Plasmon resonance biosensor for interleukin-1ß point-of-care determination: A tool for early periodontitis diagnosis.

Among pro-inflammatory cytokines, Interleukin-1ß is crucially involved in several inflammatory-based diseases and even cancer. Increased Interleukin-1ß levels in oral fluids have been proposed as an early marker of periodontitis, a broadly diffused chronic inflammatory condition of periodontal-supporting tissues, leading eventually to tooth loss. We describe the development of a portable surface-plasmon-resonance-based optical fiber probe suitably coated with an anti-Interleukin-1ß antibody monolayer. A pico-nanomolar linear range of determination was obtained in both buffer solution and saliva with a rapid (3 min) incubation and high selectivity in presence of interferents. Higher Interleukin-1ß concentration in the saliva of a periodontitis patient compared to a healthy control was determined. These measurements were validated by an automated ELISA system. Our results sustain the potential applicability of the proposed SPR-POF as diagnostic point-of-care device for real-time monitoring of salivary Interleukin-1ß, that can support early detection of oral inflammatory-based pathologies and rapid and timely therapeutic decisions.

A novel plasmonic optical-fiber-based point-of-care test for periodontal MIP-1α detection.

The analysis of salivary biomarkers as expression of periodontal health conditions has been proposed as a useful aid to conventional diagnostic approaches. In this study, we present a point-of-care test (POCT) exploiting a surface plasmon resonance (SPR)-based optical biosensor to detect salivary macrophage inflammatory protein (MIP)-1α, a promising marker of periodontitis. A plastic optical fiber (POF) was suitably modified and functionalized by an antibody self-assembled monolayer against MIP-1α for plasmonic detection. The proposed SPR-POF biosensor showed high selectivity and very low limit of detection for MIP-1α of 129 fM (1.0 pg/mL) in phosphate-buffered saline and 346 fM (2.7 pg/mL) in saliva. As a proof of concept, this POCT was also able to discriminate between a periodontitis patient and a healthy subject. The obtained results support the future application of this technology for an on-site detection and real-time monitoring of periodontal health conditions for diagnostic and therapeutic purposes.

An optical fiber-based point-of-care test for periodontal MMP-8 detection: A proof of concept.

OBJECTIVES: The evaluation of salivary biomarkers has been proposed as a simple and non-invasive aid to the conventional periodontal diagnosis based on clinical-radiographic parameters. Matrix metalloproteinase-8 (MMP-8), especially in its active form, is considered one of the most reliable biomarkers of periodontitis, and point-of-care tests (POCTs) have been proposed for its clinical monitoring. In this proof-of-concept study, a novel highly sensitive POCT based on a plastic optical fiber (POF) biosensor exploiting surface plasmon resonance (SPR) to detect salivary MMP-8 is described. METHODS: A SPR-POF biosensor was functionalized with a specific antibody to develop a surface-assembled monolayer (SAM) for the detection of total MMP-8. A white light source and a spectrometer connected to the biosensor were used to quantify MMP-8 level in both buffer and real matrix (saliva) by analysing the shift of the resonance wavelength determined by the specific antigen-antibody binding upon the SAM. RESULTS: Dose-response curves by serial dilutions of human recombinant MMP-8 were realized, obtaining a limit of detection (LOD) of 40 pM (1.76 ng/ml) in buffer and 225 pM (9.9 ng/ml) in saliva and high selectivity compared to interferent analytes (MMP-2 and IL-6). CONCLUSIONS: The proposed optical fiber-based POCT was able to detect and measure total MMP-8 with high selectivity and very low LOD in both buffer and saliva. CLINICAL SIGNIFICANCE: The SPR-POF technology may be employed to create highly sensitive biosensors to monitor salivary MMP-8 levels. The possibility of specifically detecting its active, rather than total, form need to be further investigated. If confirmed and clinically validated, such a device may represent a promising tool to make an immediate, highly sensitive and reliable diagnosis of periodontitis, and to carry out a timely and targeted therapy, possibly helping to prevent the onset of local and systemic periodontitis-related complications.

Plasmonic optical fiber biosensor development for point-of-care detection of malondialdehyde as a biomarker of oxidative stress.

