Prehospital tracheal intubation is a potentially lifesaving intervention, but is associated with prolonged time on-scene. Some services strongly advocate performing the procedure outside of the ...ambulance or aircraft, while others also perform the procedure inside the vehicle. This study was designed as a non-inferiority trial registering the rate of successful tracheal intubation and incidence of complications performed by a critical care team either inside or outside an ambulance or helicopter.
This observational multicentre study was performed between March 2020 and September 2021 and involved 12 anaesthetist-staffed critical care teams providing emergency medical services by helicopter in Denmark, Norway, and Sweden. The primary outcome was first-pass successful tracheal intubations.
Of the 422 drug-assisted tracheal intubations examined, 240 (57%) took place in the cabin of the ambulance or helicopter. The rate of first-pass success was 89.2% for intubations in-cabin vs 86.3% outside. This difference of 2.9% (confidence interval −2.4% to 8.2%) (two sided 10%, including 0, but not the non-inferiority limit Δ=−4.5) fulfils our criteria for non-inferiority, but not significant superiority. These results withstand after performing a propensity score analysis. The mean on-scene time associated with the helicopter in-cabin procedures (27 min) was significantly shorter than for outside the cabin (32 min, P=0.004).
Both in-cabin and outside the cabin, prehospital tracheal intubation by anaesthetists was performed with a high success rate. The mean on-scene time was shorter in the in-cabin helicopter cohort.
NCT04206566.
The use of industry as a criterion for selecting peers for multiples-based valuation rests on the notion that companies operating in the same industry are more likely to share fundamental value ...drivers (i.e., profitability, growth, and risk). However, such companies may not have similar characteristics in terms of these drivers and thus should not be traded at the same multiple. We analyze this issue by developing the sum of absolute rank differences (SARD) approach. The SARD approach can account for an infinite number of proxies for profitability, growth, and risk while remaining independent of industry classifications. Our results indicate that the SARD approach yields significantly more accurate valuation estimates than the industry classification approach.
Summary
Excessive bleeding represents a major complication of surgical interventions and its control is especially relevant in patients with Congenital Bleeding Disorders (CBD). In factor VII (FVII) ...deficiency, scanty data on surgery is available to guide treatment strategies. The STER (Seven Treatment Evaluation Registry) is a multi‐centre, prospective, observational, web‐based study protocol providing the frame for a structured and detailed data collection. Inhibitor occurrence was checked in a centralized fashion. Forty‐one surgical operations (24 ‘major’ and 17 ‘minor’) were performed in 34 subjects with a carefully characterized FVII deficiency under the coverage of recombinant activated Factor VII (rFVIIa). Bleeding occurred during three major interventions of orthopaedic surgery, but rFVIIa was given at very low dose in each case. An antibody to FVII was observed in one patient who underwent a multiple dental extraction. No thromboses were reported during the 30‐d follow up period. Replacement therapy with rFVIIa proved effective when suitable doses were used, which, during the period of maximum bleeding risk (the day of operation), were calculated (Receiver Operated Characteristic analysis) to be of at least 13 μg/kg/body weight per single dose and no less than three administrations. This indication is important especially in the case of major surgery.
