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Background: The potential role of n-6 PUFAs in major health outcomes remains controversial., Objectives: To examine the relationship between the major plasma n6 PUFA, linoleic acid (LA), as well as the non-LA n6 PUFAs, and total and cause-specific mortality., Methods: This was a prospective, observational, biomarker-based study in the UK Biobank. Individuals with complete information on baseline demographic, covariate and plasma PUFA levels (percent ot total fatty acids) and mortality outcomes were included (n=257,925). Multivariable-adjusted, Cox-proportional hazards models were used to predict risk of death from all-causes, and from cardiovascular disease (CVD), cancer, and other causes as a function of plasma LA and non-LA n6 levels, both continuously and by PUFA quintile (Q)., Results: Comparing LA Q5 to Q1, the hazard ratio (HR, 95% CI) for total mortality was 0.80 (0.76, 0.84; p<0.001), and this was similar for all three cause-specific death categories. On the other hand, mortality HR for non-LA n6 was 1.12 (1.08,1.17; p<0.001), and this was primarily due to increased risk for non-CVD, noncancer deaths [HR 1.29 (1.19,1.40; p<0.001)]. Exploratory analyses among the eight next most common other causes of death suggested that both the decreased risk associated with higher LA and the increased risk associated with non-LA n6 were confined to deaths from respiratory and digestive diseases., Conclusions: These findings highlight the profound differences in mortality risk related to LA and non-LA n6 PUFA levels and underscore the inappropriateness of treating n-6 PUFAs as a homogenous class with respect to health outcomes. They also support recommendations to maintain (if not increase) current LA intakes., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Introduction: Nigeria is committed to reducing industrial trans- fatty acids (iTFA) from the food supply, but the potential health gains, costs and cost-effectiveness are unknown., Methods: The effect on ischaemic heart disease (IHD) burden, costs and cost-effectiveness of a mandatory iTFA limit (≤2% of all fats) for foods in Nigeria were estimated using Markov cohort models. Data on demographics, IHD epidemiology and trans- fatty acid intake were derived from the 2019 Global Burden of Disease Study. Avoided IHD events and deaths; health-adjusted life years (HALYs) gained; and healthcare, policy implementation and net costs were estimated over 10 years and the population's lifetime. Incremental cost-effectiveness ratios using net costs and HALYs gained (both discounted at 3%) were used to assess cost-effectiveness., Results: Over the first 10 years, a mandatory iTFA limit (assumed to eliminate iTFA intake) was estimated to prevent 9996 (95% uncertainty interval: 8870 to 11 118) IHD deaths and 66 569 (58 862 to 74 083) IHD events, and to save US$90 million (78 to 102) in healthcare costs. The corresponding lifetime estimates were 259 934 (228 736 to 290 191), 479 308 (95% UI 420 472 to 538 177) and 518 (450 to 587). Policy implementation costs were estimated at US$17 million (11 to 23) over the first 10 years, and US$26 million USD (19 to 33) over the population's lifetime. The intervention was estimated to be cost-saving, and findings were robust across several deterministic sensitivity analyses., Conclusion: Our findings support mandating a limit of iTFAs as a cost-saving strategy to reduce the IHD burden in Nigeria., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form and declare the following: MM report grant support from Resolve to Save Lives and the World Health Organization; and travel support from the Nordic Dairy Congress 2022; all outside of the present work. MDH has received travel support from the American Heart Association and World Heart Federation. MDH has an appointment at The George Institute for Global Health, which has a patent, license and has received investment funding with intent to commercialise fixed-dose combination therapy through its social enterprise business, George Medicines. MDH has pending patents for heart failure polypills., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Salt Substitute and Stroke Study (SSaSS) demonstrated significant reductions in systolic blood pressure (SBP), and the risk of stroke, major cardiovascular events and total mortality with the use of potassium-enriched salt. The contribution of sodium reduction versus potassium increase to these effects is unknown. We identified four different data sources describing the association between sodium reduction, potassium supplementation and change in SBP. We then fitted a series of models to estimate the SBP reductions expected for the differences in sodium and potassium intake in SSaSS, derived from 24-h urine collections. The proportions of the SBP reduction separately attributable to sodium reduction and potassium supplementation were calculated. The observed SBP reduction in SSaSS was -3.3 mmHg with a corresponding mean 15.2 mmol reduction in 24-h sodium excretion and a mean 20.6 mmol increase in 24-h potassium excretion. Assuming 90% of dietary sodium intake and 70% of dietary potassium intake were excreted through urine, the models projected falls in SBP of between -1.67 (95% confidence interval: -4.06 to +0.73) mmHg and -5.33 (95% confidence interval: -8.58 to -2.08) mmHg. The estimated proportional contribution of sodium reduction to the SBP fall ranged between 12 and 39% for the different models fitted. Sensitivity analyses assuming different proportional urinary excretion of dietary sodium and potassium intake showed similar results. In every model, the majority of the SBP lowering effect in SSaSS was estimated to be attributable to the increase in dietary potassium rather than the fall in dietary sodium., (© 2024. The Author(s).)

Background: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium., Methods: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction., Results: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P =0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions., Conclusions: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD., Competing Interests: Disclosures Dr Murphy reports having worked as a consultant for Pharmavite (until 2021). The remaining authors have reported no relationships relevant to the contents of this article. Dr Psaty serves on the steering committee of the Yale Open Data Access Project, funded by Johnson and Johnson.

Background: The effect of marine omega-3 PUFAs on risk of stroke remains unclear., Methods: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome., Results: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P <0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P <0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P =0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P =0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD., Conclusions: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke., Competing Interests: Disclosures Dr O’Keefe reports major ownership interest in Cardiotabs. Dr Harris reports minor ownership interest in Omegaquant Analytics, LLC. Dr Sala-Vila reports travel and grant support from California Walnut Commission. Dr Mora reports compensation for consultant services from Quest Diagnostics. Dr Murphy reports compensation from Pharmavite for consultant services. Dr Bork reports grants from Karen Elise Jensens Fond. Dr Ärnlöv reports compensation from Astellas Pharma for other services; compensation from Boehringer Ingelheim for consultant services; compensation from AstraZeneca for other services; and compensation from Novartis for other services. Dr Geleijnse reports grants from National Institutes of Health to other; grants from Upfield Europe BV to other; and grants from The Dutch Heart Foundation to other. Dr Manson reports grants from National Institutes of Health and compensation from National Institutes of Health for other services. Dr Mora reports compensation from Pfizer for consultant services; employment by Brigham and Women’s Hospital; grants from National Institute of Diabetes and Digestive and Kidney Diseases; and grants from National Heart, Lung, and Blood Institute. Dr Melo van Lent reports grants from National Institutes of Health and grants from Alzheimer’s Association. Dr Mozaffarian reports grants from Rockefeller Foundation; compensation from Beren Therapeutics for other services; stock holdings in HumanCo; compensation from January Inc. for other services; compensation from Filtricine for other services; compensation from Perfect Day for other services; compensation from Tiny Organics for other services; grants from Bill and Melinda Gates Foundation; compensation from Calibrate for other services; grants from Vail Innovative Global Research; grants from Kaiser Permanente Fund at East Bay Community Foundation; compensation from DayTwo for other services; compensation from Instacart health for other services; compensation from Season Health for other services; grants from National Institutes of Health; compensation from Barilla for consultant services; stock holdings in Calibrate; compensation from Kaiser Permanente Fund for other services; compensation from HumanCo for other services

