Reliability and feasibility of gait initiation centre-of-pressure excursions using a Wii® Balance Board in older adults at risk of falling.

BACKGROUND: Impairments in dynamic balance have a detrimental effect in older adults at risk of falls (OARF). Gait initiation (GI) is a challenging transitional movement. Centre of pressure (COP) excursions using force plates have been used to measure GI performance. The Nintendo Wii Balance Board (WBB) offers an alternative to a standard force plate for the measurement of CoP excursion. AIMS: To determine the reliability of COP excursions using the WBB, and its feasibility within a 4-week strength and balance intervention (SBI) treating OARF. METHODS: Ten OARF subjects attending SBI and ten young healthy adults, each performed three GI trials after 10 s of quiet stance from a standardised foot position (shoulder width) before walking forward 3 m to pick up an object. Averaged COP mediolateral (ML) and anteroposterior (AP) excursions (distance) and path-length time (GI-onset to first toe-off) were analysed. RESULTS: WBB ML (0.866) and AP COP excursion (0.895) reliability (ICC3,1) was excellent, and COP path-length reliability was fair (0.517). Compared to OARF, healthy subjects presented with larger COP excursion in both directions and shorter COP path length. OARF subjects meaningfully improved their timed-up-and-go and ML COP excursion between weeks 1-4, while AP COP excursions, path length, and confidence-in-balance remained stable. DISCUSSION: COP path length and excursion directions probably measure different GI postural control attributes. Limitations in WBB accuracy and precision in transition tasks needs to be established before it can be used clinically to measure postural aspects of GI viably. CONCLUSIONS: The WBB could provide valuable clinical evaluation of balance function in OARF.

Author Correction: Reliability and feasibility of gait initiation centre-of-pressure excursions using a Wii® Balance Board in older adults at risk of falling.

In the original publication, the article title was incorrectly published as 'Reliability and feasibility of gait initiation centre-of-pressure excursions using a Wii® Balance Board in older adults at risk of failing'. The correct title should read as 'Reliability and feasibility of gait initiation centre-of-pressure excursions using a Wii® Balance Board in older adults at risk of falling'.

An ovine transgenic Huntington's disease model.

Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disorder caused by an expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene [Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell, 72, 971-983]. Despite identification of the gene in 1993, the underlying life-long disease process and effective treatments to prevent or delay it remain elusive. In an effort to fast-track treatment strategies for HD into clinical trials, we have developed a new large-animal HD transgenic ovine model. Sheep, Ovis aries L., were selected because the developmental pattern of the ovine basal ganglia and cortex (the regions primarily affected in HD) is similar to the analogous regions of the human brain. Microinjection of a full-length human HTT cDNA containing 73 polyglutamine repeats under the control of the human promotor resulted in six transgenic founders varying in copy number of the transgene. Analysis of offspring (at 1 and 7 months of age) from one of the founders showed robust expression of the full-length human HTT protein in both CNS and non-CNS tissue. Further, preliminary immunohistochemical analysis demonstrated the organization of the caudate nucleus and putamen and revealed decreased expression of medium size spiny neuron marker DARPP-32 at 7 months of age. It is anticipated that this novel transgenic animal will represent a practical model for drug/clinical trials and surgical interventions especially aimed at delaying or preventing HD initiation. New sequence accession number for ovine HTT mRNA: FJ457100.

Identification and optimisation of a novel series of pyrimidine based cyclooxygenase-2 (COX-2) inhibitors. Utilisation of a biotransformation approach.

Many years of work have been invested in the identification of potent and selective COX-2 inhibitors for the treatment of chronic inflammatory pain. One issue faced by workers is the balance between the lipophilicity required for potent enzyme inhibition and the physical properties necessary for drug absorption and distribution in vivo. Frequently approaches to reduce lipophilicity through introduction of polar functionality is hampered by highly challenging chemistry to prepare key molecules. We have complemented traditional synthetic chemistry with a biotransformations approach which efficiently provided access to an array of key target molecules.

Nucleus pulposus cellular longevity by telomerase gene therapy.

