Identification of Potential Biomarkers and Small Molecule Drugs for Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ): An Integrated Bioinformatics Study Using Big Data.

This study aimed to identify potential molecular mechanisms and therapeutic targets for bisphosphonate-related osteonecrosis of the jaw (BRONJ), a rare but serious side effect of bisphosphonate therapy. This study analyzed a microarray dataset (GSE7116) of multiple myeloma patients with BRONJ (n = 11) and controls (n = 10), and performed gene ontology, a pathway enrichment analysis, and a protein-protein interaction network analysis. A total of 1481 differentially expressed genes were identified, including 381 upregulated and 1100 downregulated genes, with enriched functions and pathways related to apoptosis, RNA splicing, signaling pathways, and lipid metabolism. Seven hub genes (FN1, TNF, JUN, STAT3, ACTB, GAPDH, and PTPRC) were also identified using the cytoHubba plugin in Cytoscape. This study further screened small-molecule drugs using CMap and verified the results using molecular docking methods. This study identified 3-(5-(4-(Cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxybenzo[d]isoxazol-6-yl) methoxy) phenyl) propanoic acid as a potential drug treatment and prognostic marker for BRONJ. The findings of this study provide reliable molecular insight for biomarker validation and potential drug development for the screening, diagnosis, and treatment of BRONJ. Further research is needed to validate these findings and develop an effective biomarker for BRONJ.

MicroRNA in medication related osteonecrosis of the jaw: a review.

Medication related osteonecrosis of the jaw (MRONJ) is a condition caused by inhibition of the osteoclast activity by the anti-resorptive and anti-angiogenic drugs. Clinically, there is an exposure of the necrotic bone or a fistula which fails to heal for more than 8 weeks. The adjacent soft tissue is inflamed and pus may be present as a result of the secondary infection. To date, there is no consistent biomarker that could aid in the diagnosis of the disease. The aim of this review was to explore the literature on the microRNAs (miRNAs) related to medication related osteonecrosis of the jaw, and to describe the role of each miRNA as a biomarker for diagnostic purpose and others. Its role in therapeutics was also searched. It was shown that miR-21, miR-23a, and miR-145 were significantly different in a study involving multiple myeloma patients as well as in a human-animal study while miR-23a-3p and miR-23b-3p were 12- to 14-fold upregulated compared to the control group in an animal study. The role of the microRNAs in these studies were for diagnostics, predictor of progress of MRONJ and pathogenesis. Apart from its potential diagnostics role, microRNAs have been shown to be bone resorption regulator through miR-21, miR-23a and miR-145 and this could be utilized therapeutically.

Perception Regarding the NICE Guideline on Antibiotic Prophylaxis against Infective Endocarditis Following Dental Procedures: A Cross-Sectional Study.

This study explores the opinions of Malaysian clinical specialists on the antibiotic prophylaxis against infective endocarditis (IE) as described in the 2008 National Institute for Health and Care Excellence (NICE) guideline. This cross-sectional study was performed from September 2017 to March 2019. The self-administered questionnaire comprised two sections: background information of the specialists and their opinions on the NICE guideline. The questionnaire was distributed to 794 potential participants, and 277 responded (response rate of 34.9%). In general, 49.8% of the respondents believed that clinicians should adhere to the guideline, although the majority of oral and maxillofacial surgeons (54.5%) actually disagreed with this view. The dental procedures that were perceived as presented moderate-to-high risk for IE were minor surgery for an impacted tooth with a recent episode of infection, dental implant surgery, periodontal surgery and dental extraction in patients with poor oral hygiene. The cardiac conditions that were strongly recommended for antibiotic prophylaxis were severe mitral valve stenosis or regurgitation and previous IE. Less than half of Malaysian clinical specialists agreed with the changes in the 2008 NICE guideline, contributing to their insistence that antibiotic prophylaxis is still needed for high-risk cardiac conditions and selected invasive dental procedures.

