Contribution of chronic disease to the burden of disability

Background

Population ageing is expected to lead to strong increases in the number of persons with one or more disabilities, which may result in substantial declines in the quality of life. To reduce the burden of disability and to prevent concomitant declines in the quality of life, one of the first steps is to establish which diseases contribute most to the burden. Therefore, this paper aims to determine the contribution of specific diseases to the prevalence of disability and to years lived with disability, and to assess whether large contributions are due to a high disease prevalence or a high disabling impact.

Methodology/Principal Findings

Data from the Dutch POLS-survey (Permanent Onderzoek Leefsituatie, 2001–2007) were analyzed. Using additive regression and accounting for co-morbidity, the disabling impact of selected chronic diseases was calculated, and the prevalence and years lived with ADL and mobility disabilities were partitioned into contributions of specific disease. Musculoskeletal and cardiovascular disease contributed most to the burden of disability, but chronic non-specific lung disease (males) and diabetes (females) also contributed much. Within the musculoskeletal and cardiovascular disease groups, back pain, peripheral vascular disease and stroke contributed particularly by their high disabling impact. Arthritis and heart disease were less disabling but contributed substantially because of their high prevalence. The disabling impact of diseases was particularly high among persons older than 80.

Conclusions/Significance

To reduce the burden of disability, the extent diseases such as back pain, peripheral vascular disease and stroke lead to disability should be reduced, particularly among the oldest old. But also moderately disabling diseases with a high prevalence, such as arthritis and heart disease, should be targeted.     

MRI pattern recognition in multiple sclerosis normal-appearing brain areas

Objective

Here, we use pattern-classification to investigate diagnostic information for multiple sclerosis (MS; relapsing­remitting type) in lesioned areas, areas of normal­appearing grey matter (NAGM), and normal-appearing white matter (NAWM) as measured by standard MR techniques.

Methods

A lesion mapping was carried out by an experienced neurologist for Turbo Inversion Recovery Magnitude (TIRM) images of individual subjects. Combining this mapping with templates from a neuroanatomic atlas, the TIRM images were segmented into three areas of homogenous tissue types (Lesions, NAGM, and NAWM) after spatial standardization. For each area, a linear Support Vector Machine algorithm was used in multiple local classification analyses to determine the diagnostic accuracy in separating MS patients from healthy controls based on voxel tissue intensity patterns extracted from small spherical subregions of these larger areas. To control for covariates, we also excluded group-specific biases in deformation fields as a potential source of information.

Results

Among regions containing lesions a posterior parietal WM area was maximally informative about the clinical status (96% accuracy, p<10⁻¹³). Cerebellar regions were maximally informative among NAGM areas (84% accuracy, p<10⁻⁷). A posterior brain region was maximally informative among NAWM areas (91% accuracy, p<10⁻¹⁰).

Interpretation

We identified regions indicating MS in lesioned, but also NAGM, and NAWM areas. This complements the current perception that standard MR techniques mainly capture macroscopic tissue variations due to focal lesion processes. Compared to current diagnostic guidelines for MS that define areas of diagnostic information with moderate spatial specificity, we identified hotspots of MS associated tissue alterations with high specificity defined on a millimeter scale.     

Pleomorphic configuration of the trimeric capsid proteins of Rice dwarf virus that allows formation of both the outer capsid and tubular crystals

In the double-shelled capsid of Phytoreovirus, the outer capsid attaches firmly to the 3-fold axes of the T = 1 core. It then forms a T = 13 lattice via lateral interactions among the P8 trimers (Wu et al., 2000, Virology 271, 18-25). Purified P8 molecules also assemble into hexagonal monolayers as well as tubular crystals. To explore the mechanisms of formation of these structures, the configurations of P8 trimers were compared and verified in particles of Rice dwarf virus and in tubular crystals (tubes) whose structure was determined by cryoelectron microscopy using helical reconstruction technique. Remarkable variations in intertrimer contacts were observed in the tubes and in the surface lattice of Rice dwarf virus capsid. Superposition of the atomic structure of P8 trimers in the structures analyzed by cryoelectron microscopy allowed us to identify groups of specific and stable interactions, some of which were preserved in the tubes and the quasi-equivalent T = 13 icosahedral lattice of the virion's shell. The flexible nature of the binding between P8 trimers, created via electrostatic interactions that hold radially inward, appears to allow the outer-capsid P8 trimers to envelop the ragged surface of the core, forming the double shell of an intact viral particle.     

