Administration of 4­hexylresorcinol increases p53­mediated transcriptional activity in oral cancer cells with the p53 mutation.

The p53 mutation is inherent in over 50% of human cancers. In head and neck squamous cell carcinoma, the p53 mutation is associated with a poor prognosis. 4­Hexylresorcinol (4HR) is a pharmacologic chaperone. The present study aimed to investigate the effect of 4HR on p53 transcriptional activity in oral carcinoma cells with p53 mutations. To identify conformational changes induced by 4HR administration, peptides including the DNA­binding domain from mutant and wild­type p53 were synthesized, and Fourier transform infrared spectroscopy was performed. To determine the effect of 4HR on p53 mutant carcinoma cells, western blot analysis, p53 transcriptional activity analysis, MTT assay and apoptosis immunocytochemistry were performed. The YD­15 cell line has a mutation in the DNA binding domain of p53 (Glu258Ala). When p53 Ala­258 was coupled by 4HR, the p53 Ala­258 structure lost its original conformation and approached a conformation similar to that of p53 Glu­258. In the cell experiments, 4HR administration to p53 mutant cells increased p53 transcriptional activity and the expression levels of apoptosis­associated proteins such as B­cell lymphoma 2 (BCL2), BCL2­associated X (BAX) and BCL2­associated agonist of cell death (BAD). Accordingly, 4HR administration on YD­15 cells decreased cell viability and increased apoptosis. In conclusion, 4HR is a potential substance for use in the recovery of loss­of­function in mutant p53 as a pharmacologic chaperone.

Salivary exosomal microRNAs as biomarkers for head and neck cancer detection-a literature review.

BACKGROUND: MicroRNAs (miRs) are small, non-coding mRNA molecules which regulate cellular processes in tumorigenesis. miRs were discovered in extracellular environment and biological fluids, carrying marks of head and neck squamous cell carcinoma (HNSCC). They were also identified in abundance in salivary exosomes, in which they are protected by exosome lipid barrier against enzymatic injuries and therefore, the accuracy of exosomal miR-based cancer detection increase. This systematic review aimed to reveal and inventorize the most reliable exosomal miRNAs in saliva samples which can be used as novel biomarkers for early detection of HNSCC. MATERIALS AND METHODS: A systematic literature search, according to PRISMA guideline, was performed on Pubmed and Google Academic libraries, based on specific keywords. Original articles published between 2010 and 2021 were selected. The quality of each paper was assessed using the Quality Evaluation Scoring Tool. RESULTS: At the end of selection process, five studies met the inclusion criteria. These studies analyzed twelve salivary exosomal miRs, presenting different methods of exosome and miR identification for HNSCC detection. A comprehensive explanation of the miR pathways of action was drawn and illustrated in this review. CONCLUSION: Exosomal miRs are promising biomarkers for oral cavity and oropharyngeal cancer detection. miR-10b-5p, miR-486-5p, miR-24-3p and miR-200a stand as the most useful ones in saliva sample examination.

Giant follicular cyst with maxillary sinus and pterygomaxillary space extension.

BACKGROUND: Dentigerous, follicular, cysts are developmental odontogenic cysts of reduced adamantine epithelium origin, associated with an impacted tooth. They are the second most frequent cystic pathology after inflammatory cysts. Although the frequency of dentigerous cysts associated with upper third molars is far lower than the mandibular ones, their complications are nothing but ordinary. Most of the times asymptomatic, being discovered during routine x-ray examinations, maxillary follicular cysts can grow to important size, altering the position of adjacent teeth, producing osteolysis of the nearby bone structures, as well as infectious complications, antral and orbital pathology. CASE REPORT: The present manuscript describes the clinical, radiological, pathological and therapeutical aspects of a giant follicular cyst with antral and pterygomaxillary extension, associated with an impacted upper third molar. CONCLUSION: The most efficient treatment of maxillary follicular cysts consists in the surgical removal of the lesion along with the involved tooth. Complete excision is mandatory to prevent recurrence. Extension into adjacent structures might complicate the surgery Preoperative evaluation and rigorous planning are essential, especially in large-sized lesions. Pathological examination is outmost importance in order to exclude aggressive transformations. KEY WORDS: Dentigerous follicular cyst, Maxillary sinus extension, Pterygomaxillary space.

