Iodine and plant-based diets: a narrative review and calculation of iodine content.

An increasing number of food-based recommendations promote a plant-based diet to address health concerns and environmental sustainability in global food systems. As the main sources of iodine in many countries are fish, eggs and dairy products, it is unclear whether plant-based diets, such as the EAT-Lancet reference diet, would provide sufficient iodine. This is important as iodine, through the thyroid hormones, is required for growth and brain development; adequate iodine intake is especially important before, and during, pregnancy. In this narrative review, we evaluated the current literature and estimated iodine provision from the EAT-Lancet reference diet. There is evidence that those following a strict plant-based diet, such as vegans, cannot reach the recommended iodine intake from food alone and are reliant on iodine supplements. Using the EAT-Lancet reference diet intake recommendations in combination with iodine values from UK food tables, we calculated that the diet would provide 128 µg/d (85 % of the adult recommendation of 150 µg/d and 51­64 % of the pregnancy recommendation of 200­250 µg/d). However, if milk is replaced with unfortified plant-based alternatives, total iodine provision would be just 54 µg/d (34 % and 22­27 % of the recommendations for adults and pregnancy, respectively). Plant-based dietary recommendations might place consumers at risk of iodine deficiency in countries without a fortification programme and where animal products provide the majority of iodine intake, such as the UK and Norway. It is essential that those following a predominantly plant-based diet are given appropriate dietary advice to ensure adequate iodine intake.

The impact of replacing milk with plant-based alternatives on iodine intake: a dietary modelling study.

PURPOSE: Cow's milk is the primary source of iodine in the UK, but consumption of plant-based milk alternatives (PBMA) is increasing and these products are often not fortified with iodine. We evaluated the impact that replacing current milk consumption with PBMA would have on iodine intake. METHODS: We used data from the National Diet and Nutrition Survey (2016-2019) for children (1.5-10 years), girls 11-18 years, and women of reproductive age (WRA). We used a dietary modelling approach with scenarios using brand-level iodine-fortification data (0, 13, 22.5, 27.4 and 45 µg/100 mL). Relative to usual diet, we calculated change in iodine intake, and the proportion with intake below the Lower Reference Nutrient Intake (LRNI) or above the upper limit. RESULTS: For all groups, replacement with PBMA, either unfortified or fortified at the lowest concentration, resulted in a meaningful decrease in iodine intake, and increased the proportion with intake < LRNI; compared to usual diet, iodine intake reduced by 58% in children 1.5-3 years (127 vs. 53 µg/day) and the proportion with intake < LRNI increased in girls (11-18 years; 20% to 48%) and WRA (13% to 33%) if an unfortified PBMA was used. Replacement of milk with PBMA fortified at 27.4 µg/100 mL had the lowest impact. CONCLUSION: Replacing milk with commercially available PBMAs has potential to reduce population iodine intake, depending on the fortification level. PBMAs fortified with ≥ 22.5 and < 45 µg iodine/100 mL would be required to minimize the impact on iodine intake. Research is needed on the impact of total dairy replacement.

Iodine fortification of plant-based dairy and fish alternatives: the effect of substitution on iodine intake based on a market survey in the UK.

Milk, dairy products, and fish are the main sources of iodine in the UK. Plant-based products are increasingly popular, especially with young women, which may affect iodine intake as they are naturally low in iodine; this is concerning as iodine is required for fetal brain development. We, aimed to (i) assess the iodine fortification of products sold as alternatives to milk, yoghurt, cheese and fish through a cross-sectional survey of UK retail outlets in 2020, and (ii) model the impact of substitution with such products on iodine intake, using portion-based scenarios. We identified 300 products, including plant-based alternatives to: (i) milk (n 146); (ii) yoghurt (n 76); (iii) cheese (n 67) and (iv) fish (n 11). After excluding organic products (n 48), which cannot be fortified, only 28 % (n 29) of milk alternatives and 6 % (n 4) of yoghurt alternatives were fortified with iodine, compared with 88 % (n 92) and 73 % (n 51), respectively, with Ca. No cheese alternative was fortified with iodine, but 55 % were fortified with Ca. None of the fish alternatives were iodine fortified. Substitution of three portions of dairy product (milk/yoghurt/cheese) per day with unfortified alternatives would reduce the iodine provided by 97·9 % (124 v. 2·6 µg) and substantially reduce the contribution to the adult intake recommendation (150 µg/d; 83 v. 1·8 %). Our study highlights that the majority of plant-based alternatives are not iodine fortified and that the use of unfortified alternatives put consumers at risk of iodine deficiency.

