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Scope: Legumes consumption has been proven to promote health across the lifespan; cowpeas have demonstrated efficacy in combating childhood malnutrition and growth faltering, with an estimated malnutrition prevalence of 35.6% of children in Ghana. This cowpea feeding study aimed to identify a suite of metabolic consumption biomarkers in children and adults., Methods and Results: Urine and dried blood spots (DBS) from 24 children (9-21 months) and 21 pregnant women (>18 years) in Northern Ghana are collected before and after dose-escalated consumption of four cowpea varieties for 15 days. Untargeted metabolomics identified significant increases in amino acids, phytochemicals, and lipids. The carnitine metabolism pathway is represented by 137 urine and 43 DBS metabolites, with significant changes to tiglylcarnitine and acetylcarnitine. Additional noteworthy candidate biomarkers are mansouramycin C, N-acetylalliin, proline betaine, N2, N5-diacetylornithine, S-methylcysteine, S-methylcysteine sulfoxide, and cis-urocanate. S-methylcysteine and S-methylcysteine sulfoxide are targeted and quantified in urine., Conclusion: This feeding study for cowpea biomarkers supports the utility of a suite of key metabolites classified as amino acids, lipids, and phytochemicals for dietary legume and cowpea-specific food exposures of global health importance., (© 2024 Wiley-VCH GmbH.)

Competing Interests: We declare no competing interests.

Human untargeted metabolomics studies annotate only ~10% of molecular features. We introduce reference-data-driven analysis to match metabolomics tandem mass spectrometry (MS/MS) data against metadata-annotated source data as a pseudo-MS/MS reference library. Applying this approach to food source data, we show that it increases MS/MS spectral usage 5.1-fold over conventional structural MS/MS library matches and allows empirical assessment of dietary patterns from untargeted data., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Legumes are global staple foods with multiple human health properties that merit detailed composition analysis in cooked forms. This study analyzed cowpea [ Vigna unguiculata ] (three varieties: Dagbantuya, Sangyi, and Tukara), pigeon pea [ Cajanus cajan ], and common bean [ Phaseolus vulgaris ] using two distinct ultra-performance liquid chromatography mass spectrometry (UPLC-MS) platforms and analytical workflows. Comparisons between cowpea and pigeon pea consumed in Ghana, and common bean (navy bean) from USA, revealed 75 metabolites that differentiated cowpeas. Metabolite fold-change comparisons resulted in 142 metabolites with significantly higher abundance in cowpea, and 154 higher in abundance from pigeon pea. 3-(all- trans -nonaprenyl)benzene-1,2-diol, N-tetracosanoylphytosphingosine, and sitoindoside II are novel identifications in cowpea, with notably higher abundance than other legumes tested. Cowpea variety specific markers were tonkinelin (Dagbantuya), pheophytin A (Sangyi), and linoleoyl ethanolamide (Tukara). This study identified novel cowpea and pigeon pea food metabolites that warrant continued investigation as bioactive food components following consumption in people., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Growth faltering under 5 years of age is unacceptably high worldwide, and even more children, while not stunted, fail to reach their growth potential. The time between conception and 2 years of age is critical for development. The period from 6 to 23 months, when complementary foods are introduced, coincides with a time when growth faltering and delayed neurocognitive developments are most common. Fortunately, this is also the period when diet exercises its greatest influence. Growing up in an adverse environment, with a deficient diet, as typically seen in low- and middle-income countries (LMICs), hampers growth and development of children and prevents them from realising their full developmental and economic future potential. Sufficient nutrient availability and utilisation are paramount to a child's growth and development trajectory, especially in the period after breastfeeding. This review highlights the importance of essential amino acids (EAAs) in early life for linear growth and, likely, neurocognitive development. The paper further discusses signalling through mammalian target of rapamycin complex 1 (mTORC1) as one of the main amino acid (AA)-sensing hubs and the master regulator of both growth and neurocognitive development. Children in LMICs, despite consuming sufficient total protein, do not meet their EAA requirements due to poor diet diversity and low-quality dietary protein. AA deficiencies in early life can cause reductions in linear growth and cognition. Ensuring AA adequacy in diets, particularly through inclusion of nutrient-dense animal source foods from 6 to 23 months, is strongly encouraged in LMICs in order to compensate for less than optimal growth during complementary feeding., (© 2021 FrieslandCampina. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: Kwashiorkor is a childhood syndrome of edematous malnutrition. Its precise nutritional precipitants remain uncertain despite nine decades of study. Remarkably, kwashiorkor's disturbances resemble the effects of experimental diets that are deficient in one-carbon nutrients. This similarity suggests that kwashiorkor may represent a nutritionally mediated syndrome of acute one-carbon metabolism dysfunction. Here we report findings from a cross-sectional exploration of serum one-carbon metabolites in Malawian children., Methods: Blood was collected from children aged 12-60 months before nutritional rehabilitation: kwashiorkor (N = 94), marasmic-kwashiorkor (N = 43) marasmus (N = 118), moderate acute malnutrition (N = 56) and controls (N = 46). Serum concentrations of 16 one-carbon metabolites were quantified using LC/MS techniques, and then compared across participant groups., Findings: Twelve of 16 measured one-carbon metabolites differed significantly between participant groups. Measured outputs of one-carbon metabolism, asymmetric dimethylarginine (ADMA) and cysteine, were lower in marasmic-kwashiorkor (median µmol/L (± SD): 0·549 (± 0·217) P = 0·00045 & 90 (± 40) P < 0·0001, respectively) and kwashiorkor (0·557 (± 0·195) P < 0·0001 & 115 (± 50) P < 0·0001), relative to marasmus (0·698 (± 0·212) & 153 (± 42)). ADMA and cysteine were well correlated with methionine in both kwashiorkor and marasmic-kwashiorkor., Interpretation: Kwashiorkor and marasmic-kwashiorkor were distinguished by evidence of one-carbon metabolism dysfunction. Correlative observations suggest that methionine deficiency drives this dysfunction, which is implicated in the syndrome's pathogenesis. The hypothesis that kwashiorkor can be prevented by fortifying low quality diets with methionine, along with nutrients that support efficient methionine use, such as choline, requires further investigation., Funding: The Hickey Family Foundation, the American College of Gastroenterology, the NICHD, and the USDA/ARS., Competing Interests: Declaration of Interests The authors have no conflicts or interests to disclose., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Two questions regarding the scientific literature have become grist for public discussion: 1) what place should P values have in reporting the results of studies? 2) How should the perceived difficulty in replicating the results reported in published studies be addressed? We consider these questions to be 2 sides of the same coin; failing to address them can lead to an incomplete or incorrect message being sent to the reader. If P values (which are derived from the estimate of the effect size and a measure of the precision of the estimate of the effect) are used improperly, for example reporting only significant findings, or reporting P values without account for multiple comparisons, or failing to indicate the number of tests performed, the scientific record can be biased. Moreover, if there is a lack of transparency in the conduct of a study and reporting of study results, it will not be possible to repeat a study in a manner that allows inferences from the original study to be reproduced or to design and conduct a different experiment whose aim is to confirm the original study's findings. The goal of this article is to discuss how P values can be used in a manner that is consistent with the scientific method, and to increase transparency and reproducibility in the conduct and analysis of nutrition research., (Published by Oxford University Press on behalf of the American Society for Nutrition 2021.)

