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Purpose: To optimize a 100 msec pulse for producing CEST MRI contrast and evaluate in mice. Methods: A gradient ascent algorithm was employed to generate a family of 100 point, 100 msec pulses for use in CEST pulse trains ('PRECISE'). Gradient ascent optimizations were performed for exchange rates (k ca ) = 500 s -1 , 1,500 s -1 , 2,500 s -1 , 3,500 s -1 and 4,500 s -1 and offsets (Δω) = 9.6, 7.8, 4.2 and 2.0 ppm. 7 PRECISE pulse shapes were tested on an 11.7 T scanner using a phantom containing three representative CEST agents with peak saturation B 1 = 4 µT. The pulse producing the most contrast in phantoms was then evaluated for CEST MRI pH mapping of the kidneys in healthy mice after iopamidol administration. Results: The most promising pulse in terms of contrast performance across all three phantoms was the 9.6 ppm, 2500 s -1 optimized pulse with â¼2.7 x improvement over Gaussian and â¼1.3x's over Fermi pulses. This pulse also displayed a large improvement in contrast over the Gaussian pulse after administration of iopamidol in live mice. Conclusion: A new 100 msec pulse was developed based on gradient ascent optimizations which produced better contrast compared to standard Gaussian and Fermi pulses in phantoms. This shape also showed a substantial improvement for CEST MRI pH mapping in live mice over the Gaussian shape and appears promising for a wide range of CEST applications.
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Intramolecular hydrogen bonding-based chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) contrast agents represent an innovative design strategy aiming to overcome limitations in diamagnetic CEST (diaCEST) MRI contrast agent specificity and also those associated with traditional metal-based MRI contrast agents. Ward and Balaban's proposal of small diamagnetic compounds marked a paradigm shift in contrast-based radiologic research, inspiring extensive investigations since 2000. These contrast agents leverage labile hydrogen bonds, serving as chemical exchange sites to induce saturation of water. The selective manipulation of radiofrequency (RF) allows for optimized signal contrast in soft tissue, with a significant signal amplification even at low probe concentrations, mitigating concerns about dose-dependent toxicities. This mini-review delves into the evolution of CEST MRI, its classification, and the strategic design principles of synthetic small molecules containing intramolecular hydrogen bonds. With a focus on applications and potential clinical relevance, the authors highlight the promising role of intramolecular hydrogen bonding-based CEST MRI in diverse medical contexts, especially renal imaging and pH mapping, paving the way for enhanced molecular imaging capabilities. Ongoing research endeavors aim to further optimize and expand the utility of these contrast agents, underscoring their transformative potential in clinical diagnostics and imaging.
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BACKGROUND: The provision of diversity-sensitive care is a promising approach towards reducing health disparities. Recent criticism and a scientific gap demonstrate the need for the patient perspective on diversity-sensitive care. This systematic review aims to describe the patient perspective, including patient experiences, expectations, and satisfaction with diversity-sensitive care provided by healthcare providers. METHODS: In December 2022 the Medline ALL, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO and additionally Google Scholar were searched for original studies that described or measured patient expectations, experiences, and/or satisfaction, specifically focusing on cultural or diversity competence of healthcare providers. Analysis of the collected data was performed using a convergent mixed-methods design based on thematic synthesis. RESULTS: From initially 5,387 articles, 117 were selected for full-text screening, and ultimately, 34 articles were included in this study. The concept of diversity-sensitive care was observed to comprise three components. The first component is focused on patient-centered care and includes competencies such as clear and direct communication, shared decision-making, individualized care, empathy, and consideration. The second component centers on providing culturally tailored information, adjusting care to cultural needs, working with interpreters, allyship, community partnerships, self-awareness, and cultural knowledge, and builds upon the first component. Across the first two components of diversity-sensitive care, patients have reported experiencing dissatisfaction and encountering shortcomings in their healthcare providers, sometimes resulting in the third and final component pertaining to provider care. This component underscores the importance of linguistic, ethnic, cultural, and gender concordance in delivering quality care. CONCLUSION: In conclusion, the patient perspective on diversity-sensitive care encompasses multiple components, from patient-centered care to concordant care. The components incorporate various competencies as communication skills, empathy, self-awareness and adjusting care to cultural needs. Patients reported experiencing dissatisfaction and shortcomings across all components of diversity-sensitive care provided by healthcare providers.
