The Effect of Dietary Manganese on Arterial Functional Properties

Dietary manganese affects the structure and integrity of blood vessels, as well as vessel predisposition to endothelial dysfunction and cardiovascular disease. In this thesis, we studied the role of manganese on the functional properties of rat aorta as defined by the endothelial and vascular smooth muscle cell pathways for adrenergic-mediated vasoconstriction and cholinergic-mediated vasodilation. Weanling Sprague-Dawley rats were fed a manganese deficient (MnD), adequate (MnA-control group) or supplemented (MnS) diet (\u3c1, 10-15 and 45-50ppm Mn respectively). After 14 weeks on the diet the aorta was excised and four aortic rings of three mm length were prepared from each animal. Alterations in vasoconstriction among diet groups were detected by dose-response curves to the ^-adrenergic agonist LPhenylephrine in endothelium-intact and endothelium-disrupted rings. Alterations in endothelium-dependent vasodilation among diet groups were determined by doseresponse curves to Acetylcholine. We studied the mechanism by which dietary manganese affects two different endothelium-dependent vasodilation pathways: the Larginine/ nitric oxide (NO) and the cyclooxygenase (COX) pathways. Inhibition of the enzymes for NO synthesis (NOS) with L-NMMA, and of prostanoids (COX I and II) with Mefenamic acid, determination of NOS expression, and in vitro addition of L-Arginine (substrate for NO formation) to vessel rings revealed the effect of manganese on the regulation of endothelium-mediated vasodilation and vasoconstriction. Dose-response curves to sodium nitroprusside provided data for the dietary effect on endotheliumindependent vasodilation. Supplementary dietary manganese increased adrenoreceptor-mediated vascular smooth muscle contraction, which was significantly reduced in the presence of functional endothelium. Absence of dietary manganese increased endothelial cell sensitivity to the (Xi-adrenergic vasoconstrictor agent. Manganese had a small effect on the cGMP-pathway for dilation of vascular smooth muscle but affected vasodilation primarily through an endothelium-mediated pathway, probably by preserving NO bioavailability. Inhibition of vasodilation in Mn deficiency appears to occur through an endothelium-derived vasoconstrictor, possibly thromboxane with a concomitant decrease in the synthesis of endothelium-mediated vasodilator prostanoids. Our results demonstrate that dietary manganese influences the contractile machinery of vascular smooth muscle cells and regulates the bioactivity of endothelium-mediated vasodilators to affect agonist-induced signaling pathways that participate in the regulation of vasomotor tone. This suggests possibilities for dietary intervention in blood pressure regulation

Diet-Nutrition Information Seeking, Source Trustworthiness, and Eating Behavior Changes: An International Web-Based Survey

To understand the extent to which different sources of diet and nutrition information are sought, trusted, and relied upon for making dietary changes, the present international web-based survey study gauged participants’ (n = 3419) diet-nutrition information-seeking behaviors from 22 interpersonal and general sources with varying quality, trust levels in these sources, and reliance on each source for making dietary changes. Qualitative insights were also captured regarding trustworthiness formation. The results revealed a disconnect between source popularity and perceived trustworthiness. While nutrition–health websites, Google–Internet searches, and diet–health books were most commonly consulted, participants placed the highest level of trust in nutrition scientists, nutrition professionals, and scientific journals, suggesting that frequent information seeking from a subpar source may not be a reliable predictor of the level of trust assigned to it. Although the frequency of source-seeking behaviors and source trustworthiness both contributed to dietary changes, the latter appeared to have a more pronounced influence. When a source was less trusted, there was a reduced likelihood of relying on it for changing diet. Additionally, source seeking may not always translate into effective dietary change, as shown by the less strong correlation between the two. These associations significantly differed depending on the source

