Contribution of cod liver oil-related nutrients (vitamins A, D, E and eicosapentaenoic acid and docosahexaenoic acid) to daily nutrient intake and their associations with plasma concentrations in the EPIC-Norfolk cohort

Total nutrient intake (TNI) is intake from food and supplements. This provides an assessment of nutrient adequacy and the prevalence of excessive intake, as well as the response with respect to biomarkers. Cod liver oil (CLO) is the most frequently consumed supplement in the UK, containing nutrients that might have varying influences on health. We calculated TNI for vitamins A, D and E, as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and assessed associations with the respective blood concentrations

Are diabetes self-management programmes for the general diabetes population effective for people with severe mental illness?: a systematic review.

Background: Diabetes self-management education programmes are effective in improving health outcomes in the general population with diabetes. However, it is not known if these programmes include people who also have a severe mental illness (SMI) and, if so, what their outcomes are. The aim of this review was to examine if evaluations of diabetes self-management education programmes included people with SMI, and if so, whether the interventions were beneficial for this population. Methods: The inclusion criteria for this systematic review, defined by PICOS criteria, were: Population - Adults with type 2 diabetes; Intervention - self-management education programme; Comparator – another active intervention or usual care; Outcomes of interest – inclusion of people with SMI and the clinical, behavioural and psychosocial outcomes in this population; Study design - randomised controlled trials. The following bibliographic databases were searched from January 2004 to April 2018: Cochrane Library, Medline, Embase, PsychINFO, Allied and Complimentary Medicine Database, Health Technology Assessment, NHS Economic Evaluations Database and CINAHL. Data were extracted on study characteristics, inclusion and exclusion criteria, participant and intervention characteristics, number of participants with SMI, and outcomes for people with SMI, if reported. Authors were contacted by email for missing data. Results: A total of 410 trials were included. At least 42% of trials did not recruit any participants with SMI. Only nine confirmed inclusion of participants with SMI, of which six provided data on the number recruited. These six trials recruited a total of 1009 participants, of whom 31 (3.1%) had SMI. It was not possible to assess intervention effectiveness for people with SMI as none of the trials reported outcomes for these participants. Conclusions: This systematic review confirms that people with SMI are often excluded from trials of diabetes self-management education, resulting in a lack of an evidence base on which to base treatment paths for this vulnerable population. It cannot be assumed that programmes developed for the general diabetes population meet the needs of people with SMI. Future research needs to examine if and how these programmes could be adapted for people with SMI or if new programmes are required

Mothers' reports of the difficulties that their children experience in taking methotrexate for Juvenile Idiopathic Arthritis and how these impact on quality of life

BACKGROUND: Children who take methotrexate for juvenile idiopathic arthritis may experience side effects, including nausea and vomiting, leading to anticipatory nausea in some children, and fear of injections or blood tests. The aim of this study was to examine the prevalence and extent of these difficulties and their impact on quality of life. METHODS: Participants were mothers of children with JIA who were currently taking methotrexate (MTX). Mothers completed a questionnaire about MTX that was developed for the study, two questions from the treatment subscale of the Pediatric Quality of Life Inventory (PedsQL) Rheumatology scale to assess needle-related problems and the Child Health Questionnaire 50-item parent version (CHQ-PF50) to assess health-related quality of life (HRQoL). RESULTS: 171 mothers participated in the study. More than half of children were reported to have experienced one or more of: nausea or vomiting after taking MTX, anticipatory nausea, fear of blood tests or fear of injections. There was no significant difference in reported rates of sickness or needle-related problems between MTX responders (ACR70 or above), partial responders (ACR30 or ACR50) and non-responders. In multivariate analyses, variables that were significant independent predictors of one or more MTX-related difficulties included younger age, taking MTX subcutaneously and having a larger number of currently active joints. Feeling sick after taking MTX was a significant independent predictor of poorer scores on the physical summary scale of the CHQ-PF50. Anxiety about injections and feeling sick after taking MTX were significant independent predictors of poorer scores on the psychosocial summary scale. CONCLUSIONS: Difficulties in taking MTX are experienced by a significant proportion of children with JIA and these have an adverse impact on HRQoL. Approaches to help minimize these difficulties are required

De novo design of bioactive protein switches.

Allosteric regulation of protein function is widespread in biology, but is challenging for de novo protein design as it requires the explicit design of multiple states with comparable free energies. Here we explore the possibility of designing switchable protein systems de novo, through the modulation of competing inter- and intramolecular interactions. We design a static, five-helix 'cage' with a single interface that can interact either intramolecularly with a terminal 'latch' helix or intermolecularly with a peptide 'key'. Encoded on the latch are functional motifs for binding, degradation or nuclear export that function only when the key displaces the latch from the cage. We describe orthogonal cage-key systems that function in vitro, in yeast and in mammalian cells with up to 40-fold activation of function by key. The ability to design switchable protein functions that are controlled by induced conformational change is a milestone for de novo protein design, and opens up new avenues for synthetic biology and cell engineering

Changes in waist circumference and risk of all-cause and CVD mortality: results from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort study

Abstract: Background: Measures of abdominal adiposity are strongly associated with all-cause mortality and cardiovascular disease (CVD). However, data are limited and conflicting regarding the consequences of changes in body fat distribution. The main aims of this paper are to investigate the association between changes in waist circumference (WC) and all-cause and CVD mortality and to examine these changes in relation to concurrent changes in weight. Methods: The European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study recruited 25,639 participants between 1993 and 1997, aged 39–79, a number of whom also attended a second examination (1998–2000), and were followed up to 2016 for mortality. Participants were eligible for inclusion if they had WC, weight and height measurements at both time-points; those with a self-reported history of CVD or cancer, body mass index 5 cm were 1.51 (1.29–1.75) and 1.25 (1.06–1.46) respectively. For CVD mortality in men and women with a WCG > 5 cm, the HRs were 1.84 (1.39–2.43) and 1.15 (0.85–1.55) respectively. In analyses of concurrent changes in WC and weight, the greatest risk (HRs) (95% CIs) in men occurred with weight loss and WCG: 1.80 (1.13–2.86) for all-cause and 2.22 (1.03–4.82) for CVD mortality. In women, the greatest risk for both all-cause (HR 1.50 (1.16–1.95)) and CVD mortality (HR 1.81 (1.15–2.85)) was observed in those with weight loss and maintenance of WC (WCM). Conclusions: Objectively measured WCG > 5 cm, was associated with subsequent higher total mortality risk and higher CVD mortality risk in men. Interventions focusing on preventing increase in central adiposity rather than lowering weight per se in later life may potentially have greater health benefits

Psychometric Analysis of the Adult Sickle Cell Quality of Life Measurement Information System (ACSQ-Me) in a UK Population

Background: The Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) has been shown to be a reliable and valid questionnaire measuring health-related quality of life (HRQoL) in the US sickle cell disease (SCD) population. The study objective was to test the validity and reliability of the ASCQ-Me for use in the UK. Methods: The US ASCQ-Me, Hospital Anxiety and Depression Scale (HADS), self-reported symptoms, and Medical Outcome Survey Short Form 36 (SF-36) were administered to 173 patients with SCD. Clinical severity was assessed by the number of painful episodes indicated by hospital admissions. Results: The results showed that the item banks of the UK ASCQ-Me had good internal consistency. Anxiety and depression were strongly correlated with the emotional, and social item banks of the UK ASCQ-Me, with moderate correlations between the UK ASCQ-Me item banks and SF-36 components suggesting convergent validity. A confirmatory factor analysis confirmed the conceptual framework of the scale as being the same as the US ASCQ-Me, indicating construct validity. Known groups validity was found, with the ASCQ-Me being able to differentiate by SCD severity groups. Conclusion: The analysis of the sample shows evidence of both validity and reliability of the ACCQ-Me for use in the UK SCD population