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Competência Cultural , Assistência Centrada no Paciente , Humanos , Comunicação , Diversidade Cultural , Empatia , Pessoal de Saúde/psicologia , Satisfação do PacienteRESUMO
For the improved delivery of cancer therapeutics and imaging agents, the conjugation of cell-penetrating peptides (CPPs) increases the cellular uptake and water solubility of agents. Among the various CPPs, arginine-rich peptides have been the most widely used. Combining CPPs with enzyme-responsive peptides presents an innovative strategy to target specific intracellular enzymes in cancer cells and when combined with the appropriate click chemistry can enhance theranostic drug delivery through the formation of intracellular self-assembled nanostructures. However, one drawback of CPPs is their high positive charge which can cause nonspecific binding, leading to off-target accumulation and potential toxicity. Hence, balancing cell-specific penetration, toxicity, and biocompatibility is essential for future clinical efficacy. We synthesized six cancer-specific, legumain-responsive RnAANCK peptides containing one to six arginine residues, with legumain being an asparaginyl endopeptidase that is overexpressed in aggressive prostate tumors. When conjugated to Alexa Fluor 488, R1-R6AANCK peptides exhibited a concentration- and time-dependent cell penetration in prostate cancer cells, which was higher for peptides with higher R values, reaching a plateau after approximately 120 min. Highly aggressive DU145 prostate tumor cells, but not less aggressive LNCaP cells, self-assembled nanoparticles in the cytosol after the cleavage of the legumain-specific peptide. The in vivo biocompatibility was assessed in mice after the intravenous injection of R1-R6AANCK peptides, with concentrations ranging from 0.0125 to 0.4 mmol/kg. The higher arginine content in R4-6 peptides showed blood and urine indicators for the impairment of bone marrow, liver, and kidney function in a dose-dependent manner, with instant hemolysis and morbidity in extreme cases. These findings underscore the importance of designing peptides with the optimal arginine residue length for a proper balance of cell-specific penetration, toxicity, and in vivo biocompatibility.
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Peptídeos Penetradores de Células , Neoplasias , Animais , Camundongos , Arginina/química , Peptídeos Penetradores de Células/química , Neoplasias/tratamento farmacológicoRESUMO
Inspired by the principle of in situ self-assembly, the development of enzyme-activated molecular nanoprobes can have a profound impact on targeted tumor detection. However, despite their intrinsic promise, obtaining an optical readout of enzyme activity with high specificity in native milieu has proven to be challenging. Here, a fundamentally new class of Raman-active self-assembling bioorthogonal enzyme recognition (nanoSABER) probes for targeted tumor imaging is reported. This class of Raman probes presents narrow spectral bands reflecting their vibrational fingerprints and offers an attractive solution for optical imaging at different bio-organization levels. The optical beacon harnesses an enzyme-responsive peptide sequence, unique tumor-penetrating properties, and vibrational tags with stretching frequencies in the cell-silent Raman window. The design of nanoSABER is tailored and engineered to transform into a supramolecular structure exhibiting distinct vibrational signatures in presence of target enzyme, creating a direct causality between enzyme activity and Raman signal. Through the integration of substrate-specific for tumor-associated enzyme legumain, unique capabilities of nanoSABER for imaging enzyme activity at molecular, cellular, and tissue levels in combination with machine learning models are shown. These results demonstrate that the nanoSABER probe may serve as a versatile platform for Raman-based recognition of tumor aggressiveness, drug accumulation, and therapeutic response.
