The oral microbiome of newly diagnosed tuberculosis patients; a pilot study.

BACKGROUND: Changes in oral microbiota composition (dysbiosis) have long been known to play a key role in the pathogenesis of oral and systemic diseases including respiratory diseases. However, till now, no study has assessed changes in oral microbiota following tuberculosis (TB) infection in humans. AIMS: This is the first study of its kind that aimed to investigate oral microbial dysbiosis in newly diagnosed, treatment naïve, TB patients. METHODS: Oral swab samples were collected from newly diagnosed TB patients (n = 20) and age, gender and ethnicity matched healthy controls (n = 10). DNA was extracted and microbiota analyzed by sequencing the hypervariable (V3-V4) region of the bacterial 16S rRNA gene using Illumina MiSeq platform. Bioinformatics and statistical analyses were performed using QIIME and R. RESULTS: Bacterial richness, diversity and community composition were significantly different between TB patients and healthy controls. The two groups also exhibit differential abundance at phylum, class, genus and species levels. LEfSe analysis revealed enrichment (LDA scores (log10) >2, P < 0.05) of Firmicutes (especially Streptococcus) and Actinobacteriota (especially Rothia) in TB patients relative to healthy controls. Gene function prediction analysis showed upregulation of metabolic pathways related to carbohydrates (butanoate, galactose) and fatty acids metabolism, antibiotics biosynthesis, proteosome and immune system signaling. CONCLUSION: These observations suggest significant variations in diversity, relative abundance and functional potential of oral microbiota of TB patients compared to healthy controls thereby suggesting potential role of oral bacterial dysbiosis in TB pathogenesis. However, longitudinal studies using powerful metagenomic and transcriptomic approaches are crucial to more fully understand and confrim these findings.

Erythema multiforme-like lip presentation in pemphigus vulgaris patients: a multicenter case series.

Pemphigus vulgaris (PV) is a chronic autoimmune mucocutaneous blistering disease. Autoantibodies are directed against desmogleins, leading to the formation of intraepithelial bullae. PV, as with other autoimmune mucocutaneous disorders of the oral cavity, presents diagnostic and therapeutic challenges. Approximately 50-70% of cases present first with oral lesions. The lesions commonly start as vesicles or bullae that rapidly rupture, leading to erosions and ulcerations. The palatal, gingival, buccal, and labial mucosa are the most commonly affected sites. Oral PV can mimic several other diseases that cause mucosal erosions and/or ulcerations, including erythema multiforme (EM). EM is an acute, immune-mediated, self-limited hypersensitivity condition primarily associated with herpes simplex infection. Oral lesions can be variable, but a very characteristic presentation with labial hemorrhagic erosions, ulcerations and crusting is commonly seen. In this case series, we present six cases of PV: one male patient and five female patients whose ages ranged from 34 to 65 years old. All patients presented with hemorrhage and crusting of the lips in addition to multiple intraoral erosions and ulcerations. Three patients presented with oral and skin lesions. All patients underwent biopsies, and a diagnosis of PV was confirmed. All patients were treated with steroids (topical and systemic) and variable steroid-sparing agents. This case series emphasizes that oral PV may be misdiagnosed as EM in a subgroup of patients who present with persistent lip hemorrhage and crusting. Therefore, a comprehensive history, clinical examination and incisional biopsies should be considered in such patients.

The value of a specialized second-opinion pathological diagnosis for oral and maxillofacial lesions.

OBJECTIVES: An error in the diagnosis of an oral or maxillofacial lesion could potentially be detrimental to a patient's prognosis and management. Major discrepancies between the initial and subsequent diagnoses of head and neck pathologies range from 7 to 53%. This study determined the rate of discrepancies found in the diagnoses of oral and maxillofacial lesions after a second opinion in Saudi Arabia. METHODS: A retrospective single-center study was conducted by oral and maxillofacial pathology consultants to review all cases referred for a second opinion to the oral and maxillofacial pathology laboratory between January 2015 and December 2020. If the second-opinion diagnosis matched the original diagnosis, this was described as "agreement." If the second-opinion diagnosis did not match the original diagnosis but would not change the management or prognosis of a patient, this was classified as a "minor disagreement." If the second-opinion diagnosis resulted in the changing of a patient's management or prognosis, this was categorized as a "major disagreement." Chi-square test and Fisher's exact test were used to compare data between original and second-opinion diagnoses. A p-value of less than 0.05 was considered significant. RESULTS: Of 138 cases, 59 (43%) had an initial diagnosis and a second-opinion diagnosis that were in major disagreement. The most common tumor for which there was a major disagreement was squamous cell carcinoma. No single factor influenced the occurrence of major disagreements. CONCLUSIONS: Our evaluation reiterates the importance of obtaining a second opinion from a specialist in oral and maxillofacial pathology to improve the diagnostic accuracy for lesions. A formal system for this step, in addition to the obtaining of adequate clinical and radiographic information about a patient, is mandatory for the review of difficult cases.

