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Cardiovascular magnetic resonance (CMR) is an established imaging modality with proven utility in assessing cardiovascular diseases. The ability of CMR to characterize myocardial tissue using T 1 - and T 2 -weighted imaging, parametric mapping, and late gadolinium enhancement has allowed for the non-invasive identification of specific pathologies not previously possible with modalities like echocardiography. However, CMR examinations are lengthy and technically complex, requiring multiple pulse sequences and different anatomical planes to comprehensively assess myocardial structure, function, and tissue composition. To increase the overall impact of this modality, there is a need to simplify and shorten CMR exams to improve access and efficiency, while also providing reproducible quantitative measurements. Multiparametric MRI techniques that measure multiple tissue properties offer one potential solution to this problem. This review provides an in-depth look at one such multiparametric approach, cardiac magnetic resonance fingerprinting (MRF). The article is structured as follows. First, a brief review of single-parametric and (non-Fingerprinting) multiparametric CMR mapping techniques is presented. Second, a general overview of cardiac MRF is provided covering pulse sequence implementation, dictionary generation, fast k-space sampling methods, and pattern recognition. Third, recent technical advances in cardiac MRF are covered spanning a variety of topics, including simultaneous multislice and 3D sampling, motion correction algorithms, cine MRF, synthetic multicontrast imaging, extensions to measure additional clinically important tissue properties (proton density fat fraction, T 2 *, and T 1ρ ), and deep learning methods for image reconstruction and parameter estimation. The last section will discuss potential clinical applications, concluding with a perspective on how multiparametric techniques like MRF may enable streamlined CMR protocols. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 1., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background: Transcatheter aortic valve replacement (TAVR) has become an established method of aortic stenosis treatment but suffers from the risk of heart block and pacemaker requirement. Risk stratification for patients who may develop heart block remains imperfect. Simultaneously, myocardial fibrosis as measured by cardiac magnetic resonance imaging (CMR) has been demonstrated as a prognostic indicator of ventricular recovery and mortality following TAVR. However, the association of CMR-based measures of myocardial fibrosis with post-TAVR conduction disturbances has not yet been explored., Aims: We evaluated whether myocardial fibrosis, as measured by late gadolinium enhancement and extracellular volume (ECV) from CMR would be associated with new conduction abnormalities following TAVR., Methods: One hundred seventy patients who underwent CMR within 2 months before TAVR were retrospectively reviewed. Septal late gadolinium enhancement (LGE) and ECV measurements were made as surrogates for replacement and interstitial fibrosis respectively. New conduction abnormalities were defined by the presence of transient or permanent atrioventricular block, new bundle branch blocks, and need for permanent pacemaker. Association of myocardial fibrosis and new conduction derangements were tested using receiver operator curve (ROC) and regression analysis in patients with and without pre-existing conduction issues., Results: Forty-six (27.1%) patients developed post-TAVR conduction deficits. ECV was significantly higher among patients who experienced new conduction defects (26.2 ± 3.45% vs. 24.7% ± 4.15%, p value: 0.020). A greater fraction of patients that had new conduction defects had an elevated ECV of ≥26% (54.3% vs. 36.3%, p value: 0.026). ECV ≥ 26% was independently associated with the development of new conduction defects (odds ratio [OR]: 2.364, p value: 0.030). ROC analysis revealed a significant association of ECV with new conduction defects with an area under the receiver operating characteristic curve (AUC) of 0.632 (95% confidence interval: 0.555-0.705, p value: 0.005). The combination of prior right bundle branch block (RBBB) and ECV revealed a greater AUC of 0.779 (0.709-0.839, p value: <0.001) than RBBB alone (Delong p value: 0.049). No association of LGE/ECV with new conduction defects was observed among patients with pre-existing conduction disease. Among patients without baseline conduction disease, ECV was independently associated with the development of new conduction deficits (OR: 3.685, p value: 0.008)., Conclusion: The present study explored the association of myocardial fibrosis, as measured by LGE and ECV with conduction deficits post-TAVR. Our results demonstrate an association of ECV, and thereby interstitial myocardial fibrosis, with new conduction derangement post-TAVR and introduce ECV as a potentially new risk stratification tool to identify patients at higher risk for needing post-TAVR surveillance and/or permanent pacemaker., (© 2024 Wiley Periodicals LLC.)

Background: Limited data exists regarding incidence, progression, and predictors of left atrial appendage (LAA) sealing after transcatheter LAA closure. We aimed to evaluate the incidence, progression, and predictive factors associated with LAA sealing after LAA closure., Methods: This study includes patients who underwent successful LAA closure with Watchman FLX device and had both pre- and postprocedural computed tomography (CT). Postprocedural CT was performed 45 days after LAA closure and used to evaluate residual LAA patency. Patient who had residual LAA patency at 45 days underwent 1-year follow-up CT., Results: A total of 105 patients (mean age: 75.2 ± 9.6 years; 53.3% female) who underwent successful LAA closure with Watchman FLX device and had pre- and postprocedural CT at 45 days were included. Residual patency was observed in 35 (33.3%) patients: 21 (20.0%) patients showed complete contrast opacification in LAA (complete LAA patency) while 14 (13.3%) patients showed contrast opacification only in the distal LAA (distal LAA patency). Among patients with residual LAA patency at 45 days, the rate of LAA sealing at 1 year was significantly higher in the distal LAA patency group than in the complete LAA patency group (75.0% vs. 16.7%; p = 0.019). Increased depth oversizing was associated with both distal LAA patency and complete LAA patency., Conclusion: Postprocedural CT at 45 days detected patent LAA in one-third of patients after LAA closure. LAA sealing was more frequently observed at 1 year among the distal LAA patency group than the complete LAA patency group., (© 2024 Wiley Periodicals LLC.)

Purpose: To develop a deep image prior (DIP) reconstruction for B 1 + -corrected 2D cine MR fingerprinting (MRF)., Methods: The proposed method combines low-rank (LR) modeling with a DIP to generate cardiac phase-resolved parameter maps without motion correction, employing self-supervised training to enforce consistency with undersampled spiral k-space data. Two implementations were tested: one approach (DIP) for cine T 1 , T 2 , and M 0 mapping, and a second approach (DIP with effective B 1 + estimation [DIP-B1]) that also generated an effective B 1 + map to correct for errors due to RF transmit inhomogeneities, through-plane motion, and blood flow. Cine MRF data were acquired in 14 healthy subjects and four reconstructions were compared: LR, low-rank motion-corrected (LRMC), DIP, and DIP-B1. Results were compared to diastolic ECG-triggered MRF, MOLLI, and T 2 -prep bSSFP. Additionally, bright-blood and dark-blood images calculated from cine MRF maps were used to quantify ventricular function and compared to reference cine measurements., Results: DIP and DIP-B1 outperformed other cine MRF reconstructions with improved noise suppression and delineation of high-resolution details. Within-segment variability in the myocardium (reported as the coefficient of variation for T 1 /T 2 ) was lowest for DIP-B1 (2.3/8.3%) followed by DIP (2.7/8.7%), LRMC (3.5/10.5%), and LR (15.3/39.6%). Spatial homogeneity improved with DIP-B1 having the lowest intersegment variability (2.6/4.1%). The mean bias in ejection fraction was -1.1% compared to reference cine scans., Conclusion: A DIP reconstruction for 2D cine MRF enabled cardiac phase-resolved mapping of T 1 , T 2 , M 0 , and the effective B 1 + with improved noise suppression and precision compared to LR and LRMC., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background: While studies have shown the advantages of computed tomography angiography (CTA) over transesophageal echocardiography (TEE) in left atrial appendage closure (LAAC) preprocedural planning for WATCHMAN™ legacy and FLX devices, there has been no reported long-term data for this approach., Objectives: We sought to evaluate long-term outcomes using CTA-based preprocedural planning for LAAC using the WATCHMAN™ device., Methods: A prospective analysis of 231 consecutive patients who underwent LAAC in a single, large academic hospital in the United States was conducted over a 5-year period. CTA-guided preprocedural planning was performed in all. Procedural success, adverse events, length of procedure, number of devices used, and length of stay were evaluated. Rates of death, cerebral embolism, systemic embolism, and major and minor bleeding were recorded. Adjusted predicted stroke and major bleeding rates were derived from CHA2DS2-Vasc and HAS-BLED scores, respectively., Results: From January 26, 2017, to November 23, 2021, 231 patients underwent LAAC with CTA preprocedural planning by two operating physicians. The mean age of patients was 76.5 ± 8.4. 59.7% of patients were male. Mean CHA2DS2VASc and HAS-BLED scores were 4.5 ± 1.4 and 3.9 ± 0.9, respectively. All procedures were performed with intracardiac echo (100%). The procedural success rate was 99.1%. The CTA sizing strategy accurately predicted the implant size in 93.5% of patients. Mean number of devices used was 1.10 ± 0.3. Peri-procedural complication rate was 2.2%. 6 patients were lost to follow-up. Mean follow-up was 608.94 days with a total of 377.04 patient years. Median follow-up period of 368 days (interquartile range: 209-1067 days). There were 51 deaths from all causes (13.52 per 100 patient-years), 10 cases of cerebral embolism (2.65 per 100 patient-years), 2 cases of systemic embolism (0.53 per 100 patient-years), 17 cases of major bleeding (4.50 per 100 patient-years), and 31 cases of minor bleeding (8.2 per 100 patient-years). All-cause mortality at 1, 2, and 3 years was 12.7%, 20.9%, and 29.2%, respectively. CV event rates at 1, 2, and 3 years were 2.1%, 6.6%, and 10.5%, respectively., Conclusions: CTA-based preprocedural planning is accurate in predicting device size for LAAC and associated with excellent clinical outcomes at 5 years., (© 2023 Wiley Periodicals LLC.)