The Changes in Upper Airway Volume after Orthognathic Surgery Evaluated by Individual Segmentation on CBCT Images.

Objectives:The aim of this CBCT study was to evaluate the postoperative volume changes of the rhinosinusal airway space, maxillary sinuses and nasal fossa, that occur after Le Fort I osteotomy, using individual segmentation of 3D virtual models. Material and methods:A number of 16 patients (with Class II and Class III malocclusions) who underwent a CBCT examination for orthognathic surgery at six month-interval between preoperative and postoperative evaluations were included. Patients with thickening of the sinus mucosa, craniofacial syndromes, maxillofacial trauma, rhinoplasty or other maxillofacial pathological conditions were excluded from the study. Individual segmentation of airway volumes was performed by the ITK-SNAP 2.0 software. Paired student t-test was used for the statistical examination of volume changes and Pearson's test for the assessment of intra-rate correlation. Outcomes:A statistically significant decrease in the rhinosinusal volume in Class II (9.36±3.43 cm3) and Class III malocclusions (3.65±2.96 cm3) was found after Le Fort I osteotomy. A decrease in volume was also found for maxillary sinuses (5.63±1.52 cm3 for Class II and 6.72±4.5 cm3 for Class III malocclusion). Nasal fossa decreased in volume (3.79±3.8 cm3) in Class II malocclusion patients and increased (3.07±2.39 cm3) in Class III malocclusion patients. The Pearson correlation revealed a high intra-rate agreement of measurements. Conclusion:Le Fort I osteotomy modifies the postoperative volume of rhinosinusal aerial spaces and individual segmentation on CBCT images is a useful tool to analyze the changes.

Prof. Dr. Gheorghe Bilascu. Pro patria.

Gheorghe Bilascu came to Cluj from Budapest, where he enjoyed all the privileges reserved for the high-class people in the Hungarian capital city, in 1919. He renounced this comfortable existence in order to establish the Romanian Dental Education in Cluj. When he made this choice, he was aware that he would sacrifice his life for a national ideal. The following text describes the background and events that shaped the future of Romanian dentistry in Cluj, driven by the personality of Gheorghe Bilascu.

Early and long-term changes in the muscles of the mandible following orthognathic surgery.

OBJECTIVES: The aim of the present study is to evaluate the early and long-term postoperative dimensional changes of the muscles of the mandible in patients with orthognathic surgery for class II and class III malocclusions by using ultrasonography (US). MATERIAL AND METHODS: Twenty-six patients who underwent bimaxillary orthognathic surgery for class II or class III malocclusions (14 and 12 patients, respectively) were ultrasonographically examined. The length, width, and cross-sectional area of the masseter and suprahyoid muscles were measured at three different time points: T0 (preoperatively), T1 (early postoperatively at 1 month after the surgery), and T2 (late postoperatively at 9 months). A repeated measures ANOVA was used to calculate statistically significant dimensional changes of the mandibular muscles. RESULTS: Statistically significant dimensional changes were found postoperatively in class II malocclusion patients only. The digastric muscle showed higher values for the length and lower values for the width (p < .05) at T1. The geniohyoid muscles were higher in length at T1 and lower in cross-sectional area (CSA) (p < .05) at T2. A decreased measured length and an increased measured width were found in case of the mylohyoid muscle (p < .05) at T2. The early and long-term postoperative dimensional changes of the masseter muscle were not statistically significant. CONCLUSIONS: The mandibular muscles showed a variable adaptive response to the orthognathic surgery. US should be considered for the long-term follow-up of muscular dimensional changes in class II malocclusion patients. CLINICAL RELEVANCE: From a clinical perspective, US is a reliable, non-invasive, and widely available method, which allows monitoring the postoperative muscular changes occurring in class II malocclusion patients.

Principles of biomechanics in oral implantology.

