Dual effects of NV-CoV-2 biomimetic polymer: An antiviral regimen against COVID-19.

Remdesivir (RDV) is the only antiviral drug approved for COVID-19 therapy by the FDA. Another drug LAGEVRIO™ (molnupiravir) though has not been approved yet by FDA but has been authorized on December 23, 2021, for emergency use to treat adults with mild-to moderate COVID-19 symptoms and for whom alternative COVID-19 treatment options are not clinically appropriate. The fact is that the efficacy of RDV is, however, limited in vivo though it is highly promising in vitro against SARS-CoV-2 virus. In this paper we are focusing on the action mechanism of RDV and how it can be improved in vivo. The stability of RDV alone and on encapsulation with our platform technology based polymer NV-387 (NV-CoV-2), were compared in presence of plasma in vitro and in vivo. Furthermore, a non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV CoV-2 (Polymer encapsulated Remdesivir) in both NL-63 infected and uninfected rats was done. In addition, the antiviral activity of NV-CoV-2 and NV-CoV-2-R was compared with RDV in a cell culture study. The results are (i) NV-CoV-2 polymer encapsulation protects RDV from plasma-mediated catabolism in both in vitro and in vivo, studies; (ii) Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2 and NV-CoV-2-R) showed no toxic effects. (iii) Body weight measurements and survival rates of the NL-63 infected rats were similar to the uninfected rats after treatment with NV-CoV-2 and NV-CoV-2-R. Overall, the efficacy as an antiviral regimens were found in this order as below; NV-CoV-2-R > NV-CoV-2 > RDV. Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect against different variants of the coronaviruses. First, NV-CoV-2 is an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit. All together, NV-CoV-2-R is the safest and efficient regimen against COVID-19.

Growth enhancement in containerized Pinus gerardiana seedlings inoculated with ectomycorrhizal fungi.

Mycorrhizal fungi boost host plant growth by improving roots' ability to absorb nutrients and water from the rhizosphere soil. In this study, a mass inoculum of the ectomycorrhizal fungus Scleroderma polyrhizum was produced on wheat grains and incorporated into polybags during seed sowing of Pinus gerardiana, with the expectation that the roots of the germinating seedlings would form a mycorrhizal association with S. polyrhizum. For 2 years, the seedlings' growth parameters were measured at 3-month intervals. The seedlings raised in inoculated bags exhibited ectomycorrhizal anatomy and higher growth indices like absolute growth rate, relative growth rate, sturdiness quotient, volume index, quality index etc. The growth parameters of 2-year-old inoculated seedlings were 44.36 to 94.36 percent higher than control. Shoot dry weight increased the most (94.36 percent), followed by root volume (93.59 percent), shoot fresh weight (91.42 percent), root fresh weight (79.46 percent), and collar diameter increased the least (49.30 percent). Two-year-old seedlings were outplanted in two locations: one within and one beyond its normal zone of occurrence. Inoculated seedlings fared better at both sites in terms of survival and growth. S. polyrhizum inoculation has accelerated the growth metrics of P. gerardiana seedlings. Thus, it can be recommended that the P. gerardiana nursery should be raised by artificial inoculation with S. polyrhizum to produce healthy, tall planting stock in a shorter nursery time while also lowering maintenance costs.

Mechanism of Antiviral Activities of Nanoviricide's Platform Technology based Biopolymer (NV-CoV-2).

NV-CoV-2 is a nanoviricide that is covalently bonded with polyethylene glycol (PEG) and alkyl pendants. This molecular design is used to attack many strains of coronaviruses in a broad-spectrum manner. The ligand works by competitive inhibition and binds to the same site on the S-protein of SARS-CoV that attaches to the cognate cellular receptor, ACE2. This prevents SARS-CoV from binding and infecting the cell. NV-CoV-2 is designed to bind to the free virion particles at multiple points encapsulate the virus and disable its ability to infect the cells. The multi-point binding interaction, like a nano-velcro-tape, may lead to lipid-lipid fusion of the alkyl chains in the nanoviricide micelle with the lipid envelope of the virus. The virus becomes dismantled to a capsid form before the host immune system becomes involved. This putative mechanism is orthogonal to many other anti-coronavirus agents in development. Thus, it maybe possible to produce a stronger antiviral effect when combining NV-CoV-2 therapy with other anti-coronavirus therapies such as Remdesivir (RDV). NV-CoV-2 can encapsulate other antiviral compounds as well. In this study, RDV was encapsulated and protected from serum-mediated degradation in vivo. As a result, RDV was available for a longer period of time to interact with RNA polymerase and inhibit.

