High-Resolution N-Glycan MALDI Mass Spectrometry Imaging of Subchondral Bone Tissue Microarrays in Patients with Knee Osteoarthritis.

N-glycan alterations contribute to the progression of several joint diseases, including knee osteoarthritis (KOA). However, molecular changes in KOA subchondral trabecular bone, when exposed to different joint loading forces, are still unknown. The aim of this study was, therefore, to demonstrate the feasibility to differentiate N-glycan changes in subchondral trabecular bone from four different joint loading forces of the tibial plateau regions (i.e., Lateral Anterior (L-A), Lateral Posterior (L-P), Medial Anterior (M-A), and Medial Posterior (M-P)) in KOA patients (n = 10) using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) at 20 µm spatial resolution. The degree of cartilage degeneration was evaluated histologically, and the subchondral bone tissue microarrays (TMAs) were subsequently manually constructed from formalin-fixed paraffin-embedded (FFPE) KOA osteochondral (i.e., cartilage-subchondral bone) tissues. Overall, the Osteoarthritis Research Society International (OARSI) histological grade was significantly higher and the size of chondrocytes in the superficial zone was much larger for both M-A and M-P compared to L-A and L-P of cartilage (p = 0.006, p = 0.030, p = 0.028, and p = 0.010; respectively). Among the 65 putative N-glycans observed by MALDI-MSI, 2 core fucosylated bi-antennary N-glycans, m/z 1809.64; (Hex)5(HexNAc)4(Fuc)1 and 2100.73; (NeuAc)1(Hex)5(HexNAc)4(Fuc)1, were significantly higher in intensity in M-A compared to L-A of the trabecular bone (p = 0.027, and p = 0.038, respectively). These N-glycans were then further structurally characterized by in situ MS/MS fragmentation post-MALDI-MSI. Our results demonstrate, for the first time, N-glycan alterations can occur at different joint loading forces in the KOA tibial plateau and the feasibility of subchondral bone TMA construction for N-glycan MALDI-MSI.

Complex-Type N-Glycans Are Associated with Cartilage Degeneration within Different Loading Sites of the Tibial Plateau for Knee Osteoarthritis Patients.

Abnormal N-glycosylation has been shown to play an important role in the pathogenesis of multiple diseases. However, little is known about the relationship between N-glycosylation and knee osteoarthritis (KOA) progression at the tissue level. Thus, the aim of this study was to quantify the cartilage histomorphometric changes in formalin-fixed paraffin-embedded (FFPE) tissue collected from the lateral and medial compartments of the tibial plateau KOA patients (n = 8). Subsequently, N-glycans were analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) followed by in situ MS/MS fragmentation. Overall, the Osteoarthritis Research Society International (OARSI) histological grade and cartilage surface fibrillation index were significantly higher, and chondrocyte size in the superficial zone was much larger, for the medial high-loaded cartilage compared to the lateral less-loaded cartilage. Among 92 putative N-glycans observed by MALDI-MSI, 3 complex-type N-glycans, (Hex)4(HexNAc)3, (Hex)4(HexNAc)4, and (Hex)5(HexNAc)4, and 1 oligomannose-type N-glycan, (Hex)9(HexNAc)2, were significantly higher in intensity in the medial cartilage compared to the lateral cartilage, whereas 2 tetra-antennary fucosylated-type N-glycans, (Hex)3(HexNAc)6(Fuc)2 and (Hex)3(HexNAc)6(Fuc)3, were significantly higher in intensity in the lateral cartilage than the medial cartilage. Our findings indicate that complex-type N-glycans are associated with higher severity of cartilage degeneration and may influence the cellular processes of KOA.

Examining agreement between finite element modelling methodologies in predicting pathological fracture risk in proximal femurs with bone metastases.

BACKGROUND: Finite element modelling methodologies available for assessing femurs with metastases accurately predict strength and pathological fracture risk which has led them to being considered for implementation into the clinic. However, the models available use varying material models, loading conditions, and critical thresholds. The aim of this study was to determine the agreement between finite element modelling methodologies in assessing fracture risk in proximal femurs with metastases. METHODS: CT images of the proximal femur were obtained of 7 patients who presented with a pathologic femoral fracture (fracture group) and the contralateral femur of 11 patients scheduled for prophylactic surgery (non-fracture group). Fracture risk was predicted for each patient following three established finite modelling methodologies which have previously shown to accurately predict strength and determine fracture risk: non-linear isotropic -based model, strain fold ratio -based model, Hoffman failure criteria -based model. FINDINGS: The methodologies demonstrated good diagnostic accuracy in assessing fracture risk (AUC = 0.77, 0.73, and 0.67). There was a stronger monotonic association between the non-linear isotropic and Hoffman -based models (τ = 0.74) than with the strain fold ratio model (τ = -0.24 and - 0.37). There was moderate or low agreement between methodologies in discriminating between individuals at high or low risk of fracture (κ = 0.20, 0.39, and 0.62). INTERPRETATION: The present results suggest there may be a lack of consistency in the management of pathological fractures in the proximal femur based on the finite element modelling methodologies.

The Comparison of InSb-Based Thin Films and Graphene on SiC for Magnetic Diagnostics under Extreme Conditions.

The ability to precisely measure magnetic fields under extreme operating conditions is becoming increasingly important as a result of the advent of modern diagnostics for future magnetic-confinement fusion devices. These conditions are recognized as strong neutron radiation and high temperatures (up to 350 °C). We report on the first experimental comparison of the impact of neutron radiation on graphene and indium antimonide thin films. For this purpose, a 2D-material-based structure was fabricated in the form of hydrogen-intercalated quasi-free-standing graphene on semi-insulating high-purity on-axis 4H-SiC(0001), passivated with an Al2O3 layer. InSb-based thin films, donor doped to varying degrees, were deposited on a monocrystalline gallium arsenide or a polycrystalline ceramic substrate. The thin films were covered with a SiO2 insulating layer. All samples were exposed to a fast-neutron fluence of ≈7×1017 cm-2. The results have shown that the graphene sheet is only moderately affected by neutron radiation compared to the InSb-based structures. The low structural damage allowed the graphene/SiC system to retain its electrical properties and excellent sensitivity to magnetic fields. However, InSb-based structures proved to have significantly more post-irradiation self-healing capabilities when subject to proper temperature treatment. This property has been tested depending on the doping level and type of the substrate.

Cemented Revision Hip Arthroplasty With Femoral Impaction Bone Grafting.

Long-stemmed uncemented implants are commonly used during revision hip arthroplasty but may be difficult to re-revise. Impaction bone grafting allows for the use of a shorter cemented stem during revision hip arthroplasty and may restore bone stock in patients with substantial femoral defects. Femoral impaction bone grafting is particularly beneficial in younger patients, who are more likely to require additional revision procedures in the future. The surgical technique used at our institution includes improvements to previous methods including the use of modular tamps and nonirradiated, size-profiled bone graft.