Numerous pieces of evidence demonstrate that oxidative stress impairs biological functions, speeds up aging, and has a role in a variety of human diseases, including systemic and oral inflammatory disorders, and even cancer. Therefore, technologies providing accurate measures of oxidative stress indicators or biomarkers appear essential in the identification/prevention of such diseases, and in their management. Particularly advantageous is the employement of point-of-care tests based on affordable and small biochips since they can quickly process biological samples and deliver results near the point of care for a prompt therapeutic intervention. Malondialdehyde (MDA) is a key byproduct of oxidative reaction and has been identified as an effective marker of oxidative stress. Herein, we describe the detection of MDA in buffer and in a complex matrix such as saliva, using a plasmonic optical fiber device combined with a highly selective anti-MDA antibody. The experimental results highlight the excellent performance of the proposed biosensor, as well as its ability to provide a low-cost point-of-care test (PoC-T) to be used in real life situations. We demonstrated that a single saliva dilution step and a short incubation time are required for the accurate detection of low concentrations of total MDA (free and conjugated). As a proof-of-concept of future biomedical applications, the method has been tested to determine MDA concentration in saliva of a periodontitis patient compared to that of a healthy control. The obtained findings represent the basis for developing PoC-Ts to be employed in monitoring oral diseases like periodontitis, oral cancers or systemic oxidative-stress associated pathologies. Conclusively, our study puts the ground for an oxidative stress biosensor widely-applicable to different scenarios.

Clinical and microbiological efficacy of indocyanine green-based antimicrobial photodynamic therapy as an adjunct to non-surgical treatment of periodontitis: a randomized controlled clinical trial.

OBJECTIVES: The aim of the present randomized clinical trial (RCT) with a parallel arm design was to evaluate the clinical and microbiological efficacy of repeated ICG-aPDT as an adjunct to full-mouth subgingival debridement in the treatment of periodontitis. MATERIALS AND METHODS: Twenty-four periodontitis patients were treated with full-mouth ultrasonic subgingival debridement (FMUD). Initial sites with probing depth (PD) > 4 mm were randomly assigned to receive the test (ICG-aPDT with an 810 nm diode laser) or the control treatment (off-mode aPDT) one and four weeks after FMUD. Clinical parameters were registered after 3 and 6 months. The presence of the main periodontal pathogens in subgingival samples was assessed with real-time PCR. RESULTS: Both treatment modalities resulted in significant clinical improvements at 3 and 6 months. The only significant differences in favour of the test group were found at 6 months for a higher PD reduction in initial deep pockets (PD ≥ 6 mm) and a higher percentage of closed pockets (PD ≤ 4 mm/no bleeding on probing). Limited microbiological changes were observed in both groups after treatment with no inter-group difference, except for a more significant reduction in Aggregatibacter actinomycetemcomitans and Parvimonas micra levels in the test group at 3 months. CONCLUSION: The combination of repeated ICG-aPDT and FMUD provided no benefits except for selective clinical and microbiological improvements compared to FMUD alone. CLINICAL RELEVANCE: Based on the obtained results, only limited adjunctive effects could be found for the combined use of ICG-aPDT and FMUD. Further, well-designed RCT with larger sample sizes are required to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04671394.

Towards a point-of-care test to cover atto-femto and pico-nano molar concentration ranges in interleukin 6 detection exploiting PMMA-based plasmonic biosensor chips.

Point-of-Care tests based on biomarkers, useful to monitor acute and chronic inflammations, are required for advances in medicine. In this scope, a key role is played by pro-inflammatory cytokines, of which interleukin 6 (IL-6) is generally thought as one of the most relevant. To use IL-6 in real scenarios, detection in ultra-low concentration ranges is required. In this work, two IL-6 biosensors are obtained by exploiting the combination of the same antibody self-assembled monolayer with two different plasmonic probes. This approach has demonstrated, via experimental results, that two different IL-6 concentration ranges can be explored. More specifically, IL-6 in an atto-femto molar range can be detected via polymer-based nanoplasmonic chips. On the other hand, a pico-nano molar range is obtained by a surface plasmon resonance platform in plastic optical fibers. As a proof of concept, the detection of IL-6 at the femto molar range has been obtained in Saliva and Serum. The results show that the proposed sensing approach could be useful in developing Point-of-Care devices based on a general setup with the capability to exploit both the plasmonic biosensor chips to monitor the IL-6 in the concentration range of interest, to provide an important support for the diagnosis and monitoring of oral and systemic diseases.

