The Role of Fibrin Clot Properties and Fibrinogen Nitration in the Pathology of Venous Thromboembolism.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) together comprise the disease state of venous thromboembolism (VTE). Thrombi in the veins of the lower extremities (DVT) can embolize, resulting in complete or partial occlusion of circulation through the pulmonary vasculature (PE). Despite a common etiology between DVT and PE, the cause of embolization remains mostly unknown. Research indicates that fibrin clot structure and functional properties are altered in VTE compared to healthy controls. Whether these properties differ between DVT and PE subjects remains to be determined, and may underscore possible mechanisms of embolization. Inflammation and oxidant production are involved in the pathogenesis of VTE. However, biomarkers documenting these pathways in humans are lacking. Elevated levels of nitrated fibrinogen have been documented during inflammatory and oxidative challenges and may serve as a functional biomarker in VTE. Differences in fibrin clot structure and functional properties between DVT and PE, as well as the role of nitrated fibrinogen as a biomarker of VTE were evaluated in the plasma of subjects presenting with symptoms of VTE to the emergency department at the Hospital of the University of Pennsylvania. Plasma fibrin clots derived from PE subjects showed increased establishment of viscoelastic properties and faster lysis time compared with DVT. The rate and extent of factor XIIIa crosslinking of fibrin were similar between DVT and PE. Clots from PE subjects showed decreased fiber density and no differences in fiber bundling. Together these data suggests that fibrin fibers are formed faster in PE subjects, possibly resulting in earlier lysis, which may lead to instability and embolization. Nitrated fibrinogen levels were elevated in VTE positive compared to VTE negative subjects, with no differences in fibrinogen concentration. Subjects in the highest quartile of nitrated fibrinogen had an increased risk of VTE compared with the lowest quartile. This risk persisted after univariate adjustment for advanced age, active cancer, and recent surgery, but not after multivariate adjustment for all variables. Thus, nitrated fibrinogen is an oxidative risk marker in VTE, providing a novel mechanistic link between oxidant production, inflammation, and VTE

Multiple Exciton Generation for Solar Water Splitting and Ligand Exchange Properties on PbS Quantum Dots

Quantum dots (QDs) are a staple material of various technologies such as solid-state lighting, biomedical imaging, and photovoltaics research largely due to their ease of tunability. However, their full potential remains untapped. The first part of the present study will show how QDs have the potential to yield ultra-high solar water splitting efficiency through a process called multiple exciton generation (MEG), which can multiply a single photon into several excitons. With MEG tandem devices operated under solar concentration, theoretical solar-to-hydrogen efficiencies of > 60% can be achieved, a promising figure that requires improved MEG materials. The second part of this work emphasizes how ligand exchange can be used as a highly versatile tool for 1) producing ligand-induced asymmetry on QD surfaces, which have the potential to enhance MEG, and 2) to produce well-controlled samples for studying interesting photophysical properties of QD-ligand complexes with tetracene derivatives. Asymmetry is induced on QD surfaces by the formation of a Janus-ligand shell on small PbS QDs, a property realized via ligand-binding isotherms and 2-dimensional nuclear magnetic resonance spectroscopy. Furthermore, understanding of ligand exchange was applied to determine that di-carboxylic acid functionalized tetracene ligands form binding motifs in which they are bridging (Pb atoms), hydrogen-bonding, and cross-linking PbS QDs

Untersuchung zellulärer und humoraler Immunparameter bei Patienten mit Plattenepithelkarzinomen im Kopf-/Halsbereich in Abhängigkeit von Tumorstadium und Therapieform