Pulpal and periapical tissue response after direct pulp capping with endosequence root repair material and low-level laser application.

BACKGROUND: The study aims to investigate the pulp and periapical reaction and healing after capping with EndoSequence Root Repair Material (ERRM) combined with low-level laser application. METHODS: In 6 rabbits, pulps were exposed via class V, half of the samples received a low-level diode laser at 980 nm. Thereafter, cavities were capped with regular-set ERRM. The specimens were processed for histomorphological examination after 2 weeks and two months. RESULTS: After 2 weeks, images show mild inflammation and organized odontoblasts in lased group. The non-lased group shows more severe inflammation. The predentin thickness was thicker in the lased group with statistical significance (p < 0.05). After 2 months, inflammatory cells were sparse in both lased and non-lased groups. In the periapical area, group one showed dilated blood vessels and thick fibrous connective tissues. In group two, there were more numerous maturations of PDL fibers with scattered inflammatory cells and congested blood vessel. CONCLUSIONS: Using low-level laser therapy in combination with ERRM for pulp capping shortens the inflammatory phase and enhances healing.

Retraction notice to Plexin-B1 and Semaphorin 4D Cooperate to Promote Perineural Invasion in a RhoA/ROK-Dependent Manner Am J Pathol 180 (2012) 1232-1242.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article is being retracted following correspondence from the Office of Accountability and Compliance at the University of Maryland, Baltimore. An internal investigation into this manuscript by the University of Maryland, Baltimore, found evidence that there are errors with the presentation of the standard deviations and statistical significance shown in Figure 6 which are not supported by the original data, and that these inaccuracies warrant retraction to correct the scientific record. Despite extensive efforts, the journal was unable to contact Dr. Ying-hua Yang and Dr. Hua Zhou with regard to this retraction.

Why do students skip classroom lectures: A single dental school report.

BACKGROUND: Conventional classroom lectures continue to represent a major component of the dental education system to ensure optimum delivery of knowledge. Certain number of students are less compliant and likely to skip classes which may impact the overall academic performance. The aim of this study was to investigate dental students' attitude towards classroom attendance and potential reasons for absenteeism at King Abdulaziz University-Faculty of Dentistry (KAU-FD). METHODS: This was a cross-sectional survey of all dental students actively enrolled at KAU-FD from January to June 2019. The survey included questions on demographics, average travel time to school, current dental year, most recent GPA, student's perspective toward classroom lectures. The survey was validated and distributed to all students at a pre-selected time frame. Data were analysed and presented as frequencies and percentages; chi-square test was used to explore parameters association. RESULTS: A total of 678 students consented and completed the survey. Overall, 44.3% of students were more likely to skip two classes or less per month. Second year dental students were more likely to be absent from classroom lectures (31.3%), while 3rd year dental students were less likely to do so (15.4%). Reported students' justifications for missing classes included early morning classes (47.9%), exams preparation (42%), and lecturer's weak presentation skills (41.9%). CONCLUSION: Compliance of dental students with classroom attendance has been an ongoing challenge for most programs. The current data suggests a multifactorial module for students' attitude toward classroom attendance. Future studies focusing on reasons behind classroom attendance behavior and addressing students' concerns are needed.

Correction to: Rho-mediated activation of PI(4)P5K and lipid second messengers is necessary for promotion of angiogenesis by Semaphorin 4D.

Figure 3c of this article originally contained standard deviation values which had not been calculated correctly. A single standard deviation value was used for all 5 time points for each condition.

Retraction Note to: Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression.

