bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of health care services and satisfaction with care in people with multiple sclerosis in Stockholm County: A population-based study
Authors: Gottberg K , Einarsson U , Ytterberg C , Fredrikson S , von Koch L , Holmqvist L Widén 
Published: June 2008

Objectives To explore and to describe the use of health, social, and informal care services and satisfaction with care in a population-based sample of people with multiple sclerosis (PwMS) in Stockholm County. Methods The sample consisted of 166 PwMS who participated in the Stockholm MS study. Data on the use of health care services and satisfaction with care and services in PwMS were collected through a computerized register and through home visits to PwMS using structured, face-to-face interviews. Results During the study period of 3 years, 92% had been in contact with out-patient departments of Neurology, and 76% had been in contact with other hospital out-patient departments. Some 83% were in contact with primary care, and primary care contacts constituted 54% of all out-patient care. One third of the PwMS (32%) used home help service (17%) or personal assistants (19%), and higher proportions used informal help from partners (37%). PwMS were in general satisfied with the care received, with the exception of access to coordinated rehabilitation and psychosocial counseling. The proportion of PwMS using inpatient, outpatient, and social/informal (excluding neurological) care increased with the degree of disease severity. Conclusions The great majority of PwMS use hospital specialist care and primary care in parallel, with many departments and services involved. Better accessibility of certain services, for example, psychosocial counseling and rehabilitation, and other improvements, for example efforts to provide coordinated and comprehensive care for PwMS may increase satisfaction with care and should be the focus of scientific evaluation.
Constraint-Induced Movement therapy can improve hemiparetic progressive multiple sclerosis. Preliminary findings
Authors: Mark VW , Taub E , Bashir K , Uswatte G , Delgado A , Bowman MH , Bryson CC , McKay S , Cutter GR 
Published: June 2008

Objective To evaluate whether Constraint-Induced Movement therapy (CI therapy) may benefit chronic upper extremity hemiparesis in progressive multiple sclerosis (MS). Methods Five patients with progressive MS, who had chronic upper extremity hemiparesis and evidence for learned non-use of the paretic limb in the life situation, underwent 30 hours of repetitive task training and shaping for the paretic limb over 2–10 consecutive weeks, along with physical restraint of the less-affected arm and a “transfer package” of behavioral techniques to reinforce treatment adherence. Results The patients showed significantly improved spontaneous, real-world limb use at post-treatment and 4 weeks post-treatment, along with improved fatigue ratings and maximal movement ability displayed in a laboratory motor test. Conclusions The findings suggest for the first time that slowly progressive MS may benefit from CI therapy. Further studies are needed to determine the retention of treatment responses.
Factors in the rising prevalence of multiple sclerosis in the north-east of Ireland
Authors: Gray OM , McDonnell GV , Hawkins SA 
Published: June 2008

Background Northern Ireland is recognized as an area of high risk for multiple sclerosis. The original study of Allison and Millar in 1951 found a prevalence of 51/100,000 and mean annual incidence of 2.74/100,000/year. Subsequent studies in 1961, 1986, and 1996 suggested rising prevalence – 80, 138, and 168.2/100,000, respectively. Methods In 2004, we surveyed the North-East of Northern Ireland (population 160,446, area 2030 km2) using multiple sources of case ascertainment, all satisfying the Poser criteria for definite or probable multiple sclerosis (MS) or the McDonald criteria. Results From a provisional list of 469 cases, 370 (123 males, 247 females) were identified. The prevalence was 230.6 per 100,000 (95% CI 207.0–255.4) with significantly higher prevalence in females (300.8/100,000) than males (157.0/100,000). Direct standardization to the 1961 Northern Ireland population reduced the overall prevalence rate to 200.5/100,000 (95% CI 193.2–208.0), in females to 270.2/100,000 (95% CI 258.8–282.4) and in males to 131.1/100,000 (95% CI 122.8–139.9). In 1996, incidence had risen to 9.3/100,000/year (14 cases in population of 151,000) with a higher incidence in females (10.3/100,000/year) than males (8.3/100,000/year). Conclusions Northern Ireland continues to have a rising prevalence of MS. The increase in incidence suggests a true increase in the disease.
The effect of functional electrical stimulation on the physiological cost of gait in people with multiple sclerosis
Authors: Paul L , Rafferty D , Young S , Miller L , Mattison P , McFadyen A 
Published: June 2008