Im Rahmen einer klinische Studie wurden bei Patienten mit Plattenepithelkarzinomen im Kopf­/Halsbereich Lymphozyten­Subpopulationen phänotypisch und funktionell charakteri- siert sowie deren Aktivierungszustand anhand der Bestimmung des Interleukin­2­Titers und der Konzentration von löslichem Interleukin­2­Rezeptor a (sIL­2Ra) im Plasma gemessen. Hierbei interessierte der Einfluß des Tumors bzw. der Therapieformen wie Operation, Che­ mo­, Bestrahlungstherapie und kombinierte Radio­Chemotherapie auf diese immunologischen Parameter. Die Zusammensetzung der Populationen peripherer Blutlymphozyten wird durch die Größe und Malignität des Primärtumors sowie durch Lymphknotenmetastasen beeinflußt. In der An­ fangsphase, bei einer Tumormalignität G1, ist eine starke Reduzierung der LAK­Zellaktivität zu sehen, was mit suppressiven Faktoren, wie zum Beipiel Prostaglandin­E2, abgesondert von Monozyten, in Verbindung gebracht werden könnte. Der Anteil CD3­positiver Zellen ist im G3­Stadium sehr stark erniedrigt und deutet auf eine Herunterregulierung der zu dem CD3­ Komplex gehörenden e­Kette hin. Weiterhin war bei den HNO­Tumorpatienten der Anteil der CD4­Lymphozyten auffällig erniedrigt, während die Zahl der doppeltpositiven CD4 CD8 ­ Zellen sowie die HLA­DR­Werte erhöht war. Einen Monat nach einem operativen Eingriff ließ sich eine starke Zunahme der CD25­ Expression, besonders auf T­Lymphozyten erkennen. Die Chemotherapie mit Cisplatin, Fo­ linsäure, 5­FU, Fortecortin ­ eine sogenannte Polychemotherapie ­ bewirkte eine starke Erhö­ hung der NK­Zellpopulation und eine höhere Expression des CD25­Markers auf NK­Zellen sowie eine Zunahme der LAK­Zellfunktion. Die Veränderung der NK­Zellpopulation ist wahrscheinlich auf den Einsatz von Cisplatin und 5­FU zurückzuführen. Die Bestrahlungsthe­ rapie bewirkte eine signifikante Abnahme der T­Lymphozyten, besonders der CD4­T­ Helferzellen, bei gleichzeitiger Zunahme der CD4 CD8 ­positiven Zellen. B­Zellen sind g­Strahlen sensitiv, so daß unter Bestrahlung ihr Anteil vermindert wird. Die Erhöhung der NK­Zellpopulation ist wahrscheinlich auf eine Radioresistenz dieser Lymphozytensubpopula­ tion zurückzuführen. Die Radio­Chemotherapie beinhaltet drei Zyklen mit einem Zytostatika­ gemisch: Cisplatin, 5­FU, Folinsäure, Dexametason, Rescuvolin und Fortecortin und an­ schließender Behandlung mit g­Strahlen. Die Daten der vorliegenden Studie zeigen deutlich, daß es unter dieser Radio­Chemotherapie zu einem signifikanten Abfall der CD3­ und CD2­positiven Zellen, besonders der zytotoxi­ schen T­Zellpopulation, sowie zu einer Erhöhung der CD25­exprimierenden Zellen kommt. Die Beziehungen der Zellen untereinander sind unter Operation, Betrahlung­ und Radio­ Chemotherapie nicht verändert, die Chemotherapie verursacht jedoch vermutlich ein Un­ gleichgewicht zwischen T­Helferzellen und Makrophagen bezüglich der Vermehrung von NK­Zellen. Bei Patienten ohne Therapie kam es zu einer Abnahme der CD3­positiven Zellen. Dies unterstützt die Hypothese der Herunterregulierung der e­Kette des CD3­Komplexes unter Tumoreinwirkung. Die Ergebnisse zeigen weiter, daß die alleinige Bestimmung des Interleukin­2 Proteins keine Auskunft über die Wirkung des Tumors auf die Sezernierung dieses Peptids bei einer Tumorlokalisation im Gaumen­ und Zungenbereich gibt. Erst im Verlauf der Erkrankung können Änderungen durch virale Infektionen und der Einfluß verschiedener Therapiemodali­ täten beobachtet werden. Die Konzentration von sIL­2Ra verhielt sich proportional zur Tumorgröße. Dies unterstützt die Hypothese, daß dieser Rezeptor eher vom Tumor abstammt und nicht von den infiltrierten Lymphozyten. Die Konzentration von sIL­2Ra im Plasma war abhängig von der Therapieart. Sie erreichte wesentlich höhere Werte bei Tumorpatienten im Vergleich zu den Probanden. Der niedrigste Spiegel bei Patienten fand sich bei Bestrahlungstherapie (Median = 840 U/ml), die höchsten Werte bei Patienten mit Chemotherapie (Median = 1400 U/ml). Infiltrierende CD3 ­Lymphozyten im Primärtumor, identifiziert mit einen Antikörper gegen die e­Ketten, sind im Vergleich zu metastasierten Lymphknoten signifikant erniedrigt. Unter­ suchungen der peripheren Blutlymphozyten bei Patienten mit Primärtumor ergaben eine signi­ fikante Erhöhung der CD3­Populationen bei gleichzeitiger Erniedrigung des Anteils CD45­ positiver Zellen. Es bestand für CD45­positive Zellen ein signifikanter Zusammenhang zwi­ schen peripheren Blutlymphozyten und tumorinfiltrierenden Lymphozyten

