The Effect of High-Fat Diet on Intramyocellular Lipid Content in Healthy Adults: A Systematic Review, Meta-Analysis, and Meta-Regression.

Fatty acids are stored within the muscle as intramyocellular lipids (IMCL). Some, but not all, studies indicate that following a high-fat diet (HFD), IMCL may accumulate and affect insulin sensitivity. This systematic review and meta-analysis aimed to quantify the effects of an HFD on IMCL. It also explored the potential modifying effects of HFD fat content and duration, IMCL measurement technique, physical activity status, and the associations of IMCL with insulin sensitivity. Five databases were systematically searched for studies that examined the effect of ≥3 d of HFD (>35% daily energy intake from fat) on IMCL content in healthy individuals. Meta-regressions were used to investigate associations of the HFD total fat content, duration, physical activity status, IMCL measurement technique, and insulin sensitivity with IMCL responses. Changes in IMCL content and insulin sensitivity (assessed by hyperinsulinemic-euglycemic clamp) are presented as standardized mean difference (SMD) using a random effects model with 95% confidence intervals (95% CIs). Nineteen studies were included in the systematic review and 16 in the meta-analysis. IMCL content increased following HFD (SMD = 0.63; 95% CI: 0.31, 0.94, P = 0.001). IMCL accumulation was not influenced by total fat content (P = 0.832) or duration (P = 0.844) of HFD, physical activity status (P = 0.192), or by the IMCL measurement technique (P > 0.05). Insulin sensitivity decreased following HFD (SMD = -0.34; 95% CI: -0.52, -0.16; P = 0.003), but this was not related to the increase in IMCL content following HFD (P = 0.233). Consumption of an HFD (>35% daily energy intake from fat) for ≥3 d significantly increases IMCL content in healthy individuals regardless of HFD total fat content and duration of physical activity status. All IMCL measurement techniques detected the increased IMCL content following HFD. The dissociation between changes in IMCL and insulin sensitivity suggests that other factors may drive HFD-induced impairments in insulin sensitivity in healthy individuals. This trial was registered at PROSPERO as CRD42021257984.

Effects of dietary nitrate supplementation on oral health and associated markers of systemic health: a systematic review.

Poor oral health can impact an individual's ability to eat and has been associated with an increased risk of non-communicable diseases. While the benefits of nitrate consumption on oral health were first proposed more than 20 years ago, no systematic review has been published examining effects of dietary nitrate on oral health. This systematic review investigated the effects of dietary nitrate on markers of oral health in vivo in randomized controlled trials (RCTs). Five databases (PubMed, The Cochrane Library, CINAHL, MEDLINE, and SPORTDiscus) were searched from inception until March 2023. Nine articles reporting data on 284 participants were included. Dietary nitrate was provided via beetroot juice in most studies. The duration of the interventions ranged from one day to six weeks. Dietary nitrate supplementation increased the relative abundance of several individual bacterial genera including Neisseria and Rothia. Dietary nitrate supplementation increased salivary pH and decreased salivary acidification following consumption of a sugar-sweetened beverage. Furthermore, dietary nitrate supplementation resulted in a decrease in the gingival inflammation index. The results of this systematic review suggest that dietary nitrate could represent a potential nutritional strategy to positively modify oral health by impacting the oral microbiome, altering salivary pH, and minimizing gingival inflammation.

A novel role for gag as a cis-acting element regulating RNA structure, dimerization and packaging in HIV-1 lentiviral vectors.

Clinical usage of lentiviral vectors is now established and increasing but remains constrained by vector titer with RNA packaging being a limiting factor. Lentiviral vector RNA is packaged through specific recognition of the packaging signal on the RNA by the viral structural protein Gag. We investigated structurally informed modifications of the 5' leader and gag RNA sequences in which the extended packaging signal lies, to attempt to enhance the packaging process by facilitating vector RNA dimerization, a process closely linked to packaging. We used in-gel SHAPE to study the structures of these mutants in an attempt to derive structure-function correlations that could inform optimized vector RNA design. In-gel SHAPE of both dimeric and monomeric species of RNA revealed a previously unreported direct interaction between the U5 region of the HIV-1 leader and the downstream gag sequences. Our data suggest a structural equilibrium exists in the dimeric viral RNA between a metastable structure that includes a U5-gag interaction and a more stable structure with a U5-AUG duplex. Our data provide clarification for the previously unexplained requirement for the 5' region of gag in enhancing genomic RNA packaging and provide a basis for design of optimized HIV-1 based vectors.

