Management of Acute Saddle Pulmonary Embolism in Pregnancy Following Fetal Surgery.

A 33-year-old gravidity three parity three (G3P3) woman at 34 weeks of pregnancy underwent fetal surgery to repair an open lumbosacral myelomeningocele at 22 weeks gestation and experienced preterm premature rupture of membranes as a result. She developed a saddle pulmonary embolus with signs of right heart strain while on prolonged bed rest. She was treated emergently with aspiration thrombectomy and suprarenal inferior vena cava (IVC) filter placement, followed by an uncomplicated cesarean delivery thereafter.

Synthesis of Organosilicon Ligands for Europium (III) and Gadolinium (III) as Potential Imaging Agents.

The relaxivity of MRI contrast agents can be increased by increasing the size of the contrast agent and by increasing concentration of the bound gadolinium. Large multi-site ligands able to coordinate several metal centres show increased relaxivity as a result. In this paper, an "aza-type Michael" reaction is used to prepare cyclen derivatives that can be attached to organosilicon frameworks via hydrosilylation reactions. A range of organosilicon frameworks were tested including silsesquioxane cages and dimethylsilylbenzene derivatives. Michael donors with strong electron withdrawing groups could be used to alkylate cyclen on three amine centres in a single step. Hydrosilylation successfully attached these to mono-, di-, and tri-dimethylsilyl-substituted benzene derivatives. The europium and gadolinium complexes were formed and studied using luminescence spectroscopy and relaxometry. This showed the complexes to contain two bound water moles per lanthanide centre and T1 relaxation time measurements demonstrated an increase in relaxivity had been achieved, in particular for the trisubstituted scaffold 1,3,5-tris((pentane-sDO3A)dimethylsilyl)benzene-Gd3. This showed a marked increase in the relaxivity (13.1 r1p/mM-1s-1).

Distributed Temperature Sensing to Measure Infiltration Rates Across a Groundwater Recharge Basin.

Managed aquifer recharge is used to augment groundwater resources and provide resiliency to water supplies threatened by prolonged droughts. It is important that recharge facilities operate at their maximum efficiency to increase the volume of water stored for future use. In this study, we evaluate the use of distributed temperature sensing (DTS) technology as a tool to measure high-resolution infiltration rates at a large-scale recharge facility. Fiber optic cable was laid out inside a spreading basin in a spiral pattern, at two different depths. The cables measured the propagation of diurnal surface water temperature oscillations into the basin depth. The rate of heat propagation is proportional to the velocity of the water, making it possible to estimate the infiltration rate from the temperature measurements. Our results showed that the infiltration rate calculated from DTS, averaged over the entire basin, was within 5% of the infiltration rate calculated using a conventional metering method. The high-resolution data obtained from DTS, both spatially and temporally, revealed heterogeneous infiltration rates throughout the basin; furthermore, tracking the evolution of infiltration rates over time revealed regions with consistently high infiltration rates, regions with consistently low infiltration rates, and regions that evolved from high to low rates, which suggested clogging within that region. Water utilities can take advantage of the high-resolution information obtained from DTS to better manage recharge basins and make decisions about cleaning schedule, frequency, and extent, leading to improved basin management strategies, reduced O&M costs, and increased groundwater recharge.

4-Hydroxynonenal dependent alteration of TRPV1-mediated coronary microvascular signaling.

We demonstrated previously that TRPV1-dependent regulation of coronary blood flow (CBF) is disrupted in diabetes. Further, we have shown that endothelial TRPV1 is differentially regulated, ultimately leading to the inactivation of TRPV1, when exposed to a prolonged pathophysiological oxidative environment. This environment has been shown to increase lipid peroxidation byproducts including 4-Hydroxynonenal (4-HNE). 4-HNE is notorious for producing protein post-translation modification (PTM) via reactions with the amino acids: cysteine, histidine and lysine. Thus, we sought to determine if 4-HNE mediated post-translational modification of TRPV1 could account for dysfunctional TRPV1-mediated signaling observed in diabetes. Our initial studies demonstrate 4-HNE infusion decreases TRPV1-dependent coronary blood flow in C57BKS/J (WT) mice. Further, we found that TRPV1-dependent vasorelaxation was suppressed after 4-HNE treatment in isolated mouse coronary arterioles. Moreover, we demonstrate 4-HNE significantly inhibited TRPV1 currents and Ca2+ entry utilizing patch-clamp electrophysiology and calcium imaging respectively. Using molecular modeling, we identified potential pore cysteines residues that, when mutated, could restore TRPV1 function in the presence of 4-HNE. Specifically, complete rescue of capsaicin-mediated activation of TRPV1 was obtained following mutation of pore Cysteine 621. Finally, His tag pull-down of TRPV1 in HEK cells treated with 4-HNE demonstrated a significant increase in 4-HNE binding to TRPV1, which was reduced in the TRPV1 C621G mutant. Taken together these data suggest that 4-HNE decreases TRPV1-mediated responses, at both the in vivo and in vitro levels and this dysfunction can be rescued via mutation of the pore Cysteine 621. Our results show the first evidence of an amino acid specific modification of TRPV1 by 4-HNE suggesting this 4-HNE-dependent modification of TRPV1 may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes.

Differential regulation of TRPV1 channels by H2O2: implications for diabetic microvascular dysfunction.

We demonstrated previously that TRPV1-dependent coupling of coronary blood flow (CBF) to metabolism is disrupted in diabetes. A critical amount of H2O2 contributes to CBF regulation; however, excessive H2O2 impairs responses. We sought to determine the extent to which differential regulation of TRPV1 by H2O2 modulates CBF and vascular reactivity in diabetes. We used contrast echocardiography to study TRPV1 knockout (V1KO), db/db diabetic, and wild type C57BKS/J (WT) mice. H2O2 dose-dependently increased CBF in WT mice, a response blocked by the TRPV1 antagonist SB366791. H2O2-induced vasodilation was significantly inhibited in db/db and V1KO mice. H2O2 caused robust SB366791-sensitive dilation in WT coronary microvessels; however, this response was attenuated in vessels from db/db and V1KO mice, suggesting H2O2-induced vasodilation occurs, in part, via TRPV1. Acute H2O2 exposure potentiated capsaicin-induced CBF responses and capsaicin-mediated vasodilation in WT mice, whereas prolonged luminal H2O2 exposure blunted capsaicin-induced vasodilation. Electrophysiology studies re-confirms acute H2O2 exposure activated TRPV1 in HEK293A and bovine aortic endothelial cells while establishing that H2O2 potentiate capsaicin-activated TRPV1 currents, whereas prolonged H2O2 exposure attenuated TRPV1 currents. Verification of H2O2-mediated activation of intrinsic TRPV1 specific currents were found in isolated mouse coronary endothelial cells from WT mice and decreased in endothelial cells from V1KO mice. These data suggest prolonged H2O2 exposure impairs TRPV1-dependent coronary vascular signaling. This may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes.