Prairie Carnation®: a new crop for western Canada

Non-Peer ReviewedPrairie Carnation (Saponaria vaccaria L.) is a member of the family Caryophyllaceae. The crop is intended for large-scale contract production on the prairies. Several members of this plant family are grown as ornamentals. No members of the Caryopyhllaceae are used as food or feed products in Canada. Prairie Carnation® will be used as a renewable bio-product crop to produce fine starches for cosmetics and other industries. Saponins extracted from the seed will be used for veterinary and medical applications and are being tested as a vaccine adjuvant and also as an active compound for some clinical treatments. Peptides from Saponaria seeds show antibiotic effects and are tested as cosmetic active compounds. Research has been conducted to advance crop development in 2005 and 2006 at the Alberta Research Council (ARC) in Vegreville, Alberta. Trials included seeding date, seeding rate x spatial arrangement, fertility, timing of fungicide application and crop tolerance to herbicides. Preliminary results indicate that Prairie Carnation® has considerable potential to be a commercially and agronomically successful crop

What is the effect of a decision aid in potentially vulnerable parents? Insights from the head CT choice randomized trial.

ObjectiveTo test the hypotheses that use of the Head CT Choice decision aid would be similarly effective in all parent/patient dyads but parents with high (vs low) numeracy experience a greater increase in knowledge while those with low (vs high) health literacy experience a greater increase in trust.MethodsThis was a secondary analysis of a cluster randomized trial conducted at seven sites. One hundred seventy-two clinicians caring for 971 children at intermediate risk for clinically important traumatic brain injuries were randomized to shared decision making facilitated by the DA (n = 493) or to usual care (n = 478). We assessed for subgroup effects based on patient and parent characteristics, including socioeconomic status (health literacy, numeracy and income). We tested for interactions using regression models with indicators for arm assignment and study site.ResultsThe decision aid did not increase knowledge more in parents with high numeracy (P for interaction [Pint ] = 0.14) or physician trust more in parents with low health literacy (Pint  = 0.34). The decision aid decreased decisional conflict more in non-white parents (decisional conflict scale, -8.14, 95% CI: -12.33 to -3.95; Pint  = 0.05) and increased physician trust more in socioeconomically disadvantaged parents (trust in physician scale, OR: 8.59, 95% CI: 2.35-14.83; Pint  = 0.04).ConclusionsUse of the Head CT Choice decision aid resulted in less decisional conflict in non-white parents and greater physician trust in socioeconomically disadvantaged parents. Decision aids may be particularly effective in potentially vulnerable parents

Phosphatidylethanolamine N-methyltransferase (PEMT) Knockout Mice Exhibit Worse Alcohol-Induced Liver Injury than Wildtype Mice

Phosphatidylethanolamine N-methyltransferase (PEMT) is an enzyme that catalyzes the successive transfer of 3 methyl groups from S-adenosylmethionine (SAM) to phosphatidylethanolamine (PE) to generate phosphatidylcholine (PC). PC is vital for exporting fat out of the liver, ultimately preventing hepatic steatosis. Alcohol also induces steatosis partly through damaging this pathway, so the purpose of this study was to investigate the relationship between alcohol and PEMT in the liver. PEMT -/- (KO) and wild-type (WT) mice were subjected to a chronic + binge alcohol treatment, and both serum and liver samples were analyzed. Triglyceride quantification, SAM and S-adenosylhomocysteine (SAH) levels, and histological analyses were performed on liver samples, while ALT levels were determined from serum samples. Our study showed that ethanol-fed PEMT KO mice exhibited worse liver injury compared to other treatment groups. Our results show increased triglyceride levels, increased ALT levels, decreased SAM:SAH ratio, and increased liver to body weight ratio. From these findings, we conclude that additional liver damage is observed with the combination of alcohol feeding and absence of the PEMT enzyme. The mechanism by which these two factors affect one another is a key area of future study.https://digitalcommons.unmc.edu/surp2021/1016/thumbnail.jp

