Biomarkers in Neurodegenerative Diseases: Proteomics Spotlight on ALS and Parkinson's Disease.

Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) are both characterized by pathogenic protein aggregates that correlate with the progressive degeneration of neurons and the loss of behavioral functions. Both diseases lack biomarkers for diagnosis and treatment efficacy. Proteomics is an unbiased quantitative tool capable of the high throughput quantitation of thousands of proteins from minimal sample volumes.

Intermittent parathyroid hormone increases stability and improves osseointegration of initially unstable implants.

Aims: To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants.

Methods: 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH).

Immune Response to Persistent Staphyloccocus Aureus Periprosthetic Joint Infection in a Mouse Tibial Implant Model.

Staphyloccocus aureus is one of the major pathogens in orthopedic periprosthetic joint infection (PJI), a devastating complication of total joint arthroplasty that often results in chronic and persistent infections that are refractory to antibiotics and require surgical interventions. Biofilm formation has been extensively investigated as a reason for persistent infection. The cellular composition, activation status, cytokine profile, and role of the immune response during persistent S.

RNA-seq Analysis of Peri-Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice.

The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant loosening, which is related to deficient osseointegration in cementless TJRs.

Identifying alternative antibiotics that elute from calcium sulfate beads for treatment of orthopedic infections.

There has been increasing interest in the use of a synthetic absorbable calcium sulfate (CaSO ) for local antibiotic delivery in orthopaedic infections. The purpose of this study was to quantify elution kinetics of six antibiotics (amikacin, meropenem, fosfomycin, minocycline, cefazolin, and dalbavancin) from a clinically relevant CaSO bead model and compare elution and antimicrobial activity to the current clinical gold standards: vancomycin and tobramycin. Antibiotic-loaded synthetic CaSO beads were immersed in phosphate buffered saline and incubated at 37°C.

Immune and repair responses in joint tissues and lymph nodes after knee arthroplasty surgery in mice.

The importance of a local tissue immune response in healing injured tissues such as skin and lung is well established. Little is known about whether sterile wounds elicit lymph node (LN) responses and inflammatory responses after injury of musculoskeletal tissues that are mechanically loaded during the repair response. We investigated LN and tissue immune responses in a tibial implant model of joint replacement surgery where wounded tissue is subjected to movement and mechanical loading postoperatively.

Thermal Stability and in Vitro Elution Kinetics of Alternative Antibiotics in Polymethylmethacrylate (PMMA) Bone Cement.

Background: Amikacin, meropenem, minocycline, and fosfomycin have potential clinical utility for orthopaedic infections; however, their suitability for use in polymethylmethacrylate (PMMA) is poorly understood. The purpose of this study was (1) to quantify the thermal stability of these antibiotics at clinically relevant temperatures and (2) to determine the elution pharmacodynamics of these alternative antibiotics in vitro from PMMA beads of different sizes.

Methods: Polymerization temperatures of 10-mm PMMA beads were measured over time to generate a simulated heating curve.

A method for colocalizing lineage tracing reporter and RNAscope signals on skeletal tissue section.

Fluorescent reporters have been widely used in modern biology as a powerful tool in cell lineage tracing during development and in studying the pathogenesis of diseases. RNAscope is a recently developed RNA in situ hybridization method with high specificity and sensitivity. Combined application of these two techniques on skeletal tissue is difficult and has not been done before; the reporter fluorophores in the tissue specimen bleach quickly and mRNAs degrade rapidly due to the decalcification process typically used in processing skeletal samples.

Alendronate enhances osseointegration in a murine implant model.

Administration of bisphosphonates following total joint arthroplasty might be beneficial to reduce aseptic loosening. However, their effects on peri-implant bone formation and bone-implant interface strength have not been investigated yet. We used a physiologically loaded mouse implant model to investigate the short-term effects of postoperative systemic alendronate on osseointegration.

2020 John Charnley Award: The antimicrobial potential of bacteriophage-derived lysin in a murine debridement, antibiotics, and implant retention model of prosthetic joint infection.

Aims: Current treatments of prosthetic joint infection (PJI) are minimally effective against biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target biofilm and address the unique challenges presented in this periprosthetic environment.

Methods: The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models.

Vancomycin-laden calcium phosphate-calcium sulfate composite allows bone formation in a rat infection model.

Objective: Local antibiotic delivery systems with differing chemical and mechanical properties have been developed to assist in the management of osteomyelitis. We investigated the bone conductive and resorptive capabilities of a calcium phosphate-calcium sulfate (CaP/CaS) composite compared with commercially available polymethylmethacrylate (PMMA). In addition, we compared the in vivo preventative and treatment efficacies of both biomaterials in a proven osteomyelitis model.