Postoperative administration of the acetylcholinesterase inhibitor, donepezil, interferes with bone healing and implant osseointegration in a rat model

Donepezil is an acetylcholinesterase inhibitor commonly used to treat mild to moderate Alzheimer’s disease. Its use has been associated with increased bone mass in humans and animals. However, the effect of postoperative administration of donepezil on bone healing remains unknown. Therefore, this study aimed to assess the impact of postoperative injection of donepezil on bone healing, titanium-implant osseointegration, and soft tissue healing. Twenty-two Sprague-Dawley rats were randomly assigned to receive a daily dose of either donepezil (0.6 mg/kg) or saline as a control. In each rat, a uni-cortical defect was created in the right tibia metaphysis and a custom-made titanium implant was placed in the left tibiae. After two weeks, rats were euthanized, and their bones were analysed by Micro-CT and histology. The healing of bone defect and implant osseointegration in the rats treated with donepezil were significantly reduced compared to the saline-treated rats. Histomorphometric analysis showed lower immune cell infiltration in bone defects treated with donepezil compared to the saline-treated defects. On the other hand, the healing time of soft tissue wounds was significantly shorter in donepezil-treated rats compared to the controls. In conclusion, short-term administration of donepezil hinders bone healing whereas enhancing soft tissue healing

Differences in platelet-rich plasma composition influence bone healing

Aim: Platelet-rich plasma (PRP) is an autologous blood-derived material that has been used to enhance bone regeneration. Clinical studies, however, reported inconsistent outcomes. This study aimed to assess the effect of changes in leucocyte and PRP (L-PRP) composition on bone defect healing. Materials and Methods: L-PRPs were prepared using different centrifugation methods and their regenerative potential was assessed in an in-vivo rat model. Bilateral critical-size tibial bone defects were created and filled with single-spin L-PRP, double-spin L-PRP, or filtered L-PRP. Empty defects and defects treated with collagen scaffolds served as controls. Rats were euthanized after 2 weeks, and their tibias were collected and analysed using micro-CT and histology. Results: Double-spin L-PRP contained higher concentrations of platelets than singlespin L-PRP and filtered L-PRP. Filtration of single-spin L-PRP resulted in lower concentrations of minerals and metabolites. In vivo, double-spin L-PRP improved bone healing by significantly reducing the size of bone defects (1.08 ± 0.2 mm3 ) compared to single-spin L-PRP (1.42 ± 0.27 mm3 ) or filtered L-PRP (1.38 ± 0.28 mm3 ). There were fewer mast cells, lymphocytes, and macrophages in defects treated with double-spin L-PRP than in those treated with single-spin or filtered L-PRP. Conclusion: The preparation method of L-PRP affects their composition and potential to regenerate bone

Planar σ‑Aromaticity in Ga-Doped Au Clusters

Recently, the first example of Au–Ga clusters is synthesized and characterized, which can be described by the jellium model as a superatom with 8 valence electrons that come from the joint contribution of Au and Ga atoms, opening a whole new field for further research. Here, the structure features and stability of one Ga-doped Au cluster with magic number electrons (6 and 8) are analyzed in detail. Moreover, the valence electron fillings and chemical bonding of them are also further explored. It is found that Au3Ga and Au5Ga clusters present planar configurations, and they have higher stability than that of neighbor clusters. The AIMD simulations show that these two clusters still have a good thermal stability at 500 K. The molecular orbital analyses show that the Au3Ga and Au5Ga have three and one typical delocalization orbital throughout the whole planar spaces, respectively, following the planar σ-aromaticity rule. The ELF and LOL analyses are further performed, and the results are consistent with the molecular orbital analyses. The NICSzz-scan curves confirm that the Au3Ga is more aromatic than the Au5Ga, and the reason is that the former has more delocalized electrons than the latter. Our work opens up aromaticity studies in the Au–Ga clusters

Delivery systems of local anesthetics in bone surgery: are they efficient and safe?

International audienceManagement of postoperative pain following bone surgery includes administration of local anesthetics (LAs). Smart delivery systems, including triggered systems, have been designed to provide a continuous release of LA in situ. However, these systems can provide a high level of LA locally. This review will examine the state-of-the-art regarding the LA delivery systems optimized for management of postoperative pain in bone surgery and will discuss the potential adverse effects of LAs on the overall pathways of bone healing, including the inflammation response phase, hemostasis phase, tissue repair phase and remodeling phase. There is a clinical need to document these effects and the potential impacts on the clinical outcome of the patient

The Delineation and Ecological Connectivity of the Three Parallel Rivers Natural World Heritage Site

Landscape connectivity refers to the degree of continuity between the spatially structured units of a landscape. Ecological connectivity can characterise the degree to which ecological functional areas are connected in terms of function and ecological processes. In this study, the landscape pattern index and ecosystem service values were used to evaluate the ecological functional resistance of each landscape type, taking the Three Parallel Rivers Natural World Heritage Site as an example and the habitat distribution and population size of the Yunnan snub-nosed monkey as a reference. The minimum cost distance model, combined with the barrier impact index (BEI) and ecological connectivity index (ECI), was used to determine the degree of barrier impact on the study area and the ecological connectivity of the core reserve of the heritage site in both 2000 and 2020. The resistances of the different land types and landscape heterogeneity to the ecological function of species migration between the core protected areas of the heritage site were, in descending order, those of the forest, shrubs and grass, water, unused land, cultivated land, and built-up land. In 2020, the study area had a large BEI, with areas such as built-up areas, major roads, the sides of large rivers, and arable land being significant contributors to the blockage of landscape connectivity. The overall landscape connectivity in the study area was generally low, with clear spatial differentiation and a three-column parallel distribution pattern influenced by the topography and landscape. With the adjustment of the core reserve boundaries of the heritage site, the proportion of areas with high connectivity (ECI = 4–5) increased from 11.31% in 2000 to 34.36% in 2020. This increased landscape connectivity was conducive to the migration and reproduction of large terrestrial animals, such as the Yunnan snub-nosed monkey, with increasing numbers of populations and individuals. This study provides theoretical and methodological insights into the delineation and conservation of natural heritage sites and landscape connectivity

