Systematic review on effects of experimental orthodontic tooth displacement on brain activation assessed by fMRI.

BACKGROUND: Orthodontic treatment is often accompanied by discomfort and pain in patients, which are believed to be a result of orthodontic tooth displacement caused by the mechanical forces exerted by the orthodontic appliances on the periodontal tissues. These lead to change blood oxygen level dependent response in related brain regions. OBJECTIVE: This systematic review aims to assess the impact of experimental orthodontic tooth displacement on alterations in central nervous system activation assessed by tasked based and resting state fMRI. MATERIALS AND METHODS: A literature search was conducted using online databases, following PRISMA guidelines and the PICO framework. Selected studies utilized magnetic resonance imaging to examine the brain activity changes in healthy participants after the insertion of orthodontic appliances. RESULTS: The initial database screening resulted in 791 studies. Of these, 234 were duplicates and 547 were deemed irrelevant considering the inclusion and exclusion criteria. Of the ten remaining potential relevant studies, two were excluded during full-text screening. Eight prospective articles were eligible for further analysis. The included studies provided evidence of the intricate interplay between orthodontic treatment, pain perception, and brain function. All of the participants in the included studies employed orthodontic separators in short-term experiments to induce tooth displacement during the early stage of orthodontic treatment. Alterations in brain activation were observed in brain regions, functional connectivity and brain networks, predominantly affecting regions implicated in nociception (thalamus, insula), emotion (insula, frontal areas), and cognition (frontal areas, cerebellum, default mode network). CONCLUSIONS: The results suggest that orthodontic treatment influences beyond the pain matrix and affects other brain regions including the limbic system. Furthermore, understanding the orthodontically induced brain activation can aid in development of targeted pain management strategies that do not adversely affect orthodontic tooth movement. Due to the moderate to serious risk of bias and the heterogeneity among the included studies, further clinical trials on this subject are recommended.

Intensive Longitudinal Social Sensing in Patients With Psychosis Spectrum Disorders: An Exploratory Pilot Study.

BACKGROUND: Psychosis spectrum disorders are characterized by significant alterations in social functioning, which is a major factor for patient recovery. Despite its importance, objectively quantifying the complex day-to-day social behavior in real-life settings has rarely been attempted. Here, we conducted a pilot study with wearable sensors that passively and continuously register interactions with other participants. We hypothesized that the amount and pattern of social interaction was associated with the severity of psychotic symptoms. STUDY DESIGN: We recruited 7 patients with psychosis spectrum disorders and 18 team members from a Soteria-style ward. Each participant wore a radio frequency identification badge, sending and receiving signals from nearby badges, allowing passive quantification of social interactions. In addition, symptom severity was assessed weekly by the Positive and Negative Syndrome Scale (PANSS). STUDY RESULTS: During an 11-week period, we identified 17 970 interactions among patients and staff. On average, patients spent 2.6 h per day interacting, capturing relevant aspects of daily social life. Relative daily interaction time, average interaction duration, and clustering coefficient, a measure of local network integration, were significantly associated with lower PANSS scores. Self-reported interaction time did not correlate with measured interaction time or with PANSS, indicating the importance of objective markers. CONCLUSIONS: This pilot study demonstrates the feasibility of passively recording social interaction of patients and staff at high resolution and for a long observation period in a real-life setting in a psychiatric department. We show links between quantified social interaction and psychopathology that may facilitate development and personalization of targeted treatments.

Eligibility and efficacy of a CPC- and CHX-based antiviral mouthwash for the elimination of SARS-CoV-2 from the saliva: A randomized, double-blind, controlled clinical trial.