6 mm short versus 11 mm long inter-foraminal implants in the full-arch rehabilitation of edentulous non-atrophic mandibles: 5-year results from a multicenter randomized controlled trial.

OBJECTIVE: The aim of this multicenter parallel-group randomized controlled trial is to compare, in the same clinical scenario, 6 mm short with 11 mm long implants for the rehabilitation of completely edentulous non-atrophic mandibles. MATERIALS AND METHODS: Thirty patients in three study centers received a fixed full-arch mandibular rehabilitation supported by five inter-foraminal implants, with no need for bone augmentation procedures. Patients were randomly allocated (1:1 ratio), at the time of surgery, to test (6 mm implants) or control group (11 mm implants). After 3 months, a screw-retained full-arch prosthesis was positioned (baseline). Peri-implant marginal bone level change (MBLc, primary outcome) together with implant and prosthesis survival rate, and biological/technical complications (secondary outcomes) were evaluated up to 5 years. RESULTS: Twenty seven patients were controlled at 5 years (3 drop-outs). No implant or prosthesis loss occurred. No significant intergroup difference for biological/technical complications (p > .05, Fisher's exact test) and no significant intragroup and intergroup difference in the MBLc values were registered (test -0.03 ± 0.17 mm and control -0.13 ± 0.32 mm at 5-years; p > .025, one-sided Mann-Whitney U-test). CONCLUSIONS: When used in comparable anatomic, surgical, and prosthetic conditions, no difference in the clinical and radiographic outcomes between 6-mm and 11-mm implants was observed at 5 years of follow-up. Short implants showed to be a reliable option for the rehabilitation of completely edentulous non-atrophic mandibles. There is growing clinical evidence supporting the use of short implants, even in the case of non-atrophic sites.

Short versus Longer Implants in Sites without the Need for Bone Augmentation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: The present systematic review and meta-analysis aims to analyse the clinical performance of short compared to longer implants inserted in sites without the need for bone augmentation. METHODS: The protocol of the present PRISMA-driven meta-analysis was registered on PROSPERO (CRD42021264781). Electronic and manual searches were performed up to January 2022. All Randomized Controlled Trials (RCTs) comparing short (≤6 mm) to longer (≥8.5 mm) implants placed in non-atrophic and non-augmented sites were included. The quality of the included studies was assessed using the Cochrane risk of bias tool for randomized clinical trials (RoB 2) and the quality of evidence was determined with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. A meta-analysis was performed on implant survival rate, marginal bone level change (MBLc), and technical and biological complications at the available follow-up time points. The power of the meta-analytic findings was determined by trial sequential analysis (TSA). RESULTS: From 1485 initial records, 13 articles were finally included. No significant difference was found in the survival rate between short and long implant at any follow-up (moderate quality of evidence). Significantly more bone loss for long implants at 1 and 5 years from implant placement and more technical complications with short implants at 10 years were found. No other significant inter-group differences in terms of MBLc and biological complications were detected. CONCLUSIONS: Moderate evidence exists suggesting that short implants perform as well as longer ones in the rehabilitation of edentulous sites without the need for bone augmentation. Further long-term, well-designed RCTs, however, are still needed to provide specific evidence-based clinical recommendations for an extended use of short implants in non-atrophic sites.

FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo.

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.

Influence of abutment material and modifications on peri-implant soft-tissue attachment: A systematic review and meta-analysis of histological animal studies.

