Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study

<p>Objective To investigate the association between visit-to-visit variability in blood pressure and cognitive function in old age (>70 years).</p> <p>Design Prospective cohort study.</p> <p>etting PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) study, a collaboration between centres in Ireland, Scotland, and the Netherlands.</p> <p>Participants 5461 participants, mean age 75.3 years, who were at risk of cardiovascular disease. Blood pressure was measured every three months during an average of 3.2 years. Visit-to-visit variability in blood pressure was defined as the standard deviation of blood pressure measurements between visits.</p> <p>Main outcome measures Four domains of cognitive function, testing selective attention, processing speed, and immediate and delayed memory. In a magnetic resonance imaging substudy of 553 participants, structural brain volumes, cerebral microbleeds, infarcts, and white matter hyperintensities were measured.</p> <p>Results Participants with higher visit-to-visit variability in systolic blood pressure had worse performance on all cognitive tests: attention (mean difference high versus low thirds) 3.08 seconds (95% confidence interval 0.85 to 5.31), processing speed −1.16 digits coded (95% confidence interval −1.69 to −0.63), immediate memory −0.27 pictures remembered (95% confidence interval −0.41 to −0.13), and delayed memory −0.30 pictures remembered (95% confidence interval −0.49 to −0.11). Furthermore, higher variability in both systolic and diastolic blood pressure was associated with lower hippocampal volume and cortical infarcts, and higher variability in diastolic blood pressure was associated with cerebral microbleeds (all P<0.05). All associations were adjusted for average blood pressure and cardiovascular risk factors.</p> Conclusion Higher visit-to-visit variability in blood pressure independent of average blood pressure was associated with impaired cognitive function in old age

An EBSD study of the deformation of service-aged 316 austenitic steel

Electron backscatter diffraction (EBSD) has been used to examine the plastic deformation of an ex-service 316 austenitic stainless steel at 297K and 823K (24 °C and 550 °C)at strain rates 3.5x10-3 to 4 x 10-7 s-1. The distribution of local misorientations was found to depend on the imposed plastic strain following a lognormal distribution at true strains 0.1. At 823 K (550 °C), the distribution of misorientations depended on the applied strain rate. The evolution of lattice misorientations with increasing plastic strain up to 0.23 was quantified using the metrics kernel average misorientation, average intragrain misorientation, and low angle misorientation fraction. For strain rate down to 10-5 s-1 all metrics were insensitive to deformation temperature, mode (tension vs. compression) and orientation of the measurement plane. The strain sensitivity of the different metrics was found to depend on the misorientation ranges considered in their calculation. A simple new metric, proportion of undeformed grains, is proposed for assessing strain in both aged and unaged material. Lattice misorientations build up with strain faster in aged steel than in un-aged material and most of the metrics were sensitive to the effects of thermal aging. Ignoring aging effects leads to significant overestimation of the strains around welds. The EBSD results were compared with nanohardness measurements and good agreement established between the two techniques of assessing plastic strain in aged 316 steel

Structure, dynamics and domain organization of the repeat protein Cin1 from the apple scab fungus

Venturia inaequalis is a hemi-biotrophic fungus that causes scab disease of apple. A recently-identified gene from this fungus, cin1 (cellophane-induced 1), is up-regulated over 1000-fold in planta and considerably on cellophane membranes, and encodes a cysteine-rich secreted protein of 523 residues with eight imperfect tandem repeats of ~ 60 amino acids. The Cin1 sequence has no homology to known proteins and appears to be genus-specific; however, Cin1 repeats and other repeat domains may be structurally similar. An NMR-derived structure of the first two repeat domains of Cin1 (Cin1-D1D2) and a low-resolution model of the full-length protein (Cin1-FL) using SAXS data were determined. The structure of Cin1-D1D2 reveals that each domain comprises a core helix–loop–helix (HLH) motif as part of a three-helix bundle, and is stabilized by two intra-domain disulfide bonds. Cin1-D1D2 adopts a unique protein fold as DALI and PDBeFOLD analysis identified no structural homology. A 15N backbone NMR dynamic analysis of Cin1-D1D2 showed that a short stretch of the inter-domain linker has large amplitude motions that give rise to reciprocal domain–domain mobility. This observation was supported by SAXS data modeling, where the scattering length density envelope remains thick at the domain–domain boundary, indicative of inter-domain dynamics. Cin1-FL SAXS data models a loosely-packed arrangement of domains, rather than the canonical parallel packing of adjacent HLH repeats observed in a-solenoid repeat proteins. Together, these data suggest that the repeat domains of Cin1 display a “beads-on-a-string” organization with inherent inter-domain flexibility that is likely to facilitate interactions with target ligands