Long-term high fat feeding of rats results in increased numbers of circulating microvesicles with pro-inflammatory effects on endothelial cells

Obesity and type 2 diabetes lead to dramatically increased risks of atherosclerosis and CHD. Multiple mechanisms converge to promote atherosclerosis by increasing endothelial oxidative stress and up-regulating expression of pro-inflammatory molecules. Microvesicles (MV) are small ( < 1 μm) circulating particles that transport proteins and genetic material, through which they are able to mediate cell–cell communication and influence gene expression. Since MV are increased in plasma of obese, insulin-resistant and diabetic individuals, who often exhibit chronic vascular inflammation, and long-term feeding of a high-fat diet (HFD) to rats is a well-described model of obesity and insulin resistance, we hypothesised that this may be a useful model to study the impact of MV on endothelial inflammation. The number and cellular origin of MV from HFD-fed obese rats were characterised by flow cytometry. Total MV were significantly increased after feeding HFD compared to feeding chow (P< 0·001), with significantly elevated numbers of MV derived from leucocyte, endothelial and platelet compartments (P< 0·01 for each cell type). MV were isolated from plasma and their ability to induce reactive oxygen species (ROS) formation and vascular cell adhesion molecule (VCAM)-1 expression was measured in primary rat cardiac endothelial cells in vitro. MV from HFD-fed rats induced significant ROS (P< 0·001) and VCAM-1 expression (P= 0·0275), indicative of a pro-inflammatory MV phenotype in this model of obesity. These findings confirm that this is a useful model to further study the mechanisms by which diet can influence MV release and subsequent effects on cardio-metabolic health

Mediation and Judicial Review: An empirical research study

The aim of this research is to establish an independent evidence base for identifying the value and the limits of mediation as an alternative to, or used alongside, judicial review. It has been devised in response to claims made by government and mediation providers that mediation can lead to savings in costs as well as in court time, and provide remedies and solutions to disputes that cannot be offered by the court. These claims will be considered in the specifi c context of judicial review, which not only has an important constitutional function, but, compared to other forms of civil litigation, offers flexibility, low costs and speed

Management of dyslipidaemia in an HIV-positive cohort

Background: Dyslipidaemia, secondary to both HIV and the use of antiretroviral therapy (ART) is well recognised, with HIV replication and immune status also thought to contribute to the risk. Traditionally the HIV physician has looked after HIV with primary care physicians (GP) managing non-HIV-related medical issues. However with the ageing population and the effectiveness of ART the HIV physician is diversifying to focus management strategies on preventative measures also. Method: 127 subjects were recruited. All subjects were HIV-positive males without any traditional cardiovascular disease symptoms or history. Details of patients demographics, family history, statin therapy, and primary care physician contact were collected. Baseline parameters were recorded and fasting bloods taken. Results: 127 asymptomatic HIV-positive males were recruited. 74/127 (58.3%) met the EACS criteria for statin prescription. 33/74 (44.6%) were on a statin. There was no significant difference between the class of antiretroviral prescribed, (NNRTI v PI) and lipid abnormalities (p=0.628). Hypertension and increased waist:hip ratio significantly increased the chances of the patient being hyperlipidaemic. Patients were more likely to be prescribed a statin if they were older, had hypertension, an increased waist circumference, increased Framingham risk, increased brain natriuretic peptide (BNP), or were diagnosed HIV-positive for longer (p&#x3C;0.05). Pravastatin (21/33 [63.6%]), was most commonly prescribed statin. 24.2% received their statin prescription from their HIV physician, with 75.8% receiving their prescription from their GP. 5/21 (23.8%) on pravastatin met the target verses 7/7 (100%) on atorvastatin verses 2/2 (100%) on simvastatin versus 1/3 (33.3%) on rosuvastatin (p=0.02). Meeting lipid targets was less successful in the protease inhibitor group (1/9) 11.1% versus 11/21 (52.4%) in the NNRTI group (p=0.16). Conclusion: The majority met criteria for lipid management but less than half of those were prescribed it. Of those, most received treatment from their GP. Nearly half of those on statins did not meet lipid targets. HIV physicians were most likely to prescribe pravastatin and those on pravastatin were the least likely to achieve lipid targets when compared to the other statins. HIV physicians need to diversify their knowledge base and have clearly defined management strategies for the management of dyslipidaemia

