Splitting apheresis platelets as a contingency measure for inventory shortages.

Background: Splitting apheresis platelet (PLT) units increase available inventory during shortages. The impact of prolonged storage in gas-impermeable aliquot bags on PLT quality in vitro and transfusion outcomes in patients remains uncertain.

Study Design And Methods: We assessed in vitro PLT quality and thromboelastography (TEG) in PLTs stored for 8 or 24 h in aliquot bags compared with baseline (T0).

SARS-CoV-2 infection results in upregulation of Plasminogen Activator Inhibitor-1 and Neuroserpin in the lungs, and an increase in fibrinolysis inhibitors associated with disease severity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in coagulation activation although it is usually not associated with consumption coagulopathy. D-dimers are also commonly elevated despite systemic hypofibrinolysis. To understand these unusual features of coronavirus disease 2019 (COVID-19) coagulopathy, 64 adult patients with SARS-CoV-2 infection (36 moderate and 28 severe) and 16 controls were studied.

A bispecific inhibitor of complement and coagulation blocks activation in complementopathy models via a novel mechanism.

Inhibitors of complement and coagulation are present in the saliva of a variety of blood-feeding arthropods that transmit parasitic and viral pathogens. Here, we describe the structure and mechanism of action of the sand fly salivary protein lufaxin, which inhibits the formation of the central alternative C3 convertase (C3bBb) and inhibits coagulation factor Xa (fXa). Surface plasmon resonance experiments show that lufaxin stabilizes the binding of serine protease factor B (FB) to C3b but does not detectably bind either C3b or FB alone.

Entrustable professional activities for Junior Brazilian Medical Students in community medicine.

Background: Entrustable professional activities (EPAs) have been defined to promote the workplace participation of undergraduate medical students, generally in the context of high-income countries with a focus on the secondary and tertiary health care sectors. These EPAs have limited applicability to training and health care contexts in low- to middle-income countries that have a focus on primary health care, for instance, the context of community medicine. The purpose of this article is to report the process and results of defining EPAs for undergraduate medical training in a community health care setting.

Functional aspects of evolution in a cluster of salivary protein genes from mosquitoes.

The D7 proteins are highly expressed in the saliva of hematophagous Nematocera and bind biogenic amines and eicosanoid compounds produced by the host during blood feeding. These proteins are encoded by gene clusters expressing forms having one or two odorant-binding protein-like domains. Here we examine functional diversity within the D7 group in the genus Anopheles and make structural comparisons with D7 proteins from culicine mosquitoes in order to understand aspects of D7 functional evolution.

Neutrophil and Eosinophil Extracellular Traps in Hodgkin Lymphoma.

Classic Hodgkin lymphoma (cHL), nodular sclerosis (NS) subtype, is characterized by the presence of Hodgkin/Reed-Sternberg (HRS) cells in an inflammatory background containing neutrophils and/or eosinophils. Both types of granulocytes release extracellular traps (ETs), web-like DNA structures decorated with histones, enzymes, and coagulation factors that promote inflammation, thrombosis, and tumor growth. We investigated whether ETs from neutrophils (NETs) or eosinophils (EETs) are detected in cHL, and evaluated their association with fibrosis.

Upregulation of pulmonary tissue factor, loss of thrombomodulin and immunothrombosis in SARS-CoV-2 infection.

Background: SARS-CoV-2 infection is associated with thrombotic and microvascular complications. The cause of coagulopathy in the disease is incompletely understood.

Methods: A single-center cross-sectional study including 66 adult COVID-19 patients (40 moderate, 26 severe disease), and 9 controls, performed between 04/2020 and 10/2020.

Elastase inhibitor agaphelin protects from acute ischemic stroke in mice by reducing thrombosis, blood-brain barrier damage, and inflammation.

Recently it was shown that the hematophagous salivary gland protein agaphelin exhibits multiple antithrombotic effects without promoting the risk of bleeding. Agaphelin inhibits neutrophil elastase and thereby reduces cathepsin G-induced platelet aggregation. However, it is still unclear, whether pharmacological treatment with agaphelin in brain ischemia is protective and, regarding its bleeding risk, safe.

CXCR4 and MIF are required for neutrophil extracellular trap release triggered by Plasmodium-infected erythrocytes.

Neutrophil extracellular traps (NETs) evolved as a unique effector mechanism contributing to resistance against infection that can also promote tissue damage in inflammatory conditions. Malaria infection can trigger NET release, but the mechanisms and consequences of NET formation in this context remain poorly characterized. Here we show that patients suffering from severe malaria had increased amounts of circulating DNA and increased neutrophil elastase (NE) levels in plasma.

