Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

Cocaine is one of the most widely abused illicit drugs worldwide and has long been recognised as an agent of cardiac dysfunction in numerous cases of drug overdose. Cocaine has previously been shown to up-regulate cytoskeletal rearrangements and morphological changes in numerous tissues; however, previous literature observes such changes primarily in clinical case reports and addiction studies. An investigation into the fundamental cytoskeletal parameters of migration, adhesion and proliferation were studied to determine the cytoskeletal and cytotoxic basis of cocaine in cardiac cells. Treatment of cardiac myocytes with cocaine increased cell migration and adhesion (p < 0.05), with no effect on cell proliferation, except with higher doses eliciting (1–10 μg/mL) its diminution and increase in cell death. Cocaine downregulated phosphorylation of cofilin, decreased expression of adhesion modulators (integrin-β3) and increased expression of ezirin within three hours of 1 μg/mL treatments. These functional responses were associated with changes in cellular morphology, including alterations in membrane stability and a stellate-like phenotype with less compaction between cells. Higher dose treatments of cocaine (5–10 μg/mL) were associated with significant cardiomyocyte cell death (p < 0.05) and loss of cellular architecture. These results highlight the importance of cocaine in mediating cardiomyocyte function and cytotoxicity associated with the possible loss of intercellular contacts required to maintain normal cell viability, with implications for cardiotoxicity relating to hypertrophy and fibrogenesis.     

Advanced Postirradiation Characterization of Nuclear Fuels Using Pulsed Neutrons

Methods for postirradiation characterization of bulk (cm³) irradiated materials or even spent nuclear fuels are sparse due to their extremely radioactive nature. While several methods exist to characterize smaller volumes (<?1 mm³) of such samples, selecting these volumes from larger samples is challenging. X-ray-based methods are prohibitive due to the strong γ-radiation from the sample flooding the detectors. Neutron-based methods available in the proximity of irradiation reactors allow for thermal neutron radiography or computed tomography using a small reactor source, but one cannot assess isotope distributions or microstructural features such as phases, texture, or strain from diffraction measurements due to flux limitations. We present herein a pathway to provide pulsed neutron characterization of bulk irradiated samples using time-of-flight neutron diffraction for microstructural characterization and energy-resolved neutron imaging for assessment of isotopic densities and distributions. Ultimately, laser-driven pulsed neutron sources may allow deployment of these techniques pool-side at irradiation reactors.

     

A patient-specific computational model of hypoxia-modulated radiation resistance in glioblastoma using 18F-FMISO-PET

Glioblastoma multiforme (GBM) is a highly invasive primary brain tumour that has poor prognosis despite aggressive treatment. A hallmark of these tumours is diffuse invasion into the surrounding brain, necessitating a multi-modal treatment approach, including surgery, radiation and chemotherapy. We have previously demonstrated the ability of our model to predict radiographic response immediately following radiation therapy in individual GBM patients using a simplified geometry of the brain and theoretical radiation dose. Using only two pre-treatment magnetic resonance imaging scans, we calculate net rates of proliferation and invasion as well as radiation sensitivity for a patient''s disease. Here, we present the application of our clinically targeted modelling approach to a single glioblastoma patient as a demonstration of our method. We apply our model in the full three-dimensional architecture of the brain to quantify the effects of regional resistance to radiation owing to hypoxia in vivo determined by [¹⁸F]-fluoromisonidazole positron emission tomography (FMISO-PET) and the patient-specific three-dimensional radiation treatment plan. Incorporation of hypoxia into our model with FMISO-PET increases the model–data agreement by an order of magnitude. This improvement was robust to our definition of hypoxia or the degree of radiation resistance quantified with the FMISO-PET image and our computational model, respectively. This work demonstrates a useful application of patient-specific modelling in personalized medicine and how mathematical modelling has the potential to unify multi-modality imaging and radiation treatment planning.     

Mixed-Metal MOF-74 Templated Catalysts for Efficient Carbon Dioxide Capture and Methanation

The vast chemical and structural tunability of metal–organic frameworks (MOFs) are beginning to be harnessed as functional supports for catalytic nanoparticles spanning a range of applications. However, a lack of straightforward methods for producing nanoparticle-encapsulated MOFs as efficient heterogeneous catalysts limits their usage. Herein, a mixed-metal MOF, NiMg-MOF-74, is utilized as a template to disperse small Ni nanoclusters throughout the parent MOF. By exploiting the difference in Ni O and Mg O coordination bond strength, Ni²⁺ is selectively reduced to form highly dispersed Ni nanoclusters constrained by the parent MOF pore diameter, while Mg²⁺ remains coordinated in the framework. By varying the ratio of Ni to Mg in the parent MOF, accessible surface area and crystallinity can be tuned upon thermal treatment, influencing CO₂ adsorption capacity and hydrogenation selectivity. The resulting Ni nanoclusters prove to be an active catalyst for CO₂ methanation and are examined using extended X-ray absorption fine structure and X-ray photoelectron spectroscopy. By preserving a segment of the Mg²⁺-containing MOF framework, the composite system retains a portion of its CO₂ adsorption capacity while continuing to deliver catalytic activity. The approach is thus critical for designing materials that can bridge the gap between carbon capture and CO₂ utilization.     

