24-h Exposure Research Articles

Multi-Biomarkers' Responses in Gills of Oreochromis niloticus Exposed to Glyphosate and Polyethylene Microplastic, Isolated and in Mixture.

Microplastics (MPs) and glyphosate-based herbicides (GBH) are among the most common contaminants in aquatic environments. In Brazilian rivers, both contaminants were found in elevated levels, leading to a high probability of their association, which can alter their individual effects and potentially intensify their toxicity. This study evaluated the isolated and combined effects of polyethylene microplastics (PE-MPs) and GBH on Oreochromis niloticus using multi-biomarkers of toxicity. The fish were subjected to a 96-h exposure period, with concentrations set based either isolated, PE-MPs group (5 mg L-1), GBH group (5 mg L-1), or in a group of associated contaminants (GAC), PE-MP + GBH (5 mg L-1 + 5 mg L-1). Toxicity effects were evaluated using biochemical, cytogenetic, hematological, and histopathological biomarkers. We observed change in erythrocyte parameters leading to macrocytic normochromic anemia in GAC. Leukocyte parameters indicate a nonspecific immunosuppression caused by the exposure of associated contaminants, besides the attempts to repair damage caused by PE-MPs. Histopathological markers indicate damage to tissues exposed to contaminants. Besides, there were morphophysiological adjustments on gills, with proliferation and hypertrophy of mitochondria-rich cells on GBH and GAC, besides epithelium ruptures, which were mostly present in the exposed groups. Therefore, this study indicates that PE-MPs and GBHs present toxic effects in O. niloticus with the used concentrations, intensified by the association of contaminants. Thus, multi-biomarkers were useful key to verify toxicity, providing data to the investigation of high levels of contaminant's mixture toxicity present in aquatic environments.

Intergenerational Sublethal Effects of Flonicamid on Cotton Aphid, Aphis gossypii: An Age-Stage, Two-Sex Life Table Study.

Flonicamid is a novel systemic insecticide widely used against aphids. However, the intergenerational sublethal effects of flonicamid on cotton aphid, Aphis gossypii, have not been fully studied. This study aimed to evaluate the sublethal effects of flonicamid on the biological parameters of adult A. gossypii (F0) and its subsequent intergenerational effects on the offspring (F1 generation) through age-stage, two-sex life table analysis. The results of the bioassays indicate that flonicamid exhibits significant toxicity toward adult A. gossypii, as evidenced by an LC50 value of 0.372 mg L-1 after a 48-h exposure period. The longevity, fecundity, and reproductive days of adult cotton aphids (F0) were significantly decreased when treated with the sublethal concentrations of flonicamid. The pre-adult stage exhibited an increase, whereas the adult longevity, total longevity, and fecundity experienced a notable decrease in F1 aphids after the exposure of F0 aphids to sublethal concentrations of flonicamid. Furthermore, the key demographic parameters, including r, λ, R0, and RPd, showed a significant decrease, while the total pre-reproductive period (TPRP) experienced a significant increase in the F1 generation. Collectively, our findings indicate that sublethal concentrations of flonicamid impact the demographic parameters of A. gossypii, resulting in suppression of population growth. This study presents comprehensive information on the overall impact of flonicamid on A. gossypii, which could potentially aid in managing this major pest.

Continuous Blue Light Treatment Enhances the Nutritional Value of Hydroponically Grown Eruca vesicaria L. by Improving Ascorbic Acid Biosynthesis.

