Green line hospital-territory study: A single-blind randomized clinical trial for evaluation of technological challenges of continuous wireless monitoring in internal medicine, preliminary results

Background: Wireless vital parameter continuous monitoring (WVPCM) after discharge is compared to regular monitoring to provide data on the clinical-economic impact of complex patients (CPs) discharged from Internal Medicine Units of Ospedale dei Castelli, Lazio. Primary outcome: Major complications (MC) reduction. Secondary outcomes: Patients who reached discharge criteria within the 7th day from admission; difference in MC incidence at the conclusion of the standard telemonitoring/clinical monitoring phase, 5 and 30 days after discharge; and conditions predisposing to MC occurrence. Methods: Open label randomized controlled trial with wearable wireless system that creates alerts on portable devices. Continuous glycemic monitoring is performed for patients with diabetes mellitus. Results: There were 110 patients enrolled (mean age: 76.2 years). Comorbidity: Cumulative Illness Rating Scale CIRS-CI (comorbidities index): 3.93, CIRS SI (severity index): 1.93. About 19% scored a BRASS (Blaylock Risk Assessment Screening Score) ≥20 indicating need for discharge planning requiring step-down care. Globally, 48% of patients in the control group had major complications (27 out of 56 patients), in contrast to 22% in the intervention group (12 out of 54 patients). Conclusions: Since WVPCM detects early complications during the post-discharge CPs monitoring, it increases safety and reduces inappropriate access to the Emergency Room, preventing avoidable re-hospitalizations

Global unfolding of proteins by partial NMR assignment

The effect of urea concentration on the backbone solution structure of the cyanide derivative of ferric Caretta caretta myoglobin (at pH 5.4) is reported. By addition of urea, sequential and long-range nuclear Overhauser effects (NOEs) are gradually lost. By using the residual NOE constraints to build the molecular model, a picture of the unfolding pathway was obtained. When the urea concentration is raised to 2.2 M, helices A and B appear largely disordered; helices C, D, and F loose structural constraints at 3.0 M urea. At urea concentration >6 M, the protein appears to be fully unfolded, including the GH hairpin and helix E stabilizing the prosthetic group. Reversible and cooperative denaturation isotherms obtained by following NOE peaks are considerably different from those obtained by monitoring electronic absorption changes. The reversible and cooperative urea-dependent folding-unfolding process of C. caretta myoglobin follows the minimum three-state mechanism N long left and right arrow X long left and right arrow D, where X represents a disordered globin structure (occurring at approximately 4 M urea) that still binds the heme

ADDUCTS BETWEEN MAGNETIC RESONANCE SHIFT REAGENTS AND SUBSTRATES CONTAINING EXCHANGEABLE PROTONS FOR "CEST" APPLICATIONS

Disclosed are CEST paramagnetic agents comprising a substrate (SH) containing mobile protons bonded to a paramagnetic chelate (SR) containing a metal selected from iron (ii) (high-spin configuration), iron (iii), cobalt (ii), rhodium (ii), copper (ii), nickel (ii), cerium (iii), praseodymium (iii), neodymium (iii), dysprosium (iii), erbium (iii), terbium (iii), holmium (iii), thulium (iii), ytterbium (iii) and europium (iii)

Combined high resolution NMR and 1H and 17O relaxometric study sheds light on the solution structure and dynamics of the lanthanide(III) complexes of HPDO3A

GdHPDO3A is one of the most used MRI contrast agents (CAs) for clinical use. However, unlike most of the other commercially available Gd-based CAs, only limited information is available on its solution structure and dynamics. 600 MHz high resolution 1H NMR spectra of nine LnHPDO3A complexes (Ln = Pr, Nd, Eu, Tb, Dy, Ho, Er, Tm, and Yb) have been recorded at 298 K and neutral pH. Because of the low symmetry of the Ln-chelates, each proton gives rise to a different peak. Despite the very crowded spectra, it is possible to detect the presence of two sets of resonances associated with different isomers in solution in slow exchange in the NMR time scale. In principle, the LnHPDO3A complexes may be present in solution as eight isomeric forms (four enantiomeric pairs)differing in the layout of the acetate arms (\u394 or \u39b), in the conformation of the macrocyclic ring (\u3b4\u3b4\u3b4\u3b4 or \u3bb\u3bb\u3bb\u3bb) and in the configuration of the chiral center (R or S). 1D- and 2D proton NMR spectra were measured as a function of temperature across the Lanthanide series. The data allow identifying the nature of the most abundant isomeric species in solution (e.g., \u39b(\u3bb\u3bb\u3bb\u3bb) 12R/\u39b(\u3b4\u3b4\u3b4\u3b4) 12R and their enantiomeric forms \u394(\u3b4\u3b4\u3b4\u3b4) 12S/ \u394(\u3bb\u3bb\u3bb\u3bb) 12S) and their interconversion process. Analysis of the data led us to identify the presence in solution of a third isomeric species, lacking the coordinated water molecule (q = 0), whose population becomes more relevant for the heavier lanthanides (Ln = Er 12Lu). Moreover, we have introduced an innovative way of modeling the thermodynamic equilibrium between the various isomeric forms of LnHPDO3A that can be extended to a number of other systems. This analysis enabled us to calculate the molar fractions of the two isomeric forms for GdHPDO3A (\u3c7 = 0.7 and 0.30, for SAP and TSAP, respectively). This information has allowed interpreting the slightly anomalous relaxometric properties of GdHPDO3A. In particular, we observed that the temperature dependence of the 17O NMR transverse relaxation rate of GdHPDO3A, R2, reveals an unusual trend at low temperatures and at high magnetic field strength (>9.4 T). This behavior has been attributed to the occurrence of a very large difference in the rate of water exchange, kex, for the two isomeric species (1/kex = \u3c4M = 640 \ub1 35 ns and 8.9 \ub1 0.5 ns, for the major and minor isomer respectively)

Asparagine in plums detected by CEST \u2013 MRI

Magnetic resonance imaging (MRI) relies on the topological distribution of the intense water NMR signal and may be used to report about changes in the internal structures of fruits associated to ripening, storing, pathogen infection. Herein the use of CEST\u2013MRI (chemical exchange saturation transfer) is introduced to show that in addition to structural information, insights into the presence in the fruits of specific chemicals may be gained. Asparagine is present in plums at relatively high concentration ( 4810\u201320 mM) and owns two amide protons (at 2.1 and 2.8 ppm down field from water) in slow exchange with water protons. By irradiating the amide resonances with a proper rf-field it is possible to transfer saturated magnetization to the \u201cbulk\u201d water signal. The attained change in signal intensity reflects the extent of prototropic exchange between amide and water protons that is modulated by the local pH