Physiological, pathophysiological and pharmacological aspects of exogenous and endogenous opiates

Endogenous opioid peptides have been detected not only in the central nervous system but also in the peripheral autonomic nervous system of the gastrointestinal tract and pancreas and several other organs. In addition opioid active peptides have been found in certain nutrients such as wheat gluten and bovine and human milk. Functional studies have presented evidence for a participation of endogenous opioids in the regulation of certain pituitary and gastrointestinal functions. Apart from being a physiological neuroregulator there is evidence that endogenous opioids might play a role as a pathogenetic factor in various clinical disorders. The evidence for these different aspects of opioid function is reviewed in the present article.     

Democracy in animals: the evolution of shared group decisions

A 'consensus decision' is when the members of a group choose, collectively, between mutually exclusive actions. In humans, consensus decisions are often made democratically or in an 'equally shared' manner, i.e. all group members contribute to the decision. Biologists are only now realizing that shared consensus decisions also occur in social animals (other than eusocial insects). Sharing of decisions is, in principle, more profitable for groups than accepting the 'unshared' decision of a single dominant member. However, this is not true for all individual group members, posing a question as to how shared decision making could evolve. Here, we use a game theory model to show that sharing of decisions can evolve under a wide range of circumstances but especially in the following ones: when groups are heterogeneous in composition; when alternative decision outcomes differ in potential costs and these costs are large; when grouping benefits are marginal; or when groups are close to, or above, optimal size. Since these conditions are common in nature, it is easy to see how mechanisms for shared decision making could have arisen in a wide range of species, including early human ancestors.     

Transformation of Probiotic Yeast and Their Recovery from Gastrointestinal Immune Tissues Following Oral Gavage in Mice

Development of recombinant oral therapy would allow for more direct targeting of the mucosal immune system and improve the ability to combat gastrointestinal disorders. Adapting probiotic yeast in particular for this approach carries several advantages. These strains have not only the potential to synthesize a wide variety of complex heterologous proteins but are also capable of surviving and protecting those proteins during transit through the intestine. Critically, however, this approach requires expertise in many diverse laboratory techniques not typically used in tandem. Furthermore, although individual protocols for yeast transformation are well characterized for commonly used laboratory strains, emphasis is placed here on alternative approaches and the importance of optimizing transformation for less well characterized probiotic strains. Detailing these methods will help facilitate discussion as to the best approaches for testing probiotic yeast as oral drug delivery vehicles and indeed serve to advance the development of this novel strategy for gastrointestinal therapy.     

WHEN CONCRETIZED EMOTION‐BELIEF COMPLEXES DERAIL DECISION‐MAKING CAPACITY

There is an important gap in philosophical, clinical and bioethical conceptions of decision‐making capacity. These fields recognize that when traumatic life circumstances occur, people not only feel afraid and demoralized, but may develop catastrophic thinking and other beliefs that can lead to poor judgment. Yet there has been no articulation of the ways in which such beliefs may actually derail decision‐making capacity. In particular, certain emotionally grounded beliefs are systematically unresponsive to evidence, and this can block the ability to deliberate about alternatives. People who meet medico‐legal criteria for decision‐making capacity can react to health and personal crises with such capacity‐derailing reactions. One aspect of this is that a person who is otherwise cognitively intact may be unable to appreciate her own future quality of life while in this complex state of mind. This raises troubling ethical challenges. We cannot rely on the current standard assessment of cognition to determine decisional rights in medical and other settings. We need to understand better how emotionally grounded beliefs interfere with decision‐making capacity, in order to identify when caregivers have an obligation to intervene.     