Natural and Synthetic Suppressor Mutations Defy Stability-Activity Tradeoffs.

Thermodynamic stability represents one important constraint on protein evolution, but the molecular basis for how mutations that change stability impact fitness remains unclear. Here, we demonstrate that a prevalent global suppressor mutation in TEM ß-lactamase, M182T, increases fitness by reducing proteolysis in vivo. We also show that a synthetic mutation, M182S, can act as a global suppressor and suggest that its absence from natural populations is due to genetic inaccessibility rather than fundamental differences in the protein's stability or activity.

Vitamin D Supplementation and Sunlight Exposure on Serum Vitamin D Concentrations in 2 Parallel, Double-Blind, Randomized, Placebo-Controlled Trials.

BACKGROUND: Vitamin D concentrations are a function of sunlight exposure and dietary intake. However, current dietary vitamin D recommendations do not consider differences in country-specific sunlight availability or spontaneous individual exposure. OBJECTIVES: We aimed to investigate the effects of vitamin D supplementation and sunlight exposure on vitamin D concentrations in Brazilian women living in high compared with low latitudes. METHODS: In 2 parallel, double-blind, randomized placebo-controlled trials, Brazilian women living in England (51°N) composed "without ultraviolet B (UVB) exposure" groups and those living in Brazil (16°S) composed the "with UVB exposure" groups (mean age, 31.39 ± 8.7 years). Participants received 15 µg cholecalciferol or placebo daily for 12 weeks during wintertime. Serum 25-hydroxyvitamin D [25(OH)D] concentrations, the primary outcome, were assessed by HPLC-MS/MS, vitamin D intakes were assessed by 4-day diet diaries, and sunlight exposure was assessed by UVB dosimeters. The effects of supplementation and UVB exposure were tested by the intention to treat with a linear mixed model. RESULTS: The 25(OH)D concentrations increased in both supplemented groups [from 75.1 ± 22.0 to 84.8 ± 21.0 nmol/L (P = 0.004) in the group with UVB exposure; from 38.1 ± 15.9 to 55.1 ± 12.2 nmol/L (P < 0.001) in the group without UVB exposure], with no significant changes in either placebo group. Concentrations in both supplemented groups were higher than those in the placebo group without UVB exposure (P = 0.0002 in the group with UVB exposure; P = 0.0035 in the group without UVB exposure). Postintervention 25(OH)D concentrations were significantly affected by serum 25(OH)D concentrations at baseline (P < 0.0001) and by intervention (placebo or supplement; P > 0.0001), with a large effect size (Cohen's D = 0.768), but were not affected by UVB exposure (with or without; P = 0.1386), nor by the interaction between the intervention (placebo or supplement) and UVB exposure (with or without; P = 0.9845). CONCLUSIONS: Moderate supplementation of 15 ug/d cholecalciferol, in accordance with current recommendations, supports an adequate vitamin D status in adult women, irrespective of latitude, and might concomitantly prevent an increase in parathyroid hormone. The Interaction Between Vitamin D Supplementation and Sunlight Exposure in Women Living in Opposite Latitudes (D-SOL) study was registered at clinicaltrials.gov as NCT03318029.

Home Blood Pressure Monitoring.

