Biology and Endodontics: Thinking Outside the Box.

Combining evidence-based dentistry (EBD) with years of clinician experience should have a great impact on treatment planning and decision-making for achieving the best treatment outcomes, thus warranting patient satisfaction. In addition, understanding and appreciating the role of biology on the reliance on and progress of treatment healing is also a crucial element that clinicians should always keep in mind in their dental practice. This study demonstrates that clinicians should always rely on their own clinical and radiographical test results for evaluation and judgment of any clinical situation before presenting and proceeding with any dental treatment for their patients.

The Biological and Mechanical Effect of Using Different Irrigation Methods on the Bond Strength of Bioceramic Sealer to Root Dentin Walls.

Objectives This study aimed to evaluate the biological and mechanical effect of different irrigation methods on the bond strength of Bioceramic (BC) sealer to root canal dentin walls. Material and Methods Forty-Five single-rooted teeth were decoronated and then prepared using rotary instrumentation. Teeth were randomly divided into three groups. Group 1: using the conventional syringe method; Group 2: using the ultrasonic (US) activation method; and Group 3: using the Nd:YAG laser activation method. The BC sealer (TotalFill® BC Sealer™, FKG Dentaire, Switzerland) was used for obturation according to the manufacturer's recommendation. The bond strength was evaluated using the push-out test, and the adaptation of the sealer/dentin interface was assessed using Scanning Electron Microscope (SEM). Data were analyzed by Welch's ANOVA analysis of variance and Games-Howell for pairwise comparison. The level of statistical significance was set at 95% (p-value ≤ 0.05). Results The push-out bond strength values of the Nd:YAG (6.46 ± 0.5) laser group were statistically significant than both conventional (3.33 ± 1.8) and US groups (4.21 ± 2.2). The mean gaps that were formed between the root walls and GP/BS sealer interface were statistically significant only between the Nd:YAG laser group (25.54 ± 13.8) compared to both conventional (62.00 ± 15.3) and US groups (58.82 ± 23.8) (p ≤0.05). No significant difference was found between the conventional and US groups in both rested parameters (p >0.05). Conclusion The method protocol of RC system irrigation affects the adhesion and bond strength of BS sealers to the root canal dentin walls.

Human papillomavirus and head and neck squamous cell carcinoma in a UK population: Is there an association?

Background: Human papillomavirus (HPV) is an evolving important risk factor for head and neck cancer (HNC), especially for individuals who do not smoke and drink alcohol. The aim of this study was to establish the prevalence of HPV infection and elucidate its association with head and neck squamous cell carcinoma (HNSCC) patients in UK population. Methods: The presence and association of HPV was investigated in HNSCC patients in this retrospective clinical study. Samples were obtained from archived biopsies and resections. HPV screening was performed by the use of polymerase chain reaction (PCR) using the GP5+/GP6+ and the SPF1/2 consensus as primers and by immunohistochemistry (IHC). Samples of viral warts that were IHC positive for HPV and fibroepethelial polyps (FEP) were used, as positive and negative controls, respectively. Results: The cohort included 124 patients with HNSCC with an age range of 27-97 years (median, 60 years) and a male to female ratio of 2:1. Among the 124 HNSCC, 43/124 (34.7%) were from the tongue, 74/124 (60%) presented with advanced stage III or IV disease, 112/124 (90%) had a conventional phenotype, 84/124 (68%) were moderately differentiated, and 89/124 (72%) had bands or cords at the invasive front. Of the 124 patients with HNSCC, 84/124 (68%) demonstrated the presence of HPV, 0/124 (0%) was for oral squamous cell carcinomas (OSCC). HPV16 was the associated virus type in all positive samples. However, no significant association was observed between HPV positivity and other clinico-pathological variables including age and gender of the patients, stage, and malignancy differentiation. Conclusion: The results we provide suggest that HPV infection is low in HNSCC, in general, and absent in OSCC, specifically, in this UK population during this time period. This implies that HPV infection may not play an important role in HNSCC carcinogenesis compared to other risk factors in UK population. This information can aid in more effective treatment approaches for treating UK cases of HNSCC.

Awareness of the Effect of Diabetes on Oral Health among a Population in Jeddah, Saudi Arabia.

