Control of immunity via nutritional interventions.

Nutrition affects all physiological processes including those linked to the development and function of our immune system. Here, we discuss recent evidence and emerging concepts supporting the idea that our newfound relationship with nutrition in industrialized countries has fundamentally altered the way in which our immune system is wired. This will be examined through the lens of studies showing that mild or transient reductions in dietary intake can enhance protective immunity while also limiting aberrant inflammatory responses. We will further discuss how trade-offs and priorities begin to emerge in the context of severe nutritional stress. In those settings, specific immunological functions are heightened to re-enforce processes and tissue sites most critical to survival. Altogether, these examples will emphasize the profound influence nutrition has over the immune system and highlight how a mechanistic exploration of this cross talk could ultimately lead to the design of novel therapeutic approaches that prevent and treat disease.

Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition.

Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.

Food for the brain.

Diet is a major issue facing humanity. To combat malnourishment and diseases associated with overnutrition, both research and technological breakthroughs are needed.

Bioactive glycans in a microbiome-directed food for children with malnutrition.

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Here we analyse biospecimens from a randomized, controlled trial of a microbiome-directed complementary food (MDCF-2) that produced superior rates of weight gain compared with a calorically more dense conventional ready-to-use supplementary food in 12-18-month-old Bangladeshi children with moderate acute malnutrition4. We reconstructed 1,000 bacterial genomes (metagenome-assembled genomes (MAGs)) from the faecal microbiomes of trial participants, identified 75 MAGs of which the abundances were positively associated with ponderal growth (change in weight-for-length Z score (WLZ)), characterized changes in MAG gene expression as a function of treatment type and WLZ response, and quantified carbohydrate structures in MDCF-2 and faeces. The results reveal that two Prevotella copri MAGs that are positively associated with WLZ are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2. The predicted specificities of carbohydrate-active enzymes expressed by their polysaccharide-utilization loci are correlated with (1) the in vitro growth of Bangladeshi P. copri strains, possessing varying degrees of polysaccharide-utilization loci and genomic conservation with these MAGs, in defined medium containing different purified glycans representative of those in MDCF-2, and (2) the levels of faecal carbohydrate structures in the trial participants. These associations suggest that identifying bioactive glycan structures in MDCFs metabolized by growth-associated bacterial taxa will help to guide recommendations about their use in children with acute malnutrition and enable the development of additional formulations.

Child wasting and concurrent stunting in low- and middle-income countries.

Sustainable Development Goal 2.2-to end malnutrition by 2030-includes the elimination of child wasting, defined as a weight-for-length z-score that is more than two standard deviations below the median of the World Health Organization standards for child growth1. Prevailing methods to measure wasting rely on cross-sectional surveys that cannot measure onset, recovery and persistence-key features that inform preventive interventions and estimates of disease burden. Here we analyse 21 longitudinal cohorts and show that wasting is a highly dynamic process of onset and recovery, with incidence peaking between birth and 3 months. Many more children experience an episode of wasting at some point during their first 24 months than prevalent cases at a single point in time suggest. For example, at the age of 24 months, 5.6% of children were wasted, but by the same age (24 months), 29.2% of children had experienced at least one wasting episode and 10.0% had experienced two or more episodes. Children who were wasted before the age of 6 months had a faster recovery and shorter episodes than did children who were wasted at older ages; however, early wasting increased the risk of later growth faltering, including concurrent wasting and stunting (low length-for-age z-score), and thus increased the risk of mortality. In diverse populations with high seasonal rainfall, the population average weight-for-length z-score varied substantially (more than 0.5 z in some cohorts), with the lowest mean z-scores occurring during the rainiest months; this indicates that seasonally targeted interventions could be considered. Our results show the importance of establishing interventions to prevent wasting from birth to the age of 6 months, probably through improved maternal nutrition, to complement current programmes that focus on children aged 6-59 months.

Causes and consequences of child growth faltering in low-resource settings.

