Objectives
Multiple generations of medical robots have revolutionized surgery. Their application to dental implants is still in its infancy. Co‐operating robots (cobots) have great potential to ...improve the accuracy of implant placement, overcoming the limitations of static and dynamic navigation. This study reports the accuracy of robot‐assisted dental implant placement in a preclinical model and further applies the robotic system in a clinical case series.
Materials and Methods
In model analyses, the use of a lock‐on structure at robot arm‐handpiece was tested in resin arch models. In a clinical case series, patients with single missing teeth or edentulous arch were included. Robot‐assisted implant placement was performed. Surgery time was recorded. Implant platform deviation, apex deviation, and angular deviation were measured. Factors influencing implant accuracy were analyzed.
Results
The in vitro results showed that with a lock‐on structure, the mean (SD) of platform deviation, apex deviation, and angular deviation were 0.37 (0.14) mm, 0.44 (0.17) mm, and 0.75 (0.29)°, respectively. Twenty‐one patients (28 implants) were included in the clinical case series, 2 with arches and 19 with single missing teeth. The median surgery time for single missing teeth was 23 (IQ range 20–25) min. The surgery time for the two edentulous arches was 47 and 70 min. The mean (SD) of platform deviation, apex deviation, and angular deviation was 0.54 (0.17) mm, 0.54 (0.11) mm, and 0.79 (0.22)° for single missing teeth and for 0.53 (0.17) mm, 0.58 (0.17) mm, and 0.77 (0.26)° for an edentulous arch. Implants placed in the mandible had significantly larger apex deviation than those in the maxilla.
Conclusion
Cobot‐assisted dental implant placement showed excellent positional accuracy and safety in both the in vitro study and the clinical case series. More technological development and clinical research are needed to support the introduction of robotic surgery in oral implantology. Trial registered in ChiCTR2100050885.
The SARS (severe acute respiratory syndrome) outbreak was caused by a coronavirus (CoV) named the SARS-CoV. SARS pathology is propagated both by direct cytotoxic effects of the virus and aberrant ...activation of the innate immune response. Here, we identify several mechanisms by which a SARS-CoV open reading frame (ORF) activates intracellular stress pathways and targets the innate immune response. We show that ORF8b forms insoluble intracellular aggregates dependent on a valine at residue 77. Aggregated ORF8b induces endoplasmic reticulum (ER) stress, lysosomal damage, and subsequent activation of the master regulator of the autophagy and lysosome machinery, Transcription factor EB (TFEB). ORF8b causes cell death in epithelial cells, which is partially rescued by reducing its ability to aggregate. In macrophages, ORF8b robustly activates the NLRP3 inflammasome by providing a potent signal 2 required for activation. Mechanistically, ORF8b interacts directly with the Leucine Rich Repeat domain of NLRP3 and localizes with NLRP3 and ASC in cytosolic dot-like structures. ORF8b triggers cell death consistent with pyroptotic cell death in macrophages. While in those cells lacking NLRP3 accumulating ORF8b cytosolic aggregates cause ER stress, mitochondrial dysfunction, and caspase-independent cell death.
Autophagy delivers cytoplasmic constituents to autophagolysosomes and is linked to both innate and adaptive immunity. Toll-like receptor 4 (TLR4) signaling induces autophagy and recruits Beclin-1, ...the mammalian homolog of yeast Atg6, to the receptor complex. We found that tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-mediated, Lys(63) (K63)-linked ubiquitination of Beclin-1 is critical for TLR4-triggered autophagy in macrophages. Two TRAF6-binding motifs in Beclin-1 facilitated the binding of TRAF6 and the ubiquitination of Beclin-1. Lys(117), which is strategically located in the Bcl-2 homology 3 (BH3) domain of Beclin-1, was a major site for K63-linked ubiquitination. The deubiquitinating enzyme A20 reduced the extent of K63-linked ubiquitination of Beclin-1 and limited the induction of autophagy in response to TLR signaling. Treatment of macrophages with either interferon-gamma or interleukin-1 also triggered the K63-linked ubiquitination of Beclin-1 and the formation of autophagosomes. These results indicate that the status of K63-linked ubiquitination of Beclin-1 plays a key role in regulating autophagy during inflammatory responses.
Objectives
To systematically analyze the accuracy of robotic surgery for dental implant placement.
Materials and Methods
PubMed, Embase, and Cochrane CENTRAL were searched on October 25, 2023. Model ...studies or clinical studies reporting the accuracy of robotic surgery for dental implant placement among patients with missing or hopeless teeth were included. Risks of bias in clinical studies were assessed. Meta‐analyses were undertaken.
Results
Data from 8 clinical studies reporting on 109 patients and 242 implants and 13 preclinical studies were included. Positional accuracy was measured by comparing the implant plan in presurgery CBCT and the actual implant position in postsurgery CBCT. For clinical studies, the pooled (95% confidence interval) platform deviation, apex deviation, and angular deviation were 0.68 (0.57, 0.79) mm, 0.67 (0.58, 0.75) mm, and 1.69 (1.25, 2.12)°, respectively. There was no statistically significant difference between the accuracy of implants placed in partially or fully edentulous patients. For model studies, the pooled platform deviation, apex deviation, and angular deviation were 0.72 (0.58, 0.86) mm, 0.90 (0.74, 1.06) mm, and 1.46 (1.22, 1.70)°, respectively. No adverse event was reported.
Conclusion
Within the limitation of the present systematic review, robotic surgery for dental implant placement showed suitable implant positional accuracy and had no reported obvious harm. Both robotic systems and clinical studies on robotic surgery for dental implant placement should be further developed.
The molecular mechanisms underlying the severe lung pathology that occurs during SARS-CoV infections remain incompletely understood. The largest of the SARS-CoV accessory protein open reading frames ...(SARS 3a) oligomerizes, dynamically inserting into late endosomal, lysosomal, and trans-Golgi-network membranes. While previously implicated in a non-inflammatory apoptotic cell death pathway, here we extend the range of SARS 3a pathophysiologic targets by examining its effects on necrotic cell death pathways. We show that SARS 3a interacts with Receptor Interacting Protein 3 (Rip3), which augments the oligomerization of SARS 3a helping drive necrotic cell death. In addition, by inserting into lysosomal membranes SARS 3a triggers lysosomal damage and dysfunction. Consequently, Transcription Factor EB (TFEB) translocates to the nucleus increasing the transcription of autophagy- and lysosome-related genes. Finally, SARS 3a activates caspase-1 either directly or via an enhanced potassium efflux, which triggers NLRP3 inflammasome assembly. In summary, Rip3-mediated oligomerization of SARS 3a causes necrotic cell death, lysosomal damage, and caspase-1 activation-all likely contributing to the clinical manifestations of SARS-CoV infection.
Abstract
With an increasing aging society, China is the world’s fastest growing markets for oral implants. Compared with traditional oral implants, immediate implants cause marginal bone resorption ...and increase the failure rate of osseointegration, but the mechanism is still unknown. Therefore, it is important to further study mechanisms of tension stimulus on osteoblasts and osteoclasts at the early stage of osseointegration to promote rapid osseointegration around oral implants. The results showed that exosomes containing circ_0008542 from MC3T3-E1 cells with prolonged tensile stimulation promoted osteoclast differentiation and bone resorption. Circ_0008542 upregulated Tnfrsf11a (RANK) gene expression by acting as a miR-185-5p sponge. Meanwhile, the circ_0008542 1916-1992 bp segment exhibited increased m6A methylation levels. Inhibiting the RNA methyltransferase METTL3 or overexpressing the RNA demethylase ALKBH5 reversed osteoclast differentiation and bone resorption induced by circ_0008542. Injection of circ_0008542 + ALKBH5 into the tail vein of mice reversed the same effects in vivo. Site-directed mutagenesis study demonstrated that 1956 bp on circ_0008542 is the m6A functional site with the abovementioned biological functions. In conclusion, the RNA methylase METTL3 acts on the m6A functional site of 1956 bp in circ_0008542, promoting competitive binding of miRNA-185-5p by circ_0008542, and leading to an increase in the target gene RANK and the initiation of osteoclast bone absorption. In contrast, the RNA demethylase ALKBH5 inhibits the binding of circ_0008542 with miRNA-185-5p to correct the bone resorption process. The potential value of this study provides methods to enhance the resistance of immediate implants through use of exosomes releasing ALKBH5.
The Toll-like receptors (TLR) play an instructive role in innate and adaptive immunity by recognizing specific molecular patterns from pathogens. Autophagy removes intracellular pathogens and ...participates in antigen presentation. Here, we demonstrate that not only TLR4, but also other TLR family members induce autophagy in macrophages, which is inhibited by MyD88, Trif, or Beclin 1 shRNA expression. MyD88 and Trif co-immunoprecipitate with Beclin 1, a key factor in autophagosome formation. TLR signaling enhances the interaction of MyD88 and Trif with Beclin 1, and reduces the binding of Beclin 1 to Bcl-2. These findings indicate TLR signaling via its adaptor proteins reduces the binding of Beclin 1 to Bcl-2 by recruiting Beclin 1 into the TLR-signaling complex leading to autophagy.
