Early structural cardiovascular changes on neonatal echocardiography after adverse intrauterine circumstances in identical twins
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Severity of neonatal influenza infection is driven by type I interferon and oxidative stress
Neonates exhibit increased susceptibility to respiratory viral infections, attributed to inflammation at the developing pulmonary air-blood interface. IFN I are antiviral cytokines critical to control viral replication, but also promote inflammation. Previously, we established a neonatal murine influenza virus (IV) model, which demonstrates increased mortality. Here, we sought to determine the role of IFN I in this increased mortality. We found that three-day-old IFNAR-deficient mice are highly protected from IV-induced mortality. In addition, exposure to IFNβ 24 h post IV infection accelerated death in WT neonatal animals but did not impact adult mortality. In contrast, IFN IIIs are protective to neonatal mice. IFNβ induced an oxidative stress imbalance specifically in primary neonatal IV-infected pulmonary type II epithelial cells (TIIEC), not in adult TIIECs. Moreover, neonates did not have an infection-induced increase in antioxidants, including a key antioxidant, superoxide dismutase 3, as compared to adults. Importantly, antioxidant treatment rescued IV-infected neonatal mice, but had no impact on adult morbidity. We propose that IFN I exacerbate an oxidative stress imbalance in the neonate because of IFN I-induced pulmonary TIIEC ROS production coupled with developmentally regulated, defective antioxidant production in response to IV infection. This age-specific imbalance contributes to mortality after respiratory infections in this vulnerable population.
The biomechanical evolution of the uterus and cervix and fetal growth in human pregnancy
The coordinated biomechanical performance of maternal tissues facilitates healthy pregnancy. Quantifying uterine and cervical biomechanical function has been challenging due to minimal data on the anatomy’s shape, size, and material properties across gestation. Addressing this challenge, this study quantifies structural features of human pregnancy by assessing maternal reproductive tissues and estimated fetal weight in 47 low-risk pregnancies at four gestation times. Uterocervical size and estimated fetal weight were measured via ultrasound, and cervical stiffness was measured via mechanical aspiration. Patient-specific uterocervical solid models were built for each time point, and uterocervical dimensions and cervical stiffness rate changes were assessed between time points. We found that uterine growth rates are time- and direction-dependent, with cervical softening occurring fastest in early gestation and cervical shortening fastest in late gestation. In conclusion, this work enables computational modeling platforms (i.e., digital twins) to explore the structural performance of the uterus and cervix in pregnancy.
Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice
Maternal immunisation against respiratory viruses provides protection in early life, but as antibodies wane, there can be a gap in coverage. This immunity gap might be filled by inducing pathogen-specific lung tissue-resident T cells (TRM). However, the neonatal mouse lung has a different inflammatory environment to the adult lung which affects T cell recruitment. We compared the factors affecting viral-specific TRM recruitment in the lungs of adult or neonatal mice. In contrast to adulthood, we demonstrated that RSV or influenza infection in neonatal mice recruited fewer TRM to the lungs. This was associated with reduced lung levels of CCL5 and CXCL10. Co-administration of CCL5 or CXCL10 at the time of primary T cell activation significantly increased RSV-specific TRM in the lung, protecting mice upon reinfection. These chemokine differences were reflected in responses to infection in human cord blood. Here we show a critical role for CCL5 and CXCL10 in the induction of lung TRM and a possible strategy for boosting responses.
Functional brain connectivity in early adolescence after hypothermia-treated neonatal hypoxic-ischemic encephalopathy
Neonatal hypoxic-ischemic encephalopathy (HIE) injures the infant brain during the basic formation of the developing functional connectome. This study aimed to investigate long-term changes in the functional connectivity (FC) networks of the adolescent brain following neonatal HIE treated with therapeutic hypothermia (TH).
Pregnancy outcomes among patients with complex congenital heart disease
Patients with complex congenital heart disease (CCHD) may pose a serious threat to the mother-infant safety. This study intends to explore the influencing factors for adverse pregnancy outcomes in the CCHD population. Totally 108 CCHD patients who terminated pregnancy from January 2013 to January 2023 were recruited. We collected clinical data during the pregnancy from electronic medical records. Among them, 45 patients had adverse pregnancy outcomes (41.7%) and no patient died. 5 patients with no newborn. The incidence rate of adverse pregnancy outcomes was significantly higher in patients with brain natriuretic peptide (BNP) > 100 pg/mL (OR: 2.736; 95%CI: 1.001–7.481, p = 0.049) and hypoxemia (OR: 15.46; 95%CI: 1.689–141.512, p = 0.015) and without undergoing cardiac surgical correction (OR: 3.226; 95%CI: 1.121–9.259, p = 0.03). It was confirmed by propensity score matching that no cardiac surgical correction was an independent risk factor. Maternal patients without undergoing cardiac surgical correction had poorer NYHA cardiac function (p = 0.000) and were more prone to heart failure (p = 0.027), hypoxemia (p = 0.042), pulmonary arterial hypertension (p = 0.038) and postpartum hemorrhage (p = 0.016). Moreover, these patients had prolonged Surgical Intensive Care Unit (SICU) stay (p = 0.000) and significantly higher risk of premature delivery (p = 0.005), low birth weight (p = 0.018), infection and asphyxia (p = 0.043). Corrective cardiac surgery in patients with CCHD before pregnancy significantly reduces the incidence of adverse pregnancy outcomes.
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