Home blood pressure monitoring provides important diagnostic information beyond in-office blood pressure readings and offers similar results to ambulatory blood pressure monitoring. Home blood pressure monitoring involves patients independently measuring their blood pressure with an electronic device, whereas ambulatory blood pressure monitoring involves patients wearing a portable monitor for 24 to 48 hours. Although ambulatory blood pressure monitoring is the diagnostic standard for measurement, home blood pressure monitoring is more practical and accessible to patients, and its use is recommended by the U.S. Preventive Services Task Force and the American College of Cardiology/American Heart Association. Home blood pressure monitoring generally results in lower blood pressure readings than in-office measurements, can confirm the diagnosis of hypertension after an elevated office blood pressure reading, and can identify patients with white coat hypertension or masked hypertension. Best practices for home blood pressure monitoring include using an appropriately fitting upper-arm cuff on a bare arm, emptying the bladder, avoiding caffeinated beverages for 30 minutes before taking the measurement, resting for five minutes before taking the measurement, keeping the feet on the floor uncrossed and the arm supported with the cuff at heart level, and not talking during the reading. An average of multiple readings, ideally two readings in the morning and again in the evening separated by at least one minute each, is recommended for one week. Home blood pressure readings can be used in hypertension quality measures.

Development and relative validation of a short food frequency questionnaire for assessing dietary intakes of non-alcoholic fatty liver disease patients.

PURPOSE: This work aimed to design and validate a novel short food frequency questionnaire (SFFQ) to assess habitual intakes of food items related to non-alcoholic fatty liver disease (NAFLD) in a cohort of European patients. METHODS: A 48-item SFFQ was created, with questions from existing FFQs and expert knowledge, emphasizing foods and nutrients implicated in NAFLD pathogenesis. Consenting, fibroscan-diagnosed, NAFLD patients completed the SFFQ during a short interview and were asked to complete a 4-day diet diary (4DDD) at home for return by mail. Nutritional intakes were assessed utilizing the myfood24™ food composition dataset and estimated energy requirements (EER) were calculated using sex-, age- and weight-specific equations. Agreement between the dietary instruments was assessed by Spearman correlations and Bland Altman analysis. RESULTS: Fifty-five patients completed both the SFFQ and the 4DDD within 30 weeks; 42 (76%) were diagnosed with simple steatosis, whereas 13 (24%) had biopsy-proven steatohepatitis; the majority were overweight or obese, with a median (25th; 75th percentile) BMI of 33.2 kg/m2 (29.3; 36.0). Reported energy intakes were well below EER with a median intake of 73% of requirements, suggesting widespread under-reporting. Significant correlations were observed between sugar (r = 0.408, P = 0.002), fat (r = 0.44, P = 0.001), fruits (r = 0.51, P = 0.0001) and vegetables (r = 0.40, P = 0.0024) measurements by the SFFQ and 4DDD. Bland Altman plots with regression analysis demonstrated broad comparability with the 4DDD for intakes of fat (bias - 13.8 g/day) and sugar (bias + 12.9 g/day). CONCLUSIONS: A novel SFFQ designed to be minimally burdensome to participants was effective at assessing dietary intakes in NAFLD patients.

Cooperative Changes in Solvent Exposure Identify Cryptic Pockets, Switches, and Allosteric Coupling.

Proteins are dynamic molecules that undergo conformational changes to a broad spectrum of different excited states. Unfortunately, the small populations of these states make it difficult to determine their structures or functional implications. Computer simulations are an increasingly powerful means to identify and characterize functionally relevant excited states. However, this advance has uncovered a further challenge: it can be extremely difficult to identify the most salient features of large simulation data sets. We reasoned that many functionally relevant conformational changes are likely to involve large, cooperative changes to the surfaces that are available to interact with potential binding partners. To examine this hypothesis, we introduce a method that returns a prioritized list of potentially functional conformational changes by segmenting protein structures into clusters of residues that undergo cooperative changes in their solvent exposure, along with the hierarchy of interactions between these groups. We term these groups exposons to distinguish them from other types of clusters that arise in this analysis and others. We demonstrate, using three different model systems, that this method identifies experimentally validated and functionally relevant conformational changes, including conformational switches, allosteric coupling, and cryptic pockets. Our results suggest that key functional sites are hubs in the network of exposons. As a further test of the predictive power of this approach, we apply it to discover cryptic allosteric sites in two different ß-lactamase enzymes that are widespread sources of antibiotic resistance. Experimental tests confirm our predictions for both systems. Importantly, we provide the first evidence, to our knowledge, for a cryptic allosteric site in CTX-M-9 ß-lactamase. Experimentally testing this prediction did not require any mutations and revealed that this site exerts the most potent allosteric control over activity of any pockets found in ß-lactamases to date. Discovery of a similar pocket that was previously overlooked in the well-studied TEM-1 ß-lactamase demonstrates the utility of exposons.

