Emerging Targets for the Treatment of Osteoarthritis: New Investigational Methods to Identify Neo-Vessels as Possible Targets for Embolization.

Osteoarthritis (OA) is the major cause of disability, affecting over 30 million US adults. Continued research into the role of neovascularization and inflammation related to osteoarthritis in large-animal models and human clinical trials is paramount. Recent literature on the pathogenetic model of OA has refocused on low-level inflammation, resulting in joint remodeling.

Osteoarthritis-Related Knee Pain Treated With Genicular Artery Embolization: A Systematic Review and Meta-analysis.

Background: Genicular artery embolization (GAE) is an innovative technique that has been investigated as a supplementary treatment method for chronic pain secondary to knee osteoarthritis (OA).

Purpose: To evaluate the current evidence on the effectiveness and safety of GAE for OA-related knee pain.

Study Design: Systematic review; Level of evidence, 4.

Automatic annotation of hip anatomy in fluoroscopy for robust and efficient 2D/3D registration.

Purpose: Fluoroscopy is the standard imaging modality used to guide hip surgery and is therefore a natural sensor for computer-assisted navigation. In order to efficiently solve the complex registration problems presented during navigation, human-assisted annotations of the intraoperative image are typically required. This manual initialization interferes with the surgical workflow and diminishes any advantages gained from navigation.

Augmented Reality for Acetabular Component Placement in Direct Anterior Total Hip Arthroplasty.

Background: Malposition of the acetabular component of a hip prosthesis can lead to poor outcomes. Traditional placement with fluoroscopic guidance results in a 35% malpositioning rate. We compared the (1) accuracy and precision of component placement, (2) procedure time, (3) radiation dose, and (4) usability of a novel 3-dimensional augmented reality (AR) guidance system vs standard fluoroscopic guidance for acetabular component placement.

Pose Estimation of Periacetabular Osteotomy Fragments With Intraoperative X-Ray Navigation.

Objective: State-of-the-art navigation systems for pelvic osteotomies use optical systems with external fiducials. In this paper, we propose the use of X-ray navigation for pose estimation of periacetabular fragments without fiducials.

Methods: A two-dimensional/three-dimensional (2-D/3-D) registration pipeline was developed to recover fragment pose.

Surface melt driven summer diurnal and winter multi-day stick-slip motion and till sedimentology.

Fluctuations in glacier motion are very common and are thought to be controlled by subglacial hydrology and till deformation. There are few instrumented studies that have monitored seasonal changes. We use the innovative Glacsweb subglacial in situ wireless probes, combined with dGPS and custom geophone data from an Icelandic soft-bedded temperate glacier, to show that there are two distinct seasonal styles of speed-up events.

Bilateral Eccrine Angiomatous Hamartoma with Symmetric Volar Wrist Nodules: A Case Report.

Case: We describe a 13-year-old girl with bilateral symmetric eccrine angiomatous hamartoma (EAH) on the volar aspect of the wrists. The lesions were painless and had been enlarging progressively for 1 year; the enlargement of the nodule on the right wrist was more substantial than that on the left wrist. She had palmar hyperhidrosis, which has a known association with EAH.

Plan in 2-D, execute in 3-D: an augmented reality solution for cup placement in total hip arthroplasty.

Reproducibly achieving proper implant alignment is a critical step in total hip arthroplasty procedures that has been shown to substantially affect patient outcome. In current practice, correct alignment of the acetabular cup is verified in C-arm x-ray images that are acquired in an anterior-posterior (AP) view. Favorable surgical outcome is, therefore, heavily dependent on the surgeon's experience in understanding the 3-D orientation of a hemispheric implant from 2-D AP projection images.

Post-Discharge Care Duration, Charges, and Outcomes Among Medicare Patients After Primary Total Hip and Knee Arthroplasty.

Background: In April 2016, the U.S. Centers for Medicare & Medicaid Services initiated mandatory 90-day bundled payments for total hip and knee arthroplasty for much of the country.

The ability of Sos1 to oligomerize the adaptor protein LAT is separable from its guanine nucleotide exchange activity in vivo.

The activation of the small guanosine triphosphatase Ras by the guanine nucleotide exchange factor (GEF) Sos1 (Son of Sevenless 1) is a central feature of many receptor-stimulated signaling pathways. In developing T cells (thymocytes), Sos1-dependent activation of extracellular signal-regulated kinase (ERK) is required to stimulate cellular proliferation and differentiation. We showed that in addition to its GEF activity, Sos1 acted as a scaffold to nucleate oligomerization of the T cell adaptor protein LAT (linker for activation of T cells) in vivo.

A phospholipase C-γ1-independent, RasGRP1-ERK-dependent pathway drives lymphoproliferative disease in linker for activation of T cells-Y136F mutant mice.

Mice expressing a germline mutation in the phospholipase C-γ1-binding site of linker for activation of T cells (LAT) show progressive lymphoproliferation and ultimately die at 4-6 mo age. The hyperactivated T cells in these mice show defective TCR-induced calcium flux but enhanced Ras/ERK activation, which is critical for disease progression. Despite the loss of LAT-dependent phospholipase C-γ1 binding and activation, genetic analysis revealed RasGRP1, and not Sos1 or Sos2, to be the major Ras guanine exchange factor responsible for ERK activation and the lymphoproliferative phenotype in these mice.

Deconstructing Ras signaling in the thymus.

Thymocytes must transit at least two distinct developmental checkpoints, governed by signals that emanate from either the pre-T cell receptor (pre-TCR) or the TCR to the small G protein Ras before emerging as functional T lymphocytes. Recent studies have shown a role for the Ras guanine exchange factor (RasGEF) Sos1 at the pre-TCR checkpoint. At the second checkpoint, the quality of signaling through the TCR is interrogated to ensure the production of an appropriate T cell repertoire.

Targeted Sos1 deletion reveals its critical role in early T-cell development.

Activation of the small G protein Ras is required for thymocyte differentiation. In thymocytes, Ras is activated by the Ras guanine exchange factors (RasGEFs) Sos1, Sos2, and RasGRP1. We report the development of a floxed allele of sos1 to assess the role of Sos1 during thymocyte development.

Vesicular monoamine transporter-1 (VMAT-1) mRNA and immunoreactive proteins in mouse brain.

Objective: Vesicular monoamine transporter 1 (VMAT-1) mRNA and protein were examined (1) to determine whether adult mouse brain expresses full-length VMAT-1 mRNA that can be translated to functional transporter protein and (2) to compare immunoreactive VMAT-1 proteins in brain and adrenal.

Methods: VMAT-1 mRNA was detected in mouse brain with RT-PCR. The cDNA was sequenced, cloned into an expression vector, transfected into COS-1 cells, and cell protein was assayed for VMAT-1 activity.