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Changes to ivermectin (IVM [22,23-dihydro avermectin B1a + 22,23-dihydro avermectin B1b]) toxicokinetics (TK) with and without P-glycoprotein (P-gp) inhibition by cyclosporin A (CsA) were examined in rainbow trout (Oncorhynchus mykiss). Rainbow trout were injected with 175 µg/kg 3H-IVM (8.6 µCi/mg IVM) with or without co-administration of 480 µg/kg CsA into the caudal vasculature. Fish were sacrificed at various time points (0.25, 0.5, 1, 3, 24, 48, 96, and 168 h) for organ and tissue sampling (blood, liver, kidney, gill, intestines, brain [5 regions], eye, gonad, and fat) which were analyzed for IVM-derived radioactivity. The IVM concentration decreased over time in blood, liver, kidney, and gill, while concentrations in other tissues remained constant. The highest maximum IVM concentration (Cmax) was found in kidney, followed by liver; the lowest Cmax was found in eye, followed by brain and adipose tissue. The highest % of the administered dose was found in the blood 15 min post-IVM administration, followed by the intestine at 60 min post-IVM administration. P-gp inhibition by CsA did not significantly affect calculated TK parameters (AUC [7.33 ± 0.73 - 11.5 ± 2.5 mg•h/kg], mean residence time [84.7 ± 21 - 125 ± 55 h], T1/2 [58.7 ± 15 - 86.8 ± 38 h], clearance rate [0.0152 ± 0.0033 - 0.0239 ± 0.0024 L/kg•h], or volume of distribution [1.91 ± 0.47 - 2.02 ± 0.33 L/kg]), but resulted in small but significant changes in the % administered dose found in blood and medulla. These results suggest that P-gp plays a limited role in overall IVM TK, and that its role in xenobiotic protection may be much less robust in fish than it is in mammals.

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The membrane efflux transporter P-glycoprotein (P-gp, [ABCB1, MDR1]) exports a wide range of xenobiotic compounds, resulting in a continuous first line of defense against toxicant accumulation at basal expression levels, and contributing to the multixenobiotic resistance (MXR) phenotype at elevated expression levels. Relatively little information exists on P-gp inhibition in fish by chemosensitizers, compounds which lower toxicity thresholds for harmful P-gp substrates in complex mixtures. The effects of four known mammalian chemosensitizers (cyclosporin A [CsA], quinidine, valspodar [PSC833], and verapamil) on the P-gp-mediated transport of rhodamine 123 (R123) and cortisol in primary cultures of rainbow trout (Oncorhynchus mykiss) hepatocytes were examined. Competitive accumulation assays using 25 µM R123 or cortisol and varying concentrations of chemosensitizers (0-500 µM) were used. CsA, quinidine, and verapamil inhibited R123 export (IC50 values ± SE: 132 ± 60, 83.3 ± 27.2, and 43.2 ± 13.6 µM, respectively). CsA and valspodar inhibited cortisol export (IC50 values: 294 ± 106 and 92.2 ± 34.9 µM, respectively). In an ATP depletion assay, hepatocytes incubated with all four chemosensitizers resulted in lower free ATP concentrations, suggesting that they act via competitive inhibition. Chemosensitizers that inhibit MXR transporters are an important class of environmental pollutant, and these results show that rainbow trout transporters are inhibited by similar chemosensitizers (and mostly at similar concentrations) as seen in mammals and other fish species.

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This study presents an in-depth analysis of heterogeneous aging patterns in membrane electrode assemblies (MEAs) subjected to diverse accelerated stress test (AST) conditions, simulating carbon corrosion (CC AST) and Pt particle size growth in fully humidified (Pt AST-Wet) and underhumidified (Pt AST-Dry) H2/N2 atmospheres. Multimodal characterization techniques are used to focus on heterogeneous aging patterns, primarily examining the variations in current distributions and Pt particle size maps. The findings reveal distinct characteristics of current distributions for all the AST cases, with substantial changes and strong current gradients in the CC AST case, indicative of severe performance degradation. Notably, despite significant differences in Pt particle size growth at the end-of-life (EOL), the Pt AST-Wet and Pt AST-Dry cases show minor changes in spatial current distributions. Moreover, a preferential growth of Pt particles under serpentine flow field bends in the Pt AST-Wet case is observed for the first time. This study provides crucial insights into the role of mass transport properties in shaping fuel cell performance, and highlights the need to consider factors beyond electrochemically-active surface area (ECSA) when assessing fuel cell durability.

