching from subitaneous eggs but extended the timing of laying eggs at lower concentrations and stimulated hatching dynamics and success at higher concentrations. It seems that the increased Zn body burden did not strongly impact the fitness of the studied specimens. Moreover, the different responses of the laboratory and wild populations in the Zn experiments may suggest a genetic variation in the tolerance of ostracods to metals. Therefore, experiments involving laboratory H. incongruens as analogues of wild ostracods should be cautiously interpreted. We concluded that the major toxicant in our study was Cu, while Zn could be considered a micronutrient even supporting ostracod fitness, although its higher levels are likely to exert strong toxic effects.

Preoperative visualization of mammary artery for breast reduction surgery based on computed tomography angiography

BackgroundMacromastia, characterized by an increase in breast size, poses challenges such as elevated body burden and chest oppression, potentially leading to cardiac and pulmonary overload. A crucial aspect of addressing these challenges involves preoperative planning, aiming to acquire detailed images and a 3D model of the internal mammary artery with minimal radiation exposure.PurposeThis study aimed to explore the clinical significance of computed tomography angiography (CTA) of the mammary artery in preoperative planning for breast reduction surgery.MethodsRetrospective analysis was conducted on CT images from 60 patients scheduled for breast reduction surgery in the plastic surgery department. These images were processed using a post-processing workstation to extract internal mammary arteries for subsequent 3D modeling. Radiologists and plastic surgeons collaborated to perform preoperative planning based on the 3D model and associated measurement parameters. Subsequent follow-up examinations occurred 4 to 9 months post-surgery, evaluating necrosis rates and complications of the nipple-areola complex (NAC).ResultsA total of 206 blood vessels were reconstructed and extracted in 60 patients, including 156 main arteries and 50 arterioles. There were no instance of NAC necrosis, complications, or infections in the 4–9 months follow-up period.ConclusionsPreoperative Mammary artery CTA emerged as a valuable tool, facilitating a comprehensive understanding of the internal mammary arteries and the primary blood supply in the NAC region. This approach effectively minimizes the risk of NAC supply artery injury during surgery, thereby preserving the functionality of the nipple and areola.

Liquid Biopsy: An Emerging Diagnostic, Prognostic, and Predictive Tool in Gastric Cancer.

Liquid biopsy, a minimally invasive procedure that causes minimal pain and complication risks to patients, has been extensively studied for cancer diagnosis and treatment. Moreover, it facilitates comprehensive quantification and serial assessment of the whole-body tumor burden. Several biosources obtained through liquid biopsy have been studied as important biomarkers for establishing early diagnosis, monitoring minimal residual disease, and predicting the prognosis and response to treatment in patients with cancer. Although the clinical application of liquid biopsy in gastric cancer is not as robust as that in other cancers, biomarker studies using liquid biopsy are being actively conducted in patients with gastric cancer. Herein, we aimed to review the role of various biosources that can be obtained from patients with gastric cancer through liquid biopsies, such as blood, saliva, gastric juice, urine, stool, peritoneal lavage fluid, and ascites, by dividing them into cellular and acellular components. In addition, we reviewed previous studies on the diagnostic, prognostic, and predictive biomarkers for gastric cancer using liquid biopsy and discussed the limitations of liquid biopsy and the challenges to overcome these limitations in patients with gastric cancer.

Exposure to per- and polyfluoroalkyl substances (PFAS) in North Carolina homes: results from the indoor PFAS assessment (IPA) campaign.