Late gadolinium enhancement (LGE) MRI is the non-invasive reference standard for identifying myocardial scar and fibrosis but has limitations, including difficulty delineating subendocardial scar and operator dependence on image quality. The purpose of this work is to assess the feasibility of generating multi-contrast synthetic LGE images from post-contrast T 1 and T 2 maps acquired using magnetic resonance fingerprinting (MRF). Fifteen consecutive patients with a history of prior ischemic cardiomyopathy (12 men; mean age 63  ±  13 years) were prospectively scanned at 1.5 T between Oct 2020 and May 2021 using conventional LGE and MRF after injection of gadolinium contrast. Three classes of synthetic LGE images were derived from MRF post-contrast T 1 and T 2 maps: bright-blood phase-sensitive inversion recovery (PSIR), black- and gray-blood T 2 -prepared PSIR (T 2 -PSIR), and a novel "tissue-optimized" image to enhance differentiation among scar, viable myocardium, and blood. Image quality was assessed on a 1-5 Likert scale by two cardiologists, and contrast was quantified as the mean absolute difference (MAD) in pixel intensities between two tissues, with different methods compared using Kruskal-Wallis with Bonferroni post hoc tests. Per-patient and per-segment scar detection rates were evaluated using conventional LGE images as reference. Image quality scores were highest for synthetic PSIR (4.0) and reference images (3.8), followed by synthetic tissue-optimized (3.3), gray-blood T 2 -PSIR (3.0), and black-blood T 2 -PSIR (2.6). Among synthetic images, PSIR yielded the highest myocardium/scar contrast (MAD = 0.42) but the lowest blood/scar contrast (MAD = 0.05), and vice versa for T 2 -PSIR, while tissue-optimized images achieved a balance among all tissues (myocardium/scar MAD = 0.16, blood/scar MAD = 0.26, myocardium/blood MAD = 0.10). Based on reference mid-ventricular LGE scans, 13/15 patients had myocardial scar. The per-patient sensitivity/accuracy for synthetic images were the following: PSIR, 85/87%; black-blood T 2 -PSIR, 62/53%; gray-blood T 2 -PSIR, 100/93%; tissue optimized, 100/93%. Synthetic multi-contrast LGE images can be generated from post-contrast MRF data without additional scan time, with initial feasibility shown in ischemic cardiomyopathy patients., (© 2023 John Wiley & Sons Ltd.)

Introduction: We studied the impact of the use of three-dimensional multidetector computed tomography (3D-MDCT) and fluoroscopy fusion on percutaneous left atrial appendage occlusion (LAAO) procedures in relation to procedure time, contrast volume, fluoroscopy time, and total radiation., Methods: This was a single-center, prospective, single-blinded, randomized control trial. Patients meeting criteria for LAAO were randomized to undergo LAAO with the WATCHMAN FLX TM device with and without 3D-MDCT-fluoroscopy fusion guidance using a prespecified protocol using computed tomography angiography for WATCHMAN FLX TM sizing, moderate sedation, and intracardiac echocardiography for procedural guidance., Results: Overall, 59 participants were randomly assigned to the fusion (n = 33) or no fusion (n = 26) groups. The median (interquartile range) age was 79 (75-83) years, 24 (41%) were female, and 55 (93%) were Caucasian. The median CHA 2 DS 2 VASc and HASBLED scores were 5 (4-6) and 3 (3-4), respectively. At the time of the study, 51 (53%) patients were on a direct acting oral anticoagulant. There were no significant differences between the fusion and no fusion groups in procedure time (52.4 ± 15.4 vs. 56.8 ± 19.5 min, p = .36), mean contrast volume used (33.8 ± 12.0 vs. 29.6 ± 11.5 mls, p = .19), mean fluoroscopy time (31.3 ± 9.9 vs. 28.9 ± 8.7 min, p = .32), mean radiation dose (1177 ± 969 vs. 1091 ± 692 mGy, p = .70), and radiation dose product curve (23.9 ± 20.5 vs. 35.0 ± 49.1 Gy cm 2 , p = .29). There was no periprosthetic leak in the two groups in the immediate 1-month postprocedure follow-up periods., Conclusions: There was no significant difference with and without 3D-MDCT-fluoroscopy fusion in procedure time, contrast volume use, radiation dose, and radiation dose product., (© 2023 Wiley Periodicals LLC.)

Background: The detection of unstable atherosclerosis remains elusive. Intraplaque myeloperoxidase (MPO) activity causes plaque destabilization in preclinical models, holding promise for clinical translation as a novel imaging biomarker., Objectives: The purpose of this study was to assess whether MPO activity is greater in unstable human plaques, how this relates to cardiovascular events and current/emerging non-invasive imaging techniques., Methods: Thirty-one carotid endarterectomy specimens and 12 coronary trees were collected. MPO activity was determined in 88 individual samples through the conversion of hydroethidine to the MPO-specific adduct 2-chloroethidium and compared with macroscopic validation, histology, clinical outcomes, and computed tomography-derived high and low attenuation plaques and perivascular adipose tissue. Non-parametric statistical analysis utilizing Mann-Whitney U and Kruskal-Wallis tests for univariate and group comparisons were performed., Results: Unstable compared with stable plaque had higher MPO activity (carotid endarterectomy: n = 26, 4.2 ± 3.1 vs 0.2 ± 0.3 nmol/mgp; P  < 0.0001; coronary: n = 17, 0.6 ± 0.5 vs 0.001 ± 0.003 nmol/mgp; P  = 0.0006). Asymptomatic, stroke-free patients had lower MPO activity compared to those with symptoms or ipsilateral stroke (n = 12, 3.7 ± 2.1 vs 0.1 ± 0.2 nmol/mgp; P  = 0.002). Computed tomography-determined plaque attenuation did not differentiate MPO activity (n = 30, 0.1 ± 0.1 vs 0.2 ± 0.3 nmol/mgp; P  = 0.23) and MPO activity was not found in perivascular adipose tissue., Conclusions: MPO is active within unstable human plaques and correlates with symptomatic carotid disease and stroke, yet current imaging parameters do not identify plaques with active MPO. As intraplaque MPO activity can be imaged non-invasively through novel molecular imaging probes, ongoing investigations into its utility as a diagnostic tool for high-risk atherosclerosis is warranted., Competing Interests: Dr Nadel is supported by scholarships from the 10.13039/501100000925National Health & Medical Research Council of Australia, 10.13039/501100001030National Heart Foundation, and 10.13039/501100001773University of New South Wales. Dr Stocker has received in-kind support from 10.13039/100004325AstraZeneca related to the development of MPO inhibitors, Program and Fellowship Grants from 10.13039/501100000925National Health & Medical Research Council of Australia, and Senior Scientist Grant from 10.13039/501100009287NSW Health.PERSPECTIVESCOMPETENCY IN MEDICAL KNOWLEDGE: MPO activity is higher in unstable than stable human coronary and carotid plaques, correlates with symptomatic carotid disease and stroke, and current non-invasive imaging techniques do not appear to reliably determine active MPO. TRANSLATIONAL OUTLOOK 1: As intraplaque MPO activity appears to be a hallmark of unstable human atherosclerosis and can be imaged non-invasively, further investigation into its potential utility as a diagnostic and therapeutic target is warranted. TRANSLATIONAL OUTLOOK 2: These data are supportive of preclinical data and reinforce the basis of planned Phase I and II clinical trials looking at an MPO-based molecular positron emission tomography probe for the detection of high-risk atherosclerosis., (© 2023 The Authors.)

