Expression Levels of Three Genes in Patients Who Responded (Red) and Who Did Not Respond (Blue) to IFNβ

<p>(Source: [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020033#pmed-0020033-b21" target="_blank">21</a>])</p

Static Posturography and Falls According to Pyramidal, Sensory and Cerebellar Functional Systems in People with Multiple Sclerosis

<div><p>Balance impairment is common in people with multiple sclerosis (PwMS) and frequently impacts quality of life by decreasing mobility and increasing the risk of falling. However, there are only scarce data examining the contribution of specific neurological functional systems on balance measures in MS. Therefore, the primary aim of our study was to examine the differences in posturography parameters and fall incidence according to the pyramidal, cerebellar and sensory systems functional systems in PwMS. The study included 342 PwMS, 211 women and mean disease duration of 8.2 (S.D = 8.3) years. The study sample was divided into six groups according to the pyramidal, cerebellar and sensory functional system scores, derived from the Expanded Disability Status Scale (EDSS) data. Static postural control parameters were obtained from the Zebris FDM-T Treadmill (zebris^® Medical GmbH, Germany). Participants were defined as "fallers" and "non-fallers" based on their fall history. Our findings revealed a trend that PwMS affected solely in the pyramidal system, have reduced stability compared to patients with cerebellar and sensory dysfunctions. Moreover, the addition of sensory impairments to pyramidal dysfunction does not exacerbate postural control. The patients in the pure sensory group demonstrated increased stability compared to each of the three combined groups; pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups. As for fall status, the percentage of fallers in the pure pyramidal, cerebellar and sensory groups were 44.3%, 33.3% and 19.5%, respectively. As for the combined functional system groups, the percentage of fallers in the pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups were 59.7%, 40.7% and 65%, respectively. This study confirms that disorders in neurological functional systems generate different effects on postural control and incidence of falls in the MS population. From a clinical standpoint, the present information can benefit all those engaged in physical rehabilitation of PwMS.</p></div

Skills and competitive strategy in the UK fitness industry: SKOPE Research Paper No. 43, Autumn 2003

It is widely accepted that to produce high value products and services requires a well-trained and skilled workforce. This paper seeks to make a contribution to unpicking the relationship between business strategy and skills in the service sector by presenting research findings from the UK fitness industry. This sector has been fast growing and includes companies who compete on the basis of high quality, alongside those competing largely on cost. If the route to a high skills economy is to shift firms to higher quality products, then we would expect to find that the more up-market employers make use of a workforce with higher levels of skill. The research from the fitness industry questions this simple relationship, finding that there is no clear link between competitive strategy and skills. As quality is not necessarily the impetus for improving the skills of the workforce, the paper then briefly explores the possible skill implications of a number of other developments currently taking place in the industry

Posturography parameters and fall status of the study group according to the EDSS functional system groups (n = 342).

<p>Posturography parameters and fall status of the study group according to the EDSS functional system groups (n = 342).</p

Center of pressure path length (with eyes open) according to neurological functional system groups.

<p>Center of pressure path length (with eyes open) according to neurological functional system groups.</p

Definitions of the study groups.

<p>Definitions of the study groups.</p

Sway rate (with eyes open) according to neurological functional system groups.

<p>Sway rate (with eyes open) according to neurological functional system groups.</p

Suppressed RNA-Polymerase 1 Pathway Is Associated with Benign Multiple Sclerosis

<div><p>Benign multiple sclerosis (BMS) occurs in about 15% of patients with relapsing-remitting multiple sclerosis (RRMS) that over time do not develop significant neurological disability. The molecular events associated with BMS are not clearly understood. This study sought to underlie the biological mechanisms associated with BMS. Blood samples obtained from a cohort of 31 patients with BMS and 36 patients with RRMS were applied for gene expression microarray analysis using HG-U133A-2 array (Affymetrix). Data were analyzed by Partek and pathway reconstruction was performed by Ingenuity for the most informative genes (MIGs). We identified a differing gene expression signature of 406 MIGs between BMS patients, mean±SE age 44.5±1.5 years, 24 females, 7 males, EDSS 1.9±0.2, disease duration 17.0±1.3 years, and RRMS patients, age 40.3±1.8 years, 24 females, 12 males, EDSS 3.5±0.2, disease duration 10.9±1.4 years. The signature was enriched by genes related RNA polymerase I (POL-1) transcription, general inflammatory response and activation of cell death. The most significant under-expressed pathway operating in BMS was the POL-1 pathway (p = 4.0*10⁻⁵) known while suppressed to activate P53 dependent apoptosis and to suppress NFκB induced inflammation. In accordance, of the 30 P53 target genes presented within the BMS signature, 19 had expression direction consistent with P53 activation. The transcripts within the pathway include POL-1 transcription factor 3 (RRN3, p = 4.8*10⁻⁵), POL-1 polypeptide D (POLR1D, p = 2.2*10⁻⁴), leucine-rich PPR-motif containing protein (LRPPRC p = 2.3*10⁻⁵⁾, followed by suppression of the downstream family of ribosomal genes like RPL3, 6,13,22 and RPS6. In accordance POL-1 transcript and release factor PTRF that terminates POL-1 transcription, was over-expressed (p = 4.4*10⁻³). Verification of POL-1 pathway key genes was confirmed by qRT-PCR, and RRN3 silencing resulted in significant increase in the apoptosis level of PBMC sub-populations in RRMS patients. Our findings demonstrate that suppression of POL-1 pathway induce the low disease activity of BMS.</p> </div

Suppressed POL-1 pathway activity in BMS.

<p>A schematic model demonstrating the suppressed POL-1 pathway activity in BMS leading to activation of P53 dependent apoptosis. Over-expressed genes are depicted in red, down-expressed genes in green.</p

POL-1 pathway key genes verification by qRT-PCR.

<p>White dots represent BMS patients (N = 20), black dots represent RRMS patients (N = 15). Data are presented as relative quantification values using ΔCT method. The house keeping gene GAPDH expression levels were used as internal control for sample normalization. Low level of the POL-1 pathway key genes POLR1D (p = 0.001), RRN3 (p = 0.03) and LRPPRC (p = 0.03) is demonstrated in BMB patients as compared with RRMS patients.</p