This study investigates the effect of continuous blue light (CBL) treatment on quality-related metabolites, focusing on ascorbic acid (AsA) accumulation in hydroponically grown Eruca vesicaria (L.). Plants were subjected to CBL treatment, consisting of 24-h exposure to constant-intensity blue light (48 μmol m-2 s-1) and 12-h exposure to the remaining spectrum (192 μmol m-2 s-1). The activities of key enzymes in AsA biosynthesis and recycling were analyzed, including L-galactono-1,4-lactone dehydrogenase (GalLDh), monodehydroascorbate reductase (MDhAR), dehydroascorbate reductase (DhAR), and ascorbate peroxidase (APX). The results showed a significant increase in AsA accumulation of 65.9% during the "day" and 69.1% during the "night" phases under CBL compared to controls. GalLDh activity increased by 20% during the "day phase" in CBL-treated plants. APX activity also rose significantly under CBL conditions, by 101% during the "day" and 75.6% during the "night". However, this did not affect dehydroascorbic acid levels or the activities of MDhAR and DhAR. These findings highlight the potential of tailored light treatments to enhance the nutraceutical content of horticultural species, offering valuable insights for sustainably improving food quality in controlled-environment agriculture (CEA) systems and understanding the roles of blue light in ascorbic acid biosynthesis.

Impact of polyethylene nanoplastics on human intestinal cells

Polyethylene (PE) is one of the most widely used plastics in the world. Its degradation leads to the production of small particles including microplastics and nanoplastics (NPs). Plastic particles’ presence poses a health risk. The aim of this work was to investigate the toxicity of two model surfactant-free PE NPs prepared by polymerization of ethylene from cationic and anionic water-soluble initiators on human cell lines Caco-2 and HT29-MTX. After physicochemical characterization, their acute and subacute toxicity profile, including cytotoxicity, oxidative stress, and genotoxicity, was evaluated on both cell lines. Results showed a size increase of PE NPs in culture medium. Zeta potential values close to −10 mV were no longer dependent on the initiator charge after adsorption of serum components in culture medium. However, the cellular toxicity of the cationic and anionic PE NPs was very different. A time-and-concentration dependent cytotoxic, oxidative, and genotoxic effects on Caco-2 cells were only observed for PE NPs prepared with cationic initiators. No toxicity was observed on HT29-MTX, likely due to the protective mucus layer. Genotoxicity correlated with oxidative stress of some PE NPs on Caco-2 cells was observed from a concentration of 0.1 mg.mL−1 after 48-h exposure.

The role of the carapace in the accumulation of metals from seawater in the green crab (Carcinus maenas): Studies with radio-labeled calcium, zinc, and nickel

The role of the carapace in the uptake and storage of newly accumulated metals was investigated in the green crab exposed to environmentally relevant concentrations of calcium ([Ca] = 389 mg L−1 or 9.7 mmol L−1), zinc ([Zn] = 82 μg L−1 or 1.25 μmol L−1), and nickel ([Ni] = 8.2 μg L−1 or 0.14 μmol L−1) in 12 °C seawater, using radio-tracers (45Ca, 65Zn, 63Ni). After 24-h exposure, carapace exhibited the highest concentration of newly accumulated Ca, whereas carapace and gills exhibited the highest concentrations of both newly accumulated Zn and Ni relative to other tissues. For all three metals, the carapace accounted for >85 % of the total body burden. Acute temperature changes (to 2 °C and 22 °C) revealed the highest overall temperature coefficient Q10 (2.15) for Ca uptake into the carapace, intermediate Q10 for Ni (1.87) and lowest Q10 (1.45) for Zn. New Ca uptake into the carapace continued linearly with time for 24 h, new Zn uptake gradually deviated from linearity, whereas Ni uptake reached a plateau by 6 h. Attachment of a rubber membrane to the dorsal carapace, thereby shielding about 20 % of the total crab surface area from the external water, eliminated both new Zn and Ni incorporation into the shielded carapace, whereas 36 % of new Ca incorporation persisted. When recently euthanized crabs were exposed, new Zn uptake into the carapace remained unchanged, whereas Ca and Ni uptake were reduced by 89 % and 71 %, respectively. We conclude that the carapace is a very important uptake and storage site for all three metals. All of the uptake of new Zn and new Ni, and most of the uptake of new Ca into this tissue comes directly from the external water. For Zn, the mechanism involves only physicochemical processes, whereas for Ca and Ni, life-dependent processes make the major contribution.

The selective serotonin reuptake inhibitors, sertraline and paroxetine, improve islet beta-cell mass and function in vitro.

