Personalized coronary and myocardial blood flow models incorporating CT perfusion imaging and synthetic vascular trees.

Computational simulations of coronary artery blood flow, using anatomical models based on clinical imaging, are an emerging non-invasive tool for personalized treatment planning. However, current simulations contend with two related challenges - incomplete anatomies in image-based models due to the exclusion of arteries smaller than the imaging resolution, and the lack of personalized flow distributions informed by patient-specific imaging. We introduce a data-enabled, personalized and multi-scale flow simulation framework spanning large coronary arteries to myocardial microvasculature. It includes image-based coronary anatomies combined with synthetic vasculature for arteries below the imaging resolution, myocardial blood flow simulated using Darcy models, and systemic circulation represented as lumped-parameter networks. We propose an optimization-based method to personalize multiscale coronary flow simulations by assimilating clinical CT myocardial perfusion imaging and cardiac function measurements to yield patient-specific flow distributions and model parameters. Using this proof-of-concept study on a cohort of six patients, we reveal substantial differences in flow distributions and clinical diagnosis metrics between the proposed personalized framework and empirical methods based purely on anatomy; these errors cannot be predicted a priori. This suggests virtual treatment planning tools would benefit from increased personalization informed by emerging imaging methods.

Implicit screening of abdominal aortic aneurysms among veterans using lumbar spine MRI.

BACKGROUND: Early detection of abdominal aortic aneurysms (AAAs) is critical given the high morbidity and mortality of a ruptured aneurysm. Screening ultrasound is recommended for men 65 and 75 years of age with a smoking history. However, studies have shown that the rate of ultrasound screening is low and that implicit AAA screening by abdominal imaging studies that were not originally intended for AAA screening can play a major role in AAA detection. OBJECTIVE: The main objective was to evaluate the role of lumbar spine MRIs as an implicit AAA screening study by assessing the detection rate of AAAs in a broader cohort of veterans that included screening and non-screening populations. METHODS: 4085 consecutive lumbar spine MRIs from our institution between 2/2020 and 9/2023 were retrospectively reviewed. Each study was labeled AAA present, AAA not present, or indeterminate by radiologists. The correlation between the presence of AAAs and cardiovascular risk factors was assessed using multinomial logistic regression. RESULTS: AAAs were present in 89 studies (2.2 %) from 80 patients (mean age 75.8 (56-93), M:F 10:0) and absent in 3935 cases (96.3 %) from 3310 patients (mean age 61.7 (19-100), M:F 9:1). Indeterminate cases (n = 61, 1.5 %) were mainly due to incomplete visualization (70.5 %). Mean AAA size was 3.6 cm with most AAAs (n = 43) smaller than 3.5 cm. Sixteen AAAs were 3.5-3.9 cm, 16 between 4 and 4.9cm, and 6 between 5 and 5.9 cm. Artifact precluded measurements in 8 cases. Among the AAA-positive cases, 20 had no prior documentation of AAA. Twenty-one patients with AAAs would not have met the criteria for the routine AAA screening ultrasound. Higher rates of hypertension, hyperlipidemia, and smoking were observed for the AAA cohort at 78.8 % (OR 2.037, CI 1.160-3.576, P = .013), 82.5 % (2.808, 1.543-5.110, P < .001), and 75 % (3.340, 1.979-5.638, P < .001), respectively, compared to the matched no-AAA cohort (58.2 %, 57.6 %, and 50.8 %; n = 2055). CONCLUSION: Lumbar spine MRI is a valid modality for implicit screening of AAAs. CLINICAL IMPACT: Those interpreting lumbar spine MRIs should be vigilant about assessing for AAAs, especially in men with a history of hypertension, hyperlipidemia, or tobacco smoking.

Prognostic Value of Qualitative and Quantitative Stress CMR in Patients With Known or Suspected CAD.

