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Usnic acid (UA) is one of the most abundant secondary metabolites of lichens. Its antibacterial, anti-inflammatory, antiviral, and antitumor properties make it one of the few commercially available lichens compounds. Owing to its low solubility it has limited application, for that reason encapsulation in polymeric micelles (UA-PM) has been used to solve this aspect. Then, the obtained dispersion has been incorporated into a Sepigel-based gel for skin application (UA-PM-GEL). Polymeric micelles consisting of Soluplus, Solutol HS15 and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) were characterized in terms of size, polydispersity index, Zeta potential and morphological analysis. The nanocomposite gel (UA-PM-GEL) was characterized by determining the rheological behaviour, pH, UA recovery, physical and chemical stability and texture characteristics during one-month storage. The dialysis bag method and vertical diffusion Franz cell apparatus were used to determine the UA release from UA-PM and UA-PM-GEL. Skin-PAMPA assay allowed to evaluate the influence of micelles and nanocomposite formulation on the in vitro passive permeability of UA. In addition, the antibacterial activity of UA-PM and UA-PM-GEL was evaluated on the Staphylococcus epidermidis bacterial strain. The micellar formulation significantly increased both the solubility and the permeability of the UA, as indicated by the Pe value obtained by Skin-PAMPA test. The release of the active ingredient, although more gradual than the colloidal dispersion, was not hindered by the viscosity of the gel system, as demonstrated by the release studies. The rheological properties of the gel outlined a good spreadability, adhesion and viscosity, suggesting easy application and removal from the application site. The pH values also proved to be suitable for skin application. The formulation was chemically and physically stable for 30 days, with a percentage of loss of the active ingredient less than 10 %. Finally, both the micelles and the nanocomposite gel revealed an effective antibacterial activity, representing a promising approach for the treatment of skin infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Context: Little is known about presenting clinical characteristics, tumor biology, and surgical morbidity of Cushing's disease (CD) with aging., Objective: Using a large multi-institutional dataset, we assessed diagnostic and prognostic significance of age in CD through differences in presentation, laboratory results, tumor characteristics, and postoperative outcomes., Design: Data from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) were reviewed for patients with CD treated with transsphenoidal tumor resection at 11 centers between 2003 and 2023. Outcomes assessed included comorbidities, presenting features, preoperative endocrine evaluations, perioperative characteristics, postoperative endocrine laboratory values, and complications., Results: Of the 608 patients evaluated, 496 (81.6%) were female; median age at surgery was 44 years (range, 10-78). Increasing age was associated with increasing comorbidities, frailty, rates of postoperative thromboembolic disease, Knosp grade, tumor size, and postoperative cortisol and ACTH nadirs. Conversely, increasing age was associated with decreased hallmark CD features, preoperative 24-hour urinary free cortisol, Ki-67 indices, and arginine vasopressin deficiency. Younger patients presented more frequently with weight gain, facial rounding/plethora, abdominal striae, hirsutism, menstrual irregularities, dorsocervical fat pad, and acne. Obstructive sleep apnea and infections were more common with increasing age., Conclusions: There are age-dependent differences in clinical presentation, tumor behavior, and postoperative outcomes in patients with CD. Compared to younger patients, older patients present with a less classical phenotype characterized by fewer hallmark features, more medical comorbidities, and larger tumors. Notably, age-related differences suggest a more indolent tumor behavior in older patients, potentially contributing to delayed diagnosis and increased perioperative risk. These findings underscore the need for tailored diagnostic and therapeutic approaches across age groups, with a focus on managing long-term comorbidities and optimizing surgical outcomes., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background and Purpose: Boxing is associated with a high risk of head injuries and increases the likelihood of chronic traumatic encephalopathy. This study explores the effects of sub-concussive impacts on boxers by applying both linear and nonlinear analysis methods to electroencephalogram (EEG) data., Methods: Twenty-one boxers were selected (mean ± SD, age 28.38 ± 5.5 years; weight 67.55 ± 8.90 kg; years of activity 6.76 ± 5.45; education 14.19 ± 3.08 years) and divided into 'beginner' and 'advanced' groups. The Montreal Cognitive Assessment and the Frontal Assessment Battery were administered; EEG data were collected in both eyes-open (EO) and eyes-closed (EC) conditions during resting states. Analyses of EEG data included normalized power spectral density (nPSD), power law exponent (PLE), detrended fluctuation analysis and multiscale entropy. Statistical analyses were used to compare the groups., Results: Significant differences in nPSD and PLE were observed between the beginner and advanced boxers, with advanced boxers showing decreased mean nPSD and PLE (nPSD 4-7 Hz, p = 0.013; 8-13 Hz, p = 0.003; PLE frontal lobe F3 EC, p = 0.010). Multiscale entropy analysis indicated increased entropy at lower frequencies and decreased entropy at higher frequencies in advanced boxers (F3 EC, p = 0.024; occipital lobe O1 EO, p = 0.029; occipital lobe O2 EO, p = 0.036). These changes are similar to those seen in Alzheimer's disease., Conclusion: Nonlinear analysis of EEG data shows potential as a neurophysiological biomarker for detecting the asymptomatic phase of chronic traumatic encephalopathy in boxers. This methodology could help monitor athletes' health and reduce the risk of future neurological injuries in sports., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)