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In this paper, I will examine the Goldstein-Cassirer approach to neuropathology to determine its current potential for yielding valuable insights. To this end, I will reconstruct the philosophical and theoretical underpinnings of such a standpoint in the first four sections. What will emerge is that it entails a definition of pathology as the loss of balance in the adaption of human beings to the environment, leading to a lack of proclivity to categorical behaviour and symbolic performances. Furthermore, we will see that there are behavioural alterations which are not related to the locus of lesions. In the fifth section, I will compare and contrast the holistic stances with current research in neuropsychology. The sixth section is dedicated to conclusive remarks.

IntroductionFolliculin, encoded by FLCN gene, plays a role in the mTORC1 autophagy cascade and its alterations are responsible for the Birt–Hogg–Dubé (BHD) syndrome, characterized by follicle hamartomas, kidney tumors and pneumothorax.Patient and resultsWe report a 74-years-old woman diagnosed with dementia and carrying a FLCN alteration in absence of any sign of BHD. She also carried an alteration of MAT1A gene, which is also implicated in the regulation of mTORC1.DiscussionThe MAT1A variant could have prevented the development of a FLCN-related oncological phenotype. Conversely, our patient presented with dementia that, to date, has yet to be documented in BHD. Folliculin belongs to the DENN family proteins, which includes C9orf72 whose alteration has been associated to neurodegeneration. The folliculin perturbation could affect the C9orf72 activity and our patient could represent the first human model of a relationship between FLCN and C9orf72 across the path of autophagy.

Background: The purpose of this study was to evaluate the dimensional accuracy of surgical guides for static computer-aided implant placements processed using milling or 3D printing. Methods: A comprehensive literature search was performed on electronic databases inclusive of PUBMED, SCOPUS, Cochrane Database of Systematic Reviews, EBSCO host Research Databases, and Web of Knowledge were searched without restriction to date. Studies investigating the surgical guides fabricated by milling or 3D-printing, comparing them with their computer-aided design model, and reporting outcome measures about the accuracy of the internal/external surface, the angular deviation of the sleeves, and the vertical or horizontal deviations of the sleeves’ access were included. Results: From 1928 retrieved records, 33 studies were selected; 11 out of them fulfilled the eligibility criteria. All studies analyzed printed surgical guides, while only two studies analyzed both printed and milled templates. Studies were very heterogeneous in methodology and equipment; moreover, different parameters were used for accuracy measurements which made their results not comparable and quantitative synthesis not feasible. Conclusion: There is no clear evidence to address which manufacturing technology provides surgical guides with better accuracy, although milling might achieve better results, at least in terms of reduced variation. For additive technologies, several factors could influence accuracy. Since this issue has sensible clinical implications, future studies are encouraged.

Abstract Aim This study was performed to histologically evaluate peri-coronal tissues of partially impacted and erupted third molars that did not exhibit pathologic peri-coronal radiolucency. Materials and methods Healthy patients with erupted or partially erupted (with part or all of the dental crown present in the oral cavity) mandibular third molars (classified as IA and IIA according to the Pell and Gregory classification) and vertically positioned (according to the Winter classification or erupted third molars) associated with peri coronal radiolucency of equal to or less than 2.5 mm. Associated with third molar surgery, tissue sampling from the distal area was performed, which was subjected to an anatomopathological examination to determine the histological nature. Results One hundred teeth (100 patients) were selected, and 100 specimens were analyzed. 53% of the sample were included in the non-pathological group and 47% showed pathological changes (fibrotic tissue (n 15), periodontal cyst-like (n 9), squamous epithelial metaplasia (4 cases), islands of odontogenic epithelial residues organized micro-cyst with keratocystic/ameloblastic appearance (4 cases), granulation tissue (n 8), giant cell tumour (n 4) and lobular capillary hemangioma (n 4)). Pathological changes did not have differences in incidence between the gender (p value = 0.85) and did not show any correlation with age, (p value = 0,96). Conclusions These findings suggest that radiographic appearance may not be a reliable indicator of the absence of disease within a dental follicle. Therefore, clinicians should pay attention to or follow up on even peri-coronal radiolucency of less than 2.5 mm.

Abstract Background Antibiotic prophylaxis during implant placement may improve implant short term survival. Nevertheless, use of antibiotics carries risks of adverse effects and antibiotic resistance. The aim of the present study is to compare the use of antibiotics in dental implant procedures in terms of costs and effectiveness. Methods A decision-tree model was developed using TreeAge Pro Healthcare software. Two strategies were compared: Antibiotics and No antibiotics in implant placement procedures. The costs were calculated considering direct costs for implant placement, antibiotic costs, and costs for implant replacement in case of failure. Effectiveness was defined in terms of General Oral Health Assessment Index. Outcomes were evaluated as Incremental Cost Effectiveness Ratio (ICER). One-way sensitivity analysis and Probabilistic Sensitivity Analysis were performed for the most influential variables to test parameter uncertainty. Patient and healthcare perspectives were considered. Results Antibiotic prophylaxis resulted to be cost-effective compared to no use of antibiotics (ICER = 14,692,64 and ICER = 3841,18, respectively for patient’s and healthcare perspective). The cost of antibiotics, cost of implant replacement in case of failure and probability of adverse effects significantly influenced the results. Conclusions From an individual patient perspective, antibiotic strategy can be considered cost-effective, even when the cost of antibiotic therapy increases. We can conclude that the administration of antibiotics in association with implant placement is recommended in clinical practice, as it increases the success rate and makes the treatment more effective. However, attention should be placed when healthcare perspective is considered, particularly in terms of antibiotic resistance that may impact public health and associated costs.

Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive miR patterns identified in tumor samples, as well as in serum, plasma, or saliva, from patients have significant clinical potential for use in the diagnosis and prognosis of HNSCCs and as potential therapeutic targets. The aim of this study was to identify previous systematic reviews with meta-analysis data and clinical trials that showed the most promising miRs in HNSCCs, enclosing them into a biomolecular signature to test the prognostic value on a cohort of HNSCC patients according to The Cancer Genome Atlas (TCGA). Three electronic databases (PubMed, Scopus, and Science Direct) and one registry (the Cochrane Library) were investigated, and a combination of keywords such as “signature microRNA OR miR” AND “HNSCC OR LSCC OR OSCC OR oral cancer” were searched. In total, 15 systematic literature reviews and 76 prognostic clinical reports were identified for the study design and inclusion process. All survival index data were extracted, and the three miRs (miR-21, miR-155, and miR-375) most investigated and presenting the largest number of patients included in the studies were selected in a molecular biosignature. The difference between high and low tissue expression levels of miR-21, miR-155, and miR-375 for OS had an HR = 1.28, with 95% CI: [0.95, 1.72]. In conclusion, the current evidence suggests that miRNAs have potential prognostic value to serve as screening tools for clinical practice in HNSCC follow-up and treatment. Further large-scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.

Soft tissue regeneration holds significant promise for addressing various clinical challenges, ranging from craniofacial and oral tissue defects to blood vessels, muscle, and fibrous tissue regeneration. Mesenchymal stem cells (MSCs) have emerged as a promising tool in regenerative medicine due to their unique characteristics and potential to differentiate into multiple cell lineages. This comprehensive review explores the role of MSCs in different aspects of soft tissue regeneration, including their application in craniofacial and oral soft tissue regeneration, nerve regeneration, blood vessel regeneration, muscle regeneration, and fibrous tissue regeneration. By examining the latest research findings and clinical advancements, this article aims to provide insights into the current state of MSC-based therapies in soft tissue regenerative medicine.

