New scientific paradigms for probiotics and prebiotics

The inaugural meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP) was held May 3 to May 5 2002 in London, Ontario, Canada. A group of 63 academic and industrial scientists from around the world convened to discuss current issues in the science of probiotics and prebiotics. ISAPP is a non-profit organization comprised of international scientists whose intent is to strongly support and improve the levels of scientific integrity and due diligence associated with the study, use, and application of probiotics and prebiotics. In addition, ISAPP values its role in facilitating communication with the public and healthcare providers and among scientists in related fields on all topics pertinent to probiotics and prebiotics. It is anticipated that such efforts will lead to development of approaches and products that are optimally designed for the improvement of human and animal health and well being. This article is a summary of the discussions, conclusions, and recommendations made by 8 working groups convened during the first ISAPP workshop focusing on the topics of: definitions, intestinal flora, extra-intestinal sites, immune function, intestinal disease, cancer, genetics and genomics, and second generation prebiotics. Humans have evolved in symbiosis with an estimated 1014 resident microorganisms. However, as medicine has widely defined and explored the perpetrators of disease, including those of microbial origin, it has paid relatively little attention to the microbial cells that constitute the most abundant life forms associated with our body. Microbial metabolism in humans and animals constitutes an intense biochemical activity in the body, with profound repercussions for health and disease. As understanding of the human genome constantly expands, an important opportunity will arise to better determine the relationship between microbial populations within the body and host factors (including gender, genetic background, and nutrition) and the concomitant implications for health and improved quality of life. Combined human and microbial genetic studies will determine how such interactions can affect human health and longevity, which communication systems are used, and how they can be influenced to benefit the host. Probiotics are defined as live microorganisms which, when administered in adequate amounts confer a health benefit on the host.1 The probiotic concept dates back over 100 years, but only in recent times have the scientific knowledge and tools become available to properly evaluate their effects on normal health and well being, and their potential in preventing and treating disease. A similar situation exists for prebiotics, defined by this group as non-digestible substances that provide a beneficial physiological effect on the host by selectively stimulating the favorable growth or activity of a limited number of indigenous bacteria. Prebiotics function complementary to, and possibly synergistically with, probiotics. Numerous studies are providing insights into the growth and metabolic influence of these microbial nutrients on health. Today, the science behind the function of probiotics and prebiotics still requires more stringent deciphering both scientifically and mechanistically. The explosion of publications and interest in probiotics and prebiotics has resulted in a body of collective research that points toward great promise. However, this research is spread among such a diversity of organisms, delivery vehicles (foods, pills, and supplements), and potential health targets such that general conclusions cannot easily be made. Nevertheless, this situation is rapidly changing on a number of important fronts. With progress over the past decade on the genetics of lactic acid bacteria and the recent, 2,3 and pending, 4 release of complete genome sequences for major probiotic species, the field is now armed with detailed information and sophisticated microbiological and bioinformatic tools. Similarly, advances in biotechnology could yield new probiotics and prebiotics designed for enhanced or expanded functionality. The incorporation of genetic tools within a multidisciplinary scientific platform is expected to reveal the contributions of commensals, probiotics, and prebiotics to general health and well being and explicitly identify the mechanisms and corresponding host responses that provide the basis for their positive roles and associated claims. In terms of human suffering, the need for effective new approaches to prevent and treat disease is paramount. The need exists not only to alleviate the significant mortality and morbidity caused by intestinal diseases worldwide (especially diarrheal diseases in children), but also for infections at non-intestinal sites. This is especially worthy of pursuit in developing nations where mortality is too often the outcome of food and water borne infection. Inasmuch as probiotics and prebiotics are able to influence the populations or activities of commensal microflora, there is evidence that they can also play a role in mitigating some diseases. 5,6 Preliminary support that probiotics and prebiotics may be useful as intervention in conditions including inflammatory bowel disease, irritable bowel syndrome, allergy, cancer (especially colorectal cancer of which 75% are associated with diet), vaginal and urinary tract infections in women, kidney stone disease, mineral absorption, and infections caused by Helicobacter pylori is emerging. Some metabolites of microbes in the gut may also impact systemic conditions ranging from coronary heart disease to cognitive function, suggesting the possibility that exogenously applied microbes in the form of probiotics, or alteration of gut microecology with prebiotics, may be useful interventions even in these apparently disparate conditions. Beyond these direct intervention targets, probiotic cultures can also serve in expanded roles as live vehicles to deliver biologic agents (vaccines, enzymes, and proteins) to targeted locations within the body. The economic impact of these disease conditions in terms of diagnosis, treatment, doctor and hospital visits, and time off work exceeds several hundred billion dollars. The quality of life impact is also of major concern. Probiotics and prebiotics offer plausible opportunities to reduce the morbidity associated with these conditions. The following addresses issues that emerged from 8 workshops (Definitions, Intestinal Flora, Extra-Intestinal Sites, Immune Function, Intestinal Disease, Cancer, Genomics, and Second Generation Prebiotics), reflecting the current scientific state of probiotics and prebiotics. This is not a comprehensive review, however the study emphasizes pivotal knowledge gaps, and recommendations are made as to the underlying scientific and multidisciplinary studies that will be required to advance our understanding of the roles and impact of prebiotics, probiotics, and the commensal microflora upon health and disease management.