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Neoplasias , Humanos , Neoplasias/diagnóstico por imagem , Imagem ÓpticaRESUMO
Objective: Interstitial lung disease (ILD) is relatively common in patients with lung cancer with an incidence of 7.5%. Historically pre-existing ILD was a contraindication to radical radiotherapy owing to increased radiation pneumonitis rates, worsened fibrosis and poorer survival compared with non-ILD cohorts. Herein, the clinical and radiological toxicity outcomes of a contemporaneous cohort are described. Methods: Patients with ILD treated with radical radiotherapy for lung cancer at a regional cancer centre were collected prospectively. Radiotherapy planning, tumour characteristics, and pre- and post-treatment functional and radiological parameters were recorded. Cross-sectional images were independently assessed by two Consultant Thoracic Radiologists. Results: Twenty-seven patients with co-existing ILD received radical radiotherapy from February 2009 to April 2019, with predominance of usual interstitial pneumonia subtype (52%). According to ILD-GAP scores, most patients were Stage I. After radiotherapy, localised (41%) or extensive (41%) progressive interstitial changes were noted for most patients yet dyspnoea scores (n = 15 available) and spirometry (n = 10 available) were stable. One-third of patients with ILD went on to receive long-term oxygen therapy, which was significantly more than the non-ILD cohort. Median survival trended towards being worse compared with non-ILD cases (17.8 vs 24.0 months, p = 0.834). Conclusion: Radiological progression of ILD and reduced survival were observed post-radiotherapy in this small cohort receiving lung cancer radiotherapy, although a matched functional decline was frequently absent. Although there is an excess of early deaths, long-term disease control is achievable. Advances in knowledge: For selected patients with ILD, long-term lung cancer control without severely impacting respiratory function may be possible with radical radiotherapy, albeit with a slightly higher risk of death.
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Purpose To examine the association between hypoxia and programmed cell death ligand 1 (PD-L1) expression using bioluminescence imaging (BLI) and PET/MRI in a syngeneic mouse model of triple-negative breast cancer (TNBC). Materials and Methods PET/MRI and optical imaging were used to determine the role of hypoxia in altering PD-L1 expression using a syngeneic TNBC model engineered to express luciferase under hypoxia. Results Imaging showed a close spatial association between areas of hypoxia and increased PD-L1 expression in the syngeneic murine (4T1) tumor model. Mouse and human TNBC cells exposed to hypoxia exhibited a significant increase in PD-L1 expression, consistent with the in vivo imaging data. The role of hypoxia in increasing PD-L1 expression was further confirmed by using The Cancer Genome Atlas analyses of different human TNBCs. Conclusion These results have identified the potential role of hypoxia in contributing to PD-L1 heterogeneity in tumors by increasing cancer cell PD-L1 expression. Keywords: Hypoxia, PD-L1, Triple-Negative Breast Cancer, PET/MRI, Bioluminescence Imaging Supplemental material is available for this article. © RSNA, 2023.
