Mathematical models of coagulation-are we there yet?

Background: Mathematical models of coagulation have been developed to mirror thrombin generation in plasma, with the aim of investigating how variation in coagulation factor levels regulates hemostasis. However, current models vary in the reactions they capture and the reaction rates used, and their validation is restricted by a lack of large coherent datasets, resulting in questioning of their utility.

Objectives: To address this debate, we systematically assessed current models against a large dataset, using plasma coagulation factor levels from 348 individuals with normal hemostasis to identify the causes of these variations.

Outcomes of an integrated practice unit for vulnerable emergency department patients.

Background: An integrated practice unit (IPU) that provides a multidisciplinary approach to patient care, typically involving a primary care provider, registered nurse, social worker, and pharmacist has been shown to reduce healthcare utilization among high-cost super-utilizer (SU) patients or multi-visit patients (MVP). However, less is known about differences in the impact of these interventions on insured vs. uninsured SU patients and super high frequency SUs ([Formula: see text]8 ED visits per 6 months) vs.

Managing hypertension in a Rohingya refugee camp: a brief report.

Non-communicable diseases have overtaken communicable diseases as the most common cause of death worldwide, with the majority of these deaths in low-income and middle-income countries. Hypertension alone causes over nine million deaths per year.Since 2017, around 750 000 Rohingya refugees have fled violence in Myanmar into Cox's Bazar District in Bangladesh.

Plasma Myeloperoxidase as a Potential Biomarker of Patient Response to Anti-Dementia Treatment in Alzheimer's Disease.

Background: Myeloperoxidase (MPO), a neutrophil-derived pro-inflammatory protein, co-localizes with amyloid-β (Aβ) plaques in Alzheimer's disease (AD). Anti-dementia treatment may facilitate efflux of Aβ and associated plaque proteins from the brain to the peripheral circulation, therefore providing potential biomarkers for the monitoring of donor response to drug treatment.

Objective: We investigated the diagnostic utility of MPO as a biomarker of AD, and how anti-dementia treatment alters plasma MPO concentration.

A System-Wide Investigation and Stratification of the Hemostatic Proteome in Premature Myocardial Infarction.

Introduction: Advancing understanding of key factors that determine the magnitude of the hemostatic response may facilitate the identification of individuals at risk of generating an occlusive thrombus as a result of an atherothrombotic event such as an acute Myocardial Infarction (MI). While fibrinogen levels are a recognized risk factor for MI, the association of thrombotic risk with other coagulation proteins is inconsistent. This is likely due to the complex balance of pro- and anticoagulant factors in any individual.

The voltage-gated K channel Kv1.3 modulates platelet motility and αβ integrin-dependent adhesion to collagen.

Kv1.3 is a voltage-gated K-selective channel with roles in immunity, insulin-sensitivity, neuronal excitability and olfaction. Despite being one of the largest ionic conductances of the platelet surface membrane, its contribution to platelet function is poorly understood.

Why do platelets express K channels?

Potassium ions have widespread roles in cellular homeostasis and activation as a consequence of their large outward concentration gradient across the surface membrane and ability to rapidly move through K-selective ion channels. In platelets, the predominant K channels include the voltage-gated K channel Kv1.3, and the intermediate conductance Ca-activated K channel KCa3.

The TICONC (Ticagrelor-Oncology) Study: Implications of P2Y Inhibition for Metastasis and Cancer-Associated Thrombosis.

Background: In cancer, platelets may facilitate metastatic spread by a number of mechanisms as well as contribute to thrombotic complications. Ticagrelor, a platelet antagonist- that blocks adenosine diphosphate activation of platelet P2Y receptors, is widely used in the treatment of cardiovascular disease, but its efficacy in cancer remains unknown.

Objectives: This study sought to evaluate the effect of aspirin and ticagrelor monotherapy, as well as dual antiplatelet therapy, on platelet activation in cancer.

Evidence for shear-mediated Ca entry through mechanosensitive cation channels in human platelets and a megakaryocytic cell line.

The role of mechanosensitive (MS) Ca-permeable ion channels in platelets is unclear, despite the importance of shear stress in platelet function and life-threatening thrombus formation. We therefore sought to investigate the expression and functional relevance of MS channels in human platelets. The effect of shear stress on Ca entry in human platelets and Meg-01 megakaryocytic cells loaded with Fluo-3 was examined by confocal microscopy.

Transcriptomic analysis of the ion channelome of human platelets and megakaryocytic cell lines.

Ion channels have crucial roles in all cell types and represent important therapeutic targets. Approximately 20 ion channels have been reported in human platelets; however, no systematic study has been undertaken to define the platelet channelome. These membrane proteins need only be expressed at low copy number to influence function and may not be detected using proteomic or transcriptomic microarray approaches.

Regulation of Pannexin-1 channel activity.

Pannexin-1 (Panx1) forms anion-selective channels with a permeability up to 1 kDa and represents a pathway for the release of cytosolic ATP. Several structurally similar connexin (Cx) proteins have been identified in platelets and shown to play roles in haemostasis and thrombosis. More recently, functional Panx1 channels have been demonstrated on the surface of human platelets [Taylor et al.

Gap junctions and connexin hemichannels underpin hemostasis and thrombosis.

Background: Connexins are a widespread family of membrane proteins that assemble into hexameric hemichannels, also known as connexons. Connexons regulate membrane permeability in individual cells or couple between adjacent cells to form gap junctions and thereby provide a pathway for regulated intercellular communication. We have examined the role of connexins in platelets, blood cells that circulate in isolation but on tissue injury adhere to each other and the vessel wall to prevent blood loss and to facilitate wound repair.

Piscine UDP-glucuronosyltransferase 1B.

Glucuronidation is an important detoxification pathway for organic pollutants in fish. We report here the isolation and characterisation of UDP-glucuronosyltransferases (UGT) genes from the closely related marine flatfish, plaice (Pleuronectes platessa) and flounder (Platichthys flesus). The deduced amino acid sequences share greater similarity with mammalian UGT1 family genes than UGT2 genes (44-47% and 39-40% amino acid identity, respectively) and have been designated UGT1B.