The central role of endothelium in hereditary angioedema due to C1 inhibitor deficiency

An impairment of the endothelial barrier function underlies a wide spectrum of pathological conditions. Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) can be considered the \u201cpathophysiological and clinical paradigm\u201d of Paroxysmal Permeability Diseases (PPDs), conditions characterized by recurrent transient primitively functional alteration of the endothelial sieving properties, not due to inflammatory-ischemic-degenerative injury and completely reversible after the acute flare. It is a rare yet probably still underdiagnosed disease which presents with localized, non-pitting swelling of the skin and submucosal tissues of the upper respiratory and gastrointestinal tracts, without significant wheals or pruritus. The present review addresses the pathophysiology of C1-INH-HAE with a focus on the crucial role of the endothelium during contact and kallikrein/kinin system (CAS and KKS) activation, currently available and emerging biomarkers, methods applied to get new insights into the mechanisms underlying the disease (2D, 3D and in vivo systems), new promising investigation techniques (autonomic nervous system analysis, capillaroscopy, flow-mediated dilation method, non-invasive finger plethysmography). Hints are given to the binding of C1-INH to endothelial cells. Finally, crucial issues as the local vs systemic nature of CAS/KKS activation, the episodic nature of attacks vs constant C1-INH deficiency, pros and cons as well as future perspectives of available methodologies are briefly discussed

Focused and Deep Brain Magnetic Stimulation Using New Coil Design in Mice

Deep brain transcranial magnetic stimulation (TMS) offers promising treatment for neurological disorders that originate from deeper regions of the brain, such as Parkinson\u27s disease. Coils designed for the human head need significant redesigning to stimulate selective regions of the mouse brain for advanced TMS therapy analysis. We report a focused and deep brain TMS coil for mice that is based on a two coil configuration similar to the \u27Halo coil\u27. A heterogeneous MRI derived head model of mouse was used to obtain an electric field of about 150 V/m in selective deeper regions of the brain. Focality of stimulation was quantified using the ratio of half value volume to half value of depth of electric field. A prototype of the final coil design was fabricated and characterized to compare simulated and physical magnetic field profiles

A New Troodontid Theropod Dinosaur from the Lower Cretaceous of Utah

BACKGROUND: The theropod dinosaur family Troodontidae is known from the Upper Jurassic, Lower Cretaceous, and Upper Cretaceous of Asia and from the Upper Jurassic and Upper Cretaceous of North America. Before now no undisputed troodontids from North America have been reported from the Early Cretaceous. METHODOLOGY/PRINCIPAL FINDINGS: Herein we describe a theropod maxilla from the Lower Cretaceous Cedar Mountain Formation of Utah and perform a phylogenetic analysis to determine its phylogenetic position. The specimen is distinctive enough to assign to a new genus and species, Geminiraptor suarezarum. Phylogenetic analysis places G. suarezarum within Troodontidae in an unresolved polytomy with Mei, Byronosaurus, Sinornithoides, Sinusonasus, and Troodon+(Saurornithoides+Zanabazar). Geminiraptor suarezarum uniquely exhibits extreme pneumatic inflation of the maxilla internal to the antorbital fossa such that the anterior maxilla has a triangular cross-section. Unlike troodontids more closely related to Troodon, G. suarezarum exhibits bony septa between the dental alveoli and a promaxillary foramen that is visible in lateral view. CONCLUSIONS/SIGNIFICANCE: This is the first report of a North American troodontid from the Lower Cretaceous. It therefore contributes to a fuller understanding of troodontid biogeography through time. It also adds to the known dinosaurian fauna of the Cedar Mountain Formation

The impact of puberty on the onset, frequency, location, and severity of attacks in hereditary angioedema due to C1-inhibitor deficiency: A survey from the Italian Network for Hereditary and Acquired Angioedema (ITACA)

Introduction. Hereditary angioedema due to C1-inhibitor deficiency is influenced by hormonal factors, with a more severe course of disease in women. Our study aims to deepen the impact of puberty on onset, frequency, location and severity of attacks.MethodsRetrospective data were collected through a semi-structured questionnaire and shared by 10 Italian reference centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA).ResultsThe proportion of symptomatic patients increased significantly after puberty (98.2% vs 83.9%, p=0.002 in males; 96.3% vs 68,4%, p<0.001 in females); the monthly mean of acute attacks was significantly higher after puberty, and this occurred both in females (median (IQR) = 0.41(2) in the three years before puberty vs 2(2.17) in the three years after, p<0.001) and in males (1(1.92) vs 1.25(1.56) respectively, p<0.001). The increase was greater in females. No significant differences were detected in attack location before and after puberty.DiscussionOverall, our study confirms previous reports on a more severe phenotype in the female gender. Puberty predisposes to increased numbers of angioedema attacks, in particular in female patients

