Antioxidant Rescue of Selenomethionine-Induced Teratogenesis in Zebrafish Embryos.

Selenium (Se) is an essential micronutrient that can be found at toxic concentrations in surface waters contaminated by runoff from agriculture and coal mining. Zebrafish (Danio rerio) embryos were exposed to aqueous Se in the form of selenate, selenite, and l-selenomethionine (SeMet) in an attempt to determine if oxidative stress plays a role in selenium embryo toxicity. Selenate and selenite exposure did not induce embryo deformities (lordosis and craniofacial malformation). l-selenomethionine, however, induced significantly higher deformity rates at 100 µg/L compared with controls. SeMet exposure induced a dose-dependent increase in the catalytic subunit of glutamate-cysteine ligase (gclc) and reached an 11.7-fold increase at 100 µg/L. SeMet exposure also reduced concentrations of TGSH, RGSH, and the TGSH:GSSG ratio. Pretreatment with 100 µM N-acetylcysteine significantly reduced deformities in the zebrafish embryos secondarily treated with 400 µg/L SeMet from approximately 50­10 % as well as rescued all three of the significant glutathione level differences seen with SeMet alone. Selenite exposure induced a 6.6-fold increase in expression of the glutathione-S-transferase pi class 2 (gstp2) gene, which is involved in xenobiotic transformation and possibly oxidative stress. These results suggest that aqueous exposure to SeMet can induce significant embryonic teratogenesis in zebrafish that are at least partially attributed to oxidative stress.

Bioaccumulation and speciation of selenium in fish and insects collected from a mountaintop removal coal mining-impacted stream in West Virginia.

A major contaminant of concern for mountaintop removal/valley fill (MTR/VF) coal mining is selenium (Se), an essential micronutrient that can be toxic to fish. Creek chubs (Semotilus atromaculatus), green sunfish (Lepomis cyanellus), and composite insect samples were collected in March-July, 2011-2013 at two sites within the Mud River, West Virginia. One site (MR7) receives MTR/VF coal mining effluent, while the reference site (LFMR) does not. MR7 water had significantly higher concentrations of soluble Se (p < 0.01) and conductivity (p < 0.005) compared to LFMR. MR7 whole insects contained significantly higher concentrations of Se compared to LFMR insects (p < 0.001). MR7 creek chubs had significantly higher Se in fillets, liver, and ovary tissues compared to LFMR samples (p < 0.0001, p < 0.0001, and p < 0.02, respectively). MR7 green sunfish fillets contained significantly higher Se (p < 0.0001). Histological examination showed LFMR creek chub gills contained a typical amount of parasitic infestations; however MR7 gills contained minimal to no visible parasites. X-ray absorption spectroscopic analyses revealed that MR7 whole insects and creek chub tissues primarily contained organic Se and selenite. These two species of Mud River fish were shown to specifically accumulate Se differently in tissues compartments. Tissue-specific concentrations of Se may be useful in determining potential reproductive consequences of Se exposure in wild fish populations.

Cerium oxide nanoparticles are more toxic than equimolar bulk cerium oxide in Caenorhabditis elegans.

Engineered cerium oxide nanoparticles (CeO2 NPs) are widely used in biomedical and engineering manufacturing industries. Previous research has shown the ability of CeO2 NPs to act as a redox catalyst, suggesting potential to both induce and alleviate oxidative stress in organisms. In this study, Caenorhabditis elegans and zebrafish (Danio rerio) were dosed with commercially available CeO2 NPs. Non-nano cerium oxide powder (CeO2) was used as a positive control for cerium toxicity. CeO2 NPs suspended in standard United States Environmental Protection Agency reconstituted moderately hard water, used to culture the C. elegans, quickly formed large polydisperse aggregates. Dosing solutions were renewed daily for 3 days. Exposure of wild-type nematodes resulted in dose-dependent growth inhibition detected for all 3 days (p < 0.0001). Non-nano CeO2 also caused significant growth inhibition (p < 0.0001), but the scale of inhibition was less at equivalent mass exposures compared with CeO2 NP exposure. Some metal and oxidative stress-sensitive mutant nematode strains showed mildly altered growth relative to the wild-type when dosed with 5 mg/L CeO2 NPs on days 2 and 3, thus providing weak evidence for a role for oxidative stress or metal sensitivity in CeO2 NP toxicity. Zebrafish microinjected with CeO2 NPs or CeO2 did not exhibit increased gross developmental defects compared with controls. Hyperspectral imaging showed that CeO2 NPs were ingested but not detectable inside the cells of C. elegans. Growth inhibition observed in C. elegans may be explained at least in part by a non-specific inhibition of feeding caused by CeO2 NPs aggregating around bacterial food and/or inside the gut tract.