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Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/genética , Antígeno B7-H1/genética , Ligantes , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Hipóxia , ApoptoseRESUMO
BACKGROUND: Accumulating evidence shows a role of the hospital wastewater system in the spread of multidrug-resistant organisms, such as carbapenemase producing Enterobacterales (CPE). Several sequential outbreaks of CPE on the geriatric ward of the Ghent University hospital have led to an outbreak investigation. Focusing on OXA-48 producing Citrobacter freundii, the most prevalent species, we aimed to track clonal relatedness using whole genome sequencing (WGS). By exploring transmission routes we wanted to improve understanding and (re)introduce targeted preventive measures. METHODS: Environmental screening (toilet water, sink and shower drains) was performed between 2017 and 2021. A retrospective selection was made of 53 Citrobacter freundii screening isolates (30 patients and 23 environmental samples). DNA from frozen bacterial isolates was extracted and prepped for shotgun WGS. Core genome multilocus sequence typing was performed with an in-house developed scheme using 3,004 loci. RESULTS: The CPE positivity rate of environmental screening samples was 19.0% (73/385). Highest percentages were found in the shower drain samples (38.2%) and the toilet water samples (25.0%). Sink drain samples showed least CPE positivity (3.3%). The WGS data revealed long-term co-existence of three patient sample derived C. freundii clusters. The biggest cluster (ST22) connects 12 patients and 8 environmental isolates taken between 2018 and 2021 spread across the ward. In an overlapping period, another cluster (ST170) links eight patients and four toilet water isolates connected to the same room. The third C. freundii cluster (ST421) connects two patients hospitalised in the same room but over a period of one and a half year. Additional sampling in 2022 revealed clonal isolates linked to the two largest clusters (ST22, ST170) in the wastewater collection pipes connecting the rooms. CONCLUSIONS: Our findings suggest long-term circulation and transmission of carbapenemase producing C. freundii clones in hospital sanitary installations despite surveillance, daily cleaning and intermittent disinfection protocols. We propose a role for the wastewater drainage system in the spread within and between rooms and for the sanitary installations in the indirect transmission via bioaerosol plumes. To tackle this problem, a multidisciplinary approach is necessary including careful design and maintenance of the plumbing system.
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Citrobacter freundii , Águas Residuárias , Humanos , Idoso , Citrobacter freundii/genética , Engenharia Sanitária , Estudos Retrospectivos , Hospitais , Células ClonaisRESUMO
Chemical exchange saturation transfer (CEST) MRI is a versatile molecular imaging approach that holds great promise for clinical translation. A number of compounds have been identified as suitable for performing CEST MRI, including paramagnetic CEST (paraCEST) agents and diamagnetic CEST (diaCEST) agents. DiaCEST agents are very attractive because of their excellent biocompatibility and potential for biodegradation, such as glucose, glycogen, glutamate, creatine, nucleic acids, et al. However, the sensitivity of most diaCEST agents is limited because of small chemical shifts (1.0-4.0 ppm) from water. To expand the catalog of diaCEST agents with larger chemical shifts, herein, we have systematically investigated the CEST properties of acyl hydrazides with different substitutions, including aromatic and aliphatic substituents. We have tuned the labile proton chemical shifts from 2.8-5.0 ppm from water while exchange rates varied from ~680 to 2340 s-1 at pH 7.2, which allows strong CEST contrast on scanners down to B0 = 3 T. One acyl hydrazide, adipic acid dihydrazide (ADH), was tested on a mouse model of breast cancer and showed nice contrast in the tumor region. We also prepared a derivative, acyl hydrazone, which showed the furthest shifted labile proton (6.4 ppm from water) and excellent contrast properties. Overall, our study expands the catalog of diaCEST agents and their application in cancer diagnosis.
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Here we develop a mechanism of protein optimization using a computational approach known as "genetic programming". We developed an algorithm called Protein Optimization Engineering Tool (POET). Starting from a small library of literature values, the use of this tool allowed us to develop proteins that produce four times more MRI contrast than what was previously state-of-the-art. Interestingly, many of the peptides produced using POET were dramatically different with respect to their sequence and chemical environment than existing CEST producing peptides, and challenge prior understandings of how those peptides function. While existing algorithms for protein engineering rely on divergent evolution, POET relies on convergent evolution and consequently allows discovery of peptides with completely different sequences that perform the same function with as good or even better efficiency. Thus, this novel approach can be expanded beyond developing imaging agents and can be used widely in protein engineering.
