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  • Abrahamsen Epstein posted an update 3 weeks, 1 day ago

    Cardiac amyloidosis is an under-recognized and potentially fatal cause of heart failure and other cardiovascular manifestations. It is caused by deposition of misfolded precursor proteins as fibrillary amyloid deposits in cardiac tissues. The two primary subtypes of systemic amyloidosis causing cardiac involvement are immunoglobulin light chain (AL), a plasma cell dyscrasia, and transthyretin (ATTR), itself subdivided into a hereditary subtype caused by a gene mutation of the ATTR protein, and an age-related wild type, which occurs in the absence of a gene mutation. Clinical recognition requires a high index of suspicion, inclusive of the extracardiac manifestations of both subtypes. Diagnostic workup includes screening for serum and/or urine monoclonal protein suggestive of immunoglobulin light chains, along with serum cardiac biomarker measurement and performance of cardiac imaging for findings consistent with amyloid infiltration. Modern cardiac imaging techniques, including the use of nuclear scintigraphy with bone-seeking radiotracer to noninvasively diagnose ATTR cardiac amyloidosis, have reduced reliance on the gold standard endomyocardial biopsy. Disease-modifying therapeutic approaches have evolved significantly, particularly for ATTR, and pharmacologic therapies that slow or halt disease progression are becoming available. This Canadian Cardiovascular Society/Canadian Heart Failure Society joint position statement provides evidence-based recommendations that support the early recognition and optimal diagnostic approach and management strategies for patients with cardiac amyloidosis. This includes recommendations for the symptomatic management of heart failure and other cardiovascular complications such as arrhythmia, risk stratification, follow-up surveillance, use of ATTR disease-modifying therapies, and optimal clinical care settings for patients with this complex multisystem disease. Peroxynitrite (ONOO-) plays a crucial role in the regulation of diverse pathophysiological processes, and high level of ONOO- is profound association with numerous diseases. Herein, we developed an anthraquinone-based fluorescent probe L for ONOO- determination by a new recognition mechanism amido oxidized nitroso-group by ONOO-. Probe L with amine-based recognition receptor is more selective to ONOO- than other reactive oxygen species, including H2O2 and ClO-. Furthermore, ONOO- could be rapidly detected by probe L with a Limit of Detection of 13 nM. More importantly, L could be used to monitor intracellular ONOO- in SMMC-7721 cells. Thioarsenicals, such as dimethylmonothioarsinic acid (DMMTAV) and dimethyldithioarsinic acid (DMDTAV), have been increasingly discovered as important arsenic metabolites, yet analysis of these unstable arsenic species remains a challenging task. A method based on surface-enhanced Raman spectroscopy (SERS) detection in combination with the coffee ringeffect for separation is expected to be particularly useful for analysis of thioarsenicals, thanks to minimal sample pretreatment and unique fingerprint Raman identification. see more Such a method would offer an alternative approach that overcomes limitations of conventional arsenic speciation techniques based on high performance liquid chromatography separation and mass spectrometry detection. A novel analytical method based on combination of the coffee ringeffect and SERS was developed for the speciation of thiolated arsenicals. A gold nanofilm (AuNF) was employed not only as a SERS substrate, but also as a platform for the separation of thioarsenicals. Once a drop of the thioarsenicals solution was placed onto the AuNF and evaporation of the solvent and the ring stamp formation onto AuNF began, the SERS signal intensity substantially increased from center to edge regions of the evaporated droplet due to the presence of the coffee ring effect. Through calculating the pKa’s of DMMTAV and DMDTAV and accordingly manipulating the chemical environment, separation of these thioarsenicals was realized as they travelled different distances during the development of the coffee ring. The migration distances of individual species were influenced by a radial outward flow of a solute, the thioarsenicals-AuNF interactions and a thermally induced Marangoni flow. The separation of DMMTAV (center) and DMDTAV (edge) on the coffee ring, in combination with fingerprint SERS spectra, enables the identification of these thioarsenicals by this AuNF-based coffee ring effect-SERS method. Rapid and accurate biosensing with low concentrations of the analytes is usually challenged by the diffusion limited reaction kinetics. Thus, as a remedy, long incubation times or excess amounts of the reagents are employed to ensure the reactions to go to completion. Therefore, mixing becomes both a serious problem and necessity to overcome that diffusion limitation and homogenize the samples, especially for the biochemical reactions that take place in multiwell plates. Because the current mixing platforms such as shakers/vortexers, sonicators, magnetic stirrers and acoustic mixers have disadvantages including, but not limited to, being invasive/harfmul to the samples, causing the samples to splash out or stick to the walls of the wells and allowing foreign compartments to enter the solutions in the wells. Here we propose a noninvasive and safer (considering the risk of sample loss) technology that provides electrokinetic-mixing (EKM) of the reagents placed in electrode-embedded multiwell plates where the in concentrations of AuNPs to observe the impact of mixing on MB quenching kinetics when the concentrations of the AuNPs were increased. Total quenching efficiency could go up to 90% in the presence of the AuNPs and it took about 60 min to reach stability. When the EKM was involved, fluorescence quenching time for the MBs could be reduced by up to 4.1 times. Thus, it was demonstrated that this technology may improve the kinetics of the diffusion limited biological reactions take place in multiwell plates substantially so that it may be adopted in various different sensing platforms for rapid measurements. V.

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