👤 David Marom

In the absence of universal screening for congenital cytomegalovirus (cCMV) infection, the aim of this study was to assess the outcomes of a targeted screening protocol based on maternal and neonatal risk indicators. The medical records of 2,623 neonates born in our maternal hospital between June 2016 and December 2018 and screened for cCMV infection were reviewed. Among those of the included neonates, the records of 380 CMV-negative and 19 CMV-positive neonates were randomly assigned to obtain additional comparative data. During the study period, a total of 63 neonates were identified as positive for cCMV, comprising 0.2% of the total birth cohort (63/28,982) and 2.4% of all neonates screened for cCMV (63/2,623). The comparative data analysis showed that suspected or confirmed CMV infection during pregnancy, maternal age, and maternal diabetes mellitus were found to be significantly associated with a positive cCMV diagnosis. Although symmetric small for gestational age and hearing screening failure contributed to the detection of some of the CMV-positive infants, these factors were not specific to this group. The results of the logistic regression model showed that the only factor that was significantly associated with an increased risk for a cCMV diagnosis was maternal serology suspected of CMV infection during pregnancy, with a regression coefficient estimate of 2.657 (adjusted p < 0.001). A targeted neonatal screening protocol based on multiple maternal and neonatal risk indicators is feasible but provides limited information. Our study emphasizes the importance of universal neonatal screening for the detection of neonates with cCMV. Show less

Here we describe the crystal structure of the N-terminal domain of the FK506-binding protein (FKBP) from wheat (wFKBP73), which is the first structure presenting three FK domains (wFK73₁, wFK73₂ and wFK73₃₎. The crystal model includes wFK73₂ and wFK73₃ domains and only part of the wFK73₁ domain. The wFK73₁ domain is responsible for binding FK506 and for peptidyl prolyl cis/trans isomerase (PPIase) activity, while the wFK73₂ and wFK73₃ domains lack these activities. A structure-based sequence comparison demonstrated that the absence of a large enough hydrophobic pocket important for PPIase activity, and of the conserved residues necessary for drug binding in the wFK73₂ and wFK73₃ domains explains the lack of these activities in these domains. Sequence and structural comparison between the three wFKBP73 domains suggest that the wFK73₂ domain is the most divergent. A structural comparison of the FK domains of wFKBP73 with other FKBPs containing more than one FK domain, revealed that while the overall architecture of each of the three FK domains displays a typical FKBP fold, their relative arrangement in space is unique and may have important functional implications. We suggest that the existence of FKBPs with three FK domains offers additional interactive options for these plant proteins enlarging the overall regulatory functions of these proteins. Show less