- Knee injuries and reconstruction techniques
- Osteoarthritis Treatment and Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Congenital gastrointestinal and neural anomalies
- Total Knee Arthroplasty Outcomes
- Parkinson's Disease Mechanisms and Treatments
- Intestinal Malrotation and Obstruction Disorders
- Anorectal Disease Treatments and Outcomes
- Gastrointestinal motility and disorders
- Tendon Structure and Treatment
- Bioinformatics and Genomic Networks
- Shoulder Injury and Treatment
- Musculoskeletal pain and rehabilitation
- Single-cell and spatial transcriptomics
- Lower Extremity Biomechanics and Pathologies
- Clostridium difficile and Clostridium perfringens research
- Lysosomal Storage Disorders Research
- Pelvic floor disorders treatments
- Cellular transport and secretion
- Gastrointestinal disorders and treatments
- COVID-19 Clinical Research Studies
- Congenital Diaphragmatic Hernia Studies
- Bariatric Surgery and Outcomes
- Computational Drug Discovery Methods
- Pancreatic and Hepatic Oncology Research
Children's National
2023-2024
Sanofi (United States)
2021-2024
Sanofi (France)
2024
Thomas Jefferson University
2014-2023
Nemours Children's Health System
2022-2023
Sanofi (Mexico)
2021-2022
Dupont Hospital
2018-2021
Thomas Jefferson University Hospital
2017-2021
Framingham State University
2021
Alfred I. duPont Hospital for Children
2017-2020
Iron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinson's disease (PD). Iron-loaded microglia are frequently found affected brain regions, but how iron accumulation influences physiology and contributes to neurodegeneration is poorly understood. Here we show that human induced pluripotent stem cell-derived grown a tri-culture system highly responsive susceptible ferroptosis, an iron-dependent form of cell death. Furthermore, overload causes marked...
To investigate whether cartilage degeneration is prevented or minimized following intraarticular injections of lubricin derived from human synoviocytes in culture, recombinant PRG4 (rhPRG4), synovial fluid (SF) a rat model anterior cruciate ligament (ACL) injury. Unilateral ACL transection (ACLT) was performed Lewis rats (n = 45). Nine animals were left untreated. The remaining given (50 microl/injection) either phosphate buffered saline (PBS) 9), synoviocyte (200 microg/ml; n rhPRG4 SF 9)...
Abstract Early characterization of drug targets associated with disease can greatly reduce clinical failures attributed to lack safety or efficacy. As single-cell RNA sequencing (scRNA-seq) human tissues becomes increasingly common for profiling, the insights obtained from this data could influence target selection strategies. Whilst use scRNA-seq understand biology is well established, impact in increasing probability candidate therapeutic successfully advance research clinic has not been...
Background: Lubricin and hyaluronic acid lubricate articular cartilage prevent wear. Because lubricin loss occurs after anterior cruciate ligament injury, intra-articular injections may reduce damage in the ligament–deficient knee. Purpose: This study was conducted to determine if and/or supplementation will Study Design: Controlled laboratory study. Methods: Thirty-six male rats, 3 months old, underwent unilateral transection. They were randomized 4 treatments: (1) saline...
Abstract The coefficient of friction (COF) articular cartilage is thought to increase with osteoarthritis (OA) progression, and this may occur due a decrease in lubricin concentration. objectives study were measure the COF guinea pig tibiofemoral joints different stages OA establish relationships between COF, concentrations synovial fluid, degradation status using Hartley model. Both hind limbs from 24 animals harvested: seven 3‐month‐old (no OA), 12‐month‐old (mild 10 that euthanized at 12...
Abstract Objective To investigate whether cartilage degeneration is prevented or minimized in a rat model of anterior cruciate ligament (ACL) injury following single dose‐escalated intraarticular injection lubricin derived from human synoviocytes culture. Methods Unilateral ACL transection (ACLT) the right hind limb was performed Lewis rats (n = 56). Control animals underwent capsulotomy alone, leaving intact 11). Intraarticular injections (50 μl/injection) phosphate buffered saline (PBS; n...
