Pharmacy and Wellbeing

Targeting specific protein-protein interactions (PPIs) is an attractive concept for drug development, but hard to implement since intracellular antibodies do not penetrate cells and most small-molecule drugs are considered unsuitable for PPI inhibition. A potential solution to these problems is to select intracellular antibody fragments to block PPIs, use these antibody fragments for target validation in disease models and finally derive small molecules overlapping the antibody-binding site. Here, we explore this strategy using an anti-mutant RAS antibody fragment as a competitor in a small-molecule library screen for identifying RAS-binding compounds. The initial hits are optimized by structure-based design, resulting in potent RAS-binding compounds that interact with RAS inside the cells, prevent RAS-effector interactions and inhibit endogenous RAS-dependent signalling. Our results may aid RAS-dependent cancer drug development and demonstrate a general concept for developing small...

Recreational Ecstasy/MDMA (3,4-methylenedioxymethamphetamine) users often take a variety of psychoactive drugs, but there is little empirical data on how these drug consumption patterns change with greater experience of Ecstasy. The aim of this study was to compare the polydrug usage patterns reported by non-Ecstasy users, novice Ecstasy users, moderate Ecstasy users, and heavy Ecstasy users. In a WWW study of 763 unpaid volunteers, 481 had never taken Ecstasy, whereas 282 reported they had taken it. The Ecstasy users comprised 109 novice users (1-9 occasions), 136 moderate Ecstasy users (10 -99 occasions), and 36 heavy Ecstasy users ( + 100 occasions). Each participant also reported their experience with a range of other psychoactive drugs. The Ecstasy users reported significantly greater psychoactive drug usage than the non-Ecstasy users. The novice, moderate, and heavy Ecstasy users also differed significantly from each other in the use of cocaine, amphetamine, LSD, and psilocybin mushrooms, but not of alcohol, cannabis, or cigarettes/nicotine. Experienced Ecstasy users also took significantly more MDMA tablets on each occasion, and reported a higher maximum weekly intake. The increased use of Ecstasy is associated with more intensive patterns of Ecstasy/MDMA intake, and the greater use 0306-4603/$ -see front matter D Addictive Behaviors 29 of illicit CNS stimulants and hallucinogens, but not of alcohol, nicotine, or cannabis. These results are discussed in the context of cross-tolerance and drug predisposition/preference.

Chronic use of MDMA (3,4-methylenedioxymethamphetamine), or Ecstasy, is believed to lead to impaired psychological performance, including well-documented decrements in laboratory and field tests of retrospective memory. Less is known about the impact of Ecstasy on aspects of ‘everyday’ memory, despite obvious concerns about such effects. The three studies reported here focused on the impact of chronic Ecstasy use on prospective memory (PM), associated central executive function and other aspects of day-to-day cognition. In study 1 46 regular Ecstasy users were compared with 46 Ecstasy-free controls using the Prospective Memory Questionnaire (PMQ). Ecstasy users reported significantly more errors in PM (remembering to do something in the future); these findings persisted after controlling for other drug use and the number of strategies used to aid memory. No difference was found between representative subgroups on the Lies Scale of the Eysenck Personality Questionnaire. In study 2 a different group of 30 regular Ecstasy users and 37 Ecstasy-free controls was assessed on the PMQ and on a central executive task comprising verbal fluency measures. The results confirmed the significant impairments in long- and short-term PM and revealed corresponding impairments in verbal fluency. In study 3 15 Ecstasy users, 15 cannabis users and 15 non-drug users were assessed using the Cognitive Failures Questionnaire, which requires participants to provide ratings of the frequency of various day-to-day cognitive slips. The results indicate that the Ecstasy users did not perceive their general cognitive performance to be worse than that of controls. Taken together, these results suggest that Ecstasy users have impaired PM that cannot be explained by an increased propensity to exaggerate cognitive failures. These may be attributable, in part, to central executive deficits that are due to frontal lobe damage associated with Ecstasy use. Copyright © 2001 John Wiley & Sons, Ltd.

upon-Tyne NE1 7RU, UK Rationale The recreational use of MDMA/Ecstasy (3,4-methylenedioxymethamphetamine) is associated with many psychobiological problems, but there is a paucity of data on how these relate to the level of past use. Objectives: to assess the incidence of Ecstasy-attributed problems as reported by novice, moderate and heavy users. Methods: 763 unpaid volunteers took part in a WWW study of recreational drug use. This report is based on the 282 Ecstasy users from that sample, who comprised 109 novice users (1-9 occasions), 136 moderate users (10-99 occasions), and 36 heavy users (þ100 occasions). Yes/no responses were automatically recorded to a series of questions covering psychobiological problems experienced when drug-free, which were attributed by the respondents to their Ecstasy use. Results: Depression, memory problems, anxiety, mood fluctuation, poor concentration, infections, tremors/twitches and weight loss, were all significantly associated with the extent of Ecstasy use. Thus memory problems attributed to Ecstasy were reported by 19% of novice users, 52% of heavy users and 73% of heavy users (chi-square 42.74, df ¼ 2, p < 0.001); many of the other variables showed similar trends. Conclusions The incidence of problems attributed to Ecstasy use, is directly related to the number of occasions it has been used.

