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Background. The PI3Kδ inhibitor idelalisib given in combination with rituximab in relapsed/refractory chronic lymphocytic leukemia (R/R CLL) has been associated with an objective response in 81% of cases with a median PFS of 20.3 months in a phase-3 clinical trial (Sharman et al, JCO 2019). Because the efficacy of new drugs reported in clinical trials may not translate into similar results in the day-to-day practice, we performed an observational retrospective-prospective study on the efficacy and safety of idelalisib and rituximab (IR) in R/R CLL patients treated outside of clinical trials in Italian centers belonging to the GIMEMA group. Methods. R/R CLL patients treated with IR outside of clinical trials between July 2014 and May 2017 were enrolled. Treatment was initiated at symptomatic progression; treatment response and disease progression were assessed according to the NCI criteria. The data were extracted from the medical files and entered into case record forms (CRF) by each treating physician. Computerized and manual consistency checks were performed by the GIMEMA data center on newly entered forms and queries were issued in case of inconsistencies. The primary endpoint was progression-free survival (PFS), secondary endpoints were overall response rate (ORR), the percentage of patients on treatment at 12, 24 and 36 months, overall survival (OS) and response to the subsequent anti-leukemic treatment. Results. 149 R/R CLL patients from 35 Italian centers were included in the study. The baseline characteristics are shown in Table 1. At a median follow-up of 39.4 months, the median PFS was 22.9 months (95% CI 20.5-28.8). In univariate analysis, a shorter PFS was associated with ≥3 lines of therapy (p=0.0175) (Fig. 1a). The ORR (CR + PR) was 72.5%. Age ≤70 yrs (p=0.037) and a PS grade 3 during RI treatment were neutropenia (35% of cases), gastrointestinal disorders (17%), infections (17%) and transaminitis (6%). Conclusions. The results hereby observed show that the efficacy of IR in a cohort in a real-life RR/CLL with a long follow-up is superimposable to those reported in the pivotal clinical trial, suggesting that the patient population who received IR in the day-to-day clinical practice mirrored that enrolled in the trial. Advanced clinical stage and 3 or more previous lines of therapy were associated with shorter PFS and OS. Interestingly, PFS and objective measures of efficacy such as the proportion of patients still on treatment at 12, 24 and 36 months, as well as OS, were not influenced by the TP53 status. Furthermore, the majority of patents responded to the subsequent anti-leukemic treatment and relatively durable responses were observed in patients who discontinued IR due to toxicity. Disclosures Rigolin: Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Visentin:Janssen: Honoraria; Gilead: Honoraria; Abbvie: Honoraria. Coscia:Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Farina:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Gaidano:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Sunesys: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Murru:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Varettoni:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Other: Travel/accommodations/expenses; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel/accommodations/expenses. Sportoletti:Janssen: Honoraria; AbbVie: Honoraria. Laurenti:Janssen: Honoraria; Gilead: Honoraria; AbbVie: Honoraria; Roche: Honoraria. Marasca:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria. Marchetti:Takeda: Other: Sponsored meetings; Gilead: Consultancy; Novartis: Speakers Bureau; Amgen: Speakers Bureau; AbbVie: Other: Sponsored meetings; Pfeizer: Other: Sponsored meetings. Mauro:Jannsen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Octopharma: Consultancy; Astrazeneca: Membership on an entity's Board of Directors or advisory committees. Molica:Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Pane:Amgen: Consultancy, Other: Travel Expenses, Speakers Bureau; AbbVie: Consultancy, Other: Travel Expenses, Speakers Bureau; Daiichi Sankyo: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Other: travel expenses, Speakers Bureau; Novartis pharma SAS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Other: Travel Expenses; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gozzetti:Janssen: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria. Galieni:Celgene: Honoraria; Takeda: Honoraria; AbbVie: Honoraria; Janssen: Honoraria. Krampera:Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Trentin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria. Montillo:AbbVie: Honoraria, Speakers Bureau; F. Hoffmann-La Roche: Honoraria, Research Funding; Janssen: Honoraria, Speakers Bureau; Verastem: Honoraria; Gilead: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria. Foà:Incyte: Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees. Cuneo:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a frequent orofacial malformation. The comparison of concordance rate observed in monozygotic and dizygotic twins supports high level of heritability and a strong genetic component. However, phenotype concordance for orofacial cleft in monozygotic twins is about 50%. The aim of the present investigation was to detect postzygotic events that may account for discordance in monozygotic twins. High-density SNP microarrays hybridization was used to genotype two pairs of monozygotic twins discordant for nsCL/P. Discordant SNP genotypes and copy number variants were analyzed to identify genetic differences responsible of phenotype discrepancy. A number of differences were observed, none involving known nsCL/P candidate genes or genomic regions. Considering the limitation of the study, related to the small sample size and to the large-scale investigation method, the results suggest that the detection of discordant events in other monozygotic twin pairs would be remarkable and warrant further investigations.