Per and polyfluoroalkyl substances (PFAS) are ubiquitous in the indoor environment, resulting in indoor exposure. However, a dearth of concurrent indoor multi-compartment PFAS measurements, including air, has limited our understanding of the contributions of each exposure pathway to residential PFAS exposure. As part of the Indoor PFAS Assessment (IPA) Campaign, we measured 35 neutral and ionic PFAS in air, settled dust, drinking water, clothing, and on surfaces in 11 North Carolina homes. Ionic and neutral PFAS measurements reported previously and ionic PFAS measurements reported herein for drinking water (1.4-34.1 ng L-1), dust (202-1036 ng g-1), and surfaces (4.1 × 10-4-1.7 × 10-2 ng cm-2) were used to conduct a residential indoor PFAS exposure assessment. We considered inhalation of air, ingestion of drinking water and dust, mouthing of clothing (children only), and transdermal uptake from contact with dust, air, and surfaces. Average intake rates were estimated to be 3.6 ng kg-1 per day (adults) and 12.4 ng kg-1 per day (2 year-old), with neutral PFAS contributing over 80% total PFAS intake. Excluding dietary ingestion, which was not measured, inhalation contributed over 65% of PFAS intake and was dominated by neutral PFAS because fluorotelomer alcohol (FTOH) concentrations in air were several orders of magnitude greater than ionic PFAS concentrations. Perfluorooctanoic acid (PFOA) intake was 6.1 × 10-2 ng kg-1 per day (adults) and 1.5 × 10-1 ng kg-1 per day (2 year-old), and biotransformation of 8 : 2 FTOH to PFOA increased this PFOA body burden by 14% (adults) and 17% (2 year-old), suggesting inhalation may also be a meaningful contributor to ionic PFAS exposure through biotransformation.

Mechanistic characterization of waterborne selenite uptake in the water flea, Daphnia magna, indicates water chemistry affects toxicity in coal mine-impacted waters.

Concentrations of selenium that exceed regulatory guidelines have been associated with coal mining activities and have been linked to detrimental effects on aquatic ecosystems and the organisms therein. Although the major route of selenium uptake in macroinvertebrates is via the diet, the uptake of waterborne selenite (HSeO3-), the prominent form at circumneutral pH, can be an important contributor to selenium body burden and thus selenium toxicity. In the current study, radiolabelled selenite (Se75) was used to characterize the mechanism of selenite uptake in the water flea, Daphnia magna. The concentration dependence (1-32μM) of selenite uptake was determined in 1-hour uptake assays in artificial waters that independently varied in bicarbonate, chloride, sulphate, phosphate and selenate concentrations. At concentrations representative of those found in highly contaminated waters, selenite uptake was phosphate-dependent and inhibited by foscarnet, a phosphate transport inhibitor. At higher concentrations, selenite uptake was dependent on waterborne bicarbonate concentration and inhibited by the bicarbonate transporter inhibitor DIDS (4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid). These findings suggest that concentrations of phosphate in coal mining-affected waters could alter selenite uptake in aquatic organisms and could ultimately affect the toxic impacts of selenium in such waters.

How body burden from exposure to endocrine disruptors effects accelerated aging?

This paper reviewed various studies on the effects of endocrine disruptors on human health, focusing on accelerated aging in the younger generation. In particular, we analyzed how the modern lifestyle and ignorance of endocrine disruptors in the younger generation are accelerating aging, and how the concentration of endocrine disruptor exposure in the human body affects the body's burden. Based on existing papers, we conducted a systematic review using Web of Science, Google Scholar, and Scopus to comprehensively investigate and summarize the definition of endocrine disruptors, their effects on hormones, and the physical burden of continuous exposure to endocrine disruptors. Research has shown that persistent exposure to endocrine disruptors disrupts homeostasis in the body and creates oxidative stress that can lead to aging and chronic inflammation. These characteristics were also found to be significant in the observation of telomere length, which is a measure of aging. Therefore, in order to prevent accelerated aging in the younger generation, we can suggest ways to minimize exposure to endocrine disruptors and slow down normal aging in the entire public health, including the 3040s, in the long term.

