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Graphitic carbon nitride modified with kaolin-carboxyl graphene (g-C 3 N 4 /KG) was successfully synthesized using urea as the precursor and was applied for the photocatalytic degradation of pharmaceutical compound, "cefepime." Structural and optical characteristics of g-C 3 N 4 /KG were analyzed using various characterization techniques such as FT-IR, XRD, TEM, SEM, EDX, TG, BET, DRS, and PL. The PL studies confirmed that g-C 3 N 4 /KG catalyst exhibits strong charge separation and electron flow, and enhanced visible light absorption capacity was revealed by DRS studies. Studies on the active radical species demonstrate that superoxide and hydroxy radicals play a major role in the photocatalytic degradation of cefepime and dye pollutants. g-C 3 N 4 /KG showed the complete removal MB and 85% of degradation of cefepime under solar light irradiation time of 75 min and 135 min, respectively. Additionally, possible mechanism for the breakdown of the antibiotic cefepime was presented, along with identification of the intermediates produced during the degradation process. The study demonstrates that this novel photocatalyst could be utilized to remove dyes as well as medical wastes from water under solar light., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The existence of antibiotics in aquatic streams destroys water quality and thereby poses serious ecological hitches. Photocatalysis involving nanosemiconductors is an environmentally benign technique for the mineralization of antibiotics. Herein, we prepared a new visible light-sensitive photocatalyst, zeolite Y-supported carbon-doped TiO 2 nanocomposite (zeolite Y-c-TiO 2 ), for the elimination of cefazolin antibiotic in wastewater systems. The structural and optical properties of the synthesized nanocomposites were investigated by Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDX), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Brunauer-Emmett-Teller surface area analysis (BET) as well as diffuse reflectance spectroscopy (UV-DRS) and photoluminescence spectroscopy (PL). The UV-Vis absorbance spectrum of zeolite Y-c-TiO 2 exhibited a red shift towards longer wavelength with an increase in visible light absorption as compared to pure TiO 2 nanoparticles and zeolite Y-supported TiO 2 nanocomposites (zeolite Y-TiO 2 ). Accordingly, the photocatalytic action of the zeolite Y-c-TiO 2 for the degradation of methylene blue was evaluated under solar simulator, and it turned out to be highly efficient (100%) mineralization as compared to TiO 2 -nanoparticles (42%) and zeolite Y-TiO 2 (62%) after 70 min irradiation for a 50mg L -1 methylene blue solution. Radical scavenging experiments revealed the involvement of hydroxyl radicals, superoxide radicals, and photogenerated holes in the degradation process. Consequently, zeolite Y-c-TiO 2 was applied for the photocatalytic degradation of the cefazolin antibiotic in water, and complete degradation of cefazolin (50 mg L -1 ) was observed within 6 h of solar light irradiation on zeolite Y-c-TiO 2 . The degradation pathway of cefazolin was proposed by considering various intermediates detected via LC-MS analysis. The study points to the significant potential of zeolite Y-c-TiO 2 photocatalyst for the purification of medicinal wastewater under sunlight., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel solar light active photocatalyst, TiO 2 /kaolin-graphene carboxyl nanocomposite was synthesized by hydrothermal method for the degradation of cephalosporin antibiotic, cefuroxime sodium. The synthesized photocatalyst was characterized by various analytical and spectroscopic techniques, including Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX) thermogravimetry (TG), UV-Vis diffuse reflectance spectroscopy (DRS) and photoluminescence (PL). The prepared TiO 2 /kaolin-graphene carboxyl nanocomposite exhibited efficient photocatalytic degradation of methylene blue (MB) upon illumination with the solar simulator as compared to unmodified TiO 2 . The incorporation of both kaolin and graphene carboxyl was found to immobilize TiO 2 , enhancing the visible light absorption range of TiO 2 . Scavenger study revealed that hydroxyl radicals act as the main active species in the photocatalytic degradation process. The hydroxyl group present on kaolin surface reacts with photo-generated holes to increase the amount of hydroxyl radical, and further the graphene carboxyl plays a role to impede the recombination of photo-generated electron-hole pairs. Furthermore, the synthesized photocatalyst was found to degrade cefuroxime sodium within 90 min of sunlight illumination, indicating that TiO 2 /kaolin-graphene carboxyl nanocomposites would be very beneficial for pharmaceutical waste management through the advanced oxidation process. Mass spectral analysis was also carried out for elucidating the photocatalytic degradation pathway of cefuroxime sodium., (© 2022. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