Cognitive behaviour therapy for psychosis: current evidence and future directions

The past decade has seen considerable growth in the evidence base of cognitive behavioural therapy for psychosis. Consistent reports of moderate effect sizes have led to such interventions being recommended as part of routine clinical practice. Most of this evidence is based on a generic form of CBT for psychosis applied to a heterogeneous group. An increase in the effectiveness of cognitive behavioural interventions may require new protocols. Such therapeutic developments should be based on the theoretical understanding of the psychological processes associated with specific forms of psychotic presentation. The current evidence base of CBT for psychosis is reviewed, and barriers that have held back the development of this research are discussed.

Brief cognitive behavioural therapy for extreme shape concern: an evaluation

Objectives. This study was designed to evaluate a new brief cognitive-behavioural intervention to reduce concerns about body shape. Design. Women with high levels of shape concern (N = 50) were randomly assigned to cognitive behaviour therapy or applied relaxation (AR). Baseline assessments were made and then women received their treatment immediately after this assessment, ('immediate' treatment) or 5 weeks after this assessment, during which time no treatment was given ('delayed' treatment, DT). Methods. Shape concern and related cognitions and emotions were assessed at baseline, post-treatment and at 4 and 12 week follow-up (FU). Results. Immediate treatment was superior to DT in reducing shape concerns, and this difference was maintained at 4 week FU. The cognitive behavioural intervention was more effective than AR in changing shape concern and this difference was largely maintained for 3 months. Conclusions. These initial findings support the further investigation of this brief intervention.

Deficient acquisition and consolidation: intertrial free recall performance in Alzheimer's disease and mild cognitive impairment

Previous research demonstrates that dementia of the Alzheimer type (DAT) is characterised by deficits of episodic memory, especially in the acquisition of new material. As well as this deficit in acquisition, some researchers have also argued for a deficit in consolidation in DAT. We examined acquisition and consolidation by measuring the intertrial gained and lost access in DAT, Mild Cognitive Impairment (MCI) and controls. We report findings from a study of clinical data based on assessment of patients using three free recall trials of a word list. We found that both DAT and MCI groups showed a deficit in acquisition and consolidation of items between trials relative to controls. Moreover, the DAT group was significantly impaired relative to the MCI group for both acquisition and consolidation. Correlations within each group showed that there were strong relationships between intertrial measures and standard measures of memory function. Importantly in no group was there a significant correlation between our measures of acquisition and consolidation: we argue that these measures reflect different underlying processes, and the failure to consolidate in DAT and MCI is not related to the deficit in acquisition. Finally, we showed strong correlations between our measure and dementia severity, suggesting that acquisition and consolidation both get worse as the dementia progresses.

Does training improve understanding of core concepts in cognitive behaviour therapy by people with intellectual disabilities? A randomized experiment

Background. People with intellectual disabilities (ID) experience similar or even higher rates of mental health problems than the general population and there is a need to develop appropriate treatments. Cognitive behaviour therapy (CBT) is effective for a wide range of disorders in the general population. However, there is some evidence that people with ID may lack the cognitive skills needed to take part in CBT. Aims. To test if people with ID can learn skills required for CBT, specifically the ability to distinguish between thoughts, feelings, and behaviours and to link thoughts and feelings (cognitive mediation). Method. A randomized independent groups design was used to examine the effect of training in CBT on two tasks measuring CBT skills. Thirty-four adults with ID were randomly allocated to the experimental condition ðN ¼ 18Þ or to the control condition ðN ¼ 16Þ. CBT skills were assessed blind at baseline and after the intervention. Results. The training led to significant improvements in participants’ ability to link thoughts and feelings, and this skill was generalized to new material. There was no effect of training on participants’ ability to distinguish amongst thoughts, feelings, and behaviours. People with ID can, therefore, learn some skills required for CBT. This implies that preparatory training for CBT might be useful for people with ID. The results might be applicable to other groups who find aspects of CBT difficult.