Potential role of dental pulp stem cells conditioned medium for odontoblastic differentiation

BACKGROUND: Functional bioengineered tooth regeneration using autologous or allogeneic alternative differentiated cells sources are thought to have a great potential in replacing conventional dentures. This study investigated the potential of dental pulp stem cells (DPSCs) conditioned medium for odontoblastic differentiation of Wharton's jelly mesenchymal stem cells (WJMSCs). The DPSCs derived from healthy adult permanent first molars were cultured at high confluence prior to conditioned medium collection. The WJMSCs were cultured in six different treatments, with varying ratios of culture media to DPSCs-conditioned medium. MTT assay was used to measure the rate of proliferation of WJMSCs, while immunocytochemistry staining was utilised to detect the expression of dental matrix protein 1 (DMP-1). The deposited calcium was detected and analysed via Alizarin-Red Staining (ARS). RESULTS: It was found that the proliferation of WJMSCs cultured under the mixture of complete medium and DPSCs conditioned medium showed significantly lower than the control; presumably the cells started to exit proliferative state prior differentiation. In 14 days of induction, the cells in all treatments showed osteoblastic-like morphology, calcium compound deposits were observed at day 7, 10 and 14 of differentiation suggested that DPSCs conditioned medium could lead to osteoblastic/odontoblastic differentiation. However, the DMP-1 protein can be seen only expressed minimally at day 14 of conditioned medium induction. CONCLUSIONS: In conclusion, DPSCs conditioned medium appeared as a potential odontoblastic induction approach for WJMSCs. To further investigate the stimulatory effects by DPSCs conditioned medium, specific signalling pathway need to be elucidated to enhance the differentiation efficiency.

Mesenchymal stem cells: A comprehensive methods for odontoblastic induction.

BACKGROUND: In the area of oral and maxillofacial surgery, regenerative endodontics aims to present alternative options to conventional treatment strategies. With continuous advances in regenerative medicine, the source of cells used for pulp tissue regeneration is not only limited to mesenchymal stem cells as the non-mesenchymal stem cells have shown capabilities too. In this review, we are systematically assessing the recent findings on odontoblastic differentiation induction with scaffold and non-scaffold approaches. METHODS: A comprehensive search was conducted in Pubmed, and Scopus, and relevant studies published between 2015 and 2020 were selected following the PRISMA guideline. The main inclusion criteria were that articles must be revolving on method for osteoblast differentiation in vitro study. Therefore, in vivo and human or animal clinical studies were excluded. The search outcomes identified all articles containing the word "odontoblast", "differentiation", and "mesenchymal stem cell". RESULTS: The literature search identified 99 related studies, but only 11 articles met the inclusion criteria. These include 5 odontoblastic differentiation induction with scaffold, 6 inductions without scaffolds. The data collected were characterised into two main categories: type of cells undergo odontoblastic differentiation, and odontoblastic differentiation techniques using scaffolds or non-scaffold. CONCLUSION: Based on the data analysis, the scaffold-based odontoblastic induction method seems to be a better option compared to the non-scaffold method. In addition of that, the combination of growth factors in scaffold-based methods could possibly enhance the differentiation. Thus, further detailed studies are still required to understand the mechanism and the way to enhance odontoblastic differentiation.

Predictors of osteoradionecrosis following irradiated tooth extraction.

BACKGROUND: Tooth extraction post radiotherapy is one of the most important risk factors of osteoradionecrosis of the jawbones. The objective of this study was to determine the predictors of osteoradionecrosis (ORN) which were associated with a dental extraction post radiotherapy. METHODS: A retrospective analysis of medical records and dental panoramic tomogram (DPT) of patients with a history of head and neck radiotherapy who underwent dental extraction between August 2005 to October 2019 was conducted. RESULTS: Seventy-three patients fulfilled the inclusion criteria. 16 (21.9%) had ORN post dental extraction and 389 teeth were extracted. 33 sockets (8.5%) developed ORN. Univariate analyses showed significant associations with ORN for the following factors: tooth type, tooth pathology, surgical procedure, primary closure, target volume, total dose, timing of extraction post radiotherapy, bony changes at extraction site and visibility of lower and upper cortical line of mandibular canal. Using multivariate analysis, the odds of developing an ORN from a surgical procedure was 6.50 (CI 1.37-30.91, p = 0.02). Dental extraction of more than 5 years after radiotherapy and invisible upper cortical line of mandibular canal on the DPT have the odds of 0.06 (CI 0.01-0.25, p < 0.001) and 9.47 (CI 1.61-55.88, p = 0.01), respectively. CONCLUSION: Extraction more than 5 years after radiotherapy, surgical removal procedure and invisible upper cortical line of mandibular canal on the DPT were the predictors of ORN.

