Shiga toxin down-regulates ERG protein in endothelial cells and impairs angiogenesis.

Background: Shiga toxin (Stx) can activate inflammatory signaling, leading to vascular dysfunction and promotion of a pro-thrombotic tissue microenvironment. Stx can trigger the development of the enterohemorrhagic (childhood) hemolytic uremic syndrome (eHUS), a triad of thrombocytopenia, hemolytic anemia, and acute kidney injury, often requiring dialysis. Additional features may include damage to other organs, including the gastrointestinal tract, pancreas, brain and cardiovascular system; death occurs in 2-5 %.

Safety, tolerability, and effectiveness of anticoagulation and antiplatelet therapy in hereditary hemorrhagic telangiectasia.

Background: Antithrombotic therapy (anticoagulation and antiplatelet therapy) is frequently needed in patients with hereditary hemorrhagic telangiectasia (HHT); however, data describing and guiding its use are very limited.

Objectives: To investigate the safety, tolerability, and effectiveness of antithrombotic therapy in HHT in a cohort large enough to compare agents, evaluate for baseline predictors of premature discontinuation, and evaluate hematologic support requirements and healthcare utilization before and after antithrombitc therapy initiation.

Methods: We performed a multicenter observational cohort study characterizing the outcomes of antithrombic therapy in adults with HHT.

Presentation, Management and Outcomes of Pediatric Pulmonary Embolus: A Retrospective Review.

Objectives: To review the presentation, management, and outcomes of pediatric pulmonary embolism (PE) patients treated at a single institution over 10 years to determine whether laboratory findings and clinical presentation predict disease severity.

Methods: We performed a retrospective chart review of patients treated for PE in a 14-bed pediatric intensive care unit from January 1, 2008, to December 31, 2018. Associations between clot burden and disease severity, clinical risk factors (body mass index, recent hospitalization, estrogen use), clinical presentation (heart rate, oxygen saturation), and laboratory values (white blood cell count, D-Dimer, troponin, proBNP) were performed using Student t test, χ2 tests, and 1-way analysis of variance.

Differentiation of Patients with Symptomatic Low von Willebrand Factor from Those with Asymptomatic Low von Willebrand Factor.

Background:  Accurate diagnosis of symptomatic low von Willebrand factor (VWF) remains a major challenge in von Willebrand disease (VWD). However, present tests do not adequately take into account flow forces that, at very high shear rates, reveal a weakness in the VWF-platelet glycoprotein glycoprotein Ib bond in normal subjects. The degree of this weakness is greater in symptomatic, but not asymptomatic, low VWF.

Risk of Intracranial Hemorrhage Following Intravenous tPA (Tissue-Type Plasminogen Activator) for Acute Stroke Is Low in Children.

Background and Purpose- Data regarding the safety and efficacy of intravenous tPA (tissue-type plasminogen activator) in childhood acute arterial ischemic stroke are inadequate. The TIPS trial (Thrombolysis in Pediatric Stroke; National Institutes of Health grant R01NS065848)-a prospective safety and dose-finding trial of intravenous tPA in acute childhood stroke-was closed for lack of accrual. TIPS sites have subsequently treated children with acute stroke in accordance with established institutional protocols supporting data collection on outcomes.

Coupling carbon and energy fluxes in the North Pacific Subtropical Gyre.

The major biogeochemical cycles of marine ecosystems are driven by solar energy. Energy that is initially captured through photosynthesis is transformed and transported to great ocean depths via complex, yet poorly understood, energy flow networks. Herein we show that the chemical composition and specific energy (Joules per unit mass or organic carbon) of sinking particulate matter collected in the North Pacific Subtropical Gyre reveal dramatic changes in the upper 500 m of the water column as particles sink and age.

Flow Devices to Assess Platelet Function: Historical Evolution and Current Choices.

Platelet function testing, which began more than a hundred years ago, is a time-consuming and uncertain process. Simulating hemostasis and the blood vessel microenvironment in vitro is challenging, which poses a difficulty for diagnosing platelet dysfunction and mild von Willebrand disease (VWD). In an effort to simulate the rheological microenvironment within blood vessels, several blood flow devices have been introduced since the 1980s.

Naphtho[2,3- b]carbaporphyrins.

Acid-catalyzed condensation of a benzo[ f]indane dialdehyde with a tripyrrane, followed by an oxidation step, afforded the first example of a naphtho[2,3- b]-21-carbaporphyrin. This π-extended porphyrinoid system is strongly aromatic and gave a porphyrin-like UV-vis spectrum with a Soret band at 432 nm. Protonation with TFA gave a monocation, but under highly acidic conditions a C-protonated dication was generated.

Mortality After Pediatric Arterial Ischemic Stroke.

Objectives: Cerebrovascular disease is among the top 10 causes of death in US children, but risk factors for mortality are poorly understood. Within an international registry, we identify predictors of in-hospital mortality after pediatric arterial ischemic stroke (AIS).

Methods: Neonates (0-28 days) and children (29 days-<19 years) with AIS were enrolled from January 2003 to July 2014 in a multinational stroke registry.