Growth faltering in children (low length for age or low weight for length) during the first 1,000 days of life (from conception to 2 years of age) influences short-term and long-term health and survival1,2. Interventions such as nutritional supplementation during pregnancy and the postnatal period could help prevent growth faltering, but programmatic action has been insufficient to eliminate the high burden of stunting and wasting in low- and middle-income countries. Identification of age windows and population subgroups on which to focus will benefit future preventive efforts. Here we use a population intervention effects analysis of 33 longitudinal cohorts (83,671 children, 662,763 measurements) and 30 separate exposures to show that improving maternal anthropometry and child condition at birth accounted for population increases in length-for-age z-scores of up to 0.40 and weight-for-length z-scores of up to 0.15 by 24 months of age. Boys had consistently higher risk of all forms of growth faltering than girls. Early postnatal growth faltering predisposed children to subsequent and persistent growth faltering. Children with multiple growth deficits exhibited higher mortality rates from birth to 2 years of age than children without growth deficits (hazard ratios 1.9 to 8.7). The importance of prenatal causes and severe consequences for children who experienced early growth faltering support a focus on pre-conception and pregnancy as a key opportunity for new preventive interventions.

Cis-regulatory polymorphism at fiz ecdysone oxidase contributes to polygenic evolutionary response to malnutrition in Drosophila.

We investigate the contribution of a candidate gene, fiz (fezzik), to complex polygenic adaptation to juvenile malnutrition in Drosophila melanogaster. Experimental populations maintained for >250 generations of experimental evolution to a nutritionally poor larval diet (Selected populations) evolved several-fold lower fiz expression compared to unselected Control populations. Here we show that this divergence in fiz expression is mediated by a cis-regulatory polymorphism. This polymorphism, originally sampled from a natural population in Switzerland, is distinct from a second cis-regulatory SNP previously identified in non-African D. melanogaster populations, implying that two independent cis-regulatory variants promoting high fiz expression segregate in non-African populations. Enzymatic analyses of Fiz protein expressed in E. coli demonstrate that it has ecdysone oxidase activity acting on both ecdysone and 20-hydroxyecdysone. Four of five fiz paralogs annotated to ecdysteroid metabolism also show reduced expression in Selected larvae, implying that malnutrition-driven selection favored general downregulation of ecdysone oxidases. Finally, as an independent test of the role of fiz in poor diet adaptation, we show that fiz knockdown by RNAi results in faster larval growth on the poor diet, but at the cost of greatly reduced survival. These results imply that downregulation of fiz in Selected populations was favored by selection on the nutritionally poor diet because of its role in suppressing growth in response to nutrient shortage. However, they suggest that fiz downregulation is only adaptive in combination with other changes evolved by Selected populations, which ensure that the organism can sustain the faster growth promoted by fiz downregulation.

AGA Clinical Practice Update on Diet and Nutritional Therapies in Patients With Inflammatory Bowel Disease: Expert Review.

