Mice with Reduced PAR4 Reactivity show Decreased Venous Thrombosis and Platelet Procoagulant Activity.

Background: Hypercoagulation and thrombin generation are major risk factors for venous thrombosis. Sustained thrombin signaling through PAR4 promotes platelet activation, phosphatidylserine exposure, and subsequent thrombin generation. A single-nucleotide polymorphism in PAR4 (rs2227376) changes proline to leucine extracellular loop 3 (P310L), which decreases PAR4 reactivity and is associated with a lower risk for venous thromboembolism (VTE) in a GWAS meta-analysis.

Systemically administered platelet-inspired nanoparticles to reduce inflammation surrounding intracortical microelectrodes.

Intracortical microelectrodes (IMEs) are essential for neural signal acquisition in neuroscience and brain-machine interface (BMI) systems, aiding patients with neurological disorders, paralysis, and amputations. However, IMEs often fail to maintain robust signal quality over time, partly due to neuroinflammation caused by vascular damage during insertion. Platelet-inspired nanoparticles (PIN), which possess injury-targeting functions, mimic the adhesion and aggregation of active platelets through conjugated collagen-binding peptides (CBP), von Willebrand Factor-binding peptides (VBP), and fibrinogen-mimetic peptides (FMP).

Mice with Reduced PAR4 Reactivity show Decreased Venous Thrombosis and Platelet Procoagulant Activity.

Background: Hypercoagulation and thrombin generation are major risk factors for venous thrombosis. Sustained thrombin signaling through PAR4 promotes platelet activation, phosphatidylserine exposure, and subsequent thrombin generation. A single-nucleotide polymorphism in PAR4 (rs2227376) changes proline to leucine extracellular loop 3 (P310L), which decreases PAR4 reactivity and is associated with a lower risk for venous thromboembolism (VTE) in a GWAS meta-analysis.

A surface-functionalized whole blood-based dielectric microsensor for assessment of clot firmness in a fibrinolytic environment.

Accurate assessment of fibrin clot stability can predict bleeding risk in coagulopathic conditions such as thrombocytopenia and hypofibrinogenemia. Hyperfibrinolysis - a clinical phenotype characterized by an accelerated breakdown of the fibrin clot - makes such assessments challenging by obfuscating the effect of hemostatic components including platelets or fibrinogen on clot stability. In this work, we present a biofunctionalized, microfluidic, label-free, electronic biosensor to elicit unique, specific, and differential responses from the multifactorial processes of blood coagulation and fibrinolysis ex vivo.

Visual loss and encephalopathy in a pregnant patient with hyperemesis gravidarum.

A pregnant woman in her 20s at 17 weeks of gestation, presented with symptoms of painless diminution of vision preceded by 8 weeks history of hyperemesis gravidarum. On examination, she was confused, disoriented and had gait ataxia with complete loss of vision in both eyes. Fundus examination revealed grade 4 disc oedema with superficial retinal haemorrhages.

Cuminaldehyde and Tobramycin Forestall the Biofilm Threats of Staphylococcus aureus: A Combinatorial Strategy to Evade the Biofilm Challenges.

Staphylococcus aureus, an opportunistic Gram-positive pathogen, is known for causing various infections in humans, primarily by forming biofilms. The biofilm-induced antibiotic resistance has been considered a significant medical threat. Combinatorial therapy has been considered a reliable approach to combat antibiotic resistance by using multiple antimicrobial agents simultaneously, targeting bacteria through different mechanisms of action.

Application of cuminaldehyde and ciprofloxacin for the effective control of biofilm assembly of Pseudomonas aeruginosa: A combinatorial study.

Pseudomonas aeruginosa is widely associated with biofilm-mediated antibiotic resistant chronic and acute infections which constitute a persistent healthcare challenges. Addressing this threat requires exploration of novel therapeutic strategies involving the combination of natural compounds and conventional antibiotics. Hence, our study has focused on two compounds; cuminaldehyde and ciprofloxacin, which were strategically combined to target the biofilm challenge of P.

Piperine, a phytochemical prevents the biofilm city of methicillin-resistant Staphylococcus aureus: A biochemical approach to understand the underlying mechanism.

