Assessing metal bioaccumulation from estuarine sediments: comparative experimental results for the polychaete Arenicola marina

Purpose: The purpose of this paper is to compare three approaches for providing information on the bioaccumulation potential of metals from contaminated sediments to the deposit-feeding polychaete Arenicola marina. Materials and methods: We present metal (Ag, As, Cd, Cu, Pb and Zn) bioaccumulation results from field-collected sediments quantified through direct measurements of bioaccumulated concentrations in A. marina over a period of 30days under controlled laboratory exposures and compare these results with bioaccumulated metal concentrations in field-collected organisms from the same sites of collection of the sediments used in the laboratory exposures. For the metals for which model parameters are available (Ag, As, Cd and Zn), we also compare these results with biodynamic model predictions. We considered three UK estuaries characterised by a well-reported history of trace metal contamination and bioavailability in addition to the (control) site of collection of the worms. Results and discussion: The results from laboratory-exposed organisms showed that the standard 28-day exposure duration may be adequate to identify the potential for metal bioaccumulation in this polychaete at the sites considered here. However, the time course of bioaccumulated concentrations and the comparison with measured concentrations in field-collected worms show that a steady state has not been reached, confirming the need for extended exposure periods. The worms showed symptoms of stress in feeding and growth during the initial 10days of exposure and subsequent partial recovery during the following 20days, suggesting that stress was not always caused by sediment contamination but that it was likely associated with handling and acclimation. At this last stage of the exposure, a generalised biodynamic model was used to provide estimates of bioaccumulated metal concentrations and net accumulation rates in worms. Conclusions: The results of this study highlight the number of factors that should be considered for the interpretation of bioaccumulated metal concentrations in A. marina under laboratory exposures for contaminated sediment assessment, factors that appear to be common to most deposit-feeding polychaetes. A general biodynamic model proved to be a cost-effective method for an initial estimation of the extent and pattern of metal bioaccumulation under specified exposure condition

Amphipod susceptibility to metals: Cautionary tales

Heavy metals accumulated by aquatic crustaceans in environmental studies are normally investigated using the whole body burden, with little regard paid to uptake in different tissues, to potential gender of life stage differences, or to the influence of nutrition on the test organism. This is likely to give erroneous conclusions for a dose–response relationship within the toxicity test and potentially lead to wrong conclusions for the ecological risks of metals where species may have higher sensitivities with gender and life stage than indicated or that functionally metals may be sequestered into parts of the body so are not bioavailable. This could lead to under-estimation or over-estimation of the toxicity of metals,respectively, inaccuracy of metal budget calculations and evaluation of trophic transfers of metals. This study evaluated the influences of life stage, gender, and a priori nutritional state in the uptake of the metals zinc (an essential micro-nutrient; Zn) and cadmium (a non-essential element; Cd) in the amphipod Echinogammarus marinus. The study showed that life stage, and nutritional stage did significantly influence the uptake and bioaccumulation for both metals, but only Cd showed differential uptake and bioaccumulation with gender. In addition, it was concluded that there was a significant uptake and accumulation of both metals within the exoskeleton of the amphipods, which though adding to the full body burden would add little to toxicity through lack of bioavailability. These results showed that care should be taken when interpreting results from tests normally preformed on such test organisms

Nurse Health, Work Environment, Presenteeism and Patient Safety

Presenteeism is linked to negative outcomes for patients, nurses, and health care organizations; however, we lack understanding of the relationships between nurse fatigue, burnout, psychological well-being, team vitality, presenteeism, and patient safety in nursing. Therefore, the two aims of this study were: (a) to examine the fit of a literature-derived model of the relationships between presenteeism, psychological health and well-being, fatigue, burnout, team vitality, and patient safety; and (b) to examine the role of presenteeism as a mediator between patient safety and the other model variables. Survey data were analyzed using Composite Indicator Structural Equation (CISE) modeling, a type of structural equation modeling. Model fit was acceptable with multiple significant relationships. Presenteeism due to job-stress mediated multiple relationships to patient safety. Our findings indicate that focusing on job-stress presenteeism may be relevant for this population and may offer additional insight into factors contributing to decreased nurse performance and the resulting risks to patient safety.JONAS PhilanthropiesThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation <i>In Vitro</i>.

Funder: Biotechnology and Biological Sciences Research CouncilFunder: Wellcome TrustFunder: NIHR Cambridge Biomedical Research CentreThe retinoid X receptor agonist bexarotene promotes remyelination in patients with multiple sclerosis. Murine studies have also demonstrated that RXR agonists have anti-inflammatory effects by enhancing the ability of all-trans-retinoic acid (atRA) to promote T-regulatory cell (Treg) induction and reduce Th17 differentiation in vitro. By stimulating human naïve CD4 T-cells in the presence of Treg or Th17 skewing cytokines, we show that bexarotene also tips the human Treg/Th17 axis in favor of Treg induction, but unlike murine cells this occurs independently of atRA and retinoic acid receptor signaling. Tregs induced in the presence of bexarotene express canonical markers of T-regulation and are functionally suppressive in vitro. Circulating Treg numbers did not increase in the blood of trial patients receiving bexarotene; we believe this is because Treg induction is likely to occur within tissues. These findings lend support to developing RXR agonists as treatments of autoimmune diseases, in particular multiple sclerosis

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Seasonal and dietary influences on adipose tissue and systemic gene expression in control and previously laminitic ponies

