bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARISON OF POSTOPERATIVE CLINICAL OUTCOMES BETWEEN CRUCIATE-RETAINING AND RESECTING TOTAL KNEE ARTHROPLASTY WITH A CRUCIATE-SUBSTITUTING INSERT
Authors: Kato K. , Hayashi S.
Published: November 2024

Purpose

To compare postoperative clinical outcomes between posterior cruciate ligament (PCL) retaining and resecting total knee arthroplasty (TKA) using same cruciate-substituting (CS) inserts, and to elucidate the clinical relevance of the residual PCL in cruciate-retaining TKA, considering intraoperative influence factors, such as the posterior tibial slope, posterior condylar offset, joint gap, joint balance, and joint laxity.

Methods

A total of 64 consecutive knees (44 patients) were enrolled in this study and divided into following two groups: 39 knees underwent PCL-retaining TKA group (CR group), and 25 underwent PCL-resecting TKA group (CS group). Preoperative patients’ demographic data and one-year postoperative clinical outcomes including range of motion, the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Japanese Orthopaedic Association (JOA) score, and Forgotten Joint Score-12 (FJS-12) were compared between two groups.

Results

Regarding range of motion, the average preoperative ROM was -14.3/120.0 degrees in the CR group and improved to -2.4/118.9 degrees postoperatively. In the CS group, the average preoperative ROM was -7.5/130 degrees and changed to -2.2/122.4 degrees postoperatively. There was no significant difference in the postoperative ROM between the groups (P=0.16). The KOOS (from 47.1 to 69.5 in CR group; from 41.1 to 70.8 in CS group) and JOA scores (from 59.2 to 76.9 in CR group; from 55.6 to 80.8 in CS group) were significantly improved postoperatively in both groups (P < 0.01). However, there was no significance in these postoperative scores between two groups (P = 0.09). There was also no significance in FJS-12 between two groups (70.3 in CR group and 66.9 in CS group; P=0.53).

Conclusions

Residual PCL in TKA with a CS insert would not impact one-year postoperative clinical outcomes including KOOS, JOA, and FJS-12.
TAILOR-MADE NANOSWITCHES FOR TARGETED MODULATION OF PIEZO1 MECHANOSENSING INFLUENCE STEM CELL FATE
Authors: Teixeira S. P. B. , Pardo A. , Taboada P. , Wolleb M. , Snedeker J. , Reis R. L. , Gomes M. M. E. , Domingues R. M. A.
Published: November 2024

Introduction

PIEZO mechanoreceptors are increasingly recognized to play critical roles in fundamental physiological processes like proprioception, touch, or tendon biomechanics. However, their gating mechanisms and downstream signaling are still not completely understood, mainly due to the lack of effective tools to probe these processes. Here, we developed new tailor-made nanoswitches enabling wireless targeted actuation on PIEZO1 by combining molecular imprinting concepts with magnetic systems.

Method

Two epitopes from functionally relevant domains of PIEZO1 were rationally selected in silico and used as templates for synthesizing molecularly imprinted nanoparticles (MINPs). Highly-responsive superparamagnetic zinc-doped iron oxide nanoparticles were incorporated into MINPs to grant them magnetic responsiveness. Endothelial cells (ECs) and adipose tissue-derived stem cells (ASCs) incubated with each type of MINP were cultured under or without the application of cyclical magnetomechanical stimulation. Downstream effects of PIEZO1 actuation on cell mechanotransduction signaling and stem cell fate were screened by analyzing gene expression profiles.

Result

Nanoswitches showed sub-nanomolar affinity for their respective epitope, binding PIEZO1-expressing ECs similarly to antibodies. Expression of genes downstream of PIEZO1 activity significantly changed after magnetomechanical stimulation, demonstrating that nanoswitches can transduce this stimulus directly to PIEZO1 mechanoreceptors. Moreover, this wireless actuation system proved effective for modulating the expression of genes related to musculoskeletal differentiation pathways in ASCs, with RNA-sequencing showing pronounced shifts in extracellular matrix organization, signal transduction, or collagen biosynthesis and modification. Importantly, targeting each epitope led to different signaling effects, implying distinct roles for each domain in the sophisticated function of these channels.

Conclusion

This innovative wireless actuation technology provides a promising approach for dissecting PIEZO-mediated mechanobiology and suggests potential therapeutic applications targeting PIEZO1 in regenerative medicine for mechanosensitive tissues like tendon.

Acknowledgements

EU's Horizon 2020 ERC under grant No. 772817 and Horizon Europe under grant No. 101069302; FCT/MCTES for PD/BD/143039/2018, COVID/BD/153025/2022, 10.54499/2020.03410.CEECIND/CP1600/CT0013, 10.54499/2022.05526.PTDC, 10.54499/UIDB/50026/2020, 10.54499/UIDP/50026/2020, and 10.54499/LA/P/0050/2020.
TRICARBOXYLIC ACID CYCLE INTERMEDIATE A-KETOGLUTARATE PRESERVES BONE FORMATION AND COUNTERACTS OSTEOPOROSIS DEVELOPMENT
Authors: Chen Y. S. , Lian W. S. , Lin Yu-Han , Wang Feng-Sheng
Published: November 2024

Introduction

Promoting bone mass homeostasis keeps skeleton away from osteoporosis. a-Ketoglutarate (a-KG) is an indispensable intermediate of tricarboxylic acid cycle (TCA) process for cellular energy production. a-KG mitigates cellular senescence, tissue degeneration, and oxidative stress. We investigated whether a-KG affected osteoblast activity or osteoporosis development.