Mediterranean diet adherence is associated with lower dementia risk, independent of genetic predisposition: findings from the UK Biobank prospective cohort study.

BACKGROUND: The identification of effective dementia prevention strategies is a major public health priority, due to the enormous and growing societal cost of this condition. Consumption of a Mediterranean diet (MedDiet) has been proposed to reduce dementia risk. However, current evidence is inconclusive and is typically derived from small cohorts with limited dementia cases. Additionally, few studies have explored the interaction between diet and genetic risk of dementia. METHODS: We used Cox proportional hazard regression models to explore the associations between MedDiet adherence, defined using two different scores (Mediterranean Diet Adherence Screener [MEDAS] continuous and Mediterranean diet Pyramid [PYRAMID] scores), and incident all-cause dementia risk in 60,298 participants from UK Biobank, followed for an average 9.1 years. The interaction between diet and polygenic risk for dementia was also tested. RESULTS: Higher MedDiet adherence was associated with lower dementia risk (MEDAS continuous: HR = 0.77, 95% CI = 0.65-0.91; PYRAMID: HR = 0.86, 95% CI = 0.73-1.02 for highest versus lowest tertiles). There was no significant interaction between MedDiet adherence defined by the MEDAS continuous and PYRAMID scores and polygenic risk for dementia. CONCLUSIONS: Higher adherence to a MedDiet was associated with lower dementia risk, independent of genetic risk, underlining the importance of diet in dementia prevention interventions.

Effects of a mediterranean diet on the gut microbiota and microbial metabolites: A systematic review of randomized controlled trials and observational studies.

Consumption of the Mediterranean dietary pattern (MedDiet) is associated with reduced risk of numerous non-communicable diseases. Modulation of the composition and metabolism of the gut microbiota represents a potential mechanism through which the MedDiet elicits these effects. We conducted a systematic literature search (Prospero registration: CRD42020168977) using PubMed, The Cochrane Library, MEDLINE, SPORTDiscuss, Scopus and CINAHL databases for randomized controlled trials (RCTs) and observational studies exploring the impact of a MedDiet on gut microbiota composition (i.e., relative abundance of bacteria or diversity metrics) and metabolites (e.g., short chain fatty acids). Seventeen RCTs and 17 observational studies were eligible for inclusion in this review. Risk of bias across the studies was mixed but mainly identified as low and unclear. Overall, RCTs and observational studies provided no clear evidence of a consistent effect of a MedDiet on composition or metabolism of the gut microbiota. These findings may be related to the diverse methods across studies (e.g., MedDiet classification and analytical techniques), cohort characteristics, and variable quality of studies. Further, well-designed studies are warranted to advance understanding of the potential effects of the MedDiet using more detailed examination of microbiota and microbial metabolites with reference to emerging characteristics of a healthy gut microbiome.

In Vivo Trafficking of the Anticancer Drug Tris(8-Quinolinolato) Gallium (III) (KP46) by Gallium-68/67 PET/SPECT Imaging.

KP46 (tris(hydroxyquinolinato)gallium(III)) is an experimental, orally administered anticancer drug. Its absorption, delivery to tumours, and mode of action are poorly understood. We aimed to gain insight into these issues using gallium-67 and gallium-68 as radiotracers with SPECT and PET imaging in mice. [67Ga]KP46 and [68Ga]KP46, compared with [68Ga]gallium acetate, were used for logP measurements, in vitro cell uptake studies in A375 melanoma cells, and in vivo imaging in mice bearing A375 tumour xenografts up to 48 h after intravenous (tracer level) and oral (tracer and bulk) administration. 68Ga was more efficiently accumulated in A375 cells in vitro when presented as [68Ga]KP46 than as [68Ga]gallium acetate, but the reverse was observed when intravenously administered in vivo. After oral administration of [68/67Ga]KP46, absorption of 68Ga and 67Ga from the GI tract and delivery to tumours were poor, with the majority excreted in faeces. By 48 h, low but measurable amounts were accumulated in tumours. The distribution in tissues of absorbed radiogallium and octanol extraction of tissues suggested trafficking as free gallium rather than as KP46. We conclude that KP46 likely acts as a slow releaser of gallium ions which are inefficiently absorbed from the GI tract and trafficked to tissues, including tumour and bone.