BACKGROUND: Recent studies suggest that quantitative cardiac magnetic resonance (CMR) may have more accuracy than qualitative CMR in coronary artery disease (CAD) diagnosis. However, the prognostic value of quantitative and qualitative CMR has not been compared systematically. OBJECTIVES: The objective was to conduct a systematic review and meta-analysis assessing the utility of qualitative and quantitative stress CMR in the prognosis of patients with known or suspected CAD. METHODS: A comprehensive search was performed through Embase, Scopus, Web of Science, and Medline. Studies that used qualitative vasodilator CMR or quantitative CMR assessments to compare the prognosis of patients with positive and negative CMR results were extracted. A meta-analysis was then performed to assess: 1) major adverse cardiovascular events (MACE) including cardiac death, nonfatal myocardial infarction (MI), unstable angina, and coronary revascularization; and 2) cardiac hard events defined as the composite of cardiac death and nonfatal MI. RESULTS: Forty-one studies with 38,030 patients were included in this systematic review. MACE occurred significantly more in patients with positive qualitative (HR: 3.86; 95% CI: 3.28-4.54) and quantitative (HR: 4.60; 95% CI: 1.60-13.21) CMR assessments. There was no significant difference between qualitative and quantitative CMR assessments in predicting MACE (P = 0.75). In studies with qualitative CMR assessment, cardiac hard events (OR: 7.21; 95% CI: 4.99-10.41), cardiac death (OR: 5.63; 95% CI: 2.46-12.92), nonfatal MI (OR: 7.46; 95% CI: 3.49-15.96), coronary revascularization (OR: 6.34; 95% CI: 3.42-1.75), and all-cause mortality (HR: 1.66; 95% CI: 1.12-2.47) were higher in patients with positive CMR. CONCLUSIONS: The presence of myocardial ischemia on CMR is associated with worse clinical outcomes in patients with known or suspected CAD. Both qualitative and quantitative stress CMR assessments are helpful tools for predicting clinical outcomes.

Performance of alternative manual and automated deep learning segmentation techniques for the prediction of benign and malignant lung nodules.

Purpose: We aim to evaluate the performance of radiomic biopsy (RB), best-fit bounding box (BB), and a deep-learning-based segmentation method called no-new-U-Net (nnU-Net), compared to the standard full manual (FM) segmentation method for predicting benign and malignant lung nodules using a computed tomography (CT) radiomic machine learning model. Materials and Methods: A total of 188 CT scans of lung nodules from 2 institutions were used for our study. One radiologist identified and delineated all 188 lung nodules, whereas a second radiologist segmented a subset (n=20) of these nodules. Both radiologists employed FM and RB segmentation methods. BB segmentations were generated computationally from the FM segmentations. The nnU-Net, a deep-learning-based segmentation method, performed automatic nodule detection and segmentation. The time radiologists took to perform segmentations was recorded. Radiomic features were extracted from each segmentation method, and models to predict benign and malignant lung nodules were developed. The Kruskal-Wallis and DeLong tests were used to compare segmentation times and areas under the curve (AUC), respectively. Results: For the delineation of the FM, RB, and BB segmentations, the two radiologists required a median time (IQR) of 113 (54 to 251.5), 21 (9.25 to 38), and 16 (12 to 64.25) s, respectively (p=0.04). In dataset 1, the mean AUC (95% CI) of the FM, RB, BB, and nnU-Net model were 0.964 (0.96 to 0.968), 0.985 (0.983 to 0.987), 0.961 (0.956 to 0.965), and 0.878 (0.869 to 0.888). In dataset 2, the mean AUC (95% CI) of the FM, RB, BB, and nnU-Net model were 0.717 (0.705 to 0.729), 0.919 (0.913 to 0.924), 0.699 (0.687 to 0.711), and 0.644 (0.632 to 0.657). Conclusion: Radiomic biopsy-based models outperformed FM and BB models in prediction of benign and malignant lung nodules in two independent datasets while deep-learning segmentation-based models performed similarly to FM and BB. RB could be a more efficient segmentation method, but further validation is needed.

ACR Appropriateness Criteria® Workup of Noncerebral Systemic Arterial Embolic Source.