To investigate the effects of the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine at therapeutically relevant concentrations on beta-cell mass and function. Viability was quantified in mouse insulinoma (MIN6) beta cells and mouse islets after 48-h exposure to sertraline (1-10 μM) or paroxetine (0.01-1 μM) using the Trypan blue exclusion test. The effects of therapeutic concentrations of these SSRIs on insulin secretion were determined by static incubation and perifusion experiments, while islet apoptosis was investigated by Caspase-Glo 3/7 assay, TUNEL staining and quantitative PCR analysis. Finally, proliferation of MIN6 and mouse islet beta cells was assessed by bromodeoxyuridine (BrdU) enzyme-linked immunosorbent assay and immunofluorescence. Sertraline (0.1-1 μM) and paroxetine (0.01-0.1 μM) were well tolerated by MIN6 beta cells and islets, whereas 10 μM sertraline and 1 μM paroxetine were cytotoxic. Exposure to 1 μM sertraline and 0.1 μM paroxetine significantly potentiated glucose-stimulated insulin secretion from mouse and human islets. Moreover, they showed protective effects against cytokine- and palmitate-induced apoptosis of islets, they downregulated cytokine-induced Stat1 and Traf1 mRNA expression, and they significantly increased proliferation of mouse beta cells. Our data demonstrate that sertraline and paroxetine act directly on beta cells to enhance glucose-stimulated insulin secretion and stimulate beta-cell mass expansion by increasing proliferation and decreasing apoptosis. These drugs are therefore likely to be appropriate for treating depression in people with type 2 diabetes.

Metal-contaminated sediment toxicity in a highly impacted Neotropical river: Insights from zebrafish embryo toxicity assays

The Fundão dam collapse was one of the largest mining-related disasters globally. It resulted in the release of mining tailings containing heavy metals, which contaminated the Doce River in southeastern Brazil. This study assessed the effects of acute exposure of Danio rerio embryos to sediments contaminated by mine tailings six years after the Fundão dam collapse. The study sites included P2, P3, and P4 in the upper Doce River, as well as site P1 on the Piranga River, an uncontaminated river. Sediment samples were analyzed for 10 metals/metalloid by atomic absorption spectrometry. In the assays, embryos were exposed to sediment from P1–P4 sites, and uncontaminated quartz was used as control sediment. Various biomarkers were applied to assess biological responses, and the integrated biomarker response (IBR) index was calculated for each site. Sediment samples revealed elevated levels of As, Cr, Cu, Hg, and Ni beyond Brazilian legislation limits. At 96-h exposure, embryo mortality rates exceeded 20% in P1, P2, and P3, higher than the control and P4 (p < 0.0001). Hatching rates ranged from 60 to 80% in P1, P2, and P3, lower than the control and P4 (p < 0.001). Larvae exposed to P2 sediment (closest to the Fundão dam) exhibited skeletal, physiological, and sensory malformations. Neurotoxicity was indicated by increased acetylcholinesterase activity and reduced spontaneous movements in embryos exposed to Doce River sediment. Contamination also increased metallothionein and heat shock protein 70 levels, along with changes in cell proliferation and apoptosis. Principal component analysis showed a good correlation between metals/metalloid in the sediment and larval morphometric endpoints. The IBR index highlighted suitable biomarkers for monitoring metal contamination in fish embryos. Overall, our findings suggest that sediment toxicity following the Fundão dam failure may compromise the sustainability of fish communities in the Doce River.

Exudates of Microcystis aeruginosa on oxidative stress and inflammatory responses in gills of Sinocyclocheilus grahami