DESCRIPTION: Diet plays a critical role in human health, but especially for patients with inflammatory bowel disease (IBD). Guidance about diet for patients with IBD are often controversial and a source of uncertainty for many physicians and patients. The role of diet has been investigated as a risk factor for IBD etiopathogenesis and as a therapy for active disease. Dietary restrictions, along with the clinical complications of IBD, can result in malnutrition, an underrecognized condition among this patient population. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) is to provide best practice advice statements, primarily to clinical gastroenterologists, covering the topics of diet and nutritional therapies in the management of IBD, while emphasizing identification and treatment of malnutrition in these patients. We provide guidance for tailored dietary approaches during IBD remission, active disease, and intestinal failure. A healthy Mediterranean diet will benefit patients with IBD, but may require accommodations for food texture in the setting of intestinal strictures or obstructions. New data in Crohn's disease supports the use of enteral liquid nutrition to help induce remission and correct malnutrition in patients heading for surgery. Parenteral nutrition plays a critical role in patients with IBD facing acute and/or chronic intestinal failure. Registered dietitians are an essential part of the interdisciplinary team approach for optimal nutrition assessment and management in the patient population with IBD. METHODS: This expert review was commissioned and approved by the AGA Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Gastroenterology. The best practice advice statements were drawn from reviewing existing literature combined with expert opinion to provide practical advice on the role of diet and nutritional therapies in patients with IBD. Because this was not a systematic review, formal rating of the quality of evidence or strength of the presented considerations was not performed. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Unless there is a contraindication, all patients with IBD should be advised to follow a Mediterranean diet rich in a variety of fresh fruits and vegetables, monounsaturated fats, complex carbohydrates, and lean proteins and low in ultraprocessed foods, added sugar, and salt for their overall health and general well-being. No diet has consistently been found to decrease the rate of flares in adults with IBD. A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn's disease. BEST PRACTICE ADVICE 2: Patients with IBD who have symptomatic intestinal strictures may not tolerate fibrous, plant-based foods (ie, raw fruits and vegetables) due to their texture. An emphasis on careful chewing and cooking and processing of fruits and vegetables to a soft, less fibrinous consistency may help patients with IBD who have concomitant intestinal strictures incorporate a wider variety of plant-based foods and fiber in their diets. BEST PRACTICE ADVICE 3: Exclusive enteral nutrition using liquid nutrition formulations is an effective therapy for induction of clinical remission and endoscopic response in Crohn's disease, with stronger evidence in children than adults. Exclusive enteral nutrition may be considered as a steroid-sparing bridge therapy for patients with Crohn's disease. BEST PRACTICE ADVICE 4: Crohn's disease exclusion diet, a type of partial enteral nutrition therapy, may be an effective therapy for induction of clinical remission and endoscopic response in mild to moderate Crohn's disease of relatively short duration. BEST PRACTICE ADVICE 5: Exclusive enteral nutrition may be an effective therapy in malnourished patients before undergoing elective surgery for Crohn's disease to optimize nutritional status and reduce postoperative complications. BEST PRACTICE ADVICE 6: In patients with IBD who have an intra-abdominal abscess and/or phlegmonous inflammation that limits ability to achieve optimal nutrition via the digestive tract, short-term parenteral nutrition may be used to provide bowel rest in the preoperative phase to decrease infection and inflammation as a bridge to definitive surgical management and to optimize surgical outcomes. BEST PRACTICE ADVICE 7: We suggest the use of parenteral nutrition for high-output gastrointestinal fistula, prolonged ileus, short bowel syndrome, and for patients with IBD with severe malnutrition when oral and enteral nutrition has been trialed and failed or when enteral access is not feasible or contraindicated. BEST PRACTICE ADVICE 8: In patients with IBD and short bowel syndrome, long-term parenteral nutrition should be transitioned to customized hydration management (ie, intravenous electrolyte support and/or oral rehydration solutions) and oral intake whenever possible to decrease the risk of developing long-term complications. Treatment with glucagon-like peptide-2 agonists can facilitate this transition. BEST PRACTICE ADVICE 9: All patients with IBD warrant regular screening for malnutrition by their provider by means of assessing signs and symptoms, including unintended weight loss, edema and fluid retention, and fat and muscle mass loss. When observed, more complete evaluation for malnutrition by a registered dietitian is indicated. Serum proteins are no longer recommended for the identification and diagnosis of malnutrition due to their lack of specificity for nutritional status and high sensitivity to inflammation. BEST PRACTICE ADVICE 10: All patients with IBD should be monitored for vitamin D and iron deficiency. Patients with extensive ileal disease or prior ileal surgery (resection or ileal pouch) should be monitored for vitamin B12 deficiency. BEST PRACTICE ADVICE 11: All outpatients and inpatients with complicated IBD warrant co-management with a registered dietitian, especially those who have malnutrition, short bowel syndrome, enterocutaneous fistula, and/or are requiring more complex nutrition therapies (eg, parenteral nutrition, enteral nutrition, or exclusive enteral nutrition), or those on a Crohn's disease exclusion diet. We suggest that all newly diagnosed patients with IBD have access to a registered dietitian. BEST PRACTICE ADVICE 12: Breastfeeding is associated with a lower risk for diagnosis of IBD during childhood. A healthy, balanced, Mediterranean diet rich in a variety of fruits and vegetables and decreased intake of ultraprocessed foods have been associated with a lower risk of developing IBD.