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Imageamento por Ressonância Magnética , Engenharia de Proteínas , Genes Reporter , Imageamento por Ressonância Magnética/métodos , Engenharia de Proteínas/métodos , Algoritmos , ProteínasRESUMO
PURPOSE: To assess the potential of DCE MR CEST urography for assessing renal function in mice with unilateral ureter obstruction (UUO) by simultaneous pH and renal uptake/clearance measurements following injection of iopamidol. METHODS: The right ureter of nine mice was obstructed via suture ligation. The animals were imaged at day 1, 2, and 3 post-obstruction on an 11.7T MRI scanner. Ninety-six sets of saturated CEST images at 4.3 and 5.5 ppm were collected. Renal pH values were obtained by calculating the signal ratio for these two frequencies and using a pH calibration curve. Renal time activity curves were measured as a percentage change in the post-injection CEST signal at 4.3 ppm relative to the average pre-injection signal. RESULTS: For the healthy mice, the time activity curves of both kidneys were nearly identical and displayed rapid excretion of contrast. For the UUO mice, the dynamic CEST curves for the obstructed kidneys displayed prolonged time to peak (TTP) values and delayed contrast excretion compared with the contralateral (CL) kidneys. Renal pH maps of the healthy animals showed similar acidic values for both kidneys (pH 6.65 ± 0.04 vs 6.67 ± 0.02), whereas in the obstructed kidneys there was a significant increase in pH values compared with the CL kidneys (pH 6.67 ± 0.08 vs 6.79 ± 0.11 in CL and UUO kidneys, respectively). CONCLUSION: Our findings indicate that DCE-MR-CEST urography can detect changes in renal uptake/excretion and pH homeostasis and distinguish between obstructed and unobstructed kidney as early as 1 day after UUO.
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Ureter , Obstrução Ureteral , Animais , Camundongos , Obstrução Ureteral/diagnóstico por imagem , Rim/diagnóstico por imagem , Rim/fisiologia , Imageamento por Ressonância Magnética/métodos , Concentração de Íons de Hidrogênio , UrografiaRESUMO
Since the inception of CEST MRI in the 1990s, a number of compounds have been identified as suitable for generating contrast, including paramagnetic lanthanide complexes, hyperpolarized atom cages and, most interesting, diamagnetic compounds. In the past two decades, there has been a major emphasis in this field on the identification and application of diamagnetic compounds that have suitable biosafety profiles for usage in medical applications. Even in the past five years there has been a tremendous growth in their numbers, with more and more emphasis being placed on finding those that can be ultimately used for patient studies on clinical 3 T scanners. At this point, a number of endogenous compounds present in tissue have been identified, and also natural and synthetic organic compounds that can be administered to highlight pathology via CEST imaging. Here we will provide a very extensive snapshot of the types of diamagnetic compound that can generate CEST MRI contrast, together with guidance on their utility on typical preclinical and clinical scanners and a review of the applications that might benefit the most from this new technology.
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Meios de Contraste , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
Coronavirus disease 2019 (COVID-19) is a significant cause for intensive care unit (ICU) admission worldwide. Most COVID-19 infections are associated with lower respiratory abnormalities but it has been increasingly associated with extra-pulmonary manifestations. Guillain-Barre syndrome (GBS) is a rarely diagnosed but severe disease associated with COVID-19 infection. We describe the diagnostic process behind diagnosing GBS in an elderly male who developed acute-onset quadriparesis and respiratory muscle failure associated with severe COVID-19 pneumonia in a military ICU. A 69-year-old male was admitted to the ICU for acute hypoxemic respiratory failure due to COVID-19 pneumonia. He was subsequently intubated and treated with dexamethasone and remdesivir with improvement. On hospital day 32, the patient was extubated. Three days later, he developed acute, symmetric limb quadriparesis and respiratory muscle failure requiring reintubation. Analysis of his cerebrospinal fluid showed a cytoalbuminologic dissociation, and electromyography/nerve conduction study showed slowed nerve conduction velocity. These findings are consistent with GBS. Blood cultures, serum polymerase chain reaction testing, and clinical symptoms were not suggestive of other common pathogens causing his GBS. The patient's acute GBS in the setting of recent severe COVID-19 infection strongly suggests association between the two entities, as supported by a growing body of case literature. The patient was subjected to intravenous immunoglobulin treatment and was discharged with greatly improved strength in the upper and lower extremities. Our goal in describing this case is to highlight the need for providers to consider, accurately diagnose, and treat GBS as a consequence of severe COVID-19 infection.
