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Neural tube defects (NTDs), one of the most common birth defects, are strongly associated with the variations of several single nucleotide polymorphisms (SNPs) in the MTRR gene. The gene codes a key enzyme that is involved in the rejuvenation of methionine synthase activity. An allelic variant of the protein leads to missense mutation at 49th position from isoleucine to methionine (I49M) is associated with higher disease prevalence in different populations. Here, extensive molecular dynamics simulations and interaction network analysis reveal that the 49th isoleucine is a crucial residue that allosterically regulates the dynamics between the flavin mononucleotide (FMN) and NADP(H) binding domains. I49M variation alters the functional dynamics in a way that might impede the electron transport chain along the NADP(H) → flavin adenine dinucleotide → FMN pathway. The present study provides functional insights into the effect of the genetic variations of the MTRR gene on the NTDs disease pathogenesis. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is one of the frequently observed complications in neonates with severe perinatal asphyxia. The efficacy of aminophylline in preventing or alleviating renal dysfunction in these neonates remains controversial. The current study aimed to explore whether treatment with aminophylline as adjunctive therapy is superior to standard care alone in preventing AKI in severely asphyxiated term neonates and to delineate the changes in other renal parameters. In this open-label randomized clinical trial, term neonates with severe asphyxia (n = 41) received a 5 mg/kg intravenous dose of aminophylline within the first hour after birth, in addition to standard care for birth asphyxia. The control group (n = 40) received standard care alone. Their daily urine output, weight, serum creatinine, renal functional status, and complications during the first 5 days of life were monitored and compared. The statistical package for social sciences version 25 was used for analysis. Approximately 24.39% of neonates in the aminophylline group developed AKI, compared to 35.0% in the control group (P = .088). Although urine output was generally higher in aminophylline-treated newborns than in the control group, this increase was not statistically significant (P > .05), with the most notable differences observed on the second and third postnatal days. Also, the changes in plasma creatinine levels between the two groups during this time were not statistically significant. Administering a single dose of aminophylline (5 mg/kg) within the first hour of life to severely asphyxiated term neonates might temporarily enhance urine output, but does not reduce the overall incidence of AKI., (© The Author(s) [2024]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)