Seasonal variation of cesium 134 and cesium 137 in semidomestic reindeer in Norway after the Chernobyl accident

The Chernobyl accident had a great impact on the semidomestic reindeer husbandry in central Norway. Seasonal differences in habitat and diet resulted in large variations in observed radiocesium concentrations in reindeer after the Chernobyl accident. In three areas with high values of cesium-134 and cesium-137 in lichens, the main feed for reindeer in winter, reindeer were sampled every second month to monitor the seasonal variation and the decrease rate of the radioactivity. The results are based on measurements of cesium-134 and cesium-137 content in meat and blood and by whole-body monitoring of live animals. In 1987 the increase of radiocesium content in reindeer in Vågå were 4x from August to January. The mean reductions in radiocesium content from the winter 1986/87 to the winter 1987/88 were 32%, 50% and 43% in the areas of Vågå, Østre-Namdal and Lom respectively

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PPARγ agonists negatively regulate αIIbβ3 integrin outside-in signalling and platelet function through upregulation of protein kinase A activity

BACKGROUND: Agonists for the peroxisome proliferator activated receptor PPARγ, have been shown to have inhibitory effects on platelet activity following stimulation by GPVI and GPCR agonists. OBJECTIVES: Profound effects on thrombus formation led us to suspect a role for PPARγ agonists in the regulation of integrin αIIbβ3 mediated signalling. Both GPVI and GPCR signalling pathways lead to αIIbβ3 activation, and signalling through αIIbβ3 plays a critical role in platelet function and normal haemostasis. METHODS: The effects of PPARγ agonists on the regulation of αIIbβ3 outside-in signalling was determined by monitoring the ability of platelets to adhere and spread on fibrinogen and undergo clot retraction. Effects on signalling components downstream of αIIbβ3 activation were also determined following adhesion to fibrinogen by western blotting. RESULTS: Treatment of platelets with PPARγ agonists inhibited platelet adhesion and spreading on fibrinogen and diminished clot retraction. A reduction in phosphorylation of several components of αIIbβ3 signalling, including the integrin β3 subunit, Syk, PLCγ2, FAK and Akt was also observed as a result of reduced interaction of the integrin β3 subunit with Gα13. Studies of VASP phosphorylation revealed that this was a due to an increase in PKA activity following treatment with PPARγ receptor agonists. CONCLUSIONS: This study provides further evidence for anti-platelet actions of PPARγ agonists, identifies a negative regulatory role for PPARγ agonists in the control of integrin αIIbβ3 outside-in signalling, and provides a molecular basis by which the PPARγ agonists negatively regulate platelet activation and thrombus formation

RXR ligands negatively regulate thrombosis and hemostasis

OBJECTIVE: Platelets have been found to express intracellular nuclear receptors including the Retinoid X receptors (RXRα and RXRβ). Treatment of platelets with ligands of RXR has been shown to inhibit platelet responses to ADP and thromboxane A2, however the effects on responses to other platelet agonists as well as the underlying mechanism has not been fully characterised. APPROACH AND RESULTS: The effect of 9-cis-retinoic acid (9-cis-RA), docosahexaenoic acid and synthetic ligand for RXR, methoprene acid on collagen receptor (GPVI) agonists and Thrombin stimulated platelet function; including aggregation, granule secretion, integrin activation, calcium mobilisation, integrin αIIbβ3 outside-in signalling and thrombus formation in vitro and in vivo were determined. Treatment of platelets with RXR ligands resulted in attenuation of platelet functional responses following stimulation by GPVI agonists and thrombin and inhibition of integrin αIIbβ3 outside-in signalling. Treatment with 9-cis-RA caused inhibition of thrombus formation in vitro and an impairment of thrombosis and haemostasis in vivo. Both RXR ligands stimulated protein kinase A activation, measured by VASP S157 phosphorylation, that was found to be dependent on both cAMP and NFκB activity. CONCLUSIONS: This study identifies a widespread, negative regulatory role for RXR in the regulation of platelet functional responses and thrombus formation and describes novel events that lead to the upregulation of PKA, a known negative regulator of many aspects of platelet function. This mechanism may offer a possible explanation for the cardioprotective effects described in vivo following treatment with RXR ligands

Pseudomonas aeruginosa AES-1 exhibits increased virulence gene expression during chronic infection of cystic fibrosis lung