Isoaspartate, Carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury

We had previously shown that alcohol consumption can induce cellular isoaspartate protein damage via an impairment of the activity of protein isoaspartyl methyltransferase (PIMT), an enzyme that triggers repair of isoaspartate protein damage. To further investigate the mechanism of isoaspartate accumulation, hepatocytes cultured from control or 4-week ethanol-fed rats were incubated in vitro with tubercidin or adenosine. Both these agents, known to elevate intracellular S-adenosylhomocysteine levels, increased cellular isoaspartate damage over that recorded following ethanol consumption in vivo. Increased isoaspartate damage was attenuated by treatment with betaine. To characterize isoaspartate-damaged proteins that accumulate after ethanol administration, rat liver cytosolic proteins were methylated using exogenous PIMT and 3H-S- adenosylmethionine and proteins resolved by gel electrophoresis. Three major protein bands of ~75-80 kDa, ~95-100 kDa, and ~155-160 kDa were identified by autoradiography. Column chromatography used to enrich isoaspartate-damaged proteins indicated that damaged proteins from ethanol-fed rats were similar to those that accrued in the livers of PIMT knockout (KO) mice. Carbamoyl phosphate synthase-1 (CPS-1) was partially purified and identified as the ~160kDa protein target of PIMT in ethanol-fed rats and in PIMT KO mice. Analysis of the liver proteome of 4-week ethanol-fed rats and PIMT KO mice demonstrated elevated cytosolic CPS-1 and betaine homocysteine S-methyltransferase-1 when compared to their respective controls, and a significant reduction of carbonic anhydrase-III (CA-III) evident only in ethanol-fed rats. Ethanol feeding of rats for 8 weeks resulted in a larger (~2.3-fold) increase in CPS-1 levels compared to 4- week ethanol feeding indicating that CPS-1 accumulation correlated with the duration of ethanol consumption. Collectively, our results suggest that elevated isoaspartate and CPS-1, and reduced CA-III levels could serve as biomarkers of hepatocellular injury

Pediatric Kawasaki Disease and Adult Human Immunodeficiency Virus Kawasaki-Like Syndrome Are Likely the Same Malady.

Background. Pediatric Kawasaki disease (KD) and human immunodeficiency virus (HIV)+ adult Kawasaki-like syndrome (KLS) are dramatic vasculitides with similar physical findings. Both syndromes include unusual arterial histopathology with immunoglobulin (Ig)A+ plasma cells, and both impressively respond to pooled Ig therapy. Their distinctive presentations, histopathology, and therapeutic response suggest a common etiology. Because blood is in immediate contact with inflamed arteries, we investigated whether KD and KLS share an inflammatory signature in serum.Methods. A custom multiplex enzyme-linked immunosorbent assay (ELISA) defined the serum cytokine milieu in 2 adults with KLS during acute and convalescent phases, with asymptomatic HIV+ subjects not taking antiretroviral therapy serving as controls. We then prospectively collected serum and plasma samples from children hospitalized with KD, unrelated febrile illnesses, and noninfectious conditions, analyzing them with a custom multiplex ELISA based on the KLS data.Results. Patients with KLS and KD subjects shared an inflammatory signature including acute-phase reactants reflecting tumor necrosis factor (TNF)-α biologic activity (soluble TNF receptor I/II) and endothelial/smooth muscle chemokines Ccl1 (Th2), Ccl2 (vascular inflammation), and Cxcl11 (plasma cell recruitment). Ccl1 was specifically elevated in KD versus febrile controls, suggesting a unique relationship between Ccl1 and KD/KLS pathogenesis.Conclusions. This study defines a KD/KLS inflammatory signature mirroring a dysfunctional response likely to a common etiologic agent. The KD/KLS inflammatory signature based on elevated acute-phase reactants and specific endothelial/smooth muscle chemokines was able to identify KD subjects versus febrile controls, and it may serve as a practicable diagnostic test for KD

Effect of remote ischaemic conditioning on platelet reactivity and endogenous fibrinolysis in ST-elevation myocardial infarction- a substudy of the CONDI-2/ERIC4 PPCI randomised controlled trial

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly citedBackground: Remote ischaemic conditioning (RIC) has been shown to reduce myocardial infarct size in animal models of myocardial infarction. Platelet thrombus formation is a critical determinant of outcome in ST-segment elevation myocardial infarction (STEMI). Whether the beneficial effects of RIC are related to thrombotic parameters is unclear. Methods and Results: In a pre-specified substudy of the Effect of Remote Ischaemic Conditioning on clinical outcomes in STEMI patients undergoing Primary Percutaneous Coronary Intervention (ERIC-PPCI) trial, we assessed the effect of RIC on thrombotic status. Patients presenting with STEMI were randomised to immediate RIC consisting of an automated autoRICTM cuff on the upper arm inflated to 200mmHg for 5 minutes and deflated for 5 minutes for 4 cycles (n=53) or sham (n=47). Venous blood was tested at presentation, discharge (48 h) and 6-8 weeks, to assess platelet reactivity, coagulation and endogenous fibrinolysis using the Global Thrombosis Test and thromboelastography (TEG). Baseline thrombotic status was similar in the 2 groups. At discharge, there was some evidence that the time to in vitro thrombotic occlusion under high shear stress was longer with RIC compared to sham (454±105s vs. 403±105s; mean difference 50.1s; 95% confidence interval [CI] 93.7- 6.4, P=0.025), but this was no longer apparent at 6-8 weeks. There was no difference in clot formation or endogenous fibrinolysis between the study arms at any time-point. Conclusion: RIC may reduce platelet reactivity in the first 48h post-STEMI. Further research is needed to delineate mechanisms through which RIC may reduce platelet reactivity, and whether it may improve outcomes in patients with persistent high on-treatment platelet reactivity.Peer reviewedFinal Accepted Versio