Glyphosate and AMPA in saliva and other traditional human matrices. New findings for less invasive biomonitoring to the exposure to pesticides

Human biomonitoring of the exposure to pesticides is usually performed in biological matrices such as urine and plasma. However, the possibility of using less invasive matrices allows the screening of large number of subjects. The objective of this study was to evaluate the body burden of the exposure to the most widely used herbicide, Glyphosate (GLY), and its main metabolite, the aminomethylphosphonic acid (AMPA), in different populations from the province of Córdoba (Argentina), and to propose the saliva as a matrix for possible implementation in biomonitoring of the exposure to pesticides.Glyphosate and AMPA concentrations were evaluated in urine, plasma, and saliva of subjects occupationally and environmentally exposed to pesticides from one of the most important agricultural areas of Argentina. Gas chromatography coupled to tandem mass spectrometry (MS/MS) was used for the identification and quantification of the analytes.Both GLY and AMPA were quantified in all matrices with higher detection frequency (DF) in the occupationally exposed group than in non-occupationally exposed individuals. Among evaluated matrices, the highest DF and concentration levels of GLY were found in saliva. Moreover, the only statistical difference between groups of subjects were found for GLY and AMPA concentrations in saliva, indicating the possible use of this non-invasive human matrix to evaluate different levels and scenarios of exposure. No significant correlation was found between GLY and AMPA levels in saliva and the traditional matrices (urine and blood) used to measure exposure to pesticides.This is the first report of the presence and concentrations of GLY and AMPA in human saliva samples. Results of the present study are relevant for future biomonitoring of the exposure to GLY, but also to pesticides in general. Saliva deserved further investigation as an alternative, easy, and economical matrix involving less invasive methods for biomonitoring and screenings of large populations.

Bioaccumulation of mercury in Lake Michigan painted turtles (Chrysemys picta).

Mercury (Hg) contamination of aquatic environments can lead to bioaccumulation in organisms, but most previous work has focused on fish and not on semi-aquatic reptiles such as turtles that traverse both terrestrial and aquatic habitats. Here, we analyzed total Hg (THg) concentrations in 30 painted turtles (Chrysemys picta) collected from Lake Michigan (USA) coastal wetlands in 2013 to determine if (1) turtles bioaccumulated THg from the environment, (2) concentrations differed between turtle liver and muscle tissue, and (3) tissue concentrations were related to environmental concentrations (e.g., sediment THg). All individual turtles had detectable THg concentrations in both liver and muscle tissue. On average, THg concentrations were over three times higher in liver tissue compared to muscle tissue. We found a positive linear relationship between muscle THg concentrations and turtle body mass, a proxy for age, suggesting bioaccumulation in this species. Neither liver nor muscle THg concentrations followed the sediment contaminant gradient in the wetlands. Despite this, location was a strong predictor of tissue concentration in a linear model suggesting that other site-specific characteristics may be important. Overall, our results demonstrate that painted turtles accumulate mercury in liver and muscle tissues at different rates, which may be constrained by local conditions. Further research is needed to better understand the relationship between environmental mercury concentrations and body burdens in animals like turtles that traverse habitats. In addition, long-lived turtles could be incorporated into pollution monitoring programs to provide a more holistic picture of food web contamination and ecosystem health.

THE LEVELS OF ESSENTIAL TRACE ELEMENTS IN BLOOD SERUM AND URINE OF WOMEN WITH OSTEOPOROSIS

The objective of the study was to assess serum and urinary concentrations of essential trace elements in women with osteoporosis. Material and methods. A total of 100 women aged 30-70 years old including 50 patients with osteoporosis (ICD-10: M81) and 50 healthy controls were examined. Assessment of serum and urinary trace element levels was performed using inductively-coupled plasma mass-spectrometry. Results. The obtained data demonstrate that urinary cobalt and zinc levels in women with osteoporosis were 42% and 44% lower than those in the control women. Analysis of covariance demonstrated a significant impact of osteoporosis and body mass index (BMI) values on urinary Zn concentra-tion. The influence of the presence of osteoporosis on urinary Co concentration was nearly significant. At the same time, serum Co concentration in os-teoporotic women was 21% lower than in healthy controls, while no significant difference in serum Zn levels was observed. The presence of osteopo-rosis in the examined women was also considered a key factor affecting serum Co levels independently of age and BMI values. Conclusion. Therefore, the results of the present study demonstrated the association between Zn and Co deficiency and the presence of osteoporosis in women. It is suggested that personalized correction of body burden of these trace elements may reduce the risk of osteoporosis due to osteogenic effect of zinc and cobalt. At the same time, intimate mechanisms of this association, as well as efficiency of supplementation strategies in manage-ment of osteoporosis requires further investigation.

