Medical hypotheses
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Vascular calcification is a common feature in advanced atherosclerosis and also a predictor of future cardiovascular events such as unstable angina and myocardial infarction, especially in diabetes. There is a growing body of evidence that advanced glycation end products (AGEs), senescent macroprotein derivatives formed at an accelerated rate in diabetes, exist within atherosclerotic lesions, thereby being implicated in the pathogenesis of accelerated atherosclerosis in diabetes. Indeed, we have previously shown that AGE - their receptor (RAGE) interaction could induce angiogenesis through autocrine production of vascular endothelial growth factor, suggesting its role for plaque formation and enlargement in diabetes. ⋯ Since we, along with others, have shown that nifedipine inhibits glycation of low-density lipoprotein in vitro and blocks the AGE-induced RAGE expression in endothelial cells through its anti-oxidative properties, nifedipine could inhibit vascular calcification by blocking the AGE formation or the downstream signaling in diabetes. In this paper, we would like to propose the possible ways of testing our hypothesis. Does nifedipine treatment slow down the progression of coronary calcification in diabetic patients? If the answer is yes, is this beneficial effect of nifedipine superior to that of other DHPs with equihypotensive properties? Does nifedipine treatment decrease expression levels of AGEs and RAGE in diabetic atherosclerosis? Is the unique effect of nifedipine on vascular calcification correlated with its AGE or RAGE-suppressing properties? These prospective studies will provide further valuable information whether nifedipine could prevent vascular calcification in diabetic atherosclerosis by blockade the AGE-RAGE signaling in vascular wall cells.
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The clinical assessment of sarcoidosis has been confounded by its inexact diagnostic criteria, multiorgan involvement, and effects of therapy. In this manuscript an instrument, the Sarcoidosis Three-Dimensional Assessment Instrument (STAI), is proposed to assess the clinical state of sarcoidosis. The instrument examines each organ involved with sarcoidosis separately. ⋯ Severity is based both on the decline from normal capacity as well as physical and psychosocial limitation. Disease activity takes into account changes in organ function as well as changes in therapy. Although this instrument is presently not validated, it is hoped that it will undergo study as it rationally accounts for several problems of previous assessment instruments.
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People often suggest that scientists should have a specific personality type, usually conscientious and self-critical. But this is a mistake. Science as a social system needs to be conscientious and self-critical, but scientists as people do not necessarily have to conform to that stereotype. ⋯ But the modern science superstar is more like the Nutty Professor's alter ego, nightclub singer 'Buddy Love': a sharp-suited, good-looking and charismatic charmer. While Nutty was dull but impartial, Buddy is compelling but self-seeking. Our attitude towards public scientific pronouncements should be adjusted accordingly.
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A priori hypotheses are considered a cornerstone of the scientific method. A posteriori hypotheses, on the contrary, are judged by many as inappropriate and are hardly ever acknowledged as such. Such practice is inadequate. ⋯ And yet, their unambiguous formulation in the study publication can enable others to follow up on the findings and the modified conjectures fast and thus facilitate scientific progress. In this vein, a posteriori hypotheses should be encouraged as a thinker's prime tool rather than be discouraged. Indeed, it is suggested, that information on a posteriori hypotheses should be formally required when research is published.
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Most research is 'normal science' using Thomas Kuhn's term: checking, trial-and-error improvement and incremental extrapolation of already existing paradigms. By contrast, 'revolutionary science' changes the fundamental structures of science by making new theories, discoveries or technologies. Science Nobel prizes (in Physics, Chemistry, Physiology/Medicine and Economics) have the potential to be used as a new metric for measuring revolutionary science. ⋯ Although Nobel science prizes are sporadically won by numerous nations and institutions, it seems that long term national strength in revolutionary science is mainly a result of sustaining and newly-generating multi-Nobel-winning research centres. At present these elite institutions are found almost exclusively in the USA. The USA is apparently the only nation with a research system that nurtures revolutionary science on a large scale.