Evolutionary trend toward kinetic stability in the folding trajectory of RNases H.

Proper folding of proteins is critical to producing the biological machinery essential for cellular function. The rates and energetics of a protein's folding process, which is described by its energy landscape, are encoded in the amino acid sequence. Over the course of evolution, this landscape must be maintained such that the protein folds and remains folded over a biologically relevant time scale. How exactly a protein's energy landscape is maintained or altered throughout evolution is unclear. To study how a protein's energy landscape changed over time, we characterized the folding trajectories of ancestral proteins of the ribonuclease H (RNase H) family using ancestral sequence reconstruction to access the evolutionary history between RNases H from mesophilic and thermophilic bacteria. We found that despite large sequence divergence, the overall folding pathway is conserved over billions of years of evolution. There are robust trends in the rates of protein folding and unfolding; both modern RNases H evolved to be more kinetically stable than their most recent common ancestor. Finally, our study demonstrates how a partially folded intermediate provides a readily adaptable folding landscape by allowing the independent tuning of kinetics and thermodynamics.

Winter Cholecalciferol Supplementation at 51°N Has No Effect on Markers of Cardiometabolic Risk in Healthy Adolescents Aged 14-18 Years.

Background: Epidemiologic studies have supported inverse associations between low serum 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk markers, but few randomized trials have investigated the effect of vitamin D supplementation on these markers in adolescents. Objective: The objective of this study was to investigate the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk markers in white, healthy 14- to 18-y-old adolescents in the UK (51°N) as part of the ODIN Project. Methods: In a dose-response trial, 110 adolescents (mean ± SD age: 15.9 ± 1.4 y; 43% male; 81% normal weight) were randomly assigned to receive 0, 10 or 20 µg/d vitamin D3 for 20 wk (October-March). Cardiometabolic risk markers including BMI-for-age z score (BMIz), waist circumference, systolic and diastolic blood pressure, fasting plasma triglycerides, cholesterol (total, HDL, LDL, and total:HDL), and glucose were measured at baseline and endpoint as secondary outcomes, together with serum 25(OH)D. Intervention effects were evaluated in linear regression models as between-group differences at endpoint, adjusted for the baseline value of the outcome variable and additionally for age, sex, Tanner stage, BMIz, and baseline serum 25(OH)D. Results: Mean ± SD baseline serum 25(OH)D was 49.1 ± 12.3 nmol/L and differed between groups at endpoint with concentrations of 30.7 ± 8.6, 56.6 ± 12.4, and 63.9 ± 10.6 nmol/L in the 0, 10, and 20 µg/d groups, respectively (P ≤ 0.001). Vitamin D3 supplementation had no effect on any of the cardiometabolic risk markers (all P > 0.05), except for lower HDL (-0.12 mmol/L; 95% CI: -0.21, 0.04 mmol/L; P = 0.003) and total cholesterol (-0.21 mmol/L; 95% CI: -0.42, 0.00 mmol/L; P = 0.05) in the 20 µg/d than in the 10 µg/d group, which disappeared in the fully adjusted analysis (P = 0.27 and P = 0.30, respectively). Conclusions: Supplementation with vitamin D3 at 10 and 20 µg/d, which increased serum 25(OH)D concentrations during the winter-time, had no effect on markers of cardiometabolic risk in healthy 14- to 18-y-old adolescents. This trial was registered at clinicaltrials.gov as NCT02150122.

