Cardiovascular magnetic resonance native T-2 and T-2* quantitative values for cardiomyopathies and heart transplantations:a systematic review and meta-analysis

Background: The clinical application of cardiovascular magnetic resonance (CMR) T2 and T2* mapping is currently limited as ranges for healthy and cardiac diseases are poorly defined. In this meta-analysis we aimed to determine the weighted mean of T2 and T2* mapping values in patients with myocardial infarction (MI), heart transplantation, non-ischemic cardiomyopathies (NICM) and hypertension, and the standardized mean difference (SMD) of each population with healthy controls. Additionally, the variation of mapping outcomes between studies was investigated. Methods: The PRISMA guidelines were followed after literature searches on PubMed and Embase. Studies reporting CMR T2 or T2* values measured in patients were included. The SMD was calculated using a random effects model and a meta-regression analysis was performed for populations with sufficient published data. Results: One hundred fifty-four studies, including 13,804 patient and 4392 control measurements, were included. T2 values were higher in patients with MI, heart transplantation, sarcoidosis, systemic lupus erythematosus, amyloidosis, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and myocarditis (SMD of 2.17, 1.05, 0.87, 1.39, 1.62, 1.95, 1.90 and 1.33, respectively, P < 0.01) compared with controls. T2 values in iron overload patients (SMD =-0.54, P = 0.30) and Anderson-Fabry disease patients (SMD = 0.52, P = 0.17) did both not differ from controls. T2* values were lower in patients with MI and iron overload (SMD of-1.99 and-2.39, respectively, P < 0.01) compared with controls. T2* values in HCM patients (SMD =-0.61, P = 0.22), DCM patients (SMD =-0.54, P = 0.06) and hypertension patients (SMD =-1.46, P = 0.10) did not differ from controls. Multiple CMR acquisition and patient demographic factors were assessed as significant covariates, thereby influencing the mapping outcomes and causing variation between studies. Conclusions: The clinical utility of T2 and T2* mapping to distinguish affected myocardium in patients with cardiomyopathies or heart transplantation from healthy myocardium seemed to be confirmed based on this meta-analysis. Nevertheless, variation of mapping values between studies complicates comparison with external values and therefore require local healthy reference values to clinically interpret quantitative values. Furthermore, disease differentiation seems limited, since changes in T2 and T2* values of most cardiomyopathies are similar

Validation of thoracic aortic dimensions on ECG-triggered SSFP as alternative to contrast-enhanced MRA

Objectives: Assessment of thoracic aortic dimensions with non-ECG-triggered contrast-enhanced magnetic resonance angiography (CE-MRA) is accompanied with motion artefacts and requires gadolinium. To avoid both motion artefacts and gadolinium administration, we evaluated the similarity and reproducibility of dimensions measured on ECG-triggered, balanced steady-state free precession (SSFP) MRA as alternative to CE-MRA. Methods: All patients, with varying medical conditions, referred for thoracic aortic examination between September 2016 and March 2018, who underwent non-ECG-triggered CE-MRA and SSFP-MRA (1.5 T) were retrospectively included (n = 30). Aortic dimensions were measured after double-oblique multiplanar reconstruction by two observers at nine landmarks predefined by literature guidelines. Image quality was scored at the sinus of Valsalva, mid-ascending aorta and mid-descending aorta by semi-automatically assessing the vessel sharpness. Results: Aortic dimensions showed high agreement between non-ECG-triggered CE-MRA and SSFP-MRA (r = 0.99, p < 0.05) without overestimation or underestimation of aortic dimensions in SSFP-MRA (mean difference, 0.1 mm; limits of agreement, − 1.9 mm and 1.9 mm). Intra- and inter-observer variabilities were significantly smaller with SSFP-MRA for the sinus of Valsalva and sinotubular junction. Image quality of the sinus of Valsalva was significantly better with SSFP-MRA, as fewer images were of impaired quality (3/30) than in CE-MRA (21/30). Reproducibility of dimensions was significantly better in images scored as good quality compared to impaired quality in both sequences. Conclusions: Thoracic aortic dimensions measured on SSFP-MRA and non-ECG-triggered CE-MRA were similar. As expected, SSFP-MRA showed better reproducibility close to the aortic root because of lesser motion artefacts, making it a feasible non-contrast imaging alternative. Key Points: • SSFP-MRA provides similar dimensions as non-ECG-triggered CE-MRA. • Intra- and inter-observer reproducibilities improve for the sinus of Valsalva and sinotubular junction with SSFP-MRA. • ECG-triggered SSFP-MRA shows better image quality for landmarks close to the aortic root in the absence of cardiac motion