E-Waste: a Concise Update on Global Movement, Impacts, Management, and Site Remediation

The rapid rise of electronic waste (e-waste) worldwide has become a public health concern. Wealthy countries are disposing of their e-waste to other countries taking advantage of their less stringent environmental laws and regulations. China used to receive large amounts of e-waste through Hong Kong (a free port) but banned the entry of e-waste in 2013. Salvaging or recycling different parts of the e-waste using primitive and uncontrolled techniques generated a wide range of toxic chemicals (mainly heavy metals and persistent organic pollutants). Most studies concerning the environmental and health impacts of the emitted toxic chemicals were conducted in China. The principal aim of this short article is to review the various environmental problems and health impacts of e-waste recycling, policies, management, and remediation of contaminated sites. Out of the primitive methods used for recycling, the two most destructive ones causing harm to the environment and human health are (1) Open-burning of e-waste for disposing of the salvaged e-waste and (2) Acid-stripping of electronic boards for collecting precious metals (gold, silver, platinum). There is sufficient evidence showing the associations between the toxic chemicals in different media (i.e., water, soil/sediment, air) and local food items (i.e., fish, meat, vegetables), linking with body burdens (hair, milk, placenta) of workers and residents. The epidemiological data further demonstrated the abrupt rise of several significant diseases (i.e., respiratory disease, cardiovascular disease, malignant tumors) in Taizhou (China), one of the two e-waste recycling sites. Effective policies and vigorous enforcement in managing e-waste are essential. International cooperation is necessary to prohibit the transboundary movement of e-waste. Sites contaminated by e-waste recycling contain incredibly high concentrations of toxic pollutants, which should be removed using excavation, degradation (via microbes, nanoparticles, biochar), soil washing, etc. Planting appropriate plants with associated rhizospheric microbes would achieve longer-term stability.

Urinary concentrations and elimination half-lives of parabens, benzophenones, bisphenol and triclosan in Japanese young adults.

Environmental phenols are widely distributed in the environment and human samples, suggesting potential exposure to these chemicals. We designed an intervention trial with 30 participants over 6 days to assess the urinary concentrations and half-lives of environmental phenols in Japanese young people. The target environmental phenols include three parabens (methyl paraben, ethyl paraben, and propyl paraben), two benzophenones (benzophenone 1 and 3), two bisphenols (bisphenol F and bisphenol S), and triclosan. Throughout the intervention, the participants consumed the same food and drinks and used personal care products provided by the project. The target phenols were measured in urine from the participants using a liquid chromatography-tandem mass spectrometer. We compared the measured concentrations between the study periods to better understand the exposure tendency. Some statistically significant differences were observed. All target analytes were detected in more than 50% of samples collected on Day 0 (the day before the intervention). Methyl paraben was the dominant phenol detected in urine (1640 μg/g-creatinine), followed by ethyl paraben (119 μg/g-creatinine). Downward trends in creatinine-corrected concentrations were observed for all target analytes in some instances. Non-compartment analysis was performed to estimate urinary excretion parameters. The estimated half-lives ranged from 7.69 to 20.3 h. Use of paraben-free products during the intervention period reduced the body burden.