Diet and Food and Nutrition Insecurity and Cardiometabolic Disease.

Poor nutrition is the leading cause of poor health, health care spending, and lost productivity in the United States and globally, which acts through cardiometabolic diseases as precursors to cardiovascular disease, cancer, and other conditions. There is great interest in how the social determinants of health (the conditions in which people are born, live, work, develop, and age) impact cardiometabolic disease. Food insecurity is an example of a powerful social determinant of health that impacts health outcomes. Nutrition insecurity, a distinct but related concept to food insecurity, is a direct determinant of health. In this article, we provide an overview of how diet in early life relates to cardiometabolic disease and then continue to focus on the concepts of food insecurity and nutrition insecurity. In the discussions herein we make important distinctions between the concepts of food insecurity and nutrition insecurity and provide a review of their concepts, histories, measurement and assessment devices, trends and prevalence, and links to health and health disparities. The discussions here set the stage for future research and practice to directly address the negative consequences of food and nutrition insecurity.

Trade and foreign fishing mediate global marine nutrient supply.

Fish are an important source of bioavailable micronutrients and essential fatty acids, and capture fisheries have potential to substantially reduce dietary deficiencies. Vigorous debate has focused on trade and fishing in foreign waters as drivers of inequitable distribution of volume and value of fish, but their impact on nutrient supplies from fish is unknown. We analyze global catch, trade, and nutrient composition data for marine fisheries to quantify distribution patterns among countries with differing prevalence of inadequate nutrient intake. We find foreign fishing relocates 1.5 times more nutrients than international trade in fish. Analysis of nutrient flows among countries of different levels of nutrient intake shows fishing in foreign waters predominantly (but not exclusively) benefits nutrient-secure nations, an outcome amplified by trade. Next, we developed a nutritional vulnerability framework that shows those small island developing states and/or African nations currently benefiting from trade and foreign fishing, and countries with low adaptive capacity, are most vulnerable to future changes in nutrient supplies. Climate change exacerbates vulnerabilities for many nations. Harnessing the potential of global fisheries to address dietary deficiencies will require greater attention to nutrition objectives in fisheries' licensing deals and trade negotiations.

Undernourished Household Contacts Are at Increased Risk of Tuberculosis (TB) Disease, but not TB Infection-a Multicenter Prospective Cohort Analysis.

Undernutrition is the leading risk factor for tuberculosis (TB) globally and in India. This multicenter prospective cohort analysis from India suggests that undernutrition is associated with increased risk of TB disease but not TB infection among household contacts of persons with TB.

Low vitamin B12 blood levels in sickle cell disease: Data from a large cohort study in Tanzania.

Sickle cell disease (SCD) is associated with high rates of undernutrition and stunting. Undernutrition in combination with chronic haemolysis may lead to deficiencies in micronutrients necessary for erythropoiesis. Here we examined selected levels of ferritin, vitamins B2 , B6 , B9 and B12 , and vitamin C that were measured in blood samples from 820 SCD patients from Tanzania with no history of hospital admission, infections or painful episodes in the previous 30 days. We studied children (0-8 years), early adolescents (9-14 years), late adolescents (15-17 years) and adults (≥18 years). Severely low levels of vitamin B12 were observed across the four age groups. Despite the lowered vitamin B12 concentrations, total homocysteine concentrations were normal across both genders in all age groups. We found no significant gender-related differences between the other measured micronutrients. In this large SCD population, spanning the whole life cycle, a low level of vitamin B12 was consistently found across both genders and all age groups. Given the pivotal role of vitamin B12 in cellular metabolism, particularly in erythropoiesis, more studies are required to unravel how to better detect clinically relevant vitamin B12 deficiency among SCD patients, and thus to identify more precisely those who need supplementation of vitamin B12 .

