Publications by authors named "James Hearn"

Article Synopsis
  • Patients with Waldenström macroglobulinemia (WM) experience symptoms like cytopenias, fatigue, and bleeding, often exacerbated by therapeutics like Bruton's tyrosine kinase inhibitors (BTKis).
  • A study analyzed hemostatic dysfunction in WM patients, comparing samples from untreated patients, those on BTKis, and healthy donors, using various blood tests to assess platelet function and clotting potential.
  • Results showed that WM patients had decreased platelet reticulation, slower thrombin generation, and impaired hemostatic function due to high levels of IgM, indicating serious disturbances in blood coagulation despite receiving treatment.
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Background: A myriad of risk factors and comorbidities have been determined to influence COVID-19 mortality rates; among these is pneumonia. This study considers pneumonia as a risk factor for increased mortality in patients admitted with COVID-19 in a rural healthcare system. We predicted that the presence of pneumonia of any kind would increase mortality rates in patients admitted with COVID-19.

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Article Synopsis
  • LCP1 is a gene that encodes L-plastin, an actin-bundling protein important for immune cells, and its deficiency can lead to various blood and immune issues in mice and fish.
  • This study investigated a specific genetic variant of LCP1 found in humans that was linked to an inherited immune deficiency, using genetic and cellular analysis on affected family members as well as engineered mouse and cell models.
  • Results showed that the identified genetic mutation causes significant blood cell reductions and functional defects, highlighting a unique immune disorder marked by issues in neutrophils, lymphocytes, and platelets due to partial LCP1 deficiency.
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Platelet adhesion and activation is fundamental to the formation of a hemostatic response to limit loss of blood and instigate wound repair to seal a site of vascular injury. The process of platelet aggregate formation is supported by the coagulation system driving injury-proximal formation of thrombin, which converts fibrinogen to insoluble fibrin. This highly coordinated series of molecular and membranous events must be routinely achieved in flowing blood, at vascular fluid shear rates that place significant strain on molecular and cellular interactions.

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Peripheral circadian clocks control cell proliferation and survival, but little is known about their role and regulation in megakaryocytic cells. N-methyl-D-aspartate receptor (NMDAR) regulates the central clock in the brain. The purpose of this study was to determine whether NMDAR regulates the megakaryocytic cell clock and whether the megakaryocytic clock regulates cell proliferation and cell death.

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The process of proplatelet formation (PPF) requires coordinated interaction between megakaryocytes (MKs) and the extracellular matrix (ECM), followed by a dynamic reorganization of the actin and microtubule cytoskeleton. Localized fluxes of intracellular calcium ions (Ca2+) facilitate MK-ECM interaction and PPF. Glutamate-gated N-methyl-D-aspartate receptor (NMDAR) is highly permeable to Ca2+.

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Objectives: Mesenchymal stem/stromal cells (MSCs) are a well-established cell source for cartilage engineering, but challenges remain as differentiation often results in chondrocyte hypertrophy. Chondrogenic potential also varies with MSC source and donor age. We assessed the chondrogenic potential of first-trimester and term placental MSCs and compared their response to commonly used bone marrow MSCs (BM-MSCs).

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Extracellular vesicles (EVs) are micro and nanoscale packages that circulate in all bodily fluids and play an important role in intercellular communication by shuttling biomolecules to nearby and distant cells. However, producing sufficient amounts of EVs for many types of in vitro studies using standard culture methods can be challenging, and despite the success of some bioreactors in increasing EV-production, it is still largely unknown how individual culture conditions can alter the production and content of EVs. In this study, we demonstrate a simple and inexpensive micropatterning technique that can be used to produce polystyrene microtracks over a 100 mm diameter growth surface area.

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The circadian clock is a specialized cell signalling pathway present in all cells. Loss of clock function leads to tissue degeneration and premature ageing in animal models demonstrating the fundamental importance of clocks for cell, tissue and organism health. There is now considerable evidence that the chondrocyte circadian clock is altered in OA.