Early cyanobacterial blooms studies observed that exposure to blue-green algae led to fish gills impairment. The objective of this work was to evaluate the toxic mechanisms of exudates of Microcystis aeruginosa (MaE) on fish gills. In this study, the toxic mechanism of MaE (2×106 cells/mL) and one of its main components phytosphingosine (PHS) with two concentrations 2.9 ng/mL and 145 ng/mL were conducted by integrating histopathology, biochemical biomarkers, and transcriptomics techniques in Sinocyclocheilus grahami (S. grahami) for 96 h exposure. Damaged gill tissue with epithelial hyperplasia and hypertrophy, remarkable Na+/K+-ATPase (NKA) enzyme activity, disrupted the redox homeostats including lipid peroxidation and inflammatory responses were observed in the fish of MaE exposure group. Compare to MaE exposure, two concentrations of PHS exposure appeared to be a trend of lower degree of tissue damage, NKA activity and oxidative stress, but induced obviously lipid metabolism disorder with higher triglycerides, total cholesterol and total bile acid, which might be responsible for inflammation responses in fish gill. By transcriptome analysis, MaE exposure were primarily enriched in pathways related to gill function and immune response. PHS exposure, with higher number of differentially expressed genes (DEGs), were enriched in Toll-like receptor (TLR), Mitogen-Activated Protein Kinase (MAPK) and NOD-like receptor protein 3 (NLRP3) pathways. We concluded that MaE and PHS were induced the inflammatory responses, with oxidative stress-induced inflammation for MaE exposure but lipid metabolism disorder-induced inflammation for PHS exposure. The present study provided two toxin-induced gill inflammation response pathways under cyanobacterial blooms, which could be a scientific basis for the ecological and health risk assessment in the aquatic environment.

Tinospora malabarica leaf extract fractions-derived silver nanoparticles and their spectral characterisation: evaluation of their toxicity properties against agricultural pests Spodoptera litura and Helicoverpa armigera

ABSTRACT Our study specifically delves into the synthesis of AgNPs utilizing Tinospora malabarica leaf extract fractions (Tm-LMEFs) and explore their efficacy in combating the larvae have progressed to the synthesized AgNPs (Tm-AgNPS) and the leaf methanol extract fractions (LMEFs), our investigation focused on their impact on the targeted larvae species over a 24-h exposure period. Significantly noteworthy mortality rates were observed across all Spodoptera litura and Helicoverpa armigera post-treatment, indicating pronounced efficacy. Notably, the Tm-AgNPS exhibited higher toxicity compared to the LMEFs these selected polyphagous insect pests. Quantitative analysis yielded the highest mortality (98.99%/90.44% and 55.33%/49.60%) values for the synthesized Tm-AgNPs against S. litura and H. armigera, with no observed mortality in the control group. This study marks the first instance of exploring both Tm-LMEFs, Tm-AgNPs and enzyme activity have toxicity properties against selected agriculture pests, highlighting their promising role in pest management and environmental sustainability.

Effect of long-term inorganic arsenic exposure on erythropoietin production in vitro

Arsenic is widely present in the environment in trivalent and pentavalent forms; long-term arsenic exposure due to environmental pollution has become a problem. Previous reports have shown that 24-h exposure to arsenate (as pentavalent arsenic) potentiates erythropoietin (EPO) production via reactive oxygen species (ROS) in EPO-producing HepG2 cells. However, the effects of long-term arsenate exposure on EPO production remain unclear. In HepG2 cells subcultured for 3 weeks in the presence of arsenate, EPO mRNA levels were lower than those in untreated cells. Levels of ARSENITE METHYLTRANSFERASE mRNA, as well as those of Nuclear factor erythroid 2-related factor 2, glutathione, and superoxide dismutase proteins, were increased compared to untreated cells, but levels of malondialdehyde were not significantly altered. Thus, long-term exposure to arsenate enhances ROS scavenging, suggesting that the ROS-induced accumulation of EPO mRNA is attenuated by arsenate exposure. The induction of EPO accumulation by hypoxia also was attenuated by long-term arsenate exposure, suggesting an impairment in responsivity of EPO production. Furthermore, mRNA levels of SIRTUIN-1, which affects EPO transcription, were potentiated by long-term arsenate exposure. These results suggest that long-term arsenate exposure has multiple, distinct effects on EPO production in vitro.