Method

Serum and bone specimens were biopsied from 26 patients with osteoporosis or 24 patients without osteoporosis who required spinal surgery. Ovariectomized or aged mice were fed 0.25% or 0.75% a-KG in drinking water for 8 – 12 weeks ad libitum. Bone mineral density, trabecular/cortical bone microarchitecture, mechanical strength, bone formation, and osteoclastic erosion were investigated using mCT, material testing device, in vivo calcein labelling, and TRAP histochemical staining. Serum a-KG, osteocalcin, and TRAP5b levels were quantified using ELISA kits. Bone-marrow mesenchymal cells and macrophages were incubated osteogenic and osteoclastogenic media. Histone H3K27me3 levels and enrichment were investigated using immunoblotting and chromatin precipitation-PCR.

Result

Serum a-KG levels in patients with osteoporosis were less than controls; and were correlated with T-scores of hips (R2 = 0.6471, P < 0.0001) and lumbar spine (R2 = 0.7235, P < 0.001) in osteoporosis (AUC = 0.9941, P < 0.001). a-KG supplement compromised a plethora of osteoporosis signs in ovariectomized or aged mice, including bone mass loss, trabecular bone microarchitecture deterioration, and mechanical strength loss. It elevated serum osteocalcin levels and decreased serum TRAP5b. a-KG preserved caclein-labelling bone formation and repressed osteoclast resorption. It reversed osteogenic differentiation of bone-marrow stromal cells and reduced osteoclast formation in ovariectomized mice. Mechanically, a-KG attenuated H3K27 hypermethylation and Runx2 transcription repression, improving mineralized matrix production in osteogenic cells.

Conclusion

Decreased serum a-KG is correlated with human and murine osteoporosis. a-KG reverses bone loss by repressing histone methylation in osteoblasts. This study highlighted a-KG supplement as a new biochemical option for protecting osteoporosis.
BIOMECHANICAL ANALYSIS OF ADOLESCENT IDIOPATHIC SCOLIOSIS: INVESTIGATING MUSCLE ACTIVATION ASYMMETRY DURING GAIT USING A COMPREHENSIVE THORACIC MUSCULOSKELETAL MODEL
Authors: Shayestehpour H. , Shayestehpour M. A. , Wong C. , Bencke J. , Rasmussen J.
Published: November 2024

Introduction

Adolescent Idiopathic Scoliosis (AIS) is a three-dimensional deformity of the spine with unclear etiology. Due to the asymmetry of lateral curves, there are differences in the muscle activation between the convex and concave sides. This study utilized a comprehensive thoracic spine and ribcage musculoskeletal model to improve the biomechanical understanding of the development of AIS deformity and approach an explanation of the condition.

Methods

In this study, we implemented a motion capture model using a generic rigid-body thoracic spine and ribcage model, which is kinematically determinate and controlled by spine posture obtained, for instance, from radiographs. This model is publicly accessible via a GitHub repository. We simulated gait and standing models of two AIS (averaging 15 years old, both with left lumbar curve and right thoracic curve averaging 25 degrees) and one control subject. The marker set included extra markers on the sternum and the thoracic and lumbar spine. The study was approved by the regional Research Ethics Committee (Journal number: H17034237).

Results

We investigated the difference between the muscle activation on the right and left sides including erector spinae (ES), psoas major (PS), and multifidus (MF). Results of the AIS simulations indicated that, on average throughout the gait cycle, the right ES, left PS and left MF had 46%, 44%, and 23% higher activities compared to the other side, respectively. In standing, the ratios were 28%, 40%, and 19%, respectively. However, for the control subject, the differences were under 7%, except ES throughout the gait, which was 17%.

Conclusion

The musculoskeletal model revealed distinct differences in force patterns of the right and left sides of the spine, indicating an instability phenomenon, where larger curves lead to higher muscle activations for stabilization.

Acknowledgement

The project is funded by the European Union's Horizon 2020 program through Marie Skłodowska-Curie grant No. [764644].
ROLE OF ALPHA-CGRP IN THE DEVELOPMENT OF POST-TRAUMATIC OSTEOARTHRITIS IN THE CONTEXT OF FORCED EXERCISE
Authors: Pann P. , Taheri S. , Schilling A. F. , Graessel S.
Published: November 2024

Introduction

Osteoarthritis (OA) causes pain, stiffness, and loss of function due to degenerative changes in joint cartilage and bone. In some forms of OA, exercise can alleviate symptoms by improving joint mobility and stability. However, excessive training after joint injury may have negative consequences for OA development. Sensory nerve fibers in joints release neuropeptides like alpha-calcitonin gene-related peptide (alpha-CGRP), potentially affecting OA progression. This study investigates the role of alpha-CGRP in OA pathogenesis under different exercise regimen in mice.

Method

OA was induced in C57Bl/6J WT mice and alpha-CGRP KO mice via surgical destabilization of the medial meniscus (DMM) at 12 weeks of age (N=6). Treadmill exercise began 2 weeks post-surgery and was performed for 30 minutes, 5 days a week, for 2 or 6 weeks at intense (16 m/min, 15° incline) or moderate (10 m/min, 5° incline) levels. Histomorphometric assessment of cartilage degradation (OARSI scoring), serum cytokine analysis, immunohistochemistry, and nanoCT analysis were conducted.

Result

OARSI scoring confirmed OA induction 4 weeks post-DMM surgery, with forced exercise exacerbating cartilage degradation regardless of intensity. No significant genotype-dependent differences were observed. Serum analysis revealed elevated cytokine levels associated with OA and inflammation in KO mice compared to WT mice 4 and 8 weeks post-surgery (VEGF-A, MCP-1, CXCL10, RANTES, MIP1-alpha, MIP1-beta, and RANKL). The observed effects were often exacerbated by intense exercise but rarely by DMM surgery. NanoCT analysis demonstrated increased sclerotic bone changes after 6 weeks of forced exercise in KO mice compared to WT mice.