PURPOSE: Diabetes is an ever-growing health issue in the Kingdom of Saudi Arabia. It has several oral health implications and oral health in turn affects diabetes control. The primary objective of this research was to study the awareness of the effect of diabetes on oral health among the general population in the city of Jeddah, Saudi Arabia. MATERIALS AND METHODS: A closed-ended, validated questionnaire was distributed to 506 randomly selected shopping-mall-goers. Responses were coded and entered into spreadsheet (SPSS, IBM) and frequency distribution of the responses was calculated. RESULTS: The majority of the respondents were females (62.5%), non-diabetic (80.2%) and reported a positive family history of diabetes (87.9%). Most of them (63.4%) understood the importance of discussing one's diabetes status with the dentist as it affected the treatment plan, and also knew (84.4%) that diabetes affects oral health in some way. A majority also correctly responded to how diabetes affects oral health (66.3%) and to the sequelae of untreated gum disease (87.2%). The majority of the respondents had not received any tips or information regarding the connection between diabetes and oral health. CONCLUSION: This study reported adequate knowledge of the sample with respect to diabetes-related oral health. An important finding of this study was that the majority of the study participants did not receive information leading to diabetes-related oral health awareness or knowledge from anyone, which implies that health professionals and health media do not play the requisite role in dissemination of this important aspect of public health.

Characterization of the apical bridge barrier formed following amelogenin apexification.

BACKGROUND: Recombinant amelogenin protein (RAP) is reported to induce complete root apex formation in dog model when used as apexification therapy. It also induces pulp regeneration in 85% of the treated group. Thus, the aim of this study was to investigate the nature of the remaining regenerated calcified tissues of the RAP group that showed no pulp regeneration compared to the calcium hydroxide treated group (CH). METHODS: A total of 240 dogs' open apex root canals were used, after establishment of canals contamination. Canals were cleaned, irrigated, and filled with RAP as an apexification material and compared with CH. Treated teeth were assessed by H&E, trichrome staining, and/or immunohistochemistry technique, at 1, 3, and 6 months. RESULTS: A time-dependent increase in the calcified tissue barrier was observed in the apex of the RAP-treated group compared to the CH-treated group. The newly formed dentin in this RAP group was mainly tubular dentin and was functionally attached to the bone by periodontal ligament, while the CH group showed dentin-associated mineralized tissue (DAMT) associated with the newly formed apical barrier. CONCLUSIONS: Out results suggest that RAP can be used as novel apexification material, resulting in a thickening and strengthening of the canal walls, and achieving apical closure.

DNA replication licensing factor MCM2, geminin, and Ki67 define proliferative state and are linked with survival in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is still an unabated global killer with little advancement in its survival rate. DNA replication licensing proteins and Aurora kinase A are biomarkers that play important roles in genomic stability. The expression profile of minichromosomal maintenance protein 2 (MCM2), Ki67, geminin, and Aurora-A were linked to clinicopathological and outcome parameters, survival, and DNA content in 125 cases of OSCC. Oral fibroepithelial polyps (OFEP) were controls. The OSCC tumour cells were in a rapidly proliferating state, as assessed by the increased expression profile of MCM2, Ki67, geminin, and Aurora-A and of the geminin/Ki67 ratio, and the decrease of the MCM2/Ki67 ratio, in OSCC compared with OFEP (P < 0.000). There was an association between expression of MCM2, Ki67, and geminin and tumour histologic and invasive front grade (P < 0.05). A total of 82% of the OSCC assessed had aneuploid DNA content, which was associated with increased expression intensity of Aurora-A (P = 0.01). Geminin and the geminin/Ki67 ratio were associated with TNM staging (P < 0.05), and weak expression of MCM2, Ki67, geminin, and Aurora-A were predictive of OSCC survival (P < 0.05). Dysregulation of the origin licensing pathway and the mitotic pathway are important events in OSCC, and the combined analysis of these proteins may contribute to improved treatment decisions.

Single file reciprocating systems: A systematic review and meta-analysis of the literature: Comparison of reciproc and WaveOne.

