F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets.

Mechano-dependent interactions are key to thrombus formation and hemostasis, enabling stable platelet adhesion to injured vessels. The interaction between von Willebrand factor (VWF) and the platelet receptor GPIb-IX-V is central to this process. While GPIbα connects to the actin cytoskeleton, whether actin dynamics are important for GPIbα function under hemodynamic, high shear conditions remains largely unknown.

Unveiling platelet aging with progressive β-galactose exposure as a signature of platelet senescence in humans and mice.

Not available.

Clinician-Focused Connected Health Requirements Gathering for Attention-Deficit/Hyperactivity Disorder Through Clinical Journey Mapping: Design Science Study.

Background: Many health care systems globally face severe capacity issues, with lengthening waiting lists and stretched resources. Connected health has been proposed as a game changer for health care. However, the development of connected health apps is difficult and requires multidisciplinary development teams.

Addressing the Humans in the Delivery Room-Optimising Neonatal Monitoring and Decision-Making in Transition.

During the first minutes of life, complex dynamic processes occur, facilitating a normal transition to ex utero life. In healthy term infants, these processes typically occur with minimal intervention required but are often more challenging for the preterm infant. These challenges involve not only the physiological processes encountered but also an organizational process: that of a team of healthcare providers led by a neonatologist, establishing a diagnosis based on clinical and technical information and initiating time-critical and potentially life-altering interventions.

LEANBH study: Device satisfaction study for the use of a novel connected home blood pressure system in pregnancy; a prospective cohort study.

Objectives: To investigate patients' perspectives on using the LEANBH app (home Blood Pressure BP monitoring system) and the Microlife Watch BP home monitor in a tertiary maternity hospital setting during the COVID-19 pandemic.

Study Design: 134 Participants were asked to complete an anonymous usability questionnaire on their experience of LEANBH and the Microlife Watch. The questionnaire consisted of 5 background demographics, 9 items from the system usability scale (SUS), 14 items on the usability of the LEANBH app, and 6 on the acceptability of Microlife.

A small-molecule hemostatic agent for the reversal of direct oral anticoagulant-induced bleeding.

Background: The bleeding risk associated with direct oral anticoagulants (DOACs) remains a major concern, and rapid reversal of anticoagulant activity may be required. Although specific and nonspecific hemostatic biotherapies are available, there is a need for small-molecule DOAC reversal agents that are simple and cost-effective to produce, store, and administer.

Objectives: To identify and characterize a small molecule with procoagulant activity as a DOAC reversal agent.

Assessment of the concordance between DN4 scores performed by the patient (self-assessment) or by the physician (hetero-assessment) to detect subacute neuropathic postoperative pain.

Background: Centres dedicated to chronic postsurgical pain (CPSP) have been developed, but delays for accessing to it are generally long. Teleconsultation might be a means to facilitate access to care by allowing an initial triage. CPSPs are neuropathic pain in around half of the cases and their diagnosis is mainly based on the score obtained from validated questionnaires.

MAGT1 deficiency in XMEN disease is associated with severe platelet dysfunction and impaired platelet glycoprotein N-glycosylation.

Background: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN) disease is a primary immunodeficiency due to loss-of-function mutations in the gene encoding for magnesium transporter 1 (MAGT1). Furthermore, as MAGT1 is involved in the N-glycosylation process, XMEN disease is classified as a congenital disorder of glycosylation. Although XMEN-associated immunodeficiency is well described, the mechanisms underlying platelet dysfunction and those responsible for life-threatening bleeding events have never been investigated.

ADP receptor P2Y12 is the capstone of the cross-talk between Ca mobilization pathways dependent on Ca ATPases sarcoplasmic/endoplasmic reticulum type 3 and type 2b in platelets.

Background: Blood platelet Ca stores are regulated by 2 Ca-ATPases (SERCA2b and SERCA3). On thrombin stimulation, nicotinic acid adenosine dinucleotide phosphate mobilizes SERCA3-dependent stores, inducing early adenosine 5'-diphosphate (ADP) secretion, potentiating later SERCA2b-dependent secretion.

Objectives: The aim of this study was to identify which ADP P2 purinergic receptor (P2Y1 and/or P2Y12) is(are) involved in the amplification of platelet secretion dependent on the SERCA3-dependent Ca mobilization pathway (SERCA3 stores mobilization) as triggered by low concentration of thrombin.

DOCK11 deficiency in patients with X-linked actinopathy and autoimmunity.

Dedicator of cytokinesis (DOCK) proteins play a central role in actin cytoskeleton regulation. This is highlighted by the DOCK2 and DOCK8 deficiencies leading to actinopathies and immune deficiencies. DOCK8 and DOCK11 activate CDC42, a Rho-guanosine triphosphate hydrolases involved in actin cytoskeleton dynamics, among many cellular functions.

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).

A gain-of-function filamin A mutation in mouse platelets induces thrombus instability.