Conclusion

Our results suggest an OA promoting effect of exercise in early disease stages of posttraumatic OA. Intense exercise induced inflammatory processes correlated to increased cytokine levels in the serum that might exacerbate OA pathogenesis in later stages. The neuropeptide alpha-CGRP might play a role in protecting against these adverse effects.
DOES THE ADDITION OF FLUORIDE TO BIOACTIVE GLASS AFFECT THE OSTEOGENIC AND ANGIOGENIC PROPERTIES OF BONE PROGENITOR CELLS?
Authors: Durach A. , Kunisch E. , Renkawitz T. , Westhauser F. , Brauer D. , Hohenbild F.
Published: November 2024

Introduction

Bioactive glasses (BGs) promote osteogenic differentiation of bone progenitor cells by releasing therapeutically active ions. The well-described 45S5-BG (in mol%: SiO2 46.13; P2O5 2.60; CaO 26.91; Na2O 24.35) was supplemented with CaF2 and NaF being added to the batch at nominal 5 (F5-BG) and 25 mol% (F25-BG), respectively. While the effect on physical and chemical properties has already been characterized, the biological properties require further studies. This study investigates the effects of fluoride-supplemented BGs on the osteogenic and angiogenic properties of human bone marrow mesenchymal stromal cells (BMSCs) in vitro.

Method

BMSCs were co-cultured with melt-derived 45S5-BG, F5-BG, or F25-BG in ascending concentrations (1, 2 and 3 mg/ml). At 7 days, cell number was determined by 4,6-diamidine-2-phenylindole (DAPI) staining and cell viability by fluorescein diacetate (FDA) assay. The osteogenic potential of the BGs was evaluated through alkaline phosphatase (ALP) gene expression and activity, along with bone morphogenetic protein-2 (BMP2) gene expression and protein concentration. Vascular endothelial growth factor (VEGF) gene expression and protein concentration assessed angiogenic potential. As control, BMSCs were cultured without BG exposure.

Result

All BGs significantly promoted cell number and viability, with F25-BG showing the highest count at 3 mg/ml. Osteogenic markers showed a significant decrease in ALP gene expression and activity, especially at higher concentrations. All BG groups demonstrated increased BMP2 protein concentration and gene expression compared to the control, with higher BG and fluoride concentrations correlating with greater increases in BMP2. VEGF gene expression increased in all analysed BGs. The fluoride-free BG group had the highest VEGF protein concentrations, while the F25 BG group showed the highest VEGF gene expression.

Conclusion

The fluoride-substituted BGs exhibit excellent cytocompatibility, enhance BMSC proliferation and positively affect BMP2 gene expression and levels, suggesting their potential for osteogenic differentiation. Further research is necessary to assess their proangiogenic effect and potential advantages over 45S5-BG.
MACROPHAGE-DERIVED EXTRACELLULAR VESICLES AS POTENTIAL MODULATORS OF TENDON INFLAMMATION
Authors: Cardona S. B. , Atanasov K. S. , Calvo J. , Gayà A. , Florit M. G.
Published: November 2024

Introduction

Tendinopathies represent a significant health burden, causing inflammation, pain, and reducing quality of life. The pivotal role of macrophages (Mφ) characterized by their ability to differentiate into proinflammatory (M1) or anti-inflammatory (M2) phenotypes depending on the microenvironment, has gained significant interest in tissue inflammation research. Additionally, existing literature states that the interplay between tenocytes and immune cells during inflammation involves unidentified soluble factors (SF). This study aimed to investigate the effect of extracellular vesicles (EVs) and SF derived from polarized Mφ on tendon cells to provide deeper insights of their potential therapeutic applications in the context of inflammation.

Method

Human monocytes were isolated from blood donor buffy coats and differentiated into M1, M2, and hybrid M1/M2 phenotypes. Subsequently, EVs were isolated from the conditioned media from polarized Mφ and comprehensively characterized. In parallel, the elution media containing SF was collected. Furthermore, the EVs and SF were released independently onto tenocytes from human donors, previously induced with IL-1β to simulate an inflammatory environment. Finally, mRNA levels of tendon-related markers were evaluated by qPCR after the exposure to these EVs and SF.

Result

Notably, the study found that the viability of the cells was not affected by the exposure to EVs nor SF, indicating their potential safety for therapeutic use. Moreover, the mRNA content of tendon-derived cells was evaluated following exposure to Mφ-EVs and SF revealing alterations in gene expression. Interestingly, a significant increase in the expression of tenomodulin was observed in tendon cells treated with Mφ-EVs.

Conclusion

These results mark a significant advancement in understanding the interplay between Mφ and tenocytes at a molecular level. To fully understand the underlying causes of Mφ-EVs effects, and its potential clinical application in tendon inflammatory diseases, further comprehensive research is required.

Acknowledgments

Carlos III Health Institute and the European Social Fund for contract CP21/00136 and project PI22/01686.
TRIAMCINOLONE: A MODULATOR OF CHONDROCYTE ELASTICITY AND MECHANOSENSITIVITY
Authors: Umrath F. , Liang C. , Jud S. , Alexander D. , Danalache M.
Published: November 2024

Introduction

Osteoarthritis (OA) often results from joint misloading, which affects chondrocyte calcium signaling through mechano-sensitive receptors such as Piezo1, -2, and TRPV4. Activation of Piezo1, especially under inflammatory conditions, can trigger premature chondrocyte apoptosis. Intra-articular glucocorticoid therapy, while beneficial against inflammation and pain in osteoarthritis, may induce oxidative stress and chondrotoxicity at higher doses. This study aims to assess the effects of glucocorticoids, particularly triamcinolone, on chondrocyte elasticity and mechanosignaling.