Impact of Perioperative Immunonutrition on Postoperative Outcomes for Patients Undergoing Head and Neck or Gastrointestinal Cancer Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To clarify whether perioperative immunonutrition is effective in adult patients with or without malnutrition undergoing elective surgery for head and neck (HAN) or gastrointestinal (GI) cancers. BACKGROUND: It is important to avoid postoperative complications in patients with cancer as they can compromise clinical outcomes. There is no consensus on the efficacy of perioperative immunonutrition in patients with or without malnutrition undergoing HAN or GI cancer surgery. MATERIALS AND METHODS: We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981 to 2022 using search terms related to immunonutrition and HAN or GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were total postoperative and infectious complications, defined as events with a Clavien-Dindo classification grade ≥ II that occurred within 30 days after surgery. RESULTS: Of the 4825 patients from 48 included studies, 19 had upper GI cancer, 9 had lower, and 8 had mixed cancer, whereas 12 had HAN cancers. Immunonutrition reduced the total postoperative complications (relative risk ratio: 0.78; 95% CI, 0.66-0.93; certainty of evidence: high) and infectious complications (relative risk ratio: 0.71; 95% CI, 0.61-0.82; certainty of evidence: high) compared with standard nutritional therapy. CONCLUSIONS: Nutritional intervention with perioperative immunonutrition in patients with HAN and GI cancers significantly reduced total postoperative complications and infectious complications.

Malnutrition in older adults.

Malnutrition is a highly prevalent condition in older adults, and poses a substantial burden on health, social, and aged-care systems. Older adults are vulnerable to malnutrition due to age-related physiological decline, reduced access to nutritious food, and comorbidity. Clinical guidelines recommend routine screening for malnutrition in all older adults, together with nutritional assessment and individually tailored nutritional support for older adults with a positive screening test. Nutritional support includes offering individualised nutritional advice and counselling; oral nutritional supplements; fortified foods; and enteral or parenteral nutrition as required. However, in clinical practice, the incorporation of nutritional guidelines is inadequate and low-value care is commonplace. This Review discusses the current evidence on identification and treatment of malnutrition in older adults, identifies gaps between evidence and practice in clinical care, and offers practical strategies to translate evidence-based knowledge into improved nutritional care. We also provide an overview of the prevalence, causes, and risk factors of malnutrition in older adults across health-care settings.

Burden of disease attributable to unsafe drinking water, sanitation, and hygiene in domestic settings: a global analysis for selected adverse health outcomes.

BACKGROUND: Assessments of disease burden are important to inform national, regional, and global strategies and to guide investment. We aimed to estimate the drinking water, sanitation, and hygiene (WASH)-attributable burden of disease for diarrhoea, acute respiratory infections, undernutrition, and soil-transmitted helminthiasis, using the WASH service levels used to monitor the UN Sustainable Development Goals (SDGs) as counterfactual minimum risk-exposure levels. METHODS: We assessed the WASH-attributable disease burden of the four health outcomes overall and disaggregated by region, age, and sex for the year 2019. We calculated WASH-attributable fractions of diarrhoea and acute respiratory infections by country using modelled WASH exposures and exposure-response relationships from two updated meta-analyses. We used the WHO and UNICEF Joint Monitoring Programme for Water Supply, Sanitation and Hygiene public database to estimate population exposure to different WASH service levels. WASH-attributable undernutrition was estimated by combining the population attributable fractions (PAF) of diarrhoea caused by unsafe WASH and the PAF of undernutrition caused by diarrhoea. Soil-transmitted helminthiasis was fully attributed to unsafe WASH. FINDINGS: We estimate that 1·4 (95% CI 1·3-1·5) million deaths and 74 (68-80) million disability-adjusted life-years (DALYs) could have been prevented by safe WASH in 2019 across the four designated outcomes, representing 2·5% of global deaths and 2·9% of global DALYs from all causes. The proportion of diarrhoea that is attributable to unsafe WASH is 0·69 (0·65-0·72), 0·14 (0·13-0·17) for acute respiratory infections, and 0·10 (0·09-0·10) for undernutrition, and we assume that the entire disease burden from soil-transmitted helminthiasis was attributable to unsafe WASH. INTERPRETATION: WASH-attributable burden of disease estimates based on the levels of service established under the SDG framework show that progress towards the internationally agreed goal of safely managed WASH services for all would yield major public-health returns. FUNDING: WHO and Foreign, Commonwealth & Development Office.

