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Fidel Vila-Rodriguez,1 Donna J Lang,2 Heather Baitz,3 Kristina Gicas,3 Allen E Thorton,3 Thomas S Ehmann,1 Geoff N Smith,1 Alasdair M Barr,4 Ivan J Torres,1 Lili C Kopala,1 G William MacEwan,1 Daniel J Müller,5 James L Kennedy,5 William G Honer11Department of Psychiatry, 2Division of Neuroradiology, Department of Radiology, The University of British Columbia, Vancouver, 3Department of Psychology, Simon Fraser University, Burnaby, 4Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, BC, 5Department of Psychiatry, Centre for Mental Health and Addictions, University of Toronto, Toronto, ON, CanadaBackground: Verbal memory impairment is a core feature in schizophrenia even at early stages of the disease, but its etiopathogenesis is not fully understood. The APOE-ε4 is the main genetic risk factor for late-onset Alzheimer’s disease. Our primary goal was to ascertain whether APOE-ε4 status had a pleiotropic effect in early stages of the illness.Participants and methods: A total of 86 first-episode psychosis (FEP) outpatients and 39 healthy volunteers were recruited. Demographic and clinical data, APOE genotyping, and a neuropsychological test battery including the California Verbal Learning Test – second edition (CVLT-II) were administered and assessed at study entry and at 1-year follow-up. Data were analyzed using mixed-model repeated measures, where the dependent variable was verbal memory indexed by California Verbal Learning Test (CVLT) Trials 1–5 total recall score.Results: FEP-APOE-ε4 carriers and FEP-APOE-ε4 noncarriers had similar symptom severity, clinical outcomes, premorbid and current intelligence quotient, and exposure to antipsychotics. There was a main effect of group on CVLT 1–5 (FEP =43.30 vs control =58.25; F[1, 119.7]=42.97; P

Megan F Patterson,1 Larry Borish,2,3 Joshua L Kennedy1,4 1Department of Pediatrics, Arkansas Children's Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Department of Medicine, Carter Immunology Center, University of Virginia Health Systems, Charlottesville, VA, USA; 3Department of Microbiology, Carter Immunology Center, University of Virginia Health Systems, Charlottesville, VA, USA; 4Department of Internal Medicine, Arkansas Children's Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA Abstract: Asthma is a heterogeneous syndrome that might be better described as a constellation of phenotypes or endotypes, each with distinct cellular and molecular mechanisms, rather than as a singular disease. One of these phenotypes is eosinophilic asthma. As the development of eosinophilic inflammation is categorically dependent on the biological activity of Interleukin (IL)-5, IL-5 antagonism became an obvious target for therapy in this phenotype. Early trials of monoclonal antibodies targeting the biological activity of IL-5, including reslizumab, mepolizumab, and benralizumab, were performed on asthmatics with no concern for evidence of eosinophilia. These trials were largely unsuccessful. However, during these trials, researchers recognized the need to quantify eosinophilia in asthma subjects in order to identify those asthmatics in whom these medications would be more likely to improve symptoms and lung function. Using biomarkers, such as sputum and blood eosinophilia, recent studies of these medications have shown improvements in blood and sputum eosinophilia, forced expiratory volume in 1 second, and quality of life assessments as well as reducing occurrences of exacerbations. Moving forward, better and less invasive biomarkers of eosinophilia are necessary to ensure that the correct patients are chosen to receive these medications to receive maximal benefit. Keywords: eosinophilic asthma, reslizumab, mepolizumab, benralizumab, IL-5, eosinophils