Chromophore-Free Sealing and Repair of Soft Tissues Using Mid-Infrared Light-Activated Biosealants

Poor strength, infection, leakage, long procedure times, and inflammation limit the efficacy of common tissue sealing devices in surgeries and trauma. Light-activated sealing is attractive for tissue sealing and repair, and can be facilitated by the generation of local heat following absorption of nonionizing laser energy by chromophores. Here, the inherent ability of biomaterials is exploited to absorb nonionizing, mid-infrared (midIR) light in order to engender rapid photothermal sealing and repair of soft tissue wounds. In this approach, the biomaterial simultaneously acts as a photothermal convertor as well as a biosealant, which dispenses the need for exogeneous light-absorbing nanoparticles or dyes. Biomechanical recovery, mathematical modeling, histopathology analyses, tissue strain mapping using digital imaging correlation, and visualization of the biosealant-tissue interface using hyperspectral imaging indicate superior performance of midIR sealing in live mice compared to conventional sutures and glue. The midIR-biosealant approach demonstrates rapid sealing of soft tissues, improves cosmesis, lowers potential for scarring, obviates safety concerns because of the nonionizing light used, and allows adoption of a wide diversity of biomaterials. Taken together, the studies demonstrate a novel advance both in biomaterials for surgical sealing along with the use of nonionizing midIR light, with high potential for clinical translation.     

He Bubble Concentration,Size and Strain in Implanted Aluminum by SAXS/WAXS

JOM - Alpha-radiation damage in metals is a concern for long-term radioactive storage and systems that produce nuclear energy. Accurate prediction of irradiated material properties and failure...     

Vibration suppression for monopile and spar‐buoy offshore wind turbines using the structure‐immittance approach

Offshore wind turbines have the potential to capture the high‐quality wind resource. However, the significant wind and wave excitations may result in excessive vibrations and decreased reliability. To reduce vibrations, passive structural control devices, such as the tuned mass damper (TMD), have been used. To further enhance the vibration suppression capability, inerter‐based absorbers (IBAs) have been studied using the structure‐based approach, that is, proposing specific stiffness‐damping‐inertance elements layouts for investigation. Such an approach has a critical limitation of being only able to cover specific IBA layouts, leaving numerous beneficial configurations not identified. This paper adopts the newly introduced structure‐immittance approach, which is able to cover all network layout possibilities with a predetermined number of elements. Linear monopile and spar‐buoy turbine models are first established for optimisation. Results show that the performance improvements can be up to 6.5% and 7.3% with four and six elements, respectively, compared with the TMD. Moreover, a complete set of beneficial IBA layouts with explicit element types and numbers have been obtained, which is essential for next‐step real‐life applications. In order to verify the effectiveness of the identified absorbers with OpenFAST, an approach has been established to integrate any IBA transfer functions. It has been shown that the performance benefits preserve under both the fatigue limit state (FLS) and the ultimate limit state (ULS). Furthermore, results show that the mass component of the optimum IBAs can be reduced by up to 25.1% (7,486 kg) to achieve the same performance as the TMD.     

Cerebral microbleeds and cognitive decline in a hemodialysis patient: Case report and review of literature

Cerebral microbleeds (CMBs) are small hemosiderin deposits indicative of prior cerebral microscopic hemorrhage and previously thought to be clinically silent. Recent population‐based cross‐sectional studies and prospective longitudinal cohort studies have revealed association between CMB and cognitive dysfunction. In the general population, CMBs are associated with age, hypertension, and cerebral amyloid angiopathy. In the chronic kidney disease (CKD) population, diminished estimated glomerular filtration rate has been found to be an independent risk factor for CMB, raising the possibility that a uremic milieu may predispose to microbleeds. In the end‐stage renal disease (ESRD) population on hemodialysis, the incidence of microbleeds is significantly higher compared with a control group without history of CKD or stroke. We present an ESRD patient on chronic hemodialysis with a history of gradual cognitive decline and progressive CMBs. Through this case and literature review, we illustrate the need to develop detection and prediction models to treat this frequent development in ESRD patients.