Antiphospholipid-related chorea

Chorea can be associated with autoimmune diseases such as antiphospholipid syndrome and has been associated with the isolated presence of antiphospholipid antibodies (aPL). Chorea is a rare neurological manifestation of antiphospholipid syndrome. The pathophysiological mechanisms underlying aPL-related chorea are still debated. One postulated mechanism is aPL or other autoantibody binding to brain-blood vessel endothelium, resulting in endothelial dysfunction secondary to a proinflammatory cascade, with sequalae of inflammation and local microthrombosis. Another postulated mechanism considers immune-mediated attack (aPL or antibasal ganglia antibodies) against specific basal ganglia epitopes. Here, we report a patient with isolated aPL-related chorea that followed a relapsing-remitting course. We highlight the role of brain metabolic imaging with fluorodeoxy glucose positron-emission tomography in the diagnostic workup of chorea and the challenges in the practical management of aPL-related chorea with symptomatic treatments

Nanodroplet quantification: pushing the detection limits of micro x-ray fluorescence

In this study, detection limits for a variety of elements were determined on an EDAX Eagle I1 MXRF system equipped with a polycapillary and a Rh X-ray source. Both mass, volume, and spot diameter detection limits were established using dried spot technology, where various volumes and/or masses of different elements were deposited on different substrates, dried, and quantitatively analyzed by MXRF. Preliminary results have shown that sub-nanogram levels of material can be detected in less than 200 pm diameter spot sizes deposited on thin polymer films. Specifically, detection limits were found for a given element as a function of mass deposited for a given spot volume, and volume deposited for a given mass. The effect of the presence of multiple elements in a droplet on the detection limit was also investigated. For example, the detection limit for copper was determined when it was deposited as a single Cu solution and in various multielement mixtures containing from 2 up to 10 different elements. To determine how the substrate affects the detection limit of different species, elemental dried spots were analyzed on different polymer films, including polypropylene and AP 1 . Comparisons were also made to elements deposited on different spherical, resin substrates such as polystyrene beads

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

A single administration of tetanus toxoid in biodegradable microspheres elicits T cell and antibody responses similar or superior to those obtained with aluminum hydroxide

The use of biodegradable polymer microspheres as a single dose vaccine delivery system was investigated by using tetanus toxoid (TT). In order to compare the immunogenicity of TT-microspheres (TT-MS) with aluminum hydroxide (alum)-based TT, BALB/c mice were immunized with TT in different formulations including individual or mixtures of MS and TT-alum. All TT-MS formulations elicited high proliferative and antibody responses comparable to those obtained with TT-alum formulation. Antibody levels remained elevated over a long period of time. Certain individual MS preparations elicited lower antibody titers than the MS mixtures. More importantly, the proliferative and antibody responses induced by a single injection of three TT-MS mixtures with different particle sizes and degradation rates were similar to those obtained with three injections of TT-alum. In addition, TT-MS induce similar isotypesubclass antibodies to those TT-alum induced. These results raise the possibility to obtain optimal and long-lasting immune responses by single administration of the three TT-MS mixture formulations alone

Rapid production of protein-loaded biodegradable microparticles using surface acoustic waves

We present a straightforward and rapid surface acoustic wave (SAW) atomization-based technique for encapsulating proteins into 10 μm order particles composed of a biodegradable polymeric excipient, using bovine serum albumin (BSA) as an exemplar. Scans obtained from confocal microscopy provide qualitative proof of encapsulation and show the fluorescent conjugated protein to be distributed in a relatively uniform manner within the polymer shell. An ELISA assay of the collected particles demonstrates that the BSA survives the atomization, particle formation, and collection process with a yield of approximately 55%. The SAW atomization universally gave particles with a textured morphology, and increasing the frequency and polymer concentration generally gave smaller particles (to 3 μm average) with reduced porosity