Dopamine as a potential rescue therapy for refractory proteinâ losing enteropathy in Fontanâ palliated patients

PLE is an important cause of morbidity and mortality in patients who have undergone Fontan palliation. While multiple PLE therapies have been reported, none has proved consistently effective. Patients who do not respond to â standardâ PLE therapies face poor longâ term outcomes. We report here a significant response to dopamine infusion in three patients with chronic, refractory PLE. We hypothesize that this response may be at least partially due to a dopamine effect on lymphatic receptors rather than to an augmentation of cardiac output.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137378/1/petr12925_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137378/2/petr12925.pd

Clinical significance of antiâ HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis

While VAD use in pediatric patients has previously been associated with antiâ HLA antibody production, the clinical significance of these antibodies is unclear. We investigated the clinical impact of antiâ HLA antibodies associated with VAD use in a large cohort of pediatric HTx recipients. From 2004 to 2011, pediatric cardiomyopathy patients postâ HTx (N=1288) with preâ HTx PRA levels were identified from the United Network for Organ Sharing database. PRA levels were compared between VAD patients and those with no history of MCS. Incidence of rejection and overall survival were compared between VAD and nonâ MCS groups after stratification by PRA and age. VAD recipients were more likely to produce antiâ HLA antibodies than nonâ MCS patients (25.5% vs 10.5% had PRA>10%, P10%) had a higher incidence of rejection within 15 months of HTx compared to sensitized nonâ MCS patients (57.1% vs 35.9%, P=.02). There was no intergroup difference in 15â month mortality. Among pediatric cardiomyopathy patients supported with a VAD, the presence of antiâ HLA antibodies prior to HTx is associated with an increased risk of rejection. The mechanism of the association between VADâ associated antibodies and early rejection is unclear and warrants further investigation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137732/1/petr12938_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137732/2/petr12938.pd

The impact of ischemic time on early rejection after pediatric heart transplant

Prolonged graft ischemia may be a risk factor for early rejection postâ HTx, but this has not been well studied in children. Furthermore, factors moderating the association between IT and early rejection have not been investigated. From 2004 to 2012, pediatric HTx recipients (n = 2381) were identified from the UNOS database. A ROC curve determined the optimal IT discriminating patients by the presence of early rejection. Separate univariate analyses identified factors associated with: (i) early (prior to hospital discharge) rejection, and (ii) IT. A multivariable logistic regression assessed independent risk factors for early rejection. We included interaction terms to evaluate whether IT’s independent risk effect on early rejection is moderated via interaction with associated factors found in univariate analysis. Longer IT was associated with an increased risk of early rejection. In multivariable analysis, IT > 3.1 hours was an independent risk factor for early rejection (AOR 1.44, P = .01). No interaction terms between IT and any associated factors were significant. Longer IT is an independent risk for early rejection in pediatric HTx recipients. Better understanding the association between IT and early rejection may identify interventions to mitigate this risk.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139903/1/petr13034.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139903/2/petr13034_am.pd

Differential effect of body mass index on pediatric heart transplant outcomes based on diagnosis

The impact of nutritional status on HT x waitlist mortality in children is unknown, and there are conflicting data regarding the role of nutrition in post‐ HT x survival. This study examined the influence of nutrition on waitlist and post‐ HT x outcomes in children. Children 2–18 yr listed for HT x from 1997 to 2011 were identified from the OPTN database and stratified by BMI percentile. Multivariable logistic regression evaluated the influence of BMI on waitlist mortality. Cox proportional hazard regression assessed the impact of BMI on post‐ HT x mortality. When all 2712 patients were analyzed, BMI did not impact waitlist, one‐, or five‐yr mortality. However, when stratified by diagnosis, BMI  > 95% ( AOR 1.96; 95% CI 1.24, 3.09) and BMI   95% and BMI  < 1% are independent risk factors for waitlist mortality in patients with CM, but not CHD . This suggests differing risk factors based on disease etiology, and an individualized approach to risk assessment based on diagnosis may be warranted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108679/1/petr12352.pd

Convergent evolution of pregnancy-specific glycoproteins in human and horse

Pregnancy-specific glycoproteins (PSGs) are members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family that are secreted by trophoblast cells. PSGs may modulate immune, angiogenic and platelet responses during pregnancy. Until now, PSGs are only found in species that have a highly invasive (hemochorial) placentation including humans, mice and rats. Surprisingly, analyzing the CEACAM gene family of the horse, which has a non-invasive epitheliochorial placenta, with the exception of the transient endometrial cups, we identified equine CEACAM family members that seem to be related to PSGs of rodents and primates. We identified seven genes that encode secreted PSG-like CEACAMs. Phylogenetic analyses indicate that they evolved independently from an equine CEACAM1-like ancestor rather than from a common PSG-like ancestor with rodents and primates. Significantly, expression of PSG-like genes (CEACAM44, CEACAM48, CEACAM49 and CEACAM55) was found in non-invasive as well as invasive trophoblast cells such as purified chorionic girdle cells and endometrial cup cells. Chorionic girdle cells are highly invasive trophoblast cells that invade the endometrium of the mare where they form endometrial cups and are in close contact with maternal immune cells. Therefore, the microenvironment of invasive equine trophoblast cells has striking similarities to the microenvironment of trophoblast cells in hemochorial placentas, suggesting that equine PSG-like CEACAMs and rodent and primate PSGs have undergone convergent evolution. This is supported by our finding that equine PSG-like CEACAM49 exhibits similar activity to certain rodent and human PSGs in a functional assay of platelet–fibrinogen binding. Our results have implications for understanding the evolution of PSGs and their functions in maternal–fetal interactions

