Radioprotective Cerium Oxide Nanoparticles: Molecular Imaging Investigations of CONPs’ Pharmacokinetics, Efficacy, and Mechanisms of Action

Cerium oxide nanoparticles (CONPs) are being investigated for several anti-oxidant applications in medicine. One of their most promising applications is as a radioprotective drug, an area of research in need due to the severe side effects from radiation therapy. In this work, the potential of CONPs as a radioprotective drug is examined using four criteria: favorable biodistribution/pharmacokinetics, low toxicity, ability to protect normal tissue from radiation damage, and lack of protection of tumor. The mechanisms of action of CONPs are also studied. Biodistribution was determined in radiolabeled CONPs with surface coatings including citrate, dextran T10-amine (DT10-NH2), dextran T10-polyethylene glycol (DT10-PEG), dextran T10-sulfobetaine (DT10-SB) and poly(acrylic acid) (PAA), and compared to uncoated. 89Zr was incorporated into CONPs for positron emission tomography (PET) imaging and ex vivo tissue analysis in tumor bearing mice. Compared to uncoated [89Zr]CONPs, coated [89Zr]CONPs showed improved biodistribution, including significantly enhanced renal clearance of PAA- [89Zr]CONPs. The toxicity of CONPs was evaluated in vitro and in vivo, with low toxicity at therapeutic doses. After clinically mimetic radiation therapy, pre-treatment of mice with coated and uncoated CONPs showed greater than 50% reduction of cell death in normal colon tissue, comparable to the clinically available radioprotective drug amifostine. Tumor control after irradiation of spontaneous colon tumors was unchanged with PAA-CONP pre-treatment, while citrate, DT10-PEG, and uncoated CONP pre-treatment had slightly less tumor control. Xenograft tumors were irradiated after pH normalizing treatment with sodium bicarbonate and PAA-CONP pre-treatment. Treatment of these tumors showed slightly less tumor control than irradiation alone or PAA-CONP plus irradiation, demonstrating that the acidic pH of the tumor microenvironment may be the basis of preventing CONPs’ radioprotective properties in tumor. These studies show that, among the variations of CONPs tested, PAA-CONP shows the most promise for its good biodistribution and quick clearance, low toxicity, ability to protect normal tissue, and lack of protection of tumor, meeting all the criteria set forth for an ideal radioprotective drug. Further studies on the effects of pH on CONPs actions may further elucidate their mechanisms of action, advancing them as a candidate for use as a radioprotective drug during radiation therapy

Migrant and minority community organisations: funding, sustainability and ways forward

MODA (Migrant Organisations’ Development Agency) and Middlesex University have been working together on a research project about funding and resources available to migrant and minority organisations in London. This reports presents some of its key findings. The aim of the project was to gather information about the role of minority and migrant organisations, including details about the services they provide, the community needs they address, the financial and organizational challenges they face and the creative ways they are finding to cope. The research also aimed to explore the effects of the current economic and political climate on the sector and the role played by second tier organisations and other networks

h-indices: an update on the performance of professors in nursing in the UK

Editoria

On the reactivity of zinc hydroxide acetate dihydrate in ethanol

Zinc hydroxide acetate dihydrate, Zn5(OH)8(CH 3CO2)2·2H2O, reacts in ethanol at room temperature to yield a mixture of zinc oxide and anhydrous zinc acetate. The process is driven by dehydration of the starting salt. Dehydration of Zn5(OH)8(CH3CO2) 2·2H2O also occurs when it is heated in air, but the product obtained in that case depends on the heating rate, environment and temperature. For example, when it is kept in a sealed silica capillary at 100 °C, Zn5(OH)8(CH3CO2) 2·1.5H2O is formed after 15 min, whereas treatment in the range 90-100°C in an open environment results in the formation of anhydrous zinc hydroxide acetate. Heating of any of these products further causes their decomposition to Zn(CH3CO2)2 and ZnO. The coordination bonding mode of the acetate groups in the anhydrous layered zinc hydroxide acetate prepared by reaction with ethanol was studied by using solid-state NMR spectroscopy. The presence of chelating, unidentate and bidentate bridging modes for the carbonyl carbon atom was revealed, but there was no evidence for the inclusion of ethanol in the resultant structure. Therefore, the reaction in ethanol offers a convenient strategy to prepare anhydrous zinc hydroxide acetate and/or zinc oxide, because it avoids the sensitivity of the thermally induced dehydroxlation process to time, temperature and environment. Decomposition of zinc hydroxide acetate dihydrate in ethanol can be exploited to generate ZnO nanoparticles at room temperature. The mechanism involves the removal of waters of hydration and the formation of Zn5(OH)8(CH3CO2)2 followed by the generation of Zn(CH3CO)2 and ZnO. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