Objective Functional electrical stimulation (FES) is used clinically in the management of drop foot in people suffering from neurological conditions. The aim of the study was to investigate the effects of FES, in terms of speed and physiological cost of gait, in people with multiple sclerosis (pwMS). Methods Twelve pwMS and 12 healthy matched controls walked at their own preferred walking speed (PWS) for 5 min around a 10 m elliptical course. Subjects with MS completed the protocol with and without using their FES. In addition, control subjects completed the protocol twice more walking at the same PWS of the pwMS to which they were matched. Results Wearing FES lead to a significant improvement in walking speed (0.49 ms−1 and 0.43 ms−1 with and without their FES respectively; P < 0.001) and a significant reduction in the physiological cost of gait (0.41 mL min−1 kg−1 m−1 and 0.46 mL min−1 kg−1 m−1 with and without FES respectively; P = 0.017) in pwMS. The speed of walking, oxygen uptake, and physiological cost were significantly different between pwMS and controls both at preferred and matched speeds. Although pwMS exhibit a higher physiological cost of walking, FES offers an orthotic benefit to pwMS and should be considered as a possible treatment option.
Spastic paretic hemifacial contracture in multiple sclerosis: a neglected clinical and EMG entity
Authors: Koutsis G , Kokotis P , Sarrigiannis P , Anagnostouli M , Sfagos C , Karandreas N 
Published: June 2008

Background Spastic paretic hemifacial contracture (SPHC) is an uncommon condition, originally described as a sign of brainstem neoplasia, characterized by sustained unilateral contraction of the facial muscles associated with mild ipsilateral facial paresis. SPHC has only rarely been reported in the context of multiple sclerosis (MS). To further study and assess the frequency of SPHC in patients with MS. Methods We screened clinically 500 consecutive patients with MS for the presence of SPHC and further studied electrophysiologically any cases identified. Results We identified two patients who developed the condition during the course of an MS relapse. The estimated frequency of the condition was 0.4%. Both patients had relapsing–remitting MS. SPHC was characterized on Electromyography (EMG) by continuous resting activity of irregularly firing motor unit potentials, associated with impaired recruitment of motor units on voluntary contraction. Myokymic discharges were not present. Blink reflex studies were partly consistent with midpontine lesions in the vicinity of the facial nucleus ipsilateral to SPHC. MRI showed lesions in the ipsilateral dorsolateral midpontine tegmentum. Conclusions SPHC constitutes a rare but distinct clinical and EMG entity in patients with MS.
Repeated assessment of neuropsychological deficits in multiple sclerosis using the Symbol Digit Modalities Test and the MS Neuropsychological Screening Questionnaire
Authors: Benedict RHB , Duquin JA , Jurgensen S , Rudick RA , Feitcher J , Munschauer FE , Panzara MA , Weinstock-Guttman B 
Published: June 2008

Background Brief cognitive performance tests and self-report measures of neuropsychological symptoms have been proposed for screening purposes in multiple sclerosis (MS) clinics. To better understand the reliability of screening methods, two tests, the Symbol Digit Modalities Test (SDMT) and the MS Neuropsychological Screening Questionnaire (MSNQ), were administered to 76 patients with MS and 25 healthy controls, matched on demographic characteristics. Methods Tests were administered at monthly intervals, over 6 months. In addition, the Beck Depression Inventory Fast Screen for medical patients (BDIFS) was administered to monitor for changes in depression. Our objectives were to determine the reliability of these measures and the relative contribution of cognitive impairment and depression in predicting self-report MSNQ scores. Results Results showed that both the SDMT and MSNQ have good to excellent reproducibility over repeated testing. In MS, there are minimal practice effects over successive tests, in the order of 0.2 SD for SDMT and minimal change in the MSNQ. Regression analyses modeled to predict MSNQ based on SDMT and BDIFS showed significant contribution for both, but with the majority of variance being accounted for depression. Conclusions We conclude that these brief screening tests provide some independent information about the mental status of patients with MS and are reliable, even when used in monthly, successive examinations.
EBNA-1 reactivity and HLA DRB1*1501 as statistically independent risk factors for multiple sclerosis: a case-control study
Authors: Sundström P , Nyström L , Jidell E , Hallmans G 
Published: June 2008

