Gephyrin: where do we stand, where do we go?

Gephyrin is a multifunctional protein responsible for molybdenum cofactor synthesis and the clustering of glycine and GABA(A) receptors at inhibitory synapses. Based on the structure of its two conserved domains, G and E, gephyrin is thought to form a hexagonal lattice serving as a scaffold for accessory proteins at postsynaptic sites. However, important aspects of gephyrin gene expression, protein structure and regulation, as well as the role of gephyrin in synapse formation and plasticity, remain poorly understood. Here we review the current state of knowledge about gephyrin, highlighting new research avenues based on a different structural model and a revised nomenclature for gephyrin splice variants. Unraveling the biology of gephyrin will further our understanding of glycinergic and GABAergic synapses in health and disease.     

Why do we sleep?

Slow-wave sleep consists in slowly recurring waves that are associated with a large-scale spatio-temporal synchrony across neocortex. These slow-wave complexes alternate with brief episodes of fast oscillations, similar to the sustained fast oscillations that occur during the wake state. We propose that alternating fast and slow waves consolidate information acquired previously during wakefulness. Slow-wave sleep would thus begin with spindle oscillations that open molecular gates to plasticity, then proceed by iteratively 'recalling' and 'storing' information primed in neural assemblies. This scenario provides a biophysical mechanism consistent with the growing evidence that sleep serves to consolidate memories.     

Stroke care in Spain. What do we have? What do we need?

The high level of scientific evidence which supports the recommendations for the care of acute stroke in Stroke Units (SU) with a good health care network, it does not correspond to the level of introduction in Spain. In this regard, the Cerebrovascular Diseases Study Group (GEECV) of the Spanish Society of Neurology has taken the initiative to conduct the "National Survey of Stroke Care" that will help to determine the real situation in acute stroke management in Spain just before the approval of the National Stroke Strategy (NSS) by the Ministry of Health and concludes that in the first semester of 2009 there were 39 SUs, unevenly distributed with higher concentration in Madrid and Barcelona. Although the approval of the NSS was a major achievement, much remains to be done to meet the objectives. We thank the GEECV?s initiative, which gives us an "X-ray" of the, not very satisfactory, state of stroke care in Spain in December 2008, and highlighting some achievements and the many shortcomings. Therefore, we must continue to improve, refine our data collection with records that include all available resources and all the stroke patients attended. We invite GEECV to carry out a second study to evaluate the impact of NSS and to serve as a stimulus to achieve a substantial improvement in stroke care in Spain, closer to the recommendations of the new PASI document.     

Pediatric stroke: what do we know and what do we need to know?

Stroke is a heterogeneous disorder and an important cause of mortality and chronic morbidity in children. Estimates of international incidence rates for childhood stroke have varied widely. Arterial ischemic stroke is reported to be more common than hemorrhagic stroke in children. The clinical presentation of stroke in children differs according to the child's age and stroke type and location. Several risk factors for ischemic and hemorrhagic stroke in children have been reported and include cardiac disorders, blood disorders, vasculopathies, viral infections, and arteriovenous malformations. Current treatment recommendations for stroke in children are based on small nonrandomized trials, adult stroke studies, case series, or consensus or individual expert opinion. Over half of children with stroke will develop lifelong cognitive or motor disability, and up to a third will have a recurrent stroke. International studies have provided important information on stroke in children, but major gaps in our knowledge of the disorder still exist. Currently, there is a need for prospective cohort studies in diverse populations, which utilize a consensus pediatric stroke classification system and a standard evaluation of risk factors and outcome, so that treatment and prevention strategies can be developed.     

How much sleep do we need?

There is increasing concern for sleeplessness-related risks in modern society. Some recent epidemiological data seem to support the view that many segments of the adult population have chronically inadequate sleep. On the other hand, some experts have claimed that our core, basic amount of sleep is around 6 h per night, and that the rest of our sleep can be easily curtailed, being unnecessary to fulfill any sleep need. However, experimental data on the effects of both acute and cumulative partial sleep deprivation (PSD) consistently point out that sleep restriction has substantial negative effects on sleepiness, motor and cognitive performance and mood, as well as on some metabolic, hormonal and immunological variables. As chronic PSD may have serious long-term adverse health effects, it should be avoided in the general population. In the short-term, the effects of sleep curtailment seem to accumulate linearly, while the effects of long-term PSD should be further investigated, as the few available studies are flawed by methodological weaknesses. On the other hand, there is evidence that extending sleep by 2-3 h beyond the norm produces only marginal benefits for an average individual. Finally, it is underlined that, as large individual differences do exist in the need for sleep, the search for the sleep need may be vain. A somnotypology, taking into account age, gender and the position in both the sleep-alert and the morningness-eveningness continuum, should help in the search for the actual individual sleep need. 2001 Harcourt Publishers Ltd     

Delirium: Where do we stand?

