Type 1 diabetes mellitus (T1DM) is a chronic, autoimmune disease that is characterized by total absence of insulin production. Hypertension is a common comorbidity in T1DM with complex pathophysiology, while it is also a well-recognized risk factor for the development of cardiovascular disease (CVD), as well as other microvascular diabetic complications. 相似文献
BackgroundParkinson’s disease (PD) is a chronic and progressive neurodegenerative disease with no cure, presenting a challenging diagnosis and management. However, despite a significant number of criteria and guidelines have been proposed to improve the diagnosis of PD and to determine the PD stage, the gold standard for diagnosis and symptoms monitoring of PD is still mainly based on clinical evaluation, which includes several subjective factors. The use of machine learning (ML) algorithms in spatial-temporal gait parameters is an interesting advance with easy interpretation and objective factors that may assist in PD diagnostic and follow up.Research questionThis article studies ML algorithms for: i) distinguish people with PD vs. matched-healthy individuals; and ii) to discriminate PD stages, based on selected spatial-temporal parameters, including variability and asymmetry.MethodsGait data acquired from 63 people with PD with different levels of PD motor symptoms severity, and 63 matched-control group individuals, during self-selected walking speed, was study in the experiments.ResultsIn the PD diagnosis, a classification accuracy of 84.6 %, with a precision of 0.923 and a recall of 0.800, was achieved by the Naïve Bayes algorithm. We found four significant gait features in PD diagnosis: step length, velocity and width, and step width variability. As to the PD stage identification, the Random Forest outperformed the other studied ML algorithms, by reaching an Area Under the ROC curve of 0.786. We found two relevant gait features in identifying the PD stage: stride width variability and step double support time variability.SignificanceThe results showed that the studied ML algorithms have potential both to PD diagnosis and stage identification by analysing gait parameters. 相似文献
Butyrylcholinesterase (BChE) is a serine esterase that plays a role in the detoxification of natural as well as synthetic ester-bond-containing compounds. Alterations in BChE activity are associated with a number of diseases. Cholinergic system abnormalities in particular are correlated with the formation of senile plaques in Alzheimer’s disease (AD), and administration of cholinesterase inhibitors is a common therapeutic approach used to treat AD.
Here, our aim was to study the interaction between BChE and fluoxetine.
Molecular docking simulations revealed that fluoxetine penetrated deep into the active-site gorge of BChE and that it was engaged in stabilizing noncovalent interactions with multiple subsites. In substrate kinetic studies, the Vm, Km, kcat and kcat/Km values were found to be 20.59?±?0.36?U mg?1 protein, 194?±?14?µM, 1.3?×?108?s?1 and 6.7?×?105?µM?1s?1, respectively. Based on inhibitory studies, fluoxetine appeared to inhibit BChE competitively, with an IC50 value of 104?µM and a Ki value of 36.3?±?4.7?µM.
Overall, both the low Ki value and the high number of BChE–fluoxetine interactions suggest that fluoxetine is a potent inhibitor of BChE, although in vivo mechanisms for the direct effects of BChE inhibition on various pathologies remain to be further investigated.