Background: Postsecondary education institutions, where hundreds of millions of people work and study globally, are a key setting for retail food environment interventions., Objective: We aimed to synthesize the evidence for the effectiveness of retail food environment interventions in improving the healthiness of dietary behavior of students and staff in postsecondary education settings., Methods: Academic databases were searched for randomized controlled trials (RCTs) and quasi-experimental studies published until August 2023. Studies were eligible if they assessed the impact of a retail food environment intervention on healthiness of dietary behavior (purchases or consumption) in students or staff in postsecondary education settings and targeted one of the following food environment elements: placement, price, product, or promotion. Business-related outcomes (total sales, profit, or revenue) were included as secondary outcomes. Findings were synthesized in narrative form, organized by retail food environment element. Where comparable dietary outcome data were available from ≥10 interventions, findings were pooled using random effects meta-analysis., Results: Of 10,126 studies initially identified, 55 (76% quasi-experimental) were included, describing 71 separate interventions (n = 49 single-element and n = 22 multi-element). Two-thirds (n = 47, 66%) of interventions (n = 32 single-element and n = 15 multi-element) demonstrated significant improvements in dietary behavior. Single-element interventions targeting placement (n = 1) and price (n = 3) improved dietary behavior. Most (n = 9/10, 90%) interventions targeting product availability or convenience (product element) improved dietary behavior, while n = 19/35 (54%) targeting promotion did. Pooled findings from 12 interventions reporting changes in energy content demonstrated a significant decrease in purchased or consumed energy (-7.9%; 95% confidence interval: -10.3%, -5.6%). Almost all interventions (n = 11/12, 92%) that evaluated the impact on business-related outcomes found either a significant increase or no change following the intervention., Conclusions: We established encouraging evidence supporting the role of retail food environment interventions in postsecondary education settings to support healthy dietary behaviors of students and staff., Registry: PROSPERO (International Prospective Register of Systematic Reviews, URL: https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=295836; registration number CRD42022295836)., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Fiscal policies to improve diet are a promising strategy to address the increasing burden of non-communicable disease, the leading cause of death globally. Sugar-sweetened beverage taxes are the most implemented type of fiscal policy to improve diet. Yet taxes on food, if appropriately structured and applied across the food supply, may support a larger population-level shift towards a healthier diet. Designing these policies and guiding them through the legislative process requires evidence. Equity-oriented cost-effectiveness analyses that estimate the distribution of potential health and economic gains can provide this critical evidence. Taxes on less healthy foods are rarely modelled in low-income and middle-income countries.We describe considerations for modelling the effect of a food tax, which can provide guidance for food tax policy design. This includes describing issues related to the availability, reliability and level of detail of national data on dietary habits, the nutrient content of foods and food prices; the structure of the nutrient profile model; type of tax; tax rate; pass-through rate and price elasticity. Using the Philippines as an example, we discuss considerations for using existing data to model the potential effect of a tax, while also taking into account the political and food policy context. In this way, we provide a modelling framework that can help guide policy-makers and advocates in designing a food policy to improve the health and well-being of future generations in the Philippines and elsewhere., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form and declare: MM, AS, MEH, ADK and LJA report funding from Resolve to Save Lives for the present work. MM reports grant support from the WHO and travel support from the Nordic Dairy Congress 2022; all outside of the present work. LJA reports participation in the American Heart Association Nutrition Committee and honoraria from UpToDate, outside the present work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To model the potential health gains and cost-effectiveness of a mandatory limit of industrial trans fatty acids (iTFA) in Kenyan foods., Design: Multiple cohort proportional multistate life table model, incorporating existing data from the Global Burden of Disease study, pooled analyses of observational studies and peer-reviewed evidence of healthcare and policy implementation costs., Setting: Kenya., Participants: Adults aged ≥20 years at baseline (n=50 million)., Intervention: A mandatory iTFA limit (≤2% of all fats) in the Kenyan food supply compared with a base case scenario of maintaining current trans fat intake., Main Outcome Measures: Averted ischaemic heart disease (IHD) events and deaths, health-adjusted life years; healthcare costs; policy implementation costs; net costs; and incremental cost-effectiveness ratio., Results: Over the first 10 years, the intervention was estimated to prevent ~1900 (95% uncertainty interval (UI): 1714; 2148) IHD deaths and ~17 000 (95% UI: 15 475; 19 551) IHD events, and to save ~US$50 million (95% UI: 44; 56). The corresponding estimates over the lifespan of the model population were ~49 000 (95% UI: 43 775; 55 326) IHD deaths prevented, ~113 000 (95% UI: 100 104; 127 969) IHD events prevented and some ~US$300 million (256; 331) saved. Policy implementation costs were estimated as ~US$9 million over the first 10 years and ~US$20 million over the population lifetime. The intervention was estimated to be cost saving regardless of the time horizon. Findings were robust across multiple sensitivity analyses., Conclusions: Findings support policy action for a mandatory iTFA limit as a cost-saving strategy to avert IHD events and deaths in Kenya., Competing Interests: Competing interests: MM reports grant support from Northwestern University and WHO, and travel support from the Nordic Dairy Congress 2022, all outside of the present work. LH reports grant support from the National Health and Medical Research Council, outside of the present study. LS reports consulting fees from WHO, outside of the present study., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Few simulation models have incorporated the interplay of diabetes, obesity, and cardiovascular disease (CVD); their upstream lifestyle and biological risk factors; and their downstream effects on health disparities and economic consequences., Methods: We developed and validated a US Diabetes, Obesity, Cardiovascular Disease Microsimulation (DOC-M) model that incorporates demographic, clinical, and lifestyle risk factors to jointly predict overall and racial-ethnic groups-specific obesity, diabetes, CVD, and cause-specific mortality for the US adult population aged 40 to 79 y at baseline. An individualized health care cost prediction model was further developed and integrated. This model incorporates nationally representative data on baseline demographics, lifestyle, health, and cause-specific mortality; dynamic changes in modifiable risk factors over time; and parameter uncertainty using probabilistic distributions. Validation analyses included assessment of 1) population-level risk calibration and 2) individual-level risk discrimination. To illustrate the application of the DOC-M model, we evaluated the long-term cost-effectiveness of a national produce prescription program., Results: Comparing the 15-y model-predicted population risk of primary outcomes among the 2001-2002 National Health and Nutrition Examination Survey (NHANES) cohort with the observed prevalence from age-matched cross-sectional 2003-2016 NHANES cohorts, calibration performance was strong based on observed-to-expected ratio and calibration plot analysis. In most cases, Brier scores fell below 0.0004, indicating a low overall prediction error. Using the Multi-Ethnic Study of Atherosclerosis cohorts, the c-statistics for assessing individual-level risk discrimination were 0.85 to 0.88 for diabetes, 0.93 to 0.95 for obesity, 0.74 to 0.76 for CVD history, and 0.78 to 0.81 for all-cause mortality, both overall and in three racial-ethnic groups. Open-source code for the model was posted at https://github.com/food-price/DOC-M-Model-Development-and-Validation., Conclusions: The validated DOC-M model can be used to examine health, equity, and the economic impact of health policies and interventions on behavioral and clinical risk factors for obesity, diabetes, and CVD., Highlights: We developed a novel microsimula'tion model for obesity, diabetes, and CVD, which intersect together and - critically for prevention and treatment interventions - share common lifestyle, biologic, and demographic risk factors.Validation analyses, including assessment of (1) population-level risk calibration and (2) individual-level risk discrimination, showed strong performance across the overall population and three major racial-ethnic groups for 6 outcomes (obesity, diabetes, CVD, and all-cause mortality, CVD- and DM-cause mortality)This paper provides a thorough explanation and documentation of the development and validation process of a novel microsimulation model, along with the open-source code (https://github.com/food-price/ DOCM&#95;validation) for public use, to serve as a guide for future simulation model assessments, validation, and implementation., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support for this study was provided entirely by a grant from NIH/NHLBI R01HL130735 and R01HL115189. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report.

Objective: Discomfort has been related to the poor acceptance of a mandibular advancement device (MAD) in patients with obstructive sleep apnea. The present study compared severe initial side effects between a smaller and a larger degree of mandibular advancement in patients with a good protrusive capacity., Methods: Consecutive patients with obstructive sleep apnea and a good protrusive capacity (≥8 mm) were randomized to start treatment with the mandible advanced by either 70% of maximum protrusion (Adv70%) or by 4 mm (Adv4mm) in a pilot study with a parallel design. The main outcome was tenderness or pain in the teeth or jaws using a 0-10 visual analogue scale (VAS) (from "not at all" to "very extensive") or excluded use because of side effects during the first week of treatment. Secondary outcomes included salivation problems and bite changes., Results: Eighteen patients were randomly selected and 17 patients fulfilled the study protocol. Four patients in the Adv70% group and none in the Adv4mm group reported severe tenderness or pain (VAS ≥7) on five or more of the seven days (p=0.03). The degree of mandibular advancement measured in millimeters correlated with the number of days with severe side effects, r=0.64 (p=0.006). The secondary side effects were minor., Conclusion: Starting MAD treatment with 70% mandibular advancement was related to more severe side effects during the first week of treatment compared with a smaller fixed millimeter value in patients with a good protrusive capacity in this pilot study.

Current methods for epigenomic profiling are limited in their ability to obtain genome-wide information with spatial resolution. We introduce spatial ATAC, a method that integrates transposase-accessible chromatin profiling in tissue sections with barcoded solid-phase capture to perform spatially resolved epigenomics. We show that spatial ATAC enables the discovery of the regulatory programs underlying spatial gene expression during mouse organogenesis, lineage differentiation and in human pathology., (© 2023. The Author(s).)