Background: There is a lack of consensus on what is the most appropriate treatment of moderate acute malnutrition (MAM)., Objectives: We aimed to determine if provision of ready-to-use-therapeutic food (RUTF) and antibiotics to "high-risk" MAM (HR-MAM) children in addition to nutritional counseling would result in higher recovery and less deterioration than nutrition counseling alone., Methods: At the 11 intervention clinics, HR-MAM children were given RUTF and amoxicillin along with standard nutrition counseling, for 2-12 wk. All others received 6 wk of nutrition counseling alone. HR-MAM was defined as midupper arm circumference (MUAC) <11.9 cm, weight-for-age z score (WAZ) <-3.5, mother not the main caregiver, or a child <2 y old not being breastfed. Outcomes were compared using intention-to-treat analysis., Results: Analysis included 573 children at the intervention sites and 714 children at the control sites. Of the intervention group, 317 (55%) were classified as HR-MAM. Short-term recovery was greater at the intervention sites [48% compared with 39% at week 12; risk difference (rd): 0.08; 95% CI: 0.03, 0.13]. The intervention group had lower risk of deteriorating to severe acute malnutrition (SAM) (18% compared with 24%; rd: -0.07; 95% CI: -0.11, -0.04), lower risk of dying (1.8% compared with 3.1%; rd: -0.02; 95% CI: -0.03, -0.00), and greater gains in MUAC and weight than did children at the control sites. However, by 24 wk, the risk of SAM was similar between the 2 arms (31% compared with 34%; rd: -0.03; 95% CI: -0.09, 0.02). Control group data identified recent illness, MUAC <12.0 cm, WAZ <-3, dropping anthropometry, age <12 mo, being a twin, and a history of previous SAM as risk factors for deterioration., Conclusions: Provision of RUTF and antibiotics to HR-MAM children improved short-term recovery and reduced short-term risk of deterioration. However, recovery rates were still suboptimal and differences were not sustained by 6 mo post enrollment.This trial was registered at clinicaltrials.gov as NCT03647150., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Systematic reviews have highlighted that repeated severe wasting after receiving treatment is likely to be common, but standardised measurement is needed urgently. The Council of Research & Technical Advice for Acute Malnutrition (CORTASAM) released recommendations on standard measurement of relapse (wasting within 6 months after exiting treatment as per recommended discharge criteria), regression (wasting within 6 months after exiting treatment before reaching recommended discharge criteria) and reoccurrence (wasting after 6 months of exit from treatment as per recommended discharge criteria). We provide a theoretical framework of post-treatment relapse and regression to severe wasting to guide discussions, risk factor analyses, and development and evaluations of interventions. This framework highlights that there are factors that may impact risk of relapse and regression in addition to the impact of contextual factors associated with incidence and reoccurrence of severe wasting more generally. Factors hypothesised to be associated with relapse and regression relate specifically to the nutrition and health status of the child on admission to, during and exit from treatment and treatment interventions, platforms and approaches as well as type of exit from treatment (e.g., before reaching recommended criteria). These factors influence whether children reach full recovery, and poorer nutritional and immunological status at exit from treatment are more proximate determinants of risk of severe wasting after treatment, although post-treatment interventions may modify risks. The evidence base for many of these factors is weak. Our framework can guide research to improve our understanding of risks of relapse and regression and how to prevent them and inform programmes on what data to collect to evaluate relapse. Implementation research is needed to operationalise results in programmes and reduce post-treatment severe wasting at scale., (© 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

There are no guidelines for the optimal protein quality of ready-to-supplementary food (RUSF) for moderate acute malnutrition (MAM). This randomized, controlled, double-blinded, clinical effectiveness trial evaluated two RUSFs in the treatment of MAM. Both foods contained greater than 7% dairy protein, but the protein-optimized RUSF had a calculated digestible indispensable amino acid score (DIAAS) of 95%, whereas the control RUSF had a calculated DIAAS of 63%. There were 1,737 rural Malawian children 6-59 months of age treated with 75 kcal/kg/day of either control or protein quality-optimized RUSF for up to 12 weeks. There was no difference in the proportion of children who recovered from MAM between the group that received protein-optimized RUSF (759/860, 88%) and the group that received control RUSF (766/877, 87%, difference 1%, 95% CI, -2.1 to 4.1, p = 0.61). There were no differences in time to recovery or average weight gain; nor were adverse effects reported. Both RUSFs showed indistinguishable clinical outcomes, with recovery rates higher than typically seen in treatment for MAM. The DIAAS of these two RUSFs was measured using a pig model. Unexpectedly, the protein quality of the optimized RUSF was inferior to the control RUSF: DIAAS = 82% for the protein quality optimized RUSF and 96% for control RUSF. The controlled conditions of this trial suggest that in supplementary food products for MAM, protein quality is not an independent predictor of clinical effectiveness., (© 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: Malnutrition underlies 3 million child deaths worldwide. Current treatments differentiate severe acute malnutrition (SAM) from moderate acute malnutrition (MAM) with different products and programs. This differentiation is complex and costly. The Combined Protocol for Acute Malnutrition Study (ComPAS) assessed the effectiveness of a simplified, unified SAM/MAM protocol for children aged 6-59 months. Eliminating the need for separate products and protocols could improve the impact of programs by treating children more easily and cost-effectively, reaching more children globally., Methods and Findings: A cluster-randomized non-inferiority trial compared a combined protocol against standard care in Kenya and South Sudan. Randomization was stratified by country. Combined protocol clinics treated children using 2 sachets of ready-to-use therapeutic food (RUTF) per day for those with mid-upper arm circumference (MUAC) < 11.5 cm and/or edema, and 1 sachet of RUTF per day for those with MUAC 11.5 to <12.5 cm. Standard care clinics treated SAM with weight-based RUTF rations, and MAM with ready-to-use supplementary food (RUSF). The primary outcome was nutritional recovery. Secondary outcomes included cost-effectiveness, coverage, defaulting, death, length of stay, and average daily weight and MUAC gains. Main analyses were per-protocol, with intention-to-treat analyses also conducted. The non-inferiority margin was 10%. From 8 May 2017 to 31 March 2018, 2,071 children were enrolled in 12 combined protocol clinics (mean age 17.4 months, 41% male), and 2,039 in 12 standard care clinics (mean age 16.7 months, 41% male). In total, 1,286 (62.1%) and 1,202 (59.0%), respectively, completed treatment; 981 (76.3%) on the combined protocol and 884 (73.5%) on the standard protocol recovered, yielding a risk difference of 0.03 (95% CI -0.05 to 0.10, p = 0.52; per-protocol analysis, adjusted for country, age, and sex). The amount of ready-to-use food (RUTF or RUSF) required for a child with SAM to reach full recovery was less in the combined protocol (122 versus 193 sachets), and the combined protocol cost US$123 less per child recovered (US$918 versus US$1,041). There were 23 (1.8%) deaths in the combined protocol arm and 21 (1.8%) deaths in the standard protocol arm (adjusted risk difference 95% CI -0.01 to 0.01, p = 0.87). There was no evidence of a difference between the protocols for any of the other secondary outcomes. Study limitations included contextual factors leading to defaulting, a combined multi-country power estimate, and operational constraints., Conclusions: Combined treatment for SAM and MAM is non-inferior to standard care. Further research should focus on operational implications, cost-effectiveness, and context (Asia versus Africa; emergency versus food-secure settings). This trial is complete and registered at ISRCTN (ISRCTN30393230)., Trial Registration: The trial is registered at ISRCTN, trial number ISRCTN30393230., Competing Interests: The authors have declared that no competing interests exist.