STATEMENT OF PROBLEM: How the properties of the implant-abutment unit may affect the peri-implant soft-tissue seal, whose stability is considered key to safeguarding the implant from bacterial contamination and preserve peri-implant health conditions, is unclear. PURPOSE: The purpose of this systematic review and meta-analysis of animal studies was to investigate whether material and surface properties of transmucosal implant components can influence the peri-implant soft-tissue adhesion at a histological level. MATERIAL AND METHODS: An electronic and hand search was conducted until August 2019. Histological animal studies comparing soft-tissue response to abutment or transmucosal collar with different materials and/or surface characteristics were selected by 2 independent reviewers. Risk of bias in individual studies was evaluated. Histomorphometric data on the dimension of the peri-implant attachment were recorded, and a quantitative synthesis by a meta-analysis was performed. Risk of bias in individual studies was evaluated in accordance with the Systematic Review Centre for Laboratory Animal Experimentation Risk of Bias tool. RESULTS: Eighteen relevant studies out of 1187 were identified, none with a low risk of bias for all domains. Data from only 4 studies could be meta-analyzed. Comparable results in terms of peri-implant attachment dimensions between test and control groups were found, except for a significantly higher apical junctional epithelium to coronal bone to implant (ajE-CBI) distance for chemically modified acid-etched compared with titanium machined surfaces. Non-meta-analyzable and/or qualitative results highlighted some improved properties also for microgrooved and oxidized surfaces. CONCLUSIONS: Limited data from animal studies suggest that some characteristics of the transmucosal implant components may affect peri-implant soft-tissue adhesion and stabilization but do not allow definitive conclusions. Future research should improve study design to increase the availability of comparable and suitable data on this topic.

FOXE1 Gene Dosage Affects Thyroid Cancer Histology and Differentiation In Vivo.

The transcription factor Forkhead box E1 (FOXE1) is a key player in thyroid development and function and has been identified by genome-wide association studies as a susceptibility gene for papillary thyroid cancer. Several cancer-associated polymorphisms fall into gene regulatory regions and are likely to affect FOXE1 expression levels. However, the possibility that changes in FOXE1 expression modulate thyroid cancer development has not been investigated. Here, we describe the effects of FOXE1 gene dosage reduction on cancer phenotype in vivo. Mice heterozygous for FOXE1 null allele (FOXE1+/-) were crossed with a BRAFV600E-inducible cancer model to develop thyroid cancer in either a FOXE1+/+ or FOXE1+/- genetic background. In FOXE1+/+ mice, cancer histological features are quite similar to that of human high-grade papillary thyroid carcinomas, while cancers developed with reduced FOXE1 gene dosage maintain morphological features resembling less malignant thyroid cancers, showing reduced proliferation index and increased apoptosis as well. Such cancers, however, appear severely undifferentiated, indicating that FOXE1 levels affect thyroid differentiation during neoplastic transformation. These results show that FOXE1 dosage exerts pleiotropic effects on thyroid cancer phenotype by affecting histology and regulating key markers of tumor differentiation and progression, thus suggesting the possibility that FOXE1 could behave as lineage-specific oncogene in follicular cell-derived thyroid cancer.

Periodontitis, Low-Grade Inflammation and Systemic Health: A Scoping Review.

Background and objectives: Periodontitis is a multifactorial chronic inflammatory infectious disease in which an infection is necessary, but not sufficient, for development of the condition. Individual susceptibility strictly linked to the immune and inflammatory response of the organism must also be present. Low-grade inflammation (LGI) is a systemic status of chronic sub-clinical production of inflammatory factors. This condition represents a risk factor for many chronic diseases including diabetes, cardiovascular disease, cerebrovascular disease, neurodegenerative disease and cancer. This scoping review aims to clarify, summarize and disseminate current knowledge on the possible link between periodontitis, LGI and systemic health. Materials and Methods: PRISMA Extension for Scoping Reviews guidelines were followed. An ad-hoc created keyword string was used to search the electronic databases of PubMed/Medline, Embase, The Cochrane Library and ClinicalTrials.gov. A hand search of specialized journals and their reference lists was also performed. Results: 14 studies that respected eligibility criteria were selected and analyzed. There is emerging evidence of strong links between periodontitis, LGI and systemic health. On the one hand, periodontitis influences the systemic status of LGI and on the other hand, the systemic production of inflammatory factors affects periodontitis with a bidirectional connection. Conclusions: LGI and the subsequent onset of a systemic inflammatory phenotype can be considered the common substrate of many chronic inflammatory diseases including periodontitis, with multiple mutual connections between them. Understanding of the biological principles and mechanisms underlying such a complex interrelationship could lead to significant improvements in the field of personalized diagnostics and therapeutic protocols.