Noncerebral systemic arterial embolism, which can originate from cardiac and noncardiac sources, is an important cause of patient morbidity and mortality. When an embolic source dislodges, the resulting embolus can occlude a variety of peripheral and visceral arteries causing ischemia. Characteristic locations for noncerebral arterial occlusion include the upper extremities, abdominal viscera, and lower extremities. Ischemia in these regions can progress to tissue infarction resulting in limb amputation, bowel resection, or nephrectomy. Determining the source of arterial embolism is essential in order to direct treatment decisions. This document reviews the appropriateness category of various imaging procedures available to determine the source of the arterial embolism. The variants included in this document are known arterial occlusion in the upper extremity, lower extremity, mesentery, kidneys, and multiorgan distribution that are suspected to be of embolic etiology. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Perspectives of nanomaterials in microbial remediation of heavy metals and their environmental consequences: A review.

Nanomaterials (NMs) have diverse applications in various sectors, such as decontaminating heavy metals from drinking water, wastewater, and soil. Their degradation efficiency can be enhanced through the application of microbes. As microbial strain releases enzymes, which leads to the degradation of HMs. Therefore, nanotechnology and microbial-assisted remediation-based methods help us develop a remediation process with practical utility, speed, and less environmental toxicity. This review focuses on the success achieved for the bioremediation of heavy metals by nanoparticles and microbial strains and in their integrated approach. Still, the use of NMs and heavy metals (HMs) can negatively affect the health of living organisms. This review describes various aspects of the bioremediation of heavy materials using microbial nanotechnology. Their safe and specific use supported by bio-based technology paves the way for their better remediation. We discuss the utility of nanomaterials for removing heavy metals from wastewater, toxicity studies and issues to the environment with their practical implications. Nanomaterial assisted heavy metal degradation coupled with microbial technology and disposal issues are described along with detection methods. Environmental impact of nanomaterials is also discussed based on the recent work conducted by the researchers. Therefore, this review opens new avenues for future research with an impact on the environment and toxicity issues. Also, applying new biotechnological tools will help us develop better heavy metal degradation routes.

ACR Appropriateness Criteria® Chronic Chest Pain-High Probability of Coronary Artery Disease: 2021 Update.

Management of patients with chronic chest pain in the setting of high probability of coronary artery disease (CAD) relies heavily on imaging for determining or excluding presence and severity of myocardial ischemia, hibernation, scarring, and/or the presence, site, and severity of obstructive coronary lesions, as well as course of management and long-term prognosis. In patients with no known ischemic heart disease, imaging is valuable in determining and documenting the presence, extent, and severity of obstructive coronary narrowing and presence of myocardial ischemia. In patients with known ischemic heart disease, imaging findings are important in determining the management of patients with chronic myocardial ischemia and can serve as a decision-making tool for medical therapy, angioplasty, stenting, or surgery. This document summarizes the recent growing body of evidence on various imaging tests and makes recommendations for imaging based on the available data and expert opinion. This document is focused on epicardial CAD and does not discuss the microvascular disease as the cause for CAD. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Dynamic Myocardial Perfusion CT for the Detection of Hemodynamically Significant Coronary Artery Disease.

OBJECTIVES: In this international, multicenter study, using third-generation dual-source computed tomography (CT), we investigated the diagnostic performance of dynamic stress CT myocardial perfusion imaging (CT-MPI) in addition to coronary CT angiography (CTA) compared to invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR). BACKGROUND: CT-MPI combined with coronary CTA integrates coronary artery anatomy with inducible myocardial ischemia, showing promising results for the diagnosis of hemodynamically significant coronary artery disease in single-center studies. METHODS: At 9 centers in Europe, Japan, and the United States, 132 patients scheduled for ICA were enrolled; 114 patients successfully completed coronary CTA, adenosine-stress dynamic CT-MPI, and ICA. Invasive FFR was performed in vessels with 25% to 90% stenosis. Data were analyzed by independent core laboratories. For the primary analysis, for each coronary artery the presence of hemodynamically significant obstruction was interpreted by coronary CTA with CT-MPI compared to coronary CTA alone, using an FFR of ≤0.80 and angiographic severity as reference. Territorial absolute myocardial blood flow (MBF) and relative MBF were compared using C-statistics. RESULTS: ICA and FFR identified hemodynamically significant stenoses in 74 of 289 coronary vessels (26%). Coronary CTA with ≥50% stenosis demonstrated a per-vessel sensitivity, specificity, and accuracy for the detection of hemodynamically significant stenosis of 96% (95% CI: 91%-100%), 72% (95% CI: 66%-78%), and 78% (95% CI: 73%-83%), respectively. Coronary CTA with CT-MPI showed a lower sensitivity (84%; 95% CI: 75%-92%) but higher specificity (89%; 95% CI: 85%-93%) and accuracy (88%; 95% CI: 84%-92%). The areas under the receiver-operating characteristic curve of absolute MBF and relative MBF were 0.79 (95% CI: 0.71-0.86) and 0.82 (95% CI: 0.74-0.88), respectively. The median dose-length product of CT-MPI and coronary CTA were 313 mGy·cm and 138 mGy·cm, respectively. CONCLUSIONS: Dynamic CT-MPI offers incremental diagnostic value over coronary CTA alone for the identification of hemodynamically significant coronary artery disease. Generalized results from this multicenter study encourage broader consideration of dynamic CT-MPI in clinical practice. (Dynamic Stress Perfusion CT for Detection of Inducible Myocardial Ischemia [SPECIFIC]; NCT02810795).