Background: Severe and moderate acute malnutrition (SAM and MAM) are currently treated with different food products in separate treatment programs. The development of a unified and simplified treatment protocol using a single food product aims to increase treatment program efficiency and effectiveness. This study, the first stage of the ComPAS trial, sought to assess rate of growth and energy requirements among children recovering from acute malnutrition in order to design a simplified, MUAC-based dosage protocol., Methods: We obtained secondary data from patient cards of children aged 6-59 months recovering from SAM in outpatient therapeutic feeding programs (TFPs) and from MAM in supplementary feeding programs (SFPs) in five countries in Africa and Asia. We used local polynomial smoothing to assess changes in MUAC and proportional weight gain between clinic visits and assessed their normalized differences for a non-zero linear trend. We estimated energy needs to meet or exceed the growth observed in 95% of visits., Results: This analysis used data from 5518 patients representing 33942 visits. Growth trends in MUAC and proportional weight gain were not significantly different, each lower at higher MUAC values: MUAC growth averaged 2mm/week at lower MUACs (100 to <110mm) and 1mm/week at higher MUACs (120mm to <125mm); and proportional weight gain declined from 3.9g/kg/day to 2.4g/kg/day across the same MUAC values. In 95% of visits by children with a MUAC 100mm to <125mm who were successfully treated, energy needs could be met or exceeded with 1,000 kilocalories a day., Conclusion: Two 92g sachets of Ready-to-Use Therapeutic Food (RUTF) (1,000kcal total) is proposed to meet the estimated total energy requirements of children with a MUAC 100mm to <115mm, and one 92g sachet of RUTF (500kcal) is proposed to meet half the energy requirements of children with a MUAC of 115 to <125mm. A simplified, combined protocol may enable a more holistic continuum of care, potentially contributing to increased coverage for children suffering from acute malnutrition., Competing Interests: The authors have declared that no competing interests exist.

Tackling the global burden of acute malnutrition in children remains a major public health challenge and is essential for achieving sustainable development. Despite having effective treatment options, most wasted children go untreated; treatment coverage for severe acute malnutrition (SAM) children is only about 20%. Milk is currently an essential component of effective SAM treatment, incorporated into ready-to-use therapeutic food (RUTF). Reaching the untreated children, as well as preventing SAM, requires investment in innovative and cost-efficient approaches. To date, attempts to replace or remove milk from RUTF have been either unsuccessful or unpersuasive. This is likely because milk provides the highest protein quality and density of all typical RUTF ingredients. However, alternative protein sources could provide cost savings. Alternative protein sources, especially plant-based protein alternatives, have had shown more promising progress for the treatment of children with moderate acute malnutrition. Acknowledging that cost is a major barrier to the scale-up of treatment of acute malnutrition and that alternative protein sources are a practical means to reduce cost, continued research focusing on alternative proteins is necessary., (© 2020 Nestlé Nutrition Institute, Switzerland/S. Karger AG, Basel.)

The health benefits of dietary amylase resistant starch (RS) arise from intestinal microbial fermentation and generation of short chain fatty acids (SCFA). We compared the intestinal fermentative capability of stunted and nonstunted ('healthy') children in southern India using two types of RS: high amylose maize starch (HAMS) and acetylated HAMS (HAMSA). Twenty children (10 stunted and 10 healthy) aged 2 to 5 years were fed biscuits containing HAMS (10 g/day) for two weeks followed by a 2-week washout and then HAMSA biscuits (10 g/day) for 2 weeks. Fecal samples were collected at 3-4 day intervals and pH and SCFA analyzed. At entry, stunted children had lower SCFA concentrations compared to healthy children. Both types of RS led to a significant decrease in fecal pH and increase in fecal acetate and propionate in both healthy and stunted children. However, while HAMS increased fecal butyrate in both groups of children, HAMSA increased butyrate in healthy but not stunted children. Furthermore, healthy children showed a significantly greater increase than stunted children in both acetate and butyrate when fed either RS. No adverse effects were reported with either RS. Stunted children have impaired capacity to ferment certain types of RS which has implications for choice of RS in formulations aimed at improving microbial function in stunted children.