Several distinct classes of drugs, such as anticonvulsants, immunosuppressants, and calcium channel blockers, caused gingival overgrowth. One of the main drugs associated with the gingival overgrowth is the anti-epileptic such as phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. In our study, we evaluate the effect of phenytoin, a drug whose active substance is phenytoin, on gingival fibroblasts of healthy volunteers. Gene expression of 29 genes was investigated in gingival fibroblasts’ cell culture treated with phenytoin compared with untreated cells. Among the studied genes, only 13 genes (CXCL5, CXCL10, CCR1, CCR3, CCR5, CCR6, IL-1A, IL-1B, IL-5, IL-7, IL-6R, BMP-2, and TNFSF-10) were statistically significant. All but one gene resulted downregulated after 24 h of treatment with phenytoin. BPM2 was the only, although weakly, up-expressed gene. Probably, we have not highlighted overexpression of the other inflammatory molecules because the study was performed on healthy people. Many studies show that phenytoin induces the overexpression of these cytokines but, probably, in our study, the drug does not have the same effect because we used gingival fibroblasts of healthy people.

Background: Craniofacial morphogenesis is the result of an intricate multistep network of tightly controlled spatial and temporal signalling that involves several molecules and transcription factors organized into highly coordinated pathways. Any alteration in even one step of this delicate process can lead to congenital malformations such as cleft palate. One of the first steps in embryonal orofacial development is the migration of cells from the neural crests to the branchial arches. Next, the cells have to proliferate, differentiate, move and connect to each other in order to correctly form the palate. Cell contraction, promoted by the interaction of non-muscle myosin II and actin A, is a crucial step in morphogenesis and is regulated by ROCK1 protein. Methods: A family-based association study was carried out in order to verify whether or not genetic variants of ROCK1 were associated with non-syndromic cleft palate (nsCP). Two cohorts from Italy and Iran, a total of 189 nsCP cases and their parents were enrolled. Results: The rs35996865-G allele was under-transmitted in cases of nsCP [P=.006, odds ratio (OR) = 0.63 (95% CI 0.45-0.88)]. Conclusion: This investigation reveals for the first time data supporting a role for ROCK1 in nsCP aetiology.

Gabapentin is one of the most used drugs to treat postoperative pain with antihyperalgesic properties and has a unique mechanism of action, which differentiates it from other commonly used drugs. Various studies have shown that the perioperative use of gabapentin reduces postoperative pain. In our study, fragments of gingival tissue of healthy volunteers were collected during operation. Gene expression of 29 genes was investigated in gingival fibroblasts cell culture treated with gabapentin, compared with untreated cells. Of the different chemokines and interleukins studied, only 10 were statistically significant (CCL1, CCR1, CCR4, CCR5, CCR6, ILI1A, ILI1B, IL5, IL6R, TNFSF10). The overexpression of these cytokines, obtained in many studies, leads us to think that gabapentin can interact and cause post-inflammatory gingival hyperplasia, but, probably, in our study the gabapentin has not the same effect, because we used gingival fibroblasts of healthy people.

Orofacial clefts are common congenital defects whose prevalence differs between geographical regions and ethnic groups. The inheritance is complex, involving the contribution of both genetic and environmental factors. The involvement of genes belonging to the folate pathway is still matter of debate, with strong evidences of association and conflicting results. After demonstrating the contribution, for a sample from the Italian population, of common mutations mapping on three genes of the folate pathway, our group tried to unravel their contribution in independent sample studies with different ethnicity. In the present investigation a set of 34 triads with oral cleft from Nassiriya, Iraq, has been genotyped for rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS polymorphisms. Association analysis evidenced a decreased risk of cleft for children carrying the 667G allele at TCN2 gene ( P = 0.02). This evidence further supported the relationship between polymorphisms of folate related genes and oral clefts, and outlined the relevance of studying populations having different ethnicity.

