Characterization of Left-Ventricular Thrombus Formation Using High Frequency Ultrasound

Heart failure is a leading cause of death in the United States, and cardiac thrombus, a common morbidity associated with heart failure, significantly increases a patient’s risk of embolic events. The objective of this project is to characterize left-ventricular (LV) thrombus development using high frequency ultrasound imaging in a murine model. C57BL/6J wild-type mice (n=6) were injected intraperitoneally with iron dextran five times a week for six weeks to increase oxidative stress in the heart. Granulocyte-colony stimulating factor (G-CSF) was subcutaneously injected daily during the second week to initiate stem cell migration and stimulate endothelial cell activation, thus increasing the hypercoagulability state of the blood. A high-frequency, small animal ultrasound system (Vevo2100, VisualSonics FUJIFILM Inc.) and a 40 MHz central frequency transducer were used to track LV thrombus progression and evaluate LV function weekly. Four out of six mice developed thrombus, but no significant differences in LV performance were observed when compared to mice that did not form a thrombus. Further investigation is necessary to study the role of attenuated heart function on thrombus formation. Future work will incorporate a murine model of myocardial infarction to investigate if a severely compromised heart increases the risk of or accelerates LV thrombus formation. This study will aid in identifying patients who are predisposed to thrombus formation following a heart attack, leading to more effective prevention and treatment methods

Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

Background Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. Methods We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Results Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB’s atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Conclusions Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed

Neuromuscular synaptic transmission in aged ganglioside-deficient mice

Gangliosides are sialylated glycosphingolipids that are present in high density on neuronal membranes, especially at synapses, where they are assumed to play functional or modulating roles. Mice lacking GM2/GD2-synthase express only the simple gangliosides GD3 and GM3 and develop progressive motor behaviour deficits upon ageing, apparently due to failing complex ganglioside-dependent maintenance and/or repair processes or, alternatively, toxic GM3/GD3 accumulation. We investigated the function of neuromuscular junctions (NMJs) of aged (>9 month-old) GM2/GD2-synthase null-mutant mice, because synaptic dysfunction might develop with age and could potentially contribute to the late-onset motor phenotype. In addition, we studied NMJs of old mice lacking GD3-synthase (expressing only O- and a-series gangliosides), which do not show an overt neurological phenotype but may develop subclinical synaptic deficits. Detailed electrophysiological analyses showed subtle changes in presynaptic neurotransmitter release. Acetylcholine release at 40 Hz nerve stimulation at aged GM2/GD2-synthase null-mutant NMJs ran down slightly more pronounced than at wild-type NMJs, and spontaneous acetylcholine release rate at GD3-synthase null-mutant NMJs was somewhat higher than at wild-type, selectively at 25 degrees C bath temperature. Interestingly, we observed faster kinetics of postsynaptic electrophysiological responses at aged GD3-synthase null-mutant NMJs, not previously seen by us at NMJs of young GD3-synthase null-mutants or other types of (aged or young) ganglioside-deficient mice. These kinetic changes might reflect a change in postsynaptic acetylcholine receptor behaviour. Our data indicate that it is highly unlikely that transmission failure at NMJs contributes to the progressive motor defects of aged GM2/GD2-synthase null-mutants and that, despite some kinetic changes of synaptic signals, neuromuscular transmission remains successful in aged GD3-synthase null-mutant mice. Apparently, mutual redundancy of the different gangliosides in supporting presynaptic function, as observed previously by us in young mice, remains adequate upon ageing or, alternatively, gangliosides have only relatively little direct impact on neuromuscular synaptic function, even in aged mice. (C) 2009 Elsevier Inc. All rights reserve

Reaction Between Nitrogen and Spinel in Chromium

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66029/1/j.1151-2916.1968.tb15671.x.pd

Immunological Outcomes of Allergen-Specific Immunotherapy in Food Allergy

IgE-mediated food allergies are caused by adverse immunologic responses to food proteins. Allergic reactions may present locally in different tissues such as skin, gastrointestinal and respiratory tract and may result is systemic life-threatening reactions. During the last decades, the prevalence of food allergies has significantly increased throughout the world, and considerable efforts have been made to develop curative therapies. Food allergen immunotherapy is a promising therapeutic approach for food allergies that is based on the administration of increasing doses of culprit food extracts, or purified, and sometime modified food allergens. Different routes of administration for food allergen immunotherapy including oral, sublingual, epicutaneous and subcutaneous regimens are being evaluated. Although a wealth of data from clinical food allergen immunotherapy trials has been obtained, a lack of consistency in assessed clinical and immunological outcome measures presents a major hurdle for evaluating these new treatments. Coordinated efforts are needed to establish standardized outcome measures to be applied in food allergy immunotherapy studies, allowing for better harmonization of data and setting the standards for the future research. Several immunological parameters have been measured in food allergen immunotherapy, including allergen-specific immunoglobulin levels, basophil activation, cytokines, and other soluble biomarkers, T cell and B cell responses and skin prick tests. In this review we discuss different immunological parameters and assess their applicability as potential outcome measures for food allergen immunotherapy that may be included in such a standardized set of outcome measures

Stepwise approach towards adoption of allergen immunotherapy for allergic rhinitis and asthma patients in daily practice in Belgium : a BelSACI-Abeforcal-EUFOREA statement

Allergic rhinitis (AR) affects 23-30% of the European population with equal prevalence reported in Belgium. Despite guidelines on the correct use of effective treatment, up to 40% of AR patients remain uncontrolled. Allergen immunotherapy (AIT) has been shown to improve the level of control up to 84% of patients being controlled by AIT. Recently, new guidelines for AIT have been published, supporting the clinical evidence for effectiveness of various subcutaneous and sublingual products for AIT in patients who are allergic to airborne allergens. AIT in AR patients not only reduces nasal and/or ocular symptoms but also induces tolerance and has preventive potential. Adoption of AIT into daily clinical practice in Belgium and other European countries is hampered primarily by reimbursement issues of each of the single products but also by several patient-and physician-related factors. Patients need to be better informed about the effectiveness of AIT and the different routes of administration of AIT. Physicians dealing with AR patients should inform patients on tolerance-inducing effects of AIT and are in the need of a harmonized and practical guide that supports them in selecting eligible patients for AIT, in choosing evidence-based AIT products and in following treatment protocols with proven efficacy. Therefore, a stepwise and holistic approach is needed for better adoption of AIT in the real-life setting in Belgium

Is an Impacted Morselized Graft in a Cage an Alternative for Reconstructing Segmental Diaphyseal Defects?

Large diaphyseal bone defects often are reconstructed with large structural allografts but these are prone to major complications. We therefore asked whether impacted morselized bone graft could be an alternative for a massive structural graft in reconstructing large diaphyseal bone defects. Defects in the femora of goats were reconstructed using a cage filled with firmly impacted morselized allograft or with a structural cortical autograft (n = 6 in both groups). All reconstructions were stabilized with an intramedullary nail. The goats were allowed full weightbearing. In all reconstructions, the grafts united radiographically. Mechanical torsion strength of the femur with the cage and structural cortical graft reconstructions were 66.6% and 60.3%, respectively, as compared with the contralateral femurs after 6 months. Histologically, the impacted morselized graft was replaced completely by new viable bone. In the structural graft group, a mixture of new and necrotic bone was present. Incorporation of the impacted graft into new viable bone suggests this type of reconstruction may be safer than reconstruction with a structural graft in which creeping substitution results in a mixture of viable and necrotic bone that can fracture. The data suggest that a cage filled with a loaded morselized graft could be an alternative for the massive cortical graft in reconstruction of large diaphyseal defects in an animal model