Method

Chondrocytes isolated from articular condyles obtained from patients undergoing knee replacement surgery (n= 5) were cultured for 7 days in triamcinolone acetonide (TA) at different concentrations (0.2µM – 2mM). Cytoskeletal changes were assessed by F-actin labeling. Cell elasticity was measured using atomic force microscopy (AFM). Labeling cells (n=6 patients) with the calcium-sensitive dye (Fluo-4) enabled monitoring changes in intracellular calcium fluorescence intensity during guided single-cell mechanical indentation (500 nN) by AFM.

Result

Cell exposure to 2 mM TA led to cell death and crystallization of TA in the cell culture media. However, the concentration of TA for intra-articular application is 46 times higher at 92.1 mM (40 mg/ml). The maximal pharmacological effect on viable cells was observed at 0.2 mM. AFM results showed a significant decrease of elasticity (p<0.001), alongside significantly higher calcium intensities both prior to and during mechanical stimulation in the TA-treated samples (p<0.05).

Conclusion

Administration of TA significantly impacts the mechanical properties of chondrocytes, reducing cellular elasticity while simultaneously enhancing calcium-dependent mechanosensitivity. This data suggests a correlation between glucocorticoid-induced changes in cell elasticity and cell mechanosensitivity. Finding ways to minimize the effect of glucocorticoids on cell mechanosensitivity could help to make future therapies safer and reduce side effects.
CAN 3D PLANNING HELP OPTIMIZE FEMORAL HEAD COVERAGE IN PERIACETABULAR OSTEOTOMY?
Authors: Thakur A. , Harris S. , Brkljač M. , Cobb J. , Logishetty K.
Published: November 2024

Introduction

Bernese periacetabular osteotomy (PAO) repositions the acetabulum to increase femoral head coverage (FHC) in hip dysplasia. Currently, there is a paucity of objective peri-operative metrics to plan for optimal acetabular fragment repositioning. The MSk Lab Hip 3D Planner (MSkL-HP) measures acetabular morphology and simulates PAO cuts to achieve optimal FHC. We evaluated how adjusting location and orientation of cutting planes can alter FHC.

Method

MSkL-HP simulated 274 feasible PAOs on four dysplastic hips. Femoroacetabular anatomy was landmarked to simulate cutting planes. Posterior column and ischial cuts were standardised, whilst iliac and pubic cut combinations varied. The slope of the iliac cut was either neutral (aligned to pelvis), exit point 5mm above the entry point (+5), or 5mm below (-5). The slope of the pubic cut was either 90°, 50°, or 70° (medial-to-lateral). Iliac and pubic cuts were simulated 0, 5 and 15mm - distal and medial – to a classic cut. Outcome measures were achieved LCEA, Tönnis, FHC and % bone overlap at the pubic cut. Targets were LCEA >30°, Tönnis angle <10°, and FHC >70% and minimum bone overlap ≥10%.

Results

All feasible PAOs resulted in improvement from pre-operative metrics. Personalised cutting planes provided greater benefit than standard planes. Kruskal Wallis tests showed that the iliac cut at 5mm or 15mm resulted in a greater LCEA and lower Tönnis compared to the classic cut (p<0.05). Changing location of the pubic cut, and slope of the iliac and pubic cuts did not significantly affect LCEA and Tönnis in all hips (p<0.05). Cut combinations optimising metrics were associated with a lower % pubic cut overlap.

Conclusion

MSkL-HP feasibly and reliably planned personalised PAO, measuring pre-operative and simulated post-operative objective metrics. Patient-specific pubic and iliac cuts enable greater correction whilst maintaining bone overlap. Further simulations on patients with varying morphology may improve standard techniques.
SAFETY AND PERFORMANCE OF DEXTRAN-TYRAMINE HYDROGEL IMPLANT FOR FOCAL ARTICULAR CARTILAGE LESIONS OF THE KNEE (ACTIVE): PRELIMINARY DATA OF THE SAFETY COHORT
Authors: Weiden G. V. D. , Egmond N. V. , Karperien M. , Both S. , Mastbergen S. , Emans P. , Caron J. , Custers R.
Published: November 2024

Introduction

The ACTIVE(Advanced Cartilage Treatment with Injectable-hydrogel Validation of the Effect) study investigates safety and performance of a novel dextran-tyramine hydrogel implant for treatment of small cartilage defects in the knee (0.5-2.0cm2). The hydrogel is composed of a mixture of natural polymer conjugates that are mixed intra-operatively and which cross-link in situ through a mild enzymatic reaction, providing a cell-free scaffold for cartilage repair.

Method

The ACTIVE study is split into a safety (n=10) and a performance cohort (n=36). The Knee Injury and Osteoarthritis Outcome Score (KOOS), pain (numeric rating scale, NRS), Short-Form Health Survey (SF-36) were compared at baseline and 3, 6, and 12 months after surgery. The primary performance hypothesis is an average change in the KOOS from baseline to 12 months (ΔKOOS) greater than a minimal clinically important change (MIC) of 10. No statistical tests were performed as these are preliminary data on a smaller portion of the total study.

Result

All patients of the safety cohort (n=10, mean age±SD, 30±9 years) were treated with the hydrogel for a symptomatic (NRS≥4) cartilage defect on the femoral condyle or trochlear groove (mean size±SD, 1.2±0.4cm2). No signs of an adverse foreign tissue reaction or serious adverse events were recorded within the safety cohort. At final follow-up mean KOOS±SD was 66.9±23.5, mean NRS resting±SD was 1.3±1.9, NRS activity±SD was 3.8±2.9 and mean SF-36±SD was 72.0±10.9. ΔKOOS was 21. One patient sustained new knee trauma prior to final follow-up, affecting final scores considerably. When excluded, ΔKOOS was 24(n=9).

Conclusion

These promising initial findings provide a solid basis for continuation and expansion of this unique cartilage treatment. The MIC of 10 was surpassed. Though, results should be interpreted cautiously as they are based solely on preliminary data of the first 10 patients.

