A systematic review and meta-regression analysis of the vitamin D intake-serum 25-hydroxyvitamin D relationship to inform European recommendations

The present study used a systematic review approach to identify relevant randomised control trials (RCT) with vitamin D and then apply meta-regression to explore the most appropriate model of the vitamin D intake–serum 25-hydroxyvitamin D (25(OH)D) relationship to underpin setting reference intake values. Methods included an updated structured search on Ovid MEDLINE; rigorous inclusion/exclusion criteria; data extraction; and meta-regression (using different model constructs). In particular, priority was given to data from winter-based RCT performed at latitudes >49•58°N (n 12). A combined weighted linear model meta-regression analyses of natural log (Ln) total vitamin D intake (i.e. diet and supplemental vitamin D) versus achieved serum 25(OH)D in winter (that used by the North American Dietary Reference Intake Committee) produced a curvilinear relationship (mean (95% lower CI) serum 25(OH)D (nmol/l) = 9•2 (8•5) Ln (total vitamin D)). Use of non-transformed total vitamin D intake data (maximum 1400 IU/d; 35µg/d) provided for a more linear relationship (mean serum 25(OH)D (nmol/l) = 0•044 × (total vitamin D) + 33•035). Although inputting an intake of 600 IU/d (i.e. the RDA) into the 95% lower CI curvilinear and linear models predicted a serum 25(OH)D of 54•4 and 55•2 nmol/l, respectively, the total vitamin D intake that would achieve 50 (and 40) nmol/l serum 25(OH)D was 359 (111) and 480 (260) IU/d, respectively. Inclusion of 95% range in the model to account for inter-individual variability increased the predicted intake of vitamin D needed to maintain serum 25(OH)D ≥50 nmol/l to 930 IU/d. The model used to describe the vitamin D intake–status relationship needs to be considered carefully when setting new reference intake values in Europe

Loop colostomies are safe in anorectal malformations

Aim of the study: Divided colostomy (DC) has been recommended in anorectal malformations (ARMs) with previously reported advantages of decreasing overflow into the distal limb and urinary tract infections (UTIs). Skin bridge loop colostomy (LC) is a technically easier alternative without an increase in these complications. We report our institutional experience of LC in ARM. Methods: Retrospective study (Institution-approved Clinical Audit) reviewing the clinical records of all patients with ARM undergoing stoma formation in a single UK tertiary pediatric surgical center (2000–2015). Data collected included type of ARM, associated anomalies, type and level of colostomy, time to stoma closure, complications and UTIs. Results: One hundred and eighty-two (95 female) patients underwent colostomy formation for ARM. The vast majority (171/ 94%) underwent LC; 9 (5%) had a divided colostomy (DC) and 2 (1%) had no available data. The spectrum of defects in girls included rectovestibular (62/65%), rectovaginal (4/4%) and cloaca (29/31%). In boys, 71 (82%) had a fistula to the urinary tract and 16 (18%) presented with a perineal fistula. Urological abnormalities coexisted in 87 (47.8%) patients. Thirty five (21%) patients developed UTIs. Among the 19 girls who developed UTI, 8 had rectovestibular fistula and 11 had cloaca. Of the 16 boys who developed UTI, 14 had a fistula to the urinary tract and 11 had an independent urological abnormality. The mean time from stoma formation to stoma closure was 10 (3–52) months. Complications were reported in 22 (12%) LCs. Fifteen patients (9%) developed a stoma prolapse following LC with 10 (6%) requiring surgical revision. Conclusions: This is the largest reported series of outcomes following LC for ARM. LC is easier to perform and to close, requiring minimal surgical access, with comparable complications and outcomes to those published for DC. Type of study: Retrospective comparative study. Level of evidence: III

The transformative potential of international service-learning at a university with a Christian foundation in the UK

This article draws upon the findings of a study at Liverpool Hope University (LHU) into the transformative nature of International Service-Learning (ISL) experiences for student participants. This research is concerned with the implications of these findings for professional practice, in particular how ISL is constructed in Higher Education policy and practice. Recognising the problematic nature of this endeavor, this article responds to a call for discussion around pedagogical approaches underpinning counter-cultural and critical service programmes aligned with the radical principles of the Catholic social teaching. This study is grounded in a holistic conceptualisation of transformative learning that demands looking beyond an epistemological process that involves shifts in worldview and habits of mind to an ontological process that accounts for changes to our being in the world. It investigated how LHU students describe their ongoing experience of ISL and explored the conditions for learning and the associated transformative processes and outcomes in this context. Data analysis involved phenomenological description, constant comparative thematic analysis followed by a critical, hermeneutical analysis. This article will explicate the themes of moral and spiritual learning that emerged as part of a broader framework. In particular, it was found that the development of authentic relationships between travelling companions, accompanying tutors and partners overseas is central to learning that is reciprocated and provides a model of the transformative process in this context. This article concludes that this presents a pedagogical approach grounded in social justice that enables ISL to reach its transformative potential

