Docosahexaenoic acid-rich fish oil supplementation reduces kinase associated with insulin resistance in overweight and obese midlife adults

Targeting kinases linked to insulin resistance (IR) and inflammation may help in reducing the risk of type 2 diabetes (T2D) and Alzheimer’s disease (AD) in its early stages. This study aimed to determine whether DHA-rich fish oil supplementation reduces glycogen synthase kinase (GSK-3), which is linked to both IR and AD. Baseline and post-intervention plasma samples from 58 adults with abdominal obesity (Age: 51.7 ± 1.7 years, BMI: 31.9 ± 0.8 kg/m2) were analysed for outcome measures. Participants were allocated to 2 g DHA-rich fish oil capsules (860 mg DHA + 120 mg EPA) (n = 31) or placebo capsules (n = 27) per day for 12 weeks. Compared to placebo, DHA-rich fish oil significantly reduced GSK-3β by −2.3 ± 0.3 ng/mL. An inverse correlation (p \u3c 0.05) was found between baseline insulin and IR and their changes following intervention only in participants with C-reactive protein levels higher than 2.4 mg/L. DHA-rich fish oil reduces GSK-3 and IR, suggesting a potential role of long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) in ameliorating AD risk

Gender differences in the accuracy of dietary assessment methods to measure energy intake in adults:protocol for a systematic review and meta-analysis

Introduction Diet is an important modifiable risk factor for many chronic diseases. Measurement of dietary intake usually relies on self-report, subject to multiple biases. There is a need to understand gender differences in the self-report of dietary intake and the implications of any differences in targeting nutrition interventions. Literature in this area is limited and it is currently unknown whether self-report dietary assessment methods are equally accurate for women and men. The aim of this systematic review is to determine whether there are differences by gender in reporting energy intake compared with a reference measure of total energy expenditure. Methods and analysis A comprehensive search of published original research studies will be performed in MEDLINE, Scopus, Web of Science, EMBASE, CINAHL and Cochrane library. Original research studies will be included if they were conducted in free-living/unhospitalised adults and included a measure for both women and men of (a) self-reported energy intake and (b) total energy expenditure by doubly labelled water. One author will conduct the electronic database searches, two authors will independently screen studies, conduct a quality appraisal of the included studies using standardised tools and extract data. If further information is needed, then study authors will be contacted. If appropriate, a random-effects meta-analysis will be conducted, with inverse probability weighting, to quantify differences in the mean difference in agreement between reported energy intake and measured energy expenditure between women and men, by self-report assessment method. Subgroup analyses will be conducted by participant factors, geographical factors and study quality. Ethics and dissemination All data used will be from published primary research studies or deidentified results provided at the discretion of any study authors that we contact. We will submit our findings to a peer-reviewed scientific journal and will disseminate results through presentations at international scientific conferences. PROSPERO registration number CRD42019131715

Update of the best practice dietetic management of overweight and obese children and adolescents: a systematic review protocol

To update an existing systematic review series of randomized controlled trials (RCT) that include a dietary intervention for the management of overweight or obesity in children or adolescents.Specifically, the review questions are: In randomized controlled trials of interventions which include a dietary intervention for the management of overweight or obesity in children or adolescents

Investigating the Efficacy and Cost-Effectiveness of Technology-Delivered Personalized Feedback on Dietary Patterns in Young Australian Adults in the Advice, Ideas, and Motivation for My Eating (Aim4Me) Study: Protocol for a Randomized Controlled Trial

https://doi.org/10.2196/15999Background: Web-based health interventions may be easier to access and time efficient relative to face-to-face interventions and therefore may be the most appropriate mode to engage young adults. Objective: This study aims to investigate the impact of 3 different levels of personalized web-based dietary feedback and support on changes in diet quality. Methods: The Advice, Ideas, and Motivation for My Eating (Aim4Me) study is a 12-month assessor-blinded, parallel-group randomized controlled trial evaluating the impact of 3 levels of web-based feedback on diet quality, measured using the Australian Recommended Food Score (ARFS). Participants (N=2570) will primarily be recruited via web-based methods and randomized to 1 of 3 groups. Group 1 (control) will receive the Healthy Eating Quiz, a web-based dietary assessment tool that generates a brief feedback report on diet quality. Individuals randomized to this group can use the brief feedback report to make positive dietary changes. Group 2 will receive the Australian Eating Survey, a web-based dietary assessment tool that generates a comprehensive feedback report on diet quality as well as macro- and micronutrient intake. Group 2 will use the comprehensive feedback report to assist in making positive dietary changes. They will also have access to the Aim4Me website with resources on healthy eating and tools to set goals and self-monitor progress. Group 3 will receive the same intervention as Group 2 (ie, the comprehensive feedback report) in addition to a tailored 30-min video consultation with an accredited practicing dietitian who will use the comprehensive feedback report to assist individuals in making positive dietary changes. The self-determination theory was used as the framework for selecting appropriate website features, including goal setting and self-monitoring. The primary outcome measure is change in diet quality. The completion of questionnaires at baseline and 3, 6, and 12 months will be incentivized with a monetary prize draw. Results: As of December 2019, 1277 participants have been randomized. Conclusions: The web-based delivery of nutrition interventions has the potential to improve dietary intake of young adults. However, the level of support required to improve intake is unknown

