What Do Effective Treatments for Multiple Sclerosis Tell Us about the Molecular Mechanisms Involved in Pathogenesis?

Multiple sclerosis is a potentially debilitating disease of the central nervous system. A concerted program of research by many centers around the world has consistently demonstrated the importance of the immune system in its pathogenesis. This knowledge has led to the formal testing of a number of therapeutic agents in both animal models and humans. These clinical trials have shed yet further light on the pathogenesis of MS through their sometimes unexpected effects and by their differential effects in terms of impact on relapses, progression of the disease, paraclinical parameters (MRI) and the adverse events that are experienced. Here we review the currently approved medications for the commonest form of multiple sclerosis (relapsing-remitting) and the emerging therapies for which preliminary results from phase II/III clinical trials are available. A detailed analysis of the molecular mechanisms responsible for the efficacy of these medications in multiple sclerosis indicates that blockade or modulation of both T- and B-cell activation and migration pathways in the periphery or CNS can lead to amelioration of the disease. It is hoped that further therapeutic trials will better delineate the pathogenesis of MS, ultimately leading to even better treatments with fewer adverse effects.     

The effects of "neighborhood size" in reading and lexical decision.

Assessed the effects of neighborhood size ("N")—the number of words differing from a target word by exactly 1 letter (i.e., "neighbors")—on word identification. In Exps 1 and 2, the frequency of the highest frequency neighbor was equated, and N had opposite effects in lexical decision and reading. In Exp 1, a larger N facilitated lexical decision judgments, whereas in Experiment 2, a larger N had an inhibitory effect on reading sentences that contained the words of Exp 1. Moreover, a significant inhibitory effect in Exp 2 that was due to a larger N appeared on gaze duration on the target word, and there was no hint of facilitation on the measures of reading that tap the earliest processing of a word. In Exp 3, the number of higher frequency neighbors was equated for the high-N and low-N words, and a larger N caused target words to be skipped significantly more and produced inhibitory effects later in reading, some of which were plausibly due to misidentification of the target word when skipped. Regression analyses indicated that, in reading, increasing the number of higher frequency neighbors had a clear inhibitory effect on word identification and that increasing the number of lower frequency neighbors may have a weak facilitative effect on word identification. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relation of successful dietary restriction to change in bulimic symptoms: A prospective study of adolescent girls.

Recent experimental evidence that dietary restriction results in decreased bulimic and depressive symptoms seems inconsistent with findings from prospective studies and etiologic theory. However, because the dieting manipulated in these experiments may be unrepresentative of real-world weight loss dieting, the authors tested whether successful dietary restriction was associated with decreases in these outcomes by using longitudinal data from a school-based study of 496 adolescent girls. Moderately overweight participants who evidenced successful dietary restriction showed significantly greater decreases in bulimic symptoms than weight-matched participants who did not show successful dietary restriction; however, there were no effects for depressive symptoms. In conjunction with past experimental findings, results seem to imply that successful dietary restriction curbs bulimic symptoms, suggesting that current etiologic models may need revision. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Smart Rehabilitation Devices: Part I - Force Tracking Control

Resistance exercise has been widely reported to have positive rehabilitation effects for patients with neuromuscular and orthopaedic conditions. This article presents prototypes of smart variable resistance exercise devices using magneto-rheological fluid dampers. An intelligent supervisory control for regulating the resistive force or torque of the device is developed, and is validated both numerically and experimentally. The device provides both isometric and isokinetic strength training for the human joints including knee, elbow, hip, and ankle.     

The application of a fuzzy-rule-based system in an exposition of the antecedents of sedge warbler song flight

Abstract: The utilization of a fuzzy aspect within data analysis attempts to move from a quantitative to a more qualitative investigative environment. As such, this may allow the more non‐quantitative researchers results they can use, based on sets of linguistic terms. In this paper an inductive fuzzy decision tree approach is utilized to construct a fuzzy‐rule‐based system for the first time in a biological setting. The specific biological problem considered attempts to identify the antecedents (conditions in the fuzzy decision rules) which characterize the length of song flight of the male sedge warbler when attempting to attract a mate. Hence, for a non‐quantitative investigator the resultant set of fuzzy rules allows an insight into the linguistic interpretation on the relationship between associated characteristics and the respective song flight duration.     

Social competence promotion with inner-city and suburban young adolescents: Effects on social adjustment and alcohol use.

Assessed the impact of school-based social competence training on skills, social adjustment, and self-reported substance use of 282 6th and 7th graders. Training emphasized broad-based competence promotion in conjunction with domain-specific application to substance abuse prevention. The 20-session program comprised 6 units: stress management, self-esteem, problem solving, substances and health information, assertiveness, and social networks. Findings indicated positive training effects on Ss' skills in handling interpersonal problems and coping with anxiety. Teacher ratings revealed improvements in Ss' constructive conflict resolution with peers, impulse control, and popularity. Self-report ratings indicated gains in problem-solving efficacy. Results suggest some preventive impact on self-reported substance use intentions and excessive alcohol use. In general, the program was found to be beneficial for both inner-city and suburban students. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Asymmetric oscillation of adherent targeted ultrasound contrast agents

With a lipid shell containing biotin, micron-sized bubbles bound to avidin on a porous and flexible cellulose boundary were insonified by ultrasound. The oscillation of these targeted microbubbles was observed by high-speed photography and compared to the oscillation of free-floating microbubbles. Adherent microbubbles were observed to oscillate asymmetrically in the plane normal to the boundary, and nearly symmetrically in the plane parallel to the boundary, with a significantly smaller maximum expansion in each dimension for bound than free bubbles. With sufficient transmitted pressure, a jet was produced traveling toward the boundary.     

The Influence of Cue Type on Backward Inhibition.

Backward inhibition is proposed as a process of lateral inhibition that operates during response selection in task switching, reducing interference caused by the most recently abandoned task set. The effect has been observed across a wide range of contexts but is eliminated by using spatial location to cue tasks (K. D. Arbuthnott & T. S. Woodward, 2002). The present studies replicated this finding, showing that spatial cues are also associated with greater response congruity than verbal cues, consistent with the lateral inhibition model. Spatial cues may introduce greater discriminability between competing category-response rules, reducing the need for lateral inhibition. However, when participants named the task before target presentation, backward inhibition was observed with spatial cues, suggesting that verbalization increased competition between sets, despite spatial localization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Suicide Attempt Self-Injury Interview (SASII): Development, reliability, and validity of a scale to assess suicide attempts and intentional self-injury.

The authors describe the development of the Suicide Attempt Self-Injury Interview (SASII), an instrument designed to assess the factors involved in nonfatal suicide attempts and intentional self-injury. Using 4 cohorts of participants, authors generated SASII items and evaluated them with factor and content analyses and internal consistency statistics. The final measure was assessed for reliability and validity with collateral measures. The SASII assesses variables related to method, lethality and impulsivity of the act, likelihood of rescue, suicide intent or ambivalence and other motivations, consequences, and habitual self-injury. The SASII was found to have very good interrater reliability and adequate validity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)