Vitamin D status of Irish adults: findings from the National Adult Nutrition Survey

Previous national nutrition surveys in Irish adults did not include blood samples; thus, representative serum 25-hydroxyvitamin D (25(OH)D) data are lacking. In the present study, we characterised serum 25(OH)D concentrations in Irish adults from the recent National Adult Nutrition Survey, and determined the impact of vitamin D supplement use and season on serum 25(OH)D concentrations. Of the total representative sample (n 1500, aged 18+ years), blood samples were available for 1132 adults. Serum 25(OH)D was measured via immunoassay. Vitamin D-containing supplement use was assessed by questionnaire and food diary. Concentrations of serum 25(OH)D were compared by season and in supplement users and non-users. Year-round prevalence rates for serum 25(OH)D concentration 125 nmol/l. These first nationally representative serum 25(OH)D data for Irish adults show that while only 6·7 % had serum 25(OH)D < 30 nmol/l (vitamin D deficiency) throughout the year, 40·1 % had levels considered by the Institute of Medicine as being inadequate for bone health. These prevalence estimates were much higher during winter time. While vitamin D supplement use has benefits in terms of vitamin D status, at present rates of usage (17·5 % of Irish adults), it will have only very limited impact at a population level. Food-based strategies, including fortified foods, need to be explored

General practitioners’ perspectives on campaigns to promote rapid help-seeking behaviour at the onset of rheumatoid arthritis

Objective. To explore general practitioners’ (GPs’ ) perspectives on public health campaigns to encourage people with the early symptoms of rheumatoid arthritis (RA) to seek medical help rapidly. Design. Nineteen GPs participated in four semistructured focus groups. Focus groups were audio-recorded, transcribed verbatim, and analysed using thematic analysis. Results. GPs recognised the need for the early treatment of RA and identified that facilitating appropriate access to care was important. However, not all held the view that a delay in help seeking was a clinically significant issue. Furthermore, many were concerned that the early symptoms of RA were often non-specific, and that current knowledge about the nature of symptoms at disease onset was inadequate to inform the content of a help-seeking campaign. They argued that a campaign might not be able to specifically target those who need to present urgently. Poorly designed campaigns were suggested to have a negative impact on GPs’ workloads, and would “clog up” the referral pathway for genuine cases of RA. Conclusions. GPs were supportive of strategies to improve access to Rheumatological care and increase public awareness of RA symptoms. However, they have identified important issues that need to be considered in developing a public health campaign that forms part of an overall strategy to reduce time to treatment for patients with new onset RA. This study highlights the value of gaining GPs’ perspectives before launching health promotion campaigns

An investigation into CLIL-related sections of EFL coursebooks : issues of CLIL inclusion in the publishing market

The current ELT global coursebook market has embraced CLIL as a weak form of bilingual education and an innovative component to include in General English coursebooks for EFL contexts. In this paper I investigate how CLIL is included in ELT coursebooks aimed at teenaged learners, available to teachers in Argentina. My study is based on the content analysis of four series which include a section advertised as CLIL-oriented. Results suggest that such sections are characterised by (1) little correlation between featured subject specific content and school curricula in L1, (2) oversimplification of contents, and (3) dominance of reading skills development and lower-order thinking tasks. Through this study, I argue that CLIL components become superficial supplements rather than a meaningful attempt to promote weak forms of bilingual education

Interpretation of DAS28 and its components in the assessment of inflammatory and non-inflammatory aspects of rheumatoid arthritis

