Search

Background Heart failure (HF) is the leading cause of mortality and associated with significant morbidity in adults with congenital heart disease. We sought to assess the association between HF and patient‐report outcomes in adults with congenital heart disease. Methods and Results As part of the APPROACH‐IS (Assessment of Patterns of Patient‐Reported Outcomes in Adults with Congenital Heart disease—International Study), we collected data on HF status and patient‐reported outcomes in 3959 patients from 15 countries across 5 continents. Patient‐report outcomes were: perceived health status (12‐item Short Form Health Survey), quality of life (Linear Analogue Scale and Satisfaction with Life Scale), sense of coherence‐13, psychological distress (Hospital Anxiety and Depression Scale), and illness perception (Brief Illness Perception Questionnaire). In this sample, 137 (3.5%) had HF at the time of investigation, 298 (7.5%) had a history of HF, and 3524 (89.0%) had no current or past episode of HF. Patients with current or past HF were older and had a higher prevalence of complex congenital heart disease, arrhythmias, implantable cardioverter‐defibrillators, other clinical comorbidities, and mood disorders than those who never had HF. Patients with HF had worse physical functioning, mental functioning, quality of life, satisfaction with life, sense of coherence, depressive symptoms, and illness perception scores. Magnitudes of differences were large for physical functioning and illness perception and moderate for mental functioning, quality of life, and depressive symptoms. Conclusions HF in adults with congenital heart disease is associated with poorer patient‐reported outcomes, with large effect sizes for physical functioning and illness perception. Registration URL: https://clinicaltrials.gov ; Unique identifier: NCT02150603.

Background:Systemic venous hypertension and low cardiac output are believed to be important mediators of liver injury after the Fontan procedure. Pulmonary vasodilators have the potential to improve such haemodynamics. The aim of this study was to assess the acute effects of exercise on liver stiffness and venous pressures and to assess the impact of inhaled Treprostinil on this response.Methods:In this prospective, double-blind, placebo-controlled, crossover trial, 14 patients with a Fontan circulation were randomised to inhalation of placebo and Treprostinil. Incremental and constant work rate exercise tests were performed to assess the effect of Treprostinil on exercise tolerance. Venous pressures were measured throughout and liver stiffness at rest and immediately after peak exercise.Results:Mean age was 27.8 ± 7.9 years and 66% were females. Exercise acutely increased liver stiffness by 30% (mean shear wave speed: 2.38 ± 0.71 versus 2.89 ± 0.51 ms, p = 0.02). Peripheral venous pressures increased acutely during both incremental (12.1 ± 2.4 versus 22.6 ± 8.0 mmHg, p < 0.001) and constant work rate exercise (12.5 ± 2.5 versus 23.4 ± 5.2 mmHg, p < 0.001). Overall, Treprostinil failed to attenuate exercise-induced increases in liver stiffness. Compared with placebo, Treprostinil did not significantly impact venous pressure responses, VO2peak, nor exercise endurance times.Conclusions:Peripheral venous pressure increased acutely during exercise by an average of 88% above baseline and was not altered by administration of inhaled Treprostinil. Liver stiffness measured immediately post-exercise increased acutely by an average of 30%, with no attenuation following Treprostinil inhalation.

Although recommended, most children are not routinely screened for lipid abnormalities and diabetes. We report a pilot of universal screening for diabetes, lipid abnormalities, and hypertension in the middle-school setting. Of 45 children screened, 34.8% had lipid or hemoglobin A1c abnormalities and 2 had hemoglobin A1c values in the diabetes range.

