480 research outputs found
Social Rejection in Adolescents With a Visible Facial Disfigurement: A Qualitative Study
Much of the research focusing on the difficulties experienced by young people with a visible facial disfigurement (VFD) has focused on the view from the outside (social/cultural views towards disfigurement) and the view from the inside (the psychological impact of living with a VFD). Part 1 presents a review of the literature on the attitudes of non-disfigured children towards individuals with a VFD. Sixteen studies were included in this review following a systematic search of the literature. Overall, results indicated that non-disfigured children demonstrate a negative bias towards individuals with a VFD. Part 2 presents a qualitative study which explored the lived experiences of young people with a VFD, specifically focusing on their peer relationships and experiences of social rejection relating to their appearance. Semi-structured interviews were completed with 10 adolescents (aged 11-14 years) with a range of congenital VFDs and analysed using thematic analysis. All young people described experiencing negative and unwanted attention from others. Many identified positively with their disfigured appearance and saw it as a part of who they were. In spite of this, the majority of young people did not wish to have a VFD for the rest of their lives. Part 3 presents a critical appraisal of the qualitative study. It explores the possible barriers to engaging young people in research and considers the unique contributions made by this study in considering the focus on psychopathology in the existing literature on young people with VFDs and in understanding the heterogeneity reported by this population
Fate of Zinc Oxide Nanoparticles Coated onto Macronutrient Fertilizers in an Alkaline Calcareous Soil
Citation: Milani, N., Hettiarachchi, G. M., Kirby, J. K., Beak, D. G., Stacey, S. P., & McLaughlin, M. J. (2015). Fate of Zinc Oxide Nanoparticles Coated onto Macronutrient Fertilizers in an Alkaline Calcareous Soil. Plos One, 10(5), 16. doi:10.1371/journal.pone.0126275Zinc oxide (ZnO) nanoparticles may provide a more soluble and plant available source of Zn in Zn fertilizers due to their greater reactivity compared to equivalent micron-or millimetresized (bulk) particles. However, the effect of soil on solubility, spatial distribution and speciation of ZnO nanoparticles has not yet been investigated. In this study, we examined the diffusion and solid phase speciation of Zn in an alkaline calcareous soil following application of nanoparticulate and bulk ZnO coated fertilizer products (monoammonium phosphate (MAP) and urea) using laboratory-based x-ray techniques and synchrotron-based mu-x-ray fluorescence (mu-XRF) mapping and absorption fine structure spectroscopy (mu-XAFS). Mapping of the soil-fertilizer reaction zones revealed that most of the applied Zn for all treatments remained on the coated fertilizer granule or close to the point of application after five weeks of incubation in soil. Zinc precipitated mainly as scholzite (CaZn2(PO4)(2)center dot 2H(2)O) and zinc ammonium phosphate (Zn(NH4)PO4) species at the surface of MAP granules. These reactions reduced dissolution and diffusion of Zn from the MAP granules. Although Zn remained as zincite (ZnO) at the surface of urea granules, limited diffusion of Zn from ZnO-coated urea granules was also observed for both bulk and nanoparticulate ZnO treatments. This might be due to either the high pH of urea granules, which reduced solubility of Zn, or aggregation (due to high ionic strength) of released ZnO nanoparticles around the granule/point of application. The relative proportion of Zn(OH)(2) and ZnCO3 species increased for all Zn treatments with increasing distance from coated MAP and urea granules in the calcareous soil. When coated on macronutrient fertilizers, Zn from ZnO nanoparticles (without surface modifiers) was not more mobile or diffusible compared to bulk forms of ZnO. The results also suggest that risk associated with the presence of ZnO NPs in calcareous soils would be the same as bulk sources of ZnO
Kinome and Transcriptome profiling reveal broad and distinct activities of Erlotinib, Sunitinib, and Sorafenib in the mouse heart and suggest cardiotoxicity from combined signal transducer and activator of transcription and epidermal growth factor receptor inhibition
Kinome and Transcriptome Profiling Reveal Broad and Distinct Activities of Erlotinib, Sunitinib, and Sorafenib in the Mouse Heart and Suggest Cardiotoxicity From Combined Signal Transducer and Activator of Transcription and Epidermal Growth Factor Receptor Inhibition
BACKGROUND: Most novel cancer therapeutics target kinases that are essential to tumor survival. Some of these kinase inhibitors are associated with cardiotoxicity, whereas others appear to be cardiosafe. The basis for this distinction is unclear, as are the molecular effects of kinase inhibitors in the heart.
METHODS AND RESULTS: We administered clinically relevant doses of sorafenib, sunitinib (cardiotoxic multitargeted kinase inhibitors), or erlotinib (a cardiosafe epidermal growth factor receptor inhibitor) to mice daily for 2 weeks. We then compared the effects of these 3 kinase inhibitors on the cardiac transcriptome using RNAseq and the cardiac kinome using multiplexed inhibitor beads coupled with mass spectrometry. We found unexpectedly broad molecular effects of all 3 kinase inhibitors, suggesting that target kinase selectivity does not define either the molecular response or the potential for cardiotoxicity. Using in vivo drug administration and primary cardiomyocyte culture, we also show that the cardiosafety of erlotinib treatment may result from upregulation of the cardioprotective signal transducer and activator of transcription 3 pathway, as co-treatment with erlotinib and a signal transducer and activator of transcription inhibitor decreases cardiac contractile function and cardiomyocyte fatty acid oxidation.
