Legume-supplemented feed for children hospitalised with severe malnutrition: A Phase II trial.

Children hospitalised with severe malnutrition have high mortality and readmission rates post-discharge. Current milk-based formulations target restoring ponderal growth but not modification of gut barrier integrety or microbiome which increase risk of gram-negative sepsis and poor outcomes. We propose that legume-based feeds rich in fermentable carbohydrates will promote better gut health and improve overall outcomes.We conducted an open-label Phase II trial at Mbale and Soroti Regional Referral Hospitals, Uganda involving 160 children aged 6 months-5 years with severe malnutrition (mid-upper arm circumference (MUAC) <11.5cm and/or nutritional oedema). Children were randomised to a lactose-free, chickpea-enriched legume paste feed (LF) (n=80) versus WHO standard F75/F100 feeds (n=80). Co-primary outcomes were change in MUAC and mortality to Day 90. Secondary outcomes included weight gain (>5 g/kg/day), de novo development of diarrhoea, time to diarrhoea and oedema resolution.Day 90 MUAC increase was marginally lower in LF versus WHO arm (1.1 cm (IQR 1.1) vs 1.4cm (IQR 1.40) p=0.09; Day 90 mortality was similar 11/80 (13.8%) vs 12/80 (15%) respectively OR 0.91 (95% CI 0.40 -2.07) p=0.83. There were no differences in any of the other secondary outcomes. Owing to initial poor palatability of the legume feed 10 children switched to WHO feeds. Per protocol analysis indicated a trend to lower Day 90 mortality and readmission rates in the legume feed (6/60: (10%) and (2/60: 3%) vs WHO feeds (12/71: 17.5%) and (4/71: 6%) respectively.Further refinement of legume feeds and clinical trials are warrented given the poor outcomes in children with severe malnutrition.Trial registration ISRCTN 10309022.

The double burden of malnutrition in individuals: Identifying key challenges and re-thinking research focus.

The 'double burden of malnutrition' is a global health challenge that increasingly affects populations in both low- and middle-income countries (LMICs). This phenomenon refers to the coexistence of undernutrition and overweight or obesity, as well as other diet-related non-communicable diseases, in the same population, household or even individual. While noteworthy progress has been made in reducing undernutrition in some parts of the world, in many of these areas, the prevalence of overweight and obesity is increasing, particularly in urban areas, resulting in greater numbers of people who were undernourished in childhood and have overweight or obesity in adulthood. This creates a complex and challenging situation for research experts and policymakers who must simultaneously address the public health burdens of undernutrition and overweight/obesity. This review identifies key challenges and limitations in the current research on the double burden of malnutrition in individuals, including the need for a more comprehensive and nuanced understanding of the drivers of malnutrition, the importance of context-specific interventions and the need for greater attention to the food environment and food systems. We advocate for the re-evaluation of research strategies and focus, with a greater emphasis on multidisciplinary and systems approaches and greater attention to the synergistic relationship between the biological, environmental, commercial and socio-economic determinants of malnutrition. Addressing these key challenges can enable us to better comprehend and tackle the multifaceted and dynamic issues of the double burden of malnutrition, particularly in individuals and work towards more effective and sustainable solutions.

The NF-κB1 is a key regulator of acute but not chronic renal injury.

The NF-κB family of transcription factors is important for many cellular functions, in particular initiation and propagation of inflammatory and immune responses. However, recent data has suggested that different subunits of the NF-κB family can suppress the inflammatory response. NF-κB1, from the locus nfκb1, can inhibit transcription, acting as a brake to the recognised pro-inflammatory activity of other NF-κB subunits. We tested the function of NF-κB1 in an acute (nephrotoxic serum (NTS) nephritis) and a chronic (unilateral ureteric obstruction (UUO)) model of renal injury using NF-κB1 (nfκb1-/-) knockout mice. Deficiency in NF-κB1 increased the severity of glomerular injury in NTS-induced nephritis and was associated with greater proteinuria and persistent pro-inflammatory gene expression. Induction of disease in bone marrow chimeric mice demonstrated that the absence of NF-κB1 in either bone marrow or glomerular cells increased the severity of injury. Early after UUO (day 3) there was more severe histological injury in the nfκb1-/- mice but by day 10, disease severity was equivalent in wild type and nfκb1-/- mice. In conclusion, NF-κB1 modifies acute inflammatory renal injury but does not influence chronic fibrotic injury.