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Alterations in ivermectin (IVM, 22,23-dihydro avermectin B1a+22,23-dihydro avermectin B1b) toxicokinetics following P-glycoprotein (P-gp) induction by clotrimazole (CTZ) were examined in rainbow trout (Oncorhynchus mykiss) to assess the potential importance of P-gp activity levels in xenobiotic distribution and kinetics in fish. Control and fish pretreated with CTZ (30 µmol/kg) were administered 175 µg/kg 3H-IVM into the caudal vasculature. At various time points (0.25, 0.5, 1, 3, 24, 48, 96, and 168 h) following injection, tissues (blood, liver, kidney, gill, intestines, brain [5 regions], eye, gonad and fat) were removed analyzed for IVM-derived radioactivity. IVM concentration declined in blood, liver, kidney and gill, and concentrations in other tissues remained constant over the sampling period. The highest measured concentrations were found in kidney, followed by liver, with the lowest values found in brain, eye and gonad. The highest % of the administered dose was found in the liver and kidney in the immediate hours post-administration, and in the intestines and fat at 24 h post-administration. P-gp induction by CTZ did not alter IVM distribution or any calculated toxicokinetic parameter (AUC, mean residence time, T1/2, clearance rate, volume of distribution), suggesting that P-gp induction may be limited or that P-gp plays a lesser role in xenobiotic kinetics in fish compared to mammals.

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Gas diffusion layers (GDLs) play a crucial role in heat transfer and water management of cathode catalyst layers in polymer electrolyte fuel cells (PEFCs). Thermal and water gradients can accelerate electrocatalyst degradation and therefore the selection of GDLs can have a major influence on PEFC durability. Currently, the role of GDLs in electrocatalyst degradation is poorly studied. In this study, electrocatalyst accelerated stress test studies are performed on membrane electrode assemblies (MEAs) prepared using three most commonly used GDLs. The effect of GDLs on electrocatalyst degradation is evaluated in both nitrogen (non-reactive) and air (reactive) gas environments at 100% relative humidity. In situ electrochemical characterization and extensive physical characterization is performed to understand the subtle differences in electrocatalyst degradation and correlated to the use of different GDLs. Overall, no difference is observed in the electrocatalyst degradation due to GDLs based on polarization curves at the end of life. But interestingly, MEA with a cracked microporous layer (MPL) in the GDL exhibited a higher electrocatalyst loading loss, which resulted in a lower and more heterogeneous increase in the average electrocatalyst nanoparticle size.

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Chitin is a natural N-acetylglucosamine polymer and a major structural component of fungal cell walls. Dietary chitin is mucoadhesive; anti-inflammatory effects of chitin microparticles (CMPs; 1- to 10-µm diameters) have been demonstrated in models of inflammatory bowel disease (IBD). The goals of this study were to assess (i) whether CMPs among various chitin preparations are the most effective against colitis in male and female mice and (ii) whether host chitin-binding Toll-like receptor 2 (TLR2) and CD14 are required for the anti-inflammatory effect of chitin. We found that colitis in male mice was ameliorated by CMPs and large chitin beads (LCBs; 40 to 70 µm) but not by chitosan (deacetylated chitin) microparticles, oligosaccharide chitin, or glucosamine. In fact, LCBs were more effective than CMPs. In female colitis, on the other hand, CMPs and LCBs were equally and highly effective. Neither sex of TLR2-deficient mice showed anti-inflammatory effects when treated with LCBs. No anti-inflammatory effect of LCBs was seen in either CD14-deficient males or females. Furthermore, an in vitro study indicated that when LCBs and CMPs were digested with stomach acidic mammalian chitinase (AMC), their size-dependent macrophage activations were modified, at least in part, suggesting reduced particle sizes of dietary chitin in the stomach. Interestingly, stomach AMC activity was greater in males than females. Our results indicated that dietary LCBs were the most effective preparation for treating colitis in both sexes; these anti-inflammatory effects of LCBs were dependent on host TLR2 and CD14.

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Naphthenic acids (NAs), a class of structurally diverse carboxylic acids with often complex ring structures and large aliphatic tail groups, are important by-products of many petrochemical processes including the oil sands mining activity of Northern Alberta. While it is evident that NAs have both acute and chronic harmful effects on many organisms, many aspects of their toxicity remain to be clarified. Particularly, while substantive data sets have been collected on NA toxicity in aquatic prokaryote and vertebrate model systems, to date, nothing is known about the toxic effects of these compounds on the embryonic development of aquatic invertebrate taxa, including freshwater mollusks. This study examines under laboratory conditions the toxicity of NAs extracted from oil sands process water (OSPW) and the low-molecular weight model NAs cyclohexylsuccinic acid (CHSA), cyclohexanebutyric acid (CHBA), and 4-tert-butylcyclohexane carboxylic acid (4-TBCA) on embryonic development of the snail Lymnaea stagnalis, a common freshwater gastropod with a broad Palearctic distribution. Evidence is provided for concentration-dependent teratogenic effects of both OSPW-derived and model NAs with remarkably similar nominal threshold concentrations between 15 and 20 mg/L and 28d EC50 of 31 mg/L. In addition, the data provide evidence for substantial toxicokinetic differences between CHSA, CHBA and 4-TBCA. Together, our study introduces Lymnaea stagnalis embryonic development as an effective model to assay NA-toxicity and identifies molecular architecture as a potentially important toxicokinetic parameter in the toxicity of low-molecular weight NA in embryonic development of aquatic gastropods.

