Pilot Clinical Trial to Evaluate In Situ Calcium Phosphate Cement Injection for Conservative Surgical Management of Appendicular Osteosarcoma in Dogs.

Cementoplasty is a minimally invasive procedure that consists of injecting a bone substitute into the tumor lesion to provide bone reinforcement and alleviate pain. This study aimed to demonstrate the feasibility, safety, and efficacy of cementoplasty with a calcium phosphate cement in osteosarcoma to reduce pain and preserve limb function. Throughout the 6-month study, dogs received no adjuvant therapy, and dogs' evaluations included a clinical examination, monitoring of postoperative complications, radiographic follow-up, and assessment of limb function and pain scores. Out of 12 dogs enrolled, 10 were withdrawn before study completion due to deterioration in their general condition. Nine (9) dogs were followed until D28, six until D56, and two until D183. Compared to D0, more than 50% of the dogs showed improvement in both veterinarian and owner scores at their final visit. Throughout the study, 10 major and 4 minor complications were reported, all unrelated to the procedure. This open non-controlled study provides first evidence of the feasibility, safety, and efficacy of cementoplasty procedure using a calcium phosphate bone cement to relieve pain and preserve limb function in dogs suffering from appendicular osteosarcoma.

Fluoroscopically-assisted closed reduction and percutaneous fixation of sacroiliac luxations in cats using 2.4 mm headless cannulated compression screws: Description, evaluation and clinical outcome.

OBJECTIVE: To describe fluoroscopically-assisted closed reduction and percutaneous fixation of sacroiliac-luxation (SIL) in cats and report radiographic results and long-term functional outcomes. STUDY DESIGN: Retrospective clinical study. ANIMALS: Eleven cats. METHODS: Percutaneous fixation of 17 SILs in 11 cats was performed with 2.4 mm headless cannulated compression screws under fluoroscopic guidance. Luxation-reduction, screw placement and purchase within the sacral body, pelvic canal diameter ratio (PCDR) and hemipelvic canal width ratio (HCWR) were assessed on pre- and postoperative radiographs. Radiographic follow-up was performed to assess the same parameters when available. Long-term clinical outcome was evaluated with an owner questionnaire. Wilcoxon paired-test was performed for comparison. RESULTS: Mean age and bodyweight of the cats were 3.3 ± 2.6 years and 4.0 ± 0.82 kg, respectively. Nine cats presented with concurrent pelvic injuries. Median luxation-reduction was 94.1% (IQR = 13.9) and median screw-purchase within the sacral body was 73.3% (IQR = 17.0) immediately postoperatively. One screw exited the sacral body caudally. Upon 7-week radiographic follow-up, luxation-reduction (88.3%, IQR = 20.1) and screw-purchase (70.7%, IQR = 12.8) had decreased compared to immediately postoperatively (p = .008 and p = .013 respectively). Screw migration was not observed. PCDR and HCWR measured on postoperative radiographs indicated successful restoration of the pelvic canal width. Owners reported an excellent long-term functional outcome (mean postoperative time: 19 ± 5 months). CONCLUSION: Fluoroscopically-assisted closed reduction and fixation of feline SIL using 2.4 mm headless cannulated compression screws allowed good reduction and optimal screw purchase within the sacral body. An excellent functional outcome was reported. CLINICAL SIGNIFICANCE: Minimally invasive reduction and fixation with headless compression screws should be considered in cats with SIL.

Retrospective study of the early clinical experience with a precontoured angle-stable interlocking nail for fracture repair in dogs and cats.