Refining the Enrolment Process in Emergency Medicine Research

Research in the emergency setting involving patients with acute clinical conditions is needed if there are to be advances in diagnosis and treatment. But research in these areas poses ethical and practical challenges. One of these is the general inability to obtain informed consent due to the patient’s lack of mental capacity and insufficient time to contact legal representatives. Regulatory frameworks which allow this research to proceed with a consent ‘waiver’, provided patients lack mental capacity, miss important ethical subtleties. One of these is the varying nature of mental capacity among emergency medicine patients. Not only is their capacity variable and often unclear, but some patients are also likely to be able to engage with the researcher and the context to varying degrees. In this paper we describe the key elements of a novel enrolment process for emergency medicine research that refines the consent waiver and fully engages with the ethical rationale for consent and, in this context, its waiver. The process is verbal but independently documented during the ‘emergent’ stages of the research. It provides appropriate engagement with the patient, is context-sensitive and better addresses ethical subtleties. In line with regulation, full written consent for on-going participation in the research is obtained once the emergency is passed

Lipophagy and Alcohol-Induced Fatty Liver

This review describes the influence of ethanol consumption on hepatic lipophagy, a selective form of autophagy during which fat-storing organelles known as lipid droplets (LDs) are degraded in lysosomes. During classical autophagy, also known as macroautophagy, all forms of macromolecules and organelles are sequestered in autophagosomes, which, with their cargo, fuse with lysosomes, forming autolysosomes in which the cargo is degraded. It is well established that excessive drinking accelerates intrahepatic lipid biosynthesis, enhances uptake of fatty acids by the liver from the plasma and impairs hepatic secretion of lipoproteins. All the latter contribute to alcohol-induced fatty liver (steatosis). Here, our principal focus is on lipid catabolism, specifically the impact of excessive ethanol consumption on lipophagy, which significantly influences the pathogenesis alcohol-induced steatosis. We review findings, which demonstrate that chronic ethanol consumption retards lipophagy, thereby exacerbating steatosis. This is important for two reasons: (1) Unlike adipose tissue, the liver is considered a fat-burning, not a fat-storing organ. Thus, under normal conditions, lipophagy in hepatocytes actively prevents lipid droplet accumulation, thereby maintaining lipostasis; (2) Chronic alcohol consumption subverts this fat-burning function by slowing lipophagy while accelerating lipogenesis, both contributing to fatty liver. Steatosis was formerly regarded as a benign consequence of heavy drinking. It is now recognized as the first hit in the spectrum of alcohol-induced pathologies that, with continued drinking, progresses to more advanced liver disease, liver failure, and/or liver cancer. Complete lipid droplet breakdown requires that LDs be digested to release their high-energy cargo, consisting principally of cholesteryl esters and triacylglycerols (triglycerides). These subsequently undergo lipolysis, yielding free fatty acids that are oxidized in mitochondria to generate energy. Our review will describe recent findings on the role of lipophagy in LD catabolism, how continuous heavy alcohol consumption affects this process, and the putative mechanism(s) by which this occurs

Ischaemia-reperfusion injury impairs tissue plasminogen activator release in man

AIMS: Ischaemia-reperfusion (IR) injury causes endothelium-dependent vasomotor dysfunction that can be prevented by ischaemic preconditioning. The effects of IR injury and preconditioning on endothelium-dependent tissue plasminogen activator (t-PA) release, an important mediator of endogenous fibrinolysis, remain unknown. METHODS AND RESULTS: Ischaemia-reperfusion injury (limb occlusion at 200 mmHg for 20 min) was induced in 22 healthy subjects. In 12 subjects, IR injury was preceded by local or remote ischaemic preconditioning (three 5 min episodes of ipsilateral or contralateral limb occlusion, respectively) or sham in a randomized, cross-over trial. Forearm blood flow (FBF) and endothelial t-PA release were assessed using venous occlusion plethysmography and venous blood sampling during intra-arterial infusion of acetylcholine (5-20 µg/min) or substance P (2-8 pmol/min). Acetylcholine and substance P caused dose-dependent increases in FBF (P<0.05 for all). Substance P caused a dose-dependent increase in t-PA release (P<0.05 for all). Acetylcholine and substanceP-mediated vasodilatation and substanceP-mediated t-PA release were impaired following IR injury (P<0.05 for all). Neither local nor remote ischaemic preconditioning protected against the impairment of substance P-mediated vasodilatation or t-PA release. CONCLUSION: Ischaemia-reperfusion injury induced substanceP-mediated, endothelium-dependent vasomotor and fibrinolytic dysfunction in man that could not be prevented by ischaemic preconditioning. CLINICAL TRIAL REGISTRATION INFORMATION: Reference number: NCT00789243, URL: http://clinicaltrials.gov/ct2/show/NCT00789243?term=NCT00789243andrank=1