A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Re-Evaluation of Sinocastor (Rodentia: Castoridae) with Implications on the Origin of Modern Beavers

The extant beaver, Castor, has played an important role shaping landscapes and ecosystems in Eurasia and North America, yet the origins and early evolution of this lineage remain poorly understood. Here we use a geometric morphometric approach to help re-evaluate the phylogenetic affinities of a fossil skull from the Late Miocene of China. This specimen was originally considered Sinocastor, and later transferred to Castor. The aim of this study was to determine whether this form is an early member of Castor, or if it represents a lineage outside of Castor. The specimen was compared to 38 specimens of modern Castor (both C. canadensis and C. fiber) as well as fossil specimens of C. fiber (Pleistocene), C. californicus (Pliocene) and the early castorids Steneofiber eseri (early Miocene). The results show that the specimen falls outside the Castor morphospace and that compared to Castor, Sinocastor possesses a: 1) narrower post-orbital constriction, 2) anteroposteriorly shortened basioccipital depression, 3) shortened incisive foramen, 4) more posteriorly located palatine foramen, 5) longer rostrum, and 6) longer braincase. Also the specimen shows a much shallower basiocciptal depression than what is seen in living Castor, as well as prominently rooted molars. We conclude that Sinocastor is a valid genus. Given the prevalence of apparently primitive traits, Sinocastor might be a near relative of the lineage that gave rise to Castor, implying a possible Asiatic origin for Castor

Nitrated α-Synuclein Induces the Loss of Dopaminergic Neurons in the Substantia Nigra of Rats

BACKGROUND: The pathology of Parkinson's disease (PD) is characterized by the degeneration of the nigrostriatal dopaminergic pathway, as well as the formation of intraneuronal inclusions known as Lewy bodies and Lewy neurites in the substantia nigra. Accumulations of nitrated alpha-synuclein are demonstrated in the signature inclusions of Parkinson's disease. However, whether the nitration of alpha-synuclein is relevant to the pathogenesis of PD is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, effect of nitrated alpha-synuclein to dopaminergic (DA) neurons was determined by delivering nitrated recombinant TAT-alpha-synuclein intracellular. We provide evidence to show that the nitrated alpha-synuclein was toxic to cultured dopaminergic SHSY-5Y neurons and primary mesencephalic DA neurons to a much greater degree than unnitrated alpha-synuclein. Moreover, we show that administration of nitrated alpha-synuclein to the substantia nigra pars compacta of rats caused severe reductions in the number of DA neurons therein, and led to the down-regulation of D(2)R in the striatum in vivo. Furthermore, when administered to the substantia nigra of rats, nitrated alpha-synuclein caused PD-like motor dysfunctions, such as reduced locomotion and motor asymmetry, however unmodified alpha-synuclein had significantly less severe behavioral effects. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence that alpha-synuclein, principally in its nitrated form, induce DA neuron death and may be a major factor in the etiology of PD

Developing a core outcome set for future infertility research : an international consensus development study

Acknowledgements: We would like to thank the Delphi survey and consensus development meeting participants and colleagues at the Cochrane Gynaecology and Fertility Group, University of Auckland, New Zealand. Funding: This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund, and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis, or interpretation of data, or manuscript preparation. Ben Mol is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). Siladitya Bhattacharya was supported by University of Auckland Foundation Seelye Travelling Fellowship. This article has not been externally peer reviewed. This article has been published simultaneously in Human ReproductionPeer reviewe

ATP release via anion channels

ATP serves not only as an energy source for all cell types but as an ‘extracellular messenger-for autocrine and paracrine signalling. It is released from the cell via several different purinergic signal efflux pathways. ATP and its Mg2+ and/or H+ salts exist in anionic forms at physiological pH and may exit cells via some anion channel if the pore physically permits this. In this review we survey experimental data providing evidence for and against the release of ATP through anion channels. CFTR has long been considered a probable pathway for ATP release in airway epithelium and other types of cells expressing this protein, although non-CFTR ATP currents have also been observed. Volume-sensitive outwardly rectifying (VSOR) chloride channels are found in virtually all cell types and can physically accommodate or even permeate ATP4- in certain experimental conditions. However, pharmacological studies are controversial and argue against the actual involvement of the VSOR channel in significant release of ATP. A large-conductance anion channel whose open probability exhibits a bell-shaped voltage dependence is also ubiquitously expressed and represents a putative pathway for ATP release. This channel, called a maxi-anion channel, has a wide nanoscopic pore suitable for nucleotide transport and possesses an ATP-binding site in the middle of the pore lumen to facilitate the passage of the nucleotide. The maxi-anion channel conducts ATP and displays a pharmacological profile similar to that of ATP release in response to osmotic, ischemic, hypoxic and salt stresses. The relation of some other channels and transporters to the regulated release of ATP is also discussed

Applying critical systems thinking to social prescribing: a relational model of stakeholder “buy-in”

Background Social prescribing (SP) allows health professionals to refer primary care patients toward health and wellbeing interventions and activities in the local community. Now widely implemented across the UK and adopted in other nations, questions arise concerning the modelling of present and future schemes, including challenges to full engagement encountered by stakeholders, which lie beyond the scope of traditional evaluations. Critical Systems Thinking (CST) allows for holistic analysis of fields where multiple stakeholders hold diverse interests and unequal power. Methods We use CST to (a) critically examine a developing rural social prescribing scheme from multiple stakeholder perspectives and (b) present a relational model for local social prescribing schemes. Our fieldwork included 24 in-depth interviews, regular planning meetings with key stakeholders, and discussions with those involved with national and international SP landscaping. A modified grounded theory approach was used for the analysis, and to consider the core elements of social prescribing sustainability. Results Our study confirms that local social prescribing schemes must operate with numerous stakeholder interests in mind, seeking to address real life social complexity and offer integrated solutions to multifaceted issues. Three main areas are discussed: holistic vision and boundary judgments; barriers and facilitators; relational issues and “emotional buy in”. Problems for staff include selecting suitable clients, feedback and technological issues and funding and evaluation pressures. Barriers for clients include health, transport and expense issues, also lack of prior information and GP involvement. Emotional “buy-in” emerged as essential for all stakeholders, but hard to sustain. Based on our findings we propose a positive relational model comprising shared vision, confidence and commitment; motivation and encouragement, support and wellbeing focus, collaborative relationships, communication and feedback, access to information /resources, learning in and from action, with emotional “buy-in” at its heart. Conclusion Those implementing social prescribing in different localities inevitably face hard choices about what and whom to include. Research on the sustainability of social prescribing remains limited, studies are required to ascertain which “holistic” models of social prescribing work best for which communities, who are the main beneficiaries of these approaches and how “buy-in” is best sustained