Limb proportions show developmental plasticity in response to embryo movement.

Animals have evolved limb proportions adapted to different environments, but it is not yet clear to what extent these proportions are directly influenced by the environment during prenatal development. The developing skeleton experiences mechanical loading resulting from embryo movement. We tested the hypothesis that environmentally-induced changes in prenatal movement influence embryonic limb growth to alter proportions. We show that incubation temperature influences motility and limb bone growth in West African Dwarf crocodiles, producing altered limb proportions which may, influence post-hatching performance. Pharmacological immobilisation of embryonic chickens revealed that altered motility, independent of temperature, may underpin this growth regulation. Use of the chick also allowed us to merge histological, immunochemical and cell proliferation labelling studies to evaluate changes in growth plate organisation, and unbiased array profiling to identify specific cellular and transcriptional targets of embryo movement. This disclosed that movement alters limb proportions and regulates chondrocyte proliferation in only specific growth plates. This selective targeting is related to intrinsic mTOR (mechanistic target of rapamycin) pathway activity in individual growth plates. Our findings provide new insights into how environmental factors can be integrated to influence cellular activity in growing bones and ultimately gross limb morphology, to generate phenotypic variation during prenatal development.

The association between the development of weighing technology, possession and use of weighing scales, and self-reported severity of disordered eating.

The aim of this study is to investigate David Healy's hypothesis that the development of weighing technologies significantly contributes to the development of anorexia nervosa. A newly developed questionnaire and the EAT-26 were used to investigate these ideas. The key results from this study are that a positive correlation between EAT-26 scores and the frequency of weighing (p ≤ 0.001), and that group differences were also found between the control group and those with an EAT-26 score of 20 or above on weighing scale ownership (p = 0.017), the type of scale owned (p = 0.002) and whether people weighed themselves often (p ≤ 0.001); indicating that those with a higher EAT-26 score were more likely to own weighing scales, own digital weighing scales, and weigh themselves more often. These results suggest that the increased precision and usage of weighing technologies may potentially be a causal factor in disordered eating, and as such, this idea can be extended to suggest the hypothesis that frequent and precise weighing of anorexic patients in therapy may actually be counter-productive.

Why are doctors still prescribing neuroleptics?

There are two main pharmacological methods of suppressing undesired behaviour: sedation or neuroleptics. Traditionally, the invention of neuroleptics has been hailed as one of the major clinical breakthroughs of the twentieth century, since they calmed agitation without (necessarily) causing sedation. The specifically neuroleptic form of behavioural control is achieved by making patients psychologically Parkinsonian, which entails emotional blunting and consequent demotivation. Furthermore, chronic neuroleptic usage creates dependence, so that in the long term, neuroleptics are doing most patients more harm than good. The introduction of 'atypical' neuroleptics (neuroleptically-weak but strongly sedative neuroleptics) has made only a difference in degree, and at the cost of a wide range of potentially fatal metabolic and other side-effects. For half a century, the creation of millions of Parkinsonian patients may have been misinterpreted as a 'cure' for schizophrenia. Such a wholesale re-interpretation of neuroleptic therapy represents an unprecedented disaster for the self-image and public reputation of both psychiatry and the whole medical profession. Nonetheless, except as a last resort, neuroleptics should swiftly be replaced by gentler and safer sedatives.

Diazepam with your dinner, Sir? The lifestyle drug-substitution strategy: a radical alcohol policy.

Over recent decades the drink problem in the British Isles has grown to become arguably the worst in the Western world, combining the high average alcohol intake of southern Europe with binge-drinking typical of extreme latitudes. Since the problem continues to worsen, and traditional strategies regulating price and access are probably untenable, radical new alcohol policies are required. The drug-substitution strategy is based on an assumption that most people use lifestyle drugs rationally for self-medication purposes, to achieve specific desired psychological effects, especially enhanced well-being. When there is access to an equally effective, but safer, alternative drug, then people would tend to switch to it (especially when the substitute is legal and socially-acceptable). There are several safer lifestyle drug-substitutes for alcohol, including benzodiazepines, SSRIs and marijuana. Southern Europeans use alcohol mainly as an anxiolytic social lubricant, taken in low but frequent doses with high annual per capita consumption, and for this pattern, benzodiazepines might be a medically safer lifestyle drug-substitute. Northern Europeans traditionally use alcohol in high doses as a euphoric intoxicant, and for this pattern, marijuana might be a safer and less-antisocial substitute. Since this risk-benefit calculus implies that there are better alternatives to alcohol, government policy should promote safer lifestyle drug-substitutes by removing legal barriers and altering the balance of economic and social incentives.