Background: The accuracy of surgical guides is a relevant factor in both surgical safety and prosthetic implications. The impact of widespread fabrication technologies (milling and 3D printing) was investigated. Methods: Surgical guides manufactured by means of two specific milling and 3D-printing systems were digitized and compared in a 3D analysis with the digital file of the designed guides. The surface mean 3D distance (at the surface where the teeth and mucosa made contact) and the axial and linear deviations of the sleeves’ housings were measured by means of a metrological software program. Univariate and multivariate statistical analyses were used to investigate the effects of the fabrication technology, type of support, and arch type on the surgical guides’ accuracy. Results: The median deviations of the intaglio surface in contact with the mucosa were significantly (p < 0.001) lower for the milled surgical guides (0.05 mm) than for the 3D-printed guides (−0.07 mm), in comparison with the reference STL file. The generalized estimated equation models showed that the axial deviations of the sleeves’ housings (a median of 0.82 degrees for the milling, and 1.37 degrees for the 3D printing) were significantly affected by the fabrication technology (p = 0.011) (the milling exhibited better results), the type of support (p < 0.001), and the combined effect of the fabrication technology and the sleeve-to-crest angle (p = 0.003). The linear deviation (medians of 0.12 mm for the milling and 0.21 mm for the 3D printing) of their center points was significantly affected by the type of support (p = 0.001), with the milling performing slightly better than the 3D printing. Conclusions: The magnitude of the difference might account for a limited clinical significance.

The fracture of endodontic instruments inside the canal represents a problem that is not always easy to solve. The reutilization of endodontic instruments after sterilization procedures raises the question of how these processes affect their physical and mechanical properties. Alterations can involve the surface of the instruments, as well as their cutting effectiveness, shape and resistance to torsional and cyclic fatigue. The methodology adopted for this systematic review followed the PRISMA guidelines for systematic reviews. The following search terms were used in PubMed and Scopus: “endodontic sterilization”, “endodontic autoclave”, “cyclic fatigue”, “torsional”, “cutting efficiency”, “sterilization”, “surface characteristics” and “corrosion”. After the screening phase, the application of exclusion criteria and the removal of duplicates, 51 studies were identified and divided into four outcomes: cyclic fatigue; deformation and torsional fatigue; corrosion or surface alterations; and cutting efficiency. Our study of the scientific literature highlights disagreements between studies on these effects. After autoclaving, instruments exhibit a reduction in the cutting efficiency, but NiTi alloy instruments have an improved resistance to cyclic and torsional fatigue.

COVID-19 (Coronavirus Disease 2019) is an emerging viral disease caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which leads to severe respiratory infections in humans. The first reports came in December 2019 from the city of Wuhan in the province of Hubei in China. It was immediately clear that children developed a milder disease than adults. The reasons for the milder course of the disease were attributed to several factors: innate immunity, difference in ACE2 (angiotensin-converting enzyme II) receptor expression, and previous infections with other common coronaviruses (CovH). This literature review aims to summarize aspects of innate immunity by focusing on the role of ACE2 expression and viral infections in children in modulating the antibody response to SARS-CoV-2 infection. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles deemed potentially eligible were considered, including those dealing with COVID-19 in children and providing more up-to-date and significant data in terms of epidemiology, prognosis, course, and symptoms, focusing on the etiopathogenesis of SARS-CoV-2 disease in children. The bibliographic search was conducted using the search engines PubMed and Scopus. The following search terms were entered in PubMed and Scopus: COVID-19 AND ACE2 AND Children; COVID-19 AND Immunity innate AND children. The search identified 857 records, and 18 studies were applicable based on inclusion and exclusion criteria that addressed the issues of COVID-19 concerning the role of ACE2 expression in children. The scientific literature agrees that children develop milder COVID-19 disease than adults. Milder symptomatology could be attributed to innate immunity or previous CovH virus infections, while it is not yet fully understood how the differential expression of ACE2 in children could contribute to milder disease.

In 2018, a new clinical subtype, caused by biallelic variants in the AEBP1 gene, encoding the ACLP protein, was added to the current nosological classification of the Ehlers–Danlos Syndromes (EDS). This new phenotype, provisionally termed EDS classical-like type 2 (clEDS2), has not yet been fully characterized, as only nine cases have been reported to date. Here we describe a patient, homozygous for a novel AEBP1 pathogenic variant (NM_001129.5 c.2123_2124delTG (p.Val708AlafsTer5)), whose phenotype is reminiscent of classical EDS but also includes previously unreported multiple congenital malformations. Furthermore, we briefly summarize the current principal clinical manifestations of clEDS2 and the molecular evidence surrounding the role of AEBP1 in the context of extracellular matrix homeostasis and connective tissue development. Although a different coexisting etiology for the multiple congenital malformations of our patient cannot be formally excluded, the emerging role of ACLP in TGF-β and WNT pathways may explain their occurrence and the phenotypical variability of clEDS2.

Objectives: The purpose of this systematic review of the literature is to investigate which of the epoxy-based cements and those based on Tricalciumsilicate (MTA, Bioceramic) have the best sealing capacity through the analysis of studies that have provided a survey model in vitro of bacteria leakage. Source: The articles were identified using electronic databases such as PubMed, Scopus, the search was conducted between 8.12.2020 and 31.12.2020 and a last search was conducted on 2.12.2021. Study selection: 678 records were identified and after removing the duplicates we obtain 481 records, with the first phase of screening and selection of records we reached 204 and with the application of the inclusion and exclusion criteria we selected 31 articles, only 9 studies made a direct comparison between the two endodontic cement categories and presented data that could be included in the metaanalysis. Data: The meta-analysis of first outcome shows an odds ratio of 2.70 C.I.(Confidence Interval) [1.54, 4.73], the test for overall effect has a p value = 0.0005 with a heterogeneity index of I 2 of 9%; The second outcome meta-analysis shows an Odds Ratio of 1.50 C.I. (Confidence Interval) [0.92, 2.46] with a p value of 0.10 with an I 2 of 79%. Conclusion: the sealing ability is higher for epoxy resins than for tricalcium silicate-based cements, for observation periods longer than 90 days. Clinical relevance: The knowledge of the cement that determines the best sealing ability and resistance to microbial leakage, can be of help for the dentist who has to face clinical situations such as endodontic retreatments whose failure is determined by the persistence of bacteria in the endodontic canals.

The involvement of the Histaminergic System (HS) in neuropsychiatric disease is not well-documented, and few studies have described patients affected by different neuropsychiatric conditions harbouring disruptions in genes involved in the HS. In humans, histamine is synthetised from histidine by the histidine decarboxylase enzyme encoded by the HDC gene (OMIM*142704). This is the sole enzyme in our organism able to synthetise histamine from histidine. Histamine is also contained in many different food types. We hereby describe a twenty-one-year-old female diagnosed with a borderline intellectual disability with autistic traits and other peculiar neuropsychological features carrying a 175-Kb interstitial deletion on chromosome 15q21.2. The deletion was inherited from the mother, who was affected by a severe anxiety disorder. The deleted region contains entirely the HDC and the SLC27A2 genes and partially the ATP8B4 gene. The HDC gene has been previously associated with Tourette Syndrome (TS). Based on the functional role of the HDC, we propose this gene as the best candidate to explain many traits associated with the clinical phenotype of our patient and of her mother.