Preoperative Computed Tomography Angiography Reveals Leaflet-Specific Calcification and Excursion Patterns in Aortic Stenosis.

BACKGROUND: Computed tomography-based evaluation of aortic stenosis (AS) by calcium scoring does not consider interleaflet differences in leaflet characteristics. Here, we sought to examine the functional implications of these differences. METHODS: We retrospectively reviewed the computed tomography angiograms of 200 male patients with degenerative calcific AS undergoing transcatheter aortic valve replacement and 20 male patients with normal aortic valves. We compared the computed tomography angiography (CTA)-derived aortic valve leaflet calcification load (AVLCCTA), appearance, and systolic leaflet excursion (LEsys) of individual leaflets. We performed computer simulations of normal valves to investigate how interleaflet differences in LEsys affect aortic valve area. We used linear regression to identify predictors of leaflet-specific calcification in patients with AS. RESULTS: In patients with AS, the noncoronary cusp (NCC) carried the greatest AVLCCTA (365.9 [237.3-595.4] Agatston unit), compared to the left coronary cusp (LCC, 278.5 [169.2-478.8] Agatston unit) and the right coronary cusp (RCC, 240.6 [137.3-439.0] Agatston unit; both P<0.001). However, LCC conferred the least LEsys (42.8° [38.8°-49.0°]) compared to NCC (44.8° [41.1°-49.78°], P=0.001) and RCC (47.7° [42.0°-52.3°], P<0.001) and was more often characterized as predominantly thickened (23.5%) compared to NCC (12.5%) and RCC (16.5%). Computer simulations of normal valves revealed greater reductions in aortic valve area following closures of NCC (-32.2 [-38.4 to -25.8]%) and RCC (-35.7 [-40.2 to -32.9]%) than LCC (-24.5 [-28.5 to -18.3]%; both P<0.001). By linear regression, the AVLCCTA of NCC and RCC, but not LCC, predicted LEsys (both P<0.001) in patients with AS. Both ostial occlusion and ostial height of the right coronary artery predicted AVLCCTA, RCC (P=0.005 and P=0.001). CONCLUSIONS: In male patients, the AVLCCTA of NCC and RCC contribute more to AS than that of LCC. LCC's propensity for noncalcific leaflet thickening and worse LEsys, however, should not be underestimated when using calcium scores to assess AS severity.

Machine Learning Radiomics Model for Early Identification of Small-Cell Lung Cancer on Computed Tomography Scans.

