Medical hypotheses
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Repetitive transcranial magnetic stimulation (rTMS) is a novel technique of non-invasive brain stimulation which has been used to treat several neuropsychiatric disorders such as major depressive disorder, chronic pain and epilepsy. Recent studies have shown that the therapeutic effects of rTMS are associated with plastic changes in local and distant neural networks. In fact, it has been suggested that rTMS induces long-term potentiation (LTP) and long-term depression (LTD) - like effects. ⋯ Brain-derived neurotrophic factor is a neurotrophin that plays a key role in neuronal survival and synaptic strength, which has also been studied in several neuropsychiatric disorders. There is robust evidence associating BDNF with the LTP/LTD processes, and indeed it has been proposed that BNDF might index an increase or decrease of brain activity - the 'yin and yang' BDNF hypothesis. In this article, we review the initial studies combining measurements of BDNF in rTMS clinical trials and discuss the results and potential usefulness of this instrument in the field of rTMS.
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Tobacco smoking is one of the strongest risk factors for various disorders such as lung cancers and cardiovascular disease (CVD). Further, former smokers remain at an increased risk for developing lung cancers and CVD even years after they stop smoking. These observation suggest that expression levels of some of the genes related to tobacco smoking may not return to levels similar to never smokers and could be permanently altered despite prolonged smoking cessation, thereby being involved in the development of lung cancers and CVD. ⋯ Therefore, it is conceivable that tobacco-derived AGEs are also involved in the increased risk for developing cancers and CVD in former smokers. In this paper, we would like to propose the possible ways of testing our hypotheses. Are tissue levels of AGEs still higher in former smokers, compared with age-, sex- and other confounders-matched non-smokers? If the answer is yes, are the tissue levels of AGEs following smoking cessation decreased? If we examine the effects of smoking cessation as a function of years since quitting, is the extent of decrease in tissue AGEs levels parallel to that of risk reduction for developing cancers and CVD? Further, are genes that are permanently altered despite prolonged smoking cessation identical to those that regulated by AGEs? These investigations could clarify whether tobacco-derived AGEs are involved in sustained tissue injury in former smokers.
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Despite numerous advances in intensive care medicine, sepsis remains a deadly disease. Today, conventional therapeutic approaches and mainstream scientific research mostly focus on symptomatic early goal directed organ support therapy. This includes fluid resuscitation, choice and timing of antibiotics and vasopressors, mechanical ventilation, and renal replacement strategies. ⋯ Here we hypotheses that in order to profoundly influence survival from sepsis, future therapeutic efforts in the field should concentrate on this later "hypo-immune" stage of sepsis, associated immune phenomena, and novel immunomodulatory strategies. This may lead to the development of advanced immunomodulatory therapies available for widespread clinical use. Today, in the era of antibiotics and advanced organ system support therapy, it is not the bug that kills you- survival has become a matter of whether your cellular immune system can cope.
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The modern world is characterized by progressive specialization of function and ever-larger-scale coordination of these ever-more-specialized functions. More and more of science is done by increasing-sized teams of specialists, and the ability to engage in 'teamwork' is regarded as an almost essential attribute for most scientists. But teamwork does not suit all personality types. ⋯ In conclusion, the current incentive system that encourages teamwork involves a trade-off. The majority of modestly talented scientists can probably achieve more when working as members of a team. But the very best scientists probably need to work as mavericks.
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Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterised by (inter alia) an increase in distractibility. The current front-line pharmacotherapies for the treatment of ADHD, namely the psychostimulants methylphenidate and amphetamines, have clear abuse potential, hence there is a strong need to develop new drug treatments for this disorder. Central to this process is the identification of the pathophysiological changes which underlie ADHD. ⋯ Fortunately, again, even if psychostimulants do not achieve their therapeutic effects on distractibility in ADHD by acting on the SC, then the development of drugs which dampen stimulus-related activity in the colliculus could still represent an important novel path for drug development to take. Pharmacological manipulations of this structure are able to decrease distractibility. As a consequence, sensory responsiveness in the SC may represent a new model system for use in the development of non-addictive pharmacotherapies for ADHD.