BACKGROUND AND AIMS: The principles of biomechanics comprise all the interactions between the body (tissues) and the forces acting upon it (directly or via different medical devices). Besides the mechanical aspects, the tissues response is also studied. Understanding and applying these principles is vital for the researchers in the field of oral implantology, but they must be equally known by the practitioners. From the planning stages to the final prosthetic restoration, they are involved in each and every aspect. Ignoring them inevitably leads to failure. METHODS: The first part of this paper includes a review of our current research in oral implantology (mechanical, digital and biological testing), while the second part includes a review of the available literature on certain biomechanical aspects and their implications in everyday practice. RESULTS: Our research opens new study directions and provides increased chances of success for dental implant therapy. The practical aspects of our findings, combined with the available literature (from the basic principles described more than 40 years ago to the most recent studies and technologies) can serve as a guide to practitioners for increasing their success rate. CONCLUSION: While no therapy is without failure risk, a good understanding of the biomechanics involved in oral implantology can lead to higher success rates in implant supported prosthetic restorations.

Oral surgery for combined haemophilia A and B. The dos and don'ts presented in a clinical scenario.

BACKGROUND: Haemophilia A (factor VIII deficiency), B (factor IX deficiency) and C (factor XI deficiency) are common genetic bleeding disorders. Most often they are caused by the absence or defective function of coagulation factors, causing inefficient blood clots. CASE REPORT: The present manuscript describes a rare case of a combined haemophilia A and B patient, who underwent several extractions. The therapy and clinical management is presented, in the view of surgeon as well as haematologist. CONCLUSION: These patients are a serious challenge for the oral surgeons due to an increased number of accidents and complications. Scarce literature covering this topic contributes, as well, to the difficult management. Thus, several principles must be considered when diagnosing and treating haemophilia patients. KEY WORDS: Haemophilia, Oral surgery.

Gheorghe Bȃrlea MD, PhD, pupil and collaborator of Professor Bilascu.

Being the first collaborator and assistant of Professor Gheorghe Bilascu, the founder of Cluj and National School of Dentistry, Dr. Gheorghe Bârlea kept very close to his master in developing the Dental Medicine in Cluj and in Romania, from 1908 to 1936. From the beginning of his career, he was involved in the establishment of the new Dental Clinic in the University of Superior Dacia as well as in the compilation of the teaching curriculum at the level of the avant-garde universities at that time. He was deeply involved in the recognition of Dentistry as discipline and medical practice and in the official achievement of the law and practice of this profession in Romania. Dr. Bârlea devoted his life and wotk to the cultural and social life of the Romanians, his efforts contributing to the Great Union of Romania. Passing away at an early age, Dr. Bârlea left Romanian dental profession without an important support.

Observational study of the bisphosphonate-related osteonecrosis of jaws.

INTRODUCTION: The bisphosphonate-related osteonecrosis of the jaw was first referred to in 2003. Bisphosphonates action is focused on the osteoclasts. The drastic inhibition of the osteoclastic function is harmful for the jaws which are the only bones of the human skeleton in relative contact with the external environment. The adverse effects of the bisphosphonate-related therapy include the pathology for which they are prescribed, the atypical fractures in pathological bone. METHOD: The aim of this research was to analyze the risk factors and the treatment methods in case of osteonecrosis of the jaws. To achieve these goals, the author analyzed the observation sheets of the patients admitted to the Oral and Maxillofacial Surgery Clinic during the period 2010-2015. The inclusion criteria were as follows: treatment with bisphosphonates, current or previous; the lesions of the mucous gingiva of the maxillaries followed by exposed necrotic bone, older than 8 weeks, with no tendency of healing; specific radiological image showing extended osteolysis with diffuse outline or radiopacity surrounded by radio-transparence, representing the necrotic bone sequestered; no metastasis in the necrotic maxillary bone; patient with no medical background of cervical-facial radiations. The patients who met these criteria were admitted in the study after signing the informed consent. Afterwards, the information found in the notes of the observational sheet (anamnesis, general examination and the imagistic investigation, treatment, postoperative recovery, prescription, postoperative recommendations) were gathered and submitted for statistic analysis. RESULTS: Of the 20 patients in total, 13 were women and 7 men, of ages ranging from 43 to 83. The most numerous cases were registered in the seventh age decade. All patients included in the study had lesions of the gingival maxillary mucosal areas with exposure of the subjacent necrotic bone. 60% of them were under intravenous treatment with zoledronic acid (Zometa®). A single patient was under oral treatment with bisphosphonates. 19 of these 20 patients developed osteonecrosis following a dental extraction while one case was due to the instability of the mandibular mobile prosthesis. 61% of the patients included in the study developed a necrotic process in the mandibular bone, 80% of the localizations were in the posterior area. As first intention, the choice of treatment was represented by local lavages with antiseptic solutions, general antibiotics and sequestrectomy. Of these patients, a third had relapsed and needed radical surgery treatment. CONCLUSIONS: Prevention of the bisphosphonate-related osteonecrosis of the jaw represents the best method of treatment. The development of bone sequesters damages the volume of the maxillary bone as such, reducing the chances for prosthetic functional rehabilitation of the dento-maxillary system. An increase in the quality of life by oral restoration of these patients may represent a challenge.

