Optimizing COPD Acute Care Patient Outcomes Using a Standardized Transition Bundle and Care Coordinator: A Randomized Clinical Trial.

Background: Acute exacerbations of COPD (AECOPD) are associated with high morbidity and mortality and frequent readmissions.

Research Question: What is the effectiveness of a COPD transition bundle, with and without a care coordinator, on rehospitalizations and ED revisits?

Study Design And Methods: Two patient cohorts were selected: (1) the group exposed to the transition bundle and (2) the group not exposed to the transition bundle (usual care group). Patients exposed subsequently were randomized to a care coordinator.

Fracture and Growth Are Competing Forces Determining the Fate of Conformers in Tau Fibril Populations.

Tau fibrils are pathological aggregates that can transfer between neurons and then recruit soluble Tau monomers by template-assisted conversion. The propagation of different fibril polymorphs is thought to be a contributing factor to phenotypic diversity in Alzheimer disease and other Tauopathies. We found that a homogeneous population of Tau fibrils composed of the truncated version K18 (residues 244-372) gradually converted to a new set of fibril conformers when subjected to multiple cycles of seeding and growth.

Spin Labeling and Characterization of Tau Fibrils Using Electron Paramagnetic Resonance (EPR).

Template-assisted propagation of Tau fibrils is essential for the spreading of Tau pathology in Alzheimer's disease. In this process, small seeds of fibrils recruit Tau monomers onto their ends. The physical properties of the fibrils play an important role in their propagation.

The energetics of a three-state protein folding system probed by high-pressure relaxation dispersion NMR spectroscopy.

The energetic and volumetric properties of a three-state protein folding system, comprising a metastable triple mutant of the Fyn SH3 domain, have been investigated using pressure-dependent (15) N-relaxation dispersion NMR from 1 to 2500 bar. Changes in partial molar volumes (ΔV) and isothermal compressibilities (ΔκT ) between all the states along the folding pathway have been determined to reasonable accuracy. The partial volume and isothermal compressibility of the folded state are 100 mL mol(-1) and 40 μL mol(-1)  bar(-1) , respectively, higher than those of the unfolded ensemble.

Room-temperature distance measurements of immobilized spin-labeled protein by DEER/PELDOR.

Nitroxide spin labels are used for double electron-electron resonance (DEER) measurements of distances between sites in biomolecules. Rotation of gem-dimethyls in commonly used nitroxides causes spin echo dephasing times (Tm) to be too short to perform DEER measurements at temperatures between ∼80 and 295 K, even in immobilized samples. A spirocyclohexyl spin label has been prepared that has longer Tm between 80 and 295 K in immobilized samples than conventional labels.

Amplification of Tau fibrils from minute quantities of seeds.

The propagation of Tau pathology in Alzheimer's disease (AD) is thought to proceed through templated conversion of Tau protein into fibrils and cell-to-cell transfer of elongation-competent seeds. To investigate the efficiency of Tau conversion, we adapted the protein misfolding cyclic amplification assay used for the conversion of prions. Utilizing heparin as a cofactor and employing repetitive cycles of shearing and growth, synthetic Tau fibrils and Tau fibrils in AD brain extract are progressively amplified.

Single mutations in tau modulate the populations of fibril conformers through seed selection.

Seeded conversion of tau monomers into fibrils is a central step in the progression of tau pathology in Alzheimer's disease and other neurodegenerative disorders. Self-assembly is mediated by the microtubule binding repeats in tau. There are either three or four repeats present depending on the protein isoform.

Electron spin-lattice relaxation mechanisms of rapidly-tumbling nitroxide radicals.

Electron spin relaxation times at 295 K were measured at frequencies between 250 MHz and 34 GHz for perdeuterated 2,2,6,6-tetramethyl-4-piperidone-1-oxyl (PDT) in five solvents with viscosities that result in tumbling correlation times, τR, between 4 and 50 ps and for three (14)N/(15)N pairs of nitroxides in water with τR between 9 and 19 ps. To test the impact of structure on relaxation three additional nitroxides with τR between 10 and 26 ps were studied. In this fast tumbling regime T2(-1)~T1(-1) at frequencies up to about 9 GHz.

Temperature Dependence of Electron Spin Relaxation of 2,2-diphenyl-1-picrylhydrazyl in Polystyrene.

The electron spin relaxation rates for the stable radical DPPH (2,2-diphenyl-1-picrylhydrazyl) doped into polystyrene were studied by inversion recovery and electron spin echo at X-band and Q-band between 20 and 295 K. At low concentration (340 μM, 0.01%) spin-lattice relaxation was dominated by the Raman process and a local mode.

Frequency dependence of electron spin relaxation times in aqueous solution for a nitronyl nitroxide radical and perdeuterated-tempone between 250 MHz and 34 GHz.

Electron spin relaxation times of perdeuterated tempone (PDT) 1 and of a nitronyl nitroxide (2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl) 2 in aqueous solution at room temperature were measured by 2-pulse electron spin echo (T(2)) or 3-pulse inversion recovery (T(1)) in the frequency range of 250 MHz to 34 GHz. At 9 GHz values of T(1) measured by long-pulse saturation recovery were in good agreement with values determined by inversion recovery. Below 9 GHz for 1 and below 1.

Conformational basis for asymmetric seeding barrier in filaments of three- and four-repeat tau.

Tau pathology in Alzheimer's disease is intimately linked to the deposition of proteinacious filaments, which akin to infectious prions, have been proposed to spread via seeded conversion. Here we use double electron-electron resonance (DEER) spectroscopy in combination with extensive computational analysis to show that filaments of three- (3R) and four-repeat (4R) tau are conformationally distinct. Distance measurements between spin labels in the third repeat, reveal tau amyloid filaments as ensembles of known β-strand-turn-β-strand U-turn motifs.

Comparison of Continuous Wave, Spin Echo, and Rapid Scan EPR of Irradiated Fused Quartz.

The E' defect in irradiated fused quartz has spin lattice relaxation times (T(1)) about 100 to 300 μs and spin-spin relaxation times (T(2)) up to about 200 μs, depending on the concentration of defects and other species in the sample. These long relaxation times make it difficult to record an unsaturated continuous wave (CW) electron paramagnetic resonance (EPR) signal that is free of passage effects. Signals measured at X-band (~9.

Relaxation times and line widths of isotopically-substituted nitroxides in aqueous solution at X-band.

Optimization of nitroxides as probes for EPR imaging requires detailed understanding of spectral properties. Spin lattice relaxation times, spin packet line widths, nuclear hyperfine splitting, and overall lineshapes were characterized for six low molecular weight nitroxides in dilute deoxygenated aqueous solution at X-band. The nitroxides included 6-member, unsaturated 5-member, or saturated 5-member rings, most of which were isotopically labeled.

Electron spin relaxation and heterogeneity of the 1:1 α,γ-bisdiphenylene-β-phenylallyl (BDPA)/benzene complex.

The electron spin-spin relaxation time (T(2)) for the 1:1 crystalline complex of α,γ-bisdiphenylene-β-phenylallyl (BDPA) with benzene was determined by continuous wave (CW) and rapid scan electron paramagnetic resonance (EPR). T(2) for individual BDPA particles found by simulation of rapid scan spectra or by simulation of the Lorentzian line shapes of CW spectra were in good agreement. The T(2) for small BDPA particles in air ranged from 80 to 160 ns, which corresponds to peak-to-peak Lorentzian linewidths of 0.