Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?

Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities

Differences in Walking Pattern during 6-Min Walk Test between Patients with COPD and Healthy Subjects

BACKGROUND: To date, detailed analyses of walking patterns using accelerometers during the 6-min walk test (6MWT) have not been performed in patients with chronic obstructive pulmonary disease (COPD). Therefore, it remains unclear whether and to what extent COPD patients have an altered walking pattern during the 6MWT compared to healthy elderly subjects. METHODOLOGY/PRINCIPAL FINDINGS: 79 COPD patients and 24 healthy elderly subjects performed the 6MWT wearing an accelerometer attached to the trunk. The accelerometer features (walking intensity, cadence, and walking variability) and subject characteristics were assessed and compared between groups. Moreover, associations were sought with 6-min walk distance (6MWD) using multiple ordinary least squares (OLS) regression models. COPD patients walked with a significantly lower walking intensity, lower cadence and increased walking variability compared to healthy subjects. Walking intensity and height were the only two significant determinants of 6MWD in healthy subjects, explaining 85% of the variance in 6MWD. In COPD patients also age, cadence, walking variability measures and their interactions were included were significant determinants of 6MWD (total variance in 6MWD explained: 88%). CONCLUSIONS/SIGNIFICANCE: COPD patients have an altered walking pattern during 6MWT compared to healthy subjects. These differences in walking pattern partially explain the lower 6MWD in patients with COPD

Experimental Inoculation of Juvenile Rhesus Macaques with Primate Enteric Caliciviruses

Tissue culture-adapted Tulane virus (TV), a GI.1 rhesus enteric calicivirus (ReCV), and a mixture of GII.2 and GII.4 human norovirus (NoV)-containing stool sample were used to intrastomacheally inoculate juvenile rhesus macaques (Macaca mulatta) in order to evaluate infection caused by these viruses. METHODOLOGY & FINDINGS: Two of the three TV-inoculated macaques developed diarrhea, fever, virus-shedding in stools, inflammation of duodenum and 16-fold increase of TV-neutralizing (VN) serum antibodies but no vomiting or viremia. No VN-antibody responses could be detected against a GI.2 ReCV strain FT285, suggesting that TV and FT285 represent different ReCV serotypes. Both NoV-inoculated macaques remained asymptomatic but with demonstrable virus shedding in one animal. Examination of duodenum biopsies of the TV-inoculated macaques showed lymphocytic infiltration of the lamina propria and villous blunting. TV antigen-positive (TV+) cells were detected in the lamina propria. In most of the TV+ cells TV co-localized perinuclearly with calnexin--an endoplasmic reticulum protein. A few CD20+TV+ double-positive B cells were also identified in duodenum. To corroborate the authenticity of CD20+TV+ B cells, in vitro cultures of peripheral blood mononuclear cells (PBMCs) from healthy macaques were inoculated with TV. Multicolor flow cytometry confirmed the presence of TV antigen-containing B cells of predominantly CD20+HLA-DR+ phenotype. A 2-log increase of viral RNA by 6 days post inoculation (p<0.05) suggested active TV replication in cultured lymphocytes.Taken together, our results show that ReCVs represent an alternative cell culture and animal model to study enteric calicivirus replication, pathogenesis and immunity

Photochemistry of Transition Metal Complexes Induced by Outer-Sphere Charge Transfer Excitation

The intermolecular (outer sphere, OS) interaction of a reducing and an oxidizing metal complex generates a new optical transition involving charge transfer (CT) from the electron donor to the acceptor. OS CT transitions are classified according to the redox site (metal or ligand). Generally, the interaction between donor and acceptor is facilitated by ion pairs consisting of an oxidizing complex cation and a reducing complex anion. There are also ion pairs which are composed of a metal complex and an organic counter ion as electron donor or acceptor. In addition, the review includes examples of OS CT interaction which do not involve ion pairs at all. — A short introduction into the theory is followed by the discussion of the spectroscopy of OS CT of transition metal complexes. Finally, photoreactions induced by OS CT transitions are reviewed. The optical transfer is frequently followed by a rapid back electron transfer which regenerates the starting complexes. In many cases the primary products are kinetically labile and substitution reactions compete successfully with back electron transfer. As a result stable redox products may be formed. As an alternative, the substitution can be followed by back electron transfer. Product formation appears then as a substitution of the starting complexes. The various possibilities are illustrated by appropriate examples

Navigating Complex Buildings: Cognition, Neuroscience and Architectural Design

In recent years, interest has been sparked by the overlap between architecture and neuroscience(Eberhard, 2009; 2007; Mallgrave 2010). The majority of this research appears to focus on either one of two areas: how building users experience architecture and how this may affect them emotionally or, alternatively, on the creative process of architectural design: how architects design buildings and what happens at the neurological level, during the creative act. In Eberhard’s 2009 article in Neuron, he describes the five broad areas that are studied in neuroscience as being: 1)sensation and perception, 2) learning and memory, 3) decision making, emotion and affect, and 4)movement or “how do we interact with our environment and navigate through it?” (Ibid. p.755). It can be seen that the majority of research hitherto undertaken on the boundaries between neuroscience and architecture fit into the first and fourth of these areas. This paper, in contrary to these other approaches, firmly concentrates on this latter area of study. To some extents, we are also addressing the third area, namely decision making, but only insofar as it is part of the act of wayfinding and navigation