Analysis of patient outcomes following proton radiation therapy for retinoblastoma.

Purpose: Proton radiotherapy (PRT) is used in the treatment of retinoblastoma (RB) and has the potential to minimize exposure of normal tissue to radiation and thus decrease risk of toxicity and second malignancies. However, comprehensive analyses of long-term patient outcomes are not available.

Methods: RB patients treated with PRT at our institution between 1986 and 2012 were invited to return for participation in a study designed to assess long-term outcomes.

The Importance of H in Particulate Organic Matter Stoichiometry, Export and Energy Flow.

The discipline of marine ecological stoichiometry has progressed rapidly over the past two decades, and continues to be at the forefront of microbial oceanography. Most of this effort has been focused on the elements carbon (C) and nitrogen (N), and to a lesser extent phosphorus (P), with little consideration of hydrogen (H), or the redox state of the organic matter pools despite the fact that H is the most abundant, and possibly the most important, element in biogeochemistry. Obtaining accurate estimates of the H content of organic matter, either in suspended or sinking particles, is a major analytical challenge.

Human mannose-binding lectin inhibitor prevents Shiga toxin-induced renal injury.

Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC HUS) is a worldwide endemic problem, and its pathophysiology is not fully elucidated. Here we tested whether the mannose-binding lectin (MBL2), an initiating factor of lectin complement pathway activation, plays a crucial role in STEC HUS. Using novel human MBL2-expressing mice (MBL2 KI) that lack murine Mbls (MBL2(+/+)Mbl1(-/-)Mbl2(-/-)), a novel STEC HUS model consisted of an intraperitoneal injection with Shiga toxin-2 (Stx-2) with or without anti-MBL2 antibody (3F8, intraperitoneal).

Brain endothelial dysfunction in cerebral adrenoleukodystrophy.

See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids.

Proton radiation therapy for the treatment of retinoblastoma.

Purpose: To investigate long-term disease and toxicity outcomes for pediatric retinoblastoma patients treated with proton radiation therapy (PRT).

Methods And Materials: This is a retrospective analysis of 49 retinoblastoma patients (60 eyes) treated with PRT between 1986 and 2012.

Results: The majority (84%) of patients had bilateral disease, and nearly half (45%) had received prior chemotherapy.

Second nonocular tumors among survivors of retinoblastoma treated with contemporary photon and proton radiotherapy.

Background: The leading cause of death among patients with hereditary retinoblastoma is second malignancy. Despite its high rate of efficacy, radiotherapy (RT) is often avoided due to fear of inducing a secondary tumor. Proton RT allows for significant sparing of nontarget tissue.

Shiga toxin downregulates tissue factor pathway inhibitor, modulating an increase in the expression of functional tissue factor on endothelium.

Introduction: Endothelial expression of tissue factor (TF) may play a major role in (Stx)-related hemolytic uremic syndrome. We examined human umbilical vein endothelial cell (HUVEC) monolayers to determine the interaction between TF and TF pathway inhibitor (TFPI), hypothesizing that changes in TFPI modulate TF expression.

Materials And Methods: We studied 1) cell surface expression of globotriasylceramide (Gb3, the receptor for Stx) with Stx-1 (10 pM), TNFα (20 Ng/ml), or Stx-1 plus TNFα compared to control, 2) gene expression of TF and TFPI, 3) total cellular and cell surface antigenic TF and TFPI, 4) TFPI secretion into supernatant, and 5) factor Xa production.

Bleeding risks are higher in children versus adults given prophylactic platelet transfusions for treatment-induced hypoproliferative thrombocytopenia.

Age-group analyses were conducted of patients in the prophylactic platelet dose trial (PLADO), which evaluated the relation between platelet dose per transfusion and bleeding. Hospitalized patients with treatment-induced hypoproliferative thrombocytopenia were randomly assigned to 1 of 3 platelet doses: 1.1 × 10(11), 2.

Evaluation of hemostasis in flowing blood.

Hemostasis and thrombosis are now increasingly recognized as integrally related to blood rheology and blood flow. Platelets, for example, are known to access the vessel wall in ways which depend upon the small-scale motions of neighboring erythrocytes, and access one another via collisions driven by gradients in blood flow velocity. In this context, flow devices have become a subject of great interest in the clinical assessment of bleeding disorders, especially platelet function defects and von Willebrand disease.

Assessment of a cohort of primarily pediatric patients with a presumptive diagnosis of type 1 von Willebrand disease with a novel high shear rate, non-citrated blood flow device.

Background: A precise approach to the diagnosis of von Willebrand disease (vWD) remains elusive. One important reason is that vWD is a blood flow-related disorder: a vW Factor-platelet GPIb binding defect exists in this condition under the high shear-rate (> 1000 sec-1 in whole blood; > 3000 sec-1 in PRP) conditions of physiologic blood flow which exist in the arterioles of mucous membranes, from which most bleeding in vWD occurs.

Methods: We therefore studied 28 patients (mean 18.