Closed and Open Reduction of Nasal Fractures.

AIM: The objective of this review was to determine the different types of surgical intervention in the management of nasal bone fractures, the outcomes, and complications associated with each intervention. METHODS: A search was conducted using the PubMed and Cochrane Database of Systematic Review databases from January 1, 1997 until September 9, 2017. The search strategy was constructed using the Population Intervention Comparison Outcome framework with keywords related to nasal fracture and its treatment. Two sets of independent researchers performed the analysis. Qualitative analysis was performed using the Methodological Index for Non-Randomized Studies and National Institute for Clinical Excellence methodology for randomized controlled trial checklists. RESULTS: The 4276 titles were obtained from PubMed database alone. Exclusion was made based on the title, abstract and full-text analysis. Finally, 23 papers were included and analyzed. Of the 23 papers, 13 (56.5%) were retrospective record review, 2 (8.7%) were randomized clinical trial or a randomized study and 8 case series (34.8%). 16 (69.6%) studies addressed closed reduction, 3 studies (13%) on open reduction and 4 studies (17.4%) addressed both open and closed reduction. The main focus in the outcome in all studies was accuracy of the anatomical reduction of the nasal bones. Three studies (13.0%) reported restoration of function such as breathing comfort or release in respiratory obstruction and another 3 (13.0%) addressed both cosmetic and breathing outcomes. Residual deformity was the most described complications in the studies (30.4%). In general, most of the studies were not of high quality as they lacked in some key elements in the Methodological Index for Non-Randomized Studies checklist. CONCLUSION: Both closed and open reduction provided good outcomes in cosmetic and breathing. Septoplasty is recommended to be performed simultaneously with fracture reduction.

Motorcycle helmet visor-related facial injury and its potential mechanism of injury: Evidence-based case study.

Objectives: We encountered an unusual facial laceration wound in relation to motorcycle helmet visor use during our clinical practice. We aimed to assess the prevalence of this unusual facial injury among motorcyclists who sustained facial injuries in selected hospitals and to determine the possible mechanism involved. Methods: We used our prospective cross-sectional substudy involving injured motorcyclists presenting at major trauma hospitals in Southern Klang Valley, Malaysia, between March 2010 and March 2011. of 391 subjects with facial injuries, 2 male motorcyclists sustained this laceration. The wounds were assessed and we believed that each was associated with the helmet visor. One of the visors was collected and the edge was inspected using scanning electron microscopy (SEM). Results: The prevalence of this unusual injury was 0.51% (95% confidence interval, 0.002-0.012) among motorcyclists who sustained facial injuries. Both cases were involved in a head-on collision with their colliding partners and their helmets were intact throughout the crash. The visor in case 1 was intact, but the visor in case 2 was broken. SEM analysis showed that the visor in case 1 had a potential cutting surface. We postulated that with helmet rotation in the forward and downward position and with some degree of visor bending or with a dislodged visor, the sharp-edged visor could potentially severely lacerate the face. Conclusion: This injury affects facial aesthetics and early referral to the facial surgery team is advocated. Documentation of the mechanism of injury, the patient's helmet and visor is obligatory, so that this information can be delivered to the regional road safety authority for preventive measures.

Gorham's disease of the mandible: radiological features.