Background: A stubborn persistence of child severe acute malnutrition (SAM) and continued gaps in program coverage have made identifying methods for expanding detection, diagnosis, and treatment of SAM an urgent public health need. There is growing consensus that making mid-upper arm circumference (MUAC) use more widely accessible among caregivers and community health workers (CHWs) is an important next step in further decentralizing SAM care and increasing program coverage, including the ability of CHWs to treat uncomplicated SAM in community settings., Methods: We conducted a systematic review to summarize published and operational evidence published since 2000 describing the use of MUAC for detection and diagnosis of SAM in children aged 6-59 months by caregivers and CHWs, and of management of uncomplicated SAM by CHWs, all outside of formal health care settings. We screened 1,072 records, selected 43 records for full-text screening, and identified 22 studies that met our eligibility criteria. We extracted data on a number of items, including study design, strengths, and weaknesses; intervention and control; and key findings and operational lessons. We then synthesized the qualitative findings to inform our conclusions. The issue of treating children classified as SAM based on low weight-for-height, rather than MUAC, at household level, is not addressed in this review., Findings: We found evidence that caregivers are able to use MUAC to detect SAM in their children with minimal risk and many potential benefits to early case detection and coverage. We also found evidence that CHWs are able to correctly use MUAC for SAM detection and diagnosis and to provide a high quality of care in the treatment of uncomplicated SAM when training, supervision, and motivation are adequate. However, the number of published research studies was small, their geographic scope was narrow, and most described intensive, small-scale interventions; thus, findings are not currently generalizable to public-sector health care systems., Conclusions: Scaling up the use of MUAC by caregivers and CHWs to detect SAM in household and community settings is a promising step toward improving the coverage of SAM detection, diagnosis, and treatment. Further research on scalability, applicability across a wider range of contexts, coverage impact, and cost is needed. The primary use of MUAC for SAM detection should also be explored where appropriate., (© Bliss et al.)

Hepatic steatosis is a hallmark feature of kwashiorkor malnutrition. However, the pathogenesis of hepatic steatosis in kwashiorkor is uncertain. Our objective was to develop a mouse model of childhood undernutrition in order to test the hypothesis that feeding a maize vegetable diet (MVD), like that consumed by children at risk for kwashiorkor, will cause hepatic steatosis which is prevented by supplementation with choline. A MVD was developed with locally sourced organic ingredients, and fed to weanling mice ( n = 9) for 6 or 13 days. An additional group of mice ( n = 4) were fed a choline supplemented MVD. Weight, body composition, and liver changes were compared to control mice ( n = 10) at the beginning and end of the study. The MVD resulted in reduced weight gain and hepatic steatosis. Choline supplementation prevented hepatic steatosis and was associated with increased hepatic concentrations of the methyl donor betaine. Our findings show that (1) feeding a MVD to weanling mice rapidly induces hepatic steatosis, which is a hallmark disturbance of kwashiorkor; and that (2) hepatic steatosis associated with feeding a MVD is prevented by choline supplementation. These findings support the concept that insufficient choline intake may contribute to the pathogenesis of hepatic steatosis in kwashiorkor.

Background: Acute malnutrition is a continuum condition, but severe and moderate forms are treated separately, with different protocols and therapeutic products, managed by separate United Nations agencies. The Combined Protocol for Acute Malnutrition Study (ComPAS) aims to simplify and unify the treatment of uncomplicated severe and moderate acute malnutrition (SAM and MAM) for children 6-59 months into one protocol in order to improve the global coverage, quality, continuity of care and cost-effectiveness of acute malnutrition treatment in resource-constrained settings., Methods/design: This study is a multi-site, cluster randomized non-inferiority trial with 12 clusters in Kenya and 12 clusters in South Sudan. Participants are 3600 children aged 6-59 months with uncomplicated acute malnutrition. This study will evaluate the impact of a simplified and combined protocol for the treatment of SAM and MAM compared to the standard protocol, which is the national treatment protocol in each country. We will assess recovery rate as a primary outcome and coverage, defaulting, death, length of stay, average weekly weight gain and average weekly mid-upper arm circumference (MUAC) gain as secondary outcomes. Recovery rate is defined across both treatment arms as MUAC ≥125 mm and no oedema for two consecutive visits. Per-protocol and intention-to-treat analyses will be conducted., Discussion: If the combined protocol is shown to be non-inferior to the standard protocol, updating guidelines to use the combined protocol would eliminate the need for separate products, resources and procedures for MAM treatment. This would likely be more cost-effective, increase availability of services, enable earlier case finding and treatment before deterioration of MAM into SAM, promote better continuity of care and improve community perceptions of the programme., Trial Registration: ISRCTN, ISRCTN30393230 . Registered on 16 March 2017.

Recent algorithmic advances in amplicon-based microbiome studies enable the inference of exact amplicon sequence fragments. These new methods enable the investigation of sub-operational taxonomic units (sOTU) by removing erroneous sequences. However, short (e.g., 150-nucleotide [nt]) DNA sequence fragments do not contain sufficient phylogenetic signal to reproduce a reasonable tree, introducing a barrier in the utilization of critical phylogenetically aware metrics such as Faith's PD or UniFrac. Although fragment insertion methods do exist, those methods have not been tested for sOTUs from high-throughput amplicon studies in insertions against a broad reference phylogeny. We benchmarked the SATé-enabled phylogenetic placement (SEPP) technique explicitly against 16S V4 sequence fragments and showed that it outperforms the conceptually problematic but often-used practice of reconstructing de novo phylogenies. In addition, we provide a BSD-licensed QIIME2 plugin (https://github.com/biocore/q2-fragment-insertion) for SEPP and integration into the microbial study management platform QIITA. IMPORTANCE The move from OTU-based to sOTU-based analysis, while providing additional resolution, also introduces computational challenges. We demonstrate that one popular method of dealing with sOTUs (building a de novo tree from the short sequences) can provide incorrect results in human gut metagenomic studies and show that phylogenetic placement of the new sequences with SEPP resolves this problem while also yielding other benefits over existing methods.

The United Nations declaration of 2016 as the International Year of Pulses (IYP) provided an unprecedented opportunity to showcase pulses on the global stage for their contribution to affordable nutrition, health, and sustainability. Despite the IYP's successes in stakeholder engagement, continuing to foster and strengthen partnerships and collaborations is necessary to meet the IYP goals of increased pulse production and consumption for human benefit. Shifting consumer behavior to increase pulse consumption emerged during IYP meetings as a shared priority for all stakeholders. Focusing on this shared priority provides an opportunity to strengthen collaboration among all stakeholder groups for research, education, marketing, and ingredient/food production. Although the IYP officially closed at the end of 2016, the pulse community has an opportunity to continue building successful collaborations. The future research agenda can foster increased pulse production and consumption to address global nutrition, health, and sustainability challenges, provided that it is developed with multisectorial perspectives and cross-disciplinary collaborations. But, most importantly, the research agenda for pulses must be centered more deliberately on the end consumer and how to drive shifts in behavior toward increased pulse consumption, as this is the common shared priority around which all stakeholders can rally., (© 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.)

