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Background Pineoblastoma (PB) is a rare malignant brain tumor originating in the pineal gland. Here, we provide a comprehensive epidemiological analysis of PB in the United States from 2000 to 2017. Methods Data on 1133 patients w...
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Background Pineoblastoma (PB) is a rare malignant brain tumor originating in the pineal gland. Here, we provide a comprehensive epidemiological analysis of PB in the United States from 2000 to 2017. Methods Data on 1133 patients with PB were acquired from the Central Brain Tumor Registry of the United States, in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, from 2000 to 2017. Age-adjusted incidence rates (AAIRs) per 100 000 and incidence rate ratios (IRRs) were reported for age, sex, race, and ethnicity. Using the National Program of Cancer Registries survival database, median survival and hazard ratios (HRs) were evaluated for overall survival from 2001 to 2016. Results Incidence was highest in ages 0-4 years (AAIR: 0.049, 95% CI: 0.042-0.056), decreasing as age increased. Incidence was higher among patients who are Black compared to patients who are White (IRR: 1.71, 95% CI: 1.48-1.98, P < .001), and was impacted by age at diagnosis, with Black-to-White incidence highest in children ages 5-9 years (IRR: 3.43, 95% CI: 2.36-4.94, P < .001). Overall survival was lower for males (HR: 1.39, 95% CI: 1.07-1.79, P = .013). All age groups, excluding those over 40, had improved survival compared to ages 0-4 years. Those who received surgical intervention had better survival compared to those who did not receive surgical treatment. Conclusion PB incidence is highest among children and patients who are Black, and there may be a potential interaction between these factors. Survival is worse among males, young children, and elderly adults, and those who received no surgery. Comprehensive, population-based statistics provide critical information on PB characteristics that could be useful in impacting patient care and prognosis.
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Forty-one different polymer samples, collectively called the Polymer Erosion and Contamination Experiment (PEACE) Polymers, were exposed to the low Earth orbit (LEO) environment on the exterior of the International Space Station (...
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Forty-one different polymer samples, collectively called the Polymer Erosion and Contamination Experiment (PEACE) Polymers, were exposed to the low Earth orbit (LEO) environment on the exterior of the International Space Station (ISS) for nearly 4 years as part of Materials International Space Station Experiment 2 (MISSE 2). The objective of the PEACE Polymers experiment was to determine the atomic oxygen erosion yield of a wide variety of polymeric materials after long-term exposure to the space environment. The polymers range from those commonly used for spacecraft applications, such as Teflon(R) FEP, to more recently developed polymers, such as high temperature polyimide PMR (polymerization of monomer reactants). Additional polymers were included to explore erosion yield dependence upon chemical composition. The MISSE PEACE Polymers experiment was flown in MISSE Passive Experiment Carrier 2 (PEC 2), tray 1, attached to the exterior of the ISS Quest Airlock. It was exposed to atomic oxygen along with solar and charged particle radiation. MISSE 2 was successfully retrieved during a space walk on July 30, 2005 during Discovery's STS-114 Return to Flight mission. Details on the specific polymers flown, flight sample fabrication, pre-flight and post-flight characterization techniques, and atomic oxygen fluence calculations are discussed along with a summary of the atomic oxygen erosion yield results. The MISSE 2 PEACE Polymers experiment is unique because it has the widest variety of polymers flown in LEO for a long duration and was exposed to an unusually clean LEO spacecraft environment. This experiment provides extremely valuable erosion yield data for spacecraft design purposes.
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A versatile one-pot synthetic platform for the preparation of a range of functionalized 2,6-bisbenzimidazolylpyridine (Bip) derivatives is presented. This protocol significantly reduces the cost and time of previous synthetic rout...
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A versatile one-pot synthetic platform for the preparation of a range of functionalized 2,6-bisbenzimidazolylpyridine (Bip) derivatives is presented. This protocol significantly reduces the cost and time of previous synthetic routes, while facilitating scale up to multi-gram quantities in good yields (63-90%). The previous synthetic methodology was improved through judicious choice of the reducing agent and solvent in the reduction/ring-closing step. Via this platform, we also successfully accessed a mesogenic Bip ligand and herein report initial liquid crystalline properties of this derivative. (C) 2008 Elsevier Ltd. All rights reserved.
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Background: Fibrin-rich clot formation in thrombo-occlusive pathologies is currently treated by systemic administration of plasminogen activators (e.g. tPA), to convert fibrin-associated plasminogen to plasmin for fibrinolytic act...
