Evaluation of the antibacterial and cytotoxic properties of TotalFill and NeoSEALER flo bioceramic sealers.

Aim: Evaluation of the antibacterial and cytotoxic properties of TotalFill and NeoSEALER Flo bioceramic sealers compared to AH Plus resin sealer. Materials and Methods: Modified direct contact test was used on three sets of sealers: Freshly mixed sealers, sealers that were 1-day old, and sealers that were 7-day old. After 24 h of incubation, the colony-forming units were digitally counted using Promega Colony Counter after 30 and 60 min of exposure to Enterococcus faecalis. For cytotoxic effect evaluation, 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay was performed at three different time points: 24 h, 48 h, and 120 h after adding the sealer eluates to human gingival fibroblasts, to assess cell viability. Data were analyzed using mixed model analysis of variance followed by post hoc test. Results: TotalFill bioceramic sealer showed the highest bacterial reduction against E. faecalis throughout all intervals. AH Plus showed great antibacterial activity initially which reduced drastically after 7 days. All the sealers showed a reduction in their antibacterial activity with time. TotalFill and NeoSEALER Flo showed very high cell viability in contrast to AH Plus. Conclusion: TotalFill and NeoSEALER Flo demonstrate superior antimicrobial properties against E. faecalis which reduces with time. TotalFill and NeoSEALER Flo demonstrate acceptable biocompatibility against human gingival fibroblasts, which decreased over time.

Measurement of student engagement in health professions education: a review of literature.

Student engagement is a complex multidimensional construct that has attained great interest in health professions education (HPE). Definition and conceptualization of student engagement is an important step that should drive the development of the instruments for its measurement. We have recently proposed a comprehensive framework for student engagement in HPE with a definition of engagement as student investment of time and energy in academic and non-academic experiences that include learning, teaching, research, governance, and community activities. The dimensions of student engagement in this framework included the cognitive, affective, behavioral, agentic, and socio-cultural. Guided by the student engagement framework, this non-systematic review aims to identify, critically appraise, and summarize the existing methods for measuring student engagement in HPE. Extrapolating from higher education literature, we attempted to link the theoretical perspectives of student engagement with the published methods of its measurement in HPE context. In addition, we have described the different methods of measuring student engagement including self-report surveys, real time measures, direct observation, interviews/focus groups, and the use of multiple instruments. The span of engagement dimensions measured by self-report surveys ranges from one to five dimensions. However, measurement of agentic and sociocultural dimensions of engagement in HPE is still limited and further research is required. We have also reflected on the existing methods of measuring engagement of students as active partners in HPE. The review also describes the advantages, limitations, and psychometric properties of each method for measuring student engagement. We ended the review with a guiding conclusion on how to develop and select an instrument for measuring student engagement in HPE. Finally, we addressed the gaps in the literature about measuring engagement of HPE students and future research plans.

Prediction of Lymphovascular and Perineural Invasion of Oral Squamous Cell Carcinoma by Combined Expression of p63 and Cyclin D1.

OBJECTIVES: The aim of this study was to determine the value of immune expression of p63 and cyclin D1 in the prediction of lymphovascular invasion (LVI) and perineural invasion (PNI) in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Clinical and histopathologic features of 65 subjects with histologically confirmed OSCC were collected. Tissue microarray blocks representing all subjects were prepared for the immunohistochemical quantification of the nuclear expression of p63 and cyclin D1 using immune ratio plugin of image J software. Image analysis was performed by two independent pathologists. Independent samples t-test, analysis of variance, and receiver operating characteristic curve tests were used for statistical analysis. The level of significance was set at p≤ 0.05. RESULTS: The optimum cutoff value for the prediction of LVI for p63 and cyclin D1 was found to be 100 and 93.2, respectively, while the optimum cutoff value for the prediction of PNI for p63 and cyclin D1 was found to be 95.9 and 94, respectively. p63 and cyclin D1 expression correlated with several clinicopathologic features of the studied population. p63 expression was a significant predictor of moderate/poorly differentiated OSCC compared with well-differentiated OSCC. A parallel combination of positive p63 and cyclin D1 increased the specificity of predicting LVI from 89.1% and 67.4% for either p63 or cyclin D1, respectively, to 93.5% with a positive predictive value of 92.5%. Similarly, the parallel combination of the two markers raised the specificity of predicting PNI from 70% and 77.5% for either p63 or cyclin D1, respectively, to 90% with a positive predictive value of 86.3%. CONCLUSION: Combined overexpression of nuclear markers p63 and cyclin D1 can be considered as a valuable independent predictor of LVI and PNI, and hence tumor progression, in OSCC.

Effect of different teaching/learning approaches using virtual patients on student's situational interest and cognitive load: a comparative study.

BACKGROUND: Virtual Patients (VPs) have been receiving considerable attention in medical education as an authentic learning and teaching approach. The study aimed to evaluate the effect of using different approaches of conduction of virtual patients (VPs) on students' cognitive load and situational interest. METHODS: The study is an experimental study. Two different cohorts have participated during the academic year 2019/2020 and 2020/2021. The first cohort (Group 1) was exposed to a lecture followed by an independent VPs session, and the second cohort (Group 2) was exposed to a collaborative VPs session. The situational interest and Cognitive load were compared between the two groups. All sessions are about one topic related to maxillofacial trauma. RESULTS: Findings showed that there was no significant difference between the median score of the situational interest at repeated time points during the Collaborative VPs (Group 2). However, in group 1, there was a significant difference between the median score of situational interest at repeated time points during independent VPs where the lowest score was found to be at the end of the session. Also, results showed that the collaborative VPs (Group 2) showed a high median score of situational interest than both lecture and independent VPs (Group 1). Furthermore, the study showed that there is no significant difference in the intrinsic cognitive load among the three sessions. However, the extraneous cognitive load was low in collaborative VPs (Group 2) than in both lecture and independent VPs sessions (Group 1). CONCLUSION: The use of VPs in a collaborative interactive learning activity is more effective than its use as an independent learning activity in enhancing students' situational interest and reducing cognitive load. However, giving independent VPs after the lecture with the same topic is considered a limitation of the study as this can affect the situational interest of the students by filling their gab of knowledge.

Student engagement in undergraduate medical education: A scoping review.

INTRODUCTION: Student engagement is defined as behavioural, cognitive and emotional aspects of students' academic experience in teaching, learning and research through interacting with other students, faculty and community. Despite the growing interest in the field of student engagement, medical education research in this area is still fragmented. This scoping review aims to contribute to the understanding of measurements, drivers and outcomes of medical student engagement. METHODS: The authors searched MEDLINE, PubMed, ProQuest, SCOPUS, ERIC, Science Direct and EBESCO for English articles published from 1990 until October 2021. In addition, we hand-searched key medical education journals and references in recently published articles. Using specific selection criteria, two authors independently reviewed the articles for eligibility, followed by data extraction using both quantitative and qualitative analysis. RESULTS: Of the 2136 retrieved articles, 51 studies were selected for the review, and 94% of them were published in the past 8 years. The prevailing measures of student engagement failed to cover the multidimensionality of the construct with more focus on the behavioural dimension. Quantitative methods represented two thirds of the studies with a higher frequency of cross-sectional designs and using self-reports. The identified drivers of medical students' engagement are directed mainly to modifying the context of the learning environment. These factors increased student engagement by fostering relevance of learning, positive student relationships with peers and faculty, and enhancing student agency, and sense of competence. Cognitive engagement appears to be a positive predictor of academic achievement, but the relationship with other dimensions of engagement is controversial. CONCLUSIONS: Student engagement in undergraduate medical education is an important, yet under-researched construct. The research that does exist suggests engagement to be malleable, something that can be modified by different types of interventions taking into consideration the context of education and practice. Further research is required, however, to address the gaps identified in this review.

Gingival Depigmentation Using Diode 980 nm and Erbium-YAG 2940 nm Lasers: A Split-Mouth Clinical Comparative Study.

BACKGROUND: Gingival hyperpigmentation, "black gum," refers to black discrete single or multiple pigments on the gingiva. Several factors may play a role in gingival hyperpigmentation ranging from physiologic pigmentation to manifestations of systemic diseases. Several techniques have been used for gingival depigmentation to lighten its color. METHODS: Fifteen patients exhibiting nonsmoking melanin hyperpigmentation, with the mean age of 28.6 ± 7.8 years, were recruited. The facial gingiva of the anterior teeth and premolars of each jaw was divided into two halves. The right or left side of each jaw quadrant randomly received either diode laser operating at 980 nm wavelength or erbium-YAG laser at 2940 nm. Parameters such as degree of gingival depigmentation, bleeding, pain, patient satisfaction, and wound healing were assessed and compared between the two techniques. The subjects were followed up to six months for melanin pigmentation recurrence. RESULTS: Both techniques were efficient for gingival depigmentation. Nevertheless, bleeding during surgery was statistically higher for Er:YAG laser technique as compared to diode laser. Wound healing showed statistically nonsignificant differences between the two lasers, although Er:YAG seems to give better outcomes than the diode. The patients were satisfied with both laser techniques during and after gingival depigmentation. However, the pain score was higher for Er:YAG laser than for diode laser. CONCLUSION: This study demonstrated that both lasers' techniques are efficient for gingival depigmentation. However, diode laser seems to show less painful experience and relatively better bleeding control.

Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and Plasticity.

Hypoxia, or gradients of hypoxia, occurs in most growing solid tumors and may result in pleotropic effects contributing significantly to tumor aggressiveness and therapy resistance. Indeed, the generated hypoxic stress has a strong impact on tumor cell biology. For example, it may contribute to increasing tumor heterogeneity, help cells gain new functional properties and/or select certain cell subpopulations, facilitating the emergence of therapeutic resistant cancer clones, including cancer stem cells coincident with tumor relapse and progression. It controls tumor immunogenicity, immune plasticity, and promotes the differentiation and expansion of immune-suppressive stromal cells. In this context, manipulation of the hypoxic microenvironment may be considered for preventing or reverting the malignant transformation. Here, we review the current knowledge on how hypoxic stress in tumor microenvironments impacts on tumor heterogeneity, plasticity and resistance, with a special interest in the impact on immune resistance and tumor immunogenicity.

Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta.

Amelogenesis is the process of dental enamel formation, leading to the deposition of the hardest tissue in the human body. This process requires the intricate regulation of ion transport and controlled changes to the pH of the developing enamel matrix. The means by which the enamel organ regulates pH during amelogenesis is largely unknown. We identified rare homozygous variants in GPR68 in three families with amelogenesis imperfecta, a genetically and phenotypically heterogeneous group of inherited conditions associated with abnormal enamel formation. Each of these homozygous variants (a large in-frame deletion, a frameshift deletion, and a missense variant) were predicted to result in loss of function. GPR68 encodes a proton-sensing G-protein-coupled receptor with sensitivity in the pH range that occurs in the developing enamel matrix during amelogenesis. Immunohistochemistry of rat mandibles confirmed localization of GPR68 in the enamel organ at all stages of amelogenesis. Our data identify a role for GPR68 as a proton sensor that is required for proper enamel formation.

Whole-exome sequencing, without prior linkage, identifies a mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta.

The conventional approach to identifying the defective gene in a family with an inherited disease is to find the disease locus through family studies. However, the rapid development and decreasing cost of next generation sequencing facilitates a more direct approach. Here, we report the identification of a frameshift mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta (AI). Whole-exome sequencing of three affected family members and subsequent filtering of shared variants, without prior genetic linkage, sufficed to identify the pathogenic variant. Simultaneous analysis of multiple family members confirms segregation, enhancing the power to filter the genetic variation found and leading to rapid identification of the pathogenic variant. LAMB3 encodes a subunit of Laminin-5, one of a family of basement membrane proteins with essential functions in cell growth, movement and adhesion. Homozygous LAMB3 mutations cause junctional epidermolysis bullosa (JEB) and enamel defects are seen in JEB cases. However, to our knowledge, this is the first report of dominant AI due to a LAMB3 mutation in the absence of JEB.

Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta.

Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis.

Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation amelogenesis imperfecta.

Healthy dental enamel is the hardest and most highly mineralized human tissue. Though acellular, nonvital, and without capacity for turnover or repair, it can nevertheless last a lifetime. Amelogenesis imperfecta (AI) is a collective term for failure of normal enamel development, covering diverse clinical phenotypes that typically show Mendelian inheritance patterns. One subset, known as hypomaturation AI, is characterised by near-normal volumes of organic enamel matrix but with weak, creamy-brown opaque enamel that fails prematurely after tooth eruption. Mutations in genes critical to enamel matrix formation have been documented, but current understanding of other key events in enamel biomineralization is limited. We investigated autosomal-recessive hypomaturation AI in a consanguineous Pakistani family. A whole-genome SNP autozygosity screen identified a locus on chromosome 15q21.3. Sequencing candidate genes revealed a point mutation in the poorly characterized WDR72 gene. Screening of WDR72 in a panel of nine additional hypomaturation AI families revealed the same mutation in a second, apparently unrelated, Pakistani family and two further nonsense mutations in Omani families. Immunohistochemistry confirmed intracellular localization in maturation-stage ameloblasts. WDR72 function is unknown, but as a putative beta propeller is expected to be a scaffold for protein-protein interactions. The nearest homolog, WDR7, is involved in vesicle mobilization and Ca2+-dependent exocytosis at synapses. Vesicle trafficking is important in maturation-stage ameloblasts with respect to secretion into immature enamel and removal of cleaved enamel matrix proteins via endocytosis. This raises the intriguing possibility that WDR72 is critical to ameloblast vesicle turnover during enamel maturation.

Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta.

The combination of recessively inherited cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) was first reported by Jalili and Smith in 1988 in a family subsequently linked to a locus on chromosome 2q11, and it has since been reported in a second small family. We have identified five further ethnically diverse families cosegregating CRD and AI. Phenotypic characterization of teeth and visual function in the published and new families reveals a consistent syndrome in all seven families, and all link or are consistent with linkage to 2q11, confirming the existence of a genetically homogenous condition that we now propose to call Jalili syndrome. Using a positional-candidate approach, we have identified mutations in the CNNM4 gene, encoding a putative metal transporter, accounting for the condition in all seven families. Nine mutations are described in all, three missense, three terminations, two large deletions, and a single base insertion. We confirmed expression of Cnnm4 in the neural retina and in ameloblasts in the developing tooth, suggesting a hitherto unknown connection between tooth biomineralization and retinal function. The identification of CNNM4 as the causative gene for Jalili syndrome, characterized by syndromic CRD with AI, has the potential to provide new insights into the roles of metal transport in visual function and biomineralization.