The first-row transition-metal(II) dithiolates M(SAriPr4)2 [AriPr4 = C6H3-2,6-(C6H3-2,6-iPr2)2; M = Cr (1), Mn (3), Fe (4), Co (5), Ni (6), and Zn (7)] and Cr(SArMe6)2 [2; ArMe6 = C6H3-2,6-(C6H2-2,4,6-Me3)2] and the ligand-transfer reagent (NaSAriPr4)2 (8) are described. In contrast to their M(SAriPr6)2 (M = Cr, Mn, Fe, Co, Ni, and Zn; AriPr6 = C6H3-2,6-(C6H2-2,4,6-iPr3)2) congeners, which differ from 1 and 3-6 in having p-isopropyl groups on the flanking aryl rings of the terphenyl substituents, compounds 1 and 4-6 display highly bent coordination geometries with S-M-S angles of 109.802(2)° (1), 120.2828(3)° (4), 91.730(3)° (5), and 92.68(2)° (6) as well as relatively close metal-flanking aryl ring η6 interactions with metal-centroid distances of 2.11477(6) A (1), 1.97188(3) A (2), 2.15269(6) A (4), 1.62058(9) A (5), and 1.724(8) A (6). However, the d5 (Mn) and d10 (Zn) complexes 3 and 7 display linear or near-linear coordination with no close metal-ligand distances. The nonlinear geometries of 1 and 4-6 also contrast with those of their AriPr4-substituted alkoxo and amido congeners, which have strictly linear coordination. Complexes 1-7 were synthesized by the reaction of the lithium or sodium thiolate salt with the metal dihalide or, in the case of 3, by the reaction of the thiol with the amido complex Mn[N(SiMe3)2]2. All compounds were characterized by electronic spectroscopy, X-ray crystallography, and magnetic measurements using Evans' method and SQUID magnetometry. It was concluded that, despite the large bulk of the AriPr4 substituents, the absence of p-isopropyl groups on the flanking rings of the ligand permits close secondary metal-flanking ring distances. The compounds are characterized by more intense colors and display magnetic moments that are generally lower than the spin-only values, in agreement with the covalent character of the close metal-flanking ring η6 interactions.

6Li-containing organic scintillators have been prepared and characterized as a new type of transparent, single-phase materials with pulse shape discrimination (PSD) properties for simultaneous detection of thermal and fast neutrons discriminated from gamma radiation. Tests conducted with recently developed PSD-capable plastic scintillators showed that incorporation of 6Li into the aromatic matrix with fast-neutron/gamma discrimination properties offers the additional sensitivity to thermal neutrons, substantially increasing efficiency and the energy range of neutron detection. Comparative analyses of 6Li-loaded plastic, liquid and single crystal organic scintillators provide evidence that, in addition to neutron/gamma discrimination, these novel materials have the ability for discrimination between the signatures of fast and thermal neutrons.

One of the hurdles in the discovery of antibiotics is the difficulty of linking antibacterial compounds to their cellular targets. Our laboratory has employed a genome-wide approach of over-expressing essential genes in order to identify cellular targets of antibacterial inhibitors. Our objective in this project was to develop and validate a more sensitive disk diffusion based platform of target identification (Target Identification Platform for Antibacterials version 2; TIPA II) using a collection of cell clones in an Escherichia coli mutant (AS19) host with increased outer membrane permeability. Five known antibiotics/inhibitors and 28 boron heterocycles were tested by TIPA II assay, in conjunction with the original assay TIPA. The TIPA II was more sensitive than TIPA because eight boron heterocycles previously found to be inactive to AG1 cells in TIPA assays exhibited activity to AS19 cells. For 15 boron heterocycles, resistant colonies were observed within the zones of inhibition only on the inducing plates in TIPA II assays. DNA sequencing confirmed that resistant clones harbor plasmids with fabI gene as insert, indicating that these boron heterocycles all target enoyl ACP reductase. Additionally, cell-based assays and dose response curved obtained indicated that for two boron heterocycle inhibitors, the fabI cell clone in AG1 (wild-type) host cells exhibited at least 11 fold more resistance under induced conditions than under non-induced conditions. Moreover, TIPA II also identified cellular targets of known antibacterial inhibitors triclosan, phosphomycin, trimethoprim, diazaborine and thiolactomycin, further validating the utility of the new system.

A possibility of manufacturing plastic scintillators with efficient neutron/gamma pulse shape discrimination (PSD) is demonstrated using a system of a polyvinyltoluene (PVT) polymer matrix loaded with a scintillating dye, 2,5-diphenyloxazole (PPO). Similarities and differences of conditions leading to the rise of PSD in liquid and solid organic scintillators are discussed based on the classical model of excited state interaction and delayed light formation. First characterization results are presented to show that PSD in plastic scintillators can be of the similar magnitude or even higher than in standard commercial liquid scintillators.

Neutron/gamma pulse shape discrimination (PSD) utilized for detection of high-energy neutrons with organic scintillators was investigated using a model system of mixed diphenylacetylene-stilbene single crystals of different compositions. The results of the studies, which include experimental tools of crystal growth and characterization combined with computer simulation, showed that the presence of impurities with lower bandgap energies can be a major factor influencing PSD properties of organic materials. Depending on the concentration, an impurity may suppress or increase the rate of excited triplet state interaction leading, respectively, to a complete disappearance or enhancement of PSD, consistent with a percolation threshold. The results are applied to produce novel materials with controlled decay characteristics. Single crystals with a large fraction of delayed light and enhanced PSD have been grown for high energy neutron detection, while crystals with suppressed delayed light were produced for use as low-afterglow scintillators for energetic neutron detection in time-of-flight experiments.