A Microbiota-Directed Food Intervention for Undernourished Children.

BACKGROUND: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota. METHODS: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference values at baseline and every 2 weeks during the intervention period and at 4 months. We compared the rate of change of these related phenotypes between baseline and 3 months and between baseline and 4 months. We also measured levels of 4977 proteins in plasma and 209 bacterial taxa in fecal samples. RESULTS: A total of 118 children (59 in each study group) completed the intervention. The rates of change in the weight-for-length and weight-for-age z scores are consistent with a benefit of MDCF-2 on growth over the course of the study, including the 1-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 plasma proteins and of 21 associated bacterial taxa that were positively correlated with the weight-for-length z score (P<0.001 for comparisons of both protein and bacterial taxa). These proteins included mediators of bone growth and neurodevelopment. CONCLUSIONS: These findings provide support for MDCF-2 as a dietary supplement for young children with moderate acute malnutrition and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth. (Supported by the Bill and Melinda Gates Foundation and the National Institutes of Health; ClinicalTrials.gov number, NCT04015999.).

EEG functional connectivity as a Riemannian mediator: An application to malnutrition and cognition.

Mediation analysis assesses whether an exposure directly produces changes in cognitive behavior or is influenced by intermediate "mediators". Electroencephalographic (EEG) spectral measurements have been previously used as effective mediators representing diverse aspects of brain function. However, it has been necessary to collapse EEG measures onto a single scalar using standard mediation methods. In this article, we overcome this limitation and examine EEG frequency-resolved functional connectivity measures as a mediator using the full EEG cross-spectral tensor (CST). Since CST samples do not exist in Euclidean space but in the Riemannian manifold of positive-definite tensors, we transform the problem, allowing for the use of classic multivariate statistics. Toward this end, we map the data from the original manifold space to the Euclidean tangent space, eliminating redundant information to conform to a "compressed CST." The resulting object is a matrix with rows corresponding to frequencies and columns to cross spectra between channels. We have developed a novel matrix mediation approach that leverages a nuclear norm regularization to determine the matrix-valued regression parameters. Furthermore, we introduced a global test for the overall CST mediation and a test to determine specific channels and frequencies driving the mediation. We validated the method through simulations and applied it to our well-studied 50+-year Barbados Nutrition Study dataset by comparing EEGs collected in school-age children (5-11 years) who were malnourished in the first year of life with those of healthy classmate controls. We hypothesized that the CST mediates the effect of malnutrition on cognitive performance. We can now explicitly pinpoint the frequencies (delta, theta, alpha, and beta bands) and regions (frontal, central, and occipital) in which functional connectivity was altered in previously malnourished children, an improvement to prior studies. Understanding the specific networks impacted by a history of postnatal malnutrition could pave the way for developing more targeted and personalized therapeutic interventions. Our methods offer a versatile framework applicable to mediation studies encompassing matrix and Hermitian 3D tensor mediators alongside scalar exposures and outcomes, facilitating comprehensive analyses across diverse research domains.

Biofortification of Triticum species: a stepping stone to combat malnutrition.

BACKGROUND: Biofortification represents a promising and sustainable strategy for mitigating global nutrient deficiencies. However, its successful implementation poses significant challenges. Among staple crops, wheat emerges as a prime candidate to address these nutritional gaps. Wheat biofortification offers a robust approach to enhance wheat cultivars by elevating the micronutrient levels in grains, addressing one of the most crucial global concerns in the present era. MAIN TEXT: Biofortification is a promising, but complex avenue, with numerous limitations and challenges to face. Notably, micronutrients such as iron (Fe), zinc (Zn), selenium (Se), and copper (Cu) can significantly impact human health. Improving Fe, Zn, Se, and Cu contents in wheat could be therefore relevant to combat malnutrition. In this review, particular emphasis has been placed on understanding the extent of genetic variability of micronutrients in diverse Triticum species, along with their associated mechanisms of uptake, translocation, accumulation and different classical to advanced approaches for wheat biofortification. CONCLUSIONS: By delving into micronutrient variability in Triticum species and their associated mechanisms, this review underscores the potential for targeted wheat biofortification. By integrating various approaches, from conventional breeding to modern biotechnological interventions, the path is paved towards enhancing the nutritional value of this vital crop, promising a brighter and healthier future for global food security and human well-being.

