Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response.

Osteopontin (OPN) is a multi-functional protein that is involved in various cellular processes such as cell adhesion, migration, and signaling. There is a single conserved thrombin cleavage site in OPN that, when cleaved, yields two fragments with different properties from full-length OPN. In cancer, OPN has tumor-promoting activity and plays a role in tumor growth and metastasis.

Observation of diffuse scattering in scanning helium microscopy.

In understanding the nature of contrast in the emerging field of neutral helium microscopy, it is important to identify if there is an atom-surface scattering distribution that can be expected to apply broadly across a range of sample surfaces. Here we present results acquired in a scanning helium microscope (SHeM) under typical operating conditions, from a range of surfaces in their native state, without any specialist sample preparation. We observe diffuse scattering, with an approximately cosine distribution centred about the surface normal.

Thrombin cleavage of osteopontin initiates osteopontin's tumor-promoting activity.

Background: Osteopontin (OPN) is a multifunctional proinflammatory matricellular protein overexpressed in multiple human cancers and associated with tumor progression and metastases. Thrombin cleavage of OPN reveals a cryptic binding site for α β and α β integrins.

Methods: Thrombin cleavage-resistant OPN knock-in (OPN-KI) mice were generated and compared to OPN deficient mice (OPN-KO) and wild type (WT) mice in their ability to support growth of melanoma cells.

Standardizing resolution definition in scanning helium microscopy.

Resolution is a key parameter for microscopy, but methods for standardizing its definition are often poorly defined. For a developing technique such as scanning helium microscopy, it is critical that a consensus-based protocol for determining instrument resolution is prepared as a written standard to allow both comparable quantitative measurements of surface topography and direct comparisons between different instruments. In this paper we assess a range of quantitative methods for determining instrument resolution and determine their relative merits when applied to the specific case of the scanning helium microscope (SHeM).

Long term sequelae of amygdala enlargement in temporal lobe epilepsy.

Purpose: Amygdala enlargement (AE) has been reported in drug resistant lesional and non-lesional temporal lobe epilepsy (TLE). Its contribution to development of intractability of epilepsy is at best uncertain. Our aim was to study the natural course of AE in a heterogenous group of TLE patients with follow-up imaging and clinical outcomes.

Taxonomy through the lens of neutral helium microscopy.

The field of taxonomy is critically important for the identification, conservation, and ecology of biological species. Modern taxonomists increasingly need to employ advanced imaging techniques to classify organisms according to their observed morphological features. Moreover, the generation of three-dimensional datasets is of growing interest; moving beyond qualitative analysis to true quantitative classification.

Image formation in the scanning helium microscope.

The scanning helium microscope (SHeM) is a new addition to the array of available microscopies, particularly for delicate materials that may suffer damage under techniques utilising light or charged particles. As with all other microscopies, the specifics of image formation within the instrument are required to gain a full understanding of the produced micrographs. We present work detailing the basics of the subject for the SHeM, including the specific nature of the projection distortions that arise due to the scattering geometry.

Mechanistic Modeling of the Pharmacodynamic and Pharmacokinetic Relationship of Tissue Factor Pathway Inhibitor-Neutralizing Antibody (BAY 1093884) in Cynomolgus Monkeys.

BAY 1093884 is a fully human monoclonal antibody against the tissue factor pathway inhibitor (TFPI) in development as prophylaxis in patients with hemophilia with or without inhibitors. In vitro, BAY 1093884 binds to human, mouse, and monkey TFPI. The objective of this study was to find a pharmacodynamic (PD) biomarker after administration of BAY 1093884 to normal monkeys.

Food Insecurity and Eating Behavior Relationships Among Congregate Meal Participants in Georgia.