Background: Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood., Methods: We measured serum metabolites using liquid chromatography-tandem mass spectrometry in 400 children, aged 12-59months, from rural Malawi. Gut permeability was assessed by the dual-sugar absorption test., Findings: 80.7% of children had EED. Of 677 serum metabolites measured, 21 were negatively associated and 56 were positively associated with gut permeability, using a false discovery rate approach (q<0.05, p<0.0095). Increased gut permeability was associated with elevated acylcarnitines, deoxycarnitine, fatty acid β-oxidation intermediates, fatty acid ω-oxidation products, odd-chain fatty acids, trimethylamine-N-oxide, cystathionine, and homocitrulline, and with lower citrulline, ornithine, polyphenol metabolites, hippurate, tryptophan, and indolelactate., Interpretation: EED is a syndrome characterized by secondary carnitine deficiency, abnormal fatty acid oxidation, alterations in polyphenol and amino acid metabolites, and metabolic dysregulation of sulfur amino acids, tryptophan, and the urea cycle. Future studies are needed to corroborate the presence of secondary carnitine deficiency among children with EED and to understand how these metabolic derangements may negatively affect the growth and development of young children., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Protein quality scores use the amino acid (AA) requirements of a healthy North American child. AA requirements vary with physiologic status. We estimated AA requirements for healthy North American children, children with environmental enteric dysfunction, children recovering from wasting, and children with an acute infection. The protein quality of food aid products was then calculated to determine whether it was sufficient in all these groups, and we found that it may not be adequate for all of them. Physiologic status is important when assessing the protein quality of food aid. Rates of weight gain from 8 published trials treating children with moderate acute malnutrition were abstracted, and protein quality scores from the corresponding food aid products were calculated with the use of the digestible indispensable amino acid score (DIAAS). Two DIAAS values were calculated, one in healthy children aged 1-3 y as a reference population and the other in malnourished children aged 1-3 y as a reference population. These data were used to calculate the best fit regression line between weight gain and protein quality. The slope of the regression line was greater when malnourished children were used as a reference population than when healthy children were used (0.128; 95% CI: 0.118, 0.138 compared with 0.097; 95% CI: 0.090, 0.105 measured in g · kg -1 · d -1 · DIASS U -1 ). These findings suggest that adjusting AA requirements for physiologic status may more accurately estimate the minimum protein quality of food aid products., (© 2017 American Society for Nutrition.)

Approximately 25% of the world's children aged <5 years have stunted growth, which is associated with increased mortality, cognitive dysfunction, and loss of productivity. Reducing by 40% the number of stunted children is a global target for 2030. The pathogenesis of stunting is poorly understood. Prenatal and postnatal nutritional deficits and enteric and systemic infections clearly contribute, but recent findings implicate a central role for environmental enteric dysfunction (EED), a generalized disturbance of small intestinal structure and function found at a high prevalence in children living under unsanitary conditions. Mechanisms contributing to growth failure in EED include intestinal leakiness and heightened permeability, gut inflammation, dysbiosis and bacterial translocation, systemic inflammation, and nutrient malabsorption. Because EED has multiple causal pathways, approaches to manage it need to be multifaceted. Potential interventions to tackle EED include: (1) reduction of exposure to feces and contact with animals through programs such as improved water, sanitation, and hygiene; (2) breastfeeding and enhanced dietary diversity; (3) probiotics and prebiotics; (4) nutrient supplements, including zinc, polyunsaturated fatty acids, and amino acids; (5) antiinflammatory agents such as 5-aminosalicyclic acid; and (6) antibiotics in the context of acute malnutrition and infection. Better understanding of the underlying causes of EED and development of noninvasive, practical, simple, and affordable point-of-care diagnostic tools remain key gaps. "Omics" technologies (genomics, epigenomics, transcriptomics, proteomics, and metabolomics) and stable isotope techniques (eg, 13 C breath tests) targeted at children and their intestinal microbiota will enhance our ability to successfully identify, manage, and prevent this disorder., (Copyright © 2016 by the American Academy of Pediatrics.)

Background: Protein quality refers to the amounts and ratios of essential amino acids in a food. Two methods most commonly used for determining protein quality are the protein digestibility-corrected amino acid score (PDCAAS) and the digestible indispensible amino acid score (DIAAS)., Objective: To use existing literature to compare different amino acid profiles and PDCAAS and DIAAS scores in individuals with acute inflammation and to assess their relationship with weight gain in children with severe acute malnourished (SAM)., Methods: A series stable isotope studies were previously conducted in children with SAM and acute infection, and these data were reviewed with respect to protein synthesis. Eleven published treatment trials for SAM with different therapeutic foods were analyzed to examine the relationship between protein quality scores with weight gain (g/kg/d). Protein scores were calculated with the PDCAAS and DIAAS amino acid reference patterns. A DIAAS score adjusted for the higher weight gain expected in malnourished children was also used. Bivariate correlation analysis was used to examine this relationship., Results: The protein kinetic data supported the hypothesis that a balance of amino acids that matches the composition of acute-phase proteins maximizes amino acid synthesis. Protein quality scores were highly correlated with the rate of weight gain in recovery from SAM, and the DIAAS scoring system adjusted for the higher expected weight gain had the strongest correlation with the observed weight gain., Conclusion: Protein quality scores must account for physiologic status so that they better match with needs and thus better promote health., (© The Author(s) 2016.)

Objective: To elucidate the factors influencing food intake and preferences for potential nutritional supplements to treat mild and moderate malnutrition among adult people living with HIV (PLHIV)., Design: Qualitative research using in-depth interviews with a triangulation of participants and an iterative approach to data collection., Setting: The study was conducted in a health clinic of rural Chilomoni, a southern town of Blantyre district, Malawi., Subjects: Male and female participants, aged 18-49 years (n 24), affected by HIV; health surveillance assistants of Chilomoni clinic (n 8)., Results: Six themes emerged from the in-depth interviews: (i) PLHIV perceived having a poor-quality diet; (ii) health challenges determine the preferences of PLHIV for food; (iii) liquid-thick, soft textures and subtle natural colours and flavours are preferred; (iv) preferred organoleptic characteristics of nutritional supplements resemble those of local foods; (v) food insecurity may contribute to intra-household sharing of nutritional supplements; and (vi) health surveillance assistants and family members influence PLHIV's dietary behaviours. No differences by sex were found. The emergent themes were corroborated by health surveillance assistants through participant triangulation., Conclusions: In this setting, a thickened liquid supplement, slightly sweet and sour, may be well accepted. A combination of quantitative and qualitative methods for data collection should follow to further develop the nutritional supplement and to fine tune the organoleptic characteristics of the product to the taste and requirements of PLHIV. Results of the present study provide a first approach to elucidate the factors influencing food intake and preferences for potential nutritional supplements among adult PLHIV.