In recent decades, the destructive impact of active pharmaceutical ingredients (API) present in surface and drinking water on aquatic and terrestrial life forms becomes a major concern of researchers. API like diclofenac (DCF), carbamazepine (CBZ), tetracycline (TC), and sulfamethoxazole (SME) found in water bodies cause antimicrobial resistance and are potent carcinogens and endocrine disruptors. Conventional wastewater treatment methods possess some drawbacks and were found to be insufficient for the effective removal of APIs. Visible light-assisted semiconductor photocatalysis has become an alternative choice for tackling this worse scenario. Graphitic carbon nitride, a metal-free visible light active semiconductor photocatalyst is an emerging hotspot nanomaterial whose practical utility in water purification is widely recognized. This review comes up with an insightful outlook on the panorama of recent progress in the field of g-C 3 N 4 -assisted photocatalytic systems for the eradication of APIs. In addition, the review summarizes various strategies adopted for the broad-spectrum utilization of visible light and the enhancement of charge separation of pristine g-C 3 N 4 . The mechanistic pathways followed by different pharmaceuticals during their photocatalytic degradation process were also briefly discussed.

Background: Rapid recurrence, defined as gross tumor recurrence after primary operation but prior to initiating postoperative radiation therapy (PORT), is underappreciated in head and neck cancer (HNC)., Methods: CT simulation images in patients with HNC managed surgically with adjuvant therapy at a single center between 2010 and 2017 were retrospectively reviewed., Results: A total of 194 patients with HNC were included. Rapid recurrence occurred in 39 patients (20%) with a median time from operation to CT simulation of 37 days. On multivariable analysis (MVA), extranodal extension (ENE) was the only predictor of rapid recurrence (P = .03). While rapid recurrence, ENE, and perineural invasion were all associated with poor overall survival (OS) on MVA, rapid recurrence was the strongest predictor (hazard ratio [HR] 5.47)., Conclusion: Rapid recurrence occurs at an underappreciated rate and is associated with poor survival outcomes. Patients with ENE are at highest risk and may benefit from diagnostic imaging evaluations immediately prior to PORT., (© 2020 Wiley Periodicals LLC.)