Objectives and methods The interaction between the two best documented risk factors (human leukocyte antigen [HLA] class II [DRB1*1501 positivity] and Epstein-Barr virus [elevated Epstein-Barr nuclear antigen 1 (EBNA-1) antibody reactivity]) for multiple sclerosis (MS) was studied in a case-control study of biobank samples from 109 MS cases and 212 matched referents. Results Multivariate logistic regression analysis showed that both were statistically significant in both sexes. HLA DRB1*1501-positive referents had higher EBNA-1 reactivity than HLA-negative referents. Less EBNA-1 reactivity was required to increase the MS risk in HLA DRB1*1501-positives than in HLA-negatives. Conclusion We suggest that HLA DRB1*1501-positive individuals have an increased vulnerability to EBV-induced autoimmunity.
Two opposite signaling outputs are driven by the KIR2DL1 receptor in human CD4+ T cells
Authors: Fourmentraux-Neves Emmanuelle , Jalil Abdelali , Da Rocha Sylvie , Pichon Christophe , Chouaib Salem , Bismuth Georges , Caignard Anne 
Published: June 2008

AbstractInhibitory killer Ig–like receptors (KIR), expressed by human natural killer cells and effector memory CD8+ T-cell subsets, bind HLA-C molecules and suppress cell activation through recruitment of the Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1). To further analyze the still largely unclear role of inhibitory KIR receptors on CD4+ T cells, KIR2DL1 transfectants were obtained from a CD4+ T-cell line and primary cells. Transfection of CD4+ T cells with KIR2DL1 dramatically increased the T-cell receptor (TCR)–induced production of interleukin-2 independently of ligand binding but inhibited TCR-induced activation after ligation. KIR-mediated costimulation of TCR activation involves intact KIR2DL1-ITIM phosphorylation, SHP-2 recruitment, and PKC-θ phosphorylation. Synapses leading to activation were characterized by an increase in the recruitment of p-Tyr, SHP-2, and p-PKC-θ, but not of SHP-1. Interaction of KIR2DL1 with its ligand led to a strong synaptic accumulation of KIR2DL1 and the recruitment of SHP-1/2, inhibiting TCR-induced interleukin-2 production. KIR2DL1 may induce 2 opposite signaling outputs in CD4+ T cells, depending on whether the KIR receptor is bound to its ligand. These data highlight unexpected aspects of the regulation of T cells by KIR2DL1 receptors, the therapeutic manipulation of which is currently being evaluated.
TAT-mediated intracellular delivery of NPM-derived peptide induces apoptosis in leukemic cells and suppresses leukemogenesis in mice
Authors: Zhou Yun , Du Wei , Koretsky Tara , Bagby Grover C. , Pang Qishen 
Published: June 2008

AbstractNucleophosmin (NPM) is frequently overexpressed in leukemias and other tumors. NPM has been reported to suppress oncogene-induced senescence and apoptosis and may represent a therapeutic target for cancer. We fused a NPM-derived peptide to the HIV-TAT (TAT-NPMΔC) and found that the fusion peptide inhibited proliferation and induced apoptotic death of primary fibroblasts and preleukemic stem cells. TAT-NPMΔC down-regulated several NF-κB–controlled survival and inflammatory proteins and suppressed NF-κB–driven reporter gene activities. Using an inflammation-associated leukemia model, we demonstrate that TAT-NPMΔC induced proliferative suppression and apoptosis of preleukemic stem cells and significantly delayed leukemic development in mice. Mechanistically, TAT-NPMΔC associated with wild-type NPM proteins and formed complexes with endogenous NPM and p65 at promoters of several antiapoptotic and inflammatory genes and abrogated their transactivation by NF-κB in leu-kemic cells. Thus, TAT-delivered NPM peptide may provide a novel therapy for inflammation-associated tumors that require NF-κB signaling for survival.
The largest prospective warfarin-treated cohort supports genetic forecasting
Authors: Wadelius Mia , Chen Leslie Y. , Lindh Jonatan D. , Eriksson Niclas , Ghori Mohammed J. R. , Bumpstead Suzannah , Holm Lennart , McGinnis Ralph , Rane Anders , Deloukas Panos 
Published: June 2008