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COVID-19 , Síndrome de Guillain-Barré , Militares , Masculino , Humanos , Idoso , COVID-19/complicações , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/diagnóstico , SARS-CoV-2 , Unidades de Terapia Intensiva , Quadriplegia/complicaçõesRESUMO
At the beginning of the millennium, the first chemical exchange saturation transfer (CEST) contrast agents were bio-organic molecules. However, later, metal-based CEST agents (paraCEST agents) took center stage. This did not last too long as paraCEST agents showed limited translational potential. By contrast, the CEST field gradually became dominated by metal-free CEST agents. One branch of research stemming from the original work by van Zijl and colleagues is the development of CEST agents based on polypeptides. Indeed, in the last 2 decades, tremendous progress has been achieved in this field. This includes the design of novel peptides as biosensors, genetically encoded recombinant as well as synthetic reporters. This was a result of extensive characterization and elucidation of the theoretical requirements for rational designing and engineering of such agents. Here, we provide an extensive overview of the evolution of more precise protein-based CEST agents, review the rationalization of enzyme-substrate pairs as CEST contrast enhancers, discuss the theoretical considerations to improve peptide selectivity, specificity and enhance CEST contrast. Moreover, we discuss the strong influence of synthetic biology on the development of the next generation of protein-based CEST contrast agents.
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Meios de Contraste , Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Meios de Contraste/química , Biologia Sintética , Peptídeos , Interpretação de Imagem Assistida por Computador/métodosRESUMO
Here, we describe and assess the potential of 14 newly synthesized imidazole-4,5-dicarboxyamides (I45DCs) for pH and perfusion imaging. A number of these aromatic compounds possess large labile proton chemical shifts (up to 7.7 ppm from water) because of their intramolecular hydrogen bonds and a second labile proton to allow for chemical exchange saturation transfer (CEST) signal ratio-based pH measurements. We have found that the contrast produced is strong for a wide range of substitutions and that the inflection points in the CEST signal ratio versus pH plots used to generate concentration-independent pH maps can be adjusted based on these subsitutions to tune the pH range that can be measured. These I45DC CEST agents have advantages over the triiodobenzenes currently employed for tumor and kidney pH mapping, both preclinically and in initial human studies. Finally, as CEST MRI combined with exogenous contrast has the potential to detect functional changes in the kidneys, we evaluated our highest performing anionic compound (I45DC-diGlu) on a unilateral urinary obstruction mouse model and observed lower contrast uptake in the obstructed kidney compared with the unobstructed kidney and that the unobstructed kidney displayed a pH of ~ 6.5 while the obstructed kidney had elevated pH and an increased range in pH values. Based on this, we conclude that the I45DCs have excellent imaging properties and hold promise for a variety of medical imaging applications, particularly renal imaging.
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Meios de Contraste , Prótons , Camundongos , Animais , Humanos , Concentração de Íons de Hidrogênio , Meios de Contraste/química , Imagens de Fantasmas , Imageamento por Ressonância Magnética/métodos , Imidazóis , Imagem de PerfusãoRESUMO
ABSTRACT: Louisiana has aligned its radiological emergency program with the 2017 US Environmental Protection Agency Protective Action Guides Manual but has added a child thyroid dose evacuation threshold in lieu of distributing potassium iodide to the public. The nuclear power plants will continue to align with the 1992 manual for the foreseeable future, which could lead to possible accident scenarios in which state recommendations would differ from those of the utility. The objective of this study is to predict what accident and weather conditions will lead to a differing set of recommendations. This study performs a representative set of simulations of potential nuclear power plant accidents using a combination of the RASCAL software package, provided by the Nuclear Regulatory Commission, and a Software system used by Entergy combining an older RASCAL dose modeling methodology with plant-specific input. Four preliminary results of this study are presented: a spent fuel fire where differences in whole body dose lead to very different evacuations, a loss of coolant accident in which the child thyroid dose is the determining factor, a core melt accident using stack monitors to locate the evacuation threshold point, and a spiked coolant accident that could lead to an evacuation order before the plant declares a General Emergency. Weather plays as great a role as accident conditions in determining whether the evacuation recommendations differ. The completed results of this study can provide guidance to states as they evaluate the transition to the 2017 guidelines.