STUDY DESIGN: Nonviral transfection of nucleus pulposus cells with a telomerase expression construct to assess the effects on cellular lifespan, function, karyotypic stability, and transformation properties. OBJECTIVES: To investigate whether telomerase gene therapy can extend the cellular lifespan while retaining functionality of nucleus pulposus cells in a safe manner. SUMMARY OF BACKGROUND DATA: Degeneration of the intervertebral disc is an age-related condition in which cells responsible for the maintenance and health of the disc deteriorate with age. Telomerase can extend the cellular lifespan and function of other musculoskeletal tissues, such as the heart, bones, and connective tissues. Therefore, extension of the cellular lifespan and matrix production of intervertebral disc cells may have the potential to delay the degeneration process. METHODS: Ovine nucleus pulposus cells were lipofectamine transfected in vitro with a human telomerase reverse transcriptase (hTERT) expression construct. Cellular lifespan and matrix transcript levels were determined by cumulative population doublings and real-time RT-PCR, respectively. G1-cell cycle checkpoint, p53 functionality, growth of transfected cells in anchorage-independent or serum starvation conditions, and karyotypic analysis were performed. RESULTS: Transfection was achieved successfully with 340% +/- 7% (mean +/- SD) relative telomerase activity in hTERT-transfected cells. hTERT transfection enabled a 50% extension in mean cellular lifespan and prolonged matrix production of collagen 1 and 2 for more than 282 days. Karyotypic instability was detected but G1-cell cycle checkpoint and p53 was functionally comparable to parental cells with no growth in serum starvation or anchorage-independent conditions. CONCLUSIONS: Telomerase can extend the cellular lifespan of nucleus pulposus cells and prolong the production of extracellular matrix. Safety is still unresolved, as karyotypic instability was detected but no loss of contact inhibition, mitogen dependency, or G1-cell cycle checkpoint control was evident.

Aneuploidy detection in single cells using DNA array-based comparative genomic hybridization.

The use of metaphase comparative genomic hybridization (CGH) to screen all human chromosomes for aneuploidy in preimplantation embryos is hindered by the time required to perform the analysis. We report in this paper a novel approach to manufacture a DNA microarray for CGH for the detection of aneuploidy in single cells. We spotted human chromosome-specific libraries on glass slides that were depleted of repetitive sequences and tested our array CGH method in 14 experiments using either single male and/or single female lymphocytes. For the autosomes, the mean normalized ratios were all close to the expected ratio of 1.0 with overall 300/308 (97%) of the normalized ratios falling within the range 0.75 to 1.25. It was possible to deduce the correct copy number of the X chromosome in 13/14 (92.9%) separate array CGH experiments but the Y chromosome in only 4/14 (29%). We tested our microarray CGH method on a single fibroblast from each of three cell lines containing a specific chromosome aneuploidy (trisomy 13, 15 or 18) and in each case our microarray analysis was able to obtain a diagnosis based on the fact that the aneuploid chromosome gave the highest ratio (1.32, 1.27 and 1.27 respectively) with the ratios of all other chromosomes falling within the range 0.75-1.25. Requiring just 30 h, our method may be more suitable for PGD aneuploidy screening than metaphase CGH.

Characterizing and mapping porcine endogenous retroviruses in Westran pigs.

Since porcine endogenous retroviruses (PERVs) can infect cultured human cells, they are a potential hazard to xenotransplantation. For this reason, endogenous retroviruses from the Westran (Westmead Hospital transplantation) inbred line of pigs were analyzed by using consensus primers for the type A and type B viruses to amplify 1.8-kb envelope gene fragments. After preliminary analysis with restriction enzymes KpnI and MboI, 31 clones were sequenced. Between types A and B, five recombinant clones were identified. Fifty-five percent of clones (17 of 31) had premature stop codons within the envelope protein-encoding region. Endogenous retroviruses in Westran pigs were physically mapped by fluorescence in situ hybridization (FISH) using PERV-A and PERV-B envelope clones as probes to identify at least 32 integration sites (19 PERV-A sites and 13 PERV-B sites). The chromosomal sites of integration in the Westran strain are quite different from those in the European Large White pig. The recombinant clones suggest that defective PERVs could become infective through recombination and further that PERVs might recombine with human endogenous retroviruses in xenotransplants.