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BACKGROUND AND PURPOSE: Guidelines recommend cognitive screening in acute stroke. Various instruments are available, with no consensus on a preferred tool. We aimed to describe test accuracy of brief screening tools for diagnosis of cognitive impairment and delirium in acute stroke. METHODS: We collected data on sequential stroke unit admission in a single center. Four assessors trained in cognitive testing independently performed screening and reference tests. Brief assessments comprised the following: 10- and 4-point Abbreviated Mental Test (AMT-10; AMT-4); 4-A Test (4AT); Clock Drawing Test (CDT); Cog-4; and Glasgow Coma Scale (GCS). We also recorded the multidisciplinary team's informal review using single question (SQ). We compared against reference standards of Montreal Cognitive Assessment (MoCA) and Confusion Assessment Method for delirium using usual diagnostic cutpoints. For MoCA, we described effects of lowering the diagnostic threshold to MoCA <24 and MoCA <20. We described sensitivity, specificity, and positive and negative predictive values. RESULTS: Over a 10-week period, 111 subjects had cognitive assessment data. Subjects were 50% male (n=55), and median age was 74 years (interquartile range, 64-85). AMT-4, AMT-10, and SQ all had excellent (1.00) specificity for detection of cognitive impairment, although sensitivity was poor (all <0.60). The 4AT had greatest sensitivity for detecting delirium (1.00 [confidence interval [CI], 0.74-1.00]) and reasonable specificity (0.82 [CI, 0.72-0.89]). Properties of 4AT for detection of cognitive impairment, at the traditional MoCA threshold, were also good (sensitivity, 0.86; specificity, 0.78). Using diagnostic thresholds of MoCA ≤26, <24, and <20 gave proportions with cognitive impairments of 86%, 61%, and 49%, respectively, with resulting changes in screening test properties. At lower MoCA thresholds, CDT had favorable sensitivity and specificity (MoCA <20: sensitivity, 0.93, specificity, 0.66; MoCA <24: sensitivity, 0.85, specificity, 0.77). CONCLUSIONS: Many brief screening assessments are specific but not sensitive for detection of cognitive impairment in acute stroke. Our primary analysis suggests that 4AT is a reasonable choice for delirium and cognitive screening in this setting. However, these data are based on standard MoCA diagnostic threshold and may not be suited for an acute stroke population.

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A non-precious metal catalyst for oxygen reduction in acid media, enriched in graphene sheets/bubbles during a high-temperature synthesis step, has been developed from an Fe precursor and in situ polymerized polyaniline, supported on multi-walled carbon nanotubes. The catalyst showed no performance loss for 500 hours in a hydrogen/air fuel cell. The improved durability is correlated with the graphene formation, apparently enhanced in the presence of carbon nanotubes.

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The morphology of Nafion (EW = 1000, Na+ form) in dilute solvents is investigated using small angle neutron scattering (SANS) and 19F NMR. SANS modeling indicates three types of particle morphology: (i) a well-defined cylindrical dispersion in glycerol and in ethylene glycol with different degrees of solvent penetration; (ii) a less-defined, highly solvated large particle (>200 nm) in water/isopropanol mixtures; and (iii) a random-coil conformation (true solution behavior) in N-methylpyrrolidone. These distinct morphological characteristics of Nafion are consistent with the main and side chain mobilities measured by 19F NMR.

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The prohibitive cost of platinum for catalyzing the cathodic oxygen reduction reaction (ORR) has hampered the widespread use of polymer electrolyte fuel cells. We describe a family of non-precious metal catalysts that approach the performance of platinum-based systems at a cost sustainable for high-power fuel cell applications, possibly including automotive power. The approach uses polyaniline as a precursor to a carbon-nitrogen template for high-temperature synthesis of catalysts incorporating iron and cobalt. The most active materials in the group catalyze the ORR at potentials within ~60 millivolts of that delivered by state-of-the-art carbon-supported platinum, combining their high activity with remarkable performance stability for non-precious metal catalysts (700 hours at a fuel cell voltage of 0.4 volts) as well as excellent four-electron selectivity (hydrogen peroxide yield <1.0%).