The resource theory of quantum reference frames: manipulations and monotones

Every restriction on quantum operations defines a resource theory, determining how quantum states that cannot be prepared under the restriction may be manipulated and used to circumvent the restriction. A superselection rule is a restriction that arises through the lack of a classical reference frame and the states that circumvent it (the resource) are quantum reference frames. We consider the resource theories that arise from three types of superselection rule, associated respectively with lacking: (i) a phase reference, (ii) a frame for chirality, and (iii) a frame for spatial orientation. Focussing on pure unipartite quantum states (and in some cases restricting our attention even further to subsets of these), we explore single-copy and asymptotic manipulations. In particular, we identify the necessary and sufficient conditions for a deterministic transformation between two resource states to be possible and, when these conditions are not met, the maximum probability with which the transformation can be achieved. We also determine when a particular transformation can be achieved reversibly in the limit of arbitrarily many copies and find the maximum rate of conversion. A comparison of the three resource theories demonstrates that the extent to which resources can be interconverted decreases as the strength of the restriction increases. Along the way, we introduce several measures of frameness and prove that these are monotonically nonincreasing under various classes of operations that are permitted by the superselection rule.Comment: 37 pages, 4 figures, Published Versio

The Resource Theory of Quantum States Out of Thermal Equilibrium

The ideas of thermodynamics have proved fruitful in the setting of quantum information theory, in particular the notion that when the allowed transformations of a system are restricted, certain states of the system become useful resources with which one can prepare previously inaccessible states. The theory of entanglement is perhaps the best-known and most well-understood resource theory in this sense. Here we return to the basic questions of thermodynamics using the formalism of resource theories developed in quantum information theory and show that the free energy of thermodynamics emerges naturally from the resource theory of energy-preserving transformations. Specifically, the free energy quantifies the amount of useful work which can be extracted from asymptotically-many copies of a quantum system when using only reversible energy-preserving transformations and a thermal bath at fixed temperature. The free energy also quantifies the rate at which resource states can be reversibly interconverted asymptotically, provided that a sublinear amount of coherent superposition over energy levels is available, a situation analogous to the sublinear amount of classical communication required for entanglement dilution.Comment: 4.5 pages main text, 12 pages appendix; v3: improvements to presentation of the main resul

A Comparison of Synovex ONE® Alone to Synovex Choice® Followed by Synovex Plus® as Implant Strategies for Finishing Heifers

A commercial feedlot study utilizing 1,737 crossbred heifers (initial BW 690 lb) compared the effect of two implant strategies [Synovex ONE Feedlot (day 0) or Synovex Choice (day 0) followed by Synovex Plus (day 95)] on performance and carcass characteristics. No differences were observed in carcass weight, final body weight, or gain, but heifers implanted with Synovex ONE Feedlot had slightly greater feed conversion and greater intake than heifers implanted using Synovex Choice/Synovex Plus. Heifers implanted with Synovex Choice/Synovex Plus had lower marbling score and yield grade, higher dressing percentage, and greater loin muscle area compared to heifers implanted with Synovex ONE Feedlot. Cattle implanted with Synovex ONE Feedlot showed a tendency for better quality grading compared to heifers implanted with Synovex Choice/Synovex Plus. These data suggest that implanting heifers with Synovex ONE Feedlot gives comparable growth to heifers implanted with Synovex Choice followed by Synovex Plus, with some changes in fatness when fed equal days

Adhesion of Trypanosoma cruzi Trypomastigotes to Fibronectin or Laminin Modifies Tubulin and Paraflagellar Rod Protein Phosphorylation

Background: The unicellular parasite Trypanosoma cruzi is the causative agent of Chagas disease in humans. Adherence of the infective stage to elements of the extracellular matrix (ECM), as laminin and fibronectin, is an essential step in host cell invasion. Although members of the gp85/TS, as Tc85, were identified as laminin and fibronectin ligands, the signaling events triggered on the parasite upon binding to these molecules are largely unexplored. Methodology/Principal Findings: Viable infective parasites were incubated with laminin, fibronectin or bovine serum albumin for different periods of time and the proteins were separated by bidimensional gels. The phosphoproteins were envisaged by specific staining and the spots showing phosphorylation levels significantly different from the control were excised and identified by MS/MS. The results of interest were confirmed by immunoblotting or immunoprecipitation and the localization of proteins in the parasite was determined by immunofluorescence. Using a host cell-free system, our data indicate that the phosphorylation contents of T. cruzi proteins encompassing different cellular functions are modified upon incubation of the parasite with fibronectin or laminin. Conclusions/Significance: Herein it is shown, for the first time, that paraflagellar rod proteins and alpha-tubulin, major structural elements of the parasite cytoskeleton, are predominantly dephosphorylated during the process, probably involving the ERK1/2 pathway. It is well established that T. cruzi binds to ECM elements during the cell infection process. The fact that laminin and fibronectin induce predominantly dephosphorylation of the main cytoskeletal proteins of the parasite suggests a possible correlation between cytoskeletal modifications and the ability of the parasite to internalize into host cells.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2009/52646-6]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [303539/2005-4