This study explored relationships of food insecurity with cognitive restraint, uncontrolled eating, and emotional eating behaviors among congregate meal participants in northeast Georgia [n = 118 years, age 60 years and older, mean (SD) age = 75 ( 8 ) years, 75% female, 43% Black, 53% obese (Body Mass Index ≥ 30)]. Food insecurity was assessed with a 6-item questionnaire. Scores ranged from 0 to 6 and were defined as high or marginal food security, FS, 0-1 (70%); low food security, LFS, 2-4 (20%); very low food security, VLFS, 5-6 (10%); and low and very low food security, LVLFS, 2-6 (30%).

Identification and function probing of an antithrombin IIIβ conformation-specific antibody.

Unlabelled: ESSENTIALS: Antithrombin III (AT)β binds heparin with higher affinity than ATα. A conformation-specific antibody against ATβ, TPP2009, was made to investigate ATβ in hemostasis. TPP2009 bound specifically to heparin-ATβ and greatly reduced the anticoagulant effect of AT.

Door to disposition times for obstetric triage visits: Is there a July phenomenon?

The July phenomenon refers to a change in patient outcomes within teaching hospitals with the arrival of new and inexperienced house staff at the start of the academic year (July to June). In our obstetric triage unit we retrospectively evaluated the door to disposition time (DTDT) for 1817 patients who presented across July, December and May of academic years 2009-2010 and 2010-2011. DTDT was examined for three visit levels: non-urgent, urgent and emergent.

Cryptotermes brevis (Isoptera: Kalotermitidae) in the Azores: lessons after 2 yr of monitoring in the Archipelago.

The dispersal flights of West Indian drywood termite, Cryptotermes brevis (Walker) (Isoptera: Kalotermitidae) were surveyed in the major cities of Azores. The sampling device used to estimate termite density consisted of a yellow adhesive trap (size 45 by 24 cm), placed with an artificial or natural light source in a dark attic environment. In addition, data from two other projects were used to improve the knowledge about the geographical distribution of the species.

Evaluation of the activated partial thromboplastin time assay for clinical monitoring of PEGylated recombinant factor VIII (BAY 94-9027) for haemophilia A.

Patients with haemophilia (PWH) are usually monitored by the one-stage activated partial thromboplastin time (aPTT) factor VIII (FVIII) assay. Different aPTT activators may affect clotting time (CT) and FVIII:C levels in patients treated with PEGylated FVIII. To evaluate the characteristics of PEGylated FVIII (BAY 94-9027) in various aPTT clotting assays, and to identify suitable aPTT reagents for monitoring BAY 94-9027 during the treatment of PWH, BAY 94-9027 and World Health Organization (WHO) 8th FVIII standards (WHO-8) were spiked into pooled and individual severe haemophilia A plasma at 1.

Three-dimensional microstructural imaging methods for energy materials.

Advances in the design of materials for energy storage and conversion (i.e., "energy materials") increasingly rely on understanding the dependence of a material's performance and longevity on three-dimensional characteristics of its microstructure.

Baking soda pica associated with rhabdomyolysis and cardiomyopathy in pregnancy.

Background: Pica is a commonly underappreciated disorder in pregnancy that can lead to several complications, including severe metabolic derangements and other adverse outcomes. We report a case of baking soda pica in pregnancy associated with both rhabdomyolysis and cardiomyopathy.

Case: A multigravid woman at 37 weeks of gestation presented with weakness and severe hypokalemia.

Thrombin-cleaved fragments of osteopontin are overexpressed in malignant glial tumors and provide a molecular niche with survival advantage.

Osteopontin (OPN), which is highly expressed in malignant glioblastoma (GBM), possesses inflammatory activity modulated by proteolytic cleavage by thrombin and plasma carboxypeptidase B2 (CPB2) at a highly conserved cleavage site. Full-length OPN (OPN-FL) was elevated in cerebrospinal fluid (CSF) samples from all cancer patients compared with noncancer patients. However, thrombin-cleaved OPN (OPN-R) and thrombin/CPB2-double-cleaved OPN (OPN-L) levels were markedly increased in GBM and non-GBM gliomas compared with systemic cancer and noncancer patients.

The use of galactogogues in the breastfeeding mother.

Objective: To review data regarding the efficacy of galactogogues available in the US to increase breast milk production in postpartum mothers.