PURPOSE: Small-cell lung cancer (SCLC) is the deadliest form of lung cancer, partly because of its short doubling time. Delays in imaging identification and diagnosis of nodules create a risk for stage migration. The purpose of our study was to determine if a machine learning radiomics model can detect SCLC on computed tomography (CT) among all nodules at least 1 cm in size. MATERIALS AND METHODS: Computed tomography scans from a single institution were selected and resampled to 1 × 1 × 1 mm. Studies were divided into SCLC and other scans comprising benign, adenocarcinoma, and squamous cell carcinoma that were segregated into group A (noncontrast scans) and group B (contrast-enhanced scans). Four machine learning classification models, support vector classifier, random forest (RF), XGBoost, and logistic regression, were used to generate radiomic models using 59 quantitative first-order and texture Imaging Biomarker Standardization Initiative compliant PyRadiomics features, which were found to be robust between two segmenters with minimum Redundancy Maximum Relevance feature selection within each leave-one-out-cross-validation to avoid overfitting. The performance was evaluated using a receiver operating characteristic curve. A final model was created using the RF classifier and aggregate minimum Redundancy Maximum Relevance to determine feature importance. RESULTS: A total of 103 studies were included in the analysis. The area under the receiver operating characteristic curve for RF, support vector classifier, XGBoost, and logistic regression was 0.81, 0.77, 0.84, and 0.84 in group A, and 0.88, 0.87, 0.85, and 0.81 in group B, respectively. Nine radiomic features in group A and 14 radiomic features in group B were predictive of SCLC. Six radiomic features overlapped between groups A and B. CONCLUSION: A machine learning radiomics model may help differentiate SCLC from other lung lesions.

ACR Appropriateness Criteria® Infective Endocarditis.

Infective endocarditis can involve a normal, abnormal, or prosthetic cardiac valve. The diagnosis is typically made clinically with persistently positive blood cultures, characteristic signs and symptoms, and echocardiographic evidence of valvular vegetations or valvular complications such as abscess, dehiscence, or new regurgitation. Imaging plays an important role in the initial diagnosis of infective endocarditis, identifying complications, prognostication, and informing the next steps in therapy. This document outlines the initial imaging appropriateness of a patient with suspected infective endocarditis and for additional imaging in a patient with known or suspected infective endocarditis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR appropriateness criteria infective endocarditis

Infective endocarditis can involve a normal, abnormal, or prosthetic cardiac valve. The diagnosis is typically made clinically with persistently positive blood cultures, characteristic signs and symptoms, and echocardiographic evidence of valvular vegetations or valvular complications such as abscess, dehiscence, or new regurgitation. Imaging plays an important role in the initial diagnosis of infective endocarditis, identifying complications, prognostication, and informing the next steps in therapy. This document outlines the initial imaging appropriateness of a patient with suspected infective endocarditis and for additional imaging in a patient with known or suspected infective endocarditis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Identification, expression analysis, and molecular modeling of Iron-deficiency-specific clone 3 (Ids3)-like gene in hexaploid wheat.

Graminaceous plants secrete hydroxylated phytosiderophores encoded by the genes iron-deficiency-specific clone 2 (Ids2) and iron-deficiency-specific clone 3 (Ids3). An effort was made to identify a putative ortholog of Hodeum vulgare Ids3 gene in hexaploid wheat. The protein structure of TaIDS3 was modeled using homology modeling and structural behavior of modeled structure was analyzed at 20 ns. The simulation trajectory using molecular dynamics simulation suggested the model to be stable with no large fluctuations in residues and local domain level RMSF values (< 2.4 Å). In addition, the ProFunc results also predict the functional similarity between the proteins of HvIDS3 and its wheat ortholog (TaIDS3). The TaIds3 gene was assigned to the telomeric region of chromosome arm 7AS which supports the results obtained through bioinformatics analysis. The relative expression analysis of TaIds3 indicated that the detectable expression of TaIds3 is induced after 5th day of Fe starvation and increases gradually up to 15th day, and thereafter, it decreases until 35th day of Fe-starvation. This reflects that Fe deficiency directly regulates the induction of TaIds3 in the roots of hexaploid wheat. The identification of HvIds3-like gene in wheat has opened up new opportunities to enhance the nutrient quality in wheat through biofortification program.

Transthoracic Echocardiography: Pitfalls and Limitations as Delineated at Cardiac CT and MR Imaging.