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast’s function in gingival overgrowth. To determine whether amlodipine alters the fibrotic response, we investigated its effects on treated gingival fibroblast gene expression as compared with untreated cells. Materials and Methods: Fibroblasts from ATCC® Cell Lines were incubated with amlodipine. The gene expression levels of 12 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway was investigated in treated fibroblasts cell culture, as compared with untreated cells, by real time PCR. Results: Most of the significant genes were up-regulated. (CTNND2, COL4A1, ITGA2, ITGA7, MMP10, MMP11, MMP12, MMP26) except for COL7A1, LAMB1, MMP8, and MMP16, which were down-regulated. Conclusion: These results seem to demonstrate that amlodipine has an effect on the extracellular matrix of gingival fibroblast. In the future, it would be interesting to understand the possible effect of the drug on fibroblasts of patients with amlodipine-induced gingival hyperplasia. Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast’s function in gingival overgrowth. To determine whether amlodipine alters the fibrotic response, we investigated its effects on treated gingival fibroblast gene expression as compared with untreated cells. Materials and Methods: Fibroblasts from ATCC® Cell Lines were incubated with amlodipine. The gene expression levels of 12 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway was investigated in treated fibroblasts cell culture, as compared with untreated cells, by real time PCR. Results: Most of the significant genes were up-regulated. (CTNND2, COL4A1, ITGA2, ITGA7, MMP10, MMP11, MMP12, MMP26) except for COL7A1, LAMB1, MMP8, and MMP16, which were down-regulated. Conclusion: These results seem to demonstrate that amlodipine has an effect on the extracellular matrix of gingival fibroblast. In the future, it would be interesting to understand the possible effect of the drug on fibroblasts of patients with amlodipine-induced gingival hyperplasia.

Periconceptional folic acid supplementation can reduce the risk of inborn malformations, including orofacial clefts. Polymorphisms of MTHFR, TCN2, and CBS folate-related genes seem to modulate the risk of cleft lip with or without cleft palate (CL/P) in some populations. CL/P and cleft palate only (CPO) are different malformations that share several features and possibly etiological causes. In the present investigation, we conducted a family-based, candidate gene association study of non-syndromic CPO. Three single nucleotide polymorphisms, namely, rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were investigated in a sample that included 129 Italian and 65 Asian families. No evidence of association between the three genotyped polymorphisms and CPO was found in the Italian and Asian cases, indeed the transmission disequilibrium test did not detect any asymmetry of transmission of alleles. This investigation, although with some limitation, further supports that CL/P and CPO diverge in their genetic background.

The objective of this work was a systemic evaluation of the anodizing treatment in a β-type Ti-15Mo alloy to grow a TiO2 nanostructured layer for osseointegration improvement. The technical viability of the surface modification was assessed based on the resistance to mechanical fatigue, electrochemical corrosion, and biological response. By using an organic solution of NH4 F in ethylene glycol, a well-organized array of 90 nm diameter nanotubes was obtained with a potential of 40 V for 6 h, while undefined nanotubes of 25 nm diameter were formed with a potential of 20 V for 1 h. Nevertheless, the production of the 90 nm diameter nanotubes was followed by micrometer pits that significantly reduced the fatigue performance. The undefined nanotubes of 25 nm diameter, besides the greater cell viability and improved osteoblastic cell differentiation in comparison to the as-polished surface, were not deleterious to the fatigue and corrosion properties. This result strengthens the necessity of an overall evaluation of the anodizing treatment, particularly the fatigue resistance, before suggesting it for the design of implants. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 86-96, 2019.

The objective of this study was to evaluate the effects of lozenges-containing Lactobacillus reuteri as an adjuvant treatment of peri-implant mucositis and to detect the level of L. reuteri colonization in the peri-implant tissues of treated patients. A total of 10 patients were selected. Subjects with at least one implant affected by peri-implant mucositis, with gingival index (GI) of ⩾2 in each quadrant, evaluated at the buccal aspect of all teeth. Patients included in the study were partially edentulous and had implants with mucositis or peri-implantitis. Implants with radiographic bone loss of ⩾5 mm and/or ⩾50% of the implant length were excluded, and only one implant per patient was included. Each patient received L. reuteri–containing lozenges. Microbiological sampling was performed at baseline and on day 28 and analysed by polymerase chain reaction (PCR). Our results indicate that the use of the probiotic did not influence the peri-implant microbiota in a statistically significant way, although there was a reduction in the number of periodontal and peri-implant species. The lack of statistically significant microbiological changes could be explained either by the small sample population or by the short evaluation period. Therefore, the poor colonization of L. reuteri in the peri-implant pockets can be explained by the different anatomical and histological characteristics of the interface of the dental–gingival unit with respect to the periodontal sulcus. The administration of a daily lozenge of L. reuteri for 4 weeks had a limited effect on the microbiological analysis. Probiotics provide an alternative therapeutic approach to consider in the prevention and treatment of peri-implant diseases, but further long-term prospective studies with standardized variables are needed.