Phosphatidic acid is the intermediate, from which all glycerophospholipids are synthesized. In yeast, it is generated from lysophosphatidic acid, which is acylated by Slc1p, an sn-2-specific, ...acyl-coenzyme A-dependent 1-acylglycerol-3-phosphate O-acyltransferase. Deletion of SLC1 is not lethal and does not eliminate all microsomal 1-acylglycerol-3-phosphate O-acyltransferase activity, suggesting that an additional enzyme may exist. Here we show that SLC4 (Yor175c), a gene of hitherto unknown function, encodes a second 1-acyl-sn-glycerol-3-phosphate acyltransferase. SLC4 harbors a membrane-bound O-acyltransferase motif and down-regulation of SLC4 strongly reduces 1-acyl-sn-glycerol-3-phosphate acyltransferase activity in microsomes from slc1Δ cells. The simultaneous deletion of SLC1 and SLC4 is lethal. Mass spectrometric analysis of lipids from slc1Δ and slc4Δ cells demonstrates that in vivo Slc1p and Slc4p generate almost the same glycerophospholipid profile. Microsomes from slc1Δ and slc4Δ cells incubated with 14Coleoyl-coenzyme A in the absence of lysophosphatidic acid and without CTP still incorporate the label into glycerophospholipids, indicating that Slc1p and Slc4p can also use endogenous lysoglycerophospholipids as substrates. However, the lipid profiles generated by microsomes from slc1Δ and slc4Δ cells are different, and this suggests that Slc1p and Slc4p have a different substrate specificity or have access to different lyso-glycerophospholipid substrates because of a different subcellular location. Indeed, affinity-purified Slc1p displays Mg2+-dependent acyltransferase activity not only toward lysophosphatidic acid but also lyso forms of phosphatidylserine and phosphatidylinositol. Thus, Slc1p and Slc4p may not only be active as 1-acylglycerol-3-phosphate O-acyltransferases but also be involved in fatty acid exchange at the sn-2-position of mature glycerophospholipids.
The acyl-CoA-binding proteins (ACBP) act by regulating the availability of acyl-CoA in the cytoplasm and must have essential functions in lipid metabolism. The genome of the kissing-bug Rhodnius ...prolixus encodes five proteins of this family, but little is known about them. In this study we investigated the expression and function of RpACBP-5. Feeding induced RpACBP-5 gene expression in the posterior midgut, and an increase of about four times was observed two days after the blood meal. However, the amount of protein, which was only detected in this organ, did not change during digestion. The RpACBP-5 gene was also highly expressed in pre-vitellogenic and vitellogenic oocytes. Recombinant RpACBP-5 was shown to bind to acyl-CoA of different lengths, and it exhibited nanomolar affinity to lauroyl-CoA in an isothermal titration assay, indicating that RpACBP-5 is a functional ACBP. RpACBP-5 knockdown by RNA interference did not affect digestion, egg laying and hatching, survival, or accumulation of triacylglycerol in the fat body and oocytes. Similarly, double knockdown of RpACBP-1 and RpACBP-5 did not alter egg laying and hatching, survival, accumulation of triacylglycerol in the fat body and oocytes, or the neutral lipid composition of the posterior midgut or hemolymph. These results show that RpACBP-5 is a functional ACBP but indicate that the lack of a detectable phenotype in the knockdown insects may be a consequence of functional overlap of the proteins of the ACBP family found in the insect.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study examines whether eschewing industry classifications and instead finding peers with similar fundamental value drivers is a more accurate way of assessing value. It also investigates whether ...creating peer groups with similar fundamental drivers and similar industry classifications could produce even greater value.
All mature Saccharomyces cerevisiae sphingolipids comprise inositolphosphorylceramides containing C26:0 or C24:0 fatty acids and either phytosphingosine or dihydrosphingosine. Here we analysed the ...lipid profile of lag1Δlac1Δ mutants lacking acyl-CoA-dependent ceramide synthesis, which require the reverse ceramidase activity of overexpressed Ydc1p for sphingolipid biosynthesis and viability. These cells, termed 2Δ.YDC1, make sphingolipids containing exclusively dihydrosphingosine and an abnormally wide spectrum of fatty acids with between 18 and 26 carbon atoms. Like wild-type cells, 2Δ.YDC1 cells stop growing when exposed to Aureobasidin A (AbA), an inhibitor of the inositolphosphorylceramide synthase AUR1, yet their ceramide levels remain very low. This finding argues against a current hypothesis saying that yeast cells do not require inositolphosphorylceramides and die in the presence of AbA only because ceramides build up to toxic concentrations. Moreover, W303lag1Δlac1Δypc1Δydc1Δ cells, reported to be AbA resistant, stop growing on AbA after a certain number of cell divisions, most likely because AbA blocks the biosynthesis of anomalous inositolphosphorylsphingosides. Thus, data argue that inositolphosphorylceramides of yeast, the equivalent of mammalian sphingomyelins, are essential for growth. Data also clearly confirm that wild-type strains, when exposed to AbA, immediately stop growing because of ceramide intoxication, long before inositolphosphorylceramide levels become subcritical.