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Acidente Nuclear de Fukushima , Centrais Nucleares , Acidentes , Criança , Humanos , Louisiana , Glândula TireoideRESUMO
PURPOSE: COVID-19 infection poses a significant risk of both renal injury and pulmonary embolism, producing a clinical challenge, as the criterion standard examination for pulmonary embolism, computed tomography angiography (CTA), requires the use of nephrotoxic iodinated contrast agents.Our investigation evaluated whether symptomatic COVID-19-positive patients without laboratory evidence of renal impairment are at increased risk for developing contrast-associated acute kidney injury (CA-AKI). METHOD: All COVID-19-positive patients undergoing noncontrast chest computed tomography and CTA at an apex tertiary medical center between March 1 and December 10, 2020, were retrospectively evaluated. A total of 258 renal-competent (estimated glomerular filtration rate >30) patients with baseline and 48- to 72-hour postexamination creatinine measurements were identified and analyzed for incidence of acute kidney injury (AKI) meeting the criteria for CA-AKI. RESULTS: Twenty-five of 191 patients undergoing CTA (13.1%) and 9 of the 67 undergoing noncontrast computed tomography (13.4%) experienced creatinine increases meeting the criteria for CA-AKI. Univariate and multivariate analyses accounting for known AKI risk factors revealed no correlation between iodinated contrast administration and the incidence AKI meeting the criteria for CA-AKI (univariable odds ratio, 0.97 [95% confidence interval, 0.43-2.20]; multivariable odds ratio, 0.97 [95% confidence interval, 0.40-2.36]). CONCLUSIONS: Renal-competent COVID-19 patients undergoing chest CTA may not have an increased risk of AKI. Additional studies are needed to confirm this preliminary finding.
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Injúria Renal Aguda , COVID-19 , Embolia Pulmonar , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Angiografia , Meios de Contraste/efeitos adversos , Creatinina , Taxa de Filtração Glomerular , Humanos , Incidência , Rim/diagnóstico por imagem , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: To develop a quantitative MRI method to estimate cerebrovascular reactivity (CVR) in mice. METHODS: We described an MRI procedure to measure cerebral vasodilatory response to acetazolamide (ACZ), a vasoactive agent previously used in human clinical imaging. Vascular response was determined by cerebral blood flow (CBF) measured with phase-contrast or pseudo-continuous arterial spin labeling MRI. Vasodilatory input intensity was determined by plasma ACZ level using high-performance liquid chromatography. We verified the source of the CVR MRI signal by comparing ACZ injection to phosphate-buffered saline injection and noninjection experiments. Dose dependence and feasibility of regional CVR measurement were also investigated. RESULTS: Cerebral blood flow revealed an exponential increase following intravenous ACZ injection, with a time constant of 1.62 min. In contrast, phosphate-buffered saline or noninjection exhibited a slow linear CBF increase, consistent with a gradual accumulation of anesthetic agent, isoflurane, used in this study. When comparing different ACZ doses, injections of 30, 60, 120, and 180 mg/kg yielded a linear increase in plasma ACZ concentration (p < 0.0001). On the other hand, CBF changes under these doses were not different from each other (p = 0.50). The pseudo-continuous arterial spin labeling MRI with multiple postlabeling delays revealed similar vascular responses at different postlabeling delay values. There was a regional difference in CVR (p = 0.005), with isocortex (0.81 ± 0.17%/[µg/ml]) showing higher CVR than deep-brain regions. Mice receiving multiple ACZ injections lived for a minimum of 6 months after the study without noticeable aberrant behavior or appearance. CONCLUSIONS: We demonstrated the proof-of-principle of a new quantitative CVR mapping technique in mice.