The most conspicuous element of Gorham's disease is its radiographic features, wherein massive disappearance of the mandible is observed. We report a case of an adolescent boy with massive osteolysis of the mandible in whom the diagnosis of Gorham's disease was made. A 14-year-old boy was referred to the Department of Oral and Maxillofacial Surgery, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, for the management of a massive mandibular deformity. He was diagnosed with a hemangioma-like lesion at 1 year of age. The disease had progressed for an unknown number of years. Plain X-rays and computed tomography images were examined for reconstructive surgery planning. Gorham's disease is self-limiting, but has catastrophic results. The role of imaging is huge, particularly for reconstructive surgery planning.

Corneal regeneration by induced human buccal mucosa cultivated on an amniotic membrane following alkaline injury.

Various clinical disorders and injuries, such as chemical, thermal, or mechanical injuries, may lead to corneal loss that results in blindness. PURPOSE: The aims of this study were to differentiate human buccal mucosa (BMuc) into corneal epithelial-like cells, to fabricate engineered corneal tissue using buccal mucosal epithelial cells, and to reconstruct a damaged corneal epithelium in a nude rat model. Methods: BMuc were subjected to 10 d of induction factors to investigate the potential of cells to differentiate into corneal lineages. Results: Corneal stem cell markers ß1-integrin, C/EBPδ, ABCG2, p63, and CK3 were upregulated in the gene expression analysis in induced BMuc, whereas CK3 and p63 showed significant protein expression in induced BMuc compared to the uninduced cells. BMuc were then left to reach 80% confluency after differential trypsinization. The cells were harvested and cultivated on a commercially available untreated air-dried amniotic membrane (AM) in a Transwell system in induction medium. The corneal constructs were fabricated and then implanted into damaged rat corneas for up to 8 weeks. A significant improvement was detected in the treatment group at 8 weeks post-implantation, as revealed by slit lamp biomicroscopy analysis. The structure and thickness of the corneal layer were also analyzed using histological staining and time-domain optical coherence tomography scans and were found to resemble a native corneal layer. The protein expression for CK3 and p63 were continuously detected throughout the corneal epithelial layer in the corneal construct. Conclusions: In conclusion, human BMuc can be induced to express a corneal epithelial-like phenotype. The addition of BMuc improves corneal clarity, prevents vascularization, increases corneal thickness and stromal alignment, and appears to have no adverse effect on the host after implantation.

Mandibular Canal Enlargement: Clinical and Radiological Characteristics.

Enlargement of the mandibular canal is a rare radiological finding. Clinically, it may or may not be associated with sensory deficits. We report four cases of widening of the mandibular canal observed with various methods of imaging with different clinical characteristics. We describe this unique radiological finding and elaborate the importance of quality assessment of the imaging that is vital for accurate diagnosis and treatment planning. Clinicians should be mindful when assessing the imaging whenever the size of the mandibular canal is implicated. The case ranged from a benign tumor to malignancy, radiological errors, and artifacts. A more superior imaging or treatment modality was necessary to ascertain the diagnosis.

The Clinical Features and Expression of bcl-2, Cyclin D1, p53, and Proliferating Cell Nuclear Antigen in Syndromic and Nonsyndromic Keratocystic Odontogenic Tumor.

UNLABELLED: The aim of this study was to describe the clinical features and expression of bcl-2, cyclin D1, p53, and proliferating cell nuclear antigen (PCNA) antibodies in syndromic (nevoid basal cell carcinoma syndrome [NBCCS]) and nonsyndromic patients diagnosed with keratocystic odontogenic tumor (KCOT). METHODS: This descriptive study comprised 5 patients of KCOT associated with NBCCS and 8 patients of nonsyndromic type treated in the Department of Oral Maxillofacial Surgery, Universiti Kebangsaan Malaysia Medical Centre between years 1998 and 2011. The clinical features (site, size, treatment, and recurrence), demographic characteristics, and immunohistochemistry results using antibodies of bcl-2, cyclin D1, p53, and PCNA were examined. The association of the antibody expression and the type of KCOT was analyzed using Fisher exact test. RESULTS: Altogether there were 13 patients, 5 with syndromic KCOT (1 patient met 3 major criteria of NBCCS) and 8 with sporadic KCOT. The age range for syndromic KCT was 11 to 21 years (mean 16.00 years, SD 4.36) and 10 to 54 years (median 24.50 years, interquartile range 19.00) for the nonsyndromic KCOT. Tumor recurrence occurred in 3 patients (7.7%); 1 patient from the syndromic and 2 patients from the nonsyndromic. The most positive expression was observed in PCNA for both the syndromic and nonsyndromic samples and the least positive expression involved the p53. CONCLUSION: PCNA, bcl-2 protein, and cyclin D1 expressions could be useful in evaluating the proliferative activity of the tumor and the aggressiveness of the clinical presentation; however, the authors would propose for larger sample size research for more definitive results.

