Excess salt intake contributes to hypertension and increased cardiovascular disease risk. Efforts to implement effective salt-reduction strategies require accurate data on the sources of salt consumption. We therefore performed a systematic review to identify the sources of dietary salt around the world. We systematically searched peer-reviewed and gray literature databases for studies that quantified discretionary (salt added during cooking or at the table) and nondiscretionary sources of salt and those that provided information about the food groups contributing to dietary salt intake. Exploratory linear regression analysis was also conducted to assess whether the proportion of discretionary salt intake is related to the gross domestic product (GDP) per capita of a country. We identified 80 studies conducted in 34 countries between 1975 and 2018. The majority (n = 44, 55%) collected data on dietary salt sources within the past 10 y and were deemed to have a low or moderate risk of bias (n = 75, 94%). Thirty-two (40%) studies were judged to be nationally representative. Populations in Brazil, China, Costa Rica, Guatemala, India, Japan, Mozambique, and Romania received more than half of their daily salt intake from discretionary sources. A significant inverse correlation between discretionary salt intake and a country's per capita GDP was observed (P < 0.0001), such that for every $10,000 increase in per capita GDP, the amount of salt obtained from discretionary sources was lower by 8.7% (95% CI: 5.1%, 12%). Bread products, cereal and grains, meat products, and dairy products were the major contributors to dietary salt intake in most populations. There is marked variation in discretionary salt use around the world that is highly correlated with the level of economic development. Our findings have important implications for the type of salt-reduction strategy likely to be effective in a country.

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.

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], andtrans-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 nott16:1n-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.

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 ($\le$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.

Free tissue transfer is a powerful reconstructive method for patients with substantial diabetic foot ulcers. This study aimed to perform an updated systematic review and meta-analysis investigating the flap characteristics, concurrent revascularisation rates, complications, and outcomes associated with free tissue transfer in diabetic foot ulcers. Two reviewers performed a systematic review of various databases since their inception, with no language restriction. Only data for free tissue transfer in non-traumatic diabetic foot ulcer patients were extracted from included studies where a heterogenous population was studied. Outcome data were pooled using random effects meta-analysis for binomial data. Of 632 studies identified, 67 studies encompassing 1 846 patients and 1 871 free flaps were included. A median of 18 patients [IQR 9, 37] per study, with a median age of 58.5 years [56, 63], were followed up for a median of 15 months [7, 25]. Most studies had serious risk of bias (n = 47 studies, 70%); sixteen (24%) had moderate risk of bias; and four (6%) had low risk of bias. The proportion of patients who underwent revascularisation was 75% (95% CI 60 - 87%; n = 36 studies) with a median time of 8 days between procedures. The pooled complete flap survival, major amputation, and ambulation rates were 88% (85 - 92%, n = 49 studies), 10% (7 - 14%, n = 50 studies), and 87% (80 - 92%, n = 36 studies), respectively. Mortality at individual study follow up was 6% (3 - 10%, n = 26 studies). The overall certainty of evidence was very low. Free tissue transfer may be a useful treatment modality for recalcitrant diabetic foot ulcers in selected patients. Future studies should investigate long term functional outcomes and aim to develop patient selection algorithms to select the most suitable candidates for this procedure.

Mutation in a growing spectrum of genes is known to either cause or contribute to primary or secondary microcephaly. In primary microcephaly the genetic determinants frequently involve mutations that contribute to or modulate the microtubule cytoskeleton by causing perturbations of neuronal proliferation and migration. Here we describe four patients from two unrelated families each with an infantile neurodegenerative disorder characterized by loss of developmental milestones at 9–24 months of age followed by seizures, dystonia and acquired microcephaly. The patients harboured homozygous missense mutations (A475T and A586V) in TBCD, a gene encoding one of five tubulin-specific chaperones (termed TBCA-E) that function in concert as a nanomachine required for the de novo assembly of the α/β tubulin heterodimer. The latter is the subunit from which microtubule polymers are assembled. We found a reduced intracellular abundance of TBCD in patient fibroblasts to about 10% (in the case of A475T) or 40% (in the case of A586V) compared to age-matched wild type controls. Functional analyses of the mutant proteins revealed a partially compromised ability to participate in the heterodimer assembly pathway. We show via in utero shRNA-mediated suppression that a balanced supply of tbcd is critical for cortical cell proliferation and radial migration in the developing mouse brain. We conclude that TBCD is a novel functional contributor to the mammalian cerebral cortex development, and that the pathological mechanism resulting from the mutations we describe is likely to involve compromised interactions with one or more TBCD-interacting effectors that influence the dynamics and behaviour of the neuronal cytoskeleton.