Air pollution induces morpho-functional, biochemical and biomechanical vascular dysfunction in undernourished rats

Air pollution (gases and particulate matter -PM) and child undernutrition are globally recognized stressors with significant consequences. PM and its components breach the respiratory alveolar-capillary barrier, entering the vasculature transporting not only harmful particles and its mediators but, altering vascular paracrine and autocrine functions.The aim of this study was to investigate the effects of Residual Oil Fly Ash (ROFA), on the vasculature of young animals with nutritional growth retardation (NGR). Weanling rats were fed a diet restricted 20% (NGR) compared to ad libitum intake (control-C) for 4 weeks. Rats were intranasally instilled with 1 mg/kg BW of ROFA. After 24h exposure, histological and immunohistochemical, biochemical and contractile response to NA/ACh were evaluated in aortas.ROFA induced changes in the tunica media of the aorta in all groups regarding thickness, muscular cells and expression of Connexin-43. ROFA increased TGF-β1 and decreased eNOs levels and calcium channels in C and NGR animals. An increment in cytokines IL-6 and IL-10 was observed in C, with no changes in NGR. ROFA exposure altered the vascular contractile capacity.In conclusion, ROFA exposure could increase the risk for CVD through the alteration of vascular biochemical parameters, a possible step of the endothelial dysfunction.

Analysis of Gingival Fibroblasts Behaviour in the Presence of 3D-Printed versus Milled Methacrylate-Based Dental Resins-Do We Have a Winner?

Computer-aided design and computer-aided manufacturing (CAD/CAM) techniques are based on either subtractive (milling prefabricated blocks) or additive (3D printing) methods, and both are used for obtaining dentistry materials. Our in vitro study aimed to investigate the behavior of human gingival fibroblasts exposed to methacrylate (MA)-based CAD/CAM milled samples in comparison with that of MA-based 3D-printed samples to better elucidate the mechanisms of cell adaptability and survival. The proliferation of human gingival fibroblasts was measured after 2 and 24 h of incubation in the presence of these samples using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the membrane integrity was assessed through the lactate dehydrogenase release. The level of reactive oxygen species, expression of autophagy-related protein LC3B-I, and detection of GSH and caspase 3/7 were evaluated by fluorescence staining. The MMP-2 levels were measured using a Milliplex MAP kit. The incubation with MA-based 3D-printed samples significantly reduced the viability, by 16% and 28% from control after 2 and 24 h, respectively. There was a 25% and 55% decrease in the GSH level from control after 24 h of incubation with the CAD/CAM milled and 3D-printed samples, respectively. In addition, higher levels of LC3B-I and MMP-2 were obtained after 24 h of incubation with the MA-based 3D samples compared to the CAD/CAM milled ones. Therefore, our results outline that the MA-CAD/CAM milled samples displayed good biocompatibility during 24-h exposure, while MA-3D resins are proper for short-term utilization (less than 24 h).

Synergistic valorization of rice straw and red brick demolition in development performance of lightweight cement mortars

This work deals with upgrading the undesirable agro- and industrial wastes, such as rice straw (RS), red brick demolition (RBP), and polystyrene foam (PSF), for construction purposes, as an excellent strategy to protect the environment. In this respect, the RS and its pulp fibers are modified by PSF, followed by their incorporating individually or in hybrid with RBP, in cement mortar formulation. As a substitute for fine aggregates. Six rice straw pulps used in this study were prepared from alkali, neutral, acidic, and kraft pulping agents. The effective performance of this investigated route is assessed from the mechanical properties, density, moisture resistance (thickness swelling and water absorption), measurements of the resulting mortar composites, as well as how the investigated treatment effects on behavior of RS fibers. The finding results show that the modified RS fibers, especially those results from KOH–NH4OH and neutral RS-pulping reagents, in hybrid with red brick waste provide motors with better mechanical and water resistance properties. These treated fibers have a synergistic role for including the RBP in mortar formulation to 30 %. The produced mortar has compressive strength 6.2 MPa and flexural strength 4.4 MPa, which is convenient to apply as load-bearing wall. Moreover, they provide improvement in resistance to thickness swelling and water absorption after 24-h exposure to water. The reduction in thickness swelling and water resistance reached 36.7 and 52.8 %, respectively. From the TGA measurements and SEM, it is interesting to notice that the investigated route accepts the RS fibers thermal stability and hydrophobic surface character.