AIM: This study aimed at investigating the efficacy of a 0.05% cetylpyridinium chloride-0.05% chlorhexidine (CPC-CHX) mouthwash in reducing viral load in the saliva as compared with sterile water. MATERIALS AND METHODS: Forty SARS-CoV-2 positive patients were asked to dispense 4 mL of saliva. Half the patients rinsed for 60 s with 15 mL CPC-CHX, and the remaining patients rinsed with sterile water (control). Four millilitres of saliva were collected after 15, 30 and 60 min after rinsing. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) specific for SARS-CoV-2 nucleocapsid protein were performed. For ELISA, the intact (representing the active virus) to total virus load (I/T) was calculated. RESULTS: SARS-CoV-2 copy numbers/mL from RT-qPCR tended to decrease in the control group, whereas in the CPC-CHX group, an increase was observed after T30. However, mixed linear model analysis revealed no statistical differences between groups (p = .124), time points (p = .616) and vaccinated or non-vaccinated patients (p = .953). Similarly, no impact of group (p = .880), time points (p = .306) and vaccination (p = .711) was observed for I/T ratio values. CONCLUSIONS: Within the limitation of this study, there was no evidence that the intervention reduced salivary SARS-CoV-2 viral load during the course of 60 min. Therefore, commonly used pre-procedural rinsing might not be clinically relevant.

Is online-only learning as effective as blended learning? A longitudinal study comparing undergraduate students' performance in oral radiology.

INTRODUCTION: Blended learning seems to be an effective teaching concept in oral radiology. During the COVID-19 pandemic, blended learning shifted towards online-only learning. The aim of the present study was to compare the effectiveness of pandemic online-only and pre-pandemic blended learning in three consecutive oral radiology courses (C1, C2 and C3) and to examine whether additional video-based e-learning modules (VBLMs) had a positive impact on undergraduate students' performance during pandemic semesters. MATERIALS AND METHODS: Data from 205 undergraduate dental students participating either in a blended learning or an online-only learning concept were analysed. Pre-pandemic blended learning comprised face-to-face seminars and access to an oral radiology platform (ORP). Pandemic online-only learning comprised online seminars, access to the ORP and additional VBLMs (two VBLMs for C1, four VBLMs for C2 and six VBLMs for C3). Through standardised e-exams at the beginning and end of each semester, performance in final exams and knowledge gain were compared between the two groups. RESULTS: No significant differences in scores in final exams (p = .11) and knowledge gain (p = .18) were found when comparing the pre-pandemic and pandemic groups. On course level, however, students receiving a lower number of VBLMs performed significantly worse in final exams (C1: p < .01, C2: p = .02) and showed inferior knowledge gain (C2: p < .01) during the pandemic. CONCLUSIONS: Within the limitations of the study, the present investigation confirmed that pandemic online-only learning involving VBLMs might be as effective as pre-pandemic blended learning.

SARS-CoV-2 inactivation in laboratory animal tissues with 4% formaldehyde or 5% glutaraldehyde for transfer to biosafety level 1 laboratories.

The SARS-CoV-2 pandemic required the immediate need to transfer inactivated tissue from biosafety level (BSL)-3 to BSL-1 areas to enable downstream analytical methods. No validated SARS-CoV-2 inactivation protocols were available for either formaldehyde (FA)-fixed or glutaraldehyde (GA)-fixed tissues. Therefore, representative tissue from ferrets and hamsters was spiked with 2.2 × 106 tissue culture infectious dose 50% per ml (TCID50/ml) SARS-CoV-2 or were obtained from mice experimentally infected with SARS-CoV-2. SARS-CoV-2 inactivation was demonstrated with 4% FA or 5% GA at room temperature for 72 hours by a titer reduction of up to 103.8 TCID50/ml in different animal tissues with a maximum protein content of 100 µg/mg and a thickness of up to 10 mm for FA and 8 mm for GA. Our protocols can be easily adapted for validating the inactivation of other pathogens to allow for the transfer of biological samples from BSL-3 areas to BSL-1 laboratories.

Is there any sustained effect of the coronavirus disease 2019 pandemic? - A controlled trial comparing pre- and post-pandemic oral radiology courses.