Transthoracic echocardiography ( TTE transthoracic echocardiography ) is a critical tool in the field of clinical cardiology. It often serves as one of the first-line imaging modalities in the evaluation of cardiac disease owing to its low cost, portability, widespread availability, lack of ionizing radiation, and ability to evaluate both anatomy and function of the heart. Consequently, a large majority of patients undergoing a cardiac computed tomography (CT) or magnetic resonance (MR) imaging examination will have a TTE transthoracic echocardiography available for review. Therefore, it is imperative that cardiac imagers be familiar with the fundamentals of a routine TTE transthoracic echocardiography examination and common TTE transthoracic echocardiography pitfalls and limitations that may lead to a referral for cardiac CT or MR imaging. The four standard TTE transthoracic echocardiography windows and their corresponding views will be discussed and the relevant anatomy highlighted. Common pitfalls and limitations of TTE transthoracic echocardiography will be highlighted using cardiac CT and MR imaging as the problem-solving modality. In this article, we have categorized the relevant pitfalls and limitations of TTE transthoracic echocardiography into four broad categories: (a) masses and mass mimics (crista terminalis, eustachian valve, right ventricle moderator band, atrioventricular groove fat, left ventricular band [or left ventricular false tendon], hiatal hernia, caseous calcification of the mitral annulus, lipomatous hypertrophy of the interatrial septum, cardiac tumors), (b) poorly visualized apical lesions (aneurysm, thrombus, infarct, and hypertrophic and other nonischemic cardiomyopathies), (c) evaluation for ascending thoracic aortic dissections (false positive, false negative, dissecting aneurysms), and (d) pericardial disease (acute and chronic/constrictive pericarditis, pericardial tamponade, pericardial cysts and diverticula, congenital absence of the pericardium). Online supplemental material is available for this article. ©RSNA, 2017.

Transfer of useful variability of high grain iron and zinc from Aegilops kotschyi into wheat through seed irradiation approach.

PURPOSE: To transfer the 2S chromosomal fragment(s) of Aegilops kotschyi (2S(k)) into the bread wheat genome which could lead to the biofortification of wheat with high grain iron and zinc content. MATERIALS AND METHODS: Wheat-Ae. kotschyi 2A/2S(k) substitution lines with high grain iron and zinc content were used to transfer the gene/loci for high grain Fe and Zn content into wheat using seed irradiation approach. RESULTS: Bread wheat plants derived from 40 krad-irradiated seeds showed the presence of univalents and multivalents during meiotic metaphase-I. Genomic in situ hybridization analysis of seed irradiation hybrid F2 seedlings showed several terminal and interstitial signals indicated the introgression of Ae. kotschyi chromosome segments. This proves the efficacy of seed radiation hybrid approach in gene transfer experiments. All the radiation-treated hybrid plants with high grain Fe and Zn content were analyzed with wheat group 2 chromosome-specific polymorphic simple sequence repeat markers to identify the introgression of small alien chromosome fragment(s). CONCLUSION: Radiation-induced hybrids showed more than 65% increase in grain iron and 54% increase in Zn contents with better harvest index than the elite wheat cultivar WL711 indicating effective and compensating translocations of 2S(k) fragments into wheat genome.

The right atrium: gateway to the heart--anatomic and pathologic imaging findings.

Knowledge of right atrial anatomic and pathologic imaging findings and associated clinical symptoms is important to avoid false-positive diagnoses and missed findings. Complete evaluation of the heart often requires a multimodality approach that includes radiography, echocardiography, computed tomography (CT), magnetic resonance (MR) imaging, and invasive angiography. In general, CT provides the highest spatial resolution of these modalities at the cost of radiation exposure to the patient. Echocardiography and MR imaging offer complementary and detailed information for functional evaluation without added radiation exposure. The advantages and disadvantages of each modality for the evaluation of right atrial anatomic structure, size, and pathologic findings are discussed. Cardiac MR imaging is the reference standard for evaluation of right atrial size and volume but often is too time consuming and resource intensive to perform in routine clinical practice. Therefore, established reference ranges for two-dimensional transthoracic echocardiography are often used. Right atrial pathologic findings can be broadly categorized into (a) congenital anomalies (cor triatriatum dexter, Ebstein anomaly, and aneurysm), (b) disorders of volume (tricuspid regurgitation, pathologic mimics such as a pseudoaneurysm, and atrial septal defect), (c) disorders of pressure (tricuspid stenosis, restrictive cardiomyopathy, and constrictive pericarditis), and (d) masses (pseudomasses, thrombus, lipomatous hypertrophy of the interatrial septum, lipoma, myxoma, sarcoma, and metastatic disease). Familiarity with each pathologic entity and its treatment options is essential to ensure that appropriate imaging modalities are selected. Online supplemental material is available for this article.

