Mitofusin-2 Regulates Platelet Mitochondria and Function.

Background: Single-nucleotide polymorphisms linked with the rs1474868 T allele ( [mitofusin-2] T/T) in the human mitochondrial fusion protein gene are associated with reduced platelet RNA expression and platelet counts. This study investigates the impact of MFN2 on megakaryocyte and platelet biology.

Methods: Mice with megakaryocyte/platelet deletion of ( [ conditional knockout]) were generated using Pf4-Cre crossed with floxed mice.

Characterization of all small RNAs in and comparisons across cultured megakaryocytes and platelets of healthy individuals and COVID-19 patients.

Background: The small noncoding RNAs (sncRNAs) in megakaryocytes (MKs) and platelets are not well characterized. Neither is the impact of SARS-CoV-2 infection on the sncRNAs of platelets.

Objectives: To investigate the sorting of MK sncRNAs into platelets, and the differences in the platelet sncRNAomes of healthy donors (HDs) and COVID-19 patients.

The predominant PAR4 variant in individuals of African ancestry worsens murine and human stroke outcomes.

Protease-activated receptor 4 (PAR4) (gene F2RL3) harbors a functional dimorphism, rs773902 A/G (encoding Thr120/Ala120, respectively) and is associated with greater platelet aggregation. The A allele frequency is more common in Black individuals, and Black individuals have a higher incidence of ischemic stroke than White individuals. However, it is not known whether the A allele is responsible for worse stroke outcomes.

MAPK-interacting kinase 1 regulates platelet production, activation, and thrombosis.

The MAPK-interacting kinase (Mnk) family includes Mnk1 and Mnk2, which are phosphorylated and activated in response to extracellular stimuli. Mnk1 contributes to cellular responses by regulating messenger RNA (mRNA) translation, and mRNA translation influences platelet production and function. However, the role of Mnk1 in megakaryocytes and platelets has not previously been studied.

Neutrophil cathepsin G proteolysis of protease-activated receptor 4 generates a novel, functional tethered ligand.

Platelet-neutrophil interactions regulate ischemic vascular injury. Platelets are activated by serine proteases that cleave protease-activated receptor (PAR) amino termini, resulting in an activating tethered ligand. Neutrophils release cathepsin G (CatG) at sites of injury and inflammation, which activates PAR4 but not PAR1, although the molecular mechanism of CatG-induced PAR4 activation is unknown.

Megakaryocyte-specific knockout of the Mir-99b/let7e/125a cluster lowers platelet count without altering platelet function.

The purpose of this research was to assess the effects of a microRNA (miRNA) cluster on platelet production. Human chromosome 19q13.41 harbors an evolutionarily conserved cluster of three miRNA genes (MIR99B, MIRLET7E, MIR125A) within 727 base-pairs.

Acquired von Willebrand syndrome in monoclonal gammopathy - A scoping review on hemostatic management.

Background: Acquired von Willebrand syndrome (AVWS) has been associated with monoclonal gammopathy of undetermined significance (MGUS), with limited data on its management.

Methods: We conducted a systematic literature search in Medline (Ovid), Embase, and Scopus up to September 11, 2019, for studies reporting on the management of AVWS associated with MGUS (AVWS-MGUS). Data on patient characteristics, laboratory parameters at presentation, and clinical and laboratory outcomes were extracted.

Specifications of the variant curation guidelines for ITGA2B/ITGB3: ClinGen Platelet Disorder Variant Curation Panel.

Accurate and consistent sequence variant interpretation is critical to the correct diagnosis and appropriate clinical management and counseling of patients with inherited genetic disorders. To minimize discrepancies in variant curation and classification among different clinical laboratories, the American College of Medical Genetics and Genomics (ACMG), along with the Association for Molecular Pathology (AMP), published standards and guidelines for the interpretation of sequence variants in 2015. Because the rules are not universally applicable to different genes or disorders, the Clinical Genome Resource (ClinGen) Platelet Disorder Expert Panel (PD-EP) has been tasked to make ACMG/AMP rule specifications for inherited platelet disorders.