Insulin gene polymorphisms in type I diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

Background: Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from ß-cell autoimmunity. Methods: We investigated the role of the -2221Msp(C/T) and -23HphI(A/T) polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317), Addison´s disease (AD, n = 107) or Hashimoto´s thyroiditis (HT, n = 61)], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62) as well as in healthy controls (HC, n = 275). Results: T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T) and "AA" -23HphI(A/T) polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively). The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion: We demonstrate that the allele "C" of the -2221Msp(C/T) and "A" -23HphI(A/T) insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II

Efecto sinérgico antibacteriano in vitro del extracto acuoso del ajo (allium sativum l.) y del extracto etanólico de las hojas de carqueja (baccharis trimera l.) en cepas escherichia coli 0104:h4

La presente investigación tuvo como objetivo determinar el efecto sinérgico antibacteriano in vitro del extracto acuoso del Ajo (Allium sativum L.) y del extracto etanólico de las hojas de Carqueja (Baccharis trimera L.) en cepas de Escherichia coli 0104:H4 a diversas concentraciones, para la prueba experimental se utilizó el método Kirby-Bauer (Método de difusión en agar). Gentamicina como control positivo de las bacterias. Los extractos se obtuvieron mediante el proceso de maceración (Método de Olga Lock Sing de Ugaz), en la cual se usaron las hojas deshidratadas y micropulverizadas de Carqueja (Baccharis trimera L.) y bulbos de Ajo (Allium sativum L.), durante siete días y la determinación de metabolitos segundarios se llevó a cabo mediante la marcha fitoquímica. La actividad antimicrobiana se evaluó mediante el método de Difusión en Agar frente a Escherichia coli 0104:H4. Como resultados de la investigación se evidenció que el extracto acuoso de Ajo (Allium sativum L.) al 20 por ciento presentó 10.2mm de halo de inhibición, el extracto etanólico de las hojas de Carqueja (Baccharis trimera L.) al 20 por ciento 2.2mm halo de inhibición, el efecto Sinérgico antibacteriano de ambas plantas al 20 por ciento presento 17.8mm de halo de inhibición frente a dicha bacteria mientras que el grupo control tuvo 19.20mm de halo de inhibiciónThe present investigation had the objective to determine the in vitro antibacterial synergistic effect of the aqueous extract of Garlic (Allium sativum L.) and the ethanol extract of the leaves of Carqueja (Baccharis trimera L.) in Escherichia coli 0104:H4 strains at various concentrations for the experimental test was used Kirby-Bauer method (agar diffusion method). Gentamicin as a positive control of bacteria. The extracts were obtained by the Maceration process (Olaz Lock Sing Method of Ugaz), in which the dehydrated and micropulverized leaves of Carqueja (Baccharis trimera) and bulbs of Ajo (Allium sativum L.) were used for seven days and determination of secondary metabolites was carried out by the Phytochemical March. The antimicrobial activity was evaluated using the Agar Diffusion method against Escherichia coli 0104:H4. As results of the investigation it was evidenced that the aqueous extract of Ajo (Allium sativum L.) at 20 percent presented 10.2 mm of inhibition halo, extract ethanolic effect of the leaves of Carqueja (Baccharis trimera L.) to 20 percent 2.2 mm inhibition halo, the synergistic antibacterial effect of both plants to 20 percent presented 17.8 mm of halo inhibition against said bacterium while the control group had 19.20 mm of inhibition hal

