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Objective: We assessed the added value of advanced echocardiography post hoc analysis for optimal decision-making in the Heart Valve Team (HVT) using an interactive, dynamic, live visualization system with true three-dimensional (3-D) stereo vision.
My Heart Is Stereo
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Methods: HVT scrutinized the incremental value of 3 consecutive methods of presentation of full-volume echocardiographic data sets in terms of diagnosis and possibility of repair in 11 selected patients having mitral regurgitation (MR)(Table 1). The questionnaire investigated consecutively (a) standard two-dimensional (2-D) transesophageal echocardiography, (b) single-beat 3-D zoom of the surgical view of the mitral valve, and (c) advanced 3-D volumetric rendering technology (Personal Space Station, Vesalius 3D software, PS-Medtech, Netherlands).
Conclusions: Advanced easy-to-use true 3-D echocardiography limited differences in interpretation and strengthened the confidence in understanding the mechanisms and suitability for repair of mitral valve regurgitation, typically in more complex valve pathology.
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And, basically, they're more stale and conventional than when they started! Check out their latest single, "Stereo Hearts." Let's face it: You can't get more adult-contemporary than putting Maroon 5 singer and The Voice judge Adam Levine into the mix.
Anyway, the song's main theme is the often-used love/music figure of speech. Travie's lines consist of plugging in retro music media and players like tapes, records and boom boxes. A few lines seem to work against the purpose. He compares himself to a boom box -- "all I ask is you not get mad at me/when you have to purchase mad D batteries" -- but makes himself sound like a high-maintenance dude in the process.
Along with Levine's exaggerated pronunciation of the "Oh!" sound, the chorus also plays loose with human anatomy with the heart/stereo metaphor. Here's some education: The heart actually has four chambers, two atria and two ventricles. As a result, it's more like a 4.0 system than your usual 2.0 stereo system. I guess these guys weren't health class heroes. The heart/bass drum simile in Nicki Minaj's "Super Bass" made a lot more sense than this.
Finally, as if mercifully, a line near the end of the song -- "because good music can be so hard to find" -- breaks the flimsy love/music metaphor this song is based upon.
Hmmm.
Has Travie surfed the net lately? Good music is actually pretty easy to find if you know what you want and where to look. It's way easier than finding love.
But I'm not a famous solo artist back with my old, famous band once again and, hey, Adam Levine, to boot. So maybe I just don't know about hardship.
Unless maybe Travie is just pulling the wool over our eyes. Maybe he's really just laughing at all of us, knowingly acknowledging that, for him -- a super-famous dude -- love is really easy to find.
Either way, this track needs to go in for an angioplasty. STAT.
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The heterogeneity of functional cardiomyocytes arises during heart development, which is essential to the complex and highly coordinated cardiac physiological function. Yet the biological and physiological identities and the origin of the specialized cardiomyocyte populations have not been fully comprehended. Here we report a previously unrecognised population of cardiomyocytes expressing Dbhgene encoding dopamine beta-hydroxylase in murine heart. We determined how these myocytes are distributed across the heart by utilising advanced single-cell and spatial transcriptomic analyses, genetic fate mapping and molecular imaging with computational reconstruction. We demonstrated that they form the key functional components of the cardiac conduction system by using optogenetic electrophysiology and conditional cardiomyocyte Dbh gene deletion models. We revealed their close relationship with sympathetic innervation during cardiac conduction system formation. Our study thus provides new insights into the development and heterogeneity of the mammalian cardiac conduction system by revealing a new cardiomyocyte population with potential catecholaminergic endocrine function.
In murine heart, pacemaker activity can be detected as early as embryonic day (E8.0)3. However, the formation of the CCS is not completed until perinatal stages2,4. The origin of the cell, cellular differentiation, and the maturation of the various components of the CCS, in particular the ventricular CCS, are incompletely understood. In murine hearts, it has been accepted that the Purkinje fibre (PKJ) network arises from developing trabecular cardiomyocytes through endocardially-derived inductive signals5,6,7,8. Recently, it has also been suggested that a polyclonal PKJ network forms by progressive recruitment of conductive precursors to this scaffold from a pool of bipotent progenitors9.