Comparison of Rhenium and Iodine as Contrast Agents in X-Ray Imaging.

Purpose: The majority of X-ray contrast agents (XCA) are made with iodine, but iodine-based XCA (I-XCA) exhibit low contrast in high kVp X-rays due to iodine's low atomic number (Z = 53) and K-edge (33.1 keV). While rhenium is a transition metal with a high atomic number (Z = 75) and K-edge (71.7 keV), the utilization of rhenium-based XCA (Re-XCA) in X-ray imaging techniques has not been studied in depth. Our study had two objectives: (1) to compare both the image quality and the absorbed dose of I- and Re-XCA and (2) to prepare and image a rhenium-doped scaffold. Procedures. I- and Re-XCA were prepared and imaged from 50 to 120 kVp by Micro-computed tomography (µCT) and digital radiography and from 120 to 220 kVp by planar X-ray imaging. The scans were repeated using 0.1 to 1.6 mm thick copper filters to harden the X-ray beam. A rhenium-doped scaffold was prepared via electrospinning, used to coat catheters, and imaged at 90 kVp by µCT. Results: I-XCA have a greater contrast-to-noise ratio (CNR) at 50 and 80 kVp, but Re-XCA have a greater CNR at >120 kVp. The difference in CNR is increased as the thickness of the copper filters is increased. For instance, the percent CNR improvement of rhenium over iodine is 14.2% with a 0.6 mm thick copper filter, but it is 59.1% with a 1.6 mm thick copper filter, as shown at 120 kVp by µCT. Upon coating them with a rhenium-doped scaffold, the catheters became radiopaque. Conclusions: Using Monte Carlo simulations, we showed that it is possible to reduce the absorbed dose of high kVp X-rays while allowing the acquisition of high-quality images. Furthermore, radiopaque catheters have the potential of enhancing the contrast during catheterizations and helping physicians to place catheters inside patients more rapidly and precisely.

Unsuspected Pregnancies in Hysterosalpingography: Implementation and Review of a Multi-Institutional Pre-Procedural Pregnancy Screening Protocol.

PURPOSE: Owing to the increasing average age of first-time mothers, as well as advances in assistive reproductive technology, the number of hysterosalpingography (HSG) requests has continued to rise. This increases the likelihood of patients presenting with unsuspected early pregnancies prior to HSG. Currently, there is no standard of practice for the pre-procedural screening of pregnancy prior to HSG, with most institutions using patient-reported pregnancy status and unreliable menstrual cycle dating methods. We implemented a multi-institutional pre-procedural pregnancy screening protocol in order to determine the rate of unsuspected pregnancies prior to HSG and improve the quality and safety of these procedures. METHODS: Following multi-institutional and multidisciplinary input, a consensus protocol was formulated and implemented across 9 institutions in the Lower Mainland of British Columbia, Canada. Subsequent tracking of pregnancy testing was then performed over a period of 3 years. RESULTS: Pre-implementation review of protocols demonstrated large disparities between institutions. A total of 6333 HSG examinations were scheduled in the review period following implementation. Of these, 10 patients were found to have positive pregnancy tests (0.16%), despite self-reporting that they were not pregnant or had recent menstrual bleeding. DISCUSSION: Hysterosalpingography is contraindicated in pregnancy, yet we identified 10 unsuspected pregnancies in patients who would have otherwise undergone HSG examinations with existing guidelines. While there remains insufficient data on the deleterious effects of performing HSG on an unsuspected pregnancy, the potential physical, economical, and psychosocial consequences of performing an HSG during pregnancy are sufficient to merit consideration of relatively inexpensive routine pregnancy screening prior to HSG.

Orthopaedic Surgeon Brain Radiation During Fluoroscopy: A Cadaver Model.