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Background: Fibrin-rich clot formation in thrombo-occlusive pathologies is currently treated by systemic administration of plasminogen activators (e.g. tPA), to convert fibrin-associated plasminogen to plasmin for fibrinolytic action. However, this conver-sion is not restricted to clot site only but also occurs on circulating plasminogen, causing systemic fibrinogenolysis and bleeding risks. To address this, past research has explored tPA delivery using clot-targeted nanoparticles.Objectives: We designed a nanomedicine system that can (1) target clots via binding to activated platelets and fibrin, (2) package plasmin instead of tPA as a direct fibrinolytic agent, and (3) release this plasmin triggered by thrombin for clot-localized action. Methods: Clot-targeted thrombin-cleavable nanoparticles (CTNPs) were manufactured using self-assembly of peptide-lipid conjugates. Plasmin loading and its thrombin-triggered release from CTNPs were characterized by UV-visible spectroscopy. CTNP-targeting to clots under flow was studied using microfluidics. Fibrinolytic effect of CTNP-delivered plasmin was studied in vitro using BioFlux imaging and D-dimer anal-ysis and in vivo in a zebrafish thrombosis model.Results: Plasmin-loaded CTNPs significantly bound to clots under shear flow and showed thrombin-triggered enhanced release of plasmin. BioFlux studies confirmed that thrombin-triggered plasmin released from CTNPs rendered fibrinolysis similar to free plasmin, further corroborated by D-dimer analysis. In the zebrafish model, CTNP-delivered plasmin accelerated time-to-recanalization, or completely prevented occlu-sion when infused before thrombus formation.Conclusion: Considering that the very short circulation half-life (<1 second) of plasmin prevents its systemic use but also makes it safer without off-target drug effects, clot-targeted delivery of plasmin using CTNPs can enable safer and more efficacious fibri-nolytic therapy.
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Large chromosomal aberrations occur commonly during development, resulting in complex and multisystem diseases. In spite of this high frequency, there are currently no means for correcting these disorders due to their complexity a...
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Large chromosomal aberrations occur commonly during development, resulting in complex and multisystem diseases. In spite of this high frequency, there are currently no means for correcting these disorders due to their complexity and involvement of multiple genes. Recently, several new approaches have been devised that target whole chromosomes in vitro, which are collectively referred to as Chromosome Therapies. These include silencing and selection for loss of the extra chromosome in trisomies, promotion of euploidy in an aneuploid culture, and forced loss and replacement of a chromosome. Here, we provide a review of Chromosome Therapy, and discuss potential directions for these methods clinically, as well as research applications and cellular models that can be made using these technologies. (c) 2016 Wiley Periodicals, Inc.
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Occlusive thrombosis is a central pathological event in heart attack, stroke, thromboembolism, etc. Therefore, pharmacological thrombolysis or anticoagulation is used for treating these diseases. However, systemic administration o...
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Occlusive thrombosis is a central pathological event in heart attack, stroke, thromboembolism, etc. Therefore, pharmacological thrombolysis or anticoagulation is used for treating these diseases. However, systemic administration of such drugs causes hemorrhagic side-effects. Therefore, there is significant clinical interest in strategies for enhanced drug delivery to clots while minimizing systemic effects. One such strategy is by using drug-carrying nanoparticles surface-decorated with clot-binding ligands. Efforts in this area have focused on binding to singular targets in clots, e.g. platelets, fibrin, collagen, vWF or endothelium. Targeting vWF, collagen or endothelium maybe sub-optimal since in vivo these entities will be rapidly covered by platelets and leukocytes, and thus inaccessible for sufficient nanoparticle binding. In contrast, activated platelets and fibrin are majorly accessible for particle-binding, but their relative distribution in clots is highly heterogeneous. We hypothesized that combination-targeting of 'platelets + fibrin' will render higher clot-binding efficacy of nanoparticles, compared to targeting platelets or fibrin singularly. To test this, we utilized liposomes as model nanoparticles, decorated their surface with platelet-binding peptides (PBP) or fibrin-binding peptides (FBP) or combination (PBP + FBP) at controlled compositions, and evaluated their binding to human blood clots in vitro and in a mouse thrombosis model in vivo. In parallel, we developed a computational model of nanoparticle binding to single versus combination entities in clots. Our studies indicate that combination targeting of 'platelets + fibrin' enhances the clot-anchorage efficacy of nanoparticles while utilizing lower ligand densities, compared to targeting platelets or fibrin only. These findings provide important insights for vascular nanomedicine design.
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Plasma-based treatment is a prevalent strategy to alter biological response and enhance biomaterial coating quality at the surfaces of biomedical devices and implants, especially polymeric materials. Plasma, an ionized gas, is oft...
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Plasma-based treatment is a prevalent strategy to alter biological response and enhance biomaterial coating quality at the surfaces of biomedical devices and implants, especially polymeric materials. Plasma, an ionized gas, is often thought to have negligible effects on the bulk properties of prosthetic substrates given that it alters the surface chemistry on only the outermost few nanometers of material. However, no studies to date have systematically explored the effects of plasma exposure on both the surface and bulk properties of a biomaterial. This work examines the time-dependent effects of a nonthermal plasma on the surface and bulk (i.e. mechanical) properties of polymeric implants, specifically polypropylene surgical meshes and sutures. Findings suggest that plasma exposure improved resistance to fibrinogen adsorption and Escherichia coli attachment, and promoted mammalian fibroblast attachment, although increased duration of exposure resulted in a state of diminishing returns. At the same time, it was observed that plasma exposure can be detrimental to the material properties of individual filaments (i.e. sutures), as well as the structural characteristics of knitted meshes, with longer exposures resulting in further embrittlement and larger changes in anisotropic behavior. Though there are few guidelines regarding appropriate mechanical properties of surgical textiles, the results from this investigation imply that there are ultimate exposure limits for plasma-based treatments of polymeric implant materials when structural properties must be preserved, and that the effects of a plasma on a given biomaterial should be examined carefully before translation to a clinical scenario.