The Mediterranean dietary pattern for optimising health and performance in competitive athletes: a narrative review.

Nutrition plays a key role in training for, and competing in, competitive sport, and is essential for reducing risk of injury and illness, recovering and adapting between bouts of activity, and enhancing performance. Consumption of a Mediterranean diet (MedDiet) has been demonstrated to reduce risk of various non-communicable diseases and increase longevity. Following the key principles of a MedDiet could also represent a useful framework for good nutrition in competitive athletes under most circumstances, with potential benefits for health and performance parameters. In this review, we discuss the potential effects of a MedDiet, or individual foods and compounds readily available in this dietary pattern, on oxidative stress and inflammation, injury and illness risk, vascular and cognitive function, and exercise performance in competitive athletes. We also highlight potential modifications which could be made to the MedDiet (whilst otherwise adhering to the key principles of this dietary pattern) in accordance with contemporary sports nutrition practices, to maximise health and performance effects. In addition, we discuss potential directions for future research.

Convalescent plasma for COVID-19: Donor demographic factors associated high neutralising antibody titres.

BACKGROUND: Convalescent plasma containing high levels of SARS-CoV-2 antibodies has been studied as a possible treatment for COVID-19. Better understanding of predictors of high antibody levels is needed for improving supply of high-quality therapeutic plasma. AIMS: We have evaluated demographic and clinical factors associated with the probability of a convalescent plasma donor having high SARS-CoV-2 IgG antibody levels. METHODS: A total of 29,585 convalescent plasma donors employed during the first and second waves of the COVID-19 pandemic in England were included in this study. All had been tested for SARS-CoV-2 IgG antibodies by EUROimmun ELISA. A multivariable logistic regression model was used to quantify the association of the demographic and clinical factors with high (EUROimmun S/Co>6.0) SARS-CoV-2 IgG antibody level. RESULTS: Most of the donors were male (23,024; 78%), with white ethnic background (24,598;83%) and had not been tested for SARS-CoV-2 (15,266; 52%).Overall, less than 20% of convalescent plasma donors with confirmed or suspected SARS-CoV-2 infection harboured high SARS-CoV-2 antibody levels (n = 4,978). We found that older male donors who had been hospitalised with COVID-19 were most likely to harbour high levels of antibodies. White donors were less likely to have high SARS-CoV-2 antibody levels than donors with Asian orblack ethnic backgrounds residing in affluent areas likely reflecting ethnic inequality previously associated with SARS-CoV-2 infection. DISCUSSION: In a time of great uncertainty, and predicted new waves associated with newly emerging SARS-CoV-2 variants, these results will help us to target future convalescent plasma collections.

The effect of rugby training on indirect markers of gut permeability and gut damage in academy level rugby players.

PURPOSE: To assess indirect markers of intestinal endothelial cell damage and permeability in academy rugby players in response to rugby training at the beginning and end of preseason. METHODS: Blood and urinary measures (intestinal fatty acid binding protein and lactulose:rhamnose) as measures of gastrointestinal cell damage and permeability were taken at rest and after a standardised collision-based rugby training session in 19 elite male academy rugby players (age: 20 ± 1 years, backs: 89.3 ± 8.4 kg; forwards: 111.8 ± 7.6 kg) at the start of preseason. A subsample (n = 5) repeated the protocol after six weeks of preseason training. Gastrointestinal symptoms (GIS; range of thirteen standard symptoms), aerobic capacity (30-15 intermittent fitness test), and strength (1 repetition maximum) were also measured. RESULTS: Following the rugby training session at the start of preseason, there was an increase (median; interquartile range) in intestinal fatty acid binding protein (2140; 1260-2730 to 3245; 1985-5143 pg/ml, p = 0.003) and lactulose:rhamnose (0.31; 0.26-0.34 to 0.97; 0.82-1.07, p < 0.001). After six weeks of preseason training players physical qualities improved, and the same trends in blood and urinary measures were observed within the subsample. Overall, the frequency and severity of GIS were low and not correlated to markers of endothelial damage. CONCLUSIONS: Rugby training resulted in increased intestinal endothelial cell damage and permeability compared to rest. A similar magnitude of effect was observed after six weeks of pre-season training. This was not related to the experience of GIS.