The introduction of single-file nickel-titanium (NiTi) reciprocating systems has been a major breakthrough in the field of endodontics. Thus, the aim of this study was to compare the available reciprocating systems, Reciproc and WaveOne, using a meta-analysis with different parameters. A comprehensive electronic literature search for Reciproc and WaveOne using PubMed and Google scholar was initially conducted in September 2014 and updated in September 2016. Inclusion and exclusion criteria were then established. Twenty-six studies were qualified for the systematic review, and only three studies were considered for the meta-analysis using cyclic fatigue resistance as the main parameter. The time to fracture for the Reciproc and WaveOne systems ranged from 119.7 sec to 156.4 sec and 74.8 sec to 99.6 sec, respectively. The pooled difference in mean time to fracture was longer for the Reciproc system by 45.6 sec. This difference was statistically significantly at P value < 0.001. In conclusion, our study supports the finding that Reciproc is more resistant to cyclic fatigue than WaveOne. However, with regard to other parameters, mixed results were obtained. Well-designed randomized clinical trials comparing both systems under the same experimental conditions should be done in future studies.

Vertical root fracture: Biological effects and accuracy of diagnostic imaging methods.

This review assessed the most up-to-date literature on the accuracy of detecting vertical root fractures (VRFs] using the currently available diagnostic imaging methods. In addition, an overview of the biological and clinical aspects of VRFs will also be discussed. A systematic review of the literature was initiated in December of 2015 and then updated in May of 2016. The electronic databases searched included PubMed, Emabse, Ovid, and Google Scholar. An assessment of the methodological quality was performed using a modified version of the quality assessment of diagnostic accuracy studies tool. Twenty-two studies were included in this systematic review after applying specific inclusion and exclusion criteria. Of those, 12 favored using cone beam computed tomography (CBCT) for detecting VRF as compared to periapical radiographs, whereas 5 reported no differences between the two methods. The remaining 5 studies confirmed the advantages associated with using CBCT when diagnosing VRF and described the parameters and limitations associated with this method, but they were not comparative studies. In conclusion, overwhelming evidence suggests that the use of CBCT is a preferred method for detecting VRFs. Nevertheless, additional well controlled and high quality studies are needed to produce solid evidence and guidelines to support the routine use of CBCT in the diagnosis of VRFs as a standard of care.

Head and Neck Cancer in Saudi Arabia: a Systematic Review.

BACKGROUND: Head and neck cancer (HNC) is the ninth most common cancer worldwide, and has a poor 5-year survival rate averaging 50%, which has not changed for decades. A high prevalence of HNC has been reported in the southwestern region of Saudi Arabia, as compared to other areas of the country. However, data in regards to HNC are scattered and not well documented. Thus, the aim of this systematic review was to gather all available and updated important information regarding HNC in Saudi Arabia, and highlight the gaps of knowledge in our country with regard to this disease. In addition, suggestions of solutions to overcome the current status and improve our future standard of care to fight HNC are also highlighted. MATERIALS AND METHODS: The electronic databases PubMed and Google Scholar using English-language literature were used for this systematic review, using specific inclusion and exclusion criteria and keywords. The search was performed in April 2016 and updated in June 2016. RESULTS: Our search revealed twenty-one studies that fulfilled our inclusion and exclusion criteria and that were conducted in Saudi Arabia. These studies investigated different aspects of HNC, including prevalence, risk factors, biomarkers, and assessed knowledge and awareness of both public and practitioners with regard to HNC. CONCLUSIONS: This review uncovered a big gap in our epidemiological data in cancer information in general, and head and neck cancer in particular. In addition, a lack of knowledge and awareness of both the public and health care practitioners hinders the early diagnosis of disease and negatively impact the prognosis, treatment and outcome. The Ministry of Health in Saudi Arabia should develop a more systematic way and adapt policies to gather cancer information in general, and head and neck cancer in particular, from all governmental and private sectors from all over the kingdom, and develop educational programs to raise the knowledge and awareness of HNC in the country.

Awareness and attitude toward using dental magnification among dental students and residents at King Abdulaziz University, Faculty of Dentistry.

BACKGROUND: The authors conducted a study aimed to assess the awareness and attitude among dental students and residents at King Abdulaziz University, Faculty of Dentistry (KAUFD) toward using dental magnification. METHODS: An e-questionnaire was formulated then sent to dental students and residents (n = 651). The questionnaire included questions that assessed both the awareness and attitude toward using dental magnification. Data were analyzed using IBM SPSS version 22. The chi-square test was used to establish relationships between categorical variables. RESULTS: The response rate was 69.7 % (n = 454). Of those, 78.1 % did not use magnification during dental procedures. However, 81.8 % agreed that dental magnification could enhance the accuracy and quality of their dental work. Thus, 91.6 % thought it would be useful in endodontics and 46.3 % voted for surgery. Of the 21.9 % that used magnification, dental loupes were mostly used, 55.9 %. The majority (59.4 %) of the participants believed that using dental magnification should be introduced by faculty beginning in Year I of dental school. CONCLUSIONS: Among our respondents, most of the undergraduate students did not use dental magnification nor attended courses in the use of dental magnifications. However, most of the students were aware of its significance in improving the accuracy and quality of their work.