Association between short-term pollen exposure and blood pressure in adults: A repeated-measures study

BackgroundRecent studies have related high pollen concentrations to increased cardiovascular morbidity and mortality, yet very little research concerns pre-clinical cardiovascular health, including effects on blood pressure (BP). The EPOCHAL panel study investigated the exposure-response relationship between ambient pollen exposure and systolic and diastolic BP in adults. MethodsBP was measured in 302 adults with and in 94 without pollen allergy during the pollen season, on approximately 16 days per person (6253 observations). Average individually-relevant pollen exposure in the 96 h prior to each BP measurement was calculated by summing up the averages of all ambient pollen concentrations to which the individual was found to be sensitized in a skin prick test, and which originated from seven highly allergenic pollen types (hazel, alder, birch, ash, grasses, mugwort and ragweed). Generalized additive mixed models were used to study the association between mean individually-relevant pollen exposure in the last 96 h and BP, adjusting for individual and environmental time-varying covariates. Effect modification by pollen allergy status, sex and BMI was evaluated. ResultsPositive non-linear associations between individually-relevant pollen exposure and both systolic and diastolic BP were found in the allergic but not in the non-allergic group. BP increased sharply for exposures from zero to 60/80 pollen/m3 (diastolic/systolic BP), followed by a tempered further increase at higher concentrations. Increases of 2.00 mmHg [95% confidence interval (CI): 0.80–3.19] in systolic and 1.51 mmHg [95% CI: 0.58–2.45] in diastolic BP were associated with 96-h average pollen exposure of 400 pollen/m3, compared to no exposure. Obesity and female sex were associated with larger BP increases. ConclusionsThe finding that short-term pollen concentration is associated with increased systolic and diastolic BP in persons with pollen allergy strengthens the evidence that pollen may cause systemic health effects and trigger cardiovascular events.

Evaluation of insecticide residues against spotted lanternfly (Hemiptera: Fulgoridae).

Lycorma delicatula White (Hemiptera: Fulgoridae), spotted lanternfly, is a univoltine, phloem-feeding, polyphagous and invasive insect in the United States. Although a primary host for this species is Ailanthus altissima (Mill.) Swingle, tree of heaven, L. delicatula also feeds on many other plant species, including cultivated grapevines. As this species continues to spread, it is important to develop effective management tools. Here, we evaluated the residual efficacy of 4 insecticides commonly used in tree fruit management programs: dinotefuran, bifenthrin, carbaryl, and thiamethoxam. First, all mobile life stages (early instars, late instars, and adults) of L. delicatula were exposed for 1 h to dry insecticide residues (18 h old) applied to glass or A. altissima bark surfaces. While some mortality was detected immediately following the 1 h exposure period, 100% mortality occurred within 24 h for all materials and life stages exposed on both glass and bark surfaces. To evaluate longer residual activity of these materials, groups of adult L. delicatula were introduced into cages containing A. altissima trees treated with the same individual insecticides and exposed 6 h to residues that were 18 h or 7 days old. Paired, untreated A. altissima served as controls. In these bioassays, 48 h mortality for 18 h old residue reached 95% for thiamethoxam and 100% for bifenthrin and dinotefuran. Seven-day-old bifenthrin and dinotefuran residues again yielded 100% mortality, while thiamethoxam resulted in 58% mortality, and carbaryl yielded only 13.3% and was not significantly different from the control. These results clearly document the efficacy of specific insecticide applications as management tools against L. delicatula.

Evaluation of early bacterial adhesion on CAD/CAM dental materials: an in situ study.