Acknowledgements

Study is sponsored by Hy2Care, producer of the CartRevive®(dextran-tyramine) Hydrogel implant.
VASCULAR NETWORK INVESTIGATION AFTER TISSUE ENGINEERING PROCEDURE ON SOFT TISSUE
Authors: Vettese J. , Julie M. , Evrard R. , Fieve L. , Lengelé B. , Cornu O.
Published: November 2024

Introduction

In tissue engineering, the establishment of sufficient vascularization is essential for tissue viability and functionality. Inadequate vascularization disrupts nutrients and oxygen supply. Nonetheless, regenerating intricate vascular networks represents a significant challenge. Consequently, research efforts devoted to preserving and regenerating functional vascular networks in engineered tissues are of paramount importance. The present work aims to validate a decellularisation process with preservation of the vascular network and extracellular matrix (ECM) components in fasciocutaneous flaps.

Method

Five vascularized fasciocutaneous flaps from cadaveric donors were carefully harvested from the anterolateral thigh (ALT), preserving the main perforator of the fascia lata. The entire ALT flap underwent decellularization by perfusion using a clinically validated chemical protocol. Fluoroscopy and computed tomography (CT) were used to analyze the persistence of the vascular network within the flap, pre- and post-decellularization. Histological analysis, including hematoxylin and eosin staining, and quantitative DNA assessment evaluated decellularization efficacy. Further qualitative (immunohistochemistry, IHC) and quantitative analyses were conducted to assess the preservation of ECM components, such as collagen, glycosaminoglycans, and elastin.

Result

On average, the ALT flap maintains 82% of the perfusion area (p = 0.094) post-treatment. Histological analysis confirmed decellularization efficacy and revealed structural rearrangement. Paired analysis revealed a significant decrease in DNA levels (<14.8 ng/mg of dry weight, p****< 0.0001) and well-maintained ECM. IHC indicated the persistence of elastine, collagen IV and laminin. Quantitative analysis confirmed elastin (p = 0.44) and collagen persistence (+74%, p*** = 0.001, albeit with a decrease in matrix glycosaminoglycans (-41%, p*** = 0.01)

Conclusion

Decellularization effectively removed cells, while preserving the ECM overall and maintaining some vascular network integrity. Yet, further study is needed to validate these findings, involving microCT examination of the vascular network and its ability to support cell colonization and viability.
PATHOLOGIC FRACTURE OF LONG BONES AS A COMPLICATION OF ACUTE OSTEOMYELITIS IN PAEDIATRICS: A CHALLENGING TASK FOR ORTHOPAEDIC SURGEONS
Authors: Zargarbashi R. , Vosoughi F. , Shaker F. , Mirbeyk M. , Seifi M. , Vafaee A. R.
Published: November 2024

Introduction

The management of pathologic fractures (PF) following osteomyelitis (especially acute subtype) has not been widely investigated. This is challenging due to the infection-induced destructive process causing bone architecture defects. Therefore, this study aims to assess a stepwise treatment plan for the acute incidence of PF in long bone following pediatric acute Hematogenous osteomyelitis(AHO) (the most common mechanism in children).

Method

This case series was conducted in a tertiary pediatric center. Patients with fracture incidence within the first 10 days after AHO diagnosis were included. Patients’ characteristics were retrospectively reviewed.

Result

Nine patients (7 boys, involved bone: the femur(4), tibia(3), Radius(1), and Ulna(1)) were included, with a mean age of 52.56±66.18 months (7-216) and a follow-up time of 11.62±3.61 years (6.5-16 years). The etiology in all patients was hematological(Methicillin-resistant Staphylococcus aureus).

Our stepwise treatment plan was as follows:

Intravenous antibiotics until ESR<20, then oral to ESR<5

Debridemnt surgery was performed if abscesses were detected.

Fracture type determined initial fixation: external fixation (4 patients, 2 unions) or casting (2 patients, both unions).

If the union was not obtained, internal fixation (with (2 patients) or without (2 patients) bone graft) was applied (all obtained union).

Circular external fixation was applied if the union was not obtained or leg length discrepancy occurred (1 case).

A mean of 3.2 surgical procedures (1-6) was required to control the infection, and 1.4 surgical procedures (0-4) were required to obtain union.

Except for one patient who died of septic shock, all other patients (88.8%) reached complete recovery (average length of hospital stay of 19.2 days (5-35).), and the union was obtained (the average union time of 17.25 months(4-36)) without long-term sequelae of osteomyelitis.

Conclusion

The outcome of the stepwise plan in this study suggests that acute PF following AHO in pediatrics can be managed efficiently.
FATIGUE STRENGTH ASSESSMENT OF A NOVEL LIGHT-CURABLE BONE FIXATION TECHNIQUE
Authors: Varga P. , Cameron P. , Hutchinson D. , Malkoch M. , Schwarzenberg P.
Published: November 2024

Introduction

When designing a new osteosynthesis device, the biomechanical competence must be evaluated with respect to the acting loads. In a previous study, the loads on the proximal phalanx during rehabilitation exercises were calculated. This study aimed to assess the safety of a novel customizable osteosynthesis device compared to those loads to determine when failure would occur.

Method

Forty proximal phalanges were dissected from skeletally mature female sheep and divided into four testing groups. A custom 3D printed cutting and drilling guide was used to create a reduced osteotomy and pilot holes to insert four 1.5 mm cortical screws. A novel light-curable polymer composite was used to fixate the bones with an in situ fixation patch. The constructs were tested in cyclic four-point bending in a bioreactor with ringer solution at 37°C with a valley load of 2 N. Four groups (N = 10) had increasing peak loads based on varying safety factors relative to the physiological loading (G1:100x, G2:150x, G3:175x, G4:250x). Each specimen was tested for 12,600 cycles (6 weeks of rehabilitation) or until failure occurred. After the test the thickness of the patch was measured with digital calipers and data analysis was performed in Python and R.

