A novel MRI-biomarker candidate for Alzheimer's disease composed of regional brain volume and perfusion variables.

BACKGROUND: Earlier evidence indicates that regional cerebral volume (rVOL) and blood flow (rCBF) variables carry independent information on incipient and early Alzheimer's disease (AD) and combining these modalities may increase discriminant performance. We compared single variables and combinations regarding their power for optimizing diagnostic accuracy. METHODS: Twelve cognitively normal elderly controls (CN), 30 subjects with mild cognitive impairment (MCI) and 15 with mild AD were examined by structural and perfusion-weighted magnetic resonance imaging (MRI) in single sessions at 1.5 Tesla. rVOLs were measured by manual volumetry, and rCBFs were calculated with a ROI-based co-localization technique. RESULTS: Applying single MRI variables for the differentiation of AD versus CN, the area under curve (AUC) of receiver operating characteristic curves (ROCCs) was highest for rVOL variables (maximum of 0.972 for right amygdala). A composite marker selected and weighted by logistic regression containing left amygdalar rCBF, left hippocampal and right amygdalar rVOLs gave a diagnostic accuracy for AD versus CN of 100%. Internal cross-validation revealed a reliability of 88.9%. CONCLUSIONS: Whilst external revalidation is mandatory employing a naturalistic sample containing disease controls, our phase I/II findings demonstrate that deducing composite markers from multimodal MRI acquisitions can optimize diagnostic accuracy for AD.

Electronic coherence in delta-Pu: a dynamical mean-field theory study.

A combination of density functional theory and the dynamical mean-field theory (DMFT) is used to calculate the magnetic susceptibility, heat capacity, and the temperature dependence of the valence band photoemission spectra for delta-Pu. We predict that delta-Pu has a Pauli-like magnetic susceptibility near ambient temperature, as in experiment, indicating that electronic coherence causes the absence of local moments. Additionally, we show that volume expansion causes a crossover from incoherent to coherent electronic behavior at increasingly lower temperatures.

Emergent magnetic moments produced by self-damage in plutonium.

Plutonium possesses the most complicated phase diagram in the periodic table, driven by the complexities of overlapping 5f electron orbitals. Despite the importance of the 5f electrons in defining the structure and physical properties, there is no experimental evidence that these electrons localize to form magnetic moments in pure Pu. Instead, a large temperature-independent Pauli susceptibility indicates that they form narrow conduction bands. Radiation damage from the alpha-particle decay of Pu creates numerous defects in the crystal structure, which produce a significant temperature-dependent magnetic susceptibility, chi(T), in both alpha-Pu and delta-Pu (stabilized by 4.3 atomic percent Ga). This effect can be removed by thermal annealing above room temperature. By contrast, below 35 K the radiation damage is frozen in place, permitting the evolution in chi(T) with increasing damage to be studied systematically. This result leads to a two-component model consisting of a Curie-Weiss term and a short-ranged interaction term consistent with disorder-induced local moment models. Thus, it is shown that self-damage creates localized magnetic moments in previously nonmagnetic plutonium.

Field-dependent ordered phases and Kondo phenomena in the filled skutterudite compound PrOs4As12.

Electrical resistivity, specific heat, and magnetization measurements to temperatures as low as 80 mK and magnetic fields up to 16 T were made on the filled skutterudite compound PrOs4As12. The measurements reveal the presence of two ordered phases at temperatures below approximately 2.3 K and in fields below approximately 3 T. Neutron-scattering experiments in zero field establish an antiferromagnetic ground state < 2.28 K. In the antiferromagnetically ordered state, the electronic-specific heat coefficient gamma approximately 1 J/mol x K2 below 1.6 K and 0 < or = H < or = 1.25 T. The temperature and magnetic-field dependence of the electrical resistivity and specific heat in the paramagnetic state are consistent with single-ion Kondo behavior with a low Kondo temperature on the order of 1 K. The electronic-specific heat in the paramagnetic state can be described by the resonance-level model with a large zero-temperature electronic-specific heat coefficient that decreases with increasing magnetic field from approximately 1 J/mol x K2 at 3 T to approximately 0.2 J/mol x K2 at 16 T.

Changes of the organotypic retinal organization in Borna virus-infected Lewis rats.

Retinae of Borna disease virus (BDV)-infected Lewis rats were investigated with emphasis on long-term changes in organotypic tissue organization and glia-neuron relationship. Virus inoculation was attained via intracerebral BDV injection. Following survival times ranging between two and eight months, the retinal thickness was reduced up to one third of that of controls. Photoreceptor segments were completely extinguished and the number of neurons was dramatically reduced. The typical laminar organization of the retina was largely dissolved. Electron microscopy revealed severe spongy degeneration. Large numbers of activated microglia and macrophages were found, both cell types performing very active phagocytosis. The microglial cells expressed an extraordinary phenotype as characterized by large numbers of processes, with some of them penetrating the endfeet of Müller cells and others establishing highly complex interdigitations with vacuolized swellings and endings of neuronal processes. Müller cells were not reduced in number but displayed clear indications of gliosis such as alterations in the immunoreactivity for filament proteins and glutamine synthetase, significantly thickened stem processes, and an altered pattern of K(+) currents in patch-clamp recordings. These findings demonstrate for the first time long-term neuron-glia interactions in the retina of BDV-infected rats. Moreover, the data contribute to our knowledge on structural and functional alterations accompanying persisting virus infection in the central nervous system.

Phosphodiesterase inhibition and Ca2+ sensitization.

Inhibitors of phosphodiesterase type III (PDE III) enhance cardiac contractile force by elevating the intracellular calcium concentration [Ca2+]i by impairing cAMP degradation thus increasing cAMP levels. The drugs are more effective in healthy than in failing hearts since basal cAMP production is diminished in the latter. However, long term treatment with PDE-III inhibitors does not appear to be beneficial due to increased risk of potentially lethal arrhythmias caused by augmentation of [Ca2+]i[1). This risk should be absent in Ca2+ sensitizers. Recently, thiadiazinone derivatives have been synthetized in which the potency for Ca2+ sensitization is many-fold larger than the potency for PDE-III inhibition. The Ca(2+)-sensitizing action resides in the [+]-enantiomers, while the [-]-enantiomers show weak PDE-III inhibition. In the enantiomer pair [+]-EMD 60263 and [-]-EMD 60264, only the former concentration-dependently increased force of contraction in isolated cardiac preparations and myocytes. In the Langendorff-perfused guinea-pig heart, force was reversibly increased, whereas [-]-EMD 60264 even produced a negative inotropic response despite of its PDE inhibitory activity. Heart rate, however, was reduced by both enantiomers. Perfusion pressure remained unaffected. The effects were fully reversible upon wash-out of the enantiomers. [+]-EMD 60263 also enhanced cell shortening of human myocytes from both normal and failing hearts. In contrast to the opposite effects on contractility, both enantiomers prolong the action potential duration by blocking the rapidly activating component of the delayed rectifier K+ current. Thus they also possess class III antiarrhythmic activity. The therapeutic potential of these agents has yet to be assessed in clinical studies.