Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model.

Many risk genes for the development of Alzheimer's disease (AD) are exclusively or highly expressed in myeloid cells. Microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for their survival. We designed and synthesized a highly selective brain-penetrant CSF1R inhibitor (PLX5622) allowing for extended and specific microglial elimination, preceding and during pathology development.

Can We Accurately Predict the Quadruple Hamstring Graft Diameter From Preoperative Magnetic Resonance Imaging?

Background: Anterior cruciate ligament (ACL) reconstruction with a quadruple hamstring (QH) autograft is a widely utilized procedure with good outcomes. A graft diameter less than 8 mm, however, has been associated with higher revision rates. Accurately determining the diameter of the hamstring tendon preoperatively can help surgeons plan accordingly.

BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.

Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is overexpressed in CLL and is enriched proximal to genes upregulated or expressed in CLL with known functions in disease pathogenesis and progression.

RAF inhibitors that evade paradoxical MAPK pathway activation.

Oncogenic activation of BRAF fuels cancer growth by constitutively promoting RAS-independent mitogen-activated protein kinase (MAPK) pathway signalling. Accordingly, RAF inhibitors have brought substantially improved personalized treatment of metastatic melanoma. However, these targeted agents have also revealed an unexpected consequence: stimulated growth of certain cancers.

Extensile posterior approach to the ankle with detachment of the achilles tendon for oncologic indications.

Background: We describe an extensile posterior approach to the ankle with detachment of the Achilles tendon for resection of extensive tumors involving the posterior ankle. To the best of our knowledge, this approach and its results have not been reported for oncologic indications.

Methods: The surgical technique involved detachment of the Achilles tendon, tumor resection and reconstruction of the Achilles tendon with anchor sutures, and was used in six patients.

Athletic trainers' and physical therapists' perceptions of the effectiveness of psychological skills within sport injury rehabilitation programs.

Context: Psychological skills are alleged to augment sport-injury rehabilitation; however, implementation of mental imagery within rehabilitation programs is limited.

Objective: To examine attitudes of athletic trainers (ATs) and physical therapists (PTs) on the effectiveness of mental imagery, goal setting, and positive self-talk to improve rehabilitation adherence and recovery speed of injured athletes.

Design: The ATs and PTs were contacted via electronic or physical mailings to complete a single administration survey that measured their beliefs about the effectiveness of psychological skills for increasing adherence and recovery speed of injured athletes undergoing rehabilitation.