BackgroundDietary intake sharply impacts the structure and function of the gut microbiota, which is important for childhood health. However, little is known about the microbiota of children who cannot eat by mouth. Standard enteral formulas for supplemental nutrition are low in fiber and high in processed sugars and are commonly associated with gastrointestinal side effects. In this pilot study, we examined the effects of plant‐based enteral nutrition (PBEN) upon the gut bacteria of chronically ill children.MethodsTen children (median age 3.5 years, age range 2–8 years) dependent upon conventional enteral formula were transitioned to PBEN for 2 months. Microbial diversity within fecal samples collected before and after PBEN was assessed by 16S ribosomal RNA gene sequence analysis and was compared with rectal swabs from healthy children. Fecal short‐chain fatty acids and bile acids were measured in parallel.ResultsRelative to control samples, fecal samples from study subjects were depleted of commensals (eg, Faecalibacterium) and enriched with pathogens (eg, Enterococcus). Postintervention samples from study subjects were more similar to healthy controls. Most subjects experienced PBEN‐induced alterations in the gut microbiota, but these changes varied significantly across individuals. Clinical diaries indicated that PBEN was well tolerated, with improvement in symptoms noted in several subjects.ConclusionResults from this pilot study suggest that PBEN is well tolerated and could improve the health of the microbiota in chronically ill children. This trial provides a rationale for systematic evaluation of PBEN in clinical trials of children who require supplemental nutrition.

Background Skin barrier dysfunction may precede infantile development of clinical atopic dermatitis (AD). Early‐life emollient therapy to enhance barrier function may prevent or modify AD development in high‐risk infants. Objectives (a) To determine whether daily full‐body application of an emollient with ceramide and amino acids (study emollient) can reduce the cumulative AD incidence compared to standard skin care at 1 year of age. (b) To evaluate the study emollient's effect on skin barrier function, natural moisturizing factor and the microbiome using non‐invasive biophysical and biochemical techniques. Methods We performed a single‐centre, investigator‐blinded, randomized controlled trial enrolling infants at high risk for AD development determined by family history. The intervention was full‐body once‐daily application of the study emollient. The control arm was asked to not apply full‐body emollient regularly and only use an emollient of their choice for dry skin. The primary outcome was the cumulative incidence of AD diagnosed at 12 months by a blinded investigator. Results Less than half the target sample size was enrolled (n = 100, goal sample was 208) with 28% lost to follow‐up. Across all clinical end points, a numerical trend was observed in favour of the intervention, although not statistically significant likely due to lack of power from under‐enrolment. AD was diagnosed in 13.2% vs. 25.0% at 12 months (P = 0.204) and 19.4% vs. 31.0% at 2 years (P = 0.296) in intervention vs. control groups, respectively. There were no significant differences between groups in skin barrier or microbiome assessments. While there were no serious adverse events, there were more cases of reported contact dermatitis in the intervention vs. control arms, 9.3% vs. 4.3%, respectively; however, these events were not related to the study emollient and most mild in severity. Conclusion The observed trends suggest a protective effect of daily study emollient therapy compared to control.

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Ice-free cryopreservation, known as vitrification, is an appealing approach for banking of adherent cells and tissues because it prevents dissociation and morphological damage that may result from ice crystal formation. However, current vitrification methods are often limited by the cytotoxicity of the concentrated cryoprotective agent (CPA) solutions that are required to suppress ice formation. Recently, we described a mathematical strategy for identifying minimally toxic CPA equilibration procedures based on the minimization of a toxicity cost function. Here we provide direct experimental support for the feasibility of these methods when applied to adherent endothelial cells. We first developed a concentration- and temperature-dependent toxicity cost function by exposing the cells to a range of glycerol concentrations at 21°C and 37°C, and fitting the resulting viability data to a first order cell death model. This cost function was then numerically minimized in our state constrained optimization routine to determine addition and removal procedures for 17 molal (mol/kg water) glycerol solutions. Using these predicted optimal procedures, we obtained 81% recovery after exposure to vitrification solutions, as well as successful vitrification with the relatively slow cooling and warming rates of 50°C/min and 130°C/min. In comparison, conventional multistep CPA equilibration procedures resulted in much lower cell yields of about 10%. Our results demonstrate the potential for rational design of minimally toxic vitrification procedures and pave the way for extension of our optimization approach to other adherent cell types as well as more complex systems such as tissues and organs.

Objective Eczema and food allergy start in infancy and have shared genetic risk factors that affect skin barrier. We aimed to evaluate whether skincare interventions can prevent eczema or food allergy. Design A prospectively planned individual participant data meta‐analysis was carried out within a Cochrane systematic review to determine whether skincare interventions in term infants prevent eczema or food allergy. Data sources Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to July 2020. Eligibility criteria for selected studies Included studies were randomized controlled trials of infants <1 year with healthy skin comparing a skin intervention with a control, for prevention of eczema and food allergy outcomes between 1 and 3 years. Results Of the 33 identified trials, 17 trials (5823 participants) had relevant outcome data and 10 (5154 participants) contributed to IPD meta‐analysis. Three of seven trials contributing to primary eczema analysis were at low risk of bias, and the single trial contributing to primary food allergy analysis was at high risk of bias. Interventions were mainly emollients, applied for the first 3–12 months. Skincare interventions probably do not change risk of eczema by age 1–3 years (RR 1.03, 95% CI 0.81, 1.31; I2=41%; moderate certainty; 3075 participants, 7 trials). Sensitivity analysis found heterogeneity was explained by increased eczema in a trial of daily bathing as part of the intervention. It is unclear whether skincare interventions increase risk of food allergy by age 1–3 years (RR 2.53, 95% CI 0.99 to 6.47; very low certainty; 996 participants, 1 trial), but they probably increase risk of local skin infections (RR 1.34, 95% CI 1.02, 1.77; I2=0%; moderate certainty; 2728 participants, 6 trials). Conclusion Regular emollients during infancy probably do not prevent eczema and probably increase local skin infections.