MicroRNAs have recently been proposed as non-invasive biomarkers in Oral Squamous Cell Carcinoma (OSCC). The aim of this study was to analyze the expression of a panel of miRNAs in epithelial cells collected by oral brushing from OSCCs from regenerative areas after OSCC surgical resection and from their respective normal distant mucosa. Oral brushing specimens were collected from 24 healthy donors, 14 OSCC patients with specimens from tumour and normal distant mucosa, and from 13 patients who had OSCC resection, with samples from regenerative areas after OSCC resection and normal distant mucosa. Expression levels of eight targets (miR-21, miR-375, miR-345, miR-181b, miR-146a, miR-649, miR-518b, and miR-191) were evaluated by real-time Polymerase Chain Reaction (PCR). A highly significant between-group difference was found for miR-21 (F = 6.58, p &lt, 0.001), miR-146a (F = 6.974, p &lt, 0.001), and miR-191 (F = 17.07, p &lt, 0.001). The major difference was observed between samples from healthy donors and from OSCC brushing, whereas no significant differences were observed between areas infiltrated by OSCC and their respective normal distant mucosa. Furthermore, altered expression of miR-146a and miR-191 was also observed in regenerative areas after OSCC resection. Conclusions: Oral brushing could be proposed as a noninvasive method to study microRNA expression in oral mucosa in OSCC patients.

BACKGROUND Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common congenital malformations in humans. Its average global incidence is 1.7 per 1000 live births, with wide variation according to geographical location and ethnicity. Its etiology involves both genetic and environmental factors. The aim of the present study was to confirm genetic association of a selection of 15 candidate nsCL/P loci using an independent sample of the Italian population. METHODS At least one single-nucleotide polymorphism (SNP) for each locus was genotyped in 380 nuclear trios. RESULTS Transmission disequilibrium analysis revealed significant associations for three variants at two loci (8q24 and 1p22). Two SNPs at 8q24 showed the strongest level of association, the rs987525 (PTDT = 6.81 × 10(-6) ; homozygous relative risk = 3.60 [95% confidence interval, 2.12-6.13]), and the rs17241253 (PTDT = 1.03 × 10(-5) ; homozygous relative risk = 3.75 [95% confidence interval, 2.10-6.67]). Four additional loci (at 1q32, 3q12, 8q21, and 10q25) achieved nominally significant p-values. Two SNPs at 1p36 achieved p-values of

Objective: Orofacial development is a complex process subjected to failure impairing. Indeed, the cleft of the lip and/or of the palate is among the most frequent inborn malformations. The JARID2 gene has been suggested to be involved in non-syndromic cleft lip with or without cleft palate (nsCL/P) etiology. JARID2 interacts with the polycomb repressive complex 2 (PRC2) in regulating the expression patterns of developmental genes by modifying the chromatin state. Materials and methods: Genes coding for the PRC2 components, as well as other genes active in cell differentiation and embryonic development, were selected for a family-based association study to verify their involvement in nsCL/P. A total of 632 families from Italy and Asia participated to the study. Results: Evidence of allelic association was found with polymorphisms of SNAI1; in particular, the rs16995010-G allele was undertransmitted to the nsCL/P cases [P = 0.004, odds ratio = 0.69 (95% C.I. 0.54–0.89)]. However, the adjusted significance value corrected for all the performed tests was P = 0.051. Conclusions: The findings emerging by the present study suggest for the first time an involvement of SNAI1 in the nsCL/P onset. Clinical relevance: Interestingly, SNAI1 is known to promote epithelial to mesenchymal transition by repressing E-cadherin expression, but it needs an intact PRC2 to act this function. Alterations of this process could contribute to the complex etiology of nsCL/P.

