The metabolic score for insulin resistance as a predictor of clinical outcome in stroke patients treated by intravenous thrombolysis.

BACKGROUND AND PURPOSE: Insulin resistance is associated with clinical outcomes among patients with ischemic stroke. We aimed to investigate the association between metabolic score for insulin resistance (METS-IR) and clinical outcomes in stroke patients treated by intravenous thrombolysis (IVT). METHODS: We recruited participants treated with IVT from a prospective registry including 3 stroke centers. Poor outcome was defined as a modified Rankin scale score ≥ 3 points at 90 days after the index stroke. We performed logistic regression models to investigate the association between METS-IR and the risk of poor outcome. We used the receiver operative characteristic to assess the discriminative ability and the restricted cubic spline to explore the relationship between METS-IR and the poor outcome. RESULTS: This study enrolled a total of 1074 patients (median age, 68; 63.8% male). Three hundred sixty (33.5%) patients had poor outcome after IVT. METS-IR was associated with the risk of the poor outcome with the increase of confounding factors in models (odds ratio [OR], 1.078; 95% confidence interval [CI], 1.058-1.099; P < 0.001). The area under the curve for METS-IR for predicting the poor outcome was 0.790 (95% CI, 0.761-0.819). The restricted cubic spline revealed an increasing and non-linear association between METS-IR and the poor outcome (P for non-linearity < 0.001). CONCLUSION: Our study found that METS-IR was associated with an increased risk of poor outcome after IVT. Further studies are warranted to investigate the efficacy of anti-diabetic agents regarding IR on clinical outcomes after IVT.

Ion-mediated interactions between like-charged polyelectrolytes with bending flexibility.

Ion-mediated interactions between polyelectrolytes (PEs) are crucial to the properties of flexible biopolymers such as nucleic acids and proteins but the effect of PE flexibility on such interactions has not been explicitly addressed until now. In this work, the potentials of mean force (PMFs) between like-charged PEs with different bending flexibility have been investigated by Monte Carlo simulations and a cylindrical confinement around each PE was involved to model two PEs in an array. We found that in the absence of trivalent salt, the PMFs between like-charged PEs in an array are apparently repulsive while the bending flexibility can visibly decrease the repulsive PMFs. With the addition of high trivalent salt, the PMFs become significantly attractive whereas the attractive PMFs can be apparently weakened by the bending flexibility. Our analyses reveal that the effect of bending flexibility is attributed to the increased PE conformational space, which allows the PEs to fluctuate away to decrease the monovalent ion-mediated repulsion or to weaken the trivalent ion-mediated attraction through disrupting trivalent ion-bridging configuration. Additionally, our further calculations show that the effect of bending flexibility on the ion-mediated interactions is less apparent for PEs without cylindrical confinement.

Apparent repulsion between equally and oppositely charged spherical polyelectrolytes in symmetrical salt solutions.

Ion-mediated interactions are very important for the properties of colloids and biomacromolecules such as nucleic acids and proteins. In this work, the ion-mediated interactions between equally and oppositely charged spherical polyelectrolytes (SPEs) in symmetrical divalent electrolytes have been investigated by Monte Carlo simulations, and an unexpected apparent repulsion was observed at high divalent salt concentration. Our investigations also show that the effective repulsion becomes more pronounced for SPEs with higher charge densities and for counterions with larger sizes and was found to be tightly accompanied with the over-neutralization to SPEs by condensed counterions and their release upon the approach of SPEs. Such attractive interaction can be reproduced by our proposed modified Poisson-Boltzmann model and is mainly attributed to the increase in the electrostatic repulsion between on charged SPE and the over-neutralized counterions around the other oppositely SPE with the approach of the two SPEs.

Potential of mean force between oppositely charged nanoparticles: A comprehensive comparison between Poisson-Boltzmann theory and Monte Carlo simulations.

Ion-mediated interactions between like-charged polyelectrolytes have been paid much attention, and the Poisson-Boltzmann (PB) theory has been shown to fail in qualitatively predicting multivalent ion-mediated like-charge attraction. However, inadequate attention has been paid to the ion-mediated interactions between oppositely charged polyelectrolytes. In this work, the potentials of mean force (PMF) between oppositely charged nanoparticles in 1:1 and 2:2 salt solutions were investigated by Monte Carlo simulations and the PB theory. Our calculations show that the PMFs between oppositely charged nanoparticles are generally attractive in 1:1 and 2:2 salt solutions and that such attractive PMFs become weaker at higher 1:1 or 2:2 salt concentrations. The comprehensive comparisons show that the PB theory can quantitatively predict the PMFs between oppositely charged nanoparticles in 1:1 salt solutions, except for the slight deviation at very high 1:1 salt concentration. However, for 2:2 salt solutions, the PB theory generally overestimates the attractive PMF between oppositely charged nanoparticles, and this overestimation becomes more pronounced for nanoparticles with higher charge density and for higher 2:2 salt concentration. Our microscopic analyses suggest that the overestimation of the PB theory on the attractive PMFs for 2:2 salt solutions is attributed to the underestimation of divalent ions bound to nanoparticles.

Potential of mean force between like-charged nanoparticles: Many-body effect.

Ion-mediated interaction is important for the properties of polyelectrolytes such as colloids and nucleic acids. The effective pair interactions between two polyelectrolytes have been investigated extensively, but the many-body effect for multiple polyelectrolytes still remains elusive. In this work, the many-body effect in potential of mean force (PMF) between like-charged nanoparticles in various salt solutions has been comprehensively examined by Monte Carlo simulation and the nonlinear Poisson-Boltzmann theory. Our calculations show that, at high 1:1 salt, the PMF is weakly repulsive and appears additive, while at low 1:1 salt, the additive assumption overestimates the repulsive many-body PMF. At low 2:2 salt, the pair PMF appears weakly repulsive while the many-body PMF can become attractive. In contrast, at high 2:2 salt, the pair PMF is apparently attractive while the many-body effect can cause a weaker attractive PMF than that from the additive assumption. Our microscopic analyses suggest that the elusive many-body effect is attributed to ion-binding which is sensitive to ion concentration, ion valence, number of nanoparticles and charges on nanoparticles.

Multivalent ion-mediated nucleic acid helix-helix interactions: RNA versus DNA.

Ion-mediated interaction is critical to the structure and stability of nucleic acids. Recent experiments suggest that the multivalent ion-induced aggregation of double-stranded (ds) RNAs and DNAs may strongly depend on the topological nature of helices, while there is still lack of an understanding on the relevant ion-mediated interactions at atomistic level. In this work, we have directly calculated the potentials of mean force (PMF) between two dsRNAs and between two dsDNAs in Co(NH3)6 (3+) (Co-Hex) solutions by the atomistic molecular dynamics simulations. Our calculations show that at low [Co-Hex], the PMFs between B-DNAs and between A-RNAs are both (strongly) repulsive. However, at high [Co-Hex], the PMF between B-DNAs is strongly attractive, while those between A-RNAs and between A-DNAs are still (weakly) repulsive. The microscopic analyses show that for A-form helices, Co-Hex would become 'internal binding' into the deep major groove and consequently cannot form the evident ion-bridge between adjacent helices, while for B-form helices without deep grooves, Co-Hex would exhibit 'external binding' to strongly bridge adjacent helices. In addition, our further calculations show that, the PMF between A-RNAs could become strongly attractive either at very high [Co-Hex] or when the bottom of deep major groove is fixed with a layer of water.