Spatiotemporal distribution of thrombospondin-4 and -5 in cartilage during endochondral bone formation and repair.

During skeletal development most bones are first formed as cartilage templates, which are gradually replaced by bone. If later in life those bones break, temporary cartilage structures emerge to bridge the fractured ends, guiding the regenerative process. This bone formation process, known as endochondral ossification (EO), has been widely studied for its potential to reveal factors that might be used to treat patients with large bone defects. The extracellular matrix of cartilage consists of different types of collagens, proteoglycans and a variety of non-collagenous proteins that organise the collagen fibers in complex networks. Thrombospondin-5, also known as cartilage oligomeric matrix protein (TSP-5/COMP) is abundant in cartilage, where it has been described to enhance collagen fibrillogenesis and to interact with a variety of growth factors, matrix proteins and cellular receptors. However, very little is known about the skeletal distribution of its homologue thrombospondin-4 (TSP-4). In our study, we compared the spatiotemporal expression of TSP-5 and TSP-4 during postnatal bone formation and fracture healing. Our results indicate that in both these settings, TSP-5 distributes across all layers of the transient cartilage, while the localisation of TSP-4 is restricted to the population of hypertrophic chondrocytes. Furthermore, in fractured bones we observed TSP-4 sparsely distributed in the periosteum, while TSP-5 was absent. Last, we analysed the chemoattractant effects of the two proteins on endothelial cells and bone marrow stem cells and hypothesised that, of the two thrombospondins, only TSP-4 might promote blood vessel invasion during ossification. We conclude that TSP-4 is a novel factor involved in bone formation. These findings reveal TSP-4 as an attractive candidate to be evaluated for bone tissue engineering purposes.

Task-related measures of short-interval intracortical inhibition and GABA levels in healthy young and older adults: A multimodal TMS-MRS study.

Establishing the associations between magnetic resonance spectroscopy (MRS)-assessed gamma-aminobutyric acid (GABA) levels and transcranial magnetic stimulation (TMS)-derived 'task-related' modulations in GABAA receptor-mediated inhibition and how these associations change with advancing age is a topic of interest in the field of human neuroscience. In this study, we identified the relationship between GABA levels and task-related modulations in GABAA receptor-mediated inhibition in the dominant (left) and non-dominant (right) sensorimotor (SM) cortices. GABA levels were measured using edited MRS and task-related GABAA receptor-mediated inhibition was measured using a short-interval intracortical inhibition (SICI) TMS protocol during the preparation and premotor period of a choice reaction time (CRT) task in 25 young (aged 18-33 years) and 25 older (aged 60-74 years) adults. Our results demonstrated that GABA levels in both SM voxels were lower in older adults as compared to younger adults; and higher SM GABA levels in the dominant as compared to the non-dominant SM voxel pointed to a lateralization effect, irrespective of age group. Furthermore, older adults showed decreased GABAA receptor-mediated inhibition in the preparation phase of the CRT task within the dominant primary motor cortex (M1), as compared to young adults. Finally, results from an exploratory correlation analysis pointed towards positive relationships between MRS-assessed GABA levels and TMS-derived task-related SICI measures. However, after correction for multiple comparisons none of the correlations remained significant.

Arthroscopy-assisted treatment of scaphoid and lunate cysts: Clinical evaluation of 7 cases.

Intraosseous cysts of the carpus are relatively common benign tumors. They are often discovered by chance and can cause wrist pain thereby requiring appropriate management. While conventional open surgical treatment leads to good results, it has certain disadvantages, the main one being postoperative stiffness. Arthroscopic treatment has been proposed as an alternative for lunate cysts. The present study consisted in evaluating the feasibility and outcomes of arthroscopic treatment for lunate and scaphoid cysts. The main objective was to evaluate the postoperative clinical outcomes at 3 and 18 months. The secondary objective was to evaluate the integration of a cancellous bone graft. We conducted a retrospective study of eight patients who underwent surgery between April 2010 and October 2016. Of these, four had a lunate cyst and four had a scaphoid cyst; all cysts had a dorsal operculum. Patients had disabling wrist pain that did not respond to conservative treatment. The diagnosis was confirmed by radiography and either a CT scan or an MRI. Curettage and cancellous grafts were performed under arthroscopic control. The technique was carried out successfully in all cases. One patient was lost to follow-up. At 18 months, postoperative pain was rated at 1.28 on a visual analog scale. The grip strength (measured with a Jamar dynanometer) was 77% when compared to the contralateral side. There was an improvement in joint range of motion, with an average wrist flexion of 67.5° compared to 48.3° preoperatively and an average wrist extension of 71.5° compared to 47.6° preoperatively. The Patient-Rated Wrist Evaluation (PRWE) score decreased from 69.7 to 12.7, which was a significant decrease. A good integration of the cancellous graft was confirmed at 6 months in all cases by CT scan or MRI. Curettage with a cancellous graft of lunate and scaphoid cysts under arthroscopic control is a technique that allows surgeons to obtain satisfactory clinical results with good integration of the graft.