Single crystals of a pure hydrocarbon, 1,3,5-triphenylbenzene, with properties suitable for high-energy neutron detection were grown from toluene solutions using slow evaporation and temperature reduction methods with growth rates up to 10 mm/day. Application of the rapid growth technique developed earlier for growth of large water-soluble crystals shows that crystals of aromatic compounds can be successfully grown from solutions in large volumes required for their use as scintillator materials for radiation detection.

The characterization of the unstable Ni(II) bis(silylamide) Ni{N(SiMe3 )2 }2 (1), its THF complex Ni{N(SiMe3 )2 }2 (THF) (2), and the stable bis(pyridine) derivative trans-Ni{N(SiMe3 )2 }2 (py)2 (3), is described. Both 1 and 2 decompose at ca. 25 °C to a tetrameric Ni(I) species, [Ni{N(SiMe3 )2 }]4 (4), also obtainable from LiN(SiMe3 )2 and NiCl2 (DME). Experimental and computational data indicate that the instability of 1 is likely due to ease of reduction of Ni(II) to Ni(I) and the stabilization of 4 through dispersion forces.

A set of 2-acylated 2,3,1-benzodiazaborines and some related boron heterocycles were synthesized, characterized, and tested for antibacterial activity against Escherichia coli and Mycobacterium smegmatis. By high-field solution NMR, the heretofore unknown class of 2-acyl-1-hydroxy-2,3,1-diazaborines has been found to be able to exist in several interconvertable structural forms along a continuum comprised of an open hydrazone a, a monomeric B-hydroxy diazaborine b, and an anhydro dimer c. X-Ray crystallography of one of the anhydro dimers, 17c, revealed it to have an unprecedented structure featuring a double intramolecular O→B chelation. The crystal structure of another compound, 37, showed it to be based on a new pentacyclic B heterocycle framework. Nine compounds were found to possess activities against E. coli, and two others were active against M. smegmatis. The finding that these two contain isoniazid covalently embedded in their structures suggests that they might possibly be acting as prodrugs of this well-known antituberculosis agent in vivo.

Mono- and bis-terphenyl complexes of molybdenum and tungsten with general composition M2(Ar′)(O2CR)3 and M 2(Ar′)2(O2CR)2, respectively (Ar′ = terphenyl ligand), that contain carboxylate groups bridging the quadruply bonded metal atoms, have been prepared and structurally characterized. The new compounds stem from the reactions of the dimetal tetracarboxylates, M2(O2CR)4 (M = Mo, R = H, Me, CF3; M = W, R = CF3) with the lithium salts of the appropriate terphenyl groups (Ar′ = Ar Xyl2, ArMes2, Ar Dipp2, and Ar Trip2). Substitution of one bidentate carboxylate by a monodentate terphenyl forms a M-C σ bond and creates a coordination unsaturation at the other metal atom. Hence in M2(Ar′) 2(O2CR)2 complexes the two metal atoms have formally a low coordination number and an also low electron count. However, the unsaturation seems to be compensated by a weak M-Carene bonding interaction that implicates one of the aryl substituents of the terphenyl central aryl ring, as revealed by X-ray studies performed with some of these complexes and by theoretical calculations. © 2014 American Chemical Society.

Detection of high-energy neutrons in the presence of gamma radiation background utilizes pulse-shape discrimination (PSD) phenomena in organics studied previously only with limited number of materials, mostly liquid scintillators and single crystal stilbene. The current paper presents the results obtained with broader varieties of luminescent organic single crystals. The studies involve experimental tools of crystal growth and material characterization in combination with the advanced computer modeling, with the final goal of better understanding the relevance between the nature of the organic materials and their PSD properties. Special consideration is given to the factors that may diminish or even completely obscure the PSD properties in scintillating crystals. Among such factors are molecular and crystallographic structures that determine exchange coupling and exciton mobility in organic materials and the impurity effect discussed on the examples of trans-stilbene, bibenzyl, 9,10-diphenylanthracene and diphenylacetylene.

New quadruply bonded dimolybdenum complexes of the terphenyl ligand Ar Xyl2 (Ar Xyl2 = C 6H 3-2,6-(C 6H 3-2,6-Me 2) 2) have been prepared and structurally characterized. The steric hindrance exerted by the Ar Xyl2 groups causes the Mo atoms to feature unsaturated four-coordinate structures and a formal fourteen-electron count. © 2012 The Royal Society of Chemistry