Gametophytic transcription for acid phosphatases in pollen of Cucurbita species hybrids

A microslab isoelectric focusing gel is demonstrated, using single pollen grains from F1 hybrids of Cucurbita species. When zymograms of these single pollen grains were stained to indicate the presence of acid phosphatase zones, it was seen that at least 11 out of 37, or 29.7 percent of such zones are controlled by loci that are transcribed in the microgametophyte. These results suggest that gametophytically transcribed loci may be fairly common and also that their investigation is now technically unchallengin

Pressure injury prevalence in a private health service : risks and recommendations

A pressure injury point prevalence was conducted by a private healthcare service (PHS) to determine the prevalence of pressure injuries in inpatients and to provide statistics for use in future comparison studies. The survey was conducted as part of the quality improvement programme of the PHS and the survey instrument was a modified version of a widely used existing tool. On the day of the survey, data collectors, working in pairs, performed skin inspections and completed the survey. Data were then collated and analysed. The overall pressure injury prevalence was 28.2% but with the exclusion of stage one injuries, decreased to 9.9%. Multivariate analysis revealed that the main risk factors for pressure injury development were the inability to reposition independently, older age and having a diagnosis of cancer. The major recommendations for practice change included the provision of pressure relieving devices to all patients unable to reposition independently, alteration of the Braden Scale risk score used on admission to identify older patients at risk from 16 to 18 in accordance with published literature and provision of further education to nurses about use of the Braden Scale and of pressure relieving devices. This study has also highlighted the need for further investigation into the reasons for patient non-participation in research and the direct and indirect relationships between surgery and acquisition of pressure injuries.\u

Biosimilar infliximab introduction into the gastro-enterology care pathway in a large acute Irish teaching hospital: a story behind the evidence

Background and aim: Biosimilar medicines are not considered exact replicas of originator biological medicines. As a result, prescribers can be hesitant to introduce such medicines into the clinical setting until evidence surfaces confirming their safety and effectiveness. In Ireland, a national biosimilar medicines policy is currently in development but the decision to prescribe biosimilar medicines remains at the discretion of the physician. The aim of this descriptive review is to tell the story of the evidence used by a large acute Irish teaching hospital to introduce biosimilar infliximab CT-P13 for the treatment of inflammatory bowel disease (IBD) in a safe and timely manner into routine care. Methods: To explore the evidence supporting the effective introduction of biosimilar infliximab in a large acute Irish teaching hospital, a literature review was conducted. Evidence consisted of published studies, reviews, reports, position statements, articles, clinical guidelines, and recommendations from national bodies, regulatory authorities and professional organizations. All evidence was published in English. Results and discussion: In September 2014, the accumulated evidence base provided physicians with reassurance to prescribe biosimilar infliximab CT-P13 for new patients suffering from IBD in this large acute Irish teaching hospital. In September 2016, as the evidence base grew, physicians began to safely and confidently switch patients from the originator infliximab product to the biosimilar product. Conclusion: There was a significant time lag between regulatory approval and clinical acceptance given that the European Medicines Agency had granted market authorization for biosimilar infliximab CT-P13 three years prior to the initiation of this hospital's switching process. Although conservative in their execution, the authors conclude that with the existential concern and uncertainty still surrounding biosimilar medicines, a distinct and individualized approach for biosimilar medicine implementation is required. It is with hope that the Irish biosimilar medicines policy will improve upon biosimilar medicine clinical acceptance once published