Recruitment of osteogenic cells to bone formation sites during development and fracture repair.

Recruitment of osteoblast lineage cells to their bone-forming locations is essential for skeletal development and fracture healing. In developing bones, osteoprogenitor cells invade the cartilage mold to establish the primary ossification center. Similarly, osteogenic cells infiltrate and populate the callus tissue that is formed following an injury. Proper bone development and successful fracture repair must, therefore, rely on controlled temporal and spatial navigation cues guiding the cells to the sites where new bone formation is needed. Some cellular mechanisms and molecular pathways involved have been elucidated.

[Recruitment of osteogenic cells to bone formation sites during development and fracture repair - German Version]. / Rekrutierung osteogener Zellen an den Ort der Knochenbildung während Entwicklung und Frakturheilung.

Recruitment of osteoblast lineage cells to their bone-forming locations is essential for skeletal development and fracture healing. In developing bones, osteoprogenitor cells invade the cartilage mold to establish the primary ossification center. Similarly, osteogenic cells infiltrate and populate the callus tissue that is formed following an injury. Proper bone development and successful fracture repair must, therefore, rely on controlled temporal and spatial navigation cues guiding the cells to the sites where new bone formation is needed. Some cellular mechanisms and molecular pathways involved have been elucidated.

Forkhead box O transcription factors in chondrocytes regulate endochondral bone formation.

The differentiation of embryonic mesenchymal cells into chondrocytes and the subsequent formation of a cartilaginous scaffold that enables the formation of long bones are hallmarks of endochondral ossification. During this process, chondrocytes undergo a remarkable sequence of events involving proliferation, differentiation, hypertrophy and eventually apoptosis. Forkhead Box O (FoxO) transcription factors (TFs) are well-known regulators of such cellular processes. Although FoxO3a was previously shown to be regulated by 1,25-dihydroxyvitamin D3 in osteoblasts, a possible role for this family of TFs in chondrocytes during endochondral ossification remains largely unstudied. By crossing Collagen2-Cre mice with FoxO1lox/lox;FoxO3alox/lox;FoxO4lox/lox mice, we generated mice in which the three main FoxO isoforms were deleted in growth plate chondrocytes (chondrocyte triple knock-out; CTKO). Intriguingly, CTKO neonates showed a distinct elongation of the hypertrophic zone of the growth plate. CTKO mice had increased overall body and tail length at eight weeks of age and suffered from severe skeletal deformities at older ages. CTKO chondrocytes displayed decreased expression of genes involved in redox homeostasis. These observations illustrate the importance of FoxO signaling in chondrocytes during endochondral ossification.

Cardiorespiratory fitness in a representative sample of Belgian firefighters.

BACKGROUND: An important aspect of occupational health surveillance of firefighters is cardiorespiratory fitness. In Belgium, representative data on firefighters' cardiorespiratory fitness assessed in a standardized way are lacking. AIMS: To report data on cardiorespiratory fitness, body mass index (BMI) and total body fat percentage in a large cohort of Belgian firefighters; to relate the data on cardiorespiratory fitness to the new Belgian criteria and to explore the relationship of cardiorespiratory fitness with age, BMI and total body fat. METHODS: VO2-max was assessed in male firefighters by maximal exercise test on a treadmill. Total body fat percentage was assessed by dual-energy X-ray absorptiometry. Stratified analyses of mean VO2-max and proportions of subjects that did not meet the criteria were performed for different age, total body fat percentage and BMI categories. Relationships between VO2-max and the continuous variables were explored in univariate (correlation coefficients) and multivariate analyses (multiple linear regression analysis). RESULTS: In 1225 participating firefighters (96% participation rate), mean VO2-max was 46.5 ml/kg/min. Percentages of subjects that did not meet the criteria ranged from 1 to 83% depending on age, BMI and total body fat percentage. Both in univariate and multivariate analyses, strongly significant relationships were found between VO2-max and age, BMI and total body fat percentage, the latter being the strongest predictor. CONCLUSIONS: The study provided representative data on cardiorespiratory fitness, BMI and total body fat percentage for Belgian firefighters. The findings suggest the need for a structural approach on healthy eating and regular physical exercise in firefighters.

PNET/Ewing's sarcoma of the kidney: imaging findings in two cases.

The CT-imaging findings of primary renal PNET/Ewing's sarcoma in two patients were retrospectively assessed. A large renal mass with heterogenous contrast enhancement and necrotic and hemorrhagic areas were the predominant characteristics. In adolescents or young adults presenting with a large renal mass, PNET/Ewing's sarcoma may be included in the differential diagnosis.

Fluctuation-response relations for nonequilibrium diffusions with memory.