大脑中的抉择神经元

近年来神经科学领域的进展表明,大脑中不仅存在如位置神经元之类的特异性编码感觉信息的神经元,也存在能够特异性地反映动物思考过程的神经元。在一系列以侧内顶叶(LIP)为目标的猕猴电生理实验中,人们发现LIP神经元的动作电位发放率可以反映抉择思考的过程。抉择的研究为我们打开了一个研究大脑高级认知功能的窗口。抉择神经元的发现表明了大脑的高级认知功能是基于与感觉信息处理类似的神经计算原理。     

Sensory ecology, receiver biases and sexual selection

During courtship, signals are sent between the sexes, and received signals contain information that forms the basis of decision making. Much is known about signal content, but less is known about signal design-what makes signals work efficiently? A consideration of design not only gives new insights into the evolution of signals (including novelty), but also allows the development of specific and testable predictions about the direction of evolution. Recently there has been increased interest in signal design, but this has resulted in some apparently divergent views in the literature.     

Eosinophilic disorders of the gastro-intestinal tract: an update

Eosinophilic diseases of the gastrointestinal tract, including eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), are rare chronic pathologies of the digestive system, with an immuno-mediated pathogenesis. Recent data suggest that, together with the “classic” IgE-response to allergens, also a delayed hypersensitivity mechanism could be involved in the development of eosinophilic disorders. EoE and EGE were studied only in the latest decades and as a consequence accurate data are not yet available, concerning not only pathogenesis, but also epidemiology, treatment and outcomes. The diagnosis of EoE is centered on endoscopic findings but the certainty is obtained by histological examination from biopsy samples, that has a sensitivity of 100% when based on five samples. The currently available treatments include topical corticosteroids, specific diets and endoscopic treatment. Concerning EGE, three subtypes (mucosal, muscular, and serosal) were identified. The diagnosis is based, as for EoE, on endoscopic and histological assessment, and the treatment includes pharmacological and dietetic approaches. Further studies are warranted in order to better define the etiology and pathogenesis of eosinophilic diseases of the gastrointestinal tract, and thus to develop more appropriate and specific therapies.     

Led into Temptation? Rewarding Brand Logos Bias the Neural Encoding of Incidental Economic Decisions

Human decision-making is driven by subjective values assigned to alternative choice options. These valuations are based on reward cues. It is unknown, however, whether complex reward cues, such as brand logos, may bias the neural encoding of subjective value in unrelated decisions. In this functional magnetic resonance imaging (fMRI) study, we subliminally presented brand logos preceding intertemporal choices. We demonstrated that priming biased participants' preferences towards more immediate rewards in the subsequent temporal discounting task. This was associated with modulations of the neural encoding of subjective values of choice options in a network of brain regions, including but not restricted to medial prefrontal cortex. Our findings demonstrate the general susceptibility of the human decision making system to apparently incidental contextual information. We conclude that the brain incorporates seemingly unrelated value information that modifies decision making outside the decision-maker's awareness.     

Implementation of shared decision making by physician training to optimise hypertension treatment. Study protocol of a cluster-RCT

ABSTRACT: BACKGROUND: Hypertension is one of the key factors causing cardiovascular diseases which make up the most frequent cause of death in industrialised nations. However about 60% of hypertensive patients in Germany treated with antihypertensives do not reach the recommended target blood pressure. The involvement of patients in medical decision making fulfils not only an ethical imperative but, furthermore, has the potential of higher treatment success. One concept to enhance the active role of patients is shared decision making. Until now there exists little information on the effects of shared decision making trainings for general practitioners on patient participation and on lowering blood pressure in hypertensive patients. METHODS: In a cluster-randomised controlled trial 1800 patients receiving antihypertensives will be screened with 24 h ambulatory blood pressure monitoring in their general practitioners' practices. Only patients who have not reached their blood pressure target (approximately 1200) will remain in the study (T1 -- T3). General practitioners of the intervention group will take part in a shared decision making-training after baseline assessment (T0). General practitioners of the control group will treat their patients as usual. Primary endpoints are change of systolic blood pressure and change of patients' perceived participation. Secondary endpoints are changes of diastolic blood pressure, knowledge, medical adherence and cardiovascular risk. Data analysis will be performed with mixed effects models. DISCUSSION: The hypothesis underlying this study is that shared decision making, realised by a shared decision making training for general practitioners, activates patients, facilitates patients' empowerment and contributes to a better hypertension control. This study is the first one that tests this hypothesis with a (cluster-) randomised trial and a large sample size.Trial registrationWHO International Clinical Trials: http://apps.who.int/trialsearch/Trial.aspx?TrialID=DRKS00000125.     