High prevalence of overweight/obesity in adult persons with hemophilia in Utah and a review of the literature.

: The objectives of this study were firstly to determine the prevalence of overweight/obesity in adult persons with hemophilia in Utah, and to explore the association between age, disease severity and race with body mass index (BMI), and secondly to provide recent data on the prevalence of overweight/obesity in the hemophilia population via a review of the literature. We conducted a retrospective cross section study of adult persons with hemophilia who were seen at a Utah hemophilia treatment center from 1 January 2017 to 31 December 2019. The electronic database PubMed was searched for studies with observation periods from 1 January 2012 to 31 December 2019.

Research nurses as practice facilitators to disseminate an asthma shared decision making intervention.

Background: Practice facilitation is a method of introducing and sustaining organizational change. It involves the use of skilled healthcare professionals called practice facilitators (PFs) to help address the challenges associated with implementing evidence-based guidelines and complex interventions into practice. PFs provide a framework for translating research into practice by building relationships, improving communication, fostering change, and sharing resources.

What types of dissemination of information occurred between researchers, providers and clinical staff while implementing an asthma shared decision-making intervention: a directed content analysis.

Objective: To qualitatively analyse different types of dissemination of information during monthly group calls between researchers, providers and clinical staff used to establish best practices for implementing an asthma shared decision-making (SDM) intervention. Evaluating dissemination of information can provide a better understanding of how best practices are shared, informing implementation approaches to improve the uptake of new evidence and overcome barriers.

Setting: 10 primary care practices in North Carolina.

Glanzmann thrombasthenia: genetic basis and clinical correlates.

Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet aggregation caused by quantitative or qualitative defects in integrins αIIb and β3. These integrins are encoded by the and genes and form platelet glycoprotein (GP)IIb/IIIa, which acts as the principal platelet receptor for fibrinogen. Although there is variability in the clinical phenotype, most patients present with severe mucocutaneous bleeding at an early age.

Using the Consolidated Framework for Implementation Research (CFIR) to evaluate implementation effectiveness of a facilitated approach to an asthma shared decision making intervention.

Objective: To describe the evaluation of implementation effectiveness of an asthma shared decision making (SDM) intervention at the 10 individual facilitator-led primary care practices in the ADAPT-NC Study using the Consolidated Framework for Implementation Research (CFIR).

Methods: Practices were scored across 40 CFIR constructs within 5 domains using a previously published scoring system of -2 to +2. Based on overall construct scores, practices were then classified as high, medium, or low adopters.

Sighting acute myocardial infarction through platelet gene expression.

Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event.

Longitudinal RNA-Seq Analysis of the Repeatability of Gene Expression and Splicing in Human Platelets Identifies a Platelet Splice QTL.

Rationale: Longitudinal studies are required to distinguish within versus between-individual variation and repeatability of gene expression. They are uniquely positioned to decipher genetic signal from environmental noise, with potential application to gene variant and expression studies. However, longitudinal analyses of gene expression in healthy individuals-especially with regards to alternative splicing-are lacking for most primary cell types, including platelets.

Potential Effect of Vouchers on the Completion of Self-management Education Among Patients With Diabetes.

Diabetes is a significant public health problem in eastern North Carolina, and completion of formal diabetes self-management education (DSME) is low. To seek methods to increase DSME completion, patients with diabetes in an eastern North Carolina regional health care system who had not completed DSME (n = 58) were surveyed during wellness visits to examine attitudes toward the use of vouchers (eg, coupons that purchase healthy food, exercise classes, gym memberships). There was an extremely low awareness (19%) of and referral (5%) to DSME.

Anti-apoptotic increases megakaryocyte proplatelet formation in cultures of human cord blood.

Apoptosis is a recognized limitation to generating large numbers of megakaryocytes in culture. The genes responsible have been rigorously studied in mice, but are poorly characterized in human culture systems. As CD34-positive () cells isolated from human umbilical vein cord blood were differentiated into megakaryocytes in culture, two distinct cell populations were identified by flow cytometric forward and side scatter: larger size, lower granularity (LLG), and smaller size, higher granularity (SHG).