Correction factors for oxygen and flow-rate effects on neonatal Fleisch and Lilly pneumotachometers

Objective: To assess the effects of different oxygen concentrations and flow rates on the measurement errors of neonatal pneumotachometers in heated and unheated situations and to develop correction factors to correct for these effects. Design: Prospective laboratory study. Setting: Outpatient clinic with equipment in a standardized setting. Subjects: Neonatal pneumotachometers. Interventions: In standardized conditions, the tested pneumotachometer was calibrated at a flow rate of 3 L/min with 60% oxygen and was set in series with a closed spirometer system being used as a reference. Different air-flow levels (1-9 L/min) and oxygen concentrations (21-100%) were infused into the closed system with the pneumotachometer and spirometer. Measurements and Main Results: The pneumotachometers were significantly affected by changing oxygen concentrations (p < .01) and increasing flow rates (p < .01), increasing the actually measured flow rate. Correction factors, developed by multiple regression analysis, significantly reduced the overall maximum errors of the pneumotachometers from -1.1 to 0.6 L/min to -0.5 to 0.4 L/min. Conclusions: The effects of changes in oxygen concentrations and flow rates on neonatal pneumotachometers could be considerably decreased by the use of correction factors such as were calculated in this study. This will preclude frequent calibration procedures with actual flow and oxygen levels during changes in experimental settings. Copyrigh

Ultrasound markers for prediction of complex gastroschisis and adverse outcome: longitudinal prospective nationwide cohort study

Objectives: To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value. Methods: This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.e. involving bowel atresia, volvulus, perforation or necrosis) gastroschisis at birth. Fetal biometry (abdominal circumference and estimated fetal weight), the occurrence of polyhydramnios, intra- and extra-abdominal bowel diameters and the pulsatility index (PI) of the superior mesenteric artery (SMA) were assessed. Linear mixed modeling was used to compare the individual trajectories of cases with simple and those with complex gastroschisis, and logistic regression analysis was used to estimate the strength of association between the ultrasound parameters and outcome. Results: Of 104 pregnancies with isolated fetal gastroschisis included, four ended in intrauterine death. Eighty-one (81%) liveborn infants with simple and 19 (19%) with complex gastroschisis were included in the analysis. We found no relationship between fetal biometric variables and complex gastroschisis. The SMA-PI was significantly lower in fetuses with gastroschisis than in healthy controls, but did not differentiate between simple and complex gastroschisis. Both intra- and extra-abdominal bowel diameters were larger in cases with complex, compared to those with simple, gastroschisis (P < 0.001 and P < 0.005, respectively). The presence of intra-abdominal bowel diameter ≥ 97.7th percentile on at least three occasions, not necessarily on successive examinations, was associated with an increased risk of the fetus having complex gastroschisis (relative risk, 1.56 (95% CI, 1.02–2.10); P = 0.006; positive predictive value, 50.0%; negative predictive value, 81.4%). Conclusions: This large prospective longitudinal study found that intra-abdominal bowel dilatation when present repeatedly during fetal development can differentiate between simple and complex gastroschisis; however, the positive predictive value is low, and therefore the clinical usefulness of this marker is limited

Valproic Acid Disrupts Hematopoiesis in Xenopus Laevis Through the Inhibition of Histone Deacetylase 3.

Histone deacetylases (HDACs) are important regulators of developmental processes and cellular functions. However, their role in hematopoiesis has not been determined, and in Xenopus laevis, a specific function for HDACs has yet to be identified. In the present work, we employed the class I selective HDAC inhibitor, valproic acid (VPA), to identify hdac3 as an essential mediator of primitive hematopoiesis. Exposure to VPA during gastrulation results in a marked and specific block of primitive hematopoiesis in Xenopus embryos. Furthermore, pharmacological and loss of function studies demonstrate that hdac3 functions downstream of bmp4 signaling and is specifically required for primitive erythropoiesis. We also describe here that runx1 is activated by bmp4 in an HDAC-dependent manner. Consistent with this, restoring runx1 expression partially rescues VPA mediated hematopoietic defects. We further identify that the effects of HDAC inhibition on primitive hematopoiesis is conserved in mammals, as yolk sac hematopoiesis in mouse is also blocked with exposure to VPA. Lastly, we identify a bicarbonate transporter as the primary means for VPA to enter the embryos. Our findings demonstrate for the first time a critical role for hdac3 in primitive hematopoiesis, and indicate that specific developmental defects associated with exposure to VPA, a significant teratogen in humans, arise through inhibition of class I HDACs