Using an interleukin-6 challenge to evaluate neuropsychological performance in chronic fatigue syndrome.

BACKGROUND: Individuals with acute infections experience a range of symptoms including fatigue, malaise, muscle aches, and difficulties with concentration and memory that are usually self-limited. This cluster of symptoms is otherwise, similar to those that characterize chronic fatigue syndrome (CFS). The goal of the present study was to evaluate the cognitive and psychological functioning of CFS patients and normal controls (NCs) when they both were experiencing acute influenza-like symptoms. To induce influenza-like symptoms, we administered interleukin-6 (IL-6), a cytokine that temporarily activates the acute phase immunological and endocrine responses. METHODS: Nineteen patients who met the 1994 International CFS Study Group Criteria and ten normal controls (NCs) completed routine clinical evaluations, neuropsychological tests of short-term memory, selective attention, and executive control, and self-ratings of somatic symptoms and psychological mood before, shortly following, and 1 day after IL-6 administration. RESULTS: CFS patients consistently reported more somatic symptoms, even when both groups perceived that they were ill. Both groups somatic symptoms increased during the IL-6 challenge, but the CFS patients symptoms increased more rapidly than controls. In general, the CFS patients performed similarly to NCs on the cognitive measures before, during, and after the IL-6. In contrast to predictions, IL-6 provocation did not impair the cognitive performance of either CFS patients or NCs. CONCLUSIONS: The IL-6 provocation exacerbated the patients self-reported symptoms but did not reveal notable cognitive impairments between patients and controls during cytokine-induced acute influenza-like symptoms.

Test-retest reliability of the dot test of visuospatial working memory in patients with schizophrenia and controls.

To determine the test-retest reliability of the Dot Test of Visuospatial Working Memory, this task was administered to 29 patients with schizophrenia and 19 normal controls on two consecutive days. The test involved "copying" trials followed by "delay" recall trials. For "copying" trials, subjects saw a dot and then drew it on a blank sheet of paper. For "delay" trials, subjects drew the dot following a 10-, 20-, or 30-s delay. The distance between the stimulus and the drawn dot was measured for each trial. The composite score, termed "working memory deficit," is calculated by subtracting the average of the copying trials from the average of the delay trials. Pearson correlations revealed that overall performance in each group was comparable for days 1 and 2. Intra-class correlations of "working memory deficit" on days 1 and 2 were moderate in patients and controls, suggesting that task performance for each subject was similar on the testing days. Test-retest reliability tended to be higher for 10-s delay performance in patients and controls than for longer delay periods. Further analyses suggested that there was no significant learning effect on the task from day 1 to day 2 for either group on any measure. The Dot Test of Visuospatial Working Memory, especially the composite score, has moderate test-retest reliability and is a valuable tool that can be used to assess working memory functions in studies using a repeated-measures design.

Source monitoring deficits in patients with schizophrenia; a multinomial modelling analysis.

BACKGROUND: Schizophrenia patients, particularly those with symptoms such as thought insertion, passivity experiences and hallucinations, may share an underlying cognitive deficit in monitoring the generation of their own thoughts. This deficit, which has been referred to as 'autonoetic agnosia', may result in the conclusion that self-generated thoughts come from an external source. Previous work supports this notion, yet the statistical approaches that have been used have not enabled a distinction between specific deficits suggesting autonoetic agnosia and more general cognitive dysfunction. METHODS: Autonoetic agnosia was assessed using source-monitoring paradigms in 28 patients with schizophrenia and 19 control subjects. Multinomial model analyses, which allow the distinction between deficits in recognizing information, remembering its source, and response biases, were applied to the data. RESULTS: Schizophrenia patients were impaired in discriminating between words that came from two external sources, from two internal sources, and one internal and one external source. In a condition requiring subjects to distinguish between words they had heard from those they had imagined hearing, when schizophrenic patients did not remember the source of the information, they showed a stronger bias than controls to report that it had come from an external source. CONCLUSIONS: The application of multinomial models to source monitoring data suggests that schizophrenia patients have source monitoring deficits that are not limited to the distinction between internally-generated and externally-perceived information. However, when schizophrenia patients do not remember the source of information, they may be more likely than controls to report that it came from an external source.

A quality improvement program for a clinical nurse specialist department.

This article describes the development of a quality improvement program for a clinical nurse specialist department reflecting the 10-step process described by the Joint Commission on Accreditation of Healthcare Organizations. The philosophy of continuous improvement has allowed the department to promote concurrent improvements as well as to measure and monitor selected direct and indirect patient care indicators. The department developed process indicators to verify the processes in place. The department anticipates development of outcome indicators for subsequent programs. Identified opportunities for improvement, and the changes which occurred to address those opportunities, are also described. Information regarding data collection related to resource consumption and increased collaboration with other departments, is also described.