Hypertension in adults: summary of updated NICE guidance

Hypertension is a leading global cause of morbidity and mortality. More than 25% of the adult UK population has hypertension, and in about 30% blood pressure remains uncontrolled.1 In August, the National Institute for Health and Care Excellence (NICE) published its updated guideline on the diagnosis and management of hypertension. The guideline reviews further evidence that has emerged since it was last updated in 2011 from randomised trials investigating the initiation, monitoring, and choice of antihypertensive treatment. The scope of the updated guideline has increased to also include people with type 2 diabetes, but does not make recommendations for people with chronic kidney disease, established cardiovascular disease, or hypertension in pregnancy.This article summarises the most recent recommendations from NICE and includes information considered to be most relevant to primary care clinicians. Key changes to current practice include offering drug treatment to people at a lower threshold for 10 year risk of cardiovascular disease, emphasis on maintaining blood pressure below target, and clarifying criteria for same day specialist review in people with accelerated hypertension

HST NIR Snapshot Survey of 3CR Radio Source Counterparts II: An Atlas and Inventory of the Host Galaxies, Mergers and Companions

We present the second part of an H-band (1.6 microns) atlas of z<0.3 3CR radio galaxies, using the Hubble Space Telescope Near Infrared Camera and Multi-Object Spectrometer (HST NICMOS2). We present new imaging for 21 recently acquired sources, and host galaxy modeling for the full sample of 101 (including 11 archival) -- an 87% completion rate. Two different modeling techniques are applied, following those adopted by the galaxy morphology and the quasar host galaxy communities. Results are compared, and found to be in excellent agreement, although the former breaks down in the case of strongly nucleated sources. Companion sources are tabulated, and the presence of mergers, tidal features, dust disks and jets are catalogued. The tables form a catalogue for those interested in the structural and morphological dust-free host galaxy properties of the 3CR sample, and for comparison with morphological studies of quiescent galaxies and quasar host galaxies. Host galaxy masses are estimated, and found to typically lie at around 2*10^11 solar masses. In general, the population is found to be consistent with the local population of quiescent elliptical galaxies, but with a longer tail to low Sersic index, mainly consisting of low-redshift (z<0.1) and low-radio-power (FR I) sources. A few unusually disky FR II host galaxies are picked out for further discussion. Nearby external sources are identified in the majority of our images, many of which we argue are likely to be companion galaxies or merger remnants. The reduced NICMOS data are now publicly available from our website (http://archive.stsci.edu/prepds/3cr/)Comment: ApJS, 177, 148: Final version; includes revised figures 1, 15b, and section 7.5 (and other minor changes from editing process. 65 pages, inc. 17 figure

Grapefruit juice enhances the systolic blood pressure-lowering effects of dietary nitrate-containing beetroot juice

Aims: Dietary nitrate from sources such as beetroot juice lowers blood pressure (BP) via the nitrate-nitrite-nitric oxide (NO) pathway. However, NO and nitrite are inactivated via re- oxidation to nitrate, potentially limiting their activity. Cytochrome P450-3A4 inhibition with troleandomycin prevents nitrite re-oxidation to nitrate in rodent liver. Grapefruit juice contains the CYP3A4 inhibitor furanocoumarin. We therefore hypothesized that grapefruit juice would enhance BP-lowering with beetroot juice by maintaining circulating [nitrite]. Methods: We performed a randomized, placebo-controlled, 7-hour crossover study in 11 healthy volunteers, attending on 3 occasions, receiving: a 70ml-shot of active beetroot juice (Beet- It®) and either (i) 250 ml grapefruit juice (“Active Beet+GFJ”), or (ii) 250 ml water (Buxton®, “Active Beet+H2O”); or (iii) Placebo Beet+GFJ. Results: The addition of grapefruit juice to active beetroot juice lowered systolic BP (SBP): Active Beet+GFJ versus Active Beet+H2O (P=0.02), and pulse pressure, PP (P=0.0003). Peak mean differences in SBP and PP were seen at T=5 hours: -3.3mmHg (95% CI -6.43 to -0.15) and at T=2.5 hours: -4.2 mmHg (95% CI -0.3 to -8.2), respectively. Contrary to the hypothesis, plasma [nitrite] was lower with Active Beet+GFJ versus Active Beet+H2O (P=0.006), as was salivary nitrite production (P=0.002) and saliva volume (-0.34 ml/min (95% CI -0.05 to - 0.68)). The taste score of Beet+GFJ was 1.4/10 points higher than Beet+H2O (P=0.03). This article is protected by copyright. All rights reserved. Conclusions: Grapefruit juice enhanced beetroot juice’s effect on lowering SBP and PP despite decreasing plasma [nitrite]. Besides suggesting more complex mechanisms, there is potential for maximising the clinical benefit of dietary nitrate and targeting isolated systolic hypertension