Microplastic burden in marine benthic invertebrates depends on species traits and feeding ecology within biogeographical provinces

The microplastic body burden of marine animals is often assumed to reflect levels of environmental contamination, yet variations in feeding ecology and regional trait expression could also affect a species’ risk of contaminant uptake. Here, we explore the global inventory of individual microplastic body burden for invertebrate species inhabiting marine sediments across 16 biogeographic provinces. We show that individual microplastic body burden in benthic invertebrates cannot be fully explained by absolute levels of microplastic contamination in the environment, because interspecific differences in behaviour and feeding ecology strongly determine microplastic uptake. Our analyses also indicate a degree of species-specific particle selectivity; likely associated with feeding biology. Highest microplastic burden occurs in the Yellow and Mediterranean Seas and, contrary to expectation, amongst omnivores, predators, and deposit feeders rather than suspension feeding species. Our findings highlight the inadequacy of microplastic uptake risk assessments based on inventories of environmental contamination alone, and the need to understand how species behaviour and trait expression covary with microplastic contamination.

Tracking Nano- and Microplastics Accumulation and Egestion in a Marine Copepod by Novel Fluorescent AIEgens: Kinetic Modeling of the Rhythm Behavior.

Nano- and microplastics (NMPs) are now prevalent in the marine environment. This study quantified the uptake and depuration kinetics of spherical polystyrene NMPs of different particle sizes (200 nm/30 μm) and functional groups (-NH2/-COOH) in a temperate calanoid copepod Calanus sinicus (C. sinicus), which exhibited rhythmic feeding patterns in natural environments. Aggregated-induced emission (AIE) fluorescent probes were employed to track and quantify the kinetics of NMPs with excellent photostability and biocompatibility. The results showed that C. sinicus consumed all NMPs types, with preference of NMPs to small size and amino group. Increased diatom concentrations also inhibited the bioaccumulation of NMPs. Influenced by rhythmic behavior, the bioaccumulation of NMPs by C. sinicus was nonstationary during the 6 h uptake phase. After 1-3 h of rapid uptake, the body burden peaked and then slowly declined. During the 3 h depuration phase, C. sinicus rapidly and efficiently removed NMPs with a mean half-life of only 0.23 h. To further quantify the body burden of C. sinicus under the influence of rhythmic feeding behavior, a biokinetic model was established, and the Markov chain Monte Carlo method was used to estimate the parameter distribution. Our results highlighted that copepods exhibited unique rhythmic feeding behavior under environmentally relevant concentrations of NMPs exposure, which may influence the bioaccumulation, trophic transfer, and environmental fate of NMPs.

Role Of Selenium and Vitamins E And C In Combating Cadmium Bioaccumulation in The Selected Tissues of Rats: A Therapeutic Approach

The aim of the present investigation is to check the therapeutic role of selenium (Se) and vitaminE and C on cadmium (Cd) induced bioaccumulation in liver, kidney and testis of Cd treated rats. Wistar strain male albino rats were treated with cadmium chloride at a dose of 1/10th of LD50 /48h i.e. 22.5 mg/Kg body weight for 7, 15 and 30 days (d) time intervals. Then 15d Cd treated rats were divided into two groups. Group I supplemented with Se (1mg/kg body weight) and II group received combination of Se, vitamins E (300mg/kg) and C (200mg/kg) and observed for 7, 15 and 30days. After specific time intervals, rats were decapitated and tissues such as liver, kidney and testis were isolated and used for the estimation of Cd bioaccumulation levels by using Atomic Absorption Spectrophotometer (AAS – Schimadzu AA6300). There was a significant elevation in Cd concentrations in the test tissues with increased period of Cd treatment. Maximum Cd accumulation was found in 30d Cd treated rat kidney (42.80±0.30μg / gm). However, there was a significant reduction in Cd bioaccumulation with Se and vitamin E and C supplementation. Maximum decrease in Cd accumulation was found in 30d rat kidney (5.04 ±0.08μg / gm) supplemented with the combination of Se andvitamin E and C. Our findings clearly envisage that combined supplementation of Se and vitamin E and C is more effective in reducing the Cd body burden when compared to the individual mode of supplementation.

