Evaluation of primary stability of single implants placed in fresh extraction sockets: a clinical trial

ABSTRACTDental implants have been used for the last 20 years. With the latest modern developments, however, minimally invasive protocols and immediate implants are currently used. The aim of this study was to evaluate the primary stability of a new implant design. Thirty immediate implants were placed and they all achieved successful osseointegration. Primary stability was reached with all the implants after the first apical threads. Within the limitations of the present study, the immediate implant approach seems to be a predictable treatment option, especially in conjunction with a specifically designed implant system

A Narrative Review on Oral and Periodontal Bacteria Microbiota Photobiomodulation, through Visible and Near-Infrared Light: From the Origins to Modern Therapies

Photobiomodulation (PBM) consists of a photon energy transfer to the cell, employing non-ionizing light sources belonging to the visible and infrared spectrum. PBM acts on some intrinsic properties of molecules, energizing them through specific light wavelengths. During the evolution of life, semiconducting minerals were energized by sun radiation. The molecules that followed became photoacceptors and were expressed into the first proto-cells and prokaryote membranes. Afterward, the components of the mitochondria electron transport chain influenced the eukaryotic cell physiology. Therefore, although many organisms have not utilized light as an energy source, many of the molecules involved in their physiology have retained their primordial photoacceptive properties. Thus, in this review, we discuss how PBM can affect the oral microbiota through photo-energization and the non-thermal effect of light on photoacceptors (i.e., cytochromes, flavins, and iron-proteins). Sometimes, the interaction of photons with pigments of an endogenous nature is followed by thermal or photodynamic-like effects. However, the preliminary data do not allow determining reliable therapies but stress the need for further knowledge on light-bacteria interactions and microbiota management in the health and illness of patients through PBM

Effectiveness of dual-wavelength (Diodes 980 Nm and 635 Nm) laser approach as a non-surgical modality in the management of periodontally diseased root surface: a pilot study

Conventional periodontal therapies have been widely discussed in the literature. The results of these therapies, surgically and non-surgically, have demonstrated high predictability and stable maintenance over time. With some clinical indications, such as inflamed sites with consistent bleeding on probing (BOP), it can be challenging for the root planning procedure to achieve predictable outcomes. Therefore, the aim and objectives of the present study were to evaluate whether the dual-wavelength (980 and 635 nm) laser therapy at lower power settings can be beneficial as a combined non-invasive modality in the management of periodontally diseased root surface in terms of improving the periodontal parameters. Thirty-five healthy patients were enrolled in this study. All patients had at least one pocket in the anterior and posterior teeth with initial periodontal pocket depth (PPD) > 6 mm associated with evidence of clinical inflammation, i.e. bleeding on probing (BOP++ or BOP+++) with no gingival recession. The treatment protocol utilized combined therapy of conventional debridement immediately followed by application of dual-wavelength laser therapy (photo-ablation and photodynamic therapies) at lower power settings. The results showed that all the pockets of involved teeth had an average gain of 3 mm of the clinical attachment level with no sign of BOP and reduction in the mobility of the teeth 35 days post-operatively. Thus, the utilization of the dual-wavelength approach of laser-assisted therapy at lower power settings appears to provide a promising and predictable non-invasive clinical approach in the management of compromised periodontally involved teeth

Comparison of the Clinical Outcomes of Titanium and Zirconia Implant Abutments: A Systematic Review of Systematic Reviews

Background: Dental implants are widely used and in order to answer to esthetic demands, zirconia has been introduced as an abutment material as an alternative to titanium. Several studies have been published on this topic, but the results have been often inconsistent. The objective of the present study is to systematically analyze the existing literature comparing clinical outcomes of titanium and zirconia implant abutments. The study was designed as a systematic review of systematic reviews. Methods: This systematic review is in accordance with the Transparent Reporting of Systematic Reviews and Meta-analyses. A MEDLINE/PubMed, Cochrane Database of Systematic Reviews and SCOPUS literature search was performed up to and including June 2021. Data were extracted independently by two reviewers and tAMSTAR2 was used to assess the quality of the systematic reviews. Results: The electronic search identified 1146 papers, and 175 duplicates were removed. After manual screening, 954 studies were excluded and the final analysis was conducted on 11 papers. Both mechanical and esthetic outcomes and biological complications were analyzed. Conclusions: It can be concluded that titanium abutments have a better mechanical resistance than zirconia ones. Plaque accumulation is reported to be slightly higher on titanium but without any significant inflammatory process. The esthetic outcomes seem to be more related to the thickness (>3 mm) of the soft tissues than to the abutment material

535. Increasing Accuracy and Precision of Vector Integration Site Identification of Sequencing Reads With a New Bioinformatics Framework

In hematopoietic stem cell (HSC) gene therapy (GT) applications patients are transplanted with autologuos HSCs that have been ex-vivo genetically modified with integration competent vectors to express a therapeutic transgene. Specific PCR techniques coupled to next generation sequencing and bioinformatics analysis allow the high throughput retrieval, sequencing and mapping of proviral/genomic DNA junctions present in the blood and bone marrow derived cell populations sampled at different time points after therapy. The increase in sequences available for IS mapping is accompanied by an increase in false positives derived by sequencing errors or sequencing read parsing and mapping on the reference genome. In particular, by analyzing IS datasets form vector marked human and mouse tumor cells, clones with defined integration sites and GT patients, we observed that when multiple sequences arising from the same IS are aligned on the reference genome >10% mapped near (+/- 4 bases) the true insertion site. Without correction, these misaligned sequences not only result in an overestimation of the overall number of IS but in some cases also in the generation of false common insertion sites, worrisome hallmarks of insertional mutagenesis. To mitigate this issue we and others, based on empirical observations, merge sequencing reads mapping within +/- 3 bp into a single IS. Although this adjustment reduces the impact of the "wobbling" around the true ISs, a dedicated method and model is still missing.To further increase the accuracy of genomic positioning of sequencing reads we developed a new bioinformatics framework as post-processing plugin for pipelines that correctly partitions sequencing reads in a given genomic position by considering the relative abundance and distribution of each sequence cluster using local modes and Gaussian scores through an adaptive approach that varies the parameters of the Gaussian curve and proposes different solutions. To chose the best solution, the algorithm first evaluates each solution by exploiting 100 simulations of the input reads and then selects the resulting best solution using the Kolmogorov-Smirnov test. The simulation step is designed to test the mappability of the IS genomic interval and to quantify the impact of the observed nucleotide variations of the reads with respect to the reference genome (PCR artifacts or real genomic differences) that may lead to different mapping results that justify a larger span of the mapped reads surrounding the putative IS. The algorithm returns the list of IS and relative number of reads with the p-value of the best solution.We performed 3 ad-hoc in vitro experiments on a cell clone with 6 known IS in which we measured the precision of IS placement obtaining an average of 100% with our new method whereas <30% using our previous method based on a rigid sliding window approach of 4 bp. We applied our new approach to our clinical trial datasets obtaining improvements in IS genomic placement and overestimation with a reduction of potential false IS of 3% without changing the biological results