Pseudomonas aeruginosa, the leading cause of morbidity and mortality in people with cystic fibrosis (CF), adapts for survival in the CF lung through both mutation and gene expression changes. Frequent clonal strains such as the Australian Epidemic Strain-1 (AES-1), have increased ability to establish infection in the CF lung and to superimpose and replace infrequent clonal strains. Little is known about the factors underpinning these properties. Analysis has been hampered by lack of expression array templates containing CF-strain specific genes. We sequenced the genome of an acute infection AES-1 isolate from a CF infant (AES-1R) and constructed a non-redundant micro-array (PANarray) comprising AES-1R and seven other sequenced P. aeruginosa genomes. The unclosed AES-1R genome comprised 6.254Mbp and contained 6957 putative genes, including 338 not found in the other seven genomes. The PANarray contained 12,543 gene probe spots; comprising 12,147 P. aeruginosa gene probes, 326 quality-control probes and 70 probes for non-P. aeruginosa genes, including phage and plant genes. We grew AES-1R and its isogenic pair AES-1M, taken from the same patient 10.5 years later and not eradicated in the intervening period, in our validated artificial sputum medium (ASMDM) and used the PANarray to compare gene expression of both in duplicate. 675 genes were differentially expressed between the isogenic pairs, including upregulation of alginate, biofilm, persistence genes and virulence-related genes such as dihydroorotase, uridylate kinase and cardiolipin synthase, in AES-1M. Non-PAO1 genes upregulated in AES-1M included pathogenesis-related (PAGI-5) genes present in strains PACS2 and PA7, and numerous phage genes. Elucidation of these genes' roles could lead to targeted treatment strategies for chronically infected CF patients. © 2011 Naughton et al

Postnatal care following hypertensive disorders of pregnancy: a qualitative study of views and experiences of primary and secondary care clinicians

Objectives To explore clinicians' views and experiences of caring for postnatal women who had hypertensive disorders of pregnancy (HDP), awareness of relevant National Institute for Health and Care Excellence (NICE) guidance to inform their postnatal management, the extent to which NICE guidance was implemented, barriers and facilitators to implementation and how care could be enhanced to support women's future health. Design A qualitative study using semistructured interviews. Thematic analysis was used for coding and theme generation. Setting Four National Health Service maternity units and three general practice clinics in South-East and South-West London. Participants A maximum variation, purposive sample of 20 clinicians with experience of providing postnatal care to women following HDP. Results Four main themes were generated: variation in knowledge and clinical practice; communication and education; provision of care; locus of responsibility for care. Perceived barriers to implementation of NICE guidance included lack of postnatal care plans and pathways, poor continuity of care, poor antihypertensive medication management, uncertainty around responsibility for postnatal care and women's lack of awareness of the importance of postnatal follow-up for their future health. Some clinicians considered that women were discharged from inpatient care too soon, as primary care clinicians did not have specialist knowledge of HDP management. Most clinicians acknowledged the need for better planning, communication and coordination of care across health settings. Conclusions Evidence of longer term consequences for women's health following HDP is accumulating, with potential for NICE guidance to support better outcomes for women if implemented. Clinicians responsible for postnatal care following HDP should ensure that they are familiar with relevant NICE guidance, able to implement recommendations and involve women in decisions about ongoing care and why this is important. The continued low priority and resources allocated to postnatal services will continue to promote missed opportunities to improve outcomes for women, their infants and families

Three Stages of Lysozyme Thermal Stabilization by High and Medium Charge Density Anions

Addition of high and medium charge density anions (phosphate, sulfate, and chloride) to lysozyme in pure water demonstrates three stages for stabilization of the protein structure. The first two stages have a minor impact on lysozyme stability and are probably associated with direct interaction of the ions with charged and partial charges on the protein’s surface. There is a clear transition between the second and third stages; in the case of sodium chloride, disodium sulfate and disodium hydrogen phosphate this is at 550, 210, and 120 mM, respectively. Stabilization of lysozyme can be explained by the free energy required to hydrate the protein as it unfolds. At low ion concentrations, the protein’s hydration layer is at equilibrium with the bulk water. After the transition, bulk water is depleted and the protein is competing for water with the ions. With competition for water between the protein and the ions at higher salt concentrations, the free energy required to hydrate the interior of the protein rises and it is this that stabilizes the protein structure

Understanding the ongoing learning needs of Australian metropolitan, rural and remote paediatricians: Evaluation of a neurology outreach programme

Aim: The purpose of this study was to evaluate whether a neurology outreach teaching programme delivered via video-teleconferencing (6 × 60 min live sessions every 6–8 weeks) is acceptable, contributes to understanding and meets the neurology learning needs of Australian paediatricians from metropolitan, rural and remote areas. Methods: A sample of six NSW sites that joined the neurology outreach programme between 2017 and 2019 (Arm 1) and six interstate sites from QLD, WA and TAS who commenced the programme in 2020 (Arm 2) participated. A mixed-methods survey explored participants' learning needs and value of the programme. Results: Forty-six participants submitted programme evaluation surveys (26 arm 1, 20 arm 2); 9 were removed due to insufficient data (n = 37). Quantitative and qualitative data showed the programme was acceptable in format, relevant to practice, appropriate for clinician learning needs, and engaging. Clinicians reported improvement in understanding and confidence. Participants felt more connected/less isolated and up-to-date. Participants reported a positive impact from the programme on approach to neurological problems and ensuing consults, and more differentiated and appropriate paediatric neurology referrals. Conclusion: This study validates the live video-teleconference outreach model as an acceptable, effective and important means of providing continuing neurology education for Australian paediatricians