Dehydroepiandrosterone sulphate as a putative protective factor against tardive dyskinesia

AbstractBackgroundTardive dyskinesia (TD) is a potentially irreversible consequence of long term treatment with antipsychotic drugs which is according to a well-known theory believed to be related to oxidative stress induced neurotoxicity. Dehydroepiandrosterone (DHEA) is an endogenous antioxidant with neuroprotective activity. The biosynthesis of DHEA depends upon the activity of cytochrome P450c17α (CYP17). The gene that encodes for CYP17 has a (T34C) single nucleotide polymorphism which enhances CYP17 transcription and expression.ObjectiveTo test the hypothesis that carriership of a more active CYP17 variant would result in higher DHEA(S) levels and protect against neurotoxicity which results in orofaciolingual TD (TDof), limb-truncal TD (TDlt) or both (TDsum).MethodTardive dyskinesia was assessed cross-sectionally in 146 Caucasian psychiatric inpatients from Siberia.ResultsPatients who are carriers of the Cyp17 genotype CC have less chance of developing TD compared to patients who are carriers of the Cyp17 genotypes TC or TT (p<0.05). However, these carriers have significant lower circulating DHEAS levels compared to carriers of the Cyp17 genotypes TC and TT (p<0.05). Conversely, carriers of the CYP17 T-allele have significant elevated DHEAS levels. After correcting for gender and age no significant relationship between Cyp17 genotype CC, the T-allelle and the C-allele and the DHEAS concentration of patients was observed.ConclusionsAlthough an association between the CYP17 CC genotype and TD is indicated, our findings do not support the hypothesis that this is mediated through increased DHEA(S) levels. We believe that the relationship between this polymorphism and neuroprotective effects of steroids is more complex and cannot be elucidated without taking the posttranslational regulation of the enzyme into account

Photoprocesses in protoplanetary disks

Circumstellar disks are exposed to intense ultraviolet radiation from the young star. In the inner disks, the UV radiation can be enhanced by more than seven orders of magnitude compared with the average interstellar field, resulting in a physical and chemical structure that resembles that of a dense photon-dominated region (PDR). This intense UV field affects the chemistry, the vertical structure of the disk, and the gas temperature, especially in the surface layers of the disk. The parameters which make disks different from traditional PDRs are discussed, including the shape of the UV radiation field, grain growth, the absence of PAHs, the gas/dust ratio and the presence of inner holes. New photorates for selected species, including simple ions, are presented. Also, a summary of available cross sections at Lyman alpha 1216 A is made. Rates are computed for radiation fields with color temperatures ranging from 4000 to 30,000 K, and can be applied to a wide variety of astrophysical regions including exo-planetary atmospheres. The importance of photoprocesses is illustrated for a number of representative disk models, including disk models with grain growth and settling.Comment: A website with the final published version and all photodissociation cross sections and rates can be found at http://www.strw.leidenuniv.nl/~ewine/phot

Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue Conditioning and Their Association

Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol), sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for “placebo responders.” However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non-specific effects of acupuncture may contribute to the analgesic effect observed in genuine acupuncture analgesia.National Center for Complementary and Alternative Medicine (U.S.) (R01AT005280

LiMeS-Lab:An Integrated Laboratory for the Development of Liquid–Metal Shield Technologies for Fusion Reactors

The liquid metal shield laboratory (LiMeS-Lab) will provide the infrastructure to develop, test, and compare liquid metal divertor designs for future fusion reactors. The main research topics of LiMeS-lab will be liquid metal interactions with the substrate material of the divertor, the continuous circulation and capillary refilling of the liquid metal during intense plasma heat loading and the retention of plasma particles in the liquid metal. To facilitate the research, four new devices are in development at the Dutch Institute for Fundamental Energy Research and the Eindhoven University of Technology: LiMeS-AM: a custom metal 3D printer based on powder bed fusion; LiMeS-Wetting, a plasma device to study the wetting of liquid metals on various substrates with different surface treatments; LiMeS-PSI, a linear plasma generator specifically adapted to operate continuous liquid metal loops. Special diagnostic protection will also be implemented to perform measurements in long duration shots without being affected by the liquid metal vapor; LiMeS-TDS, a thermal desorption spectroscopy system to characterize deuterium retention in a metal vapor environment. Each of these devices has specific challenges due to the presence and deposition of metal vapors that need to be addressed in order to function. In this paper, an overview of LiMeS-Lab will be given and the conceptual designs of the last three devices will be presented.</p

The placebo effect in the motor domain is differently modulated by the external and internal focus of attention