The objective was to compare biomarkers of articular cartilage metabolism in synovial fluid from Hartley guinea pig knees, with and without anterior cruciate ligament transection (ACLT), establish whether detectable differences biomarker levels exist between primary secondary osteoarthritis (OA). Synovial lavages knees were obtained 3-month (control group) 12-month (primary OA animals. Another group animals (posttraumatic underwent unilateral ACLT at 3 months, samples 9 months postsurgery....
Background: Lubricin, or proteoglycan 4 (PRG4), is a glycoprotein responsible for joint boundary lubrication. PRG4 has been shown previously to be down-regulated after traumatic injury such as meniscal tear. Preliminary evidence suggests that intra-articular injection of will reduce cartilage damage in rat models surgically induced posttraumatic osteoarthritis. Objective: To determine the efficacy full-length recombinant human lubricin (rhPRG4) reducing medial destabilization (DMM)...
Background: Neuronopathic Gaucher disease (nGD) is a rare neurodegenerative disorder caused by biallelic mutations in GBA and buildup of glycosphingolipids lysosomes. Neuronal injury cell death are prominent pathological features; however, the role individual types involvement microglia, blood-derived macrophages, immune infiltrates nGD pathophysiology remains enigmatic. Methods: Here, using single-cell resolution mouse brains, lipidomics, newly generated biomarkers, we found induction...
Abstract Bariatric surgery results in durable weight loss and improved comorbidities. The objectives of this study were to examine the efficacy gastric bypass reducing comorbid burden improving metabolic status among morbidly obese adolescents. medical records 15 patients retrospectively reviewed. Changes markers determined at baseline, 1 2 years post‐operatively. Comparative analysis demonstrated significant improvement weight, BMI, insulin, HbA1C, C‐peptide, %B, %S, IR, cholesterol,...
Infection with Campylobacter jejuni serotype HS:19 is associated the development of Guillain-Barré syndrome (GBS). To determine whether a particular clone GBS, multilocus enzyme electrophoresis (MLEE) was used to analyze worldwide collection isolates. There were 34 electropherotypes (ETs) in 3 phylogenetic clusters among 83 C. Cluster I contained all strains, and single ET (ET4) accounted for most strains. strains did not occur any other clusters. ET4 isolates from different geographic...
<h3>Objective</h3> With increasing emphasis on early and frequent mobilisation of patients in acute care, safe patient handling practices need to be integrated into these quality initiatives. We completed a programme evaluation within the context hospital-wide care improvement initiative that utilised systems approach equipment plans. <h3>Methods</h3> Baseline 12-month follow-up surveys 1832 direct workers assessed work self-reported pain while an employee payroll injury database provided...
A pendulum test with a whole articular joint serving as the fulcrum is commonly used to measure bulk coefficient of friction (COF). In such tests it universally assumed that energy loss due frictional damping only, and accordingly decay amplitude linear time. The purpose this work was determine whether measurement COF improved when viscous exponential are incorporated into lumped-parameter model. Various models range values for were constructed. resulting fitted an function (including both...
Abstract Background The Open Targets (OT) Platform integrates a wide range of data sources on target-disease associations to facilitate identification potential therapeutic drug targets treat human diseases. However, due the complexity that are usually functionally pleiotropic and efficacious for multiple indications, challenges in identifying novel target indication remain. Specifically, persistent need exists new methods integration association evidence biological knowledge bases via...
We performed an integrated cross-sectional analysis of relationships between long-term care work environments, employee and resident satisfaction, quality patient care.Facility-level data came from a network 203 skilled nursing facilities in 13 states the eastern United States owned or managed by one company. K-means cluster was applied to investigate clustered associations safe handling program (SRHP) performance, outcomes, rates workers' compensation claims, satisfaction.Facilities...