Factors related to mean corpuscular volume in p.C282Y homozygotes.

Introduction: The aim of this study was to define the relationships between factors other than transferrin saturation (TS) to mean corpuscular volume (MCV) and macrocytosis (MCV > 100 fL) in p.C282Y (rs1800562) homozygotes.

Methods: We studied white post-screening participants with p.

Hypertension Severity as Quantified by Hypertension Daily Dose and Blood Pressure With Risk of Stroke in REGARDS.

Background: It is unknown how blood pressure (BP) relates to stroke risk across levels of hypertension daily dose (HDD)-quantified antihypertensive medication intensity.

Methods And Results: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study enrolled 30 239 participants from the 48 contiguous US states in 2003 to 2007 with in-person follow-up in 2013 to 2016 (Visit 2). We included those without prior stroke at Visit 2, treating this visit as T.

Incidence and Risk Factors for New and Recurrent Infarcts in Adults With Sickle Cell Disease.

Background: Most adults with sickle cell disease will experience a silent cerebral infarction (SCI) or overt stroke. Identifying patient subgroups with increased stroke incidence is important for future clinical trials focused on stroke prevention. Our 3-center prospective cohort study tested the primary hypothesis that adults with sickle cell disease and SCIs have a greater incidence of new stroke or SCI compared with those without SCI.

Social Determinants of Health and Incident Apparent Treatment-Resistant Hypertension Among White and Black US Adults: The REGARDS Study.

Background: We examined the association of multilevel social determinants of health with incident apparent treatment-resistant hypertension (aTRH).

Methods And Results: We analyzed data from 2774 White and 2257 Black US adults from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study taking antihypertensive medication without aTRH at baseline to estimate the association of social determinants of health with incident aTRH. Selection of social determinants of health was guided by the Healthy People 2030 domains of education, economic stability, social context, neighborhood environment, and health care access.

Using the consolidated framework for implementation research (CFIR) to guide implementation of cardio-oncology services.

Introduction: Cardio-oncology focuses on diagnosing and preventing adverse cardiovascular outcomes in cancer patients. Interdisciplinary cardio-oncology services address the spectrum of prevention, detection, monitoring, and treatment of cancer patients at risk of cardio-toxicity and aim to improve the continuum of cardiac care for oncology patients. The goal of this study was to engage clinician and administrative stakeholders to assess multilevel needs, barriers, and expectations regarding cardio oncology services.

Sustained Increases in Cardiomyocyte Protein -Linked β-N-Acetylglucosamine Levels Lead to Cardiac Hypertrophy and Reduced Mitochondrial Function Without Systolic Contractile Impairment.

Background Lifestyle and metabolic diseases influence the severity and pathogenesis of cardiovascular disease through numerous mechanisms, including regulation via posttranslational modifications. A specific posttranslational modification, the addition of -linked β- acetylglucosamine (-GlcNAcylation), has been implicated in molecular mechanisms of both physiological and pathologic adaptations. The current study aimed to test the hypothesis that in cardiomyocytes, sustained protein -GlcNAcylation contributes to cardiac adaptations, and its progression to pathophysiology.

A phase 1 first-in-human study of GS-0189, an anti-signal regulatory protein alpha (SIRPα) monoclonal antibody, in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL).

Signal regulatory protein alpha (SIRPα) is the receptor for cluster of differentiation (CD)47, a potent "don't eat me" signal for macrophages. Disruption of CD47-SIRPα signaling in the presence of prophagocytic signals can lead to enhanced phagocytosis of tumor cells, resulting in a direct antitumor effect; agents targeting this pathway have shown efficacy in non-Hodgkin lymphoma (NHL) and other tumor types. GS-0189 is a novel anti-SIRPα humanized monoclonal antibody.

Risk of Postdischarge Bleeding From Dual Antiplatelet Therapy After Percutaneous Coronary Intervention Among US Black and White Adults.

Background Dual antiplatelet therapy after percutaneous coronary intervention reduces myocardial infarctions but increases bleeding. The risk of bleeding may be higher among Black patients for unknown reasons. Bleeding risk scores have not been validated among Black patients.

Development and implementation of an electronic Clinical Dementia Rating and Financial Capacity Instrument-Short Form.

