Maximizing the benefits and minimizing the risks of intervention programs to address micronutrient malnutrition: symposium report.

Interventions to address micronutrient deficiencies have large potential to reduce the related disease and economic burden. However, the potential risks of excessive micronutrient intakes are often not well determined. During the Global Summit on Food Fortification, 9-11 September 2015, in Arusha, a symposium was organized on micronutrient risk-benefit assessments. Using case studies on folic acid, iodine and vitamin A, the presenters discussed how to maximize the benefits and minimize the risks of intervention programs to address micronutrient malnutrition. Pre-implementation assessment of dietary intake, and/or biomarkers of micronutrient exposure, status and morbidity/mortality is critical in identifying the population segments at risk of inadequate and excessive intake. Dietary intake models allow to predict the effect of micronutrient interventions and their combinations, e.g. fortified food and supplements, on the proportion of the population with intakes below adequate and above safe thresholds. Continuous monitoring of micronutrient intake and biomarkers is critical to identify whether the target population is actually reached, whether subgroups receive excessive amounts, and inform program adjustments. However, the relation between regular high intake and adverse health consequences is neither well understood for many micronutrients, nor do biomarkers exist that can detect them. More accurate and reliable biomarkers predictive of micronutrient exposure, status and function are needed to ensure effective and safe intake ranges for vulnerable population groups such as young children and pregnant women. Modelling tools that integrate information on program coverage, dietary intake distribution and biomarkers will further enable program makers to design effective, efficient and safe programs

Neurocognitive disorders in the elderly: altered functional resting-state hyperconnectivities in postoperative delirium patients

Postoperative delirium (POD) represents a confusional state during days/weeks after surgery and is particularly frequent in elderly patients. Hardly any fMRI studies were conducted to understand the underlying pathophysiology of POD patients. This prospective observational cohort study aims to examine changes of specific resting-state functional connectivity networks across different time points (pre- and 3-5 months postoperatively) in delirious patients compared to no-POD patients. Two-hundred eighty-three elderly surgical patients underwent preoperative resting-state fMRI (46 POD). One-hundred seventy-eight patients completed postoperative scans (19 POD). For functional connectivity analyses, three functional connectivity networks with seeds located in the orbitofrontal cortex (OFC), nucleus accumbens (NAcc), and hippocampus were investigated. The relationship of POD and connectivity changes between both time points (course connectivity) were examined (ANOVA). Preoperatively, delirious patients displayed hyperconnectivities across the examined functional connectivity networks. In POD patients, connectivities within NAcc and OFC networks demonstrated a decrease in course connectivity [max. F = 9.03, p = 0.003; F = 4.47, p = 0.036, resp.]. The preoperative hyperconnectivity in the three networks in the patients at risk for developing POD could possibly indicate existing compensation mechanisms for subtle brain dysfunction. The observed pathophysiology of network function in POD patients at least partially involves dopaminergic pathways

Use of Compartmental Modeling and Retinol Isotope Dilution to Determine Vitamin A Stores in Young People with Sickle Cell Disease Before and After Vitamin A Supplementation

BACKGROUND: Suboptimal plasma retinol concentrations have been documented in US children with sickle cell disease (SCD) hemoglobin SS type (SCD-HbSS), but little is known about vitamin A kinetics and stores in SCD. OBJECTIVES: The objectives were to quantify vitamin A total body stores (TBS) and whole-body retinol kinetics in young people with SCD-HbSS and use retinol isotope dilution (RID) to predict TBS in SCD-HbSS and healthy peers as well as after vitamin A supplementation in SCD-HbSS subjects. METHODS: Composite plasma [ RESULTS: Model-predicted group mean TBS for subjects with SCD-HbSS was 428 μmol, equivalent to ∼11 mo of stored vitamin A; vitamin A disposal rate was 1.3 μmol/d. Model-predicted TBS was similar to that predicted by RID at 3 d postdosing (mean, 389 μmol; ∼0.3 μmol/g liver); TBS predictions at 3 compared with 28 d were not significantly different. Mean TBS in healthy peers was similar (406 μmol). RID-predicted TBS for subjects with SCD-HbSS was not significantly affected by vitamin A supplementation at either dose. CONCLUSIONS: Despite differences in plasma retinol concentrations, TBS was the same in subjects with SCD-HbSS compared with healthy peers. Because 56 d of vitamin A supplementation at levels 1.2 to 2.6 times the Recommended Dietary Allowance did not increase TBS in these subjects with SCD-HbSS, further work will be needed to understand the effects of SCD on retinol metabolism. This trial was registered as NCT03632876 at clinicaltrials.gov

Multiassay nutritional metabolomics profiling of low vitamin A status versus adequacy is characterized by reduced plasma lipid mediators among lactating women in the Philippines: A pilot study