BACKGROUND: The aims of this study were to quantify exposure of the surgeon's brain to radiation during short cephalomedullary (SC) nailing, to extrapolate lifetime dose, and to determine the effects of personal protective equipment (PPE) on brain dose. METHODS: Two cadaveric specimens were used: (1) a whole cadaveric body representing the patient, with a left nail inserted to act as the scatter medium, and (2) an isolated head-and-neck cadaveric specimen representing a surgeon, with radiation dosimeters placed in specific locations in the brain. The "patient" cadaver's left hip was exposed in posteroanterior and lateral radiographic planes. Measurements were performed without shielding of the head-and-neck specimen and then repeated sequentially with different PPE configurations. An average surgeon career was estimated to be 40 years (ages 25 to 65 years) with the caseload obtained from the department's billing data. RESULTS: The mean radiation dose to the surgeon brain without PPE was 3.35 µGy (95% confidence interval [CI]: 2.4 to 4.3) per nail procedure. This was significantly reduced with use of a thyroid collar (2.94 µGy [95% CI: 1.91 to 3.91], p = 0.04). Compared with use of the thyroid collar in isolation, there was no significant additional reduction in radiation when the collar was used with leaded glasses (2.96 µGy [95% CI: 2.15 to 3.76], p = 0.97), with a lead cap (3.22 µGy [95% CI: 2.31 to 4.13], p = 0.55), or with both (2.31 µGy [95% CI: 1.61 to 3.01], p = 0.15). The extrapolated lifetime dose over 40 working years for SC nailing without PPE was 2,146 µGy (95% CI: 1,539 to 2,753), with an effective dose of 21.5 µSv. CONCLUSIONS: The extrapolated cumulative lifetime radiation to a surgeon's brain from SC nailing based on our institution's workload and technology is low and comparable with radiation during a one-way flight from London to New York. Of note, we studied only one of many fluoroscopy-aided procedures and likely underestimated total lifetime exposure if exposures from other procedures are included. This study also demonstrates that thyroid collars significantly reduce brain dose for this procedure whereas other head/neck PPE such as lead caps appear to have minimal additional effect. This study provides a methodology for future studies to quantify brain dose for other common orthopaedic procedures. CLINICAL RELEVANCE: This study, based on our institutional data, demonstrates that although the lifetime brain dose from SC nailing is low, thyroid collars significantly reduce this dose further. As such, in accordance with the "as low as reasonably achievable" radiation exposure principle, radiation safety programs and individual surgeons should consider use of thyroid collars in this setting.

Multidisciplinary Development of Mobile Radiography Guidelines Reduced the Number of Inappropriate Mobile Exams in Patients Receiving Chest Radiographs in British Columbia.

AIM: To decrease the number of mobile chest radiograph requests for inpatients in British Columbia who are medically able to tolerate transport to the main department by introducing and implementing request criteria. METHOD: Concerns regarding inappropriate mobile exam requests in patients receiving chest radiography were surveyed at 28 medical imaging sites. In response, a multidisciplinary team composed a set of mobile radiography request guidelines incorporating feedback from all sites. These were successfully implemented along with in-person education to 21 sites. The number of adult annual mobile chest radiographs was tracked from 2014 to 2018, and informal feedback was obtained from participating sites. RESULTS: The percentage of mobile chest radiographs of all chest radiographs performed between 2014 and 2018 decreased by 3.2%, while the total number of all chest radiographs performed during this time, including both departmental and mobile, increased by 1.9%. Sites reported positive engagement with the initiative and expressed need for ongoing education to optimize its effect. CONCLUSION: Implementation of request guidelines with in-person education helped to reduce inappropriate mobile exams in patients receiving chest radiographs in British Columbia between 2014 and 2018. These guidelines promote patient safety through reduced radiation exposure, empower radiographers to mitigate inappropriate requests, and help to optimize use of limited hospital resources by reducing inappropriate mobile exams where routine departmental exams are more suitable.

Peer Review Tool for General Radiography Technologists Improves Image Quality.

PURPOSE: Quality improvement is vital to ensure health-care providers meet optimal patient care standards. Within our jurisdiction, accreditation requires image peer review as part of the quality assurance program. We propose a method to improve quality assurance in radiography by implementing a novel software-based peer review system for radiography technologists. METHODS: This is a retrospective study. A peer review tool was developed in Microsoft Excel and Visual Basic. The tool has 14 image quality criteria, which were selected based on national and international criteria, each containing standardized answers ensuring a common scoring regime. The tool provides data analysis and storage of all peer reviews performed. Radiography supervisors utilized the tool to evaluate image quality of various body parts at 28 hospitals. The tool enabled each Medical Imaging Department to objectively score images at their own hospital. Approximately 2% of all radiographs were randomly chosen for peer review. Additionally, the tool allowed for regional analysis based on hospital, body part, and quality criterion. RESULTS: Initial findings exposed equipment-related issues such as worn imaging plates, artifacts, and poor exposures, which prompted increased preventative maintenance. Other documented issues included foreign objects, inadequate collimation and centering, and inconsistent usage of lead markers. After identifying quality assurance-related issues, hospitals implemented education, resulting in improved overall image quality scores in subsequent audits. CONCLUSION: The peer review tool helped identify and correct various issues affecting image quality and ensures our program meets required accreditation standards. Furthermore, staff found utilizing the tool to identify areas for improvement improved collaboration, ongoing education, and support between staff.

