Social vulnerability and prefrontal cortical function in elderly people: a report from the Canadian Study of Health and Aging.

Background: Prefrontal cortical lobe function is related to social behavior in humans. We investigated whether performance on tests of prefrontal cortical function was associated with social vulnerability. Associations with non-frontal cognitive function were investigated for comparison.

Human papillomavirus E1 and E2 mediated DNA replication is not arrested by DNA damage signalling.

Integration of human papillomaviruses into that of the host promotes genomic instability and progression to cancer; factors that promote integration remain to be fully identified. DNA damage agents can promote double strand breaks during DNA replication providing substrates for integration and we investigated the ability of DNA damage to regulate HPV E1 and E2 mediated DNA replication. Results demonstrate that HPV E1 and E2 replication is not arrested following DNA damage, both in vivo and in vitro, while replication by SV40 Large T antigen is arrested and ATR is the candidate kinase for mediating the arrest.

International development of the patient-reported outcome indices for multiple sclerosis (PRIMUS).

Background: The Patient-Reported Indices for Multiple Sclerosis (PRIMUS) comprises a suite of three scales for assessing symptoms, activity limitations, and quality of life in multiple sclerosis (MS). It was developed in the UK and has been shown to have excellent psychometric properties. This study describes the adaptation of eight language versions for Canadian English, Canadian French, French, German, Italian, Spanish, Swedish, and US English.

Assessing the functional significance of ecstasy-related memory deficits using a virtual paradigm.

Rationale/objectives: Previous research shows that the use of ecstasy results in working memory and executive impairments in some users. The present study sought to assess the functional significance of such deficits using a virtual reality task.

Methods: Twenty-three ecstasy-polydrug users and 26 nonusers were recruited.

TbPRMT6 is a type I protein arginine methyltransferase that contributes to cytokinesis in Trypanosoma brucei.

Arginine methylation is a widespread posttranslational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). In Saccharomyces cerevisiae and mammals, this modification affects multiple cellular processes, such as chromatin remodeling leading to transcriptional regulation, RNA processing, DNA repair, and cell signaling. The protozoan parasite Trypanosoma brucei possesses five putative PRMTs in its genome.

Structure of the Trypanosoma brucei p22 protein, a cytochrome oxidase subunit II-specific RNA-editing accessory factor.

Kinetoplastid RNA (k-RNA) editing is a complex process in the mitochondria of kinetoplastid protozoa, including Trypanosoma brucei, that involves the guide RNA-directed insertion and deletion of uridines from precursor-mRNAs to produce mature, translatable mRNAs. k-RNA editing is performed by multiprotein complexes called editosomes. Additional non-editosome components termed k-RNA-editing accessory factors affect the extent of editing of specific RNAs or classes of RNAs.

International development of the Unidimensional Fatigue Impact Scale (U-FIS).

Objective: The 22-item Unidimensional Fatigue Impact Scale (U-FIS) provides an index of the impact of fatigue on patients with multiple sclerosis (MS). The objective is to produce eight new language versions of the U-FIS: Canadian-English, Canadian-French, French, German, Italian, Spanish, Swedish, and US-English.

Methods: The U-FIS was translated via two translation panels.

Assessment of cognitive function in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis by computerized neuropsychological tests.

Objective: Computerized neuropsychological testing may facilitate screening for cognitive impairment in systemic lupus erythematosus (SLE). This study was undertaken to compare patients with SLE, patients with rheumatoid arthritis (RA), and patients with multiple sclerosis (MS) with healthy controls using the Automated Neuropsychological Assessment Metrics (ANAM).

Methods: Patients with SLE (n = 68), RA (n = 33), and MS (n = 20) were compared with healthy controls (n = 29).

Everyday and prospective memory deficits in ecstasy/polydrug users.

The impact of ecstasy/polydrug use on real-world memory (i.e. everyday memory, cognitive failures and prospective memory [PM]) was investigated in a sample of 42 ecstasy/polydrug users and 31 non-ecstasy users.

Butyrylcholinesterase activity in multiple sclerosis neuropathology.

Butyrylcholinesterase (BuChE) is an enzyme capable of hydrolysing a wide variety of esters including acetylcholine, a molecule involved in neurotransmission and modulation of immune cell activity. In the brain, BuChE is expressed in white matter and certain populations of neurons and glia. Multiple sclerosis (MS) is an autoimmune disease affecting white matter characterized by neuroinflammation and neurodegeneration in the central nervous system.

Disease progression among multiple sclerosis patients before and during a disease-modifying drug program: a longitudinal population-based evaluation.

Randomized controlled trials have demonstrated the efficacy of disease-modifying drugs (DMDs) in persons with relapsing-remitting multiple sclerosis (MS) and secondary progressive MS with superimposed relapses. However, these brief studies of selected patients have focused mainly on reducing attacks and must be complemented by evaluations in 'realworld' clinical settings to establish the effectiveness of DMD programs in slowing disease progression and to inform health policy and program decision-making. We assessed the effectiveness of DMDs as administered in a comprehensive publicly funded drug insurance program that provides DMDs to a geographically defined population of MS patients who meet specific eligibility criteria.

Executive working memory deficits in abstinent ecstasy/MDMA users: a critical review.

