Reduction of visual and auditory stimuli to reduce pain during venipuncture in premature infants. Study protocol for a randomized controlled trial.

AIM: To evaluate the efficacy of the reduction of visual and auditory stimuli on pain during venipuncture in premature newborns of 32-36 weeks of gestation. DESIGN: Open, randomized, non-blind parallel clinical trial. METHOD: Study to take place at the neonatal intensive care unit of a University Hospital in 2019-2021. Fifty-six recently born babies between 32-36 weeks of gestation will participate. The dependent variable is the level of pain determined using the premature infant pain profile instrument. The intervention will be assigned randomly using the random.org software. Data analysis will be carried out using the IBM SPSS v.25 software assuming a level of significance of 5%. DISCUSSION: The evidence for the efficacy of reducing sensory stimulation and its effect on pain in minor procedures has not been studied in depth. There are no studies that evaluate the reduction of visual and auditory stimuli in a combined way. IMPACT: It is easy to incorporate the reduction of visual and auditory stimuli into nursing practice. The results of this study could have a direct impact on clinical practice. Trial registered at clinicaltrials.gov: NCT04041635.

Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans.

SCOPE: Trisomy for human chromosome 21 results in Down syndrome (DS), which is among the most complex genetic perturbations leading to intellectual disability. Accumulating data suggest that overexpression of the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), is a critical pathogenic mechanisms in the intellectual deficit. METHODS AND RESULTS: Here we show that the green tea flavonol epigallocatechin-gallate (EGCG), a DYRK1A inhibitor, rescues the cognitive deficits of both segmental trisomy 16 (Ts65Dn) and transgenic mice overexpressing Dyrk1A in a trisomic or disomic genetic background, respectively. It also significantly reverses cognitive deficits in a pilot study in DS individuals with effects on memory recognition, working memory and quality of life. We used the mouse models to ensure that EGCG was able to reduce DYRK1A kinase activity in the hippocampus and found that it also induced significant changes in plasma homocysteine levels, which were correlated with Dyrk1A expression levels. Thus, we could use plasma homocysteine levels as an efficacy biomarker in our human study. CONCLUSION: We conclude that EGCG is a promising therapeutic tool for cognitive enhancement in DS, and its efficacy may depend of Dyrk1A inhibition.