Estimation of the radiation dose for pediatric CBCT indications: a prospective study on ProMax3D.

BACKGROUND: An increasing number of CBCT units and a wide variability of radiation doses have been reported in dentistry lately. AIM: To estimate the effective, cumulative, and organ absorbed doses in children exposed to CBCT over 2 years. DESIGN: A prospective study was conducted in children who underwent CBCT diagnostic imaging with the ProMax3D machine. Organ and effective doses were calculated by Monte Carlo simulation using 5- and 8-year-old pediatric voxel phantoms. Extrapolation procedures were applied to estimate doses for other ages and CBCT protocols used in clinical conditions. RESULTS: The median effective dose was 137.9 µSv, and the median cumulative dose was 231.4 µSv. Statistically significant differences in the effective doses and cumulative doses were found for various indications of CBCT in children (P < 0.001). The median absorbed organ dose for brain and thyroid was significantly higher for the clinical condition that required large FOVs (2.5 mGy and 1.05 mGy, respectively) compared to medium (0.19 and 0.51 mGy) and small FOVs (0.07 and 0.24 mGy; P < 0.05). The radiation dose of salivary glands did not vary significantly with FOV. CONCLUSION: The results revealed the variation of CBCT doses and the influence of FOV size in pediatric exposure.

Custom Implant for Reconstruction of Mandibular Continuity Defect.

PURPOSE: The purpose of this study was to compare the daily food intake rate and the rate of screw loosening between 2 groups of rabbits with mandibular continuity defects: custom implant (CI) group and 5-hole mini-plate group. MATERIALS AND METHODS: Two types of cylindrical implants were printed, and their physical strength was compared. In this study using rabbits, 1 group (n = 5) received a CI for the reconstruction of a mandibular continuity defect (CI group) and the other group (n = 5) received a 5-hole mini-plate without a bone graft (reconstruction plate [RP] group). After reconstruction, the daily food intake rate and the rate of screw loosening were examined postoperatively. Histologic examination in the CI group was performed 3 months after the operation. RESULTS: The design that mimicked the mandible showed greater physical strength. The amount of time required to achieve 50% recovery was shorter in the CI group than in the RP group (P = .011). The total number of loosened screws in the CI group was lower than that in the RP group at 3 months postoperatively (P = .008). New bone formation in the porous CI was evident in the CI group. CONCLUSIONS: Rabbits with mandibular continuity defects treated with CIs for reconstruction showed faster recovery of the daily food intake rate and fewer loosened screws than those treated with a 5-hole mini-plate without bone graft.

Bone regeneration is associated with the concentration of tumour necrosis factor-α induced by sericin released from a silk mat.