Background: Cardiac MRI plays an important role in the diagnosis and follow-up of patients with congenital heart disease (CHD). Gadolinium-based contrast agents are often needed to overcome flow-related and off-resonance artifacts that can impair the quality of conventional noncontrast 3D imaging. As serial imaging is often required in CHD, the development of robust noncontrast 3D MRI techniques is desirable., Purpose: To assess the clinical utility of noncontrast enhanced magnetization transfer and inversion recovery prepared 3D free-breathing sequence (MTC-BOOST) compared to conventional 3D whole heart imaging in patients with CHD., Study Type: Prospective, image quality., Population: A total of 27 adult patients (44% female, mean age 30.9 ± 14.8 years) with CHD., Field Strength/sequence: A 1.5 T; free-breathing 3D MTC-BOOST sequence., Assessment: MTC-BOOST was compared to diaphragmatic navigator-gated, noncontrast T2 prepared 3D whole-heart imaging sequence (T2prep-3DWH) for comparison of vessel dimensions, lumen-to-myocardium contrast ratio (CR), and image quality (vessel wall sharpness and presence and type of artifacts) assessed by two experienced cardiologists on a 5-point scale., Statistical Tests: Mann-Whitney test, paired Wilcoxon signed-rank test, Bland-Altman plots. P < 0.05 was considered statistically significant., Results: MTC-BOOST significantly improved image quality and CR of the right-sided pulmonary veins (PV): (CR: right upper PV 1.06 ± 0.50 vs. 0.58 ± 0.74; right lower PV 1.32 ± 0.38 vs. 0.81 ± 0.73) compared to conventional T2prep-3DWH imaging where the PVs were not visualized in some cases due to off-resonance effects. MTC-BOOST demonstrated resistance to degradation of luminal signal (assessed by CR) secondary to accelerated or turbulent flow conditions. T2prep-3DWH had higher image quality scores than MTC-BOOST for the aorta and coronary arteries; however, great vessel dimensions derived from MTC-BOOST showed excellent agreement with standard T2prep-3DWH imaging., Data Conclusion: MTC-BOOST allows for improved contrast-free imaging of pulmonary veins and regions characterized by accelerated or turbulent blood flow compared to standard T2prep-3DWH imaging, with excellent agreement of great vessel dimensions., Evidence Level: 1 TECHNICAL EFFICACY: Stage 2., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Trypanosoma evansi is an important hemoparasite of a variety of animal species worldwide. This parasite is a threat to the health of domestic animals as well as wild animals, particularly those managed in captivity. The current study investigated the presence of T. evansi in captive tigers ( Panthera tigris tigris ) and lions ( Panthera leo ) in Pakistan. In total, 24 blood samples from 11 tigers and 3 lions (n = 14) were collected during the course of roughly 3 yr (2016-2018). Eighteen samples were subjected to both microscopic and molecular evaluation for the presence of T. evansi ; the remaining 6 samples were processed for PCR only. Of the 18 samples tested by both methods, 3 (16%) and 8 (44%) were positive by microscopy and PCR, respectively. This highlights the higher sensitivity of PCR over microscopy for detection of trypanosomes. Of the 24 total samples evaluated by PCR, 12 (50%) were positive. The three sequences obtained showed 99% identity with variant surface glycoprotein genes of the different isolates of T. evansi . The sensitivity, specificity, positive predictive value, and negative predictive value of microscopy in identifying T. evansi was 37.5, 100, 100, and 66.7%, respectively, considering PCR as the gold standard. We recommend rigorous monitoring of captive tigers and lions for hemoparasites, particularly in winter and early spring in areas with high infection rate of this parasite, preferably via PCR.

Chronic kidney disease (CKD) is associated with high cardiovascular risk and mortality. Myeloperoxidase (MPO) has been linked to adverse events in patients with mild-moderate CKD. We sought to investigate whether MPO levels are associated with adverse outcomes in patients with CKD. We studied participants with mild to moderate CKD in the prospective chronic renal insufficiency cohort (CRIC). We followed patients for incident heart failure (HF), death, and composite outcome (myocardial infarction, incident peripheral arterial disease, cerebrovascular accident and death). A total of 3872 patients were included (2702 without CVD, 1170 with CVD). After multiple adjustments, doubling of MPO in patients with prior CAD was associated with risk of HF (HR 1.15 [1.01-1.30], P = 0.032) and mortality (HR 1.16 [1.05-1.30], P = 0.005), and composite outcome of MI, PAD, CVA and death (HR 1.12 [1.01-1.25], P = 0.031). In this cohort of patients with mild to moderate CKD and CAD, MPO levels are independently associated with incident HF, all-cause mortality, and a composite outcome., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Prior studies have suggested significant underutilization of statins in women and worse cardiovascular outcomes. Data examining the impact of real-world coronary artery calcium (CAC) scoring to improve utilization of preventive therapies and outcomes is limited., Methods: In a prospective registry study of low cost or no-cost CAC scoring between 2014 and 19 (CLARIFY Study, Clinicaltrials.gov NCT04075162), we sought to study the association of CAC scoring on statin utilization, blood lipids (LDL, total cholesterol, triglycerides), downstream ischemic testing (coronary angiography and stress testing), coronary revascularization and outcomes (MI, stroke, death) in women compared with men. Eligibility for statin initiation was defined as atherosclerotic cardiovascular disease pooled cohort equation (ASCVD-PCE) ≥ 7.5% and CAC≥100/≥75th percentile., Results: A total of 52,151 patients (26,336 women and 25,815 men) were enrolled. Women were more likely to have CAC 0 (51% vs 30%, P <0.001). Among patients not eligible for statin by PCE, CAC reclassified statin eligibility in a smaller proportion of women than men (25.4% vs 30%, P <0.001), while among patients eligible for statin by PCE, CAC was more likely to downgrade risk/statin eligibility in women than men (30.1% vs 48.4%, P <0.001). After CAC scoring, statin initiation was similar in women and men, but high-intensity statin use was lower in women (CAC-adjusted HR 0.76 [0.70-0.83], P <0.001). Women had similar reduction in LDL cholesterol levels compared with men. There was no difference between men and women with respect to CAC-stratified major adverse cardiovascular events., Conclusion: CAC scoring primarily served to downgrade statin eligibility in women compared with men. Women had similar CAC risk-guided reductions in LDL cholesterol compared with men., Competing Interests: None of the authors have disclosures related to the contents of this manuscript., (© 2022 The Author(s). Published by Elsevier B.V.)

Background The care for patients with type 2 diabetes necessitates a multidisciplinary team approach to reduce cardiovascular risk, but implementation of effective integrated strategies has been limited. Methods and Results We conceptualized and initiated a patient-centered, team-based intervention called Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) at University Hospitals Cleveland Medical Center. Patients with type 2 diabetes at high risk for cardiovascular events, including those with established atherosclerotic cardiovascular disease, elevated coronary artery calcium score >100, chronic heart failure with reduced ejection fraction, and/or chronic kidney disease stages 2 to 4 were included. Herein, we present the year 1 results for the program. From May 2020 through August 2021, there were 417 referrals. Among 206 eligible patients, 113 (55%) completed a baseline and ≥1 follow-up visit through December 2021, with mean (SD) time of 105 (34) days between baseline and first follow-up visits. Mean age was 59 years, with 49% women and 37% Black patients. Patients had significant reductions from baseline in glycosylated hemoglobin (-10.8%), total cholesterol (-7.9%), low-density lipoprotein cholesterol (-13.5%), systolic blood pressure (-4.0%), and body mass index (-2.7%) ( P ≤0.001 for all). In addition, among the 129 (63%) eligible patients not on sodium-glucose cotransporter 2 inhibitor or glucagon-like peptide-1 receptor agonist at baseline, 81% were prescribed evidence-based therapy with sodium-glucose cotransporter 2 inhibitor (n=66 [51%]) and/or glucagon-like peptide-1 receptor agonist (n=67 [52%]) to reduce the risk of cardiovascular disease in the initial 3-month follow-up period. Conclusions A team-based, patient-centered approach to high-risk disease management appears to be a promising paradigm for care delivery associated with greater use of evidence-based therapies and improved control of multiple cardiovascular risk factors.

Background: While there is recent data suggesting an advantage of computed tomography angiography (CTA) over transesophageal echocardiography (TEE) for preprocedural left atrial appendage closure (LAAC) planning, there is limited published experience for sizing strategies. Device sizing for LAAC may be challenging and noninvasive algorithms that improve this selection process are warranted., Objectives: We sought to evaluate the safety and the feasibility for the implementation of a novel CTA-based sizing methodology for WATCHMAN™ FLX device in a series of patients undergoing LAAC using the TruPlan™ software package., Methods: A prospective analysis of 136 consecutive patients who underwent LAAC over a 12-month period in a single, large academic hospital in the United States was conducted. CTA-guided preprocedural planning and intracardiac echocardiography (ICE) was performed in all. Procedural success, adverse events, length of procedure, number of devices used, and length of stay were evaluated., Results: A total of 136 patients who underwent LAAC procedure with WATCHMAN™ FLX platform between October 1, 2020 until September 30, 2021 were included. The pre-specified protocol using CTA and ICE was implemented in all patients (100%). Mean CHA 2 DS 2 VASc score was 4.4 ± 1.3 and the mean HAS-BLED score was 3.9 ± 0.8. ICE-guided 100% transseptal puncture success rate was 100% with 98.5% of overall procedural success rate. Preprocedural CTA sizing strategy accurately predicted the implanted size in 91.1% of patients. Ten patients (7.4%) required another sized device and 2 cases were aborted. At 45-day follow-up, only 1 patient (0.7%) had significant peri-device leak (≥5 mm) on TEE., Conclusions: CTA-based preprocedural sizing methodology for WATCHMAN™ FLX in LAAC was safe, feasible and associated with excellent procedural outcomes. Further studies are warranted to confirm if the features specific to TruPlan™ may reduce the number of deployment attempts, the number of devices utilized in the procedure, and the risk of complications., (© 2022 Wiley Periodicals LLC.)