Among the cognitive strategies that can facilitate motor performance in sport and physical practice, a prominent role is played by the direction of the focus of attention and the placebo effect. Consistent evidence converges in indicating that these two cognitive functions can influence the motor outcome, although no study up-to-now tried to study them together in the motor domain. In this explorative study, we combine for the first time these approaches, by applying a placebo procedure to increase force and by manipulating the focus of attention with explicit verbal instructions. Sixty healthy volunteers were asked to perform abduction movements with the index finger as strongly as possible against a piston and attention could be directed either toward the movements of the finger (internal focus, IF) or toward the movements of the piston (external focus, EF). Participants were randomized in 4 groups: two groups underwent a placebo procedure (Placebo-IF and Placebo-EF), in which an inert treatment was applied on the finger with verbal information on its positive effects on force; two groups underwent a control procedure (Control-IF and Control-EF), in which the same treatment was applied with overt information about its inefficacy. The placebo groups were conditioned about the effects of the treatment with a surreptitious amplification of a visual feedback signalling the level of force. During the whole procedure, we recorded actual force, subjective variables and electromyography from the hand muscles. The Placebo-IF group had higher force levels after the procedure than before, whereas the Placebo-EF group had a decrease of force. Electromyography showed that the Placebo-IF group increased the muscle units recruitment without changing the firing rate. These findings show for the first time that the placebo effect in motor performance can be influenced by the subject\u2019s attentional focus, being enhanced with the internal focus of attention

People’s understanding of verbal risk descriptors in patient information leaflets : a cross-sectional national survey of 18- to 65-year-olds in England

Introduction Evidence suggests the current verbal risk descriptors used to communicate side effect risk in patient information leaflets (PILs) are overestimated. Objectives The aim was to establish how people understand the verbal risk descriptors recommended for use in PILs by the European Commission (EC), and alternative verbal risk descriptors, in the context of mild and severe side effects. Methods A cross-sectional online survey was carried out by a market research company recruiting participants aged between 18 and 65 years living in England. Data were collected between 18 March and 1 April 2016. Participants were given a hypothetical scenario regarding the risk of mild or severe medication side effects and asked to estimate how many out of 10,000 people would be affected for each of the verbal risk descriptors being tested. Results A total of 1003 participants were included in the final sample. The risks conveyed by the EC recommended verbal risk descriptors were greatly overestimated by participants. Two distinct distributions were apparent for participant estimates of side effect risks: those for ‘high risk’ verbal descriptors (e.g. ‘common’, ‘likely’, ‘high chance’) and those for ‘low risk’ verbal descriptors (e.g. ‘uncommon’, ‘unlikely’, ‘low chance’). Within these two groups, the distributions were near to identical regardless of what adverb (e.g. very, high, fair) or adjective (e.g. common, likely, chance) was used. The EC recommended verbal risk descriptors were more likely to be understood in accordance with their intended meanings when describing severe side effects. Very few demographic or psychological factors were consistently associated with how well participants understood the EC recommended verbal risk descriptors. Discussion The current verbal risk descriptors used in PILs are ineffective at best and misleading at worst. Discontinuing the use of verbal risk descriptors would limit the likelihood of people overestimating the risk of side effects

Changes in perception of treatment efficacy are associated to the magnitude of the nocebo effect and to personality traits

The nocebo effect in motor performance consists in a reduction of force and increase of fatigue following the application of an inert treatment that the recipient believes to be effective. This effect is variable across individuals and it is usually stronger if conditioning -exposure to the active effect of the treatment- precedes a test session, in which the treatment is inert. In the current explorative study we used a conditioning procedure to investigate whether subjective perception of treatment effectiveness changes between the conditioning and the test session and whether this change is related to dispositional traits and to the nocebo-induced reduction of force. Results showed that 56.1% of participants perceived the treatment as more effective in the test than in the conditioning session, had a more pronounced reduction of force, felt more effort and sense of weakness and were characterized by lower levels of optimism and higher anxiety traits compared to the other 43.9% of participants, who conversely perceived the treatment as less effective in the test session than in the conditioning. These findings highlight for the first time a link between changes in perception of treatment effectiveness, personality traits and the magnitude of the nocebo response in motor performance

Language development after cochlear implantation: an epigenetic model

Growing evidence supports the notion that dynamic gene expression, subject to epigenetic control, organizes multiple influences to enable a child to learn to listen and to talk. Here, we review neurobiological and genetic influences on spoken language development in the context of results of a longitudinal trial of cochlear implantation of young children with severe to profound sensorineural hearing loss in the Childhood Development after Cochlear Implantation study. We specifically examine the results of cochlear implantation in participants who were congenitally deaf (N = 116). Prior to intervention, these participants were subject to naturally imposed constraints in sensory (acoustic–phonologic) inputs during critical phases of development when spoken language skills are typically achieved rapidly. Their candidacy for a cochlear implant was prompted by delays (n = 20) or an essential absence of spoken language acquisition (n = 96). Observations thus present an opportunity to evaluate the impact of factors that influence the emergence of spoken language, particularly in the context of hearing restoration in sensitive periods for language acquisition. Outcomes demonstrate considerable variation in spoken language learning, although significant advantages exist for the congenitally deaf children implanted prior to 18 months of age. While age at implantation carries high predictive value in forecasting performance on measures of spoken language, several factors show significant association, particularly those related to parent–child interactions. Importantly, the significance of environmental variables in their predictive value for language development varies with age at implantation. These observations are considered in the context of an epigenetic model in which dynamic genomic expression can modulate aspects of auditory learning, offering insights into factors that can influence a child’s acquisition of spoken language after cochlear implantation. Increased understanding of these interactions could lead to targeted interventions that interact with the epigenome to influence language outcomes with intervention, particularly in periods in which development is subject to time-sensitive experience