Medical research funding may have over-expanded and be due for collapse.

The continual and uninterrupted expansion of medical research funding is generally assumed to be a permanent feature of modern societies, but this expectation may turn out to be mistaken. Sciences tend to go through boom and bust phases. Twentieth century physics is an example where huge increases in funding followed an era of scientific breakthroughs. Speculative over-expansion led to diminishing returns on investment, then a collapse in funding. We predict that medicine will follow the same trajectory. After prolonged over-funding of the 'basic-to-applied' model of clinical innovation, and a progressive shift towards Big Science organization, medical research has become increasingly inefficient and ineffective. Although incremental improvements to existing treatment strategies continue, the rate of significant therapeutic breakthroughs has been declining for three decades. Medical science now requires rationalization and modernization. From this perspective, the current level of medical research funding looks like a bubble due to burst.

Delirium and psychotic symptoms--an integrative model.

Delirium may be a common cause of psychotic symptoms such as hallucinations, bizarre delusions and thought-disorder, even in conditions such as schizophrenia, mania and depression, where delirium has traditionally been excluded by definition. This situation is a consequence of the insensitivity of current clinical criteria for the diagnosis of delirium, which recognize only the most severe forms of functional brain impairment (including disorientation and clouding of consciousness). Serial electroencephalograms (EEGs) are the most sensitive method for detecting delirium, and until such studies are performed, the true incidence of delirium in psychotic patients will not be known. The suggested causal mechanism of delirium in psychosis is sleep disruption. Sleep is essential for maintenance of memory circuits, which otherwise suffer progressive synaptic weakening due to molecular turnover. When sleep is disrupted, memory circuits deteriorate, and subsequent activation of incompetent circuits can generate psychotic symptoms. Induction of physiologically normal sleep would therefore be expected to produce significant clinical improvement in patients with psychotic symptoms. Furthermore, the 'anti-delirium' action of electroconvulsive therapy may account for its effectiveness in alleviating a wide range of psychiatric and neurological pathologies.

The potential for pharmacological treatment of unpleasant psychological symptoms to increase personal fulfillment in old age.

As some people get older, they experience a decline in their subjective sense of fulfillment. Life may become less rewarding, happiness diminished in intensity. This is usually regarded as an inevitable consequence of the ageing process: regrettable, but a circumstance to which stoical endurance is the only constructive response. This situation is potentially avoidable, for some individuals at least; not at some indefinite point in the future, but now. By using existing and available drugs in a novel fashion to treat the unpleasant psychological symptoms associated with ageing, a substantial improvement in the quality of life may be obtained.

The malaise theory of depression: major depressive disorder is sickness behavior and antidepressants are analgesic.

The malaise theory of depression constitutes a re-conceptualization and re-definition of major depressive disorder (MDD). It is proposed that the state or emotion of malaise should be considered the core symptom of depression, rather than sadness of mood. The syndrome of MDD is identified as a consequence of inappropriate sickness behavior mediated by immune activation including abnormalities in cytokines. Antidepressants are suggested to exert their specifically beneficial effects through an analgesic effect on the core dysphoric symptoms of malaise. These ideas are consistent with a substantial body of published literature and lead to a wide range of testable predictions.

The 'anti-delirium' theory of electroconvulsive therapy action.

It is proposed that electroconvulsive therapy (ECT) is not specifically mood-elevating or anti-depressant but that its effect is as an anti-delirium intervention. I suggest that ECT exerts its primary therapeutic effects by inducing a generalized epileptic seizure which operates on the brain like a deep and restorative sleep that acts rapidly to resolve delirium. Provided that the diagnosis is made using sufficiently sensitive criteria, delirium is here assumed to be a common feature of many so-called 'functional' psychoses - frequently occurring as a consequence of sleep deprivation, and leading to symptoms such as hallucinations, bizarre delusions and psychomotor retardation. Testable predictions of this 'anti-delirium' theory of ECT action are described.