Background and objective: Diabetes mellitus (DM) refers to a group of metabolic disorders characterized by hyperglycemia resulting from impaired secretion or action of insulin. The high levels of glucose in the blood can negatively affect the healing processes through alterations in vascularization, bone remodeling, and with increased susceptibility to infections. Diabetes mellitus is therefore a risk factor not only for many systemic diseases, but also for localized problems such as peri-implantitis. The objective of this systematic review was to identify a clear relationship between peri-implant inflammation indices and glycemic levels, through the investigation of prospective studies that report data on a short-term follow-up period. Our hypothesis was that peri-implant inflammatory indices may already present themselves in a statistically significant way as altered in patients with DM compared to patients without DM. Materials and methods: This review was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Results: More than 992 records were identified in the PubMed, Scopus, and Cochrane Central Register of Controlled Trial electronic databases and only seven studies were included in the meta-analysis. The results of the meta-analysis report worse outcomes in patients with DM, even in the short period of six months, for peri-implatitis inflammation indices, such as Marginal bone loss (standardized (Std). mean difference (MD) 12\6 months 0.81 [0.45, 1.17]\1.82 [0.53, 3.10]), Bleeding on probing (Std. MD 12\6 months 2.84 [1.34, 4.34]\3.44 [1.41, 5.50]), Probing depth (Std. MD 12\6 months 1.14 [0.60, 1.68]\2.24 [0.66, 3.83]), and the plaque index (Std. MD 12 months 2.83 [0.09, 5.57]). Conclusion: The literature linking glycaemic control to peri-implant disease is highly heterogeneous due to lack of consistency of the definition of peri-implantitis and its clinical indicators among studies. Therefore, interpretation of finding and relevance to clinical practice should be considered on individual bases. In the era of personalized medicine, the clinician should utilize individualized information from translational researches and analyze all risk factors to provide the patient with evidence-based treatment options.

OBJECTIVES:To investigate the role of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in the development of dental disorders. METHODS:The first outcome was review of the role of reflux in the development of dental disorders in adults. The second outcome was review of the potential pathophysiological mechanisms underlying the association between reflux and dental disorders. Three investigators screened publications for eligibility and exclusion based on predetermined criteria through a literature search conducted on PubMed, Cochrane Library, and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS:From 386 publications, 24 studies were kept for analysis. Objective approaches were used in 16 studies to confirm GERD diagnosis. Pharyngeal reflux episodes (LPR) were considered in 2 studies. No study considered nonacid reflux. The study results supported a higher prevalence of dental erosion and caries in reflux patients compared with healthy individuals. Patients with dental erosion have a higher prevalence of reflux than controls. The pathophysiological mechanisms would involve changes in the saliva physiology. No study investigated the microbiota modifications related to reflux although the findings are supporting the critical role of microbiota change in the development of dental disorders. There is an important heterogeneity between studies about diagnostic methods and clinical outcome evaluation. CONCLUSION:The involvement of reflux in the development of dental disorders is not formally demonstrated and requires future investigations considering pharyngeal acid and nonacid reflux episodes and in particular their potential impact on oral microbiota.

(1) Background: An accurate prediction of cancer survival is very important for counseling, treatment planning, follow-up, and postoperative risk assessment in patients with Oral Squamous Cell Carcinoma (OSCC). There has been an increased interest in the development of clinical prognostic models and nomograms which are their graphic representation. The study aimed to revise the prognostic performance of clinical-pathological prognostic models with internal validation for OSCC. (2) Methods: This systematic review was performed according to the Cochrane Handbook for Diagnostic Test Accuracy Reviews chapter on searching, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, and the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). (3) Results: Six studies evaluating overall survival in patients with OSCC were identified. All studies performed internal validation, while only four models were externally validated. (4) Conclusions: Based on the results of this systematic review, it is possible to state that it is necessary to carry out internal validation and shrinkage to correct overfitting and provide an adequate performance for optimism. Moreover, calibration, discrimination and nonlinearity of continuous predictors should always be examined. To reduce the risk of bias the study design used should be prospective and imputation techniques should always be applied to handle missing data. In addition, the complete equation of the prognostic model must be reported to allow updating, external validation in a new context and the subsequent evaluation of the impact on health outcomes and on the cost-effectiveness of care.

Background: Hyaluronans exist in different forms, accordingly with molecular weight and degree of crosslinking. Here, we tested the capability to induce osteogenic differentiation in hDPSCs (human dental pulp stem cells) of three hyaluronans forms: linear pharmaceutical-grade hyaluronans at high and (HHA) low molecular weight (LHA) and hybrid cooperative complexes (HCC), containing both sizes. Methods: hDPSCs were treated with HHA, LHA, HCC for 7, 14 and 21 days. The effects of hyaluronans on osteogenic differentiation were evaluated by qRT-PCR and WB of osteogenic markers and by Alizarin Red S staining. To identify the involved pathway, CD44 was analyzed by immunofluorescence, and YAP/TAZ expression was measured by qRT-PCR. Moreover, YAP/TAZ inhibitor-1 was used, and the loss of function of YAP/TAZ was evaluated by qRT-PCR, WB and immunofluorescence. Results: We showed that all hyaluronans improves osteogenesis. Among these, HCC is the main inducer of osteogenesis, along with overexpression of bone related markers and upregulating CD44. We also found that this biological process is subordinate to the activation of YAP/TAZ pathway. Conclusions: We found that HA’s molecular weight can have a relevant impact on HA performance for bone regeneration, and we unveil a new molecular mechanism by which HA acts on stem cells.

Introduction: Tooth autotransplantation is the repositioning of an erupted, partially erupted, or non-erupted autologous tooth from one site to another within the same individual. Several factors influence the success rate of the autotransplant, such as the stage of root development, the morphology of the tooth, the surgical procedure selected, the extraoral time, the shape of the recipient socket, the vascularity of the recipient bed, and the vitality of the cells of the periodontal ligament. The aim of this scoping review was to provide the most up-to-date information and data on the clinical principles of the third-molar autograft and thus provide clinical considerations for its success. Materials and methods: This review was conducted based on PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews). The research was conducted by searching for keywords in three databases—PubMed, Scopus and Google Scholar—by two independent reviewers following the PRISMA protocol, from which 599 records were identified. Conclusions: Third-molar autotransplantation is a valid solution to replace missing teeth. The key to the success of this technique is the surgical procedure, which must be as atraumatic as possible to preserve the periodontal ligament of the tooth to be transplanted. The success rate is also linked to the stage of development of the root, with a worse prognosis in the case of a complete root.

Background: Nitric Oxide (NO) has a role in immunitary defense, regulation of mucosal blood flow and mucus production, regulation of smooth muscle contraction, cerebral blood flow, glucose regulation, and mitochondrial function. NO can be synthetized endogenously through the L-arginine-NO pathway or it can be absorbed by the human intestine through the dietary intake. Most of the ingested NO is in the form of nitrate (NO3−). NO3− is a substrate of oral and intestinal microbiota and, at the end of the catabolic pathway, NO is released. Using antibacterial mouthwashes leads to an alteration of salivary NO3− metabolism, however, with unclear consequences on the circulating NO levels. The aim of this study is to perform a systematic review in order to elucidate if the alterations of oral microbiota lead to modifications in plasma NO content.Methods: Electronic databases were screened, using the following terms: [“oral bacteria” and (nitrate OR nitrite OR nitric)]. Clinical studies reporting NO3− and NO2− measurements in blood and their correlation to oral microbiota variations were included. We focused on the correlation between the changes in oral microbiota and plasma concentrations of nitrites (primary outcome). Subsequently, we investigated if modifications in oral microbiota could lead to changes in blood pressure and salivary NO2− concentration (secondary outcome).Results: Six studies, for a total of 82 participants were included in this review. In four studies, the use of mouthwash correlated to a reduction of plasma nitrite concentration (p < 0.05); Two studies did not find any difference in plasma nitrate or nitrite concentration. In five studies, a correlation between blood pressure (BP) changes and antibacterial mouthwashing emerged. Anyway, only three studies suggested a significant increase of systolic BP following mouthwashing compared with controls.Conclusions: Although, the role of oral bacteria has been unequivocally demonstrated in the regulation of salivary NO3− metabolism, their influence on plasma concentration of NO species remains ambiguous. Further studies with larger sample size are required in order to demonstrate if an alteration in oral microbiota composition may influence the blood content of NO3−/NO2−/NO and all the linked biological processes.