Result

All samples survived in G1, and all failed in G4. G2 and G3 had 1 and 8 failures, respectively. There was no significant difference in patch thickness in all survivor samples against failures (p = 0.131), however, there was a significant difference in the displacement amplitude in the final cycle (0.072 mm vs. 0.15 mm; p < 0.001).

Conclusion

This study found the survival and failure limits of a novel osteosynthesis device as a function of physiological loading. These results indicate that such fixations could withstand 100x the loading for typical non-weightbearing rehabilitation. Further studies are needed to confirm the safety for other conditions.
EXPLORING THE LINK BETWEEN CHRONIC STRESS AND OSTEOARTHRITIS IN A MURINE MODEL
Authors: Rösch G. , Rapp A. E. , Tsai P. L. , Kohler H. , Taheri S. , Schilling A. F. , Zaucke F. , Slattery D. , Lanzl Z. J.
Published: November 2024

Introduction

Osteoarthritis (OA) is a chronic degenerative disease of the entire joint leading to joint stiffness and pain (PMID:33571663). Recent evidence suggests that the sympathetic nervous system (SNS) plays a role in the pathogenesis of OA (PMID:34864169). A typical cause for long-term hyperactivity of the SNS is chronic stress. To study the contribution of increased sympathetic activity, we analyzed the progression of OA in chronically stressed mice.

Method

We induced OA in male C57BL/6J mice by destabilizing the medial meniscus (DMM)(PMID:17470400) and exposed half of these mice to chronic unpredictable mild stress (CUMS)(PMID:28808696). Control groups consisted of sham-operated mice with and without CUMS exposure. After 12 weeks, CUMS efficacy was determined by assessing changes in body weight gain and activity of mice, measuring splenic norepinephrine and serum corticosterone levels. OA progression was studied by histological analysis of cartilage degeneration and synovitis, and by μCT to evaluate changes in calcified cartilage and subchondral bone microarchitecture. A dynamic weight-bearing system was used to assess OA-related pain.

Result

CUMS resulted in significantly decreased body weight gain and activity, as well as increased splenic norepinephrine and serum corticosterone concentrations compared to the respective controls. Surprisingly, already DMM alone resulted in elevated stress hormone levels. CUMS significantly exacerbated cartilage degeneration and synovial inflammation and increased OA pain in DMM mice. The underlying cellular and molecular mechanisms are currently being analyzed using FACS, single cell RNAseq, and spatial proteomics.

Conclusion

Overall, chronic stress exacerbates OA severity and pain. Moreover, increased levels of stress hormones were observed in OA mice without CUMS induction, suggesting a complex bi-directional interaction between the SNS and OA. Targeting the autonomic nervous system, such as attenuating the SNS but also stimulating the activity of the parasympathetic nervous system, as a counterpart of the SNS, may therefore be promising for novel preventive or causal treatments of OA.
WHARTON’S JELLY MESENCHYMAL STROMAL CELL-DERIVED EXTRACELLULAR VESICLES ATTENUATE PYROPTOSIS IN SYNOVIAL FLUID-TREATED HUMAN OSTEOARTHRITIC CHONDROCYTES
Authors: Tilotta V. , Vadalà G. , Giacomo G. D. , Colaiacomo C. , Cicione C. , Ambrosio L. , Russo F. , Denaro V. , Papalia R.
Published: November 2024

Introduction

Osteoarthritis (OA) is a predominant chronic degenerative disease exerting a deep impact on quality of life and healthcare systems. Recent evidences suggest that pyroptosis, a programmed cell death characterized by inflammatory cytokine release, may play a significant role in modulating OA pain. The aim of the study is to investigate the potential role of extracellular vesicles derived from umbilical cord Wharton's jelly (WJ-MSC EVs) in the attenuation of the pyroptotic process on human chondrocytes (hOAC) pre-treated with synovial fluid in a 3D in vitro model.

Method

EVs isolated by tangential filtration of the conditioned medium of WJ-MSCs were characterized for: morphology by TEM, surface markers by WB and size by NTA. Confocal microscopy was used to identify PKH26-labelled EVs and monitor their incorporation into hOACs. The hOACs from surgical waste material of patients undergoing knee replacement, expanded, encapsulated in alginate beads were pre-treated with synovial fluid for 24 h (SF) and subsequently co-incubated with WJ-MSC EVs. We examined viability (CCK-8), metabolic activity (MTT), nitrite production (Griess) activation of the pyroptotis (IF), DNA quantification (PicoGreen) and gene expression levels of extracellular matrix (ECM) components (qPCR). One-way ANOVA analysis was used to compare the groups under exam and data were expressed as mean ± S.D

Result

WJ-MSC EVs increased hOACs viability and metabolic activity. The production of nitrites is significantly decreased compared sample group treated with SF. WJ-MSC EVs inhibited inflammasomes NLRP3 (nucleotide-binding domain, leucine-rich repeat pyrin domain containing 3) activation. The ECM catabolic genes decreased compared to the inflamed SF group for ADAMTS-5 and MMP-1.