PURPOSE/OBJECTIVES: Due to the coronavirus disease 2019 (COVID-19) pandemic, undergraduate education shifted towards online-only formats from April 2020 until July 2021. Previous research indicated a negative effect on students' competence development, and it remains unclear whether blended learning concepts could provide compensation. Therefore, the present study aimed to compare pre- to post-pandemic students' performance in standardized baseline (BL) and final exams (FE), as well as the associated knowledge gain (KG) in three consecutive undergraduate blended learning-based oral radiology courses (C1-3). METHODS: Ninety-four students participated during two pre-pandemic semesters (October 17-July 18), and ninety-eight students during two post-pandemic semesters (October 21-July 22). Before the pandemic, conventional face-to-face lectures were combined with an oral radiology platform. Two years into the COVID-19 pandemic, additional video-based e-learning modules were adopted from the pandemic online-only curriculum. In each semester, skills and KG were assessed by conducting standardized BL and FE. Students' performance in BL, FE, and the associated KG during pre-pandemic semesters was compared to post-pandemic semesters. RESULTS: In post-pandemic courses, students showed significantly lower BL scores, whereas KG was significantly higher in post- compared to pre-pandemic semesters (27.42% vs. 10.64%, p < 0.001, respectively). FE scores in C1 significantly improved from pre- to post-pandemic semesters. CONCLUSIONS: Within the limitations of our study, the lower BL scores confirmed the negative effect of the pandemic on competence development. Blended learning concepts seem to compensate for this effect and enable students to return to pre-pandemic levels. Future studies are needed to assess the additional impact of video-based e-learning modules.

Non-invasive oral implant position assessment: An ex vivo study using a 3D industrial scan as the reference model to mimic the clinical situation.

AIM: To introduce an objective method to evaluate the accuracy of implant position assessment in partially edentulous patients by comparing different techniques (conventional impression, intraoral scan, CBCT) to a reference 3D model obtained with an industrial scanner, the latter mimicking the clinical situation. MATERIALS AND METHODS: Twenty-nine implants were placed in four human cadaver heads using a fully guided flapless protocol. Implant position was assessed using (a) a conventional impression, (b) an intraoral scan, and (c) CBCT and compared to an industrial scan. Three-dimensional models of intraoral scan body and implant were registered to the arch models and the deviation at implant shoulder, apex, and the angle of deviation were compared to each other as well as to the reference model. RESULTS: The three assessment techniques showed statistically significant deviations (p < .01) from the industrial scan, for all measurements, with no difference between the techniques. The maximum deviation at the implant shoulder was 0.16 mm. At the implant apex this increased to 0.38 mm. The intraoral scan deviated significantly more than the CBCT (0.12 mm, p < .01) and the conventional impression (0.10 mm, p = .02). The maximum implant angle deviation was 1.0°. The intraoral scan deviated more than the conventional impression (0.3°, p = .02). CONCLUSION: All assessment techniques deviated from the reference industrial scan, but the differences were relatively small. Intraoral scans were slightly less accurate than both conventional impressions and CBCT. Depending on the application, however, this inaccuracy may not be clinically relevant.

Efficacy of different mouthwashes against COVID-19: A systematic review and network meta-analysis.

To evaluate the effectiveness of antiseptic mouthwashes in reducing SARS-CoV-2 load clinically and in vitro. A systematic electronic search (MEDLINE/Scopus/Cochrane) was conducted to identify prospective clinical and in vitro studies published between 2019 included and 16 June 2023 assessing the effectiveness of mouthwashes in reducing SARS-CoV-2 load in saliva or surrogates. Data were summarized in tables and a network meta-analysis was performed for clinical trials. Thirty-five studies (14 RCTs, 21 in vitro) fulfilled the inclusion criteria. The risk of bias was judged to be high for 2 clinical and 7 in vitro studies. The most commonly test product was chlorhexidine alone or in combination with other active ingredients, followed by povidone-iodine, hydrogen peroxide and cetylpyridinium chloride. Overall, the descriptive analysis revealed the effectiveness of the mouthwashes in decreasing the salivary viral load both clinically and in vitro. Network meta-analysis demonstrated a high degree of heterogeneity. Among these studies, only chlorhexidine 0.20% was associated to a significant Ct increase in the saliva 5 min after rinsing compared to non-active control (p = 0.027). Data from clinical and in vitro studies suggested the antiviral efficacy of commonly used mouthwashes. Large well-balanced trials are needed to identify the best rinsing protocols.

Micro finite element analysis of continuously loaded mini-implants - A micro-CT study in the rat tail model.

Implant migration has been described as a minor displacement of orthodontic mini-implants (OMIs) when subjected to constant forces. Aim of this study was to evaluate the impact of local stresses on implant migration and bone remodelling around constantly loaded OMIs. Two mini-implants were placed in one caudal vertebra of 61 rats, connected by a nickel­titanium contraction spring, and loaded with different forces (0.0, 0.5, 1.0, 1.5 N). In vivo micro-CT scans were taken immediately and 1, 2 (n = 61), 4, 6 and 8 (n = 31) weeks post-op. Nine volumes of interest (VOIs) around each implant were defined. To analyse stress values, micro-finite element models were created. Bone remodelling was analysed by calculating the bone volume change between scans performed at consecutive time points. Statistical analysis was performed using a linear mixed model and likelihood-ratio-tests, followed by Tuckey post hoc tests when indicated. The highest stresses were observed in the proximal top VOI. In all VOIs, stress values tended to reach their maximum after two weeks and decreased thereafter. Bone remodelling analysis revealed initial bone loss within the first two weeks and bone gain up to week eight, which was noted especially in the highest loading group. The magnitude of local stresses influenced bone remodelling and it can be speculated that the stress related bone resorption favoured implant migration. After a first healing phase with a high degree of bone resorption, net bone gain representing consolidation was observed.

CYP19A1 mediates severe SARS-CoV-2 disease outcome in males.

Male sex represents one of the major risk factors for severe COVID-19 outcome. However, underlying mechanisms that mediate sex-dependent disease outcome are as yet unknown. Here, we identify the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (also known as aromatase) as a host factor that contributes to worsened disease outcome in SARS-CoV-2-infected males. We analyzed exome sequencing data obtained from a human COVID-19 cohort (n = 2,866) using a machine-learning approach and identify a CYP19A1-activity-increasing mutation to be associated with the development of severe disease in men but not women. We further analyzed human autopsy-derived lungs (n = 86) and detect increased pulmonary CYP19A1 expression at the time point of death in men compared with women. In the golden hamster model, we show that SARS-CoV-2 infection causes increased CYP19A1 expression in the lung that is associated with dysregulated plasma sex hormone levels and reduced long-term pulmonary function in males but not females. Treatment of SARS-CoV-2-infected hamsters with a clinically approved CYP19A1 inhibitor (letrozole) improves impaired lung function and supports recovery of imbalanced sex hormones specifically in males. Our study identifies CYP19A1 as a contributor to sex-specific SARS-CoV-2 disease outcome in males. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may furnish a new therapeutic strategy for individualized patient management and treatment.

Autoclaving-induced dimensional changes of three-dimensional printed surgical guides: An in vitro study.