Acyl-CoA-binding protein (ACBP) is a 10 kDa protein that binds C12-C22 acyl-CoA esters with high affinity. In vitro and in vivo experiments suggest that it is involved in multiple cellular tasks ...including modulation of fatty acid biosynthesis, enzyme regulation, regulation of the intracellular acyl-CoA pool size, donation of acyl-CoA esters for beta-oxidation, vesicular trafficking, complex lipid synthesis and gene regulation. In the present study, we delineate the evolutionary history of ACBP to get a complete picture of its evolution and distribution among species. ACBP homologues were identified in all four eukaryotic kingdoms, Animalia, Plantae, Fungi and Protista, and eleven eubacterial species. ACBP homologues were not detected in any other known bacterial species, or in archaea. Nearly all of the ACBP-containing bacteria are pathogenic to plants or animals, suggesting that an ACBP gene could have been acquired from a eukaryotic host by horizontal gene transfer. Many bacterial, fungal and higher eukaryotic species only harbour a single ACBP homologue. However, a number of species, ranging from protozoa to vertebrates, have evolved two to six lineage-specific paralogues through gene duplication and/or retrotransposition events. The ACBP protein is highly conserved across phylums, and the majority of ACBP genes are subjected to strong purifying selection. Experimental evidence indicates that the function of ACBP has been conserved from yeast to humans and that the multiple lineage-specific paralogues have evolved altered functions. The appearance of ACBP very early on in evolution points towards a fundamental role of ACBP in acyl-CoA metabolism, including ceramide synthesis and in signalling.
Besides serving as essential substrates for β-oxidation and synthesis of triacylglycerols and more complex lipids like sphingolipids and sterol esters, long-chain fatty acyl-CoA esters are ...increasingly being recognized as important regulators of enzyme activities and gene transcription. Acyl-CoA binding protein, ACBP, has been proposed to play a pivotal role in the intracellular trafficking and utilization of long-chain fatty acyl-CoA esters. Depletion of acyl-CoA binding protein in yeast results in aberrant organelle morphology incl. fragmented vacuoles, multi-layered plasma membranes and accumulation of vesicles of variable sizes. In contrast to synthesis and turn-over of glycerolipids, the levels of very-long-chain fatty acids, long-chain bases and ceramide are severely affected by Acb1p depletion, suggesting that Acb1p, rather than playing a general role, serves specific roles in cellular lipid metabolism.
Detailed analysis of lipid species can be challenging due to their structural diversity and wide concentration range in cells, tissues, and biofluids. To address these analytical challenges, we ...devised a reproducible, sensitive, and integrated lipidomics workflow based on normal-phase liquid chromatography–Fourier transform mass spectrometry (LC–FTMS) and LC–ITMS2 (ion trap tandem mass spectrometry) for profiling and structural analysis of lipid species. The workflow uses a normal-phase LC system for efficient separation of apolar and polar lipid species combined with sensitive and specific analysis powered by a chip-based nanoelectrospray ion source and a hybrid ion trap–orbitrap mass spectrometer. The workflow was executed using a primary LC–FTMS survey routine for identification and profiling of lipid species based on high-mass accuracy and retention time followed by a targeted LC–ITMS2 routine for characterizing the fatty acid moieties of identified lipid species. We benchmarked the performance of the workflow by characterizing the chromatographic properties of the LC–MS system for general lipid analysis. In addition, we demonstrate the efficacy of the workflow by reporting a study of low-abundant triacylglycerol and ceramide species in mouse brain cerebellum and 3T3-L1 adipocytes, respectively. The workflow described here is generic and can be extended for detailed lipid analysis of sample matrices having a wide range of lipid compositions.
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