The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figures 1B and 1D, the cell lines are different and all published histograms show SEMA4D mRNA level whereas Excel data have two histograms showing SEMA4D expression and two histograms showing VEGF expression. In Figure 2B, the metadata for one image shows different treatment conditions than those reported in the article. The published image labelled "VEGF + VEGFR-2 shRNA" has a metadata label of S4d-plexinB1 shRNA2". In Figure 2E, statistical significance was shown in the published figure for four comparisons, but upon recalculation, one comparison noted as significant was not. In Figure 6A, the lower left image is labelled "VEGF shRNA" in the published figure, but the metadata label is "S4DshRNA-HN121-20X". In Figure 6C, specifically, within columns 2-4, for each antibody used for immunocytochemistry, the three images have been swapped so that the original images do not match the shRNA labels in the figure (the labels for the two antibodies were correct). In Figure 7D, the first published image is labelled as "IgG" in the paper, but the metadata show a label of "Restore (V+S).tif". The third published image has a label of "anti-VEGF IgG", and the metadata show a label of "con sh.tif". Due to these errors, the Editors-in-Chief have found that the results are no longer reliable.

Prevalence and policy of occupational violence against oral healthcare workers: systematic review and meta-analysis.

BACKGROUND: Occupational violence is considered unlawful in professional environments worldwide. In the healthcare industry, including dentistry, the safety of workers is essential, and it is of the utmost importance to ensure patient and employee safety and provide quality care. This study aimed to evaluate the prevalence of violence and associated workplace policies among oral healthcare professionals. Additionally, it aimed to identify the factors associated with violence and their impact on oral healthcare workers. METHODS: A systematic review and analysis of the literature was conducted using PubMed, ScienceDirect, Scopus, Web of Science, Cochrane Library and ProQuest. Original articles written in English and published between January 1992 and August 2019 were included in the analysis. RESULTS: A total of 980 articles were found, and eight were selected for analysis. The violence experienced by healthcare workers included both physical and non-physical forms, such as shouting, bullying, and threatening; it also included sexual harassment. The impact of violence on workers manifested as impaired quality of work, psychological problems, and, although rare, quitting the job. With regard to dental healthcare, awareness of occupational violence policies among dental professionals has not been previously reported in the literature. CONCLUSIONS: The increasing incidence of occupational violence against oral healthcare workers indicates the need for the implementation of better protective measures to create a safe working environment for dental professionals. There is a current need for increasing awareness of workplace violence policies and for the detection and reporting of aggression and violence at dental facilities.

Oral Cancer and Twitter: An Analysis of Oral Cancer Awareness Month Tweets.

OBJECTIVE: The objective of this research was to assess Twitter usage during Oral Cancer Awareness Month and explore the content and engagement related to oral cancer. METHODS: A comprehensive search was performed using relevant hashtags and keywords related to oral cancer on Twitter throughout the oral cancer awareness month, April 2022. All extracted tweets that match the inclusion criteria were analyzed for content, users were classified, and their countries were identified. RESULT: A total of 5551 English tweets were identified during Oral Cancer Awareness Month, and 5543 were included in the analysis covering a wide range of oral cancer-related topics. The analyzed tweets encompassed a diverse range of topics, from cancer and oral health to oncology, cancer research, cancer awareness, and even discussions related to alcohol. We found that the majority of users who post on Twitter were individuals. The most common tweets were posted from the USA. CONCLUSIONS: This study provides an analysis of Twitter activity during Oral Cancer Awareness Month, highlighting the diverse range of content being shared, offering valuable insights. The findings demonstrate the importance of leveraging social media platforms to disseminate information and raise awareness. With a strategic approach to social media, organizations and individuals worldwide have the power to amplify their message, attract attention, and effectively advocate for oral cancer awareness.

Pediatric oral pathology in Saudi Arabia: A 10-year retrospective study at an academic dental hospital.

Introduction: Pediatric oral pathology encompasses a wide range of diseases and conditions affecting the oral cavity in children. In this study we conducted an analysis on a dataset from one academic center in Saudi Arabia to investigate the prevalence of various oral lesions in pediatric patients. Methods: To conduct this study we analyzed oral pathology reports of pediatric patients (age range: 0-18 years) who underwent biopsies at our institution's oral pathology laboratory between January 2012 and December 2022. The data we collected included demographic information and diagnostic findings. Statistical analysis was performed to determine the prevalence rates of and associations between different variables. Results: The study analyzed a total of 183 pediatric cases with oral pathologies. The most common conditions observed were mucocele (12 %), periapical granuloma (7.7 %), dentigerous cyst (6.6 %), and radicular cyst (6.6 %). Some conditions showed variations in prevalence based on age and gender. For example, mucoceles were more prevalent among patients who were 6-12 years of age and female. Conclusion: This retrospective study provides valuable insights into the prevalence and demographic characteristics of pediatric oral pathologies. By understanding the prevalence of conditions in this population and recognizing differences in distribution compared with those cited in other studies, we highlighted the importance of considering regional and demographic influences. Further prospective studies are needed to investigate factors that may contribute to these variations.