Low nutritional value of complementary foods is associated with high incidence of childhood growth stunting in low-income countries. This study was done to test a hypothesis that dietary complementation with lipid-based nutrient supplements (LNS) promotes linear growth and reduces the incidence of severe stunting among at-risk infants. A total of 840 6-month-old healthy infants in rural Malawi were enrolled to a randomised assessor-blinded trial. The participants received 12-month supplementation with nothing, milk-LNS, soy-LNS, or corn-soy blend (CSB). Supplements provided micronutrients and approximately 280 kcal energy per day. Outcomes were incidence of severe and very severe stunting [length-for-age z-score, (LAZ) < -3.00 and <-3.50, respectively], and change in LAZ. The incidence of severe stunting was 11.8%, 8.2%, 9.1% and 15.5% (P = 0.098) and that of very severe stunting 7.4%, 2.9%, 8.0% and 6.4% (P = 0.138) in control, milk-LNS, soy-LNS and CSB groups, respectively. Between 9 and 12 months of age, the mean change in LAZ was -0.15, -0.02, -0.12 and -0.18 (P = 0.045) for control, milk-LNS, soy-LNS and CSB groups, respectively. There was no significant between-group difference in linear growth during other age-intervals. Although participants who received milk-LNS had the lowest incidence of severe and very severe stunting, the differences between the groups were smaller than expected. Thus, the results do not provide conclusive evidence on a causal association between the LNS supplementation and the lower incidence of stunting. Exploratory analyses suggest that provision of milk-LNS, but not soy-LNS promotes linear growth among at-risk infants mainly between 9 and 12 months of age., (© 2013 John Wiley & Sons Ltd.)

Introduction: The development of the intestinal gut is largely influenced by early nutrition. Infant immunity is challenged by the exposure of the gut to foreign bodies, which mediate inflammation of the gut. This study assessed the levels of gut inflammation in relation to the percentage of breastmilk consumed/the exclusivity of breastfeeding in South African infants. This is the first study to examine markers of gut inflammation in infants in relation to exclusivity of breastfeeding measured by a gold standard method., Methodology: Twenty-four black South African infants were included in this study. The categorization of different degrees of exclusivity of breastfeeding was made using an objective gold standard method developed by the International Atomic Energy Agency (deuterium dilution method). Markers of gut inflammation were measured noninvasively by sampling stool from the infants averaging 6 months of age. Gut inflammation was investigated by running multiple Droplet Digital™ (Bio-Rad, Hercules, CA) polymerization chain reaction tests profiling a panel of five mRNA probes (interleukin-8 [IL-8], S100 calcium-binding protein A8 [S100A8], Toll-like receptor-4, human leukocyte antigen on chromosome 6 region 6p21.31, and defensin alpha 8). These mRNA biomarkers expressions were tested in proportion to number of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) copies as GAPDH is constitutively expressed in most cells., Results: Two previously described robust mRNA markers of gut inflammation (S100A8 and IL-8) were found to correlate significantly to the percentage of breastmilk intake (r(2) = 0.4302, p = 0.0004 and r(2) = 0.3633, p = 0.002, respectively) in the range of 75-100% in 22 samples analyzed., Conclusions: This study using objective methodology has shown that higher percentages of breastmilk intake are associated with significantly lower levels of gut inflammation. This further supports the health benefits observed in exclusively breastfed infants.

The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota's viral component in populations at risk for malnutrition.

Beginning in fiscal year 2013, scores based on the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) constitute 30% of incentive-based payments from Medicare's Value-Based Purchasing (VBP) initiative. Yet there is little empirical work to understand hospital approaches to improving the patient experience. In this study, chief patient experience officers at 416 VHA hospitals were surveyed to assess the relationship between organizational characteristics and publicly reported HCAHPS scores. Of 416 institutions, 143 (34.4%) participated. Respondents reported that boards (68%) and chief executive officers (81%) viewed the patient experience as extremely important. In contrast, they reported that in only 15% and 34% of hospitals, respectively, physicians and nurses were supportive of efforts to improve the patient experience. Hospitals with collaborative cultures and higher physician engagement had higher VBP total HCAHPS scores (6.9 points and 8.2 points higher, respectively; both P < .05). These areas should be addressed to improve the patient experience in provider organizations., (© The Author(s) 2014.)

Background: Environmental enteropathy is subclinical inflammation of the upper gastrointestinal tract associated with reduced linear growth in developing countries. Usually investigators have used biopsy or a dual sugar absorption test to assess environmental enteropathy. Such tests are time and resource intensive, restricting their utility as screening methods. Serum endotoxin core antibody (EndoCab) concentration is a potential indicator of intestinal inflammation and integrity, and thus may be useful to predict environmental enteropathy. We analyzed the association of serum EndoCab levels versus linear growth and lactulose-mannitol assay results in 2-5 year old rural Malawian children., Methods: This was an observational study of 388 rural, asymptomatic Malawian children who had anthropometric measurements taken at least every 3 months since birth. In June and July 2011, dual sugar permeability tests were performed and serum samples were drawn for EndoCab assays. Pearson correlation, Student's t test and multivariable linear regression were used to compare ln EndoCab concentrations with height-for-age z scores (HAZ) at time of sampling and 3 months later. Identical analysis was also performed for ln EndoCab versus measurements from dual sugar permeability testing performed in conjunction with serum sampling. In a subgroup of children with anthropometric data in the months prior to serum sampling, Pearson correlation was used to estimate the relationship between ln EndoCab and recent linear growth., Results: Ln EndoCab concentrations were not correlated with HAZ at time of measurement (B = -0.078, P = 0.14) nor change in HAZ over the subsequent 3 months HAZ (B = -0.018, P = 0.27). EndoCab concentration was not associated with %lactulose excretion (B < 0.001, P = 0.98) nor the lactulose:mannitol ratio (B = 0.021, P = 0.62). Subgroup analysis also did not reveal any significant association between EndoCab and recent growth., Conclusion: EndoCab titers were not correlated with measurements of growth or intestinal permeability in rural pre-school aged Malawian children.

Ready-to-use therapeutic foods (RUTFs) are a key component of a life-saving treatment for young children who present with uncomplicated severe acute malnutrition in resource limited settings. Increasing recognition of the role of balanced dietary omega-6 and omega-3 polyunsaturated fatty acids (PUFA) in neurocognitive and immune development led two independent groups to evaluate RUTFs. Jones et al. (BMC Med 13:93, 2015), in a study in BMC Medicine, and Hsieh et al. (J Pediatr Gastroenterol Nutr 2015), in a study in the Journal of Pediatric Gastroenterology and Nutrition, reformulated RUTFs with altered PUFA content and looked at the effects on circulating omega-3 docosahexaenoic acid (DHA) status as a measure of overall omega-3 status. Supplemental oral administration of omega-3 DHA or reduction of RUTF omega-6 linoleic acid using high oleic peanuts improved DHA status, whereas increasing omega-3 alpha-linolenic acid in RUTF did not. The results of these two small studies are consistent with well-established effects in animal studies and highlight the need for basic and operational research to improve fat composition in support of omega-3-specific development in young children as RUTF use expands.

