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The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or "grooves" were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332493 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115089 | PLOS |
Eur J Pharmacol
September 2025
Departamento de Química and Institute for advanced research in chemical Science (IAdChem), Facultad de Ciencias, Módulo 13, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
The Skp2-Cks1 protein-protein interaction (PPI) within the SCF ubiquitin ligase acts as a co-receptor for phosphorylated CDK inhibitors-most prominently p27-relieving CDK inhibition and advancing the cell cycle, a dependency accentuated in RB-pathway-defective cancers. Crystallographic and cryo-EM analyses delineate a composite pocket formed by the Skp2 leucine-rich-repeat groove and the phosphate-recognition site of Cks1; Cks1-centered open-closed motions further influence druggability. Using HTRF/TR-FRET and AlphaScreen biochemistry, alongside cell-based target-engagement readouts in some studies, three small-molecule classes have emerged that disrupt this PPI: 1,3-diphenyl-pyrazines and triazolo[1,5-a]pyrimidines (lead E35) with low-micromolar potency, and "Skp2E3LI" compounds with micromolar cellular activity.
View Article and Find Full Text PDFSTAR Protoc
September 2025
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen 9700 RB, the Netherlands. Electronic address:
Research on multimorbidity patterns promotes our understanding of the common pathological mechanisms that underlie co-occurring diseases. Here, we present a protocol to infer multimorbidity clusters in the form of disease topics from large-scale diagnosis data using treeLFA, a topic model based on the Bayesian binary non-negative matrix factorization. We describe steps for installing software, preparing input data, and training the model.
View Article and Find Full Text PDFOrthop Surg
September 2025
Orthopedic Surgery Department, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Lateral patellar dislocation (LPD) is a musculoskeletal condition characterized by a complex etiology. Despite significant advancements in management strategies, it continues to pose considerable challenges. Critical anatomic risk factors previously identified include trochlear dysplasia (TD), patella alta, and elevated tibial tubercle-trochlear groove (TT-TG) distance, with TD being the most significant.
View Article and Find Full Text PDFJ Neurol Surg B Skull Base
October 2025
Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Objective: Olfactory groove meningiomas (OGM) commonly present with olfactory deficits and compression of the frontal lobes. Given the relationship to dietary behaviors, our objective was to evaluate the relationship between OGMs and postoperative weight loss.
Methods: Retrospective review of primary resection of meningiomas between 2017 and 2023 at a single institution was conducted.
J Acoust Soc Am
September 2025
Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio 45207, USA.
Midsagittal ultrasound images depict much of the tongue surface from root to tip, providing important articulatory information about tongue shape. However, portions of the tip can be obscured due to shadowing from the mandible bone and sublingual airspace. Also, tongue curvature or grooving within the elevational beam width can cause ambiguous or double-edge artifacts that obfuscate the midsagittal tongue surface.
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