Background: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial., Objectives: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF., Methods: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis., Results: Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively., Conclusions: In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained., Competing Interests: Funding Support and Author Disclosures The Fatty Acid Research Institute retrospectively provided a small honorarium to a subset of the analysts who participated in this study, but it had no role in the design, analysis, manuscript writing, nor decision to submit for publication. Detailed funding information for the individual cohorts can be found in the Supplemental Appendix, specifically Supplemental Table 4. None of the funders/sponsors played any role in the collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Dr O'Donoghue is a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Amgen, Novartis, Janssen, and AstraZeneca; and has received consulting fees from Amgen, Novartis, Janssen, and AstraZeneca. Dr Albert has received consulting fees from Boston Scientific, Medtronic, Novartis, and Element Science. Dr Morrow is a member of the TIMI Study group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott Laboratories, Amgen, Anthos Therapeutics, Arca Biopharma, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc, Daiichi-Sankyo, Eisai, Intarcia, Janssen, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron, Roche, Siemens, The Medicines Company, and Zora Biosciences; and has received consulting fees from ARCA, InCarda, Inflammatix, Merck, Novartis, and Roche Diagnostics. Dr O’Keefe has a major ownership interest in Cardiotabs (a company that markets supplements including omega-3). Dr Mozaffarian, outside of the submitted work, has received research funding from the Gates Foundation, The Rockefeller Foundation, and the Vail Institute for Global Research; has received personal fees from Acasti Pharma, Barilla, Danone, and Motif FoodWorks; has served on the scientific advisory board of Beren Therapeutics, Brightseed, Calibrate, DayTwo (ended June 20, 2023), Elysium Health, Filtricine, Foodome, HumanCo, January Inc, Perfect Day, Season, and Tiny Organics; has stock ownership in Calibrate and HumanCo; and has chapter royalties from UpToDate. Dr Harris holds stock in OmegaQuant Analytics, LLC (a laboratory that offers blood fatty acid testing); and is on the Scientific Advisory Boards for the Schiff Institute Science and Innovation, Synspira, and the Seafood Nutrition Partnership. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Mycoprotein is a fungal source of protein that is increasingly consumed as an ingredient in meat analogs., Objectives: This study aimed to systematically review and meta-analyze the effects of mycoprotein intake on selected biomarkers of human health., Methods: This study was registered in PROSPERO (CRD42022308980). We searched the PubMed, Scopus, and Embase databases to identify randomized control trials in any language until 16 August, 2022. Trials were included if they administered a mycoprotein intervention against a nonmycoprotein control arm and if reported outcomes included blood lipids, blood glucose, insulin, blood pressure, or body weight. Eligible trials were assessed for risk of bias using the Cochrane risk-of-bias tool for randomized trials. An inverse-variance-weighted, random-effects meta-analysis model was used to assess the effects of intake across each biomarker., Results: Nine trials that included 178 participants with a mean follow-up of 13 d were included, with 4 reporting on blood lipids and 5 reporting on postprandial blood glucose or insulin. The overall reduction of total cholesterol was -0.55 mmol/L (95% CI: -0.85 to -0.26; P < 0.001) in the mycoprotein group compared to control, but no clear effects on HDL cholesterol, LDL cholesterol, or TGs were found (all P > 0.05). There were no reductions in postprandial blood glucose concentrations at 30, 60, 90 or 120 min. Postprandial blood insulin concentration was reduced by -76.51 pmol/L (95% CI: -150.75 to -2.28; P = 0.043) at 30 min, with no detectable effects at 60, 90, or 120 min., Conclusions: Mycoprotein intake may have important effects on blood lipids, but the evidence base is limited by the small sample sizes and short intervention periods of the contributing trials. The protocol for this systematic review has been registered in PROSPERO as CRD42022308980., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

There is now widespread recognition within the world of sleep medicine of the increasing importance of dental sleep medicine and, in particular, the role of oral appliance therapy (OAT) in the management of adults with obstructive sleep apnoea (OSA). For the purpose of this review, the term OAT refers to a custom-made intra-oral appliance, which acts to posture the mandible in a forward and downward direction, away from its natural resting position. Whilst nasally applied continuous positive airway pressure remains the "gold standard" in nonsurgical OSA management, OAT remains the recognised alternative treatment.This review of OAT aims to provide an evidence-based update on our current understanding of their mode of action, exploring the potential anatomical and physiological impact of their use in preventing collapse of the upper airway; the current clinical practice guidelines, including the recently published National Institute of Clinical Excellence 2021 guidance, in conjunction with the American Academy of Sleep Medicine and American Academy of Dental Sleep Medicine; optimal design features, comparing the role of custom-made versus noncustom OAT devices and the importance of titration in achieving a dose-dependent effect; patient predictors, preference and adherence to OAT; its impact on a range of both patient- and clinician-centred health outcomes, with a comparison with CPAP; the limitations and side-effects of providing OAT; and, finally, a look at future considerations to help optimise the delivery and outcomes of OAT., Competing Interests: Conflict of interest: A. Johal reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from British Association of Oral Surgeons and Edinburgh Sleep Medicine Course, outside the submitted work. F.R. Almeida reports grants from American Academy of Dental sleep medicine, outside the submitted work; and receipt of oral appliances at no charge from Somnomed, outside the submitted work. M. Marklund reports payment for a webinar from the European Orthodontic Society, outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Introduction: We conducted a systematic review and meta-analysis to review the relationship between midlife dyslipidemia and lifetime incident dementia., Methods: The databases Medline, Embase, Scopus, Web of Science, and Cochrane were searched from inception to February 20, 2022. Longitudinal studies examining the relationship between midlife lipid levels on dementia, dementia subtypes, and/or cognitive impairment were pooled using inverse-variance weighted random-effects meta-analysis., Results: Seventeen studies (1.2 million participants) were included. Midlife hypercholesterolemia was associated with increased incidence of mild cognitive impairment (effect size [ES] = 2.01; 95% confidence interval [CI] 1.19 to 2.84; I 2 = 0.0%) and all-cause dementia (ES = 1.14; 95% CI: 1.07 to 1.21; I 2 = 0.0%). Each 1 mmol/L increase in low-density lipoprotein was associated with an 8% increase (ES = 1.08, 95% CI: 1.03 to 1.14; I 2 = 0.3%) in incidence of all-cause dementia., Discussion: Midlife dyslipidemia is associated with an increased risk of cognitive impairment in later life., Competing Interests: Author disclosures are available in the supporting information., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Background: In 2021, the World Health Organization (WHO) set sodium benchmarks for packaged foods to guide countries in setting feasible and effective sodium reformulation programs. We modeled the dietary and health impact of full compliance with the WHO's sodium benchmarks in Australia and compared it to the potential impact of Australia's 2020 sodium reformulation targets., Methods: We used nationally representative data on food and sodium intake, sodium levels in packaged foods, and food sales volume to estimate sodium intake pre- and post-implementation of the WHO and Australia's sodium benchmarks for 24 age-sex groups. Using comparative risk assessment models, we then estimated the potential deaths, incidence, and disability-adjusted life years averted from cardiovascular disease, chronic kidney disease, and stomach cancer based on the reductions in sodium intake., Results: Compliance with the WHO's sodium benchmarks for packaged foods in Australia could lower mean adult sodium intake by 404 mg/day, corresponding to a 12% reduction. This could prevent about 1770 deaths/year (95% uncertainty interval 1168-2587), corresponding to 3% of all cardiovascular disease, chronic kidney disease, and stomach cancer deaths in Australia, and prevent some 6900 (4603-9513) new cases, and 25 700 (17 655-35 796) disability-adjusted life years/year. Compared with Australian targets, the WHO benchmarks will avert around 3 and a half times more deaths each year (1770 versus 510)., Conclusions: Substantially greater health impact could be achieved if the Australian government strengthened its current sodium reformulation program by adopting WHO's more stringent and comprehensive sodium benchmarks.

Background: It is unclear whether moderate differences in dietary carbohydrate quantity and quality influence plasma FAs in the lipogenic pathway in healthy adults., Objectives: We investigated the effects of different carbohydrate quantities and quality on plasma palmitate concentrations (primary outcome) and other saturated and MUFAs in the lipogenic pathway., Methods: Twenty healthy participants were randomly assigned, and 18 (50% women; age: 22-72 y; BMI: 18.2-32.7 kg/m 2 and BMI was measured in kg/m 2 ) started the cross-over intervention. During each 3-wk period (separated by a 1-wk washout period), 3 diets were consumed (all foods provided) in random order: low-carbohydrate (LC) (38% energy (E) carbohydrates, 25-35 g fiber/d, 0% E added sugars); high-carbohydrate/high-fiber (HCF) (53% E carbohydrates, 25-35 g fiber/d, 0% E added sugars); and high-carbohydrate/high-sugar (HCS) (53% E carbohydrates, 19-21 g fiber/d, 15% E added sugars). Individual FAs were measured proportionally to total FAs by GC in plasma cholesteryl esters, phospholipids, and TGs. False discovery rate-adjusted repeated measures ANOVA [ANOVA-false discovery rate (FDR)] was used to compare outcomes., Results: The self-reported intakes of carbohydrates and added- and free sugars were; 30.6% E and 7.4% E in LC, 41.4% E and 6.9% E in HCF, and 45.7% E and 10.3% in HCS. Plasma palmitate did not differ between the diet periods (ANOVA FDR P > 0.43, n = 18). After HCS, myristate concentrations in cholesterol esters and phospholipids were ≥19% higher than LC and ≥22% higher than HCF (P = 0.005). After LC, palmitoleate in TG was 6% lower compared with HCF and 7% compared with HCS (P = 0.041). Body weight differed (≤0.75 kg) between diets before FDR correction., Conclusions: Different carbohydrate quantity and quality do not influence plasma palmitate concentrations after 3 wk in healthy Swedish adults, whereas myristate increased after the moderately higher intake of carbohydrate/high-sugar, but not carbohydrate/high-fiber. Whether plasma myristate is more responsive than palmitate to differences in carbohydrate intake requires further study, especially considering that participants deviated from the planned dietary targets. J Nutr 20XX;xx:xx-xx. This trial was registered at clinicaltrials.gov as NCT03295448., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In most African countries, the prevalence of industrially produced trans -fatty acids (iTFA) in the food supply is unknown. We estimated the number and proportion of products containing specific (any hydrogenated edible oils) and non-specific (vegetable fat, margarine, and vegetable cream) ingredients potentially indicative of iTFAs among pre-packaged foods collected in Kenya and Nigeria. We also summarized the number and proportion of products that reported trans -fatty acids levels and the range of reported trans -fatty acids levels. In total, 99 out of 5668 (1.7%) products in Kenya and 310 out of 6316 (4.9%) products in Nigeria contained specific ingredients indicative of iTFAs. Bread and bakery products and confectioneries in both countries had the most foods that contained iTFAs-indicative ingredients. A total of 656 products (12%) in Kenya and 624 products (10%) in Nigeria contained non-specific ingredients that may indicate the presence of iTFAs. The reporting of levels of trans- fatty acids was low in both Kenya and Nigeria (11% versus 26%, respectively, p < 0.001). With the increasing burden of ischemic heart disease in Kenya and Nigeria, the rapid adoption of WHO best-practice policies and the mandatory declaration of trans- fatty acids are important for eliminating iTFAs.