Ready-to-use therapeutic foods (RUTFs) are solid foods that were developed by changing the formulation of the existing liquid diet, F-100, recommended by the World Health Organization (WHO) for the rapid catch-up phase of the treatment of children suffering from severe acute malnutrition (SAM). The resulting products proved highly effective in promoting weight gain in both severely and moderately wasted children and adults, including those infected with HIV. The formulation of the existing RUTFs, however, has never been optimized to maximize linear growth, vitamin and mineral status, and functional outcomes. The high milk content of RUTFs makes it an expensive product, and using lower quantities of milk seems desirable. However, the formulation of alternative, less expensive but more effective versions of RUTF faces difficult challenges, as there are uncertainties regarding the effect in terms of protein quality, antinutrient content, and flatulence factors that will result from the replacement of current dairy ingredients by less expensive protein-rich ingredients. The formulation of alternative RUTFs will require further research on these aspects, followed by efficacy studies comparing the future RUTFs to the existing formulations.

A pattern of changes in the microbiome composition have been observed in the normal maturation of the human gut. Perturbations from this pattern have been described in malnourished humans and reproduced in animal models of severe malnutrition. Treatment and prevention of malnutrition in the future may be more effective if the interventions not only restore body composition, but the composition of the microbiome as well.

Ready-to-use foods are one of the available strategies for the treatment of moderate acute malnutrition (MAM), but challenges remain in the use of these products in programs at scale. This paper focuses on two challenges: the need for cheaper formulations using locally available ingredients that are processed in a safe, reliable, and financially sustainable local production facility; and the effective use of these products in large-scale community-based programs. Linear programming tools can be used successfully to design local compositions that are in line with international guidelines, low in cost, and acceptable, and the efficacy of these local formulations in the treatment of MAM was recently demonstrated in Malawi. The production of local formulations for programs at scale relies on the existence of a reliable and efficient local production facility. Technical assistance may be required in the development of sustainable business models at an early stage in the process, taking into account the stringent product quality and safety criteria and the required investments. The use of ready-to-use products, as of any food supplement, in programs at scale will be affected by the practice of household sharing and diversion of these products for other uses. Additional measures can be considered to account for sharing. These products designed for the treatment and prevention of MAM are to be used in community-based programs and should therefore be used in conjunction with other interventions and designed so that they do not replace the intake of other foods and breastmilk. Remaining challenges and implications for the (operations) research agenda are discussed.

Globally, zinc deficiency is widespread, despite decades of research highlighting its negative effects on health, and in particular upon child health in low-income countries. Apart from inadequate dietary intake of bioavailable zinc, other significant contributors to zinc deficiency include the excessive intestinal loss of endogenously secreted zinc and impairment in small intestinal absorptive function. Such changes are likely to occur in children suffering from environmental (or tropical) enteropathy (EE)-an almost universal condition among inhabitants of developing countries characterized by morphologic and functional changes in the small intestine. Changes to the proximal gut in environmental enteropathy will likely influence the nature and amount of zinc delivered into the large intestine. Consequently, we reviewed the current literature to determine if colonic absorption of endogenous or exogenous (dietary) zinc could contribute to overall zinc nutriture. Whilst we found evidence that significant zinc absorption occurs in the rodent colon, and is favoured when microbially-fermentable carbohydrates (specifically resistant starch) are consumed, it is unclear whether this process occur in humans and/or to what degree. Constraints in study design in the few available studies may well have masked a possible colonic contribution to zinc nutrition. Furthermore these few available human studies have failed to include the actual target population that would benefit, namely infants affected by EE where zinc delivery to the colon may be increased and who are also at risk of zinc deficiency. In conducting this review we have not been able to confirm a colonic contribution to zinc absorption in humans. However, given the observations in rodents and that feeding resistant starch to children is feasible, definitive studies utilising the dual stable isotope method in children with EE should be undertaken.

Background: There is evidence to support the use of lipid-based nutrient supplements (LNSs) to promote child growth and development in low-income countries, but there is also a concern regarding the safety of using iron-fortified products in malaria-endemic areas., Objective: The objective of this study was to test the hypothesis that 6- to 18-mo-old rural Malawian children receiving iron-containing (6 mg/d) LNSs would not have excess morbidity compared with infants receiving no supplementation., Methods: A randomized controlled trial allocated 840 children to receive daily supplementation with 54 g/d LNS with milk protein base (milk-LNS), 54 g/d LNS with soy protein base (soy-LNS), 71 g/d corn-soy blend (CSB), or no supplementation from 6 to 18 mo of age. Morbidity was compared using a non-inferiority margin set at 20% excess morbidity in supplemented groups compared with the nonsupplemented group., Results: Baseline characteristics were similar across groups. The proportion of days with febrile illness between 6 and 18 mo was 4.9%, and there were no differences between the groups: 4.9% (95% CI: 4.3, 5.5%), 4.5% (95% CI: 3.9, 5.1%), 4.7% (95% CI: 4.1, 5.3%), and 5.5% (95% CI: 4.7-6.3%) in the milk-LNS, soy-LNS, CSB, and control groups, respectively. The proportion of days with respiratory problems and diarrhea between 6 and 18 mo also did not differ between groups. Compared with controls, the incident rate ratio (95% CI) for clinical malaria was 0.80 (0.59, 1.09), 0.77 (0.56, 1.06), and 0.79 (0.58, 1.08) in milk-LNS, soy-LNS, and CSB, respectively, with 95% CIs confirming non-inferiority. The incidence of febrile episodes, diarrhea, respiratory problems or admission to hospital, prevalence of malaria parasitemia throughout the follow-up, and mean change in hemoglobin concentration from baseline were also similar between the groups., Conclusions: Daily supplementation with 54 g of milk-based or soy protein-based LNS or 71 g of CSB did not result in increases in malaria or respiratory morbidity in children in a malaria-endemic setting. However, we could not conclude whether LNSs did or did not increase diarrheal morbidity. This trial was registered at clinicaltrials.gov as NCT00524446., (© 2014 American Society for Nutrition.)

Severe acute malnutrition is a devastating condition afflicting under-5 children in many developing countries, but concentrated in sub-Saharan Africa. This paper examines the development of home-based lipid-nutrient therapeutic foods for the treatment of acute malnutrition in sub-Saharan Africa and the adoption of these therapies as a standard of care for non-complicated cases of acute malnutrition. Several of the early key clinical and operational effectiveness trials are discussed as well as the adoption of home-based treatment as a standard operating procedure in regions where malnutrition is present.