Coronaviruses (CoV) have recently emerged as potentially serious pathogens that can cause significant human morbidity and death. The severe acute respiratory syndrome (SARS)-CoV was identified as the ...etiologic agent of the 2002-2003 international SARS outbreak. Yet, how SARS evades innate immune responses to cause human disease remains poorly understood. In this study, we show that a protein encoded by SARS-CoV designated as open reading frame-9b (ORF-9b) localizes to mitochondria and causes mitochondrial elongation by triggering ubiquitination and proteasomal degradation of dynamin-like protein 1, a host protein involved in mitochondrial fission. Also, acting on mitochondria, ORF-9b targets the mitochondrial-associated adaptor molecule MAVS signalosome by usurping PCBP2 and the HECT domain E3 ligase AIP4 to trigger the degradation of MAVS, TRAF3, and TRAF 6. This severely limits host cell IFN responses. Reducing either PCBP2 or AIP4 expression substantially reversed the ORF-9b-mediated reduction of MAVS and the suppression of antiviral transcriptional responses. Finally, transient ORF-9b expression led to a strong induction of autophagy in cells. The induction of autophagy depended upon ATG5, a critical autophagy regulator, but the inhibition of MAVS signaling did not. These results indicate that SARS-CoV ORF-9b manipulates host cell mitochondria and mitochondrial function to help evade host innate immunity. This study has uncovered an important clue to the pathogenesis of SARS-CoV infection and illustrates the havoc that a small ORF can cause in cells.
Aim
To compare the 3‐year clinical, radiographic and economic outcomes of short‐6‐mm implants and longer implants combined with osteotome sinus floor elevation (OSFE) in the posterior maxilla.
...Material and Methods
This study enrolled 225 patients (225 implants with diameter of 4.1 mm and 4.8 mm) with a posterior maxillary residual bone height (RBH) of 6–8 mm. Patients were randomly divided into three groups: Group 1 (6 mm implants alone), Group 2 (8 mm implants + OSFE) and Group 3 (10 mm implants + OSFE). The following outcomes were recorded at 1 and 3‐year examinations: implant survival, probing pocket depth (PPD), bleeding on probing (BOP), modified plaque index (mPI), marginal bone loss (MBL), biological and technical complications, complication‐free survival and treatment costs.
Results
At the 3‐year follow‐up, 199 patients (Group 1: 67; Group 2: 62; Group 3: 70) were re‐examined. Implant survival rates were 91.80%, 97.08% and 100.00% in groups 1, 2 and 3. Implant survival rate in Group 1 was significantly lower than that in Group 3 (p = 0.029). A multivariate Cox model showed that the short‐6‐mm implants with wide diameter had a protective effect on implant survival (hazard ratio: 0.59, p = 0.001). No significant differences in BOP%, PPD, mPI, MBL and complication‐free survival rate were found among the three groups. The average costs of retreatment were 8.31%, 1.96% and 0.56% of the total costs in groups 1, 2 and 3. The cost to avoid a 1% increase in implant loss associated with 6‐mm implants over a 3‐year period was 369 CNY (56 USD) using a 10‐mm implant with OSFE and 484 CNY (74 USD) using an 8‐mm implant with OSFE.
Conclusion
In the moderately atrophic posterior maxillae, the three treatments showed acceptable clinical, radiographic and economic outcomes with up to 3‐year follow‐up. 10‐mm implants combined with OSFE showed more favourable implant survival and fewer maintenance costs in comparison with short‐6‐mm implants, which were less expensive.
Aims
To assess the long‐term clinical and radiographic results of implants placed using osteotome sinus floor elevation (OSFE) with or without bone grafting.
Materials and methods
Forty‐five patients ...were randomly assigned into two groups: Group 1 (OSFE with deproteinized bovine bone mineral) and Group 2 (OSFE without grafting). The patients were recalled at 1, 3, 5 and 10 years after surgery. The implant survival, endo‐sinus bone gain (ESBG), marginal bone loss (MBL), peri‐implant bone height (PBH, distance from the most coronal level to the most apical level of bone‐to‐implant contact), prosthesis survival and hardware complications, and peri‐implant soft tissue conditions were assessed.
Results
Forty patients attended the 10‐year examination. Mean residual bone height was 4.58 ± 1.28 mm. The 10‐year cumulative survival rate was 90.7% for Group 1 and 95.0% for Group 2. The PBH was 5.89 ± 1.24 mm for Group 1 and 5.74 ± 1.43 mm for Group 2 at 10 years. The ESBG of both groups remained stable after 3 years. Two‐thirds of the implants were free of hardware complications. No significant differences in MBL and peri‐implant tissue parameters were found.
Conclusion
OSFE with or without grafting both yielded predictable clinical outcomes with similar PBH (ClinicalTrials.gov. NCT01619956).
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