The effects of malaria in pregnancy on utero- and fetoplacental blood flow and fetal growth: a longitudinal Doppler ultrasound study from Kinshasa, Democratic Republic of Congo

Malaria during pregnancy is thought to affect both uterine and umbilical artery blood flow, leading to decreased oxygen and nutrient exchange between the mother and fetus, and ultimately to intrauterine growth restriction. We examined the effect of concurrent malaria on changes in uterine artery and umbilical artery resistance indices over gestational age. We used data from 177 pregnant women enrolled in a longitudinal Doppler ultrasound study. Women with high uterine artery and umbilical artery resistance had neonates that weighed less and were smaller. Compared to multigravidae with no malaria, primigravidae with concurrent malaria had an 11-13% increase in uterine artery resistance. Compared to women with no concurrent malaria and a male fetus, concurrent malaria caused an acute 10-14% increase in umbilical artery resistance among women female fetus, while women with a male fetus and concurrent malaria had a 2-3% increase in umbilical artery resistance. We also examined the effect of early pregnancy malaria parasitemia ([less than or equal to] 20 weeks' gestation) on subsequent changes in uteroplacental blood flow and fetal growth among a subset of 128 women with early pregnancy malaria exposure data. Early pregnancy malaria infection affected placentation, reflected by changes in uterine artery blood flow. Among nourished women, early pregnancy malaria decreased uterine artery resistance (-0.036; 95% CI: -0.065, -0.0058), but among undernourished women, early pregnancy malaria increased uterine artery resistance (+0.022; 95% CI: -0.031, 0.074). Among primigravidae, early pregnancy malaria decreased umbilical artery resistance, reflecting adaptive villous angiogenesis with early pregnancy malaria. Primigravidae with early pregnancy malaria had 3.6 times the risk of subsequent IUGR (95% CI: 2.1, 6.2) compared to multigravidae with no early pregnancy malaria. Our findings point to both the acute effects of concurrent parasitemia and the effects of early pregnancy malaria on placental development. The acute effects of malaria on placental blood flow indicate the need for management and control strategies during pregnancy. Early pregnancy malaria infection leads to changes in placentation, villous angiogenesis, and intrauterine growth restriction. Our findings support the initiation of malaria prevention and control efforts earlier in pregnancy

Serum Iron Level is Associated with Time to Antibiotics in Cystic Fibrosis

Background: Serum levels of hepcidin‐25, a peptide hormone that reduces blood iron content, are elevated when patients with cystic fibrosis (CF) develop pulmonary exacerbation (PEx). Because hepcidin‐25 is unavailable as a clinical laboratory test, we questioned whether a one‐time serum iron level was associated with the subsequent number of days until PEx, as defined by the need to receive systemic antibiotics (ABX) for health deterioration. Methods: Clinical, biochemical, and microbiological parameters were simultaneously checked in 54 adults with CF. Charts were reviewed to determine when they first experienced a PEx after these parameters were assessed. Time to ABX was compared in subgroups with and without specific attributes. Multivariate linear regression was used to identify parameters that significantly explained variation in time to ABX. Results: In univariate analyses, time to ABX was significantly shorter in subjects with Aspergillus‐positive sputum cultures and CF‐related diabetes. Multivariate linear regression models demonstrated that shorter time to ABX was associated with younger age, lower serum iron level, and Aspergillus sputum culture positivity. Conclusions: Serum iron, age, and Aspergillus sputum culture positivity are factors associated with shorter time to subsequent PEx in CF adults

Frontline Science: Rapid adipose tissue expansion triggers unique proliferation and lipid accumulation profiles in adipose tissue macrophages

Obesityâ related changes in adipose tissue leukocytes, in particular adipose tissue macrophages (ATMs) and dendritic cells (ATDCs), are implicated in metabolic inflammation, insulin resistance, and altered regulation of adipocyte function. We evaluated stromal cell and white adipose tissue (WAT) expansion dynamics with high fat diet (HFD) feeding for 3â 56 days, quantifying ATMs, ATDCs, endothelial cells (ECs), and preadipocytes (PAs) in visceral epididymal WAT and subcutaneous inguinal WAT. To better understand mechanisms of the early response to obesity, we evaluated ATM proliferation and lipid accumulation. ATMs, ATDCs, and ECs increased with rapid WAT expansion, with ATMs derived primarily from a CCR2â independent resident population. WAT expansion stimulated proliferation in resident ATMs and ECs, but not CD11c+ ATMs or ATDCs. ATM proliferation was unperturbed in Csf2â and Rag1â deficient mice with WAT expansion. Additionally, ATM apoptosis decreased with WAT expansion, and proliferation and apoptosis reverted to baseline with weight loss. Adipocytes reached maximal hypertrophy at 28 days of HFD, coinciding with a plateau in resident ATM accumulation and the appearance of lipidâ laden CD11c+ ATMs in visceral epididymal WAT. ATM increases were proportional to tissue expansion and adipocyte hypertrophy, supporting adipocyteâ mediated regulation of resident ATMs. The appearance of lipidâ laden CD11c+ ATMs at peak adipocyte size supports a role in responding to ectopic lipid accumulation within adipose tissue. In contrast, ATDCs increase independently of proliferation and may be derived from circulating precursors. These changes precede and establish the setting in which largeâ scale adipose tissue infiltration of CD11c+ ATMs, inflammation, and adipose tissue dysfunction contributes to insulin resistance.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142947/1/jlb10097_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142947/2/jlb10097.pd

Estimation of Gestational Age via Image Analysis of Anterior Lens Capsule Vascularity in Preterm Infants: A Pilot Study

