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Cyclodextrins (CDs) are cyclic carbohydrate polymers that hold significant promise for drug delivery and industrial applications. Their effectiveness depends on their ability to encapsulate target molecules with strong affinity and specificity, but quantifying affinities in these systems accurately is challenging for a variety of reasons. Computational methods represent an exceptional complement to in vitro assays because they can be employed for existing and hypothetical molecules, providing high resolution structures in addition to a mechanistic, dynamic, kinetic, and thermodynamic characterization. Here, we employ potential of mean force (PMF) calculations obtained from guided metadynamics simulations to characterize the 1:1 inclusion complexes between four different modified βCDs, with different type, number, and location of substitutions, and two sterol molecules (cholesterol and 7-ketocholesterol). Our methods, validated for reproducibility through four independent repeated simulations per system and different post processing techniques, offer new insights into the formation and stability of CD-sterol inclusion complexes. A systematic distinct orientation preference where the sterol tail projects from the CD's larger face and significant impacts of CD substitutions on binding are observed. Notably, sampling only the CD cavity's wide face during simulations yielded comparable binding energies to full-cavity sampling, but in less time and with reduced statistical uncertainty, suggesting a more efficient approach. Bridging computational methods with complex molecular interactions, our research enables predictive CD designs for diverse applications. Moreover, the high reproducibility, sensitivity, and cost-effectiveness of the studied methods pave the way for extensive studies of massive CD-ligand combinations, enabling AI algorithm training and automated molecular design., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AMA, RGF, AP, and MSO report financial support was provided by Cyclarity Therapeutics. Inc. AMA, RGF, AP, and MSO report a relationship with Cyclarity Therapeutics Inc that. includes: employment, consultation or advisory, equity or stocks, and travel reimbursement. RGF and AP report a relationship with the company MD.USE that includes: employment. and equity or stocks., (© 2024 The Authors.)

7-Ketocholesterol (7KC) is a toxic oxysterol that is associated with many diseases and disabilities of aging, as well as several orphan diseases. 7KC is the most common product of a reaction between cholesterol and oxygen radicals and is the most concentrated oxysterol found in the blood and arterial plaques of coronary artery disease patients as well as various other disease tissues and cell types. Unlike cholesterol, 7KC consistently shows cytotoxicity to cells and its physiological function in humans or other complex organisms is unknown. Oxysterols, particularly 7KC, have also been shown to diffuse through membranes where they affect receptor and enzymatic function. Here, we will explore the known and proposed mechanisms of pathologies that are associated with 7KC, as well speculate about the future of 7KC as a diagnostic and therapeutic target in medicine., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

As a significant number of stroke victims exhibit cognitive impairment, neuropsychological assessments can enhance poststroke management by identifying pertinent cognitive sequelae and providing salient care recommendations. However, due to operational differences between traditional neuropsychology and stroke services, neuropsychological assessments often remain underutilized in stroke care. We developed a novel care model that incorporated neuropsychological testing into a comprehensive stroke program using the modified vascular cognitive impairment (VCI) half-hour assessment protocol proposed by the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN). The test batteries were administered during the patients' acute admissions and then again upon follow-up in the multidisciplinary stroke clinic. Patient and provider satisfaction was then evaluated. Surveys revealed high provider satisfaction with improved clinic efficacy, improved data turnaround time, and with value neuropsychology services added to the comprehensive stroke program. Results from the 18-item industry standard Press-Ganey surveys showed all scores above 4.4/5.0 for patient satisfaction. This clinic garnered high provider and patient satisfaction after the first year. The (modified) NINDS-CSN VCI assessment protocol demonstrated clinical feasibility, suggestive of an efficient method of providing focused neuropsychological services in a clinical setting that otherwise prohibits traditional, comprehensive cognitive assessments.