Improvements in vascular health by a low-fat diet, but not a high-fat diet, are mediated by changes in adipocyte biology

<p>Abstract</p> <p>Background</p> <p>Low-fat (LF) and high-fat (HF) weight loss diets improve brachial artery flow-mediated dilation (FMD) in obese individuals, although results are conflicting. Moreover, the role that adipose tissue plays in mediating these diet-related effects are unknown.</p> <p>Objective</p> <p>This study examined how modulations in FMD by HF and LF diets relate to changes in adipocyte parameters.</p> <p>Design</p> <p>Obese subjects (n = 17) were randomized to a HF diet (60% kcal as fat) or a LF diet (25% kcal as fat) for 6 weeks. Both groups were restricted by 25% of energy needs.</p> <p>Results</p> <p>Body weight decreased (<it>P <</it>0.05) in both groups (HF: -6.6 ± 0.5 kg, LF: -4.7 ± 0.6 kg). Fat mass and waist circumference were reduced (<it>P <</it>0.05) in the LF group only (-4.4 ± 0.3 kg; -3.6 ± 0.8 cm, respectively). FMD improved (<it>P <</it>0.05) in the LF group (7.4 ± 0.8% to 9.8 ± 0.8; 32% increase) and was impaired in the HF group (8.5 ± 0.6% to 6.9 ± 0.7; 19% reduction). Increases in plasma adiponectin (<it>P <</it>0.05, 16 ± 5%), and decreases in resistin (<it>P <</it>0.05, -26 ± 11%), were shown by the LF diet only. Greater decreases in leptin were observed with LF (-48 ± 9%) versus HF (-28 ± 12%) (<it>P <</it>0.05, diet × time). Increased FMD by the LF diet was associated with increased adiponectin, and decreased fat mass, waist circumference, leptin, and resistin.</p> <p>Conclusion</p> <p>Beneficial modulations in vascular health by LF diets may be mediated by improvements in adipocyte parameters.</p

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

Effect of dietary restriction and subsequent re-alimentation on the transcriptional profile of bovine ruminal epithelium

peer-reviewedCompensatory growth (CG) is utilised worldwide in beef production systems as a management approach to reduce feed costs. However the underlying biology regulating the expression of CG remains to be fully elucidated. The objective of this study was to examine the effect of dietary restriction and subsequent re-alimentation induced CG on the global gene expression profile of ruminal epithelial papillae. Holstein Friesian bulls (n = 60) were assigned to one of two groups: restricted feed allowance (RES; n = 30) for 125 days (Period 1) followed by ad libitum access to feed for 55 days (Period 2) or (ii) ad libitum access to feed throughout (ADLIB; n = 30). At the end of each period, 15 animals from each treatment were slaughtered and rumen papillae harvested. mRNA was isolated from all papillae samples collected. cDNA libraries were then prepared and sequenced. Resultant reads were subsequently analysed bioinformatically and differentially expressed genes (DEGs) are defined as having a Benjamini-Hochberg P value of <0.05. During re-alimentation in Period 2, RES animals displayed CG, growing at 1.8 times the rate of their ADLIB contemporary animals in Period 2 (P < 0.001). At the end of Period 1, 64 DEGs were identified between RES and ADLIB, with only one DEG identified at the end of Period 2. When analysed within RES treatment (RES, Period 2 v Period 1), 411 DEGs were evident. Genes identified as differentially expressed in response to both dietary restriction and subsequent CG included those involved in processes such as cellular interactions and transport, protein folding and gene expression, as well as immune response. This study provides an insight into the molecular mechanisms underlying the expression of CG in rumen papillae of cattle; however the results suggest that the role of the ruminal epithelium in supporting overall animal CG may have declined by day 55 of re-alimentation.SMW received financial assistance from Science Foundation Ireland (SFI) contract no 09/ RFP/GEN2447

Patient experience feedback in UK hospitals : What types are available and what are their potential roles in quality improvement (QI)?