Implantation of mechanical circulatory support (MCS) devices-ventricular assist devices and the total artificial heart-has emerged as a vital therapy for advanced and end-stage heart failure. Unfortunately, MCS patients face the requirement of life-long antiplatelet and anticoagulant therapy to combat thrombotic complications resulting from the dynamic and supraphysiologic shear stress conditions associated with such devices, whose effect on platelet activation is poorly understood. We developed a syringe-capillary viscometer-the "platelet hammer"-that repeatedly exposed platelets to average shear stresses up to 1000 dyne/cm(2) for as short as 25 ms. Platelet activation state was measured using a modified prothrombinase assay, with morphological changes analyzed using scanning electron microscopy. We observed an increase in platelet activation state and post-high shear platelet activation rate, or sensitization, with an increase in stress accumulation (SA), the product of shear stress and exposure time. A significant increase in platelet activation state was observed beyond an SA of 1500 dyne-s/cm(2) , with a marked increase in pseudopod length visible beyond an SA of 1000 dyne-s/cm(2) . Utility of the platelet hammer extends to studies of other shear-dependent pathologies, and may assist development of approaches to enhance the safety and effectiveness of MCS devices and objective antithrombotic pharmacotherapy management., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Imaging is an essential tool in the management of head and neck cancer. Oral, oropharyngeal, laryngeal, and hypopharyngeal lesions are initially imaged with computed tomography (CT) because it allows rapid image acquisition and reduces artifacts related to respiration and swallowing, which can degrade image quality and limit evaluation. Sinonasal, nasopharyngeal, and salivary gland tumors are better approached with MRI because it allows for better delineation of tumor extent. PET/CT is usually reserved for advanced disease to evaluate for distant metastatic disease and posttreatment residual and recurrent disease. Imaging is best used in combination with expert clinical and physical examination., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Mechanical circulatory support (MCS) devices, such as ventricular assist devices and the total artificial heart, have emerged as a vital therapy for advanced and end-stage heart failure. However, MCS patients face life-long antiplatelet and anticoagulant therapy to minimize thrombotic complications resulting from the dynamic and supraphysiologic device-associated shear stress conditions, whose effect on platelet activation is poorly understood. We repeatedly exposed platelets to average shear stresses up to 1000 dyne/cm(2) for as short as 25 ms in the "platelet hammer," a syringe-capillary viscometer. Platelet activation state was measured using a modified prothrombinase assay and morphological changes analyzed using scanning electron microscopy. An increase in stress accumulation (SA), the product of shear stress and exposure time, led to an increase in the platelet activation state and post-high shear platelet activation rate, or sensitization. A significant increase in platelet activation state was observed beyond an SA of 1500 dyne-s/cm(2), with a marked increase in pseudopod length visible beyond an SA of 1000 dyne-s/cm(2). The platelet hammer may be used to study other shear-dependent pathologies and may ultimately enhance the safety and effectiveness of MCS devices and objective antithrombotic pharmacotherapy management.

Ventricular assist devices (VADs) are implanted in patients with end-stage heart failure to provide both short- and long-term hemodynamic support. Unfortunately, bleeding and thromboembolic complications due to the severely disturbed, dynamic flow conditions generated within these devices require complex, long-term antiplatelet and anticoagulant therapy. While several studies have examined the effectiveness of one such agent, aspirin, under flow conditions, data comparing the efficacy of in vitro and in vivo metabolized aspirin is lacking. Two sets of studies were conducted in vitro with purified human platelets circulating for 30 min in a flow loop containing the DeBakey VAD (MicroMed Cardiovascular, Houston, TX, USA): (a) 20 μM aspirin was added exogenously in vitro to platelets isolated from aspirin-free subjects, and (b) platelets were obtained from donors 2 h (n = 14) and 20 h (n = 13) after ingestion of 1,000 mg aspirin. Near real-time platelet activation state (PAS) was measured with a modified prothrombinase-based assay. Platelets exposed to aspirin in vitro and in vivo (metabolized) showed 28.2 and 25.3 % reduction in platelet activation rate, respectively, compared to untreated controls. Our results demonstrate that in vitro treatment with antiplatelet drugs such as aspirin is as effective as in vivo metabolized aspirin in testing the effect of reducing shear-induced platelet activation in the VAD. Using the PAS assay provides a practical in vitro alternative to in vivo testing of antiplatelet efficacy, as well as for testing the thrombogenic performance of devices during their research and development.