Evaluation of Optimized Procedures for High-Precision Lead Isotope Analyses of Seawater by Multiple Collector Inductively Coupled Plasma Mass Spectrometry.

The application of Pb isotopes to marine geochemistry is currently hindered by challenges associated with the analysis of Pb isotopes in seawater. The current study evaluates the performance of multiple collector inductively coupled plasma mass spectrometry (MC-ICP-MS) measurements of seawater Pb isotope compositions following Pb separation by either solid-phase extraction with Nobias Chelate PA-1 resin or coprecipitation with Mg(OH)2 and using either a Pb double spike or external normalization to Tl for mass bias correction. The four analytical combinations achieve results of similar quality when measuring 1-7 ng of seawater Pb, with reproducibilities (two standard deviations, 2SD) of 100-1200 ppm for 206Pb/207Pb and 208Pb/207Pb and 300-1700 ppm for ratios involving the minor 204Pb isotope. All four procedures enable significantly improved sample throughput compared to an established thermal ionization mass spectrometry (TIMS) double-spike method and produce unbiased seawater Pb isotope compositions with similar or improved precision. Nobias extraction is preferable to coprecipitation due to its greater analytical throughput and suitability for analyses of large seawater samples with high Si(OH)4 contents. The most accurate Pb isotope data are produced following Nobias extraction and double-spike correction as such analyses are least susceptible to matrix effects. However, Nobias extraction with Tl normalization constitutes an attractive alternative as, unlike the double-spike procedure, only a single mass spectrometric measurement is required, which improves analytical throughput and optimizes Pb consumption for analysis. Despite the advantages of solid-phase extraction, coprecipitation represents a useful Pb separation technique for samples with low to moderate Si contents as it is inexpensive, simple to implement, and the data are only marginally less accurate, especially when combined with a Pb double spike for mass bias correction.

Appetite and energy intake responses to breakfast consumption and carbohydrate supplementation in hypoxia.

PURPOSE: The purpose of experiment one was to determine the appetite, acylated ghrelin and energy intake response to breakfast consumption and omission in hypoxia and normoxia. Experiment two aimed to determine the appetite, acylated ghrelin and energy intake response to carbohydrate supplementation after both breakfast consumption and omission in hypoxia. METHODS: In experiment one, twelve participants rested and exercised once after breakfast consumption and once after omission in normobaric hypoxia (4300 m: FiO2 ~11.7%) and normoxia. In experiment two, eleven participants rested and exercised in normobaric hypoxia (4300 m: FiO2 ~11.7%), twice after consuming a high carbohydrate breakfast and twice after breakfast omission. Participants consumed both a carbohydrate (1.2g·min-1 glucose) and a placebo beverage after breakfast consumption and omission. Measures of appetite perceptions and acylated ghrelin were taken at regular intervals throughout both experiments and an ad-libitum meal was provided post-exercise to quantify energy intake. RESULTS: Breakfast consumption had no significant effect on post exercise energy intake or acylated ghrelin concentrations, despite reductions in appetite perceptions. As such, breakfast consumption increased total trial energy intake compared with breakfast omission in hypoxia (7136 ± 2047 kJ vs. 5412 ± 1652 kJ; p = 0.02) and normoxia (9276 ± 3058 vs. 6654 ± 2091 kJ; p < 0.01). Carbohydrate supplementation had no effect on appetite perceptions or acylated ghrelin concentrations after breakfast consumption or omission. As such, carbohydrate supplementation increased total energy intake after breakfast consumption (10222 ± 2831 kJ vs. 7695 ± 1970 kJ p < 0.01) and omission (8058 ± 2574 kJ vs. 6174 ± 2222 kJ p = 0.02). CONCLUSION: Both breakfast consumption and carbohydrate supplementation provide beneficial dietary interventions for increasing energy intake in hypoxic conditions.