Sterilization processes guarantee the sterility of dental instruments but can negatively affect instrument features by altering their physical and mechanical properties. The endodontic instrumentation can undergo a series of alterations, ranging from corrosion to variation in the cutting angle and then changes in the torsional properties and torsional fatigue resistance. This systematic literature review and meta-analysis aims to investigate alterations to the cutting efficiency of endodontic instruments that are induced by procedures for their disinfection and sterilization. Methodologies adopted for this investigation follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. The following were used as search terms on PubMed and Scopus: “endodontic sterilization”, “endodontic autoclave”, “cyclic fatigue”, “torsional”, “cutting efficiency”, “sterilization”, “surface characteristics”, and “corrosion”. At the end of the selection process, 36 articles were identified, and seven of them are included in this systematic review. The results of a meta-analysis conducted for the use of 10 autoclaving cycles shows a standardized mean difference (SMD) of 0.80 with a p-value equal to 0.04 with respect to effect on cutting efficiency. The network meta-analysis, through direct and indirect comparison between the different autoclave cycles (0, 1, 5, 10, and 15 cycles), revealed that treatment involving 15 autoclave cycles produced the most robust results in terms of having the greatest effects in terms of altered cutting efficiency with a probability of 57.7% and a SUCRA (surface under the cumulative ranking) of 80%. The alterations in the effects on cutting efficiency appear to be triggered after five cycles of sterilization by heat (autoclave). In conclusion, the meta-analysis of the data indicates that the autoclave sterilization protocol must not be repeated more than five times to preserve cutting efficiency. Within the limitations of this review, we can therefore establish that sterilization by autoclaving alone results in steel and NiTi instruments becoming less efficient in cutting after five cycles, as measured by a reduction in cutting efficiency.

The Rhopalurus junceus is a scorpion belonging to the Buthidae family that finds its habitat in Cuba. This scorpion is known by the common name of “Blue Scorpion”. The venom is used on the island of Cuba as an alternative cure for cancer and, more recently, in the research of active components for biomedicine. Recently, the venom has been tested in several studies to investigate its effects on cancer cell lines, and the initial results of in vitro studies demonstrated how this poison can be effective on certain carcinoma cell lines (Hela, SiHa, Hep-2, NCI-H292, A549, MDA-MB-231, MDA-MB-468, and HT-29). The aim of this review is, therefore, to describe the effects of the venom on carcinoma lines and to investigate all anti-cancer properties studied in the literature. The research was conducted using four databases, Pub Med, Scopus, EBSCO, and Web of Science, through the use of keywords, by two independent reviewers following the PRISMA protocol, identifying 57 records. The results led to a total of 13 articles that met the eligibility criteria. The data extracted for the purpose of meta-analysis included the IC50 of the venom on carcinoma cell lines. The results of the meta-analysis provided a pooled mean of the IC50 of 0.645 mg/mL (95% CI: 0.557, 0.733), with a standard error (SE) = 0.045, p < 0.001. The analysis of the subgroups, differentiated by the type of cell line used, provided insight regarding how the scorpion venom was effective on the cell lines of lung origin (NCI-H292, A549, and MRC-5) with a pooled mean of IC50 0.460 mg/mL (95% CI: 0.290, 0.631) SE (0.087) p < 0.001. The results described in the literature for in vitro studies are encouraging, and further investigations should be carried out and deepened.

The present study aimed to perform a systematic critical appraisal of the methodological quality of systematic reviews (SRs) on the effect of autologous platelet concentrates (APCs) in the treatment of periodontal intraosseous defects and to provide a synthesis of the main clinical findings available. An electronic and hand search was performed up to February 2020; 14 systematic reviews of randomized controlled trials (RCTs), of which 11 were meta-analyses, were included. Only one SR fully satisfied all 11 items of the AMSTAR (“A Measurement Tool to Assess Systematic Reviews”) checklist for methodological quality evaluation, 3 SRs were classified of high quality, 8 of medium quality, and 2 of low quality. There is some evidence on the beneficial additive effect of APCs in the surgical treatment of intraosseous defects when used alone or in combination with bone grafts. APCs did not show any advantage when used together with guided tissue regeneration (GTR) or enamel matrix derivative (EMD). Undertaking SRs which adhere to rigorous standards and protocols is strongly recommended. There are increasing data on the positive adjunctive effect of APCs in the surgical treatment of intraosseous defects but, due to the heterogeneity of the available primary studies, the quality of evidence remains rather low and further long-term well-designed RCTs are encouraged.

In recent years there has been a lot of talk about toothpastes with a particular chemical compound: stannous fluoride (SnF2). Its presence is currently still highly controversial, as the latter could have negative health effects. The different companies that produce toothpastes express its dosage in ppm. The purpose of this systematic literature review is to analyze all randomized clinical trials in the literature over the last 10 years and to draw clear results on the function of stannous fluoride, for this purpose the authors performed a Mann–Whitney U Test. Materials: The first analysis of the literature produced a number greater than 800 results, subsequently applying the inclusion and exclusion criteria, and following a manual analysis of the results, 26 manuscripts have been obtained. Results: From the results analyzed in this review, it could be shown that stannous fluoride does not present important contraindications, if not those commonly reported for fluorine. A meta-analysis on enamel loss has been conducted, it shows that SnF2 products provide better results with a p < 0.05 value. Conclusion: This compound could have significant effects in favor of erosion and recalcification of the enamel, on the biofilm formation, gingival inflammation, and in addition, it could be an important aid in the removal of tooth stains and halitosis.

Head and neck squamous cell carcinoma (HNSCC) is one of the main neoformations of the head–neck region and is characterized by the presence of squamous carcinomatous cells of the multi-layered epithelium lining the oral cavity, larynx, and pharynx. The annual incidence of squamous cell carcinoma of the head and neck (HNSCC) comprises approximately 600,000 new cases globally. Currently, the 5-year survival from HNSCC is less than 50%. Surgical, radiotherapy, and chemotherapy treatments strongly compromise patient quality of life. MicroRNAs (miRNAs) are a family of small noncoding endogenous RNAs that function in regulating gene expression by regulating several biological processes, including carcinogenesis. The main upregulated microRNAs associated with oral carcinoma are miR-21, miR-455-5p, miR-155-5p, miR-372, miR-373, miR-29b, miR-1246, miR-196a, and miR-181, while the main downregulated miRNAs are miR-204, miR-101, miR-32, miR-20a, miR-16, miR-17, and miR-125b. miR-21 represents one of the first oncomirs studied. The present systematic review work was performed based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocol. A search was carried out in the PubMed and Scopus databases with the use of keywords. This search produced 628 records which, after the elimination of duplicates and the application of the inclusion and exclusion criteria, led to 7 included articles. The heterogeneity of the studies according to the odds ratio was high, with a Q value of 26.616 (p < 0.001), and the I2 was 77.457% for specificity. The heterogeneity was high, with a Q value of 25.243 (p < 0.001) and the I2 was 76.231% for sensitivity. The heterogeneity of data showed a Q value of 27.815 (p < 0.001) and the I2 was 78.429%. Therefore, the random-effects model was selected. The diagnostic odds ratio was 7.620 (95% CI 3.613–16.070). The results showed that the sensitivity was 0.771 (95% CI 0.680–0.842) (p < 0.001) while, for specificity, we found 0.663 (95% CI 0.538–0.770) (p < 0.001). The negative likelihood ratio (NLR) was 0.321 (95% CI 0.186–0.554), and the positive likelihood ratio (PLR) was 2.144 (95% CI 1.563–2.943). The summary ROC plot demonstrates that the diagnostic test presents good specificity and sensitivity, and the area under the curve (AUC), as calculated from the graph, was 0.79.