The SHED-IT community trial study protocol: a randomised controlled trial of weight loss programs for overweight and obese men

<p>Abstract</p> <p>Background</p> <p>Obesity is a major cause of preventable death in Australia with prevalence increasing at an alarming rate. Of particular concern is that approximately 68% of men are overweight/obese, yet are notoriously difficult to engage in weight loss programs, despite being more susceptible than women to adverse weight-related outcomes. There is a need to develop and evaluate obesity treatment programs that target and appeal to men. The primary aim of this study is to evaluate the efficacy of two relatively low intensity weight loss programs developed specifically for men.</p> <p>Methods and Design</p> <p>The study design is an assessor blinded, parallel-group randomised controlled trial that recruited 159 overweight and obese men in Newcastle, Australia. Inclusion criteria included: BMI 25-40 (kg/m²); no participation in other weight loss programs during the study; pass a health-screening questionnaire and pre-exercise risk assessment; available for assessment sessions; access to a computer with e-mail and Internet facilities; and own a mobile phone. Men were recruited to the SHED-IT (Self-Help, Exercise and Diet using Internet Technology) study via the media and emails sent to male dominated workplaces. Men were stratified by BMI category (overweight, obese class I, obese class II) and randomised to one of three groups: (1) SHED-IT <it>Resources </it>- provision of materials (DVD, handbooks, pedometer, tape measure) with embedded behaviour change strategies to support weight loss; (2) SHED-IT <it>Online </it>- same materials as SHED-IT <it>Resources </it>plus access to and instruction on how to use the study website; (3) Wait-list Control. The intervention programs are three months long with outcome measures taken by assessors blinded to group allocation at baseline, and 3- and 6-months post baseline. Outcome measures include: weight (primary outcome), % body fat, waist circumference, blood pressure, resting heart rate, objectively measured physical activity, self-reported dietary intake, sedentary behaviour, physical activity and dietary cognitions, sleepiness, quality of life, and perceived sexual health. Generalised linear mixed models will be used to assess all outcomes for the impact of group (<it>Resources</it>, <it>Online</it>, and <it>Control</it>), time (treated as categorical with levels baseline, 3-months and 6-months) and the group-by-time interaction. These three terms will form the base model. 'Intention-to-treat' analysis will include all randomised participants.</p> <p>Discussion</p> <p>Our study will compare evidence-based and theoretically driven, low cost and easily disseminated strategies specifically targeting weight loss in men. The SHED-IT community trial will provide evidence to inform development and dissemination of sustainable strategies to reduce obesity in men.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry (ACTRN12610000699066)</p

The association between genetically elevated polyunsaturated fatty acids and risk of cancer

BACKGROUND: The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain. METHODS: Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures. FINDINGS: Genetically elevated PUFA desaturase activity was associated (P < 0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR = 1.00 [95% CI: 0.99-1.01]; Pheterogeneity = 0.25), urinary system cancers (1.03 [0.99-1.06], Pheterogeneity = 0.51), nervous system cancers (0.99 [0.95-1.03], Pheterogeneity = 0.92) or blood cancers (1.01 [0.98-1.04], Pheterogeneity = 0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P < 0.0006) with increased risk of inflammatory bowel disease but not bleeding. INTERPRETATION: The PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease. FUNDING: Cancer Resesrch UK (C52724/A20138, C18281/A19169). UK Medical Research Council (MR/P014054/1). National Institute for Health Research (NIHR202411). UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4). National Cancer Institute (R00 CA215360). National Institutes of Health (U01 CA164973, R01 CA60987, R01 CA72520, U01 CA74806, R01 CA55874, U01 CA164973 and U01 CA164973)

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

The validity of dietary assessment methods to accurately measure energy intake in children and adolescents who are overweight or obese: a systematic review

The accurate assessment of energy intake in children and adolescents is an important outcome measure for clinical and population-based research. This systematic review aimed to determine the validity of dietary assessment methods to measure energy intake in children and adolescents who are classified as overweight or obese by comparison with doubly labelled water. Five electronic databases were searched using keywords. Of the 5263 papers identified, seven papers describing six studies met the inclusion criteria. Studies were included in the review if participants were classified as overweight or obese, aged 0–18 years old, if they estimated energy intake via a dietary assessment method and if they compared this to total energy expenditure measured via the doubly labelled water method. All studies were cross-sectional in nature, and each used one dietary assessment method, including 14-day-food record (FR; n = 1), 24 h dietary recall (n = 1), 8-day FR (n = 1), 9-day FR (n = 1), 3-day FR (n = 1) and diet history interview (n = 1). Sample sizes ranged from 9 to 59 participants, with the majority of studies including less than 30 participants (n = 4). Mis-reporting was evident in all of the studies, with under-reporting (n = 5) more frequent than over-reporting (n = 1). Findings from this review suggest that a 24-h dietary recall and diet history interview were the most accurate methods at the group level for children aged 4–14 years, where the parent or combined child and parent were the reporters