Medical hypotheses
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Malignant hyperthermia (MH) is a life-threatening disease that occurs during general anaesthesia following exposure to succinylcholine (SCh), a depolarizing muscle relaxant, and volatile anaesthetics. Susceptibility to MH most commonly arises from mutations in the RyR1 gene, the Ca2+ release channel of skeletal muscle. ⋯ Without dantrolene, the reported mortality of f-MH is as high as 42.3%. Based on the participation of catecholamine in the hyperhaemodynamic response of f-MH and the demonstrated effective control of catecholamine release of magnesium sulfate, combined with the fact that magnesium and calcium have opposite effects on muscle contraction, I hypothesized that magnesium sulfate could be a choice for delaying the progression of f-MH while waiting for dantrolene treatment.
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The neural correlates of consciousness and the mechanisms by which general anesthesia (GA) modulate such correlates to induce loss of consciousness (LOC) has been described as one of the biggest mysteries of modern medicine. Several cellular targets and neural circuits have been identified that play a critical role in LOC induced by GA, including the GABAA receptor and ascending arousal nuclei located in the basal forebrain, hypothalamus, and brain stem. General anesthetics (GAs) including propofol and inhalational agents induce LOC in part by potentiating chloride influx through the GABAA receptor, leading to neural inhibition and LOC. ⋯ GAs and neurotransmitters also act as preconditioning agents and the GABAA receptor inhibitor bicuculline, which reverses propofol anesthesia, also activates AMPK in cortical neurons. We propose the novel hypothesis that cellular stress-induced AMPK activation links wakefulness, arousal, and consciousness with paradoxical excitation and accelerated emergence from anesthesia. Because AMPK activators including metformin and nicotine promote proliferation and differentiation of neural stem cells located in the subventricular zone and the dentate gyrus, AMPK activation may also enhance brain repair and promote potential recovery from disorders of consciousness (i.e. minimally conscious state, vegetative state, coma).
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Urinary tract infections are among the most common infectious diseases worldwide, primarily caused by uropathogenic Escherichia coli (UPEC) strains that harbor type I pili and P pili on the surface. Standard E. coli therapy still entails antibiotic consumption, but urinary tract infections tend to recur at a very high rate. Due to the emergence of antibiotic resistant strains of UPEC, as well as high infection recurrence rates, there is a need for new approaches to efficiently treat and prevent urinary tract infections. ⋯ More specifically, polyphenol mannosides (due to the structural similarities with the most potent biaryl inhibitors) can act as high-affinity FimH ligands, while cranberry-associated polyphenol moiety can additionally inhibit the PapG-mediated adhesion. Proposed compound may also contribute to the antioxidant capacity of the human organism. In conclusion, this dual-target hypothesis for the prevention and treatment of UPEC infections represents an important foundation for further research on this topic.
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Inhalational anesthetics such as isoflurane, desflurane and halothane are the mainstay medications for surgical procedures; upon inhalation, they produce anesthesia described as reversible unconsciousness with the features of amnesia, sleep, immobility and analgesia. To date, how they produce anesthesia is unknown. This study proposes that carbonic anhydrase enzymes are likely targets mediating the actions of inhalational anesthetics. ⋯ Finally, there is a great deal of similarities between the physiological actions of inhalational anesthetics and carbonic anhydrase inhibitors; moreover well-known side effects of inhalational anesthetics could be associated with the inhibition of carbonic anhydrases. Therefore, this article presents a hypothesis that the anesthetic actions of inhalational anesthetics could be due to their inhibitory effects on the carbonic anhydrases. Investigating this hypothesis might lead to the development of new safer anesthetics, and more importantly it might reveal an endogenous anesthetic pathway, in which the carbonic anhydrase system is a component along with the GABA-A and NMDA receptor systems.
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Fundamental to the advancement of scientific knowledge is unbiased, accurate and validated measurement techniques. Recent United Nations and landmark Nature publications highlight the global uptake of mobile technology and the staggering potential for big data to encourage people to be physically active and to influence health policy. However, concerns exist about inconsistencies in smartphone health apps. ⋯ Consumer-grade wearable devices appear unsuitable to detect steps in people with slow, short or non-stereotypical gait patterns. Specifically, there is a risk of systematically undercounting the steps by obese people, females or people from different ethnic groups resulting in biases when reporting associations between physical inactivity and obesity. More research is required to develop smartphone apps suitable for all people of the heterogeneous global population.