Substrate oxidation and the influence of breakfast in normobaric hypoxia and normoxia.

PURPOSE: Previous research has reported inconsistent effects of hypoxia on substrate oxidation, which may be due to differences in methodological design, such as pre-exercise nutritional status and exercise intensity. This study investigated the effect of breakfast consumption on substrate oxidation at varying exercise intensities in normobaric hypoxia compared with normoxia. METHODS: Twelve participants rested and exercised once after breakfast consumption and once after omission in normobaric hypoxia (4300 m: FiO2 ~ 11.7%) and normoxia. Exercise consisted of walking for 20 min at 40%, 50% and 60% of altitude-specific [Formula: see text]O2max at 10-15% gradient with a 10 kg backpack. Indirect calorimetry was used to calculate carbohydrate and fat oxidation. RESULTS: The relative contribution of carbohydrate oxidation to energy expenditure was significantly reduced in hypoxia compared with normoxia during exercise after breakfast omission at 40% (22.4 ± 17.5% vs. 38.5 ± 15.5%, p = 0.03) and 60% [Formula: see text]O2max (35.4 ± 12.4 vs. 50.1 ± 17.6%, p = 0.03), with a trend observed at 50% [Formula: see text]O2max (23.6 ± 17.9% vs. 38.1 ± 17.0%, p = 0.07). The relative contribution of carbohydrate oxidation to energy expenditure was not significantly different in hypoxia compared with normoxia during exercise after breakfast consumption at 40% (42.4 ± 15.7% vs. 48.5 ± 13.3%, p = 0.99), 50% (43.1 ± 11.7% vs. 47.1 ± 14.0%, p = 0.99) and 60% [Formula: see text]O2max (54.6 ± 17.8% vs. 55.1 ± 15.0%, p = 0.99). CONCLUSIONS: Relative carbohydrate oxidation was significantly reduced in hypoxia compared with normoxia during exercise after breakfast omission but not during exercise after breakfast consumption. This response remained consistent with increasing exercise intensities. These findings may explain some of the disparity in the literature.

Near Misses in Financial Trading: Skills for Capturing and Averting Error.

OBJECTIVE: The aims of this study were (a) to determine whether near-miss incidents in financial trading contain information on the operator skills and systems that detect and prevent near misses and the patterns and trends revealed by these data and (b) to explore if particular operator skills and systems are found as important for avoiding particular types of error on the trading floor. BACKGROUND: In this study, we examine a cohort of near-miss incidents collected from a financial trading organization using the Financial Incident Analysis System and report on the nontechnical skills and systems that are used to detect and prevent error in this domain. METHOD: One thousand near-miss incidents are analyzed using distribution, mean, chi-square, and associative analysis to describe the data; reliability is provided. RESULTS: Slips/lapses (52%) and human-computer interface problems (21%) often occur alone and are the main contributors to error causation, whereas the prevention of error is largely a result of teamwork (65%) and situation awareness (46%) skills. No matter the cause of error, situation awareness and teamwork skills are used most often to detect and prevent the error. CONCLUSION: Situation awareness and teamwork skills appear universally important as a "last line" of defense for capturing error, and data from incident-monitoring systems can be analyzed in a fashion more consistent with a "Safety-II" approach. APPLICATION: This research provides data for ameliorating risk within financial trading organizations, with implications for future risk management programs and regulation.

Vitamin D for the management of asthma.

