Search

Background and Objective: Preclinical studies suggest that curcumin might be a potential neuroprotective agent in Parkinson's disease (PD). This clinical trial aimed to evaluate the efficacy of adding nanomicelle curcumin on improving the motor and non-motor symptoms of PD patients and their quality of life., Material and Methods: Idiopathic PD patients aged ≥30≥ 30 whose symptoms were under control were included in this pilot, randomized, triple-blind, placebo-controlled, add-on trial. Eligible patients were randomly assigned to either the curcumin (n = 30, 80 mg/day) or placebo (n = 30) groups and were followed for nine months. Primary outcomes were the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Parkinson's Disease Questionnaire (PDQ-39). These variables, along with demographic data, drug history, and possible side effects of curcumin, were gathered at the beginning of the study and every three months. A mixed effects model was used to compare the group-by-time interaction, followed by post hoc analysis., Results: Although the mean MDS-UPDRS and PDQ-39 scores were not significantly different between the curcumin and placebo groups at any time points, MDS-UPDRS part III (P = 0.04) showed a significant difference in its overall trend between the study groups. However, post hoc analysis failed to spot this difference at study time points. The most common side effects of curcumin were nausea and vomiting (P = 0.25) and gastroesophageal reflux (P = 0.42)., Conclusion: While curcumin is a well-tolerated natural compound, this trial was unsuccessful in showing its efficacy in quality of life and clinical symptoms of PD patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: There is controversy regarding Alberta Stroke Program Early CT Score (ASPECTS) and platelet indices as predictors of outcome in patients with acute ischemic stroke (AIS). We aimed to assess the prognostic value of ASPECTS, mean platelet volume (MPV), plateletcrit (PCT), and platelet count (Plt) in 3-month and 1-year functional outcomes of AIS patients, both independently and in combination., Methods: This prospective study was conducted in Shams Al-shomuos and Ghaem hospitals of Mashhad, Iran from June 2019 to January 2021. Overall, 553 patients above 18 years old with first-ever anterior circulation AIS met the eligibility criteria and were included. Clinical, hematologic, radiologic, and demographic data of patients were recorded at baseline. The 3-month and 1-year functional outcome was evaluated by modified Rankin Scale (mRS). Multivariate logistic regression was used to determine the independent predictors of poor functional outcome (mRS>2) and mortality., Results: The mean age of the patients was 65.50 ± 14.41 years and 282 patients (51%) were male. ASPECTS ≤ 7 was an independent predictor of both poor function (OR=1.94, 95%CI=1.04-3.62, P = 0.04) and mortality (OR=2.02, 95%CI=1.14-3.58, P = 0.02) at 1 year. MPV was also a strong predictor of 3-month (OR=3.88, 95%CI=2.04-7.38, P = 0.02) and 1-year (OR=3.32, 95%CI=1.91-5.78, P = 0.01) mortality, as well as 3-month (OR=3.25, 95%CI=1.80-5.86, P < 0.001) and 1-year (OR=4.35, 95%CI=2.36-8.02, P < 0.001) poor function. For 1-year poor function (OR=9.33, 95%CI=2.19-39.73, P = 0.003) and mortality (OR=6.40, 95%CI=2.09-19.64, P = 0.001), ASPECTS combined with all platelet indices found to be a more robust independent predictor compared to each variable alone., Conclusion: Although MPV is an independent predictor of both 3-month and 1-year poor function and mortality in AIS patients, ASPECTS ≤ 7 was found to be a risk factor for 1-year poor function and mortality. Moreover, the prognostic value of both platelet indices and ASPECTS are greater when they are combined together in AIS patients., (Copyright © 2021. Published by Elsevier B.V.)

Collagen fibril is a major component of connective tissues such as bone, tendon, blood vessels, and skin. The mechanical properties of this highly hierarchical structure are greatly influenced by the presence of covalent cross-links between individual collagen molecules. This study investigates the viscoelastic behavior of a collagen lysine-lysine cross-link based on creep simulations with applied forces in the range or 10 to 2000pN using steered molecular dynamics (SMD). The viscoelastic model of the cross-link was combined with a system composed by two segments of adjacent collagen molecules hence representing a reduced viscoelastic model for a simplified micro-fibril. It was found that the collagen micro-fibril assembly had a steady-state Young׳s modulus ranging from 2.24 to 3.27GPa, which is in agreement with reported experimental measurements. The propagation of longitudinal force wave along the molecule was implemented by adding a delay element to the model. The force wave speed was found to be correlated with the speed of one-dimensional elastic waves in rods. The presented reduced model with three degrees of freedom can serve as a building block for developing models of the next level of hierarchy, i.e., a collagen fibril., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Unique mechanical properties of collagen molecule make it one of the most important and abundant proteins in animals. Many tissues such as connective tissues rely on these properties to function properly. In the past decade, molecular dynamics (MD) simulations have been used extensively to study the mechanical behavior of molecules. For collagen, MD simulations were primarily used to determine its elastic properties. In this study, constant force steered MD simulations were used to perform creep tests on collagen molecule segments. The mechanical behavior of the segments, with lengths of approximately 20 (1X), 38 (2X), 74 (4X), and 290 nm (16X), was characterized using a quasi-linear model to describe the observed viscoelastic responses. To investigate the mechanisms of the viscoelastic behavior, hydrogen bonds (H-bonds) rupture/formation time history of the segments were analyzed and it was shown that the formation growth rate of H-bonds in the system is correlated with the creep growth rate of the segment (β=2.41βH). In addition, a linear relationship between H-bonds formation growth rate and the length of the segment was quantified. Based on these findings, a general viscoelastic model was developed and verified here, using the smallest segment as a building block, the viscoelastic properties of larger segments could be predicted. In addition, the effect of temperature control methods on the mechanical properties were studied, and it was shown that application of Langevin Dynamics had adverse effect on these properties while the Lowe-Anderson method was shown to be more appropriate for this application. This study provides information that is essential for multi-scale modeling of collagen fibrils using a bottom-up approach., (Copyright © 2015 Elsevier Ltd. All rights reserved.)