Effective strategies in ending weight stigma in healthcare

Weight stigma impacts negatively healthcare quality and hinders public health goals. The aim of this review was to identify strategies for minimizing weight bias among healthcare professionals and explore future research directions. An electronic search was performed in PubMed, PsycINFO and Scopus (until June 2020). Studies on weight stigma reduction in healthcare students, trainees and professionals were assessed based on specific inclusion and exclusion criteria. A narrative synthesis was undertaken to analyze emerging themes. We identified five stigma reduction strategies in healthcare: (i) increased education, (ii) causal information and controllability, (iii) empathy evoking, (iv) weight-inclusive approach, and (v) mixed methodology. Weight stigma needs to be addressed early on and continuously throughout healthcare education and practice, by teaching the genetic and socioenvironmental determinants of weight, and explicitly discussing the sources, impact and implications of stigma. There is a need to move away from a solely weight-centric approach to healthcare to a health-focused weight-inclusive one. Assessing the effects of weight stigma in epidemiological research is equally important. The ethical argument and evidence base for the need to reduce weight stigma in healthcare and beyond is strong. Although evidence on long-term stigma reduction is emerging, precautionary action is needed

Nutriepigenetics and cardiovascular disease

Purpose of review: We present a current perspective of epigenetic alterations that can lead to cardiovascular disease (CVD) and the potential of dietary factors to counteract their actions. In addition, we discuss the challenges and opportunities of dietary treatments as epigenetic modifiers for disease prevention and therapy. Recent findings: Recent epigenome-wide association studies along with candidate gene approaches and functional studies in cell culture and animal models have delineated mechanisms through which nutrients, food compounds and dietary patterns may affect the epigenome. Several risk factors for CVD, including adiposity, inflammation and oxidative stress, have been associated with changes in histone acetylation, lower global DNA methylation levels and shorter telomere length. A surplus of macronutrients such as in a high-fat diet or deficiencies of specific nutrients such as folate and other B-vitamins can affect the activity of DNA methyltransferases and histone-modifying enzymes, affecting foetal growth, glucose/lipid metabolism, oxidative stress, inflammation and atherosclerosis. Bioactive compounds such as polyphenols (resveratrol, curcumin) or epigallocatechin may activate deacetylases Sirtuins (SIRTs), histone deacetylases or acetyltransferases and in turn the response of inflammatory mediators. Adherence to cardioprotective dietary patterns, such as the Mediterranean diet (MedDiet), has been associated with altered methylation and expression of genes related to inflammation and immuno-competence. Summary: The mechanisms through which nutrients and dietary patterns may alter the cardiovascular epigenome remain elusive. The research challenge is to determine which of these nutriepigenetic effects are reversible, so that novel findings translate into effective dietary interventions to prevent CVD or its progression

Genomic Research to Identify Novel Pathways in the Development of Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is a common disease with a large heritable component. There is a need to improve our understanding of AAA pathogenesis in order to develop novel treatment paradigms. Genomewide association studies have revolutionized research into the genetic variants that underpin the development of many complex diseases including AAA. This article reviews the progress that has been made to date in this regard, including mechanisms by which loci identified by GWAS may contribute to the development of AAA. It also highlights potential post-GWAS analytical strategies to improve our understanding of the disease further

Iron deficiency anaemia: experiences and challenges.

Iron deficiency remains the largest nutritional deficiency worldwide and the main cause of anaemia. Severe iron deficiency leads to anaemia known as iron deficiency anaemia (IDA), which affects a total of 1·24 billion people, the majority of whom are children and women from resource-poor countries. In sub-Saharan Africa, iron deficiency is frequently exacerbated by concomitant parasitic and bacterial infections and contributes to over 120 000 maternal deaths a year, while it irreparably limits the cognitive development of children and leads to poor outcomes in pregnancy.Currently available iron compounds are cheap and readily available, but constitute a non-physiological approach to providing iron that leads to significant side effects. Consequently, iron deficiency and IDA remain without an effective treatment, particularly in populations with high burden of infectious diseases. So far, despite considerable investment in the past 25 years in nutrition interventions with iron supplementation and fortification, we have been unable to significantly decrease the burden of this disease in resource-poor countries.If we are to eliminate this condition in the future, it is imperative to look beyond the strategies used until now and we should make an effort to combine community engagement and social science approaches to optimise supplementation and fortification programmes