OBJECTIVES: Surgical guides are frequently used for dental implant placement. The aim of this study was to evaluate the impact of the 3D printing process itself and subsequent steam autoclaving on the dimensional stability of five different resin/printer combinations (RPCs). MATERIALS AND METHODS: Fifty identical surgical guides (10 per group) were produced consisting of five RPCs. Half of the guides (5 per group) were steam autoclaved with cycle 1 (121°C, 1 bar, 20.5 min) and the other half with cycle 2 (134°C, 2 bar, 5.5 min). All guides were scanned with a structured-light (SL) 3D scanner before (T0) and after (T1) autoclaving. Linear measurements along the x-, y-, and z-axes were performed at landmarks on the original STL file and on SL scans at T0 and T1, respectively. Wilcoxon signed-rank test, Kruskal-Wallis test, and linear mixed-effects models were performed, depending on the analysis. RESULTS: Three-dimensional printing was associated with significant dimensional alterations for all RPCs. Steam autoclaving using cycle 1 was associated with significant shrinkage in x- (1 RPC), y- (2 RPCs), and z-direction (2 RPCs), while cycle 2 was also associated with shrinkage in x- (2 RPCs), y- (1 RPC), and z-direction (1 RPC). One resin did not present any dimensional changes independently of the cycle. CONCLUSIONS: The majority of the guides presented minor but significant shrinkage due to 3D printing itself and both steam autoclaving cycles, the extent varied between different RPCs. Whether these changes compromise implant placement accuracy remains to be investigated.

Clinical efficacy of guided bone regeneration in peri-implantitis defects. A network meta-analysis.

Guided bone regeneration (GBR) at peri-implantitis-related bone defects involves the placement of bone-filler particles in the intrabony defects and the application of a barrier membrane. The efficacy of different GBR-supported reconstructive measures as well as their potential superiority compared to non-GBR-supported treatment strategies for bone defects at peri-implantitis sites, however, remains unclear. Therefore, this analysis was designed to evaluate the long-term (≥12 months) clinical efficacy of GBR-supported reconstructive surgical therapy for peri-implantitis-related bone defects. In terms of resolving inflammation, the implementation of GBR protocols applying xenogenic bone substitutes yielded a higher reduction of bleeding on probing and probing depth value compared to the GBR protocol applying autogenous bone. Furthermore, for the changes in bleeding on probing and probing depths, GBR approaches using xenogenic bone showed superiority over the non-GBR treatments. Xenogenic bone with or without a barrier membrane was associated with improved radiographic bone levels and less soft tissue recession compared to the use of a GBR protocol implementing autogenous bone. Nonetheless, when interpreting this findings, the limited number of available studies with low to serious risk of bias and the short follow-up periods limited to 12 months should be considered.

Hamster model for post-COVID-19 alveolar regeneration offers an opportunity to understand post-acute sequelae of SARS-CoV-2.

COVID-19 survivors often suffer from post-acute sequelae of SARS-CoV-2 infection (PASC). Current evidence suggests dysregulated alveolar regeneration as a possible explanation for respiratory PASC, which deserves further investigation in a suitable animal model. This study investigates morphological, phenotypical and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters. We demonstrate that CK8+ alveolar differentiation intermediate (ADI) cells occur following SARS-CoV-2-induced diffuse alveolar damage. A subset of ADI cells shows nuclear accumulation of TP53 at 6- and 14-days post infection (dpi), indicating a prolonged arrest in the ADI state. Transcriptome data show high module scores for pathways involved in cell senescence, epithelial-mesenchymal transition, and angiogenesis in cell clusters with high ADI gene expression. Moreover, we show that multipotent CK14+ airway basal cell progenitors migrate out of terminal bronchioles, aiding alveolar regeneration. At 14 dpi, ADI cells, peribronchiolar proliferates, M2-macrophages, and sub-pleural fibrosis are observed, indicating incomplete alveolar restoration. The results demonstrate that the hamster model reliably phenocopies indicators of a dysregulated alveolar regeneration of COVID-19 patients. The results provide important information on a translational COVID-19 model, which is crucial for its application in future research addressing pathomechanisms of PASC and in testing of prophylactic and therapeutic approaches for this syndrome.

Influence of antiresorptive/antiangiogenic therapy on the extension of experimentally induced peri-implantitis lesions.