The Jet and Circumnuclear Environment of 3C 293

We present the new HST near-infrared polarimetry, broad and narrow-band imaging, and MERLIN 4.5GHz Multi-Frequency Synthesis radio imaging of 3C 293, a unique radio galaxy whose host is an obvious merger remnant, in an exceptionally under-dense region of space. We have discovered near-infrared, optical, and ultra-violet synchrotron emission from the jet. In the optical, the jet is mostly obscured by a dust lane, but three knots are clear in our HST NICMOS images at 1.6 and 2.0 microns, clearly aligning with features in the radio. The outer jet knot is highly polarized (~15%) at 2 microns, confirming the synchrotron emission mechanism. The radio-IR spectral index steepens significantly with distance from the nucleus, as in 3C 273 and in contrast to M 87. The inner knot is visible (with hindsight) on the WFPC2 and STIS images obtained for the earlier 3CR HST snapshot surveys. There is no [Fe II] emission seen associated with the jet, constraining the role of shock-induced ionisation by the jet. Overall there is a strong implication that the NIR jet emission is indeed synchrotron. From our NIR images, the core of the galaxy is clearly identifiable with the main feature in the western extension of the radio ``jet'' image, although no unresolved AGN component is identifiable even at K-band, consistent with an FRII-like nucleus obscured by an optically thick torus. The galaxy appears to have a single nucleus, with any multiple nuclei falling within the central </~100 pc.Comment: ApJ accepted. 31 pages, 12 figures reproduced here at low resolution. High resolution version available from http://www.stsci.edu/~floyd/BIBLIOTECA/3c293

A worked example of "best fit" framework synthesis: A systematic review of views concerning the taking of some potential chemopreventive agents

<p>Abstract</p> <p>Background</p> <p>A variety of different approaches to the synthesis of qualitative data are advocated in the literature. The aim of this paper is to describe the application of a pragmatic method of qualitative evidence synthesis and the lessons learned from adopting this "best fit" framework synthesis approach.</p> <p>Methods</p> <p>An evaluation of framework synthesis as an approach to the qualitative systematic review of evidence exploring the views of adults to the taking of potential agents within the context of the primary prevention of colorectal cancer.</p> <p>Results</p> <p>Twenty papers from North America, Australia, the UK and Europe met the criteria for inclusion. Fourteen themes were identified <it>a priori </it>from a related, existing conceptual model identified in the literature, which were then used to code the extracted data. Further analysis resulted in the generation of a more sophisticated model with additional themes. The synthesis required a combination of secondary framework and thematic analysis approaches and was conducted within a health technology assessment timeframe.</p> <p>Conclusion</p> <p>The novel and pragmatic "best fit" approach to framework synthesis developed and described here was found to be fit for purpose. Future research should seek to test further this approach to qualitative data synthesis.</p

Growth Arrest of BCR-ABL Positive Cells with a Sequence-Specific Polyamide-Chlorambucil Conjugate

Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, has significantly improved the clinical outcome of patients with CML. However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML. Although alternative Bcr-Abl tyrosine kinase inhibitors have been developed to overcome drug resistance, a cocktail therapy of different kinase inhibitors and additional chemotherapeutics may be needed for complete remission of CML in some cases. Chlorambucil has been used for treatment of B cell chronic lymphocytic leukemia, non-Hodgkin's and Hodgkin's disease. Here we report that a DNA sequence-specific pyrrole-imidazole polyamide-chlorambucil conjugate, 1R-Chl, causes growth arrest of cells harboring both unmutated BCR-ABL and three imatinib resistant strains. 1R-Chl also displays selective toxicities against activated lymphocytes and a high dose tolerance in a murine model

A qualitative study of cardiovascular disease risk communication in NHS Health Check using different risk calculators: protocol for the RIsk COmmunication in NHS Health Check (RICO) study. BMC family practice, 20(1), 11.

Background NHS Health Check is a national cardiovascular disease (CVD) risk assessment programme for 40–74 year olds in England, in which practitioners should assess and communicate CVD risk, supported by appropriate risk-management advice and goal-setting. This requires effective communication, to equip patients with knowledge and intention to act. Currently, the QRISK®2 10-year CVD risk score is most common way in which CVD risk is estimated. Newer tools, such as JBS3, allow manipulation of risk factors and can demonstrate the impact of positive actions. However, the use, and relative value, of these tools within CVD risk communication is unknown. We will explore practitioner and patient CVD risk perceptions when using QRISK®2 or JBS3, the associated advice or treatment offered by the practitioner, and patients’ responses. Methods RIsk COmmunication in NHS Health Check (RICO) is a qualitative study with quantitative process evaluation. Twelve general practices in the West Midlands of England will be randomised to one of two groups: usual practice, in which practitioners use QRISK®2 to assess and communicate CVD risk; intervention, in which practitioners use JBS3. Twenty Health Checks per practice will be video-recorded (n = 240, 120 per group), with patients stratified by age, gender and ethnicity. Post-Health Check, video-stimulated recall (VSR) interviews will be conducted with 48 patients (n = 24 per group) and all practitioners (n = 12–18), using video excerpts to enhance participant recall/reflection. Patient medical record reviews will detect health-protective actions in the first 12-weeks following a Health Check (e.g., lifestyle referrals, statin prescription). Risk communication, patient response and intentions for health-protective behaviours in each group will be explored through thematic analysis of video-recorded Health Checks (using Protection Motivation Theory as a framework) and VSR interviews. Process evaluation will include between-group comparisons of quantitatively coded Health Check content and post-Health Check patient outcomes. Finally, 10 patients with the most positive intentions or behaviours will be selected for case study analysis (using all data sources). Discussion This study will produce novel insights about the utility of QRISK®2 and JBS3 to promote patient and practitioner understanding and perception of CVD risk and associated implications for patient intentions with respect to health-protective behaviours (and underlying mechanisms). Recommendations for practice will be developed

An Integrated Microfluidic Device for Monitoring Changes in Nitric Oxide Production in Single T-Lymphocyte (Jurkat) Cells

A considerable amount of attention has been focused on the analysis of single cells in an effort to better understand cell heterogeneity in cancer and neurodegenerative diseases. Although microfluidic devices have several advantages for single cell analysis, few papers have actually demonstrated the ability of these devices to monitor chemical changes in perturbed biological systems. In this paper, a new microfluidic channel manifold is described that integrates cell transport, lysis, injection, electrophoretic separation, and fluorescence detection into a single device, making it possible to analyze individual cells at a rate of 10 cells/min in an automated fashion. The system was employed to measure nitric oxide (NO) production in single T-lymphocytes (Jurkat cells) using a fluorescent marker, 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA). The cells were also labeled with 6-carboxyfluorescein diacetate (6-CFDA) as an internal standard. The NO production by control cells was compared to that of cells stimulated using lipopolysaccharide (LPS), which is known to cause the expression of inducible nitric oxide synthase (iNOS) in immune-type cells. Statistical analysis of the resulting electropherograms from a population of cells indicated a twofold increase in NO production in the induced cells. These results compare nicely to a recently published bulk cell analysis of NO

Identification of Amazonian Trees with DNA Barcodes

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