Conclusion

Our results supported the potential use of WJ-MSC EVs as a cell-free strategy for OA, overcoming the side effects of cell-therapy. Moreover, WJ-MSC EVs are able to mitigate SF-treated hOACs pyroptotic death, attenuate ECM degradation and oxidative stress counteracting the inflamed status in OA development and progression.
A MULTIMODAL IODINATED GADOLINIUM-GOLD NANOMATERIAL AS CONTRAST AGENT FOR CARTILAGE IMAGING
Authors: Lu C. , Lian W. , Wu R. , Lin Y. , Su C. , Chen C. , Tai M. , Chen Y. , Wang S. , Wang F.
Published: November 2024

Introduction

Cartilage damage is a critical aspect of osteoarthritis progression, but effective imaging strategies remain limited. Consequently, multimodal imaging approaches are receiving increased attention. Gold nanomaterials, renowned for their therapeutic and imaging capabilities, hold promise in drug development. However, their potential for cartilage imaging is rarely discussed. Here, we developed a versatile nanomaterial, AuNC@BSA-Gd-I, for cartilage detection. By leveraging electrostatic interactions with sulfated glycosaminoglycans (sGAG), the AuNC@BSA-Gd-I can effectively penetrate damaged cartilage while accumulating minimally in healthy cartilage. This probe can be visualized or detected using CT, MRI, IVIS, and a gamma counter, providing a comprehensive approach to cartilage imaging. Additionally, we compared the imaging abilities, cartilage visualization capacities, and versatility of currently disclosed multimodal gold nanomaterials with those of AuNC@BSA-Gd-I.

Method

The physicochemical properties of nanomaterials were measured. The potential for cartilage visualization of these nanomaterials was assessed using an in vitro porcine model. The sGAG content in cartilage was determined using the dimethylmethylene blue (DMMB) assay to establish the correlation between sGAG concentration and imaging intensity acquired at each modality.

Results

The cartilage imaging abilities of AuNC@BSA-Gd-I for CT, MRI, and optical imaging were verified, with each imaging intensity demonstrating a strong correlation with the sGAG content (MRI; R2=0.93, CT; R2=0.83, IVIS; R2=0.79). Furthermore, AuNC@BSA-Gd-131I effectively accumulated in defective cartilage tissue compared to healthy cartilage (23755.38 ± 5993.61 CPM/mg vs. 11699.97 ± 794.93 CPM/mg). Additionally, current gold nanomaterials excelled in individual imaging modalities but lacked effective multimodal imaging ability.

Conclusion

Compared to current multimodal gold nanomaterials, AuNC@BSA-Gd-I demonstrates the potential to image cartilage across multiple medical instruments, providing investigators with a more powerful, visible, and convenient approach to detect cartilage defects.

Acknowledgements

This work was financially supported by the National Health Research Institute, Taiwan (NHRI-EX112-11029SI), the National Science and Technology Council (NSTC 112-2314-B-182A-105-MY3), and Chang Gung Memorial Hospital, Taiwan (CMRPG8N0781 and CMRPG8M1281-3).
MUSCLE STRENGTH AND POWER IN PATIENTS WITH CHRONIC PAIN AFTER TOTAL KNEE ARTHROPLASTY: SECONDARY ANALYSIS FROM A RANDOMIZED CONTROLLED TRIAL
Authors: Larsen J. B. , Skou S. T. , Laursen M. , Bruun N. H. , Bandholm T. , Arendt-Nielsen L. , Madeleine P.
Published: November 2024

Introduction

There is a lack of evidence-based treatments for patients with chronic pain after total knee arthroplasty (TKA). It is well-established that knee extensor and flexor muscle strength are markedly impaired following TKA, but no studies have examined muscle strength and power in patients with chronic pain after TKA. Therefore, the aim was to investigate if neuromuscular exercises and pain neuroscience education (PNE) were superior to PNE alone for improvement of muscle strength and power in patients with chronic pain after TKA.

Method

This report presents the exploratory analysis of a randomized controlled trial (NCT03886259). Participants with chronic moderate-to-severe average daily pain intensity and no signs of prosthesis failure at least one year after primary TKA were included. Participants were randomized to receive either supervised neuromuscular exercise and PNE or the same PNE sessions alone. The outcomes were changes from baseline to 12-months for peak leg extension power and maximum muscle strength, measured during maximal voluntary isometric contractions, for the knee extensors and flexors.

Result

Sixty-nine participants (age 62.2±7.2, 40 females) were included. No between-group differences were observed for peak leg extension power (difference 13.6 Watts, 95% CI -22.2 to 49.3), maximum knee extensor muscle strength (difference -20.9 Newtons, 95% CI -65.8 to 24.0) or maximum knee flexor muscle strength (difference 8.6 Newtons, 95% CI -11.9 to 29.1). Peak leg extension power (26.3 Watts, 95% CI 4.3 to 48.3) and maximum knee flexor muscle strength (19.7 Newtons, 95% CI 7.6 to 31.9) improved significantly in the neuromuscular exercise and PNE group with no significant improvements observed in the PNE alone group.

Conclusion

Neuromuscular exercise and PNE did not improve muscle strength and power compared to PNE alone in patients with chronic pain after TKA.

Acknowledgements

This study was funded by the Danish Rheumatism Association, the Svend Andersen Foundation and Lions Club Denmark.
A Scoping Review on Food Insecurity Among Asian Americans
Authors: Huynh Victoria N. , Pham Nhat-Ha T. , Ro Suji , Wafford Q. Eileen , Vu Milkie
Published: November 2024

Abstract: We conducted a scoping review to address the knowledge gap concerning the prevalence of food insecurity and participation in food assistance programs among Asian Americans. In 2022, we searched nine databases for peer-reviewed articles. A team of four authors screened 900 records, identifying 35 studies. Ten studies reported food insecurity prevalence for Asian origin groups: 8.3%–41.1% for Filipinos, 13.1%–28.2% for Vietnamese, 6.6%–22.2% for Koreans, 2.3%–11.2% for Japanese, and 47.6% for Hmong. Fourteen studies used Asian language-specific standardized data collection instruments, and nine noted community engagement. Factors associated with food insecurity included lower income, education, acculturation, and limited English proficiency. Studies suggested that SNAP benefits were insufficient, and one reported that barriers to participation involved negative administrative experiences. Our review highlights the need for disaggregated data, multilingual data collection, and community involvement to address food insecurity. Policies and interventions should consider cultural norms, backgrounds, and unique challenges of different Asian groups.
Defining what Matters: Use of Q Methodology to Identify Food Values among People Living with HIV Affected by Food Insecurity
Authors: Wetherill Marianna S. , Caywood Lacey T. , Hartwell Micah L. , Bakhsh Casey , Weiser Sheri D.
Published: November 2024