BACKGROUND: Several clinical trials of vitamin D to prevent asthma exacerbation and improve asthma control have been conducted in children and adults, but a meta-analysis restricted to double-blind, randomised, placebo-controlled trials of this intervention is lacking. OBJECTIVES: To evaluate the efficacy of administration of vitamin D and its hydroxylated metabolites in reducing the risk of severe asthma exacerbations (defined as those requiring treatment with systemic corticosteroids) and improving asthma symptom control. SEARCH METHODS: We searched the Cochrane Airways Group Trial Register and reference lists of articles. We contacted the authors of studies in order to identify additional trials. Date of last search: January 2016. SELECTION CRITERIA: Double-blind, randomised, placebo-controlled trials of vitamin D in children and adults with asthma evaluating exacerbation risk or asthma symptom control or both. DATA COLLECTION AND ANALYSIS: Two review authors independently applied study inclusion criteria, extracted the data, and assessed risk of bias. We obtained missing data from the authors where possible. We reported results with 95% confidence intervals (CIs). MAIN RESULTS: We included seven trials involving a total of 435 children and two trials involving a total of 658 adults in the primary analysis. Of these, one trial involving 22 children and two trials involving 658 adults contributed to the analysis of the rate of exacerbations requiring systemic corticosteroids. Duration of trials ranged from four to 12 months, and the majority of participants had mild to moderate asthma. Administration of vitamin D reduced the rate of exacerbations requiring systemic corticosteroids (rate ratio 0.63, 95% CI 0.45 to 0.88; 680 participants; 3 studies; high-quality evidence), and decreased the risk of having at least one exacerbation requiring an emergency department visit or hospitalisation or both (odds ratio (OR) 0.39, 95% CI 0.19 to 0.78; number needed to treat for an additional beneficial outcome, 27; 963 participants; 7 studies; high-quality evidence). There was no effect of vitamin D on % predicted forced expiratory volume in one second (mean difference (MD) 0.48, 95% CI -0.93 to 1.89; 387 participants; 4 studies; high-quality evidence) or Asthma Control Test scores (MD -0.08, 95% CI -0.70 to 0.54; 713 participants; 3 studies; high-quality evidence). Administration of vitamin D did not influence the risk of serious adverse events (OR 1.01, 95% CI 0.54 to 1.89; 879 participants; 5 studies; moderate-quality evidence). One trial comparing low-dose versus high-dose vitamin D reported two episodes of hypercalciuria, one in each study arm. No other study reported any adverse event potentially attributable to administration of vitamin D. No participant in any included trial suffered a fatal asthma exacerbation. We did not perform a subgroup analysis to determine whether the effect of vitamin D on risk of severe exacerbation was modified by baseline vitamin D status, due to unavailability of suitably disaggregated data. We assessed two trials as being at high risk of bias in at least one domain; neither trial contributed data to the analysis of the outcomes reported above. AUTHORS' CONCLUSIONS: Meta-analysis of a modest number of trials in people with predominantly mild to moderate asthma suggests that vitamin D is likely to reduce both the risk of severe asthma exacerbation and healthcare use. It is as yet unclear whether these effects are confined to people with lower baseline vitamin D status; further research, including individual patient data meta-analysis of existing datasets, is needed to clarify this issue. Children and people with frequent severe asthma exacerbations were under-represented; additional primary trials are needed to establish whether vitamin D can reduce the risk of severe asthma exacerbation in these groups.

Associations between anxiety, depression, and weight status during and after pregnancy: A systematic review and meta-analysis.

Previous work has found adverse mental health symptomology in women living with obesity, compared with those of healthy weight, around the time of pregnancy. This meta-analysis aimed to explore the association between anxiety, depression, and weight status in women living with obesity before, during, and after pregnancy. Bibliographic databases were systematically searched, and 14 studies were included, which aimed to assess the association between excess weight and anxiety or depression outcomes in women before, during, or after pregnancy. Data were analyzed via narrative synthesis and random effects multi-level meta-analyses. Scores on mental health indices were significantly greater (indicative of worse anxiety/depression) in women with obesity compared to women of a healthy weight, around the time of pregnancy (SMD = 0.21 [95% CI: 0.11-0.31; 95% prediction intervals: 0.13-0.56], I2  = 73%, p < 0.01). Depressive symptoms were greater during and after pregnancy (SMD = 0.23 [95% CI: 0.13-0.34; 95% prediction intervals: -0.12 to 0.59], I2  = 75.0%, p < 0.01), and trait anxiety symptoms were greater during pregnancy (SMD = 0.24 [95% CI: 0.01-0.47; 95% prediction intervals: -0.25 to 0.72], I2  = 83.7%, p = 0.039) in women living with obesity, compared to those of healthy weight. Narrative evidence suggests that socioeconomic status and ethnicity may modify the relationship between obesity and mental health symptomology. The findings indicate that maternal obesity is associated with greater anxiety and depression symptoms. These findings may inform the design of maternal weight management interventions.

