Deciphering the Magnetostructural Criteria in DyIII^{III} and HoIII^{III} Macrocycle-Based Single-Molecule Magnets with Pseudo- D5h_{5h} Symmetry: A Combined Single-Crystal Hysteresis and Theoretical Study

The employment of the metal-ion-assisted [1+1] Schiff-base condensation has led to complexes [Ln(LN5)(Ph3SiO)2](PF6), where LnIII = DyIII (1-Dy) and HoIII (1-Ho), with close-to-ideal D5h local symmetry. For the Kramers DyIII system, slow magnetization relaxation was observed up to 64 K yielding a sizable Ueff value of 963 K, whereas the non-Kramers HoIII compound exhibited no out-of-phase signals at T > 2 K. Single-crystal magnetic hysteresis measurements uncovered the magnetization blockage of 1-Dy at T < 4 K with typical butterfly shaped loops, while open rectangular-shaped hysteresis loops were observed for 1-Ho below 0.2 K. Doping of the 1-Ho compound into a diamagnetic YIII matrix unveiled the hyperfine-driven QTM steps reflected by staircase-like hysteresis loops for 1-Ho@Y. Detailed analysis through ab initio calculations has shed light on the low-lying energy levels of both compounds leading to well-isolated and pure ground states of mJ = ±15/2 and mJ = ±8 for 1-Dy and 1-Ho, respectively. The magnetization relaxation for 1-Dy advances through the third excited state, whereas the significant tunnel splitting (Δtun) of ∼0.15 cm–1 in the ground state of 1-Ho has fostered the onset of fast tunneling relaxation

Unveiling new [1+1] Schiff-base macrocycles towards high energy-barrier hexagonal bipyramidal Dy( iii ) single-molecule magnets †

The employment of the [1+1] condensation approach for the preparation of new macrocyclic scaffolds (LN6 and LN3O3) towards high-performance Dy(iii) single-molecule magnets (SMMs) with pseudo-D6h symmetry is described. Engineering of the macrocycles denticity from LN6 to LN3O3 leads to a mononuclear SMM with a large Ueff value of 1300 K. The experimental results are supported by ab initio calculations, which indicate relaxation of the magnetization via the second-excited state

Establishing a hepatitis C continuum of care among HIV/hepatitis C virus-coinfected individuals in EuroSIDA

Objectives The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Methods Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. Results Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P <0.0001). Conclusions In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.Peer reviewe

Dobutamine 3D strain in the left anterior descending subtended ventricular territory: evidence for relationship with the respective velocity flow reserve

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Three dimensional speckle tracking imaging (3DST), provides an evolving means to interrogate left ventricular (LV) function. However, its clinical application still remains limited. Purpose Purpose of the study was to interrogate the relationship between regional deformation by 3DST in left anterior descending artery (LAD) subtended territory and the respective coronary flow reserve (CFR). Methods Fifty patients aged 63 ± 6 years with chronic coronary syndromes were studied. Patients had no evidence of dobutamine (DOB) induced ischemia in LAD territory. Distal LAD CFR was estimated by adenosine Doppler echo (140mg/kg/min). 3DST derived integral strain (IS) and respective components (longitudinal -LS, circumferential –CS, radial -RS) were estimated by a full volume sweep (3.5 MHz sector probe) at &amp;gt;20 volumes/sec. A 16 LV sectors (sc) polar map was provided (Artida,Toshiba) with 10/16 sectors (sc) analysed, 6 sc being the conventional LAD territory (sc: 3,4,5,6,7,8) and another 4 sc being adjacent ones (sc: 1, 2, 9, 10). 3D datasets acquired at rest (R) and low dose DOB (20mg/kg/min). LV mass was automatically measured from volumetric data sets and its variability during cardiac cycle was considered as an index of coherence for true LV borders recognition. Results CFR was &amp;gt;2 in all pts (range 2.0-4.2, 2.74 + 0.46). Mean variability of LV mass between R and DOB was 0.044 (range: -0.090-0.008, p = ns). 3DST strain was related with LAD CFR as follows: 1.For IS: at R: sc1: r = 0.38, p = 0.023, sc3: r = 0.44, p = 0.006, sc5: r = 0.35, p = 0.03, sc9: r = 0.50, p = 0.002. At DOB sc7: r = 0.31, p = 0.05. 2.For LS: at R: sc5: r=-0.40, p = 0.01. 3.For CS: at R: sc5: r=-0.33, p = 0.02, sc5: r=-0.46, p = 0.004. 4.For RS: at R: sc9: r=-0.38, p = 0.08. The % changes of regional IS post DOB compared to R were also related with CFR LAD in the sectors sc1 and sc3 (r = 0.34, p = 0.05, and p = 0.40, p = 0.002 respectively). Conclusion 3DST derived LV deformation indices in the LAD territory are related with the respective CFR. LV regional integral strain has a stronger relationship with LAD CFR when compared to the partial vectors. The 3DST derived deformation indices seem sensitive enough to reproduce the flow function relationship in the LAD territory. Thus, potential applicability has to be supported. </jats:sec