On-line surveys are now an important tool for data collection on the World Wide Web (the Web). Determining the psychometric properties of key constructs such as disorientation, ease of use and flow is of paramount importance in establishing the quality of users' interactions with web sites. The current study used techniques of experimental research and on-line surveys to investigate the psychometric properties of existing instruments for measuring these constructs using two response formats: visual analogue scale and Likert scale. A 2 Â 2 design with response format and orientation support as independent variables was used. Ninety participants carried out an information retrieval task using an experimental on-line shopping site before completing the scales. Factor analysis confirmed the existence of three distinct scales that possessed high reliability. Evidence for validity, and to a lesser extent, sensitivity, was found. Although psychometric results generally converged, some differences between the two response formats were found. A framework for the comprehensive investigation of response formats of on-line questionnaires is proposed as a basis for future research. Practical implications for the on-line measurement of the quality of users' interactions with web-based systems are discussed. r

Usability is paramount for the success of Web sites. This study aims to contribute towards Web design guidelines for usability through an empirical investigation into two Web page design parameters. Using a 2 X 4 mixed measures experimental design, we studied the effects of frame layout and background contrast on visual search performance. One hundred and eighty-nine undergraduates carried out a visual search task using mock Web pages. Analysis showed an effect of layout both on accuracy and speed measures, with frames located at the top or left of the screen leading to better performance. No main effect of contrast was found, although there was an interaction between layout and contrast in reaction time for hits. Preference for frame layout was dependent on background contrast. The results are discussed in terms of visual search processes and design recommendations are given.

Most web sites are heavily text-based. Previous research has indicated that the way in which this text is presented may have a significant impact on usability. This paper reports findings from two experiments that explored the influence of font type and line length on a range of performance and subjective measures. Experiment 1 used a visual search task and Experiment 2 examined information retrieval. Overall, there was little impact of font on task performance, although the effect of line length was significant, with longer line lengths facilitating better scanning (Experiment 1) and shorter line lengths leading to better subjective outcomes (Experiments 1 and 2). Implications of these results for the design of web pages are discussed and recommendations given. r

Paul van Schaik is a psychologist with an interest in human-computer interaction, and cognitive psychology; he is a Professor of Psychology in the School of Social Sciences and Law at Teesside University. Jonathan Ling is a psychologist with an interest in human-computer interaction, cognitive performance and perception; he is a research fellow in the Faculty of Applied Sciences at the University of Sunderland.

We would like to thank Dr Lemon for his interest in our review and for opening up this correspondence. Nevertheless, we do not perceive any inaccuracies in our account of the paper by . There was no mention of BAL being zero during testing in the hangover phase in the 1993 paper, and we reported this. Furthermore, our account does not contradict what Lemon says in his letter-Lemon et al. (1993) did not find any neuropsychological effects in the hangover testing phase. Finally, our review acknowledges possible mechanisms underlying hangover beyond those closely related to alcohol consumption, including sleep deprivation. Nevertheless, it is valuable for Lemon to add to the record that BAL was indeed zero during testing in the hangover phase in , and it is useful to highlight that the study used a demonstrably sensitive test (divided attention) that showed acute intoxication effects of alcohol and yet found no hangover effects.

Aims: Alcohol misuse is a prime social and health problem in the UK. This paper presents a critical review of literature on the performance effects in the morning after binge drinking -during the alcohol hangover. Several pathophysiological changes that both follow and outlast acute intoxication may give rise to alcohol hangover effects. We have identified 27 English language peer-reviewed studies that investigate aspects of psychological performance during alcohol hangover following controlled alcohol ingestion. However, the majority of studies had basic methodological shortcomings. Of eight laboratory studies rigorous enough to warrant serious attention, only two showed effects. We interpret these largely negative findings as evidence of an insensitivity that is intrinsic to laboratorybased studies of performance under the influence of alcohol. Several studies have investigated the cognitive consequences of hangover subsequent to naturalistic consumption, where participants have chosen what and where to drink. Although these studies have tended to show effects, participants were always informed at the outset that hangover effects were to be assessed, and participants knew which was the hangover condition. Under these circumstances expectancy effects have possibly contaminated the results significantly. Therefore, naturalistic alcohol consumption studies (and laboratory studies that did not employ a placebo) can be considered as being suggestive of hangover effects, but should not be interpreted as providing definitive evidence of such effects. In conclusion, although there is empirical evidence showing impaired performance as a result of the alcohol hangover, future studies should confirm these findings and overcome the shortcomings of previous research.

Chronic alcohol abuse has a detrimental effect on retrospective memory. Less is known about its putative effects on everyday memory. This study looked at self-ratings of prospective memory (PM) (memory for future events). After controlling for other drug and strategy use, chronic heavy alcohol users showed global impairments in PM, when compared to matched controls. The underlying mechanisms are discussed.