Methicillin-resistant Staphylococcus aureus (MRSA), a drug-resistant human pathogen causes several nosocomial as well as community-acquired infections involving biofilm machinery. Hence, it has gained a wide interest within the scientific community to impede biofilm-induced MRSA-associated health complications. The current study focuses on the utilization of a natural bioactive compound called piperine to control the biofilm development of MRSA.

Combinatorial application of cuminaldehyde and gentamicin shows enhanced antimicrobial and antibiofilm action on Pseudomonas aeruginosa.

The emergence of biofilm-induced drug tolerance poses a critical challenge to public healthcare management. Pseudomonas aeruginosa, a gram-negative opportunistic bacterium, is involved in various biofilm-associated infections in human hosts. Towards this direction, in the present study, a combinatorial approach has been explored as it is a demonstrably effective strategy for managing microbial infections.

Platelet-inspired synthetic nanoparticles improve hemostasis and hemodynamics in a rabbit model of abdominal hemorrhage.

Background: Early platelet transfusion is associated with reduced mortality in traumatic hemorrhage. However, platelet usage is severely limited because of the challenges of donor availability, platelet portability, and storage. Here, we report on a bioinspired synthetic platelet (SP) nanoconstruct that utilizes liposome surface-decoration with peptides that mimic injury site-specific platelet adhesion to von Willebrand Factor and collagen, and fibrinogen-mediated platelet aggregation.

The Coexisting Neuromyelitis Optica Spectrum Disorder and Systemic Lupus Erythematosus: A Therapeutic Challenge.

Neuromyelitis Optica (NMO), or Devic's disease, is an immune-mediated, usually relapsing, central nervous system (CNS) demyelination disorder associated with optic neuritis and transverse myelitis. It is characterised by the presence of longitudinally extensive transverse myelitis (LETM) and antibodies against water channel aquaporin-4 (AQP4-immunoglobulin G [IgG]). The term NMO spectrum disorder (NMOSD) includes patients with limited forms of NMO who are at risk of recurrence.

Military Medicine and Medical Research as a Source of Inspiration and Innovation to Solve National Security and Health Challenges in the 21st Century.

The history of military medicine and research is rife with examples of novel treatments and new approaches to heal and cure soldiers and others impacted by war's devastation. In the 21st century, new threats, like climate change, are combined with traditional threats, like geopolitical conflict, to create novel challenges for our strategic interests. Extreme and inaccessible environments provide heightened risks for warfighter exposure to dangerous bacteria, viruses, and fungi, as well as exposure to toxic substances and extremes of temperature, pressure, or both providing threats to performance and eroding resilience.

Topical Synthetic Platelets Loaded With Gentamicin Decrease Bacteria in Deep Partial-Thickness Burns.

Introduction: Prolonged inflammation and infection in burns may cause inadequate healing. Platelet granules contain anti-inflammatory mediators that impact wound healing. Synthetic platelets (SPs) avoid portability and storage difficulties of natural platelets and can be loaded with bioactive agents.

A Multichannel Portable Platform With Embedded Thermal Management for Miniaturized Dielectric Blood Coagulometry.

This article presents a standalone, multichannel, miniaturized impedance analyzer (MIA) system for dielectric blood coagulometry measurements with a microfluidic sensor termed ClotChip. The system incorporates a front-end interface board for 4-channel impedance measurements at an excitation frequency of 1 MHz, an integrated resistive heater formed by a pair of printed-circuit board (PCB) traces to keep the blood sample near a physiologic temperature of 37 °C, a software-defined instrument module for signal generation and data acquisition, and a Raspberry Pi-based embedded computer with 7-inch touchscreen display for signal processing and user interface. When measuring fixed test impedances across all four channels, the MIA system exhibits an excellent agreement with a benchtop impedance analyzer, with rms errors of ≤0.

Piperine, a Plant Alkaloid, Exhibits Efficient Disintegration of the Pre-existing Biofilm of Staphylococcus aureus: a Step Towards Effective Management of Biofilm Threats.