Objective: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD)., Design: Pooled analysis., Data Sources: A consortium of 19 studies from 12 countries identified up to May 2020., Study Selection: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate., Data Extraction and Synthesis: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis., Main Outcome Measures: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m 2 . In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m 2 and <75% of baseline rate., Results: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I 2 =9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I 2 =0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I 2 =5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m 2 ), hypertension, diabetes, and coronary heart disease at baseline., Conclusions: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest and declare: support from Australian National Health and Medical Research Council Career Development Fellowship and the University of New South Wales Safety Net Fellowship for the submitted work; MM reports research funding from Resolve to Save Lives, World Health Organisation and North western University, and support as invited speaker in the Nordic Dairy Congress 2022. CMR and LMS report research funding from the US National Institute of Health (NIH). CMR reports participation on the Data Safety Monitoring Boards of the SUPER and ADEPT trials and leadership role as associate editor of Diabetes Care. ACvW reports research funding from Jaap Schouten Foundation. JMG reports research funding from Jaap Schouten Foundation, EU Horizon 2020, and Ministry of Health, Welfare and Sports, The Netherlands, and leadership role as the Vice President of the Dutch Health Council. EKH reports research funding from Dutch Kidney Foundation. FI and NGF receive the MRC Epidemiology Unit core support. NGF reports research fundings from the NIHR Cambridge Biomedical Research Centre Theme on Nutrition, Diet and Lifestyle. JT declares conference support from the University of Antioquia, Colombia and possession of stocks from Orion Pharma. MU declares possession of stocks from Orion Pharma. WSH declares possession of stock in OmegaQuant Analytics, LLC (a laboratory that offers blood fatty acid testing to healthcare providers, researchers and consumers). PSS reports research funding from the National Health and Medical Research Council of Australia and honoraria from Biogen Australia and Roche Australia. ACW reports research funding from the US Department of Agriculture/Agricultural Research Service, NIH, National Cattlemen’s Beef Association and Hass Avocado Board Avocado Nutrition Research Center. JA has received research honoraria for lectures from AstraZeneca and Novartis, and has participated in the advisory board for AstraZeneca and Boerhinger Ingelheim, unrelated to the present study. UR reports research funding from Swedish Research Council Forma and Swedish Diabetes Foundation. RM reports research funding from the US NIH, Gates Foundation, Nestle and Danone, and consulting fees from Development Initiatives with leadership role as chair of the Independent Expert Group, Global Nutrition Report. AT declares as co-chair of ClinGen Gout Genetic Curation Panel and reports research funding from the US National Institute of Health; AK reports research funding from the German Research Foundation. DM reports research funding from the US NIH, the Gates Foundation, The Rockefeller Foundation, Vail Innovative Global Research, and the Kaiser Permanente Fund at East Bay Community Foundation; personal fees from Acasti Pharma and Barilla; scientific advisory board, Beren Therapeutics, Brightseed, Calibrate, Elysium Health, Filtricine, HumanCo, Instacart, January Inc., Perfect Day, Tiny Organics, and (ended) Day Two, Discern Dx, and Season Health; stock ownership in Calibrate and HumanCo; and chapter royalties from UpToDate. No other relationships or activities that could appear to have influenced the submitted work were reported., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

We examined the prevalence and magnitude of price promotions among purchases of packaged foods and beverages in Australia, as well as the contribution of price-promoted foods and beverages to apparent energy intake. We utilized grocery purchase data from a nationally representative panel of 10 000 households in 2019 (NielsenIQ Homescan panel), combined with a food nutrition dataset (FoodSwitch). Nutritional quality was defined using the Australian and New Zealand Health Star Rating (HSR), where products with an HSR <3.5 were classified as 'less healthy' and products with an HSR ≥3.5 were classified as 'healthy'. Apparent energy intake was expressed as the total energy content of all purchased products per day per capita. Price promotions were claimed by panel members. Overall, four-in-ten packaged products (41%) were purchased on price promotion. Compared to 'healthy' products, 'less healthy' products were more frequently purchased on price promotion (33% vs 48%, respectively, p < 0.001), but had a similar mean magnitude of price discount (both 22%). Low socio-economic status (SES) households consumed 18% more energy from 'less healthy' packaged products on price promotion than high SES households (1141 vs 970 kJ/day/capita, p < 0.001). In conclusion, restricting price promotions for 'less healthy' packaged foods and beverages could potentially improve diet quality and dietary inequalities in Australia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The worldwide control rate for hypertension is dismal. An inadequate number of physicians to treat patients with hypertension is one key obstacle. Innovative health system approaches such as delegation of basic tasks to non-physician health workers (task-sharing) might alleviate this problem. Massive scale up of population-wide hypertension management is especially important for low- and middle-income countries such as India., Methods: Using constrained optimization models, we estimated the hypertension treatment capacity and salary costs of staff involved in hypertension care within the public health system of India and simulated the potential effects of (1) an increased workforce, (2) greater task-sharing among health workers, and (3) extended average prescription periods that reduce treatment visit frequency (e.g., quarterly instead of monthly)., Findings: Currently, only an estimated 8% (95% uncertainty interval 7%-10%) of ∼245 million adults with hypertension can be treated by physician-led services in the Indian public health system (assuming the current number of health workers, no greater task-sharing, and monthly visits for prescriptions). Without task-sharing and with continued monthly visits for prescriptions, the least costly workforce expansion to treat 70% of adults with hypertension would require ∼1.6 (1.0-2.5) million additional staff (all non-physicians), with ∼INR 200 billion (≈USD 2.7 billion) in additional annual salary costs. Implementing task-sharing among health workers (without increasing the overall time on hypertension care) or allowing a 3-month prescription period was estimated to allow the current workforce to treat ∼25% of patients. Joint implementation of task-sharing and a longer prescription period could treat ∼70% of patients with hypertension in India., Interpretation: The combination of greater task-sharing and extended prescription periods could substantially increase the hypertension treatment capacity in India without any expansion of the current workforce in the public health system. By contrast, workforce expansion alone would require considerable, additional human and financial resources., Funding: Resolve to Save Lives, an initiative of Vital Strategies, was funded by grants from Bloomberg Philanthropies; the Bill and Melinda Gates Foundation; and Gates Philanthropy Partners (funded with support from the Chan Zuckerberg Foundation)., Competing Interests: All authors have completed the ICMJE uniform disclosure form and declare: MM, RC, PP, DN, LJA, and KM, report funding from Resolve to Save Lives for the present work. MM and RC report grant support from World Health Organization, outside of the present work. RC also reports grant support from Bloomberg Philanthropies and Pan-American Health Organization; travel support from Bloomberg Philanthropies and Carey Business School, Johns Hopkins University; and honorarium from Foreign Affairs; all outside the present work. LJA reports honoraria from UpToDate, outside the present work., (© 2022 Published by Elsevier Ltd.)