Evaluation of Head and Neck Cancer Awareness and Screening Status in Jeddah, Saudi Arabia.

BACKGROUND: Head and neck cancer (HNC) is one of the deadliest cancers worldwide. Early detection is a key determinant of HNC prognosis. Hence, raising awareness of this disease may improve survival rates. The present study evaluated the level of awareness and screening status for HNC in the general population of Jeddah, Saudi Arabia. MATERIALS AND METHODS: An e-questionnaire was distributed during our HNC awareness campaign at the Red Sea Mall in Jeddah. The questions assessed HNC knowledge and screening status among participants. RESULTS: Of the 112 respondents, 68% indicated that they had no knowledge of HNC. Social media was the major source of information (39%) for respondents. The majority (40%) believed that it was the joint responsibility of dentists, dental hygienists, and general physicians to screen for HNC; 82% had never been screened. CONCLUSIONS: Knowledge and awareness of HNC must be increased in the general population and among dental health professionals.

A Novel Sirtuin-3 Inhibitor, LC-0296, Inhibits Cell Survival and Proliferation, and Promotes Apoptosis of Head and Neck Cancer Cells.

BACKGROUND: The survival rate of patients with head and neck squamous cell carcinoma (HNSCC) stands at approximately 50% and this has not improved in decades. This study developed a novel sirtuin-3 (SIRT3) inhibitor (LC-0296) and examined its role in altering HNSCC tumorigenesis. MATERIALS AND METHODS: The effect of the SIRT3 inhibitor, LC-0296, on cell survival, proliferation, and apoptosis, and reactive oxygen species levels in HNSCC cells were studied. RESULTS: LC-0296 reduces cell proliferation and promotes apoptosis of HNSCC cells but not of normal human oral keratinocytes. This inhibitory effect is mediated, in part, via modulation of reactive oxygen species levels. Additionally, LC-0296 works synergistically to increase the sensitivity of HNSCC cells to radiation and cisplatin treatment. CONCLUSION: Development of novel SIRT3 inhibitors, such as LC-0296, might enable the development of new targeted therapies to treat and improve the survival rate of patients with head and neck cancer.

Sirtuin-3 (SIRT3) and the Hallmarks of Cancer.

Sirtuins (SIRT1-SIRT7), the mammalian homologs of the silent information regulator 2 (Sir2) in Saccharomyces cerevisiae, have been a major focus of study in the scientific community this past decade because of their emerging role in cancer biology and other age-related diseases. Emerging functions for this unique family of enzymes include roles in genomic stability, angiogenesis, metabolism, and anoikis. Here, we review recent developments on the role of sirtuins in cancer with a particular focus on SIRT3 and its role in the hallmarks of cancer and as a potential drug target for cancer treatment.

Receptor-interacting protein (RIP) and Sirtuin-3 (SIRT3) are on opposite sides of anoikis and tumorigenesis.

BACKGROUND: Regulating cross-talk between anoikis and survival signaling pathways is crucial to regulating tissue processes and mitigating diseases like cancer. Previously, the authors demonstrated that anoikis activates a signaling pathway involving the CD95/Fas-mediated signaling pathway that is regulated by receptor-interacting protein (RIP), a kinase that shuttles between Fas-mediated cell death and integrin/focal adhesion kinase (FAK)-mediated survival pathways. Because it is known that sirtuin-3 (SIRT3), a nicotinamide adenine dinucleotide-dependent deacetylase, regulates cell survival, metabolism, and tumorigenesis, the authors hypothesized that SIRT3 may engage in cross-talk with Fas/RIP/integrin/FAK survival-death pathways in cancer cell systems. METHODS: Using immunohistochemical staining, immunoblotting, human tissue microarrays, and overexpression and suppression approaches in vitro and in vivo, the roles of RIP and SIRT3 were examined in oral squamous cell carcinoma (OSCC) anoikis resistance and tumorigenesis. RESULTS: RIP and SIRT3 had opposite expression profiles in OSCC cells and tissues. Stable suppression of RIP enhanced SIRT3 levels, whereas stable suppression of SIRT3 did not impact RIP levels in OSCC cells. The authors observed that, as OSCC cells became anoikis-resistant, they formed multicellular aggregates or oraspheres in suspension conditions, and their expression of SIRT3 increased as their RIP expression decreased. Also, anoikis-resistant OSCC cells with higher SIRT3 and low RIP expression induced an increased tumor burden and incidence in mice, unlike their adherent OSCC cell counterparts. Furthermore, stable suppression of SIRT3 inhibited anoikis resistance and reduced tumor incidence. CONCLUSIONS: The current results indicted that RIP is a likely upstream, negative regulator of SIRT3 in anoikis resistance, and an anoikis-resistant orasphere phenotype defined by higher SIRT3 and low RIP expression contributes to a more aggressive phenotype in OSCC development.