Tierra Grande: Journal of the Real Estate Center at Texas A&M University

Quarterly journal providing information related to various aspects of real estate buying and ownership

Tierra Grande: Journal of the Real Estate Center at Texas A&M University

Quarterly journal providing information related to various aspects of real estate buying and ownership

Antigenic Characterization of H3 Subtypes of Avian Influenza A Viruses from North America

Besides humans, H3 subtypes of influenza A viruses (IAVs) can infect various animal hosts, including avian, swine, equine, canine, and sea mammal species. These H3 viruses are both antigenically and genetically diverse. Here, we characterized the antigenic diversity of contemporary H3 avian IAVs recovered from migratory birds in North America. Hemagglutination inhibition (HI) assays were performed on 37 H3 isolates of avian IAVs recovered from 2007 to 2011 using generated reference chicken sera. These isolates were recovered from samples taken in the Atlantic, Mississippi, Central, and Pacific waterfowl migration flyways. Antisera to all the tested H3 isolates cross-reacted with each other and, to a lesser extent, with those to H3 canine and H3 equine IAVs. Antigenic cartography showed that the largest antigenic distance among the 37 avian IAVs is about four units, and each unit corresponds to a 2 log 2 difference in the HI titer. However, none of the tested H3 IAVs cross-reacted with ferret sera derived from contemporary swine and human IAVs. Our results showed that the H3 avian IAVs we tested lacked significant antigenic diversity, and these viruses were antigenically different from those circulating in swine and human populations. This suggests that H3 avian IAVs in North American waterfowl are antigenically relatively stable. Además de infectar a los seres humanos, los subtipos H3 del virus de la influenza A (IAVs) pueden infectar a varios huéspedes animales, incluyendo aves, porcinos, equinos, caninos, y especies de mamíferos marinos. Estos virus H3 son tanto antigénica y genéticamente diversos. En este estudio, se caracterizó la diversidad antigénica de virus H3 contemporáneos recuperados de aves migratorias en América del Norte. Se realizaron pruebas de inhibición de la hemaglutinación (HI) en 37 H3 aislamientos de origen aviar recuperados de 2007 a 2011 usando sueros de pollo de referencia. Estos aislamientos fueron recuperados de las muestras tomadas de las rutas migratorias de aves acuáticas del Atlántico, Mississippi, Centro y del Pacífico. Los antisueros de todos los aislamientos H3 analizados mostraron reacciones cruzadas entre sí y en menor medida, con aquellos virus H3 de origen canino y equino. La cartografía antigénica demostró que la mayor distancia antigénica entre los 37 virus de este tipo de aves es de aproximadamente cuatro unidades, y cada unidad corresponde a una diferencia de dos logaritmos en el título de inhibición de la hemaglutinación. Sin embargo, ninguno de los virus H3 de este tipo mostró reacción cruzada con sueros de hurón específicos para virus de cerdos y humanos contemporáneos. Estos resultados mostraron que los virus H3 de origen aviar que se analizaron carecían de diversidad antigénica significativa y estos virus fueron antigénicamente diferentes de las que circulan en poblaciones de cerdos y de humanos. Esto sugiere que los virus H3 de aves acuáticas de América del Norte son relativamente estables antigénicamente

Tierra Grande: Journal of the Real Estate Center at Texas A&M University

Quarterly journal providing information related to various aspects of real estate buying and ownership

Somatic MED12 mutations are associated with poor prognosis markers in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. We performed systematic database search and identified highly specific MED12 mutations in CLL patients. To study this further, we collected three independent sample series comprising over 700 CLL samples and screened MED12 exons 1 and 2 by direct sequencing. Mutations were identified at significant frequency in all three series with a combined mutation frequency of 5.2% (37/709). Positive mutation status was found to be associated with unmutated IGHV and ZAP70 expression, which are well-known poor prognosis markers in CLL. Our results recognize CLL as the first extrauterine cancer type where 5'terminus of MED12 is mutated at significant frequency. Functional analyses have shown that these mutations lead to dissociation of Cyclin C-CDK8/19 from the core Mediator and to the loss of Mediator-associated CDK kinase activity. Additional studies on the role of MED12 mutation status as a putative prognostic factor as well as mutations' exact tumorigenic mechanism in CLL are warranted.Peer reviewe