Pharmacological interventions for the management of children and adolescents living with obesity-An update of a Cochrane systematic review with meta-analyses.

IMPORTANCE: The effectiveness of anti-obesity medications for children and adolescents is unclear. OBJECTIVE: To update the evidence on the benefits and harms of anti-obesity medication. DATA SOURCES: Cochrane CENTRAL, MEDLINE, ClinicalTrials.gov and WHO ICTRP (1/1/16-17/3/23). STUDY SELECTION: Randomized controlled trials ≥6 months in people <19 years living with obesity. DATA EXTRACTION AND SYNTHESIS: Screening, data extraction and quality assessment conducted in duplicate, independently. MAIN OUTCOMES AND MEASURES: Body mass index (BMI): 95th percentile BMI, adverse events and quality of life. RESULTS: Thirty-five trials (N = 4331), follow-up: 6-24 months; age: 8.8-16.3 years; BMI: 26.2-41.7 kg/m2. Moderate certainty evidence demonstrated a -1.71 (95% confidence interval [CI]: -2.27 to -1.14)-unit BMI reduction, ranging from -0.8 to -5.9 units between individual drugs with semaglutide producing the largest reduction of -5.88 kg/m2 (95% CI: -6.99 to -4.77, N = 201). Drug type explained ~44% of heterogeneity. Low certainty evidence demonstrated reduction in 95th percentile BMI: -11.88 percentage points (95% CI: -18.43 to -5.30, N = 668). Serious adverse events and study discontinuation due to adverse events did not differ between medications and comparators, but medication dose adjustments were higher compared to comparator (10.6% vs 1.7%; RR = 3.74 [95% CI: 1.51 to 9.26], I2 = 15%), regardless of approval status. There was a trend towards improved quality of life. Evidence gaps exist for children, psychosocial outcomes, comorbidities and weight loss maintenance. CONCLUSIONS AND RELEVANCE: Anti-obesity medications in addition to behaviour change improve BMI but may require dose adjustment, with 1 in 100 adolescents experiencing a serious adverse event.

Associations between Vegetable Nitrate Intake and Cardiovascular Disease Risk and Mortality: A Systematic Review.

Consumption of nitrate-rich vegetables increases nitric oxide bioavailability, lowers blood pressure, and improves endothelial function. These effects could also translate into reduced cardiovascular disease (CVD) risk and mortality. This systematic review aimed to investigate the associations between habitual vegetable nitrate intake and CVD incidence and mortality. A secondary aim was to identify factors that moderate the relationship between vegetable nitrate intake and CVD incidence/mortality. Seven databases (PubMed, MEDLINE, Embase, Scopus, Web of Science, CINAHL, and APA PsycINFO) were searched from inception to 13 February 2023. Observational studies quantifying vegetable nitrate intake in participants aged 18+ years through self-reported dietary exposure and assessing incidence or mortality from CVD overall, or individual CVD subtypes, were eligible. Five studies including a total of 63,155 participants were included. There was an inverse association between vegetable nitrate intake and most reported CVD outcomes. Reported risk reductions tended to plateau at moderate intake, suggesting a possible ceiling effect. The risk of bias across all studies was low. The results of this systematic review suggest a potential role for vegetable nitrate in reducing CVD risk and mortality. Further randomised controlled trials are now required to corroborate these findings.

Adherence to the Eatwell Guide and cardiometabolic, cognitive and neuroimaging parameters: an analysis from the PREVENT dementia study.