Validating blood microsampling for per- and polyfluoroalkyl substances quantification in whole blood

Microsampling allows the collection of blood samples using a method which is inexpensive, simple and minimally-invasive, without the need for specially-trained medical staff. Analysis of whole blood provides a more holistic understanding of per- and polyfluoroalkyl substances (PFAS) body burden. Capillary action microsamplers (Trajan hemaPEN®) allow the controlled collection of whole blood as dried blood spots (DBS) (four 2.74 µL ± 5 %). The quantification of 75 PFAS from DBS was evaluated by comparing five common extraction techniques. Spiked blood (5 ng/mL PFAS) was extracted by protein precipitation (centrifuged; filtered), acid-base liquid-liquid extraction, trypsin protease digestion, and weak anion exchange (WAX) solid-phase extraction with analysis by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Filtered protein precipitation was the most effective extraction method, recovering 72 of the 75 PFAS within 70 to 130 % with method reporting limit (MRL) for PFOS of 0.17 ng/L and ranging between 0.05 ng/mL and 0.34 ng/mL for all other PFAS. The optimised method was applied to human blood samples to examine Inter- (n = 7) and intra-day (n = 5) PFAS blood levels in one individual. Sixteen PFAS were detected with an overall Σ16PFAS mean = 6.3 (range = 5.7–7.0) ng/mL and perfluorooctane sulfonate (branched and linear isomers, ΣPFOS) = 3.3 (2.8–3.7) ng/mL being the dominant PFAS present. To the authors knowledge, this minimally invasive self-sampling protocol is the most extensive method for PFAS in blood reported and could be a useful tool for large scale human biomonitoring studies.

NIMG-07. LONG-TERM FOLLOW-UP OF SCHWANNOMA GROWTH BEHAVIOR IN ADULT SCHWANNOMATOSIS PATIENTS USING WHOLE-BODY MRI

Abstract BACKGROUND The schwannomatoses include NF2-related schwannomatosis (NF2-SWN, formerly known as “NF2”) and non-NF2-related schwannomatosis (e.g. SMARCB1- and LZTR1-related schwannomatosis) and are caused by distinct germline pathogenic variants on chromosome 22. Patients may develop cranial, peripheral, and/or spinal nerve schwannomas. Except for vestibular schwannomas, the long-term growth behavior of schwannomas is unknown but this is important to guide patient surveillance and selection for treatment. Whole-body MRI (WBMRI) can detect whole-body schwannoma burden. METHODS 16 NF2-SWN and 12 non-NF2-SWN patients with WBMRI acquired between 2007-2010 underwent a repeat WBMRI between 2018-2022. Non-vestibular schwannomas were segmented on short tau inversion recovery (STIR) sequences. Tumor volume was calculated using a 3D tumor quantification software (3DQI). Tumor growth and shrinkage were defined as a volume change ³20% over the entire study period. RESULTS Median time between scans was 10.3 years. Median age was 43.5 years at baseline and 54 years at follow-up. Excluding resected tumors, 102 schwannomas (49 NF2-SWN, 53 non-NF2-SWN) were analyzed. 62/102 (61%) tumors grew >20% (65% NF2-SWN, 57% non-NF2-SWN); median growth was 96% in NF2-SWN and 94% in non-NF2-SWN. 24/102 (24%) tumors shrank >20% (20% NF2-SWN, 26% non-NF2-SWN); median shrinkage was 49% in NF2-SWN and 40% in non-NF2-SWN. 29 new tumors developed between scans (16 NF2-SWN, 13 non-NF2-SWN). Of 32 NF2-SWN tumors exposed to systemic or radiation therapy, 63% grew and 31% shrank. Of 7 non-NF2-SWN tumors exposed to treatment, 29% grew and 42% shrank. 11 non-NF2-SWN tumors shrank spontaneously without treatment. Spontaneous tumor shrinkage was not observed in NF2-SWN. CONCLUSIONS About 60% of SWN-associated schwannomas grow significantly over a decade. Spontaneous shrinkage is only observed in non-NF2-SWN tumors whereas, in NF2-SWN patients, about 60% of tumors grow despite treatment, suggesting a more aggressive tumor phenotype in NF2-SWN. Correlation of MRI findings with patient-reported outcomes and hormone exposure history are ongoing.

