Effect of Simulated Mastication on the Retention of Locator Attachments for Implant-Supported Overdentures: An In Vitro Pilot Study.

PURPOSE: Limited information is currently available relative to the effect of masticatory loads on the retentive properties of Locator attachments. The aims of this in vitro study were to assess and compare the effect of simulated mastication on the retention of white, pink, and blue Locator inserts for overdentures retained by 2 implants. MATERIALS AND METHODS: Thirty specimens simulating a nonanatomic edentulous flat ridge with two implants and an overdenture were divided into 3 groups according to the color of the fitted insert: transparent clear group (n = 10), pink group (n = 10), and blue group (n = 10). Retention forces were measured in an axial direction initially and after 100,000 cycles of simulated masticatory loads. One-way ANOVA followed by Tukey's post hoc tests were used to compare retention values and percentage retention loss between the 3 groups with significance set at p = 0.05. RESULTS: The 3 groups presented significant differences in retention at baseline (9.95 ± 1.91 N, 15.43 ± 4.08 N, and 41.73 ± 9.29 N for the blue, pink, and clear groups, respectively) and after simulated mastication (6.37 ± 2.64 N, 14.00 ± 3.89 N, 38.20 ± 5.11 N for the blue, pink, and clear groups, respectively). Within the same group, cyclic loading did not significantly affect retention in the clear and pink groups, while the blue inserts showed a significant retention loss (-37%) after loading. CONCLUSIONS: The results suggest that short-term simulated mastication affects the extra-light blue inserts but not the more-retentive inserts.

Correlation between Temporomandibular Joints and Nasal Cavity Width in Growing Patients after Rapid Maxillary Expansion.

AIM: The study tests the correlation between the enlargement of the nasal cavity width, interglenoid fossa distance, and intercondylar distance after rapid maxillary expansion (RME) in growing patients. MATERIALS AND METHODS: Cone beam computed tomography (CBCT) was performed for 25 patients presenting a bilateral crossbite (11 males, 14 females, and mean age 11.6 ± 1.6 years) at baseline (T0) and at 6 months after RME (T2), T1 being the end of expander activation. Images were digitized for linear measurements using specific software. Values were compared at the nasal width, interglenoid fossa distance, and intercondylar distance to test the correlation in the transverse dimension. RESULTS: At T0, a correlation already existing between the interglenoid fossa distance and the intercondylar distance persisted at T2. The correlation between the nasal cavity width and interglenoid fossa distance nonexistent at T0 ended toward statistically significant at T2. Additionally, the lateral position of the condyles was not correlated with the nasal cavity width neither at T0 or T2. CONCLUSION: A correlation between the interglenoid fossa distance and intercondylar distance was exhibited 6 months after RME. The correlation between the nasal cavity width and interglenoid fossa distance was close to significant at T2.

Contribution of capsaicin-sensitive innervation to the continuous eruption of the rat mandibular incisors.

A major component of tooth innervation is made of capsaicin-sensitive primary afferents (CSPA). These fibers play a key role in tooth pain and inflammation; little is known, however, about the role of CSPA in tooth eruption. The aim of this study was to examine the role of the capsaicin-sensitive afferents in the process of eruption of intact rat incisors. CSPA fibers in several rat groups, were subjected to one of the following experimental procedures: systemic chemical ablation, systemic ablation followed by chemical sympathectomy and localized activation. The observed effects on incisor eruption were compared to those made on controls. The total amount of eruption in control/naïve rats, measured over a total period of 144 h, was 3.18 ± 0.07 mm and decreased to 2.43 ± 0.08 mm (n = 7; p < 0.001) following systemic ablation of CSPA. Further decrease to 2.24 ± 0.08 mm (n = 7; p < 0.001) was noticed when chemical sympathectomy was added to CSPA ablation. The average rate of eruption was 1.7 ± 0.25 mm following CSPA activation, compared to an average of 0.8 ± 0.07 mm for controls (n = 7; p < 0.001). Capsaicin sensitive fibers play an important role in tooth homeostasis, and intact neural supply is required for tooth growth under normal conditions.

