Medical hypotheses
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Critically ill patients are at high risk of developing serious neurological dysfunctions including delirium and long-term neurocognitive impairment. Here a novel mechanism is proposed for this highly deleterious condition. A growing body of evidence has shown that critical illness and its treatment can lead to de novo cerebral atrophy including white and grey matter abnormalities, delirium, and neurocognitive decline. ⋯ In combination with exposure to other ICU related threats to neurocognitive function, prolonged decoupling of this circuit may lead to deleterious neurodegenerative consequences such as excitotoxicity. Over time this has the potential to result in apoptosis and long-term cognitive impairment. Delirium appears to be a good candidate for the causal mechanism of ICU related cognitive decline and may be a critical point of intervention.
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Reducing sugars can react non-enzymatically with the amino groups of proteins to form reversible Schiff bases, and then Amadori products. These early glycation products undergo further complex reactions such as rearrangement, dehydration and condensation to become irreversibly cross-linked, heterogeneous fluorescent derivatives termed "advanced glycation end products" (AGEs). The pathological role of the non-enzymatic glycation of proteins has become increasingly evident in various types of disorders such as diabetic vascular complications, neurodegenerative diseases, and melanoma growth and metastasis. ⋯ Further, we have shown that atorvastain blocks the AGE-signaling to C-reactive protein (CRP) expression in human hepatoma cells in vitro via anti-oxidative properties. These observations led us to speculate that atorvastatin could be a promising remedy for treating patients with AGE-related disorders. In this paper, we would like to propose the possible ways of testing our hypotheses. (1) Does atorvastatin treatment reduce the development and progression of diabetic vascular complications with normocholesterolemic patients? If the answer is yes, is this beneficial effect of atorvastatin superior to that of other cholesterol-lowering agents with equihypolipidemic properties? (2) Are these beneficial effects of atorvastain attributed to its AGE-lowing properties? Does the blockade by atorvastain of the AGE signaling pathway, in other words, the suppression of 8-hydroxydeoxyguanosine and CRP levels by atorvastatin treatment, contribute to its cardioprotective properties? (3) Does the treatment with atorvastatin decrease the incidence of neurodegenerative disorders such as Alzheimer's disease and/or prolong the survival of these patients? (4) How about the effects of atorvastatin on the incidence of malignant melanoma? These prospective studies will provide further valuable information whether the blockade by atorvastatin of the AGE formation or the AGE-downstream signaling could be clinically relevant.
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Editorial Historical Article
Measuring revolutionary biomedical science 1992-2006 using Nobel prizes, Lasker (clinical medicine) awards and Gairdner awards (NLG metric).
The Nobel prize for medicine or physiology, the Lasker award for clinical medicine, and the Gairdner international award are given to individuals for their role in developing theories, technologies and discoveries which have changed the direction of biomedical science. These distinctions have been used to develop an NLG metric to measure research performance and trends in 'revolutionary' biomedical science with the aim of identifying the premier revolutionary science research institutions and nations from 1992-2006. I have previously argued that the number of Nobel laureates in the biomedical field should be expanded to about nine per year and the NLG metric attempts to predict the possible results of such an expansion. ⋯ The University of Oxford, UK, was the only institution outside of the USA which featured as a significant centre of revolutionary biomedical science. Long-term success at the highest level of revolutionary biomedical science (and probably other sciences) probably requires a sufficiently large number of individually-successful large institutions in open competition with one another--as in the USA. If this model cannot be replicated within smaller nations, then it implies that such arrangements need to be encouraged and facilitated in multi-national units.
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The Thomson Scientific Impact Factor (IF) for Medical Hypotheses has risen to 1.299 for 2006. This means that the IF has more than doubled since 2004, when it stood at 0.607. Using Elsevier's Scopus database; in 2004 there were 437 citations to Medical Hypotheses papers published in the previous two years--by 2006 this had trebled to 1216 citations. ⋯ Since Medical Hypotheses is performing adequately by such criteria, this provides a powerful answer to those who fetishize peer review and regard any other system of evaluation as suspect. Journal review procedures are merely a means to the end, and the end is a journal that serves a useful function in the dynamic process of science. Medical Hypotheses can now claim to perform such a role.
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Perhaps the biggest challenge facing neuroscience at the dawn of the 21st century is understanding the relationship between mind, consciousness and the brain. Editorials in recent years have highlighted the difficulties faced by cognitive neuroscience in attempting to answer questions regarding the nature, as well as the mechanism by which subjective experiences and our sense of consciousness may arise through neuronal processes. Current scientific views regarding the origin of consciousness vary widely and range from an 'epiphenomenon' arising from neuronal networks, to neuronal quantum processes, to a separate undiscovered scientific entity. ⋯ This is despite the well demonstrated finding that cerebral functioning as measured by electrical activity of the brain ceases during cardiac arrest, thus raising the possibility that human mind and consciousness may continue to function in the absence of brain function. In this article the broad theories for the causation of consciousness are reviewed as well as a novel method to study consciousness during cardiac arrest. This may provide a unique experimental method to determine the nature of human mind and consciousness as well as its relationship with the brain.