CONCLUSIONS: Collectively our findings indicate that preclinical kinome and transcriptome profiling may predict the cardiotoxicity of novel kinase inhibitors, and suggest caution for the proposed therapeutic strategy of combined signal transducer and activator of transcription/epidermal growth factor receptor inhibition for cancer treatment
Foreign Direct Investment, Aggregate Demand Conditions and Exchange Rate Nexus: A Panel Data Analysis of BRICS Economies
In this study, we attempt to provide underlying theoretical and empirical explanations for exchange rate appreciation due to foreign capital influx and aggregate demand conditions in the BRICS economies. The empirical analysis is based on a panel dataset of BRICS countries over the time period 1992–2013 to substantiate our theoretical findings. For panel co-integration, Pedroni and Johansen-Fisher panel co-integration tests are conducted to compare co-integration among panel countries. We also analyze the results from Dumitrescu-Hurlin panel causality test among variables and use Granger Causality to test for the causal patterns in each of the individual countries. Our findings showed that the exchange rate volatility is directly affected by the flows of FDI, GDP per capita, Capital formulation and House hold consumption. The results have profound implications in terms of exchange rate stability in the BRICS countries and associated risks
High regioselectivity in electrochemical α-methoxylation of N-protected cyclic amines
N-Protecting groups of α-substituted cyclic amines strongly affected the regioselectivity in electrochemical methoxylation of these compounds. Namely, N-acyl derivatives were transformed into α′-methoxylated compounds, while N-cyano derivatives changed into α-methoxylated derivatives. Furthermore, Lewis acid catalyzed nucleophilic substitution of the α-methoxylated compounds protected with cyano group afforded α,α-disubstituted cyclic amines
Effect of weathering product assemblages on Pb bioaccessibility in mine waste: implications for risk management
Local Suppression of T Cell Responses by Arginase-Induced L-Arginine Depletion in Nonhealing Leishmaniasis
The balance between T helper (Th) 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is primarily expressed locally at the site of pathology. The high arginase activity causes local depletion of L-arginine, which impairs the capacity of T cells in the lesion to proliferate and to produce interferon-γ, while T cells in the local draining lymph nodes respond normally. Healing, induced by chemotherapy, resulted in control of arginase activity and reversal of local immunosuppression. Moreover, competitive inhibition of arginase as well as supplementation with L-arginine restored T cell effector functions and reduced pathology and parasite growth at the site of lesions. These results demonstrate that in nonhealing leishmaniasis, arginase-induced L-arginine depletion results in impaired T cell responses. Our results identify a novel mechanism in leishmaniasis that contributes to the failure to heal persistent lesions and suggest new approaches to therapy
Doxorubicin exposure causes subacute cardiac atrophy dependent upon the striated muscle-specific ubiquitin ligase Muscle Ring Finger-1
Background Anthracycline chemotherapeutics, such as doxorubicin, are used widely in the treatment of numerous malignancies. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that often presents as heart failure due to dilated cardiomyopathy years after anthracycline exposure. Recent data from animal studies indicate that anthracyclines cause cardiac atrophy. The timing of onset and underlying mechanisms are not well defined, and the relevance of these findings to human disease is unclear. Methods and Results Wild-type mice were sacrificed 1 week after intraperitoneal administration of doxorubicin (1-25 mg/kg), revealing a dose-dependent decrease in cardiac mass ( R2=0.64; P<0.0001) and a significant decrease in cardiomyocyte cross-sectional area (336±29 versus 188±14 µm2; P<0.0001). Myocardial tissue analysis identified a dose-dependent upregulation of the ubiquitin ligase, MuRF1 (muscle ring finger-1; R2=0.91; P=0.003) and a molecular profile of muscle atrophy. To investigate the determinants of doxorubicin-induced cardiac atrophy, we administered doxorubicin 20 mg/kg to mice lacking MuRF1 (MuRF1-/-) and wild-type littermates. MuRF1-/- mice were protected from cardiac atrophy and exhibited no reduction in contractile function. To explore the clinical relevance of these findings, we analyzed cardiac magnetic resonance imaging data from 70 patients in the DETECT-1 cohort and found that anthracycline exposure was associated with decreased cardiac mass evident within 1 month and persisting to 6 months after initiation. Conclusions Doxorubicin causes a subacute decrease in cardiac mass in both mice and humans. In mice, doxorubicin-induced cardiac atrophy is dependent on MuRF1. These findings suggest that therapies directed at preventing or reversing cardiac atrophy might preserve the cardiac function of cancer patients receiving anthracyclines
- …