Objective: To compare the growth of HIV-exposed children receiving 1 of 2 complementary foods after prevention of mother-to-child HIV transmission through maternal lifelong antiretroviral therapy (ART)., Methods: In rural Malawi, 280 HIV-infected pregnant women were consecutively identified and offered ART, without consideration of their CD4 counts. Mothers were supported to exclusively breast-feed and children tested for HIV status at 1.5 and 5.5 months of age. From this group, 248 HIV-exposed children were enrolled and randomized to receive micronutrients with either whole milk powder or a ready-to-use complementary food (RUF), until the child reached 12 months of age. Children were followed until 18 months of age., Results: HIV-free survival at 12 months was 90% (95% confidence interval: 87% to 94%). Exclusive breast-feeding for the first 6 months of life was practiced in 97% of the children. At 12 months of age, 89% of the children continued to be breast-fed. At 6 months of age, infants had a weight-for-height z score of 0.7 ± 1.1 (mean ± SD) and length-for-age z score of -1.3 ± 1.2. The decrease in length-for-age z score among children receiving RUF at 12 months of age was greater than that seen in those receiving milk powder (-0.3 ± 0.8 vs -0.1 ± 0.7, P = 0.04). Mean weight-for-height z score was >0 at 12 and 18 months of age in both groups., Conclusions: HIV-free survival ≥90% at 12 months was achieved with maternal ART while either milk powder or RUF as a complementary food preserved child anthropometry. Breast-feeding by mothers receiving ART was acceptable.

Aim: To assess whether using lipid-based nutrient supplements (LNS) to complement the diets of infants and young children affected when they achieved selected developmental milestones., Methods: In rural Malawi, 840 6-month-old healthy infants were enrolled to a randomised trial. Control participants received no supplements, others were provided with milk-containing LNS, soy-containing LNS or corn-soy blend (CSB) for 12 months. Outcomes were the age at which they achieved key milestone: motor (walking with assistance, standing and walking alone, running), social (drinking from a cup and eating by themselves) and language (saying single comprehensible words and waving goodbye)., Results: The mean age at which the subjects walked with assistance was 42.5, 42.3, 42.7 and 43.2 weeks in the control, milk-LNS, soy-LNS and CSB groups, respectively (p = 0.748). There were also no significant differences in the mean age at standing alone (45.0, 44.9, 45.1 and 46.3 weeks), walking alone (54.6, 55.1, 55.3, 56.5 weeks), running (64.6, 63.7, 64.8, 65.9 weeks) or any other social or language milestones (each p > 0.10)., Conclusion: The findings do not support a hypothesis that providing tested formulations and doses of micronutrient-fortified LNS or CSB would have an impact on when young children in rural Malawi achieved selected developmental milestones., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background and Objective: Transcriptomic analysis of fecal samples is an emerging method for the diagnosis of gastrointestinal pathology because it is noninvasive and requires minute volumes of analyte; however, detection of mRNA in low copy numbers in human stool is challenging. Our objective was to develop a method for detecting human mRNA suggestive of environmental enteropathy (EE) in feces., Methods: Stool samples from 70 Malawian children, 34 without EE and 36 with EE, as defined by dual sugar absorption, were used to develop the methodology for mRNA detection. Multiple RNA isolation techniques and polymerase chain reaction formats were tested to detect 38 potential mRNA biomarkers suggestive of EE, and the results compared., Results: RNA isolation using magnetic bead extraction best recovered host mRNA in stool, and digital droplet polymerase chain reaction was the most sensitive format to detect low copy numbers of mRNA. In all of the 70 samples, >20 copies of glyceraldehyde-3-phosphate dehydrogenase/200 mg of stool were detected. Copy numbers of potential biomarkers were normalized to glyceraldehyde-3-phosphate dehydrogenase, to account for interspecimen differences in concentration of human mRNA. Of the 38 transcripts chosen for initial evaluation, 24 had copy numbers >10 in all of the samples tested. Of the 6 potential markers measured in all of the 70 samples, REG4 best differentiated children with and without EE., Conclusions: A reproducible and reliable method to quantify human mRNA in stool present in low copy numbers has been developed, and may prove useful in investigations of EE and possibly other inflammatory gut conditions.

Variation of surface adhesins, such as the Plasmodium falciparum erythrocyte invasion ligand PfRh4, is critical for virulence and immune evasion in many microbes. While phenotypic switching is linked to transcriptional changes and chromatin function, the determinants of switching frequency remain poorly defined. By expressing a prokaryotic DNA methylase in P. falciparum, we directly assayed accessibility of transcriptionally active and silent chromatin at the PfRh4 locus. Parasites selected for in vivo PfRh4 activation show a reversible increase in promoter accessibility and exhibit perinuclear repositioning of the locus from a silent to a conserved activation domain. Forced activation of a proximal gene results in a similar repositioning of the PfRh4 locus, with a concomitant increase in PfRh4 activation in a subpopulation of parasites and promoter accessibility correlating with actively transcribed loci. Thus, nuclear repositioning is associated with increased P. falciparum switching frequency, while promoter accessibility is tightly linked to clonally active PfRh4 promoters., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This position paper is based on the premise that those who ride seated in wheelchairs are entitled to equivalent occupant safety when they are traveling in motor vehicles. The document summarizes research and best practice for safety and selection of crashworthy wheelchairs with the requisite features required by the WC19 safety standard when it is necessary for individuals to use a wheelchair as a seat in a motor vehicle. Recommendations are based on data from accident and injury databases, prior research and a synopsis of the design, testing, performance and labeling requirements of ANSI and ISO voluntary industry standards for wheelchair transportation safety. This paper is intended for an audience of consumers, rehabilitation and health care professionals, manufacturers of wheelchairs and wheelchair transportation equipment and those who make reimbursement and public policy decisions.

This retrospective observational study of 140 HIV-infected children with uncomplicated malnutrition in urban Malawi tested the hypothesis that initiation of antiretroviral therapy (ART) within 21 days of outpatient therapeutic feeding (prompt ART) improved clinical outcomes. Children receiving prompt ART were more likely to recover nutritionally (86% vs. 60%, P < 0.01) and had higher rates of weight gain (3.6 vs. 1.6 g/k/day; P = 0.02). Logistic regression modeling found prompt ART was associated with increased likelihood of nutritional recovery (odds ratio: 5.4, 95% confidence interval: 2.0 to 14.5). This suggests that prompt ART is associated with improved outcomes in HIV-infected Malawian children with uncomplicated malnutrition.