Do Dietary Supplements and Nutraceuticals Have Effects on Dental Implant Osseointegration? A Scoping Review.

Several factors affect dental implant osseointegration, including surgical issues, bone quality and quantity, and host-related factors, such as patients' nutritional status. Many micronutrients might play a key role in dental implant osseointegration by influencing some alveolar bone parameters, such as healing of the alveolus after tooth extraction. This scoping review aims to summarize the role of dietary supplements in optimizing osseointegration after implant insertion surgery. A technical expert panel (TEP) of 11 medical specialists with expertise in oral surgery, bone metabolism, nutrition, and orthopedic surgery performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP identified micronutrients from the "European Union (EU) Register of nutrition and health claims made on foods" that have a relationship with bone and tooth health, and planned a PubMed search, selecting micronutrients previously identified as MeSH (Medical Subject Headings) terms and adding to each of them the words "dental implants" and "osseointegration". The TEP identified 19 studies concerning vitamin D, magnesium, resveratrol, vitamin C, a mixture of calcium, magnesium, zinc, and vitamin D, and synthetic bone mineral. However, several micronutrients are non-authorized by the "EU Register on nutrition and health claims" for improving bone and/or tooth health. Our scoping review suggests a limited role of nutraceuticals in promoting osseointegration of dental implants, although, in some cases, such as for vitamin D deficiency, there is a clear link among their deficit, reduced osseointegration, and early implant failure, thus requiring an adequate supplementation.

6-mm-short and 11-mm-long implants compared in the full-arch rehabilitation of the edentulous mandible: A 3-year multicenter randomized controlled trial.

OBJECTIVE: The aim of this multicenter parallel-group randomized controlled trial is to compare 6-mm-short with 11-mm-long implants in the rehabilitation of totally edentulous mandible in a completely comparable clinical situation, from anatomical, surgical, and prosthetic point of view. MATERIAL AND METHODS: Thirty patients were selected in three study centers to receive a fixed full-arch mandibular rehabilitation supported by five inter-foraminal implants. Patients were randomly allocated, at the time of surgery, half to the test group (6-mm-long implants) and half to the control group (11-mm-long implants). No bone augmentation procedure was performed. After 3 months, a screw-retained full-arch prosthesis with distal cantilevers was positioned (baseline). Peri-implant marginal bone level change (MBLc), implant and prosthesis survival rate, and biological/technical complications were evaluated after 1 and 3 years. RESULTS: Thirty subjects (150 implants) were evaluated after 1 year and 28 (140 implants) after 3 years. No implant or prosthesis loss occurred. No significant inter-group difference for biological/technical complications was registered. No statistically significant (p > .025) intra-group or inter-group difference in the mean MBLc values was registered. The mean MBLc was 0.01 ± 0.19 mm and -0.04 ± 0.21 mm at 1 year, and -0.10 ± 0.24 mm and 0.02 ± 0.25 mm at 3 years (test and control groups, respectively). CONCLUSIONS: 6-mm-short implants may be a reliable option when used in the rehabilitation of total edentulous mandibles. These results need to be confirmed by longer follow-up data from well-designed randomized controlled clinical trials.

Double knock-out of Hmga1 and Hipk2 genes causes perinatal death associated to respiratory distress and thyroid abnormalities in mice.

The serine-threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) modulates important cellular functions during development, acting as a signal integrator of a wide variety of stress signals, and as a regulator of transcription factors and cofactors. We have previously demonstrated that HIPK2 binds and phosphorylates High-Mobility Group A1 (HMGA1), an architectural chromatinic protein ubiquitously expressed in embryonic tissues, decreasing its binding affinity to DNA. To better define the functional role of HIPK2 and HMGA1 interaction in vivo, we generated mice in which both genes are disrupted. About 50% of these Hmga1/Hipk2 double knock-out (DKO) mice die within 12 h of life (P1) for respiratory failure. The DKO mice present an altered lung morphology, likely owing to a drastic reduction in the expression of surfactant proteins, that are required for lung development. Consistently, we report that both HMGA1 and HIPK2 proteins positively regulate the transcriptional activity of the genes encoding the surfactant proteins. Moreover, these mice display an altered expression of thyroid differentiation markers, reasonably because of a drastic reduction in the expression of the thyroid-specific transcription factors PAX8 and FOXE1, which we demonstrate here to be positively regulated by HMGA1 and HIPK2. Therefore, these data indicate a critical role of HIPK2/HMGA1 cooperation in lung and thyroid development and function, suggesting the potential involvement of their impairment in the pathogenesis of human lung and thyroid diseases.