The advent of implantable blood-recirculating devices such as left ventricular assist devices and prosthetic heart valves provides a viable therapy for patients with end-stage heart failure and valvular disease. However, device-generated pathological flow patterns result in thromboembolic complications that require complex and lifelong anticoagulant therapy, which entails hemorrhagic risks and is not appropriate for certain patients. Optimizing the thrombogenic performance of such devices utilizing numerical simulations requires the development of predictive platelet activation models that account for variations in shear-loading rates characterizing blood flow through such devices. Platelets were exposed in vitro to both dynamic and constant shear stress conditions emulating those found in blood-recirculating devices in order to determine their shear-induced activation and sensitization response. Both these behaviors were found to be dependent on the shear loading rates, in addition to shear stress magnitude and exposure time. We then critically examined several current models and evaluated their predictive capabilities using these results. Shear loading rate terms were then included to account for dynamic aspects that are either ignored or partially considered by these models, and model parameters were optimized. Independent optimization for each of the two types of shear stress exposure conditions tested resulted in different sets of best-fit constants, indicating that universal optimization may not be possible. Inherent limitations of the current models require a paradigm shift from these integral-based discretized power law models to better address the dynamic conditions encountered in blood-recirculating devices.

Abstract The receptor for the globular heads of C1q, gC1qR/p33, is a widely expressed cellular protein, which binds to diverse ligands including plasma proteins, cellular proteins, and microbial ligands. In addition to C1q, gC1qR also binds high molecular weight kininogen (HK), which also has two other cell surface sites, namely, cytokeratin 1 and urokinase plasminogen activator receptor (uPAR). On endothelial cells (ECs), the three molecules form two closely associated bimolecular complexes of gC1qR/cytokeratin 1 and uPAR/cytokeratin 1. However, by virtue of its high affinity for HK, gC1qR plays a central role in the assembly of the kallikrein-kinin system, leading to the generation of bradykinin (BK). BK in turn is largely responsible for the vascular leakage and associated inflammation seen in angioedema patients. Therefore, blockade of gC1qR by inhibitory peptides or antibodies may not only prevent the generation of BK but also reduce Clq-induced or microbial-ligand-induced inflammatory responses. Employing synthetic peptides and gClqR deletion mutants, we confirmed previously predicted sites for C1q (residues 75-96) and HK (residues 204-218) and identified additional sites for both C1q and HK (residues 190-202), for C1q (residues 144-162), and for HIV-1 gp41 (residues 174-180). With the exception of residues 75-96, which is located in the alphaA coiled-coil N-terminal segment, most of the identified residues form part of the highly charged loops connecting the various beta-strands in the crystal structure. Taken together, the data support the notion that gC1qR could serve as a novel molecular target for the design of antibody-based and/or peptide-based therapy to attenuate acute and/or chronic inflammation associated with vascular leakage and infection.

Mechanical circulatory support (MCS) devices provide both short and long term hemodynamic support for advanced heart failure patients. Unfortunately these devices remain plagued by thromboembolic complications associated with chronic platelet activation--mandating complex, lifelong anticoagulation therapy. To address the unmet need for enhancing the thromboresistance of these devices to extend their long term use, we developed a universal predictive methodology entitled Device Thrombogenicity Emulation (DTE) that facilitates optimizing the thrombogenic performance of any MCS device--ideally to a level that may obviate the need for mandatory anticoagulation. DTE combines in silico numerical simulations with in vitro measurements by correlating device hemodynamics with platelet activity coagulation markers--before and after iterative design modifications aimed at achieving optimized thrombogenic performance. DTE proof-of-concept is demonstrated by comparing two rotary Left Ventricular Assist Devices (LVADs) (DeBakey vs HeartAssist 5, Micromed Houston, TX), the latter a version of the former following optimization of geometrical features implicated in device thrombogenicity. Cumulative stresses that may drive platelets beyond their activation threshold were calculated along multiple flow trajectories and collapsed into probability density functions (PDFs) representing the device 'thrombogenic footprint', indicating significantly reduced thrombogenicity for the optimized design. Platelet activity measurements performed in the actual pump prototypes operating under clinical conditions in circulation flow loops--before and after the optimization with the DTE methodology, show an order of magnitude lower platelet activity rate for the optimized device. The robust capability of this predictive technology--demonstrated here for attaining safe and cost-effective pre-clinical MCS thrombo-optimization--indicates its potential for reducing device thrombogenicity to a level that may significantly limit the extent of concomitant antithrombotic pharmacotherapy needed for safe clinical device use.