To understand the osteogenic effect of the middle layer of the silk cocoon, sericin was examined for its cellular effects associated with tumor necrosis factor-α (TNF-α) signaling in this study. The fragmented sericin proteins in the silk mat were evaluated for the TNF-α expression level in murine macrophages. The concentration of protein released from silk mats was higher in the outermost and the innermost layers than in the middle layers, and the protein released from the silk mat was identified as sericin. The level of TNF-α in murine macrophages was dependent on the applied concentration of sericin, and the expression of genes associated with osteogenesis in osteoblast-like cells was dependent on the applied concentration of TNF-α. In animal experiments, silk mats from the middle layers led to a higher regenerated bone volume than silk mats from the innermost layer or the outermost layer. If TNF-α protein was incorporated into the silk mats from the middle layers, bone regeneration was suppressed compared with unloaded silk mats from the middle layers. Accordingly, silk mats from the silk cocoon can be considered to be a fragmented sericin-secreting carrier, and the level of sericin secretion is associated with TNF-α induction and bone regeneration.

Biography of Professor Cornel Tiberiu Opris. Professional maturity.

Professor Cornel Tiberiu Opris was the founder and Chair of the Clinic and University Department of Oral and Maxillofacial Surgery in Cluj, after the Education Reform of 1948. The article illustrates how the founder of these institutions led a valiant struggle for obtaining and arranging a location for the newly established Faculty of Dentistry, within the Institute of Medicine and Pharmacy. Professor Cornel Tiberiu Opris established himself as the most prodigious researcher at the Faculty for over a quarter-century, until his retirement, introducing his original conception in the therapeutic and surgical field. He created in Cluj-Napoca a specialist medical school by imposing national prestige for the institution that he led.

Evaluation of the Biocompatibility of New Fiber-Reinforced Composite Materials for Craniofacial Bone Reconstruction.

This study aims to assess the biocompatibility of new advanced fiber-reinforced composites (FRC) to be used for custom-made cranial implants. Four new formulations of FRC were obtained using polymeric matrices (combinations of monomers bisphenol A glycidylmethacrylate [bis-GMA], urethane dimethacrylate [UDMA], triethylene glycol dimethacrylate [TEGDMA], hydroxyethyl methacrylate [HEMA]) and E-glass fibers (300 g/mp). Every FRC contains 65% E-glass and 35% polymeric matrix. Composition of polymeric matrices are: bis-GMA (21%), TEGDMA (14%) for FRC1; bis-GMA (21%), HEMA (14%) for FRC2; bis-GMA (3.5%), UDMA (21%), TEGDMA (10.5%) for FRC3, and bis-GMA (3.5%), UDMA (21%), HEMA (10.5%) for FRC4. Cytotoxicity test was performed on both human dental pulp stem cells and dermal fibroblasts. Viability was assessed by tetrazolium dye colorimetric assay. Subcutaneous implantation test was carried out on 40 male Wistar rats, randomly divided into 4 groups, according to the FRC tested. Each group received subcutaneous dorsal implants. After 30 days, intensity of the inflammatory reaction, tissue repair status, and presence of the capsule were the main criteria assessed. Both cell populations showed no signs of cytotoxicity following the FRC exposures. In terms of cytotoxicity, the best results were obtained by FRC3 followed by FRC2, FRC4, and FRC1. FRC3 showed also the mildest inflammatory reaction and this correlated both with the noncytotoxic behavior and the presence of a well-organized capsule. The composite biomaterials developed may constitute an optimized alternative of the similar materials used for the reconstruction of craniofacial bone defects. According to authors' studies, the authors conclude that FRC3 is the best formulation regarding the biological behavior.

Antibacterial coating on biocomposites for cranio-facial reconstruction.

BACKGROUND AND AIMS: Despite the fact that implants are sterilized, antiseptic techniques are applied and systemic antibiotics are routinely administered prior to and after craniofacial surgery, infection rates between 3% and 40% are still reported for alloplastic implants, urging for implant removal. The present study focuses on the development of a fiber-reinforced composite (FRC) implant for craniofacial reconstruction with antimicrobial properties. METHODS: A new fiber-reinforced composite coated with gentamicin was developed and tested for bacterial adherence and antibacterial efficiency, using two of the most involved bacterial strains in the postoperative infections: Staphylococcus aureus and Pseudomonas aeruginosa. RESULTS: Bacteria were efficiently inactivated in direct contact with gentamicin coatings (p<0.05). The inhibition zone for Staphylococcus aureus ranged from 17.21 mm to 20.13 mm and for Pseudomonas aeruginosa ranged from 12.93 mm to 15.33 mm. Although no significant statistical results were found for bacterial adhesion and gentamicin concentration, (Staphylococcus aureus: ß= -0.974; p=0.144>0.05 and Pseudomonas aeruginosa: ß = -0.921; p=0.255>0.05), a negative relation was observed, indicating the reversed relation between the antibiotic dosage and the bacterial adherence. CONCLUSION: The results of the two applied microbiological protocols used in the study suggested that gentamicin eluting coating inhibited not only the bacterial growth, but also led to a lower initial bacterial adhesion to the surface of the implant. Thus, antibiotic coating of craniofacial implants may reduce the infection rate related to reconstructive surgery.