The objective of this work was a systemic evaluation of the anodizing treatment in a β-type Ti-15Mo alloy to grow a TiO

Gene expression and cell behavior are regulated by several factors, including small non-coding RNAs. MicroRNAs affecting cell growth, differentiation, and apoptosis are thought to play an important role in tumorigenesis. The levels of miR-146 appear to be associated with cancer development and progression, including that of oral squamous cell carcinoma. The aim of this investigation was to ascertain whether the single nucleotide polymorphism, rs2910164, mapping in the MIR146A gene, has a role in oral squamous cell carcinoma progression. A genetic association study was performed with a sample set of 346 oral squamous cell carcinomas collected in Italy. Our data indicate that the rs2910164 polymorphism is not associated with tumor development. However, a slight increase in the frequency of the variant allele was observed in Stage II tumors. Further investigations are needed to verify a possible role of the variant allele or rs2910164 in oral squamous cell carcinoma progression.

Studies aimed at evidencing genetic causes for neural tube defect (NTD) occurrence have often provided the inspiration for orofacial cleft aetiology investigations. The correlation between the two congenital malformations is provided by the similar incidence timing and the involvement of structures localized in the midline of the embryo. This connection is corroborated by the existence of a number of genes involved in both malformations. In this article, we considered the dihydrofolate reductase ( DHFR ) gene, previously seen implicated in NTDs, as a candidate for cleft lip with or without cleft palate (CL/P) risk. Four SNPs mapping on the DHFR gene were genotyped for 400 Italian CL/P triads, using TaqMan ® approach. The rs1677693 provided evidence of association, even if at borderline level ( P value 0.049). In particular, the variant allele seems to have a protective effect OR = 0.80 (95% C.I. 0.64–0.99). Moreover, the combination of rs1677693(A)-rs1650723(G) alleles showed a significant association OR 0.64 (95% C.I. 0.47–0.86) ( P value = 0.006). This represents the first attempt to demonstrate a role for DHFR in CL/P aetiology, howbeit the study of such gene deserves a deepening.

Background. Titanium is the gold standard for dental implants, since it has demonstrated excellent biocompatibility and osseointegration properties. The rate of osseointegration is however affected by the surface morphology and peri-implant infections may affect fixture and the long-term osseointegration outcome. Thus chemical composition of a coating at the implant-abutment junction (IAJ) surface is expected to play a key role in preventing bacterial infection. Purpose. In the present study a new antimicrobial polysiloxane coating functionalized with chlorexidine digluconate (PXT) has been tested in an in vitro model. Materials and methods. Twenty implants were coated in the internal chamber with PXT and twenty were used as controls. Results and conclusions. Ten of the coated implants, preliminarily tested against Gram positive and negative bacteria and fungi, showed a complete inactivation of the microbial species after a 15 min contact. On the remaining ten treated implants a series of microbiological tests and PCR analysis, after contamination of the implant external medium, in which the implant have been immersed, with genetic modified Tannerella forsythia (TF) and Porphyromonas Gingivalis (PG), leads to the conclusion that the coating is capable of inactivating the microbial species penetrating the internal of the implant through the implant abutment junction.

Purpose The aim of our study is to evaluate the ability of a new type of implant (Konus Implant System®, Industrie biomediche e farmaceutiche, Italy) to isolate the internal of an implant-abutment connection from the external environment. Materials and methods To identify the capability of the implant to protect the internal space from the external environment, the passage of genetically modified Escherichia coli across implant-abutment interface was evaluated. Implants were immerged in a bacterial culture for twenty-four hours and then bacteria amount was measured inside implant-abutment interface with Real-time PCR. Results Bacteria were detected inside all studied implants, with a median percentage of 18% for Porphiromonas Gingivalis and 19% for Tannerella Forsythia. Conclusion The reported results are similar to previous work. Konus Implant System® showed bacterial leakage similar respect others implant systems (18% Porphiromonas Gingivalis, 19% Tannerella Forsitya versus 20% of Bicon© and Ankylos ® systems). In spite of the limits of our study, none two-piece implant system has been demonstrated to perfectly close the gap between implant and abutment.

Purpose. Implant dentistry has become one of the most successful dentistry techniques for replacing missing teeth. The success rate of implant dentistry is above 80%. However, peri-implantitis is a later complication of implant dentistry that if untreated, can lead to implant loss. One of the hypotized causes of peri-implantis is the bacterial leakage at the level of implant-abutment connection. Bacterial leakage is favored to the presence of a micro gap at the implant-abutment interface, allowing microorganisms to penetrate and colonize the inner part of the implant leading to biofilm accumulation and consequently to peri-implantitis development. Materials and methods. To identify the capability of the implant to protect the internal space from the external environment, the passage of genetically modified Escherichia coli across implant-abutment interface was evaluated. Implants were immerged in a bacterial culture for twenty-four hours and then bacteria amount was measured inside implant-abutment interface with Real-time PCR. Results. Bacteria were detected inside all studied implants, with a median percentage of 9%. Conclusions. The reported results are better to those of previous studies carried out on different implant systems. Until now, none implant-abutment system has been proven to seal the gap between implant and abutment.

Nowadays, research on orthopedic and dental implants is focused on titanium alloys due to their appropriated mechanical properties and corrosion resistance in the body environment. Another important aspect to be investigated is their surface topography, which is very important to osseointegration. The aim of this study was to assess dental pulp stem cells response to different titanium surface topography modified. Mesenchymal stem cell marker ENG was significantly decreased in stem cells cultivated in modified titanium surface respect to machined titanium surface, indicating the differentiation effect of this biomaterial on stem cells. The obtained results can be relevant to better understand the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects.

The molecular basis of orofacial development is largely unknown and needs to be unravelled. Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial malformation, with an incidence of about 1/700 live births, although variable according to ethnicity. Being a multifactorial disease, it arises as a result of an interplay between genetic and environmental factors. Several approaches have been developed to identify susceptibility genes. Genes belonging to the folate/homocysteine pathway are attracting increasing interest because folate supplementation before and during early pregnancy can reduce the risk of NSCL/P. We performed a family based association study in order to assess if a genetic variant of RFC1 could be involved in NSCL/P onset. We genotyped 404 unrelated probands and their relatives for three biallelic polymorphic variants (rs1051266, rs4818789 and rs3788205), that were selected because they produced conflicting results on previous investigations. Evidence of association was found between the investigated polymorphisms and NSCL/P in our sample of the Italian population, albeit with weak significance levels. Results from this investigation provided a support of previous studies suggesting a role of RFC1 in NSCL/P aetiology, reinforcing the concept that genetic predisposition to NSCL/P varies enormously within different ethnic groups.

none 9 si Objective Orofacial clefts (OFCs) are one of the most common birth defects in humans. They are the subject of a number of investigations aimed at elucidating the bases of their complex mode of inheritance involving both genetic and environmental factors. Genes belonging to the folate pathway have been among the most studied. The aim of the investigation was to replicate previous studies reporting evidence of association between polymorphisms of folate related genes and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P), using three independent samples of different ancestry: from Tibet, Bangladesh and Iran, respectively. Design Specifically, the polymorphisms rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were tested. Results A decreased risk of NSCL/P was observed in patients presenting the C677T variant at MTHFR gene (relative risk for heterozygotes = 0.53; 95% confidence interval [C.I.] = 0.32-0.87). The investigated polymorphisms mapping at TCN2 and CBS genes did not provide any evidence of association. Conclusion Overall, these results indicate that NSCL/P risk factors differ among populations and confirm the importance of testing putative susceptibility variants in different genetic backgrounds. Martinelli, Marcella; Girardi, Ambra; Cura, Francesca; Nouri, Nayereh; Pinto, Valentina; Carinci, Francesco; Morselli, Paolo Giovanni; Salehi, Mansoor; Scapoli, Luca Martinelli, Marcella; Girardi, Ambra; Cura, Francesca; Nouri, Nayereh; Pinto, Valentina; Carinci, Francesco; Morselli, Paolo Giovanni; Salehi, Mansoor; Scapoli, Luca