OBJECTIVES: To investigate the extension of experimentally induced peri-implantitis lesions under various antiresorptive and antiangiogenic medications. MATERIAL AND METHODS: Fourty-eight albino rats had randomly received the following medications (dual application, n = 8 each): (1) amino-bisphosphonate (zoledronate) (Zo), (2) RANKL inhibitor (denosumab) (De), (3) antiangiogenic (bevacizumab) (Be), (4) Zo+Be, (5) De+Be, or (6) no medication (Co). Ligature- and lipopolysaccharide-induced peri-implantitis lesions were established at 2 maxillary implants over a period of 16 weeks. Histological (e.g., apical extension and surface area of the inflammatory cell infiltrate-aICT, ICT; defect length; defect width; CD68 positive cells) and bone micromorphometric (µCT) outcomes were assessed. The animal was defined as a statistical unit. RESULTS: A total of n = 38 animals (Zo = 6, De = 6, Be = 8, Zo + Be = 6, De + Be = 5, Co = 7) were analyzed. ICT's were commonly marked by a positive CD68 antigen reactivity. Comparable median aICT (lowest-Zo: 0.53 mm; highest-Be: 1.22 mm), ICT (lowest-De + Be: 0.00 mm2; highest-Co: 0.49 mm2), defect length (lowest-Zo: 0.90 mm; highest-Co: 1.93 mm) and defect width (lowest-De+Be: 1.27 mm; highest-Be: 1.80 mm) values were noted in all test and control groups. Within an inner (diameter: 0.8 mm) cylindric volume of interest, the bone microstructure did not significantly differ between groups. CONCLUSIONS: The present analysis did not reveal any marked effects of various antiresorptive/ antiangiogenic medications on the extension of experimentally induced peri-implantitis lesions. CLINICAL RELEVANCE: The extension of peri-implantitis lesions may not be facilitated by the antiresorptive and antiangiogenic medications investigated.

Effectiveness of modified and control protocols for the surgical therapy of combined peri-implantitis-related defects. A retrospective analysis.

OBJECTIVES: To compare the clinical effectiveness of control and two modified protocols for surgical therapy of combined peri-implantitis-related defects. MATERIALS AND METHODS: A total of n = 36 patients (n = 40 implants) diagnosed with combined supra- and intrabony defects were identified for this retrospective analysis. All protocols considered access flap surgery, granulation tissue removal and implant surface decontamination using a titanium brush. The control combined protocol included implantoplasty at supracrestal/ buccal- and reconstructive therapy at intrabony components using a particulate natural bone mineral + a native collagen membrane (CM) (n = 11 patients, n = 11 implants, CP). The modified protocols included the augmentation at both supra- and intrabony defect components using either a collagen-stabilized natural bone mineral (BOC) (n = 15 patients, n = 15 implants, MP1), or BOC mixed with autogenous bone chips + CM (n = 10 patients, n = 14 implants, MP2). Linear mixed effects analyses were used to assess the changes in clinical parameters (i.e., bleeding on probing - BOP, probing pocket depth - PD, and mucosal recession - MR) over time (i.e., 6 and 12 months) and the impact of the treatment groups (CP, MP1, MP2). RESULTS: At 12 months, median BOP and PD reductions amounted to -58.33% and - 1.16 mm in the MP1, to -62.50% and -1.95 mm in the MP2, and to -66.67% and -0.83 mm in the CP groups, respectively. The associated MR changes ranged between 0.00 and 0.08 mm. The survival rates were 100% in all groups. CONCLUSIONS: All treatment protocols were associated with short-term improvements in the clinical parameters investigated.

Mediterranean diet component oleic acid increases protective lipid mediators and improves trabecular bone in a Porphyromonas gingivalis inoculation model.