Strong interaction with other particles or feedback from the medium on a Brownian particle entail memory effects in the effective dynamics. That motivates the extension of the fluctuation-dissipation theorem to nonequilibrium Langevin systems with memory. An important application is to the nonequilibrium modification of the Sutherland-Einstein relation between diffusion and mobility in the case of strong memory. Nonequilibrium corrections include the time correlation between the dynamical activity and the velocity of the particle, which in turn leads to information about the correlations between the driving force and the particle's displacement.

A variational principle for computing nonequilibrium fluxes and potentials in genome-scale biochemical networks.

We derive a convex optimization problem on a steady-state nonequilibrium network of biochemical reactions, with the property that energy conservation and the second law of thermodynamics both hold at the problem solution. This suggests a new variational principle for biochemical networks that can be implemented in a computationally tractable manner. We derive the Lagrange dual of the optimization problem and use strong duality to demonstrate that a biochemical analogue of Tellegen's theorem holds at optimality. Each optimal flux is dependent on a free parameter that we relate to an elementary kinetic parameter when mass action kinetics is assumed.

[Results of the treatment of basal thumb osteoarthritis by Rubis II prosthesis after more than 5 years. A retrospective study of 118 cases]. / Résultats à plus de cinq ans du traitement de la rhizarthrose par la prothèse Rubis II. À propos de 118 implantations.

OBJECTIVES: The goal of the work was to evaluate the mid-term results of the Rubis II® trapeziometacarpal prosthesis for the treatment of basal thumb osteoarthritis. METHODS: From 1997 to 2003, 118 trapeziometacarpal prostheses Rubis II® were implanted at Saint-Quentin's Hospital. Seventy-seven have been clinically and radiologically reviewed. The average follow-up was of 88 months. Sixteen patients were reviewed by phone. Fourteen patients were lost to contact and two died (13.5% of cases). Nine prostheses were removed (7.6% of cases). RESULTS: Among the reviewed prostheses, 76.6% of patients had no pain, the others had moderate pain. Postoperatively, the average opposition according to Kapandji's scale was 9.52. The average key-pinch force was similar on both sides. All reviewed patients were satisfied or very satisfied. No radiological loosening was noted. Nine removals were necessary; for post-traumatic dislocation in six cases, post-traumatic fracture of the trapezium in two cases, and inflammatory reaction with no infection in one case. The survival rate of the prosthesis was 93% at five years. CONCLUSIONS: The Rubis II® prosthesis presents a satisfactory survival rate after five years and good clinical results. The design of the implant could explain the absence of loosening. The main risk of the Rubis II prosthesis seems to be the post-traumatic dislocation occurring mostly during the first two years after surgery.

Self ordering threshold and superradiant backscattering to slow a fast gas beam in a ring cavity with counter propagating pump.

We study the dynamics of a fast gaseous beam in a high Q ring cavity counter propagating a strong pump laser with large detuning from any particle optical resonance. As spontaneous emission is strongly suppressed the particles can be treated as polarizable point masses forming a dynamic moving mirror. Above a threshold intensity the particles exhibit spatial periodic ordering enhancing collective coherent backscattering which decelerates the beam. Based on a linear stability analysis in their accelerated rest frame we derive analytic bounds for the intensity threshold of this selforganization as a function of particle number, average velocity, kinetic temperature, pump detuning and resonator linewidth. The analytical results agree well with time dependent simulations of the N-particle motion including field damping and spontaneous emission noise. Our results give conditions which may be easily evaluated for stopping and cooling a fast molecular beam.

[Primary hepatic lymphoma of MALT-type: a tumor that can simulate a liver metastasis]. / Le lymphome primitif hépatique de type MALT: une tumeur rare pouvant simuler une métastase hépatique.

Primary hepatic lymphomas are rare tumors. We report a case of a 72 year-old woman with a past history of colonic adenocarcinoma who presented primary hepatic lymphoma of MALT-type. The patient had been operated on 3 years before for colonic adenocarcinoma, pT3N0, revealed by a bowel obstructive syndrome. She had been treated by chemotherapy for 6 months. During the follow-up, the computed tomography-scan (CT-scan) revealed the presence of a not well-demarcated mass in segment III of the liver, measuring 4 cm in diameter. The tumor was hypodense and was not enhanced on dynamic study. The mass was already present on the initial CT-scan. Left lobectomy was performed with the diagnosis of liver metastasis of the colonic adenocarcinoma. Surgical specimen showed a tumor composed of a dense infiltrate of small lymphocytes positive for B-cell markers on immunohistochemistry. The tumor contained reactive lymphoid follicles and there were numerous lympho-epithelial biliary lesions. The patient is alive and free of disease 2 years after the diagnosis. Primary hepatic lymphoma of MALT-type is a low-grade B cell lymphoma. Twenty-five cases had been reported in the literature so far. The patients were 16 females and 9 males, mean age 63.5 years. The pathogenesis is still unclear but half of the patients had a past history of chronic inflammatory liver disease (hepatitis B or C virus infection, ascaris infection, primary biliary cirrhosis) or malignant neoplasm. This tumor has a good prognosis; it is usually limited to the liver and surgical resection cures the patient in most cases.