Outcome measures for individuals with stroke: Process and recommendations from the American Physical Therapy Association neurology section task force

Background and PurposeThe use of standardized outcome measures (OMs) can support clinicians’ development of appropriate care plans, guide educators in curricular decisions, and enhance the methodological quality and generalizability of clinical trials. The purposes of this case report are: (1) to describe a framework and process for assessing psychometrics and clinical utility of OMs used poststroke; (2) to describe a consensus process used to develop recommendations for stroke-related OMs in clinical practice, research, and professional (entry-level) physical therapist education; (3) to present examples demonstrating how the recommendations have been utilized to date; and (4) to make suggestions for future efforts.Case DescriptionA task force of 7 physical therapists with diverse clinical and research expertise in stroke rehabilitation used a 3-stage, modified Delphi consensus process to develop recommendations on OM use. An evidence-based systematic review template and a 4-point rating scheme were used to make recommendations on OM use by care setting and patient acuity, for research, and for inclusion in professional education.OutcomesAn initial list of 77 OMs was developed based on input from numerous professional sources. Screening measures and duplicate measures were eliminated. Fifty-six OMs received full review. Measures spanned the constructs of body structure/function (21), activity (28), and participation (14). Fourteen measures received a rating of “highly recommend.”DiscussionUse of highly recommended OMs may provide a common set of tools enabling comparisons across patients, interventions, settings, and studies. The use of a clearly defined, comprehensive assessment template may facilitate the pooling of data on OMs and contribute to best practice guidelines. Educational recommendations may inform curricular decisions.</jats:sec

A possible mechanism for cold denaturation of proteins at high pressure

We study cold denaturation of proteins at high pressures. Using multicanonical Monte Carlo simulations of a model protein in a water bath, we investigate the effect of water density fluctuations on protein stability. We find that above the pressure where water freezes to the dense ice phase ($\approx2$ kbar), the mechanism for cold denaturation with decreasing temperature is the loss of local low-density water structure. We find our results in agreement with data of bovine pancreatic ribonuclease A.Comment: 4 pages for double column and single space. 3 figures Added references Changed conten

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

African Americans, Gentrification, and Neoliberal Urbanization: the Case of Fort Greene, Brooklyn

This article examines the gentrification of Fort Greene, which is located in the western part of black Brooklyn, one of the largest contiguous black urban areas in the USA. Between the late 1960s and 2003, gentrification in Fort Greene followed the patterns discovered by scholars of black neighborhoods; the gentrifying agents were almost exclusively black and gentrification as a process was largely bottom-up because entities interested in the production of space were mostly not involved. Since 2003, this has changed. Whites have been moving to Fort Greene in large numbers and will soon represent the numerical majority. Public and private interventions in and around Fort Greene have created a new top-down version of gentrification, which is facilitating this white influx. Existing black residential and commercial tenants are replaced and displaced in the name of urban economic development

A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a “candidate interactome” (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms

Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis

BACKGROUND:Recent data from animal models of multiple sclerosis (MS) and from a pilot study indicated a possible beneficial impact of statins on MS. METHODOLOGY/PRINCIPAL FINDINGS:Safety, tolerability and effects on disease activity of atorvastatin given alone or in combination with interferon-beta (IFN-beta) were assessed in a phase II open-label baseline-to-treatment trial in relapsing-remitting MS (RRMS). Patients with at least one gadolinium-enhancing lesion (CEL) at screening by magnetic resonance imaging (MRI) were eligible for the study. After a baseline period of 3 monthly MRI scans (months -2 to 0), patients followed a 9-month treatment period on 80 mg atorvastatin daily. The number of CEL in treatment months 6 to 9 compared to baseline served as the primary endpoint. Other MRI-based parameters as well as changes in clinical scores and immune responses served as secondary endpoints. Of 80 RRMS patients screened, 41 were included, among them 16 with IFN-beta comedication. The high dose of 80 mg atorvastatin was well tolerated in the majority of patients, regardless of IFN-beta comedication. Atorvastatin treatment led to a substantial reduction in the number and volume of CEL in two-sided multivariate analysis (p = 0.003 and p = 0.008). A trend towards a significant decrease in number and volume of CEL was also detected in patients with IFN-beta comedication (p = 0.060 and p = 0.062), in contrast to patients without IFN-beta comedication (p = 0.170 and p = 0.140). Immunological investigations showed no suppression in T cell response but a significant increase in IL-10 production. CONCLUSIONS/SIGNIFICANCE:Our data suggest that high-dose atorvastatin treatment in RRMS is safe and well tolerated. Moreover, MRI analysis indicates a possible beneficial effect of atorvastatin, alone or in combination with IFN-beta, on the development of new CEL. Thus, our findings provide a rationale for phase II/III trials, including combination of atorvastatin with already approved immunomodulatory therapy regimens. TRIAL REGISTRATION:ClinicalTrials.gov NCT00616187

The effect of massage on localized lumbar muscle fatigue

BACKGROUND: There is not enough evidence to support the efficacy of massage for muscle fatigue despite wide utilization of the modality in various clinical settings. This study investigated the influence of massage application on localized back muscle fatigue. METHODS: Twenty-nine healthy subjects participated in two experimental sessions (massage and rest conditions). On each test day, subjects were asked to lie in the prone position on a treatment table and perform sustained back extension for 90 seconds. Subjects then either received massage on the lumbar region or rested for a 5 minute duration, then repeated the back extension movement. The median frequency (MDF), mean power frequency (MNF), and root mean square (RMS) amplitude of electromyographic signals during the 90 second sustained lumbar muscle contraction were analyzed. The subjective feeling of fatigue was then evaluated using the Visual Analogue Scale (VAS). RESULTS: MDF and MNF significantly declined with time under all conditions. There was no significant difference in MDF, MNF or RMS value change between before and after massage, or between rest and massage conditions. There was a significant increase in fatigue VAS at the end of the 2(nd) back extension with rest condition. There was a significant difference in fatigue VAS change between massage and rest condition. CONCLUSIONS: A significant difference was observed between massage and rest condition on VAS for muscle fatigue. On EMG analysis, there were no significant differences to conclude that massage stimulation influenced the myoelectrical muscle fatigue, which is associated with metabolic and electrical changes