Dissociated neural processing for decisions in managers and non-managers

Functional neuroimaging studies of decision-making so far mainly focused on decisions under uncertainty or negotiation with other persons. Dual process theory assumes that, in such situations, decision making relies on either a rapid intuitive, automated or a slower rational processing system. However, it still remains elusive how personality factors or professional requirements might modulate the decision process and the underlying neural mechanisms. Since decision making is a key task of managers, we hypothesized that managers, facing higher pressure for frequent and rapid decisions than non-managers, prefer the heuristic, automated decision strategy in contrast to non-managers. Such different strategies may, in turn, rely on different neural systems. We tested managers and non-managers in a functional magnetic resonance imaging study using a forced-choice paradigm on word-pairs. Managers showed subcortical activation in the head of the caudate nucleus, and reduced hemodynamic response within the cortex. In contrast, non-managers revealed the opposite pattern. With the head of the caudate nucleus being an initiating component for process automation, these results supported the initial hypothesis, hinting at automation during decisions in managers. More generally, the findings reveal how different professional requirements might modulate cognitive decision processing.     

Consistent Implementation of Decisions in the Brain

Despite the complexity and variability of decision processes, motor responses are generally stereotypical and independent of decision difficulty. How is this consistency achieved? Through an engineering analogy we consider how and why a system should be designed to realise not only flexible decision-making, but also consistent decision implementation. We specifically consider neurobiologically-plausible accumulator models of decision-making, in which decisions are made when a decision threshold is reached. To trade-off between the speed and accuracy of the decision in these models, one can either adjust the thresholds themselves or, equivalently, fix the thresholds and adjust baseline activation. Here we review how this equivalence can be implemented in such models. We then argue that manipulating baseline activation is preferable as it realises consistent decision implementation by ensuring consistency of motor inputs, summarise empirical evidence in support of this hypothesis, and suggest that it could be a general principle of decision making and implementation. Our goal is therefore to review how neurobiologically-plausible models of decision-making can manipulate speed-accuracy trade-offs using different mechanisms, to consider which of these mechanisms has more desirable decision-implementation properties, and then review the relevant neuroscientific data on which mechanism brains actually use.     

Response of the polyphagous whitefly Bemisia tabaci B-biotype (Hemiptera: Aleyrodidae) to crop diversification - influence of multiple sensory stimuli on activity and fecundity

A fundamental question concerning crop diversification is which mechanisms determine pest population size in polycultures compared to monocultures. It has been proposed that polyphagous insects experience a difficulty in decision-making when selecting food and oviposition sites in the presence of different host plants. This hypothesis was tested in the extremely polyphagous whitefly Bemisia tabaci (Gennadius) B-biotype, where behaviour (movement) and fecundity of females were compared in choice and no-choice experiments in the laboratory. Two parallel tests, one on different crops, including cucumber, bean and tomato, and one on different tomato cultivars, were conducted using both a mixture of crops and of tomato cultivars, as opposed to the same crop or cultivar respectively. Bemisia tabaci showed a distinct behavioural preference for cucumber when exposed to different crops simultaneously suggesting that B. tabaci has no difficulty in choosing a host plant, i.e. in making a decision, when one of the plants offered in the choice test is a high-ranking host plant. Conversely, when only low-ranking hosts of similar, but not identical, signatures were present, female whiteflies appeared to have difficulty in making a decision, resulting in increased movement and reduced fecundity. This is consistent with both the hypothesis that polyphagous insects have a problem selecting a host plant when given multiple choices and with the hierarchy threshold model, under which egg loads are lessened between periods of searching for better host plants. The study illustrates how insect behaviour can be affected by inter-cropping not only with different crops, but also with different cultivars of the same crop, thus potentially providing a simple and efficient way of reducing whitefly population build-up.     