Prevention of cardiovascular disease is currently guided by probabilistic risk scores that may misclassify individual risk and commit many middle-aged patients to prolonged pharmacotherapy. The coronary artery calcium (CAC) score, although endorsed for intermediate-risk patients, is not widely adopted because of barriers in reimbursement. The impact of removing cost barrier on cardiovascular outcomes in real-world settings is not known. Within the University Hospitals Health System (Cleveland, Ohio), CAC was offered to patients with at least 1 cardiovascular risk factor at low charge between 2014 and 2017 ($99) and no charge from January 1, 2018 onward. CAC use and access, patient characteristics, reclassification of risk compared with the pooled cohort equations (PCEs) for atherosclerotic vascular disease, statin use, changes in parameters of cardiometabolic health, downstream cardiovascular testing, downstream coronary revascularization, and cardiovascular outcomes were evaluated. A total of 52,151 patients underwent CAC testing over the study period. Median 10-year PCE for atherosclerotic vascular disease, in the entire cohort was 8.3% (4.0% to 15.9%). Among patients with PCE >20%, 21% had CAC <100, whereas 37% of those with PCE <7.5% had CAC ≥100. Among patients who were not on statin before CAC testing, 1-year statin prescription was 24% and was significantly associated with higher CAC scores. Total cholesterol, low-density lipoprotein cholesterol, and triglycerides all decreased significantly 1-year after CAC, and the degree of decrease was strongly linked with CAC scores. One year after CAC, 14% underwent noninvasive ischemic evaluation, 1.4% underwent invasive coronary angiography, and 0.9% underwent revascularization. The majority (74%) of revascularization procedures occurred in patients with CAC >400. In conclusion, reducing or removing the cost burden of CAC leads to significant test uptake by patients, which is followed by reclassification of statin eligibility, increases in the use of preventive medications, and improvement in risk factors, with very low rates of invasive downstream testing., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The World Health Organization (WHO) and the Food and Agriculture Organization (FAO) have developed strategies to control trypanosomiasis in humans and livestock in endemic areas. These require a better understanding of the distribution of different Trypanosoma species and improved predictions of where they might appear in the future, based on accurate diagnosis and robust surveillance systems. Here, we describe a metabarcoding deep amplicon sequencing method to identify and determine the Trypanosoma species in co-infecting communities. First, four morphological verified Trypanosoma species (T. brucei, T. congolense, T. vivax and T. theileri) were used to prepare test DNA pools derived from different numbers of parasites to evaluate the method's detection threshold for each of the four species and to assess the accuracy of their proportional quantification. Having demonstrated the accurate determination of species composition in Trypanosoma communities, the method was applied to determine its detection threshold using blood samples collected from cattle with confirmed Trypanosoma infections based on a PCR assay. Each sample showed a different Trypanosoma species composition based on the proportion of MiSeq reads. Finally, we applied the assay to field samples to develop new insight into the species composition of Trypanosoma communities in cattle, camels, buffalo, horses, sheep, and goat in endemically infected regions of Pakistan. We confirmed that Trypanosoma evansi is the major species in Pakistan and for the first time showed the presence of Trypanosoma theileri. The metabarcoding deep amplicon sequencing method and bioinformatics pathway have several potential applications in animal and human research, including evaluation of drug treatment responses, understanding of the emergence and spread of drug resistance, and description of species interactions during co-infections and determination of host and geographic distribution of trypanosomiasis in humans and livestock., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Percutaneous left atrial appendage occlusion (LAAO) with the Watchman device is FDA approved for stroke prevention in patients with nonvalvular atrial fibrillation who have an appropriate indication. During the COVID-19 pandemic, a same-day discharge protocol (SDDP) was employed to improve resource utilization, relieve hospital occupation, and reduce the possible risk of in-hospital virus transmission., Objectives: We sought to analyze the safety, feasibility, and cost effectiveness for SDDP in patients receiving LAAO., Methods: A prospective analysis of 142 consecutive patients, 119 treated prior to SDDP and 23 who underwent SDDP following LAAO with cardiac computed tomography angiography (CTA)-guided pre-procedural planning and intracardiac echocardiogram (ICE). Procedures were performed in a single, large academic hospital in the United States. In-hospital and 45-day procedural success, adverse events, length of procedure, and length-of-stay were evaluated., Results: Baseline patient characteristics including mean CHA2DS2VASc scores and mean HAS-BLED scores were similar in both groups. All procedures were successful. There was no significant difference in rates of procedural complications or in-hospital adverse events. The mean procedure time in the SDDP group was 11 minutes longer than in the conventional group (62.1 ± 5.9 vs 51.1 ± 21; P=.01). Outcomes at 45-day follow-up were similar. SDDP was associated with a reduced length of stay compared with conventional strategy and a 15% reduction in total costs., Conclusions: Same-day discharge strategy for LAAO appears safe, feasible and could become the new standard approach for LAAO. A protocol including CTA pre-procedural planning, ICE-guided deployment and conscious sedation reduces hospital occupation and lowers costs.

Aims: Cytokines, soluble mediators of immunity, are key factors of the innate and adaptive immune system. They are secreted from and interact with various types of immune cells to manipulate host body's immune cell physiology for a counter-attack on the foreign body. A study was designed to explore the mechanism of Toxoplasma gondii ( T. gondii ) resistance from host immune response., Methods and Results: The published data on aspect of host (murine and human) immune response against T. gondii was taken from Google scholar and PubMed. Most relevant literature was included in this study. The basic mechanism of immune response starts from the interactions of antigens with host immune cells to trigger the production of cytokines (pro-inflammatory and anti-inflammatory) which then act by forming a cytokinome (network of cytokine). Their secretory equilibrium is essential for endowing resistance to the host against infectious diseases, particularly toxoplasmosis. A narrow balance lying between Th1, Th2, and Th17 cytokines (as demonstrated until now) is essential for the development of resistance against T. gondii as well as for the survival of host. Excessive production of pro-inflammatory cytokines leads to tissue damage resulting in the production of anti-inflammatory cytokines which enhances the proliferation of Toxoplasma . Stress and other infectious diseases (human immunodeficiency virus (HIV)) that weaken the host immunity particularly the cellular component, make the host susceptible to toxoplasmosis especially in pregnant women., Conclusion: The current review findings state that  in vitro  harvesting of IL12 from DCs, Np and MΦ upon exposure with  T. gondii  might be a source for therapeutic use in toxoplasmosis. Current review also suggests that therapeutic interventions leading to up-regulation/supplementation of SOCS-3, IL12, and IFNγ to the infected host could be a solution to sterile immunity against  T. gondii  infection. This would be of interest particularly in patients passing through immunosuppression owing to any reason like the ones receiving anti-cancer therapy, the ones undergoing immunosuppressive therapy for graft/transplantation, the ones suffering from immunodeficiency virus (HIV) or having AIDS. Another imortant suggestion is to launch the efforts for a vaccine based on GRA6Nt or other similar antigens of T. gondii  as a probable tool to destroy tissue cysts.

Background: A coronary artery calcium (CAC) score of zero confers a low but nonzero risk of atherosclerotic cardiovascular events (CVD) in asymptomatic patient populations, and additional risk stratification is needed to guide preventive interventions. Soluble tumor necrosis factor receptors (sTNFR-1 and sTNFR-2) are shed in the context of TNF-alpha signaling and systemic inflammation, which play a role in atherosclerosis and plaque instability. We hypothesized that serum sTNFR-1 concentrations may aid in cardiovascular risk stratification among asymptomatic patients with a CAC score of zero., Methods: We included all participants with CAC=0 and baseline sTNFR-1 measurements from the prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA). The primary outcome was a composite CVD event (myocardial infarction, stroke, coronary revascularization, cardiovascular death)., Results: The study included 1471 participants (mean age 57.6 years, 64% female), with measured baseline sTNFR-1 ranging from 603 pg/mL to 5544 pg/mL (mean 1294 pg/mL ±378.8 pg/mL). Over a median follow-up of 8.5 years, 37 participants (2.5%) experienced a CVD event. In multivariable analyses adjusted for Framingham Score, doubling of sTNFR-1 was associated with a 3-fold increase in the hazards of CVD (HR 3.0, 95% CI: 1.48-6.09, P = 0.002), which remained significant after adjusting for traditional CVD risk factors individually (HR 2.29; 95% CI: 1.04-5.06, P =0.04). Doubling of sTNFR-1 was also associated with progression of CAC >100, adjusted for age (OR 2.84, 95% CI: 1.33-6.03, P =0.007)., Conclusions: sTNFR-1 concentrations are associated with more CVD events in participants with a CAC score of zero. Utilizing sTNFR-1 measurements may improve cardiovascular risk stratification and guide primary prevention in otherwise low-risk individuals., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© Pathogens and Immunity 2021.)

Objectives: We reviewed the periprocedural events, accuracy of device selection, and outcomes of a series of patients receiving percutaneous left atrial appendage occlusion (LAAO) with cardiac computed tomography angiography (CTA)-guided preprocedural planning and intracardiac echocardiography (ICE)-guided device deployment., Background: Percutaneous LAAO with the Watchman device (Boston Scientific) is approved by the United States Food and Drug Administration for stroke prevention in patients with non-valvular atrial fibrillation with a demonstrated contraindication to oral anticoagulation. Cardiac CTA preprocedural planning with utilization of an ICE-guided deployment may be associated with favorable outcomes., Methods: A prospective analysis of 71 non-consecutive patients who underwent LAAO over an 18-month period with cardiac CTA-guided preprocedural planning and ICE was conducted. Procedures were performed in a single large, academic hospital in the United States. Procedural success, correlation of CTA preprocedural device sizing with final device size utilization, adverse events, length of procedure, and length of stay were evaluated., Results: Preprocedural cardiac CTA-guided device sizing was consistent with the final deployed device in 69 patients (97.2%) evaluated in this case series. Procedure success rate was 100%. All implants were performed using Watchman devices, 45 (63.4%) with the original 2.5 platform and 26 (36.6%) with the Watchman FLX platform. All patients were treated with conscious sedation and the mean length of stay was 1.45 ± 0.72 days. Only 2 adverse events occurred and both resolved., Conclusions: Cardiac CTA-guided preprocedural planning resulted in accurate device sizing in this patient sample and may be used in conjunction with ICE and conscious sedation for a same-day discharge strategy in select patients.