Nitrated Fibrinogen is A Biomarker of Oxidative Stress in Venous Thromboembolism

The pathogenesis of venous thromboembolism (VTE) is linked to inflammation and oxidant production, although specific markers for these pathways with pathological relevance to VTE have not been explored. The coagulant protein fibrinogen is posttranslationally modified by nitric oxide-derived oxidants to nitrated fibrinogen in both acute and chronic inflammatory states. Therefore, nitrated fibrinogen may serve as a marker of inflammation and oxidative stress in VTE. To test this hypothesis we enrolled subjects (n=251) presenting with suspected VTE at the University of Pennsylvania Hospital emergency department, 50 (19.9%) of whom were positive by imaging or 90-day follow-up. Mean nitrated fibrinogen was elevated in VTE-positive (62.7 nM, 95% CI 56.6–68.8) compared to VTE-negative patients (54.2 nM, 95% CI 51.4–57.1; P\u3c0.01). Patients in the highest quartile of nitrated fibrinogen had an increased risk of VTE compared with patients in the lowest quartile (OR 3.30; 95% CI 1.25–8.68; P\u3c0.05). This risk persisted after univariate adjustment for age, active cancer, and recent surgery, but not after multivariate adjustment. Mean fibrinogen levels measured either by the Clauss assay or by ELISA were not different between VTE-negative and VTE-positive patients. These data indicate that nitrated fibrinogen is an oxidative risk marker in VTE, providing a novel mechanistic link between oxidant production, inflammation, and VTE

Closed Loop Wind Tunnel

A subsonic wind tunnel was designed and built for the University of Texas at Tyler laboratories as a senior design project. The students tested different models and matched their theoretical calculations to the experimental wind tunnel values. The wind tunnels components are made from half inch Birch Plywood because of its accessibility and durability. The test section has a plexiglass door for a clear visual of the test model. The tunnel is 106 inches long with supports that allow us to connect a return section made by another senior design group (HEC24) making it a closed loop tunnel. The design consists of four major sections connected by removable bolts for ease of assembly, disassembly, and transport. The fan is exhaust and is 2418 CFM, 400W, and has a speed controller. Load cells and a DAQ (Data acquisition tool) are used to measure the drag and lift force in LabVIEW. Load cells are mounted on a 3D printed slider mechanism allowing movement in the x direction for drag. Both load cells rated to measure force between 0 and 5 kgf in tension and the vertical tension rod measuring lift force is also the airfoil mount. According to computational fluid dynamic simulations, wind velocities of at least 50 MPH occur in the test chamber. From testing, the max wind speed in the test chamber is 22 mph. More experimental data coming soon when purchase orders arrive (manometer) and the LabVIEW is fully functional. Although the final assembly is complete, further testing needs to be done to calculate for different testing models. Computational fluid dynamics simulations were performed to reenact what the test model should be experiencing in the wind tunnel. These simulations provide theoretical data that can be compared to the actual data once testing is complete

Money Follows the Person: Transitioning Nursing Home Residents into the Community

Introduction. Research has shown that admission to nursing homes (NH) is associated with decline in several measures of well-being; transitioning out of a NH into the community is a positive predictor for quality of life. Currently, the State of Vermont offers several housing options for Medicaid eligible NH residents; however, there are very few opportunities to fully integrate into the communityhttps://scholarworks.uvm.edu/comphp_gallery/1090/thumbnail.jp

Stress-induced O-GlcNAcylation: an adaptive process of injured cells

In the 30 years, since the discovery of nucleocytoplasmic glycosylation, O-GlcNAc has been implicated in regulating cellular processes as diverse as protein folding, localization, degradation, activity, post-translational modifications, and interactions. The cell co-ordinates these molecular events, on thousands of cellular proteins, in concert with environmental and physiological cues to fine-tune epigenetics, transcription, translation, signal transduction, cell cycle, and metabolism. The cellular stress response is no exception: diverse forms of injury result in dynamic changes to the O-GlcNAc subproteome that promote survival. In this review, we discuss the biosynthesis of O-GlcNAc, the mechanisms by which O-GlcNAc promotes cytoprotection, and the clinical significance of these data