Background: Consumption of ultra-processed foods is associated with increased risk of obesity and non-communicable diseases. Little is known about current patterns of ultra-processed foods intake in Australia. The aim of this study was to examine the amount and type of ultra-processed foods purchased by Australian households in 2019 and determine whether purchases differed by socio-economic status (SES). We also assessed whether purchases of ultra-processed foods changed between 2015 and 2019.  METHODS: We used grocery purchase data from a nationally representative consumer panel in Australia to assess packaged and unpackaged grocery purchases that were brought home between 2015 to 2019. Ultra-processed foods were identified according to the NOVA system, which classifies foods according to the nature, extent and purpose of industrial food processing. Purchases of ultra-processed foods were calculated per capita, using two outcomes: grams/day and percent of total energy. The top food categories contributing to purchases of ultra-processed foods in 2019 were identified, and differences in ultra-processed food purchases by SES (Index of Relative Social Advantage and Disadvantage) were assessed using survey-weighted linear regression. Changes in purchases of ultra-processed foods between 2015 to 2019 were examined overall and by SES using mixed linear models., Results: In 2019, the mean ± SD total grocery purchases made by Australian households was 881.1 ± 511.9 g/d per capita. Of this, 424.2 ± 319.0 g/d per capita was attributable to purchases of ultra-processed foods, which represented 56.4% of total energy purchased. The largest food categories contributing to total energy purchased included mass-produced, packaged breads (8.2% of total energy purchased), chocolate and sweets (5.7%), biscuits and crackers (5.7%) and ice-cream and edible ices (4.3%). In 2019, purchases of ultra-processed foods were significantly higher for the lowest SES households compared to all other SES quintiles (P < 0.001). There were no major changes in purchases of ultra-processed foods overall or by SES over the five-year period., Conclusions: Between 2015 and 2019, ultra-processed foods have consistently made up the majority of groceries purchased by Australians, particularly for the lowest SES households. Policies that reduce ultra-processed food consumption may reduce diet-related health inequalities., (© 2022. The Author(s).)

Background: Salt substitution (ie, replacement of table and cooking salt with potassium-enriched salt substitutes) is a promising strategy to reduce blood pressure and prevent cardiovascular disease, particularly in countries like India where there is high sodium intake, mainly from discretionary salt, and low potassium intake. Life-threatening hyperkalemia from increased potassium intake is a postulated concern for individuals with chronic kidney disease., Methods: We used comparative risk assessment models to estimate the number of (1) cardiovascular deaths averted due to blood pressure reductions; (2) potential hyperkalemia-related deaths from increased potassium intake in individuals with advanced chronic kidney disease; and (3) net averted deaths from nationwide salt substitution in India. We evaluated a conservative scenario, based on a large, long-term pragmatic trial in rural China; and an optimistic scenario informed by our recent trial in India. Sensitivity analyses were conducted to assess the robustness of the findings., Results: In the conservative scenario, a nationwide salt substitution intervention was estimated to result in ≈214 000 (95% uncertainty interval, 92 764-353 054) averted deaths from blood pressure reduction in the total population and ≈52 000 (22 961-80 211) in 28 million individuals with advanced chronic kidney disease, while ≈22 000 (15 221-31 840) hyperkalemia-deaths might be caused by the intervention. The corresponding estimates for the optimistic scenario were ≈351 000 (130 470-546 255), ≈66 000 (24 925-105 851), and ≈9000 (4251-14 599). Net benefits were consistent across sensitivity analyses., Conclusions: Modeling nationwide salt substitution in India consistently estimated substantial net benefits, preventing around 8% to 14% of annual cardiovascular deaths. Even allowing for potential hyperkalemia risks there were net benefits estimated for individuals with chronic kidney disease.

The purpose of this paper is to evaluate the quality of information and guidance on dietary sodium reduction available on consumer-facing websites. Google Trends was used to identify the five most-used search terms related to dietary sodium reduction. For each term, websites on the first two pages were collected (n = 18-20). Of 93 websites collected, 24 were excluded due to defective links, duplicate websites, or not being consumer-focused. The remaining 69 websites were evaluated using a novel instrument, JHU-SALT, that includes 14 questions on topics related to salt reduction. The questions are grouped into three domains ("information," "guidance," and "accuracy"). For each question, websites were scored using a 3-step ordinal scale ("topic not addressed," "topic somewhat addressed," or "topic addressed adequately"). Only three of 14 JHU-SALT questions were addressed adequately by a majority of websites. Many websites provided information on the adverse health effects of a high sodium diet (74%, n = 51) or mentioned intake recommendations (64%, n = 44). Information on fundamental concepts was largely missing. The majority of websites (80%, n = 55) provided information on lifestyle strategies to reduce blood pressure, but most did not provide guidance to help implement those strategies. While missing information was common, misinformation was uncommon. The DISCERN questionnaire was utilized as well. Consumers seeking information and guidance on dietary sodium reduction will find that most available websites provide accurate but limited information, and insufficient guidance on how to lower sodium intake. Websites that provide both relevant information and guidance are needed to help consumers effectively reduce dietary sodium., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Objectives: The Salt Substitute and Stroke Study (SSaSS) recently reported blood pressure-mediated benefits of a potassium-enriched salt substitute on cardiovascular outcomes and death. This study assessed the effects of salt substitutes on a breadth of outcomes to quantify the consistency of the findings and understand the likely generalisability of the SSaSS results., Methods: We searched PubMed, Embase and the Cochrane Library up to 31 August 2021. Parallel group, step-wedge or cluster randomised controlled trials reporting the effect of salt substitute on blood pressure or clinical outcomes were included. Meta-analyses and metaregressions were used to define the consistency of findings across trials, geographies and patient groups., Results: There were 21 trials and 31 949 participants included, with 19 reporting effects on blood pressure and 5 reporting effects on clinical outcomes. Overall reduction of systolic blood pressure (SBP) was -4.61 mm Hg (95% CI -6.07 to -3.14) and of diastolic blood pressure (DBP) was -1.61 mm Hg (95% CI -2.42 to -0.79). Reductions in blood pressure appeared to be consistent across geographical regions and population subgroups defined by age, sex, history of hypertension, body mass index, baseline blood pressure, baseline 24-hour urinary sodium and baseline 24-hour urinary potassium (all p homogeneity >0.05). Metaregression showed that each 10% lower proportion of sodium choloride in the salt substitute was associated with a -1.53 mm Hg (95% CI -3.02 to -0.03, p=0.045) greater reduction in SBP and a -0.95 mm Hg (95% CI -1.78 to -0.12, p=0.025) greater reduction in DBP. There were clear protective effects of salt substitute on total mortality (risk ratio (RR) 0.89, 95% CI 0.85 to 0.94), cardiovascular mortality (RR 0.87, 95% CI 0. 81 to 0.94) and cardiovascular events (RR 0.89, 95% CI 0.85 to 0.94)., Conclusions: The beneficial effects of salt substitutes on blood pressure across geographies and populations were consistent. Blood pressure-mediated protective effects on clinical outcomes are likely to be generalisable across population subgroups and to countries worldwide., Trial Registration Number: CRD42020161077., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyze tumor heterogeneity in needle biopsies collected before and after treatment with androgen deprivation therapy. By doing so, we are able to couple clinical responsiveness and morphological information such as Gleason score to transcriptome-wide data. Our data-driven analysis of transcriptomes identifies several distinct intratumoral cell populations, characterized by their unique gene expression profiles. Certain cell populations present before treatment exhibit gene expression profiles that match those of resistant tumor cell clusters, present after treatment. We confirm that these clusters are resistant by the localization of active androgen receptors to the nuclei in cancer cells post-treatment. Our data also demonstrates that most stromal cells adjacent to resistant clusters do not express the androgen receptor, and we identify differentially expressed genes for these cells. Altogether, this study shows the potential to increase the power in predicting resistant tumors., (© 2022. The Author(s).)

Background: High carbohydrate, i.e., sugars, intake potentially drives the liver into a lipogenic state leading to elevated plasma fatty acids. Excessive intake of saturated fat and sugar-sweetened soda induces liver fat accumulation, but studying the effect of high intake from sugar-sweetened soda on the de novo lipogenesis (DNL) fatty acids in long-term randomized trials is lacking., Objective: To study the effect of consuming 1 L/day of sugar-sweetened soda, semi-skimmed milk (milk), aspartame-sweetened soda or water over 24 weeks on DNL-derived fatty acids (i.e., palmitate (primary outcome) and other saturated and monounsaturated fatty acids), and markers of stearoyl-CoA desaturase activity (SCD1) in plasma phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG)., Design and Methods: A randomized parallel study was conducted simultaneously at Aarhus University Hospital and Copenhagen University, Denmark, including ( n = 41) individuals aged 20-50 years, with BMI of 26-40 kg/m 2 , and without diabetes. The groups consisted of 9 individuals in the sugar-sweetened soda, 10 in the milk, 11 in the aspartame-sweetened soda, and 11 in the water. The change at 24 weeks was assessed and compared across the groups using ANCOVA and mixed-effects models. Correlations of fatty acid changes with liver fat accumulation (magnetic resonance imaging) were explored., Results: After 24 weeks, the groups differed in palmitate proportions in PL, oleate in CE and PL, and palmitoleate and SCD1 in all fractions ( p < 0.05). Compared with water, the relative proportion of palmitate in PL increased by approximately 1% during both sugar-sweetened soda ( p = 0.011) and milk ( p = 0.006), whereas oleate and palmitoleate increased only during sugar-sweetened soda (CE 2.77%, p < 0.001; PL 1.51%, p = 0.002 and CE 1.46%, PL 0.24%, TG 1.31%, all p < 0.001, respectively). Liver fat accumulation correlated consistently with changes in palmitoleate, whereas correlations with palmitate and oleate were inconsistent across lipid fractions., Conclusions: Although both sugar-sweetened soda and milk increased palmitate in PL, only excess intake of sugar-sweetened soda increased palmitoleate in all lipid fractions and correlated with liver fat. In contrast, isocaloric milk intake did not increase plasma monounsaturated fatty acids., Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT00777647], identifier [NCT00777647]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bajahzer, Bruun, Rosqvist, Marklund, Richelsen and Risérus.)

Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer 1 . Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics 2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy., (© 2022. The Author(s).)

Obstructive sleep apnoea is a challenging medical problem due to its prevalence, its impact on quality of life and performance in school and professionally, the implications for risk of accidents, and comorbidities and mortality. Current research has carved out a broad spectrum of clinical phenotypes and defined major pathophysiological components. These findings point to the concept of personalised therapy, oriented on both the distinct clinical presentation and the most relevant pathophysiology in the individual patient. This leads to questions of whether sufficient therapeutic options other than positive airway pressure (PAP) alone are available, for which patients they may be useful, if there are specific indications for single or combined treatment, and whether there is solid scientific evidence for recommendations. This review describes our knowledge on PAP and non-PAP therapies to address upper airway collapsibility, muscle responsiveness, arousability and respiratory drive. The spectrum is broad and heterogeneous, including technical and pharmaceutical options already in clinical use or at an advanced experimental stage. Although there is an obvious need for more research on single or combined therapies, the available data demonstrate the variety of effective options, which should replace the unidirectional focus on PAP therapy., Competing Interests: Conflict of interest: W. Randerath reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Weinmann, Heinen & Löwenstein, Resmed, Jazz Pharmaceuticals, Inspire, Philips Respironics, Bioprojet, and Vanda Pharma; and support for attending meetings and/or travel received from Heinen & Löwenstein, Resmed, Jazz Pharmaceuticals, Inspire, Philips Respironics and Bioprojet; participation on a data safety monitoring or advisory board for Bioprojet, Jazz Pharmaceuticals and Philips Respironics. He is Head of European Respiratory Society Assembly 4 (Sleep Disordered Breathing) and an associate editor of this journal. J. Steier is a named inventor on a patent for KCL/GSTT (Apparatus for treatment of snoring and sleep apnoea; WO2016124739A1) outside the submitted work. J. Verbraecken reports grants or contracts received from Philips Respironics, Heinen & Löwenstein, ResMed, Total Care, Fisher & Paykel, Bioprojet, Jazz Pharmaceutics, AirLiquide, Total Care, Westfalen Medical, Somnomed, Medidis, Wave Medical, OSG, Mediq Tefa, NightBalance, Accuramed, Bekaert Deslee Academy, UCB Pharma, Vivisol and Inspire Medical Systems, outside the submitted work; consulting fees received from Vemedia; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events received from Sanofi, Agfa-Gevaert, Astra-Zeneca, TotalCare, Springer and OSA Academy; support for attending meetings and/or travel received from Bioprojet; participation on a data safety or advisory board for Bioprojet, Oxford Pharmagenesis, Idorsia, MSD and Desitin. He was President (until August 2021) and is Past President of the Belgian Association for Sleep Research and Sleep medicine (since September 2021), and is an associate editor of this journal. The remaining authors have nothing to disclose., (Copyright ©The authors 2022.)

Consumption of trans fatty acids (TFA) is associated with adverse health outcomes and is a considerable burden on morbidity and mortality globally. TFA may be generated by common cooking practices and hence contribute to daily dietary intake. We performed a systematic review and meta-analysis to investigate the relationship between heating edible oils and change in their TFA content. A systematic search of experimental studies investigating the effect of various methods of heating on TFA content of edible oils was conducted in Medline and Embase since their inception up to 1 October 2020 without language restrictions. Comparable data were analysed using mixed multilevel linear models taking into account individual study variation. Thirty-three studies encompassing twenty-one different oils were included in this review. Overall, heating to temperatures <200 °C had no appreciable impact on different TFA levels. Between 200 and 240 °C, levels of C18:2 t (0.05% increase per 10 °C rise in temperature, 95% CI: 0.02 to 0.05%), C18:3t (0.18%, 95% CI: 0.14 to 0.21%), and total TFA (0.38%, 95% CI: 0.20 to 0.55%) increased with temperature. A further increase in total TFA was observed with prolonged heating between 200 and 240 °C. Our findings suggest that heating edible oils to common cooking temperatures (≤200 °C) has minimal effect on TFA generation whereas heating to higher temperatures can increase TFA level. This provides further evidence in favour of public health advice that heating oils to very high temperatures and prolonged heating of oils should be avoided.

Objective: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis., Research Design and Methods: We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged ≥18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics., Results: During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P ≥ 0.1)., Conclusions: Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels., (© 2022 by the American Diabetes Association.)

Background: n-3 and n-6 PUFAs have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters., Objectives: We sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium., Methods: Harmonized, de novo, individual-level analyses were performed and pooled across 12 cohorts. Participants were 35-96 y old and from 5 nations. Circulating measures included α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), DHA, EPA + DPA + DHA, linoleic acid, and arachidonic acid. Sleep duration (10 cohorts, n = 18,791) was categorized as short (≤6 h), 7-8 h (reference), or long (≥9 h). Difficulty falling asleep (8 cohorts, n = 12,500) was categorized as yes or no. Associations between PUFAs, sleep duration, and difficulty falling sleeping were assessed by cross-sectional multinomial logistic regression using standardized protocols and covariates. Cohort-specific multivariable-adjusted ORs per quintile of PUFAs were pooled with inverse-variance weighted meta-analysis., Results: In pooled analysis adjusted for sociodemographic characteristics and health status, participants with higher very long-chain n-3 PUFAs were less likely to have long sleep duration. In the top compared with the bottom quintiles, the multivariable-adjusted ORs (95% CIs) for long sleep were 0.78 (95% CI: 0.65, 0.95) for DHA and 0.76 (95% CI: 0.63, 0.93) for EPA + DPA + DHA. Significant associations for ALA and n-6 PUFA with short sleep duration or difficulty falling sleeping were not identified., Conclusions: Participants with higher concentrations of very long-chain n-3 PUFAs were less likely to have long sleep duration. While objective biomarkers reduce recall bias and misclassification, the cross-sectional design limits assessment of the temporal nature of this relation. These novel findings across 12 cohorts highlight the need for experimental and biological assessments of very long-chain n-3 PUFAs and sleep duration., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: The Australian Government will soon be releasing a series of sugar reformulation targets for packaged foods., Objective: To estimate the amount of added sugar purchased from packaged food and beverages and the relative contribution that food categories and food companies made to these purchases in 2018. The secondary objective was to examine differences in purchases of added sugar across income levels., Design: Cross-sectional study., Participants/setting: We used 1 year of grocery purchase data from a nationally representative panel of Australian households (the NielsenIQ Homescan panel), combined with a packaged food and beverage database (FoodSwitch)., Main Outcome Measures: Added sugar purchases (grams per day per capita), purchase-weighted added sugar content (grams per 100 g) and total weight of products (with added sugar) purchased (grams per day per capita)., Statistical Analyses Performed: Food categories and food companies were ranked according to their contribution to added sugar purchases. Differences in added sugar purchases by income levels were assessed by 1-factor analysis of variance., Results: Added sugar information was available from 7188 households and across 26,291 unique foods and beverages. On average, the amount of added sugar acquired from packaged foods and beverages was (mean ± SE) 35.9 ± 0.01 g/d per capita. Low-income households purchased 11.0 g/d (95% CI: 10.9-11.0 g/d, P < .001) more added sugar from packaged products than high-income households per capita. The top 10 food categories accounted for 82.2% of added sugar purchased, largely due to purchases of chocolate and sweets, soft drinks, and ice cream and edible ices. Out of 994 food companies, the top 10 companies contributed to 62.1% of added sugar purchases., Conclusions: The Australian Government can strengthen their proposed sugar reduction program by adding further category-specific targets, prioritizing engagement with key food companies and considering a broader range of policies to reduce added sugar intakes across the Australian population., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Despite medical, dietary, and lifestyle recommendations and drug advancements, hypertension persists as among the most prevalent noncommunicable diseases in the US population, and control remains elusive. Uncontrolled hypertension may increase the risk of serious illness from various other health challenges, including cardiovascular and renal responses. Adoption of a healthy diet is a consistent core element of lifestyle modifications that are recommended for mitigation of hypertension. The dietary sodium-to-potassium ratio is recognized as having promising potential in the regulation of blood pressure. In fact, the understanding of the relation between this ratio and blood pressure was documented as a key evidence gap in the 2019 National Academies of Sciences, Engineering, and Medicine report that revised recommended intake levels for both sodium and potassium. Although notable animal and human evidence supports this point, fundamental to developing a specific dietary recommendation for a sodium-to-potassium ratio is a well-designed human intervention trial. The successful translatability of such a trial will require careful consideration of study elements, including the study population, duration, blood pressure measurement, and dietary intervention, among other factors. This paper addresses these decision points and serves as supporting documentation for a research group or organization with the interest and means to address this important data gap, which will undoubtedly be foundational for advancing dietary guidance and would inform the next iteration of Dietary Reference Intakes for sodium and potassium., (Published by Oxford University Press on behalf of the American Society for Nutrition 2021.)