Background: DAS28 is interpreted as the inflammatory disease activity of RA. Non-inflammatory pain mechanisms can confound assessment. We aimed to examine the use of DAS28 components or DAS28-derived measures that have been published as indices of non-inflammatory pain mechanisms, to inform interpretation of disease activity. Methods: Data were used from multiple observational epidemiology studies of people with RA. Statistical characteristics of DAS28 components and derived indices were assessed using baseline and follow up data from British Society for Rheumatology Biologics Registry participants [1] commencing anti-TNF therapy (n = 10813), or [2] changing between non-biologic DMARDs (n=2992), [3] Early Rheumatoid Arthritis Network participants (n=813), and [4] participants in a cross-sectional study exploring fibromyalgia and pain thresholds (n=45). Repeatability was tested in 34 patients with active RA. Derived indices were the proportion of DAS28 attributable to patient-reported components (DAS28-P), tender-swollen difference and tender:swollen ratio. Pressure pain detection threshold (PPT) was used as an index of pain sensitisation. Results: DAS28, tender joint count, visual analogue scale, DAS28-P, tender-swollen difference and tender:swollen ratio were more strongly associated with pain, PPT and fibromyalgia status than were swollen joint count or erythrocyte sedimentation rate. DAS28-P, tender-swollen difference and tender:swollen ratio better predicted pain over 1 year than did DAS28 or its individual components. Conclusions: DAS28 is strongly associated both with inflammation and with patient-reported outcomes. DAS28-derived indices such as tender-swollen difference are associated with non-inflammatory pain mechanisms, can predict future pain and should inform how DAS28 is interpreted as an index of inflammatory disease activity in RA

Proceedings of the Rank Forum on Vitamin D

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations . 75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations

RACK(1) to the future - a historical perspective

Abstract This perspective summarises the first and long overdue RACK1 meeting held at the University of Limerick, Ireland, May 2013, in which RACK1&apos;s role in the immune system, the heart and the brain were discussed and its contribution to disease states such as cancer, cardiac hypertrophy and addiction were described. RACK1 is a scaffolding protein and a member of the WD repeat family of proteins. These proteins have a unique architectural assembly that facilitates protein anchoring and the stabilisation of protein activity. A large body of evidence is accumulating which is helping to define the versatile role of RACK1 in assembling and dismantling complex signaling pathways from the cell membrane to the nucleus in health and disease. In this commentary, we first provide a historical perspective on RACK1. We also address many of the pertinent and topical questions about this protein such as its role in transcription, epigenetics and translation, its cytoskeletal contribution and the merits of targeting RACK1 in disease. Historical perspective It has been 20 years since RACK1 was cloned as the first identified binding protein for Protein Kinase C (PKC), and the road the Mochly-Rosen group took toward its discovery was not trivial. The role of scaffolding proteins in the temporal and spatial regulation of signal transduction seems obvious today, however, this was not the case in the late 1980s when Prof. Daria Mochly-Rosen developed the hypothesis that anchoring/scaffolding proteins control the specificity of substrate phosphorylation and function of Protein Kinase C (PKC) isozymes. An alpha phage display library/overlay assay strategy was used to identify binding proteins that interact with active PKC isoforms. To this day Dr. Ron remembers when one gene product was identified and was termed RACK1 for Receptor for Activated C Kinase RACK1 as a scaffolding protein The conserved seven blade propeller structure of RACK1 facilitates the folding order into constituent propeller blades. These propeller blades are intrinsic to RACK1&apos;s protein binding capacity and allow RACK1 to function as a signaling hub RACK1: a scaffolding protein with a central role in transcription, epigenetics &amp; translation RACK1 has a strong effect on transcription and translation by acting at critical points; principally the ribosomal small subunit and via nuclear translocation and regulation of chromatin and transcriptional complexes RACK1 and cytoskeletal proteins: a new frontier The cellular cytoskeleton, whose major components comprise of actin, microtubules and intermediate filaments, maintains cellular integrity and regulates multiple cellular functions including migration RACK1 as a potential therapeutic target As the number of binding partners and validated cellular functions for RACK1 has increased, so has its link with an array of disease states [38] are amongst the first describing beta-propeller/small molecule complexes. Interestingly, the report by Senisterra et al. Concluding comments There are, of course, numerous remaining questions that are of great interest. For example, how can one protein play such an important role in many and diverse biological functions? Is it possible that a number of RACK1 binding partners share common binding sites on RACK1? Is RACK1 function and/or expression levels regulated by posttranslational modifications such as phosphorylation, sumoylation and ubiquitination? Does RACK1 contribute to a large number of disease states and can RACK1 be used as a target for drug development? These are exciting times for RACK1 biologists. As more and more research areas converge on RACK1, we can expect answers to these questions to unfold. RACK1 biology would benefit greatly from detailed mechanistic mathematical modelling and quantitative experimentation to help us comprehend how RACK1 functions in systems biology, beyond its role as a scaffolding protein. We look forward to the next RACK1 conference, which we have no doubt will bring more exciting new data on the role of our favorite protein in cellular functions