Abstract
Genetic variants of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) are known to influence warfarin dose, but the effect of other genes has not been fully elucidated. We genotyped 183 polymorphisms in 29 candidate genes in 1496 Swedish patients starting warfarin treatment, and tested for association with response. CYP2C9*2 and *3 explained 12% (P = 6.63 × 10−34) of the variation in warfarin dose, while a single VKORC1 SNP explained 30% (P = 9.82 × 10−100). No SNP outside the CYP2C gene cluster and VKORC1 regions was significantly associated with dose after correction for multiple testing. During initiation of therapy, homozygosity for CYP2C9 and VKORC1 variant alleles increased the risk of over-anticoagulation, hazard ratios 21.84 (95% CI 9.46; 50.42) and 4.56 (95% CI 2.85; 7.30), respectively. One of 8 patients with CYP2C9*3/*3 (12.5%) experienced severe bleeding during the first month compared with 0.27% of other patients (P = .066). A multiple regression model using the predictors CYP2C9, VKORC1, age, sex, and druginteractions explained 59% of the variance in warfarin dose, and 53% in an independent sample of 181 Swedish individuals. In conclusion, CYP2C9 and VKORC1 significantly influenced warfarin dose and predicted individuals predisposed to unstable anticoagulation. Our results strongly support that initiation of warfarin guided by pharmacogenetics would improve clinical outcome.
SNPAnalyzer 2.0: A web-based integrated workbench for linkage disequilibrium analysis and association analysis
Authors: Yoo Jinho , Lee Youngbok , Kim Yujung , Rha Sun Young , Kim Yangseok 
Published: June 2008

Abstract

Background
Since the completion of the HapMap project, huge numbers of individual genotypes have been generated from many kinds of laboratories. The efforts of finding or interpreting genetic association between disease and SNPs/haplotypes have been on-going widely. So, the necessity of the capability to analyze huge data and diverse interpretation of the results are growing rapidly.

Results
We have developed an advanced tool to perform linkage disequilibrium analysis, and genetic association analysis between disease and SNPs/haplotypes in an integrated web interface. It comprises of four main analysis modules: (i) data import and preprocessing, (ii) haplotype estimation, (iii) LD blocking and (iv) association analysis. Hardy-Weinberg Equilibrium test is implemented for each SNPs in the data preprocessing. Haplotypes are reconstructed from unphased diploid genotype data, and linkage disequilibrium between pairwise SNPs is computed and represented by D', r2 and LOD score. Tagging SNPs are determined by using the square of Pearson's correlation coefficient (r2). If genotypes from two different sample groups are available, diverse genetic association analyses are implemented using additive, codominant, dominant and recessive models. Multiple verified algorithms and statistics are implemented in parallel for the reliability of the analysis.

Conclusion
SNPAnalyzer 2.0 performs linkage disequilibrium analysis and genetic association analysis in an integrated web interface using multiple verified algorithms and statistics. Diverse analysis methods, capability of handling huge data and visual comparison of analysis results are very comprehensive and easy-to-use.
Proteomic analysis of lamellar bodies isolated from rat lungs
Authors: Wang Pengcheng , Chintagari Narendranath Reddy , Narayanaperumal Jeyaparthasarathy , Ayalew Sahlu , Hartson Steven , Liu Lin 
Published: June 2008

Abstract

Background
Lamellar bodies are lysosome-related secretory granules and store lung surfactant in alveolar type II cells. To better understand the mechanisms of surfactant secretion, we carried out proteomic analyses of lamellar bodies isolated from rat lungs.