The aims of the study were to determine whether adipose tissue global gene expression (i) differs between never laminitic (NL) and previously laminitic (PL) ponies; (ii) is influenced by season and/or a diet designed to simulate spring grass and (iii) differences seen also occur systemically in peripheral blood mononuclear cells (PBMCs). Subcutaneous adipose tissue and PBMCs were obtained from six NL and six PL ponies on three occasions; summer, winter (season study) and in winter after consuming a diet simulating spring grass for seven days (diet study). Adipose tissue global gene expression was determined using a 44K equine specific microarray, validated using multiplex quantitative real time PCR (qRT-PCR) and analysed using GeneSpring software and Ingenuity Pathway Analysis. PBMC gene expression was quantified using qRT-PCR. The total number of genes whose expression differed (=2-fold change, p=0.01) between PL and NL ponies was greater in summer (192 genes) compared to winter (58 genes); 40/192 genes influenced by disease in the summer were also seasonally regulated and were predominantly associated with inflammation. The genes modified by dietary intervention and PBMC gene expression did not follow the same pattern as the season study. Thus, adipose tissue global gene expression differed between NL and PL ponies most in summer compared to winter, and these differentially expressed genes predominantly related to inflammation

Social Network Characteristics and Salivary Cortisol in Healthy Older People

Psychobiological research on aging in humans has been confounded by individual differences that have not been adequately characterized in the literature. This paper is an attempt to shed light on this issue by examining the impact of social network characteristics predictive of successful aging on salivary cortisol among 78 older Chinese people in Hong Kong. Eight salivary cortisol samples were collected each day for two consecutive days from immediately after awakening to 12 hours later. Two components of the cortisol diurnal cycle, response to awakening and diurnal decline, were examined in relation to social network characteristics including size, emotional support, and cultivation. ANOVAs with repeated measured were run to examine influences of the three social network characteristics on the cortisol awakening response and diurnal decline, with the effects of gender, age, socioeconomic status, and waking time controlled. Results indicated that those who spent more time and effort in developing and strengthening their social ties (i.e., those high in “cultivation”) exhibited a significantly greater rise in cortisol in the morning and a significantly steeper decline over the day, thus attesting to more effective activation and deactivation of the HPA axis. Network cultivation reflected a positive motivation to nurture social relationships more than the other two network characteristics. Its effect on cortisol might stem from the positivity underlying the motivation

Three-dimensional scapular morphology is associated with rotator cuff tears and alters the abduction moment arm of the supraspinatus.

BACKGROUND: Numerous studies have reported an association between rotator cuff injury and two-dimensional measures of scapular morphology. However, the mechanical underpinnings explaining how these shape features affect glenohumeral joint function and lead to injury are poorly understood. We hypothesized that three-dimensional features of scapular morphology differentiate asymptomatic shoulders from those with rotator cuff tears, and that these features would alter the mechanical advantage of the supraspinatus. METHODS: Twenty-four individuals with supraspinatus tears and twenty-seven age-matched controls were recruited. A statistical shape analysis identified scapular features distinguishing symptomatic patients from asymptomatic controls. We examined the effect of injury-associated morphology on mechanics by developing a morphable model driven by six degree-of-freedom biplanar videoradiography data. We used the model to simulate abduction for a range of shapes and computed the supraspinatus moment arm. FINDINGS: Rotator cuff injury was associated with a cranial orientation of the glenoid and scapular spine (P = .011, d = 0.75) and/or decreased subacromial space (P = .001, d = 0.94). The shape analysis also identified previously undocumented features associated with superior inclination and subacromial narrowing. In our computational model, warping the scapula from a cranial to a lateral orientation increased the supraspinatus moment arm at 20° of abduction and decreased the moment arm at 160° of abduction. INTERPRETATIONS: Three-dimensional analysis of scapular morphology indicates a stronger relationship between morphology and cuff tears than two-dimensional measures. Insight into how morphological features affect rotator cuff mechanics may improve patient-specific strategies for prevention and treatment of cuff tears

Idd9.2 and Idd9.3 Protective Alleles Function in CD4+ T-Cells and Nonlymphoid Cells to Prevent Expansion of Pathogenic Islet-Specific CD8+ T-Cells

OBJECTIVE - Multiple type 1 diabetes susceptibility genes have now been identified in both humans and mice, yet mechanistic understanding of how they impact disease pathogenesis is still minimal. We have sought to dissect the cellular basis for how the highly protective mouse Idd9 region limits the expansion of autoreactive CD8 T-cells, a key cell type in destruction of the islets. RESEARCH DESIGN AND METHODS - We assess the endogenous CD8 T-cell repertoire for reactivity to the islet antigen glucose-6-phosphatase-related protein (IGRP). Through the use of adoptively transferred T-cells, bone marrow chimeras, and reconstituted severe combined immunodeficient mice, we identify the protective cell types involved. RESULTS - IGRP-specific CD8 T-cells are present at low frequency in the insulitic lesions of Idd9 mice and could not be recalled in the periphery by viral expansion. We show that Idd9 genes act extrinsically to the CD8 T-cell to prevent the massive expansion of pathogenic effectors near the time of disease onset that occurs in NOD mice. The subregions Idd9.2 and Idd9.3 mediated this effect. Interestingly, the Idd9.1 region, which provides significant protection from disease, did not prevent the expansion of autoreactive CD8 T-cells. Expression of Idd9 genes was required by both CD4 T-cells and a nonlymphoid cell to induce optimal tolerance. CONCLUSIONS - Idd9 protective alleles are associated with reduced expansion of IGRP-specific CD8 T-cells. Intrinsic expression of protective Idd9 alleles in CD4 T-cells and nonlymphoid cells is required to achieve an optimal level of tolerance. Protective alleles in the Idd9.2 congenic subregion are required for the maximal reduction of islet-specific CD8 T-cells