The nature of culture: technological variation in chimpanzee predation on army ants revisited

Chimpanzee (Pan troglodytes) predation on army ants (Dorylus, subgenus Anomma) is an impressive example of skillful use of elementary technology, and it has been suggested to reflect cultural differences among chimpanzee communities. Alternatively, the observed geographic diversity in army-ant-eating may represent local behavioral responses of the chimpanzees to the anti-predator traits of the army ant species present at the different sites. We examined assemblages of available prey species, their behavior and morphology, consumption by chimpanzees, techniques employed, and tool lengths at 14 sites in eastern, central, and western Africa. Where army ants are eaten, tool length and concomitant technique are a function of prey type. Epigaeically foraging species with aggressive workers that inflict painful bites are harvested with longer tools and usually by the "pull-through" technique; species foraging in leaf-litter with less aggressive workers that inflict less painful bites are harvested with short tools and by the "direct-mouthing" technique. However, prey species characteristics do not explain several differences in army-ant-eating between Bossou (Guinea) and Ta? (Ivory Coast), where the same suite of prey species is available and is consumed. Moreover, the absence of army-ant-eating at five sites cannot be explained by the identity of available prey species, as all the species found at these sites are eaten elsewhere. We conclude that some of the observed variation in the predator-prey relationship of chimpanzees and army ants reflects environmental influences driven by the prey, while other variation is not linked to prey characteristics and may be solely sociocultural.     

A rationally designed oligopeptide shows significant conformational changes upon binding to sulphate ions

Oligopeptides that interact with oxoanions were developed by rational design methods. The substrate-binding site of the enzyme purine nucleoside phosphorylase served as a model for the design of the ionophores. The amino acids involved in the complexation of oxoanions were linked through flexible spacer residues. These spacers were chosen such that the relative orientation of the interacting amino acids was conserved. Several peptide sequences were preselected based on intermolecular H-bond frequencies. These frequencies were calculated from molecular dynamics trajectories of the corresponding peptide–anion complexes and used to score the binding properties of the peptides. The most promising peptides were prepared using solid phase peptide synthesis. Anion binding of the peptide ionophores was screened using circular dichroism (CD) and confirmed by NMR spectroscopy. CD measurements performed in methanol revealed a significant conformational change of a linear undecapeptide upon binding to sulphate ions. Two-dimensional-NMR experiments confirmed that a conformation with high helical content is formed in the presence of sulphate ions. These conformational changes induced by the anion stimulate the development of new transduction mechanisms in chemical sensors.     

Divalent cations cooperatively stabilize close membrane contacts in myelin

Intact nerve myelin compacts to a dehydrated structure of closely apposed membranes when exposed to isotonic solutions at least 10 mM in calcium or tetracaine. The repeat period of the membrane pair in the compacted structure measured by X-ray diffraction is about 126 Å in both central and peripheral mammalian nerve myelins whereas the normal periods are about 158 and 178 Å, respectively. The electron density profile of compacted myelin shows an asymmetric membrane unit with thickness similar to that of the symmetric bilayer of flocculated myelin lipids. The centrosymmetrically averaged myelin membrane profile is similar to that of the lipid bilayer except at the surface where residual protein is concentrated. Dispersions of extracted total myelin lipids flocculate under similar conditions to those causing myelin compaction, indicating that similar forces act in both processes. Compaction is always accompanied by lateral segregation of intramembrane particles out of the close-packed domains. Lateral displacement of intramembrane proteins from compacted domains can be driven by the attraction of the lipid surfaces for each other. Rates of compaction vary with compacting reagent, concentration, tissue, and temperature, and probably reflect the permeability of the tissue. Extensive compaction by calcium or tetracaine leads to disruption and vesiculation of the spirally wrapped myelin membranes.     

Chromosomal in situ suppression hybridization after Giemsa banding

Summary We report the successive application of classical Giemsa banding and chromosomal in situ suppression hybridization in clinical cytogenetics. The use of both techniques within one protocol requires an additional fixation of the chromosome preparations and an improved suppression of the labelled repetitive sequences. The combination of these two cytological techniques allows the high resolution mapping of translocated Y-chromosomal sequences in the chromosome set of an XX-male.     

Diffraction diagnosis of protein folding in gap junction connexons.

To diagnose the regular polypeptide conformation in gap junction membranes, the x-ray intensities diffracted from oriented specimens have been separated into a modulated component due to the coherently ordered portion of the channel-forming pairs of connexon hexamers and a diffuse component due to the disordered parts. The spherically averaged ordered protein diffraction, in the resolution range 15-4 A, was compared with intensity curves calculated from the Fourier transforms of proteins representative of the major tertiary structural classes. From this comparison the alpha-helical content of the ordered portion of the connexon was estimated to be approximately 60%. Calculation of cylindrically averaged patterns for oriented distributions of alpha-helical and beta-sheet proteins demonstrated that the ratio of the modulated diffracted intensity near 5 A spacing on the meridian and 10 A spacing on the equator observed from the gap junctions can be accounted for by alpha-helical segments inclined relative to the connexon axis. Model dimers of connexonlike hexamers were constructed from alpha-helix bundle proteins to correlate features in the calculated diffraction patterns with the model parameters. On the basis of these correlations, the ordered gap junction diffraction data indicate that alpha-helical segments centered at 38 A from the midplane of the gap have a mean radial location approximately 24 A from the hexamer axis, and an axial projected length of approximately 35 A. Thus, these alpha-helical segments traverse the hydrocarbon core of the lipid bilayer, as expected for the four hydrophobic sequences of the connexin molecule.