The advent of new technologies in the field of medicine and dentistry is giving improvements that lead the clinicians to have materials and procedures able to improve patients’ quality of life. In dentistry, the last digital techniques offer a fully digital computerized workflow that does not include the standard multiple traditional phases. The purpose of this study is to evaluate all clinical trials and clinical randomized trials related to the digital or dental impression technique in prosthetic dentistry trying to give the readers global information about advantages and disadvantages of each procedure. Data collection was conducted in the main scientific search engines, including articles from the last 10 years, in order to obtain results that do not concern obsolete impression techniques. Elsevier, Pubmed and Embase have been screened as sources for performing the research. The results data demonstrated how the working time appears to be improved with digital workflow, but without a significant result (P = 0.72596). The papers have been selected following the Population Intervention Comparison Outcome (PICO) question, which is related to the progress on dental impression materials and technique. The comparison between dentists or practitioners with respect to classic impression procedures, and students open to new device and digital techniques seem to be the key factor on the final impression technique choice. Surely, digital techniques will end up supplanting the analogical ones altogether, improving the quality of oral rehabilitations, the economics of dental practice and also the perception by our patients.

Actinomyces are anaerobic, rod-shaped, Gram-positive bacteria. They are associated with persistent extraradicular endodontic infections, with possible involvement of the soft tissues of the maxillofacial district. Many studies reported conflicting data on the presence of bacteria of the genus Actinomyces in endodontic infections. The aim of this systematic review of the literature was to determine the real prevalence of such bacteria in primary and/or secondary endodontic infections and in cases of persistence with extraradicular involvement. This systematic review was performed according to the PRISMA protocol. A search was carried out through the Scopus and PubMed databases of potentially eligible articles through the use of appropriate keywords. The literature research resulted in preliminary 2240 records which, after the elimination of overlaps and the application of inclusion and exclusion criteria, led to the inclusion of 46 articles focusing on three outcomes (primary outcome: number of teeth with the presence of a persistent extraradicular infection in which the presence of Actinomyces was ascertained; secondary outcome: number of teeth with endodontic infection in which the presence of Actinomyces was assessed; tertiary outcome: difference in the prevalence of bacteria of the genus Actinomyces between primary endodontic infections and secondary endodontic infections). Results of the meta-analysis show how bacteria of the genus Actinomyces are present in primary and secondary intraradicular infections and in those with persistence with a prevalence (ratio between teeth with actinomyces and teeth with infection) ranging from 0.091 up to 0.130 depending on the subgroups analyzed.

The evidence of a connection between the peripheral inflammatory processes and neurodegenerative diseases of the central nervous system is becoming more apparent. This review of the related literature highlights the most recent clinical, epidemiological, and in vitro studies trying to investigate possible connections between periodontal bacteria and the onset and progression of Alzheimer’s disease. This review was conducted by searching databases such as PubMed and Scopus using keywords or combinations such as Alzheimer’s Disease AND periodontal or dementia AND periodontitis OR periodontal. After eliminating overlaps and screening the articles not related to these issues, we identified 1088 records and proceeded to the selection of articles for an evaluation of the associative assumptions. The hypothesis suggested by the authors and confirmed by the literature is that the bacterial load and the inflammatory process linked to periodontal disease can intensify inflammation at the level of the central nervous system, favoring the occurrence of the disease. The analysis of the literature highlights how periodontal disease can directly contribute to the peripheral inflammatory environment by the introduction of periodontal or indirect pathogenic bacteria and proinflammatory cytokines locally produced at the periodontal level following bacterial colonization of periodontal defects.

The aim of the study was to examine the biochemical and structural changes occurring in the periodontal ligament (PDL) during orthodontic-force application using micro-Raman spectroscopy ( μ -RS). Adolescent and young patients who needed orthodontic treatment with first premolar extractions were recruited. Before extractions, orthodontic forces were applied using a closed-coil spring that was positioned between the molar and premolar. Patients were randomly divided into three groups, whose extractions were performed after 2, 7, and 14 days of force application. From the extracted premolars, PDL samples were obtained, and a fixation procedure with paraformaldehyde was adopted. Raman spectra were acquired for each PDL sample in the range of 1000−3200 cm − 1 and the more relevant vibrational modes of proteins (Amide I and Amide III bands) and CH 2 and CH 3 modes were shown. Analysis indicated that the protein structure in the PDL samples after different time points of orthodontic-force application was modified. In addition, changes were observed in the CH 2 and CH 3 high wavenumber region due to local hypoxia and mechanical force transduction. The reported results indicated that μ -RS provides a valuable tool for investigating molecular interchain interactions and conformational modifications in periodontal fibers after orthodontic tooth movement, providing quantitative insight of time occurring for PDL molecular readjustment.

Endodontic canal disinfection procedures that use sodium hypochlorite, and subsequently, heat sterilization procedures can alter the surface of endodontic instruments, described as corrosion and micropitting. These phenomena can be visualized on the surface of the instruments by SEM and atomic force microscopy analyses. The endodontic instruments used in probing, pre-enlargement, and shaping phases are made of steel alloy or nickel-titanium alloy (NiTi) and are subject to torsional, flexor, and cyclic fatigue; indeed, reuse of these instruments must be done with the knowledge that these instruments are subject to fracture following stress caused during their use. Fracture of the instrument within the canal is an eventuality that can lead to failure of the treatment, and therefore it is important to try to reduce situations that can contribute to the fracture. This review was performed based on the PRISMA protocol. Studies were identified through bibliographic research using electronic databases. A total of 1036 records were identified on the PubMed and Scopus databases. After screening the articles, restricted by year of publication (1979 to 2019), there were 946 records. With the application of the eligibility criteria (all the articles pertaining to the issue of sterilization in endodontics), there were 228 articles. There were 104 articles after eliminating overlaps. There were 50 articles that discussed the influence of sterilization procedures on the surface characteristics of endodontic instruments, and 26 articles that measured parameters on surface alteration. Applying the inclusion and exclusion criteria resulted in a total of eleven articles for quantitative analysis. Four articles were in reference to the primary outcome, eight articles to secondary outcome, and five articles to tertiary outcome. The meta-analysis showed a statistically significant surface alteration effect after five autoclaves and after immersion in the canal irrigants after 10 min.

The increment of recording atypical oral manifestation in young patients often related to systematic disease is today a challenge for the therapists. Sometime, the presence of tooth enamel lesions correlated with soft tissue lesions is just a symptom or a trigger sign for a deeper and undetermined disease. Recently, high impact has been developed toward the influence of the diet as a controlled and modifiable factor in patients affected by celiac pathologies. The celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten that appears in genetically predisposed patients. Gluten is a proline-rich and glutamine-rich protein present in wheat (gliadin), barley (hordein), and rye (secalin). The gluten-free diet (GFD) seems to better influence the oral health status of the CD patients. For this reason, the main objective of this revision was to analyze the international data highlighting the relationship between celiac patients and the oral health impact profile. A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database. Authors conducted the search of articles in the English language published from 2008 to 2018. The first analysis with filters recorded 67 manuscripts accordingly with the selected keywords. Finally, a number of 16 appropriate published papers were comprehended in the review. The studies were different in terms of the structure, findings, outcomes, and diet quality evaluation, and for this reason, it was not possible to accomplish a meta-analysis of the recorded data. This manuscript offers some observational evidence to justify the advantages of gluten-free diets related to a better oral health status in the patients involved.