Staphylococcus aureus causes a range of chronic infections in humans by exploiting its biofilm machinery and drug-tolerance property. Although several strategies have been proposed to eradicate biofilm-linked issues, here, we have explored whether piperine, a bioactive plant alkaloid, can disintegrate an already existing Staphylococcal biofilm. Towards this direction, the cells of S.

Platelets and hemostatic proteins are co-localized with chronic neuroinflammation surrounding implanted intracortical microelectrodes.

Intracortical microelectrodes induce vascular injury upon insertion into the cortex. As blood vessels rupture, blood proteins and blood-derived cells (including platelets) are introduced into the 'immune privileged' brain tissues at higher-than-normal levels, passing through the damaged blood-brain barrier. Blood proteins adhere to implant surfaces, increasing the likelihood of cellular recognition leading to activation of immune and inflammatory cells.

Efficacy of platelet-inspired hemostatic nanoparticles on bleeding in von Willebrand disease murine models.

The lack of innovation in von Willebrand disease (VWD) originates from many factors including the complexity and heterogeneity of the disease but also from a lack of recognition of the impact of the bleeding symptoms experienced by patients with VWD. Recently, a few research initiatives aiming to move past replacement therapies using plasma-derived or recombinant von Willebrand factor (VWF) concentrates have started to emerge. Here, we report an original approach using synthetic platelet (SP) nanoparticles for the treatment of VWD type 2B (VWD-2B) and severe VWD (type 3 VWD).

Direct delivery of plasmin using clot-anchoring thrombin-responsive nanoparticles for targeted fibrinolytic therapy.

Background: Fibrin-rich clot formation in thrombo-occlusive pathologies is currently treated by systemic administration of plasminogen activators (e.g. tPA), to convert fibrin-associated plasminogen to plasmin for fibrinolytic action.

Identifying barriers to shared decision-making about bariatric surgery in two large health systems.

Objective: Prior research suggests shared decision-making (SDM) could improve patient and health care provider communication about bariatric surgery. The aim of this work was to identify and prioritize barriers to SDM around bariatric surgery to help guide implementation of SDM.

Methods: Two large US health care systems formed multidisciplinary teams to facilitate the implementation of SDM around bariatric surgery.

Glioma stem cells activate platelets by plasma-independent thrombin production to promote glioblastoma tumorigenesis.

Background: The interaction between platelets and cancer cells has been underexplored in solid tumor models that do not metastasize, for example, glioblastoma (GBM) where metastasis is rare. Histologically, it is known that glioma stem cells (GSCs) are found in perivascular and pseudsopalisading regions of GBM, which are also areas of platelet localization. High platelet counts have been associated with poor clinical outcomes in many cancers.

Platelet-Inspired Intravenous Nanomedicine for Injury-Targeted Direct Delivery of Thrombin to Augment Hemostasis in Coagulopathies.

Severe hemorrhage associated with trauma, surgery, and congenital or drug-induced coagulopathies can be life-threatening and requires rapid hemostatic management via topical, intracavitary, or intravenous routes. For injuries that are not easily accessible externally, hemostatic approaches are needed. The clinical gold standard for this is transfusion of blood products, but due to donor dependence, specialized storage requirements, high risk of contamination, and short shelf life, blood product use faces significant challenges.

Safety profile of repeated infusion of platelet-like nanoparticles in healthy dogs.

Objective: To assess the safety and efficacy of the platelet-like nanoparticle (PLN), and to assess its safety in repeated administration.

Animals: 6 purpose-bred dogs.

Procedures: The PLN was administered IV at 3 different doses using a randomized crossover design.

Nanomedicine platform for targeting activated neutrophils and neutrophil-platelet complexes using an α-antitrypsin-derived peptide motif.

Targeted drug delivery to disease-associated activated neutrophils can provide novel therapeutic opportunities while avoiding systemic effects on immune functions. We created a nanomedicine platform that uniquely utilizes an α-antitrypsin-derived peptide to confer binding specificity to neutrophil elastase on activated neutrophils. Surface decoration with this peptide enabled specific anchorage of nanoparticles to activated neutrophils and platelet-neutrophil aggregates, in vitro and in vivo.