537. New Graph-Based Algorithm for Comprehensive Identification and Tracking Retroviral Integration Sites

Vector integration sites (IS) in hematopoietic stem cell (HSC) gene therapy (GT) applications are stable genetic marks, distinctive for each independent cell clone and its progeny. The characterization of IS allows to identify each cell clone and individually track its fate in different tissues or cell lineages and during time, and is required for assessing the safety and efficacy of the treatment. Bioinformatics pipelines for IS detection used in GT identify the sequence reads mapping in the same genomic position of the reference genome as a single IS but discard those ambiguously mapped in multiple genomic regions. The loss of such significant portion of patients' IS may hide potential malignant events thus reducing the reliability of IS studies. We developed a novel tool that is able to accurately identify IS in any genomic region even if composed by repetitive genomic sequences. Our approach exploits an initial genome free analysis of sequencing reads by creating an undirected graph in which nodes are the input sequences and edges represent valid alignments (over a specific identity threshold) between pairs of nodes. Through the analysis and decomposition of the graph, the method identifies indivisible subgraphs of sequences (clusters), each of them corresponding to an IS. Once extracted the consensus sequence of the clusters and aligned on the reference genome, we collect the alignment results and the annotation labels from RepeatMasker. By combining the set of genomic coordinates and the annotation labels, the method retraces the initial sequence graph, statistically validates the clusters through permutation test and produces the final list of IS. We tested the reliability of our tool on 3 IS datasets generated from simulated sequencing reads with incremental rate of nucleotide variations (0%, 0.25% and 0.5%) and real data from a cell line with known IS and we compared out tool to VISPA and UClust, used for GT studies. In the simulated datasets our tool demonstrated precision and recall ranging 0.85-0.97 and 0.88-0.99 respectively, producing the aggregate F-score ranging 0.86-0.98 which resulted higher than VISPA and UClust. In the experimental case of sequences from LAM-PCR products, our tool and VISPA were able to identify all the 6 known ISs for >98% of the reads produced, while UClust identified only 5 out 6 ISs. We then used our tool to reanalyze the sequencing reads of our GT clinical trial for Metachromatic Leukodystrophy (MLD) completing the hidden portion of IS. The overall number of ISs, sequencing reads and estimated actively re-populating HSCs was increased by an average fold ~1.5 with respect the previously published data obtained through VISPA whereas the diversity index of the population did not change and no aberrant clones in repeats occurred. Our tool addresses and solves important open issues in retroviral IS identification and clonal tracking, allowing the generation of a comprehensive repertoire of IS

Photobiomodulation by Near-Infrared 980-nm Wavelengths Regulates Pre-Osteoblast Proliferation and Viability through the PI3K/Akt/Bcl-2 Pathway

Background: bone tissue regeneration remains a current challenge. A growing body of evidence shows that mitochondrial dysfunction impairs osteogenesis and that this organelle may be the target for new therapeutic options. Current literature illustrates that red and near-infrared light can affect the key cellular pathways of all life forms through interactions with photoacceptors within the cells' mitochondria. The current study aims to provide an understanding of the mechanisms by which photobiomodulation (PBM) by 900-nm wavelengths can induce in vitro molecular changes in pre-osteoblasts. Methods: The PubMed, Scopus, Cochrane, and Scholar databases were used. The manuscripts included in the narrative review were selected according to inclusion and exclusion criteria. The new experimental set-up was based on irradiation with a 980-nm laser and a hand-piece with a standard Gaussian and flat-top beam profile. MC3T3-E1 pre-osteoblasts were irradiated at 0.75, 0.45, and 0.20 W in continuous-wave emission mode for 60 s (spot-size 1 cm2) and allowed to generate a power density of 0.75, 0.45, and 0.20 W/cm2 and a fluence of 45, 27, and 12 J/cm2, respectively. The frequency of irradiation was once, three times (alternate days), or five times (every day) per week for two consecutive weeks. Differentiation, proliferation, and cell viability and their markers were investigated by immunoblotting, immunolabelling, fluorescein-FragELTM-DNA, Hoechst staining, and metabolic activity assays. Results and conclusions: The 980-nm wavelength can photobiomodulate the pre-osteoblasts, regulating their metabolic schedule. The cellular signal activated by 45 J/cm2, 0.75 W and 0.75 W/cm2 consist of the PI3K/Akt/Bcl-2 pathway; differentiation markers were not affected, nor do other parameters seem to stimulate the cells. Our previous and present data consistently support the window effect of 980 nm, which has also been described in extracted mitochondria, through activation of signalling PI3K/Akt/Bcl-2 and cyclin family, while the Wnt and Smads 2/3-β-catenin pathway was induced by 55 J/cm2, 0.9 W and 0.9 W/cm

Immediate versus delayed loading: comparison of primary stability loss after miniscrew placement in orthodontic patients-a single-centre blinded randomized clinical trial

Introduction: The aim of this randomized clinical trial was to compare torque recordings at insertion time and 1 week post-placement between immediately loaded orthodontic miniscrews and an unloaded control group. Trial design: This RCT was designed as parallel with an allocation ratio of 1:1. Methods: Eligibility criteria to enroll patients were: needs of fixed orthodontic treatment, no systemic disease, absence of using drugs altering bone metabolism. All patients were consecutively treated in a private practice and the miniscrews were placed by the same author. Patients received ORTHOImplant (3M Unitek) miniscrews and they were blindly divided in two groups: group 1 screws were unloaded between T0 and T1, group 2 received immediately loaded screws with NiTi coil. For each patient, maximum insertion torque (MIT) was evaluated at T0. After 1 week, without loading, the screw torque was measured again (T1) and at the end of the treatment maximal removal torque was evaluated (T2). Torque variation in the first week was considered as the primary outcome. Randomization: A randomization list was created for the group assignment, with an allocation ratio of 1:1. Blinding: The study was single blinded in regard of the statistical analysis. Results: Patients enrolled in the clinical trial were 51 for a total of 81 miniscrews. The recruitment started in November 2012 and the observation period ended in August 2014. Twenty-six and twenty-five patients were analysed in group 1 and 2, respectively. The MIT mean in each placement time was 18.25 Ncm (SD = 3.00), 11.41 Ncm (SD = 3.51) and 10.52 Ncm (SD = 5.14) at T0, T1, and T2 time, respectively. In group 1, the torque decrease between T1 and T0 was statistically higher compared to group 2 (P value = 0.003). Statistically significant effects of the placement times on MIT were found (P value &lt;0.0001). No serious harm was observed. Limitations: This study was performed using only direct force on the miniscrew and not using the miniscrew as an indirect anchorage. It was not possible to obtain quantitative data on bone quality or root proximity to miniscrews. Conclusions: A significant stability loss was observed in the first week in both groups; Group 1 showed a statistically higher torque loss in the first week when compared to the immediately loaded group. There were statistically significant effects of the measurement times on MIT and of the miniscrew location on MIT. The overall failure rate was 7.4%. Trial registration: This trial was not registered. Protocol: The protocol was not published before trial commencement

Torque loss after miniscrew placement: An in-vitro study followed by a clinical trial

7noTo evaluate torque loss a week after insertion, both in an in vivo and an in vitro experimental setup were designed. In the in vivo setup a total of 29 miniscrews were placed in 20 patients who underwent orthodontic treatment. Maximum insertion torque (MIT) was evaluated at insertion time (T1). A week later, insertion torque was measured again by applying a quarter turn (T2); no load was applied on the screw during the first week. In the in vitro setup a total of 20 miniscrews were placed in pig rib bone samples. MIT was evaluated at insertion time (T1). Bone samples were kept in saline solution and controlled environment for a week during which the solution was refreshed every day. Afterwards, torque was measured again by applying a quarter turn (T2). The comparison of MIT over time was done calculating the percentage difference of the torque values between pre- and post-treatment and using the parametric two independent samples t-test or the non-parametric Mann–Whitney test. After a week unloaded miniscrews showed a mean loss of rotational torque of 36.3% and 40.9% in in vitro and in in vivo conditions, respectively. No statistical differences were found between the two different setups. Torque loss was observed after the first week in both study models; in vitro experimental setup provided a reliable study model for studying torque variation during the first week after insertion.openopenMigliorati, Marco; Drago, Sara; Barberis, Fabrizio; Schiavetti, Irene; Dalessandri, Domenico; Benedicenti, Stefano; Biavati, Armando SilvestriniMigliorati, Marco; Drago, Sara; Barberis, Fabrizio; Schiavetti, Irene; Dalessandri, Domenico; Benedicenti, Stefano; Biavati, Armando Silvestrin