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Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects ...
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Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects hemostatic capabilities and causes substantial hemorrhagic risks. This issue can be potentially resolved by designing technologies that allow thrombus-targeted delivery and site-specific action of thrombolytic drugs. To this end, leveraging a liposomal platform, we have developed platelet microparticle (PMP)-inspired nanovesicles (PMINs), that can protect encapsulated thrombolytic drugs in circulation to prevent off-target uptake and action, anchor actively onto thrombus via PMP-relevant molecular mechanisms and allow drug release via thrombus-relevant enzymatic trigger. Specifically, the PMINs can anchor onto thrombus via heteromultivalent ligand-mediated binding to active platelet integrin GPIlb-Illa and P-selectin, and release the thrombolytic payload due to vesicle destabilization triggered by clot-relevant enzyme phospholipase-A2. Here we report on the evaluation of clot-targeting efficacy, lipase-triggered drug release and resultant thrombolytic capability of the PMINs in vitro, and subsequently demonstrate that intravenous delivery of thrombolytic-loaded PMINs can render targeted fibrinolysis without affecting systemic hemostasis, in vivo, in a carotid artery thrombosis model in mice. Our studies establish significant promise of the PMIN technology for safe and site-targeted nanomedicine therapies in the vascular compartment. (C) 2017 Published by Elsevier Ltd.
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Thermoresponsive poly (N-isopropylacrylamide) (PNIPAM) has many analogs that exhibit cononsolvency behavior in mixtures of water and an alcohol. Cononsolvency is characterized by a combination of good solvents for a polymer that r...
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Thermoresponsive poly (N-isopropylacrylamide) (PNIPAM) has many analogs that exhibit cononsolvency behavior in mixtures of water and an alcohol. Cononsolvency is characterized by a combination of good solvents for a polymer that results in decreased solubility. In this work, the cononsolvency behavior of linear PNIPAM, four-arm (4f) star PNIPAM, and linear poly(N-n-propylacrylamide) (PNnPAM), with terminal groups that vary in hydrophobicity, were investigated in mixtures of water and propanol. Polymers were synthesized by RAFT polymerization and subsequently functionalized with one pot aminolysis/thiol-ene chemistry. Turbidimetry measurements and dynamic light scattering (DLS) were used to study the cononsolvency behavior by determining the critical solution temperature (T-c). The measurements show that the size and shape of the hydrophobic region of both the solvent and n-alkyl acrylamide monomer affect T-c and the phase transition behavior. The findings suggest methods to impart multiresponsiveness to soft material systems.
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Environmental temperature can alter body size and thermal tolerance, yet the effects of temperature rise on the size-tolerance relationship remain unclear. Terrestrial ectotherms with larger body sizes typically exhibit greater to...
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Environmental temperature can alter body size and thermal tolerance, yet the effects of temperature rise on the size-tolerance relationship remain unclear. Terrestrial ectotherms with larger body sizes typically exhibit greater tolerance of high (and low) temperatures. However, while warming tends to increase tolerance of high temperatures through phenotypic plasticity and evolutionary change, warming tends to decrease body size through these mechanisms and thus might indirectly contribute to worse tolerance of high temperatures. These contrasting effects of warming on body size, thermal tolerance, and their relationship are increasingly important in light of global climate change. Here, we used replicated urban heat islands to explore the size-tolerance relationship in response to warming. We performed a common garden experiment with a small acorn-dwelling ant species collected from urban and rural populations across three different cities and reared under five laboratory rearing temperatures from 21 to 29 degrees C. We found that acorn ant body size was remarkably insensitive to laboratory rearing temperature (ant workers exhibited no phenotypic plasticity in body size across rearing temperature) and among populations experiencing cooler rural versus warmer urban environmental temperatures (no evolved differences in body size between urban and rural populations). Further, this insensitivity of body size to temperature was highly consistent across each of the three cities we examined. Because body size was robust to temperature variation, previously described plastic and evolved shifts in heat (and cold) tolerance in acorn ant responses to urbanization were shown to be independent of shifts in body size. Indeed, genetic (colony-level) correlations between heat and cold tolerance traits and body size revealed no significant association between size and tolerance. Our results show how typical trait correlations, such as between size and thermal tolerance, might be decoupled as populations respond to contemporary environmental change.
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