Winter Cholecalciferol Supplementation at 55°N Has No Effect on Markers of Cardiometabolic Risk in Healthy Children Aged 4-8 Years.

Background: Low serum 25-hydroxyvitamin D [25(OH)D] has been associated with unfavorable cardiometabolic risk profiles in many observational studies in children, but very few randomized controlled trials have investigated this. Objective: We explored the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk markers in young, white, 4- to 8-y-old healthy Danish children (55°N) as part of the pan-European ODIN project. Methods: In the ODIN Junior double-blind, placebo-controlled, dose-response trial, 119 children (mean ± SD age: 6.7 ± 1.5 y; 36% male; 82% normal weight) were randomly allocated to 0, 10 or 20 µg/d of vitamin D3 for 20 wk (October-March). Cardiometabolic risk markers including BMI-for-age z score (BMIz), waist circumference, systolic and diastolic blood pressure, serum triglycerides and cholesterol (total, LDL, HDL, and total:HDL), plasma glucose and insulin, and whole-blood glycated hemoglobin were measured at baseline and endpoint as secondary outcomes together with serum 25(OH)D. Intervention effects were evaluated in linear regression models as between-group differences at endpoint adjusted for baseline value of the outcome, and additionally for age, sex, baseline serum 25(OH)D, BMIz, time since breakfast, and breakfast content. Results: Mean ± SD serum 25(OH)D was 56.7 ± 12.3 nmol/L at baseline and differed between groups at endpoint with concentrations of 31.1 ± 7.5, 61.8 ± 10.6, and 75.8 ± 11.5 nmol/L in the 0-, 10-, and 20 µg/d groups, respectively (P < 0.0001). Vitamin D3 supplementation had no effect on any of the cardiometabolic risk markers in analyses adjusted for baseline value of the outcome (all P ≥ 0.05), and additional covariate adjustment did not change the results notably. Conclusions: Preventing the winter decline in serum 25(OH)D with daily vitamin D3 supplementation of 10 or 20 µg had no cardiometabolic effects in healthy 4- to 8-y-old Danish children. This trial was registered at www.clinicaltrials.gov as NCT02145195.

Discovery of multiple hidden allosteric sites by combining Markov state models and experiments.

The discovery of drug-like molecules that bind pockets in proteins that are not present in crystallographic structures yet exert allosteric control over activity has generated great interest in designing pharmaceuticals that exploit allosteric effects. However, there have only been a small number of successes, so the therapeutic potential of these pockets--called hidden allosteric sites--remains unclear. One challenge for assessing their utility is that rational drug design approaches require foreknowledge of the target site, but most hidden allosteric sites are only discovered when a small molecule is found to stabilize them. We present a means of decoupling the identification of hidden allosteric sites from the discovery of drugs that bind them by drawing on new developments in Markov state modeling that provide unprecedented access to microsecond- to millisecond-timescale fluctuations of a protein's structure. Visualizing these fluctuations allows us to identify potential hidden allosteric sites, which we then test via thiol labeling experiments. Application of these methods reveals multiple hidden allosteric sites in an important antibiotic target--TEM-1 ß-lactamase. This result supports the hypothesis that there are many as yet undiscovered hidden allosteric sites and suggests our methodology can identify such sites, providing a starting point for future drug design efforts. More generally, our results demonstrate the power of using Markov state models to guide experiments.

Thermodynamic system drift in protein evolution.