Non-pulsatile traumatic pseudoaneurysm of the internal maxillary artery following trauma to mandible.

Traumatic pseudoaneurysm involving the maxillary artery is rare. Owing to its anatomic location, internal maxillary artery is usually protected by its surrounding structures. Formation of pseudoaneurysm usually takes place after several weeks to months of the initial injury. In this case, we reported a pseudoaneurysm arising from left internal maxillary artery following blunt injuries within 3 hours after a road accident and the treatment with endovascular embolization with titanium coils prior to open reduction and internal fixation of the fractured mandibles.

Schwannoma of the tongue in a ten-year old child.

The case of a 10-year-old girl is presented who had a slow-growing, painless swelling on the left side of the tongue since six months. This was associated with disturbances in mastication and phonation. Examination revealed a 5 cm x 4 cm. globular smooth, mobile mass on left side of the tongue. There was no neurological deficit and no neck nodes palpable. She underwent excision of the mass under general anaesthesia. Complete enucleation with primary closure was carried out. The patient had an uneventful postoperative recovery and histological evaluation was consistent with schwannoma. The patient was recurrence free after one year.

A retrospective study of oral and maxillofacial injuries in Seremban Hospital, Malaysia.

INTRODUCTION: Aetiology of oral and maxillofacial injuries in this country includes motorvehicle accident (MVA), fall, industrial accidents and others. Among these causes, MVA accident is the predominant cause of injury in Malaysia. MATERIALS AND METHODS: A retrospective record review was carried out using hospital records of all patients who sustained oral and maxillofacial injury at the Department of Oral Surgery, Seremban Hospital, Negeri Sembilan, Malaysia between 1998 and 2002. Information related to demographics, aetiology of trauma, vehicles involved in collision, location of injuries and treatment modalities were reviewed. RESULTS: Two thousand nine hundred and eighty-six patients sustained oral and maxillofacial injuries. Of these patients, 79.2% were men and the remaining were women. Among all the races, Malays had the highest involvement (50.6%) followed by Indians (24.5%), Chinese (19.6%) and others (5.3%). There were statistically significant results on the association of aetiology and the ethnic groups, in the age group of 30 years or less and male gender (P < 0.001). The most common injury was the soft-tissue injury followed by dental and dentoalveolar injuries and bony fracture. Among all facial fractures, 66.3% were managed conservatively, 13% were treated surgically and 19.7% did not have any intervention. In relation to dental and dentoalveolar injuries, 64.8% had treatment in the form of splinting, restorations or dental extraction. The rest of the patients (35.2%) were referred to their dentists or did not have any active treatment at Seremban Hospital. CONCLUSION: Most of the dental and facial injuries in Seremban Hospital were caused by MVA and were predominantly managed using conservative methods.

A retrospective study of ranula in two centres in Malaysia.

INTRODUCTION: Ranula is a mucous extravasation cyst which occurs as a result of trauma or obstruction of the sublingual or minor salivary gland or the duct itself. PATIENTS AND RESULTS: 14 patients were seen at Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur and Hospital Tunku Ampuan Afzan, Kuantan, Malaysia between 2000 to 2006. There were six cases of intra-oral ranula and eight plunging ranula. Twelve patients underwent surgical intervention while two refused surgery. Four patients (33.3%) from those who had surgical intervention returned with recurrence; two (16.7%) had marsupialization and the other two (16.7%) had excision of the pseudocyst intraorally. CONCLUSION: Excision and marsupialization remain as the treatment of choice in our centres.