Background: Filaminopathies A are rare disorders affecting the brain, intestine, or skeleton, characterized by dominant X-linked filamin A (FLNA) gene mutations. Macrothrombocytopenia with functionally defective platelets is frequent. We have described a filaminopathy A male patient, exhibiting a C-terminal frame-shift FLNa mutation (Berrou et al.

Thermal grill illusion of pain in patients with chronic pain: a clinical marker of central sensitization?

The thermal grill illusion of pain (TGIP) is a paradoxical burning pain sensation elicited by the simultaneous application of innocuous cutaneous warm and cold stimuli with a thermode ("thermal grill") consisting of interlaced heated and cooled bars. Its neurophysiological mechanisms are unclear, but TGIP may have some mechanisms in common with pathological pain, including central sensitization in particular, through the involvement of N-methyl- d -aspartate receptors. However, few studies have investigated TGIP in patients with chronic pain and its clinical relevance is uncertain.

Characteristics of Hospital Workers Using a Wellbeing Center Implemented During the COVID-19 Pandemic to Prevent the Emotional Impacts of the Crisis.

Introduction: The COVID-19 pandemic has posed an unprecedented challenge worldwide for healthcare workers (HCWs) and other hospital employees. Disruptions in work and personal life may have led to mental health problems. To prevent or limit the severity of such issues, a local initiative has been implemented in a French hospital: a dedicated lounge, also called "" (literally bubble and meaning safe space) has been created to provide a quiet caring environment and health support.

Antithrombotic potential of a single-domain antibody enhancing the activated protein C-cofactor activity of protein S.

Background: Protein S (PS) is a natural anticoagulant acting as a cofactor for activated protein C (APC) in the proteolytic inactivation of activated factors V (FVa) and VIII (FVIIIa), but also for tissue factor pathway inhibitor α (TFPIα) in the inhibition of activated factor X (FXa).

Objective: For therapeutic purposes, we aimed at generating single-domain antibodies (sdAbs) that could specifically modulate the APC-cofactor activity of PS in vivo.

Methods: A llama-derived immune library of sdAbs was generated and screened on recombinant human PS by phage display.

New insights into regulation of αIIbβ3 integrin signaling by filamin A.

Background: Filamin (FLN) regulates many cell functions through its scaffolding activity cross-linking cytoskeleton and integrins. FLN was shown to inhibit integrin activity, but the exact mechanism remains unclear.

Objectives: The aim of this study was to evaluate the role of filamin A (FLNa) subdomains on the regulation of integrin αIIbβ3 signaling.

A thrombopoietin receptor agonist to rescue an unusual platelet transfusion-induced reaction in a p.V1316M-associated von Willebrand disease type 2B patient.

Unlabelled: This report describes the first case of splenic injury in a patient with p.V1316M-associated von Willebrand disease type 2B (VWD2B) with chronic thrombocytopenia, successfully treated with nonoperative management including von Willebrand factor (VWF) replacement therapy, and platelet transfusions relayed by a thrombopoietin receptor agonist (TPO-RA, Eltrombopag). Eltrombopag was initially introduced to rescue an unusual post-platelet-transfusion reaction exacerbating the thrombocytopenia.

Anti-inflammatory Activity of the Protein Z-Dependent Protease Inhibitor.

The protein Z (PZ)-dependent plasma protease inhibitor (ZPI) is a glycoprotein that inhibits factor XIa and, in the presence of PZ, FXa. Recently, ZPI has been shown to be an acute-phase protein (APP). As usually APPs downregulate the harmful effects of inflammation, we tested whether ZPI could modulate the increase of cytokines observed in inflammatory states.

French soldiers who died during both World Wars: from recovery to repatriation.

The study of human remains from the first and the second World War is important for enhancing our understanding of that historical period. Despite the fact that the period has been well-documented previously, gaps remain, particularly as a result of the destruction of archives. In fact, for just WWI, more than 700,000 soldiers from both sides remain missing.

Embedding the Pillars of Quality in Health Information Technology Solutions Using "Integrated Patient Journey Mapping" (IPJM): Case Study.

Background: Health information technology (HIT) and associated data analytics offer significant opportunities for tackling some of the more complex challenges currently facing the health care sector. However, to deliver robust health care service improvements, it is essential that HIT solutions be designed by parallelly considering the 3 core pillars of health care quality: clinical effectiveness, patient safety, and patient experience. This requires multidisciplinary teams to design interventions that both adhere to medical protocols and achieve the tripartite goals of effectiveness, safety, and experience.

NAADP/SERCA3-Dependent Ca Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation.

Rationale: Ca signaling is a key and ubiquitous actor of cell organization and its modulation controls many cellular responses. SERCAs (sarco-endoplasmic reticulum Ca-ATPases) pump Ca into internal stores that play a major role in the cytosolic Ca concentration rise upon cell activation. Platelets exhibit 2 types of SERCAs, SERCA2b and SERCA3 (SERCA3 deficient mice), which may exert specific roles, yet ill-defined.