The year in cardiology: heart failure

No abstract available

Exploiting zinc oxide re-emission to fabricate periodic arrays

The synthesis of hexagonal ring-shaped structures of zinc oxide using nanosphere lithography and metal/metal oxide sputtering is demonstrated. This synthesis exploits the surface re-emission of zinc oxide to deposit material in regions lying out of the line-of-sight of the sputtering source. These rings can nucleate the hydrothermal growth of zinc oxide crystals. Control over the growth could be exercised by varying growth solution concentration or temperature or by applying an external potential. © 2010 American Chemical Society

New clues to metabolic regulation through changes in the thiol redox proteome

Comunicaciones a congreso

P50 addressing the vocational development of young people with long-term health conditions in health care settings:a systematic review and mixed methods synthesis

INTRODUCTION/BACKGROUND: Long term health conditions (LTHC) such as rheumatic conditions have significant impact on the biopsychosocial development of young people (YP) including vocational development. Educational transitions are prominent during adolescence and young adulthood yet not all transitional care programmes in rheumatology address this area [1]. The aim of this study was to identify and synthesise the benefits and experiences of addressing the vocational development of YP with LTHC in health care settings. DESCRIPTION/METHOD: A mixed methods synthesis approach [2] was employed. We systematically searched 10 bibliographic databases. Restrictions were applied on publication date (1996-2020) and publication language (English). Articles reporting quantitative and/or qualitative primary research on addressing vocational needs/issues of YP with LTHC in health care settings were included. YP was defined as 10-24 years [3]. Two reviewers independently screened records using predetermined inclusion/exclusion criteria [4]. Quality appraisal was undertaken following study selection. Qualitative data were synthesised thematically. Quantitative data were synthesised narratively, given that a pooled synthesis was not considered appropriate. A cross-study synthesis integrated findings from both the qualitative and quantitative syntheses. DISCUSSION/RESULTS: 43 articles were included. The quality of qualitative evidence was good; however, the quality of quantitative evidence was poor. The thematic synthesis of stakeholders’ perspectives (n = 23 qualitative studies) resulted in seven recommendations for interventions: provide skills training; provide psychological support; offer to liaise with key stakeholders in educational/workplace settings; provide specialist career advice; provide information, signposting and facilitate access to supporting services; provide/facilitate access to social support; provide flexible care and optimal disease management to support education/employment transitions. The narrative synthesis summarised the results of 17 interventions. The cross-study synthesis mapped interventions against the set of recommendations arising from stakeholders’ perspectives: four interventions met five recommendations; two interventions met four recommendations; five interventions met three recommendations; six interventions met two recommendations. Transitional care interventions were the type of intervention that most comprehensively met the recommendations. The way in which interventions addressed vocational issues was not always clear, with some interventions addressing them directly and others indirectly. No interventions had vocational issues as the core, defining component of the intervention. KEY LEARNING POINTS/CONCLUSION: Existing stakeholder evidence highlights that vocational development is an important area to address in the care of YP with LTHC such as rheumatic diseases. The resulting set of recommendations provides guidance for future research in this area and transitional care developments in rheumatology. Further work in this area should address these aspects to enable better quality evidence and ensure consistency. References [1] Clemente D et al. Pediatr Rheumatol Online J. 2017 Jun 9;15(1):49. [2] Kavanagh, J et al Synthesizing Qualitative Research: Choosing the Right Approach. Wiley-Blackwell, Chichester, UK, pp. 113–136 [3] World Health Organization, 2001. The second decade: improving adolescent health and development. Geneva. [4] Farre A et al. PROSPERO 2016 CRD42016051359