Microglial Piezo1 senses Aß fibril stiffness to restrict Alzheimer's disease.

The pathology of Alzheimer's disease (AD) is featured with extracellular amyloid-ß (Aß) plaques, whose impact on the mechanical properties of the surrounding brain tissues is unclear. Microglia sense and integrate biochemical cues of the microenvironment. However, whether the microglial mechanosensing pathways influence AD pathogenesis is unknown. Here, we surveyed the elevated stiffness of Aß-plaque-associated tissues and observed the selective upregulation of the mechanosensitive ion channel Piezo1 in Aß-plaque-associated microglia. Piezo1 sensed the stiffness stimuli of Aß fibrils and subsequently induced Ca2+ influx for microglial clustering, phagocytosis, and compacting of Aß plaques. Microglia lacking Piezo1 led to the exacerbation of Aß pathology and cognitive decline, whereas pharmacological activation of microglial Piezo1 ameliorated brain Aß burden and cognitive impairment in 5 × FAD mice. Together, our results reveal that Piezo1, a mechanosensor of Aß fibril stiffness in microglia, represents a potential therapeutic target for AD.

Short Implants versus Longer Implants with Sinus Floor Elevation: A Systemic Review and Meta-Analysis of Randomized Controlled Trials with a Post-Loading Follow-Up Duration of 5 Years.

This study compared the outcome of fixed prostheses supported by short implants (<8 mm) and longer implants (≥8 mm) with an elevated sinus floor after 5 years of follow-up. The literature searches were performed electronically and manually in PubMed, EMBASE, and Web of Science databases to identify relevant articles published from 1 January 2013 to 31 January 2020. We selected eligible studies using inclusion criteria and assessed their quality. From 1688 identified studies, five randomized controlled trials were included. Between the short implant group and the control group, the implant failure-related pooled risk ratio (RR) was 3.64 (p = 0.07). The RR for technical complications was 2.61 (p = 0.0002), favoring longer implants. Marginal peri-implant bone loss after 1 and 5 years of function showed statistically significant less bone loss at short implants (1 year: mean difference = 0.21 mm; p < 0.00001; 5 years: mean difference = 0.26 mm; p = 0.02). The implant failure and the biological failure of both groups were similar after 5 years of follow-up. Short implants could be an alternative to long implants with an elevated sinus floor for atrophic maxillae in aging populations. Studies with larger trials and longer periods of follow-up (10 years) remain essential.

Comparison of Implant Placement Accuracy in Healed and Fresh Extraction Sockets between Static and Dynamic Computer-Assisted Implant Surgery Navigation Systems: A Model-Based Evaluation.

The aim of this model-base study was to compare the accuracy of implant placement between static and dynamic computer-assisted implant surgery (CAIS) systems in a fresh extraction socket and healed ridge. A randomized in vitro study was conducted. Twenty 3D-printed maxillary models and 80 implants were used. One experienced researcher placed the implants using either the static navigation or dynamic navigation system. Accuracy was measured by overlaying the real position in the postoperative CBCT on the virtual presurgical placement of the implant in a CBCT image. Descriptive and bivariate analyses of the data were performed. In the fresh sockets, the mean deviation was 1.24 ± 0.26 mm (entry point), 1.69 ± 0.34 mm (apical point), and 3.44 ± 1.06° (angle discrepancy) in the static CAIS group, and 0.60 ± 0.29 mm, 0.78 ± 0.33 mm, and 2.47 ± 1.09° in the dynamic CIAS group, respectively. In the healed ridge, the mean deviation was 1.09 ± 0.17 mm and 1.40 ± 0.30 mm, and 2.12 ± 1.11° in the static CAIS group, and 0.80 ± 0.29 mm, 0.98 ± 0.37 mm, and 1.69 ± 0.76° in the dynamic CIAS group, respectively. Compared with the static CAIS system, the dynamic CAIS system resulted in significantly lower entry and apical errors in both fresh sockets and healed ridges. Differences in bone morphology therefore seem to have little effect on accuracy in the dynamic CAIS group.

HDAC3-Regulated PGE2 Production by Microglia Induces Phobic Anxiety Susceptibility After Stroke and Pointedly Exploiting a Signal-Targeted Gamma Visual Stimulation New Therapy.