Low vitamin A (VA) status is common among lactating women in low-income countries. Lactation has substantial effects on mother's metabolism and VA is required in multiple biological processes, including growth, vision, immunity, and reproduction. The objective of this pilot study was to use metabolomics profiling to conduct a broad, exploratory assessment of differences in plasma metabolites associated with low VA status versus VA adequacy in lactating women. Plasma samples from lactating women who participated in a survey in Samar, Philippines, were selected from a cross-sectional study based on plasma retinol concentrations indicating low (VA-; n = 5) or adequate (VA+; n = 5) VA status (plasma retinol <0.8 or >1.05 µmol/L). The plasma results collected from 6 metabolomics assays (oxylipins, endocannabinoids, bile acids, primary metabolomics, biogenic amines, and lipidomics) were compared by group using liquid chromatography mass spectrometry. Twenty-eight metabolites were altered in the VA- versus VA+ status groups, with 24 being lipid mediators (P < .05). These lipid mediators included lower concentrations of arachidonic acid- and eicosapentaenoic acid-derived oxylipins, as well as lysophospholipids and sphingolipids, in the VA- group (P < .05). Chemical similarity enrichment analysis identified hydroxy-eicosatetraenoic acids, hydroxy-eicosapentaenoic acids, and dihydroxy-eicosatetraenoic acids as significantly altered oxylipin clusters (P < .0001, false discovery rate [FDR] P < .0001), as well as sphingomyelins, saturated lysophosphatidylcholines, phosphatidylcholines, and phosphatidylethanolamines (P < .001, FDR P < .01). The multiassay nutritional metabolomics profiling of low VA status compared with adequacy in lactating women was characterized by reduced lipid mediator concentrations. Future studies with stronger study designs and larger sample size are needed to confirm and validate these preliminary results

Association of oily fish intake, sex, age, BMI and APOE genotype with plasma long-chain n-3 fatty acid composition

n-3 Fatty acids are associated with better cardiovascular and cognitive health. However, the concentration of EPA, DPA and DHA in different plasma lipid pools differs and factors influencing this heterogeneity are poorly understood. Our aim was to evaluate the association of oily fish intake, sex, age, BMI and APOE genotype with concentrations of EPA, DPA and DHA in plasma phosphatidylcholine (PC), NEFA, cholesteryl esters (CE) and TAG. Healthy adults (148 male, 158 female, age 20–71 years) were recruited according to APOE genotype, sex and age. The fatty acid composition was determined by GC. Oily fish intake was positively associated with EPA in PC, CE and TAG, DPA in TAG, and DHA in all fractions (P≤0·008). There was a positive association between age and EPA in PC, CE and TAG, DPA in NEFA and CE, and DHA in PC and CE (P≤0·034). DPA was higher in TAG in males than females (P<0·001). There was a positive association between BMI and DPA and DHA in TAG (P<0·006 and 0·02, respectively). APOE genotype×sex interactions were observed: the APOE4 allele associated with higher EPA in males (P=0·002), and there was also evidence for higher DPA and DHA (P≤0·032). In conclusion, EPA, DPA and DHA in plasma lipids are associated with oily fish intake, sex, age, BMI and APOE genotype. Such insights may be used to better understand the link between plasma fatty acid profiles and dietary exposure and may influence intake recommendations across population subgroups

Perioperative Levels of IL8 and IL18, but not IL6, are Associated with Nucleus Basalis Magnocellularis Atrophy Three Months after Surgery

Past studies have observed that brain atrophy may accelerate after surgical procedures. Furthermore, an association of systemic inflammation with neurodegeneration has been described. We hypothesize that postoperative interleukin (IL) levels in circulation as well as the perioperative change in interleukin levels are associated with increased postoperative atrophy in the Nucleus basalis magnocellularis (of Meynert, NBM) which is the major source of cortical acetylcholine. We analyzed data from the BioCog cohort which included patients ≥ 65 years presenting for elective major surgery (≥ 60min). Blood samples were taken before surgery and on the first postoperative day. Magnetic resonance imaging of the brain and neuropsychological assessments were conducted before surgery and after three months follow-up. We used linear regression analysis to determine the association of three interleukins (IL6, IL8 and IL18) with NBM atrophy (in % volume change from baseline before surgery to follow-up), as well as to examine the associations of NBM atrophy and volume with postoperative cognitive ability and perioperative cognitive change. Receiver-operating curves were used to determine the prognostic value of preoperative interleukin levels. For IL8 (N = 97) and IL18 (N = 217), but not IL6 (N = 240), we observed significant associations of higher postoperative IL levels at the first postoperative day with higher NBM atrophy at three months after surgery. Subsequent analyses suggested that in both IL8 and IL18, this association was driven by a more general association of chronically elevated IL levels and NBM atrophy, reflected by preoperative IL concentrations, rather than IL response to surgery, measured as the difference between pre- and postoperative IL concentrations. At follow-up, NBM volume was positively associated with the level of cognitive performance, but NBM atrophy was not significantly related to perioperative cognitive change. Prognostic value of preoperative IL concentrations for NBM atrophy was low. Our results suggest that an association of postoperative interleukin levels with NBM atrophy is driven by preoperatively elevated interleukins due to pre-existing inflammation, rather than perioperative change in interleukin levels in response to surgery and anesthesia. The BioCog study has been registered at clinicaltrials.gov on Oct 15, 2014 (NCT02265263). Graphical Abstract: (Figure presented.)