Introduction: Anterior lens capsule vascularity (ALCV) is resorbed in the developing fetus from 27 to 35 weeks gestation. In this pilot study, we evaluated the feasibility and validity of combining smartphone ophthalmoscope videos of ALCV and image analysis for gestational age estimation.Methods: ALCV videos were captured longitudinally in preterm neonates from delivery using a PanOptic® Ophthalmoscope with an iExaminer® adapter (Welch-Allyn). ALCV video frames were manually selected and quantified using semi-automatic image analysis. A predictive model based on ALCV features was compared to gold-standard ultrasound gestational age estimates.Results: A total of 64 image-capture sessions were carried out in 24 neonates. Ultrasound-estimated gestational age and ALCV-predicted gestational age estimates indicate that the two methods are similar (r = 0.78, p < 0.0001). ALCV estimates of gestational age were within 0.11 ± 1.3 weeks of ultrasound estimates. In the final model, gestational age was predicted within ± 1 week for 54% and within ± 2 weeks for 86% of the measures.Conclusions: This novel application of smartphone ophthalmoscopy and ALCV image analysis may provide a safe, accurate and non-invasive technology to estimate postnatal gestational age, especially in low income countries where gestational age may not be known at birth

Forgiveness-Reconciliation and Communication-Conflict-Resolution Interventions Versus Retested Controls in Early Married Couples

The first 6 months of marriage are optimal for marriage enrichment interventions. The Hope-Focused Approach to couple enrichment was presented as two 9-hr interventions--(a) Handling Our Problems Effectively (HOPE), which emphasized communication and conflict resolution, and (b) Forgiveness and Reconciliation through Experiencing Empathy (FREE). HOPE and FREE were compared with repeated assessment controls. Couples were randomly assigned and were assessed at pretreatment (t1); 1 month posttreatment (t2) and at 3- (t3), 6- (t4), and 12-month (t5) follow-ups using self-reports. In addition to self-report measures, couples were assessed at t1, t2, and t5 using salivary cortisol, and behavioral coding of decision making. Of 179 couples who began the study, 145 cases were analyzed. Both FREE and HOPE produced lasting positive changes on self-reports. For cortisol reactivity, HOPE and FREE reduced reactivity at t2, but only HOPE at t5. For coded behaviors, control couples deteriorated; FREE and HOPE did not change. Enrichment training was effective regardless of the focus of the training

Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound study

Abstract Background During early pregnancy, the placenta develops to meet the metabolic demands of the foetus. The objective of this analysis was to examine the effect of malaria parasitaemia prior to 20 weeks’ gestation on subsequent changes in uterine and umbilical artery blood flow and intrauterine growth restriction. Methods Data were analysed from 548 antenatal visits after 20 weeks’ gestation of 128 women, which included foetal biometric measures and interrogation of uterine and umbilical artery blood flow. Linear mixed effect models estimated the effect of early pregnancy malaria parasitaemia on uterine and umbilical artery resistance indices. Log-binomial models with generalized estimating equations estimated the effect of early pregnancy malaria parasitaemia on the risk of intrauterine growth restriction. Results There were differential effects of early pregnancy malaria parasitaemia on uterine artery resistance by nutritional status, with decreased uterine artery resistance among nourished women with early pregnancy malaria and increased uterine artery resistance among undernourished women with early pregnancy malaria. Among primigravidae, early pregnancy malaria parasitaemia decreased umbilical artery resistance in the late third trimester, likely reflecting adaptive villous angiogenesis. In fully adjusted models, primigravidae with early pregnancy malaria parasitaemia had 3.6 times the risk of subsequent intrauterine growth restriction (95% CI: 2.1, 6.2) compared to the referent group of multigravidae with no early pregnancy malaria parasitaemia. Conclusions Early pregnancy malaria parasitaemia affects uterine and umbilical artery blood flow, possibly due to alterations in placentation and angiogenesis, respectively. Among primigravidae, early pregnancy malaria parasitaemia increases the risk of intrauterine growth restriction. The findings support the initiation of malaria parasitaemia prevention and control efforts earlier in pregnancy

Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation.

TREM2 is a pattern recognition receptor, expressed on microglia and myeloid cells, detecting lipids and Aβ and inducing an innate immune response. Missense mutations (e.g., R47H) of TREM2 increase risk of Alzheimer's disease (AD). The soluble ectodomain of wild-type TREM2 (sTREM2) has been shown to protect against AD in vivo, but the underlying mechanisms are unclear. We show that Aβ oligomers bind to cellular TREM2, inducing shedding of the sTREM2 domain. Wild-type sTREM2 bound to Aβ oligomers (measured by single-molecule imaging, dot blots, and Bio-Layer Interferometry) inhibited Aβ oligomerization and disaggregated preformed Aβ oligomers and protofibrils (measured by transmission electron microscopy, dot blots, and size-exclusion chromatography). Wild-type sTREM2 also inhibited Aβ fibrillization (measured by imaging and thioflavin T fluorescence) and blocked Aβ-induced neurotoxicity (measured by permeabilization of artificial membranes and by loss of neurons in primary neuronal-glial cocultures). In contrast, the R47H AD-risk variant of sTREM2 is less able to bind and disaggregate oligomeric Aβ but rather promotes Aβ protofibril formation and neurotoxicity. Thus, in addition to inducing an immune response, wild-type TREM2 may protect against amyloid pathology by the Aβ-induced release of sTREM2, which blocks Aβ aggregation and neurotoxicity. In contrast, R47H sTREM2 promotes Aβ aggregation into protofibril that may be toxic to neurons. These findings may explain how wild-type sTREM2 apparently protects against AD in vivo and why a single copy of the R47H variant gene is associated with increased AD risk.European Unio