Postdeployment military mental health training: Cross-national evaluations

Deployments increase risk for adjustment problems in service members. To mitigate this increased risk, mental health training programs have been developed and implemented in several nations. As part of a coordinated effort, three nations adapted a U.S. mental health training program that had been validated by a series of group randomized trials demonstrating improvement in postdeployment adjustment. Implementation of evidence-based programs in a new context is challenging: How much of the original program needs to remain intact in order to retain its utility? User satisfaction rates can provide essential data to assess how well a program is accepted. This article summarizes service member ratings of postdeployment mental health training and compares ratings from service members across four nations. The participating nations (Canada, New Zealand, United Kingdom, and the United States) administered mental health training to active duty military personnel in their respective nations. Following the training, military personnel completed an evaluation of the training. Overall, across the four nations, more than 70% of military personnel agreed or strongly agreed that they were satisfied with the mental health training. Although some differences in evaluations were observed across nations, components of training that were most important to overall satisfaction with the training were strikingly similar across nations. Fundamentally, it appears feasible that despite cultural and organizational differences, a mental health training program developed in one nation can be successfully adapted for use in other nations

The Psychogeriatric Assessment Scales: a multidimensional alternative to categorical diagnoses of dementia and depression in the elderly

The Psychogeriatric Assessment Scales (PAS) provide an assessment of the clinical changes seen in dementia and depression. Principal components analysis and latent trait analysis were used to develop a set of scales to summarize these clinical changes. There are three scales derived from an interview with the subject (Cognitive Impairment, Depression, Stroke) and three from an interview with an informant (Cognitive Decline, Behaviour Change, Stroke). Results are reported on the reliability and validity of these scales using data from clinical samples in Sydney and Geneva and a population sample from Canberra. The scales were found to have excellent validity when judged against clinical diagnoses of dementia and depression and could distinguish Alzheimer's from vascular dementia. Cut-off points were developed to indicate correspondence between scale scores and clinical diagnoses. Percentile rank norms were developed from the Canberra population sample. The PAS is easy to administer and score and can be used by lay interviewers after training. It is intended for application both in research and in services for the elderl

Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site

<p>Abstract</p> <p>Background</p> <p>Ricin is a potent toxin and known bioterrorism threat with no available antidote. The ricin A-chain (RTA) acts enzymatically to cleave a specific adenine base from ribosomal RNA, thereby blocking translation. To understand better the relationship between ligand binding and RTA active site conformational change, we used a fragment-based approach to find a minimal set of bonding interactions able to induce rearrangements in critical side-chain positions.</p> <p>Results</p> <p>We found that the smallest ligand stabilizing an open conformer of the RTA active site pocket was an amide group, bound weakly by only a few hydrogen bonds to the protein. Complexes with small amide-containing molecules also revealed a switch in geometry from a parallel towards a splayed arrangement of an arginine-tryptophan cation-pi interaction that was associated with an increase and red-shift in tryptophan fluorescence upon ligand binding. Using the observed fluorescence signal, we determined the thermodynamic changes of adenine binding to the RTA active site, as well as the site-specific binding of urea. Urea binding had a favorable enthalpy change and unfavorable entropy change, with a ΔH of -13 ± 2 kJ/mol and a ΔS of -0.04 ± 0.01 kJ/(K*mol). The side-chain position of residue Tyr80 in a complex with adenine was found not to involve as large an overlap of rings with the purine as previously considered, suggesting a smaller role for aromatic stacking at the RTA active site.</p> <p>Conclusion</p> <p>We found that amide ligands can bind weakly but specifically to the ricin active site, producing significant shifts in positions of the critical active site residues Arg180 and Tyr80. These results indicate that fragment-based drug discovery methods are capable of identifying minimal bonding determinants of active-site side-chain rearrangements and the mechanistic origins of spectroscopic shifts. Our results suggest that tryptophan fluorescence provides a sensitive probe for the geometric relationship of arginine-tryptophan pairs, which often have significant roles in protein function. Using the unusual characteristics of the RTA system, we measured the still controversial thermodynamic changes of site-specific urea binding to a protein, results that are relevant to understanding the physical mechanisms of protein denaturation.</p