Oral squamous cell carcinoma with synchronous follicular lymphoma: A rare case report.

The occurrence of oral squamous cell carcinoma synchronously with lymphoma arising primarily in cervical lymph nodes is rare. Here, we report a case representing an infrequent finding. A 66-year-old male who was diagnosed with right mandibular squamous cell carcinoma and was subsequently found to have a nodal follicular lymphoma as a second malignancy. The patient underwent surgical resection for the oral squamous cell carcinoma with right selective neck dissection. The multidisciplinary team's postoperative treatment strategy involved adjuvant radiotherapy for the oral squamous cell carcinoma, while adopting a close follow-up approach for the follicular lymphoma. After an 18-month follow-up, there were no evidence of disease progression. This case report highlights the diagnostic challenges of synchronous primary malignancies occurring in the head and neck region. It also underscores the importance to conduct a comprehensive clinical and histopathological examination to rule out the possibility of synchronous neoplasms.

Utilization of nanotechnology and experimental design in the development and optimization of a posaconazole‒calendula oil nanoemulgel for the treatment of mouth disorders.

Introduction: Essential oil‒based nanoemulsions (NEs) are the subjects of extensive investigation due to their potential to address a variety of oral health issues. NEs are delivery systems that improve lipid medicine solubility and distribution to intended sites. The goal of the current study was to create and enhance a self-nanoemulsifying drug delivery paradigm based on calendula oil (CO) and decorated with chitosan (CS) that could deliver posaconazole (PSZ) for the treatment of gingivitis. Method: Employing a response-surface Box‒Behnken design, PSZ-CO-CS NEs were created with varying amounts of PSZ (10, 15, and 20 mg), percentages of CO (6%, 12%, and 18%), and percentages of CS (0.5%, 1.5%, and 2.5%). Results and conclusion: The optimized formulation resulted in a 22-mm bacterial growth suppression zone, 25-mm fungal growth inhibition zone, droplet sizes of 110 nm, and a viscosity of 750 centipoise (cP). Using the appropriate design, the ideal formulation was produced; it contained 20 mg of PSZ, 18% of CO, and 1.35% of CS. Furthermore, the optimal formulation had a more controlled drug release, larger inhibition zones of bacterial and fungal growth, and desirable rheologic properties. Additionally, the optimized formulation substantially lowered the ulcer index in rats when tested against other formulations. Thus, this investigation showed that PSZ-CO-CS NEs could provide efficient protection against microbially induced gingivitis.

Detection of Specific Immunoglobulins in the Saliva of Patients With Mild COVID-19.

Saliva has many advantages over blood as a biofluid, so using it for measuring and monitoring antibody responses in COVID-19 would be highly valuable. To assess the value of saliva-based IgG and IgM/IgA antibody testing in COVID-19, this cross-sectional pilot study evaluated the accuracy of salivary and serum IgG and IgM/IgA for detecting mild COVID-19 and their correlation. Fifty-one patients with mild COVID-19 (14-28 days post-symptom onset) were included in the study. Enzyme-linked immunosorbent assays (ELISA) were used to measure IgG and IgM/IgA responses to SARS-CoV-2 spike protein in both serum and saliva samples using a slightly modified protocol for saliva samples. Saliva-based IgG testing had 30% sensitivity and 100% specificity, with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 50%. Saliva-based IgM/IgA testing had 13.2% sensitivity and 100% specificity, with a PPV of 100% and an NPV of 28.3%. Blood and saliva IgG values were positively correlated. Saliva currently has limited diagnostic value for COVID-19 testing, at least for mild disease. Nevertheless, the significant positive correlation between blood and saliva IgG titers indicates that saliva might be a complementary biofluid for assessing systemic antibody responses to the virus, especially if the assay is further optimized across the full disease spectrum.

Plexin-B1 and semaphorin 4D cooperate to promote perineural invasion in a RhoA/ROK-dependent manner.