Concurrent chronic lymphocytic leukemia/small lymphocytic lymphoma and hairy cell leukemia: clinical, pathologic and molecular features.

Simultaneous occurrence of hairy cell leukemia (HCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (termed CLL) is very rare. Clinical characteristics, pathology and management of these cases have not been well described. We present six patients with CLL and HCL or HCL variant (HCL-v).

Development of I-ixolaris as a theranostic agent: metastatic melanoma preclinical studies.

Tissue factor (TF), a blood coagulation protein, plays an important role in tumor growth, invasion, and metastasis. Ixolaris, a tick-derived non-immunogenic molecule that binds to TF, has demonstrated in vivo inhibitory effect on murine models of melanoma, including primary growth and metastasis. This work aimed to: I) develop an efficient and stable labeling technique of ixolaris with Iodine-131(I); II) compare the biodistribution of I and I-ixolaris in tumor-free and melanoma-bearing mice; III) evaluate whether I-ixolaris could serve as an antimetastatic agent.

Agaphelin modulates the activation of human bronchial epithelial cells induced by lipopolysaccharide and IL-4.

Sand fly saliva presents molecules with potential to development of compounds for treatment of inflammatory diseases. Agaphelin, isolated from the saliva of the mosquito Anopheles gambiae, demonstrates anti-inflammatory properties such as neutrophils chemotaxis inhibition. Here, we extend these results and evaluated the role of agaphelin (0.

NMR structure determination of Ixolaris and factor X(a) interaction reveals a noncanonical mechanism of Kunitz inhibition.

Ixolaris is a potent tick salivary anticoagulant that binds coagulation factor Xa (FXa) and zymogen FX, with formation of a quaternary tissue factor (TF)/FVIIa/ FX(a)/Ixolaris inhibitory complex. Ixolaris blocks TF-induced coagulation and PAR2 signaling and prevents thrombosis, tumor growth, and immune activation. We present a high-resolution structure and dynamics of Ixolaris and describe the structural basis for recognition of FX.

Ixonnexin from Tick Saliva Promotes Fibrinolysis by Interacting with Plasminogen and Tissue-Type Plasminogen Activator, and Prevents Arterial Thrombosis.

Tick saliva is a rich source of modulators of vascular biology. We have characterized Ixonnexin, a member of the "Basic-tail" family of salivary proteins from the tick Ixodes scapularis. Ixonnexin is a 104 residues (11.

H, N and C resonance assignments of Ixolaris, a tissue factor pathway inhibitor from the tick salivary gland.

Ixolaris is a two-Kunitz tick salivary gland protein identified in Ixodes scapularis that presents sequence homology to TFPI (tissue factor pathway inhibitor). It binds to the coagulation enzyme factor Xa (FXa) or to its zymogen form, FX, and further inhibits tissue factor/FVIIa complex (extrinsic Xnase compex). Differently from TFPI, Ixolaris does not bind to the active site cleft of FXa.

Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy.

In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. A better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events.

Recombinant expression of Ixolaris, a Kunitz-type inhibitor from the tick salivary gland, for NMR studies.

Ixolaris is an anticoagulant protein identified in the tick saliva of Ixodes scapularis. Ixolaris contains 2 Kunitz like domains and binds to Factor Xa or Factor X as a scaffold for inhibition of the Tissue Factor (TF)/Factor VIIa (FVIIa). In contrast to tissue factor pathway inhibitor (TFPI), however, Ixolaris does not bind to the active site cleft of FXa.

Laboratory and clinical predictors of 30-day survival for patients on Extracorporeal Membrane Oxygenation (ECMO): 8-Year experience at Albert Einstein College of Medicine, Montefiore Medical Center.

Purpose: Survival of patients on ECMO has remained stable in every population. Laboratory values predictors of survival are required to improve patient care.

Materials And Methods: Clinical Looking Glass software was used to assess Electronic Medical Records (EMRs) of patients at Albert Einstein College of Medicine, Montefiore Medical Center (2007-2014).

Incidental primary mediastinal choriocarcinoma diagnosed by endobronchial ultrasound-guided fine needle aspiration in a patient presenting with transient ischemic attack and stroke.

We describe a case of a 41-year old male patient with no significant prior medical history who presents with symptoms of Transient Ischemic Attack and stroke. Magnetic Resonance Imaging (MRI) of the brain identified areas of ischemia in the left side, and angiography showed occlusion of the left Medial Cerebral Artery (MCA). Cardiac Transthoracic Echocardiogram (TTE) for stroke evaluation incidentally noted a mediastinal abnormality leading to cancer work-up.