OBJECTIVE: To report indications, outcomes, and complications with a precontoured angle-stable interlocking nail (CAS-ILN). ANIMALS: 90 client-owned animals. METHODS: Dogs and cats treated with the CAS-ILN between 2020 and 2022 were retrospectively reviewed. Collected data included body weight, fracture configuration, percentage of medullary canal filled, limb alignment, complications, and follow-up. Favorable outcomes were defined when full functional restoration was observed. RESULTS: Thirty-eight dogs and 52 cats were included. Median body weight was 4.3 kg (range, 1.5 to 6.7 kg) for cats and 25 kg (range, 6.8 to 54 kg) for dogs. A total of 54 femurs, 31 tibias, and 5 humeri were treated, including 65 comminuted fractures and 26 metaphyseal fractures. The median percentage of medullary canal occupied by the nail was 76.5% (range, 53% to 97.6%). Radiographic postoperative bone alignment was good in 85.5% (59/69) and satisfactory in 10 cases. The median duration of follow-up (57/90) was 476 days (range, 56 to 1,057 days). In the perioperative period (0 to 12 weeks), lameness had resolved or was mild in all (51/52) but 1 case. In the long-term postoperative period (> 12 months), 97.1% (34/35) of cases showed restoration of full function and 1 case had an unacceptable function. An overall complication rate of 11.5% (7/61) was reported including 1 catastrophic and 6 major complications. CLINICAL RELEVANCE: Long-term functional outcomes following the CAS-ILN were favorable in 97.1% (34/35) of cases. Complication rates were comparable to previous studies. The CAS-ILN appears to be an alternative surgical option for most long-bone fracture repairs.

Polyclonal antibodies selectively inhibit tumor growth and invasion and synergize with immune checkpoint inhibitors.

Heterologous polyclonal antibodies (pAb) were shown to possess oncolytic properties a century ago with reported clinical responses. More recent preclinical models confirmed pAb efficacy, though their ability to tackle complex target antigens reduces susceptibility to tumor escape. Owing to the recent availability of glyco-humanized pAb (GH-pAb) with acceptable clinical toxicology profile, we revisited use of pAb in oncology and highlighted their therapeutic potential against multiple cancer types. Murine antitumor pAb were generated after repeated immunization of rabbits with murine tumor cell lines from hepatocarcinoma, melanoma, and colorectal cancers. Antitumor pAb recognized and showed cytotoxicity against their targets without cross-reactivity with healthy tissues. In vivo, pAb are effective alone; moreover, these pAb synergize with immune checkpoint inhibitors like anti-PD-L1 in several cancer models. They elicited an antitumor host immune response and prevented metastases. The anticancer activity of pAb was also confirmed in xenografted NMRI nude mice using GH-pAb produced by repeated immunization of pigs with human tumor cell lines. In conclusion, the availability of bioengineered GH-pAb allows for revisiting of passive immunotherapy with oncolytic pAb to fight against solid tumor and cancer metastasis.

Combination of CT-Guided Microwave Ablation and Cementoplasty as a Minimally Invasive Limb-Sparing Approach in a Dog with Appendicular Osteosarcoma.

Image-guided microwave ablation and cementoplasty are minimally invasive techniques that have been used as part of a limb-sparing approach in the treatment of appendicular bone tumors in humans. The objective of this case report was to describe the feasibility and result of microwave ablation (MWA) and cementoplasty in a dog with stage-1 osteoblastic appendicular osteosarcoma of the right distal radius. A microwave antenna was inserted in the osteolytic area using computed tomography (CT) guidance. Three ablation cycles of 5 min at 60 watts were performed. Immediately after the MWA procedure, a tricalcium phosphate-based cement was injected through the bone trocar to consolidate the ablated zone. Adjuvant chemotherapy with six sessions of carboplatin was performed, without major complication. Response to the treatment was evaluated according to RECIST criteria every 6 weeks. Twenty-four hours after MWA, the dog was pain-free and had excellent mobility. Based on CT measurements, a reduction of the size of the lytic area was observed at the 2-month and at the 7-month follow-up (from 13% to 25% of the longest diameter), classified as stable disease according to RECIST criteria. The dog died 18 months after the initial diagnosis due to distant metastases.

Calcium Phosphate Cements Combined with Blood as a Promising Tool for the Treatment of Bone Marrow Lesions.

The solid phase of a commercial calcium phosphate (Graftys® HBS) was combined with ovine or human blood stabilized either with sodium citrate or sodium heparin. The presence of blood delayed the setting reaction of the cement by ca. 7-15 h, depending on the nature of the blood and blood stabilizer. This phenomenon was found to be directly related to the particle size of the HBS solid phase, since prolonged grinding of the latter resulted in a shortened setting time (10-30 min). Even though ca. 10 h were necessary for the HBS blood composite to harden, its cohesion right after injection was improved when compared to the HBS reference as well as its injectability. A fibrin-based material was gradually formed in the HBS blood composite to end-up, after ca. 100 h, with a dense 3D organic network present in the intergranular space, thus affecting the microstructure of the composite. Indeed, SEM analyses of polished cross-sections showed areas of low mineral density (over 10-20 µm) spread in the whole volume of the HBS blood composite. Most importantly, when the two cement formulations were injected in the tibial subchondral cancellous bone in a bone marrow lesion ovine model, quantitative SEM analyses showed a highly significant difference between the HBS reference versus its analogue combined with blood. After a 4-month implantation, histological analyses clearly showed that the HBS blood composite underwent high resorption (remaining cement: ca. 13.1 ± 7.3%) and new bone formation (newly formed bone: 41.8 ± 14.7%). This was in sharp contrast with the case of the HBS reference for which a low resorption rate was observed (remaining cement: 79.0 ± 6.9%; newly formed bone: 8.6 ± 4.8%). This study suggested that the particular microstructure, induced by the use of blood as the HBS liquid phase, favored quicker colonization of the implant and acceleration of its replacement by newly formed bone. For this reason, the HBS blood composite might be worth considering as a potentially suitable material for subchondroplasty.

Micromolding-based encapsulation of mesenchymal stromal cells in alginate for intraarticular injection in osteoarthritis.

Osteoarthritis (OA) is an inflammatory joint disease that affects cartilage, subchondral bone, and joint tissues. Undifferentiated Mesenchymal Stromal Cells are a promising therapeutic option for OA due to their ability to release anti-inflammatory, immuno-modulatory, and pro-regenerative factors. They can be embedded in hydrogels to prevent their tissue engraftment and subsequent differentiation. In this study, human adipose stromal cells are successfully encapsulated in alginate microgels via a micromolding method. Microencapsulated cells retain their in vitro metabolic activity and bioactivity and can sense and respond to inflammatory stimuli, including synovial fluids from OA patients. After intra-articular injection in a rabbit model of post-traumatic OA, a single dose of microencapsulated human cells exhibit properties matching those of non-encapsulated cells. At 6 and 12 weeks post-injection, we evidenced a tendency toward a decreased OA severity, an increased expression of aggrecan, and a reduced expression of aggrecanase-generated catabolic neoepitope. Thus, these findings establish the feasibility, safety, and efficacy of injecting cells encapsulated in microgels, opening the door to a long-term follow-up in canine OA patients.

Microbiota of the Digestive Glands and Extrapallial Fluids of Clams Evolve Differently Over Time Depending on the Intertidal Position.

The Manila clam (Ruditapes philippinarum) is the second most exploited bivalve in the world but remains threatened by diseases and global changes. Their associated microbiota play a key role in their fitness and acclimation capacities. This study aimed at better understanding the behavior of clam digestive glands and extrapallial fluids microbiota at small, but contrasting spatial and temporal scales. Results showed that environmental variations impacted clam microbiota differently according to the considered tissue. Each clam tissue presented its own microbiota and showed different dynamics according to the intertidal position and sampling period. Extrapallial fluids microbiota was modified more rapidly than digestive glands microbiota, for clams placed on the upper and lower intertidal position, respectively. Clam tissues could be considered as different microhabitats for bacteria as they presented different responses to small-scale temporal and spatial variabilities in natural conditions. These differences underlined a more stringent environmental filter capacity of the digestive glands.

A New Animal Model of Laryngeal Transplantation.

Only three laryngeal transplants have been described in the literature to date, and none of the techniques has enabled a completely satisfactory functional result to be obtained. This article presents a new model of laryngeal transplantation, with quality of revascularisation of the transplant being the principal objective and optimisation of the various steps of the procedure, with the integration of a new reinnervation technique as a secondary objective. We present a preclinical animal study. Three pig larynges removed in vivo underwent allotransplantation according to the same protocol. The quality of the revascularisation was examined immediately after the surgery as well as by endoscopy for one animal on the fourth day after the operation. The mean time of cold ischaemia was 3 h 15 min. The anaesthetic tolerance of the pigs was excellent. Revascularisation was achieved and judged to be excellent for the three transplants immediately after the operation and the endoscopy performed for one pig on the fourth day after the operation confirmed this result. The anatomical similarities also enabled the application and integration of an innovative technique of laryngeal reinnervation into the various phases of the operation. We describe a reliable and reproducible animal model for laryngeal transplantation. Its application in humans can be envisaged.

Quantifying maerl (rhodolith) habitat complexity along an environmental gradient at regional scale in the Northeast Atlantic.

Maerl beds are ecologically important marine biogenic habitats founded on a few species of free-living coralline algae that aggregate and form highly complex rhodoliths. The high biodiversity found in these habitats have been mainly justified by the structural complexity that they provide. However, few attempts to quantify this complexity have been made. Maerl species distribution, density, rhodolith growth forms, and shapes vary with environmental conditions. Hydrodynamics and depth have been shown to drive morphology. Using species-specific metrics such as sphericity and branching density, as well as diameter and fractal dimension at the rhodolith level, and maerl density at the habitat level, we quantified the habitat complexity within ten maerl beds at a regional scale (along ∼400 km of the coastline of Brittany in Western France). Using both long-term monitoring data and environmental models, we investigated how maerl habitat complexity varies among beds and which environmental conditions drive those differences. The effects of currents, exposure to wind-generated waves, temperature and sediment granulometry were evaluated. We confirmed variations in complexity in maerl beds at the habitat and rhodolith levels at local and regional scales, which might have ecological and conservational implications for their associated biodiversity. The analysed environmental conditions drive around a third of the variance in habitat complexity. Sediment granulometry is the main driver of maerl habitat complexity in Brittany, while the isolated effects of depth and hydrodynamics accounted for less than 5% of the variability each. Our results have important implications for paleoecology, and we suggest that maerl facies should be interpreted carefully. Our study provides a first attempt at explicitly quantifying maerl habitat complexity, and further contributes to the understanding of this fundamental ecological question.

Standardized and axially vascularized calcium phosphate-based implants for segmental mandibular defects: A promising proof of concept.

The reconstruction of massive segmental mandibular bone defects (SMDs) remains challenging even today; the current gold standard in human clinics being vascularized bone transplantation (VBT). As alternative to this onerous approach, bone tissue engineering strategies have been widely investigated. However, they displayed limited clinical success, particularly in failing to address the essential problem of quick vascularization of the implant. Although routinely used in clinics, the insertion of intrinsic vascularization in bioengineered constructs for the rapid formation of a feeding angiosome remains uncommon. In a clinically relevant model (sheep), a custom calcium phosphate-based bioceramic soaked with autologous bone marrow and perfused by an arteriovenous loop was tested to regenerate a massive SMD and was compared to VBT (clinical standard). Animals did not support well the VBT treatment, and the study was aborted 2 weeks after surgery due to ethical and animal welfare considerations. SMD regeneration was successful with the custom vascularized bone construct. Implants were well osseointegrated and vascularized after only 3 months of implantation and totally entrapped in lamellar bone after 12 months; a healthy yellow bone marrow filled the remaining space. STATEMENT OF SIGNIFICANCE: Regenerative medicine struggles with the generation of large functional bone volume. Among them segmental mandibular defects are particularly challenging to restore. The standard of care, based on bone free flaps, still displays ethical and technical drawbacks (e.g., donor site morbidity). Modern engineering technologies (e.g., 3D printing, digital chain) were combined to relevant surgical techniques to provide a pre-clinical proof of concept, investigating for the benefits of such a strategy in bone-related regenerative field. Results proved that a synthetic-biologics-free approach is able to regenerate a critical size segmental mandibular defect of 15 cm3 in a relevant preclinical model, mimicking real life scenarii of segmental mandibular defect, with a full physiological regeneration of the defect after 12 months.

Generation of Cross-Specialty Consensus Statements on Soft Tissue Management via a Modified Delphi Method.

BACKGROUND: Soft tissue management (STM) training programs for surgeons are largely tradition based, and substantial differences exist among different surgical specialties. The lack of comprehensive and systematic clinical evidence on how surgical techniques and implants affect soft tissue healing makes it difficult to develop evidence-based curricula. As a curriculum development group (CDG), we set out to find common grounds in the form of a set of consensus statements to serve as the basis for surgical soft tissue education. METHODS: Following a backward planning process and Kern's six-step approach, the group selected 13 topics to build a cross-specialty STM curriculum. A set of statements based on the curriculum topics were generated by the CDG through discussions and a literature review of three topics. A modified Delphi process including one round of pilot voting through a face-to-face CDG meeting and two rounds of web-based survey involving 22 panelists were utilized for the generation of consensus statements. RESULTS: Seventy-one statements were evaluated, and 56 statements reached the 80% consensus for "can be taught as is." CONCLUSIONS: Using a modified Delphi method, a set of cross-specialty consensus statements on soft tissue management were generated. These consensus statements can be used as a foundation for multi-specialty surgical education. Similar methods that combine expert experience and clinical evidence can be used to develop specialty-specific consensus on soft tissue handling.

Mechanical evaluation of a novel angle-stable interlocking nail in a gap fracture model.

OBJECTIVE: To describe the mechanical characteristics of a novel angle-stable interlocking nail (NAS-ILN) and compare them to those of a locking compression plate (LCP) by using a gap-fracture model. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Synthetic bone models. METHODS: Synthetic bone models simulating a 50 mm diaphyseal comminuted canine tibial fracture were treated with either a novel angle-stable interlocking nail (NAS-ILN) or a locking compression plate (LCP). Maximal axial deformation and load to failure in compression and 4-point bending, as well as maximal angular deformation, slack, and torque to failure in torsion, were statistically compared (P < .05). RESULTS: In compression, the maximal axial deformation was lower for NAS-ILN (0.11 mm ± 0.03) than for LCP (1.10 mm ± 0.22) (P < .0001). The ultimate load to failure was higher for NAS-ILN (803.58 N ± 29.52) than for LCP (328.40 N ± 11.01) (P < .0001). In torsion, the maximal angular deformation did not differ between NAS-ILN (22.79° ± 1.48) and LCP (24.36° ± 1.45) (P = .09). The ultimate torque to failure was higher for NAS-ILN (22.45 Nm ± 0.24) than for LCP (19.10 Nm ± 1.36) (P = .001). No slack was observed with NAS-ILN. In 4-point bending, the maximal axial deformation was lower for NAS-ILN (3.19 mm ± 0.49) than for LCP (4.17 mm ± 0.34) (P = .003). The ultimate bending moment was higher for NAS-ILN (25.73 Nm, IQR [23.54-26.86] Nm) than for LCP (16.29 Nm, IQR [15.66-16.47] Nm) (P = .002). CONCLUSION: The NAS-ILN showed greater stiffness in compression and 4-point bending, and a greater resistance to failure in compression, torsion, and 4-point bending, than LCP. CLINICAL IMPACT: Based on these results, NAS-ILNs could be considered as alternative implants for the stabilization of comminuted fractures.

A novel autotransfusion device saving erythrocytes and platelets used in a 72 h survival swine model of surgically induced controlled blood loss.

BACKGROUND: The purpose of this study was to develop a swine model of surgically induced blood loss to evaluate the performances of a new autotransfusion system allowing red blood cells and platelets preservation while collecting, washing and concentrating hemorrhagic blood intraoperatively. METHODS: Two types of surgically induced blood loss were used in 12 minipigs to assess system performance and potential animal complications following autotransfusion: a cardiac model (cardiopulmonary bypass) and a visceral model (induced splenic bleeding). Animal clinical and hematological parameters were evaluated at different time-points from before bleeding to the end of a 72-hour post-transfusion period and followed by a post-mortem examination. System performances were evaluated by qualitative and quantitative parameters. RESULTS: All animals that received the autotransfusion survived. Minimal variations were seen on the red blood cell count, hemoglobin, hematocrit at the different sampling times. Coagulation tests failed to show any hypo or hypercoagulable state. Gross and histologic examination didn't reveal any thrombotic lesions. Performance parameters exceeded set objectives in both models: heparin clearance (≥ 90%), final heparin concentration (≤ 0.5 IU/mL), free hemoglobin washout (≥ 90%) and hematocrit (between 45% and 65%). The device treatment rate of diluted blood was over 80 mL/min. CONCLUSIONS: In the present study, both animal models succeeded in reproducing clinical conditions of perioperative cardiac and non-cardiac blood loss. Sufficient blood was collected to allow evaluation of autotransfusion effects on animals and to demonstrate the system performance by evaluating its capacity to collect, wash and concentrate red blood cells and platelets. Reinfusion of the treated blood, containing not only concentrated red blood cells but also platelets, did not lead to any postoperative adverse nor thrombogenic events. Clinical and comparative studies need to be conducted to confirm the clinical benefit of platelet reinfusion.

Optimization of an O2-balanced bioartificial pancreas for type 1 diabetes using statistical design of experiment.

A bioartificial pancreas (BAP) encapsulating high pancreatic islets concentration is a promising alternative for type 1 diabetes therapy. However, the main limitation of this approach is O2 supply, especially until graft neovascularization. Here, we described a methodology to design an optimal O2-balanced BAP using statistical design of experiment (DoE). A full factorial DoE was first performed to screen two O2-technologies on their ability to preserve pseudo-islet viability and function under hypoxia and normoxia. Then, response surface methodology was used to define the optimal O2-carrier and islet seeding concentrations to maximize the number of viable pseudo-islets in the BAP containing an O2-generator under hypoxia. Monitoring of viability, function and maturation of neonatal pig islets for 15 days in vitro demonstrated the efficiency of the optimal O2-balanced BAP. The findings should allow the design of a more realistic BAP for humans with high islets concentration by maintaining the O2 balance in the device.

Evidence that Pacific tuna mercury levels are driven by marine methylmercury production and anthropogenic inputs.

Pacific Ocean tuna is among the most-consumed seafood products but contains relatively high levels of the neurotoxin methylmercury. Limited observations suggest tuna mercury levels vary in space and time, yet the drivers are not well understood. Here, we map mercury concentrations in skipjack tuna across the Pacific Ocean and build generalized additive models to quantify the anthropogenic, ecological, and biogeochemical drivers. Skipjack mercury levels display a fivefold spatial gradient, with maximum concentrations in the northwest near Asia, intermediate values in the east, and the lowest levels in the west, southwest, and central Pacific. Large spatial differences can be explained by the depth of the seawater methylmercury peak near low-oxygen zones, leading to enhanced tuna mercury concentrations in regions where oxygen depletion is shallow. Despite this natural biogeochemical control, the mercury hotspot in tuna caught near Asia is explained by elevated atmospheric mercury concentrations and/or mercury river inputs to the coastal shelf. While we cannot ignore the legacy mercury contribution from other regions to the Pacific Ocean (e.g., North America and Europe), our results suggest that recent anthropogenic mercury release, which is currently largest in Asia, contributes directly to present-day human mercury exposure.

Injectable silanized hyaluronic acid hydrogel/biphasic calcium phosphate granule composites with improved handling and biodegradability promote bone regeneration in rabbits.

Biphasic calcium phosphate (BCP) granules are osteoconductive biomaterials used in clinics to favor bone reconstruction. Yet, poor cohesivity, injectability and mechanical properties restrain their use as bone fillers. In this study, we incorporated BCP granules into in situ forming silanized hyaluronic acid (Si-HA) and hydroxypropylmethylcellulose (Si-HPMC) hydrogels. Hydrogel composites were shown to be easily injectable (F < 30 N), with fast hardening properties (<5 min), and similar mechanical properties (E∼ 60 kPa). In vivo, both hydrogels were well tolerated by the host, but showed different biodegradability with Si-HA gels being partially degraded after 21d, while Si-HPMC gels remained stable. Both composites were easily injected into critical size rabbit defects and remained cohesive. After 4 weeks, Si-HPMC/BCP led to poor bone healing due to a lack of degradation. Conversely, Si-HA/BCP composites were fully degraded and beneficially influenced bone regeneration by increasing the space available for bone ingrowth, and by accelerating BCP granules turnover. Our study demonstrates that the degradation rate is key to control bone regeneration and that Si-HA/BCP composites are promising biomaterials to regenerate bone defects.

Collateral effects of targeting the nucleus pulposus via a transpedicular or transannular surgical route: a combined X-ray, MRI, and histological long-term descriptive study in sheep.

PURPOSE: In the context of regenerative medicine strategies, based in particular on the injection of regenerative cells, biological factors, or biomaterials into the nucleus pulposus (NP), two main routes are used: the transpedicular approach (TPA) and the transannular approach (TAA). The purpose of our study was to compare the long-term consequences of the TPA and the TAA on intervertebral disc (IVD) health through a longitudinal follow-up in an ovine model. METHODS: The TPA and the TAA were performed on 12 IVDs from 3 sheep. Six discs were left untreated and used as controls. The route and injection feasibility, as well as the IVD environment integrity, were assessed by MRI (T2-weighted signal intensity), micro-CT scan, and histological analyses (Boos' scoring). The sheep were assessed at 1, 3, and 7 months. RESULTS: Both the TPA and the TAA allowed access to the NP. They both induced NP degeneration, as evidenced by a decrease in the T2wsi and an increase in the Boos' scores. The TPA led to persistent end-plate defects and herniation of NP tissue (Schmorl's node-like) after 7 months as well as the presence of osseous fragments in the NP. CONCLUSIONS: The TPA induced more severe lesions in IVDs and vertebrae compared to the TAA. The lesions induced by the TPA are reason to consider whether or not this route is optimal for studying IVD regenerative medicine approaches.

Stable mercury concentrations of tropical tuna in the south western Pacific ocean: An 18-year monitoring study.

Global anthropogenic mercury (Hg) emissions to the atmosphere since industrialization are widely considered to be responsible for a significant increase in surface ocean Hg concentrations. Still unclear is how those inputs are converted into toxic methylmercury (MeHg) then transferred and biomagnified in oceanic food webs. We used a unique long-term and continuous dataset to explore the temporal Hg trend and variability of three tropical tuna species (yellowfin, bigeye, and skipjack) from the southwestern Pacific Ocean between 2001 and 2018 (n = 590). Temporal trends of muscle nitrogen (δ15N) and carbon (δ13C) stable isotope ratios, amino acid (AA) δ15N values and oceanographic variables were also investigated to examine the potential influence of trophic, biogeochemical and physical processes on the temporal variability of tuna Hg concentrations. For the three species, we detected significant inter-annual variability but no significant long-term trend for Hg concentrations. Inter-annual variability was related to the variability in tuna sampled lengths among years and to tuna muscle δ15N and δ13C values. Complementary AA- and model-estimated phytoplankton δ15N values suggested the influence of baseline processes with enhanced tuna Hg concentrations observed when dinitrogen fixers prevail, possibly fuelling baseline Hg methylation and/or MeHg bioavailability at the base of the food web. Our results show that MeHg trends in top predators do not necessary capture the increasing Hg concentrations in surface waters suspected at the global oceanic scale due to the complex and variable processes governing Hg deposition, methylation, bioavailability and biomagnification. This illustrates the need for long-term standardized monitoring programs of marine biota worldwide.