Introduction: To address the need for remote assessments of cognitive decline and dementia, we developed and administered electronic versions of the Clinical Dementia Rating (CDR®) and the Financial Capacity Instrument-Short Form (FCI-SF) (F-CAP), called the eCDR and eFCI, respectively.

Methods: The CDR and FCI-SF were adapted for remote, unsupervised, online use based on item response analysis of the standard instruments. Participants completed the eCDR and eFCI first in clinic, and then at home within 2 weeks.

Cytokines and Production of Aberrantly -Glycosylated IgA1, the Main Autoantigen in IgA Nephropathy.

Immunoglobulin A (IgA) nephropathy is the most common primary glomerulonephritis worldwide, with no disease-specific treatment and up to 40% of patients progressing to kidney failure. IgA nephropathy (IgAN), characterized by IgA1-containing immunodeposits in the glomeruli, is considered to be an autoimmune disease in which the kidneys are injured as innocent bystanders. Glomerular immunodeposits are thought to originate from the circulating immune complexes that contain aberrantly -glycosylated IgA1, the main autoantigen in IgAN, bound by IgG autoantibodies.

Lipoprotein(a) and the Risk for Coronary Heart Disease and Ischemic Stroke Events Among Black and White Adults With Cardiovascular Disease.

Background It is unclear whether lipoprotein(a) is associated with coronary heart disease (CHD) and ischemic stroke events in White and Black adults with atherosclerotic cardiovascular disease (ASCVD). Methods and Results We conducted a case-cohort analysis, including Black and White REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants ≥45 years of age with prevalent ASCVD (ie, CHD or stroke) at baseline between 2003 and 2007. Baseline lipoprotein(a) molar concentration was measured in participants with ASCVD who experienced a CHD event by December 2017 (n=1166) or an ischemic stroke by September 2019 (n=492) and in a random subcohort of participants with prevalent ASCVD (n=1948).

Verbal fluency response times predict incident cognitive impairment.

Introduction: In recent decades, researchers have defined novel methods for scoring verbal fluency tasks. In this work, we evaluate novel scores based on speed of word responses.

Methods: We transcribed verbal fluency recordings from 641 cases of incident cognitive impairment (ICI) and matched controls, all participants in a large national epidemiological study.

Age-Dependent Relationship of Hypertension Subtypes With Incident Heart Failure.

Background The prevalence of hypertension subtypes changes with age. However, little is known regarding the age-dependent association of hypertension subtypes with incident heart failure (HF). Methods and Results We conducted an observational cohort study including 2 612 570 people (mean age, 44.

Proportional constrained longitudinal data analysis models for clinical trials in sporadic Alzheimer's disease.

Introduction: Clinical trials for sporadic Alzheimer's disease generally use mixed models for repeated measures (MMRM) or, to a lesser degree, constrained longitudinal data analysis models (cLDA) as the analysis model with time since baseline as a categorical variable. Inferences using MMRM/cLDA focus on the between-group contrast at the pre-determined, end-of-study assessments, thus are less efficient (eg, less power).

Methods: The proportional cLDA (PcLDA) and proportional MMRM (pMMRM) with time as a categorical variable are proposed to use all the post-baseline data without the linearity assumption on disease progression.

Acclimation to a High-Salt Diet Is Sex Dependent.

Background Premenopausal women are less likely to develop hypertension and salt-related complications than are men, yet the impact of sex on mechanisms regulating Na homeostasis during dietary salt challenges is poorly defined. Here, we determined whether female rats have a more efficient capacity to acclimate to increased dietary salt intake challenge. Methods and Results Age-matched male and female Sprague Dawley rats maintained on a normal-salt (NS) diet (0.

Whole-blood cytokine secretion assay as a high-throughput alternative for assessing the cell-mediated immunity profile after two doses of an adjuvanted SARS-CoV-2 recombinant protein vaccine candidate.

Objectives: We previously described the Phase I-II evaluation of SARS-CoV-2 recombinant protein candidate vaccine, CoV2-PreS-dTM, with AF03- or AS03-adjuvant systems (ClinicalTrials.gov, NCT04537208). Here, we further characterise the cellular immunogenicity profile of this vaccine candidate using a whole-blood secretion assay in parallel to intracellular cytokine staining (ICS) of cryopreserved peripheral blood mononuclear cells (PBMCs).