Clinicians are likely to encounter delirium frequently, particularly in inpatient and intensive care settings. However, delirium is underrecognized and undertreated because of its heterogeneous and fluctuating presentation and due to the limitations in resources and training in contemporary clinical settings. Translation of current knowledge about delirium into clinical practice may improve patient care and benefit public health economics. Hence, this review comprehensively discusses the phenomenology and pathophysiology of delirium and its presenting features, risk factors, differential diagnoses, assessment, prognosis, and treatment with antipsychotics; the goal is to facilitate better prevention, recognition, and treatment of delirium. Available research is reviewed, limitations of the research are discussed, and future directions for further delirium research are identified.     

Schizophrenia today: what do we know-and how sure are we?

The growth of our understanding of the biology and treatment of schizophrenia is still very much a work in progress. In this article, which introduces a series of papers presented at a conference entitled "Schizophrenia: Doing the Right Thing Well," held at Northcoast Behavioral Healthcare System (Cleveland, May 2000), the authors provide a short overview of what is known about schizophrenia today. He briefly reviews findings concerning epidemiology, phenomenology and course, neurobiology, and treatment, and highlights some of the most significant findings to date as well as areas needing further research. Early evaluation and treatment, in advance of the florid presentation of the illness, offer much hope, but only if our knowledge of the diagnostic specificity of prodromal and neurodevelopmental precursors can be enhanced. Significant advances in medication treatment have been made, and the newer antipsychotic medications overall have a more benign adverse-effect profile than the older agents, although the specter of endocrine/metabolic complications looms as a significant long-term concern. The authors conclude that, although many advances in our understanding of the etiology and treatment of schizophrenia have been made, much remains to be learned.     

Recovery-based practice: do we know what we mean or mean what we know?

The concept of recovery is now widely promoted as the guiding principle for the provision of mental health services in Australia and overseas. While there is increasing pressure on service providers to ensure that services are recovery oriented, the way in which recovery-based practice is operationalized at the coalface presents a number of challenges. These are discussed in the context of five key questions that address (i) the appropriateness of recovery as a focus for service delivery, (ii) the distinction between recovery as a process and an outcome, (iii) the assessment of recovery initiatives, (iv) the alignment of recovery with current service delivery models, and (v) the risks associated with recovery-based practice. It is argued that these questions provide a framework for a debate that must extend beyond patients and providers of mental health services to the broader public, whose attitudes will ultimately determine the possibilities and limits of recovery-oriented practice.     

Brain temperature: what do we know?

This review article presents a summary of recent efforts to understand brain temperature and its regulation under different conditions. Brain temperature has a crucial influence on brain processes. Its regulation is the outcome of the balance of core and arterial blood temperatures, cerebral blood flow, brain metabolism, functional conditions, and external temperature. However, the relationship between these factors is not fully understood and several uncertainties remain. There are no satisfactory normative data on temperatures throughout the brain, but new technologies promise to fill this gap. Brain temperature changes with brain functional activation and under pathological conditions in ways that are not understood. A full understanding of brain temperature control is mandatory to optimize attempts at brain cooling during clinical conditions such as stroke and head injury.     

Why do we need nongenomic glucocorticoid mechanisms?

Glucocorticoids (GCs) are a class of steroid hormones that have been known to be involved in various physiological processes and to play a pivotal role in preserving basal and stress-related homeostasis. GCs are also widely used clinically as anti-inflammatory, immunosuppressive, anti-shock drugs. It is believed traditionally that GCs exert most of their effects genomically. In addition to the well-known classical genomic mechanisms, GCs also affect various functions via rapid, nongenomic mechanisms. The therapeutic benefits of nongenomic GC actions have been exploited in clinical medicine, especially with high-dose pulsed glucocorticoid administration. However, it is certainly not the case that the inherent nongenomic glucocorticoid mechanisms evolved only for their clinical utility. Here, we review the recent literature on nongenomic actions of GCs related to stress and the physiological significance of these actions, and we propose reasons why nongenomic mechanisms of GC actions are needed.