AIM: Therapeutic modulation of bacterial-induced inflammatory host response is being investigated in gingival inflammation and periodontal disease pathology. Therefore, dietary intake of the monounsaturated fatty acid (FA) oleic acid (OA (C18:1)), which is the main component of Mediterranean-style diets, and saturated FA palmitic acid (PA (C16:0)), which is a component of Western-style diets, was investigated for their modifying potential in an oral inoculation model of Porphyromonas gingivalis. MATERIALS AND METHODS: Normal-weight C57BL/6-mice received OA- or PA-enriched diets (PA-ED, OA-ED, PA/OA-ED) or normal standard diet for 16 weeks and were inoculated with P. gingivalis/placebo (n = 12/group). Gingival inflammation, alveolar bone structure, circulating lipid mediators, and in vitro cellular response were determined. RESULTS: FA treatment of P. gingivalis-lipopolysaccharide-incubated gingival fibroblasts (GFbs) modified inflammatory activation, which only PA exacerbated with concomitant TNF-α stimulation. Mice exhibited no signs of acute inflammation in gingiva or serum and no inoculation- or nutrition-associated changes of the crestal alveolar bone. However, following P. gingivalis inoculation, OA-ED improved oral trabecular bone micro-architecture and enhanced circulating pro-resolving mediators resolvin D4 (RvD4) and 4-hydroxydocosahexaenoic acid (4-HDHA), whereas PA-ED did not. In vitro experiments demonstrated significantly improved differentiation in RvD4- and 4-HDHA-treated primary osteoblast cultures and reduced the expression of osteoclastogenic factors in GF. Further, P. gingivalis infection of OA-ED animals led to a serum composition that suppressed osteoclastic differentiation in vitro. CONCLUSIONS: Our results underline the preventive impact of Mediterranean-style OA-EDs by indicating their pro-resolving nature beyond anti-inflammatory properties.

Characterization of a Stemness-Optimized Purification Method for Human Dental-Pulp Stem Cells: An Approach to Standardization.

Human dental pulp stem cells (hDPSCs) are promising for oral/craniofacial regeneration, but their purification and characterization is not yet standardized. hDPSCs from three donors were purified by magnetic activated cell sorting (MACS)-assisted STRO-1-positive cell enrichment (+), colony derivation (c), or a combination of both (c/+). Immunophenotype, clonogenicity, stemness marker expression, senescence, and proliferation were analyzed. Multilineage differentiation was assessed by qPCR, immunohistochemistry, and extracellular matrix mineralization. To confirm the credibility of the results, repeated measures analysis and post hoc p-value adjustment were applied. All hDPSC fractions expressed STRO-1 and were similar for several surface markers, while their clonogenicity and expression of CD10/44/105/146, and 166 varied with the purification method. (+) cells proliferated significantly faster than (c/+), while (c) showed the highest increase in metabolic activity. Colony formation was most efficient in (+) cells, which also exhibited the lowest cellular senescence. All hDPSCs produced mineralized extracellular matrix. Regarding osteogenic induction, (c/+) revealed a significant increase in mRNA expression of COL5A1 and COL6A1, while osteogenic marker genes were detected at varying levels. (c/+) were the only population missing BDNF gene transcription increase during neurogenic induction. All hDPSCs were able to differentiate into chondrocytes. In summary, the three hDPSCs populations showed differences in phenotype, stemness, proliferation, and differentiation capacity. The data suggest that STRO-1-positive cell enrichment is the optimal choice for hDPSCs purification to maintain hDPSCs stemness. Furthermore, an (immuno) phenotypic characterization is the minimum requirement for quality control in hDPSCs studies.

Two-piece zirconia implants in the posterior mandible and maxilla: A cohort study with a follow-up period of 9 years.