On the other hand, catecholamines, the canonical sympathetic neurotransmitter, are known to be essential for cardiac development: mice deficient in catecholamine synthetic enzymes tyrosine hydroxylase (Th)10 and dopamine beta-hydroxylase (Dbh)11,12, died in utero with cardiac developmental defects. There is also mixed evidence around the role of catecholamines in establishing and maintaining normal cardiac rhythm13,14,15,16. However, the true importance and source of these catecholamines for the CCS development remain uncertain16.
Recent refinement of transcriptomic technologies including single-cell RNA sequencing (scRNA-Seq) and spatial enhanced resolution omics sequencing (Stereo-seq) 17,18 has facilitated the interrogation of cell populations with increasing classification power, revealing and characterizing novel cell types. Several studies have applied such approaches, particularly scRNA-Seq, to investigate cardiogenesis, focusing on subpopulations of cells isolated using predefined genes19,20,21,22. Given the complexity and incomplete understanding of the CCS morphogenesis and maturation, it is important to establish a molecular approach that enables simultaneous analysis of global organ-wide spatial gene expression patterns without biasing against cellular heterogeneity. We thus co-opted Stereo-seq, a newly established high-resolution large-field spatially resolved transcriptomics technique17,18, with scRNA-Seq, to map the transcriptional landscape of the CCS formation and maturation in the murine heart. This led to the identification of an unreported cardiomyocyte population expressing Dbh. Our subsequent lineage tracing analysis revealed that Dbh+-derived CMs first emerged in the sinus venosus at E12.5, subsequently contributed to both atrial and ventricular CCS components in the process of cardiogenesis and became more prominent in the CCS from perinatal stages to adults. Using optogenetic electrophysiological interrogation of DbhCre/ChR2-tdTomato mice, we further confirmed that Dbh+-derived CMs function as part of the ventricular CCS. We then performed electrophysiological characterization of cardiac conduction using ex vivo isolated hearts from a Dbhcko(-MHCCre/Dbh-flox) cardiomyocyte-specific Dbh deletion model to confirm that Dbhcko hearts have slowed atrioventricular conduction. Furthermore, catecholaminergic-type vesicles were identified in adult cardiomyocytes in the Dbh+-CMs-rich atrioventricular junction. Collectively, our data provide a transcriptomic landscape of the CCS in the murine heart which reveals Dbh-expressing cardiomyocytes contributing to the formation and function of the CCS in the mammalian heart.
a Summary of workflow: whole embryos (E8.5, E10.5) or whole hearts (E12.5, E14.5, E16.5, P3) were sampled for single cell RNA sequencing. Slices of whole heart from E12.5, E14.5, and P3 were sampled for Stereo-seq spatial transcriptomics. We used 10X Genomics and Stereo-seq for sequencing. We performed quality control before we clustered and labelled cells based on their gene expression. We performed a range of downstream analyses with both single-cell RNA sequencing and Stereo-seq data. b PHATE plot of the cellular landscape of the cardiomyocyte lineage. Numbered labels indicate the cell type with the corresponding colour on the PHATE plot, with full names below. (See Supplementary Data 2 for interactive version). c PHATE plot of the Dbh+ cardiomyocyte subpopulation in the developing murine heart. Numbered labels indicate the cell type with the corresponding colour on the PHATE plot, with full names below and are common with panel b. (See Supplementary Data 3 for interactive version). d Heatmap demonstrating selected marker genes for each population identified in the cardiomyocyte lineage. Yellow indicates high expression and purple indicates low expression. Gene expression values were normalised across heatmap rows, and then across columns. VMs ventricular cardiomyocytes, AMs atrial cardiomyocytes, SAN sinoatrial node, AMCCS atrial cardiac conduction system, AVN atrioventricular node, PKJ Purkinje fibres, pHT primary heart tube, ED-CMs endocardial gene-rich cardiomyocytes, Dev-CMs developing cardiomyocytes, HFs heart fields. 152ee80cbc
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