In the present paper, the author aims at laying the foundations of a symbolics of technical gesture, according to the thesis that symbolic faculty is another face of the technological one, and that they are both in truth two sides of the same coin. Accordingly, the author suggests to rename the whole dimension as “meta-environmentality”. The analysis is carried out on the basis of a specific comparison between Cassirer’s definition of “animal symbolicum” and its scientific consistence in the light of modern palaeontology. “Animal symbolicum” is here compared with Leroi-Gourhan’s homo technologicus, and Cassirer’s ideas on human identity tested starting from paleoanthropological data. The result of the inquiry lead us to recognize the urgency of integrating Cassirer’s argument with the primacy of the technological capacity, but a deep analysis of the characterizing attributes of the latter compels us to uphold the symbolic attitude of the technological dimension. The author then sketches a basic description ofthe guidelines of a symbolic theory of technology (especially §§ 6-7), and tries to show how the basic elements of such an approach were familiar both to Cassirer and Leroi-Gourhan. As a consequence of the whole theory, the author elaborates a chronological analysis of human identity, whose basic result is the determination of the future as main temporal dimension of human acting.

Tooth transplantation can be considered a valid and predictable treatment option for rehabilitating young patients with permanent teeth loss. This study presents several cases of successful autogenous tooth transplantation with a 6-9 months follow-up. Tooth auto-transplantation can be considered a reasonable option for replacing missing teeth when a donor tooth is available. The auto-transplantation of a right mandibular third molar with compromised function and esthetics to replace the residual roots resulting from coronal destruction due to extensive carious lesion of the second molar in the same quadrant as shown in the presented cases can result a viable treatment alternative especially in a young patient that cannot undergo dental implant therapy. Transplantation of mature third molar seems to be a promising method for replacing a lost permanent molar tooth and restoring esthetics and function. This clinical procedure showed excellent functional and esthetical long-term results in the analyzed cases.

Among the many plants used in traditional medicine we have the plants of the genus Asphodelus, which are present in the Mediterranean area in North Africa and South East Asia, and have been used by indigenous peoples until recently for various pathologies, including: Psoriasis, alopecia areata, acne, burns, nephrolithiasis, toothache, and local inflammation. The scientific literature over the last five years has investigated the various effects of the metabolites extracted from plants of the genus Asphodelus, paying attention to the diuretic, antihypertensive, antimicrobial, anti-inflammatory, and antioxidant effects, and it also has begun to investigate the antitumor properties on tumor cell lines. Studies have been identified through bibliographic research on electronic databases. A total of 574 records were identified on the PubMed, Scopus, Web of Science, and EBSCO databases. After having proceeded to the screening of the articles with the application of the eligibility criteria (all the articles pertaining to the issue Asphodelus), we arrived at a number of 163 articles, and then after the elimination of overlaps, to 82 articles. There are 11 articles which investigate the possible uses of plants of the genus Asphodelus in oral medicine. In oral medicine, the possible uses investigated by the scientific literature are for the treatment of neoplastic (melanoma and oral cancer), viral (herpetic viruses), and microbial diseases (candida, bacteriosis, leishmaniasis), and in the affection of the skin.

The fluorescence method is an innovative technique used by pathologists for examining body mucosa, and for the abnormalities tissue screening, potentially leading to the earlier discovery of pre-cancer, cancer or other disease processes. The early detection is one of the best mechanisms for enabling treatment success, increasing survival rates and maintaining a high quality of life. The purpose of this review is to evaluate the clinical efficiency of this diagnostic tool applied to the oral cavity (VELscope®). A literature systematic review has been performed. The initial research provided 53 results after applying the inclusion and exclusion criteria, and after a manual screening of the abstracts by the authors, only 25 results were eligible for review. The results and data contained in all the researches, no older than 10 years, were manually evaluated, and provided useful information on this diagnostic method. The VELscope® mean value about sensitivity and specificity resulted of 70.19% and 65.95%, respectively, by results analysis, but despite this some studies disagree about its clinical effectiveness, and this diagnostic method is still much debated in scientific and clinical medical literature. Surely being able to have efficient and effective tools from this point of view could help the clinician in the diagnosis, and also make timelier the pharmacological or surgical therapy, improving the quality of life of the patient, and in some cases guaranteeing a longer survival term.

Sterilization is a fundamental step in the reuse of endodontic instruments. The sterilization procedure involves disinfection, cleaning, washing, drying, packaging, and sterilization by heat. Heat sterilization can lead to changes in the physical and mechanical properties of dental instruments. These changes can affect the external surfaces via micropitting, corrosion, a reduction in cutting capacity, and/or an influence on the resistance to cyclic fatigue or to torsional fatigue. In this study, we examined the modification of the torsional properties of endodontic instruments after hot sterilization, and compared the properties with instruments not subjected to hot sterilization cycles in terms of resistance to torsional fatigue and deflection angle in NiTi and steel instruments. The following work was performed based on the PRISMA indications. Studies were identified through bibliographic research using electronic databases. A total of 725 records were identified in the PubMed and Scopus databases. A total of 685 records remained after exclusion by year of publication (1979 to 2019). With the application of the eligibility criteria (all articles pertaining to the issue of sterilization in endodontics), we found 146 articles, which decreased to 130 articles after elimination of duplications. There were 45 articles that studied the influences of sterilization procedures on the physical and mechanical characteristics of the instruments, and 12 that measured parameters related to resistance to torsional fatigue. Applying the inclusion and exclusion criteria resulted in a total of eight articles for quantitative analysis. The meta-analysis results show a pejorative effect of torsional fatigue for NiTi instruments subjected to heat sterilization compared to the non-sterilized control.

Many people nowadays undergo treatments to improve their aesthetics, often neglecting the general state of health. Aesthetics and appearance have become of prime importance, perhaps correlating with of the advent of social networks and digital photographs. One of the most requested aesthetic treatments for dentists is dental bleaching through the use of whitening gels. Dental bleaching is a treatment which involves an improvement in the chrome of the teeth in a short time, and this treatment appears not invasive for the patients. In-office and at-home bleaching treatments can be found. The purpose of this scientific study is to evaluate all of the advantages and disadvantages of this medical treatment. In this study, were report information and items related to bleaching side effects. Dentists often find themselves in disagreement on this topic. The PICO (Population/Intervention/Comparison/Outcome) question investigated was: Are dental patients who have dental bleaching an increased risk of teeth damage? All of the data in the literature has been collected, and all of the side effects of this treatment were evaluated. 263 studies emerged from initial research; only 14 were screened after screening, as they contained sufficient data to evaluate the side effects of treatment. One certain thing emerged; among the contraindications to the treatment of dental bleaching dentinal hypersensitivity could be cited. In fact, one of the most reported undesirable effects regards this problem. Other studies have evaluated pain, color improvement and duration, or patient satisfaction. Dental bleaching is a treatment that aims to improve the aesthetics of our patients; this is also reflected from a psychological point of view and therefore has effects on general health. However, the whitening treatment is not suitable for everyone and must be carefully evaluated by a specialist. This treatment also entails maintenance by the patient and therefore better compliance to normal oral hygiene procedures.