Genetic Susceptibility for Coronary Heart Disease and Type 2 Diabetes Complications

Type II diabetes (T2D) 3 represents a major public health challenge, with the WHO having estimated a current prevalence of 346 million worldwide. Cardiovascular disease, including coronary heart disease (CHD), stroke, and peripheral vascular disease, is one of the major complications of T2D, and the development of new strategies to tackle this problem is undoubtedly necessary. Although the association between diabetes and cardiovascular risk is well established, the pathologic basis of CHD in patients with T2D may differ from that in the general population. Whether this relationship has a genetic component is not fully understood. With regard to understanding the genetic basis of complex diseases, genomewide association studies (GWASs) have led to an unprecedented number of well-validated variants associated with complex diseases. There is now considerable interest in understanding both the mechanism by which these variants confer risk and whether the variants identified will be useful for predicting complex disease phenotypes. A recent report by Qi et al. (1 ) addressed 2 questions in this regard: (a) Are single-nucleotide polymorphisms (SNPs) identified by GWASs of CHD associated with the risk of CHD in T2D, and (b) can these variants be combined in a score that will aid prediction of CHD risk in T2D? In investigating these questions, Qi and coworkers genotyped 12 CHD susceptibility loci in 3 nested case-control studies of CHD in T2D: the Nurses' Health Study, the Health Professional Follow-Up Study, and the Joslin Heart Study. As expected, the chromosome 9p21 CHD risk locus showed a strong association with CHD risk, whereas 4 other loci [PHACTR1 4 (phosphatase and ac- None of the other variants tested showed associations with CHD below the significance threshold (P ϭ 0.05), although the authors noted that 2 of the loci examined [MRAS (muscle RAS oncogene homolog) and KCNE2 (potassium voltage-gated channel, Isk-related family, member 2)] had summary effect sizes in the direction opposite to that described in previous reports. Although it may be tempting to speculate on the reasons for this result, the 95% CI for the summary odds ratios crosses the line of null effect, and the study had limited power to detect overall effects. Therefore, these results should be interpreted with caution. The authors then constructed a simple unweighted genetic risk score (GRS) based on the number of risk alleles carried (each individual will carry 0, 1, or 2 risk alleles at each locus) and assessed the performance of the GRS in predicting CHD. In common with other reports of studies that used a similar methodology, the discriminative performance of the GRS was modest (area under the ROC curve, 0.5782). Addition of the GRS to a panel of clinical risk factors did lead to a modest improvement in both the area under the ROC curve and the net reclassification index. Two important features that could have aided in discrimination but were not included in the clinical parameters are the duration of diabetes in patients who developed CHD and the age of diabetes diagnosis

Effects of exclusive breastfeeding promotion interventions on child outcomes: a systematic review and meta-analysis

INTRODUCTION: Interventions promoting exclusive breastfeeding (EBF) may benefit infant health outcomes, but evidence is inconsistent. The objective of this review was to assess the effect of interventions promoting EBF on health outcomes in infants and children under 7 years of age. METHODS: A literature search was conducted using EMBASE, MEDLINE, CINAHL, Cochrane Central, Cochrane Database of Systematic Reviews, and WHO International Clinical Trials Registry Platform from inception to April 2022. Inclusion criteria were randomized or cluster-randomized controlled trials aiming to increase EBF that reported effects on offspring growth, morbidity and/or mortality up to age 7 years. The primary outcome was infant/child growth. Secondary outcomes were infant morbidity and mortality and exclusive breastfeeding rates. Data were pooled using a random-effects model. RESULTS: 32 studies (40 papers) were identified. No effect on infant/child growth was observed. EBF promotion interventions significantly improved EBF rates up to 6 months (n=25; OR 3.15; 95%CI 2.36,4.19) and significantly reduced the odds of respiratory illness at 0-3 months by 59% (n=2; OR 0.41; 95%CI 0.20,0.84) but not at later time-points. A borderline significant effect was observed for diarrhea (n=12; OR 0.84; 95%CI 0.70,1.00). Effects on hospitalizations or mortality were not significant. DISCUSSION/CONCLUSION: EBF promotion interventions improve EBF rates and might yield modest reductions in infant morbidity without affecting infant/child growth. Future studies should investigate the cost-effectiveness of these interventions and examine potential benefits on other health outcomes

The IHAT-GUT Iron Supplementation Trial in Rural Gambia: Barriers, Facilitators, and Benefits.