In Vitro Effect of Mastication on the Retention and Wear of Locator Attachments in a Flat Mandibular Ridge Model.

PURPOSE: The effect of masticatory loads on the retention of overdenture attachments is poorly documented. The aim of this in vitro study is to assess the effect of simulated mastication on the retentive properties and dimensions of Locator inserts. MATERIALS AND METHODS: 30 specimens simulating nonanatomic edentulous flat ridges with two implant replicas each were fabricated. Overdenture units were connected to the implants with Locator attachments and 3 types of inserts: transparent (Group T; n = 10 pairs), pink (Group P; n = 10 pairs), and blue (Group B; n = 10 pairs). The overdenture units were subjected to simulated bi-axial masticatory loads of 68.6 N. Locator retention was assessed using axial dislodging forces at baseline (T0) and following 100,000 (T1) and 200,000 (T2) masticatory cycles. The inner diameter of the insert (XY) and the diameter of the central core (AB) were measured under stereomicroscope at T0 and T2. Retention changes and dimensional variations of the inserts were statistically analyzed. RESULTS: The 3 groups showed significantly different retentions with the highest values recorded for group T followed by group P, and finally group B at T0, T1, and T2. Groups T and P were not affected by loading while group B showed a significant mean retention loss from T0 to T1. XY and AB were significantly different between the 3 color-coded inserts at baseline and at T2. No correlation could be established between retention changes and dimensional variations of the 3 types of inserts. CONCLUSIONS: Within the limitations of this in vitro study, simulated mastication seems to significantly affect the extra-light blue Locator inserts but not the more-retentive ones. The transparent and pink inserts may require less frequent replacements and could therefore be recommended under clinical conditions.

Effect of Rapid Maxillary Expansion on Condyle-fossa Relationship in Growing Patients.

AIM: This study tests whether rapid maxillary expansion (RME) exerts long term effects on interglenoid fossa distance and condyle fossa relationship. MATERIALS AND METHODS: Consecutive growing patients aged 8 to 13 years were allocated either to the RME group or control group. Cone-beam computed tomography was performed at baseline and at 6 months. Specific software was used to determine fixed landmarks. Multivariate Analysis of Covariance (MANCOVA) models were used, with time by group interaction, using age as a covariate. RESULTS: Twenty-seven patients with a mean age of 11.4 ± 1.5 years were included. There was an overall significant group by time interaction (p = 0.012, effect size 0.59). Change in the lateral position of the glenoid fossa, the primary outcome, was reached (p = 0.008, effect size 0.258). Change in the laterolateral position of the center of the condyle, and the co-primary outcome was also significant (p = 0.011, effect size = 0.24). Nasal cavity width increased (p = 0.065, effect size = 0.14). There was an initial asymmetry in the horizontal position of the condyles that was carried on with no effect of RME. CONCLUSION: Rapid maxillary expansion (RME) produces a significant increase in the interglenoid fossa distance and displacement of the mandibular condyles at 6 months in growing patients compared to a control group. CLINICAL SIGNIFICANCE: The current study shows that RME is effective during growth, widening the interglenoid fossa distance and the lateral positions of the condyles and eventually enlarging the nasal cavity, without causing asymmetry.

Breaking down the Contradictory Roles of Histone Deacetylase SIRT1 in Human Breast Cancer.

Breast cancer (BC) is the most common type of cancer in women worldwide; it is a multifactorial genetic disease. Acetylation and deacetylation are major post-translational protein modifications that regulate gene expression and the activity of a myriad of oncoproteins. Aberrant deacetylase activity can promote or suppress tumorigenesis and cancer metastasis in different types of human cancers, including breast cancer. Sirtuin-1 (SIRT1) is a class-III histone deacetylase (HDAC) that deacetylates both histone and non-histone targets. The often-described 'regulator of regulators' is deeply implicated in apoptosis, gene regulation, genome maintenance, DNA repair, aging, and cancer development. However, despite the accumulated studies over the past decade, the role of SIRT1 in human breast cancer remains a subject of debate and controversy. The ambiguity surrounding the implications of SIRT1 in breast tumorigenesis stems from the discrepancy between studies, which have shown both tumor-suppressive and promoting functions of SIRT1. Furthermore, studies have shown that SIRT1 deficiency promotes or suppresses tumors in breast cancer, making it an attractive therapeutic target in cancer treatment. This review provides a comprehensive examination of the various implications of SIRT1 in breast cancer development and metastasis. We will also discuss the mechanisms underlying the conflicting roles of SIRT1, as well as its selective modulators, in breast carcinogenesis.

TIP60: an actor in acetylation of H3K4 and tumor development in breast cancer.

AIM: The acetyltransferase TIP60 is reported to be downregulated in several cancers, in particular breast cancer, but the molecular mechanisms resulting from its alteration are still unclear. MATERIALS & METHODS: In breast tumors, H3K4ac enrichment and its link with TIP60 were evaluated by chromatin immunoprecipitation-qPCR and re-chromatin immunoprecipitation techniques. To assess the biological roles of TIP60 in breast cancer, two cell lines of breast cancer, MDA-MB-231 (ER-) and MCF-7 (ER+) were transfected with shRNA specifically targeting TIP60 and injected to athymic Balb-c mice. RESULTS: We identified a potential target of TIP60, H3K4. We show that an underexpression of TIP60 could contribute to a reduction of H3K4 acetylation in breast cancer. An increase in tumor development was noted in sh-TIP60 MDA-MB-231 xenografts and a slowdown of tumor growth in sh-TIP60 MCF-7 xenografts. CONCLUSION: This is evidence that the underexpression of TIP60 observed in breast cancer can promote the tumorigenesis of ER-negative tumors.

SIRT1-dependent epigenetic regulation of H3 and H4 histone acetylation in human breast cancer.

Breast cancer is the most frequently diagnosed malignancy in women worldwide. It is well established that the complexity of carcinogenesis involves profound epigenetic deregulations that contribute to the tumorigenesis process. Deregulated H3 and H4 acetylated histone marks are amongst those alterations. Sirtuin-1 (SIRT1) is a class-III histone deacetylase deeply involved in apoptosis, genomic stability, gene expression regulation and breast tumorigenesis. However, the underlying molecular mechanism by which SIRT1 regulates H3 and H4 acetylated marks, and consequently cancer-related gene expression in breast cancer, remains uncharacterized. In this study, we elucidated SIRT1 epigenetic role and analyzed the link between the latter and histones H3 and H4 epigenetic marks in all 5 molecular subtypes of breast cancer. Using a cohort of 135 human breast tumors and their matched normal tissues, as well as 5 human-derived cell lines, we identified H3k4ac as a new prime target of SIRT1 in breast cancer. We also uncovered an inverse correlation between SIRT1 and the 3 epigenetic marks H3k4ac, H3k9ac and H4k16ac expression patterns. We showed that SIRT1 modulates the acetylation patterns of histones H3 and H4 in breast cancer. Moreover, SIRT1 regulates its H3 acetylated targets in a subtype-specific manner. Furthermore, SIRT1 siRNA-mediated knockdown increases histone acetylation levels at 6 breast cancer-related gene promoters: AR, BRCA1, ERS1, ERS2, EZH2 and EP300. In summary, this report characterizes for the first time the epigenetic behavior of SIRT1 in human breast carcinoma. These novel findings point to a potential use of SIRT1 as an epigenetic therapeutic target in breast cancer.

Effect of Rapid Maxillary Expansion on Glenoid Fossa and Condyle-Fossa Relationship in Growing Patients (MEGP): Study Protocol for a Controlled Clinical Trial.

AIMS AND OBJECTIVES: Rapid maxillary expansion (RME) is an orthodontic nonsurgical procedure aiming at increasing the width of the maxilla by opening mainly the intermaxillary suture in patients presenting a transverse maxillary skeletal deficiency. The objectives of the current prospective controlled clinical and radiographic study are to evaluate the hypothesis that RME in growing patients will result in radiographic changes at the level of interglenoid fossa distance, condyle-fossa relationship, and nasal cavity widths compared to the group who received no treatment initially and served as untreated control. MATERIALS AND METHODS: In this prospective controlled clinical and radiographic study, forty healthy growing patients selected from a school-based population following a large screening campaign, ranging in age between 8 and 13 years, presenting a maxillary constriction with bilateral crossbite, and candidates for RME are being recruited. The first group will include participants willing to undergo treatment (n = 25) and the other group will include those inclined to postpone (n = 15). RESULTS: The primary outcome is to compare radiologically the interglenoid fossa distance and the condyle-fossa relationship; nasal cavity width will be a secondary outcome. A multivariable analysis of Covariance model will be used, with the assessment of the time by group interaction, using age as covariate. The project protocol was reviewed and approved by the Ethics Committee of the Lebanese University, National Institute in Lebanon (CUEMB process number 31/04/2015). The study is funded by the Lebanese University and Centre National de Recherche Scientifique, Lebanon (Number: 652 on 14/04/2016). CONCLUSION: This prospective controlled clinical trial will give information about the effect of RME on the glenoid fossa and condyle-fossa relationship and its impact on the nasal cavity width. TRIAL REGISTRATION: Retrospectively registered in BioMed Central (DOI10.1186/ISRCTN77788053).

A new metabolic gene signature in prostate cancer regulated by JMJD3 and EZH2.

Histone methylation is essential for gene expression control. Trimethylated lysine 27 of histone 3 (H3K27me3) is controlled by the balance between the activities of JMJD3 demethylase and EZH2 methyltransferase. This epigenetic mark has been shown to be deregulated in prostate cancer, and evidence shows H3K27me3 enrichment on gene promoters in prostate cancer. To study the impact of this enrichment, a transcriptomic analysis with TaqMan Low Density Array (TLDA) of several genes was studied on prostate biopsies divided into three clinical grades: normal (n = 23) and two tumor groups that differed in their aggressiveness (Gleason score ≤ 7 (n = 20) and >7 (n = 19)). ANOVA demonstrated that expression of the gene set was upregulated in tumors and correlated with Gleason score, thus discriminating between the three clinical groups. Six genes involved in key cellular processes stood out: JMJD3, EZH2, MGMT, TRA2A, U2AF1 and RPS6KA2. Chromatin immunoprecipitation demonstrated collocation of EZH2 and JMJD3 on gene promoters that was dependent on disease stage. Gene set expression was also evaluated on prostate cancer cell lines (DU 145, PC-3 and LNCaP) treated with an inhibitor of JMJD3 (GSK-J4) or EZH2 (DZNeP) to study their involvement in gene regulation. Results showed a difference in GSK-J4 sensitivity under PTEN status of cell lines and an opposite gene expression profile according to androgen status of cells. In summary, our data describe the impacts of JMJD3 and EZH2 on a new gene signature involved in prostate cancer that may help identify diagnostic and therapeutic targets in prostate cancer.

Modulation of incisor eruption in rats by sympathetic efferents.

INTRODUCTION: Intact neural supply is necessary for tooth eruption. Sympathetic denervation accelerates or decelerates the eruption rate depending on the tooth condition (intact or injured). The aim of this study is to reexamine the role of the sympathetic innervation, through the observation of the effects of pre or post ganglionic chemical sympathectomy on the eruption of intact rat incisors. MATERIALS AND METHODS: Different groups of rats were subjected to either ganglionic or peripheral chemical sympathectomy and the observed effects on incisor eruption were compared to those made on intact/sham groups or on rats subjected to inferior alveolar nerve (IAN) lesion. RESULTS: The total amount of eruption in control/naïve rats, measured over a total period of 144 h, was 3 ±â€¯0.15 mm and decreased to 2.57 ±â€¯0.06 mm (n = 8; p < 0.01) or 2.8 ±â€¯0.10 mm (n = 8; p < 0.05) following treatment with guanethidine and hexamethonium, respectively. This amount decreased to 1.8 ±â€¯0.14 mm (p < 0.001 vs. control, n = 7; or p < 0.01 vs. sham, n = 5) in rats subjected to IAN lesion. CONCLUSION: Sympathectomy delayed tooth eruption. Blocking the sympathetic effectors with guanethidine exerted more potent effects than ganglionic block with hexamethonium. Intact sympathetic supply is required for tooth growth under normal conditions.

Development of an Arabic Version of the Hiroshima University-Dental Behavioral Inventory: Cross-cultural Adaptation, Reliability, and Validity.

The Hiroshima University-Dental Behavioral Inventory (HU-DBI) has not been adequately translated to the Arabic language. The aim of this study is the translation and cultural adaption of the English HU-DBI into standard Arabic. The English HU-DBI was translated into Arabic by three bilingual dental academics. A nonmedical professional performed backward translation into English. The three bilinguals compared both English versions and accordingly modified the Arabic version. English and Arabic versions were answered by 58 bilingual participants. Focus groups and cognitive interviews were conducted to pretest the working version, after which the final Arabic version was tested for test-retest validity on 58 dental students. Bilingual validity and test-retest validity were assessed using the kappa statistic. Responses were similar in the English and Arabic versions for bilingual individuals and on both tests in the test-retest sample. Kappa values ranged from 0.85 to 1.00 for bilingual validity and between 0.82 and 1.00 for test-retest reliability. In conclusion, the Arabic HU-DBI will enable the assessment of knowledge and attitudes toward oral diseases and their prevention in Arab countries and will allow meaningful comparisons between different countries in the region.

Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression.

BACKGROUND: H3K27me3 histone marks shape the inhibition of gene transcription. In prostate cancer, the deregulation of H3K27me3 marks might play a role in prostate tumor progression. METHODS: We investigated genome-wide H3K27me3 histone methylation profile using chromatin immunoprecipitation (ChIP) and 2X400K promoter microarrays to identify differentially-enriched regions in biopsy samples from prostate cancer patients. H3K27me3 marks were assessed in 34 prostate tumors: 11 with Gleason score > 7 (GS > 7), 10 with Gleason score ≤ 7 (GS ≤ 7), and 13 morphologically normal prostate samples. RESULTS: Here, H3K27me3 profiling identified an average of 386 enriched-genes on promoter regions in healthy control group versus 545 genes in GS ≤ 7 and 748 genes in GS > 7 group. We then ran a factorial discriminant analysis (FDA) and compared the enriched genes in prostate-tumor biopsies and normal biopsies using ANOVA to identify significantly differentially-enriched genes. The analysis identified ALG5, EXOSC8, CBX1, GRID2, GRIN3B, ING3, MYO1D, NPHP3-AS1, MSH6, FBXO11, SND1, SPATS2, TENM4 and TRA2A genes. These genes are possibly associated with prostate cancer. Notably, the H3K27me3 histone mark emerged as a novel regulatory mechanism in poor-prognosis prostate cancer. CONCLUSIONS: Our findings point to epigenetic mark H3K27me3 as an important event in prostate carcinogenesis and progression. The results reported here provide new molecular insights into the pathogenesis of prostate cancer.

Dual SIRT1 expression patterns strongly suggests its bivalent role in human breast cancer.

Breast cancer is the most common cancer in women, and the leading cause of cancer death in women worldwide. SIRT1 (silent mating type information regulation 2 homolog) 1 is a class-III histone deacetylase involved in apoptosis regulation, DNA repair and tumorigenesis. However, its role in breast carcinoma remains controversial, as both tumor-suppressive and tumor-promoting functions have been reported. Also, there are very few reports available where expression of SIRT1 is comprehensively analyzed in breast tumors classified by molecular subtype. Here, using a cohort of 50 human breast tumors and their matched normal tissues, we investigated SIRT1 expression levels in the 5 molecular subtypes of breast cancer according to the St Gallen classification (2013). Tumors and their corresponding normal tissue samples were collected from all patients, and SIRT1 mRNA and protein expression levels were then examined by real-time quantitative polymerase chain reaction and immunoblotting, respectively. After statistical analysis, the results showed a dual expression profile of SIRT1 in human breast carcinoma, with significant overexpression in luminal and HER2-enriched subtypes and significantly reduced expression in the triple-negative subtype. We also found an inverse correlation between SIRT1 expression and breast cancer aggressivity. These novel findings suggest that SIRT1 plays a dual role in breast tumors depending on its expression rate and the molecular subtype of the cancer. Our data also point to a potential role for SIRT1 as a prognostic biomarker in breast cancer.