The endothelial cell receptor complex for kininogen (HK) comprises gC1qR, cytokeratin 1, and urokinase-type plasminogen activator receptor and is essential for activation of the kinin system that leads to bradykinin (BK) generation. Of these, gC1qR/p33 constitutes a high affinity site for HK - the BK precursor - and is therefore critical for the assembly of the kinin-generating cascade. Previous studies have identified a putative HK site within the C-terminal domain (residues 204-218) of gC1qR recognized by mAb 74.5.2. In these studies, we used information from the crystal structure of gC1qR, to engineer several deletion (Δ) mutants and test their ability to bind and/or support BK generation. While deletion of residues 204-218 (gC1qRΔ204-218), showed significantly reduced binding to HK, BK generation was not affected when tested by a sensitive bradykinin immunoassay. In fact, all of the gC1qR deletion mutants supported BK generation with the exception of gC1qRΔ154-162 and a point mutation in which Trp 233 was substituted with Gly. Binding studies also identified the existence of two additional sites at residues 144-162 and 190-202. Moreover, binding of HK to a synthetic peptide 190-202 was inhibited by mAbs 48 and 83, but not by mAb 74.5.2. Since a single residue separates domains 190-202 and 204-218, they may be part of a highly stable HK binding pocket and therefore a potential target for drug design to prevent vascular permeability and inflammation.

Trileaflet polymeric prosthetic aortic valves (AVs) produce hemodynamic characteristics akin to the natural AV and may be most suitable for applications such as transcatheter implantation and mechanical circulatory support (MCS) devices. Their success has not yet been realized due to problems of calcification, durability, and thrombosis. We address the latter by comparing the platelet activation rates (PARs) of an improved polymer valve design (Innovia LLC) made from poly(styrene-block-isobutylene-block-styrene) (SIBS) with the commercially available Carpentier-Edwards Perimount Magna Aortic Bioprosthetic Valve. We used our modified prothrombinase platelet activity state (PAS) assay and flow cytometry methods to measure platelet activation of a pair of 19 mm valves mounted inside a pulsatile Berlin left ventricular assist device (LVAD). The PAR of the polymer valve measured with the PAS assay was fivefold lower than that of the tissue valve (p = 0.005) and fourfold lower with flow cytometry measurements (p = 0.007). In vitro hydrodynamic tests showed clinically similar performance of the Innovia and Magna valves. These results demonstrate a significant improvement in thrombogenic performance of the polymer valve compared with our previous study of the former valve design and encourage further development of SIBS for use in heart valve prostheses.

Patients implanted with mechanical heart valves (MHV) or with ventricular assist devices that use MHV require mandatory lifelong anticoagulation for secondary stroke prevention. We recently developed a novel Device Thrombogenicity Emulator (DTE) methodology that interfaces numerical and experimental approaches to optimize the thrombogenic performance of the device and reduce the bleeding risk associated with anticoagulation therapy. Device Thrombogenicity Emulator uses stress-loading waveforms in pertinent platelet flow trajectories that are extracted from highly resolved numerical simulations and emulates these flow conditions in a programmable hemodynamic shearing device (HSD) by which platelet activity is measured. We have previously compared two MHV, ATS and the St. Jude Medical, and demonstrated that owing to its nonrecessed hinge design, the ATS valve offers improved thrombogenic performance. In this study, we further optimize the ATS valve thrombogenic performance, by modifying various design features of the valve, intended to achieve reduced thrombogenicity: 1) optimizing the leaflet-housing gap clearance; 2) increasing the effective maximum opening angle of the valve; and 3) introducing a streamlined channel between the leaflet stops of the valve that increases the effective flow area. We have demonstrated that the DTE optimization methodology can be used as test bed for developing devices with significantly improved thombogenic performance.