Guidelines for the evaluation and management of sleep disorders from national societies provide recommendations that may be regionally appropriate but may not always be practical or relevant in other parts of the world. A task force of experts from the World Sleep Society's (WSS) International Sleep Medicine Guidelines Committee and Sleep and Breathing Disorders Taskforce reviewed the American Academy of Sleep Medicine's Clinical Practice Guideline on the Treatment of Adult Obstructive Sleep Apnea (OSA) with Positive Airway Pressure with respect to its relevance and applicability to the practice of sleep medicine by sleep specialists in various regions of the world. To improve the evaluation of the guideline, surveys were sent by the senior author and the WSS to approximately 800 sleep doctors around the world to query the availability of OSA treatments in their respective region. The task force and the WSS guidelines committee endorsed the AASM's CPAP guidelines with respect to the indications for PAP therapy, utilization of different PAP modalities, and concurrent strategies to improve outcomes, noting appropriate caveats for universal applicability., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Treatment of obstructive sleep apnoea (OSA) in adults is evolving, as new therapies have been explored and introduced in clinical practice, while other approaches have been refined or reconsidered. In this European Respiratory Society (ERS) guideline on non-continuous positive airway pressure (CPAP) therapies for OSA, we present recommendations determined by a systematic review of the literature. It is an update of the 2011 ERS statement on non-CPAP therapies, advanced into a clinical guideline. A multidisciplinary group of experts, including pulmonary, surgical, dentistry and ear-nose-throat specialists, methodologists and patient representatives considered the most relevant clinical questions (for both clinicians and patients) relating to the management of OSA. Eight key clinical questions were generated and a systematic review was conducted to identify published randomised clinical trials that answered these questions. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the quality of the evidence and the strength of recommendations. The resulting guideline addresses gastric bypass surgery, custom-made dual-block mandibular advancement devices, hypoglossal nerve stimulation, myofunctional therapy, maxillo-mandibular osteotomy, carbonic anhydrase inhibitors and positional therapy. These recommendations can be used to benchmark quality of care for people with OSA across Europe and to improve outcomes., Competing Interests: Conflicts of Interest: W. Randerath reports personal fees received from Weinmann, Heinen & Löwenstein, Resmed, Inspire, Philips Respironics, and Bioprojet, outside the submitted work. Conflicts of interest: J. Verbraecken reports receiving payments to institution for lectures, presentations, speakers bureaus, manuscript writing or educational events from SomnoMed and Inspire Medical Systems, outside the submitted work. Participation on a Data Safety Monitoring Board or Advisory Board for ResMed Narval, payments to institution, outside the submitted work. Conflicts of interest: C.A.L. de Raaff has nothing to disclose. Conflicts of interest: J. Heder reports grants received from ResMed, outside the submitted work. Lecture fees from Bayer Pharma and Jazz Pharmaceuticals outside the submitted work. Patent filed and granted for Pharmacological therapy in OSA. Participation on a data safety monitoring board or advisory board for DSMB. Conflicts of interest: S. Herkenrath has nothing to disclose. Conflicts of interest: W. Hohenhorst has nothing to disclose. Conflicts of interest: T. Jakob has nothing to disclose. Conflicts of interest: O. Marrone has nothing to disclose. Conflicts of interest: M. Marklund has nothing to disclose. Conflicts of interest: W.T. McNicholas has nothing to disclose. Conflicts of interest: R.L. Morgan has nothing to disclose. Conflicts of interest: J-L. Pépin reports grants and research funds from (payments made to the institutions) Air Liquide Foundation, Agiradom, AstraZeneca, Fisher and Paykel, Mutualia, Philips, Resmed and Vitalaire, outside the submitted work. Consulting fees from: Agiradom, AstraZeneca, Boehringer Ingelheim, Jazz pharmaceutical, Night Balance, Philips, Resmed, and Sefam, outside the submitted work. Conflicts of interest: S. Schiza has nothing to disclose. Conflicts of interest: N. Skoetz reports support for the present manuscript from the European Respiratory Society. Personal payments received from Cochrane outside the submitted work. Conflicts of interest: D. Smyth has nothing to disclose. Conflicts of interest: J. Steier reports receiving grants from the British Lung Foundation, outside the submitted work. Payments of honoraria received from Jazz Pharmaceuticals and Sanofi. Named inventor on pending patent WO2016124739A1. President of the British Sleep Society. Conflicts of interest: T. Tonia acts as an ERS methodologist. Conflicts of interest: W. Trzepizur has nothing to disclose. Conflicts of interest: P-H. van Mechelen has nothing to disclose. Conflicts of interest: P. Wijkstra has nothing to disclose., (Copyright ©The authors 2021.)

Sodium and potassium appear to interact with each other in their effects on blood pressure with potassium supplementation having a greater blood pressure lowering-effect when sodium intake is high. Whether the effect of sodium reduction on blood pressure varies according to potassium intake levels is unclear. We carried out a systematic review and meta-analysis to examine the impact of baseline potassium intake on blood pressure response to sodium reduction in randomized trials in adult populations, with sodium and potassium intake estimated from 24-h urine samples. We included 68 studies involving 5708 participants and conducted univariable and multivariable meta-regression. The median intake of baseline potassium was 67.7 mmol (Interquartile range: 54.6-76.4 mmol), and the mean reduction in sodium intake was 128 mmol (95% CI: 107-148). Multivariable meta-regression that included baseline 24-h urinary potassium excretion, age, ethnicity, baseline blood pressure, change in 24-h urinary sodium excretion, as well as the interaction between baseline 24-h urinary potassium excretion and change in 24-h urinary sodium excretion did not identify a significant association of baseline potassium intake levels with the blood pressure reduction achieved with a 50 mmol lowering of sodium intake (p > 0.05 for both systolic and diastolic blood pressure). A higher starting level of blood pressure was consistently associated with a greater blood pressure reduction from reduced sodium consumption. However, the nonsignificant findings may subject to the limitations of the data available. Additional studies with more varied potassium intake levels would allow a more confident exclusion of an interaction., (© 2021. Crown.)

Background: Countries around the world are putting in place sugar reformulation targets for packaged foods to reduce excess sugar consumption. The Australian government released its voluntary sugar reformulation targets for nine food categories in 2020. We estimated the potential impact of these targets on household sugar purchases and examined differences by income. For comparison, we also modelled the potential impact of the UK sugar reduction targets on per capita sugar purchases as the UK has one of the most comprehensive sugar reduction strategies in the world., Methods: Grocery purchase data from a nationally representative consumer panel (n=7,188) in Australia was linked with a large database (FoodSwitch) with product-specific sugar content information for packaged foods (n=25,261); both datasets were collected in 2018. Potential reductions in per capita sugar purchases were calculated overall and by food category. Differences in sugar reduction across income level were assessed by analysis of variance., Results: In 2018, the total sugar acquired from packaged food and beverage purchases consumed at-home was 56.1 g/day per capita. Australia's voluntary reformulation targets for sugar covered 2,471/25,261 (9.8%) unique products in the FoodSwitch dataset. Under the scenario that all food companies adhered to the voluntary targets, sugar purchases were estimated to be reduced by 0.9 g/day per capita, which represents a 1.5% reduction in sugar purchased from packaged foods. However, if Australia adopted the UK targets, over twice as many products would be covered (n=4,667), and this would result in a more than four times greater reduction in sugar purchases (4.1 g/day per capita). It was also estimated that if all food companies complied with Australia's voluntary sugar targets, reductions to sugar would be slightly greater in low-income households compared with high-income households by 0.3 g/day (95%CI 0.2 - 0.4 g/day, p<0.001)., Conclusions: Sugar-reduction policies have the potential to substantially reduce population sugar consumption and may help to reduce health inequalities related to excess sugar consumption. However, the current reformulation targets in Australia are estimated to achieve only a small reduction to sugar intakes, particularly in comparison to the UK's sugar reduction program., (© 2021. The Author(s).)

Background: The Australian Government recently established sodium targets for packaged foods to encourage voluntary reformulation to reduce population sodium consumption and related diseases. We modeled the health impact of Australia's sodium reformulation targets and additional likely health gains if more ambitious, yet feasible sodium targets had been adopted instead., Methods and Findings: Using comparative risk assessment models, we estimated the averted deaths, incidence, and disability-adjusted life years (DALYs) from cardiovascular disease (CVD), chronic kidney disease (CKD) and stomach cancer after implementation of (a) Australia's sodium targets (overall and by individual companies); (b) United Kingdom's targets (that covers more product categories); and (c) an optimistic scenario (sales-weighted 25th percentile sodium content for each food category included in the UK program). We used nationally representative data to estimate pre- and post-intervention sodium intake, and other key data sources from the Global Burden of Disease study. Full compliance with the Australian government's sodium targets could prevent approximately 510 deaths/year (95% UI, 335 to 757), corresponding to about 1% of CVD, CKD, and stomach cancer deaths, and prevent some 1,920 (1,274 to 2,600) new cases and 7,240 (5,138 to 10,008) DALYs/year attributable to these diseases. Over half (59%) of deaths prevented is attributed to reformulation by 5 market-dominant companies. Compliance with the UK and optimistic scenario could avert approximately an additional 660 (207 to 1,227) and 1,070 (511 to 1,856) deaths/year, respectively, compared to Australia's targets. The main limitation of this study (like other modeling studies) is that it does not prove that sodium reformulation programs will prevent deaths and disease events; rather, it provides the best quantitative estimates and the corresponding uncertainty of the potential effect of the different programs to guide the design of policies., Conclusions: There is significant potential to strengthen Australia's sodium reformulation targets to improve its health impact. Promoting compliance by market-dominant food companies will be critical to achieving the potential health gains., Competing Interests: The authors have declared that no competing interests exist.