Fit of pressed crowns fabricated from two CAD-CAM wax pattern process plans: A comparative in vitro study.

STATEMENT OF PROBLEM: Subtractive and additive computer-aided design and computer-aided manufacturing (CAD-CAM) wax pattern processing are 2 methods of fabricating a pressed ceramic crown. Whether a subtractive milled wax pattern or a pattern from the micro-stereolithography additive process produces lithium disilicate crowns with better marginal and internal fit is unclear. MATERIALS AND METHODS: Ten silicone impressions were made for a prepared canine tooth. Each die received 2 lithium disilicate (IPS e.max) copings, 1 from milled wax blocks and 1 from additive wax. The replica technique was used to measure the fit by scanning electron microscopy at ×80 magnification. Collected data were analyzed using the paired Student t test for the marginal and internal fit. For the occlusal fit, the difference in scores did not follow a normal distribution, and the Wilcoxon signed rank test was used (α=.05). RESULTS: The mean marginal, axial, and occlusal fit showed no significant differences when the 2 CAD-CAM manufacturing processes were compared (P>.05). For the marginal fit, the mean (±SD) values were 105.1 µm ±39.6 with the milled process and 126.2 µm ±25.2 for the additive process. The mean values were 98.1 µm ±26.1 for the axial fit in the milled process and 106.8 µm ±21.2 in the additive process. For the occlusal fit, median values (interquartile interval) were 199.0 µm (141.5 to 269.9) for subtractive manufacturing and 257.2 µm (171.6 to 266.0) for micro-SLA manufacturing. CONCLUSIONS: No significant difference was found between the fit of the 2 techniques. The mean values of axial and occlusal median values were 10 and 5 to 6 times greater than machine's nominal values.

Epigenetic Modifications with DZNep, NaBu and SAHA in Luminal and Mesenchymal-like Breast Cancer Subtype Cells.

BACKGROUND/AIM: Numerous studies have shown that breast cancer and epigenetic mechanisms have a very powerful interactive relation. The MCF7 cell line, representative of luminal subtype and the MDA-MB 231 cell line representative of mesenchymal-like subtype were treated respectively with a Histone Methyl Transferase Inhibitors (HMTi), 3-Deazaneplanocin hydrochloride (DZNep), two histone deacetylase inhibitors (HDACi), sodium butyrate (NaBu), and suberoylanilide hydroxamic acid (SAHA) for 48 h. MATERIALS AND METHODS: Chromatin immunoprecipitation (ChIP) was used to observe HDACis (SAHA and NaBu) and HMTi (DZNep) impact on histones and more specifically on H3K27me3, H3K9ac and H3K4ac marks with Q-PCR analysis of BRCA1, SRC3 and P300 genes. Furthermore, the HDACi and HMTi effects on mRNA and protein expression of BRCA1, SRC3 and P300 genes were checked. In addition, statistical analyses were used. RESULTS: In the MCF7 luminal subtype with positive ER, H3k4ac was significantly increased on BRCA1 with SAHA. On the contrary, in the MDA-MB 231 breast cancer cell line, representative of mesenchymal-like subtype with negative estrogen receptor, HDACis had no effect. Also, DZNEP decreased significantly H3K27me3 on BRCA1 in MDA-MB 231. Besides, on SRC3, a significant increase for H3K4ac was obtained in MCF7 treated with SAHA. And DZNEP had no effect in MCF7. Also, in MDA-MB 231 treated with DZNEP, H3K27me3 significantly decreased on SRC3 while H3K4ac was significantly increased in MDA-MB-231 treated with SAHA or NaBu for P300. CONCLUSION: Luminal and mesenchymal-like breast cancer subtype cell lines seemed to act differently to HDACis (SAHA and NaBu) or HMTi (DZNEP) treatments.