Proteins from thermophiles are generally more thermostable than their mesophilic homologs, but little is known about the evolutionary process driving these differences. Here we attempt to understand how the diverse thermostabilities of bacterial ribonuclease H1 (RNH) proteins evolved. RNH proteins from Thermus thermophilus (ttRNH) and Escherichia coli (ecRNH) share similar structures but differ in melting temperature (T(m)) by 20 °C. ttRNH's greater stability is caused in part by the presence of residual structure in the unfolded state, which results in a low heat capacity of unfolding (ΔCp) relative to ecRNH. We first characterized RNH proteins from a variety of extant bacteria and found that Tm correlates with the species' growth temperatures, consistent with environmental selection for stability. We then used ancestral sequence reconstruction to statistically infer evolutionary intermediates along lineages leading to ecRNH and ttRNH from their common ancestor, which existed approximately 3 billion years ago. Finally, we synthesized and experimentally characterized these intermediates. The shared ancestor has a melting temperature between those of ttRNH and ecRNH; the T(m)s of intermediate ancestors along the ttRNH lineage increased gradually over time, while the ecRNH lineage exhibited an abrupt drop in Tm followed by relatively little change. To determine whether the underlying mechanisms for thermostability correlate with the changes in T(m), we measured the thermodynamic basis for stabilization--ΔCp and other thermodynamic parameters--for each of the ancestors. We observed that, while the T(m) changes smoothly, the mechanistic basis for stability fluctuates over evolutionary time. Thus, even while overall stability appears to be strongly driven by selection, the proteins explored a wide variety of mechanisms of stabilization, a phenomenon we call "thermodynamic system drift." This suggests that even on lineages with strong selection to increase stability, proteins have wide latitude to explore sequence space, generating biophysical diversity and potentially opening new evolutionary pathways.

Systematic Review: Nutrition and Physical Activity in the Management of Paediatric Nonalcoholic Fatty Liver Disease.

OBJECTIVES: The aim of the study was to evaluate efficacy of nutrition and physical activity interventions in the clinical management of paediatric nonalcoholic fatty liver disease. The prevalence of paediatric nonalcoholic fatty liver disease continues to rise alongside childhood obesity. Weight loss through lifestyle modification is currently first-line treatment, although supplementation of specific dietary components may be beneficial. METHODS: Medline, CINAHL, EMBASE, Scopus, and Cochrane Libraries were systematically searched to identify randomized controlled trials assessing nutritional and physical activity interventions. Primary outcome measures were changes to liver biomarkers assessed by imaging, histology, or serum liver function tests. Study quality was evaluated using the American Dietetic Association Quality Criteria Checklist. RESULTS: Fifteen articles met eligibility criteria investigating nutritional supplementation (vitamin E [n = 6], probiotics [n = 2], omega-3 fatty acids [n = 5]), dietary modification (low glycaemic load [n = 1] and reducing fructose intake [n = 1]). No randomized controlled trials examining physical activity interventions were identified. Vitamin E was ineffective at improving alanine transaminase levels, whereas omega-3 fatty acids decreased hepatic fat content. Probiotics gave mixed results, whereas reduced fructose consumption did not improve primary outcome measures. A low glycaemic load diet and a low-fat diet appeared equally effective in decreasing hepatic fat content and transaminases. Most studies were deemed neutral as assessed by the American Dietetic Association Quality Criteria Checklist. CONCLUSIONS: The limited evidence base inhibits the prescription of specific dietary and/or lifestyle strategies for clinical practice. General healthy eating and physical activity guidelines, promoting weight loss, should remain first-line treatment until high-quality evidence emerges that support specific interventions that offer additional clinical benefit.

Tackling the dual burden of malnutrition in pregnancy - pregnancy after weight loss surgery.

