Dietary tryptophan-rich protein hydrolysate can acutely impact physiological and psychological measures of mood and stress in healthy adults.

BACKGROUND: Tryptophan is the precursor to the mood regulating neurotransmitter serotonin. Its brain bioavailability from food can be dependent on the dietary source. Egg protein hydrolysate (EPH), a dietary supplement rich in tryptophan, has previously shown to acutely impact cognition, mood and stress benefits at 2 g dose. No data exist on the acute effects of lower doses in a food matrix. METHODS: This exploratory study tested the acute effects of low-doses EPH (0.5, 1 g) in a food matrix on cognition, mood and stress. The study employed a double-blinded randomized controlled parallel design in 45 participants with three arms. The effects of the interventions were measured after a multi-task cognitive stressor on blood biomarkers, self-reported mood states, performances of attention, autonomic parameters and, emotional reactivity responses from electroencephalographic recording. RESULTS: As compared to the reference, the 1 g EPH dose increased tryptophan bioavailability from baseline, and, both doses improved heart rate variability parameters related to parasympathetic activation while showing differences in the late neural response to negative versus neutral emotions. Post-hoc analyses indicated a gender difference in the baseline tryptophan bioavailability and further examination suggested the change in mood rating depends on the interaction between gender and change from baseline of tryptophan bioavailability. CONCLUSIONS: Overall, this study suggests that low levels of tryptophan rich EPH in a food matrix positively impact mood or stress in acute settings and adds to the body of evidence linking tryptophan and dietary sources thereof with these benefits. Confirmatory randomized controlled trials are needed to confirm these findings.Trial registration number: CER-VD N°2019-00218.

Safety and efficacy of a probiotic-containing infant formula supplemented with 2'-fucosyllactose: a double-blind randomized controlled trial.

BACKGROUND: Human milk oligosaccharides (HMOs) have important and diverse biological functions in early life. This study tested the safety and efficacy of a starter infant formula containing Limosilactobacillus (L.) reuteri DSM 17938 and supplemented with 2'-fucosyllactose (2'FL). METHODS: Healthy infants < 14 days old (n = 289) were randomly assigned to a bovine milk-based formula containing L. reuteri DSM 17938 at 1 × 107 CFU/g (control group; CG) or the same formula with added 1.0 g/L 2'FL (experimental group; EG) until 6 months of age. A non-randomized breastfed group served as reference (BF; n = 60). The primary endpoint was weight gain through 4 months of age in the formula-fed infants. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, stooling characteristics, adverse events (AEs), fecal microbiota and metabolism, and gut immunity and health biomarkers in all feeding groups. RESULTS: Weight gain in EG was non-inferior to CG as shown by a mean difference [95% CI] of 0.26 [-1.26, 1.79] g/day with the lower bound of the 95% CI above the non-inferiority margin (-3 g/day). Anthropometric Z-scores, parent-reported stooling characteristics, gastrointestinal symptoms and associated behaviors, and AEs were comparable between formula groups. Redundancy analysis indicated that the microbiota composition in EG was different from CG at age 2 (p = 0.050) and 3 months (p = 0.052), approaching BF. Similarly, between sample phylogenetic distance (weighted UniFrac) for BF vs EG was smaller than for BF vs CG at 3-month age (p = 0.045). At age 1 month, Clostridioides difficile counts were significantly lower in EG than CG. Bifidobacterium relative abundance in EG tracked towards that in BF. Fecal biomarkers and metabolic profile were comparable between CG and EG. CONCLUSION: L. reuteri-containing infant formula with 2'FL supports age-appropriate growth, is well-tolerated and may play a role in shifting the gut microbial pattern towards that of breastfed infants. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov ( NCT03090360 ) on 24/03/2017.

The single-index/Cox mixture cure model.

In survival analysis, it often happens that a certain fraction of the subjects under study never experience the event of interest, that is, they are considered "cured." In the presence of covariates, a common model for this type of data is the mixture cure model, which assumes that the population consists of two subpopulations, namely the cured and the non-cured ones, and it writes the survival function of the whole population given a set of covariates as a mixture of the survival function of the cured subjects (which equals one), and the survival function of the non-cured ones. In the literature, one usually assumes that the mixing probabilities follow a logistic model. This is, however, a strong modeling assumption, which might not be met in practice. Therefore, in order to have a flexible model which at the same time does not suffer from curse-of-dimensionality problems, we propose in this paper a single-index model for the mixing probabilities. For the survival function of the non-cured subjects we assume a Cox proportional hazards model. We estimate this model using a maximum likelihood approach. We also carry out a simulation study, in which we compare the estimators under the single-index model and under the logistic model for various model settings, and we apply the new model and estimation method on a breast cancer data set.