BACKGROUND: Phobic anxiety present after stroke (called poststroke anxiety, PSA) can hamper the rehabilitation of patients and disrupt their usual activities. Besides, the symptoms and mechanisms of PSA are different from those in nonstroke populations that have generalized anxiety disorder. What's more, the treatment approaches for phobic anxiety are confined to unitary or general methods with poor efficiency. METHODS: Behavioural test screen combined bioinformatics analysis explored molecular changes between generalized anxiety disorder in nonstroke mice (restraint stress, RS) and photothrombotic stroke mice exposed to environmental stress (PTS + RS, mimicking PSA). Multiple molecular biological and neurobiological methods were employed to explain mechanisms in vitro and in vivo. And exploiting gamma flicker stimulation device for therapy. RESULTS: Microglial (MG) overactivation is a prominent characteristic of PTS + RS. HDAC3 was mainly upregulated in activated-microglia from damaged cortex and that local prostaglandin E2 (PGE2) production increased in MG via HDAC3-mediated activation of NF-κB signalling by p65 deacetylation. A high content of PGE2 in damaged ischaemic cortex could diffuse freely to amygdala, eliciting anxiety susceptibility of PSA via EP2. Importantly, gamma flicker stimulation relieved anxious behaviour of PTS + RS by modulating the HDAC3/Cox1/EP2 network at some extent. CONCLUSIONS: HDAC3-regulated PGE2 production by microglia constitutes phobic anxiety susceptibility after stroke and a protective approach of gamma visual stimulation can be a candidate new therapy.

Digital workflow for prosthetically driven implant navigation surgery in a fully edentulous patient: a case report.

BACKGROUND: Dynamic navigation has important potential advantages over the static approach for fully edentulous patients. To the best of the authors' knowledge, this is the first published case report describing the use of a dynamic implant navigation technique for a fully edentulous patient. CASE REPORT: A 55-year-old female presented for the replacement of missing teeth. Treatment with an implant-supported fixed dental prosthesis was proposed. A digital navigation implant surgery/immediate provisionalization protocol was used. An acrylic resin denture was fabricated as a radiographic guide. Digital data were obtained through the double scan technique, and a prosthetically driven 3D implant positioning was designed. Four titanium mini screws were inserted into the mandible for registration. The first implant was inserted in a freehand manner and attached to a patient tracker. After calibration and registration, the navigation system was set up. The other five implants were inserted using the navigation system. The procedure followed for the maxilla was similar. After surgery, a loading procedure was performed within 24 h. RESULTS: Following implant placement, a postoperative CBCT scan was performed. The results showed that all implants were placed precisely, in accordance with the treatment plan. CONCLUSION: From the results obtained it appears that a fully digital workflow for prosthetically driven implant navigation surgery is suitable for the treatment of fully edentulous patients requiring an implant-supported fixed restoration. High-level evidence is needed to determine the accuracy and precision of this workflow.

Clinical assessment of implant-supported full-arch immediate prostheses over 6 months of function.

OBJECTIVE: To assess the clinical outcomes of implant-supported full-arch immediate prosthesis over 6 months of functions and analyze the risk factors of prosthetic complications. MATERIALS AND METHODS: This retrospective cohort study included patients who were treated with implant-supported full-arch restoration under immediate loading protocol between April 2008 and June 2016, and who wore the immediate prosthesis for more than 6 months. Medical charts were reviewed for the patients' general information, implant information, prosthetic information, and details of any prosthetic complications. Prosthetic complications were classified as follows: class I, prosthesis loosening; class II, fewer than three artificial teeth fractured; class III, three or more artificial teeth fractured; and class IV, resin base fractures. A cox proportional hazards ratio model was adopted to analyze the potential risk factors for class IV complications. RESULTS: A total of 114 patients (mean age, 56.73 ± 10.19 years) and 144 prostheses were included. The average wearing time for the immediate prosthesis was 21.9 months, and 62 (54.39%) patients experienced prosthetic complications, 30 of whom suffered from complications more than once. The most common complications were class II complications (12.3%) during the first 6 months of functioning and class IV complications (28.1%) during the entire function period. Class II complications were more common in the anterior region, while class IV complications occurred more often in the posterior region. The multivariable Cox proportional hazards regression model showed that a prosthesis in the maxilla (HR = 3.37, P = .001) and fiber reinforcement (HR = 0.39, P = .021) were significantly related to class IV complications. CONCLUSIONS: Implant-supported full-arch immediate prosthesis functioning over 6 months have a high prevalence of prosthetic complications. Fiber-reinforcement could reduce the prevalence of class IV complications when acrylic immediate prosthesis functioned longer than 6 months. Avoiding using the anterior teeth of the immediate prosthesis to tear pliable but strong food may prevent tooth fracture.