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Ionotropic glutamate receptors include -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), kainate receptors (KAR), and -methyl-D-aspartate receptors (NMDAR). All function as cation channels; AMPAR and KAR are more permeable to sodium and NMDAR to calcium ions. Compared to the brain, receptor assemblies in platelets are unusual, suggesting distinctive functionalities.

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The -methyl-D-aspartate receptor (NMDAR) provides a pathway for glutamate-mediated inter-cellular communication, best known for its role in the brain but with multiple examples of functionality in non-neuronal cells. Data previously published by others and us provided evidence that NMDARs regulate platelet and red blood cell (RBC) production. Here, we summarize what is known about these hematopoietic roles of the NMDAR.

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The release of calcium ions (Ca) from the endoplasmic reticulum (ER) and related store-operated calcium entry (SOCE) regulate maturation of normal megakaryocytes. The -methyl-D-aspartate (NMDA) receptor (NMDAR) provides an additional mechanism for Ca influx in megakaryocytic cells, but its role remains unclear. We created a model of NMDAR hypofunction in Meg-01 cells using CRISPR-Cas9 mediated knockout of the gene, which encodes an obligate, GluN1 subunit of the NMDAR.

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Management of Diaphorina citri Kuwayama (Hemiptera: Liviidae) populations is one of the major strategies for reducing the spread and incidence of huanglongbing (HLB). HLB is putatively caused by Candidatus Liberibacter spp. (Rhizobiales: Phyllopbacteriaceae) that are transmitted to citrus by psyllid vectors.

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Background: -methyl-d-aspartate receptors (NMDARs) contribute calcium influx in megakaryocytic cells but their roles remain unclear; both pro- and anti-differentiating effects have been shown in different contexts.

Objectives: The aim of this study was to clarify NMDAR contribution to megakaryocytic differentiation in both normal and leukemic cells.

Methods: Meg-01, Set-2, and K-562 leukemic cell lines were differentiated using phorbol-12-myristate-13-acetate (PMA, 10 nmol L) or valproic acid (VPA, 500 μmol L).

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Objective(s): To evaluate the frequency of surgical site infections before and after implementation of a comprehensive, multidisciplinary perioperative glycemic control initiative.

Study Methods: As part of a CUSP (Comprehensive Unit-based Safety Program) initiative, between January 5 and December 18, 2015, we implemented comprehensive, multidisciplinary glycemic control initiative to reduce SSI rates in patients undergoing major pelvic surgery for a gynecologic malignancy ('Group II'). Key components of this quality of care initiative included pre-operative HbA1c measurement with special triage for patients meeting criteria for diabetes or pre-diabetes, standardization of available intraoperative insulin choices, rigorous pre-op/intra-op/post-op glucose monitoring with control targets set to maintain BG ≤10mmol/L (180mg/dL) and communication/notification with primary care providers.

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GluN1 is a mandatory component of N-methyl-D-aspartate receptors (NMDARs) best known for their roles in the brain, but with increasing evidence for relevance in peripheral tissues, including platelets. Certain anti-GluN1 antibodies reduce brain infarcts in rodent models of ischaemic stroke. There is also evidence that human anti-GluN1 autoantibodies reduce neuronal damage in stroke patients, but the underlying mechanism is unclear.

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Chemotherapy with taxanes such as paclitaxel (PTX) is a key component of triple negative breast cancer (TNBC) treatment. PTX is used in combination with other drugs in both the adjuvant setting and in advanced breast cancer. Because a proportion of patients respond poorly to PTX or relapse after its use, a greater understanding of the mechanisms conferring resistance to PTX is required.

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In a public health disaster, such as an influenza pandemic, the focus of medical care shifts from the needs of the individual to those of the community, so that the greatest good for the greatest number may be achieved. In a pandemic it will be necessary to maximize the benefit derived from all available local resources. Triage is the device employed to decide which patients will receive these limited medical resources.

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The purpose of this study was to determine if discrepancies exist between upright and inverted seated positions in isometric maximal voluntary contraction (MVC) elbow flexor force, MVC force produced in the first 100 ms (F100), MVC rate of force development, electromyographic (EMG) activity of the biceps and triceps as well as heart rate and blood pressure. The results showed significantly (p < 0.01) higher MVC force (543.

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