Fast to Forgive,Slow to Retaliate: Intuitive Responses in the Ultimatum Game Depend on the Degree of Unfairness

Evolutionary accounts have difficulty explaining why people cooperate with anonymous strangers they will never meet. Recently models, focusing on emotional processing, have been proposed as a potential explanation, with attention focusing on a dual systems approach based on system 1 (fast, intuitive, automatic, effortless, and emotional) and system 2 (slow, reflective, effortful, proactive and unemotional). Evidence shows that when cooperation is salient, people are fast (system 1) to cooperate, but with longer delays (system 2) they show greed. This is interpreted within the framework of the social heuristic hypothesis (SHH), whereby people overgeneralize potentially advantageous intuitively learnt and internalization social norms to ‘atypical’ situations. We extend this to explore intuitive reactions to unfairness by integrating the SHH with the ‘fast to forgive, slow to anger’ (FFSA) heuristic. This suggests that it is advantageous to be prosocial when facing uncertainty. We propose that whether or not someone intuitively shows prosociality (cooperation) or retaliation is moderated by the degree (certainty) of unfairness. People should intuitively cooperate when facing mild levels of unfairness (fast to forgive) but when given longer to decide about another''s mild level of unfairness should retaliate (slow to anger). However, when facing severe levels of unfairness, the intuitive response is always retaliation. We test this using a series of one-shot ultimatum games and manipulate level of offer unfairness (50:50 60:40, 70:30, 80:20, 90:10) and enforced time delays prior to responding (1s, 2s, 8s, 15s). We also measure decision times to make responses after the time delays. The results show that when facing mildly unfair offers (60:40) people are fast (intuitive) to cooperate but with longer delays reject these mildly unfair offers: ‘fast to forgive, and slow to retaliate’. However, for severely unfair offers (90:10) the intuitive and fast response is to always reject.     

The use of bacterial spore formers as probiotics

The field of probiosis has emerged as a new science with applications in farming and aqaculture as alternatives to antibiotics as well as prophylactics in humans. Probiotics are being developed commercially for both human use, primarily as novel foods or dietary supplements, and in animal feeds for the prevention of gastrointestinal infections, with extensive use in the poultry and aquaculture industries. The impending ban of antibiotics in animal feed, the current concern over the spread of antibiotic resistance genes, the failure to identify new antibiotics and the inherent problems with developing new vaccines make a compelling case for developing alternative prophylactics. Among the large number of probiotic products in use today are bacterial spore formers, mostly of the genus Bacillus. Used primarily in their spore form, these products have been shown to prevent gastrointestinal disorders and the diversity of species used and their applications are astonishing. Understanding the nature of this probiotic effect is complicated, not only because of the complexities of understanding the microbial interactions that occur within the gastrointestinal tract (GIT), but also because Bacillus species are considered allochthonous microorganisms. This review summarizes the commercial applications of Bacillus probiotics. A case will be made that many Bacillus species should not be considered allochthonous microorganisms but, instead, ones that have a bimodal life cycle of growth and sporulation in the environment as well as within the GIT. Specific mechanisms for how Bacillus species can inhibit gastrointestinal infections will be covered, including immunomodulation and the synthesis of antimicrobials. Finally, the safety and licensing issues that affect the use of Bacillus species for commercial development will be summarized, together with evidence showing the growing need to evaluate the safety of individual Bacillus strains as well as species on a case by case by basis.     