Aim: The objective of this study was to compare the efficacy of supportive periodontal therapy (i.e., scaling and root planning [SRP]) alone versus Aquolab ® ozone therapy used in association with SRP in the treatment of chronic periodontitis in adult patients. Materials and Methods: A total of 20 patients with a diagnosis of chronic periodontitis (40 localized chronic periodontitis sites) were enrolled. None of these patients have previously received any surgical or nonsurgical periodontal therapy and demonstrated radiographic evidence of moderate bone loss. Two nonadjacent sites in separate quadrants were selected in each patient to verify treatment efficacy (split-mouth design). Microbial analysis was analyzed at baseline and the 7 th day after treatment. SPSS program and paired simple statistic t-test were used to detect statistically significant differences. Results: There was a statistically significant reduction of Tannerella forsythia loading in sites treated with ozone therapy respect to those treated with SPR alone. A similar trend was obtained also for additional 5 species and for total bacterial loading (CBT). These results were obtained with a single local application of ozone therapy just after SPR and with a molecular control 7 th day after treatment. Conclusion : Aquolab ® ozone therapy in is effective in reducing the CBT in pockets of patients affected by periodontitis. It is an efficacy medical device to be used as adjuvant therapy to be added to SRP in the management of moderate to severe chronic periodontitis.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect which is strongly associated with genetic factors. Previous studies in several populations showed a significant correlation between IRF6 rs642961 polymorphism and NSCL/P. The aim of this study is to indicate the correlation of IRF6 rs642961 polymorphism and NSCL/P in Iranian NSCL/P families. In this study, we analyzed IRF6 rs642961 genotype in 352 individuals from 102 Iranian nuclear families affected by NSCL/P using iPlex assay on a Sequenom MassARRAY platform. Hardy-Weinberg equilibrium and Mendelian error checking were performed by Haploview 4.2. Allelic association analysis was conducted with family-based association tests implemented in FBAT program v2.03. The family-based association analysis revealed no significant association between IRF6 rs642961 genotypes and an increased NSCL/P risk. In contrast to other Asian populations, our study indicates that the IRF6 rs642961 polymorphism cannot be a risk factor for NSCL/P in an Iranian population. Genetic factors have an important role in NSCL/P, among which interferon regulatory factor 6 (IRF6) has been reported as a risk factor for NSCL/P in several populations; however, our data indicated no significant association between IRF6 polymorphism and NSCL/P in an Iranian population. Objectives: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect which is strongly associated with genetic factors. Previous studies in several populations showed a significant correlation between IRF6 rs642961 polymorphism and NSCL/P. The aim of this study is to indicate the correlation of IRF6 rs642961 polymorphism and NSCL/P in Iranian NSCL/P families.Material and methods: In this study, we analyzed IRF6 rs642961 genotype in 352 individuals from 102 Iranian nuclear families affected by NSCL/P using iPlex assay on a Sequenom MassARRAY platform. Hardy–Weinberg equilibrium and Mendelian error checking were performed by Haploview 4.2. Allelic association analysis was conducted with family-based association tests implemented in FBAT program v2.03.Results: The family-based association analysis revealed no significant association between IRF6 rs642961 genotypes and an increased NSCL/P risk.Conclusions: In contrast to other Asian populations, our study indicates that the IRF6 rs642961 polymorphism cannot be a risk factor for NSCL/P in an Iranian population.Clinical relevance: Genetic factors have an important role in NSCL/P, among which interferon regulatory factor 6 (IRF6) has been reported as a risk factor for NSCL/P in several populations; however, our data indicated no significant association between IRF6 polymorphism and NSCL/P in an Iranian population.

Background The ATP-binding cassette transporter B1 (ABCB1) gene codes for a membrane efflux pump localized in epithelial cells. Together with other Permeability-glycoproteins in the small and large intestine, its product represents a barrier against xenobiotics, bacterial toxins, drugs and other substances introduced with diet, including carcinogens. The aim of this investigation was to verify the possible contribution of ABCB1 single nucleotide polymorphisms (SNPs) to the genetic risk of colorectal cancer (CRC). Results DNA obtained from the peripheral blood of 98 CRC patients and 100 healthy controls was genotyped for the three selected SNPs: 1236C > T (rs1128503), 2677G > T/A (rs2032582), and 3435C > T (rs1045642). Molecular data were analyzed to asses allele and haplotype association with CRC. No evidence of an association between ABCB1 alleles and CRC occurrence as a whole was found. However, ABCB1 showed either association with carcinoma of the sigmoid colon, and appeared able to influence the sex ratio among CRC patients. These two effects seemed to act independently based on multivariate analysis. We showed that ABCB1 polymorphisms were able to influence CRC susceptibility related to tumor localization and patient gender. Conclusions We suggest that sensitivity to undetermined risk factors could depend on the genetic background of ABCB1 locus, with a mechanism that also depends on patient gender. Electronic supplementary material The online version of this article (doi:10.1186/s12929-014-0089-8) contains supplementary material, which is available to authorized users.

Introduction: About 30% of the general population manifests periodontal disease (PD). Patients with parents with a compromised periodontal condition may need prosthetic or implantology treatment (PIT), therefore those patients are at increased risk of developing PD during or after dental treatment. Hence the use of a genetic test for identify those most at risk of PD and submit them to very closely oral hygiene protocols, is mandatory. PIT of these patients must be done safely having previously assessed the risk of developing PD. Polymorphisms of IL6 and IL10 constitute risk factors for chronic periodontitis, so the use of a genetic test is fundamental to ensure a correct preventive protocol and plaque control in healthy patients.