Scientific opinion on the tolerable upper intake level for preformed vitamin A and β-carotene

Following two requests from the European Commission, the EFSA Panel onNutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientificopinion on the revision of the tolerable upper intake level (UL) for preformed vitamin A and β-carotene. Systematic reviews of the literature were conducted forpriority adverse health effects of excess vitamin A intake, namely teratogenicity,hepatotoxicity and endpoints related to bone health. Available data did not allowto address whether β-carotene could potentiate preformed vitamin A toxicity.Teratogenicity was selected as the critical effect on which to base the UL for preformed vitamin A. The Panel proposes to retain the UL for preformed vitamin A of 3000 μg RE/day for adults. This UL applies to men and women, including women of child-bearing age, pregnant and lactating women and post-menopausal women. This value was scaled down to other population groups using allometric scaling (body weight0.75), leading to ULs between 600 μg RE/day (infants 4–11 months) and 2600 μg RE/day (adolescents 15–17 years). Based on available intake data, European populations are unlikely to exceed the UL for preformed vitamin A if consumption of liver, offal and products thereof is limited to once per month or less. Women who are planning to become pregnant or who are pregnant are advised not to consume liver products. Lung cancer risk was selected as the critical effect of excess supplemental β-carotene. The available data were not sufficient and suitable to characterise a dose–response relationship and identify a reference point; therefore, no UL could be established. There is no indication that β-carotene intake from the background diet is associated with adverse health effects. Smokers should avoid consuming food supplements containing β-carotene. The use of supplemental β-carotene by the general population should be limited to the purpose of meeting vitamin A requirements

Hepatic lipoprotein export and remission of human type 2 diabetes after weight loss

The role of hepatic lipoprotein metabolism in diet-induced remission of type 2 diabetes is currently unclear. Here, we determined the contributions of hepatic VLDL1-triglyceride production rate and VLDL1-palmitic acid content to changes in intra-pancreatic fat and return of first phase insulin response in a subgroup of the Diabetes Remission Clinical Trial. Liver fat, VLDL1-triglyceride production, and intra-pancreatic fat decreased after weight loss and remained normalized after 24 months of remission. First-phase insulin response remained increased only in those maintaining diabetes remission. Compared with those in remission at 24 months, individuals who relapsed after initial remission had a greater rise in the content of VLDL1-triglyceride and VLDL1-palmitic acid, re-accumulated intra-pancreatic fat, and lost first-phase response by 24 months. Thus, we observed temporal relationships between VLDL1-triglyceride production, hepatic palmitic acid flux, intra-pancreatic fat, and β-cell function. Weight-related disordered fat metabolism appears to drive development and reversal of type 2 diabetes

Nursing students' perceptions of a video-based serious game's educational value: A pilot study

BACKGROUND: Despite an increasing number of serious games (SGs) in nursing education, few evaluation studies specifically address their educational value in terms of face, content, and construct validity. OBJECTIVES: To assess nursing students' perceptions of a video-based SG in terms of face, content, and construct validity. In addition, the study assessed perceptions of usability, individual factors, and preferences regarding future use. DESIGN: A pilot study was conducted. SETTING AND PARTICIPANTS: An SG prototype was implemented as part of two simulation courses in nursing education: one for home health care and one for hospital medical-surgical wards. The SG aimed to teach clinical reasoning and decision-making skills to nursing students caring for patients with chronic obstructive pulmonary disease. A total of 249second-year nursing students participated in pilot testing of the SG. METHOD: A paper-based survey was used to assess students' perceptions of the SG's educational value. RESULTS: Overall, students from both simulation courses perceived the SG as educationally valuable and easy to use. No significant differences were found in perceptions of educational value between nursing students with previous healthcare experience versus those with none. However, significantly more students in the home healthcare simulation course indicated that the SG tested their clinical reasoning and decision-making skills. Students from both the medical-surgical and home healthcare simulation courses suggested that more video-based SGs should be developed and used in nursing education. CONCLUSIONS: Overall, the survey results indicate that the participants perceived the SG as educationally valuable, and that the SG has potential as an educational tool in nursing education, especially in caring for patients with chronic diseases and in home healthcare simulation. Showing a SG's educational value and user acceptance among nursing students may justify the development and application of more SGs in nursing education