The aim of this paper was to highlight the most widely antibiotic protocols applied to the dental field, especially in the surgical treatment of impacted wisdom teeth. Once these protocols were screened, all the possible advantages or disadvantages for each drug and each posology were recorded in this review. In recent years, the need to use these protocols has been debated in the literature. The data obtained by this review underlined how antibiotic protocols applied to oral surgery treatments only included surgeries performed on patients who did not present other systemic pathologies. The first literature review obtained 140 results, and then after the application of the inclusion criteria, 12 papers were selected. The results showed that the most commonly used protocol involved the use of penicillin and clavulanate, obtaining safe clinical and prophylactic results in the management of infections. This widely used protocol seems to guarantee high predictability and safety. The presented review highlights the current possibility of antibiotic resistance affecting patients due to drug misuse. Further clinical studies are required to state specific guidelines; however, oral surgeons involved in third molar surgery should evaluate the local and general health conditions of the patients before suggesting any drug measures for patients.

Background: Nowadays, patients involved in antiplatelet therapy required special attention during oral surgery procedures, due to the antiplatelet drugs assumption. The motivations of the assumption may be different and related to the patient’s different systemic condition. For this reason, accordingly to the current international guidelines, different protocols can be followed. The aim of this work is to analyze how the dentist’s approach to these patients has changed from the past to the present, evaluating the risk exposure for the patients. Methods: This review paper considered different published papers in literature through quoted scientific channels, going in search of “ancient” works in such a way as to highlight the differences in the protocols undertaken. The analyzed manuscripts are in the English language, taking into consideration reviews, case reports, and case series in such a way as to extrapolate a sufficient amount of data and for evaluating the past therapeutic approaches compared to those of today. Results: Colleagues in the past preferred to subject patients to substitution therapy with low molecular weight anticoagulants, by suspending antiplatelet agents to treatment patients, often for an arbitrary number of days. The new guidelines clarify everything, without highlighting an increased risk of bleeding during simple oral surgery in patients undergoing antiplatelet therapy. Conclusion: Either patients take these medications for different reasons, because of cardiovascular pathologies, recent cardiovascular events, or even for simple prevention, although the latest research shows that there is no decrease of cardiovascular accidents in patients who carry out preventive therapy. Surely, it will be at the expense of the doctor to assess the patient’s situation and risk according to the guidelines. For simple oral surgery, it is not necessary to stop therapy with antiplatelet agents because the risk of bleeding has not increased, and is localized to a post-extraction alveolus or to an implant preparation, compared to patients who do not carry out this therapy. From an analysis of the results it emerges that the substitutive therapy should no longer be performed and that it is possible to perform oral surgery safely in patients who take antiplatelet drugs, after a thorough medical history. Furthermore, by suspending therapy, we expose our patients to more serious risks, concerning their main pathology, where present.

Haemophiliacs are hereditary coagulopathies whose basic anomaly consists of the quantitative or qualitative alteration of one or more plasma proteins in the coagulation system. The objective of this review is to analyse all risk factors, predispositions and alterations to the oral-maxillofacial district in patients with haemophilia. The broader assessment also includes the psychological aspects that could affect the treatment and maintenance of oral conditions. The study takes into consideration all the works in the literature in the last 10 years. Works that present oral, dental and psychological changes in haemophilia patients have been combined. A total of 16 studies were analysed carefully evaluating and explaining all the alterations and risk factors that this disease provides. The aim of the review is to report all the anomalies reported in the literature for these patients, and to direct and update the clinician in the treatment of haemophilia patients.

Epigenetic regulation has been considered an important mechanism for influencing stem cell differentiation. In particular, histone deacetylases (HDACs) have been shown to play a role in the osteoblast differentiation of mesenchymal stem cells (MSCs). In this study, the effect of the HDAC inhibitor, valproic acid (VPA), on bone formation in vivo by MSCs was determined. Surprisingly, VPA treatment, unlike other HDAC inhibitors, produced a well-organized lamellar bone tissue when MSCs–collagen sponge constructs were implanted subcutaneously into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice, although a decrease of osteocalcin (OC) expression was observed. Consequently, we decided to investigate the molecular mechanisms by which VPA exerts such effects on MSCs. We identified the glucocorticoid receptor (GR) as being responsible for that downregulation, and suggested a correlation between GR and HDAC2 inhibition after VPA treatment, as evidenced by HDAC2 knockdown. Furthermore, using co-immunoprecipitation analysis, we showed for the first time in the cytoplasm, binding between GR and HDAC2. Additionally, chromatin immunoprecipitation (ChIP) assays confirmed the role of GR in OC downregulation, showing recruitment of GR to the nGRE element in the OC promoter. In conclusion, our results highlight the existence of a cross-talk between GR and HDAC2, providing a mechanistic explanation for the influence of the HDAC inhibitor (namely VPA) on osteogenic differentiation in MSCs. Our findings open new directions in targeted therapies, and offer new insights into the regulation of MSC fate determination.

Background: In recent years, many advances have been made in the fields of bioengineering and biotechnology. Many methods have been proposed for the in vitro study of anatomical structures and alloplastic structures. Many steps forward have been made in the field of prosthetics and grafts and one of the most debated problems lies in the biomimetics and biocompatibility of the materials used. The contact surfaces between alloplastic material and fabric are under study, and this has meant that the surfaces were significantly improved. To ensure a good contact surface with the cells of our body and be able to respond to an attack by a biofilm or prevent the formation, this is the true gold standard. In the dental field, the study of the surfaces of contact with the bone tissue of the implants is the most debated, starting from the first concepts of osteointegration. Method: The study searched MEDLINE databases from January 2008 to November 2018. We considered all the studies that talk about nanosurface and the biological response of the latter, considering only avant-garde works in this field. Results: The ultimate aim of this study is to point out all the progress made in the field of bioengineering and biotechnologies about nanosurface. Surface studies allow you to have alloplastic materials that integrate better with our body and allow more predictable rehabilitations. Particularly in the field of dental implantology the study of surfaces has allowed us to make huge steps forward in times of rehabilitation. Overcoming this obstacle linked to the time of osseointegration, however, today the real problem seems to be linked to the “pathologies of these surfaces„, or the possible infiltration, and formation of a biofilm, difficult to eliminate, being the implant surface, inert. Conclusions: The results of the present investigation demonstrated how nanotechnologies contribute substantially to the development of new materials in the biomedical field, being able to perform a large number of tests on the surface to advance research. Thanks to 3D technology and to the reconstructions of both the anatomical structures and eventually the alloplastic structures used in rehabilitation it is possible to consider all the mechanical characteristics too. Recent published papers highlighted how the close interaction between cells and the biomaterial applied to the human body is the main objective in the final integration of the device placed to manage pathologies or for rehabilitation after a surgical tumor is removed.

Hydrocolloids were the first elastic materials to be used in the dental field. Elastic impression materials include reversible (agar-agar), irreversible (alginate) hydrocolloids and synthetic elastomers (polysulfides, polyethers, silicones). They reproduce an imprint faithfully, providing details of a high definition despite the presence of undercuts. With the removal of the impression, being particularly rich in water, the imprints can deform but later adapt to the original shape due to the elastic properties they possess. The advantages of using alginate include the low cost, a better tolerability on the part of the patient, the ease of manipulation, the short time needed for execution, the instrumentation and the very simple execution technique and possibility of detecting a detailed impression (even in the presence of undercuts) in a single step. A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database. Authors conducted a search of articles in written in English published from 2008 to 2018. All the relevant studies were included in the search with respect to the characteristics and evolution of new marine derived materials. Much progress has been made in the search for new marine derived materials. Conventional impression materials are different, and especially with the advent of digital technology, they have been suffering from a decline in research attention over the last few years. However, this type of impression material, alginates (derived from marine algae), have the advantage of being among the most used in the dental medical field.

