Surgical Management for Advanced Heart Failure in Adults with Congenital Heart Disease

Adults with congenital heart disease (ACHD) have emerged as a new patient population that poses a variety of treatment and management obstacles. This chapter discusses the diagnosis of heart failure and treatment challenges faced by ACHD specifically addressing when to initiate mechanical circulatory support versus heart transplantation. It is evident that the ACHD population presents with a variety of unique challenges and considerations that still need to be explored. Addressing each of these issues will vastly change and improve how ACHD patients are approached from a treatment standpoint and ultimately provide more advantageous clinical options that can successfully handle the complexities presented by this population

Identification of Protein Targets of Reactive Metabolites of Tienilic Acid in Human Hepatocytes

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx300103jTienilic acid (TA) is a uricosuric diuretic that was withdrawn from the market only months after its introduction because of reports of serious incidents of drug-induced liver injury including some fatalities. Its hepatotoxicity is considered to be primarily immunoallergic in nature. Like other thiophene compounds, TA undergoes biotransformation to a S-oxide metabolite which then reacts covalently with cellular proteins. To identify protein targets of TA metabolites, we incubated [14C]-TA with human hepatocytes, separated cellular proteins by 2D gel electrophoresis, and analyzed proteins in 36 radioactive spots by tryptic digestion followed by LC-MS/MS. Thirty one spots contained at least one identifiable protein. Sixteen spots contained only one of 14 non-redundant proteins which were thus considered to be targets of TA metabolites. Six of the 14 were also found in other radioactive spots that contained from 1 to 3 additional proteins. Eight of the 14 had not been reported to be targets for any reactive metabolite other than TA. The other 15 spots each contained from 2–4 identifiable proteins, many of which are known targets of other chemically reactive metabolites, but since adducted peptides were not observed, the identity of the adducted protein(s) in these spots is ambiguous. Interestingly, all the radioactive spots corresponded to proteins of low abundance, while many highly abundant proteins in the mixture showed no radioactivity. Furthermore, of approximately 16 previously reported protein targets of TA in rat liver (Methogo, R., Dansette, P. and Klarskov, K. (2007) Int. J. Mass Spectrom., 268, 284–295), only one (fumarylacetoacetase) is among the 14 targets identified in this work. One reason for this difference may be statistical, given that each study identified a small number of targets from among thousands present in hepatocytes. Another may be the species difference (i.e. rat vs. human), and still another may be the method of detection of adducted proteins (i.e. Western blot vs. C-14). Knowledge of human target proteins is very limited. Of more than 350 known protein targets of reactive metabolites, only 42 are known from human and only 21 of these are known to be targets for more than one chemical. Nevertheless, the demonstration that human target proteins can be identified using isolated hepatocytes in vitro should enable the question of species differences to be addressed more fully in the future

Brain-Wide Correspondence of Neuronal Epigenomics and Distant Projections

Single-cell analyses parse the brain’s billions of neurons into thousands of ‘cell-type’ clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use

COMPARISON BETWEEN HUGONIOT AND SOME ISENTROPIC RELEASE CURVES OF COPPER IN THE PRESSURE RANGE 70 GPa - 150 GPa

Avec un canon à gaz léger une série d'expériences a été réalisée afin de déterminer les positions relatives de l'hugoniot et de quelques isentropiques de détente du cuivre. Les instants de fonctionnement des soixante douze sondes utilisées à chaque expérience sont enregistrés par un multichronomètre digital. Dans le domaine expérimental couvert 70 GPa - 150 GPa les résultats des points de l'isentropique du cuivre, dans le plan pression - vitesse matérielle, obtenus pour l'aluminium et le magnésium se situent"au-dessous" de la polaire de choc du cuivre du projectile. Lorsque la pression de choc dans le cuivre augmente - de 70 GPa à 150 GPa - l'écart - en vitesse matière - entre ces deux courbes décroît régulièrement de 100 m/s à 15 m/s.With a two stage light gas gun, experiments have been performed in order to compare the hugoniot curve and some isentropic release curve of copper. The working times of the seventy two pins used at each shot are recorded with a digital multichannel chronometer. In the 70 GPa - 150 GPa experimental range, the isentropic result from Al and Mg targets, in the pressure - material velocity diagram are "under" the copper shock polar of the projectile. In this range, when increasing the copper shock pressure, the material velocity discrepancy (between the two curves) decreases from 100 m/s to 15 m/s

Peuplier : suivi phytosanitaire en pépinière : part. 2 Parasites du feuillage, des rameaux et des tiges

Some main diseases can infect poplars in nursery and affect set production for both qualitative and quantitative aspects. The production of sets with commercial standards can be reduced because of vigour losses due to foliar pathogens attacks. Furthermore bark necrosis can induce mortality and sets infected by bacterial cankers cannot be sold. Production of healthy and vigorous sets is consequently a priority for nurserymen. Fertilization and sanitary following up contribute to reach this objective. After a first leaflet about insects, the second one concerns the main elements for diagnosis and protection means against the major diseases affecting poplar sets production. / Un certain nombre de parasites sévissent en pépinière et affectent la production des plants qualitativement et quantitativement. L'obtention de plants répondant aux normes dimensionnelles en vigueur peut être compromise par les réductions de croissance dues aux attaques de parasites foliaires. Les parasites d'écorce causent des mortalités et les tumeurs d'origine bactérienne obligent à éliminer les plants atteints. La production de plants sains et vigoureux constitue donc un objectif prioritaire. Une fertilisation équilibrée et une surveillance phytosanitaire y contribuent. Après une première fiche consacrée aux insectes ravageurs, ce document fournit les éléments essentiels de diagnostic et de lutte envers les principales maladies susceptibles d'affecter la production de plants