A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model.

Prostate cancer (PCa) has been linked to fat intake, but the effects of both different dietary fat levels and types remain inconsistent and incompletely characterised. The effects on PCa in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model of an elevated fat (20 % of energy as fat) diet containing 155 g of whole walnuts were compared to those of an elevated fat (20 % of energy as soyabean oil) diet with matched macronutrients, tocopherols as well as a low-fat (8 % of energy as soyabean oil) diet. Mice, starting at 8 weeks of age, consumed one of the three different diets ad libitum; and prostates, livers and blood were obtained after 9, 18 or 24 weeks of feeding. No differences were observed in whole animal growth rates in either high-fat (HF) diet group, but prostate tumour weight and growth rate were reduced in the walnut diet group. Walnut diet group prostate weight, plasma insulin-like growth factor 1, resistin and LDL were lower at 18 weeks, while no statistically significant prostate weight differences by diet were seen at 9 or 24 weeks. Multiple metabolites in the livers differed by diet at 9 and 18 weeks. The walnut diet's beneficial effects probably represent the effects of whole walnuts' multiple constituents and not via a specific fatty acid or tocopherols. Moreover, as the two HF diets had dissimilar effects on prostate tumour growth rate and size, and yet had the same total fat and tocopherol composition and content, this suggests that these are not strongly linked to PCa growth

A Core outcome set for childhood epilepsy treated with ketogenic diet therapy (CORE-KDT study): international parent and health professional consensus.

OBJECTIVE: Ketogenic diet therapy (KDT) can result in benefits (seizure and non-seizure related) for children with drug resistant epilepsy. However, clinical trials report a wide range of outcomes making synthesis of evidence difficult, and do not adequately reflect parent views on important outcomes for their child. To address this, we established the first international parent, health professional and researcher consensus to develop a core outcome set, guided by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative (COMET registration #1116). METHODS: Ethical approval was granted (London-Surrey REC19/LO/1680). A scoping review and interviews with parents identified a comprehensive list of potentially important outcomes, followed by a two-round online Delphi survey of parents and health professionals to prioritise outcomes of importance for inclusion in a core outcome set. This informed a stakeholder consensus meeting and consultation process to finalise the core outcome set. RESULTS: In total, 97 outcomes were identified; 90 from the scoping review and seven from parent interviews. These were rationalised to 77 by the study advisory group, then rated in the first Delphi round by 49 parents and 96 health professionals who suggested 12 new outcomes for rating in round two. 66% of participants (30 parents and 66 professionals) completed round two, where 22 outcomes met criteria for inclusion. In the consensus meeting (9 parents and 13 professionals), 27 undecided outcomes were discussed and scored; one further outcome reached consensus for inclusion. After consultation and ratification, 14 outcomes across five domains were included in the core outcome set. SIGNIFICANCE: A core outcome set for childhood epilepsy treated with KDT has been developed, incorporating the views of international parents and professionals. Implementation in research and clinical settings will standardise outcome selection and reporting, facilitate data synthesis and ultimately enhance the relevance of outcomes to parents, researchers and health professionals

Interaction of nitrogen dioxide with human plasma Antioxidant depletion and oxidative damage

AbstractNitrogen dioxide (NO*2) is often present in inhaled air and may be generated in vivo from nitric oxide. Exposure of human blood plasma to NO*2 caused rapid losses of ascorbic acid, uric acid and protein thiol groups, as well as lipid peroxidation and depletions of α-tocopherol, bilirubin and ubiquinol-10. No increase in protein carbonyls was detected. Supplementation of plasma with ascorbate decreased the rates of lipid peroxidation. α-tocopherol depletion and loss of uric acid. Uric acid supplementation decreased rates of lipid peroxidation but not the loss of α-tecopherol. We conclude that ascorbic acid, protein -SH groups, uric acid and α-tocopherol may be important agents protecting against NO*2 in vivo. If these antioxidants are depleted, peroxidation of lipids occurs and might contribute to the toxicity of NO*2