BACKGROUND: The Eatwell guide reflects the UK government's recommendations for a healthy and balanced diet. Previous research has identified associations between healthy eating patterns and both cardiovascular and brain health, although there is little evidence specifically focusing on the Eatwell Guide. To date no research has investigated associations between the Eatwell Guide and risk for future dementia. METHODS: Data from the PREVENT dementia cohort study baseline visit was used in this analysis. Binary and graded Eatwell Guide scores (BEWG, GEWG) were created from a self-reported Food Frequency Questionnaire. The CAIDE score was included as the primary outcome measure to represent risk for future Alzheimer's disease. Secondary outcome measures included cardiometabolic health measures and brain health measures. Generalised additive models were run in R. RESULTS: A total of 517 participants were included in the analysis, with a mean BEWG score of 4.39 (± 1.66) (out of a possible 12 points) and GEWG score of 39.88 (± 6.19) (out of a possible 60 points). There was no significant association between either Eatwell Guide score and the CAIDE score (BEWG ß: 0.07, 95% confidence interval (CI): -0.07, 0.22; GEWG ß: 0.02, 95% CI: -0.02, 0.06) or any measures of brain health. There was a significant association between higher GEWG score and lower systolic and diastolic blood pressure and body mass index (BMI) (systolic ß: -0.24, 95% CI: -0.45, -0.03; diastolic ß: -0.16, 95% CI: -0.29, -0.03; BMI ß: -0.09, 95% CI: -0.16, -0.01). CONCLUSIONS: Although not directly associated with the CAIDE score, the Eatwell Guide dietary pattern may be beneficial for dementia prevention efforts through the modification of hypertension and obesity, which are both known risk factors for dementia. Future work could replicate these findings in other UK-based cohorts as well as further development of Eatwell Guide scoring methodologies.

Adherence to the Eatwell Guide and population and planetary health: A Rank Prize Forum report.

This report summarises a Forum conducted in June 2023 to explore the current state of the knowledge around the Eatwell Guide, which is the UK government's healthy eating tool, in relation to population and planetary health. The 1.5-day Forum highlighted the limited, albeit promising evidence linking higher adherence to the Eatwell Guide with favourable health outcomes, including reduced overall mortality risk, lower abdominal obesity in post-menopausal women and improved cardiometabolic health markers. Similarly, evidence was presented to suggest that higher adherence to the Eatwell Guide is associated with reduced greenhouse gas emissions. Presentations were given around cultural adaptations of the Eatwell Guide, including African Heritage and South Asian versions, which are designed to increase the acceptability and uptake of the Eatwell Guide in these communities in the United Kingdom. Presentations highlighted ongoing work relevant to the applications of the Eatwell Guide in randomised controlled trials and public health settings, including the development of a screening tool to quantify Eatwell Guide adherence. The Forum ended with a World Café-style event, in which the strengths and limitations of the Eatwell Guide were discussed, and directions for future research were identified. This Forum report serves as a primer on the current state of the knowledge on the Eatwell Guide and population and planetary health and will be of interest to researchers, healthcare professionals and public health officials.

The impact of Allied Health Professionals on the primary and secondary prevention of obesity in young children: A scoping review.

Allied Health Professionals (AHPs) have the capacity to promote healthy behaviours in young children through routine 'contact points', as well as structured weight management programmes. This scoping review aims to evaluate the impact of AHPs in the prevention of obesity in young children. Databases were searched for relevant evidence between 1st January 2000 and 17th January 2022. Eligibility criteria included primary evidence (including, but not limited to; randomized controlled trials, observational studies, service evaluations) evaluating the impact of AHPs on the primary and secondary prevention of obesity in young children (mean age under 5 years old). AHP-related interventions typically demonstrated improvements in outcomes such as nutritional behaviour (e.g. lower sweetened drink intake), with some reductions in screen time. However, changes in weight outcomes (e.g. body mass index (BMI) z-score, BMI) in response to an AHP intervention were inconsistent. There was insufficient data to determine moderating effects, however tentative evidence suggests that those with a lower socioeconomic status or living in an underprivileged area may be more likely to lose weight following an AHP intervention. There was no evidence identified evaluating how AHPs use routine 'contact points' in the prevention of obesity in young children. AHP interventions could be effective in optimizing weight and nutritional outcomes in young children. However, more research is required to determine how routine AHP contact points, across the range of professional groups may be used in the prevention of obesity in young children.