INTRODUCTION: In most sub-Saharan African countries iron deficiency anaemia remains highly prevalent in children and this has not changed in the last 25 years. Supplementation with iron hydroxide adipate tartrate (IHAT) was being investigated in anaemic children in a phase two clinical trial (termed IHAT-GUT), conducted at the Medical Research Council Unit the Gambia at the London School of Hygiene and Tropical Medicine (LSHTM) (abbreviated as MRCG hereof). This qualitative study aimed to explore the personal perceptions of the trial staff in relation to conducting a clinical trial in such settings in order to highlight the health system specific needs and strengths in the rural, resource-poor setting of the Upper River Region in the Gambia. METHODS: Individual interviews (n = 17) were conducted with local trial staff of the IHAT-GUT trial. Data were analysed using inductive thematic analysis. RESULTS: Potential barriers and facilitators to conducting this clinical trial were identified at the patient, staff, and trial management levels. Several challenges, such as the rural location and cultural context, were identified but noted as not being long-term inhibitors. Participants believed the facilitators and benefits outnumbered the barriers, and included the impact on education and healthcare, the ambitious and knowledgeable locally recruited staff, and the local partnership. CONCLUSIONS: While facilitators and barriers were identified to conducting this clinical trial in a rural, resource-poor setting, the overall impact was perceived as beneficial, and this study is a useful example of community involvement and partnership for further health improvement programs. To effectively implement a nutrition intervention, the local health systems and context must be carefully considered through qualitative research beforehand

Negative impact of the first COVID-19 lockdown upon health-related behaviours and psychological wellbeing in people living with severe and complex obesity in the UK

Background: Coronavirus disease 2019 (COVID-19) has led to unprecedented changes in the way we live, particularly for people at higher risk of severe illness from COVID-19. People with pre-existing health conditions have been markedly impacted and, in some instances, left unsupported due to reduced provision of routine healthcare services. People living with obesity (PLWO) are identified as at higher risk of severe illness from COVID-19 infection. Currently, there is a paucity of evidence about the impact of the first COVID-19 lockdown on PLWO, including those accessing weight management and bariatric surgery services (WMS). Methods:543 adults (16 80 years) with obesity (BMI>30 kg/m2) were recruited between 14th May and 9th July 2020 through social media advertisements, professional and patient obesity organisations and WMS. Participants completed an online survey regarding the impact of the first COVID-19 lockdown upon, mental health, well-being, health-related behaviours, risk mitigating behaviours, access to WMS and weight stigma. Findings: During the first COVID-19 lockdown, the majority of PLWO reported deterioration of their mental health and health-related behaviours such as diet, physical activity (PA) and sleep. With 55% reporting an unhealthier diet, 61% reduced PA and 80% worsening of their sleep. Higher depression and lower wellbeing scores were found to associate with the greatest adverse impact upon health-related behaviours. PLWO who were attending WMS prior to the first lockdown reported a greater deterioration of their diet, with nearly 50% reporting worsening of their diet and PA worsening compared to PLWO who were not attending WMS. Most participants took two or more risk mitigating actions (73%). PLWO attending WMS reported reduced access (44%) with insufficient information (49%) from their clinical service providers. The majority of participants reported no change in perceived weight stigma. Interpretation: This study shows the detrimental impact of the first COVID-19 lockdown on PLWO in relation to health-related behaviours, mental health and access to WMS. Our findings show that PLWO with poor mental health and those attending WMS were most adversely impacted and highlights the need for greater mental health support and continued provision of support from WMS for PLWO during future lockdowns. Funding: This research was funded through National Institute for Health Research University College London Hospitals Biomedical Research Centre funding