The CORE-KDT study: a mixed methods protocol to establish core outcomes for refractory childhood epilepsy treated with ketogenic diet therapy

Background: A core outcome set defines the minimum outcomes that should be included in clinical trials, audit or practice. The aim being to increase the quality and relevance of research by ensuring consistency in the measurement and reporting of outcomes. Core outcome sets have been developed for a variety of disease states and treatments. However, there is no established set of core outcomes for refractory childhood epilepsy treated with ketogenic diet therapy. This should be developed using a patient-centred approach to ensure the outcomes measured are relevant to patients and clinical practice. Methods: This is a mixed methods study of four phases to develop a core outcome set for refractory childhood epilepsy treated with ketogenic diet therapy. In phase 1, a systematic scoping review of the literature will establish which outcomes are measured in trials of refractory epilepsy treated with ketogenic diet therapy. In phase 2, qualitative interviews with parents and carers will aim to identify the outcomes of importance to these stakeholders. Phase 3 will see a comprehensive list of outcomes collated from the first two phases, grouped into domains according to an outcome taxonomy. Phase 4 will invite parents, health care professionals and researchers to participate in a two-round Delphi study to rate the importance of the presented outcomes. Following which, the core outcome set will be ratified at a face to face consensus meeting. Discussion: This study will guide outcome measurement in future studies of childhood epilepsy treated with ketogenic diet therapy and clinical practice through audit and service evaluation

Drug-resistant epilepsy and ketogenic diet therapy – a qualitative study of families’ experiences.

Abstract Background A diagnosis of drug-resistant epilepsy is life changing for a family. Ketogenic diet therapy (KDT) can offer hope when other treatments have failed. However, it often requires a significant change in daily routine and dietary habits. This qualitative descriptive study aimed to explore families’ experiences of epilepsy and KDT. Methods Parents of a child aged ≤18 years with epilepsy, currently or recently treated with KDT, were recruited from the UK and internationally via UK Ketogenic Diet (KD) centres, charities, and social media. Semi-structured interviews were audio recorded, transcribed verbatim, anonymised, coded using Nvivo (V12), and inductive thematic analysis undertaken. Results Twenty-one parents participated. Four themes and 12 subthemes emerged: 1. ‘Epilepsy is all consuming’ explored the impact of epilepsy on the family. 2. ‘KD provides a window to new opportunities’ explores the motivators for KDT and positive outcomes. 3. ‘The reality of KD’ explores day to day life and how families adapt to KD. 4. ‘Looking to the future’ explores the factors that may make KD easier for families. All were glad their child trialled KD, even when less successful. The importance of a support network including family, friends, charity organisations and the KD team was evident across all themes. Conclusions We conclude with five recommendations to help support families in their management of KDT; Improved access to KDT and transition to adult services, access to quality education and support, enhanced variety of KD foods, regular social education and finally consideration of peer mentoring

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

<b>Background</b> Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.<p></p> <b>Methods and findings</b> The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.<p></p> <b>Conclusions</b> Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems

Peer relations and emotion regulation of children with emotional and behavioural difficulties with and without a developmental disorder

Children with emotional and behavioural difficulties (EBD) and those who also have developmental disorders, such as attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), can experience the same adverse consequences in their peer interactions and relationships. This present study compared the emotion regulation and peer relationships of children aged 8-12 years (M = 9.86 years, SD = 1.49) with EBD (N = 33) and children with EBD plus a diagnosed developmental disorder (N = 28). Multivariate analysis of variance (MANOVA) with Bonferroni adjusted alpha levels revealed no significant main effect for emotion regulation according to EBD status. There was, however, a multivariate main effect for sex, with females presenting with higher levels of negative emotional intensity (e. g., frustration, anger, aggression) than males. A second MANOVA revealed no significant main effect for peer relationships according to EBD status and sex. Significant correlations revealed that the EBD-only group experienced greater adverse peer interactions than the EBD-plus-developmental disorder group. These findings are important for educators and researchers involved in the development and evaluation of prevention and intervention programms for children with EBD