Comparison of the CTDI and AAPM report No. 111 methodology in adult, adolescent, and child head phantoms for MSCT and dental CBCT scanners.

This study investigates the dosimetry methodology proposed by the American Association of Physicists in Medicine (AAPM) task group 111 and compares with the computed tomography dose index (CTDI) method and the SEDENTEXCT DI method on one clinical multislice CT and two dental cone beam CT (CBCT) scanners using adult, adolescent, and child head phantoms. Following the AAPM method, the normalized (100 mAs) equilibrium doses ([Formula: see text]) for Toshiba Aquilion One MSCT computed using dose measurements from the central hole of the phantom ([Formula: see text]), the peripheral hole of the phantom, ([Formula: see text]), and by the [Formula: see text] equation ([Formula: see text]) are in the range from 20 to 25 mGy. For i-CAT Next Generation dental CBCT, the normalized [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] by the two SEDENTEXCT DI methods are in the range from 12 to 15 mGy. Fitting the AAPM equation is not possible for the limited scan lengths available on the CS 9300 dental CBCT. This study offers a simple CTDI-like measurement that can approximate the AAPM [Formula: see text] in clinical CBCT scanners capable of providing four or more scan lengths.

A Radiographic Diagnostic Reference Level Survey Using Patient and Phantom Data.

A diagnostic reference level (DRL) survey was conducted for seven common radiographic projections across an integrated health region, covering 27 hospitals and clinics. The projections surveyed were Chest Posterior-Anterior (PA) and Lateral, Abdomen Supine and Upright, L-spine Anterior-Posterior (AP) and Lateral, and Pelvis. Dose area product (DAP) values were collected from patient examinations in 43 digital radiography (DR) rooms and in 18 conventional rooms which use computed radiography (CR). In each room, data were collected for between 10 and 20 patient exposures for each surveyed projection. In addition, for each projection and room, a DAP value was measured for the exposure of a uniform acrylic phantom of standardized thickness. DAP values in DR rooms were found to be significantly lower than in CR rooms (p < 0.05). Therefore, DR and CR rooms were analyzed separately. Based on the survey results, separate DRLs are presented for DR and CR rooms, for both patient and phantom DAP values. DRLs have been set at the 75th percentile values; 25th percentile and median values are also presented to characterize the range of observed values. When identifying which rooms were above the DRLs, the patient and phantom data identified a partially different set of rooms. Possible reasons for these differences, including uncertainties in the patient data, are discussed.

Radiation Dose Survey for Common Computed Tomography Exams: 2013 British Columbia Results.

In 2013 Health Canada conducted a national survey of computed tomography (CT) radiation usage. We analysed contributions from all 7 public health authorities in the province of British Columbia, which covered scanner age, number of slices, and common adult protocols (≥ 19 years: 70 ± 20 kg, head, chest, abdomen/pelvis, and trunk). Patient doses were recorded for common protocols. Diagnostic reference levels (DRLs) was calculated using scanner data with >10 patient doses recorded for each protocol. Data was analysed based on image reconstruction (filtered backprojection vs iterative reconstruction [IR] vs IR available but not in use). Provincial response was 92%, with 59 of 64 CT data used for analysis. The average scanner age was 5.5 years old, with 39% of scanners installed between 2008-2013; 78.5% of scanners were multislice (>64 slices), and 44% of scanners had IR available. Overall British Columbia DRLs were: head = 1305, chest = 529, abdomen/pelvis = 819, and trunk = 1225. DRLs were consistent with Health Canada recommendations and other Canadian published values, but above international standards. For sites with IR available, less than 50% used this technology routinely for head, chest and trunk exams. Overall, use of IR reduced radiation usage between 11%-32% compared to filtered backprojection, while sites using IR vs IR available used 30%/43% less radiation for head/chest exams (P < .05). No significant difference was observed for abdomen/pelvis exams (P = .385). With the fast pace of CT technical advancement, DRLs should reflect the technology used, instead of just globally applied to anatomical regions. Federal guidelines should be updated at a higher frequency to reflect new technology. In addition, new technologies must be utilised to optimize image quality vs radiation usage.

Canadian Association of Radiologists Radiation Protection Working Group: Automated Patient-Specific Dose Registries­What Are They and What Are They Good for?