Background: High intake of added sugar is linked to weight gain and cardiometabolic risk. In 2018, the US National Salt and Sugar Reduction Initiative proposed government-supported voluntary national sugar reduction targets. This intervention's potential effects and cost-effectiveness are unclear., Methods: A validated microsimulation model, CVD-PREDICT (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends), coded in C++, was used to estimate incremental changes in type 2 diabetes, cardiovascular disease (CVD), quality-adjusted life-years (QALYs), costs, and cost-effectiveness of the US National Salt and Sugar Reduction Initiative policy. The model was run at the individual level, incorporating the annual probability of each person's transition between health statuses on the basis of risk factors. The model incorporated national demographic and dietary data from the National Health and Nutrition Examination Survey across 3 cycles (2011 through 2016), added sugar-related diseases from meta-analyses, and policy costs and health-related costs from established sources. A simulated nationally representative US population was created and followed until age 100 years or death, with 2019 as the year of intervention start. Findings were evaluated over 10 years and a lifetime from health care and societal perspectives. Uncertainty was evaluated in a 1-way analysis by assuming 50% industry compliance and probabilistic sensitivity analyses through a second-order Monte Carlo approach. Model outputs included averted diabetes cases, CVD events and CVD deaths, QALYs gained, and formal health care cost savings, stratified by age, race, income, and education., Results: Achieving the US National Salt and Sugar Reduction Initiative sugar reduction targets could prevent 2.48 million CVD events, 0.49 million CVD deaths, and 0.75 million diabetes cases; gain 6.67 million QALYs; and save $160.88 billion net costs from a societal perspective over a lifetime. The policy became cost-effective (<150 000/QALYs) at 6 years, highly cost-effective (<50 000/QALYs) at 7 years, and cost-saving at 9 years. Results were robust from a health care perspective, with lower (50%) industry compliance, and in probabilistic sensitivity analyses. The policy could also reduce disparities, with greatest estimated health gains per million adults among Black or Hispanic individuals, lower income, and less educated Americans., Conclusions: Implementing and achieving the US National Salt and Sugar Reduction Initiative sugar reformation targets could generate substantial health gains, equity gains, and cost savings.

The power of machine learning (ML) in feature identification can be harnessed for determining quantities in experiments that are difficult to measure directly. However, if an ML model is trained on simulated data, rather than experimental results, the differences between the two can pose an obstacle to reliable data extraction. Here we report on the development of ML-based diagnostics for experiments on high-intensity laser-matter interactions. With the intention to accentuate robust, physics-governed features, the presence of which is tolerant to such differences, we test the application of principal component analysis, data augmentation and training with data that has superimposed noise of gradually increasing amplitude. Using synthetic data of simulated experiments, we identify that the approach based on the noise of increasing amplitude yields the most accurate ML models and thus is likely to be useful in similar projects on ML-based diagnostics.

The enormous burden of diet-related chronic diseases has prompted interest in healthy food prescription programs. Yet, the impact of such programs remains unclear. The aim of this study was to conduct a systematic review of healthy food prescription programs and evaluate their impact on dietary behavior and cardiometabolic parameters by meta-analysis. A systematic search was carried out in Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials databases since their inception to 3 January, 2020 without language restriction. A systematic search of interventional studies investigating the effect of healthy food prescription on diet quality and/or cardiometabolic risk factors including BMI, systolic (SBP) and diastolic blood pressure (DBP), glycated hemoglobin (HbA1c), or blood lipids was carried out. Thirteen studies were identified for inclusion, most of which were quasi-experimental (pre/post) interventions without a control group (n = 9). Pooled estimates revealed a 22% (95% CI: 12, 32; n = 5 studies, n = 1039 participants; I2 = 97%) increase in fruit and vegetable consumption, corresponding to 0.8 higher daily servings (95% CI: 0.2, 1.4; I2 = 96%). BMI decreased by 0.6 kg/m2 (95% CI: 0.2, 1.1; I2 = 6.4%) and HbA1c by 0.8% (95% CI: 0.1, 1.6; I2 = 92%). No significant change was observed in other cardiometabolic parameters. These findings should be interpreted with caution in light of considerable heterogeneity, methodological limitations of the included studies, and moderate to very low certainty of evidence. Our results support the need for well-designed, large, randomized controlled trials in various settings to further establish the efficacy of healthy food prescription programs on diet quality and cardiometabolic health., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Prostate cancer is a common cancer type in men, yet some of its traits are still under-explored. One reason for this is high molecular and morphological heterogeneity. The purpose of this study was to develop a method to gain new insights into the connection between morphological changes and underlying molecular patterns. We used artificial intelligence (AI) to analyze the morphology of seven hematoxylin and eosin (H&E)-stained prostatectomy slides from a patient with multi-focal prostate cancer. We also paired the slides with spatially resolved expression for thousands of genes obtained by a novel spatial transcriptomics (ST) technique. As both spaces are highly dimensional, we focused on dimensionality reduction before seeking associations between them. Consequently, we extracted morphological features from H&E images using an ensemble of pre-trained convolutional neural networks and proposed a workflow for dimensionality reduction. To summarize the ST data into genetic profiles, we used a previously proposed factor analysis. We found that the regions were automatically defined, outlined by unsupervised clustering, associated with independent manual annotations, in some cases, finding further relevant subdivisions. The morphological patterns were also correlated with molecular profiles and could predict the spatial variation of individual genes. This novel approach enables flexible unsupervised studies relating morphological and genetic heterogeneity using AI to be carried out.

Background: We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality., Methods and Findings: We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose-response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case-cohort, or nested case-control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≤3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels., Conclusions: In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms., Competing Interests: The authors have declared that no competing interests exist.

Widespread use of reduced-sodium salts can potentially lower excessive population-level dietary sodium intake. This study aimed to identify key barriers and facilitators to implementing reduced-sodium salt as a population level intervention. Semi-structured interviews were conducted with key informants from academia, the salt manufacturing industry, and government. We used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to inform our interview guides and data analysis. Eighteen key informants from nine countries across five World Health Organization regions participated in the study from January 2020 to July 2020. Participants were concerned about the lack of robust evidence on safety for specific populations such as those with renal impairment. Taste and price compared to regular salt and an understanding of the potential health benefits of reduced-sodium salt were identified as critical factors influencing the adoption of reduced-sodium salts. Higher production costs, low profit return, and reduced market demand for reduced-sodium salts were key barriers for industry in implementation. Participants provided recommendations as potential strategies to enhance the uptake. There are presently substantial barriers to the widespread use of reduced-sodium salt but there are also clear opportunities to take actions that would increase uptake.

Excess sodium consumption and insufficient potassium intake contribute to high blood pressure and thus increase the risk of heart disease and stroke. In low-sodium salt, a portion of the sodium in salt (the amount varies, typically ranging from 10 to 50%) is replaced with minerals such as potassium chloride. Low-sodium salt may be an effective, scalable, and sustainable approach to reduce sodium and therefore reduce blood pressure and cardiovascular disease at the population level. Low-sodium salt programs have not been widely scaled up, although they have the potential to both reduce dietary sodium intake and increase dietary potassium intake. This article proposes a framework for a successful scale-up of low-sodium salt use in the home through four core strategies: availability, awareness and promotion, affordability, and advocacy. This framework identifies challenges and potential solutions within the core strategies to begin to understand the pathway to successful program implementation and evaluation of low-sodium salt use.

Underconsumption of dietary fiber is prevalent worldwide and is associated with multiple adverse health conditions. Despite the importance of fiber, the labeling of fiber content on packaged foods and beverages is voluntary in most countries, making it challenging for consumers and policy makers to monitor fiber consumption. Here, we developed a machine learning approach for automated and systematic prediction of fiber content using nutrient information commonly available on packaged products. An Australian packaged food dataset with known fiber content information was divided into training ( n = 8986) and test datasets ( n = 2455). Utilization of a k-nearest neighbors machine learning algorithm explained a greater proportion of variance in fiber content than an existing manual fiber prediction approach ( R 2 = 0.84 vs. R 2 = 0.68). Our findings highlight the opportunity to use machine learning to efficiently predict the fiber content of packaged products on a large scale.