Fasciola gigantica and Fasciola hepatica are digenetic trematodes causing fasciolosis in ruminants. The host and geographical distribution of both Fasciola species are influenced by environmental and climatic conditions favouring survival and development of free-living stages and intermediate hosts, and livestock management practices. The aim of the present study was to describe the host distribution of the two Fasciola species in buffalo, cattle, goats, and sheep in the Balochistan and Punjab provinces of Pakistan. 359 flukes were collected from a total of 32 livers from the four livestock species. Deep amplicon sequencing of the internal transcribed spacer region 2 of ribosomal DNA (rDNA ITS-2) and mitochondrial nicotinamide adenine dinucleotide dehydrogenase 1 (mtDNA ND-1) loci confirmed co-infection of F. hepatica and F. gigantica in Balochistan and single species F. gigantica infection in Punjab. In Balochistan, co-infections and hybrids of both Fasciola species were identified in cattle, with more F. hepatica detected than F. gigantica. However, F. hepatica was the only species identified in goats, and F. gigantica was the only species identified in buffalo. In Punjab, all flukes were confirmed as F. gigantica in each of the four livestock species. Overall, the results indicate differences in the host and geographical distribution of F. gigantica and F. hepatica, and provide useful knowledge for the development of control strategies for livestock and humans., (Copyright © 2021. Published by Elsevier B.V.)

In order to replace Pt CE in dye sensitized solar cell (DSSC) with simple and low cost, copper polypyyrol functionalized multiwall carbon nanotubes (Cu-PPy-FWCNTS) nanocomposite CE was fabricated by two step electrodeposition method on the stainless-steel substrate. The surface morphology, electrical conductivity, electrochemical properties of Cu-PPy-FWCNTS nanocomposite CE electrodes were observed by using verity of techniques such as scanning electron microscopy, a four-probe method and electrochemical workstation. The Fourier transform infrared (FTIR) spectroscopy confirms the presence of FMWCNTS into PPy-FMWCNTS nanocomposite and XRD analysis verified the Cu nanostructures had come into being. The cyclic voltammogram and Tafel polarization measurement demonstrated that solution processed Cu-PPy-FWCNTS nanocomposites CE had smaller charge transfer resistance R ct (4.31 Ω cm 2 ) and higher electrocatalytic performance for I 3 - /I - redox solution. Finally, the photovoltaic efficiency of DSSC assembled with Cu-PPy-FWCNTS nanocomposite CE and Platinized CE were compared. The results revealed that the photovoltaic efficiency of DSSC with Cu-PPy-FWCNTS nanocomposites CE reached (7.1%), which is superior to Platinized CE (6.4%). The higher photovoltaic efficiency of the Cu-PPy-FMWCNTS film is due to copper nanostructures that lead to higher cathodic current density (2.35 mA/cm 2 ). The simple fabrication method, excellent electrocatalytic and photovoltaic properties permit the Cu-PPy-FWCNTS nanocomposites credible alternative CE to save the cost of DSSC., (© 2021. The Author(s).)

Fasciola gigantica is considered to be a major pathogen causing fasciolosis in the Indian subcontinent, resulting in production losses of millions of dollars in the livestock industry. Understading the dispersal origin and the patterns of spread of F. gigantica is important. A total of 53 Fasciola flukes collected from buffaloes and goats in Punjab, Pakistan between 2017 and 2018 were identified as F. gigantica based on the multiplex PCR for the phosphoenolpyruvate carboxykinase (pepck) and the PCR-restriction fragment length polymorphism (RFLP) for DNA polymerase delta (pold). A significant genetic difference between F. gigantica from buffaloes and goats was indicated by the genetic analyses of mitochondrial markers, NADH dehydrogenase subunit 1 (nad1) and cytochrome C oxidase subunit 1 (cox1). Phylogenetic analysis of the seventeen nad1 haplotypes of F. gigantica from Pakistan with those in neighbouring countries of the Indian subcontinent revealed that all the haplotypes identified in Pakistan were clustered in haplogroup A. fasciola gigantica with the eight haplotypes might be expanded in Pakistan from Indian origin, along with the migration of the domestic animals, since they were related to Indian haplotypes. In contrast, the remaining nine haplotypes were not shared with any neighbouring countries, suggesting independent origin, probably from neighbouring Middle East countries. However, cautious interpretation is required due to the very limited samples size of this study. Our study provides a proof of concept for a method that could be used to investigate the epidemiology of F. gigantica., (Copyright © 2021. Published by Elsevier B.V.)

Background: The widespread clinical application of coronary cardiovascular magnetic resonance (CMR) angiography (CMRA) for the assessment of coronary artery disease (CAD) remains limited due to low scan efficiency leading to prolonged and unpredictable acquisition times; low spatial-resolution; and residual respiratory motion artefacts resulting in limited image quality. To overcome these limitations, we have integrated highly undersampled acquisitions with image-based navigators and non-rigid motion correction to enable high resolution (sub-1 mm 3 ) free-breathing, contrast-free 3D whole-heart coronary CMRA with 100% respiratory scan efficiency in a clinically feasible and predictable acquisition time., Objectives: To evaluate the diagnostic performance of this coronary CMRA framework against coronary computed tomography angiography (CTA) in patients with suspected CAD., Methods: Consecutive patients (n = 50) with suspected CAD were examined on a 1.5T CMR scanner. We compared the diagnostic accuracy of coronary CMRA against coronary CTA for detecting a ≥ 50% reduction in luminal diameter., Results: The 50 recruited patients (55 ± 9 years, 33 male) completed coronary CMRA in 10.7 ± 1.4 min. Twelve (24%) had significant CAD on coronary CTA. Coronary CMRA obtained diagnostic image quality in 95% of all, 97% of proximal, 97% of middle and 90% of distal coronary segments. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were: per patient (100%, 74%, 55%, 100% and 80%), per vessel (81%, 88%, 46%, 97% and 88%) and per segment (76%, 95%, 44%, 99% and 94%) respectively., Conclusions: The high diagnostic image quality and diagnostic performance of coronary CMRA compared against coronary CTA demonstrates the potential of coronary CMRA as a robust and safe non-invasive alternative for excluding significant disease in patients at low-intermediate risk of CAD.

Numerous systems are being employed in daily life where two entities authenticate each other over a range of distance. The distance involved is relatively small, but still attacks were documented. The distance bounding (DB) protocol was introduced to cater to security requirements. The schemes, however, are still prone to several threats; mainly the Relay Attack (Terrorist and Mafia Fraud). In Mafia Fraud, an attempts are made to get accepted as the prover either by replaying of messages or by the help a malicious key. In Terrorist fraud, an attempt is made to extract the secret from the verifying entity, either by extracting the key from the message captured or by physically tempering the verifying/proving entity. Therefore the mitigation of these attacks needs to be done; as to not put computational overhead on the scheme. The paper presents a comprehensive and comparative performance analysis of twelve DB protocols based on defined metrics. It also proposes a protocol which incorporates the design elements needed for added security, is computationally easy to implement and resistant to most of the threats mentioned. Analysis of the protocol is carried out against the security requirements., Competing Interests: The authors declare there are no competing interests., (©2021 Sultan et al.)

A 74-year-old man presented with presyncope and non-sustained monomorphic ventricular tachycardia in the setting of acute coronary syndrome. On coronary angiogram, a calcified myocardial scar was revealed, which was later identified as the ventricular tachycardia focus via electrophysiological study., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To develop a novel gadolinium-free model-based quantitative magnetization transfer (qMT) technique to assess macromolecular changes associated with myocardial fibrosis., Methods: The proposed sequence consists of a two-dimensional breath-held dual shot interleaved acquisition of five MT-weighted (MTw) spoiled gradient echo images, with variable MT flip angles (FAs) and off-resonance frequencies. A two-pool exchange model and dictionary matching were used to quantify the pool size ratio (PSR) and bound pool T2 relaxation ( T 2 B ). The signal model was developed and validated using 25 MTw images on a bovine serum albumin (BSA) phantom and in vivo human thigh muscle. A protocol with five MTw images was optimized for single breath-hold cardiac qMT imaging. The proposed sequence was tested in 10 healthy subjects and 5 patients with myocardial fibrosis and compared to late gadolinium enhancement (LGE)., Results: PSR values in the BSA phantom were within the confidence interval of previously reported values (concentration 10% BSA = 5.9 ± 0.1%, 15% BSA = 9.4 ± 0.2%). PSR and T 2 B in thigh muscle were also in agreement with literature (PSR = 10.9 ± 0.3%, T 2 B = 6.4 ± 0.4 us). In 10 healthy subjects, global left ventricular PSR was 4.30 ± 0.65%. In patients, PSR was reduced in areas associated with LGE (remote: 4.68 ± 0.70% vs. fibrotic: 3.12 ± 0.78 %, n = 5, P < .002)., Conclusion: In vivo model-based qMT mapping of the heart was performed for the first time, with promising results for non-contrast enhanced assessment of myocardial fibrosis., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Pyrimethamine was first introduced for the treatment of malaria in Asia and Africa during the early 1980s, replacing chloroquine, and has become the first line of drugs in many countries. In recent years, development of pyrimethamine resistance in Plasmodium vivax has become a barrier to effective malaria control strategies. Here, we describe the use of meta-barcoded deep amplicon sequencing technology to assess the evolutionary origin of pyrimethamine resistance by analysing the flanking region of dihydrofolate reductase (dhfr) locus. The genetic modelling suggests that 58R and 173L single mutants and 58R/117N double mutants are present on a single lineage; suggesting a single origin of these mutations. The triple mutants (57L/58R/117N, 58R/61M/117N and 58R/117N/173L) share the lineage of 58R/117N, suggesting a common origin. In contrast, the 117N mutant is present on two separate lineages suggesting that there are multiple origins of this mutation. We characterised the allele frequency of the P. vivax dhfr locus. Our results support the view that the single mutation of 117N and double mutations of 58R/117N arise commonly, whereas the single mutation of 173L and triple mutations of 57L/58R/117N, 58R/61M/117N and 58R/117N/173L are less common. Our work will help to inform mitigation strategies for pyrimethamine resistance in P. vivax., (Copyright © 2021. Published by Elsevier B.V.)