The aim of this research was to determine if there are differences in early bacterial adhesion among CAD/CAM dental materials after 24h exposure in the oral environment. One hundred twenty specimens were prepared according to the manufacturer's recommendations and divided into six groups: RBC (resin-based composite), PMMA (polymethyl methacrylate), PEEK (polyether ether ketone), ZP (zirconia polished), ZG (zirconia glazed), and cobalt-chromium alloy (CoCr alloy). Twenty healthy participants were instructed to carry an intraoral device with six specimens, one per group, for 24h. Thereafter, real-time polymerase chain reaction (qPCR) and scanning electron microscopy (SEM) analyses enabled quantification and 2D view of biofilm formed on the specimens' surfaces. Kruskal-Wallis test and Dunn's post hoc analysis were used for inter-group comparison and data were presented as median (minimum-maximum). RBC specimens accumulated less bacteria, in comparison with ZG (p = 0.017) and PEEK specimens (p = 0.030), that dominated with the highest amount of adhered bacterial biofilm. PMMA, CoCr, and ZP specimens adhered more bacteria than RBC (p > 0.05), and less than ZG (p > 0.05) and PEEK (p > 0.05). The bacterial number varied considerably among participants. The obtained results enable a closer view into the susceptibility of CAD/CAM materials to microorganisms during the presence in the oral environment, which can be beneficial for a proper selection of these materials for a variety of dental restorations.

Plasmodium falciparum alters the trophoblastic barrier and stroma villi organization of human placental villi explants.

The sequestration of Plasmodium falciparum infected erythrocytes in the placenta, and the resulting inflammatory response affects maternal and child health. Despite existing information, little is known about the direct impact of P. falciparum on the placental barrier formed by trophoblast and villous stroma. This study aimed to assess placental tissue damage caused by P. falciparum in human placental explants (HPEs). HPEs from chorionic villi obtained of human term placentas (n = 9) from normal pregnancies were exposed to P. falciparum-infected erythrocytes (IE) for 24h. HPEs were embedded in paraffin blocks and used to study tissue damage through histopathological and histochemical analysis and apoptosis using TUNEL staining. Culture supernatants were collected to measure cytokine and angiogenic factors and to determine LDH activity as a marker of cytotoxicity. A subset of archived human term placenta paraffin-embedded blocks from pregnant women with malaria were used to confirm ex vivo findings. Plasmodium falciparum-IE significantly damages the trophoblast layer and the villous stroma of the chorionic villi. The increased LDH activity and pathological findings such as syncytial knots, fibrin deposits, infarction, trophoblast detachment, and collagen disorganization supported these findings. The specific damage to the trophoblast and the thickening of the subjacent basal lamina were more pronounced in the ex vivo infection. In contrast, apoptosis was higher in the in vivo infection. This disparity could be attributed to the duration of exposure to the infection, which significantly varied between individuals naturally exposed over time and the 24-h exposure in the ex vivo HPE model. Exposure to P. falciparum-IE induces a detachment of the syncytiotrophoblast, disorganization of the stroma villi, and an increase in apoptosis, alterations that may be associated with adverse results such as intrauterine growth restriction and low birth weight.

Increase in Plasma S100B Concentration Is Associated With Decrements in Spatial Processing During Acute High-Altitude Exposure

Vasogenic edema consequent to blood-brain barrier (BBB) permeability may contribute to cognitive performance decrements during acute exposure to high altitude. S100B is a putative marker of BBB permeability, but S100B responses to high altitude are poorly characterized and the relation to cognitive performance is unknown. To test the hypothesis that S100B increases upon ascent to high altitude and that increase is associated with changes in cognitive performance, 41 healthy Soldiers (mean±SD; age=26±5yr) were tested at their baseline residence (SL, 331m), transported to Taos, NM (2845m), then immediately hiked (n=21) or were driven (n=20) to a high-altitude (HA, 3600m) facility. Plasma S100B was measured at 06:00 throughout the study; twice at SL and again after the first night at HA (16h exposure). The automated neuropsychological assessment metric (ANAM) was administered four times at SL and once at HA to assess sustained attention, working memory, spatial processing, computation, executive function, and reaction time. ANAM performance was assessed using throughput scores, a metric considering both response speed and accuracy. The last SL morning assessment and the HA morning assessment (19h exposure) were used to generate ΔANAM scores. Correlations between ΔS100B and ΔANAM scores were significant for 1 of 9 modules, simultaneous spatial processing (SPD; r=-0.401; p=0.009). S100B increased (5.3%, p=0.02) from SL to HA while SPD scores decreased (8.2%, p=0.05). Using the reliable change index (RCI) to dichotomize individuals into those demonstrating a decrease in performance that exceeded measurement error and day-to-day variability (responders; RCI &lt;-1.64; n=7) and those who did not (non-responders; RCI &gt;-1.64; n=34) revealed that responders experienced a greater increase (+12.3%, p=0.01) in S100B from SL to HA relative to non-responders (+3.4%, p=0.14) Findings suggest that acute exposure to 3600m may increase BBB permeability, as indicated from plasma S100B concentrations, and the increased BBB permeability may be mechanistically associated with spatial processing decrements. Funding: USAMRDC, PRMRP. Authors’ views not offcial U.S. Army or DoD policy. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