The dual burden of malnutrition is characterised by the coexistence of undernutrition alongside overweight/obesity and diet-related noncommunicable diseases. It is a paradox which disproportionately affects women and is applicable to those who become pregnant after weight loss surgery. Obesity before and during pregnancy is associated with increased risk of adverse perinatal outcomes in both mother and child. Overall lifestyle interventions targeting weight loss in the preconception period have not proven effective, with people, and women in particular, increasingly seeking weight loss surgery. In women with severe obesity, surgery may normalise hormonal abnormalities and improve fertility. In those who become pregnant after surgery, evidence suggests a better overall obstetric outcome compared to those with severe obesity managed conservatively; however, there is heightened risk of maternal nutritional deficiencies and infants born small for gestational age. Specifically, pregnancy soon after surgery, in the catabolic phase when rapid weight loss is occurring, has the potential for poor outcomes. Lifelong micronutrient supplementation is required, and there is considerable risk of malnutrition if nutritional aftercare guidelines are not adhered to. It is therefore recommended that pregnancy is delayed until a stable weight is achieved and is supported by individualised advice from a multidisciplinary team. Further research is required to better understand how weight loss surgery affects the chances of having a healthy pregnancy and to ultimately improve nutritional management and patient care. In this review, we aim to summarise the evidence and guidance around nutrition during pregnancy after weight loss surgery.

Micronutrient supplement recommendations in pregnancy vary across a geographically diverse range of countries: a narrative review.

Specific food supplements are essential during preconception and pregnancy to ensure adequate intake of vitamins and minerals to support fetal growth and development and metabolic changes in the maternal body. Our objective was to identify food supplement recommendations, particularly those of folic acid, iron, Vitamin D, and iodine, during preconception and/or pregnancy across a geographically diverse range of countries. Further, we investigated whether country location and income-level related to the recommendations. We performed an electronic search and identified country-specific preconception and pregnancy food supplement recommendations, policy documents, and official guidelines of national organizations informing recommendations. To ensure the data were as accurate as possible, country-specific experts were contacted. Data were collected in 2017 and reevaluated in 2022. Country income level was determined by the World Bank classification. Each inspected country (n = 43) recommended folic acid supplementation, typically 400 µg/day, before and during pregnancy. About half of the countries recommended an iron supplement (dose range, 16-195 mg/day) and one quarter Vitamin D (typically 10 µg/d in higher latitudes) and iodine (150-200 µg/day). Country location and income level had some influence on the recommendations. Vitamin D was more often recommended in higher latitude, high-income countries. Almost all upper-middle and lower-middle income countries recommended iron supplementation, whereas less than one third of high-income countries had a corresponding recommendation. Findings suggest that food supplement recommendations for pregnant women vary across countries, likely influenced by geographic location as well as income level. These data may be used in the harmonization of food supplement recommendations.

Standard Nutritional Assessment Tools Are Unable to Predict Loss of Muscle Mass in Patients Due to Undergo Pancreatico-Duodenectomy: Highlighting the Need for Detailed Nutritional Assessment.

BACKGROUND AND METHODS: Pancreatico-duodenectomy (PD) carries significant morbidity and mortality, with very few modifiable risk factors. Radiological evidence of sarcopenia is associated with poor outcomes. This retrospective study aimed to analyse the relationship between easy-to-use bedside nutritional assessment techniques and radiological markers of muscle loss to identify those patients most likely to benefit from prehabilitation. RESULTS: Data were available in 184 consecutive patients undergoing PD. Malnutrition was present in 33-71%, and 48% had a high visceral fat-to-skeletal muscle ratio, suggestive of sarcopenic obesity (SO). Surgical risk was higher in patients with obesity (OR 1.07, 95%CI 1.01-1.14, p = 0.031), and length of stay was 5 days longer in those with SO (p = 0.006). There was no correlation between skeletal muscle and malnutrition using percentage weight loss or the malnutrition universal screening tool (MUST), but a weak correlation between the highest hand grip strength (HGS; 0.468, p < 0.001) and the Global Leadership in Malnutrition (GLIM) criteria (-0.379, p < 0.001). CONCLUSIONS: Nutritional assessment tools give widely variable results. Further research is needed to identify patients at significant nutritional risk prior to PD. In the meantime, those with malnutrition (according to the GLIM criteria), obesity or low HGS should be referred to prehabilitation.

Differential effects of disulfide bond formation in TEM-1 versus CTX-M-9 ß-lactamase.