Expected utility violations evolve under status-based selection mechanisms

The expected utility theory of decision making under uncertainty, a cornerstone of modern economics, assumes that humans linearly weight “utilities” for different possible outcomes by the probabilities with which these outcomes occur. Despite the theory's intuitive appeal, both from normative and from evolutionary perspectives, many experiments demonstrate systematic, though poorly understood, patterns of deviation from EU predictions. This paper offers a novel theoretical account of such patterns of deviation by demonstrating that EU violations can emerge from evolutionary selection when individual “status” affects inclusive fitness. In humans, battles for resources and social standing involve high-stakes decision making, and assortative mating ensures that status matters for fitness outcomes. The paper therefore proposes grounding the study of decision making under uncertainty in an evolutionary game-theoretic framework.     

Automating assistance for safety critical decisions

Computer systems are increasingly being introduced to assist in decision making, including hazardous decision making. To ensure effective assistance, decision procedures should be theoretically sound, flexible in operation (particularly in unpredictable environments) and effectively accountable to human supervisors and auditors. Strengths and weaknesses of classical statistical decision models are discussed from these perspectives. It is argued that more can be learned from human decision behaviour than has traditionally been assumed, and this motivates the concept of a symbolic decision procedure (SDP). The SDP is defined, described in terms of first-order (predicate) logic, and its use illustrated in a decision support system for medicine. We point out that the classical numerical decision procedure is a special case of a generalized symbolic procedure, and discuss the potential for rigorous formalization of the latter. We conclude that symbolic decision procedures may meet requirements for assisting human operators in hazardous situations more satisfactorily than classical decision procedures.     

Acupuncture and moxibustion for stress-related disorders

Acupuncture and moxibustion, which medical doctors are licensed by the government of Japan to perform, can improve the psychological relationship between doctors and patients, especially when it is disturbed by a “game”, a dysfunctional interpersonal interaction that is repeated unintentionally. This advantage is due to the essential properties of acupuncture and moxibustion. Acupuncture and moxibustion are helpful in treating somatoform disorders, especially musculoskeletal symptoms. In Japan, a holistic acupuncture and moxibustion therapy called Sawada-style has been developed. This is based on fundamental meridian points that are considered to have effects on central, autonomic nervous, immune, metabolic, and endocrine systems to regulate the whole body balance. In addition, some of the fundamental points have effects on Qi, blood, and water patterns associated with major depression, generalized anxiety disorder, eating disorders, and somatoform disorders. The fixed protocol of Sawada-style would be suitable for large-scale, randomized, controlled studies in the future. Recent systematic reviews indicate that electroacupuncture would be a useful addition to antidepressant therapy for some symptoms accompanying fibromyalgia. Acupuncture and moxibustion are also recommended for irritable bowel syndrome, instead of Western drug therapy. Surprisingly, the dorsal prefrontal cerebral cortex, which is associated with a method of scalp acupuncture applied for gastrointestinal disorders, has been found to be activated in patients with irritable bowel syndrome. It is quite possible that regulation of this cortical area is related to the effect of scalp acupuncture. This acupuncture method can be effective not only for irritable bowel syndrome but also for other stress-related gastrointestinal disorders.     

Altruism and mental disorders

Data suggest that the theories of kin selection and reciprocal altruism are viable working models to explain altruistic behavior. It remains to be demonstrated if these models can explain the behavior of persons with mentaL disorders for whom altruistic behavior is reported to be reduced. This paper addresses this issue. Part I reviews proximate factors that are thought to influence both altruistic decision making and interindividual variation in altruistic behavior. The focus is on trait signaling by potential beneficiaries and the evaluation of signals and altruistic decision making by potential altruists. In Part II, points developed in Part I are combined with clinical and empirical findings to analyze data on personality disorders and dysthymic disorder. The analysis leads to three causal hypotheses: Reduced altruistic behavior may be an evolved strategy, a consequence of dysfunctional recognition systems or algorithms, and/or a secondary response to an increase in symptoms. Different disorders and features of disorders are explained by each hypothesis.