Enamel Matrix Derivative and Autogenous Bone Graft for Periodontal Regeneration of Intrabony Defects in Humans: A Systematic Review and Meta-Analysis.

The combination of enamel matrix derivative (EMD) with an autogenous bone graft in periodontal regeneration has been proposed to improve clinical outcomes, especially in case of deep non-contained periodontal defects, with variable results. The aim of the present systematic review and meta-analysis was to assess the efficacy of EMD in combination with autogenous bone graft compared with the use of EMD alone for the regeneration of periodontal intrabony defects. A literature search in PubMed and in the Cochrane Central Register of Controlled Trials was carried out on February 2019 using an ad-hoc search string created by two independent and calibrated reviewers. All randomized controlled trials (RCTs) comparing a combination of EMD and autogenous bone graft with EMD alone for the treatment of periodontal intrabony defects were included. Studies involving other graft materials were excluded. The requested follow-up was at least 6 months. There was no restriction on age or number of patients. Standard difference in means between test and control groups as well as relative forest plots were calculated for clinical attachment level gain (CALgain), probing depth reduction (PDred), and gingival recession increase (RECinc). Three RCTs reporting on 79 patients and 98 intrabony defects were selected for the analysis. Statistical heterogeneity was detected as significantly high in the analysis of PDred and RECinc (I2 = 85.28%, p = 0.001; I2 = 73.95%, p = 0.022, respectively), but not in the analysis of CALgain (I2 = 59.30%, p = 0.086). Standard difference in means (SDM) for CALgain between test and control groups amounted to -0.34 mm (95% CI -0.77 to 0.09; p = 0.12). SDM for PDred amounted to -0.43 mm (95% CI -0.86 to 0.01; p = 0.06). SDM for RECinc amounted to 0.12 mm (95% CI -0.30 to 0.55. p = 0.57). Within their limits, the obtained results indicate that the combination of enamel matrix derivative and autogenous bone graft may result in non-significant additional clinical improvements in terms of CALgain, PDred, and RECinc compared with those obtained with EMD alone. Several factors, including the surgical protocol used (e.g. supracrestal soft tissue preservation techniques) could have masked the potential additional benefit of the combined approach. Further well-designed randomized controlled trials, with well-defined selection criteria and operative protocols, are needed to draw more definite conclusions.

The Role of Autologous Platelet Concentrates in Alveolar Socket Preservation: A Systematic Review.

Prevention of alveolar bone resorption after tooth extraction may be useful for implant rehabilitation of the edentulous site minimizing the future need for bone augmentation procedures. A number of studies have investigated the efficacy of autologous platelet concentrates for the preservation of the alveolar bone volume after tooth extraction. Although encouraging results have been published, the available data are still controversial. The aim of the present systematic review was to assess the effect of platelet concentrates on alveolar socket preservation after tooth extraction. A literature search was carried out up to September 2017 for prospective controlled trials in which a test group using exclusively a platelet concentrate was compared with a control group in which extraction sockets were left to heal spontaneously. Seven controlled clinical trials published between 2010 and 2016 were included. A total of 320 extractions (170 tests and 150 controls) in 190 patients was considered. A great heterogeneity was found in terms of study design, methodological aspects, and outcome evaluation. For this reason, a quantitative analysis followed by meta-analysis was not possible, and only a descriptive analysis on the role of platelet concentrates in alveolar socket preservation was carried out. There is growing evidence that platelet concentrates may be advantageously used in postextraction sites, mainly to improve soft tissue healing and to reduce postoperative symptoms. Data about their potential in preserving the alveolar bone volume are still scarce and controversial, although recently encouraging results have been presented using more reliable and accurate evaluation technologies, such as the computed tomography. Further, well-designed and methodologically standardized investigations are strongly demanded to reach a higher level of evidence on this topic.

Vitamin D modulatory effect on cytokines expression by human gingival fibroblasts and periodontal ligament cells.