BACKGROUND & OBJECTIVES: The comparative uses of different types of patient experience (PE) feedback as data within quality improvement (QI) are poorly understood. This paper reviews what types are currently available and categorizes them by their characteristics in order to better understand their roles in QI. METHODS: A scoping review of types of feedback currently available to hospital staff in the UK was undertaken. This comprised academic database searches for "measures of PE outcomes" (2000-2016), and grey literature and websites for all types of "PE feedback" potentially available (2005-2016). Through an iterative consensus process, we developed a list of characteristics and used this to present categories of similar types. MAIN RESULTS: The scoping review returned 37 feedback types. A list of 12 characteristics was developed and applied, enabling identification of 4 categories that help understand potential use within QI-(1) Hospital-initiated (validated) quantitative surveys: for example the NHS Adult Inpatient Survey; (2) Patient-initiated qualitative feedback: for example complaints or twitter comments; (3) Hospital-initiated qualitative feedback: for example Experience Based Co-Design; (4) Other: for example Friends & Family Test. Of those routinely collected, few elicit "ready-to-use" data and those that do elicit data most suitable for measuring accountability, not for informing ward-based improvement. Guidance does exist for linking collection of feedback to QI for some feedback types in Category 3 but these types are not routinely used. CONCLUSION: If feedback is to be used more frequently within QI, more attention must be paid to obtaining and making available the most appropriate types

The NIRS Analysis Package: Noise Reduction and Statistical Inference

Near infrared spectroscopy (NIRS) is a non-invasive optical imaging technique that can be used to measure cortical hemodynamic responses to specific stimuli or tasks. While analyses of NIRS data are normally adapted from established fMRI techniques, there are nevertheless substantial differences between the two modalities. Here, we investigate the impact of NIRS-specific noise; e.g., systemic (physiological), motion-related artifacts, and serial autocorrelations, upon the validity of statistical inference within the framework of the general linear model. We present a comprehensive framework for noise reduction and statistical inference, which is custom-tailored to the noise characteristics of NIRS. These methods have been implemented in a public domain Matlab toolbox, the NIRS Analysis Package (NAP). Finally, we validate NAP using both simulated and actual data, showing marked improvement in the detection power and reliability of NIRS

A Cyclin-Dependent Kinase that Promotes Cytokinesis through Modulating Phosphorylation of the Carboxy Terminal Domain of the RNA Pol II Rpb1p Sub-Unit

In Schizosaccharomyces pombe, the nuclear-localized kinase, Lsk1p, promotes cytokinesis by positively regulating the Septation Initiation Network (SIN). Although a member of the cyclin-dependent kinase (CDK) family, neither a cyclin partner nor a physiological target has been identified. In this report we identify a cyclin, Lsc1p, that physically interacts and co-localizes with Lsk1p. Furthermore, lsk1Δ, lsc1Δ, as well as kinase-dead lsk1-K306R mutants, display highly similar cytokinesis defects. Lsk1p is related to CDKs that phosphorylate the carboxy-terminal domain (CTD) of the largest sub-unit of RNA polymerase II (Rpb1p). Interestingly, we find that Lsk1p and Lsc1p are required for phosphorylation of Ser-2 residues found in the heptad repeats of the CTD. To determine if Rpb1p could be a physiological target, we replaced the native rpb1 gene with a synthetic gene encoding a Rpb1p protein in which Ser-2 was substituted with the non-phosphorylatable amino-acid alanine in all heptads. Cells carrying this allele were similar to lsk1Δ mutants: They were viable, displayed genetic interactions with the SIN, and were unable to complete cytokinesis upon perturbation of the cell division machinery. We conclude that Ser-2 phosphorylation of the CTD heptads plays a novel physiological role in the regulation of cytokinesis

Real-Time, Real World Learning—Capitalising on Mobile Technology

This chapter explores the adoption of Web 2.0 technologies to promote active learning by students and to both mediate and enhance classroom instruction. Web 2.0 refers to open source, web-enabled applications (apps) that are driven by user-manipulated and user-generated content (Kassens-Noor, 2012). These apps are often rich in user participation, have dynamic content, and harness the collective intelligence of users (Chen, Hwang, & Wang, 2012). As such, these processes create “active, context based, personalised learning experiences” (Kaldoudi, Konstantinidis, & Bamidis, 2010, p. 130) that prioritise learning ahead of teaching. By putting the learner at the centre of the education process educators can provide environments that enhance employability prospects and spark a passion for learning that, hopefully, lasts a lifetime. As such, we critique an active learning approach that makes use of technology such as mobile applications (apps), Twitter, and augmented reality to enhance students’ real world learning. Dunlap and Lowenthal (2009) argue that social media can facilitate active learning as they recreate informal, free-flowing communications that allow students and academics to connect on a more emotional level. Furthermore, their use upskills students in the technical complexities of the digital world and also the specialised discourses that are associated with online participation, suitable for real world learning and working (Fig. 16.1). Three case studies explore the benefits of Web 2.0 processes. The first details the use of Twitter chats to connect students, academics, and industry professionals via online synchronous discussions that offer a number of benefits such as encouraging concise writing from students and maintaining on-going relationships between staff, students, and industry contacts. The second details a location-based mobile app that delivers content to students when they enter a defined geographical boundary linked to an area of a sports precinct. Finally, we explore the use of augmented reality apps to enhance teaching in Human Geography and Urban Studies