Professor Gheorghe Bilascu's contribution to the development of science and culture in Romania.

When speaking about Professor Gheorghe Bilascu (1863-1926) and his major contribution to the establishment of Romanian medical education in Cluj, he should be considered not only in terms of scientist and creator of the Dental School, but also through his commitment to the development of science and culture in Romania. A wealthy dentist in Budapest where he graduated from the Dental School, he supported a lot of Romanian students to attend schools and universities in the Budapest, thus contributing to the development of culture in his own country. Finally, he left his private practice in the Capital of Hungary to come to Cluj to support the efforts of building the Dental School and profession in Romania. This paper illustrates the contribution that Professor Gheorghe Bilascu made to the development of higher education in Romania, as well as his support of the local culture.

The ultrasonographic diagnosis of cystic cervical lesions: a pictorial essay.

The importance of ultrasonographic (US) examination in the evaluation of the superficial structures of the head and neck region is increasing due to the widespread availability of modern equipment (such as high-frequency transducers) and modern techniques. In the case of a cervical lesion, ultrasound is usually the first imaging method used to assess the changes. First of all, US is capable of differentiating between cystic and solid structures, and based on the US appearance correlated with the age of the patient, location and growing pattern, the appropriate diagnosis is possible with a high accuracy. The aim of the present paper is to describe the US features of the most common cystic lesions encountered in the head and neck region.

Micro-CT and histological analysis of Ti6Al7Nb custom made implants with hydroxyapatite and SiO2-TiO2 coatings in a rabbit model.

BACKGROUND AND AIM: Bone defect reconstruction in the maxillofacial area comes as a necessity after traumatic, oncological or congenital pathology. Custom made implant manufacturing, such as selective laser melting (SLM), is very helpful when bone reconstruction is needed. In the present study we assessed the osseointegration of custom made implants made of Ti6Al7Nb with two different coatings: SiO2-TiO2 and hydroxyapatite, by comparing the bone mineral density (BMD) measured on micro-CT and the histological mineralized bone surrounding the implants. METHODS: Custom made - cylindrical type - implants were produced by selective laser melting, coated with SiO2-TiO2 and hydroxyapatite and implanted in the rabbit femur. The animals (divided into 3 groups) were sacrificed at 1, 3 and 6 months and the implants were removed together with the surrounding bone. Bone mineral density and histological examination of the bone-implant surface was performed for each group. RESULTS: BMD and histological examination of the samples determined the quantity of mineralized bone at the implant site, showing a good percentage of mineralized bone for the coated implants at 1, 3 and 6 months. The measurements for the implants without coating showed a significant lower quantity of mineralized bone at 3 months compared with the implants with coating, and a good quantity of mineralized bone at 6 months, showing a process of demineralization followed by remineralization in the last month. The measurements of BMD showed similar results with the histological examination. CONCLUSIONS: The use of micro-CT and the measurement of BMD are a reliable, minimally invasive and a quick method of osseointegration assessment.

Selective laser melted titanium implants: a new technique for the reconstruction of extensive zygomatic complex defects.

The restoration of extensive zygomatic complex defects is a surgical challenge owing to the difficulty of accurately restoring the normal anatomy, symmetry, proper facial projection and facial width. In the present study, an extensive post-traumatic zygomatic bone defect was reconstructed using a custom-made implant that was made with a selective laser melting (SLM) technique. The computer-designed implant had the proper geometry and fit perfectly into the defect without requiring any intraoperative adjustments. A one-year follow-up revealed a stable outcome with no complications.