SIRT3 and cancer: tumor promoter or suppressor?

Sirtuins (SIRT1-7), the mammalian homologues of the Sir2 gene in yeast, have emerging roles in age-related diseases, such as cardiac hypertrophy, diabetes, obesity, and cancer. However, the role of several sirtuin family members, including SIRT1 and SIRT3, in cancer has been controversial. The aim of this review is to explore and discuss the seemingly dichotomous role of SIRT3 in cancer biology with particular emphasis on its potential role as a tumor promoter and tumor suppressor. This review will also discuss the potential role of SIRT3 as a novel therapeutic target to treat cancer.

Sirtuin-3 (SIRT3), a novel potential therapeutic target for oral cancer.

BACKGROUND: Several sirtuin family members (SIRT1-7), which are evolutionarily conserved NAD-dependent deacetylases, play an important role in carcinogenesis. However, their role in oral cancer has not yet been investigated. Therefore, the objective of this study was to investigate whether sirtuins play a role in oral cancer carcinogenesis. METHODS: The expression levels of all sirtuins in several oral squamous cell carcinoma (OSCC) cell lines were compared with normal human oral keratinocytes and observed that SIRT3 was highly expressed. Therefore, tissue microarrays were used to evaluate the clinical relevance of this overexpression. SIRT3 down-regulation in OSCC cell proliferation and survival was investigated and analyzed by using cell-proliferation and cell-viability assays. Ionizing radiation and cisplatin were used to investigate whether SIRT3 down-regulation could increase the sensitivity of OSCC to both treatments. To further assess the in vivo role of SIRT3 in OSCC carcinogenesis, a floor-of-mouth oral cancer murine model was used to study the effect of SIRT3 down-regulation on OSCC tumor growth in immunodeficient mice. RESULTS: The current results demonstrated for the first time that SIRT3 is overexpressed in OSCC in vitro and in vivo compared with other sirtuins. Down-regulation of SIRT3 inhibited OSCC cell growth and proliferation and increased OSCC cell sensitivity to radiation and cisplatin treatments in vitro. SIRT3 down-regulation also reduced tumor burden in vivo. CONCLUSIONS: The current investigation revealed a novel role for SIRT3 in oral cancer carcinogenesis as a promoter of cell proliferation and survival, thus implicating SIRT3 as a new potential therapeutic target to treat oral cancer.

Characterization of Treponema denticola pyrF encoding orotidine-5'-monophosphate decarboxylase.

The Treponema denticola ATCC 35405 genome annotation contains most of the genes for de novo pyrimidine biosynthesis. To initiate characterization of pyrimidine synthesis in Treponema, we focused on TDE2110 (the putative pyrF, encoding orotidine-5'-monophosphate decarboxlyase). Unlike the parent strain, an isogenic pyrF mutant was resistant to 5-fluoroorotic acid. In complex medium, growth of the pyrF mutant was independent of added uracil, indicating activity of a uracil uptake/salvage pathway. Transcription of pyrF was greatly reduced in T. denticola grown in excess uracil, demonstrating that de novo pyrimidine synthesis is regulated and suggesting a feedback mechanism. Treponema denticola PyrF complemented uracil auxotrophy in an Escherichia coli pyrF mutant. This study provides biochemical confirmation of T. denticola genome predictions of de novo and salvage pyrimidine pathways and provides proof of concept that pyrF has potential as a selectable marker in T. denticola.