Targeted optical fluorescence imaging:a meta-narrative review and future perspectives

Purpose: The aim of this review is to give an overview of the current status of targeted optical fluorescence imaging in the field of oncology, cardiovascular, infectious and inflammatory diseases to further promote clinical translation. Methods: A meta-narrative approach was taken to systematically describe the relevant literature. Consecutively, each field was assigned a developmental stage regarding the clinical implementation of optical fluorescence imaging. Results: Optical fluorescence imaging is leaning towards clinical implementation in gastrointestinal and head and neck cancers, closely followed by pulmonary, neuro, breast and gynaecological oncology. In cardiovascular and infectious disease, optical imaging is in a less advanced/proof of concept stage. Conclusion: Targeted optical fluorescence imaging is rapidly evolving and expanding into the clinic, especially in the field of oncology. However, the imaging modality still has to overcome some major challenges before it can be part of the standard of care in the clinic, such as the provision of pivotal trial data. Intensive multidisciplinary (pre-)clinical joined forces are essential to overcome the delivery of such compelling phase III registration trial data and subsequent regulatory approval and reimbursement hurdles to advance clinical implementation of targeted optical fluorescence imaging as part of standard practice

First HARPSpol discoveries of magnetic fields in massive stars

In the framework of the Magnetism in Massive Stars (MiMeS) project, a HARPSpol Large Program at the 3.6m-ESO telescope has recently started to collect high-resolution spectropolarimetric data of a large number of Southern massive OB stars in the field of the Galaxy and in many young clusters and associations. In this Letter, we report on the first discoveries of magnetic fields in two massive stars with HARPSpol - HD 130807 and HD 122451, and confirm the presence of a magnetic field at the surface of HD 105382 that was previously observed with a low spectral resolution device. The longitudinal magnetic field measurements are strongly varying for HD 130807 from $\sim$-100 G to $\sim$700 G. Those of HD 122451 and HD 105382 are less variable with values ranging from $\sim$-40 to -80 G, and from $\sim$-300 to -600 G, respectively. The discovery and confirmation of three new magnetic massive stars, including at least two He-weak stars, is an important contribution to one of the MiMeS objectives: the understanding of origin of magnetic fields in massive stars and their impacts on stellar structure and evolution.Comment: 4 pages, 2 figures, accepted for publication in A&A Lette

Discovery of a strong magnetic field in the rapidly rotating B2Vn star HR 7355

We report the detection of a strong, organized magnetic field in the helium-variable early B-type star HR 7355 using spectropolarimetric data obtained with ESPaDOnS on the 3.6-m Canada-France-Hawaii Telescope within the context of the Magnetism in Massive Stars (MiMeS) Large Program. HR 7355 is both the most rapidly rotating known main-sequence magnetic star and the most rapidly rotating helium-strong star, with $v \sin i$ = 300 $\pm$ 15 km s$^{-1}$ and a rotational period of 0.5214404 $\pm$ 0.0000006 days. We have modeled our eight longitudinal magnetic field measurements assuming an oblique dipole magnetic field. Constraining the inclination of the rotation axis to be between $38^{\circ}$ and $86^{\circ}$, we find the magnetic obliquity angle to be between $30^{\circ}$ and $85^{\circ}$, and the polar strength of the magnetic field at the stellar surface to be between 13-17 kG. The photometric light curve constructed from HIPPARCOS archival data and new CTIO measurements shows two minima separated by 0.5 in rotational phase and occurring 0.25 cycles before/after the magnetic extrema. This photometric behavior coupled with previously-reported variable emission of the H$\alpha$ line (which we confirm) strongly supports the proposal that HR 7355 harbors a structured magnetosphere similar to that in the prototypical helium-strong star, $\sigma$ Ori E.Comment: 6 pages, 3 figures. Accepted for publication in MNRAS Letter

Revisiting the Rigidly Rotating Magnetosphere model for sigma Ori E. I. Observations and Data Analysis

