Iron transport across the human placenta is regulated by hepcidin.

BACKGROUND: Transport of iron across the placenta is critical for appropriate development of the fetus. Iron deficiency during pregnancy remains a major public health concern, particularly in low- and middle-income countries, often exacerbated by infectious diseases leading to altered iron trafficking via inflammatory responses. Herein, we investigate the role of hepcidin, a master regulator of iron homeostasis, on regulation of iron transport across trophoblast cells. METHODS: We utilized the Jeg-3 choriocarcinoma cell line for analysis of the expression of transferrin receptor, ferritin, and ferroportin as well as the export of 59Fe in the presence of hepcidin. Placental tissue from human term pregnancies was utilized for immunohistochemistry. RESULTS: Hepcidin treatment of Jeg-3 cells decreased the expression of ferroportin and transferrin receptor (TfR) and reduced the cellular export of iron. Lower expression of TfR on the syncytiotrophoblast was associated with the highest levels of hepcidin in maternal circulation, and ferroportin expression was positively associated with placental TfR. Placentas from small-for-gestational-age newborns had significantly lower levels of ferroportin and ferritin gene expression at delivery. CONCLUSIONS: Our data suggest that hepcidin plays an important role in the regulation of iron transport across the placenta, making it a critical link in movement of iron into fetal circulation. IMPACT: Hepcidin has a direct impact on iron transport across the human placenta. This study provides the first evidence of direct regulation of iron efflux from human trophoblast cells by hepcidin. These data extend our understanding of iron transport across the maternal-fetal interface, a process critical for fetal health and development.

Depression and Frailty in Patients With End-Stage Liver Disease Referred for Transplant Evaluation.

End-stage liver disease (ESLD) patients are believed to have a high prevalence of depression, although mental health in ESLD has not been studied comprehensively. Further, the relationship between depression and severity of liver disease is unclear. Using baseline data from a large prospective cohort study (N = 500) of frailty in ESLD patients, we studied the association of frailty with depression. Frailty was assessed with the five-component Fried Frailty Index. Patients were assigned a composite score of 0 to 5, with scores ≥3 considered frail. Depression was assessed using the 15-question Geriatric Depression Scale, with a threshold of ≥6 indicating depression; 43.2% of patients were frail and 39.4% of patients were depressed (median score 4, range 0-15). In multivariate analysis, frailty was significantly associated with depression (odds ratio 2.78, 95% confidence interval 1.87-4.15, p < 0.001), whereas model for ESLD score was not associated with depression. After covariate adjustment, depression prevalence was 3.6 times higher in the most-frail patients than the least-frail patients. In conclusion, depression is common in ESLD patients and is strongly associated with frailty but not with severity of liver disease. Transplant centers should address mental health issues and frailty; targeted interventions may lower the burden of mental illness in this population.

Th2 cytokines are associated with persistent hepatic fibrosis in human Schistosoma japonicum infection.

We conducted a prospective cohort study in Leyte, the Philippines, among 611 Schistosoma japonicum-infected participants 7-30 years old, all of whom were treated with praziquantel at baseline. To detect hepatic fibrosis, abdominal ultrasound was performed at baseline and 12 months after treatment. Stool for assessment of S. japonicum infection was collected at baseline and at 3, 6, 9, and 12 months after treatment. Cytokines (interleukin [IL]-4, IL-5, IL-10, IL-13, tumor necrosis factor- alpha , and interferon- gamma ) produced by peripheral-blood mononuclear cells in response to soluble worm antigen preparation (SWAP), soluble egg antigen (SEA), and control medium were measured once 4 weeks after treatment. IL-4 to SWAP and IL-10 to both SWAP and SEA were associated with the presence of baseline fibrosis after adjustment for potential confounding variables (P<.03, for all). In participants with fibrosis at baseline, IL-4 to SWAP and IL-5 and IL-13 to both SWAP and SEA were associated with persistent fibrosis at 12 months after treatment (P<.05, for all). Males showed consistently stronger T helper 2 (Th2) cytokine responses to both SWAP and SEA than did females (P<.02, for all). These results suggest an independent role for Th2-biased cytokine responses to S. japonicum antigens in persistent hepatic fibrosis and indicate that Th2 cytokines may contribute to the male-biased prevalence of fibrosis.

Progression of stunting and its predictors among school-aged children in western Kenya.

OBJECTIVE: The objectives of this study were (1) to assess whether a cohort of school-aged children experiences progression of stunting over a 2-y-period of observation and (2) to identify baseline nutritional and body composition risk factors for the progression of stunting. METHODS: As part of a large-scale, randomized controlled trial assessing the impact of insecticide-treated bednets (ITNs) on nutritional status, we longitudinally followed a cohort of school-aged children over a 2-y-period in western Kenya. Anthropometric measurements were made at four time points from which Z-scores for height-for-age (HAZ), weight-for-age (WAZ), and body mass index (BMIZ) were calculated. Two measures of body composition, upper arm fat area and upper arm muscle area, were derived from mid-upper arm circumference (MUAC) and triceps skinfold thickness. RESULTS: Subjects experienced a mean change in HAZ from baseline to 9 months of -0.16 [-0.19, -0.13], from baseline to 16 months of -0.18 [-0.22, -0.15], and from baseline to 24 months of -0.36 [-0.41, -0.31]. Thus, the average individual's change in HAZ at the three follow-up time points is significantly less than zero, meaning that, on average, the cohort is deviating further from NCHS reference medians over time. The baseline nutritional measure that explained the greatest amount of variance in the progression of stunting was the upper arm muscle area Z-score (F=8.1; P=0.005). CONCLUSIONS: This longitudinal study provides further evidence from a distinct ecological setting regarding the progression of undernutrition during middle childhood in the developing world. It suggests that school-aged children in the developing world do not experience catch-up growth or remain stable. Rather, they continue to deviate from NCHS standards, accruing greater height deficits with age. In addition, absolute lean body mass explained the most variability in the progression of stunting, which supports cross-sectional findings from other studies.

Comparison of self-reported and observed water contact in an S. mansoni endemic village in Brazil.

Estimates of exposure are critical for immuno-epidemiologic and intervention studies in human schistosomiasis. Direct observation of human water contact patterns is both costly and time consuming. To address these issues, we determined whether individuals residing in a Schistosoma mansoni endemic village in Brazil could accurately self-report their water contact patterns. We compared the results of a water contact questionnaire to the present gold standard, direct observation of water contact in 86 volunteers, aged 8--29. We administered a survey to estimate volunteers' frequency and type of water contact and directly measured each volunteers' water contact patterns during 5 weeks of detailed water contact observations. We found a poor correlation between self reported frequency of contact and directly observed exposure (rho=0.119, P=NS). The questionnaire data was supplemented by information about average body surface area of exposure and duration of contact for specific activities derived from observations of this cohort. This 'supplemented questionnaire' data was significantly correlated with their exposure index (rho=0.227, P=0.05). It provides a starting point from which questionnaires may develop to provide a more cost-effective and less labor intensive method of assessing water contact exposure at the level of the individual.