Neural correlates of true and false memory in mild cognitive impairment

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer’s disease, which has been described as a ‘disconnection syndrome’.

Thinking for speaking and linguistic relativity among bilinguals: towards a new research agenda

This article evaluates how the different papers in this special issue fill a gap in our understanding of cognitive processes that are being activated when second language learners or bilinguals prepare to speak. All papers are framed in Slobin’s (1987) Thinking for Speaking theory, and aim to test whether the conceptualisation patterns that were learned in early childhood can be relearned or restructured in L2 acquisition. In many papers the focus is on identifying constraints on this restructuring process. Among these constraints, the role of typological differences between languages is investigated in great depth. The studies involve different types of learners, language combinations and tasks. As all informants were given verbal rather than non-verbal tasks, the focus is here on the effects of conceptual transfer from one language on another, and not on the effects of language on non-linguistic cognition. The paper also sketches different avenues for further research in this field and proposes that researchers working in this field might want to take up the challenge of investigating whether speakers of different languages perceive motion outside explicitly verbal contexts differently, as this will enable us to gain an understanding of linguistic relativity effects in this domain. Studying which teaching methods can help learners to restructure their conceptualisation patterns may also shed new light on the aspects of discourse organization and motion event construal that are most difficult for learners.

Combined neurostimulation and neuroimaging in cognitive neuroscience: past, present, and future

Modern neurostimulation approaches in humans provide controlled inputs into the operations of cortical regions, with highly specific behavioral consequences. This enables causal structure–function inferences, and in combination with neuroimaging, has provided novel insights into the basic mechanisms of action of neurostimulation on dis- tributed networks. For example,more recent work has established the capacity of transcranialmagnetic stimulation (TMS) to probe causal interregional influences, and their interaction with cognitive state changes. Combinations of neurostimulation and neuroimaging now face the challenge of integrating the known physiological effects of neu- rostimulationwith theoretical and biologicalmodels of cognition, for example,when theoretical stalemates between opposing cognitive theories need to be resolved. This will be driven by novel developments, including biologically informedcomputational network analyses for predicting the impactofneurostimulationonbrainnetworks, as well as novel neuroimaging and neurostimulation techniques. Such future developments may offer an expanded set of tools withwhich to investigate structure–function relationships, and to formulate and reconceptualize testable hypotheses about complex neural network interactions and their causal roles in cognition

Updating existing emotional memories involves the frontopolar/orbitofrontal cortex in ways that acquiring new emotional memories does not

In life, we must often learn new associations to people, places, or things we already know. The current fMRI study investigated the neural mechanisms underlying emotional memory updating. Nineteen participants first viewed negative and neutral pictures and learned associations between those pictures and other neutral stimuli, such as neutral objects and encoding tasks. This initial learning phase was followed by a memory updating phase, during which participants learned picture-location associations for old pictures (i.e., pictures previously associated with other neutral stimuli) and new pictures (i.e., pictures not seen in the first phase). There was greater frontopolar/orbito-frontal (OFC) activity when people learned picture–location associations for old negative pictures than for new negative pictures, but frontopolar OFC activity did not significantly differ during learning locations of old versus new neutral pictures. In addition, frontopolar activity was more negatively correlated with the amygdala when participants learned picture–location associations for old negative pictures than for new negative or old neutral pictures. Past studies revealed that the frontopolar OFC allows for updating the affective values of stimuli in reversal learning or extinction of conditioning [e.g., Izquierdo, A., & Murray, E. A. Opposing effects of amygdala and orbital PFC lesions on the extinction of instrumental responding in macaque monkeys. European Journal of Neuroscience, 22, 2341–2346, 2005]; our findings suggest that it plays a more general role in updating associations to emotional stimuli.