Metastasis to the sinonasal tract from sigmoid colon adenocarcinoma.

INTRODUCTION: Metastatic adenocarcinoma from the gastrointestinal tract to the sinonasal tract is rare. The histological morphology of this lesion is indistinguishable from the colonic variant of primary sinus adenocarcinoma or intestinal-type adenocarcinoma (ITAC). CLINICAL PICTURE: This is a report of a case of metastatic adenocarcinoma of colorectal origin to the paranasal sinuses in a 52-year-old female who was previously treated for adenocarcinoma of the sigmoid colon. A histologic study of the surgical specimen from the sinonasal cavity demonstrated a tumour identical to the patient's prior primary tumour of the colon. The sinonasal neoplastic tissue showed marked positivity for carcinoembryonic antigen and expressed cytokeratin 20, which differentiates metastatic colonic adenocarcinoma from ITAC. TREATMENT/OUTCOME: The patient received palliative radiation but died 3 months after the diagnosis. CONCLUSION: Distinguishing metastatic adenocarcinoma from gastrointestinal tract from ITAC can be difficult. In view of the resemblance, immunohistochemical staining can help in differentiating them. It is important to recognise these as metastatic lesions as the treatment is mainly palliative.

Pattern of maxillofacial injuries in motorcyclists in Malaysia.

Motorcycle casualties represent significant number in road traffic accidents in Malaysia, and among all the injuries, facial injuries pose many significant problems physiologically, functionally, and aesthetically. The aim of this study was to analyze the pattern of maxillofacial as well as other injuries in motorcyclists who were seen at Hospital Universiti Kebangsaan Malaysia.Patients' records from January 2004 to December 2005 were reviewed. Data related to demographics, vehicle/object involved in collision, involvement as a rider or pillion, whether a helmet was worn or not, location of injuries on the face/facial bones, and other associated injuries were collected.A total of 113 cases of motorcycle accidents were recorded; 106 males and 7 females were involved. Mean age was 25.8 years. Among all the races, Malay had the highest involvement (72.3%), followed by Chinese (14.3%), Indians (8.9%), and others (5.4%). The types of collision were either a single-vehicle collision (i.e., skidded) or with another vehicle/s or object (e.g., tree, stone, or lamppost). The injuries were mainly seen on the lower face (46.9%) followed by midface (25.7%) and a combination of the midface and lower face (15%) and others (12.4%). The most frequent other associated injuries recorded were orthopedic and head injuries.

Necrotizing gingivitis: a possible oral manifestation of ticlopidine-induced agranulocytosis.

Agranulocytosis is a rare complication of ticlopidine and can be life-threatening. We report a case of ticlopidine-induced agranulocytosis and neutropenia (neutrophil count of 0.1 x 10(9)/L) with necrotizing gingivitis in a 54-year-old Malaysian-Chinese female. She was started on ticlopidine 250 mg twice daily 3 weeks prior to this hospital admission. We started her on intravenous metronidazole and amoxicillin and clavulanic acid (Augmentin) and concurrently stopped ticlopidine. A series of clinical and laboratory investigations were carried out and a final diagnosis of necrotizing gingivitis possibly secondary to agranulocytosis was made. The patient was discharged home after 2 weeks of hospitalisation.

Autotransplantation of maxillary canine following removal of compound odontome: a case report.

Obstruction remains as an important cause of failure in the eruption of a tooth. In this article, a 15-year-old girl was presented with retained upper left primary canine (63) and first primary molar (64), while the contralateral permanent canine (13) and premolars (14 and 15) have erupted. Upon radiographic examination, a mass which was diagnosed later to be compound odontome was detected. The treatment consisted of surgical removal of the odontome, extraction of the primary canine (63) and left permanent canine (23), and transplantation of the permanent canine (23). The management of this case and the literature related to autotransplantation are discussed.