Needle-free injection: Dental infiltration anesthesia

This study aimed to develop an optimal Needle-Free Liquid Jet Injection (NFLJI) technique for dental infiltration anesthesia and evaluate its clinical safety and feasibility. The fluid dynamics of NFLJI in the dentoalveolar region were investigated using soft tissue phantoms supported by rigid glass. NFLJIs were performed at different incident angles and recorded using a high-speed camera. Accordingly, an optimal NFLJI for infiltration anesthesia was developed and validated on cadavers, then assessed in two pilot Randomized Controlled Trials (RCT): one for validating the safety of optimal NFLJI technique, the other for evaluating its feasibility and safety. High-speed videos showed that perpendicular NFLJIs induced significantly more regurgitation than oblique NFLJIs, which was confirmed in cadavers. Clinical trials revealed that perpendicular NFLJIs induced a high risk of bleeding (83.3%) and laceration (83.3%), whereas oblique NFLJIs induced a low risk of bleeding (33.3%) and laceration (16.7%). Moreover, the preliminary success rates of oblique NFLJIs and needle injections were both 83.3%. The recruitment took 3–5 weeks with a rate of 100%. Oblique NFLJIs could be a promising approach for dental infiltration anesthesia, causing minimal drug regurgitation with a relatively low risk of complication. The pilot RCTs confirmed the feasibility for conducting a non-inferiority RCT.This research was sponsored by the Natural Sciences and Engineering Research Council of Canada (543972-19 and 366077487). The first author was sponsored by the Clifford C.F. Wong Fellowship, réseau de Recherche en Santé Buccodentaire et Osseuse and Alpha-Omega Foundation of Canada from McGill University, and the Doctoral fellowship from the Chinese Scholarship Council

NSAID chronotherapy after impacted third molar extraction: a randomized controlled trial

Objectives: Postoperative pain management impacts patients’ quality of life and morbidity. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are widely used for this following a 3-doses-per-day regime. However, pain and inflammation follow a circadian rhythm, and animal models assessing the scheduling of NSAID administration (e.g., chronotherapy) have shown that while their use during the active phase of the day enhances postoperative recovery, their administration during the resting phase could have detrimental effects. This observation has led us to hypothesize that night administration of NSAID might be unnecessary in post-surgical scenarios. Therefore, a randomized clinical trial was conducted to test this hypothesis in surgical third molar extractions. Materials and methods: Seventy (18–35 years) healthy participants requiring surgical removal of impacted lower third molars were recruited and randomized into a double-blind placebo-controlled study. For three days postoperatively, the treatment group (n = 33) received ibuprofen (400 mg) at 8 AM, 1 PM, and a placebo at 8 PM, while the control group (n = 37) received ibuprofen (400 mg) at 8 AM, 1 PM, and 8 PM. Pain severity was assessed by visual analog scale (VAS) and healing indicators including facial swelling, mouth opening, and C-reactive protein blood levels were also measured. Results: Pain VAS measures showed a circadian variation peaking at night. Also, no significant differences were observed between the two groups of the study in terms of postoperative pain scores (estimate: 0.50, 95% CI = [− 0.38, 1.39]) or any other healing indicator. Conclusions: Postoperative pain follows a circadian rhythm. Moreover, night administration of ibuprofen might not provide any significant benefits in terms of pain management and control of inflammation, and two doses during the day only could be sufficient for pain management after surgical interventions. Knowledge transfer statement: Even though this study cannot rule out the possibility that a reduced regime is different than a standard regime, nocturnal doses of ibuprofen seem to have no clinical significance in the short term, and the results of this study provide evidence in favor of reducing ibuprofen administration from three doses to two doses only after third molar surgery.This study was funded by Jordan University of Science and Technology in Irbid, Jordan (funding number: 20170307)

Differences in platelet‐rich plasma composition influence bone healing

Aim: Platelet-rich plasma (PRP) is an autologous blood-derived material that has been used to enhance bone regeneration. Clinical studies, however, reported inconsistent outcomes. This study aimed to assess the effect of changes in leucocyte and PRP (L-PRP) composition on bone defect healing. Materials and Methods: L-PRPs were prepared using different centrifugation methods and their regenerative potential was assessed in an in-vivo rat model. Bilateral critical-size tibial bone defects were created and filled with single-spin L-PRP, double-spin L-PRP, or filtered L-PRP. Empty defects and defects treated with collagen scaffolds served as controls. Rats were euthanized after 2 weeks, and their tibias were collected and analysed using micro-CT and histology. Results: Double-spin L-PRP contained higher concentrations of platelets than singlespin L-PRP and filtered L-PRP. Filtration of single-spin L-PRP resulted in lower concentrations of minerals and metabolites. In vivo, double-spin L-PRP improved bone healing by significantly reducing the size of bone defects (1.08 ± 0.2 mm3) compared to single-spin L-PRP (1.42 ± 0.27 mm3) or filtered L-PRP (1.38 ± 0.28 mm3). There were fewer mast cells, lymphocytes, and macrophages in defects treated with double-spin L-PRP than in those treated with single-spin or filtered L-PRP. Conclusion: The preparation method of L-PRP affects their composition and potential to regenerate bone.Depto. de Especialidades Clínicas OdontológicasFac. de OdontologíaTRUEpu