To investigate how disulfide bonds can impact protein energy landscapes, we surveyed the effects of adding or removing a disulfide in two ß-lactamase enzymes, TEM-1 and CTX-M-9. The homologs share a structure and 38% sequence identity, but only TEM-1 contains a native disulfide bond. They also differ in thermodynamic stability and in the number of states populated at equilibrium: CTX-M-9 is two-state whereas TEM-1 has an additional intermediate state. We hypothesized that the disulfide bond is the major underlying determinant for these observed differences in their energy landscapes. To test this, we removed the disulfide bridge from TEM-1 and introduced a disulfide bridge at the same location in CTX-M-9. This modest change to sequence modulates the stabilities-and therefore populations-of TEM-1's equilibrium states and, more surprisingly, creates a novel third state in CTX-M-9. Unlike TEM-1's partially folded intermediate, this third state is a higher-order oligomer with reduced cysteines that retains the native fold and is fully active. Sub-denaturing concentrations of urea shifts the equilibrium to the monomeric form, allowing the disulfide bond to form. Interestingly, comparing the stability of the oxidized monomer with a variant lacking cysteines reveals the disulfide is neither stabilizing nor destabilizing in CTX-M-9, in contrast with the observed stabilization in TEM-1. Thus, we can conclude that engineering disulfide bonds is not always an effective stabilization strategy even when analogous disulfides exist in more stable structural homologs. This study also illustrates how homo-oligomerization can result from a small number of mutations, suggesting complex formation might be easily accessed during a protein family's evolution.

Tackling (Childhood) Obesity through a Voluntary Food Reformulation Policy: A Repeated Cross-Sectional Study Investigating Nutritional Changes in the Out-of-Home Sector.

The Childhood Obesity Plan aimed to reduce sugar and energy in foods through a voluntary sugar-reduction programme. Our primary objective was to determine whether this implementation strategy had been successful, focusing on the out-of-home sector. We used a repeated cross-sectional design to evaluate nutritional changes in desserts served by leading chain restaurants. We extracted nutrition information from online menus in autumn/winter 2020, for comparison with baseline (2017) and interim (2018) values extracted from third-party datasets. We assessed compliance with the 20% sugar-reduction target and category-specific energy targets by product category and for pooled desserts. Overall, sugar/portion and energy/portion decreased by 11% and 4%, respectively. Policy targets were achieved in one of five categories (ice-cream: -38% sugar, p < 0.001; -30% energy, p < 0.001). Secondary outcomes were analysed for subgroups with the necessary data. Few chains significantly reduced sugar and/or energy across their dessert range. Energy/portion was positively associated with portion weight and sugar/portion but not with sugar/100 g. More than half of adults' desserts contained excessive sugar and/or saturated fat compared with dietary guidelines. Children's desserts less frequently exceeded guidelines. These results demonstrate that voluntary measures can drive substantial change when technical, commercial, and operational barriers can be overcome.

Do Patients Benefit from Micronutrient Supplementation following Pancreatico-Duodenectomy?

Pancreatico-duodenectomy (PD) includes resection of the duodenum and use of the proximal jejunum in a blind loop, thus reducing the absorptive capacity for vitamins and minerals. Several studies have analysed the frequency of micronutrient deficiencies, but there is a paucity of data on those taking routine supplements. A retrospective review of medical notes was undertaken on 548 patients under long-term follow-up following PD in a tertiary hepato-pancreatico-biliary centre. Data were available on 205 patients from 1-14 years following PD, and deficiencies were identified as follows: vitamin A (3%), vitamin D (46%), vitamin E (2%), iron (42%), iron-deficiency anaemia (21%), selenium (3%), magnesium (6%), copper (1%), and zinc (44%). Elevated parathyroid hormone was present in 11% of cases. There was no significant difference over time (p > 0.05). Routine supplementation with a vitamin and mineral supplement did appear to reduce the incidence of biochemical deficiency in vitamin A, vitamin E, and selenium compared to published data. However, iron, vitamin D, and zinc deficiencies were prevalent despite supplementation and require surveillance.