Accurate identification of left ventricular masses (LVM) can be challenging, and if incorrect, may have devastating consequences. While transthoracic echocardiography is often the first test to identify intracardiac masses, cardiac MRI (CMRI) allows for better anatomical definition and tissue characterisation. We present a case of a 51-year-old man who presented with 4 weeks of shortness of breath, found on echocardiogram to have severely reduced LV function and a 2.5×4.0 cm LVM with a hypolucent/cystic core. Due to the unusual appearance, CMRI was required for confirmation of an LV thrombus. This case highlights the importance of multimodality imaging in the discovery and identification of LVM., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

A study was designed to improve understanding of the genetics of Theileria annulata populations in sympatric cattle and Asian buffalo (Bubalus bubalus). The study was undertaken in the Punjab province of Pakistan, where the prevalence of tropical theileriosis is high. Parasite materials were collected from infected animals in defined regions, where cattle and Asian buffalo are kept together. Six satellite DNA markers and a mitochondrial cytochrome b marker were used to explore the multiplicity of T. annulata infection and patterns of emergence and spread of different parasite genotypes. The results show differences in the numbers of unique satellite locus alleles, suggesting that T. annulata is genetically more diverse in cattle- than in buffalo-derived populations. Heterozygosity (H e ) indices based on satellite and cytochrome b loci data show high levels of genetic diversity among the cattle- and buffalo-derived T. annulata populations. When considered in the context of high parasite transmission rates and frequent animal movements between different regions, the predominance of multiple T. annulata genotypes and multiple introductions of infection may have practical implications for the spread of parasite genetic adaptations; such as those conferring vaccine cross-protection against different strains affecting cattle and Asian buffalo, or resistance to antiprotozoal drugs., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: The free-breathing 3D whole-heart T 2 -prepared Bright-blood and black-blOOd phase SensiTive inversion recovery (BOOST) cardiovascular magnetic resonance (CMR) sequence was recently proposed for simultaneous bright-blood coronary CMR angiography and black-blood late gadolinium enhancement (LGE) imaging. This sequence enables simultaneous visualization of cardiac anatomy, coronary arteries and fibrosis. However, high-resolution (< 1.4 × 1.4 × 1.4 mm 3 ) fully-sampled BOOST requires long acquisition times of ~ 20 min., Methods: In this work, we propose to extend a highly efficient respiratory-resolved motion-corrected reconstruction framework (XD-ORCCA) to T 2 -prepared BOOST to enable high-resolution 3D whole-heart coronary CMR angiography and black-blood LGE in a clinically feasible scan time. Twelve healthy subjects were imaged without contrast injection (pre-contrast BOOST) and 10 patients with suspected cardiovascular disease were imaged after contrast injection (post-contrast BOOST). A quantitative analysis software was used to compare accelerated pre-contrast BOOST against the fully-sampled counterpart (vessel sharpness and length of the left and right coronary arteries). Moreover, three cardiologists performed diagnostic image quality scoring for clinical 2D LGE and both bright- and black-blood 3D BOOST imaging using a 4-point scale (1-4, non-diagnostic-fully diagnostic). A two one-sided test of equivalence (TOST) was performed to compare the pre-contrast BOOST images. Nonparametric TOST was performed to compare post-contrast BOOST image quality scores., Results: The proposed method produces images from 3.8 × accelerated non-contrast-enhanced BOOST acquisitions with comparable vessel length and sharpness to those obtained from fully- sampled scans in healthy subjects. Moreover, in terms of visual grading, the 3D BOOST LGE datasets (median 4) and the clinical 2D counterpart (median 3.5) were found to be statistically equivalent (p < 0.05). In addition, bright-blood BOOST images allowed for visualization of the proximal and middle left anterior descending and right coronary sections with high diagnostic quality (mean score > 3.5)., Conclusions: The proposed framework provides high-resolution 3D whole-heart BOOST images from a single free-breathing acquisition in ~ 7 min.

Food adulteration has a direct impact on public health, religious faith, fair-trades, and wildlife. In the present study, a reliable and sensitive assay has been developed for verifying meat adulteration in food chain. The multiplex PCR system was optimised for identification of chicken, cow/buffalo, sheep/goat, horse/donkey, pork, and dog DNAs in a single reaction mixture simultaneously. The primers were designed using 12 S rRNA gene sequences with fragment size in the range of 113 bp to 800 bp, which can be easily visualised on agarose gel electrophoresis making the technique economical. After validation of accuracy, specificity, and sensitivity, commercially available meat products ( n = 190) were screened, comprising both raw and cooked meat samples. The results demonstrated a high rate of adulteration (54.5%) in meat products. The technique developed here can be easily used for screening of different meat products for export and import purposes as well as for food inspection and livestock diagnostic laboratories.

Coronary artery disease remains the leading cause of cardiovascular morbidity and mortality. Invasive X-ray angiography and coronary computed tomography angiography are established gold standards for coronary luminography. However, they expose patients to invasive complications, ionizing radiation, and iodinated contrast agents. Among a number of imaging modalities, coronary cardiovascular magnetic resonance (CMR) angiography may be used in some cases as an alternative for the detection and monitoring of coronary arterial stenosis, with advantages including its versatility, excellent soft tissue characterization, and avoidance of ionizing radiation and iodinated contrast agents. In this review, we explore the recent advances in motion correction, image acceleration, and reconstruction technologies that are bringing coronary CMR angiography closer to widespread clinical implementation., Competing Interests: Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The soil cadmium (Cd) contamination is a ubiquitous environmental problem that has resulted from intense irrigation with wastewater. This pot trial was conducted with aim to produce safe food with Cd tolerant wheat cultivar in wastewater irrigated soils. For this purpose, two wheat cultivars NARC-2011 (Cd tolerant) and Shafaq-2006 (Cd sensitive) were screened out and selected, after conducting a pilot trial of twelve local wheat cultivars against Cd stress. Both cultivars were grown in naturally contaminated soils with Cd concentrations (4.18, 3.23, 2.29 and 1.25 mg kg -1 ). After harvesting, NARC-2011 showed significant photosynthetic attributes, grain biochemical parameters and yield. Additionally, Cd concentrations in edible grains of NARC-2011 cultivars were found within standard limits (200 mg kg -1 ), in all contaminated soils. Furthermore, a marked decrease in Cd bioavailability was noted with cultivar NARC-2011, where contribution of mobile Cd fractions (exchangeable and reducible) percentage was decreased, while immobile Cd fractions percentage increased (oxidizable and residual). Fourier transform infrared (FTIR) spectroscopy reflects the maturity and stability of humic and fulvic like acid fractions and revealed that humification of these compounds after prolonged sludge enriched wastewater irrigation lowered the Cd availability. The wheat cultivar NARC-2011 (Cd tolerant) could be opted to grow on soils irrigated with wastewater for a long time, as Cd bioavailability decreased with ageing due to stabilized humic substances and varietal tolerance., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The domestic Nili-Ravi water buffalo (Bubalus bubalis) is the best dairy animal contributing 68% to total milk production in Pakistan. In this study, we identified genome-wide single nucleotide polymorphisms (SNPs) to estimate various population genetic parameters such as diversity, pairwise population differentiation, linkage disequilibrium (LD) distribution and for genome-wide association study for milk yield and body weight traits in the Nili-Ravi dairy bulls that they may pass on to their daughters who are retained for milking purposes. The genotyping by sequencing approach revealed 13,039 reference genome-anchored SNPs with minor allele frequency of 0.05 among 167 buffalos. Population structure analysis revealed that the bulls were grouped into two clusters (K = 2), which indicates the presence of two different lineages in the Pakistani Nili-Ravi water buffalo population, and we showed the extent of admixture of these two lineages in our bull collection. LD analysis revealed 4169 significant SNP associations, with an average LD decay of 90 kb for these buffalo genome. Genome-wide association study involved a multi-locus mixed linear model for milk yield and body weight to identify genome-wide male effects. Our study further illustrates the utility of the genotyping by sequencing approach for identifying genomic regions to uncover additional demographic complexity and to improve the complex dairy traits of the Pakistani Nili-Ravi water buffalo population that would provide the lot of economic benefits to dairy industry., Competing Interests: The authors have declared that no competing interests exist.

Aim: Human Immunodeficiency Virus (HIV) patients commonly experience dyspnea for which an immediate cause may not be always apparent. In this prospective cohort study of HIV patients with exercise limitation, we use cardiopulmonary exercise testing (CPET) coupled with exercise cardiovascular magnetic resonance (CMR) to elucidate etiologies of dyspnea., Methods and Results: Thirty-four HIV patients on antiretroviral therapy with dyspnea and exercise limitation (49.7 years, 65% male, mean absolute CD4 count 700) underwent comprehensive evaluation with combined rest and maximal exercise treadmill CMR and CPET. The overall mean oxygen consumption (VO 2 ) peak was reduced at 23.2 ± 6.9 ml/kg/min with 20 patients (58.8% of overall cohort) achieving a respiratory exchange ratio > 1. The ventilatory efficiency (VE)/VCO 2 slope was elevated at 36 ± 7.92, while ventilatory reserve (VE: maximal voluntary ventilation (MVV)) was within normal limits. The mean absolute right ventricular (RV) and left ventricular (LV) contractile reserves were preserved at 9.0% ± 11.2 and 9.4% ± 9.4, respectively. The average resting and post-exercise mean average pulmonary artery velocities were 12.2 ± 3.9 cm/s and 18.9 ± 8.3 respectively, which suggested lack of exercise induced pulmonary artery hypertension (PAH). LV but not RV delayed enhancement were identified in five patients. Correlation analysis found no relationship between peak VO 2 measures of contractile RV or LV reserve, but LV and RV stroke volume correlated with PET CO 2 (p = 0.02, p = 0.03)., Conclusion: Well treated patients with HIV appear to have conserved RV and LV function, contractile reserve and no evidence of exercise induced PAH. However, we found evidence of impaired ventilation suggesting a non-cardiopulmonary etiology for dyspnea.