OBJECTIVES: Long-term follow-up observations of zirconia implants are rare. This study aimed at evaluating the clinical performance of two-piece zirconia implants in the posterior jaws over 9 years. MATERIALS AND METHODS: Sixty partially edentulous patients were treated with two-piece zirconia implants. In eight no primary stability could be achieved. Fifty-two patients received the final restoration (i.e., cemented fibreglass abutments and all-ceramic crowns). After 2 years, 2 implants failed and 4 dropouts were recorded. The remaining 46 patients with one target implant each were recalled at 9 years. Besides implant survival, clinical parameters at the implant level (plaque index-PI, bleeding on probing-BOP, probing depth-PD, mucosal recession-MR) were recorded and compared with previously collected data. Mechanical and technical complications were assessed. RESULTS: Thirty patients responded. The mean observation period was of 111.1 ± 2.2 months. One implant was lost. Data recorded from the remaining 29 implants were analysed. PI values increased overtime. Mean BOP and PD remained unchanged during follow-up. No additional cases of peri-implantitis were recorded over the 10 diagnosed during the first 2 years of follow-up. No significant changes in mean MR values were detected over time, with 65% of the all included implants exhibiting no recession at 9 years and all the others, but one, a maximum MR of 1 mm. Three technical and 6 mechanical complications occurred in 7 patients between 2- and 9-years (6.9% and 20.7%, respectively, at patient level). CONCLUSION: Within the limitations of the present study, a high survival rate was registered. Albeit frequent mechanical and technical complications, two-piece zirconia implants could represent a valid solution for the replacement of single teeth in the posterior jaws.

Effect of peri-implant mucosal thickness on esthetic outcomes and the efficacy of soft tissue augmentation procedures: Consensus report of group 2 of the SEPA/DGI/OF workshop.

OBJECTIVES: The aim of this study was to comprehensively assess the literature in terms of the effect of peri-implant mucosal thickness on esthetic outcomes and the efficacy of soft tissue augmentation procedures to increase the mucosal thickness with autogenous grafts or soft tissue substitutes. MATERIAL AND METHODS: Two systematic reviews (SR) were performed prior to the consensus meeting to assess the following questions. Review 1, focused question: In systemically healthy patients with an implant-supported fixed prosthesis, what is the influence of thin as compared to thick peri-implant mucosa on esthetic outcomes? Review 2, focused question 1: In systemically healthy humans with at least one dental implant (immediate or staged implant), what is the efficacy of connective tissue graft (CTG), as compared to absence of a soft tissue grafting procedure, in terms of gain in peri-implant soft tissue thickness (STT) reported by randomized controlled clinical trials (RCTs) or controlled clinical trials (CCTs)? Review 2, focused question 2: In systemically healthy humans with at least one dental implant (immediate or staged implant), what is the efficacy of CTG, as compared to soft tissue substitutes, in terms of gain in peri-implant STT reported by RCTs or CCTs? The outcomes of the two SRs, the consensus statements, the clinical implications, and the research recommendations were discussed and subsequently approved at the consensus meeting during the group and plenary sessions. CONCLUSIONS: There was a tendency of superior esthetic outcomes in the presence of a thick mucosa. The connective tissue graft remains the standard of care in terms of increasing mucosa thickness.

SARS-CoV-2 Infection Dysregulates Cilia and Basal Cell Homeostasis in the Respiratory Epithelium of Hamsters.

Similar to many other respiratory viruses, SARS-CoV-2 targets the ciliated cells of the respiratory epithelium and compromises mucociliary clearance, thereby facilitating spread to the lungs and paving the way for secondary infections. A detailed understanding of mechanism involved in ciliary loss and subsequent regeneration is crucial to assess the possible long-term consequences of COVID-19. The aim of this study was to characterize the sequence of histological and ultrastructural changes observed in the ciliated epithelium during and after SARS-CoV-2 infection in the golden Syrian hamster model. We show that acute infection induces a severe, transient loss of cilia, which is, at least in part, caused by cilia internalization. Internalized cilia colocalize with membrane invaginations, facilitating virus entry into the cell. Infection also results in a progressive decline in cells expressing the regulator of ciliogenesis FOXJ1, which persists beyond virus clearance and the termination of inflammatory changes. Ciliary loss triggers the mobilization of p73+ and CK14+ basal cells, which ceases after regeneration of the cilia. Although ciliation is restored after two weeks despite the lack of FOXJ1, an increased frequency of cilia with ultrastructural alterations indicative of secondary ciliary dyskinesia is observed. In summary, the work provides new insights into SARS-CoV-2 pathogenesis and expands our understanding of virally induced damage to defense mechanisms in the conducting airways.