Results
With peptide mass fingerprinting by Matrix Assisted Laser Desorption/Ionization – Time of Flight mass spectrometry, 44 proteins were identified with high confidence. These proteins fell into diverse functional categories: surfactant-related, membrane trafficking, calcium binding, signal transduction, cell structure, ion channels, protein processing and miscellaneous. Selected proteins were verified by Western blot and immunohistochemistry.

Conclusion
This proteomic profiling of lamellar bodies provides a basis for further investigations of functional roles of the identified proteins in lamellar body biogenesis and surfactant secretion.
Functional characterization of endogenous siRNA target genes in Caenorhabditis elegans
Authors: Asikainen Suvi , Heikkinen Liisa , Wong Garry , Storvik Markus 
Published: June 2008

Abstract

Background
Small interfering RNA (siRNA) molecules mediate sequence specific silencing in RNA interference (RNAi), a gene regulatory phenomenon observed in almost all organisms. Large scale sequencing of small RNA libraries obtained from C. elegans has revealed that a broad spectrum of siRNAs is endogenously transcribed from genomic sequences. The biological role and molecular diversity of C. elegans endogenous siRNA (endo-siRNA) molecules, nonetheless, remain poorly understood. In order to gain insight into their biological function, we annotated two large libraries of endo-siRNA sequences, identified their cognate targets, and performed gene ontology analysis to identify enriched functional categories.

Results
Systematic trends in categorization of target genes according to the specific length of siRNA sequences were observed: 18- to 22-mer siRNAs were associated with genes required for embryonic development; 23-mers were associated uniquely with post-embryonic development; 24–26-mers were associated with phosphorus metabolism or protein modification. Moreover, we observe that some argonaute related genes associate with siRNAs with multiple reads. Sequence frequency graphs suggest that different lengths of siRNAs share similarities in overall sequence structure: the 5' end begins with G, while the body predominates with U and C.

Conclusion
These results suggest that the lengths of endogenous siRNA molecules are consequential to their biological functions since the gene ontology categories for their cognate mRNA targets vary depending upon their lengths.
The trypanosome transcriptome is remodelled during differentiation but displays limited responsiveness within life stages
Authors: Koumandou V Lila , Natesan Senthil Kumar A , Sergeenko Tatiana , Field Mark C 
Published: June 2008

Abstract

Background
Trypanosomatids utilise polycistronic transcription for production of the vast majority of protein-coding mRNAs, which operates in the absence of gene-specific promoters. Resolution of nascent transcripts by polyadenylation and trans-splicing, together with specific rates of mRNA turnover, serve to generate steady state transcript levels that can differ in abundance across several orders of magnitude and can be developmentally regulated. We used a targeted oligonucleotide microarray, representing the strongly developmentally-regulated T. brucei membrane trafficking system and ~10% of the Trypanosoma brucei genome, to investigate both between-stage, or differentiation-dependent, transcriptome changes and within-stage flexibility in response to various challenges.

Results
6% of the gene cohort are developmentally regulated, including several small GTPases, SNAREs, vesicle coat factors and protein kinases both consistent with and extending previous data. Therefore substantial differentiation-dependent remodeling of the trypanosome transcriptome is associated with membrane transport. Both the microarray and qRT-PCR were then used to analyse transcriptome changes resulting from specific gene over-expression, knockdown, altered culture conditions and chemical stress. Firstly, manipulation of Rab5 expression results in co-ordinate changes to clathrin protein expression levels and endocytotic activity, but no detectable changes to steady-state mRNA levels, which indicates that the effect is mediated post-transcriptionally. Secondly, knockdown of clathrin or the variant surface glycoprotein failed to perturb transcription. Thirdly, exposure to dithiothreitol or tunicamycin revealed no evidence for a classical unfolded protein response, mediated in higher eukaryotes by transcriptional changes. Finally, altered serum levels invoked little transcriptome alteration beyond changes to expression of ESAG6/7, the transferrin receptor.

Conclusion
While trypanosomes regulate mRNA abundance to effect the major changes accompanying differentiation, a given differentiated state appears transcriptionally inflexible. The implications of the absence of a transcriptome response in trypanosomes for both virulence and models of life cycle progression are discussed.