Attacking human implants: a new generation of cybercrime

Human ICT implants, such as RFID implants, cochlear implants, cardiac pacemakers, Deep Brain Stimulation, bionic limbs connected to the nervous system, and networked cognitive prostheses, are becoming increasingly complex. With ever-growing data processing functionalities in these implants, privacy and security become vital concerns. Electronic attacks on human ICT implants can cause significant harm, both to implant subjects and to their environment. This paper explores the vulnerabilities which human implants pose to crime victimisation in light of recent technological developments, and analyses how the law can deal with emerging challenges of what may well become the next generation of cybercrime: attacks targeted at technology implanted in the human body. After a state-of-the-art description of relevant types of human implants and a discussion how these implants challenge existing perceptions of the human body, we describe how various modes of attacks, such as sniffing, hacking, data interference, and denial of service, can be committed against implants. Subsequently, we analyse how these attacks can be assessed under current substantive and procedural criminal law, drawing on examples from UK and Dutch law. The possibilities and limitations of cybercrime provisions (eg, unlawful access, system interference) and bodily integrity provisions (eg, battery, assault, causing bodily harm) to deal with human-implant attacks are analysed. Based on this assessment, the paper concludes that attacks on human implants are not only a new generation in the evolution of cybercrime, but also raise fundamental questions on how criminal law conceives of attacks. Traditional distinctions between physical and non-physical modes of attack, between human bodies and things, between exterior and interior of the body need to be re-interpreted in light of developments in human implants. As the human body and technology become increasingly intertwined, cybercrime legislation and body-integrity crime legislation will also become intertwined, posing a new puzzle that legislators and practitioners will sooner or later have to solve.

A new rapid detection threshold method for use with older adults: reducing fatigue whilst maintaining accuracy

Taste and smell detection threshold measurements are frequently time consuming especially when the method involves reversing the concentrations presented to replicate and improve accuracy of results. These multiple replications are likely to cause sensory and cognitive fatigue which may be more pronounced in elderly populations. A new rapid detection threshold methodology was developed that quickly located the likely position of each individuals sensory detection threshold then refined this by providing multiple concentrations around this point to determine their threshold. This study evaluates the reliability and validity of this method. Findings indicate that this new rapid detection threshold methodology was appropriate to identify differences in sensory detection thresholds between different populations and has positive benefits in providing a shorter assessment of detection thresholds. The results indicated that this method is appropriate at determining individual as well as group detection thresholds.

Linguistic relativity in SLA: towards a new research programme

The purpose of the current article is to support the investigation of linguistic relativity in second language acquisition and sketch methodological and theoretical prerequisites toward developing the domain into a full research program. We identify and discuss three theoretical-methodological components that we believe are needed to succeed in this enterprise. First, we highlight the importance of using nonverbal methods to study linguistic relativity effects in second language (L2) speakers. The use of nonverbal tasks is necessary in order to avoid the circularity that arises when inferences about nonverbal behavior are made on the basis of verbal evidence alone. Second, we identify and delineate the likely cognitive mechanisms underpinning cognitive restructuring in L2 speakers by introducing the theoretical framework of associative learning. By doing so, we demonstrate that the extent and nature of cognitive restructuring in L2 speakers is essentially a function of variation in individual learners’ trajectories. Third, we offer an in-depth discussion of the factors (e.g., L2 proficiency and L2 use) that characterize those trajectories, anchoring them to the framework of associative learning, and reinterpreting their relative strength in predicting L2 speaker cognition

Televised Whorf: cognitive restructuring in advanced foreign language learners as a function of audio-visual media exposure

The encoding of goal-oriented motion events varies across different languages. Speakers of languages without grammatical aspect (e.g., Swedish) tend to mention motion endpoints when describing events, e.g., “two nuns walk to a house,”, and attach importance to event endpoints when matching scenes from memory. Speakers of aspect languages (e.g., English), on the other hand, are more prone to direct attention to the ongoingness of motion events, which is reflected both in their event descriptions, e.g., “two nuns are walking.”, and in their non-verbal similarity judgements. This study examines to what extent native speakers of Swedish (n = 82) with English as a foreign language (FL) restructure their categorisation of goal-oriented motion as a function of their English proficiency and experience with the English language (e.g., exposure, learning). Seventeen monolingual native English speakers from the United Kingdom (UK) were engaged for comparison purposes. Data on motion event cognition were collected through a memory-based triads matching task, in which a target scene with an intermediate degree of endpoint orientation was matched with two alternative scenes with low and high degrees of endpoint orientation, respectively. Results showed that the preference among the Swedish speakers of L2 English to base their similarity judgements on ongoingness rather than event endpoints was correlated with their use of English in their everyday lives, such that those who often watched television in English approximated the ongoingness preference of the English native speakers. These findings suggest that event cognition patterns may be restructured through the exposure to FL audio-visual media. The results thus add to the emerging picture that learning a new language entails learning new ways of observing and reasoning about reality.