We have obtained 18 new high-resolution spectropolarimetric observations of the B2Vp star sigma Ori E with both the Narval and ESPaDOnS spectropolarimeters. The aim of these observations is to test, with modern data, the assumptions of the Rigidly Rotating Magnetosphere (RRM) model of Townsend & Owocki (2005), applied to the specific case of sigma Ori E by Townsend et al. (2005). This model includes a substantially offset dipole magnetic field configuration, and approximately reproduces previous observational variations in longitudinal field strength, photometric brightness, and Halpha emission. We analyze new spectroscopy, including H I, He I, C II, Si III and Fe III lines, confirming the diversity of variability in photospheric lines, as well as the double S-wave variation of circumstellar hydrogen. Using the multiline analysis method of Least-Squares Deconvolution (LSD), new, more precise longitudinal magnetic field measurements reveal a substantial variance between the shapes of the observed and RRM model time-varying field. The phase resolved Stokes V profiles of He I 5876 A and 6678 A lines are fit poorly by synthetic profiles computed from the magnetic topology assumed by Townsend et al. (2005). These results challenge the offset dipole field configuration assumed in the application of the RRM model to sigma Ori E, and indicate that future models of its magnetic field should also include complex, higher-order components.Comment: 13 pages, 8 figures. Accepted for publication in MNRA

Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality

Liver Fat Content in Type 2 Diabetes: Relationship With Hepatic Perfusion and Substrate Metabolism

OBJECTIVE - Hepatic steatosis is common in type 2 diabetes. It is causally linked to the features of the metabolic syndrome, liver cirrhosis, and cardiovascular disease. Experimental data have indicated that increased liver fat may impair hepatic perfusion and metabolism. The aim of the current study was to assess hepatic parenchymal perfusion, together with glucose and fatty acid metabolism, in relation to hepatic triglyceride content. RESEARCH DESIGN AND METHODS - Fifty-nine men with well controlled type 2 diabetes and 18 age-matched healthy normoglycemic men were studied using positron emission tomography to assess hepatic tissue perfusion, insulin-stimulated glucose, and fasting fatty acid metabolism, respectively, in relation to hepatic triglyceride content, quantified by proton magnetic resonance spectroscopy. Patients were divided into two groups with hepatic triglyceride content below (type 2 diabeteslow) or above (type 2 diabetes-high) the median of 8.6%. RESULTS - Type 2 diabetes-high patients had the highest BMI and A1C and lowest whole-body insulin sensitivity (ANOVA, all P < 0.001). Compared with control subjects and type 2 diabeteslow patients, type 2 diabetes-high patients had the lowest hepatic parenchymal perfusion (P = 0.004) and insulin-stimulated hepatic glucose uptake (P = 0.013). The observed decrease in hepatic fatty acid influx rate constant, however, only reached borderline significance (P = 0.088). In type 2 diabetic patients, hepatic parenchymal perfusion (r = -0.360, P = 0.007) and hepatic fatty acid influx rate constant (r = -0.407, P = 0.007) correlated inversely with hepatic triglyceride content. In a pooled analysis, hepatic fat correlated with hepatic glucose uptake (r = -0.329, P = 0.004). CONCLUSIONS - In conclusion, type 2 diabetic patients with increased hepatic triglyceride content showed decreased hepatic parenchymal perfusion and hepatic insulin mediated glucose uptake, suggesting a potential modulating effect of hepatic fat on hepatic physiology. © 2010 by the American Diabetes Association

Assay platform for clinically relevant metallo-beta-lactamases

Metallo-β-lactamases (MBLs) are a growing threat to the use of almost all clinically used β-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-β-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (São Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4-chloroisoquinolinols as potential pan MBL inhibitors

Magnetic Field Generation in Stars

Enormous progress has been made on observing stellar magnetism in stars from the main sequence through to compact objects. Recent data have thrown into sharper relief the vexed question of the origin of stellar magnetic fields, which remains one of the main unanswered questions in astrophysics. In this chapter we review recent work in this area of research. In particular, we look at the fossil field hypothesis which links magnetism in compact stars to magnetism in main sequence and pre-main sequence stars and we consider why its feasibility has now been questioned particularly in the context of highly magnetic white dwarfs. We also review the fossil versus dynamo debate in the context of neutron stars and the roles played by key physical processes such as buoyancy, helicity, and superfluid turbulence,in the generation and stability of neutron star fields. Independent information on the internal magnetic field of neutron stars will come from future gravitational wave detections. Thus we maybe at the dawn of a new era of exciting discoveries in compact star magnetism driven by the opening of a new, non-electromagnetic observational window. We also review recent advances in the theory and computation of magnetohydrodynamic turbulence as it applies to stellar magnetism and dynamo theory. These advances offer insight into the action of stellar dynamos as well as processes whichcontrol the diffusive magnetic flux transport in stars.Comment: 41 pages, 7 figures. Invited review chapter on on magnetic field generation in stars to appear in Space Science Reviews, Springe