Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n [ 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the

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Long-chain acylcarnitines accumulate during myocardial ischemia and contribute to membrane dysfunction in ischemic zones. On the basis of the 3-fold selectivity for saturated fatty acid accumulation during myocardial ischemia, it was implicitly assumed that saturated long chain acylcarnitine molecular species predominantly accumulated in ischemic myocardium. By exploiting the analytical power of electrospray ionization mass spectroscopy, we now report that unsaturated acylcarnitines are the predominant molecular species of acylcarnitine which accumulate during myocardial ischemia (rank order: octadecadienoyl carnitine > octadecanoyl carnitine > hexadecanoyl carnitine > octadecanoyl carnitine). The aliphatic chain distribution of myocardial acylcarnitine molecular species identified by electrospray ionization mass spectroscopy was independently substantiated by sequential HPLC purification and capillary gas chromatography. Detailed analysis of the individual molecular species of long-chain acylcarnitine demonstrated that fatty acyl chain elongation was prominent in ischemic myocardium (e.g., following 20 min of ischemia, greater than 15% of the accumulated acylcarnitines consisted of 20-carbon unsaturated molecular species). Chain-elongated lipids were essentially confined to the long chain acylcarnitine pool since [9,10-3H]octadec-9'-enoic acid was converted to [3H]eicosenoyl carnitine (12% of the radiolabeled acylcarnitine pool) in ischemic hearts without substantive amounts of [3H]eicosenoyl residues in the fatty acid, triglyceride, and phospholipid pools. Collectively, these results demonstrate the preponderance of unsaturated acylcarnitines in ischemic myocardium and document the metabolic compartmentation of downstream products of fatty acyl chain elongation in the acylcarnitine pool during ischemia.

Protein kinase C (PKC) translocation to specific subcellular membrane loci after cellular stimulation is mediated, in part, through its interaction with diacylglycerol, phosphatidylserine, and calcium. Herein, we present multiple lines of evidence which demonstrate that purified rabbit brain PKC undergoes specific acylation with palmitoyl CoA that facilitates its interaction with membrane bilayers. First, incubation of purified rabbit brain PKC with [14C]palmitoyl CoA (5 microM) resulted in the radiolabeling of an 80 kDa band demonstrated by SDS-PAGE and autoradiography, while incubation of PKC with other acyl CoA molecular species (e.g., [3H]myristoyl CoA or [14C]arachidonoyl CoA), fatty acids (e.g., [14C]palmitic and [14C]arachidonic acid), or [14C]diacylglycerol did not result in the incorporation of radiolabel. Second, multiple extractions of [14C]palmitoyl CoA-treated PKC with butanol did not remove the radiolabeled moiety from the 80 kDa PKC band. Third, incubation of the [14C]palmitoyl CoA-radiolabeled PKC moiety with neutral hydroxylamine, hydrochloric acid, or sodium hydroxide released incorporated radiolabel which identified the association between PKC and palmitic acid as a covalent thioester linkage. Fourth, formation of the [14C]palmitoyl CoA-radiolabeled PKC adduct could be prevented by pretreatment of PKC with either dithiobis(nitrobenzoic acid) or N-ethylmaleimide. Fifth, limited trypsinolysis of palmitoylated PKC demonstrated that palmitic acid was exclusively present in the regulatory fragment of PKC without detectable amounts of palmitic acid associated with the catalytic fragment. Sixth, palmitoylated PKC was resolved from its nonpalmitoylated counterpart by Mono Q chromatography, and palmitoylated PKC preferentially associated with cellular membranes while nonpalmitoylated PKC did not. Both palmitoylated and nonpalmitoylated PKC were activated by phosphatidylserine, diacylglycerol, and calcium ion. Collectively, these results demonstrate the acylation of PKC by palmitoyl CoA and identify a novel mechanism which may facilitate the interaction of PKC with biologic membranes.