Design and synthesis of new of 3-(benzo[d]isoxazol-3-yl)-1-substituted pyrrolidine-2, 5-dione derivatives as anticonvulsants.

A series of 3-(benzo[d]isoxazol-3-yl)-N-substituted pyrrolidine-2, 5-dione (7a-7d, 8a-8d, 9a-9c) have been prepared and evaluated for their anticonvulsant activities. Preliminary anticonvulsant activity was performed using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests after intraperitoneal (ip) injection into mice, which are the most widely employed models for early identification of anticonvulsant candidate. The acute neurological toxicity (NT) was determined applying rotorod test. The quantitative evaluation after oral administration in rats showed that the most active was 3-(benzo[d]isoxazol-3-yl)-1-(4-fluorophenyl) pyrrolidine-2, 5-dione (8a) with ED50 values of 14.90 mg/kg. Similarly the most potent in scPTZ was 3-(benzo[d]isoxazol-3-yl)-1-cyclohexylpyrrolidine-2, 5-dione (7d) with ED50 values of 42.30 mg/kg. These molecules were more potent and less neurotoxic than phenytoin and ethosuximide which were used as reference antiepileptic drugs.

Pharmacokinetic interaction between febuxostat and morin in rats.

BACKGROUND: Due to wide consumption of flavonoids in the dietary supplement, and an imperative role of CYPs and P-glycoprotein inhibition in drug disposition. So there is increasing scientific interest in drug-flavonoid interactions. OBJECTIVE: The present study aims to investigate the effect of morin, a flavonoid, on the pharmacokinetics of febuxostat in rats. METHODS: A simple ultra-performance liquid chromatography method has been developed for the calculation of febuxostat in 100 µl rat plasma using febuxostat D7 as an internal standard (IS). The assay procedure involved a single-step, liquid-liquid extraction of febuxostat and IS from plasma with methanol. Pharmacokinetic parameters of febuxostat were determined in rats after an oral administration of febuxostat (5 mg/kg) to rats in the control, coadministered and pretreated groups of morin (10 mg/kg). RESULTS: Compared to the control rats given febuxostat alone, the Cmax and AUC of febuxostat increased by 18 - 20 and 47 - 50%, respectively, in rats pretreated with morin. The plasma half-life (t1/2) of the pretreated group is increased by 2.5-fold compared with the control group. Consequently, relative bioavailability values of febuxostat in the rats pretreated with morin were significantly higher (p < 0.05) than those from the control and coadministered groups. Increased bioavailability indicates that the presence of morin could be effective in inhibiting CYP1A1, CYP1A2 and CYP3A4-mediated metabolism and/or effective in inhibiting P-glycoprotein-mediated cellular efflux of febuxostat. CONCLUSION: The presence of morin significantly enhanced the oral exposure of febuxostat, suggesting that concurrent use of morin or morin-containing dietary supplements with febuxostat should be verified to avoid drug-flavonoid interactions.

Design and synthesis of (5-amino-1, 2, 4-triazin-6-yl)(2-(benzo[d] isoxazol-3-yl) pyrrolidin-1-yl)methanone derivatives as sodium channel blocker and anticonvulsant agents.

A series of novel (5-amino-3-substituted-1, 2, 4-triazin-6-yl) (2-(6-halo-substituted benzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5a-5r was synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test and neurotoxicity was evaluated by the rotorod test. The MES test showed that (5-amino-3-phenyl-1, 2, 4-triazin-6-yl)(2-(6-fluorobenzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5c was found to be the most potent compound with ED50 value of 6.20 mg/kg (oral/rat) and a protective index (PI = ED50/TD50) value of >48.38, which was much higher than the PI of the reference drug phenytoin. To explain the possible mechanism of action of selected derivatives 5 b, 5 c, 5 i and 5 o, their influence on sodium channel was evaluated in vitro.