Land Law, Property Ideologies and the British-Irish relationship

English and Irish land law are deeply influenced by the historical context of the British-Irish relationship, yet property scholarship comparing the two jurisdictions is surprisingly rare. The current Brexit negotiations provide a timely reminder of the strategic importance of property and trade relations between the two countries; and of their related-but-different legal cultures. In this article we examine how the property cultures of England and Ireland were shaped by the politics and practices of land tenure, by competing economic and property ideologies, and by the influence of both on national identity and statehood in both jurisdictions. The article reveals the role of local contexts and events in shaping land reform, and demonstrates the fertile potential of the comparative frame to contextualise each jurisdiction’s doctrines and practices. As domestic land law systems are drawn together in the context of emerging EU jurisdiction over areas like mortgage credit, each jurisdiction’s underpinning ideological commitments have important implications for the ease – or not – of attempts to harmonize member state practices. We explain the alignments and divergences between domestic underpinnings of Irish and English law, and reflect on the implications of our findings for contemporary property problems in the context of evolving economic and political relationships between the UK and Ireland

Testing effectiveness of the revised Cape Town modified early warning and SBAR systems: a pilot pragmatic parallel group randomised controlled trial

Abstract Background Nurses’ recognition of clinical deterioration is crucial for patient survival. Evidence for the effectiveness of modified early warning scores (MEWS) is derived from large observation studies in developed countries. Methods We tested the effectiveness of the paper-based Cape Town (CT) MEWS vital signs observation chart and situation-background-assessment-recommendation (SBAR) communication guide. Outcomes were: proportion of appropriate responses to deterioration, differences in recording of clinical parameters and serious adverse events (SAEs) in intervention and control trial arms. Public teaching hospitals for adult patients in Cape Town were randomised to implementation of the CT MEWS/SBAR guide or usual care (observation chart without track-and-trigger information) for 31 days on general medical and surgical wards. Nurses in intervention wards received training, as they had no prior knowledge of early warning systems. Identification and reporting of patient deterioration in intervention and control wards were compared. In the intervention arm, 24 day-shift and 23 night-shift nurses received training. Clinical records were reviewed retrospectively at trial end. Only records of patients who had given signed consent were reviewed. Results We recruited two of six CT general hospitals. We consented 363 patients and analysed 292 (80.4%) patient records (n = 150, 51.4% intervention, n = 142, 48.6% control arm). Assistance was summoned for fewer patients with abnormal vital signs in the intervention arm (2/45, 4.4% versus (vs) 11/81, 13.6%, OR 0.29 (0.06–1.39)), particularly low systolic blood pressure. There was a significant difference in recording between trial arms for parameters listed on the MEWS chart but omitted from the standard observations chart: oxygen saturation, level of consciousness, pallor/cyanosis, pain, sweating, wound oozing, pedal pulses, glucose concentration, haemoglobin concentration, and “looks unwell”. SBAR was used twice. There was no statistically significant difference in SAEs (5/150, 3.3% vs 3/143, 2.1% P = 0.72, OR 1.61 (0.38–6.86)). Conclusions The revised CT MEWS observations chart improved recording of certain parameters, but did not improve nurses’ ability to identify early signs of clinical deterioration and to summon assistance. Recruitment of only two hospitals and exclusion of patients too ill to consent limits generalisation of results. Further work is needed on educational preparation for the CT MEWS/SBAR and its impact on nurses’ reporting behaviour. Trial registration Pan African Clinical Trials Registry, PACTR201406000838118. Registered on 2 June 2014, www.pactr.org