Rasch analysis of the Multiple Sclerosis Impact Scale (MSIS-29)

<p>Abstract</p> <p>Background</p> <p>Multiple Sclerosis (MS) is a degenerative neurological disease that causes impairments, including spasticity, pain, fatigue, and bladder dysfunction, which negatively impact on quality of life. The Multiple Sclerosis Impact Scale (MSIS-29) is a disease-specific health-related quality of life (HRQoL) instrument, developed using the patient's perspective on disease impact. It consists of two subscales assessing the physical (MSIS-29-PHYS) and psychological (MSIS-29-PSYCH) impact of MS. Although previous studies have found support for the psychometric properties of the MSIS-29 using traditional methods of scale evaluation, the scale has not been subjected to a detailed Rasch analysis. Therefore, the objective of this study was to use Rasch analysis to assess the internal validity of the scale, and its response format, item fit, targeting, internal consistency and dimensionality.</p> <p>Methods</p> <p>Ninety-two persons with definite MS residing in the community were recruited from a tertiary hospital database. Patients completed the MSIS-29 as part of a larger study. Rasch analysis was undertaken to assess the psychometric properties of the MSIS-29.</p> <p>Results</p> <p>Rasch analysis showed overall support for the psychometric properties of the two MSIS-29 subscales, however it was necessary to reduce the response format of the MSIS-29-PHYS to a 3-point response scale. Both subscales were unidimensional, had good internal consistency, and were free from item bias for sex and age. Dimensionality testing indicated it was not appropriate to combine the two subscales to form a total MSIS score.</p> <p>Conclusion</p> <p>In this first study to use Rasch analysis to fully assess the psychometric properties of the MSIS-29 support was found for the two subscales but not for the use of the total scale. Further use of Rasch analysis on the MSIS-29 in larger and broader samples is recommended to confirm these findings.</p

Effects of metal-on-metal wear on the host immune system and infection in hip arthroplasty

Methods We reviewed the available literature on the influence of degradation products of MOM bearings in total hip arthroplasties on infection risk. Results Wear products were found to influence the risk of infection by hampering the immune system, by inhibiting or accelerating bacterial growth, and by a possible antibiotic resistance and heavy metal co-selection mechanism. Interpretation Whether or not the combined effects of MOM wear products make MOM bearings less or more prone to infection requires investigation in the near future

Berberine Attenuates Experimental Autoimmune Encephalomyelitis in C57 BL/6 Mice

Berberine, an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-inflammatory and neuroprotective effects. However, there are no reports about the effects and mechanisms of berberine in experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS).Female C57 BL/6 mice immunized with myelin oligodendrocyte glycoprotein 35–55 amino acid peptide were treated with berberine at the day of disease onset and medication was administered daily until mice were sacrificed. Blood–brain barrier (BBB) permeability and the alteration of matrix metalloproteinase-2 (MMP-2, 72 kDa) and matrix metalloproteinase-9 (MMP-9, 92 kDa) in the brain and cerebrospinal fluid (CSF) of EAE mice were detected by quantitative measurement for Evan's blue (EB) content, Western blot and gelatin zymography respectively. The results showed that berberine attenuated clinical and pathological parameters of EAE, reduced the permeability of BBB, inhibited the activity and expression of MMP-9 but not MMP-2 in the CSF and brain of EAE mice.These findings suggest that berberine is effective to attenuate the clinical severity of EAE in C57 BL/6 mice by reducing the permeability of BBB, decreasing the expression and activity of MMP-9, and decreasing the inflammatory infiltration. We think that berberine might be a potential therapeutic agent for MS

Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana

Transketolase (TKT) is part of the non-oxidative branch of the pentose phosphate pathway (PPP). Here we describe the impact of removing this enzyme from the pathogenic protozoan Leishmania mexicana. Whereas the deletion had no obvious effect on cultured promastigote forms of the parasite, the Δtkt cells were not infective to mice. Δtkt promastigotes were more susceptible to oxidative stress and various leishmanicidal drugs than wild-type, and metabolomics analysis revealed profound changes to metabolism in these cells. In addition to changes consistent with those directly related to the role of TKT in the PPP, central carbon metabolism was substantially decreased, the cells consumed significantly less glucose, flux through glycolysis diminished, and production of the main end products of metabolism was decreased. Only minor changes in RNA abundance from genes encoding enzymes in central carbon metabolism, however, were detected although fructose-1,6-bisphosphate aldolase activity was decreased two-fold in the knock-out cell line. We also showed that the dual localisation of TKT between cytosol and glycosomes is determined by the C-terminus of the enzyme and by engineering different variants of the enzyme we could alter its sub-cellular localisation. However, no effect on the overall flux of glucose was noted irrespective of whether the enzyme was found uniquely in either compartment, or in both

T2-weighted cardiovascular magnetic resonance in acute cardiac disease

Cardiovascular magnetic resonance (CMR) using T2-weighted sequences can visualize myocardial edema. When compared to previous protocols, newer pulse sequences with substantially improved image quality have increased its clinical utility. The assessment of myocardial edema provides useful incremental diagnostic and prognostic information in a variety of clinical settings associated with acute myocardial injury. In patients with acute chest pain, T2-weighted CMR is able to identify acute or recent myocardial ischemic injury and has been employed to distinguish acute coronary syndrome (ACS) from non-ACS as well as acute from chronic myocardial infarction

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies.

Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is characterized by inflammatory demyelinating lesions in the spinal cord and optic nerve, potentially leading to paralysis and blindness. NMO can usually be distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG antibodies against the astrocytic water channel aquaporin-4 (AQP4). Differentiation from MS is crucial, because some MS treatments can exacerbate NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood-brain barrier disruption and oligodendrocyte injury. Current NMO treatments include general immunosuppressive agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19--all initially developed for other indications--are under clinical evaluation for repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently theoretical, treatment options include reduction of AQP4 expression, disruption of AQP4 orthogonal arrays, enhancement of complement inhibitor expression, restoration of the blood-brain barrier, and induction of immune tolerance. Despite the many therapeutic options in NMO, no controlled clinical trials in patients with this condition have been conducted to date

The MOBILIZE Boston Study: Design and methods of a prospective cohort study of novel risk factors for falls in an older population

<p>Abstract</p> <p>Background</p> <p>Falls are the sixth leading cause of death in elderly people in the U.S. Despite progress in understanding risk factors for falls, many suspected risk factors have not been adequately studied. Putative risk factors for falls such as pain, reductions in cerebral blood flow, somatosensory deficits, and foot disorders are poorly understood, in part because they pose measurement challenges, particularly for large observational studies.</p> <p>Methods</p> <p>The MOBILIZE Boston Study (MBS), an NIA-funded Program Project, is a prospective cohort study of a unique set of risk factors for falls in seniors in the Boston area. Using a door-to-door population-based recruitment, we have enrolled 765 persons aged 70 and older. The baseline assessment was conducted in 2 segments: a 3-hour home interview followed within 4 weeks by a 3-hour clinic examination. Measures included pain, cerebral hemodynamics, and foot disorders as well as established fall risk factors. For the falls follow-up, participants return fall calendar postcards to the research center at the end of each month. Reports of falls are followed-up with a telephone interview to assess circumstances and consequences of each fall. A second assessment is performed 18 months following baseline.</p> <p>Results</p> <p>Of the 2382 who met all eligibility criteria at the door, 1616 (67.8%) agreed to participate and were referred to the research center for further screening. The primary reason for ineligibility was inability to communicate in English. Results from the first 600 participants showed that participants are largely representative of seniors in the Boston area in terms of age, sex, race and Hispanic ethnicity. The average age of study participants was 77.9 years (s.d. 5.5) and nearly two-thirds were women. The study cohort was 78% white and 17% black. Many participants (39%) reported having fallen at least once in the year before baseline.</p> <p>Conclusion</p> <p>Our results demonstrate the feasibility of conducting comprehensive assessments, including rigorous physiologic measurements, in a diverse population of older adults to study non-traditional risk factors for falls and disability. The MBS will provide an important new data resource for examining novel risk factors for falls and mobility problems in the older population.</p