Growth Hormone Therapy in Decompensated Cirrhosis: An Open-Label, Randomized Control Trial.

INTRODUCTION: Effect of long-term growth-hormone (GH) therapy in decompensated cirrhosis (DC) is unknown. We studied the safety and efficacy of GH therapy on malnutrition, nitrogen metabolism, and hormonal changes in patients with DC. METHODS: Patients with DC were randomized to standard medical therapy plus GH (group A; n = 38) or standard medical therapy alone (group B; n = 38). Body mass index, midarm muscle circumference (MAMC), hand grip strength (HGS), liver frailty index (LFI), skeletal muscle index (SMI), nitrogen balance, Child-Turcotte-Pugh, model for end-stage liver disease, quality of life (QOL), serum albumin, GH, insulin like growth factor-1, and acid labile subunit (ALS) were assessed at baseline and at 12 months. RESULTS: The mean difference between baseline and 12-months in SMI (-6.122 [-9.460 to -2.785] cm 2 /m 2 ), body mass index (-2.078 [-3.584 to -0.5718] kg/m 2 ), MAMC (-1.960 [-2.928 to -0.9908] cm), HGS (-5.595 [-7.159 to -4.031] kg), albumin (-0.3967 [-0.6876 to -0.1057] g/dL), LFI (0.3328 [0.07786-0.5878]), Child-Turcotte-Pugh (0.9624 [0.1435-1.781]), model for end-stage liver disease (1.401 [0.04698-2.75]), insulin-like growth factor-1 (-6.295 [-11.09 to -1.495] ng/dL), and ALS (-8.728 [-14.12 to -3.341] pg/mL) were statistically significantly better ( P < 0.05) in group A. There was no improvement in nutritional parameters, clinical scores, QOL scores, or nitrogen balance in group B. The mean difference between group A and B in SMI, HGS, MAMC, LFI, ALS, physical component summary, and mental component summary at 12 months was also statistically significant. Survival at 12 months was similar in both groups ( P = 0.35). No serious adverse events were observed. DISCUSSION: Long-term use of GH is safe in DC and leads to improvement in malnutrition and possibly QOL. However, there is no improvement in 12-month survival (NCT03420144).

Malnutrition and maternal vaccination against typhoid toxin.

Children are particularly susceptible to typhoid fever caused by the bacterial pathogen Salmonella Typhi. Typhoid fever is prevalent in developing countries where diets can be less well-balanced. Here, using a murine model, we investigated the role of the macronutrient composition of the diet in maternal vaccination efficacies of two subunit vaccines targeting typhoid toxin: ToxoidVac and PltBVac. We found that maternal vaccinations protected all offspring against a lethal-dose typhoid toxin challenge in a balanced, normal diet (ND) condition, but the declined protection in a malnourished diet (MD) condition was observed in the PltBVac group. Despite the comparable antibody titers in both MD and ND mothers, MD offspring had a significantly lower level of typhoid toxin neutralizing antibodies than their ND counterparts. We observed a lower expression of the neonatal Fc receptor on the yolk sac of MD mothers than in ND mothers, agreeing with the observed lower antibody titers in MD offspring. Protein supplementation to MD diets, but not fat supplementation, increased FcRn expression and protected all MD offspring from the toxin challenge. Similarly, providing additional typhoid toxin-neutralizing antibodies to MD offspring was sufficient to protect all MD offspring from the toxin challenge. These results emphasize the significance of balanced/normal diets for a more effective maternal vaccination transfer to their offspring.