Differential Developmental Neurotoxicity and Tissue Uptake of the Per- and Polyfluoroalkyl Substance Alternatives, GenX and PFBS.

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals with several applications. Multiple adverse health effects are reported for longer carbon chain (≤C8) PFAS. Shorter carbon chain PFAS, [e.g., hexafluoropropylene oxide dimer acid (HFPO-DA; GenX) and perfluorobutanesulfonic acid (PFBS)] were introduced as alternatives. Past studies indicate that longer-chain PFAS are neurotoxic targeting the dopamine pathway, but it is not known if shorter-chain PFAS act similarly. This study aimed to evaluate developmental neurotoxicity and tissue uptake of GenX and PFBS using the zebrafish (Danio rerio). First, acute toxicity was assessed by measuring LC50 at 120 h postfertilization (hpf). Body burden was determined after embryonic exposure (1-72 hpf) to sublethal concentrations of GenX or PFBS by LC-ESI-MS/MS. Locomotor activity using a visual motor response assay at 120 hpf and dopamine levels at 72 hpf was assessed after embryonic exposure. PFBS was more acutely toxic and bioaccumulative than GenX. GenX and PFBS caused hyperactivity at 120 hpf, but stronger behavioral alterations were observed for PFBS. An increase in whole organism dopamine occurred at 40 ppb of GenX, while a decrease was observed at 400 ppb of PFBS. Differences detected in dopamine for these two PFAS indicate differential mechanisms of developmental neurotoxicity.

Disruption of hypoxia-inducible factor-2α in neutrophils decreases colitis-associated colon cancer.

Neutrophils are abundant immune cells in the colon tumor microenvironment. Studies have shown that neutrophils are recruited into hypoxic foci in colon cancer. However, the impact of hypoxia signaling on neutrophil function and its involvement in colon tumorigenesis remain unclear. To address this, we generated mice with a deletion of hypoxia-inducible factor (HIF)-1α or HIF-2α in neutrophils driven by the MRP8Cre (HIF-1αΔNeu) or (HIF-2αΔNeu) and littermate controls. In an azoxymethane (AOM)/dextran sulfate sodium (DSS) model of colon cancer, the disruption of neutrophils-HIF-1α did not result in any significant changes in body weight, colon length, tumor size, proliferation, or burden. However, the disruption of HIF-2α in neutrophils led to a slight increase in body weight, a significant decrease in the number of tumors, and a reduction in tumor size and volume compared with their littermate controls. Histological analysis of colon tissue from mice with HIF-2α-deficient neutrophils revealed notable reductions in proliferation as compared with control mice. In addition, we observed reduced levels of proinflammatory cytokines, such as TNF-α and IL-1β, in neutrophil-specific HIF-2α-deficient mice in both the tumor tissue as well as the neutrophils. Importantly, it is worth noting that the reduced tumorigenesis associated with HIF-2α deficiency in neutrophils was not evident in already established syngeneic tumors or a DSS-induced inflammation model, indicating a potential role of HIF-2α specifically in colon tumorigenesis. In conclusion, we found that the loss of neutrophil-specific HIF-2α slows colon tumor growth and progression by reducing the levels of inflammatory mediators.NEW & NOTEWORTHY Despite the importance of hypoxia and neutrophils in colorectal cancer (CRC), the contribution of neutrophil-specific HIFs to colon tumorigenesis is not known. We describe that neutrophil HIF-1α has no impact on colon cancer, whereas neutrophil HIF-2α loss reduces CRC growth by decreasing proinflammatory and immunosuppressive cytokines. Furthermore, neutrophil HIF-2α does not reduce preestablished tumor growth or inflammation-induced colitis. The present study offers novel potential of neutrophil HIF-2α as a therapeutic target in CRC.