Rationale, Aims, and Objectives: While different imaging and treatment options are available in acute coronary syndrome (ACS) care, there is a lack of data regarding their use across Europe. We examined the diagnostic and treatment strategies in patients with known or suspected ACS as reported by physicians and identified variations in responses across European countries and geographical areas., Method: A web-based clinician survey focusing on ACS imaging and revascularization treatments was circulated through email distribution lists and websites of European professional societies in the field of cardiology. We collected information on respondents' clinical setting and specialty. Reported percentages of patients receiving imaging or treatment modalities and percentages of clinicians reporting to use modalities in a range of clinical scenarios were analyzed. Statistical comparisons were performed., Results: In total, 69 responses were received (Sweden [n = 20], United Kingdom [n = 16], Northern/Western Europe [n = 17], Southern Europe [n = 9], and Central Europe [n = 7]). Considerable variations between geographical areas were seen in terms of reported diagnostic modalities and treatment strategies. For example, when presented with the scenario of a theoretical 45-year-old smoking female with a suspected ACS, 56% of UK clinicians reported to use coronary computed tomography angiography, compared to only 10% of Swedish clinicians (P = .002). Large variations were observed regarding the reported use of fractional flow reserve by physicians for non-culprit lesions during invasive management of myocardial infarction patients (44% in Sweden, 31% in the United Kingdom, and 30% in Northern/Western Europe vs non-use in Central and Southern Europe)., Conclusions: In this survey, respondents reported different diagnostic and treatment strategies in ACS care. These variations seem to have geographic components. Larger studies or real world data are needed to verify these observations and investigate their causes. More research is needed to compare the quality and efficiency of ACS care across countries and explore pathways for improvement., (© 2020 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Objective: Evidence from preclinical and clinical studies has demonstrated that myocardial infarction promotes atherosclerosis progression. The impact of focal vascular inflammation on the progression and phenotype of remote atherosclerosis remains unknown. Approach and Results: We used a novel ApoE -/- knockout mouse model of sustained arterial inflammation, initiated by mechanical injury in the abdominal aorta. Using serial in vivo molecular MRI and ex vivo histology and flow cytometry, we demonstrate that focal arterial inflammation triggered by aortic injury, accelerates atherosclerosis in the remote brachiocephalic artery. The brachiocephalic artery atheroma had distinct histological features including increased plaque size, plaque permeability, necrotic core to collagen ratio, infiltration of more inflammatory monocyte subsets, and reduced collagen content. We also found that arterial inflammation following focal vascular injury evoked a prolonged systemic inflammatory response manifested as a persistent increase in serum IL-6 (interleukin 6). Finally, we demonstrate that 2 therapeutic interventions-pravastatin and minocycline-had distinct anti-inflammatory effects at the plaque and systemic level., Conclusions: We show for the first time that focal arterial inflammation in response to vascular injury enhances systemic vascular inflammation, accelerates remote atheroma progression and induces plaques more inflamed, lipid-rich, and collagen-poor in the absence of ischemic myocardial injury. This inflammatory cascade is modulated by pravastatin and minocycline treatments, which have anti-inflammatory effects at both plaque and systemic levels that mitigate atheroma progression.

Tick infestation is a leading cause of tick-worry and tick-borne diseases in livestock and associated economic losses in tropical and subtropical regions of the world. The cattle and buffalo populations in Pakistan are exposed to tick infestation throughout the year, but very little is known about the biology, diversity and distribution of tick species across different agro-ecological zones (AEZ) of the country. The present study aimed to investigate the prevalence (number of bovines infested with ticks out of the investigated population) and diversity of hard ticks infesting bovines in 30 villages located in five distinct AEZs (i.e. Arid, Indus delta, Northern irrigated plain, Sandy desert and Southern irrigated plain). We collected a total of 774 ticks (adult and nymphs) from cattle (n = 116) and water buffaloes (n = 88) on small-holder dairy farms (with <10 bovids per establishment) from September to November 2017. The overall tick prevalence was 46.1% (cattle: 47.9%; buffaloes: 44%), which varied significantly from 22.2% in the Indus delta to 70.5% in the Sandy desert. Tick prevalence was slightly higher in female (46.5%) than male animals (45%), and higher in calves (i.e. ≤ 1 year of age) (55%) than in young animals (i.e. up to 3 years of age) (39%) and adults (48%). Five tick species - Hyalomma anatolicum, Hyalomma hussaini, Hyalomma scupense, Rhipicephalus microplus and Rhipicephalus annulatus - were identified morphologically and then genetically. Genetic identification, achieved using the sequences of two mitochondrial (cytochrome c oxidase subunit 1 and 16S) and one nuclear ribosomal (second internal transcribed spacer) regions, was consistent with the morphological findings. Phylogenetic analyses of the DNA sequence data sets showed that the five species of tick identified here were closely related to the same species or closely related species from within and outside of Pakistan. Of five presently recognised taxa within the R. microplus complex, two were identified herein, including the R. microplus clade C and R. annulatus. This investigation provides the first genetic evidence of the occurrence of R. annulatus in Pakistan as well as Hy. hussaini and Hy. scupense in bovines specifically in the provinces of Sindh and Punjab, respectively. The present findings emphasise the importance of combining morphological and molecular approaches to study the diversity of ticks. Further longitudinal studies are required to establish seasonal variations in the prevalence and distribution of bovine ticks in different AEZs of Pakistan., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Aims: The optimal timing for pulmonary valve replacement in asymptomatic patients with repaired Tetralogy of Fallot (rTOF) and pulmonary regurgitation remains uncertain but is often guided by increases in right ventricular (RV) end-diastolic volume. As cardiopulmonary exercise testing (CPET) performance is a strong prognostic indicator, we assessed which cardiovascular magnetic resonance (CMR) parameters correlate with reductions in exercise capacity to potentially improve identification of high-risk patients., Methods and Results: In all, 163 patients with rTOF (mean age 24.5 ± 10.2 years) who had previously undergone CMR and standardized CPET protocols were included. The indexed right and left ventricular end-diastolic volumes (RVEDVi, LVEDVi), right and left ventricular ejection fractions (RVEF, LVEF), indexed RV stroke volume (RVSVi), and pulmonary regurgitant fraction (PRF) were quantified by CMR and correlated with CPET-determined peak oxygen consumption (VO2) or peak work. On univariable analysis, there was no significant correlation between RVEDVi and PRF with peak VO2 or peak work (% Jones-predicted). In contrast, RVEF and RVSVi had significant correlations with both peak VO2 and peak work that remained significant on multivariable analysis. For a previously established prognostic peak VO2 threshold of <27 mL/kg/min, receiver-operating characteristic curve analysis demonstrated a Harrell's c of 0.70 for RVEF (95% confidence interval 0.61-0.79) with a sensitivity of 88% for RVEF <40%., Conclusion: In rTOF, CMR indices of RV systolic function are better predictors of CPET performance than RV size. An RVEF <40% may be useful to identify prognostically significant reductions in exercise capacity in patients with varying degrees of RV dilatation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Various PCR based methods have been described for the diagnosis of malaria, but most depend on the use of Plasmodium species-specific probes and primers; hence only the tested species are identified and there is limited available data on the true circulating species diversity. Sensitive diagnostic tools and platforms for their use are needed to detect Plasmodium species in both clinical cases and asymptomatic infections that contribute to disease transmission. We have recently developed for the first time a novel high throughput 'haemoprotobiome' metabarcoded DNA sequencing method and applied it for the quantification of haemoprotozoan parasites (Theleria and Babesia) of livestock. Here, we describe a novel, high throughput method using an Illumina MiSeq platform to demonstrate the proportions of Plasmodium species in metabarcoded DNA samples derived from human malaria patients. Plasmodium falciparum and Plasmodium vivax positive control gDNA was used to prepare mock DNA pools of parasites to evaluate the detection threshold of the assay for each of the two species. The different mock pools demonstrate the accurate detection ability and to show the proportions of each of the species being present. We then applied the assay to malaria-positive human samples to show the species composition of Plasmodium communities in the Punjab province of Pakistan and in the Afghanistan-Pakistan tribal areas. The diagnostic performance of the deep amplicon sequencing method was compared to an immunochromatographic assay that is widely used in the region. The deep amplicon sequencing showed that P. vivax was present in 69.8%, P. falciparum in 29.5% and mixed infection in 0.7% patients examined. The immunochromatographic assay showed that P. vivax was present in 65.6%, P. falciparum in 27.4%, mixed infection 0.7% patients and 6.32% malaria-positive cases were negative in immunochromatographic assay, but positive in the deep amplicon sequencing. Overall, metabarcoded DNA sequencing demonstrates better diagnostic performance, greatly increasing the estimated prevalence of Plasmodium infection. The next-generation sequencing method using metabarcoded DNA has potential applications in the diagnosis, surveillance, treatment, and control of Plasmodium infections, as well as to study the parasite biology., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

