Introduction:The recently proposed YEARS algorithm was shown to safely exclude pulmonary embolism (PE) and reduce the use of computed tomography pulmonary angiography (CTPA) among pregnant women with suspected PE. Our aim was to externally validate this finding.
Methods:We performed a post hoc analysis of a prospective management outcome study for PE diagnosis in pregnant women. PE was diagnosed with an algorithm that combined the revised Geneva score, D-dimer testing, bilateral lower-limb compression ultrasonography, and CTPA. All women had a 3-month follow-up. All of the items necessary to use the YEARS algorithm were prospectively collected at the time of the study.
Results:Of the 395 women included in the original study, 371 were available for the present analysis. The PE prevalence was 6.5%. Ninety-one women had no YEARS items, and 280 had one or more items. When the YEARS items were combined with D-dimer levels (<1000 ng/mL in women with no items, and <500 ng/mL in women with one or more items), 77 women (21%) met the criteria for PE exclusion and would
Membrane proteins are present in both cardiac T-tubule (TTM) and outer surface membrane (OSM), although at a different density. Classical pharmacology does not allow to explore the function of a membrane protein separately in OSM vs. TTM. Here, we developed a technology based on size exclusion to explore the function of β-adrenergic receptors (β-ARs) located in the OSM. We synthetized a PEG-Iso molecule by covalent linking between isoprenaline (Iso) and a 5000 Da PolyEthylene-Glycol (PEG). Using confocal microscopy, we show that PEGylation constrains molecules outside the T-tubule network. PEG-Iso produced similar effects as Iso on ICa,L, sarcomere shortening and Ca2+ transients. However, PEG-Iso increased [cAMP]i with a lower efficacy than Iso, produced a much lower stimulation of nuclear PKA activity than Iso but a larger stimulation of cytosolic PKA at equivalent levels of [cAMP]i. Our results show that activation of OSM β-ARs is sufficient to activate cytosolic PKA and excitation-contraction coupling, but insufficient to activate nuclear PKA or nuclear protein phosphorylation for which additional activation of TTM β-ARs is needed.
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