Data Sources: Literature was sought using PubMed (1966-June 2012) and EMBASE (1973-June 2012). Search terms included breastfeeding, breast milk, lactation, galactogogue, metoclopramide, oxytocin, fenugreek, milk thistle, silymarin, growth hormone, thyroid releasing hormone, medroxyprogesterone, domperidone, goat's rue, beer, Asparagus racemosus, shatavari, Medicago sativa, alfalfa, Onicus benedictus, blessed thistle, Galega officinalis, brewer's yeast, and herbals.

"Early" versus "late" 23-week infant outcomes.

Objective: To determine whether survival is different in "early" (23(0/7)-23(3/7) weeks) vs "late" (23(4/7)-23(6/7) weeks) infants.

Study Design: Records of 126 consecutive liveborn infants delivered at 23(0/7) to 23(6/7) weeks' gestation from 2001-2010 were examined using the Vermont Oxford Network database. Infants born at 23 0/7 to 23 3/7 weeks were grouped into "early" and those at 23 4/7 to 23 6/7 weeks were "late.

Thrombin generates previously unidentified C5 products that support the terminal complement activation pathway.

The coagulation and complement pathways simultaneously promote homeostasis in response to injury but cause tissue damage when unregulated. Mechanisms by which they cooperate are poorly understood. To delineate their interactions, we studied the effects of thrombin and C5 convertase on C5 in purified and plasma-based systems, measuring release of the anaphylatoxin C5a, and generation of C5b, the initial component of the lytic membrane attack complex.

Stiff person syndrome and pregnancy.

Background: Stiff person syndrome, also known as Moersche-Woltman syndrome, is a debilitating disorder that is rarely seen in the pregnant patient. It is characterized by muscle spasms triggered by startle, voluntary movement, or tactile or emotional stimuli, occurring predominantly in the axial musculature.

Case: A woman diagnosed with stiff person syndrome became pregnant 2 months after her diagnosis.

Safety of the HPV Bivalent and Quadrivalent Vaccines During Pregnancy.

Objective: To evaluate the safety of the human papillomavirus (HPV) bivalent and quadrivalent vaccines in pregnancy.

Data Source: PubMed (1966-August 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, and pregnancy. References were reviewed for relevant information.

Enhanced abdominal aortic aneurysm formation in thrombin-activatable procarboxypeptidase B-deficient mice.

Objective: To determine whether procarboxypeptidase B (pCPB)(-/-) mice are susceptible to accelerated abdominal aortic aneurysm (AAA) development secondary to unregulated OPN-mediated mural inflammation in the absence of CPB inhibition.

Methods And Results: Thrombin/thrombomodulin cleaves thrombin-activatable pCPB or thrombin-activatable fibrinolysis inhibitor, activating CPB, which inhibits the generation of plasmin and inactivates proinflammatory mediators (complement C5a and thrombin-cleaved osteopontin [OPN]). Apolipoprotein E(-/-)OPN(-/-) mice are protected from experimental AAA formation.

What has been learnt from the thrombin-activatable fibrinolysis inhibitor-deficient mouse?

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a circulating zymogen that is activated physiologically by the thrombin/thrombomodulin complex to activated TAFI (TAFIa) which is a basic carboxypeptidase. Substrates include fibrin, leading to a reduction in rate of plasmin generation, and several proinflammatory mediators such as bradykinin, thrombin-cleaved osteopontin and complement factor C5a. TAFI-deficient mice have no phenotype without being challenged and TAFIa appears to play a limited role in physiological fibrinolysis in vivo.

Polyphosphate binds with high affinity to exosite II of thrombin.

Background: Polyphosphate (a linear polymer of inorganic phosphate) is secreted from platelet dense granules, and we recently showed that it accelerates factor V activation by thrombin.

Objective: To examine the interaction of polyphosphate with thrombin.

Methods And Results: Thrombin, but not prothrombin, altered the electrophoretic migration of polyphosphate in gel mobility assays.