Objectives Recently, defects in the protein kinase mTOR (mammalian target of rapamycin) and its associated pathway have been correlated with hemimegalencephaly (HME). mTOR acts as a central regulator of important physiological cellular functions such as growth and proliferation, metabolism, autophagy, death, and survival. This study was aimed at identifying specific variants in mTOR signaling pathway genes in patients diagnosed with HME. Methods Using amplicon and whole exome sequencing (WES) of resected brain and paired blood samples from five HME patients, we were able to identify pathogenic mosaic variants in the mTOR pathway genes MTOR, PIK3CA, and DEPDC5. Results These results strengthen the hypothesis that somatic variants in PI3K‐Akt‐mTOR pathway genes contribute to HME. We also describe one patient presenting with a pathogenic variant on DEPDC5 gene, which reinforces the role of DEPDC5 on cortical structural changes due to mTORC1 hyperactivation. These findings also provide insights into when in brain development these variants occurred. An early developmental variant is expected to affect a larger number of cells and to result in a larger malformation, whereas the same variant occurring later in development would cause a minor malformation. Significance In the future, numerous somatic variants in known or new genes will undoubtedly be revealed in resected brain samples, making it possible to draw correlations between genotypes and phenotypes and allow for a genetic clinical diagnosis that may help to predict a given patient's outcome.

Due to the utilization of milk proteins such as whey protein (WP) and casein as sports nutrition ergogenic aids, the present study investigated the effects of the association of WP and casein in a ratio of 80:20, a similar ratio of human breast milk, on blood branched-chain amino acid (BCAA) profiles, markers of protein metabolism and delayed onset muscle soreness (DOMS), after a single bout of resistance exercise. A double-blind, crossover and acute study was carried out with ten men (age 29 ± 8 years; BMI: 25.4 ± 2.9 kg/m2; 77 ± 12 kg; 1.74 ± 0.09 m); each one consumed the following supplements randomly, one per session: WP, CAS (casein), WP/CAS (80% WP/20% CAS), CAS/WP (80% CAS/20% WP) and PLA (placebo). They were also subjected to the following evaluations: the one repetition maximum (1RM) test; resistance training session; blood extraction during each session to determine the BCAA profile; two food records; 3-day evaluation of DOMS (24 h, 48 h and 72 h) and nitrogen balance in each treatment. The intervention resulted in similar nitrogen urinary, creatinine and urea plasma levels and showed a positive nitrogen balance in all the trials. Regarding the BCAAs, the peak occurred at 60 min post-ingestion and remained higher until 120 min for WP, WP/CAS and CAS/WP. The DOMS was significantly lower for WP, WP/CAS and CAS/WP compared to the CAS and PLA treatments. There were no advantages in the association of WP and CAS in the BCAAs profile when compared to WP itself, but it induced a lower DOMS compared to CAS and PLA (Clinical Trial registration number: clinicaltrials.gov, NCT04648384).