P1382 Evidence for longitudinal aorta strain relationship with noninvasive left ventricular myocardial work: another component for the ventricular-aorta coupling?

Abstract The force required to produce longitudinal strain of the aorta represents an often overlooked mechanical load imposed on the left ventricle (LV). 2D speckle tracking strain analysis (2D-SpTa) may be applied on aorta wall in order to evaluate regional longitudinal strain (AoSTR). A noninvasive method for measuring LV myocardial work (MW) has been recently proposed, based on 2D-SpTa combined with estimated pressure curve. Aim of the study was to assess the relationship of both LV conventional functional indices and the new MW ones with the aorta function estimated by AoSRT in normals and to interrogate the potential effect of aging. Methods Fifty four normals, 24 males (M) and 30 females(F), age: 52 ± 13 (25-75 years), were selectively studied, provided that they had an efficient image quality to apply both AFI analysis for MW estimation and ascending aorta interrogation for AoLSTR (EchoPac GE) . LAoLSTR was measured in the posterior aorta wall (apical long axis view). Aortic wall borders were traced longitudinally adjusting width using 4 points of interest. The first point was put at the sinotubular junction and approximately 3-4 cm of the ascending aorta were analyzed. 2D-SpTa divided the regions of interest into proximal, middle and distal segments and the respective peak LAoSTR were considered. The following indexes of MW were estimated: GWI (global work index = total work from mitral valve closure to mitral valve opening), GCW (global constructive work = total work contributing to pump function, namely due to shortening during isovolumic contraction and ejection and lengthening during isovolumic relaxation), GWW (global wasted work = elongation during isovolumic contraction/ejection and shortening during isovolumic relaxation), GWE (global work efficiency = fraction of GCW/[GCW + GWW]). AFI derived LV strain (LVGS), biplane LV ejection fraction and stroke volume (SV) were also calculated. Results LAoSTR in any wall position was not affected by age. LAoLSTR of the proximal segment was related to both EF and LVGS (r = 0.31, p = 0.03 and r=-0.28 p = 0.05, respectively). Middle and distal LAoSTR were not related to either EF or LVGS. SV was not related to any of LAoSTR. LAoSTR of the proximal segment was related to both GWI and GCW ( r = 0.34 p = 0.016 and r = 0,31 p = 0.03 respectively). LAoSTR of the middle and distal segments were not related with any LV MW parameters. Conclusion Longitudinal aorta strain evaluation by 2D-SpTa is feasible and it is related with functional performance of the LV estimated by either conventional or MW indices based on 2D-SpTa. Moreover , the longitudinal performance of the proximal segment of the aorta above the sinotubular junction is linked to the constructive component of the LV myocardial work thus providing an alternative evidence for the LV ventricular–aorta coupling which was independent from aging. </jats:sec

The effect of endothelial Nitric Oxide Synthase G894T and T786C polymorphisms on Hypoxia-Inducible Factor-1 alpha expression in Sickle Cell Disease

Hypoxia-Inducible Factor-1α (HIF-1α) expression is upregulated in Sickle Cell Disease (SCD) and correlates with various laboratory markers of disease severity. Nitric Oxide plays a pivotal role in SCD pathophysiology and endothelial Nitric Oxide Synthase (NOS3) polymorphisms affect prognosis and laboratory parameters. This study questions the effect of NOS3 G894T and T786C polymorphisms on HIF-1α expression in SCD. We show that G894T polymorphism is a significant predictor of HIF-1α expression. Its effect is exerted independently of hemolysis/hemoglobin fragment concentrations, as shown in multiple regression analysis. Our results establish a novel modulator of HIF-1α expression on the mRNA level and indirectly support the role of nitric oxide in the pathophysiology of SCD. © 2021 Elsevier Inc