UV-C side-emitting optical fiber-based disinfection: a promising approach for infection control in tight channels.

The growth of pathogenic bacteria in moist and wet surfaces and tubing of medically relevant devices results in serious infections in immunocompromised patients. In this study, we investigated and demonstrated the successful implementation of a UV-C side-emitting optical fiber in disinfecting medically relevant pathogenic bacteria (Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus [MRSA]) within tight channels of polytetrafluoroethylene (PTFE). PTFE is a commonly used material both in point-of-use (POU) water treatment technologies and medical devices (dental unit water line [DUWL], endoscope). For a 1-m-long PTFE channel, up to ≥6 log inactivation was achieved using a 1-m-long UV side-emitting optical fiber (SEOF) with continuous 16-h exposure of low UV-C radiation ranging from ~0.23 to ~29.30 μW/cm2. Furthermore, a linear model was used to calculate the inhibition zone constant (k`), which enables us to establish a correlation between UV dosage and the extent of inactivated surface area (cm2) for surface-bound Escherichia coli on a nutrient-rich medium. The k` value for an irradiance ranging from ~150 to ~271.50 μW/cm2 was calculated to be 0.564 ± 0.6 cm·cm2/mJ. This study demonstrated the efficacy of SEOFs for disinfection of medically relevant microorganisms present in medically and domestically relevant tight channels. The impact of the results in this study extends to the optimization of operational efficiency in pre-existing UV surface disinfection setups that currently operate at UV dosages exceeding the optimal levels.IMPORTANCEGermicidal UV radiation has gained global recognition for its effectiveness in water and surface disinfection. Recently, various works have illustrated the benefit of using UV-C side-emitting optical fibers (SEOFs) for the disinfection of tight polytetrafluoroethylene (PTFE) channels. This study now demonstrates its impact for disinfection of medically relevant organisms and introduces critical design calculations needed for its implementation. The flexible geometry and controlled emission of light in these UV-SEOFs make them ideal for light distribution in tight channels. Moreover, the results presented in this manuscript provide a novel framework that can be employed in various applications, addressing microbial contamination and the disinfection of tight channels.

Characterization of the genetic determinants of context-specific DNA methylation in primary monocytes

To better understand inter-individual variation in sensitivity of DNA methylation (DNAm) to immune activity, we characterized effects of inflammatory stimuli on primary monocyte DNAm (n= 190). We find that monocyte DNAm is site-dependently sensitive to lipopolysaccharide (LPS), with LPS-induced demethylation occurring following hydroxymethylation. We identify 7,359 high-confidence immune-modulated CpGs (imCpGs) that differ in genomic localization and transcription factor usage according to whether they represent a gain or loss in DNAm. Demethylated imCpGs are profoundly enriched for enhancers and colocalize to genes enriched for disease associations, especially cancer. DNAm is age associated, and we find that 24-h LPS exposure triggers approximately 6months of gain in epigenetic age, directly linking epigenetic aging with innate immune activity. By integrating LPS-induced changes in DNAm with genetic variation, we identify 234 imCpGs under local genetic control. Exploring shared causal loci between LPS-induced DNAm responses and human disease traits highlights examples of disease-associated loci that modulate imCpG formation.