Fasciola spp. are responsible for over 3 billion US dollars of production loss annually in livestock and cause widespread zoonotic disease. Nevertheless, understating of the emergence and spread of the trematode species is poor. The multiplicity of F. gigantica infection and its spread is potentially influenced by multiple factors, including the abundance of suitable intermediate hosts, climatic conditions favouring the completion of the parasite's lifecycle, and translocation of infected animals, or free-living parasite stages between regions. Here we describe the development of a 'tremabiome' metabarcoding sequencing method to explore the numbers of F. gigantica genotypes per infection and patterns of parasite spread, based on genetic characteristics of the mitochondrial NADH dehydrogenase 1 (mt-ND-1) locus. We collected F. gigantica from three abattoirs in the Punjab and Balochistan provinces of Pakistan, and our results show a high level of genetic diversity in 20 F. gigantica populations derived from small and large ruminants consigned to slaughter in both provinces. This implies that F. gigantica can reproduce in its definitive hosts through meiosis involving cross- and self-breeding, as described in the closely related species, Fasciola hepatica. The genetic diversity between the 20 populations derived from different locations also illustrates the impact of animal movements on gene flow. Our results demonstrate the predominance of single haplotypes, consistent with a single introduction of F. gigantica infection in 85% of the hosts from which the parasite populations were derived. This is consistent with clonal reproduction in the intermediate snail hosts., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: To enable free-breathing whole-heart sub-millimeter resolution coronary magnetic resonance angiography (CMRA) in a clinically feasible scan time by combining low-rank patch-based undersampled reconstruction (3D-PROST) with a highly accelerated non-rigid motion correction framework., Methods: Non-rigid motion corrected CMRA combined with 2D image-based navigators has been previously proposed to enable 100% respiratory scan efficiency in modestly undersampled acquisitions. Achieving sub-millimeter isotropic resolution with such techniques still requires prohibitively long acquisition times. We propose to combine 3D-PROST reconstruction with a highly accelerated non-rigid motion correction framework to achieve sub-millimeter resolution CMRA in less than 10 min. Ten healthy subjects and eight patients with suspected coronary artery disease underwent 4-5-fold accelerated free-breathing whole-heart CMRA with 0.9 mm 3 isotropic resolution. Vessel sharpness, vessel length and image quality obtained with the proposed non-rigid (NR) PROST approach were compared against translational correction only (TC-PROST) and a previously proposed NR motion-compensated technique (non-rigid SENSE) in healthy subjects. For the patient study, image quality scoring and visual comparison with coronary computed tomography angiography (CCTA) were performed., Results: Average scan times [min:s] were 6:01 ± 0:59 (healthy subjects) and 8:29 ± 1:41 (patients). In healthy subjects, vessel sharpness of the left anterior descending (LAD) and right (RCA) coronary arteries were improved with the proposed non-rigid PROST (LAD: 51.2 ± 8.8%, RCA: 61.2 ± 9.1%) in comparison to TC-PROST (LAD: 43.8 ± 5.1%, P = 0.051, RCA: 54.3 ± 8.3%, P = 0.218) and non-rigid SENSE (LAD: 46.1 ± 5.8%, P = 0.223, RCA: 56.7 ± 9.6%, P = 0.50), although differences were not statistically significant. The average visual image quality score was significantly higher for NR-PROST (LAD: 3.2 ± 0.6, RCA: 3.3 ± 0.7) compared with TC-PROST (LAD: 2.1 ± 0.6, P = 0.018, RCA: 2.0 ± 0.7, P = 0.014) and non-rigid SENSE (LAD: 2.3 ± 0.5, P = 0.008, RCA: 2.5 ± 0.7, P = 0.016). In patients, the proposed approach showed good delineation of the coronaries, in agreement with CCTA, with image quality scores and vessel sharpness similar to that of healthy subjects., Conclusions: We demonstrate the feasibility of combining high undersampling factors with non-rigid motion-compensated reconstruction to obtain high-quality sub-millimeter isotropic CMRA images in ~ 8 min. Validation in a larger cohort of patients with coronary artery disease is now warranted.

Aims: Dysfunctional matrix turnover is present at sites of abdominal aortic aneurysm (AAA) and leads to the accumulation of monomeric tropoelastin rather than cross-linked elastin. We used a gadolinium-based tropoelastin-specific magnetic resonance contrast agent (Gd-TESMA) to test whether quantifying regional tropoelastin turnover correlates with aortic expansion in a murine model. The binding of Gd-TESMA to excised human AAA was also assessed., Methods and Results: We utilized the angiotensin II (Ang II)-infused apolipoprotein E gene knockout (ApoE-/-) murine model of aortic dilation and performed in vivo imaging of tropoelastin by administering Gd-TESMA followed by late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) and T1 mapping at 3 T, with subsequent ex vivo validation. In a cross-sectional study (n = 66; control = 11, infused = 55) we found that Gd-TESMA enhanced MRI was elevated and confined to dilated aortic segments (control: LGE=0.13 ± 0.04 mm2, control R1= 1.1 ± 0.05 s-1 vs. dilated LGE =1.0 ± 0.4 mm2, dilated R1 =2.4 ± 0.9 s-1) and was greater in segments with medium (8.0 ± 3.8 mm3) and large (10.4 ± 4.1 mm3) compared to small (3.6 ± 2.1 mm3) vessel volume. Furthermore, a proof-of-principle longitudinal study (n = 19) using Gd-TESMA enhanced MRI demonstrated a greater proportion of tropoelastin: elastin expression in dilating compared to non-dilating aortas, which correlated with the rate of aortic expansion. Treatment with pravastatin and aspirin (n = 10) did not reduce tropoelastin turnover (0.87 ± 0.3 mm2 vs. 1.0 ± 0.44 mm2) or aortic dilation (4.86 ± 2.44 mm3 vs. 4.0 ± 3.6 mm3). Importantly, Gd-TESMA-enhanced MRI identified accumulation of tropoelastin in excised human aneurysmal tissue (n = 4), which was confirmed histologically., Conclusion: Tropoelastin MRI identifies dysfunctional matrix remodelling that is specifically expressed in regions of aortic aneurysm or dissection and correlates with the development and rate of aortic expansion. Thus, it may provide an additive imaging marker to the serial assessment of luminal diameter for surveillance of patients at risk of or with established aortopathy., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Bovine babesiosis is an infectious protozoan disease and causes significant economic losses in terms of production loss and mortality. The genus Babesia belongs to the family Babesiidae order piroplasmida and is transmitted by ticks globally. The signs of disease are particularly prominent in old or immuno-compromised animals. The spleen plays a vital role in defence against hemoparasites like Babesia. A young cross-bred cow calf of about 3 months of age was splenectomised to propagate Babesia in vivo experimentally. Prior to splenectomy, the calf was examined through microscopy and PCR analysis and was found negative for any kind of piroplasms including Babesia. The calf was completely splenectomised, but the calf was naturally infected during its postoperative period. The calf expired after naturally acquiring Babesia bigemina and Theileria annulata during the 11 th day of postoperative period owing to increased parasitaemia, exhibiting typical mixed parasitic infection stigmata e.g. reddish urine, elevated temperature up to 41.38°C. This study concluded that complete splenectomy along with dexamethasone administration in the postop period caused exceptional increase in parasitaemia. This parasitaemia couldn't be countered by any symptomatic treatment because of the absence of spleen and greatly reduced immunity of the animal.

Objective: CD73 is an ectonucleotidase which catalyzes the conversion of AMP (adenosine monophosphate) to adenosine. Adenosine has been shown to be anti-inflammatory and vasorelaxant. The impact of ectonucleotidases on age-dependent atherosclerosis remains unclear. Our aim was to investigate the role of CD73 in age-dependent accumulation of atherosclerosis. Approach and results: Mice doubly deficient in CD73 and ApoE (apolipoprotein E; ( cd73 - /- /apoE -/- ) were generated, and the extent of aortic atherosclerotic plaque was compared with apoE -/- controls at 12, 20, 32, and 52 weeks. By 12 weeks of age, cd73 -/- /apoE -/- mice exhibited a significant increase in plaque (1.4±0.5% of the total vessel surface versus 0.4±0.1% in apoE -/- controls, P <0.005). By 20 weeks of age, this difference disappeared (2.9±0.4% versus 3.3±0.7%). A significant reversal in phenotype emerged at 32 weeks (9.8±1.2% versus 18.3±1.4%; P <0.0001) and persisted at the 52 week timepoint (22.4±2.1% versus 37.0±2.1%; P <0.0001). The inflammatory response to aging was found to be comparable between cd73 -/- /apoE -/- mice and apoE -/- controls. A reduction in lipolysis in CD73 competent mice was observed, even with similar plasma lipid levels ( cd73 -/- /apoE -/- versus apoE -/- at 12 weeks [16.2±0.7 versus 9.5±1.4 nmol glycerol/well], 32 weeks [24.1±1.5 versus 7.4±0.4 nmol/well], and 52 weeks [13.8±0.62 versus 12.7±2.0 nmol/well], P <0.001)., Conclusions: At early time points, CD73 exerts a subtle antiatherosclerotic influence, but with age, the pattern reverses, and the presence of CD73 promoted suppression of lipid catabolism.