Abstract: Objectives/Background. To inform the development of a "food is medicine" (FIM) intervention, the present study aimed to describe how people living with HIV (PLWH) prioritize daily food choices in the context of food insecurity. Methods. Interviews with PLWH experiencing various levels of food insecurity (n=24) were conducted using Q-Methodology. Participants ranked 57 food-choice value statements from "most like me" to "least like me" in a process called forced distribution. We then identified different viewpoints and shared perspectives through factor analysis. Results. Although food cost was a salient value, distinct viewpoints prioritized: 1) creative expression and sensory appeal; 2) disease management within physical limitations; 3) safety, familiarity, household practicality; 4) mainstream convenience; and 5) disease prevention and socioemotional coping. Discussion. Heterogeneous viewpoints on the relative importance of sensory appeal, functional capabilities, family food preferences, and other factors may affect whether and how future FIM participants use foods and related resources.
Addressing Food Insecurity During the COVID-19 Pandemic: An Academic Research Group's Response to a Major Social Determinant of Health
Authors: Drucker Gabriela , Rausch John , Swierad Ewelina , Sawyer Vanessa , Noble James M. , Gazdick Rachael , Rosa Marisol De La , Eimicke Joseph , Williams Olajide
Published: November 2024

Abstract: We developed and implemented a novel food assistance intervention to address rapidly increasing food insecurity during COVID-19. Parents of children from underserved schools enrolled in our National Institutes of Health-funded research participated in a food security needs assessment survey. The tool used validated instruments to assess household food security status and barriers to accessing food assistance. The intervention provided a resource information sheet or direct home food deliveries. We evaluated the intervention using a quasi-experimental design, with baseline serving as the control. One hundred and ninety (190) parents participated. Of the completed responses, 46.0% were food-insecure, 41.0% faced one or more barriers, and 17.9% families qualified for home deliveries. Post-intervention, 72.4% of high-needs families reported deliveries helped "to a great extent"; 29.6% reported no remaining barriers (p<.005, Fischer's exact test). Implementation of a novel food security research tool and two-level food assistance intervention was feasible, highlighting the role community-based researchers can serve in supporting research participants' emerging needs as they become evident.
Formative Evaluation of a Grocery Store-Based Nutrition Incentive Program in a Primarily Rural State
Authors: Moghaddami Christopher S. , Wetherill Marianna S. , Comeau Richard , Young Leslie , Williams Mary B.
Published: November 2024

Summary: Increasing the reach of nutrition incentive programs (NIP) requires their successful implementation beyond farmers markets into grocery stores. This report describes our approach to formative evaluation and key lessons during the expansion of the Double Up Oklahoma (DUO) NIP into 10 grocery stores over a two-year period.
Genograms, Viewing Human Issues Contextually, and the Role of Alfred Adler: Perhaps the First Family Therapist
Authors: McGoldrick Monica , Petry Sueli
Published: November 2024

ABSTRACT: The article discusses Alfred Adler’s systemic orientation and family history. Adler had a holistic approach, viewing psychology as based on individuals’ background, genetics, physical makeup, family constellation, individual life cycle or “movement through life,” and how that style was enacted with others.
Utilizing Class Meetings to Teach Essential Social-Emotional Skills and Build Community
Authors: Gfroerer Kelly , Edwards Dana , Dwight Eva
Published: November 2024

ABSTRACT: This article explores how educators can utilize class meetings to teach essential social-emotional skills and build community. Drawing on Adlerian Psychology and Positive Discipline, practical examples are provided to demonstrate how class meetings foster a sense of belonging and significance, thereby improving student resiliency and overall well-being. Outcomes of class meetings on enhancing student communication and collaborative problem-solving among diverse students and school settings are explored. Students’ perspectives about their class meeting experiences and subsequent outcomes are included. The importance of intentional facilitation in creating a cohesive and supportive environment that encourages students’ active participation is discussed. The authors offer practical recommendations for educators seeking to implement class meetings. Possible barriers to effective class meetings are shared, as are solutions to overcome common obstacles.
The Use of Early Recollections in Adlerian Psychotherapy: A Forgotten Contribution of Four Adlerian Women
Authors: Shifron Rachel
Published: November 2024

ABSTRACT: The article overviews the contributions of Adlerian women in the studies of early recollections (ERs). Much of that work and many of the names are likely little known to contemporary readers and clinicians. The author highlights the theoretical and methodological contributions of Alice Friedmann, Eleanor B. Hedvig, Helene Papanek, and Lucy K. Ackerknecht. The author demonstrates historical development in the use of ERs in therapy, mirrored in the studies that were conducted by four women researchers. The author concludes with an articulation of the Adlerian model for working with ERs in psychotherapy and supervision, stressing the power of ERs in presenting the individual’s strengths and creative abilities.
Adlerian Women’s Age-Specific Approaches to Emotional and Behavioral Issues: A Historical Review
Authors: John Karen
Published: November 2024

ABSTRACT: This review summarizes and synthesizes 10 articles written between 1929 and 1991 by women on age-specific case conceptualizations and treatment approaches. As part of an initiative to raise awareness of the substantial contributions of women scholars and clinicians to Individual Psychology, the articles were drawn from Adler University collections and Marina Bluvshtein’s private archives. Articles are presented in eight life-cycle periods, from infancy and toddlerhood through older adulthood and end of life. At all ages, the difficulties were discovered to be rooted in fears, discouragement, self-centered compensatory striving for superiority and perfection to overcome perceived deficits. The authors’ empathy, reassurance, belief in the child’s or adult’s ability to grow, and express social interest promoted their greater well-being and positive movement.