Plasmodium falciparum Malaria Elicits Inflammatory Responses that Dysregulate Placental Amino Acid Transport

Placental malaria (PM) can lead to poor neonatal outcomes, including low birthweight due to fetal growth restriction (FGR), especially when associated with local inflammation (intervillositis or IV). The pathogenesis of PM-associated FGR is largely unknown, but in idiopathic FGR, impaired transplacental amino acid transport, especially through the system A group of amino acid transporters, has been implicated. We hypothesized that PM-associated FGR could result from impairment of transplacental amino acid transport triggered by IV. In a cohort of Malawian women and their infants, the expression and activity of system A (measured by Na+-dependent 14C-MeAIB uptake) were reduced in PM, especially when associated with IV, compared to uninfected placentas. In an in vitro model of PM with IV, placental cells exposed to monocyte/infected erythrocytes conditioned medium showed decreased system A activity. Amino acid concentrations analyzed by reversed phase ultra performance liquid chromatography in paired maternal and cord plasmas revealed specific alterations of amino acid transport by PM, especially with IV. Overall, our data suggest that the fetoplacental unit responds to PM by altering its placental amino acid transport to maintain adequate fetal growth. However, IV more profoundly compromises placental amino acid transport function, leading to FGR. Our study offers the first pathogenetic explanation for FGR in PM

The mediating sex-specific effect of psychological distress on the relationship between adverse childhood experiences and current smoking among adults

<p><b>Abstract</b></p> <p><b>Background</b></p> <p>Research suggests that ACEs have a long-term impact on the behavioral, emotional, and cognitive development of children. These disruptions can lead to adoption of unhealthy coping behaviors throughout the lifespan. The present study sought to examine psychological distress as a potential mediator of sex-specific associations between adverse childhood experiences (ACEs) and adult smoking.</p> <p><b>Method</b></p> <p>Data from 7,210 Kaiser-Permanente members in San Diego California collected between April and October 1997 were used.</p> <p><b>Results</b></p> <p>Among women, psychological distress mediated a significant portion of the association between ACEs and smoking (21% for emotional abuse, 16% for physical abuse, 15% for physical neglect, 10% for parental separation or divorce). Among men, the associations between ACEs and smoking were not significant.</p> <p><b>Conclusions</b></p> <p>These findings suggest that for women, current smoking cessation strategies may benefit from understanding the potential role of childhood trauma.</p