Medical radiation should be used appropriately and with a dose as low as reasonably achievable. Dose monitoring technologies have been developed that automatically accumulate patient dose indicators, providing effective dose estimates and patient-specific dose histories. Deleterious radiation related events have prompted increased public interest in the safe use of medical radiation. Some view individualized patient dose histories as a tool to help manage the patient dose. However, it is imperative that dose monitoring technologies be evaluated on the outcomes of dose reduction and effective patient management. Patient dose management needs to be consistent with the widely accepted linear no-threshold model of stochastic radiation effects. This essay reviews the attributes and limitations of dose monitoring technologies to provoke discussion regarding resource allocation in the current fiscally constrained health care system.

Acute pulmonary embolism: from morphology to function.

This article reviews the current diagnostic strategies for patients with suspected pulmonary embolism (PE) focusing on the current first choice imaging modality, computed tomographic pulmonary angiography (CTPA). Diagnostic strengths and weaknesses and associated cost-effectiveness of the diagnostic pathways will be discussed. The radiation dose risk of these pathways will be described and techniques to minimize dose will be reviewed. Finally the impact of new dual energy applications which have the potential to provide additional functional information will be briefly reviewed. Imaging plays a vital role in the diagnostic pathway for clinically suspected PE. CT has been established as the most robust morphologic imaging tool for the evaluation of patients with suspected PE. This conclusion is based on the high diagnostic utility of CT for the detection of PE and its unique capacity for accurate diagnosis of conditions that can mimic the clinical presentation of PE. Although current cost-effectiveness evaluations have established CT as integral in the PE diagnostic pathway, failure to acknowledge the impact of alternate diagnosis represents a current knowledge gap. The emerging dual energy capacity of current CT scanners offers the potential to evaluate both pulmonary vascular morphology and ventilation perfusion relationships within the lung parenchyma at high spatial resolution. This dual assessment of lung morphology and lung function at low (< 5 millisievert) radiation dose represents a substantial advance in PE imaging.

Scanner and kVp dependence of measured CT numbers in the ACR CT phantom.

Quality control testing of CT scanners in our region includes a measurement of CT numbers in the American College of Radiology (ACR) CT phantom using a standardized protocol. CT number values are clinically relevant in determining the composition of various tissues in the body. Accuracy is important in the characterization of tumors, assessment of coronary calcium, and identification of urinary stone composition. Effective quality control requires that tolerance ranges of CT number values be defined: a measured value outside the range indicates the need for further investigation and possible recalibration of the scanner. This paper presents the results of CT number measurements on 36 scanners (25 GE, 10 Siemens and 1 Toshiba) at each available kVp. Among the five materials (solid water, air, polyethylene, acrylic, bone-equivalent) the measured CT numbers exhibit manufacturer and kVp dependence, which should be taken into account when defining tolerances. With this scan protocol, air and solid water values are significantly higher on GE scanners than on Siemens scanners (p-value < 0.01 at each kVp). The CT numbers of polyethylene and acrylic increase with kVp, while the bone-equivalent CT number decreases. These results are used to define manufacturer- and kVp-specific tolerance ranges for the CT numbers of each material in this phantom, which will be used in our quality control program.

Pulmonary CT angiography as first-line imaging for PE: image quality and radiation dose considerations.

OBJECTIVE: This article reviews dose reduction techniques in pulmonary CT angiography (CTA) for imaging pulmonary embolism (PE). Dose reduction technologies covered include tube current modulation, kilovoltage modulation, scanning length modification, dynamic z-axis collimation, iterative reconstruction, and dual-energy CT. Age- and weight-specific imaging techniques are suggested. CONCLUSION: Pulmonary CTA plays a vital role in imaging PE. Using dose reduction technologies can provide high-quality diagnostic imaging with a significant reduction in patient dose.

Health Canada Safety Code 35: awareness of the impacts for diagnostic radiology in Canada.

Health Canada Safety Code 35 brings Canada's diagnostic imaging radiation output and protection standards to an international level. This Safety Code is comprehensive and will have broad implications for most health care facilities. This Safety Code outlines quality control procedures that will ultimately reduce patient dose while providing the best quality diagnostic images, all within a safe working environment. However, the Safety Code has some important omissions and errors of which radiologists should be aware, especially if they act as radiation safety officers. We hope that highlighting these issues will be the beginning of an ongoing dialogue between Health Canada, radiologists, medical physicists, and technologists that will not only bring awareness of Safety Code 35 but will provide a basis for updating, correcting, and improving future revisions of the Safety Code.