BACKGROUND: It has been demonstrated that vitamin D exerts several functions other than those implied in the bone homeostasis. It has been published the vitamin D can act on many cells and tissues behaving also as a modulatory factor in the immune responses. The aim of our study was to evaluate the effect of active vitamin D3 (VD) on the expression of pro-inflammatory and anti-inflammatory cytokines (IL-6, IL-8, IL-10 and IL-12) in human gingival fibroblasts (hGF) and human periodontal ligament cells (hPDLc) triggered by Porphyromonas gingivalis and Streptococcus pyogenes. METHODS: Primary hGF and hPDLc pretreated or not by VD (10-8 mol/L) were exposed to P. gingivalis and S. pyogenes for 24 h. Production of IL-6, IL-8, IL-10 and IL-12 was evaluated by immunoenzymatic assay. mRNA of the same cytokines were evaluated by PCR. RESULTS: IL-6 secretion increased by 25.2% (±2.1) up to 51% (±3.3) in VD treated hGF and hPDLc exposed to P. gingivalis and S. pyogenes, compared to VD not treated cells. IL-8 secretion decreased approximately by 30% in VD-treated hGF and hPDLc compared to VD not-treated cells. IL-12 secretion decreased by 60%. On the contrary, anti-inflammatory cytokine IL-10 increased by approximately 200%. mRNA PCR confirmed these results. CONCLUSIONS: Within the limits of the study, the obtained results support the hypothesis of a modulatory role of VD on periodontal cells exposed to bacterial infection, reducing their inflammatory response and increasing the secretion of anti-inflammatory and modulatory cytokines. Consequently, it could be speculated that vitamin D assessment, and its possible implementation in deficiency cases, could play a role in periodontal treatment.

The Use of Poly-d,l-lactic Acid (PDLLA) Devices for Bone Augmentation Techniques: A Systematic Review.

Poly-d,l-lactic acid (PDLLA) has been proposed in dentistry for regenerative procedures in the form of membranes, screws, and pins. The aim of this review was to evaluate the efficacy of bone augmentation techniques using PDLLA devices. A literature search was carried out by two independent and calibrated reviewers. All interventional and observational studies assessing the efficacy of bone augmentation techniques using PDLLA devices were included. Six studies were included. The relevant variability of design and methods impeded any qualitative or quantitative comparison. Ease of handling, absence of a re-entry phase, moldability of foils, and good soft-tissue response were appreciated characteristics of PDLLA devices. Some drawbacks such as the risk of membrane exposition, a prolonged adsorbability, and a tendency to a fibrous encapsulation of the PDLLA devices have been described, although the clinical significance of these findings is unclear. Clinical data about PDLLA devices for bone regeneration are very scarce and heterogenous. Well-designed randomized controlled trials comparing the use of PDLLA foils and pins with conventional membranes for bone regeneration are strongly encouraged in order to understand the real clinical benefits/drawbacks of this technique.

Tissue- and Cell Type-Specific Expression of the Long Noncoding RNA Klhl14-AS in Mouse.

lncRNAs are acquiring increasing relevance as regulators in a wide spectrum of biological processes. The extreme heterogeneity in the mechanisms of action of these molecules, however, makes them very difficult to study, especially regarding their molecular function. A novel lncRNA has been recently identified as the most enriched transcript in mouse developing thyroid. Due to its genomic localization antisense to the protein-encoding Klhl14 gene, we named it Klhl14-AS. In this paper, we highlight that mouse Klhl14-AS produces at least five splicing variants, some of which have not been previously described. Klhl14-AS is expressed with a peculiar pattern, characterized by diverse relative abundance of its isoforms in different mouse tissues. We examine the whole expression level of Klhl14-AS in a panel of adult mouse tissues, showing that it is expressed in the thyroid, lung, kidney, testis, ovary, brain, and spleen, although at different levels. In situ hybridization analysis reveals that, in the context of each organ, Klhl14-AS shows a cell type-specific expression. Interestingly, databases report a similar expression profile for human Klhl14-AS. Our observations suggest that this lncRNA could play cell type-specific roles in several organs and pave the way for functional characterization of this gene in appropriate biological contexts.