Perineural invasion (PNI) is a tropism of tumor cells for nerve bundles located in the surrounding stroma. It is a pathological feature observed in certain tumors, referred to as neurotropic malignancies, that severely limits the ability to establish local control of disease and results in pain, recurrent growth, and distant metastases. Despite the importance of PNI as a prognostic indicator, its biological mechanisms are poorly understood. The semaphorins and their receptors, the plexins, compose a family of proteins originally shown to be important in nerve cell adhesion, axon migration, and proper central nervous system development. Emerging evidence has demonstrated that these factors are expressed in tissues outside of the nervous system and represent a widespread signal transduction system that is involved in the regulation of motility and adhesion in different cell types. We believe that the plexins and semaphorins, which are strongly expressed in both axons and many carcinomas, play a role in PNI. In this study, we show that plexin-B1 is overexpressed in tissues and cell lines from neurotropic malignancies and is attracted to nerves that express its ligand, semaphorin 4D, in a Rho/Rho kinase-dependent manner. We also demonstrate that nerves are attracted to tumors through this same system of proteins, suggesting that both plexin-B1 and semaphorin 4D are important in the promotion of PNI.

The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma.

Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors.

Impact of worst pattern of invasion on prognosis of oral squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: The relationship between the worst pattern of invasion (WPOI) and the prognosis of oral squamous cell carcinoma (OSCC) remains controversial. This systematic review and meta-analysis was performed to determine the impact of the WPOI on the prognosis of OSCC. METHODS: Studies from six databases were assessed for quality using the Newcastle-Ottawa Scale, and data were analyzed using Stata software. RESULTS: Eighteen studies involving 3954 patients showed that patients with a WPOI of 4 to 5 had significantly worse overall survival, disease-specific survival, and disease-free survival than patients with a WPOI of 1 to 3. Significant associations of the WPOI with locoregional recurrence and mortality were found. CONCLUSION: A higher WPOI was significantly associated with a worse prognosis of OSCC across various outcomes. Incorporating the WPOI into standard histopathological assessments may guide personalized treatments and improve outcomes.

The effect of low-level laser on the quality of dentin barrier after capping with bioceramic material: A histomorphometric analysis.

The study aims to investigate the quality of dentin barriers and pulp reaction to EndoSequence Root Repair Material (ERRM) combined with low-level laser application. In eight dogs, pulps were exposed via class V, half of the samples received low-level diode laser at 870 nm. Thereafter, cavities were capped with fast-set or regular-set ERRM. The specimens were processed for histomorphological and immunohistochemical examination after 2 weeks and 2 months. Dentin bridges were observed in all samples, and 87.5% were complete. The low-level laser group had significantly more reparative dentin area than the non-lased group (p < 0.05). The dentin bridges were found to have an unprecedented tubularity of 43%-89%. Tiny dentin island formation was observed within the material particles. Initial mild-to-moderate inflammatory reactions were observed, which subsided after 2 months. RUNX2 and osteocalcin staining were evident for all samples at both time intervals. Low-level laser combined with bioactive ERRM is effective in inducing reparative dentin formation.

Salivary Oxidative Stress and Antioxidant Capacity in Smokeless Tobacco (Naswar) Users.

Background: Naswar, a smokeless tobacco product, commonly consumed in Pakistan, is associated with a 10-fold increase in the risk of oral cancer. However, little is known about Naswar's underlying toxicity mechanisms. Objective: The current study aimed to investigate the effects of Naswar use on oral health and salivary parameters. Methods: A case-control study was conducted among Naswar users (n=42) and age-matched healthy controls (n=42) in Pakistan in 2019. Participant data were collected using questionnaires. Decayed, missing, and filled teeth (DMFT) scores were computed during clinical examinations. Unstimulated whole saliva was collected to assess salivary flow rate, pH, and salivary total oxidative stress (TOS)/total antioxidant capacity (TAC) using commercially available kits. Participants' oral health parameters were compared between cases and controls using ANOVA. Results: No significant differences were observed between the two groups in terms of age, oral health, and hygiene practices and mean DMFT score. Mean salivary pH and the salivary flow rate was significantly (p<0.001) higher in Naswar users (7.7 and 0.71 mL/minute, respectively) than in non-users (6.95 and 0.52 mL/minute, respectively). Although TOS and TAC were not significantly different between the groups, Naswar users generally had a higher TOS (51.6±42 µmol/L) and lower TAC (0.55±0.18 mmol/L) than non-users (TOS 45.5±38.2 µmol/L and TAC 0.57±0.17 mmol/L). Correlational analysis also revealed a significant positive correlation between DMFT score and Naswar use duration (r=0.796, p<0.001) and the number of dips/units consumed each day (r=0.515; p<0.001). Conclusion: Habitual Naswar use is associated with increased salivary flow rate, pH, and TOS, and reduced TAC levels in Pakistani adults compared to non-users. The pro-oxidant changes may contribute toward deleterious effects of Naswar use including oral cancer.