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Carbon-supported Se/Ru(Se) catalysts of a broad range of composition were synthesized via a reduction procedure in which a mixture of RuCl3, SeO2 and Black Pearl carbon was treated with NaBH4 in basic media at room temperature. Physical characterization of the catalyst was performed by X-ray diffraction, energy dispersive X-ray spectroscopy and by high resolution transmission electron microscopy. The effect of NaOH addition during the reduction by NaBH4 and the impact of a post-reduction thermal treatment at 500 degrees C were interrogated. The activity of the catalyst towards the oxygen reduction reaction was studied by the use of a rotating disk electrode. It was found that the half-wave potential for the oxygen reduction reaction was about 0.78 V vs. RHE. The Se-to-Ru ratio and metal loading on carbon were optimized for the oxygen reduction reaction and the optimized catalyst was tested at the cathode of a polymer electrolyte fuel cell. The stability of the Se/Ru(Se) catalyst was evaluated by electrochemical cycling and by leaching the catalyst in 0.5 M H2SO4 at 80 degrees C.

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Catalytic activity of the Pt(111)/Os surface toward methanol electrooxidation was optimized by exploring a wide range of Os coverage. Various methods of surface analyses were used, including electroanalytical, STM, and XPS methods. The Pt(111) surface was decorated with nanosized Os islands by spontaneous deposition, and the Os coverage was controlled by changing the exposure time to the Os-containing electrolyte. The structure of Os deposits on Pt(111) was characterized and quantified by in situ STM and stripping voltammetry. We found that the optimal Os surface coverage of Pt(111) for methanol electrooxidation was 0.7 +/- 0.1 ML, close to 1.0 +/- 0.1 Os packing density. Apparently, the high osmium coverage Pt(111)/Os surface provides more of the necessary oxygen-containing species (e.g., Os-OH) for effective methanol electrooxidation than the Pt(111)/Os surfaces with lower Os coverage (vs e.g., Ru-OH). Supporting evidence for this conjecture comes from the CO electrooxidation data, which show that the onset potential for CO stripping is lowered from 0.53 to 0.45 V when the Os coverage is increased from 0.2 to 0.7 ML. However, the activity of Pt(111)/Os for methanol electrooxidation decreases when the Os coverage is higher than 0.7 +/- 0.1 ML, indicating that Pt sites uncovered by Os are necessary for sustaining significant methanol oxidation rates. Furthermore, osmium is inactive for methanol electrooxidation when the platinum substrate is absent: Os deposits on Au(111), a bulk Os ingot, and thick films of electrodeposited Os on Pt(111), all compare poorly to Pt(111)/Os. We conclude that a bifunctional mechanism applies to the methanol electrooxidation similarly to Pt(111)/Ru, although with fewer available Pt sites. Finally, the potential window for methanol electrooxidation on Pt(111)/Os was observed to shift positively versus Pt(111)/Ru. Because of the difference in the Os and Ru oxophilicity under electrochemical conditions, the Os deposit provides fewer oxygen-containing species, at least below 0.5 V vs RHE. Both higher coverage of Os than Ru and the higher potentials are required to provide a sufficient number of active oxygen-containing species for the effective removal of the site-blocking CO from the catalyst surface when the methanol electrooxidation process occurs.

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We provide an electrochemical and structural characterization by in situ STM of Au(111)/Os electrodes prepared by spontaneous deposition of Os on Au(111). Surfaces with Os coverage values up to the saturation coverage were examined, from 10%. Using comparisons to previous work on Au(111)/Ru, Pt(111)/Ru, and Pt(111)/Os, we find that we may now generalize that Os deposits spontaneously faster than Ru and has a greater tendency to form 3-D structures. Additionally, the Au(111) substrate shows preferential step and near-step decoration in both cases, although it is less pronounced for Os than Ru. We also investigated the incremental dissolution of the Os from Au(111), to better understand electrochemical dissolution processes in general and to better control the Os deposit structure. The application of controlled electrochemical treatments (cyclic voltammetry up to increasingly positive values) significantly increased the dispersion of the Os deposit by generating smaller, more widely spaced islands. Upon voltammetry up to 0.75 V, the Au(111)/Os surface showed evidence of alloying and the formation of 3-D structures suggestive of strong Os-Os (oxidized) species interactions. The CO stripping results show the Au(111)/Os is not particularly effective for this reaction, but such results help to complete the overall picture of NM-NM catalytic combinations. Although the Au(111)/Os system itself is not catalytically active, the electrochemical manipulation of the deposit structure demonstrated here may be applied to other noble metal/noble metal (NM/NM) catalytic substrates to find optimal deposit morphologies.