Aims: This review examined studies of executive functioning in abstinent ecstasy (3,4-methylenedioxymethamphetamine, MDMA) users on tasks which had been empirically mapped onto updating, shifting, inhibition and accessing long-term memory executive processes. Studies of some aspects of visuospatial memory performance were also included because of the investment of executive resources in such tasks.

Methods: Thirty-three studies were identified for the review following searches of the Psychinfo and Medline databases.

Sleep impairment in ecstasy/polydrug and cannabis-only users.

The present study investigated aspects of sleep quality in ecstasy and cannabis users. Two-hundred and twenty seven participants (117 ecstasy/polydrug users, 53 cannabis users and 57 drug naive participants) took part. The participants completed measures of daytime sleepiness, and indicators of sleep quality.

The association between the negative effects attributed to ecstasy use and measures of cognition and mood among users.

In self reports, abstinent ecstasy/polydrug users claim that they experience certain ongoing affective and psychological changes including elevated anxiety, arousal, and depression. In addition, various aspects of cognition (e.g.

Distinct and overlapping functions of MRP1/2 and RBP16 in mitochondrial RNA metabolism.

Mitochondrial RNA metabolism in Trypanosoma brucei is a complex process involving both extensive RNA editing and control of RNA stability. MRP1/2 and RBP16 are two factors that have been implicated in regulating the editing and stability of specific mRNAs. These two factors exhibit similar nonspecific RNA binding and RNA-annealing activities, suggesting that some of their actions may have been previously masked by functional redundancy.

Epilepsy, psychosocial and cognitive functioning.

This article will provide an overview of the psychosocial and cognitive problems that people with epilepsy (PWE) experience as consequence of the condition and its treatment. Psychosocial problems will be discussed in light of how they impact on quality of life. The review will discuss the stigma, myths and stereotypes that PWE encounter and the implications of these for important psychological outcomes including; anxiety, depression, self-esteem, sense of mastery and cognitive dysfunction.

The development and validation of the Unidimensional Fatigue Impact Scale (U-FIS).

Background: The multidimensional assessment of fatigue is complicated by the interrelation of its multiple causes and effects.

Objective: The purpose of the research was to develop a unidimensional assessment of fatigue (U-FIS).

Methods: Data collected with the Fatigue Impact Scale (FIS) were subjected to Rasch analysis to identify potential problems with the scale.

Cost-effectiveness of disease-modifying therapies in the management of multiple sclerosis for the Medicare population.

Objective: To evaluate the cost-effectiveness of disease-modifying therapies (DMTs) for the management of multiple sclerosis (MS) compared to best supportive care in the United States.

Methods: Cost-effectiveness analysis was undertaken using a state transition model of disease natural history and the impact of DMTs for the representative Medicare beneficiary with MS. Costs and outcomes were evaluated from the health-care payer perspective using a 50-year time horizon.

Knee resistance during passive stretch in patients with hypertonia.

The aims of the study were to determine by a portable method (1) whether velocity-dependent changes in knee resistance in patients with spastic paresis differ from those in non-disabled subjects, and (2) whether biomechanical measures of resistance can differentiate between neural and other factors that contribute to hypertonia (increased resistance). Biomechanical (hand-hold dynamometer, electrogoniometer) and bioelectrical (EMG) measures of resistance were evaluated under static (slow stretch) and dynamic (fast stretch) conditions in twenty patients with hypertonia and 19 non-disabled subjects. Measures calculated for non-disabled subjects (control limbs) were compared to those calculated for patients (spastic limbs).

Structural-activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-kappaB mediated IL-6 production.

We herein describe the synthesis and anti-inflammatory properties of a small library of imidazoline-based NF-kappaB inhibitors. The structure-activity relationship of various substituents on an imidazoline core structure was evaluated for the ability to inhibit NF-kappaB mediated IL-6 production. Optimization of the scaffolds was pursued by correlating luciferase-based NF-kappaB reporter assays with inhibition of IL-6 production in IL-1beta stimulated human blood.

A type III protein arginine methyltransferase from the protozoan parasite Trypanosoma brucei.

Arginine methylation is a widespread post-translational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). The ancient protozoan parasite, Trypanosoma brucei, possesses five putative PRMTs, a relatively large number for a single-celled eukaryote. Trypanosomatids lack gene regulation at the level of transcription, instead relying on post-transcriptional control mechanisms that act at the levels of RNA turnover, translation, and editing, all processes that likely involve multiple RNA-binding proteins, which are common targets of arginine methylation.

Nuclear factor-kappaB mediated inhibition of cytokine production by imidazoline scaffolds.

The mammalian nuclear transcription factor NF-kappaB is responsible for the transcription of multiple cytokines, including the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). Elevated levels of pro-inflammatory cytokines play an important role in the pathogenesis of inflammatory disorders such as rheumatoid arthritis (RA). Inhibition of the pro-inflammatory transcription factor NF-kappaB has therefore been identified as a possible therapeutic treatment for RA.

Development and validation of a computational musculoskeletal model of the elbow and forearm.

Computational modeling is a powerful tool to study normal, injured, and repaired joint function. Existing musculoskeletal models of the elbow have all limited their applicability by assuming fixed joint axes of rotation or prescribing specific kinematics. The purpose of this study was to develop and validate a model of the elbow and forearm whereby joint behavior was dictated by articular contact, ligamentous constraints, muscle loading, and external perturbations.