Human dental pulp stem cells (hDPSCs), selected from the stromal-vascular fraction of dental pulp, are ecto-mesenchymal stem cells deriving from neural crests, successfully used in human bone tissue engineering. For their use in human therapy GMP procedures are required. For instance, the use of fetal bovine serum (FBS) is strongly discouraged in clinical practice due to its high risk of prions and other infections for human health. Alternatively, clinical grade sera have been suggested, including the New Zealand FBS (NZ-FBS). Therefore, the aim of this study was to evaluate the behavior of hDPSCs expanded in culture medium containing NZ-FBS. Since it was widely demonstrated hDPSCs display relevant capabilities to differentiate into osteogenic and angiogenic lineages, we performed a comparative study to assess if these features are also retained by cultivating the cells with a safer serum never tested on this cell line. hDPSCs were grown using NZ-FBS and conventional (C-FBS) for 7, 14 and 21 days, in both 2D and 3D cultures. Growth curves, expression of bone-related markers, calcification and angiogenesis were evaluated. NZ-FBS induced significant cell growth with respect to C-FBS and promoted an earlier increase expression of osteogenic markers, in particular of those involved in the formation of mineralized matrix (BSP and OPN) within 14 days. In addition, hDPSCs cultured in presence of NZ-FBS were found to produce higher mRNA levels of the angiogenic factors, such as VEGF and PDGFA. Taken together, our results highlight that hDPSCs proliferate, enhance their osteogenic commitment and increase angiogenic factors in NZ-FBS containing medium. These features have also been found when hDPSC were seeded on the clinical-grade collagen I scaffold (Bio-Gide®), leading to the conclusion that for human therapy some procedures and above all the use of GMP-approved materials have no negative impact.

The purpose of the present study was to see if there is a correlation between the effect of interferons in crevicular fluid and periodontitis, evaluating literature. Interferon gamma (IFN-γ) is an immunoregulatory cytokine that, when activated by its receptor, plays an important role in the activation of inflammatory processes, which are the basis of periodontal disease. Stem cells in the periodontal ligament, like stem cells from other tissues, have immunomodulatory capacity and are regulated by some cytokines such as interferon-γ (IFN-γ). The study searched MEDLINE databases from 2008 to 2018. Clinical human in vitro and in vivo studies had reported a correlation between interferon and periodontitis. The initial search obtained 359 citations. After screening and determination of eligibility, nine articles were included in the review. Significant (p < 0.05) increases in IFN-γ gene expression were observed in some studies in the chronic periodontitis group. In some cases it was suggested that molecular mechanisms underlie the possible roles of IFN-γ in the inhibition of osteoclastogenesis. Neopterin belongs to the chemical group known as pteridines. It is synthesised by human macrophages upon stimulation with the interferon-gamma. Neopterin concentrations in body fluids are high in the case of infections, immune diseases or graft rejection. In the chronic periodontitis group, this marker is significantly higher. These studies underlined the clinical evidence between interferons in the crevicular fluid and inflammatory response of periodontitis. However, there is a lack of scientific evidence that could lead the clinician to an interferon-modulated therapy because of periodontitis.

The aim of the present investigation was to systematically analyse the literature on the facial bone reconstruction defect using marine collagen or not and to evaluate a predictable treatment for their clinical management. The revision has been performed by searched MEDLINE and EMBASE databases from 2007 to 2017. Clinical trials and animal in vitro studies that had reported the application of bone substitutes or not for bone reconstruction defect and using marine collagen or other bone substitute material were recorded following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The first selection involved 1201 citations. After screening and evaluation of suitability, 39 articles were added at the revision process. Numerous discrepancies among the papers about bone defects morphology, surgical protocols, and selection of biomaterials were found. All selected manuscripts considered the final clinical success after the facial bone reconstruction applying bone substitutes. However, the scientific evidence regarding the vantage of the appliance of a biomaterial versus autologous bone still remains debated. Marine collagen seems to favor the dimensional stability of the graft and it could be an excellent carrier for growth factors.

Background. Lichen sclerosus (LS) is an autoimmune inflammatory skin disease that leads to tissue sclerosis. Actually, the first-line treatment consists of local steroid as clobetasol propionate (CP). Polydeoxyribonucleotide (PDRN) has demonstrated anti-inflammatory effects through the reduction of cytokine production and growth stimulation of fibroblast. Objective. To evaluate the efficacy of intradermal administration of PDRN in male patients suffering from genital lichen sclerosus in addition to topical 0.05% CP, as compared to administering 0.05% CP without PDRN injection. Patients/Methods. A group of male patients (n = 28; aged 25 to 65) suffering from LS were observed during topical therapy or subdermal in addition to topical therapy. Disease activity at baseline was evaluated on Investigator’s Global Assessment (IGA) and the Dermatology Life Quality Index (DLQI). We used polydeoxyribonucleotide in a commercial preparation for human use and a topical CP emulsion. Results. After therapy, in all group A patients there has been a regression of most of clinical pathological signs, while there has been a moderate improvement in all group B patients. Conclusions. On site intradermal administration of PDRN, associated with CP 0.05% cream, seemed to be associated with a clinical improvement of lichen sclerosus better than CP used in single therapy.

The aim of this study was to evaluate the behavior of human Dental Pulp Stem Cells (DPSCs), as well as human osteoblasts, when challenged on a Biocoral scaffold, which is a porous natural hydroxyapatite. For this purpose, human DPSCs were seeded onto a three-dimensional (3D) Biocoral scaffold or on flask surface (control). Either normal or rotative (3D) cultures were performed. Scanning electron microscopic analyses, at 8, 24 and 48 h of culture showed that cells did not adhere on the external surface, but moved into the cavities inside the Biocoral structure. After 7, 15 and 30 days of culture, morphological and molecular analyses suggested that the Biocoral scaffold leads DPSCs to hook into the cavities where these cells quickly start to secrete the extra cellular matrix (ECM) and differentiate into osteoblasts. Control human osteoblasts also moved into the internal cavities where they secreted the ECM. Histological sections revealed a diffuse bone formation inside the Biocoral samples seeded with DPSCs or human osteoblasts, where the original scaffold and the new secreted biomaterial were completely integrated and cells were found within the remaining cavities. In addition, RT-PCR analyses showed a significant increase of osteoblast-related gene expression and, above all, of those genes highly expressed in mineralized tissues, including osteocalcin, OPN and BSP. Furthermore, the effects on the interaction between osteogenesis and angiogenesis were observed and substantiated by ELISA assays. Taken together, our results provide clear evidence that DPSCs differentiated into osteoblasts, forming a biocomplex made of Biocoral, ECM and differentiated cells.

This study retrospectively evaluated the influence of prosthetic features on marginal bone level changes around bone-level implants with an external hex connection. A total of 100 patients with 166 implants and cemented crowns were included. Demographic and clinical data were collected. Prosthetic features were radiographically evaluated, including emergence angle (EA), emergence profile (EP), crown-implant ratio (CIR), and abutment height. Marginal bone levels were measured on intraoral radiographs taken at baseline and after at least 1 year. The correlation between prosthetic features and marginal bone loss (MBL) was then investigated. The mean follow-up time was 43.94 months. Implant length varied between 5 and 13 mm. The mean height of the abutments used was 1.55 mm. EA measured an average 30.62 degrees (± 13.20) mesially and 29.45 degrees (± 13.07) distally. The CIR was 0.99 (± 0.26). The mean MBL was 0.19 mm on the mesial side and 0.20 mm on distal side of the implants. Significant positive associations emerged between MBL and implant length (P < .005) and with EA (P < .05). A convex profile of the crown was shown to be associated with a higher distal MBL (P = .025) compared to concave and str aight profiles. [ABSTRACT FROM AUTHOR]