Purpose The light-emitting diodes (LEDs) have been applied in oral surgery for tissue stimulation and wound healing. Several Authors have highlighted that fibroblasts subjected to phototherapy have an increased viability, proliferation, biomodulation of inflammatory cytokines and genes expression. It remains to be determined which are the best irradiation parameters (energy, wavelength, power) for each type of cell in order to obtain the best bio-stimulation. The aim of this study was to investigate the effects of LED irradiation on primary human gingival fibroblast cells (HGF) on DSP, ELN, HAS1, ELANE, HYAL1, RPL13 genes activation using Real Time PCR. These genes activation is directly connected with elastin protein production and HGF functionality. Materials and methods Human gingival tissue biopsies were obtained from three healthy patients during extraction of teeth. The gingival pieces were fragmented with a scalpel and transferred in culture dishes for allow the cells growth. Human gingival fibroblasts at the second passage were seeded on multiple 6-well plates and were stimulated with three different light-emitting diodes (LEDs) fixture. After irradiation, the cells were trypsinized, harvested and lysed for RNA extraction. Genes expression was quantified using Real Time PCR. Results We didn't found significant differences in genes activation of HGF of the three different LEDs. The LED irradiation seems to be directly correlated with the elastin and hyaluronoglucosaminidase 1 genes activation that are directly connected with proteins production and HGF functionality. Conclusions HGF show an increased deposition of elastin as well as enhanced expression of collagen type I, which is the main protein related to the synthesis and of the collagen-rich matrix.

Titanium (Ti) is the most widely used material in implantology for dental, orthopedic and maxillofacial purposes due to their excellent biocompatibility and mechanical properties Several data suggest that implant anchorage to bone and soft tissue can be modulated by surface characteristics. Fibroblasts are the soft tissues cells concerned in producing extracellular matrix and collagen. The aim of this work is to compare five different titanium surface treatments in order to investigate which one had the best behavior using Human Fibroblast (HFb) after seven days in culture medium. The expression levels of some adhesion and traction-resistance related genes (COL11A1, COL2A1, COL9A1, DSP, ELN, HAS1, and TFRC) were analyzed using real time Reverse Transcription-Polymerase Chain Reaction (real time RT-PCR). Titanium disks can lead to implant integration promoting the production of protein involved in cell-cell and cell-matrix adhesion and in stress-resistance, required for a good outcome in dental implantology

HLA-G is believed to act as an anti-inflammatory molecule in Multiple Sclerosis (MS). The 3′ untranslated region of the HLA-G gene is characterized by two polymorphisms, DEL/INS14bp and +3142C>G, which control soluble HLA-G (sHLA-G) production. The influence of these two HLA-G variants on sHLA-G serum and cerebrospinal fluid (CSF) levels was investigated in 69 Relapsing-Remitting MS patients grouped in magnetic resonance imaging (MRI) inactive and active disease. Serum and CSF sHLA-G levels were more elevated in high than in low DEL/INS 14bp and +3142C>G sHLA-G producers and were different among the various combined HLA-G genotypes in both MRI inactive and active diseases. The highest and the lowest sHLA-G values were identified in MS patients with C/C,DEL/DEL and G/G,INS/INS genotypes, respectively. Our preliminary findings suggest that serum and CSF sHLA-G levels in MS could be influenced by HLA-G polymorphisms irrespective of the inflammatory microenvironment.

Purpose: The aim of this study was to investigate the effect of a new anatase coating with antibacterial properties (Bactercline anatase coating [BAC]) on dental implants in the commitment of stem cells derived from adipose tissue to osteoblasts. Materials and Methods: Using real-time reverse transcription polymerase chain reaction, the quantitative expression of specific genes, such as transcriptional factors (runx2 and sp7), bone-related genes (spp1, col1a1, col3a1, alpl, and fosl1), and mesenchymal stem cells marker (eng), was examined. Results: BAC caused induction of bone-related genes such as sp7, fosl1, alpl, and spp1. In contrast, the expression of runx2, col3a1, and col1a1 was decreased in stem cells treated with BAC with respect to untreated cells. Conclusion: The obtained results are relevant to better understand the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects. Copyright © 2012 by Lippincott Williams & Wilkins.